Clinical Focus

  • Interventional Neuroradiology
  • Cerebrovascular Disorders
  • Stroke Treatment and Imaging
  • Brain Aneurysms
  • Arteriovenous Malformations
  • Diagnostic Radiology

Academic Appointments

Administrative Appointments

  • Chief, Interventional Neuroradiology, Stanford University Medical Center (1992 - Present)
  • Director of Neuroradiology, Stanford Stroke Center (1991 - Present)

Professional Education

  • Fellowship:Stanford University School of Medicine Registrar (1988) CA
  • Residency:LAC and USC Medical Center (1986) CA
  • Board Certification: Neuroradiology, American Board of Radiology (1996)
  • Board Certification: Diagnostic Radiology, American Board of Radiology (1986)
  • Certificate Added Qualification, Neuroradiology, American Board of Radiology (1996)
  • Maintenance Certification, Neuroradiology, American Board of Radiology (2009)
  • Internship:Boston City Hospital (1981) MA
  • Medical Education:Boston Univ Medical Center (1980) MA

Research & Scholarship

Current Research and Scholarly Interests

Interventional neuroradiology; cerebral arteriovenous malformations; stroke treatment and imaging; cerebral aneurysms

Clinical Trials

  • Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 Not Recruiting

    This is a study to evaluate the hypothesis that FDA cleared thrombectomy devices plus medical management leads to superior clinical outcomes in acute ischemic stroke patients at 90 days when compared to medical management alone in appropriately selected subjects with the Target mismatch profile and an MCA (M1 segment) or ICA occlusion who can be randomized and have endovascular treatment initiated between 6-16 hours after last seen well.

    Stanford is currently not accepting patients for this trial.

    View full details


2018-19 Courses


All Publications

  • Persistent Target Mismatch Profile >24 Hours After Stroke Onset in DEFUSE 3. Stroke Christensen, S., Mlynash, M., Kemp, S., Yennu, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023392


    Background and Purpose- Efficacy of endovascular thrombectomy has been demonstrated up to 24 hours after stroke onset in patients selected with perfusion imaging. We hypothesized that a persistent favorable perfusion profile exists in some patients beyond 24 hours from the onset and can be predicted by a lower baseline hypoperfusion intensity ratio, which indicates favorable collaterals. Methods- We identified control arm patients from the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with a diffusion weighted imaging and perfusion magnetic resonance imaging performed 24 hours following randomization and compared imaging and clinical variables between patients with persistent mismatch versus patients who no longer had a mismatch 24 hours after randomization. Results- Eighteen percent of the control arm patients had a persistent favorable profile >38 hours after last known well time. These patients had similar baseline diffusion weighted imaging and Tmax >6 seconds volumes as patients whose initially favorable perfusion profile became unfavorable (diffusion weighted imaging lesion 7 versus 17 mL; P=0.17, Tmax >6 seconds 98 versus 100 mL; P=0.48) yet experienced less infarct growth (15 versus 59 mL; P<0.001) and had 3-fold smaller infarct volumes (15 versus 59 mL; P<0.001) 24 hours after randomization. Patients with a persistent favorable perfusion profile had a significantly lower hypoperfusion intensity ratio on baseline imaging (0.2 versus 0.4; P<0.01). Favorable clinical outcome at 90 days occurred in only 10% of the persistent mismatch patients. Conclusions- About 20% of patients with a middle cerebral artery or internal carotid artery occlusion who present in an extended time window and are not treated with thrombectomy have a persistent mismatch for at least an additional 24 hours. These patients have a favorable hypoperfusion intensity ratio at presentation, may experience delayed infarct expansion, and have poor clinical outcomes. Clinical trials are needed to determine if patients with a favorable perfusion profile benefit from reperfusion beyond 24 hours. Clinical Trial Registration- URL: . Unique identifier: NCT02586415.

    View details for DOI 10.1161/STROKEAHA.118.023392

    View details for PubMedID 30735466

  • Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window: A Subanalysis From the DEFUSE 3 Trial. JAMA neurology Sarraj, A., Mlynash, M., Savitz, S. I., Heit, J. J., Lansberg, M. G., Marks, M. P., Albers, G. W. 2019


    Importance: Although thrombectomy benefit was maintained in transfer patients with ischemic stroke in early-window trials, overall functional independence rates were lower in thrombectomy and medical management-only groups.Objective: To evaluate whether the imaging-based selection criteria used in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) trial would lead to comparable outcome rates and treatment benefits in transfer vs direct-admission patients.Design, Setting, and Participants: Subgroup analysis of DEFUSE 3, a prospective, randomized, multicenter, blinded-end point trial. Patients were enrolled between May 2016 and May 2017 and were followed up for 90 days. The trial comprised 38 stroke centers in the United States and 182 patients with stroke with a large-vessel anterior circulation occlusion and initial infarct volume of less than 70 mL, mismatch ratio of at least 1.8, and mismatch volume of at least 15 mL, treated within 6 to 16 hours from last known well. Patients were stratified based on whether they presented directly to the study site or were transferred from a primary center. Data were analyzed between July 2018 and October 2018.Interventions or Exposures: Endovascular thrombectomy plus standard medical therapy vs standard medical therapy alone.Main Outcomes and Measures: The primary outcome was the distribution of 90-day modified Rankin Scale scores.Results: Of the 296 patients who consented, 182 patients were randomized (66% were transfer patients and 34% directly presented to a study site). Median age was 71 years (interquartile range [IQR], 60-79 years) vs 70 years (IQR, 59-80 years); 69 transfer patients were women (57%) and 23 of the direct group were women (37%). Transfer patients had longer median times from last known well to study site arrival (9.43 vs 9 hours) and more favorable collateral profiles (based on hypoperfusion intensity ratio): median for transfer, 0.35 (IQR, 0.18-0.47) vs 0.42 (IQR, 0.25-0.56) for direct (P=.05). The primary outcome (90-day modified Rankin Scale score shift) did not differ in the direct vs transfer groups (direct OR, 2.9; 95% CI, 1.2-7.2; P=.01; transfer OR, 2.6; 95% CI, 1.3-4.8; P=.009). The overall functional independence rate (90-day modified Rankin Scale score 0-2) in the thrombectomy group did not differ (direct 44% vs transfer 45%) nor did the treatment effect (direct OR, 2.0; 95% CI, 0.9-4.4 vs transfer OR, 3.1; 95% CI, 1.6-6.1). Thrombectomy reperfusion rates, mortality, and symptomatic intracranial hemorrhage rates did not differ.Conclusions and Relevance: In late-window patients selected by penumbral mismatch criteria, both the favorable outcome rate and treatment effect did not decline in transfer patients. These results have health care implications indicating transferring potential candidates for late-window thrombectomy is associated with substantial clinical benefits and should be encouraged.Trial Registration: identifier: NCT02586415.

    View details for DOI 10.1001/jamaneurol.2019.0118

    View details for PubMedID 30734042

  • Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3. Stroke Rao, V., Christensen, S., Yennu, A., Mlynash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023177


    Background and Purpose- Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume. Methods- Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses. Results- Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization ( r=0.83; P<0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization ( r=0.77; P<0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125; r=0.83; P<0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes. Conclusions- The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients. Clinical Trial Registration- URL: . Unique identifier: NCT02586415.

    View details for DOI 10.1161/STROKEAHA.118.023177

    View details for PubMedID 30727840

  • DEFUSE 3 Non-DAWN Patients. Stroke Leslie-Mazwi, T. M., Hamilton, S., Mlynash, M., Patel, A. B., Schwamm, L. H., Lansberg, M. G., Marks, M., Hirsch, J. A., Albers, G. W. 2019: STROKEAHA118023310


    Background and Purpose- DAWN (Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) established thrombectomy for patients with emergent large vessel occlusions presenting 6 to 24 hours after symptom onset. Given the greater inclusivity of DEFUSE 3, we evaluated the effect of thrombectomy in DEFUSE 3 patients who would have been excluded from DAWN. Methods- Eligibility criteria of the DAWN trial were applied to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large, National Institutes of Health Stroke Scale (NIHSS) score 6 to 9, and modified Rankin Scale score of 2. Subgroups were compared with the DEFUSE 3 non-DAWN and entire DEFUSE 3 cohorts. Results- There were 71 DEFUSE 3 non-DAWN patients; 31 patients with NIHSS 6 to 9, 33 with core too large, and 13 with premorbid modified Rankin Scale score of 2 (some patients met multiple criteria). For core-too-large patients, median 24-hour infarct volume was 119 mL (interquartile range, 74.6-180) versus 31.5 mL (interquartile range, 17.6-64.3) for core-not-too-large patients ( P<0.001). Complications and functional outcomes were similar between the groups. Thrombectomy in core-too-large patients compared with the remaining DEFUSE 3 non-DAWN patients conveyed benefit for functional outcome (odds ratio, 20.9; CI, 1.3-337.8). Comparing the NIHSS 6 to 9 group with the NIHSS ≥10 patients, modified Rankin Scale score 0 to 2 outcomes were achieved in 74% versus 22% ( P<0.001), with mortality in 6% versus 23% ( P=0.024), respectively. For patients with NIHSS 6 to 9 compared with the remaining DEFUSE 3 non-DAWN patients, thrombectomy trended toward a better chance of functional outcome (odds ratio, 1.86; CI, 0.36-9.529). Conclusions- Patients with pretreatment core infarct volumes <70 mL but too large for inclusion by DAWN criteria demonstrate benefit from endovascular therapy. More permissive pretreatment core thresholds in core-clinical mismatch selection paradigms may be appropriate. In contrast to data supporting a beneficial treatment effect across the full range of NIHSS scores in the entire DEFUSE 3 population, only a trend toward benefit of thrombectomy in patients with NIHSS 6 to 9 was found in this small subgroup.

    View details for DOI 10.1161/STROKEAHA.118.023310

    View details for PubMedID 30727856

  • Results From DEFUSE 3. Stroke de Havenon, A., Mlynash, M., Kim-Tenser, M. A., Lansberg, M. G., Leslie-Mazwi, T., Christensen, S., McTaggart, R. A., Alexander, M., Albers, G., Broderick, J., Marks, M. P., Heit, J. J., DEFUSE 3 Investigators 2019: STROKEAHA118023407


    Background and Purpose- The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. We sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window. Methods- This is a prespecified analysis of DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). We included patients with computed tomography angiography as their baseline imaging and rated collateral status using the validated scales described by Tan and Maas. The primary outcome is functional independence (modified Rankin scale score of ≤2). Additional outcomes include the full range of the modified Rankin scale, baseline ischemic core volume, change from baseline in the ischemic core volume at 24 hours, and death at 90 days. Results- Of the 130 patients in our cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis (30% versus 39%; P=0.3) or after adjustment for treatment arm (odds ratio [95% CI], 0.61 [0.26-1.45]). Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant ( P=0.8). Collateral status also did not affect the rate of stroke-related death (n [%], good versus poor collaterals, 18/97 [19%] versus 8/33 [24%], P=0.5]. Conclusions- In DEFUSE 3 patients, good leptomeningeal collaterals on single phase computed tomography angiography were not predictive of functional independence or death and did not impact the treatment effect of endovascular thrombectomy. These unexpected findings require further study to confirm their validity and to better understand the role of collaterals for stroke patients with anterior circulation large vessel occlusion in the late therapeutic window. Clinical Trial Registration- URL: . Unique identifier: NCT02586415.

    View details for DOI 10.1161/STROKEAHA.118.023407

    View details for PubMedID 30726184

  • Association of Thrombectomy With Stroke Outcomes Among Patient Subgroups: Secondary Analyses of the DEFUSE 3 Randomized Clinical Trial. JAMA neurology Lansberg, M. G., Mlynash, M., Hamilton, S., Yeatts, S. D., Christensen, S., Kemp, S., Lavori, P. W., Gutierrez, S. O., Broderick, J., Heit, J., Marks, M. P., Albers, G. W., DEFUSE 3 Investigators 2019


    Importance: The DEFUSE 3 randomized clinical trial previously demonstrated benefit of endovascular thrombectomy for acute ischemic stroke in the 6- to 16-hour time window. For treatment recommendations, it is important to know if the treatment benefit was universal.Objective: To determine the outcomes among patients who may have a reduced effect of thrombectomy, including those who are older, have milder symptoms, or present late.Design, Setting, and Participants: DEFUSE 3 was a randomized, open-label, blinded end point trial conducted from May 2016 to May 2017. This multicenter study included 38 sites in the United States. Of 296 patients who were enrolled in DEFUSE 3, 182 patients met all inclusion criteria and were randomized and included in the intention-to-treat analysis, which was conducted in August 2017. These patients had acute ischemic strokes due to an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion computed tomography or magnetic resonance imaging. The study was stopped early for efficacy.Interventions: Endovascular thrombectomy plus medical management vs medical management alone.Main Outcomes and Measures: Functional outcome at day 90, assessed on the modified Rankin Scale. Multivariate ordinal logistic regression was used to calculate the adjusted proportional association between endovascular treatment and clinical outcome (shift in the distribution of modified Rankin Scale scores expressed as a common odds ratio) among patients of different ages, baseline stroke severities, onset-to-treatment times, locations of the arterial occlusion, and imaging modalities used to document the presence of salvageable tissue (computed tomography vs magnetic resonance imaging).Results: This study included 182 patients (median [interquartile range] age, 70 [59-80] years; median [interquartile range] National Institutes of Health Stroke Scale score, 16 [11-21], and 92 women [51%]). In the overall cohort, independent predictors of better functional outcome were younger age, lower baseline National Institutes of Health Stroke Scale score, and lower serum glucose level. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1 (95% CI, 1.8-5.4). There was no significant interaction between this treatment effect and age (P=.93), National Institutes of Health Stroke Scale score (P=.87), time to randomization (P=.56), imaging modality (P=.49), or location of the arterial occlusion (P=.54).Conclusions and Relevance: Endovascular thrombectomy, initiated up to 16 hours after last known well time in patients with salvageable tissue on perfusion imaging, benefits patients with a broad range of clinical features. Owing to the small sample size of this study, a pooled analysis of late time window endovascular stroke trials is needed to confirm these results.Trial Registration: identifier: NCT02586415.

    View details for DOI 10.1001/jamaneurol.2018.4587

    View details for PubMedID 30688974

  • Surgical Treatment of Recurrent Previously Coiled and/or Stent-Coiled Intracerebral Aneurysms: A Single-Center Experience in a Series of 75 Patients. World neurosurgery Liu, J. J., Nielsen, T. H., Abhinav, K., Lee, J., Han, S. S., Marks, M. P., Do, H. M., Dodd, R. L., Steinberg, G. K. 2019


    BACKGROUND: Endovascular treated cerebral aneurysms have a greater recurrence rate compared to microsurgical clip ligation. Despite recent endovascular advances, microsurgical clip ligation might be the treatment of choice for certain previously endovascular treated recurrent aneurysms. We report on our single-center experience with 76 previously coiled and/or stent-coiled aneurysms.OBJECTIVE: To analyse the surgical and radiological outcome after clipping of previous endovascular treated recurrent cerebral aneurysms.METHODS: Patients were retrospectively identified. Demographic data, aneurysm size, location, perioperative coil extraction, occlusion rate and complication rate was recorded. Patients were divided into a previously coiled-only group (COG) and a previously stent-assisted coiled group (SAC).RESULTS: Seventy-five patients with seventy-six aneurysms were included. Sixty-nine patients were included in the COG, seven patients in the SAC. Complete or acceptable near-complete occlusion was obtained in 95% of patients in the COG and 57% in the SAC. Two patients in the COG (2.9%) died postoperatively from a major stroke. One patient died from re-hemorrhage after wrapping of an aneurysm. Minor complications occurred in 8.7%. In the SAC the mortality was 0% with one major stroke (14.2%), 1 (14.2%) minor stroke and 1 (14.2%) cranial nerve palsy. Intraoperative coil extraction and previous stent-assisted coiling were significant predictors of complication rate (p=0.025 and p=0.0036 respectively). Previous stent-assisted coiling was a significant predictor of incomplete occlusion (p=0.036).CONCLUSIONS: Microsurgical clipping of previously endovascular treated recurrent aneurysms is an effective treatment with high obliteration rates. Previously stent-assisted coiling and intraoperative coil extraction are predictors of worse outcome and incomplete occlusion.

    View details for DOI 10.1016/j.wneu.2018.12.171

    View details for PubMedID 30639494

  • Endovascular Treatment in the DEFUSE 3 Study. Stroke Marks, M. P., Heit, J. J., Lansberg, M. G., Kemp, S., Christensen, S., Derdeyn, C. P., Rasmussen, P. A., Zaidat, O. O., Broderick, J. P., Yeatts, S. D., Hamilton, S., Mlynash, M., Albers, G. W. 2018


    BACKGROUND AND PURPOSE: Endovascular therapy in an extended time window has been shown to be beneficial in selected patients. This study correlated angiographic outcomes of patients randomized to endovascular therapy with clinical and imaging outcomes in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3).METHODS: Angiograms were assessed for the primary arterial occlusive lesion and the modified Thrombolysis in Cerebral Infarction (TICI) score at baseline and the final modified TICI score. Clinical outcomes were assessed using an ordinal analysis of 90-day modified Rankin Scale and a dichotomous analysis for functional independence (modified Rankin Scale score of 0-2). TICI scores were correlated with outcome, types of device used for thrombectomy, and 24-hour follow-up imaging.RESULTS: TICI 2B-3 reperfusion was achieved in 70 of 92 patients (76%). TICI 2B-3 reperfusion showed a more favorable distribution of Rankin scores compared with TICI 0-2A; odds ratio, 2.77; 95% confidence interval, 1.17-6.56; P=0.019. Good functional outcome (90-day modified Rankin Scale score of 0-2) increased with better TICI scores (P=0.0028). There was less disability comparing TICI 3 patients to TICI 2B patients (P=0.037). Successful reperfusion (TICI 2B-3) was independent of the device used, the site of occlusion (internal carotid artery or M1) or adjunctive use of carotid angioplasty and stenting. Significantly less infarct growth at 24 hours was seen in TICI 3 patients compared with TICI 0-2A (P=0.0015) and TICI 2B (P=0.0002) patients.CONCLUSIONS: Thrombectomy in an extended time window demonstrates similar rates of TICI 2B-3 reperfusion to earlier time window studies. Successful reperfusion was independent of the device used, the site of occlusion or adjunctive use of carotid angioplasty and stenting. TICI 3 reperfusion was more likely to result in low rates of infarct growth at 24 hours and good functional outcome at 90 days.CLINICAL TRIAL REGISTRATION: URL: Unique identifier: NCT02586415.

    View details for DOI 10.1161/STROKEAHA.118.022147

    View details for PubMedID 29986935

  • Thrombectomy for Stroke with Selection by Perfusion Imaging REPLY NEW ENGLAND JOURNAL OF MEDICINE Albers, G. W., Marks, M. P., Lansberg, M. G. 2018; 378 (19): 1849–50
  • Thrombectomy for Stroke with Selection by Perfusion Imaging NEW ENGLAND JOURNAL OF MEDICINE Vinny, P., Vishnu, V. Y., Srivastava, M. 2018; 378 (19): 1849

    View details for Web of Science ID 000431774400019

    View details for PubMedID 29745632

  • Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke STROKE Tsai, J. P., Mlynash, M., Christensen, S., Kemp, S., Kim, S., Mishra, N. K., Federau, C., Nogueira, R. G., Jovin, T. G., Devlin, T. G., Akhtar, N., Yavagal, D. R., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W., Lansberg, M. G., CRISP Investigators 2018; 49 (4): 952-+


    This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke.We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0-2) at day 90 and radiographic outcomes at day 5.Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence (P=0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P=0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49-166] versus 43 [18-81] mL; P=0.006) and larger final infarct volumes (110 [61-155] versus 48 [21-99] mL; P=0.001).Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

    View details for DOI 10.1161/STROKEAHA.117.018858

    View details for Web of Science ID 000429153900035

    View details for PubMedID 29581341

    View details for PubMedCentralID PMC5875452

  • Early Cerebral Vein After Endovascular Ischemic Stroke Treatment Predicts Symptomatic Reperfusion Hemorrhage. Stroke Cartmell, S. C., Ball, R. L., Kaimal, R., Telischak, N. A., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018


    Parenchymal hemorrhage (PH) after endovascular mechanical thrombectomy in acute ischemic stroke leads to worse outcomes. Better clinical and imaging biomarkers of symptomatic reperfusion PH are needed to identify patients at risk. We identified clinical and imaging predictors of reperfusion PH after endovascular mechanical thrombectomy with attention to early cerebral veins (ECVs) on postreperfusion digital subtraction angiography.We performed a retrospective cohort study of consecutive acute ischemic stroke patients undergoing endovascular mechanical thrombectomy at our neurovascular referral center. Clinical and imaging characteristics were collected from patient health records, and random forest variable importance measures were used to identify predictors of symptomatic PH. Predictors of secondary outcomes, including 90-day mortality, functional dependence (modified Rankin Scale score, >2), and National Institutes of Health Stroke Scale shift, were also determined. Diagnostic test characteristics of ECV for symptomatic PH were determined using a receiver operating characteristic analysis. Differences between patients with and without symptomatic PH were assessed with Fisher exact test and the Wilcoxon rank sum (Mann-Whitney U test) test at the 0.05 significance level.Of 64 patients with anterior circulation large-vessel occlusion identified, 6 (9.4%) developed symptomatic PH. ECV was the strongest predictor of symptomatic PH with more than twice the importance of the next best predictor, male sex. Although ECV was also predictive of 90-day mortality and functional dependence, other characteristics were more important than ECV for these outcomes. The sensitivity and specificity of ECV alone for subsequent hemorrhage were both 0.83, with an area under the curve of 0.83 and 95% confidence interval of 0.66 to 1.00.ECV on postendovascular mechanical thrombectomy digital subtraction angiography is highly diagnostic of subsequent symptomatic reperfusion hemorrhage in this data set. This finding has important implications for post-treatment management of blood pressure and anticoagulation.

    View details for DOI 10.1161/STROKEAHA.118.021402

    View details for PubMedID 29739912

  • Sofia intermediate catheter and the SNAKE technique: safety and efficacy of the Sofia catheter without guidewire or microcatheter construct. Journal of neurointerventional surgery Heit, J. J., Wong, J. H., Mofaff, A. M., Telischak, N. A., Dodd, R. L., Marks, M. P., Do, H. M. 2018; 10 (4): 401–6


    Neurointerventional surgeries (NIS) benefit from supportive endovascular constructs. Sofia is a soft-tipped, flexible, braided single lumen intermediate catheter designed for NIS. Sofia advancement from the cervical to the intracranial circulation without a luminal guidewire or microcatheter construct has not been described.To evaluate the efficacy and safety of the new Sofia Non-wire Advancement techniKE (SNAKE) for advancement of the Sofia into the cerebral circulation.Consecutive patients who underwent NIS using Sofia were identified. Patient information, SNAKE use, and patient outcome were determined from electronic medical records. Sofia advancement to the cavernous internal carotid artery or the V2/V3 segment junction of the vertebral artery was the primary outcome measure. Secondary outcomes included arterial vasospasm and arterial dissection.263 Patients (181 females, 69%) who underwent a total of 305 NIS using Sofia were identified. SNAKE (SNAKE+) was used in 187 procedures (61%). Two hundred and ninety-three procedures (96%) were technically successful, which included 184 SNAKE+ NIS and 109 SNAKE- NIS. Primary outcome was achieved in all SNAKE+ procedures, but not in five SNAKE- procedures (2%). No arterial dissections were identified among 305 interventions. In the intracranial circulation, a single SNAKE+ patient (0.5%) had non-flow limiting arterial vasospasm involving the petrous internal carotid. Three SNAKE+ patients (1.6%) and one SNAKE- patient (0.8%) demonstrated external carotid artery branch artery vasospasm during dural arteriovenous fistula or facial arteriovenous malformation treatment.SNAKE is a safe and effective technique for Sofia advancement. Sofia is a highly effective and safe intermediate catheter for a variety of NIS.

    View details for DOI 10.1136/neurintsurg-2017-013256

    View details for PubMedID 28768818

  • Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? Journal of neurointerventional surgery Wolman, D. N., Iv, M., Wintermark, M., Zaharchuk, G., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018


    Acute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).This retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.Two hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529).AIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.

    View details for DOI 10.1136/neurintsurg-2018-013784

    View details for PubMedID 29555872

  • Reduced Intravoxel Incoherent Motion Microvascular Perfusion Predicts Delayed Cerebral Ischemia and Vasospasm After Aneurysm Rupture. Stroke Heit, J. J., Wintermark, M., Martin, B. W., Zhu, G., Marks, M. P., Zaharchuk, G., Dodd, R. L., Do, H. M., Steinberg, G. K., Lansberg, M. G., Albers, G. W., Federau, C. 2018


    Proximal artery vasospasm and delayed cerebral ischemia (DCI) after cerebral aneurysm rupture result in reduced cerebral perfusion and microperfusion and significant morbidity and mortality. Intravoxel incoherent motion (IVIM) magnetic resonance imaging extracts microvascular perfusion information from a multi-b value diffusion-weighted sequence. We determined whether decreased IVIM perfusion may identify patients with proximal artery vasospasm and DCI.We performed a pilot retrospective cohort study of patients with ruptured cerebral aneurysms. Consecutive patients who underwent a brain magnetic resonance imaging with IVIM after ruptured aneurysm treatment were included. Patient demographic, treatment, imaging, and outcome data were determined by electronic medical record review. Primary outcome was DCI development with proximal artery vasospasm that required endovascular treatment. Secondary outcomes included mortality and clinical outcomes at 6 months.Sixteen patients (11 females, 69%;P=0.9) were included. There were no differences in age, neurological status, or comorbidities between patients who subsequently underwent endovascular treatment of DCI (10 patients; DCI+ group) and those who did not (6 patients; DCI- group). Compared with DCI- patients, DCI+ patients had decreased IVIM perfusion fractionf(0.09±0.03 versus 0.13±0.01;P=0.03), reduced diffusion coefficientD(0.82±0.05 versus 0.92±0.07×10-3mm2/s;P=0.003), and reduced blood flow-related parameterfD* (1.18±0.40 versus 1.83±0.40×10-3mm2/s;P=0.009). IVIM pseudodiffusion coefficientD* did not differ between DCI- (0.011±0.002) and DCI+ (0.013±0.005 mm2/s;P=0.4) patients. No differences in mortality or clinical outcome were identified.Decreased IVIM perfusion fractionfand blood flow-related parameterfD* correlate with DCI and proximal artery vasospasm development after cerebral aneurysm rupture.

    View details for DOI 10.1161/STROKEAHA.117.020395

    View details for PubMedID 29439196

  • Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. The New England journal of medicine Albers, G. W., Marks, M. P., Kemp, S., Christensen, S., Tsai, J. P., Ortega-Gutierrez, S., McTaggart, R. A., Torbey, M. T., Kim-Tenser, M., Leslie-Mazwi, T., Sarraj, A., Kasner, S. E., Ansari, S. A., Yeatts, S. D., Hamilton, S., Mlynash, M., Heit, J. J., Zaharchuk, G., Kim, S., Carrozzella, J., Palesch, Y. Y., Demchuk, A. M., Bammer, R., Lavori, P. W., Broderick, J. P., Lansberg, M. G. 2018; 378 (8): 708–18


    Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms.We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90.The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18).Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 number, NCT02586415 .).

    View details for DOI 10.1056/NEJMoa1713973

    View details for PubMedID 29364767

  • Intraoperative neurophysiologic monitoring (IONM) changes associated with a case of delayed thalamic infarct: Implications for postoperative management. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Ghavami, F., Choudhri, O., Marks, M., Lopez, J. R. 2017


    Treatment of cerebral aneurysms poses a risk of cerebral hemorrhage and/or ischemia; these potential sequelae are usually associated with changes in intraoperative neurophysiologic monitoring (IONM) modalities. Our case demonstrates a patient with significant changes in IONM during the treatment of a right posterior cerebral artery aneurysm who did not develop neurologic deficits until three days postoperatively. IONM changes can represent a guide in postoperative patient management and may pose grounds for closer monitoring of patients with IONM changes that do not develop immediate postoperative deficits.

    View details for DOI 10.1016/j.jocn.2017.10.035

    View details for PubMedID 29066230

  • Management of Arteriovenous Malformations Associated with Developmental Venous Anomalies: A Literature Review and Report of 2 Cases WORLD NEUROSURGERY Zhang, M., Connolly, I. D., Teo, M. K., Yang, G., Dodd, R., Marks, M., Zuccarello, M., Steinberg, G. K. 2017; 106: 563–69


    Classification of cerebrovascular malformations has revealed intermediary lesions that warrant further review owing to their unusual presentation and management. We present 2 cases of arteriovenous malformation (AVM) associated with a developmental venous anomaly (DVA), and discuss the efficacy of previously published management strategies.Two cases of AVMs associated with DVA were identified, and a literature search for published cases between 1980 and 2016 was conducted. Patient demographic data and clinical features were documented.In case 1, a 29-year-old female presenting with parenchymal hemorrhage and left homonymous hemianopia was found to have a right parieto-occipital AVM fed from the anterior cerebral, middle cerebral, and posterior cerebral arteries, with major venous drainage to the superior sagittal sinus. In case 2, imaging in a 34-year-old female evaluated for night tremors and incontinence revealed a left parietal AVM with venous drainage to the superior sagittal sinus. Including our 2 cases, 22 cases of coexisting AVMs and DVAs have been reported in the literature. At presentation, 68% had radiographic evidence of hemorrhage. Stereotactic radiosurgery was performed in 7 cases, embolization in 6 cases, surgical resection in 4 cases, and multimodal therapy in 5 cases. Radiography at follow-up demonstrated successful AVM obliteration in 67% of cases (12 of 18).Patients with coexisting AVMs and DVAs tend to have a hemorrhagic presentation. Contrary to traditional AVM management, in these cases it is important to preserve the draining vein via the DVA to ensure a safe, sustained circulatory outflow of the associated brain parenchyma while achieving safe AVM obliteration.

    View details for DOI 10.1016/j.wneu.2017.07.042

    View details for Web of Science ID 000415850400071

    View details for PubMedID 28735125

  • Clot Imaging in Large Vessel Occlusion Strokes. Topics in magnetic resonance imaging Wong, J. H., Marks, M. P. 2017; 26 (3): 121-125


    Advances in mechanical thrombectomy techniques have resulted in improved, recanalization and functional outcomes in acute stroke, as demonstrated in recent, randomized trials comparing mechanical thrombectomy with thrombolysis. In conjunction with the technological advancements in thrombectomy devices, there has been better appreciation of stricter patient selection criteria for endovascular therapy based on pre-procedural imaging, including clot location, infarct volume, and penumbral territory at risk. Pre-procedural imaging performed to assess suitability for endovascular therapy commonly provides information on clot characteristics, such as clot location, length, density, and susceptibility, which can influence and may predict the efficacy of intravenous and endovascular treatments. The purpose of this review is to evaluate the role of clot imaging in acute large vessel occlusion strokes and discuss the relevance of clot imaging to thrombolytic and endovascular therapy.

    View details for DOI 10.1097/RMR.0000000000000127

    View details for PubMedID 28277464

  • CT Perfusion to Predict Response to Recanalization in Ischemic Stroke. Annals of neurology Lansberg, M. G., Christensen, S., Kemp, S., Mlynash, M., Mishra, N., Federau, C., Tsai, J. P., Kim, S., Nogueria, R. G., Jovin, T., Devlin, T. G., Akhtar, N., Yavagal, D. R., Haussen, D., Dehkharghani, S., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W. 2017


    To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging.Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1-20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5-27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4-140).The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856.

    View details for DOI 10.1002/ana.24953

    View details for PubMedID 28486789

  • Embolization Followed by Radiosurgery for the Treatment of Brain Arteriovenous Malformations (AVMs) WORLD NEUROSURGERY Marks, M. P., Marcellus, M. L., Santarelli, J., Dodd, R. L., Do, H. M., Chang, S. D., Adler, J. R., Mlynash, M., Steinberg, G. K. 2017; 99: 471-476


    Embolization has been proposed to reduce the size of the arteriovenous malformation (AVM) nidus in advance of radiosurgical treatment. Embolization followed by radiosurgery for brain AVMs, however, is controversial.We assessed the impact of embolization on nidal size before radiosurgical treatment and evaluated cure rates and complications by using embolization followed by radiosurgery.A retrospective review of our institutional AVM database identified 91 patients treated from 1995 to 2009 with embolization followed by radiosurgery. Pre- and postembolization AVM volumes were measured with angiography, and the modified radiation-based AVM scores (RBAS) also were calculated pre- and postembolization. RBAS determined from pre-embolization volumes were correlated with postradiosurgical obliteration.Median AVM volume declined from 18.8 mL (interquartile range, 10.2-32.2 mL) to 9.9 mL (3.1-19.2 mL) after embolization, P < 0.00003. Median RBAS scores decreased from 2.6 mL (1.8-3.9 mL) to 1.8 mL (1.0-2.8 mL), P < 0.00003. Two of 91 (2.2%) had new fixed deficits after embolization; however, no patient had new disabling deficits (modified Rankin Scale score >2). A total of 71 of 91 (79%) have had >3 years' follow-up, and 40 (56%) had complete obliteration, with 38 (53%) having excellent outcomes (complete obliteration without neurologic decline). Excellent outcome was seen in 90% of patients with modified RBAS score <1, 66% of patients with score 1-1.5, 50% patients with score 1.5-2, and 43% of patients with score >2.These data suggest that embolization of brain AVMs can safely and effectively reduce the treatment volume before radiosurgery. Combined therapy with embolization and radiosurgery does not appear to adversely affect rates of excellent outcome.

    View details for DOI 10.1016/j.wneu.2016.12.059

    View details for Web of Science ID 000397190100066

  • Clinical and Arterial Spin Labeling Brain MRI Features of Transitional Venous Anomalies. Journal of neuroimaging : official journal of the American Society of Neuroimaging Zhang, M., Telischak, N. A., Fischbein, N. J., Steinberg, G. K., Marks, M., Zaharchuk, G., Heit, J. J., Iv, M. 2017


    Transitional venous anomalies (TVAs) are rare cerebrovascular lesions that resemble developmental venous anomalies (DVAs), but demonstrate early arteriovenous shunting on digital subtraction angiography (DSA) without the parenchymal nidus of arteriovenous malformations (AVMs). We investigate whether arterial spin labeling (ASL) magnetic resonance imaging (MRI) can distinguish brain TVAs from DVAs and guide their clinical management.We conducted a single-center retrospective review of patients with brain parenchymal DVA-like lesions with increased ASL signal on MRI. Clinical histories and follow-up information were obtained. Two readers assessed ASL signal location relative to the vascular lesion on MRI and, if available, the presence of arteriovenous shunting on DSA.Thirty patients with DVA-like lesions with increased ASL signal were identified. Clinical symptoms prompted MRI evaluation in 83%. Symptoms did not localize to the venous anomaly in 90%. Ten percent presented with acute symptoms, only one of whom presented with hemorrhage. ASL signal in relation to the venous anomaly was identified in: 50% in the adjacent parenchyma, 33% in the lesion, 7% in a distal draining vein/sinus, and 10% in at least two of these sites. Follow-up DSA confirmed arteriovenous shunting in 71% of ASL-positive venous anomalies. Interrater agreement was very good (κ = .81-1.0, P < .001).A DVA-like lesion with increased ASL signal likely represents a TVA with arteriovenous shunting. Our study indicates that these lesions are usually incidentally detected and have a lower risk of hemorrhage than AVMs. ASL-MRI may be a useful tool to identify TVAs and guide further management of patients with TVAs.

    View details for DOI 10.1111/jon.12487

    View details for PubMedID 29205641

  • Pipeline embolization device retraction and foreshortening after internal carotid artery blister aneurysm treatment. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Heit, J. J., Telischak, N. A., Do, H. M., Dodd, R. L., Steinberg, G. K., Marks, M. P. 2017; 23 (6): 614–19


    Background Subarachnoid hemorrhage (SAH) secondary to rupture of a blister aneurysm (BA) results in high morbidity and mortality. Endovascular treatment with the pipeline embolization device (PED) has been described as a new treatment strategy for these lesions. We present the first reported case of PED retraction and foreshortening after treatment of a ruptured internal carotid artery (ICA) BA. Case description A middle-aged patient presented with SAH secondary to ICA BA rupture. The patient was treated with telescoping PED placement across the BA. After 5 days from treatment, the patient developed a new SAH due to re-rupture of the BA. Digital subtraction angiography revealed an increase in caliber of the supraclinoid ICA with associated retraction and foreshortening of the PED that resulted in aneurysm uncovering and growth. Conclusions PED should be oversized during ruptured BA treatment to prevent device retraction and aneurysm regrowth. Frequent imaging follow up after BA treatment with PED is warranted to ensure aneurysm occlusion.

    View details for DOI 10.1177/1591019917722514

    View details for PubMedID 28758549

    View details for PubMedCentralID PMC5814067

  • Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with intracranial vascular anomalies JOURNAL OF NEUROSURGERY-PEDIATRICS Teo, M., Johnson, J. N., Bell-Stephens, T. E., Marks, M. P., Do, H. M., Dodd, R. L., Bober, M. B., Steinberg, G. K. 2016; 18 (6): 717-723


    OBJECTIVE Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a rare genetic disorder. Features of it include extremely small stature, severe microcephaly, and normal or near-normal intelligence. Previous studies have found that more than 50% of patients with MOPD II have intracranial vascular anomalies, but few successful surgical revascularization or aneurysm-clipping cases have been reported because of the diminutive arteries and narrow surgical corridors in these patients. Here, the authors report on a large series of patients with MOPD II who underwent surgery for an intracranial vascular anomaly. METHODS In conjunction with an approved prospective registry of patients with MOPD II, a prospectively collected institutional surgical database of children with MOPD II and intracranial vascular anomalies who underwent surgery was analyzed retrospectively to establish long-term outcomes. RESULTS Ten patients with MOPD II underwent surgery between 2005 and 2012; 5 patients had moyamoya disease (MMD), 2 had intracranial aneurysms, and 3 had both MMD and aneurysms. Patients presented with transient ischemic attack (TIA) (n = 2), ischemic stroke (n = 2), intraparenchymal hemorrhage from MMD (n = 1), and aneurysmal subarachnoid hemorrhage (n = 1), and 4 were diagnosed on screening. The mean age of the 8 patients with MMD, all of whom underwent extracranial-intracranial revascularization (14 indirect, 1 direct) was 9 years (range 1-17 years). The mean age of the 5 patients with aneurysms was 15.5 years (range 9-18 years). Two patients experienced postoperative complications (1 transient weakness after clipping, 1 femoral thrombosis that required surgical repair). During a mean follow-up of 5.9 years (range 3-10 years), 3 patients died (1 of subarachnoid hemorrhage, 1 of myocardial infarct, and 1 of respiratory failure), and 1 patient had continued TIAs. All of the surviving patients recovered to their neurological baseline. CONCLUSIONS Patients with MMD presented at a younger age than those in whom aneurysms were more prevalent. Microneurosurgery with either intracranial bypass or aneurysm clipping is extremely challenging but feasible at expert centers in patients with MOPD II, and good long-term outcomes are possible.

    View details for DOI 10.3171/2016.6.PEDS16243

    View details for Web of Science ID 000388783200012

  • Initial experience with SOFIA as an intermediate catheter in mechanical thrombectomy for acute ischemic stroke. Journal of neurointerventional surgery Wong, J. H., Do, H. M., Telischak, N. A., Moraff, A. M., Dodd, R. L., Marks, M. P., Ingle, S. M., Heit, J. J. 2016


    The benefits of mechanical thrombectomy for emergent large vessel occlusion (ELVO) have been established. Combined mechanical/aspiration (Solumbra) and a direct aspiration as a first pass technique (ADAPT) are valid procedures requiring an intermediate catheter for clot suction. Recently, SOFIA (Soft torqueable catheter Optimized For Intracranial Access) was developed as a single lumen flexible catheter with coil and braid reinforcement, but its suitability for mechanical thrombectomy had not been evaluated.To describe our initial experience with SOFIA in acute stroke intervention and evaluate its efficacy and safety.All patients with ELVO undergoing endovascular stroke intervention with SOFIA were identified. Demographic, presentation, treatment, and complication data were recorded. Primary outcome was Thrombolysis in Cerebral Infarction (TICI) 2b/3 revascularization rate and the number of passes required. Secondary outcomes included complication rates and discharge National Institute of Health Stroke Scale (NIHSS) score.33 patients with a mean age of 72 years were treated for ELVO with SOFIA and IV tissue plasminogen activator was administered in 67%. Vessel occlusion involved the internal carotid artery (15.2%), M1 (48.5%), and M2 (24.2%) segments, and posterior circulation (12.1%). Median presentation NIHSS score was 14 (IQR 11-19) and discharge NIHSS 4 (IQR 2-14). The Solumbra technique represented 94% of treatments and ADAPT 3%. The TICI 2b/3 revascularization rate was 94%, including 48.5% TICI 3 with an average of 1.6 passes. The symptomatic reperfusion hemorrhage rate was 6%. Procedural complications occurred in four patients, but were unrelated to SOFIA. Mortality was 21%, secondary to failed revascularization, hemorrhagic transformation, and baseline medical condition.Mechanical and aspiration thrombectomy with SOFIA is safe and effective with high revascularization rates. Its trackability, stability, and luminal size make SOFIA suitable for stroke intervention.

    View details for DOI 10.1136/neurintsurg-2016-012750

    View details for PubMedID 27789787

  • Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology Leigh, R., Christensen, S., Campbell, B. C., Marks, M. P., Albers, G. W., Lansberg, M. G. 2016; 87 (3): 263-269


    This study sought to confirm the relationship between the degree of blood-brain barrier (BBB) damage and the severity of intracranial hemorrhage (ICH) in a population of patients who received endovascular therapy.The degree of BBB disruption on pretreatment MRI scans was analyzed, blinded to follow-up data, in the DEFUSE 2 cohort in which patients had endovascular therapy within 12 hours of stroke onset. BBB disruption was compared with ICH grade previously established by the DEFUSE 2 core lab. A prespecified threshold for predicting parenchymal hematoma (PH) was tested.Of the 108 patients in the DEFUSE 2 trial, 100 had adequate imaging and outcome data and were included in this study; 24 developed PH. Increasing amounts of BBB disruption on pretreatment MRIs was associated with increasing severity of ICH grade (p = 0.004). BBB disruption on the pretreatment scan was associated with PH (p = 0.020) with an odds ratio for developing PH of 1.69 for each 10% increase in BBB disruption (95% confidence interval 1.09-2.64), although a reliably predictive threshold was not identified.The amount of BBB disruption on pretreatment MRI is associated with the severity of ICH after acute intervention. This relationship has now been identified in patients receiving IV, endovascular, and combined therapies. Further study is needed to determine its role in guiding treatment.

    View details for DOI 10.1212/WNL.0000000000002862

    View details for PubMedID 27316247

  • Detection of Cortical Venous Drainage and Determination of the Borden Type of Dural Arteriovenous Fistula by Means of 3D Pseudocontinuous Arterial Spin-Labeling MRI AMERICAN JOURNAL OF ROENTGENOLOGY Amukotuwa, S. A., Heit, J. J., Marks, M. P., Fischbein, N., Bammer, R. 2016; 207 (1): 163-169


    The risk of intracranial dural arteriovenous fistula is linked to its pattern of venous drainage (Borden type), in particular the presence of cortical venous drainage. The purpose of this study was to assetss the accuracy of 3D pseudocontinuous arterial spin-labeling (ASL) MRI for noninvasive delineation of venous drainage.This retrospective study included 34 patients with a dural arteriovenous fistula who had undergone both digital subtraction angiography (DSA) and 3D pseudocontinuous ASL MRI. Two neuroradiologists blinded to the DSA results independently assessed ASL images for the presence of cortical vein hyperintensity (cortical venous drainage) and the distribution of venous hyperintensity (Borden type). DSA was used as the reference standard. The sensitivity and specificity of 3D pseudocontinuous ASL MRI for the detection of cortical venous drainage were determined. Intermodality and interobserver agreement for Borden type was determined by use of the weighted kappa statistic.Three-dimensional pseudocontinuous ASL MRI had high sensitivity (91%) and specificity (96%) for the detection of cortical venous drainage. Borden type was correctly identified with very good intermodality (weighted κ = 0.82) and interobserver (weighted κ = 0.85) agreement in 88% of patients.Three-dimensional pseudocontinuous ASL MRI is highly accurate for the detection of cortical venous drainage and determination of Borden type. With this technique, high-risk fistulas requiring treatment can be reliably differentiated from low-risk lesions. Although it cannot replace DSA, incorporating 3D pseudocontinuous ASL into an MRI protocol for assessment of dural arteriovenous fistula can facilitate treatment planning.

    View details for DOI 10.2214/AJR.15.15171

    View details for Web of Science ID 000378658500028

    View details for PubMedID 27082987

  • Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials Consensus Recommendations and Further Research Priorities STROKE Warach, S. J., Luby, M., Albers, G. W., Bammer, R., Bivard, A., Campbell, B. C., Derdeyn, C., Heit, J. J., Khatri, P., Lansberg, M. G., Liebeskind, D. S., Majoie, C. B., Marks, M. P., Menon, B. K., Muir, K. W., Parsons, M. W., Vagal, A., Yoo, A. J., Alexandrov, A. V., Baron, J., Fiorella, D. J., Furlan, A. J., Puig, J., Schellinger, P. D., Wintermark, M. 2016; 47 (5): 1389-1398


    The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

    View details for DOI 10.1161/STROKEAHA.115.012364

    View details for Web of Science ID 000375049700044

    View details for PubMedID 27073243

  • Effect of endovascular reperfusion in relation to site of arterial occlusion. Neurology Lemmens, R., Hamilton, S. A., Liebeskind, D. S., Tomsick, T. A., Demchuk, A. M., Nogueira, R. G., Marks, M. P., Jahan, R., Gralla, J., Yoo, A. J., Yeatts, S. D., Palesch, Y. Y., Saver, J. L., Pereira, V. M., Broderick, J. P., Albers, G. W., Lansberg, M. G. 2016; 86 (8): 762-770


    To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL).We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions.Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7).The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

    View details for DOI 10.1212/WNL.0000000000002399

    View details for PubMedID 26802090

  • Acute Preoperative Infarcts and Poor Cerebrovascular Reserve Are Independent Risk Factors for Severe Ischemic Complications following Direct Extracranial-Intracranial Bypass for Moyamoya Disease AMERICAN JOURNAL OF NEURORADIOLOGY Antonucci, M. U., Burns, T. C., Pulling, T. M., Rosenberg, J., Marks, M. P., Steinberg, G. K., Zaharchuk, G. 2016; 37 (2): 228-235


    Severe ischemic changes are a rare but devastating complication following direct superficial temporal artery to MCA bypass in patients with Moyamoya disease. This study was undertaken to determine whether preoperative MR imaging and/or cerebrovascular reserve assessment by using reference standard stable xenon-enhanced CT could predict such complications.Among all adult patients undergoing direct bypass at our institution between 2005 and 2010 who received a clinically interpretable xenon-enhanced CT examination, we identified index cases (patients with >15-mL postoperative infarcts) and control cases (patients without postoperative infarcts and without transient or permanent ischemic symptoms). Differences between groups were evaluated by using the Mann-Whitney U test. Univariate and multivariate generalized linear model regression was used to test predictors of postoperative infarct.Six index cases were identified and compared with 25 controls. Infarct size in the index cases was 95 ± 55 mL. Four of 6 index cases (67%), but no control patients, had preoperative acute infarcts. Baseline CBF was similar, but cerebrovascular reserve was significantly lower in the index cases compared with control cases. For example, in the anterior circulation, median cerebrovascular reserve was -0.4% (range, -38.0%-16.6%) in index versus 26.3% (range, -8.2%-60.5%) in control patients (P = .003). Multivariate analysis demonstrated that the presence of a small preoperative infarct (regardless of location) and impaired cerebrovascular reserve were independent, significant predictors of severe postoperative ischemic injury.Acute infarcts and impaired cerebrovascular reserve on preoperative imaging are independent risk factors for severe ischemic complications following superficial temporal artery to MCA bypass in Moyamoya disease.

    View details for DOI 10.3174/ajnr.A4535

    View details for Web of Science ID 000369111200013

    View details for PubMedCentralID PMC4752884

  • Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology Lansberg, M. G., Cereda, C. W., Mlynash, M., Mishra, N. K., Inoue, M., Kemp, S., Christensen, S., Straka, M., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2015; 85 (8): 708-714


    To evaluate whether time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on MRI.Patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion-diffusion target mismatch were included. Reperfusion was defined as a decrease in the perfusion lesion volume of at least 50% between baseline and early follow-up. Good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. Lesion growth was defined as the difference between the baseline and the early follow-up diffusion-weighted imaging lesion volumes.Among 78 patients with the target mismatch profile (mean age 66 ± 16 years, 54% women), reperfusion was associated with increased odds of good functional outcome (adjusted odds ratio 3.7, 95% confidence interval 1.2-12, p = 0.03) and attenuation of lesion growth (p = 0.02). Time to treatment did not modify these effects (p value for the time × reperfusion interaction is 0.6 for good functional outcome and 0.3 for lesion growth). Similarly, in the subgroup of patients with reperfusion (n = 46), time to treatment was not associated with good functional outcome (p = 0.2).The association between endovascular reperfusion and improved functional and radiologic outcomes is not time-dependent in patients with a perfusion-diffusion mismatch. Proof that patients with mismatch benefit from endovascular therapy in the late time window should come from a randomized placebo-controlled trial.

    View details for DOI 10.1212/WNL.0000000000001853

    View details for PubMedID 26224727

  • Use of thromboelastography to tailor dual-antiplatelet therapy in patients undergoing treatment of intracranial aneurysms with the Pipeline embolization device. Journal of neurointerventional surgery McTaggart, R. A., Choudhri, O. A., Marcellus, M. L., Brennan, T., Steinberg, G. K., Dodd, R. L., Do, H. M., Marks, M. P. 2015; 7 (6): 425-430


    Platelet function testing is controversial and not well studied in patients with neurovascular disease.To evaluate the performance of thromboelastography (TEG) as a platelet function test in neurovascular patients treated with the Pipeline embolization device (PED).A prospective protocol was instituted for platelet function testing in patients undergoing repair of intracranial aneurysms with the PED. All patients received dual antiplatelet therapy (DAT) and their response to both P2Y12 inhibitors and aspirin was quantified with TEG. Each patient's DAT induction strategy was tailored based on the percentage ADP-induced and percentage arachidonic acid-induced platelet inhibition reported by TEG. Data collected included clinical presentation, aneurysm characteristics, treatment details, and periprocedural events. Patients were followed up clinically and/or angiographically at 30 days, 6 months, and 1 year.Thirty-four PED procedures were performed on 31 patients. TEG results altered the DAT strategy in 35% of patients. Technical success with the Pipeline placement was 100%. Two patients had minor strokes and five had transient ischemic attacks (TIAs). There have been no hemorrhagic complications. No patient had permanent neurologic deficits. Six of eight (75%) of patients with thromboembolic/TIA events were ADP-induced hyporesponders by TEG. Our 6- and 12-month angiographic occlusion rates were 78.9% and 89.5%, respectively. The 19 major branches covered by the PED that were assessed by follow-up imaging have all remained patent.Platelet function testing with TEG altered our DAT induction strategy in a significant number of cases. No hemorrhagic or disabling thromboembolic complications were seen in this series. Future studies should compare methods of platelet function testing and, possibly, no platelet function testing in neurovascular patients undergoing flow diversion and/or stent-assisted treatment of intracranial aneurysms.

    View details for DOI 10.1136/neurintsurg-2013-011089

    View details for PubMedID 24739599

  • Reperfusion of Very Low Cerebral Blood Volume Lesion Predicts Parenchymal Hematoma After Endovascular Therapy STROKE Mishra, N. K., Christensen, S., Wouters, A., Campbell, B. C., Straka, M., Mlynash, M., Kemp, S., Cereda, C. W., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2015; 46 (5): 1245-1249


    Ischemic stroke patients with regional very low cerebral blood volume (VLCBV) on baseline imaging have increased risk of parenchymal hemorrhage (PH) after intravenous alteplase-induced reperfusion. We developed a method for automated detection of VLCBV and examined whether patients with reperfused-VLCBV are at increased risk of PH after endovascular reperfusion therapy.Receiver operating characteristic analysis was performed to optimize a relative CBV threshold associated with PH in patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study. Regional reperfused-VLCBV was defined as regions with low relative CBV on baseline imaging that demonstrated normal perfusion (Tmax <6 s) on coregistered early follow-up magnetic resonance imaging. The association between VLCBV, regional reperfused-VLCBV and PH was assessed in univariate and multivariate analyses.In 91 patients, the greatest area under the curve for predicting PH occurred at an relative CBV threshold of <0.42 (area under the curve, 0.77). At this threshold, VLCBV lesion volume ≥3.55 mL optimally predicted PH with 94% sensitivity and 63% specificity. Reperfused-VLCBV lesion volume was more specific (0.74) and equally sensitive (0.94). In total, 18 patients developed PH, of whom 17 presented with VLCBV (39% versus 2%; P=0.001), all of them had regional reperfusion (47% versus 0%; P=0.01), and 71% received intravenous alteplase. VLCBV lesion (odds ratio, 33) and bridging with intravenous alteplase (odds ratio, 3.8) were independently associated with PH. In a separate model, reperfused-VLCBV remained the single independent predictor of PH (odds ratio, 53).These results suggest that VLCBV can be used for risk stratification of patients scheduled to undergo endovascular therapy in trials and routine clinical practice.

    View details for DOI 10.1161/STROKEAHA.114.008171

    View details for Web of Science ID 000353559800032

    View details for PubMedID 25828235

    View details for PubMedCentralID PMC4414872

  • Interhospital variation in reperfusion rates following endovascular treatment for acute ischemic stroke. Journal of neurointerventional surgery Liggins, J. T., Mlynash, M., Jovin, T. G., Straka, M., Kemp, S., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2015; 7 (4): 231-233


    Patients who have successful reperfusion following endovascular therapy for acute ischemic stroke have improved clinical outcomes. We sought to determine if the chance of successful reperfusion differs among hospitals, and if hospital site is an independent predictor of reperfusion.Nine hospitals recruited patients in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), a prospective cohort study of endovascular stroke treatment conducted between 2008 and 2011. Patients were included for analysis if they had a baseline Thrombolysis in Cerebral Infarction (TICI) score of 0 or 1. Successful reperfusion was defined as a TICI reperfusion score of 2b or 3 at completion of the procedure. Collaterals were assessed using the Collateral Flow Grading System and were dichotomized as poor (0-2) or good (3-4). The association between hospital site and successful reperfusion was first assessed in an unadjusted analysis and subsequently in a multivariate analysis that adjusted for predictors of successful reperfusion.36 of 89 patients (40%) achieved successful reperfusion. The rate of reperfusion varied from 0% to 77% among hospitals in the univariate analysis (χ(2) p<0.001) but hospital site did not remain as an independent predictor of reperfusion in multivariate analysis (p=0.81) after adjustment for the presence of good collaterals (p<0.01) and use of the Merci retriever (p<0.05).Reperfusion rates vary among hospitals, which may be related to differences in treatment protocols and patient characteristics. Additional studies are needed to identify all of the factors that underlie this variability as this could lead to strategies that reduce interhospital variability in reperfusion rates and improve clinical outcomes.

    View details for DOI 10.1136/neurintsurg-2014-011115

    View details for PubMedID 24662608

  • Alberta Stroke Program Early Computed Tomographic Scoring Performance in a Series of Patients Undergoing Computed Tomography and MRI: Reader Agreement, Modality Agreement, and Outcome Prediction. Stroke; a journal of cerebral circulation McTaggart, R. A., Jovin, T. G., Lansberg, M. G., Mlynash, M., Jayaraman, M. V., Choudhri, O. A., Inoue, M., Marks, M. P., Albers, G. W. 2015; 46 (2): 407-412


    In this study, we compare the performance of pretreatment Alberta Stroke Program Early Computed Tomographic scoring (ASPECTS) using noncontrast CT (NCCT) and MRI in a large endovascular therapy cohort.Prospectively enrolled patients underwent baseline NCCT and MRI and started endovascular therapy within 12 hours of stroke onset. Inclusion criteria for this analysis were evaluable pretreatment NCCT, diffusion-weighted MRI (DWI), and 90-day modified Rankin Scale scores. Two expert readers graded ischemic change on NCCT and DWI using the ASPECTS. ASPECTS scores were analyzed with the full scale or were trichotomized (0-4 versus 5-7 versus 8-10) or dichotomized (0-7 versus 8-10). Good functional outcome was defined as a 90-day modified Rankin Scale score of 0 to 2.Seventy-four patients fulfilled our study criteria. The full-scale inter-rater agreement for CT-ASPECTS and DWI-ASPECTS was 0.579 and 0.867, respectively. DWI-ASPECTS correlated with functional outcome (P=0.004), whereas CT-ASPECTS did not (P=0.534). Both DWI-ASPECTS and CT-ASPECTS correlated with DWI volume. The receiver operating characteristic analysis revealed that DWI-ASPECTS outperformed both CT-ASPECTS and the time interval between symptom onset and start of the procedure for predicting good functional outcome (modified Rankin Scale score, ≤2) and DWI volume ≥70 mL.Inter-rater agreement for DWI-ASPECTS was superior to that for CT-ASPECTS. DWI-ASPECTS outperformed NCCT ASPECTS for predicting functional outcome at 90 days.

    View details for DOI 10.1161/STROKEAHA.114.006564

    View details for PubMedID 25538199

  • Cerebral angioplasty using the Scepter XC dual lumen balloon for the treatment of vasospasm following intracranial aneurysm rupture JOURNAL OF NEUROINTERVENTIONAL SURGERY Heit, J. J., Choudhri, O., Marks, M. P., Dodd, R. L., Do, H. M. 2015; 7 (1): 56-61


    Cerebral vasospasm following subarachnoid hemorrhage (SAH) results in significant morbidity and mortality. Intra-arterial administration of calcium channel blockers or intracranial angioplasty may be performed when non-invasive medical management fails to prevent neurologic deterioration. Technical improvements in balloon catheters are expected to improve the success and safety of cerebral angioplasty.To describe our initial experience with the new Scepter XC balloon catheter in cerebral vasospasm treatment following SAH.All patients who underwent cerebral angioplasty using the Scepter XC balloon for the treatment of medically refractory cerebral vasospasm after SAH were identified. Patient demographic information, procedural details, and outcome were obtained from electronic medical records.Five consecutive patients undergoing vasospasm treatment with cerebral angioplasty using the Scepter XC were identified. All treated patients had medically refractory vasospasm that was moderate or severe. Angioplasty of the supraclinoid internal carotid artery, the A1 and A2 segments of the anterior cerebral artery, the M1 and M2 segments of the middle cerebral artery, the V4 segment of the vertebral artery, and the basilar artery was performed. All angioplasty procedures were technically successful, and the degree of vasospasm improved significantly following angioplasty. There were no complications related to the cerebral angioplasty procedures.The Scepter XC balloon catheter is safe and effective in the treatment of cerebral vasospasm following SAH. The excellent trackability and stability of the balloon catheter and the extra compliant design of the balloon represent technical advancements in the endovascular armamentarium in the treatment of cerebral vasospasm.

    View details for DOI 10.1136/neurintsurg-2013-011043

    View details for Web of Science ID 000346242600015

    View details for PubMedID 24385556

  • Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome JOURNAL OF NEUROINTERVENTIONAL SURGERY Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 6 (10): 724-728
  • Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial INTERNATIONAL JOURNAL OF STROKE Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R. A., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 9 (7): 860-865

    View details for DOI 10.1111/ijs.12271

    View details for Web of Science ID 000342581900013

  • Multimodality Evaluation of Dural Arteriovenous Fistula with CT Angiography, MR with Arterial Spin Labeling, and Digital Subtraction Angiography: Case Report JOURNAL OF NEUROIMAGING Alexander, M., McTaggart, R., Santarelli, J., Fischbein, N., Marks, M., Zaharchuk, G., Do, H. 2014; 24 (5): 520-523


    Dural arteriovenous fistulae (DAVF) are cerebrovascular lesions with pathologic shunting into the venous system from arterial feeders. Digital subtraction angiography (DSA) has long been considered the gold standard for diagnosis, but advances in noninvasive imaging techniques now play a role in the diagnosis of these complex lesions. Herein, we describe the case of a patient with right-side pulsatile tinnitus and DAVF diagnosed using computed tomography angiography, magnetic resonance with arterial spin labeling, and DSA. Implications for imaging analysis of DAVFs and further research are discussed.

    View details for DOI 10.1111/jon.12032

    View details for Web of Science ID 000341990200015

  • Multimodality evaluation of dural arteriovenous fistula with CT angiography, MR with arterial spin labeling, and digital subtraction angiography: case report. Journal of neuroimaging Alexander, M., McTaggart, R., Santarelli, J., Fischbein, N., Marks, M., Zaharchuk, G., Do, H. 2014; 24 (5): 520-523


    Dural arteriovenous fistulae (DAVF) are cerebrovascular lesions with pathologic shunting into the venous system from arterial feeders. Digital subtraction angiography (DSA) has long been considered the gold standard for diagnosis, but advances in noninvasive imaging techniques now play a role in the diagnosis of these complex lesions. Herein, we describe the case of a patient with right-side pulsatile tinnitus and DAVF diagnosed using computed tomography angiography, magnetic resonance with arterial spin labeling, and DSA. Implications for imaging analysis of DAVFs and further research are discussed.

    View details for DOI 10.1111/jon.12032

    View details for PubMedID 23746119

  • O-034 Carotid Artery Angioplasty versus Stenting in Acute Ischemic Stroke. Journal of neurointerventional surgery Choudhri, O., Gupta, M., Feroze, A., Albers, G., Lansberg, M., Do, H., Dodd, R., Marcellus, M., Marks, M. 2014; 6: A18-9


    Acute ischemic stroke secondary to cervical carotid artery occlusion can lead to significant morbidity and mortality. Acute carotid occlusion may be managed by carotid angioplasty, stenting, or both. The use of carotid stents requires patients to be placed on dual antiplatelet agents, which may contribute to increased haemorrhage risk. We undertook this study to evaluate outcomes for angioplasty alone versus stenting in the setting of acute carotid occlusion.All patients treated from 2008 to 2013 with acute cervical internal carotid artery occlusions that had intervention within eight hours of symptom onset were included. NIHSS were recorded preceding intervention, and clinical outcomes were assessed using mRS at 90 days. All imaging and angiographic data were reviewed for pre-procedural ASPECT scores, pre- and post- TICI reperfusion scores, and intracranial haemorrhage as defined by PH grading score for haemorrhage. Demographic and treatment factors were correlated with good functional outcome (mRS < 2 at 90 days and a comparison was made for patients undergoing angioplasty alone versus stenting. All patients who underwent carotid stent were placed on dual antiplatelet agents while angioplasty patients received aspirin only.Twenty-four patients (15 males, 9 females; mean age, 67 years) satisfied the inclusion criteria. Seventeen patients underwent placement of carotid stent and 7 patients had angioplasty alone. Patients in both subgroups were comparable across characteristics including comorbidities, time for onset to recanalization, ASPECTS, and IV tPA use. 35% of patients who underwent stenting had good functional outcomes, versus 71% of patients treated with angioplasty alone, although these differences were not statistically significant. No differences were seen for the two treatment groups comparing time from onset to recanalization, baseline ASPECTS, and IV tPA use. Additionally, increased age (p = 0.049) and post-treatment parenchymal haemorrhage- PH1 or PH2 (p = 0.016) correlated with poor outcomes (mRS > 2). All parenchymal haemorrhages (6/17) and deaths (5/17) fell within the stenting subgroup (35.3% and 29.4%, respectively).This data suggest that patients undergoing angioplasty alone in the setting of acute internal carotid artery occlusion may have improved functional outcome at 90-day compared to those undergoing stenting. This study was limited by a small sample size and a larger study would be needed to confirm these findings.angioplasty, stenting, acute ischemic stroke, carotid occlusion.O. Choudhri: None. M. Gupta: None. A. Feroze: None. G. Albers: None. M. Lansberg: None. H. Do: None. R. Dodd: None. M. Marcellus: None. M. Marks: None.

    View details for DOI 10.1136/neurintsurg-2014-011343.34

    View details for PubMedID 25064877

  • Endovascular treatment of a tentorial dural arteriovenous fistula. Neurosurgical focus Choudhri, O., Marks, M. P. 2014; 37 (1): 1-?


    Tentorial dural arteriovenous fistulae are rare intracranial fistulae, in which the fistula pocket is present within the leaves of tentorium cerebelli. These tentorial fistulae can be rarely present near the galenic complex, where they can engorge the deep venous system and cause symptoms of venous hypertension. We present an interesting case of endovascular treatment of a galenic tentorial dural arteriovenous fistula in a patient with headaches and imbalance. The fistula was accessed through the artery of Davidoff and Schecter from the posterior cerebral artery supplying the fistula. The fistula was completely embolized using Onyx and with preservation of vein of Galen. The video can be found here: .

    View details for DOI 10.3171/2014.V2.FOCUS14184

    View details for PubMedID 24983732

  • Endovascular management of cerebral venous sinus thrombosis. Neurosurgical focus Choudhri, O., Feroze, A., Marks, M. P., Do, H. M. 2014; 37 (1): 1-?


    Cerebral venous sinus thrombosis (CVST) is characterized by formation of widespread thrombus within the cerebral venous sinus system. CVST can cause venous hypertension, venous infarcts, hemorrhage and seizures. It is managed in most cases with systemic anticoagulation through the use of heparin to resolve the thrombus. Patients that demonstrate clinical deterioration while on heparin are often treated with endovascular strategies to recanalize the sinuses. We present the case of a patient with widespread CVST, involving his superior sagittal sinuses and bilateral transverse sigmoid sinuses, who was treated with a combination of endovascular therapies. The video can be found here: .

    View details for DOI 10.3171/2014.V2.FOCUS14186

    View details for PubMedID 24983720

  • Comparison of magnetic resonance imaging mismatch criteria to select patients for endovascular stroke therapy. Stroke; a journal of cerebral circulation Mishra, N. K., Albers, G. W., Christensen, S., Marks, M., Hamilton, S., Straka, M., Liggins, J. T., Kemp, S., Mlynash, M., Bammer, R., Lansberg, M. G. 2014; 45 (5): 1369-1374


    The Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study has shown that clinical response to endovascular reperfusion differs between patients with and without perfusion-diffusion (perfusion-weighted imaging-diffusion-weighted imaging, PWI-DWI) mismatch: patients with mismatch have a favorable clinical response to reperfusion, whereas patients without mismatch do not. This study examined whether alternative mismatch criteria can also differentiate patients according to their response to reperfusion.Patients from the DEFUSE 2 study were categorized according to vessel occlusion on magnetic resonance angiography (MRA) and DWI lesion volume criteria (MRA-DWI mismatch) and symptom severity and DWI criteria (clinical-DWI mismatch). Favorable clinical response was defined as an improvement of ≥8 points on the National Institutes of Health Stroke Scale (NIHSS) by day 30 or an NIHSS score of ≤1 at day 30. We assessed, for each set of criteria, whether the association between reperfusion and favorable clinical response differed according to mismatch status.A differential response to reperfusion was observed between patients with and without MRA-DWI mismatch defined as an internal carotid artery or M1 occlusion and a DWI lesion <50 mL. Reperfusion was associated with good functional outcome in patients who met these MRA-DWI mismatch criteria (odds ratio [OR], 8.5; 95% confidence interval [CI], 2.3-31.3), whereas no association was observed in patients who did not meet these criteria (OR, 0.5; 95% CI, 0.08-3.1; P for difference between the odds, 0.01). No differential response to reperfusion was observed with other variations of the MRA-DWI or clinical-DWI mismatch criteria.The MRA-DWI mismatch is a promising alternative to DEFUSE 2's PWI-DWI mismatch for patient selection in endovascular stroke trials.

    View details for DOI 10.1161/STROKEAHA.114.004772

    View details for PubMedID 24699054

  • Effect of collateral blood flow on patients undergoing endovascular therapy for acute ischemic stroke. Stroke; a journal of cerebral circulation Marks, M. P., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Kemp, S., McTaggart, R., Inoue, M., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 45 (4): 1035-1039


    Our aim was to determine the relationships between angiographic collaterals and diffusion/perfusion findings, subsequent infarct growth, and clinical outcome in patients undergoing endovascular therapy for ischemic stroke.Sixty patients with a thrombolysis in cerebral infarction (TICI) score of 0 or 1 and internal carotid artery/M1 occlusion at baseline were evaluated. A blinded reader assigned a collateral score using a previous 5-point scale, from 0 (no collateral flow) to 4 (complete/rapid collaterals to the entire ischemic territory). The analysis was dichotomized to poor flow (0-2) versus good flow (3-4). Collateral score was correlated with baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging volume, perfusion-weighted imaging volume (Tmax ≥6 seconds), TICI reperfusion, infarct growth, and modified Rankin Scale score at day 90.Collateral score correlated with baseline National Institutes of Health Stroke Scale (P=0.002) and median volume of tissue at Tmax ≥6 seconds (P=0.009). Twenty-nine percent of patients with poor collateral flow had TICI 2B-3 reperfusion versus 65.5% with good flow (P=0.009). Patients with poor collaterals who reperfused (TICI 2B-3) were more likely to have a good functional outcome (modified Rankin Scale score 0-2 at 90 days) compared with patients who did not reperfuse (odds ratio, 12; 95% confidence interval, 1.6-98). There was no difference in the rate of good functional outcome after reperfusion in patients with poor collaterals versus good collaterals (P=1.0). Patients with poor reperfusion (TICI 0-2a) showed a trend toward greater infarct growth if they had poor collaterals versus good collaterals (P=0.06).Collaterals correlate with baseline National Institutes of Health Stroke Scale, perfusion-weighted imaging volume, and good reperfusion. However, target mismatch patients who reperfuse seem to have favorable outcomes at a similar rate, irrespective of the collateral score. Unique identifier: NCT01349946.

    View details for DOI 10.1161/STROKEAHA.113.004085

    View details for PubMedID 24569816

  • Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort. Stroke; a journal of cerebral circulation Olivot, J. M., Mlynash, M., Inoue, M., Marks, M. P., Wheeler, H. M., Kemp, S., Straka, M., Zaharchuk, G., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1018-1023


    We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2).Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days.Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014.HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

    View details for DOI 10.1161/STROKEAHA.113.003857

    View details for PubMedID 24595591

  • Patients with single distal MCA perfusion lesions have a high rate of good outcome with or without reperfusion INTERNATIONAL JOURNAL OF STROKE Lemmens, R., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Marks, M. P., Davis, S. M., Donnan, G. A., Albers, G. W., Lansberg, M. G. 2014; 9 (2): 156-159


    Reperfusion is associated with good functional outcome after stroke. However, minimal data are available regarding the effect of reperfusion on clinical outcome and infarct growth in patients with distal MCA branch occlusions.The aim of this study was to evaluate this association and to determine the impact of the perfusion-diffusion mismatch.Individual patient data from three stroke studies (EPITHET, DEFUSE and DEFUSE 2) with baseline MRI profiles and reperfusion status were pooled. Patients were included if they had a single cortical perfusion lesion on their baseline MRI that was consistent with a distal MCA branch occlusion. Good functional outcome was defined as a score of 0-2 on the modified Rankin Scale at day 90 and infarct growth was defined as change in lesion volume between the baseline DWI and the final T2/FLAIR.Thirty patients met inclusion criteria. Eighteen (60%) had a good functional outcome and twenty (67%) had reperfusion. Reperfusion was not associated with good functional outcome in the overall cohort (OR: 1·0, 95% CI 0·2-4·7) and also not in the subset of patients with a PWI-DWI mismatch (n = 17; OR: 0·7, 95% CI 0·1-5·5). Median infarct growth was modest and not significantly different between patients with (0 ml) and without reperfusion (6 ml); P = 0·2.The overall high rate of good outcomes in patients with distal MCA perfusion lesions might obscure a potential benefit from reperfusion in this population. A larger pooled analysis evaluating the effect of reperfusion in patients with distal MCA branch occlusions is warranted as confirmation of our results could have implications for the design of future stroke trials.

    View details for DOI 10.1111/ijs.12230

    View details for Web of Science ID 000329829700005

    View details for PubMedID 24373557

    View details for PubMedCentralID PMC3907940

  • The case for angioplasty in patients with symptomatic intracranial atherosclerosis. Frontiers in neurology McTaggart, R. A., Marks, M. P. 2014; 5: 36-?


    Intracranial atherosclerotic disease (ICAD) is likely the most common cause of stroke worldwide and remains highly morbid even with highly monitored medical therapy. Recent results of the SAMMPRIS trial, which randomized patients to stenting plus aggressive medical management versus aggressive medical management alone have shown that additional treatment of intracranial atherosclerotic lesions with the Wingspan stent is inferior to aggressive medical management alone. In light of these results, there has been renewed interest in angioplasty alone to treat symptomatic ICAD. This article will briefly review the natural history of ICAD and discuss the possible future for endovascular treatment of ICAD with primary intracranial angioplasty in appropriately selected patients.

    View details for DOI 10.3389/fneur.2014.00036

    View details for PubMedID 24782816

  • The case for angioplasty in patients with symptomatic intracranial atherosclerosis FRONTIERS IN NEUROLOGY McTaggart, R. A., Marks, M. P. 2014; 5
  • Recommendations on Angiographic Revascularization Grading Standards for Acute Ischemic Stroke A Consensus Statement STROKE Zaidat, O. O., Yoo, A. J., Khatri, P., Tomsick, T. A., von Kummer, R., Saver, J. L., Marks, M. P., Prabhakaran, S., Kallmes, D. F., Fitzsimmons, B. M., Mocco, J., Wardlaw, J. M., Barnwell, S. L., Jovin, T. G., Linfante, I., Siddiqui, A. H., Alexander, M. J., Hirsch, J. A., Wintermark, M., Albers, G., Woo, H. H., Heck, D. V., Lev, M., Aviv, R., Hacke, W., Warach, S., Broderick, J., Derdeyn, C. P., Furlan, A., Nogueira, R. G., Yavagal, D. R., Goyal, M., Demchuk, A. M., Bendszus, M., Liebeskind, D. S. 2013; 44 (9): 2650-2663

    View details for DOI 10.1161/STROKEAHA.113.001972

    View details for Web of Science ID 000329982500066

    View details for PubMedID 23920012

  • Comparison of the response to endovascular reperfusion in relation to site of arterial occlusion. Neurology Lemmens, R., Mlynash, M., Straka, M., Kemp, S., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2013; 81 (7): 614-618


    We explored the relationship between the site of vascular occlusion and the response to endovascular treatment in patients with acute ischemic stroke and also considered the impact of mismatch profile.DEFUSE-2 was a prospective cohort study of patients treated with endovascular therapy. Patients with internal carotid artery (ICA) and middle cerebral artery (MCA) involvement were included in this substudy. Mismatch and reperfusion status was assessed on MRI. Favorable clinical response was defined as an improvement of at least 8 points on the NIH Stroke Scale.Reperfusion rates were comparable in both groups (61% for ICA and 59% for MCA). In the setting of reperfusion, percentages of favorable clinical response were similar between patients with stroke due to ICA (65%) and MCA (63%) occlusions. When reperfusion was not achieved, favorable outcomes were less frequent with obstructions of the ICA (9%) than the MCA (52%). Among target mismatch patients, the adjusted odds ratio for favorable clinical response associated with reperfusion was 39.7 (95% confidence interval 1.4-1,132.8) for ICA occlusions vs 5.1 (95% confidence interval 1.4-19.3) for MCA occlusions.Endovascular reperfusion is associated with favorable clinical response regardless of the location of the arterial occlusion. This association is strongest for target mismatch patients with ICA occlusions. Target mismatch patients with either ICA or MCA occlusions appear to be good candidates for endovascular reperfusion therapy.

    View details for DOI 10.1212/WNL.0b013e3182a08f07

    View details for PubMedID 23851962

  • Clinical outcomes strongly associated with the degree of reperfusion achieved in target mismatch patients: pooled data from the diffusion and perfusion imaging evaluation for understanding stroke evolution studies. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Straka, M., Kemp, S., Jovin, T. G., Tipirneni, A., Hamilton, S. A., Marks, M. P., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (7): 1885-1890


    BACKGROUND AND PURPOSE: To investigate relationships between the degree of early reperfusion achieved on perfusion-weighted imaging and clinical outcomes in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. We hypothesized that there would be a strong correlation between the degree of reperfusion achieved and clinical outcomes in target mismatch (TMM) patients. METHODS: The degree of reperfusion was calculated on the basis of the difference in perfusion-weighted imaging volumes (time to maximum of tissue residue function [Tmax]>6 s) between the baseline MRI and the early post-treatment follow-up scan. Patients were grouped into quartiles, on the basis of degree of reperfusion achieved, and the association between the degree of reperfusion and clinical outcomes in TMM and no TMM patients was assessed. Favorable clinical response was determined at day 30 on the basis of the National Institutes of Health Stroke Scale and good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. RESULTS: This study included 121 patients; 98 of these had TMM. The median degree of reperfusion achieved was not different in TMM patients (60%) versus No TMM patients (64%; P=0.604). The degree of reperfusion was strongly correlated with both favorable clinical response (P<0.001) and good functional outcome (P=0.001) in TMM patients; no correlation was present in no TMM. The frequency of achieving favorable clinical response or good functional outcome was significantly higher in TMM patients in the highest reperfusion quartile versus the lower 3 quartiles (88% versus 41% as odds ratio, 10.3; 95% confidence interval, 2.8-37.5; and 75% versus 34% as odds ratio, 5.9; 95% confidence interval, 2.1-16.7, respectively). A receiver operating characteristic curve analysis identified 90% as the optimal reperfusion threshold for predicting good functional outcomes. CONCLUSIONS: The degree of reperfusion documented on perfusion-weighted imaging after reperfusion therapies corresponds closely with clinical outcomes in TMM patients. Reperfusion of ≥90% of the perfusion lesion is an appropriate goal for reperfusion therapies to aspire to.

    View details for DOI 10.1161/STROKEAHA.111.000371

    View details for PubMedID 23704106

  • Delayed retraction of the pipeline embolization device and corking failure: pitfalls of pipeline embolization device placement in the setting of a ruptured aneurysm. Neurosurgery McTaggart, R. A., Santarelli, J. G., Marcellus, M. L., Steinberg, G. K., Dodd, R. L., Do, H. M., Marks, M. P. 2013; 72 (2): onsE245-51


    : The safety of flow-diverting stents for the treatment of ruptured intracranial aneurysms is unknown.: A 35-year-old woman with a ruptured dissecting aneurysm of the intradural right vertebral artery and incorporating the right posterior inferior cerebellar artery was treated with a Pipeline Embolization Device (PED). Five days after reconstruction of the diseased right vertebral segment, she was treated for vasospasm, and retraction of the PED was observed, leaving her dissecting aneurysm unprotected. A second PED was placed with coverage of the aneurysm, but vasospasm complicated optimal positioning of the device.: In addition to the potential risks of dual antiplatelet therapy in these patients, this case illustrates 2 pitfalls of flow-diverting devices in vessels in vasospasm: delayed retraction of the device and difficulty positioning the device for deployment in the setting of vasospasm.: ANR, aneurysmPED, Pipeline Embolization DevicePICA, posterior inferior cerebellar arterySAH, subarachnoid hemorrhage.

    View details for DOI 10.1227/NEU.0b013e31827fc9be

    View details for PubMedID 23190640

  • Delayed Retraction of the Pipeline Embolization Device and Corking Failure: Pitfalls of Pipeline Embolization Device Placement in the Setting of a Ruptured Aneurysm NEUROSURGERY McTaggart, R. A., Santarelli, J. G., Marcelus, M. L., Steinberg, G. K., Dodd, R. L., Do, H. M., Marks, M. P. 2013; 72 (6): 237-237


    : The safety of flow-diverting stents for the treatment of ruptured intracranial aneurysms is unknown.: A 35-year-old woman with a ruptured dissecting aneurysm of the intradural right vertebral artery and incorporating the right posterior inferior cerebellar artery was treated with a Pipeline Embolization Device (PED). Five days after reconstruction of the diseased right vertebral segment, she was treated for vasospasm, and retraction of the PED was observed, leaving her dissecting aneurysm unprotected. A second PED was placed with coverage of the aneurysm, but vasospasm complicated optimal positioning of the device.: In addition to the potential risks of dual antiplatelet therapy in these patients, this case illustrates 2 pitfalls of flow-diverting devices in vessels in vasospasm: delayed retraction of the device and difficulty positioning the device for deployment in the setting of vasospasm.: ANR, aneurysmPED, Pipeline Embolization DevicePICA, posterior inferior cerebellar arterySAH, subarachnoid hemorrhage.

    View details for DOI 10.1227/NEU.0b013e31827fc9be

    View details for Web of Science ID 000319535100029

  • MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study LANCET NEUROLOGY Lansberg, M. G., Straka, M., Kemp, S., Mlynash, M., Wechsler, L. R., Jovin, T. G., Wilder, M. J., Lutsep, H. L., Czartoski, T. J., Bernstein, R. A., Chang, C. W., Warach, S., Fazekas, F., Inoue, M., Tipirneni, A., Hamilton, S. A., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2012; 11 (10): 860-867


    Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion.In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data.138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8·8 (95% CI 2·7-29·0) in the target mismatch group and 0·2 (0·0-1·6) in the no target mismatch group (p=0·003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4·0, 95% CI 1·3-12·2) in the target mismatch group, but not in the no target mismatch group (1·9, 0·2-18·7).Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted.National Institute for Neurological Disorders and Stroke.

    View details for DOI 10.1016/S1474-4422(12)70203-X

    View details for Web of Science ID 000309634300011

    View details for PubMedID 22954705

  • Cerebral proliferative angiopathy JOURNAL OF NEUROINTERVENTIONAL SURGERY Marks, M. P., Steinberg, G. K. 2012; 4 (5)


    Cerebral proliferative angiopathy is a rare lesion marked by diffuse intravascular shunting, which should be differentiated from brain arteriovenous malformations. A patient is presented with cerebral proliferative angiopathy and documented progressive development of hypervascular shunting involving extensive portions of the left hemisphere. The patient had angiographic and laboratory evidence of angiogenesis and a progressive neurologic deterioration which corresponded to the development of her lesion. This is the first case which documents the progressive proliferative changes seen with this abnormality.

    View details for DOI 10.1136/neurintsurg-2011-010027

    View details for Web of Science ID 000308738800005

    View details for PubMedID 21990497

  • A Simplified Method for Administration of Intra-Arterial Nicardipine for Vasospasm With Cervical Catheter Infusion NEUROSURGERY Pandey, P., Steinberg, G. K., Dodd, R., Do, H. M., Marks, M. P. 2012; 71: 77-85


    Cerebral vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage. Nicardipine has previously been used to treat vasospasm through superselective intracranial microcatheter injections.To evaluate a simple method of treatment of vasospasm with slow infusion of nicardipine from a cervical catheter.Twenty-seven patients with symptomatic vasospasm were treated over 4 years with cervical catheter infusions. Nicardipine was infused at 20 mg/h for 30 to 60 minutes. Angioplasty was used in severe cases at the operator's discretion. Outcome at discharge and follow-up was evaluated with Glasgow Outcome Scale.Twenty-seven patients (17 women, 12 men) received intra-arterial therapy for vasospasm. Vasospasm treatment was done at a mean post-hemorrhage date of 7.2 days (range, 4-15 days). They underwent 48 sessions of treatment (mean, 1.8 per patient) in 72 separate arterial territories. Twelve patients underwent multiple treatments. The mean dose used per session was 19.2 mg (range, 5-50 mg). Four patients underwent angioplasty for severe vasospasm. Twenty-two patients (81.5%) had clinical improvement after the infusion. Angiographic improvement was seen in 86.1% of the vessels analyzed, which had moderate or severe spasm before infusion. Overall, 17 patients (62.9%) had good outcome (Glasgow Outcome Scale score, 4 and 5) at discharge, 11 had poor outcome, and 1 patient died. Follow-up was available in 19 patients, and 18 were doing well (Glasgow Outcome Scale score, 4 and 5).Intra-arterial nicardipine is an effective and safe treatment for cerebral vasospasm. In most patients, infusion can be performed from the cervical catheter, with microcatheter infusion and angioplasty reserved for the more severe and resistant cases.

    View details for DOI 10.1227/NEU.0b013e3182426257

    View details for Web of Science ID 000308328300032

    View details for PubMedID 22105209

  • Multimodality management of Spetzler-Martin Grade III arteriovenous malformations JOURNAL OF NEUROSURGERY Pandey, P., Marks, M. P., Harraher, C. D., Westbroek, E. M., Chang, S. D., Do, H. M., Levy, R. P., Dodd, R. L., Steinberg, G. K. 2012; 116 (6): 1279-1288


    Grade III arteriovenous malformations (AVMs) are diverse because of their variations in size (S), location in eloquent cortex (E), and presence of central venous drainage (V). Because they may have implications for management and outcome, the authors evaluated these variations in the present study.Between 1984 and 2010, 100 patients with Grade III AVMs were treated. The AVMs were categorized by Spetzler-Martin characteristics as follows: Type 1 = S1E1V1, Type 2 = S2E1V0, Type 3 = S2E0V1, and Type 4 = S3E0V0. The occurrence of a new neurological deficit, functional status (based on modified Rankin Scale [mRS] score) at discharge and follow-up, and radiological obliteration were correlated with demographic and morphological characteristics.One hundred patients (49 female and 51 male; age range 5-68 years, mean 35.8 years) were evaluated. The size of AVMs was less than 3 cm in 28 patients, 3-6 cm in 71, and greater than 6 cm in 1; 86 AVMs were located in eloquent cortex and 38 had central drainage. The AVMs were Type 1 in 28 cases, Type 2 in 60, Type 3 in 11, and Type 4 in 1. The authors performed embolization in 77 patients (175 procedures), surgery in 64 patients (74 surgeries), and radiosurgery in 49 patients (44 primary and 5 postoperative). The mortality rate following the management of these AVMs was 1%. Fourteen patients (14%) had new neurological deficits, with 5 (5%) being disabling (mRS score > 2) and 9 (9%) being nondisabling (mRS score ≤ 2) events. Patients with Type 1 AVMs (small size) had the best outcome, with 1 (3.6%) in 28 having a new neurological deficit, compared with 72 patients with larger AVMs, of whom 13 (18.1%) had a new neurological deficit (p < 0.002). Older age (> 40 years), malformation size > 3 cm, and nonhemorrhagic presentation predicted the occurrence of new deficits (p < 0.002). Sex, eloquent cortex, and venous drainage did not confer any benefit. In 89 cases follow-up was adequate for data to be included in the obliteration analysis. The AVM was obliterated in 78 patients (87.6%), 69 of them (88.5%) demonstrated on angiography and 9 on MRI /MR angiography. There was no difference between obliteration rates between different types of AVMs, size, eloquence, and drainage. Age, sex, and clinical presentation also did not predict obliteration.Multimodality management of Grade III AVMs results in a high rate of obliteration, which was not influenced by size, venous drainage, or eloquent location. However, the development of new neurological deficits did correlate with size, whereas eloquence and venous drainage did not affect the neurological complication rate. The authors propose subclassifying the Grade III AVMs according to their size (< 3 and ≥ 3 cm) to account for treatment risk.

    View details for DOI 10.3171/2012.3.JNS111575

    View details for Web of Science ID 000304294000022

    View details for PubMedID 22482792

  • Neuroradiologic Correlates of Cognitive Impairment in Adult Moyamoya Disease AMERICAN JOURNAL OF NEURORADIOLOGY Mogensen, M. A., Karzmark, P., Zeifert, P. D., Rosenberg, J., Marks, M., Steinberg, G. K., Dorfman, L. J. 2012; 33 (4): 721-725


    MMD has been shown to result in impairment of executive functioning in adults. The purpose of this study was to correlate presurgical neuropsychological assessments with the severity of primary MMD as measured by CBF and CVR and with secondary damage from MMD as estimated by cortical stroke and WMD.A retrospective analysis of 31 adult patients with MMD was performed. Xe-CT was used to obtain CBF and CVR, and MRI was reviewed to grade cortical stroke and WMD. Two tests of executive functioning (FAS and TMT-B) were correlated with imaging findings. A multiple regression analysis was performed.There was a significant overall positive relationship between mean CBF and FAS (P = .038) and TMT-B scores (P = .014). A significant negative relationship was present between the WMD score and the FAS (P = .009) and TMT-B scores (P = .015). Per-region analysis demonstrated that FAS and TMT-B scores were significantly decreased by the presence of a posterior stroke (P < .0001 and P = .001) or WMD (P = .006 and P = .004). All patients with posterior parieto-occipital WMD or stroke also had secondary disease in the anterior regions.Impaired executive functioning in adults with MMD is most strongly associated secondary damage in the form of WMD or cortical stroke. The effect is most profound with parieto-occipital lobe involvement, likely a reflection of overall disease severity. Increasing global WMD burden may be a better indicator of cognitive decline than cortical infarction. Patients with higher baseline CBF seem to have better cognitive functioning.

    View details for DOI 10.3174/ajnr.A2852

    View details for Web of Science ID 000302842900024

    View details for PubMedID 22173751

  • Clinical Implications of Internal Carotid Artery Flow Impairment Caused by Filter Occlusion during Carotid Artery Stenting AMERICAN JOURNAL OF NEURORADIOLOGY Kwon, O., Kim, S. H., Jacobsen, E. A., Marks, M. P. 2012; 33 (3): 494-499


    Membrane filters are EPDs, which preserve ICA flow during CAS. However, ICA flow arrest may occur with filter use. This report describes the angiographic, clinical, and histopathologic features of the filter occlusion.Sixty-one consecutive patients with cervical carotid stenosis treated by CAS by using a single type of filter device were evaluated. All patients were on dual antiplatelet treatment and fully heparinized. Prestent dilation was performed in all patients. Poststent dilation was performed in 15 patients. Control angiograms were obtained and evaluated after each step of the CAS procedure. All filters were inspected for debris, and if present, histology was obtained.CAS was successfully performed in all cases with <20% residual stenosis. Filter occlusion occurred in 6 patients (9.8%). It developed immediately after stent deployment in 4, and after a second prestent dilation in 2. Five of the 6 had severe carotid stenosis. In all patients, filter withdrawal led to immediate and complete restoration of ICA flow. In 1 patient, acute embolic M1 occlusion occurred immediately after filter withdrawal but was successfully treated with thrombolysis. None of filter-occlusion group had permanent neurologic deficits. Gross and microscopic examinations demonstrated that the pores of the filters were occluded mainly by fibrin. Postoperative diffusion MR imaging revealed no difference between filter-occlusion and non-filter-occlusion groups.ICA flow arrest due to filter occlusion during CAS is relatively common and occurs more frequently in severe stenosis. It resolves rapidly after filter removal and does not appear to worsen outcome.

    View details for DOI 10.3174/ajnr.A2818

    View details for Web of Science ID 000301870300021

    View details for PubMedID 22173773

  • Is There a Future for Endovascular Treatment of Intracranial Atherosclerotic Disease After Stenting and Aggressive Medical Management for Preventing Recurrent Stroke and Intracranial Stenosis (SAMMPRIS)? STROKE Marks, M. P. 2012; 43 (2): 580-584


    The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke and Intracranial Stenosis (SAMMPRIS) trial, a randomized clinical trial comparing aggressive medical management to stenting with aggressive medical management for symptomatic intracranial stenosis, was prematurely halted when a high rate of periprocedural events was found in the stent arm. The trial also demonstrated a high rate of stroke with medical management. This article explores possible reasons for these outcomes and discusses some weaknesses of the trial. Against this background endovascular therapy should continue to be explored in the treatment of this disease.

    View details for DOI 10.1161/STROKEAHA.111.645507

    View details for Web of Science ID 000299798300055

    View details for PubMedID 22246690

  • Cerebral CT Perfusion Using an Interventional C-Arm Imaging System: Cerebral Blood Flow Measurements AMERICAN JOURNAL OF NEURORADIOLOGY Ganguly, A., Fieselmann, A., Marks, M., Rosenberg, J., Boese, J., Deuerling-Zheng, Y., Straka, M., Zaharchuk, G., Bammer, R., Fahrig, R. 2011; 32 (8): 1525-1531


    CTP imaging in the interventional suite could reduce delays to the start of image-guided interventions and help determine the treatment progress and end point. However, C-arms rotate slower than clinical CT scanners, making CTP challenging. We developed a cerebral CTP protocol for C-arm CBCT and evaluated it in an animal study.Five anesthetized swine were imaged by using C-arm CBCT and conventional CT. The C-arm rotates in 4.3 seconds plus a 1.25-second turnaround, compared with 0.5 seconds for clinical CT. Each C-arm scan had 6 continuous bidirectional sweeps. Multiple scans each with a different delay to the start of an aortic arch iodinated contrast injection and a novel image reconstruction algorithm were used to increase temporal resolution. Three different scan sets (consisting of 6, 3, or 2 scans) and 3 injection protocols (3-mL/s 100%, 3-mL/s 67%, and 6-mL/s 50% contrast concentration) were studied. CBF maps for each scan set and injection were generated. The concordance and Pearson correlation coefficients (ρ and r) were calculated to determine the injection providing the best match between the following: the left and right hemispheres, and CT and C-arm CBCT.The highest ρ and r values (both 0.92) for the left and right hemispheres were obtained by using the 6-mL 50% iodinated contrast concentration injection. The same injection gave the best match for CT and C-arm CBCT for the 6-scan set (ρ = 0.77, r = 0.89). Some of the 3-scan and 2-scan protocols provided matches similar to those in CT.This study demonstrated that C-arm CBCT can produce CBF maps that correlate well with those from CTP.

    View details for DOI 10.3174/ajnr.A2518

    View details for Web of Science ID 000295706200027

    View details for PubMedID 21757522

    View details for PubMedCentralID PMC3171629

  • Arterial Spin-Labeling MRI Can Identify the Presence and Intensity of Collateral Perfusion in Patients With Moyamoya Disease STROKE Zaharchuk, G., Do, H. M., Marks, M. P., Rosenberg, J., Moseley, M. E., Steinberg, G. K. 2011; 42 (9): 2485-U183


    Determining the presence and adequacy of collateral blood flow is important in cerebrovascular disease. Therefore, we explored whether a noninvasive imaging modality, arterial spin labeling (ASL) MRI, could be used to detect the presence and intensity of collateral flow using digital subtraction angiography (DSA) and stable xenon CT cerebral blood flow as gold standards for collaterals and cerebral blood flow, respectively.ASL and DSA were obtained within 4 days of each other in 18 patients with Moyamoya disease. Two neurointerventionalists scored DSA images using a collateral grading scale in regions of interest corresponding to ASPECTS methodology. Two neuroradiologists similarly scored ASL images based on the presence of arterial transit artifact. Agreement of ASL and DSA consensus scores was determined, including kappa statistics. In 15 patients, additional quantitative xenon CT cerebral blood flow measurements were performed and compared with collateral grades.The agreement between ASL and DSA consensus readings was moderate to strong, with a weighted kappa value of 0.58 (95% confidence interval, 0.52-0.64), but there was better agreement between readers for ASL compared with DSA. Sensitivity and specificity for identifying collaterals with ASL were 0.83 (95% confidence interval, 0.77-0.88) and 0.82 (95% confidence interval, 0.76-0.87), respectively. Xenon CT cerebral blood flow increased with increasing DSA and ASL collateral grade (P<0.05).ASL can noninvasively predict the presence and intensity of collateral flow in patients with Moyamoya disease using DSA as a gold standard. Further study of other cerebrovascular diseases, including acute ischemic stroke, is warranted.

    View details for DOI 10.1161/STROKEAHA.111.61646

    View details for Web of Science ID 000294342800031

    View details for PubMedID 21799169

    View details for PubMedCentralID PMC3164217

  • Management of Pediatric Intracranial Arteriovenous Malformations: Experience With Multimodality Therapy NEUROSURGERY Darsaut, T. E., Guzman, R., Marcellus, M. L., Edwards, M. S., Tian, L., Do, H. M., Chang, S. D., Levy, R. P., Adler, J. R., Marks, M. P., Steinberg, G. K. 2011; 69 (3): 540-556


    Successful management of pediatric arteriovenous malformations (AVMs) often requires a balanced application of embolization, surgery, and radiosurgery.To describe our experience treating pediatric AVMs.We analyzed 120 pediatric patients (< 18 years of age) with AVMs treated with various combinations of radiosurgery, surgery, and endovascular techniques.Between 1985 and 2009, 76 children with low Spetzler-Martin grade (1-3) and 44 with high-grade (4-5) AVMs were treated. Annual risk of hemorrhage from presentation to initial treatment was 4.0%, decreasing to 3.2% after treatment initiation until confirmed obliteration. Results for AVM obliteration were available in 101 patients. Initial single-modality therapy led to AVM obliteration in 51 of 67 low-grade (76%) and 3 of 34 high-grade (9%) AVMs, improving to 58 of 67 (87%) and 9 of 34 (26%), respectively, with further treatment. Mean time to obliteration was 1.8 years for low-grade and 6.4 years for high-grade AVMs. Disabling neurological complications occurred in 4 of 77 low-grade (5%) and 12 of 43 high-grade (28%) AVMs. At the final clinical follow-up (mean, 9.2 years), 48 of 67 patients (72%) with low-grade lesions had a modified Rankin Scale score (mRS) of 0 to 1 compared with 12 of 34 patients (35%) with high-grade AVMs. On multivariate analysis, significant risk factors for poor final clinical outcome (mRS ≥ 2) included baseline mRS ≥ 2 (odds ratio, 9.51; 95% confidence interval, 3.31-27.37; P < .01), left-sided location (odds ratio, 3.03; 95% confidence interval, 1.11-8.33; P = .03), and high AVM grade (odds ratio, 4.35; 95% confidence interval, 1.28-14.28; P = .02).Treatment of pediatric AVMs with multimodality therapy can substantially improve obliteration rates and may decrease AVM hemorrhage rates. The poor natural history and risks of intervention must be carefully considered when deciding to treat high-grade pediatric AVMs.

    View details for DOI 10.1227/NEU.0b013e3182181c00

    View details for Web of Science ID 000293586200005

    View details for PubMedID 21430584

  • Xenon-Enhanced Cerebral Blood Flow at 28% Xenon Provides Uniquely Safe Access to Quantitative, Clinically Useful Cerebral Blood Flow Information: A Multicenter Study AMERICAN JOURNAL OF NEURORADIOLOGY Carlson, A. P., Brown, A. M., Zager, E., Uchino, K., Marks, M. P., Robertson, C., Sinson, G. P., Marmarou, A., Yonas, H. 2011; 32 (7): 1315-1320


    Xe-CT measures CBF and can be used to make clinical treatment decisions. Availability has been limited, in part due to safety concerns. Due to improvements in CT technology, the concentration of inhaled xenon gas has been decreased from 32% to 28%. To our knowledge, no data exist regarding the safety profile of this concentration. We sought to better determine the safety profile of this lower concentration through a multicenter evaluation of adverse events reported by all centers currently performing xenon/CT studies in the US.Patients were prospectively recruited at 7 centers to obtain safety and efficacy information. All studies were performed to answer a clinical question. All centers used the same xenon delivery system. CT imaging was used during a 4.3-minute inhalation of 28% xenon gas. Vital signs were monitored on all patients throughout each procedure. Occurrence and severity of adverse events were recorded by the principal investigator at each site.At 7 centers, 2003 studies were performed, 1486 (74.2%) in nonventilated patients. The most common indications were occlusive vascular disease and ischemic stroke; 93% of studies were considered clinically useful. Thirty-nine studies (1.9%) caused respiratory suppression of >20 seconds, all of which resolved spontaneously. Shorter respiratory pauses occurred in 119 (5.9%), and hyperventilation, in 34 (1.7%). There were 53 additional adverse events (2.9%), 7 of which were classified as severe. No adverse event resulted in any persistent neurologic change or other sequelae.Xe-CT CBF can be performed safely, with a very low risk of adverse events and, to date, no risk of permanent morbidity or sequelae. On the basis of the importance of the clinical information gained, Xe-CT should be made widely available.

    View details for DOI 10.3174/ajnr.A2522

    View details for Web of Science ID 000294275100030

    View details for PubMedID 21700787

  • Intraoperative Angiography for Cranial Dural Arteriovenous Fistula AMERICAN JOURNAL OF NEURORADIOLOGY Pandey, P., Steinberg, G. K., Westbroek, E. M., Dodd, R., Do, H. M., Marks, M. P. 2011; 32 (6): 1091-1095


    IA is a valuable adjunct during surgery for a variety of neurovascular diseases; however, there are no reported series describing IA for DAVFs. This study was undertaken to evaluate the safety and efficacy of IA for DAVFs.A retrospective review of DAVF surgical cases during a 20-year period was conducted, and cases with IA were evaluated. Clinical details, surgical and angiographic findings, and postoperative outcomes were reviewed. The incidence of residual fistula on IAs, the utility of the surgical procedure, and the incidence of false-negative findings on IA were also determined.IA was performed in 29 patients (31 DAVFs) for DAVFs. The distribution of the fistulas was the following: transverse-sigmoid (n = 9), tentorial (n = 6), torcular (n = 3), cavernous sinus (n = 4), SSS (n = 4), foramen magnum (n = 3), and temporal-middle fossa (n = 2). Twelve patients had undergone prior embolization, while 6 patients had unsuccessful embolization procedures. Thirty-eight surgeries were performed for DAVF in 29 patients, and IA was performed in 34 surgeries. Forty-four angiographic procedures were performed in the 34 surgeries. Nine patients underwent multiple angiographies. In 11 patients (37.9%), IA revealed residual fistula after the surgeon determined that no lesion remained. This led to further exploration at the same sitting in 10 patients, while in 1 patient, further surgery was performed at a later date. False-negative findings on IA occurred in 3 patients (10.7%).IA is an important adjunct in surgery for DAVF. In this series, it resulted in further surgical treatment in 37.9% of patients. However, there was a 10% false-negative rate, which justified subsequent postoperative angiography.

    View details for DOI 10.3174/ajnr.A2443

    View details for Web of Science ID 000292066600024

    View details for PubMedID 21622580

  • Predictors of Clinical and Angiographic Outcome After Surgical or Endovascular Therapy of Very Large and Giant Intracranial Aneurysms NEUROSURGERY Darsaut, T. E., Darsaut, N. M., Chang, S. D., Silverberg, G. D., Shuer, L. M., Tian, L., Dodd, R. L., Do, H. M., Marks, M. P., Steinberg, G. K. 2011; 68 (4): 903-915


    Risk factors for poor outcome in the treatment of very large (≥20-24 mm) and giant (≥25 mm) intracranial aneurysms remain incompletely defined.To present an aggregate clinical series detailing a 24-year experience with very large and giant aneurysms to identify and assess the relative importance of various patient, aneurysm, and treatment-specific characteristics associated with clinical and angiographic outcomes.The authors retrospectively identified 184 aneurysms measuring 20 mm or larger (85 very large, 99 giant) treated at Stanford University Medical Center between 1984 and 2008. Clinical data including age, presentation, and modified Rankin Scale (mRS) score were recorded, along with aneurysm size, location, and morphology. Type of treatment was noted and clinical outcome measured using the mRS score at final follow-up. Angiographic outcomes were completely occluded, occluded with residual neck, partly obliterated, or patent with modified flow.After multivariate analysis, risk factors for poor clinical outcome included a baseline mRS score of 2 or higher (odds ratio [OR], 0.23; 95% confidence interval [CI]: 0.08-0.66; P = .01), aneurysm size of 25 mm or larger (OR, 3.32; 95% CI: 1.51-7.28; P < .01), and posterior circulation location (OR, 0.18; 95% CI: 0.07-0.43; P < .01). Risk factors for incomplete angiographic obliteration included fusiform morphology (OR, 0.25; 95% CI: 0.10-0.66; P < .01), posterior circulation location (OR, 0.33; 95% CI: 0.13-0.83; P = .02), and endovascular treatment (OR, 0.14; 95% CI: 0.06-0.32; P < .01). Patients with incompletely occluded aneurysms experienced higher rates of posttreatment subarachnoid hemorrhage and had increased mortality compared with those with completely obliterated aneurysms.Our results suggest that patients with poor baseline functional status, giant aneurysms, and aneurysms in the posterior circulation had a significantly higher proportion of poor outcomes at final follow-up. Fusiform morphology, posterior circulation location, and endovascular treatment were risk factors for incompletely obliterated aneurysms.

    View details for DOI 10.1227/NEU.0b013e3182098ad0

    View details for Web of Science ID 000288123100038

    View details for PubMedID 21221025



    To integrate three-dimensional (3D) digital rotation angiography (DRA) and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a targeting methodology enabling comprehensive image-guided robotic radiosurgery of arteriovenous malformations (AVMs).DRA geometric integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA acquisition modes with preset C-arm positions were configured. The geometric reproducibility of the presets was determined, and its impact on localization accuracy was evaluated. An imaging protocol composed of anterior-posterior and lateral DSA series in combination with a DRA run without couch displacement between acquisitions was introduced. Software was developed for registration of DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm with respect to the estimated geometry of the set positions and (b) potential patient motion between image series. Within the software, correlated navigation of registered DRA and DSA images was incorporated to localize AVMs within a 3D image coordinate space. Subsequent treatment planning and delivery followed a standard image-guided robotic radiosurgery process.DRA spatial distortions were typically smaller than 0.3 mm throughout a 145-mm × 145-mm × 145-mm volume. With 2D-3D image registration, localization uncertainties resulting from the achievable reproducibility of the C-arm set positions could be reduced to about 0.2 mm. Overall system-related localization uncertainty within the DRA coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical treatments with this technique were initiated.The integration of DRA and DSA into the process of nidus localization increases the confidence with which radiosurgical ablation of AVMs can be performed when using only an image-guided technique. Such an approach can increase patient comfort, decrease time pressure on clinical and technical staff, and possibly reduce the number of cerebral angiograms needed for a particular patient.

    View details for DOI 10.1016/j.ijrobp.2010.05.015

    View details for Web of Science ID 000288471500036

    View details for PubMedID 20801584

  • Angiographic Staging Of 215 Moyamoya Patients: Defining A New Modified Staging And Correlating Results To Patient Demographics And Clinical Findings International Stroke Conference Khan, N., Marks, M. P., Petralia, J., Tunovic, E., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2011: E201–E201
  • Failure of Primary Percutaneous Angioplasty and Stenting in the Prevention of Ischemia in Moyamoya Angiopathy CEREBROVASCULAR DISEASES Khan, N., Dodd, R., Marks, M. P., Bell-Stephens, T., Vavao, J., Steinberg, G. K. 2011; 31 (2): 147-153


    Moyamoya disease (MMD) is an idiopathic progressive arteriopathy affecting the proximal intracranial vasculature. To date only 4 case reports on intracranial angioplasty or stenting as treatment of this disease exist. We present 5 adult patients with MMD who failed angioplasty and/or stenting who remained symptomatic despite endovascular treatment or presented with recurrent symptoms and recurrence of stenosis/occlusion on angiography requiring subsequent extracranial-intracranial revascularization.Five adult MMD patients who underwent endovascular treatment with angioplasty or stenting were referred for further evaluation and treatment from outside hospitals. Data were collected from clinical referral notes and angiograms or reports. All patients underwent repeat 6-vessel cerebral angiography to assess the extent of disease and results of prior endovascular treatment.Six endovascular procedures were performed in all 5 patients. Internal carotid artery (ICA) balloon angioplasty and Wingspan stenting was performed in 2 patients (3 arteries). One patient had ICA-M1 angioplasty without stenting. Two patients had M1 angioplasty and Wingspan stenting. All patients developed repeat transient ischemic attacks following treatment attributable to the vascular territories of endovascular treatment. Repeat endovascular treatment was performed in 3 patients at a mean of 4 months (range = 2-6). Two went on to a third endovascular treatment due to progression of disease in the angioplastied/stented vessel. The average time of symptom recurrence after initial endovascular therapy was 1.8 months (0-4 months). Follow-up angiography when referred to our institution demonstrated 70-90% instent restenosis of the stented vessel in 3 and occlusion in 1 patient. Due to persistence of symptoms cerebral revascularization was performed in all patients.MMD is a progressive angiopathy. Angioplasty and stenting may temporarily improve the cerebral blood flow and decrease cerebral ischemic events but do not appear to be durable nor provide long-term prevention against future ischemic events.

    View details for DOI 10.1159/000320253

    View details for Web of Science ID 000291815300006

    View details for PubMedID 21135550

  • Capsular warning syndrome caused by middle cerebral artery stenosis JOURNAL OF THE NEUROLOGICAL SCIENCES Lee, J., Albers, G. W., Marks, M. P., Lansberg, M. G. 2010; 296 (1-2): 115-120


    The capsular warning syndrome is a term used to describe recurrent stereotyped lacunar transient ischemic attacks (TIAs). This syndrome is associated with a high risk of developing a completed stroke. The presumed mechanism for this syndrome is angiopathy of a lenticulostriate artery. We describe the case of a 33-year-old man who presented with the capsular warning syndrome who was successfully treated with angioplasty. The patient's capsular warning syndrome manifested as recurrent episodes of transient left hemiparesis. Symptoms recurred one to three times daily despite treatment with antithrombotics. Cerebral angiography demonstrated stenosis of the right middle cerebral artery (MCA) with decreased flow to a dominant lenticulostriate artery. Angioplasty of the right middle cerebral artery increased flow to the lenticulostriate artery and the TIAs resolved following the procedure. In select cases intracranial angioplasty, may be an effective treatment for patients with capsular warning syndrome.

    View details for DOI 10.1016/j.jns.2010.06.003

    View details for Web of Science ID 000281272300022

    View details for PubMedID 20619422

    View details for PubMedCentralID PMC2932463

  • Frameless image guided robotic radiosurgery of arteriovenous malformation localized on spatially correlated digital subtraction and C-arm CT angiography images JOURNAL OF NEUROINTERVENTIONAL SURGERY Hristov, D., Adler, J. R., Gibbs, I. C., Dodd, R., Marks, M., Chang, S. D., Do, H. M. 2010; 2 (3): 252-254


    A case is reported of frameless image guided robotic radiosurgery for an arteriovenous malformation (AVM). C-arm CT (CACT) and concurrent digital subtraction angiography images were used for AVM localization within the CACT volume. Treatment planning was performed on CT images registered with the CACT dataset. During delivery, a robotic linear accelerator tracked the target based on localization with frequent stereoscopic x-ray imaging. This case demonstrates that a frameless approach to AVM radiosurgery is possible.

    View details for DOI 10.1136/jnis.2009.001941

    View details for Web of Science ID 000281357900019

    View details for PubMedID 21990637

  • Combined Arterial Spin Label and Dynamic Susceptibility Contrast Measurement of Cerebral Blood Flow MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Straka, M., Marks, M. P., Albers, G. W., Moseley, M. E., Bammer, R. 2010; 63 (6): 1548-1556


    Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC-CBF quantitation is challenging due to many uncertainties, including partial- volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patient-specific correction factor, the ratio of ASL- and DSC-CBF, calculated only in short-arrival-time regions (as determined by the DSC-based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold-standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI-based CBF to xenon CT CBF (coefficient of variation) was 90 +/- 30% (33%) for combined ASL and DSC CBF, 43 +/- 21% (47%) for DSC, and 91 +/- 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease.

    View details for DOI 10.1002/mrm.22329

    View details for Web of Science ID 000278164400015

    View details for PubMedID 20512858

    View details for PubMedCentralID PMC2905651

  • Diagnostic Accuracy of MRI in Spontaneous Intra-cerebral Hemorrhage (DASH): Initial Results International Stroke Conference Wijman, C. A., Snider, R. W., Venkatasubramanian, C., Caulfield, A. F., Buckwalter, M., Eyngorn, I., Fischbein, N., Gean, A., Schwartz, N., Lansberg, M., Mlynash, M., Kemp, S., Thai, D., Narayana, R. K., Marks, M., Bammer, R., Moseley, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E210–E211
  • Efficacy of endovascular stenting in dural venous sinus stenosis for the treatment of idiopathic intracranial hypertension NEUROSURGICAL FOCUS Arac, A., Lee, M., Steinberg, G. K., Marcellus, M., Marks, M. P. 2009; 27 (5)


    Multiple pathophysiological mechanisms have been proposed for the increased intracranial pressure observed in idiopathic intracranial hypertension (IIH). The condition is well characterized, with intractable headaches, visual obscurations, and papilledema as dominant features, mainly affecting obese women. With the advent of MR venography and increased use of cerebral angiography, there has been recent emphasis on the significant number of patients with IIH found to have associated nonthrombotic dural venous sinus stenosis. This has led to a renewed interest in endovascular stenting as a treatment for IIH. However, the assumption that venous stenosis leads to a high pressure gradient that decreases CSF resorption through arachnoid villi requires further evidence. In this paper, the authors analyze the published results to date of dural venous sinus stenting in patients with IIH. They also present a case from their institution for illustration. The pathophysiological mechanism in IIH requires further elucidation, but venous sinus stenosis with subsequent intracranial hypertension appears to be an important mechanism in at least a subgroup of patients with IIH. Among these patients, 78% had complete relief or improvement of their main presenting symptoms after endovascular stenting. Resolution or improvement in papilledema was seen in 85.1% of patients. Endovascular stenting should be considered whenever venous sinus stenosis is diagnosed in patients with IIH.

    View details for DOI 10.3171/2009.9.FOCUS09165

    View details for Web of Science ID 000271373800014

    View details for PubMedID 19877792

  • Clinical outcome after 450 revascularization procedures for moyamoya disease JOURNAL OF NEUROSURGERY Guzman, R., Lee, M., Achrol, A., Bell-Stephens, T., Kelly, M., Do, H. M., Marks, M. P., Steinberg, G. K. 2009; 111 (5): 927-935


    Moyamoya disease (MMD) is a rare cerebrovascular disease mainly described in the Asian literature. To address a lack of data on clinical characteristics and long-term outcomes in the treatment of MMD in North America, the authors analyzed their experience at Stanford University Medical Center. They report on a consecutive series of patients treated for MMD and detail their demographics, clinical characteristics, and long-term surgical outcomes.Data obtained in consecutive series of 329 patients with MMD treated microsurgically by the senior author (G.K.S.) between 1991 and 2008 were analyzed. Demographic, clinical, and surgical data were prospectively gathered and neurological outcomes assessed in postoperative follow-up using the modified Rankin Scale. Association of demographic, clinical, and surgical data with postoperative outcome was assessed by chi-square, uni- and multivariate logistic regression, and Kaplan-Meier survival analyses.The authors treated a total of 233 adult patients undergoing 389 procedures (mean age 39.5 years) and 96 pediatric patients undergoing 168 procedures (mean age 10.1 years). Direct revascularization technique was used in 95.1% of adults and 76.2% of pediatric patients. In 264 patients undergoing 450 procedures (mean follow-up 4.9 years), the surgical morbidity rate was 3.5% and the mortality rate was 0.7% per treated hemisphere. The cumulative 5-year risk of perioperative or subsequent stroke or death was 5.5%. Of the 171 patients presenting with a transient ischemic attack, 91.8% were free of transient ischemic attacks at 1 year or later. Overall, there was a significant improvement in quality of life in the cohort as measured using the modified Rankin Scale (p < 0.0001).Revascularization surgery in patients with MMD carries a low risk, is effective at preventing future ischemic events, and improves quality of life. Patients in whom symptomatic MMD is diagnosed should be offered revascularization surgery.

    View details for DOI 10.3171/2009.4.JNS081649

    View details for Web of Science ID 000271375500012

    View details for PubMedID 19463046

  • Geography, Structure, and Evolution of Diffusion and Perfusion Lesions in Diffusion and Perfusion Imaging Evaluation For Understanding Stroke Evolution (DEFUSE) STROKE Olivot, J., Mlynash, M., Thijs, V. N., Purushotham, A., Kemp, S., Lansberg, M. G., Wechsler, L., Gold, G. E., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (10): 3245-3251


    The classical representation of acute ischemic lesions on MRI is a central diffusion-weighted imaging (DWI) lesion embedded in a perfusion-weighted imaging (PWI) lesion. We investigated spatial relationships between final infarcts and early DWI/PWI lesions before and after intravenous thrombolysis in the Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study.Baseline and follow-up DWI and PWI lesions and 30-day fluid-attenuated inversion recovery scans of 32 patients were coregistered. Lesion geography was defined by the proportion of the DWI lesion superimposed by a Tmax (time when the residue function reaches its maximum) >4 seconds PWI lesion; Type 1: >50% overlap and Type 2: < or = 50% overlap. Three-dimensional structure was dichotomized into a single lesion (one DWI and one PWI lesion) versus multiple lesions. Lesion reversal was defined by the percentage of the baseline DWI or PWI lesion not superimposed by the early follow-up DWI or PWI lesion. Final infarct prediction was estimated by the proportion of the final infarct superimposed on the union of the DWI and PWI lesions.Single lesion structure with Type 1 geography was present in only 9 patients (28%) at baseline and 4 (12%) on early follow-up. In these patients, PWI and DWI lesions were more likely to correspond with the final infarcts. DWI reversal was greater among patients with Type 2 geography at baseline. Patients with multiple lesions and Type 2 geography at early follow-up were more likely to have early reperfusion.Before thrombolytic therapy in the 3- to 6-hour time window, Type 2 geography is predominant and is associated with DWI reversal. After thrombolysis, both Type 2 geography and multiple lesion structure are associated with reperfusion.

    View details for DOI 10.1161/STROKEAHA.109.558635

    View details for Web of Science ID 000270229800016

    View details for PubMedID 19679845

    View details for PubMedCentralID PMC2753724

  • Improving Dynamic Susceptibility Contrast MRI Measurement of Quantitative Cerebral Blood Flow using Corrections for Partial Volume and Nonlinear Contrast Relaxivity: A Xenon Computed Tomographic Comparative Study JOURNAL OF MAGNETIC RESONANCE IMAGING Zaharchuk, G., Bammer, R., Straka, M., Newbould, R. D., Rosenberg, J., Olivot, J., Mlynash, M., Lansberg, M. G., Schwartz, N. E., Marks, M. M., Albers, G. W., Moseley, M. E. 2009; 30 (4): 743-752


    To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold-standard CBF method, xenon computed tomography (xeCT).Eighteen patients with cerebrovascular disease underwent xeCT and MRI within 36 h. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed.Mean xeCT CBF was 43.3 +/- 13.7 mL/100g/min (mean +/- SD). BB correction decreased CBF by a factor of 4.7 +/- 0.4, but did not affect precision. The least-biased CBF measurement was with BB but without PV correction (45.8 +/- 17.2 mL/100 g/min, coefficient of variation [COV] = 32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3 +/- 10.8 mL/100 g/min, COV = 27%). Between patients correlation was moderate even with both corrections (R = 0.53).Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI-based CBF maps. However, there remain challenges given the moderate between-patient correlation, which limit diagnostic confidence of such measurements in individual patients.

    View details for DOI 10.1002/jmri.21908

    View details for Web of Science ID 000270522900007

    View details for PubMedID 19787719

    View details for PubMedCentralID PMC2851938

  • Relationships Between Cerebral Perfusion and Reversibility of Acute Diffusion Lesions in DEFUSE Insights from RADAR STROKE Olivot, J., Mlynash, M., Thijs, V. N., Purushotham, A., Kemp, S., Lansberg, M. G., Wechsler, L., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (5): 1692-1697


    Acute ischemic lesions with restricted diffusion can resolve after early recanalization. The impact of superimposed perfusion abnormalities on the fate of acute diffusion lesions is unclear.Data were obtained from DEFUSE, a prospective multicenter study of patients treated with IV tPA 3 to 6 hours after stroke onset. Thirty-two patients with baseline diffusion and perfusion lesions and 30 day FLAIR scans were coregistered. The acute diffusion lesion was divided into 3 regions according to the Tmax delay of the superimposed perfusion lesion: normal baseline perfusion; mild-moderately hypoperfused (2 s8 s). The reversal rate was calculated as the percentage of the acute diffusion lesion that did not overlap with the final infarct on 30-day FLAIR. Diffusion reversal rates were compared based on whether a favorable clinical response occurred and whether early recanalization was achieved.On average, 54% of the acute diffusion lesion volume had normal perfusion. Diffusion reversal rates were significantly increased among cases with favorable clinical response and in patients with early recanalization, especially in regions with normal baseline perfusion. The portion of the diffusion lesion with normal perfusion had significantly higher mean apparent diffusion coefficient values and reversal rates.Acute ischemic lesions with restricted diffusion are most likely to recover if reperfusion occurs within 6 hours of symptom onset, and reversibility is associated with early recanalization and favorable clinical outcome. We propose the term RADAR (Reversible Acute Diffusion lesion Already Reperfused) to describe regions of acute restricted diffusion with normal perfusion.

    View details for DOI 10.1161/STROKEAHA.108.538082

    View details for Web of Science ID 000265579800027

    View details for PubMedID 19299632

  • Optimal Tmax Threshold for Predicting Penumbral Tissue in Acute Stroke STROKE Olivot, J., Mlynash, M., Thijs, V. N., Kemp, S., Lansberg, M. G., Wechsler, L., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (2): 469-475


    We sought to assess whether the volume of the ischemic penumbra can be estimated more accurately by altering the threshold selected for defining perfusion-weighting imaging (PWI) lesions.DEFUSE is a multicenter study in which consecutive acute stroke patients were treated with intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset. Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Baseline and posttreatment PWI volumes were defined according to increasing Tmax delay thresholds (>2, >4, >6, and >8 seconds). Penumbra salvage was defined as the difference between the baseline PWI lesion and the final infarct volume (30-day fluid-attenuated inversion recovery sequence). We hypothesized that the optimal PWI threshold would provide the strongest correlations between penumbra salvage volumes and various clinical and imaging-based outcomes.Thirty-three patients met the inclusion criteria. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by Tmax >6 seconds versus Tmax >2 seconds, as was the difference in median penumbra salvage volume in patients with a favorable versus an unfavorable clinical response. Among patients who did not experience early reperfusion, the Tmax >4 seconds threshold provided a more accurate prediction of final infarct volume than the >2 seconds threshold.Defining PWI lesions based on a stricter Tmax threshold than the standard >2 seconds delay appears to provide more a reliable estimate of the volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours after symptom onset. A threshold between 4 and 6 seconds appears optimal for early identification of critically hypoperfused tissue.

    View details for DOI 10.1161/STROKEAHA.108.526954

    View details for Web of Science ID 000262784900021

    View details for PubMedID 19109547

  • Patients with Acute Stroke Treated with Intravenous tPA 3-6 Hours after Stroke Onset: Correlations between MR Angiography Findings and Perfusion- and Diffusion-weighted Imaging in the DEFUSE Study RADIOLOGY Marks, M. P., Olivot, J., Kemp, S., Lansberg, M. G., Bammer, R., Wechsler, L. R., Albers, G. W., Thijs, V. 2008; 249 (2): 614-623


    To study magnetic resonance (MR) angiography findings in patients with acute stroke treated with intravenous tissue plasminogen activator (tPA) in relationship to perfusion- and diffusion-weighted imaging changes and clinical outcome.Patients treated with intravenous tPA 3-6 hours after stroke onset (with informed consent) were evaluated in a HIPAA-compliant multicenter prospective study approved by all institutional review boards. MR imaging and MR angiography studies were performed before and 3-6 hours after treatment. MR angiography studies that were technically adequate at both time points were evaluated for occlusion, decreased flow, any early recanalization, and degree of recanalization. These results were compared with favorable clinical response (an improvement in National Institutes of Health Stroke Scale score of >or=8 points at 30 days or a modified Rankin scale score of 0 or 1 at 30 days) in patients with and those without mismatch between perfusion- and diffusion-weighted imaging at baseline.Seventy-four patients were enrolled in the initial investigation; pre- and posttreatment MR angiography studies were both technically adequate in 62 patients. MR angiography demonstrated occlusion or decreased flow in 46 patients. Patients with isolated middle cerebral artery (MCA) occlusion and early recanalization at MR angiography had higher rates of favorable clinical response than those with tandem internal carotid artery-MCA occlusion and early recanalization (P = .05). Any early recanalization was not associated with favorable clinical response, but degree of recanalization did correlate with favorable clinical response (P = .048). Favorable clinical response was more frequently seen in patients with mismatch between perfusion- and diffusion-weighted imaging findings at baseline who experienced early recanalization than in those who did not have early recanalization (odds ratio = 6.2; 95% confidence interval: 1.3, 30.2; P = .021). No relationship between early recanalization and favorable clinical response was seen in patients without mismatch.Early recanalization seen at MR angiography before and after treatment coupled with diffusion- and perfusion-weighted imaging data may predict clinical outcome in patients with stroke treated with tPA 3-6 hours after symptom onset.

    View details for DOI 10.1148/radiol.2492071751

    View details for Web of Science ID 000260215400027

    View details for PubMedID 18936316

  • Magnetic resonance imaging in the evaluation of acute stroke. Topics in magnetic resonance imaging Olivot, J. M., Marks, M. P. 2008; 19 (5): 225-230


    The ability to use physiologic imaging with either magnetic resonance (MR) or computed tomography to help define irreversibly injured brain (the infarct core) and tissue at risk of infarct (reversible ischemic penumbra) holds great promise in the future treatment of stroke. The physiologic principles and concepts underlying the evaluation for mismatch between injured tissue and tissue at risk are similar for the 2 imaging techniques. Multimodal MR imaging (diffusion-weighted imaging/perfusion-weighted imaging/MR angiography) provides a validated penumbral selection criteria based on the results of 2 clinical trials (diffusion and perfusion imaging evaluation for understanding stroke evolution and echoplanar imaging thrombolysis evaluation). Computed tomographic perfusion parameters have also been calculated to optimize final infarct prediction. Both techniques await further study to prove their capability of selecting cases for short-term recanalization/reperfusion therapy.

    View details for DOI 10.1097/RMR.0b013e3181aaf37c

    View details for PubMedID 19512854

  • The MRA-DWI mismatch identifies patients with stroke who are likely to benefit from reperfusion STROKE Lansberg, M. G., Thijs, V. N., Bammer, R., Olivot, J., Marks, M. P., Wechsler, L. R., Kemp, S., Albers, G. W. 2008; 39 (9): 2491-2496


    The aim of this exploratory analysis was to evaluate if a combination of MR angiography (MRA) and diffusion-weighted imaging (DWI) selection criteria can be used to identify patients with acute stroke who are likely to benefit from early reperfusion.Data from DEFUSE, a study of 74 patients with stroke who received intravenous tissue plasminogen activator in the 3- to 6-hour time window and underwent MRIs before and approximately 4 hours after treatment were analyzed. The MRA-DWI mismatch model was defined as (1) a DWI lesion volume less than 25 mL in patients with a proximal vessel occlusion; or (2) a DWI lesion volume less than 15 mL in patients with proximal vessel stenosis or an abnormal finding of a distal vessel. Favorable clinical response was defined as an improvement on the National Institutes of Health Stroke Scale score of at least 8 points between baseline and 30 days or a National Institutes of Health Stroke Scale score

    View details for DOI 10.1161/STROKEAHA.107.508572

    View details for Web of Science ID 000258727000015

    View details for PubMedID 18635861

  • Relationships between infarct growth, clinical outcome, and early recanalization in Diffusion and perfusion imaging For Understanding Stroke Evolution (DEFUSE) STROKE Olivot, J., Mlynash, M., Thijs, V. N., Kemp, S., Lansberg, M. G., Wechsler, L., Schlaug, G., Bammer, R., Marks, M. P., Albers, G. W. 2008; 39 (8): 2257-2263


    The purpose of this study was to determine the relationships between ischemic lesion growth, recanalization, and clinical response in stroke patients with and without a perfusion/diffusion mismatch.DEFUSE is an open label multicenter study in which 74 consecutive acute stroke patients were treated with intravenous tPA 3 to 6 hours after stroke onset. Magnetic resonance imaging (MRI) scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Lesion growth was defined as the difference between the final infarct volume (30 day FLAIR) and the baseline diffusion lesion. Baseline MRI profiles were used to categorize 44 patients into Mismatch versus Absence of Mismatch subgroups. Early recanalization was assessed in 28 patients with an initial vessel lesion on magnetic resonance angiography. Infarct growth was compared based on whether a favorable clinical response (FCR) occurred and whether early recanalization was achieved.In the Mismatch subgroup, FCR was associated with less infarct growth P=0.03 and early recanalization was predictive of both FCR (odds ratio: 22, P=0.047) and reduced infarct growth P=0.024. There was no significant relationship between recanalization, infarct growth, and clinical outcome in the Absence of Mismatch subgroup. A threshold of <7 cc of growth had the highest sensitivity and specificity for predicting a FCR in Mismatch patients (odds ratio: 65, P=0.015, sensitivity 82%, specificity 75%).In contrast to Absence of Mismatch patients, significant associations between recanalization, reduced infarct growth, and favorable clinical response were documented in patients with a perfusion/diffusion mismatch who were treated with tPA within 3 to 6 hours after stroke onset. These findings support the Mismatch hypothesis but require validation in a larger study.

    View details for DOI 10.1161/STROKEAHA.107.511535

    View details for Web of Science ID 000257993400011

    View details for PubMedID 18566302

  • Multimodality treatment of posterior fossa arteriovenous malformations JOURNAL OF NEUROSURGERY Kelly, M. E., Guzman, R., Sinclair, J., Bell-Stephens, T. E., Bower, R., Hamilton, S., Marks, M. P., Do, H. M., Chang, S. D., Adler, J. R., Levy, R. P., Steinberg, G. K. 2008; 108 (6): 1152-1161


    Posterior fossa arteriovenous malformations (AVMs) are relatively uncommon and often difficult to treat. The authors present their experience with multimodality treatment of 76 posterior fossa AVMs, with an emphasis on Spetzler-Martin Grades III-V AVMs.Seventy-six patients with posterior fossa AVMs treated with radiosurgery, surgery, and endovascular techniques were analyzed.Between 1982 and 2006, 36 patients with cerebellar AVMs, 33 with brainstem AVMs, and 7 with combined cerebellar-brainstem AVMs were treated. Natural history data were calculated for all 76 patients. The risk of hemorrhage from presentation until initial treatment was 8.4% per year, and it was 9.6% per year after treatment and before obliteration. Forty-eight patients had Grades III-V AVMs with a mean follow-up of 4.8 years (range 0.1-18.4 years, median 3.1 years). Fifty-two percent of patients with Grades III-V AVMs had complete obliteration at the last follow-up visit. Three (21.4%) of 14 patients were cured with a single radiosurgery treatment, and 4 (28.6%) of 14 with 1 or 2 radiosurgery treatments. Twenty-one (61.8%) of 34 patients were cured with multimodality treatment. The mean Glasgow Outcome Scale (GOS) score after treatment was 3.8. Multivariate analysis performed in the 48 patients with Grades III-V AVMs showed radiosurgery alone to be a negative predictor of cure (p = 0.0047). Radiosurgery treatment alone was not a positive predictor of excellent clinical outcome (GOS Score 5; p > 0.05). Nine (18.8%) of 48 patients had major neurological complications related to treatment.Single-treatment radiosurgery has a low cure rate for posterior fossa Spetzler-Martin Grades III-V AVMs. Multimodality therapy nearly tripled this cure rate, with an acceptable risk of complications and excellent or good clinical outcomes in 81% of patients. Radiosurgery alone should be used for intrinsic brainstem AVMs, and multimodality treatment should be considered for all other posterior fossa AVMs.

    View details for DOI 10.3171/JNS/2008/108/6/1152

    View details for Web of Science ID 000256245300024

    View details for PubMedID 18518720

  • Experimental study of intracranial hematoma detection with flat panel detector C-arm CT AMERICAN JOURNAL OF NEURORADIOLOGY Arakawa, H., Marks, M. P., Do, H. M., Bouley, D. M., Strobel, N., Moore, T., Fahrig, R. 2008; 29 (4): 766-772


    Intracranial hemorrhage is a commonly acknowledged complication of interventional neuroradiology procedures, and the ability to image hemorrhage at the time of the procedure would be very beneficial. A new C-arm system with 3D functionality extends the capability of C-arm imaging to include soft-tissue applications by facilitating the detection of low-contrast objects. We evaluated its ability to detect small intracranial hematomas in a swine model.Intracranial hematomas were created in 7 swine by autologous blood injection of various hematocrits (19%-37%) and volumes (1.5-5 mL). Four animals received intravascular contrast before obtaining autologous blood (group 1), and 3 did not (group 2). We scanned each animal by using the C-arm CT system, acquiring more than 500 images during a 20-second rotation through more than 200 degrees . Multiplanar reformatted images with isotropic resolution were reconstructed on the workstation by using product truncation, scatter, beam-hardening, and ring-artifact correction algorithms. The brains were harvested and sliced for hematoma measurement and compared with imaging findings.Five intracranial hematomas were created in group 1 animals, and all were visualized. Six were created in group 2, and 3 were visualized. One nonvisualized hematoma was not confirmed at necropsy. All the others in both groups were confirmed. In group 1 (with contrast), small hematomas were detectable even when the hematocrit was 19%-20%. In group 2 (without contrast) C-arm CT was able to detect small hematomas (<1.0 cm(2)) created with hematocrits of 29%-37%. The area of hematoma measured from the C-arm CT data was, on average, within 15% of the area measured from harvested brain.The image quality obtained with this implementation of C-arm CT was sufficient to detect experimentally created small intracranial hematomas. This capability should provide earlier detection of hemorrhagic complications that may occur during neurointerventional procedures.

    View details for DOI 10.3174/ajnr.A0898

    View details for Web of Science ID 000255129700029

    View details for PubMedID 18202240

  • Neurologic complications of arteriovenous malformation embolization using liquid embolic agents AMERICAN JOURNAL OF NEURORADIOLOGY Jayaraman, M. V., Marcellus, M. L., Hamilton, S., Do, H. M., Campbell, D., Chang, S. D., Steinberg, G. K., Marks, M. P. 2008; 29 (2): 242-246


    Embolization of arteriovenous malformations (AVMs) is commonly used to achieve nidal volume reduction before microsurgical resection or stereotactic radiosurgery. The purpose of this study was to examine the overall neurologic complication rate in patients undergoing AVM embolization and analyze the factors that may determine increased risk.We performed a retrospective review of all patients with brain AVMs embolized at 1 center from 1995 through 2005. Demographics, including age, sex, presenting symptoms, and clinical condition, were recorded. Angiographic factors including maximal nidal size, presence of deep venous drainage, and involvement of eloquent cortex were also recorded. For each embolization session, the agent used, number of pedicles embolized, the percentage of nidal obliteration, and any complications were recorded. Complications were classified as the following: none, non-neurologic (mild), transient neurologic deficit, and permanent nondisabling and permanent disabling deficits. The permanent complications were also classified as ischemic or hemorrhagic. Modified Rankin Scale (mRS) scores were collected pre- and postembolization on all patients. Univariate regression analysis of factors associated with the development of any neurologic complication was performed.Four hundred eighty-nine embolization procedures were performed in 192 patients. There were 6 Spetzler-Martin grade I (3.1%), 26 grade II (13.5%), 71 grade III (37.0%), 57 grade IV (29.7%), and 32 grade V (16.7%) AVMs. Permanent nondisabling complications occurred in 5 patients (2.6%) and permanent disabling complications or deaths occurred in 3 (1.6%). In addition, there were non-neurologic complications in 4 patients (2.1%) and transient neurologic deficits in 22 (11.5%). Five of the 8 permanent complications (2.6% overall) were ischemic, and 3 of 8 (1.6% overall) were hemorrhagic. Of the 178 patients who were mRS 0-2 pre-embolization, 4 (2.3%) were dependent or dead (mRS >2) at follow-up. Univariate analysis of risk factors for permanent neurologic deficits following embolization showed that basal ganglia location was weakly associated with a new postembolization neurologic deficit.Embolization of brain AVMs can be performed with a high degree of technical success and a low rate of permanent neurologic complications.

    View details for DOI 10.3174/ajnr.A0793

    View details for Web of Science ID 000253345200013

    View details for PubMedID 17974613

  • Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke STROKE Lansberg, M. G., Thijs, V. N., Bammer, R., Kemp, S., Wijman, C. A., Marks, M. P., Albers, G. W. 2007; 38 (8): 2275-2278


    Studies evaluating predictors of tPA-associated symptomatic intracerebral hemorrhage (SICH) have typically focused on clinical and CT-based variables. MRI-based variables have generally not been included in predictive models, and little is known about the influence of reperfusion on SICH risk.Seventy-four patients were prospectively enrolled in an open-label study of intravenous tPA administered between 3 and 6 hours after symptom onset. An MRI was obtained before and 3 to 6 hours after tPA administration. The association between several clinical and MRI-based variables and tPA-associated SICH was determined using multivariate logistic regression analysis. SICH was defined as a > or = 2 point change in National Institutes of Health Stroke Scale Score (NIHSSS) associated with any degree of hemorrhage on CT or MRI. Reperfusion was defined as a decrease in PWI lesion volume of at least 30% between baseline and the early follow-up MRI.SICH occurred in 7 of 74 (9.5%) patients. In univariate analysis, NIHSSS, DWI lesion volume, PWI lesion volume, and reperfusion status were associated with an increased risk of SICH (P<0.05). In multivariate analysis, DWI lesion volume was the single independent baseline predictor of SICH (odds ratio 1.42; 95% CI 1.13 to 1.78 per 10 mL increase in DWI lesion volume). When early reperfusion status was included in the predictive model, the interaction between DWI lesion volume and reperfusion status was the only independent predictor of SICH (odds ratio 1.77; 95% CI 1.25 to 2.50 per 10 mL increase in DWI lesion volume).Patients with large baseline DWI lesion volumes who achieve early reperfusion appear to be at greatest risk of SICH after tPA therapy.

    View details for DOI 10.1161/STROKEAHA.106.480475

    View details for Web of Science ID 000248455100016

    View details for PubMedID 17569874

  • Endovascular embolization of the swine rete mirabile with Eudragit-E 100 polymer 73rd Annual Meeting of the American-Association-of-Neurological-Surgeons/Congress of Neurological Surgeons Cerebrovascular Section/American-Society-of-Interventional-and-Therapeutic-Neuroradiology Arakawa, H., Murayama, Y., DAVIS, C. R., Howard, D. L., Baumgardner, W. L., Marks, M. P., Do, H. M. AMER SOC NEURORADIOLOGY. 2007: 1191–96


    Both adhesive and nonabrasive embolic agents are available for arteriovenous malformation (AVM) embolization. The purpose of this study was to evaluate a novel ethanol-based nonadhesive liquid embolic material in a swine AVM model.Eudragit (copolymer of methyl and butyl methacrylate and dimethylaminoethyl methacrylate) was dissolved in 50% ethanol and 50% iopamidol. Eudragit was injected into 9 retia mirabilia (RMs). Ethanol and iopamidol mixture were injected into 4 RMs for comparison. Three RMs embolized with Eudragit mixture were evaluated both angiographically and histopathologically acutely (3-24 hours) and at 30 days and 90 days after embolization.No procedural complications from Eudragrit embolization were noted, including retention or adhesion of the microcatheter. Various degrees of inflammation were observed in the acute and 30-day specimens. Two RMs showed partial recanalization on both histopathology and follow-up angiography in the 30-day group. Arterial fibrosis and calcification were observed in the 30- and 90-day specimens. The internal elastic lamina was disrupted in the 30- and 90-day specimens, but there was no evidence of Eudragit extravasation or hemorrhage. Endothelial damage was seen in all specimens and was particularly severe in the 30- and 90-day specimens.Eudragit polymer induced inflammation in thrombosis similar to n-butyl 2-cyanoacrylate, but without the disadvantages of perivascular hemorrhage and extravasation of embolization material. Although recanalization of some embolized RMs was noted, further investigation into Eudragit as a potentially useful embolic material for brain AVMs is warranted.

    View details for DOI 10.3174/ajnr.A0536

    View details for Web of Science ID 000247395800044

    View details for PubMedID 17569986

  • Surgical and endovascular management of symptomatic posterior circulation fusiform aneurysms JOURNAL OF NEUROSURGERY Coert, B. A., Chang, S. D., Do, H. M., Marks, M. P., Steinberg, G. K. 2007; 106 (5): 855-865


    Patients with fusiform aneurysms can present with subarachnoid hemorrhage (SAH), mass effect, ischemia, or unrelated symptoms. The absence of an aneurysm neck impedes the direct application of a clip and endovascular coil deployment. To evaluate the effects of their treatments, the authors retrospectively analyzed a consecutive series of patients with posterior circulation fusiform aneurysms treated at Stanford University Medical Center between 1991 and 2005.Forty-nine patients (mean age 53 years, male/female ratio 1.2:1) treated at the authors' medical center form the basis of the analysis. Twenty-nine patients presented with an SAH. The patients presenting without SAH had cranial nerve dysfunction (five patients), symptoms of mass effect (eight patients), ischemia (six patients), or unrelated symptoms (one patient). The aneurysms were located on the vertebral artery (VA) or posterior inferior cerebellar artery (PICA) (21 patients); vertebrobasilar junction (VBJ) or basilar artery (BA) (18 patients); and posterior cerebral artery (PCA) (10 patients). Pretreatment clinical grades were determined using the Hunt and Hess scale; for patients with unruptured aneurysms (Hunt and Hess Grade 0) functional subgrades were added. Outcome was evaluated using the Glasgow Outcome Scale (GOS) score during a mean follow-up period of 33 months. Overall long-term outcome was good (GOS Score 4 or 5) in 59%, poor (GOS Score 2 or 3) in 16%, and fatal (GOS Score 1) in 24% of the patients. In a univariate analysis, poor outcome was predicted by age greater than 55 years, VBJ location, pretreatment Hunt and Hess grade in patients presenting with SAH, and incomplete aneurysm thrombosis after endovascular treatment. In a multivariate analysis, age greater than 55 years was the confounding factor predicting poor outcome. Stratification by aneurysm location removed the effect of age. Of 13 patients with residual aneurysm after treatment, five (38%) subsequently died of SAH (three patients) or progressive mass effect/brainstem ischemia (two patients).Certain posterior circulation aneurysm locations (PCA, VA-PICA, and BA-VBJ) represent separate disease entities affecting patients at different ages with distinct patterns of presentation, treatment options, and outcomes. Favorable overall long-term outcome can be achieved in 90% of patients with PCA aneurysms, in 60% of those with VA-PICA aneurysms, and in 39% of those with BA-VBJ aneurysms when using endovascular and surgical techniques. The natural history of the disease was poor in patients with incomplete aneurysm thrombosis after treatment.

    View details for Web of Science ID 000246047800008

    View details for PubMedID 17542530

  • Dissection of the V4 segment of the vertebral artery: clinicoradiologic manifestations and endovascular treatment EUROPEAN RADIOLOGY Yoon, W., Seo, J. J., Kim, T. S., Do, H. M., Jayaraman, M. V., Marks, M. P. 2007; 17 (4): 983-993


    Intracranial vertebral artery (VA) dissection has three clinical presentations: ischemia, hemorrhage, and mass effect. Imaging findings of intracranial VA dissections vary according to clinical presentation. Irregular stenosis or occlusion of the VA is the most common finding in patients with posterior fossa infarction, whereas a dissecting aneurysm is the main feature in those with acute subarachnoid hemorrhage. A chronic, giant, dissecting aneurysm can cause mass effect on the brain stem or cranial nerves, as well as distal embolism. Magnetic resonance imaging is useful for detection of intramural hematomas and intimal flaps, both of which are diagnostic of VA dissection. Multidetector computed tomography angiography is increasingly used for diagnosis of VA dissection. Catheter angiography is still beneficial for evaluation of precise endoluminal morphology of the dissection before surgical or endovascular intervention. Endovascular treatment is now considered a major therapeutic option for patients with a ruptured dissecting aneurysm or a chronic dissecting aneurysm. Anticoagulation therapy is currently considered the initial treatment of choice in patients with posterior circulation ischemic symptoms. Endovascular treatment, such as stent-assisted angioplasty or coil occlusion at the dissection site, can be performed in selected patients with posterior fossa ischemic symptoms.

    View details for DOI 10.1007/s00330-006-0272-8

    View details for Web of Science ID 000244753900014

    View details for PubMedID 16670864

  • Morphologic assessment of middle cerebral artery aneurysms for endovascular treatment. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Jayaraman, M. V., Do, H. M., Versnick, E. J., Steinberg, G. K., Marks, M. P. 2007; 16 (2): 52-56


    Aneurysms of the middle cerebral artery (MCA) trifurcation region are underrepresented in large series of endovascularly treated aneurysms. The purpose of our study was to evaluate the incidence of specific morphologic features of MCA bifurcation aneurysms that may affect suitability for endovascular treatment.We evaluated 53 consecutive patients with 58 bifurcation or trifurcation MCA aneurysms seen for angiographic evaluation during a 4-year period at our institution. All angiograms were reviewed for: aneurysm size (largest dimension, dome and neck size), branch vessels originating from the aneurysm sac, straightening of the aneurysm wall to suggest intramural thrombus, calcification in the region of the aneurysm, stenosis of the parent vessel, and presence of daughter sacs.Of 58 aneurysms, 51 (88%) had a dome to neck ratio less than 2:1. Branch vessel incorporation in the aneurysm sac was seen in 23/58 (40%), straightening suggestive of thrombus in 14/58 (24%), calcification in 2/58 (3%), parent vessel stenosis in 1/58 (2%), and daughter sacs in 4/58 (7%).The majority of MCA aneurysms have morphologic features such as a dome to neck ratio less than 2:1 or branch vessel incorporation that may make them unsuitable for endovascular treatment using conventional intra-aneurysmal coiling.

    View details for PubMedID 17689394

  • Treatment of traumatic cervical arteriovenous fistulas with N-butyl-2-cyanoacrylate AMERICAN JOURNAL OF NEURORADIOLOGY Jayaraman, M. V., Do, H. M., Marks, M. P. 2007; 28 (2): 352-354


    We report 2 cases of traumatic arteriovenous fistulas in the neck treated with transarterial embolization with n-butyl-2-cyanoacrylate (n-BCA). In both cases, covered stent placement across the fistula to preserve the artery was not possible. Detachable coil placement was attempted in one case but was not successful. Both fistulas were successfully treated with n-BCA embolization. To our knowledge, these are the first 2 such cases reported of high-flow cervical arteriovenous fistulas treated with n-BCA embolization.

    View details for Web of Science ID 000244263200038

    View details for PubMedID 17297011

  • Hemorrhage rate in patients with Spetzler-Martin grades IV and V arteriovenous malformations - Is treatment justified? STROKE Jayaraman, M. V., Marcellus, M. L., Do, H. M., Chang, S. D., Rosenberg, J. K., Steinberg, G. K., Marks, M. P. 2007; 38 (2): 325-329


    We sought to examine the prospective annual risk of hemorrhage in patients harboring Spetzler-Martin grades IV and V arteriovenous malformations (AVMs) before and after initiation of treatment.Medical records of 61 consecutive patients presenting with Spetzler-Martin grades IV and V AVMs were retrospectively reviewed for demographics, angiographic features, presenting symptom(s), and time of all hemorrhage events, before or after treatment initiation. Pretreatment hemorrhage rates (excluding hemorrhages at presentation) and posttreatment rates were subsequently calculated. Modified Rankin Scale (mRS) scores before and after treatment were recorded.The annual pretreatment hemorrhage rate for all patients was 10.4% per year (95% CI, 2.2 to 15.4%), 13.9% (95% CI, 3.5 to 22.1%) in patients with hemorrhagic presentation and 7.3% (2.6 to 14.3%) in patients with nonhemorrhagic presentation. Posttreatment hemorrhage rates were 6.1% per year (95% CI, 2.5 to 13.2%) for all patients, 5.6% (95% CI, 2.1 to 11.8%) for patients presenting with hemorrhage and 6.4% (95% CI, 1.6 to 10.1%) in patients with nonhemorrhagic presentation. A noninferiority test showed that the posttreatment hemorrhage rate was less than or equal to the pretreatment hemorrhage rate (P<0.0001), with some indication that the reduction was greatest in patients with hemorrhagic presentation. Of the 62 patients, 51 (82%) had an mRS score of 0 to 2 before treatment, and 47 (76%) had an mRS score of 0 to 2 at the last follow-up after treatment.The annual rate of hemorrhage in grades IV and V AVMs is higher in this series than reported for all AVMs, which may reflect some referral bias in this single-center study. Nevertheless, initiation of treatment does not appear to increase the rate of subsequent hemorrhage. Treatment for these lesions may be warranted, given their poor natural history.

    View details for DOI 10.1161/

    View details for Web of Science ID 000244122600036

    View details for PubMedID 17194881

  • Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study ANNALS OF NEUROLOGY Albers, G. W., Thijs, V. N., Wechsle, L., Kemp, S., Schlaug, G., Skalabrin, E., Bammer, R., Kakuda, W., Lansberg, M. G., Shuaib, A., Coplin, W., Hamilton, S., Moseley, M., Marks, M. P. 2006; 60 (5): 508-517


    To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset.We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved.Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile.For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

    View details for DOI 10.1002/ana.20976

    View details for Web of Science ID 000242545100006

    View details for PubMedID 17066483

  • Proof-of-principle phase II MRI studies in stroke - Sample size estimates from dichotomous and continuous data STROKE Donnan, G. A., Davis, S. M., Phan, T. G., Ludbrook, J., Byrnes, G., Parsons, M., Barber, A. P., Reutens, D. C., Rose, S. E., Chalk, J., Demchuk, A. M., Coutts, S. B., Simon, J. E., Tomanek, A., Roether, J., Weiller, C., Fiehler, J., Thomalla, G., Kucinski, T., Schellinger, P. D., Hacke, W., Gass, A., Szabo, K., Hennerici, M., Siebler, M., Villringer, A., Junge-Huelsing, G. J., Pedraza, S., Davalos, A., Castillo, J., Albers, G. W., Lansberg, M. G., Thijs, V. N., Bammer, R., Moseley, M. E., Marks, M., Warach, S., Baird, A., Kidwell, C., Saver, J., Sorensen, G., Fisher, M., Nighoghossian, N., Muir, K. 2006; 37 (10): 2521-2525


    Since the failure of a number of phase III trials of neuroprotection in ischemic stroke, the need for smaller phase II studies with MRI surrogates has emerged. There is, however, little information available about sample size requirements for such phase II trials and rarely enough patients in single studies to make robust estimates. We have formed an international collaborative group to assemble larger datasets and from these have generated sample size tables for MRI-based infarct expansion as the outcome measure.Twelve centers from Australia, Europe, and North America contributed data from patients with hemispheric ischemic stroke. Infarct expansion was defined from initial diffusion-weighted images and later fluid-attenuated inversion recover or T2 images. Sample size estimates were calculated from data on infarct expansion ratios treated as dichotomous or continuous variables. A nonparametric approach was used because the distribution of infarct expansion was resistant to all forms of transformation.As an example, a 20% absolute reduction in infarct expansion ratio (< or = 1), 80% power, and alpha = 0.05 requires 99 patients in each arm. To achieve an equivalent effect size with a continuous approach requires 61 patients.These tables will be useful in planning phase II trials of therapy with the use of MRI outcome measures. For positive studies, biologically plausible surrogates such as these may provide a rationale for proceeding to phase III trials.

    View details for DOI 10.1161/01.STR.0000239696.61545.4b

    View details for Web of Science ID 000240938700021

    View details for PubMedID 16931782

  • Outcomes of surgery for resection of regions of symptomatic radiation injury after stereotactic radiosurgery for arteriovenous malformations NEUROSURGERY Massengale, J. L., Levy, R. P., Marcellus, M., Moes, G., Marks, M. P., Steinberg, G. K. 2006; 59 (3): 553-559


    Although radiation injury after stereotactic radiosurgery (SRS), including radiation necrosis (RN), is often treated with surgical resection, detailed outcome data are lacking after resection of symptomatic radiation-injured regions with imaging characteristics suspicious for RN after SRS for arteriovenous malformations (AVM). We present outcomes in seven such patients.We conducted a retrospective chart review of seven patients with AVMs of Spetzler-Martin Grades II (n = 1), III (n = 2), and IV (n = 4) who underwent helium ion, proton beam, or gamma knife SRS and required resection of RN-suspicious tissue 1 to 24 months after post-SRS symptom onset. Postoperative outcomes included Karnofsky Performance Scale (KPS) score and time to symptomatic improvement.Symptomatic improvement required at least 9 months in the three patients with large regions suspicious for RN (>or=4 cm), whereas of four patients with smaller regions (<4 cm), three showed improvement within 2 months (P < 0.05). The remaining patient, who showed no benefit, underwent resection 2 years after the onset of RN symptoms (compared with

    View details for DOI 10.1227/01.NEU.0000227476.95859.F1

    View details for Web of Science ID 000240623900013

    View details for PubMedID 16955037

  • Rates of delayed rebleeding from intracranial aneurysms are low after surgical and endovascular treatment STROKE Johnston, S. C., Dowd, C. F., Lawton, M. T., Gress, D. R., Higashida, R. T., Halbach, V. V., Zhao, S., Katsura, K. H., Fong, K. J., Douglas, V. C., Ventura, R., Elkins, J. S., Nguyen-Huynh, M. N., McDougall, C. G., Spetzler, R. F., Zabramski, J. M., Jahnke, H. K., Piepgras, D. G., Nichols, D. A., Gravenhof, D. R., Herzig, D., Mawad, M. E., Meyer, D., Steinberg, G. K., Marks, M. P., Luu, D., Yi, H., Duckwiler, G. R., Martin, N. A., Adapon, H., Giannotta, S. L., Larsen, D. W., Teitelbaum, G. P., Fishback, D., Thomson, E., Samson, D. S., Purdy, P. D., Replogle, R. E., Thomas, J. 2006; 37 (6): 1437-1442


    Although results of the randomized International Subarachnoid Aneurysm Trial suggested that coil embolization was superior to surgical clipping 1 year after treatment, a paucity of data on long-term outcomes has been a major concern.In an ambidirectional cohort study, 9 institutions with expertise in intracranial aneurysm treatment identified all ruptured saccular aneurysms treated 1996 to 1998. After an initial medical record review, all patients meeting entry criteria were contacted by postal questionnaire or telephone. Possible reruptures were adjudicated independently by a neurologist, a neurosurgeon, and a neurointerventional radiologist. Rates of delayed (>1 year) and early rerupture and retreatment were evaluated using Kaplan-Meier survival analysis and the log-rank test.A total of 1010 patients (711 surgically clipped, 299 treated with coil embolization) were included. Patients treated with coil embolization were older, more likely to have smaller aneurysms arising from the posterior circulation, and less likely to have middle cerebral artery aneurysms. Rerupture of the index aneurysm after 1 year occurred in 1 patient treated with coil embolization during 904 person-years of follow-up (annual rate 0.11%) and in no patients treated with surgical clipping during 2666 person-years (P=0.11). Aneurysm retreatment after 1 year was more frequent in patients treated with coil embolization (P<0.0001), but major complications were rare during retreatment.Rerupture of aneurysms treated by either coil embolization or surgical clipping is rare after the first year. Late retreatment is more common after coil embolization than after clipping but complication rates are low. Thus, late events are unlikely to overwhelm differences between procedures at 1-year follow-up.

    View details for DOI 10.1161/01.STR.0000221331.01830.ce

    View details for Web of Science ID 000237925000029

    View details for PubMedID 16627789

  • Angioplasty for symptomatic intracranial stenosis - Clinical outcome STROKE Marks, M. P., Wojak, J. C., Al-Ali, F., Jayaraman, M., Marcellus, M. L., Connors, J. J., Do, H. M. 2006; 37 (4): 1016-1020


    Medical treatment of symptomatic intracranial stenosis carries a high risk of stroke. This study was done to evaluate the clinical and angiographic outcomes after intracranial angioplasty for this disease.A total of 120 patients with 124 intracranial stenoses were treated by primary angioplasty. All patients had neurologic symptoms (stroke or transient ischemic attack) attributable to intracranial stenoses > or =50%. Angiograms were evaluated before and after angioplasty for the degree of stenosis.Pretreatment stenoses varied from 50% to 95% (mean 82.2+/-10.2). Post-treatment stenoses varied from 0% to 90% (mean 36.0+/-20.1). There were 3 strokes and 4 deaths (all neurological) within 30 days of the procedure, giving a combined periprocedural stroke and death rate of 5.8%. A total of 116 patients (96.7%) were available for a mean follow-up time of 42.3 months. There were 6 patients who had a stroke in the territory of treatment and 5 additional patients with stroke in other territories. Ten deaths occurred during the follow-up period, none of which were neurological. Including the periprocedural stroke and deaths, this yielded an annual stroke rate of 3.2% in the territory of treatment and a 4.4% annual rate for all strokes.Intracranial angioplasty can be performed with a high degree of technical success and a low risk of complications. Long-term clinical follow-up of intracranial angioplasty patients demonstrates a risk of future strokes that compares favorably to patients receiving medical therapy.

    View details for DOI 10.1161/01.STR.0000206142.03677.c2

    View details for Web of Science ID 000236292100022

    View details for PubMedID 16497979

  • MRI characteristics of cerebral air embolism from a venous source NEUROLOGY Caulfield, A. F., Lansberg, M. G., Marks, M. P., Albers, G. W., Wijman, C. A. 2006; 66 (6): 945-946

    View details for Web of Science ID 000236292300037

    View details for PubMedID 16567722

  • Progression of unilateral Moyamoya disease: A clinical series CEREBROVASCULAR DISEASES Kelly, M. E., Bell-Stephens, T. E., Marks, M. P., Do, H. M., Steinberg, G. K. 2006; 22 (2-3): 109-115


    The natural history of unilateral moyamoya disease (MMD) in adult patients is not clearly described in the literature. We present a series of 18 patients with unilateral MMD and analyze the risk factors for progression to bilateral disease.A retrospective review of 157 MMD patients treated at Stanford University Medical Center from 1991 to 2005 identified 28 patients with unilateral MMD (defined as none, equivocal or mild involvement on the contralateral side).Eighteen patients (5 males and 13 females) were identified with unilateral MMD and angiographic follow-up of > or =5 months. Mean radiologic follow-up (+/- standard error of the mean) was 19.3 +/- 3.4 months and mean clinical follow-up was 24.5 +/- 3.7 months. Five patients had childhood onset MMD and 13 patients had adult onset disease. Angiographic progression from unilateral to bilateral disease was seen in 7 patients (38.9%) at a mean follow-up of 12.7 +/- 2.4 months. Four of the 7 patients had significant clinical and radiologic progression requiring surgical intervention. Five of 7 patients that progressed had adult onset MMD. The presence of equivocal or mild stenotic changes of the contralateral anterior cerebral artery (ACA), middle cerebral artery (MCA) or internal carotid artery (ICA) was an important predictor of progression (p < 0.01); 6 of 8 patients (75%) with equivocal or mild contralateral disease progressed, whereas only 1 of 10 patients (10.0%) with no initial contralateral disease progressed to bilateral MMD. One patient had mild or equivocal MCA, ICA and ACA stenosis at the time of initial diagnosis and this patient progressed.Contralateral progression in the adult form occurs more commonly than previously reported. The presence of minor changes in the contralateral ACA, intracranial ICA and MCA is an important predictor of increased risk of progression. Patients with a completely normal angiogram on the contralateral side have a very low risk of progression.

    View details for DOI 10.1159/000093238

    View details for Web of Science ID 000243591900005

    View details for PubMedID 16685122

  • Mechanical thrombectomy following intravenous thrombolysis in the treatment of acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Fields, J. D., Albers, G. W., Jayaraman, M. V., Do, H. M., Marks, M. P. 2005; 62 (11): 1763-1765


    The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment.To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study.Case studies at a university hospital.Patients treated with intravenous thrombolytics within 3 hours of symptom onset subsequently underwent computed tomographic angiography. If an occlusion of a proximal cerebral vessel was shown by a computed tomographic angiogram, mechanical thrombectomy was performed. Patients were observed for 1 month after treatment.National Institutes of Health Stroke Scale (NIHSS) score.The computed tomographic angiography of 2 patients showed complete occlusion of the M1 branch of the middle cerebral artery following administration of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases, blood flow through the occluded artery was restored with mechanical thrombectomy and dramatic neurologic improvement occurred. There were no complications. The NIHSS scores were 0 and 2 at 1-month follow-up.Treatment with intravenous thrombolytics followed by mechanical thrombectomy may improve outcomes in acute stroke patients and a pilot safety trial is warranted.

    View details for Web of Science ID 000233250900017

    View details for PubMedID 16286552

  • Clinical importance of microbleeds in patients receiving IV thrombolysis NEUROLOGY Kakuda, W., Thijs, V. N., Lansberg, M. G., Bammer, R., Wechsler, L., Kemp, S., Moseley, M. E., Marks, M. P., Albers, G. W. 2005; 65 (8): 1175-1178


    Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA).The authors prospectively evaluated patients with acute ischemic stroke treated with IV tPA between 3 and 6 hours of symptom onset. MRI scans, including GRE imaging, were performed prior to tPA treatment, 3 to 6 hours after treatment and at day 30. The authors compared the frequency of hemorrhagic complications after thrombolysis in patients with and without MBs on their baseline GRE imaging.Seventy consecutive patients (mean age, 71 +/- 29 years; 31 men, 39 women) were included. MBs were identified in 11 patients (15.7%) on baseline GRE imaging. There was no significant difference in the frequency of either symptomatic or asymptomatic hemorrhagic complications after thrombolysis between patients with and without MBs at baseline. None of the 11 patients with MBs (0%) at baseline had a symptomatic intracerebral hemorrhage compared with 7 of 59 patients who did not have baseline MBs (11.9%). In addition, no patients with baseline MBs had asymptomatic hemorrhagic transformation observed at the site of any pre-treatment MB.The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset.

    View details for Web of Science ID 000232813600008

    View details for PubMedID 16247042

  • Visual field preservation after curative multi-modality treatment of occipital lobe artemovenous malformations NEUROSURGERY Sinclair, J., Marks, M. P., Levy, R. P., Adler, J. R., Chang, S. D., Lopez, J. R., Do, H. M., Bell-Stephens, T. E., Lim, M., Steinberg, G. K. 2005; 57 (4): 655-666


    Occipital lobe arteriovenous malformations (AVMs) provide challenging management decisions because of their proximity to the visual cortex and optic radiations. Preservation of visual function throughout treatment is the mainstay of therapeutic planning. We reviewed visual field (VF) outcomes of all patients who received curative treatment for occipital AVMs at Stanford University to evaluate the efficacy of different treatment strategies.We conducted a retrospective review of 55 patients with occipital AVMs treated at Stanford University between 1984 and 2003. Clinical presentation, AVM morphology, and treatment modality were correlated with VF function before and after therapeutic intervention.Of 55 patients, 48 (87.3%) underwent multimodality AVM treatment (7 patients < 3 yr from radiosurgery were excluded from final analysis). One patient died from intracerebral hemorrhage 11 months post-radiosurgery, and five patients deferred further treatment. Forty-two patients (87.5%) were cured, with no residual AVM on final angiography. Curative therapeutic modalities used included embolization alone (2 patients), microsurgery alone (6 patients), microsurgery with radiosurgery (1 patient), microsurgery with embolization (23 patients), radiosurgery with embolization (4 patients), and embolization with radiosurgery and microsurgery (6 patients). Mean follow-up was 5.8 years including treatment. VF follow-up was available in all 42 patients. Twenty-eight (66.7%) patients experienced no change in VFs, six (14.3%) patients with previously abnormal VFs improved, and eight (19.0%) patients showed worsening of VFs (although none developed a new homonymous VF deficit). Duration of treatment was related to VF outcome in patients who presented without a history of AVM-related hemorrhage.Occipital AVMs can be safely cured using multimodality strategies with minimal risk to visual function despite the proximity of these lesions to the visual cortex and associated pathways.

    View details for DOI 10.1227/01.NEU.0000175547.05291.85

    View details for Web of Science ID 000236681500018

    View details for PubMedID 16239877

  • Prospective analysis of clinical outcomes after percutaneous vertebroplasty for painful osteoporotic vertebral body fractures AMERICAN JOURNAL OF NEURORADIOLOGY Do, H. M., Kim, B. S., Marcellus, M. L., CURTIS, L., Marks, M. P. 2005; 26 (7): 1623-1628


    Previous studies have retrospectively reported the positive effects of percutaneous vertebroplasty. The purpose of our study was to evaluate prospectively the effects of vertebroplasty on mobility, analgesic use, pain, and SF-36 (short-form 36-item) scales for patients with painful vertebral compression fractures that are refractory to medical therapy.We prospectively followed 167 patients who received 207 vertebroplasty treatment sessions for stabilization of 264 symptomatic vertebral compression fractures between August 1999 and January 2003. The average age of patients was 74.6 years (SD = 12.2 years), and 76% were women. Pre- and postprocedural measurements of pain, mobility, analgesic use, and SF-36 scales were compared at 1 month after the procedure and between 6 months and 3 years after the procedure with the SF-36 scales.Respective pre- and post-treatment pain scores were 8.71 (SE = 0.1) and 2.77 (SE = 0.18; P < .00001). Respective pre- and post-treatment analgesic use scores were 2.93 (SE = 0.9) and 1.64 (SE = 0.09; P < .00001). Respective pre- and post-treatment activity levels were 2.66 (SE = 0.1) and 1.64 (SE = 0.11; P < .00001). There was a statistically significant improvement on nine of 10 SF-36 scales (P < .001) after 1 month and on eight of 10 SF-36 scales (P < .02) at long-term follow-up.Percutaneous vertebroplasty offers statistically significant benefits in decreasing pain, decreasing use of analgesics, and increasing mobility in appropriately selected patients. Percutaneous vertebroplasty also offers a statistically significant benefit in most SF-36 scales at both short- and long-term follow-up.

    View details for Web of Science ID 000231182800004

    View details for PubMedID 16091504

  • Neurotransplantation for patients with subcortical motor stroke: a Phase 2 randomized trial JOURNAL OF NEUROSURGERY Kondziolka, D., Steinberg, G. K., Wechsler, L., Meltzer, C. C., Elder, E., Gebel, J., DeCesare, S., Jovin, T., Zafonte, R., Lebowitz, J., Flickinger, J. C., Tong, D., Marks, M. P., Jamieson, C., Luu, D., Bell-Stephens, T., Teraoka, J. 2005; 103 (1): 38-45


    No definitive treatment exists to restore lost brain function following a stroke. Transplantation of cultured neuronal cells has been shown to be safe and effective in animal models of stroke and safe in a Phase 1 human trial. In the present study the authors tested the usefulness of human neuron transplantation followed by participation in a 2-month stroke rehabilitation program compared with rehabilitation alone in patients with substantial fixed motor deficits associated with a basal ganglia stroke.Human neuronal cells (LBS-Neurons; Layton BioScience, Inc.) were delivered frozen and then thawed and formulated on the morning of surgery. The entry criteria in this randomized, observer-blinded trial of 18 patients included age between 18 and 75 years, completed stroke duration of 1 to 6 years, presence of a fixed motor deficit that was stable for at least 2 months, and no contraindications to stereotactic surgery. Patients were randomized at two centers to receive either 5 or 10 million implanted cells in 25 sites (seven patients per group) followed by participation in a stroke rehabilitation program, or to serve as a nonsurgical control group (rehabilitation only; four patients). The surgical techniques used were the same at both centers. All patients underwent extensive pre- and postoperative motor testing and imaging. Patients received cyclosporine A for 1 week before and 6 months after surgery. The primary efficacy measure was a change in the European Stroke Scale (ESS) motor score at 6 months. Secondary outcomes included Fugl-Meyer, Action Research Arm Test, and Stroke Impact Scale scores, as well as the results of other motor tests. Nine strokes were ischemic in origin and nine were hemorrhagic. All 14 patients who underwent surgery (ages 40-70 years) underwent uncomplicated surgeries. Serial evaluations (maximum duration 24 months) demonstrated no cell-related adverse serological or imaging-defined effects. One patient suffered a single seizure, another had a syncopal event, and in another there was burr-hole drainage of an asymptomatic chronic subdural hematoma. Four of seven patients who received 5 million cells (mean improvement 6.9 points) and two of seven who received 10 million cells had improved ESS scores at 6 months; however, there was no significant change in the ESS motor score in patients who received cell implants (p = 0.756) compared with control or baseline values (p = 0.06). Compared with baseline, wrist movement and hand movement scores recorded on the Fugl-Meyer Stroke Assessment instrument were not improved (p = 0.06). The Action Research Arm Test gross hand-movement scores improved compared with control (p = 0.017) and baseline (p = 0.001) values. On the Stroke Impact Scale, the 6-month daily activities score changed compared with baseline (p = 0.045) but not control (p = 0.056) scores, and the Everyday Memory test score improved in comparison with baseline (p = 0.004) values.Human neuronal cells can be produced in culture and implanted stereotactically into the brains of patients with motor deficits due to stroke. Although a measurable improvement was noted in some patients and this translated into improved activities of daily living in some patients as well, this study did not find evidence of a significant benefit in motor function as determined by the primary outcome measure. This experimental trial indicates the safety and feasibility of neuron transplantation for patients with motor stroke.

    View details for Web of Science ID 000231000200011

    View details for PubMedID 16121971

  • Safety and efficacy of mechanical embolectomy in acute ischemic stroke - Results of the MERCI trial STROKE Smith, W. S., Sung, G., Starkman, S., Saver, J. L., Kidwell, C. S., Gobin, Y. P., Lutsep, H. L., Nesbit, G. M., Grobelny, T., Rymer, M. M., Silverman, I. E., Higashida, R. T., Budzik, R. F., Marks, M. P. 2005; 36 (7): 1432-1438


    The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA.We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients.Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score < or =2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01).A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.

    View details for DOI 10.1161/01.STR.0000171066.25248.1d

    View details for Web of Science ID 000230190600021

    View details for PubMedID 15961709

  • Mechanical thrombectomy for acute stroke AMERICAN JOURNAL OF NEURORADIOLOGY Versnick, E. J., Do, H. M., Albers, G. W., Tong, D. C., Marks, M. P. 2005; 26 (4): 875-879


    We evaluated a mechanical thrombectomy protocol to treat acute stroke and report the angiographic results and clinical outcomes.Patients with anterior circulation strokes <8 hours and posterior circulation strokes <12 hours were treated at a single center over 10 months. Patients were excluded if they were candidates for intravenous tissue plasminogen activator (tPA). Treatment involved one of two mechanical thrombectomy devices. Retrieval was augmented by low-dose intra-arterial tPA if needed. Outcome was measured by using the Modified Rankin score.Ten patients were treated: five with anterior circulation strokes, four with posterior circulation strokes, and one with embolic strokes involving both circulations. Mean National Institutes of Health Stroke Scale score at presentation was 24.6 +/- 10.9. In eight patients (80%), revascularization was successful (Thrombolysis in Acute Myocardial Infarction score, 3). Mean time from symptom onset to initiation of the procedure was 6 hours (5.3 hours for anterior circulation and 7.0 hours for posterior circulation). Mean time for recanalization from the start of the procedure was 1.17 +/- 0.58 hours for the six anterior circulation strokes and 2.75 +/- 1.34 hours in the two posterior circulation strokes. Five patients died within 48 hours; all had posterior circulation strokes. Mean Modified Rankin score at 90 days was 1.4.In this small series, mechanical thrombectomy of acute stroke appeared to improve recanalization rates compared with intra-arterial thrombolysis. No hemorrhagic complications occurred. Further study is required to determine the role of these techniques.

    View details for Web of Science ID 000228273400036

    View details for PubMedID 15814937

  • Intracranial Angioplasty without stenting for symptomatic atherosclerotic stenosis: Long-term follow-up AMERICAN JOURNAL OF NEURORADIOLOGY Marks, M. P., Marcellus, M. L., Do, H. M., Schraedley-Desmond, P. K., Steinberg, G. K., Tong, D. C., Albers, G. W. 2005; 26 (3): 525-530


    Angioplasty and stent placement have been reported for the treatment of intracranial stenosis. This study was undertaken to assess the efficacy and long-term clinical outcome of angioplasty without stent placement for patients with symptomatic intracranial stenosis.A retrospective study was done to evaluate 36 patients with 37 symptomatic atherosclerotic intracranial stenosis who underwent primary balloon angioplasty. All patients had symptoms despite medical therapy. Thirty-four patients were available for follow-up ranging from 6 to 128 months. Mean follow-up was 52.9 months.Mean pretreatment stenosis was 84.2% before angioplasty and 43.3% after angioplasty. The periprocedural death and stroke rate was 8.3% (two deaths and one minor stroke). Two patients had strokes in the territory of angioplasty at 2 and 37 months after angioplasty. The annual stroke rate in the territory appropriate to the site of angioplasty was 3.36%, and for those patients with a residual stenosis of > or =50% it was 4.5%. Patients with iatrogenic dissection (n=11) did not have transient ischemic attacks or strokes after treatment.Results of long-term follow-up suggest that intracranial angioplasty without stent placement reduces the risk of further stroke in symptomatic patients.

    View details for Web of Science ID 000227628500016

    View details for PubMedID 15760860

  • Revascularization of the posterior circulation SKULL BASE-AN INTERDISCIPLINARY APPROACH Coert, B. A., Chang, S. D., Marks, M. P., Steinberg, G. K. 2005; 15 (1): 43-62


    The primary objective of revascularization procedures in the posterior circulation is the prevention of vertebrobasilar ischemic stroke. Specific anatomical and neurophysiologic characteristics such as posterior communicating artery size affect the susceptibility to ischemia. Current indications for revascularization include symptomatic vertebrobasilar ischemia refractory to medical therapy and ischemia caused by parent vessel occlusion as treatment for complex aneurysms. Treatment options include endovascular angioplasty and stenting, surgical endarterectomy, arterial reimplantation, extracranial-to-intracranial anastomosis, and indirect bypasses. Pretreatment studies including cerebral blood flow measurements with assessment of hemodynamic reserve can affect treatment decisions. Careful blood pressure regulation, neurophysiologic monitoring, and neuroprotective measures such as mild brain hypothermia can help minimize the risks of intervention. Microscope, microinstruments and intraoperative Doppler are routinely used. The superficial temporal artery, occipital artery, and external carotid artery can be used to augment blood flow to the superior cerebellar artery, posterior cerebral artery, posterior inferior cerebellar artery, or anterior inferior cerebellar artery. Interposition venous or arterial grafts can be used to increase length. Several published series report improvement or relief of symptoms in 60 to 100% of patients with a reduction of risk of future stroke and low complication rates.

    View details for Web of Science ID 000227387600005

    View details for PubMedID 16148983

  • Diffusion-weighted MR imaging in acute ischemia: Value of apparent diffusion coefficient and signal intensity thresholds in predicting tissue at risk and final infarct size AMERICAN JOURNAL OF NEURORADIOLOGY Na, D. G., Thijs, V. N., Albers, G. W., Moseley, M. E., Marks, M. P. 2004; 25 (8): 1331-1336


    Identifying tissue at risk for infarction is an important goal of stroke imaging. This study was performed to determine whether pixel-based apparent diffusion coefficient (ADC) and signal intensity ratio are helpful diffusion-weighted (DW) imaging metrics to predict tissue at risk for infarction.Twelve patients presenting with acute hemispheric strokes underwent DW imaging within 7 hours of symptom onset. Region of interest (ROI), pixel-based ADC, and signal intensity analyses were performed at initial DW imaging to assess area of infarct growth, final infarct area, and normal tissue.Pixel-based analysis was less accurate than ROI-based analysis for evaluating infarct growth or final infarct with ADC, ADC ratio, and signal intensity ratios. In pixel-based analysis, signal intensity ratios were better than ADCs or ADC ratios for identifying tissue at risk (accuracy, 67.4%) and for predicting final infarct (accuracy, 79.9%). Linear regression analysis demonstrated a strong correlation between lesion volume on quantitative DW images or ADC maps and final infarct volume (P < .001). When receiver operating characteristic (ROC) curves were used to determine optimal cutoffs for ADC and DW image values, the region of infarct growth was significantly correlated with only the mismatch between initial qualitative DW image and quantitative DW image signal intensity ratio (cutoff value, 1.19; R = 0.652; P = .022).Pixel-based thresholds applied to ADC or DW image signal intensity maps were not accurate prognostic measures of tissue at risk. Quantitative DW images or ADC maps may provide added information not obtained by visual inspection of the qualitative DW image map.

    View details for Web of Science ID 000224110000006

    View details for PubMedID 15466327

  • Alteration in the venous drainage of a dural arteriovenous fistula following angioplasty AMERICAN JOURNAL OF NEURORADIOLOGY Gutierrez, A., Do, H. M., Marks, M. P. 2004; 25 (6): 1086-1088


    The pattern of venous drainage from a dural arteriovenous fistula (DAVF) has been shown to affect the natural history of these lesions. Angioplasty and stent placement of the dural sinuses have been described to improve outflow in venous hypertensive states and may improve the venous drainage pattern from a DAVF. We report the case of a patient with a benign but stenosed type IIa transverse sinus DAVF who underwent angioplasty to improve venous outflow. This resulted in conversion of the DAVF to a more malignant type IIb drainage pattern with reflux into the cortical venous system.

    View details for Web of Science ID 000222067600035

    View details for PubMedID 15205154

  • Association of early CT abnormalities, infarct size, and apparent diffusion coefficient reduction in acute ischemic stroke 27th International Stroke Conference Somford, D. M., Marks, M. P., Thijs, V. N., Tong, D. C. AMER SOC NEURORADIOLOGY. 2004: 933–38


    Diffusion-weighted (DW) imaging is more sensitive for early ischemia than CT, and apparent diffusion coefficient (ADC) mapping permits quantification of the severity of cytotoxic edema. We examined the relationship between early CT findings, ischemic lesion volume on DW images, and edema subtype.Patients in whom early signs of ischemia were detected on baseline CT scans were scored CT positive. Baseline DW lesion volumes were compared between the CT-positive and CT-negative patients. In CT-positive patients, we outlined the CT-positive part of the DW lesion and transferred these regions of interest to the corresponding DW sections. The ADC values of the outlined CT-positive areas were then compared with the ADC values of the CT-negative areas within patients. Lesions with significantly increased T2 hyperintensity were excluded to correct for the effect of early vasogenic edema on ADC measurements.Twenty-four patients with cerebral ischemia in whom both CT and DW imaging were performed within 8 hours of symptom onset were entered into the study. Patients with early CT signs of infarction (n = 12) had significantly larger DW lesion volumes than did patients without early CT abnormalities (mean volume, 62.8 versus 14.6 mL; P =. 002). In patients displaying early CT abnormalities, CT-positive regions of the DW lesion had lower relative ADC (rADC) values than did the CT-negative regions, when lesions with significant T2 hyperintensity were excluded (mean rADC, 0.65 versus 0.75; P =.037).These findings support the hypothesis that early CT signs of infarction indicate more extensive and severe cerebral ischemia, as reflected by lower ADC.

    View details for Web of Science ID 000222067600007

    View details for PubMedID 15205126

  • Neurophysiological monitoring in the endovascular therapy of aneurysms AMERICAN JOURNAL OF NEURORADIOLOGY Liu, A. Y., Lopez, J. R., Do, H. M., Steinberg, G. K., Cockroft, K., Marks, M. P. 2003; 24 (8): 1520-1527


    Endovascular aneurysm therapy has associated risks of ischemic complications. We undertook this study to evaluate the efficacy of neurophysiological monitoring (NPM) techniques in the detection of ischemic changes that may be seen during endovascular treatment of cerebral aneurysms.Thirty-five patients underwent NPM during endovascular treatment of cerebral aneurysms. The patients underwent a total of 50 endovascular procedures, including balloon test occlusion (19 patients), GDC embolization (22 patients), and permanent vessel occlusion (nine patients). NPM included electroencephalography, somatosensory evoked potentials, and/or brain stem auditory evoked potentials, depending on the location of the aneurysm.NPM changes were seen in nine (26%) of 35 patients and altered the management in five (14%) of 35 patients. In three of the five cases, NPM changes were observed without corresponding neurologic physical examination changes after balloon test occlusion (performed while the patients were under general anesthesia in two cases). In the two other cases in which NPM changes altered management, ischemia was detected at the time of intra-aneurysmal therapy while the patients were under general anesthesia. Overall, 18 of 35 patients underwent a total of 19 balloon test occlusion procedures. Of the 17 remaining patients, 13 underwent aneurysm coiling, two were not treated because of inability to safely place coils, and two were treated for distal aneurysms. Two patients developed transient neurologic deficits without concurrent NPM changes, representing false-negative NPM test results.NPM is a valuable adjunct to endovascular treatment of cerebral aneurysms. Our study suggests that these monitoring techniques may reduce ischemic complications and can be used to help guide therapeutic decisions.

    View details for Web of Science ID 000185400100007

    View details for PubMedID 13679263

  • Parent vessel occlusion for vertebrobasilar fusiform and dissecting aneurysms AMERICAN JOURNAL OF NEURORADIOLOGY Leibowitz, R., Do, H. M., Marcellus, M. L., Chang, S. D., Steinberg, G. K., Marks, M. P. 2003; 24 (5): 902-907


    Previous reports of outcome with permanent vessel occlusion (PVO) for large, giant, or fusiform aneurysms in the posterior circulation have been limited. We undertook this study to evaluate the perioperative (within 30 days) and follow-up outcomes for patients treated with permanent occlusion of the vertebral artery for vertebrobasilar fusiform and dissecting aneurysms.Thirteen consecutive patients were studied. Two groups were defined for the study. Group I patients underwent PVO to achieve complete thrombosis of the aneurysm. Group II patients underwent PVO to reduce flow to the aneurysm where complete thrombosis was not desirable. Modified Rankin scores were obtained at presentation and at follow-up (follow-up range, 1-76 months; mean, 22.0 months).All group I aneurysms were shown to be thrombosed on the angiograms obtained at the immediate follow-up examinations. Improvement in outcome scores was achieved by all group I patients. Improvement in Rankin scores after endovascular treatment was statistically significant (P =.026). All group II patients had complete occlusion of the vertebral artery; however, continued filling of the fusiform aneurysm was still observed. Four patients in group II died during the follow-up period. Two of these deaths were attributable to the aneurysms. Of the remaining three patients, two experienced clinical worsening and one remained stable.In this series, PVO for chronic fusiform and acute dissecting aneurysms of the vertebrobasilar system proved to be a useful therapeutic endovascular technique. Long-term outcomes suggest that patients with aneurysms involving only one vertebral artery, where complete thrombosis can be achieved, have better clinical outcomes than those who have aneurysms involving the basilar artery or both vertebral arteries, where complete thrombosis cannot achieved by using PVO.

    View details for Web of Science ID 000183021100024

    View details for PubMedID 12748092

  • Deep arteriovenous malformations of the basal ganglia and thalamus: natural history JOURNAL OF NEUROSURGERY Fleetwood, I. G., Marcellus, M. L., Levy, R. P., Marks, M. P., Steinberg, G. K. 2003; 98 (4): 747-750


    Patients with arteriovenous malformations (AVMs) in a deep location and with deep venous drainage are thought to be at higher risk for hemorrhage than those with AVMs in other locations. Despite this, the natural history of AVMs of the basal ganglia and thalamus has not been well studied.The authors retrospectively evaluated a cohort of 96 patients with AVMs in the basal ganglia and thalamus with respect to the tendency of these lesions to hemorrhage between the time of detection and their eventual successful management. The 96 patients studied had a mean age of 22.7 years at diagnosis, and 51% were male. Intracranial hemorrhage (ICH) was the event leading to clinical detection in 69 patients (71.9%), and 85.5% of these patients were left with hemiparesis. After diagnosis, 25 patients bled a total of 49 times. The cumulative clinical follow up after detection but before surgical management was 500.2 patient-years. The risk of hemorrhage after detection of an AVM of the basal ganglia or thalamus was 9.8% per patient-year.The rate of ICH in patients with AVMs of the basal ganglia or thalamus (9.8%/year) is much higher than the rate in patients with AVMs in other locations (2-4%/year). The risk of incurring a neurological deficit with each hemorrhagic event is high. Treatment of these patients at specialized centers is recommended to prevent neurological injury from a spontaneous ICH.

    View details for Web of Science ID 000181922400006

    View details for PubMedID 12691399

  • Aneurysmal subarachnoid hemorrhage in patient's with Hunt and Hess grade 4 or 5: Treatment using the Guglielmi detachable coil system AMERICAN JOURNAL OF NEURORADIOLOGY Weir, R. U., Marcellus, M. L., Do, H. M., Steinberg, G. K., Marks, M. P. 2003; 24 (4): 585-590


    Patients in poor clinical condition (Hunt and Hess grade 4 or 5) after subarachnoid hemorrhage (SAH) have historically fared poorly and many often were excluded from aggressive treatment. Early aggressive surgical treatment of SAH can produce good-quality survival for a higher percentage of patients than previously reported. We assessed the outcome of patients with Hunt and Hess grade 4 or 5 who were treated with Guglielmi detachable coil (GDC) embolization.We retrospectively evaluated the records of 27 consecutive grade 4 and 5 patients with 29 aneurysms treated within 72 hours of SAH by using GDCs. Percentage aneurysm occlusion after embolization, perioperative complications, and symptoms of vasospasm were evaluated. Outcome was assessed with the Glasgow Outcome Scale.Sixteen patients (59%) were grade 4, and 11 (41%) were grade 5. Eighteen (67%) had one aneurysm, six (22%) had two aneurysms, and three (11%) had three aneurysms. Twenty-nine aneurysms were treated. Fourteen (48%) were completely occluded, and four (14%) were nearly completely occluded (>/=95% occlusion) at embolization. Eleven aneurysms (38%) had partial coiling (<95% occlusion). In the 27 patients, one technical (4%) and one clinical (4%) complication occurred at embolization. No rehemorrhage occurred in any patients (follow-up, 6-44 months; mean, 23 months). Twenty-five (92%) had vasospasm, and seven required endovascular treatment because of worsening clinical status. Sixteen patients (59%) died within 30 days of SAH. Eight patients (30%) had a good clinical outcome at a mean follow-up of 23 months.Patients with Hunt and Hess grade 4 or 5 after SAH can undergo successful coil embolization of the aneurysms despite their poor medical condition and a high frequency of vasospasm at the time of treatment. Morbidity and mortality rates with this disease are still high. These findings compare favorably with those published in surgical series for aggressively treated patients with Hunt and Hess grade 4 or 5.

    View details for Web of Science ID 000182422900008

    View details for PubMedID 12695185

  • N-butyl cyanoacrylate embolization of cerebral arteriovenous malformations: Results of a prospective, randomized, multi-center trial AMERICAN JOURNAL OF NEURORADIOLOGY Purdy, P., Horowitz, M., Kopitnik, T., Samson, D., Dion, J., Joseph, G., Dawson, R., Owens, D., Barrow, D., Barr, J., Powers, S., Cockroft, K., Holmes, B., Sumas, M., Wallace, R., Masaryk, T., Perl, J., Chyatte, D., Tomsick, T., Tew, J. M., van Loveren, H., Zuccarello, M., Marks, M., Norbash, A., Steinberg, G., Halbach, V., Higashida, R., Dowd, C., Lawton, M., Wilson, C., McDougall, C., Spetzler, R., Nesbit, G., Barnwell, S., Nichols, D., Thielen, K., Atkinson, J., Meyer, F., Piepgras, D., Choi, I. S., Day, J. D., Berenstein, A., Setton, A., Pryor, J., Niimi, Y., Flamm, E., DeNardo, A., Scott, J., Murtagh, F. R. 2002; 23 (5): 748-755


    Liquid N-butyl cyanoacrylate (n-BCA) use for the treatment of arteriovenous malformations (AVM) in the brain has become part of medical practice. However, no study has led to the Food and Drug Administration's approval of n-BCA for intravascular use. The purpose of this study was to verify the effectiveness and safety of an n-BCA/Tantalum Powder/Ethiodized Oil mixture, compared with conventional treatment (Trufill polyvinyl alcohol [PVA]) for preoperative embolization of cerebral AVM.Between October 15, 1996, and March 24, 1999, 104 patients at 13 centers were prospectively randomized to undergo embolization using an n-BCA/Tantalum Powder/Ethiodol mixture or Trufill PVA. The pre-embolization therapy goals were determined in terms of the number of pedicles to be embolized and the percent of nidus reduction expected. Embolization results were evaluated by a central laboratory. Subsequent surgical resection data were recorded. Safety evaluation data included recording device complications, procedure complications, and intracranial events/overall neurologic outcomes, which could be either device-related, procedure-related, or both.The reduction of AVM dimensions (79.4% in the n-BCA group and 86.9% in the PVA group) and the mean number of vessels embolized (2.2 in the n-BCA group and 2.1 in the PVA group) was similar in the two groups. Coils were used more commonly with PVA embolization (P<.0001). No differences were detected in surgical resection time, number of patients who required transfusion, volume and number of transfusion units, or type and volume of fluid replacement. Glasgow Outcome Scale scores were not significantly different between the two groups before treatment, after embolization, or after resection. Two of 42 patients who underwent resection and had been treated with n-BCA experienced post-resection hematoma, compared with eight of 45 patients who underwent resection and had been treated with PVA (P<.05).This prospective, randomized trial showed that n-BCA is equivalent to PVA as a preoperative embolic agent for treatment of cerebral AVM as determined by percent of nidus reduction and number of feeding pedicles embolized.

    View details for Web of Science ID 000175599300003

    View details for PubMedID 12006271

  • The role of radiosurgery in the treatment of giant arteriovenous malformations 5th Meeting of the International-Stereotactic-Radiosurgery-Society Chang, S. D., Levy, R. P., Marks, M. P., Marcellus, M., Steinberg, G. K. KARGER. 2002: 42–53
  • Relationship between severity of MR perfusion deficit and DWI lesion evolution NEUROLOGY Thijs, V. N., Adami, A., Neumann-Haefelin, T., Moseley, M. E., Marks, M. P., Albers, G. W. 2001; 57 (7): 1205-1211


    To assess whether a quantitative analysis of the severity of the early perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that can distinguish between critical and noncritical hypoperfusion.Patients with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom onset and again after 4 to 7 days. Patients with early important decreases in points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were created. These hemodynamic parameters were correlated with the degree of recruitment of the baseline PWI lesion by the DWI lesion.Twelve patients had an initial PWI > DWI mismatch of >20%. A linear relationship was observed between the initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted final infarct size.Among patients who have had an acute stroke with PWI > DWI, who do not have dramatic early clinical improvement, the degree of expansion of the initial DWI lesion correlates with the severity of the initial perfusion deficit as measured by the mean transit time and the cerebral blood volume.

    View details for Web of Science ID 000171415400010

    View details for PubMedID 11591836

  • Hyperperfusion syndrome with hemorrhage after angioplasty for middle cerebral artery stenosis AMERICAN JOURNAL OF NEURORADIOLOGY Liu, A. Y., Do, H. M., Albers, G. W., Lopez, J. R., Steinberg, G. K., Marks, M. P. 2001; 22 (8): 1597-1601


    Hyperperfusion syndrome is a well-documented complication of carotid endarterectomy, as well as internal carotid artery angioplasty and stent placement. We report a similar complication after distal intracranial (middle cerebral artery [MCA] M2 segment) angioplasty. To our knowledge, this is the first report of hyperperfusion syndrome after intracranial angioplasty of a distal MCA branch.

    View details for Web of Science ID 000171119500028

    View details for PubMedID 11559514

  • Prediction of hemorrhagic transformation following acute stroke - Role of diffusion- and perfusion-weighted magnetic resonance imaging ARCHIVES OF NEUROLOGY Tong, D. C., Adami, A., Moseley, M. E., Marks, M. P. 2001; 58 (4): 587-593


    Acute diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic resonance imaging (MRI) findings may correlate with secondary hemorrhagic transformation (HT) risk in patients with stroke. This information could be of value, particularly in individuals being considered for thrombolytic therapy.To determine the relationship between DWI and PWI findings and the risk of secondary HT in patients with acute stroke.Retrospective case series.Academic medical center.Twenty-seven patients with acute stroke capable of being evaluated with DWI/PWI 8 hours or less after symptom onset.Apparent diffusion coefficient values, perfusion delay measurements, and subsequent MRI or computed tomographic scans detected HT.The mean +/- SD apparent diffusion coefficient of ischemic regions that experienced HT was significantly lower than the overall mean +/- SD apparent diffusion coefficient of all ischemic areas analyzed (0.510 +/- 0.140 x 10(-3) mm(2)/s vs 623 +/- 0.113 x 10(-3) mm(2)/s; P =.004). This difference remained significant when comparing the HT-destined ischemic areas with the non-HT-destined areas within the same ischemic lesion (P =.02). Patients receiving recombinant tissue-type plasminogen activator (rt-PA) experienced HT significantly earlier than patients not receiving rt-PA (P =.002). Moreover, a persistent perfusion deficit in the area of subsequent hemorrhage at 3 to 6 hours after the initial MRI scan was identified in significantly more patients who experienced HT than in those who did not (83% vs 30%; P =.03).Both DWI and PWI scans detect abnormalities that are associated with HT. These findings support a role for MRI in identifying patients who are at increased risk for secondary HT following acute ischemic stroke.

    View details for Web of Science ID 000167935900008

    View details for PubMedID 11295989

  • EPAR therapy system for treatment of acute stroke: Safety study results Lutsep, H. L., Campbell, M., Clark, W. M., Jansen, O., Lefkowitz, M. A., Marks, M. P., Norbash, A., Putman, C., Schumacher, M. LIPPINCOTT WILLIAMS & WILKINS. 2001: 319–19
  • Comparison of diffusion-weighted MRI and CT in acute stroke - Reply NEUROLOGY Marks, M. P., Albers, G., Lansberg, M. 2000; 55 (11): 1760-1760
  • Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis STROKE Thijs, V. N., Lansberg, M. G., Beaulieu, C., Marks, M. P., Moseley, M. E., Albers, G. W. 2000; 31 (11): 2597-2602


    The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome.We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score >/=85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis.Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score >/=85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI.DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.

    View details for Web of Science ID 000165107100009

    View details for PubMedID 11062281

  • Relationship between apparent diffusion coefficient and subsequent hemorrhagic transformation following acute ischemic stroke STROKE Tong, D. C., Adami, A., Moseley, M. E., Marks, M. P. 2000; 31 (10): 2378-2384


    A method for identifying patients at increased risk for developing secondary hemorrhagic transformation (HT) after acute ischemic stroke could be of significant value, particularly in patients being considered for thrombolytic therapy. We hypothesized that diffusion-weighted MRI might aid in the identification of such patients.We retrospectively analyzed 17 patients with ischemic stroke who received diffusion-weighted MRI within 8 hours of symptom onset and who also received follow-up neuroimaging within 1 week of initial scan. The apparent diffusion coefficient (ADC) for each pixel in the whole ischemic area was calculated, generating a histogram of values. Areas subsequently experiencing HT were then compared with areas not experiencing HT to determine the relationship between ADC and subsequent HT.A significantly greater percentage of pixels possessed lower ADCs (40% of the pixels possessed values

    View details for Web of Science ID 000089655900016

    View details for PubMedID 11022067

  • Advantages of adding diffusion-weighted magnetic resonance imaging to conventional magnetic resonance imaging for evaluating acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Norbash, A. M., Marks, M. P., Tong, D. C., Moseley, M. E., Albers, G. W. 2000; 57 (9): 1311-1316


    Accurate localization of acute ischemic lesions in patients with an acute stroke may aid in understanding the etiology of their stroke and may improve the management of these patients.To determine the yield of adding diffusion-weighted magnetic resonance imaging (DWI) to a conventional magnetic resonance imaging (MRI) protocol for acute stroke.A prospective cohort study.A referral center.Fifty-two patients with a clinical diagnosis of acute stroke who presented within 48 hours after symptom onset were included. An MRI scan was obtained within 48 hours after symptom onset. A neuroradiologist (A.M.N.) and a stroke neurologist (G.W.A.) independently identified suspected acute ischemic lesions on MRI sequences in the following order: (1) T2-weighted and proton density-weighted images, (2) fluid-attenuated inversion recovery images, and (3) diffusion-weighted images and apparent diffusion coefficient maps.Diagnostic yield and interrater reliability for the identification of acute lesions, and confidence and conspicuity ratings of acute lesions for different MRI sequences.Conventional MRI correctly identified at least one acute lesion in 71% (34/48) to 80% (39/49) of patients who had an acute stroke; with the addition of DWI, this percentage increased to 94% (46/49) (P<.001). Conventional MRI showed only moderate sensitivity (50%-60%) and specificity (49%-69%) compared with a "criterion standard." Based on the diffusion-weighted sequence, interrater reliability for identifying acute lesions was moderate for conventional MRI (kappa = 0.5-0.6) and good for DWI (kappa = 0.8). The observers' confidence with which lesions were rated as acute and the lesion conspicuity was significantly (P<.01) higher for DWI than for conventional MRI.During the first 48 hours after symptom onset, the addition of DWI to conventional MRI improves the accuracy of identifying acute ischemic brain lesions in patients who experienced a stroke.

    View details for Web of Science ID 000089283000010

    View details for PubMedID 10987898

  • Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients NEUROLOGY Albers, G. W., Lansberg, M. G., Norbash, A. M., Tong, D. C., O'Brien, M. W., Woolfenden, A. R., Marks, M. P., Moseley, M. E. 2000; 54 (8): 1562-1567


    To determine whether diffusion-weighted imaging (DWI) could identify potentially clinically relevant findings in patients presenting more than 6 hours after stroke onset when compared with conventional MRI.MRI with both conventional (T2 and proton density images) and echoplanar imaging (DWI and apparent diffusion coefficient maps) was performed 6 to 48 hours after symptom onset (mean, 27 hours) in 40 consecutive patients with acute stroke. All acute lesions were identified first on conventional images, then on DWI, by a neuroradiologist who was provided with the suspected lesion location, based on a neurologist's examination before imaging. Abnormalities were rated as potentially clinically relevant if they were detected only on DWI and 1) confirmed the acute symptomatic lesion to be in a different vascular territory than suspected clinically, 2) revealed multiple lesions in different vascular territories suggestive of a proximal source of embolism, or 3) clarified that a lesion, thought to be acute on conventional imaging, was not acute.The initial clinical impression of lesion localization was incorrect in 12 patients (30%). Clinically significant findings were detected by DWI alone in 19 patients (48%). DWI demonstrated the symptomatic lesion in a different vascular territory than suspected clinically or by conventional MRI in 7 patients (18%) and showed acute lesions in multiple vascular distributions in 5 patients (13%). In 8 patients (20%), DWI clarified that lesions thought to be acute on conventional MRI were actually old.In patients imaged 6 to 48 hours after stroke onset, DWI frequently provided potentially clinically relevant findings that were not apparent on conventional MRI.

    View details for Web of Science ID 000086642000007

    View details for PubMedID 10762494

  • Comparison of diffusion-weighted MRI and CT in acute stroke NEUROLOGY Lansberg, M. G., Albers, G. W., Beaulieu, C., Marks, M. P. 2000; 54 (8): 1557-1561


    To compare diffusion-weighted MRI (DWI) and CT with respect to accuracy of localizing acute cerebral infarction; sensitivity, specificity, and interrater reliability for identifying more than one-third middle cerebral artery (MCA) territory involvement; and correlation of acute lesion volume with final infarct volume.Nineteen consecutive stroke patients underwent CT and DWI within 7 hours of stroke onset and a follow-up DWI examination 36 hours after symptom onset, which served as the "gold standard" for lesion location and extent of MCA involvement. Each scan was evaluated for acute ischemic lesions by two experienced observers. After 30 days, T2-weighted MRI was obtained for assessment of the final infarct volume.The acute CT and DWI scans were obtained on average 2.6 and 5.1 hours after symptom onset. On DWI the acute lesion was identified correctly in all instances and on CT it was identified correctly in 42 to 63% of patients. Sensitivity for detection of more than 33% MCA involvement was better for DWI (57 to 86%) than for CT (14 to 43%), whereas specificity was excellent for both. Interrater reliability was moderately good for both (kappa, 0.6 for DWI; 0.5 for CT). A positive correlation (r = 0.79; p = 0.001) existed between lesion volume on acute DWI and final infarct volume, whereas no correlation was found between CT volume and final infarct volume.When compared with CT, DWI was more accurate for identifying acute infarction and more sensitive for detection of more than 33% MCA involvement. In addition, lesion volume on acute DWI, but not on acute CT, correlated strongly with final infarct volume. Additional studies are required to demonstrate whether these advantages of DWI are clinically relevant in the management of patients with acute stroke.

    View details for Web of Science ID 000086642000006

    View details for PubMedID 10762493

  • Neurosurgical and neuroendovascular management of Takayasu's arteritis NEUROSURGERY Stoodley, M. A., Thompson, R. C., Mitchell, R. S., Marks, M. P., Steinberg, G. K. 2000; 46 (4): 841-851


    The roles of surgical and endovascular treatments for patients with Takayasu's arteritis are not clear. We report our experience in the neurosurgical and/or neuroendovascular treatment of patients with Takayasu's arteritis who exhibited ischemic neurological symptoms.Between 1994 and 1998, seven patients with Takayasu's arteritis and neurological symptoms were treated at the Stanford University Medical Center. All patients were angiographically evaluated and received maximal medical therapy. Cerebral blood flow studies were performed for six patients. Three patients underwent surgical revascularization procedures alone, two underwent combinations of surgical and endovascular procedures, and two underwent endovascular treatment alone.The most common neurological symptoms were dysequilibrium, syncope, and visual disturbances. The characteristic angiographic features of Takayasu's arteritis were identified for all patients. The subclavian arteries and proximal carotid and vertebral arteries were involved in all patients. Two patients exhibited improvement of their symptoms after endovascular treatment alone. There were two deaths after surgery, involving patients with severe global cerebral hypoperfusion. All other surgically treated patients exhibited improvement of their symptoms, with patent grafts, up to 4 years after surgery. Cerebral blood flow improved after treatment.Improvement of symptoms can be achieved with surgical revascularization and/or endovascular treatment. Staged revascularization might be better than one-stage bilateral high-flow grafting for patients with severe global hypoperfusion.

    View details for Web of Science ID 000086360100034

    View details for PubMedID 10764257

  • Basilar artery stenosis: clinical and neuroradiographic features. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Woolfenden, A. R., Tong, D. C., Norbash, A. M., Ali, A. O., Marks, M. P., O'Brien, M. W., Albers, G. W. 2000; 9 (2): 57-63


    Although basilar artery stenosis (BAS) is an important cause of posterior circulation stroke, few reports detail the clinical and neuroradiological features of patients with BAS.A retrospective review of symptomatic BAS patients who were evaluated by our Stroke Center.Twenty-eight patients were followed-up for a median of 16 months. Transient ischemic attacks (TIAs) specific for posterior circulation involvement were common (12/19 patients with TIA), were often multiple, and frequently preceded a posterior circulation stroke. The proximal (13/28) and mid (10/28) basilar arteries were the most common sites of stenosis. Brain infarction most often affected the pons, but also frequently involved the cerebellum and thalamus. Concomitant vertebral artery disease was prevalent (12/18 patients who underwent conventional cerebral angiography). Stroke mechanisms included artery to artery embolus, basilar branch disease, and hypoperfusion. The same-territory recurrent stroke rate was 8.2% per year. Most patients in the series were treated with warfarin. No patients suffered a recurrent stroke while on a therapeutic dose of warfarin (international normalized ratio [INR], 2.0 to 3.0). Angioplasty was performed in 6 patients.The same-territory stroke recurrence rate was 8.2% per year. Warfarin (INR, 2.0 to 3.0) appeared to be effective in preventing recurrent strokes. Angioplasty of the basilar artery was technically feasible. Symptomatic BAS typically affected the proximal and mid-basilar artery and most often caused infarction in the pons. The mechanisms for stroke were heterogeneous. TIAs frequently preceded a posterior circulation stroke.

    View details for PubMedID 17895197

  • Planned direct dual-modality treatment of complex broad-necked intracranial aneurysms: Four technical case reports NEUROSURGERY Cockroft, K. M., Marks, M. P., Steinberg, G. K. 2000; 46 (1): 226-230


    Treatment of complex, broad-based intracranial aneurysms with either microsurgical clipping or endovascular coiling alone is sometimes impossible. In this study, we report the planned combined endovascular and microsurgical treatment of four complex, wide-necked aneurysms in four patients.Three of the four patients presented with subarachnoid hemorrhage. The fourth patient presented with a progressive neurological deficit secondary to an associated arteriovenous malformation. Three of the aneurysms were located in the posterior circulation (two broad-necked basilar apex aneurysms and one bilobed vertebrobasilar junction aneurysm with a wide-necked ventral component). The fourth aneurysm was a broad-based paraclinoid/cavernous-carotid lesion.One of the patients with a basilar apex aneurysm and the patient with the paraclinoid aneurysm underwent surgery intended to create a narrow neck that would be amenable to future coiling. The patient with the bilobed vertebrobasilar junction aneurysm underwent surgery to treat the broad-necked ventral lobe, whereas the dorsal lobe, with the neck partially buried in the brainstem, was treated endovascularly. The second patient with a basilar apex aneurysm was in poor clinical condition after subarachnoid hemorrhage and was therefore treated with coil embolization to reduce the risk of rebleeding. After the patient made a good clinical recovery, the residual aneurysm was surgically clipped. Angiographic follow-up documented the complete obliteration of all four aneurysms. Clinically, all patients had good to excellent outcomes after a follow-up period of 6 to 30 months.Complex, broad-necked aneurysms that may be difficult to treat with a single mode of therapy can be safely and successfully treated with a combination of endovascular and microsurgical techniques. For patients with broad-based aneurysms that are difficult to access surgically without incurring significant morbidity, microsurgical clipping may be used as the initial procedure to create a smaller neck. Alternatively, for patients who are in poor clinical condition after subarachnoid hemorrhage and who harbor a broad-necked aneurysm in a surgically formidable location, partial coiling may be used initially to reduce the short-term risk of rebleeding.

    View details for Web of Science ID 000084540200123

    View details for PubMedID 10626956

  • Treatment of intracranial arteriovenous malformations in the elderly population Chang, S. D., Lopez, J. R., Marks, M. P., Levy, R. P., Adler, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2000: 325–25
  • The treatment of giant intracranial arteriovenous malformations using multimodality therapy Chang, S. D., Lopez, J. R., Levy, R. P., Marks, M. P., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2000: 324–24
  • Long-term outcomes after carotid stent placement for treatment of carotid artery dissection NEUROSURGERY Liu, A. Y., Paulsen, R. D., Marcellus, M. L., Steinberg, G. K., Marks, M. P. 1999; 45 (6): 1368-1373


    To assess the long-term outcomes after stent placement for the treatment of carotid artery dissections.Between 1992 and 1998, seven patients underwent stenting procedures for treatment of extracranial carotid artery dissections resulting from various causes, including trauma (n = 2), iatrogenesis (n = 2), spontaneous development (n = 2), and fibromuscular dysplasia (n = 1). Stenting procedures were performed for large, nonhealing, dissection-induced pseudoaneurysms (four cases) or severe preocclusive stenosis (three cases). A total of 11 stents were placed (Palmaz stents, n = 8; Wallstents, n = 3). Radiological follow-up examinations were performed after a mean period of 17.7 months (range, 1-67 mo), using conventional or computed tomographic angiography. Clinical follow-up data were obtained after a mean period of 42.9 months (range, 13-72 mo).All stent placements resulted in complete resolution of dissection-induced stenosis. For two of the four patients with aneurysms, the lesions occluded spontaneously at the time of the procedure. The third patient required coil embolization of the pseudoaneurysm. One patient exhibited progressive shrinkage of the aneurysm in serial follow-up examinations, with healing after 18 months. No clinical complications were associated with the procedures. One patient exhibited progression to asymptomatic occlusion 3 months after stenting. The remaining six patients exhibited no significant changes in luminal diameters. All patients remained in clinically stable condition, with no ischemic symptoms, during more than 3.5 years (mean period) of follow-up monitoring.This experience suggests that stents placed for treatment of extracranial carotid artery dissections remain patent and patients remain free of symptoms on a long-term basis. Additional studies will be required to determine the optimal types of stents and intervals for follow-up monitoring using imaging.

    View details for Web of Science ID 000084092000055

    View details for PubMedID 10598705

  • Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: Evolution of lesion volume and correlation with clinical outcome ANNALS OF NEUROLOGY Beaulieu, C., de Crespigny, A., Tong, D. C., Moseley, M. E., Albers, G. W., Marks, M. P. 1999; 46 (4): 568-578


    A prospective longitudinal diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI/PWI) study of stroke patients (n = 21) at five distinct time points was performed to evaluate lesion evolution and to assess whether DWI and PWI can accurately and objectively demonstrate the degree of ischemia-induced deficits within hours after stroke onset. Patients were scanned first within 7 hours of symptom onset and then subsequently at 3 to 6 hours, 24 to 36 hours, 5 to 7 days, and 30 days after the initial scan. Lesion evolution was dynamic during the first month after stroke. Most patients (18 of 19, 95%) showed increased lesion volume over the first week and then decreased at 1 month relative to 1 week (12 of 14, 86%). Overall, lesion growth appeared to depend on the degree of mismatch between diffusion and perfusion at the initial scan. Abnormal volumes on the acute DWI and PWI (<7 hours) correlated well with initial National Institutes of Health (NIH) stroke scale scores, outcome NIH stroke scale scores, and final lesion volume. DWI and PWI can provide an early measure of metabolic and hemodynamic insufficiency, and thus can improve our understanding of the evolution and outcome after acute ischemic stroke.

    View details for Web of Science ID 000082914500004

    View details for PubMedID 10514093

  • A standardized MRI stroke protocol: Comparison with CT in hyperacute intracerebral hemorrhage STROKE Tong, D. C., Albers, G. W., Yenari, M. A., Marks, M. P. 1999; 30 (9): 1974-1975

    View details for Web of Science ID 000082278400047

    View details for PubMedID 10471453

  • Direct and combined revascularization in pediatric moyamoya disease NEUROSURGERY Golby, A. J., Marks, M. P., Thompson, R. C., Steinberg, G. K. 1999; 45 (1): 50-58


    Surgical revascularization of moyamoya disease can improve neurological outcomes, compared with the natural history of the disease or the results of medical treatment. Controversy exists regarding whether direct or indirect revascularization yields better outcomes. This study involves a single-center experience with direct anastomosis and is the first North American series using direct revascularization for pediatric patients with moyamoya disease.Twelve patients (age range, 5-17 yr; mean age, 10.2 yr) underwent direct revascularization of 21 hemispheres. Two patients had experienced failure of previous indirect revascularization procedures, with continued clinical deterioration. Superficial temporal artery-middle cerebral artery anastomosis was performed in 19 hemispheres (with concurrent encephaloduroarteriosynangiosis in 6). Middle meningeal artery-middle cerebral artery anastomosis and omental transposition were each performed in one hemisphere. Follow-up periods ranged from 12 to 65 months (mean, 35 mo), and monitoring included neurological examinations, angiography, magnetic resonance imaging, and cerebral blood flow studies.The neurological conditions of all patients were stable or improved after surgery. None of the patients developed new strokes, and no new ischemic lesions were seen in magnetic resonance imaging scans. All grafts evaluated by follow-up angiography were patent. Postoperative cerebral blood flow studies showed significantly improved blood flow (54.4 versus 42.5 ml/100 g/min; P = 0.017, n = 4) and hemodynamic reserve (70.3 versus 43.9 ml/100 g/min; P = 0.009, n = 4), compared with preoperative studies.Surgical revascularization by direct anastomosis in pediatric patients is technically feasible, is well tolerated, and can improve the progressive natural history, the angiographic appearance, and the cerebral blood flow abnormalities associated with the disease. Direct revascularization has the advantage of providing immediate and high-flow revascularization and is particularly useful for patients who have experienced failure of previous indirect revascularization procedures.

    View details for Web of Science ID 000081201500030

    View details for PubMedID 10414566

  • Evaluation of early reperfusion and IV tPA therapy using diffusion- and perfusion-weighted MRI NEUROLOGY Marks, M. P., Tong, D. C., Beaulieu, C., Albers, G. W., de Crespigny, A., Moseley, M. E. 1999; 52 (9): 1792-1798


    To characterize the effects of recombinant tissue plasminogen activator (rt-PA) therapy and early reperfusion on diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) changes observed following acute ischemic injury.Twelve patients were evaluated prospectively using echo planar DWI and bolus tracking PWI. Six patients received i.v. rt-PA 0.9 mg/kg and were compared with six patients who did not. Patients receiving rt-PA were initially imaged (T1) 3 to 5 hours postictus (mean, 4 hours 20 minutes) whereas those not treated with tissue plasminogen activator (tPA) were imaged 4 to 7 hours postictus (mean, 5 hours, 25 minutes). Follow-up imaging was performed 3 to 6 hours (T2), 24 to 36 hours (T3), 5 to 7 days (T4), and 30 days (T5) after the first scan in all patients. Lesion volumes were measured on both DWI and time-to-peak maps constructed from PW images.PWI was performed successfully at T1 and T3 in 11 of 12 patients. In the group that received i.v. tPA, initial PWI volumes were less than DWI volumes in five of six patients (83%), whereas only one of five patients (20%) not receiving tPA had PWI < DWI volume (p = 0.08). PWI normalized by 24 to 36 hours (T3) in 6 of 11 patients (early reperfusers), with 5 of 6 of these early reperfusers having received tPA. The aggregate apparent diffusion coefficient (ADC) values for the early reperfusers were consistently higher at T2 (p = 0.04), T3 (p = 0.002), and T4 (p = 0.0005). Five of six patients with early reperfusion demonstrated regions of elevated ADC within the ischemic zone (mean ipsilateral ADC/contralateral ADC, 1.46 +/- 0.19) by 24 to 36 hours, whereas none of the nonearly reperfusers showed these regions of elevated ADC (p = 0.015).Early reperfusion is seen more frequently with i.v. tPA therapy. In addition, the study showed that ADC may undergo early increases that are tied closely to reperfusion, and marked ADC heterogeneity may exist within the same lesion. Early reperfusion is seen more frequently with i.v. tPA therapy.

    View details for Web of Science ID 000080758500014

    View details for PubMedID 10371525

  • Correlation of magnetic resonance characteristics and histopathological type of angiographically occult vascular malformations NEUROSURGERY Vanefsky, M. A., Cheng, M. L., Chang, S. D., Norbash, A., Snipe, J., Marks, M. P., Steinberg, G. K. 1999; 44 (6): 1174-1180
  • Recanalization and rupture of a giant vertebral artery aneurysm after Hunterian ligation: Case report NEUROSURGERY Chang, S. D., Marks, M. P., Steinberg, G. K. 1999; 44 (5): 1117-1120


    Recanalization and subsequent rupture of giant aneurysms of the posterior circulation after Hunterian ligation is an extremely rare event that has been noted to occur with basilar apex, basilar trunk, and vertebrobasilar junction aneurysms. We report the case of a giant, previously unruptured right vertebral artery aneurysm, which recanalized from the contralateral vertebral artery and subsequently ruptured after previously performed angiography showed complete thrombosis of the aneurysm.A 72-year-old woman presented with headaches, ataxia, and lower extremity weakness. A giant 3-cm right vertebral artery aneurysm was found during the patient evaluation.Because of the size of the aneurysm and the absence of a discrete neck, Hunterian ligation was performed. After treatment, angiograms showed no filling of the aneurysm from either the right or left vertebral artery. Nine days later, after the patient developed lethargy and nausea, repeat angiography showed that a small portion of the aneurysmal base had recanalized. The next day, the patient had a massive subarachnoid hemorrhage and subsequently died.We think that this is a previously undescribed complication associated with direct arterial ligation of giant vertebral artery aneurysms. Patients with aneurysms treated using Hunterian ligation need to be followed up closely. Even aneurysms that have minimal recanalization are at risk for subarachnoid hemorrhage.

    View details for Web of Science ID 000079903800096

    View details for PubMedID 10232546

  • Outcome of angioplasty for atherosclerotic intracranial stenosis STROKE Marks, M. P., Marcellus, M., Norbash, A. M., Steinberg, G. K., Tong, D., Albers, G. W. 1999; 30 (5): 1065-1069


    We sought to assess the long-term outcome and efficacy of percutaneous transluminal angioplasty in the treatment of symptomatic intracranial atherosclerotic stenoses.Twenty-three patients with fixed symptomatic intracranial stenoses were treated over a 5-year period with percutaneous transluminal angioplasty. Patients who underwent successful angioplasty were followed up for 16 to 74 months (mean, 35.4 months).An angioplasty that resulted in decreased stenosis was performed in 21 of 23 patients (91.3%). In 1 case a stenosis could not be safely crossed, and in another balloon dilatation resulted in vessel rupture. This vessel rupture resulted in the 1 periprocedural death in the series. In follow-up there was 1 stroke in the same vascular territory as the angioplasty and 2 strokes in the series overall. This yielded an annual stroke rate of 3.2% for strokes in the territory appropriate to the site of angioplasty.Intracranial angioplasty can be performed with a high degree of technical success. The long-term clinical follow-up available in this series suggests that it may reduce the risk of future stroke in patients with symptomatic intracranial stenoses.

    View details for Web of Science ID 000080091700026

    View details for PubMedID 10229745

  • Embolization of basal ganglia and thalamic arteriovenous malformations NEUROSURGERY Paulsen, R. D., Steinberg, G. K., Norbash, A. M., Marcellus, M. L., Marks, M. P. 1999; 44 (5): 991-996


    Basal ganglia and thalamic arteriovenous malformations (AVMs) show a poor natural history and have proven difficult to treat. We report the safety and efficacy of presurgical and preradiosurgical embolization of these deep central lesions and describe the contribution of embolization to multimodality treatment.Thirty-eight patients with basal ganglia and/or thalamic AVMs underwent embolization in a total of 69 sessions. Seven of the 38 patients (18.4%) presented with hemorrhage, and 23 of 38 (60.5%) exhibited neurological deficits before therapy. Thirty patients (78.9%) underwent embolization with a liquid adhesive (cyanoacrylate), and five of these patients also underwent embolization with polyvinyl alcohol. Five patients (13.2%) were treated with polyvinyl alcohol or polyvinyl alcohol and silk. One patient (2.6%) underwent embolization alone, 19 (50.0%) underwent embolization followed by radiosurgery, 5 (13.2%) underwent embolization plus microsurgical resection, and 13 (34.2%) patients were treated using all three modalities.Three patients did not undergo embolization because of the morphological features of the AVMs and poor endovascular access. The patients who underwent embolization achieved AVM volume reductions of 10 to 100% (mean, 49.7%). Fifteen patients (39.5%) achieved complete obliteration of their AVMs, one with embolization alone, three with embolization followed by radiosurgery, five with embolization plus microsurgical resection, and six with a combination of all three modalities. At the time of the last follow-up imaging session, embolization combined with radiosurgery (19 patients) yielded a mean volume reduction of 81.1%, and all three modalities (13 patients) yielded a mean reduction of 84.6%. Four permanent neurological deficits resulted from embolization (5.8% of procedures, 10.5% of patients). The embolization-related complication rate was higher in the earlier years (1984-1989) of this series.Endovascular embolization plays an important role in multimodality treatment of AVMs involving the basal ganglia and/or thalamus. Embolization can result in obliteration of a significant volume of the AVM and may allow complete obliteration of the AVM when combined with microsurgical resection and/or stereotactic radiosurgery.

    View details for Web of Science ID 000079903800030

    View details for PubMedID 10232532

  • Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis JOURNAL OF PEDIATRICS Smith, A. L., Doershuk, C., Goldmann, D., Gore, E., Hilman, B., Marks, M., Moss, R., Ramsey, B., Redding, G., Rubio, T., Williams-Warren, J., Wilmott, R., Wilson, H. D., YOGEV, R. 1999; 134 (4): 413-421


    We determined whether a beta-lactam and an aminoglycoside have efficacy greater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. Study design: Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization.No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P =.034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy.We conclude that the combination of a beta-lactam and an aminoglycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.

    View details for Web of Science ID 000079648400006

    View details for PubMedID 10190914

  • Embolization of rolandic cortex arteriovenous malformations NEUROSURGERY Paulsen, R. D., Steinberg, G. K., Norbash, A. M., Marcellus, M. L., Lopez, J. R., Marks, M. P. 1999; 44 (3): 479-484


    To evaluate the safety and efficacy of preradiosurgical and presurgical embolization of arteriovenous malformations (AVMs) involving the rolandic cortex.Seventeen consecutive patients with rolandic AVMs seen during a 31-month period (December 1994-July 1997) were evaluated. All patients underwent superselective sodium amobarbital testing to determine any changes in the results of the neurological examinations before undergoing embolization. In 16 of 17 patients (94.1%), somatosensory evoked potentials augmented physical examinations. Patients were embolized with N-butyl cyanoacrylate (Histoacryl; B. Braun, Melsungen, Germany) and iophendylate (Ethiodol; Savage Labs, Melville, NY). Rigid control of the mean arterial pressure (65-75 mm Hg) was maintained in all patients for 24 to 48 hours after embolization.Twenty-three embolization sessions were performed in 17 patients (mean, 1.5 sessions/patient), and a total of 40 feeding arteries were embolized. Two patients were unable to undergo embolization because of positive results of the amobarbital testing despite repeated attempts to reposition a microcatheter in the AVM circulation. In one case, somatosensory evoked potentials and the results of the physical examination were both positive; in the other case, only the somatosensory evoked potentials were used (in a pediatric patient under general anesthesia). All patients with AVMs that were embolized experienced a significant size reduction of their lesions (range, 20-95%; mean, 63%). There were no permanent complications. Four procedures (10% of the procedures, 23% of the patients) resulted in minor transient neurological deficits, with patients' conditions returning to baseline. Thirteen patients subsequently underwent radiosurgery, three underwent surgical resection, and one underwent combined surgery and radiosurgery. Complete obliteration of the lesions has been achieved in four patients to date (three who underwent surgery and one who underwent radiosurgery), with the remainder undergoing further follow-up.When properly evaluated before treatment, rolandic AVMs can be embolized with a high success rate (measured by completed embolization and size reduction) and a low complication rate.

    View details for Web of Science ID 000078716500020

    View details for PubMedID 10069584

  • Evaluation of early computed tomographic findings in acute ischemic stroke STROKE Marks, M. P., Holmgren, E. B., Fox, A. J., Patel, S., von Kummer, R., Froehlich, J. 1999; 30 (2): 389-392


    Detection of large, hypoattenuated brain-tissue volume on hyperacute CT scan has been suggested as an exclusion criterion for early intravenous tissue plasminogen activator (IV-tPA) treatment. This study assessed the reliability of detection for these findings and their relationship to outcome.Fifty hyperacute CT scans (<6 hours after ictus) were selected from a randomized trial evaluating IV-tPA (ATLANTIS trial). Three neuroradiologists blinded to all clinical information evaluated scans for degree of MCA territory involvement (<33% or >33%) and the presence of a hyperdense MCA. Evaluations were compared with 24-hour scan results, 30-day infarct volumes, and baseline NIH stroke scale scores (NIHSS).Readers reliably evaluated the degree of MCA territory hypodensity (intraclass correlation=0.53, P<0.001), with all 3 readers agreeing in 36 of 50 cases (72%). They correctly called >33% involvement with a sensitivity of 60% to 85% and a specificity of 86% to 97%. The baseline NIHSS was higher when >33% MCA hypodensity was seen (P=0. 021). Detection of significant hypodensity (>33%) correlated with poorer outcome. When >33% hypodensity was not detected, mean 30-day infarct volumes were 27.0 to 33.0 cm3, versus 84.3 to 123.1 cm3 when >33% hypodensity was present (P=0.002).Detection of MCA territory hypodensity on hyperacute CT scans is a sensitive, prognostic, and reliable indicator of the amount of MCA territory undergoing infarction.

    View details for Web of Science ID 000078381600018

    View details for PubMedID 9933276

  • Correlation of magnetic resonance characteristics and histopathological type of angiographically occult vascular malformations Neurosurgery Vanefsky, M. A., Cheng, M. L., Chang, S. D., Norbash, A., Snipe, J., Marks, M. P., Steinberg, G. K. 1999; 44 (6): 1174–80; discussion 1180–81


    OBJECTIVE: Histological and radiological classification of vascular malformations has previously been attempted in an effort to understand their nature and predict their biological behavior. There exists a subgroup of vascular malformations that are angiographically occult and share a common magnetic resonance imaging (MRI) appearance but may differ in their behavior. We sought to determine any correlation between MRI features and final histopathological diagnosis. METHODS: We reviewed our series of 72 patients with angiographically occult vascular malformations operated on at Stanford University Medical Center between 1988 and 1993. Radiographic magnetic resonance images and histopathological specimens were retrospectively evaluated for various diagnostic features. RESULTS: Our data indicate that lesions exhibiting a ring of hemosiderin are associated with the presence of a cavernous malformation (CM) component (86% of CMs versus 33% of non-CM lesions). A lesion associated with edema, mass effect, or a single prominent blood product on MRI correlates with the presence of an arteriovenous malformation (AVM) component. Sixty-three percent of AVMs and 80% of lesions with partial AVM components showed edema, compared with 8% of CMs and 0% of venous malformations. Sixty percent of AVMs and 63% of lesions with partial AVM components showed a single prominent blood product, compared with 8% of CMs and 0% of venous malformations. Finally, 60% of AVMs exhibited mass effect, compared with 20% of CMs. Additionally, an expansile hemorrhage is suggestive of an AVM. CONCLUSION: This study is the first to demonstrate that a particular MRI appearance of an angiographically occult vascular malformation is suggestive of an AVM component. This may have important implications with regard to the behavior of the lesion and planning of future treatment.

    View details for PubMedID 10371616

  • Unruptured intracranial aneurysms - Risk of rupture and risks of surgical intervention NEW ENGLAND JOURNAL OF MEDICINE Wiebers, D., Whisnant, J., Forbes, G., Meissner, I., Brown, R., Piepgras, D., Huston, J., Nichols, D., O'Fallon, W., Peacock, J., Jaeger, L., Kassell, N., Kongable-Beckman, G., Torner, J., Rajput, M., Drake, C., Kurtzke, J., Marler, J., Walker, M., Meyer, F., Atkinson, J., Marsh, W., Thielen, K., Ferguson, G., Barr, H., Lownie, S., Hachinski, V., Fox, A., Sahjpaul, R., Parrent, A., Mayer, C., Lindsay, K., Teasdale, E., Bone, I., Fatukasi, J., Lindsay, M., Cail, W., Sagher, O., Davis, M., Sengupta, R., Bates, D., Gholkar, A., Murdy, J., Wilson, S., Praharaj, S., Partridge, G., Reynolds, C., Hind, N., Ogilvy, C., Crowell, R., Gress, D., Schaefer, P., Choi, I., Buckley, D., Sloan, K., King, D., Giannotta, S., Ameriso, S., Teitelbaum, T., Thomson, E., Fishback, D., Vajda, J., Nyary, I., Czirjak, S., Horvath, M., Szikora, I., Pasztor, E., Varady, P., Erdos, A., Edner, G., Wahlgren, N., Lindqvist, M., Antonsson, A., Da Pian, R., Pasqualin, A., Chioffi, F., Beltramello, A., Zampieri, G., Benati, A., Rossi, G., Ronkainen, A., Hernesniemi, J., Vapalahti, M., Rinne, J., Luukkonen, M., Vihavainen, M., Savolainen, S., Koivisto, T., Leivo, S., Helin, K., Steinberg, G., Marks, M., Vanefsky, M., Norbash, A., Thompson, R., Bell, T., Marcellus, M., Meyer, A., Kerr, R., Adams, C., Molyneux, A., Vinden, S., Bacon, F., Shrimpton, J., Parker, S., Day, A., Nadeau, S., Stachniak, J., Friedman, W., Fessler, R., Peters, K., Jacob, R., Roper, S., Smith, A., LaFrentz, P., Howard, M., Loftus, C., Adams, H., Crosby, D., Rogers, M., Broderick, J., Tew, J., Brott, T., van Loveren, H., Yeh, H., Zuccarello, M., Tomsick, T., Gaskill-Shipley, M., Minneci, L., McMahon, N., Castel, J., Orgogozo, J., Loiseau, H., Bourgeois, P., Berge, J., Dousset, V., Cuny, E., RICHARD, M., Agbi, C., Hugenholtz, H., Benoit, B., Morrish, W., Wee, R., Grahovac, S., Pratt, L., Mortensen, M., Andreoli, A., Testa, C., Comani, V., Trevisan, C., Limoni, P., Carlucci, F., Leonardi, M., Sturiale, C., Pendl, G., Eder, H., Klein, G., Eder, M., Leber, K., Horner, T., Leipzig, T., Payner, T., DeNardo, A., Scott, J., Redelman, K., Fisher, W., Rosner, M., Vitek, G., Hand, M., Flack, W. F., Sichez, J., Pertuiset, B., Fohanno, D., Marsault, C., Casasco, A., Biondi, A., Capelle, L., Duffau, H., Winn, H., Grady, M., NEWELL, D., Longstreth, W., Thompson, P., Bybee, H., Jones, D., Findlay, J., Petruk, K., Steinke, D., Ashforth, R., Stenerson, P., Schindel, D., Vanderhoven, H., Neves, J., Zager, E., Flamm, E., Raps, E., Hurst, R., Parrott, S., Sellers, M., Torchia, M., Anderson, B., West, M., Fewer, D., Hill, N., Sutherland, G., Ross, I., McClarty, B., Brownstone, R., Williams, O., Narotam, P., Christane, L., McGinn, G., Gladish, D., Kirkpatrick, P., Pickard, J., Antoun, N., Simpson, D., Higgins, N., Turner, C., Tebbs, S., Holness, R., Malloy, D., Phillips, S., Maloney, W., Molina-de-Orozco, V., Baxter, B., Connolly-Campbell, K., MacDougall, A., Gentili, F., Wallace, M., ter Brugge, K., Willinsky, R., Tymianski, M., Rickards, L., Tucker, W., Lambert, C., Montanera, W., Rychlewski, C., Flood, C., Villani, R., Sganzerla, E., Tomei, G., Bettinelli, A., Leonardi, M., Ceccarelli, G., Righini, A., Bello, L., Marras, C., Nelson, R., Lewis, T., Renowden, C., Clarke, Y., Varian, L., Chyatte, D., Sila, C., Perl, J., Masaryk, T., Porterfield, R., Shaw, M., Foy, P., Nixon, T., Dunn, L., Clitheroe, N., Smith, T., Eldridge, P., Humphrey, P., Wiseman, J., Hawkins, K., Owen, L., Ost, K., Saminaden, S., Mohr, G., Schondorf, R., Carlton, J., Maleki, M., Just, N., Brien, S., Entis, S., Tampieri, D., Simons, N., Mooij, J., Metzemackers, J., Hew, J., Beks, J., Van der Veen, A., Bosma, I., Sprengers, M., Rinkel, G., van Gijn, J., Ramos, L., Tulleken, C., Greebe, P., Van Vliet, F., Borgesen, S., Jespersen, B., Boge-Rasmussen, T., Willumsen, L., Homer, D., Eller, T., Carpenter, J., Meyer, J., Munson, R., Small, B., Nussbaum, E., Heros, R., Latchaw, R., Camarata, P., Lundgren, J., Mattsen, N., Whittle, I., Sellar, R., O'Sullivan, M., Steers, A., Statham, P., Malcolm, G., Price, R., Hoffman, B., Yonas, H., Wechsler, L., Thompson-Dobkin, J., Jungreis, C., Kassam, A., Kirby, L., Parent, A., Lewis, A., Azordegan, P., Smith, R., Alexander, L., GORDON, D., Russell, W., Brown, R., Benashvili, G., Perry, R., Scalzo, D., Mandybur, G., Morgan, C., Karanjia, P., Madden, K., Kelman, D., Gallant, T., Vanderspek, H., Choucair, A., Neal, J., Mancl, K., Saveland, H., Brandt, L., Holtas, S., Trulsson, B., MacDonald, R., Weir, B., Mojtahedi, S., Amidei, C., Vermeulen, M., Bosch, D., Hulsmans, F., Albrecht, K., Roos, Y., Vet, A., Gorissen, A., Mechielsen, M., Martin, N., Gobin, Y., Saver, J., Vinuela, F., Duckwiler, G., Kelly, D., Frazee, J., da Graca, R., Gravori, T., Illingworth, R., Richards, P., Wade, J., Colquhoun, I., Bashir, E., Shortt, S., Weaver, J., Fisher, M., Stone, B., Chaturvedi, S., Davidson, R., Davidson, K., Giombini, S., Solero, C., Boiardi, A., Cimino, C., Valentini, S., Silvani, A., Alberts, M., Friedman, A., Gentry, A., Hoffman, K., Hughes, R., Lillihei, K., Earnest, M., Nichols, J., Kindt, G., Anderson, A., Levy, S., Nichols, J., Smith, R., Breeze, R., Noonan, V., Gress, D., Dowd, C., Vanwestrop, J., Wilson, C., Berger, M., Hannegan, L., Heros, R., Marcos, J., Ugarte, L., Kitchen, N., Taylor, W., Kumar, M., Grieve, J., Durity, F., Boyd, M., Fairholm, D., Griesdale, D., Honey, C., Redekop, G., Toyota, B., Turnbull, I., Woodhurst, W., Zwimpfer, T., Teal, P., Grabe, D., Brevner, A., Piepgras, A., Schmiedek, P., Schwartz, A., Weber, T., Biller, J., Brem, S., Cybulski, G., Chadwick, L., Bronstein, K., Pietila, T., Brock, M., Krug, D., Krznaric, I., Hernesniemi, J., Kivisaari, R. 1998; 339 (24): 1725-1733
  • Microsurgical resection of incompletely obliterated intracranial arteriovenous malformations following stereotactic radiosurgery NEUROLOGIA MEDICO-CHIRURGICA Chang, S. D., Steinberg, G. K., Levy, R. P., Marks, M. P., Frankel, K. A., Shuster, D. L., Marcellus, M. L. 1998; 38: 200-207


    Radiosurgery is effective in obliterating small arteriovenous malformations (AVMs), but less successful in thrombosing larger AVMs. This study reviewed patients who underwent surgical resection of their large AVMs following failed radiosurgical obliteration. AVMs from 36 patients (aged 7 to 64 years, mean 29.9) were surgically resected 1 to 11 years after radiosurgery. Initial AVM volumes were 0.7 to 117 cm3 (mean 21.6 cm3), and radiosurgical doses ranged from 4.6 to 45 Gray equivalent (GyE) (mean 21.1 GyE). Thirty AVMs (83%) were located in eloquent tissue. Venous drainage was deep (14), superficial (13), or both (9). Spetzler grades were II (2), III (12), IV (18), and V (4). Nine patients suffered rehemorrhage after radiosurgery but prior to surgery, while three patients developed radiation necrosis. Twenty-seven patients underwent endovascular embolization prior to surgery. During microsurgical resection, the AVMs were found to be significantly less vascular and more easily resected, compared to AVMs in patients who had not received radiosurgery. Histology showed endothelial proliferation with hyaline and mineralization in vessel walls. Partial or complete thrombosis of some AVM vessels, and evidence of vessel and brain necrosis were noted in many cases. Clinical outcome was excellent or good in 34 cases, with two patients dying of rebleeding from residual AVM. Five patients were neurologically worse following microsurgical resection. Final outcome was largely related to the pretreatment grade. Radiosurgery several years prior to surgical resection appears useful in treating unusually large and complex AVMs.

    View details for Web of Science ID 000078035900037

    View details for PubMedID 10235006

  • CT in ischemic stroke NEUROIMAGING CLINICS OF NORTH AMERICA Marks, M. P. 1998; 8 (3): 515-?


    Previously, CT was considered insensitive in the evaluation of the acute ischemic stroke patient; however, more recently detection of early CT findings has proved to be of prognostic value in the evaluation of these patients. The use of CT coupled with early acute phase therapy of stroke such as thrombolytic therapy has been shown to improve outcome in the acute stroke patient.

    View details for Web of Science ID 000075914800003

    View details for PubMedID 9673310

  • The management of patients with arteriovenous malformations and associated intracranial aneurysms NEUROSURGERY Thompson, R. C., Steinberg, G. K., Levy, R. P., Marks, M. P. 1998; 43 (2): 202-211


    Few published studies have focused specifically on the unique management issues encountered in treating patients with arteriovenous malformations (AVMs) and associated intracranial aneurysms. The primary objective of this study was to retrospectively review the clinical and radiographic features of these patients.Medical records of all patients seen at Stanford University Hospital between 1988 and 1996 with a diagnosis of AVMs were retrospectively reviewed. Aneurysms were identified by conventional angiography and characterized by size, number, and location relative to the AVMs. AVMs were graded according to the Spetzler-Martin scale. Odds ratios were calculated for the risk of intracranial hemorrhage. Variables included age, sex, number of aneurysms, and AVM grade.Forty-five of 600 patients (7.5%) were identified as having coexisting intracranial aneurysms. All 45 patients had high-flow malformations, and 58% had AVMs of Spetzler-Martin Grade IV or higher. A majority of patients had multiple aneurysms. There was a statistically significant increase in AVM hemorrhage in female patients (odds ratio, 8.53 [1.87-38.98]; P < 0.005). There was no statistically significant correlation between the development of hemorrhage and either age, AVM grade, or the number of aneurysms. Twenty-three patients (51%) presented with intracranial hemorrhage: bleeding occurred from the AVMs in 15 and from ruptured aneurysms in 5, and the source of the bleeding could not be determined in 3. Overall, nine patients (20%) bled from ruptured aneurysms: five at presentation, two during or within 3 weeks of AVM treatment, and two from new aneurysms. Two of these nine patients died as a direct result of aneurysmal subarachnoid hemorrhage. Five patients (11%) developed new aneurysms.Aneurysms associated with AVMs are at risk for rupture before, during, and immediately after treatment of the AVMs. New aneurysms may arise in patients with high-flow AVMs. The risk of intracranial hemorrhage from either source is higher in female patients. To reduce the complications of intracranial hemorrhage in these patients, we recommend a management protocol designed to treat the aneurysms by surgical or endovascular means before administering definitive therapy for the AVMs. Meticulous intraoperative blood pressure control and fluid management during aneurysm surgery is critical to avoid hemorrhage from the AVMs.

    View details for Web of Science ID 000074979500006

    View details for PubMedID 9696071

  • Angiographically defined primary angiitis of the CNS - Is it really benign? NEUROLOGY Woolfenden, A. R., Tong, D. C., Marks, M. P., Ali, A. O., Albers, G. W. 1998; 51 (1): 183-188


    Primary angiitis of the CNS (PACNS) is a diagnostically challenging disorder. In patients whose diagnosis is ascertained solely by cerebral angiography without histologic verification, a benign monophasic clinical course with favorable response to a brief course of immunosuppressive therapy is often reported.We performed a retrospective review of patients with PACNS seen at the Stanford Stroke Center.Patients were followed for a median of 27.5 months. Acute focal deficits (9 of 10) and headache (3 of 10) were the most frequent presenting symptoms. Significant recurrent neurologic symptoms occurred in 5 of 10 patients before the initiation of immunosuppressive treatment. Three of six patients had recurrent symptoms during prednisone therapy alone, whereas only one of seven patients had recurrent symptoms while receiving combination immunosuppressive therapy. None had recurrent stroke during immunosuppressive treatment. Dynamic arterial changes were seen in four of five patients who underwent follow-up angiography that often, but not always, correlated with disease activity.Patients with angiographically defined PACNS frequently did not have a benign outcome or monophasic course. Repeat angiography was useful in supporting the diagnosis of PACNS, but did not always correlate with disease activity. A prospective multicenter collaborative effort is required to better define the clinical course and optimal treatment of PACNS.

    View details for Web of Science ID 000075151800037

    View details for PubMedID 9674800

  • Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute (< 6.5 hour) ischemic stroke NEUROLOGY Tong, D. C., Yenari, M. A., Albers, G. W., O'Brien, M., Marks, M. P., Moseley, M. E. 1998; 50 (4): 864-870


    Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI are powerful new techniques for the assessment of acute cerebral ischemia. However, quantitative data comparing the severity of clinical neurologic deficit with the results of DWI or PWI in the earliest phases of stroke are scarce. Such information is vital if MRI is potentially to be used as an objective adjunctive measure of stroke severity and outcome.The authors compared initial DWI and PWI lesion volumes with subsequent 24-hour neurologic deficit as determined by National Institutes of Health Stroke Scale (NIHSS) score in acute stroke patients. Initial DWI and PWI volumes were also compared with T2W MRI lesion volume at 1 week to assess the accuracy of these MRI techniques for the detection of acute cerebral ischemia.Patients with stroke underwent MRI scanning within 6.5 hours of symptom onset. Lesion volumes on DWI and PWI were measured and compared with 24-hour NIHSS score. Initial DWI and PWI volumes were also compared with T2W lesion size at 1 week.There was a high correlation between 24-hour NIHSS score and lesion volume as determined by PWI (r = 0.96, p < 0.001) or DWI (r = 0.67, p = 0.03). A similar high correlation was seen between T2W stroke size at 7 days and initial DWI and PWI lesion size (r = 0.99, p < 0.00001).Both DWI and PWI are highly correlated with severity of neurologic deficit by 24-hour NIHSS score. These findings may have substantial implications for the use of MRI scanning in the assessment and management of acute stroke patients.

    View details for Web of Science ID 000073187300010

    View details for PubMedID 9566364

  • Neuropsychological recovery from childhood moyamoya disease BRAIN & DEVELOPMENT Bowen, M., Marks, M. P., Steinberg, G. K. 1998; 20 (2): 119-123


    These reports describe mental recovery from childhood moyamoya disease wherein comprehensive and valid neuropsychological testing is administered in serial fashion. Two young children diagnosed with moyamoya disease underwent procedures to achieve bilateral revascularization. Neuropsychological studies were administered pre-operatively in one case and in serial fashion post-operatively through longer-term follow-up in both cases. Results indicated a trend of gradual improvements in both cases. The disease process and its postulated neuroanatomical and hemodynamic relationship to the psychometric findings are discussed.

    View details for Web of Science ID 000072610300011

    View details for PubMedID 9545184

  • Endovascular management of an aneurysm arising from posterior inferior cerebellar artery originated at the level of C2. Radiation medicine Abe, T., Kojima, K., Singer, R. J., Marks, M. P., Watanabe, M., OHTSURU, K., Nishimura, H., Hayabuchi, N. 1998; 16 (2): 141-143


    A 22-year-old man was admitted with a spontaneous subarachnoid hemorrhage. Right vertebral angiography demonstrated an aneurysm arising from a distal segment of an anomalous posterior inferior cerebellar artery (PICA) at the level of C 1. The PICA originated from the third segment of the vertebral artery at the level of C2. The lesion was treated with endovascular techniques, and the patient suffered no residual neurological deficits.

    View details for PubMedID 9650904

  • Coexistence of occult vascular malformations and developmental venous anomalies in the central nervous system: MR evaluation Annual Meeting of the American-Society-of-Neuroradiology Abe, T., Singer, R. J., Marks, M. P., Norbash, A. M., Crowley, R. S., Steinberg, G. K. AMER SOC NEURORADIOLOGY. 1998: 51–57


    We sought to determine the prevalence of coexistent occult vascular malformations (OVMs) and developmental venous anomalies (DVAs) and to investigate the relationship between them.One hundred two patients with OVMs were examined with precontrast and postcontrast T1-weighted MR imaging and with noncontrast T2-weighted MR imaging. Seventy-two patients had surgery, with subsequent pathologic confirmation of the final diagnosis.Coexistent DVAs and OVMs were present in 23 (23%) of 102 patients. Seventy-nine patients had OVMs without DVAs, and in this population, multiple OVMs (from two to 10 or more) were seen in 13 patients (16%). In contrast, multiple OVMs were seen in 10 (43%) of 23 patients with coexisting OVMs and DVAs. Twenty-five (83%) of 30 OVMs coexisting with DVAs were infratentorial. In 72 patients with surgically resected OVMs, 49 (68%) had pathologically confirmed cavernous malformations. Among the patients with coexistent DVAs, seven (46%) had cavernous malformations, four (27%) had thrombosed arteriovenous malformations, and four (27%) had vascular malformations that were not classifiable.Our study revealed a high prevalence of OVMs with coexistent DVAs, and a high percentage of these were in the posterior fossa. Contrast-enhanced MR imaging may increase the probability of finding these lesions, and therefore should be considered part of the preoperative evaluation, since the finding of unexpected coexistent lesions may affect surgical management.

    View details for Web of Science ID 000071026700016

    View details for PubMedID 9432157

  • Evaluation of early CT signs of ischemic infarction Marks, M. P., Holmgren, E. B., Fox, A. J., Patel, S., von Kummer, R., Froelich, J. LIPPINCOTT WILLIAMS & WILKINS. 1998: 310–10
  • Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke ANNALS OF NEUROLOGY Lutsep, H. L., Albers, G. W., deCrespigny, A., Kamat, G. N., Marks, M. P., Moseley, M. E. 1997; 41 (5): 574-580


    Diffusion-weighted imaging (DWI) detects small changes in water diffusion that occur in ischemic brain. This study evaluated the clinical usefulness of a phase-navigated spin-echo DWI sequence compared with T2-weighted magnetic resonance imaging (T2W MRI) in patients with cerebral ischemia and assessed apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI) changes over time. ADC values and T2 ratios of image intensity were measured from the region of ischemia and from the corresponding contralateral brain region. The clinical histories of patients with DWI scans obtained over the course of 1 year were reviewed to ascertain whether DWI aided in clinical diagnosis or management. Of 103 scans obtained a mean of 10.4 days after symptom onset, DWI detected six lesions not seen on T2WI and discriminated two new infarcts from old lesions. DWI was most useful within 48 hours of the ictus. The evolution of ADC values and T2 ratios was evaluated in 26 cases with known symptom onset times. ADC values were low at less than 1 week after stroke onset and became elevated at chronic time points. T2 ratios were near normal acutely, increasing thereafter. DWI was superior to T2W MRI in detecting acute stroke, whereas both techniques assisted in determining lesion age.

    View details for Web of Science ID A1997WZ80900004

    View details for PubMedID 9153518

  • Intracavernous anterior cerebral artery origin with associated arteriovenous malformations: A developmental analysis: Case report NEUROSURGERY Singer, R. J., Abe, T., Taylor, W. H., Marks, M. P., Norbash, A. M. 1997; 40 (4): 829-831


    This case demonstrates an unusual association between arteriovenous malformations and an intracavernous anterior cerebral artery origin. To the best of our knowledge, this relationship has not been previously described. Identification and understanding of this relationship are important in pre-embolization and surgical planning and in offering some insight into neurovascular development.The patient presented with severe recurring headaches and an otherwise nonfocal neurological examination. He maintained a stable neurological course throughout evaluation and therapy.The patient underwent endovascular embolization of the arteriovenous malformations without consequence. He was then scheduled for radiosurgical treatment planning.This case demonstrates an unusual neurovascular anomaly with associated arteriovenous malformations. To the best of our knowledge, this is the first reported case of such an association. An understanding of anomalous angioarchitecture and neurovascular development is essential for prudent endov ascular and surgical planning.

    View details for Web of Science ID A1997WQ29900084

    View details for PubMedID 9092857

  • Covered stent placement for neurovascular disease AMERICAN JOURNAL OF NEURORADIOLOGY Singer, R. J., Dake, M. D., Norbash, A., Abe, T., Marcellus, M. L., Marks, M. P. 1997; 18 (3): 507-509


    We describe an endovascular technique in which covered stents were used to occlude a parent vessel. In one patient, with a giant paraclinoid aneurysm, a Gortex-covered Palmaz stent was used to occlude the cervical internal carotid artery and to create thrombosis in the aneurysm. In the second patient, with a high-flow vertebrojugular fistula, a hooded stent provided definitive treatment after an attempt to close the fistula by detachable balloon therapy failed. Follow-up of these patients revealed stable stent position and no untoward effects of permanent vessel occlusion.

    View details for Web of Science ID A1997WQ52300019

    View details for PubMedID 9090412

  • Arterial vascular abnormality accompanying cerebral cortical dysplasia AMERICAN JOURNAL OF NEURORADIOLOGY Abe, T., Singer, R. J., Marks, M. P., Kojima, K., Watanabe, M., Uchida, M., Hayabuchi, N. 1997; 18 (1): 144-146


    We report a case of dysplastic arterial vascular abnormality in a 32-year-old man with overlying neuronal cell migration disorder. MR images showed a thickened left insular cortex adjacent to the abnormal vascular network. These findings suggest the possibility of leptomeningeal damage during neuronal cell migration as the cause of the overlying vasculopathy. The true pathogenesis of these seemingly associated abnormalities is unknown.

    View details for Web of Science ID A1997WC66800020

    View details for PubMedID 9010533

  • Computed tomography angiography NEUROIMAGING CLINICS OF NORTH AMERICA Marks, M. P. 1996; 6 (4): 899-?


    Spiral computed tomography angiography is a relatively new noninvasive technique capable of rapid imaging of the carotid artery. Computed tomography angiography usually is performed in a 30-second scan time and images iodinated contrast as it fills the vascular lumen. Studies comparing computed tomography angiography with conventional angiography show sensitivities and specificities that rival any of the other noninvasive imaging techniques for the detection of carotid artery stenosis and occlusion.

    View details for Web of Science ID A1996VP57800010

    View details for PubMedID 8824139

  • Computed tomography slice-by-slice target-volume delineation for stereotactic proton irradiation of large intracranial arteriovenous malformations: An iterative approach using angiography, computed tomography, and magnetic resonance imaging INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Levy, R. P., Schulte, R. W., Frankel, K. A., Steinberg, G. K., Marks, M. P., Lane, B., Heilbronn, L. H., Meinass, H. J., Galindo, R. A., Slater, J. D., Slater, J. M. 1996; 35 (3): 555-564


    Target-volume delineation for stereotactic irradiation is problematic for large and irregularly shaped arteriovenous malformations (AVMs). The purpose of this report is to quantify modifications in the target volume that result from iterative treatment planning that incorporates multimodality imaging data.Stereotactic neuroimaging procedures were performed for 20 consecutive patients with AVM volumes > 10 cm3. Angiographically defined extrema were transformed into computed tomography (CT) space. The resulting target contours were then modified by a multidisciplinary treatment planning team after iterative review of angiographic, CT, and magnetic resonance imaging (MRI) data. Volumes of interest and dose-volume histograms for proton irradiation were calculated before and after iterative target delineation.Initial (angiographically defined) target volumes ranged from 15.3 to 96.1 cm3 (mean, 43.6 cm3). Final (iteratively defined) target volumes ranged from 10.7 to 114.0 cm3 (mean, 38.4 cm3). The volume of presumed normal tissue excluded by iterative planning ranged from 2.6 to 47.0 cm3 (mean, 15.5 cm3). Initially untargeted AVM, most commonly obscured by embolization material, was identified in all cases (range, 0.3 to 57.8 cm3; mean, 10.3 cm3). Corresponding dose-volume histograms demonstrated marked differences regarding lesion coverage and sparing of normal tissue structures.Iterative target-volume delineation resulted in significant modifications from initial, angiographically defined target volumes. Substantial amounts of apparently normal tissue were excluded from the final target, and additional abnormal vascular structures were identified for incorporation. We conclude that an iterative multimodality approach to target-volume delineation may improve the overall results for stereotactic irradiation of large and complex AVMs.

    View details for Web of Science ID A1996UT72400018

    View details for PubMedID 8655380

  • Surgical resection of large incompletely treated intracranial arteriovenous malformations following stereotactic radiosurgery JOURNAL OF NEUROSURGERY Steinberg, G. K., Chang, S. D., Levy, R. P., Marks, M. P., Frankel, K., Marcellus, M. 1996; 84 (6): 920-928


    Although radiosurgery is effective in obliterating small arteriovenous malformations (AVMs), it has a lower success rate for thrombosing larger AVMs. The authors surgically resected AVMs from 33 patients ranging in age from 7 to 64 years (mean 30.4 years) 1 to 11 years after radiosurgery. Initial AVM volumes were 0.8 to 117 cm3 (mean 21.6 cm3), and doses ranged from 4.6 to 45 GyE (mean 21.2 GyE). Of 27 AVMs in eloquent or critical areas, 10 were located in language, motor, sensory, or visual cortex, 11 in the basal ganglia/thalamus, one each in the brainstem, hypothalamus, and cerebellum, and three in the corpus callosum. Venous drainage was deep in 13, superficial in 12, or both in eight lesions. Spetzler-Martin grades were II in one, III in 12, IV in 16, and V in four patients. Eight patients experienced rebleeding after radiosurgery but prior to surgery. Three patients developed radiation necrosis and 25 underwent endovascular embolization prior to surgery. At surgery the AVMs were found to be markedly less vascular, partially thrombosed, and more easily resected, compared to those seen in patients who had not undergone radiosurgery. Pathological investigation showed endothelial proliferation with hyaline and calcium in vessel walls. There was partial or complete thrombosis of some AVM vessels and evidence of vessel and brain necrosis in many cases. Complete resection was achieved in 28 patients and partial resection in five. Clinical outcome was excellent or good in 31 cases, and two patients died of rebleeding from residual AVM. Four patients' conditions worsened following microsurgical resection. Final clinical outcome was largely related to the pretreatment grade. Radiosurgery several years prior to open microsurgery may prove to be a useful adjunct in treating unusually large and complex AVMs.

    View details for Web of Science ID A1996UM58700003

    View details for PubMedID 8847585

  • Acute and chronic stroke: Navigated spin-echo diffusion-weighted MR imaging RADIOLOGY Marks, M. P., deCrespigny, A., Lentz, D., Enzmann, D. R., Albers, G. W., Moseley, M. E. 1996; 199 (2): 403-408


    The authors evaluated a phase-navigated spin-echo (SE) motion-correction sequence for use at diffusion-weighted (DW) magnetic resonance (MR) imaging after cerebral infarction.Twenty-nine patients underwent 32 conventional T2-weighted fast SE and SE DW imaging after stroke (n=25), transient ischemic attack (n=3), or reversible ischemic neurologic deficit (n=1). Imaging was performed in a standard head holder with standard padding. Apparent diffusion coefficient (ADC) maps were constructed.DW images depicted high signal intensity compatible with localization of the ischemic symptoms in all cases. Lesions were depicted more clearly on DW than on T2-weighted images. On DW images, acute infarct ADC values were uniformly low (mean, 0.401x10(-5) cm2/sec =+/- 0.143 [standard deviation]) compared with control ADC values (mean, 0.754x10(-5) cm2/sec +/- 0.201). ADC values of chronic infarcts were supranormal (mean, 1.591x10(-5) cm2/sec +/- 0.840) compared with control values (mean, 0.788x10(-5) cm2/sec +/- 0.166). DW imaging did not show a change after transient ischemic attack. with reversible ischemic neurologic deficit, however, hyperintensity on DW images and low ADC resolved after symptoms abated.Clinical phase-navigated SE DW imaging improved early diagnosis of stroke and helped differentiate acute from chronic stroke. Changes on DW images are reversed after symptoms resolve.

    View details for Web of Science ID A1996UG01100018

    View details for PubMedID 8668785

  • Vertebral artery stenting following percutaneous transluminal angioplasty - Technical note JOURNAL OF NEUROSURGERY Storey, G. S., Marks, M. P., Dake, M., Norbash, A. M., Steinberg, G. K. 1996; 84 (5): 883-887


    The authors report initial results and follow up using stent placement to treat atherosclerotic stenosis in vertebral arteries. Three patients with severe atherosclerotic vascular disease underwent vertebral artery stent placement using a balloon expandable stent. Medical therapy (aspirin and warfarin) and conventional percutaneous angioplasty failed to resolve the disease and the patients developed symptomatic restenosis within 3 months of angioplasty. Two patients had symptoms of anterior circulation ischemia with carotid artery occlusions and reduced supply to the anterior circulation from the stenosed vertebral arteries. One patient had recurrent posterior circulation symptoms. Stents were successfully placed in all three, resulting in immediate reversal of stenosis and resolution of symptoms. Clinical follow-up study (mean 9 months) has shown no recurrent symptoms in the patient with posterior circulation symptoms, but the two patients with anterior circulation ischemia did develop recurrent symptoms. Angiographic follow up in these two patients at 3 months and 1 year, however, demonstrated continued patency of vertebral artery lumina. They underwent extracranial-intracranial bypass surgery to relieve their symptoms. This experience suggests stents can be placed without complication in the proximal vertebral arteries and may have an adjunctive role in the treatment of atherosclerotic cerebrovascular disease following unsuccessful angioplasty.

    View details for Web of Science ID A1996UG54000028

    View details for PubMedID 8622166

  • Cost-effectiveness of endovascular therapy in the surgical management of cerebral arteriovenous malformations AMERICAN JOURNAL OF NEURORADIOLOGY Jordan, J. E., Marks, M. P., Lane, B., Steinberg, G. K. 1996; 17 (2): 247-254


    To determine the economic effect of endovascular therapy in conjunction with surgery for cerebral arteriovenous malformations.Twenty-five patients with arteriovenous malformations treated with embolization and surgical excision or embolization alone were compared with reported results in 475 patients who underwent surgery only. Respective mean morbidity and mortality rates were calculated and a cost-effectiveness analysis was performed in terms of costs of hospitalization, professional fees, and other direct procedural and indirect costs. Quality-adjusted life-years saved were also calculated.The net effective treatment cost per cure was $71 366 (in 1992 dollars) for embolization and surgery compared with $78 506 for surgery alone. This resulted in a 9% average savings per treated patient. Cost per quality-adjusted life-year calculations resulted in a cost of $6734 for embolization and surgery and $9814 for surgical treatment alone, with savings as high as 34% when endovascular therapy was used.Endovascular therapy in conjunction with surgery resulted in significant economic benefits for treatment of cerebral arteriovenous malformations.

    View details for Web of Science ID A1996TW23400015

    View details for PubMedID 8938294

  • MELAS: Clinical and pathologic correlations with MRI, xenon/CT, and MR spectroscopy NEUROLOGY Clark, J. M., Marks, M. P., Adalsteinsson, E., Spielman, D. M., Shuster, D., Horoupian, D., Albers, G. W. 1996; 46 (1): 223-227


    We describe the clinical, imaging, and pathologic findings in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient experienced her first stroke-like episode at age forty-four. Brain MRI, obtained at symptom onset, at 3 weeks, and at 1 year, revealed migrating T2-weighted hyperintensities in the temporal/parietal and occipital cortices and later revealed atrophy. Abnormal cerebrovascular reserve was evident on xenon/CT four days after the first MRI. MR spectroscopy at 1 year revealed increased lactate in both the occipital and temporal lobes. Histologic sections demonstrated spongy degeneration of the cortex that was most prominent at the crests of the gyri. Electron microscopy of the blood vessels showed increased numbers of abnormal mitochondria within the vascular smooth muscle and in endothelial cells. We hypothesize that the stroke-like episodes in MELAS may be due to impaired autoregulation secondary to the impaired metabolic activity of mitochondria in the endothelial and smooth muscle cells of blood vessels.

    View details for Web of Science ID A1996TR67100045

    View details for PubMedID 8559380

  • Xe/CT evaluation of chronic ischemic states 3rd International Conference on Xenon/CT CBF Marks, M. P. WILEY-BLACKWELL PUBLISHING, INC. 1996: 68–68
  • Techniques for reducing interventional neuroradiologic skin dose: Tube position rotation and supplemental beam filtration AMERICAN JOURNAL OF NEURORADIOLOGY Norbash, A. M., BUSICK, D., Marks, M. P. 1996; 17 (1): 41-49


    To limit the side effects of interventional neuroradiologic radiation, such as epilation, by applying a technique involving tube position rotation and by adding a supplemental inexpensive primary beam filter; and to show the dose effect of modifying technical factors.Combined skin dose from fluoroscopy and digital subtraction angiography was measured with an array of 16 thermoluminescent dosimeters during interventional neuroradiologic procedures in 12 control subjects, in 18 patients whose procedures included addition of an inexpensive primary beam filter (0.5 mm aluminum/0.076 mm copper), and in 10 patients in whom the tube position was rotated, additional primary beam filtration was used, and close attention was paid to technique.Maximum thermoluminescent dosimetric measurements obtained with existing machine filtration ranged from 0.31 to 2.70 Gy in the control group (mean, 1.51 +/- 0.88); 0.25 to 2.42 Gy in the group with additional filtration alone (mean 0.96 + 0.64; average dose reduction, 36%); and 0.13 to 1.23 Gy in the group with additional filtration, tube position rotation, and close attention to technique (mean, 0.58 +/- 0.34; average dose reduction, 63%). Differences were statistically significant.Greater than 50% skin dose reductions were documented during interventional neuroradiologic procedures by combining tube position rotation, supplemental primary beam filtration, and technical modifications.

    View details for Web of Science ID A1996TP96800008

    View details for PubMedID 8770248

  • In vitro evaluation of coils for endovascular therapy AMERICAN JOURNAL OF NEURORADIOLOGY Marks, M. P., Tsai, C., CHEE, H. 1996; 17 (1): 29-34


    To evaluate the physical characteristics and behavior of coils for endovascular therapy.Mechanically detachable coils were constructed with simple helical (4 mm X 10 cm and 8 mm X 30 cm) and pretzel shapes (4 mm X 5 cm) made from three metals using 0.003- and 0.004-in wire. Stiffness or pliability, frictional resistance, shape memory, and coil stability were evaluated in vitro.The 0.004-in wire stock coils proved significantly stiffer when compared with the 0.003-in coils. Tungsten coils proved least pliable; platinum coils were intermediate in stiffness; and nitinol coils were softest. Frictional resistance in the catheter was greatest for stiffer coils. The 5-cm pretzel coil consistently created more frictional force than the 10- or 30-cm simple helical coils. Despite a shorter length, the 4-mm simple helical coil exerted more frictional force than the 8-mm coil. Stiffer metal coils constructed of larger-diameter wire (0.004 in) were more stable than softer coils.Stiffer coils exert greater frictional forces within the catheter and a greater resistive force during bending but are more stable after placement. Frictional forces also depend on the complex three-dimensional shape of the coil and the diameter of the turns in that shape rather than coil length. These data suggest that a family of coils of different metals is optimal for varied intravascular needs.

    View details for Web of Science ID A1996TP96800006

    View details for PubMedID 8770246

  • Clinical aspects of DWI NMR IN BIOMEDICINE Moseley, M. E., Butts, K., Yenari, M. A., Marks, M., deCrespigny, A. 1995; 8 (7-8): 387-396


    Diffusion-weighted MR imaging (DWI) is capable of imaging ischemia-induced changes in water protons in either animal or man. Technical developments are described that allow the routine clinical utility of DWI in a stroke setting to provide objective criteria beyond the neurological exam by which the pathophysiology of stroke can be evaluated. To date, DWI has provided unique information concerning detection and evaluation of acute, symptomatic lesions from older, chronic strokes, detection and localization of small deep infarcts and reversible ischemic neurologic deficits and transient ischemia. Clinical DWI studies suggest that the temporal behaviour of ADC can critically improve the evaluation of clinical ischemia.

    View details for Web of Science ID A1995UL58700011

    View details for PubMedID 8739275

  • Vascular malformations. Magnetic resonance imaging clinics of North America Marks, M. P. 1995; 3 (3): 485-491


    MR angiography supplements conventional MR imaging in the diagnosis and evaluation of patients with arteriovenous malformations. MR angiography may also have a significant role in the planning and follow up of patients undergoing radiosurgical treatment. The technique has a much more limited role in the evaluation of vascular formations with low flow or no flow, such as developmental venous anomalies, cavernous malformations, and capillary telangiectasis.

    View details for PubMedID 7584252



    To evaluate the use of spiral computed tomographic (CT) angiography in the analysis of the arteries of the circle of Willis and compare these results with magnetic resonance (MR) angiography and conventional angiography.The results in 17 patients who underwent examination were prospectively studied in a blinded fashion. The presence or absence of the arteries of the circle of Willis was determined by using maximum intensity projection reconstructions from CT angiography and MR angiography. These results were compared with results from conventional angiography.Similar sensitivities were determined for CT angiography (88.5%) and MR angiography (85.5%); however, MR angiography was found to differ significantly (P = .005) from conventional angiography. No significant differences (P > .05) were found between the two modalities and conventional angiography in the detection of the anterior, middle, or posterior cerebral arteries or the anterior communicating artery.Spiral CT angiography is highly sensitive in the detection of arterial anatomy in the circle of Willis and is a reliable alternative to MR angiography.

    View details for Web of Science ID A1995QU71700026

    View details for PubMedID 7724764



    The principal barrier to clinical application of diffusion-weighted MR imaging is the severe image degradation caused by patient motion. One way to compensate for motion effects is the use of a "navigator echo" phase correction scheme. In this work, a modification of this technique is introduced, in which the phase correction step is performed in the frequency domain (i.e., after the readout Fourier transform). This significantly improves the robustness of the navigator echo approach and, when combined with cardiac gating, allows diagnostic quality diffusion-weighted images of the brain to be routinely obtained on standard clinical scanner hardware. The technique was evaluated in phantom studies and in 23 humans (3 normal volunteers and 20 patients). Diffusion anisotropy and apparent diffusion coefficient maps were generated from the image data and showed decreased apparent diffusion in acute stroke lesions and, in several cases, increased apparent diffusion in chronic stroke lesions.

    View details for Web of Science ID A1995QV05800017

    View details for PubMedID 7596277



    To compare the detectability of vertebral metastatic disease on T1-weighted, short-inversion-time inversion recovery (STIR), fast spin-echo (FSE), fat-saturated FSE, and inversion recovery FSE (IRFSE) MR sequences using percent contrast and contrast-to-noise ratios.Patients with proved metastatic disease underwent imaging on a 1.5-T MR system with sagittal T1-weighted (800/20/2 [repetition time/echo time/excitations]) (91 patients), STIR (1400/43/2; inversion time, 140) (91 patients), FSE (4000/180/2) (46 patients), fat-saturated FSE (4000/180/2) (16 patients), and IRFSE (29 patients) sequences. Percent contrast and contrast-to-noise ratio were calculated for the lesions. The number of metastatic lesions detected with each of the pulse sequences was also calculated.Mean percent contrast was, for T1-weighted sequence, -42.2 +/- 1%; STIR, 262 +/- 34%; FSE, 121 +/- 21%; fat-saturated FSE, 182 +/- 6%; and IRFSE, 272 +/- 47%. The mean contrast-to-noise ratio for T1-weighted was -4.63 +/- 1.7; STIR, 10.8 +/- .98; FSE, 4.16 +/- .76; fat-saturated FSE, 4.87 +/- .19; and IRFSE, 5.2 +/- .87. STIR and IRFSE showed the highest number of lesions, followed by T1-weighted, fat-saturated FSE, and FSE sequences. T1-weighted sequences showed 94%, FSE 55%, and fat-saturated FSE 78% of the lesions detected. Epidural metastatic lesions were better depicted on T1-weighted, FSE, and fat-saturated FSE sequences.STIR was superior to both T1-weighted and FSE (with and without fat saturation) for detection of metastatic lesions, in terms of both percent contrast and contrast-to-noise ratio and visibility. IRFSE was equal to STIR for the detection of metastasis by both subjective and objective criteria. T1-weighted, FSE, and fat-saturated FSE sequences were superior to STIR and IRFSE in the detection of epidural metastatic disease. IRFSE provided faster scanning time, which could be translated into greater resolution.

    View details for Web of Science ID A1995QG57400009

    View details for PubMedID 7726074



    We report two cases in which combined surgical clipping and endovascular coils have been used to treat intracranial aneurysms. In one case, a 59-year-old woman with multiple episodes of subarachnoid hemorrhage had an anterior communicating artery aneurysm, which was initially treated with coils and then clipped to occlude the aneurysm securely. In the second case, a broad-based cavernous aneurysm could not be completely surgically occluded, but surgical clipping did decrease the aneurysm neck size, allowing it to be successfully treated with coils.

    View details for Web of Science ID A1995QB20600006

    View details for PubMedID 7900585

  • Assessment of patients with arteriovenous malformations 2nd International Conference on Xenon/CT CBF Marks, M. P. FUTURA PUBL CO INC. 1995: 223–228


    Computed tomography scans of the head and early neurodevelopmental assessment (Bayley Scales of Infant development) were recorded for 24 surviving infants who received venovenous extracorporeal membrane oxygenation and were compared with those of infants treated with venoarterial bypass matched by diagnosis and oxygenation index before extracorporeal membrane oxygenation. A comparable neuroradiographic and early neurodevelopmental outcome was documented for survivors of venoarterial and venovenous extracorporeal membrane oxygenation.

    View details for Web of Science ID A1994PA95200025

    View details for PubMedID 8040782

  • THE ANATOMY OF THE POSTERIOR COMMUNICATING ARTERY AS A RISK FACTOR FOR ISCHEMIC CEREBRAL INFARCTION NEW ENGLAND JOURNAL OF MEDICINE Schomer, D. F., Marks, M. P., Steinberg, G. K., Johnstone, I. M., Boothroyd, D. B., Ross, M. R., Pelc, N. J., Enzmann, D. R. 1994; 330 (22): 1565-1570


    After the occlusion of an internal carotid artery the principal source of collateral flow is through the arteries of the circle of Willis, but the size and patency of these arteries are quite variable. Study of the anatomy of the collateral pathways in patients with internal-carotid-artery occlusion with or without infarction in the watershed area of the deep white matter may identify patterns that afford protection from ischemic infarction.Using conventional magnetic resonance imaging and three-dimensional phase-contrast magnetic resonance angiography, we evaluated 29 consecutive patients (32 hemispheres at risk) with angiographically proved occlusion of the internal carotid artery. Four collateral pathways to the occluded vessel were evaluated: the proximal segment of the anterior cerebral artery, the posterior communicating artery, the ophthalmic artery, and leptomeningeal collateral vessels from the posterior cerebral artery.Only features of the ipsilateral posterior communicating artery were related to the risk of watershed infarction. The presence of posterior communicating arteries measuring at least 1 mm in diameter was associated with the absence of watershed infarction (13 hemispheres, no infarcts; P < 0.001). Conversely, there were 4 watershed infarcts in the 6 hemispheres with posterior communicating arteries measuring less than 1 mm in diameter and 10 infarcts in the 13 hemispheres with no detectable flow in the ipsilateral posterior communicating artery.A small (< 1 mm in diameter) or absent ipsilateral posterior communicating artery is a risk factor for ischemic cerebral infarction in patients with internal-carotid-artery occlusion.

    View details for Web of Science ID A1994NN21500004

    View details for PubMedID 8177246



    To evaluate mechanically detachable coil designs capable of controlled and instantaneous release within an aneurysm or vascular space.Three mechanically detachable coil designs, clamped ball, looped ribbon, and interlocking cylinder, were evaluated using in vitro and in vivo testing to study reliability of coil release, retractability, and coil behavior in a microcatheters. In vitro tests were performed using a glass side-wall aneurysm model and conventional microcatheters. In vivo experiments in rabbits included aneurysm models (side-wall and bifurcation) and arterial occlusions (carotid and renal).All three designs deployed coils easily and were able to retract coils after partial deployment. Motion was seen in previously released coils and in the catheter when using the clamped ball and looped ribbon designs. The interlocking cylinder design did not cause similar motion. When compared with the other two designs, the interlocking cylinder had significantly greater separation forces between coil pusher and coil while in the catheter. Frictional forces within the catheter were lower for the interlocking cylinder mechanically detachable coil design than for a commercially available conventional coil and coil pusher system. During in vivo testing, the mechanically detachable coil design operated smoothly in the catheter, providing good release and retraction in aneurysms and straight vessels.The interlocking cylinder mechanically detachable coil design is superior to the other two tested designs. The mechanically detachable coil was reliably delivered and detached in in vivo testing for the treatment of aneurysms and for the occlusion of blood vessels.

    View details for Web of Science ID A1994NL03200004

    View details for PubMedID 8059648



    To report initial clinical experience with stent placement in the cerebrovascular circulation.Four patients underwent arterial or venous stent placement. Two patients had cervical internal carotid artery dissections, with aneurysms and stenoses of the distal cervical carotid artery. Two patients had venous occlusive disease involving the major dural sinuses, with substantial pressure gradients across the stenoses.Immediately after stent placement, the true arterial lumina returned to normal diameter and both carotid aneurysms were more than 90% occluded. Follow-up angiography demonstrated continued improvement in the arterial aneurysms. Both patients with dural sinus venous occlusive disease showed substantial improvement of the sinus stenoses and substantial reversal of the pressure gradients after venous stent placement. At follow-up, these patients have done well.This preliminary experience suggests there may be a role for stents in the management of arterial and venous cerebrovascular disease, including carotid artery dissection and venous occlusive disease.

    View details for Web of Science ID A1994NG95500026

    View details for PubMedID 8153318



    To determine whether there is a physiologic explanation for the predisposition of patients with certain angiographic characteristics to symptoms of hemorrhage and steal.Superselective transcatheter feeding arterial pressure and mean arterial pressure measurements were obtained before embolotherapy in 32 patients with cerebral arteriovenous malformations. Pressures were correlated with previously described angioarchitectural characteristics predisposing to hemorrhage and steal. These included size of the arteriovenous malformation, feeding artery length, venous drainage pattern, and angiomatous change.The feeding arterial pressure and feeding arterial pressure/mean arterial pressure ratios were significantly decreased in patients with angiomatous change. Feeding arterial pressure and feeding arterial pressure/mean arterial pressure ratios progressively decreased as lesions went from peripheral, to mixed, to central venous drainage. A trend for lower feeding arterial pressure was also demonstrated with greater feeding pedicle length. A statistically significant correlation could not be demonstrated between feeding arterial pressure or feeding arterial pressure/mean arterial pressure ratios and size of the arteriovenous malformation, hemorrhage, or symptoms of steal.Feeding arterial pressure measurements help provide a physiologic basis for the relationship between certain angiographic characteristics and hemorrhage and steal symptoms in patients with arteriovenous malformation.

    View details for Web of Science ID A1994NL03200002

    View details for PubMedID 8059646



    Recent experimental and clinical reports suggest that the intracisternal administration of recombinant tissue plasminogen activator (tPA) within 72 hours of subarachnoid hemorrhage decreases the incidence of severe angiographic and clinical vasospasm. In this report, we present four of eight patients with aneurysmal subarachnoid hemorrhage who developed angiographic and clinical vasospasm with delayed neurological deterioration, despite the use of intracisternal tPA after early aneurysm clipping. One patient did not clear her massive subarachnoid hemorrhage with tPA; one patient had extremely poor collateral flow with occlusion of one cervical internal carotid artery and 80% stenosis of the other cervical internal carotid artery; the other two patients had a subarachnoid hemorrhage 7 to 12 days after their sentinel hemorrhage. Three patients ultimately made excellent or good recoveries, and one was left with hemiparesis. The four other patients treated by this protocol did not develop vasospasm. We conclude that intracisternal tPA may not prevent vasospasm in certain patients. This may relate to inadequate clearing of the subarachnoid clot, pre-existing poor collateral supply, or the occurrence of prior subarachnoid hemorrhage.

    View details for Web of Science ID A1994NH38600010

    View details for PubMedID 8052377



    To measure mean blood flow in individual cerebral arteries (carotid, basilar, anterior cerebral, middle cerebral, and posterior cerebral) using a cine phase contrast MR pulse sequence.Ten healthy volunteers (22 to 38 years of age) were studied. The cine phase-contrast section was positioned perpendicular to the vessel of interest using oblique scanning planes. This pulse sequence used a velocity encoding range of 60 to 250 cm/sec. From the velocity and area measurements on the cine images, mean blood flow was calculated in milliliters per minute and milliliters per cardiac cycle. In the same subjects, transcranial Doppler measurements of blood velocity in these same vessels were also obtained.There was no difference in blood flow in the paired cerebral arteries. Carotid arteries had mean blood flow in the range of 4.8 +/- 0.4 ml/cycle, the basilar artery 2.4 +/- 0.2 ml/cycle, the middle cerebral artery 1.8 +/- 0.2 ml/cycle, the distal anterior cerebral artery 0.6 +/- 0.1 ml/cycle, and the posterior cerebral artery 0.8 +/- 0.1 ml/cycle. Overall, there was poor correlation between MR-measured and transcranial Doppler-measured peak velocity.Although careful attention to technical detail is required, mean blood flow measurements in individual cerebral vessels is feasible using a cine phase-contrast MR pulse sequence.

    View details for Web of Science ID A1994MT25700021

    View details for PubMedID 8141043

  • Neuropsychological improvements following endovascular embolization of arteriovenous malformation. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Bowen, M., Steinberg, G. K., Marks, M., ACOSTA, Y. 1994; 4 (3): 194-199


    Two right-handed patients with large, left-hemisphere arteriovenous malformations (AVM) underwent serial endovascular embolization and neuropsychological testing procedures. One patient presented with hemorrhage, hemiplegia, and aphasia; the other patient presented with a seizure only with multiple cognitive impairments. Case 1 was assessed for motor-sensory skills in the left hand and for visual recall (nondominant hemisphere). Case 2 was administered a more global assessment of cognitive functions. Both patients demonstrated significant improvements in neuropsychological functions 1 month following endovascular embolization with >50% reduction in AVM volume. The nature and extent of these improvements are discussed with respect to intervention-related, reversed impairments.

    View details for DOI 10.1016/S1052-3057(10)80186-7

    View details for PubMedID 26486060

  • Migraine and vertebrobasilar dissection: Case reports. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Yenari, M. A., Steinberg, G. K., Marks, M. P. 1994; 4 (1): 36-41


    We report two patients with chronic migraine headaches who developed vertebrobasilar arterial dissections. In both cases, there was a change in both the character and location of the headaches, which prompted further evaluation with magnetic resonance imaging and angiography, which led to the diagnosis. Other possible risk factors for dissection in these patients included hypertension, exercise, and chiropractic manipulation. Both patients were treated with anticoagulation and recovered with little to no neurologic deficit. A review of the literature relating migraine and arterial dissection suggests that there may be an association. Although more extensive controlled studies are needed to demonstrate the significance of this association, we suggest that the diagnosis of cervicocranial arterial dissection be strongly considered in migraine patients who develop an abrupt change in the nature of their headaches.

    View details for DOI 10.1016/S1052-3057(10)80144-2

    View details for PubMedID 26487533



    This is a report of a 37-year-old man who, while lifting a heavy box, developed severe low-back pain radiating into the right anterior thigh. The only clinical signs were paraspinal muscle spasm and a positive femoral nerve stretch test on the right. An electromyographic study demonstrated denervation in the right L2, L3, and L4 myotomes and paraspinal muscles. Magnetic resonance imaging (MRI) showed a large L1-2 anterior epidural hematoma compressing the spinal cord. The patient's pain gradually improved with conservative management and he returned to light work after 4 weeks. Repeat electromyographic and MRI studies were normal, indicating a resolution of the radiculopathy and hematoma. The diagnosis and management of spontaneous epidural hematomas are discussed.

    View details for Web of Science ID A1994MT13500015

    View details for PubMedID 8153808



    Cine phase-contrast (PC) magnetic resonance (MR) pulse sequences have been used to measure blood flow in a variety of vessels. Because the cine PC sequence is time-consuming, this prospective study was undertaken to compare it with an ungated PC technique for measuring average blood flow in individual cerebral arteries to potentially achieve substantial time savings. The following cerebral arteries were studied in 10 healthy volunteers: carotid, basilar, middle cerebral, anterior cerebral, and posterior cerebral. Imaging planes were placed perpendicular to the vessel of interest, and velocity encoding, ranging from 40 to 250 cm/sec, was matched to individual arteries. Good correlation between cine and ungated PC blood flow measurements was obtained for both high- and low-flow vessels, with an overall correlation coefficient of .978. The ungated PC sequence, because of its short imaging time, allows measurement of the blood volume flow rate in the circle of Willis in approximately 20 minutes, a clinically acceptable time.

    View details for Web of Science ID A1993LX79600003

    View details for PubMedID 8400555



    The authors describe the use of intraarterial papaverine to treat vasospasm following subarachnoid hemorrhage. Two cases are reported: a 40-year-old woman with a posterior communicating artery aneurysm and a 67-year-old man with a posterior cerebral artery aneurysm. Both patients developed symptomatic, angiographically demonstrated vasospasm that responded to papaverine infusion.

    View details for Web of Science ID A1993LM07000009

    View details for PubMedID 8352152



    Spiral CT allows continuous data to be acquired rapidly, and if a correctly timed IV bolus of contrast material is given, spiral CT angiography can be performed. This study was designed to evaluate spiral CT angiography with maximum-intensity-projection reconstructions for assessing the degree of carotid artery stenosis.Spiral CT angiography (of 28 carotid bifurcations in 14 patients) was compared in a blinded fashion with conventional angiography (of 28 bifurcations) and with two-dimensional time-of-flight MR angiography (of 12 bifurcations) to assess degree of stenosis. A nonblinded comparison of the contour of the lumen at the site of stenosis was then made between conventional angiography, spiral CT angiography, and MR angiography. The degree of stenosis was measured in each internal carotid artery and categorized as mild (< 30%), moderate (30-69%), or severe (70-99%) stenosis or as occlusion. Maximum-intensity-projection images were used for the evaluations; however, if calcification was circumferential and the lumen of the carotid artery could not be analyzed in the area of the calcification, the axial source images were used.The results of CT angiography and conventional angiography agreed overall in 25 (89%) of 28 cases (r = .921, p = .05, Spearman rank correlation). The presence of severe stenosis or occlusion was correctly identified in seven of seven cases. In the moderate and mild stenosis categories, 18 (86%) of 21 were correctly identified (r = .802, p = .122). Three internal carotid arteries (11%) had circumferential calcification that necessitated evaluation of the axial source images, and the measurements obtained from the axial images agreed well with angiographic findings. MR angiography correlated well with the various categories of stenosis. However, when we compared MR angiography directly with CT angiography and conventional angiography, we found that the degree of stenosis was overestimated when MR angiography was used.Our results show that spiral CT angiography shows normal and abnormal carotid anatomy well when compared with conventional angiography. The short examination time and clear depiction of arterial caliber in areas of stenosis are significant advantages of spiral CT angiography compared with MR angiography.

    View details for Web of Science ID A1993LW01300025

    View details for PubMedID 8498231


    View details for Web of Science ID A1993KM93500032

    View details for PubMedID 8430563



    Previous reports of embolization of cerebral arteriovenous malformations (AVMs) have evaluated the technique as adjunctive therapy prior to surgery or radiosurgery; our aim is to assess the role of embolization following radiosurgery.Six patients previously treated with radiosurgery and showing no response as judged by cerebral angiography were embolized 24 to 55 months (mean 34.3 months) after initial radiosurgery.In five of six, a significant volume reduction was achieved ranging from 60%-100% (mean 74%). One patient was treated with embolization alone and the AVM has remained fully thrombosed 2 years after treatment. Three patients underwent surgical resection for cure after embolization, and two patients had repeat radiosurgery to a significantly smaller AVM volume. One patient had an asymptomatic carotid dissection at embolization; however, no clinically apparent complications occurred in the treatment group.Embolization can be used after radiosurgery to assist in the management of those AVMs that have not responded to initial treatment.

    View details for Web of Science ID A1993KR57000004

    View details for PubMedID 8456702


    View details for Web of Science ID A1993KG28900014

    View details for PubMedID 8470393

  • CRANIAL HYPERTROPHIC INTERSTITIAL NEUROPATHY AMERICAN JOURNAL OF NEURORADIOLOGY Jordan, J. E., Lane, B., Marks, M., Chang, Y., Weinberger, M. 1992; 13 (6): 1552-1554


    The authors describe a patient with complex cranial neuropathy caused by pathologically proved hypertrophic interstitial neuropathy. Plain and contrast-enhanced MR studies were performed prior to surgical exploration. Surgical complications caused the patient's death and a complete pathology study was done. Though nonspecific, MR proved helpful in determining the extent of disease and areas of anatomic involvement.

    View details for Web of Science ID A1992JY53100011

    View details for PubMedID 1442431

  • CT ANGIOGRAPHY WITH SPIRAL CT AND MAXIMUM INTENSITY PROJECTION RADIOLOGY Napel, S., Marks, M. P., Rubin, G. D., Dake, M. D., McDonnell, C. H., Song, S. M., Enzmann, D. R., Jeffrey, R. B. 1992; 185 (2): 607-610


    The authors describe a technique for obtaining angiographic images by means of spiral computed tomography (CT), preprocessing of reconstructed three-dimensional sections to suppress bone, and maximum intensity projection. The technique has some limitations, but preliminary results in 48 patients have shown excellent anatomic correlation with conventional angiography in studies of the abdomen, the circle of Willis in the brain, and the extracranial carotid arteries. With continued development and evaluation, CT angiography may prove useful as a screening tool or replacement for conventional angiography in some patients.

    View details for Web of Science ID A1992JV36000058

    View details for PubMedID 1410382

  • Spiral CT creates 3-D neuro, body angiograms. Diagnostic imaging Rubin, G. D., Napel, S., Dake, M. D., Walker, P. J., McDonnell, C. H., Marks, M. P., Jeffrey, R. B. 1992; 14 (8): 66-74

    View details for PubMedID 10147535



    This study assessed the ability of magnetic resonance (MR) imaging to identify vascular characteristics of cerebral arteriovenous malformations (AVMs) which are predictive of hemorrhage. The study also evaluated the sensitivity and specificity of spin-echo (SE) and gradient-recalled-echo (GRE) imaging in the detection of prior clinical hemorrhage on the basis of location of the hemorrhage (parenchymal, intraventricular, or subarachnoid). Fifty patients with high-flow AVMs were evaluated. Twenty-four (48%) patients had prior clinical hemorrhage documented at computed tomography or MR imaging at the time of bleeding. Central venous drainage (P less than .001), central AVM location (P less than .001), and peri- or intraventricular AVM location (P less than .01) correlated positively with prior clinical hemorrhage. Intranidus aneurysms and angiomatous change could not be detected with MR. Nineteen of the 24 patients with prior hemorrhage underwent both SE and GRE imaging. Hypointensity, indicating the presence of iron from prior hemorrhage, was demonstrated in 14 of 19 T2-weighted SE images (sensitivity, 74%) and in 18 of 19 GRE images (sensitivity, 95%). No patient without a prior episode of clinical bleeding demonstrated evidence of iron deposition at MR imaging (specificity, 100%).

    View details for Web of Science ID A1992HV57800026

    View details for PubMedID 1584926



    Patients with cerebral arteriovenous malformations (AVMs) have an increased risk of hemorrhage if an intranidal aneurysm is present. Angiograms from 125 patients with cerebral AVMs were evaluated, and 15 (12%) had intranidal aneurysms. All 15 patients had a history of bleeding. Five patients underwent particulate or liquid embolization before surgical excision of or radiation therapy for the AVM. All aneurysms were thrombosed at the time of embolization. Ten patients underwent radio-surgery alone. Eight of the 10 underwent angiographic follow-up (mean, 33 months); seven patients showed complete obliteration of the AVM without residual aneurysm. Histologic evaluation showed intranidal aneurysms to be thin-walled vascular structures, and they are the likely site for AVM hemorrhage. Embolization is an effective method for achieving thrombosis of the intranidal aneurysm and may be beneficial in patients undergoing radiation therapy because of a long latency period between treatment and thrombosis of the AVM.

    View details for Web of Science ID A1992HQ88400012

    View details for PubMedID 1561335



    This study evaluated a phase-contrast cine magnetic resonance (MR) imaging technique capable of simultaneously allowing determination of velocity and volume flow rate (VFR) in both carotid arteries and the basilar artery. Forty patients were studied; 24 were neurologically normal, and 16 had intracerebral arteriovenous malformations (AVMs). In the normal group, mean basilar flow was significantly less than mean carotid flow. Mean velocity and VFR showed a significant decline with age in the basilar artery. Carotid artery flow and total cerebral blood flow did not decline with age. In the AVM patients, flow and velocity measurements were significantly elevated in all three arteries. Flow in the carotid artery ipsilateral to the AVM was significantly greater than flow in the contralateral carotid artery. VFR increased in all three arteries with increasing AVM volume. Four patients underwent partial embolization, and a corresponding decrease in flow was observed. Phase-contrast cine MR imaging provides rapid, simultaneous, noninvasive velocity and VFR measurement in the major intracranial arteries.

    View details for Web of Science ID A1992HA58600033

    View details for PubMedID 1732966



    Advances in imaging hardware for positron emission tomography and single-photon emission CT, coupled with a wide variety of radiopharmaceutical agents, have allowed these techniques to be used in the evaluation of neoplasm, stroke, epilepsy, and dementia. Cerebral perfusion agents continue to be the mainstay of single-photon emission CT imaging but, in addition to the evaluation of ischemia, it has seen an increasing role in the study of dementia, neuropsychiatric disorders, and seizures. Positron emission tomography scanning has had similar applications but it is playing a greater part in the evaluation of neoplasms, including primary gliomas and pituitary adenomas. Stable-xenon CT has shown value in the study of ischemia associated with meningitis, sickle cell disease, chronic subdural hematomas, and cerebral arteriovenous malformations. MR diffusion imaging shows promise in the evaluation of white matter pathology and some tumors.

    View details for Web of Science ID A1992HD51900013

    View details for PubMedID 1739606

  • Charged-particle radiosurgery for intracranial vascular malformations. Neurosurgery clinics of North America FABRIKANT, J. I., Levy, R. P., Steinberg, G. K., Phillips, M. H., Frankel, K. A., Lyman, J. T., Marks, M. P., Silverberg, G. D. 1992; 3 (1): 99-139


    Heavy charged-particle radiation has unique physical characteristics that offer several advantages over photons and protons for stereotactic radiosurgery of intracranial AVMs. These include improved dose distributions with depth in tissue, small angle of lateral scattering, and sharp distal fall-off of dose in the Bragg ionization peak. Under multi-institutionally approved clinical trials, we have used stereotactic helium-ion Bragg peak radiosurgery to treat approximately 400 patients with symptomatic, surgically inaccessible vascular malformations at the UCB-LBL 184-in synchrocyclotron and bevatron. Treatment planning for stereotactic heavy charged-particle radiosurgery for intracranial vascular disorders integrates anatomic and physical information from the stereotactic cerebral angiogram and stereotactic CT and MR imaging scans for each patient, using computerized treatment-planning calculations for optimal isodose contour distribution. The shape of an intracranial AVM is associated strongly with its treatability and potential clinical outcome. In this respect, heavy charged-particle radiosurgery has distinct advantages over other radiosurgical methods; the unique physical properties allow the shaping of individual beams to encompass the contours of large and complexly shaped AVMs, while sparing important adjacent neural structures. We have had a long-term dose-searching clinical protocol in collaboration with SUMC and UCSF and have followed up over 300 patients for more than 2 years. Initially, treatment doses ranged from 45 GyE to 35 GyE. Currently, total doses up to 25 GyE are delivered to treatment volumes ranging from 0.1 cm3 to 70 cm3. This represents a relatively homogeneous dose distribution, with the 90% isodose surface contoured to the periphery of the lesion; there is considerable protection of normal adjacent brain tissues, and most of the brain receives no radiation exposure. Dose selection depends on the volume, shape, and location of the AVM and several other factors, including the volume of normal brain that must be traversed by the plateau portion of the charged-particle beam. The first 230 patients have been evaluated clinically to the end of 1989. Using the clinical grading of Drake, about 90% of the patients had an excellent or good neurologic grade, about 5% had a poor grade, and about 5% had progression of disease and died, or died as a result of unrelated intercurrent illness. Neuroradiologic follow-up to the end of 1989 indicated the following rates of complete angiographic obliteration 3 years after treatment: 90% to 95% for AVM treatment volumes less than 4 cm3, 90% to 95% for volumes 4 to 14 cm3, and 60% to 70% for volumes greater than 14 cm3.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for PubMedID 1633456


    View details for Web of Science ID A1991GM67500008

    View details for PubMedID 1763727



    In patients with intracerebral arteriovenous malformations (AVMs), symptoms attributed to steal can lead to progressive debilitating deficits. This study was undertaken to determine which morphologic features of the AVM could be correlated with clinical symptoms of steal. Over a 4-year period, 65 patients with intracranial AVMs were evaluated with angiography supplemented by MR (46 cases) and CT (19 cases). Eleven characteristics of AVM vascular architecture were studied; these included size, lobar location, periventricular/intraventricular location, arterial stenosis, arteriovenous fistulae, angiomatous change (the presence of dilated transcortical collateral circulation), venous drainage pattern (central, cortical, mixed), venous stenosis, venous aneurysm or ectasia, venous variation, and delayed drainage. These characteristics were correlated with a history of clinical steal, which was seen in nine (14%) of 65 patients. Three characteristics were found to correlate highly with steal: angiomatous change (p less than .0001), size (p less than .0001), and peripheral venous drainage (p = .045). The mean size of the AVM nidus was 31.3 cm3 for the entire group of patients, 105.0 cm3 for patients with steal, and 19.5 cm3 for those without steal symptoms. Angiomatous change was seen in six (9%) of 65 patients; all six of these had clinical steal. The association of clinical steal with AVM size, angiomatous change, and peripheral venous drainage may contribute to establishing a prognosis and treatment planning. When a patient's symptoms are caused by steal, treatment with subtotal excision or partial embolization may be beneficial.

    View details for Web of Science ID A1991FJ90400022

    View details for PubMedID 2058499



    The stable xenon CT method of measuring cerebral blood flow has been investigated in research studies for over 10 years. Recently, it has been gaining clinical acceptance, primarily owing to a combination of several unique advantages it holds over other cerebral blood flow measurement techniques. The accuracy of this technique in quantifying low cerebral blood flow gives it a unique application in cases of brain death and acute stroke and it can be repeated after an interval of 20 min. making it possible to evaluate autoregulation and cerebrovascular reserve. Furthermore, cerebral blood flow information is directly coupled to CT anatomy. Although it is more difficult to administer than a standard CT scan, careful monitoring can ensure patient safety during the examination. In this article we review the physiologic and technical bases for the clinical application of xenon CT-derived quantitative cerebral blood flow information and discuss the advantages and disadvantages of the technique. We also describe its current clinical applications, including its usefulness in the evaluation of acute stroke, occlusive vascular disease, carotid occlusion testing, vasospasm, arteriovenous malformations, and head trauma management.

    View details for Web of Science ID A1991EZ75200001

    View details for PubMedID 1902015



    89 patients with angiographically documented arteriovenous malformations were treated with helium ion Bragg peak radiation. The rate of complete angiographic obliteration 2 years after radiation was 94% in those lesions smaller than 4 cm3 (2.0 cm in diameter), 75% for those 4-25 cm3 and 39% for those larger than 25 cm3 (3.7 cm in diameter); at 3 years after radiation, the corresponding obliteration rates were 100, 95 and 70%. Major clinical complications occurred in 10 patients (8 permanent, 2 transient) between 3 and 21 months after treatment; all were in the initial stage of the protocol (higher radiation doses). 10 patients bled from residual malformation between 4 and 34 months after treatment. Seizures were improved in 63% and headaches in 68% of patients. Excellent or good clinical outcome was achieved in 94% of patients. Compared to the natural history and risks of surgery for these difficult malformations, we consider these results encouraging. Heavy-charged-particle radiation is a valuable therapy for surgically inaccessible symptomatic cerebral arteriovenous malformations. The current procedure has two disadvantages: the prolonged latent period before complete obliteration and the small risk of serious neurological complications.

    View details for Web of Science ID A1991HG99200005

    View details for PubMedID 1808653



    Between July 1983 and July 1989, we treated 35 patients with surgically inaccessible, symptomatic angiographically occult vascular malformations (AOVMs) using stereotactic heavy-charged-particle radiosurgery. AOVMs were located in the brainstem (19), thalamus or internal capsule (9), basal ganglia (3), deep cerebral hemisphere and motor area (3), or cerebellopontine angle (1). All patients presented with clinical and radiological evidence of previous hemorrhage, usually with multiple episodes of hemorrhage. Treatment volumes ranged from 80 to 15,200 mm3 and treatment doses from 7.7 to 34.6 Gy. Mean follow-up was 40 months, with 31 patients followed for at least 2 years. Clinical outcome was excellent in 46%, good in 34% and poor in 14%; 6% died. Twenty-seven patients in excellent and good condition prior to treatment remained stable or improved neurologically. Two patients initially in poor condition, who had previously received conventional radiotherapy, died at 9 and 14 months after treatment, respectively. Six patients experienced recurrent hemorrhage 2-60 months following treatment. Three of these patients made a complete recovery. Although a larger number of treated patients must be followed over longer periods of time, stereotactic heavy-particle radiotherapy may be a valuable treatment modality for surgically inaccessible intracranial AOVMs.

    View details for Web of Science ID A1991HG99200007

    View details for PubMedID 1808656

  • Endovascular therapy for intracranial vascular lesions. Western journal of medicine Steinberg, G. K., Lane, B., Marks, M. P. 1990; 153 (5): 542-543

    View details for PubMedID 2148042



    The most serious and frequent complication of intracranial arteriovenous malformations (AVMs) is intracranial hemorrhage. Identification of patients at greatest risk for intracranial bleeding would be beneficial. Detailed analysis of vascular architecture was performed in 65 patients with intracranial AVMs to identify the vascular characteristics that correlated with hemorrhage. Fifteen characteristics were assessed. Hemorrhage was present in 45 patients (69%). The following characteristics correlated positively with hemorrhage (Fisher-Irwin exact test): central venous drainage (P less than .0001), periventricular or intraventricular location of the AVM (P = .0002), and intranidal aneurysm (P = .028). The following characteristics correlated negatively with hemorrhage: angiomatous change (P = .0005), peripheral venous drainage (P = .005), and mixed venous drainage (P = .021). Multivariate linear discriminant analysis demonstrated that central venous drainage, angiomatous change (negatively predictive), intranidal aneurysm, and periventricular or intraventricular location of the AVM were the most discriminating or predictive characteristics of hemorrhage. Detailed analysis of the vascular architecture of intracranial AVMs helped identify features that strongly correlate with clinical hemorrhage and have important prognostic implications for the treatment of patients with these lesions.

    View details for Web of Science ID A1990DV57900040

    View details for PubMedID 2389040



    We describe 5 individuals (from three separate families) with a progressive neurological disorder characterized by sensorimotor peripheral polyneuropathy, cranial neuropathies (external ophthalmoplegia, deafness), and the syndrome of chronic intestinal pseudo-obstruction. Magnetic resonance imaging showed widespread abnormality of the cerebral and cerebellar white matter in the 2 patients studied. Autopsy examination in 3 revealed widespread endoneurial fibrosis and demyelination in the peripheral nervous system, possibly secondary to axonal atrophy, and poorly defined changes in cerebral white matter (leukoencephalopathy). The cranial nerves and spinal roots were less severely involved and the neurons in the brainstem and spinal cord were intact. The fatal gastrointestinal dysmotility was due to a severe visceral neuropathy. We suggest that these patients manifested a hereditary disorder with distinctive clinical, radiological, and neuropathological features, and propose the acronym POLIP to emphasize the distinctive tetrad of polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction.

    View details for Web of Science ID A1990DZ68600007

    View details for PubMedID 2173474



    Angiographically occult vascular malformations of the optic nerve and chiasm are extremely rare. Before the advent of magnetic resonance imaging (MRI), it was difficult to diagnose these lesions preoperatively. We report MRI scan findings of optic chiasm cavernous angiomas in two patients with chiasmal syndrome. MRI was useful in localizing the vascular malformation and delineating its characteristics, especially chronic hemorrhage. One patient underwent biopsy of the lesion. The other patient underwent complete microsurgical resection of the malformation with the carbon dioxide laser with preservation of vision. Occult vascular malformations of the optic nerve and chiasm may be a more common cause of visual deterioration than previously recognized. The MRI scan is the imaging modality of choice for diagnosing and following these lesions. In certain patients, these vascular malformations may be amenable to complete surgical removal with stabilization or improvement of visual function.

    View details for Web of Science ID A1990DV49200023

    View details for PubMedID 2234344



    Heavy-charged-particle radiation has several advantages over protons and photons for the treatment of intracranial lesions; it has an improved physical distribution of the dose deep in tissue, a small angle of lateral scattering, and a sharp distal falloff of the dose.We present detailed clinical and radiologic follow-up in 86 patients with symptomatic but surgically inaccessible cerebral arteriovenous malformations that were treated with stereotactic helium-ion Bragg-peak radiation. The doses ranged from 8.8 to 34.6 Gy delivered to volumes of tissue of 0.3 to 70 cm3.Two years after radiation treatment, the rate of complete obliteration of the lesions, as detected angiographically, was 94 percent for lesions smaller than 4 cm3, 75 percent for those of 4 to 25 cm3, and 39 percent for those larger than 25 cm3. After three years, the rates of obliteration were 100, 95, and 70 percent, respectively. Major neurologic complications occurred in 10 patients (12 percent), of whom 8 had permanent deficits. All these complications occurred in the initial stage of the protocol, before the maximal dose of radiation was reduced to 19.2 Gy. In addition, hemorrhage occurred in 10 patients from residual malformations between 4 and 34 months after treatment. Seizures and headaches were less severe in 63 percent of the 35 and 68 percent of the 40 patients, respectively, who had them initially.Given the natural history of these inaccessible lesions and the high risks of surgery, we conclude that heavy-charged-particle radiation is an effective therapy for symptomatic, surgically inaccessible intracranial arteriovenous malformations. The current procedure has two disadvantages: a prolonged latency period before complete obliteration of the vascular lesion and a small risk of serious neurologic complications.

    View details for Web of Science ID A1990DM62600005

    View details for PubMedID 2359429



    Twenty patients with capillary/cavernous hemangiomas of the periorbital area (eyelid, eyebrow, nose extending to canthus) have been treated with a variety of techniques. Six patients were treated by yttrium-aluminum-garnet (YAG) laser photocoagulation and direct injection of steroids. Rapid shrinkage of the hemangiomas occurred in all patients, and 2 infants whose eye was totally occluded by the hemangioma had their eyes rapidly opened. YAG laser excision with or without previous photocoagulation plus injection and with arteriogram plus superselective embolization was performed in the other 14 patients. Results were satisfactory in all patients.

    View details for Web of Science ID A1990DC73900002

    View details for PubMedID 2350150

  • NEUROPATHOLOGY OF POLIP SYNDROME Horoupian, D. S., DORFMAN, L. J., SIMON, L. T., Marks, M., Herrick, M. K., Wasserstein, P., Smith, M. E. LIPPINCOTT WILLIAMS & WILKINS. 1990: 313–13


    A massive cavernous hemangioma of the face in an 11 month old child has been successfully resected utilizing a combination of laser and non-laser techniques. The hemangioma was initially treated twice with YAG laser photocoagulation plus direct injection of steroids. This treatment promptly stopped the rapid growth and induced blanching as well as a 25% shrinkage with each treatment. Arteriogram with superselective embolization produced a further shrinkage of the hemangioma. Finally, the contact YAG laser with sapphire scalpel tips was utilized for complete and cosmetically satisfactory hemangioma resection. The treatment of a massive cavernous hemangioma by a combination of modalities is discussed.

    View details for Web of Science ID A1990DG14700001

    View details for PubMedID 2345471



    Twenty patients with supratentorial arteriovenous malformations (AVMs) were evaluated with angiography, conventional CT, and stable xenon CT to determine cerebral blood flow. Contralateral and ipsilateral regions of interest relative to the AVM were evaluated from cerebral blood flow maps and correlated with angiography. A significant decrease in cerebral blood flow was observed in the ipsilateral cortical gray matter adjacent to the AVM relative to the corresponding contralateral cortex (mean difference = 9.52 ml/100 g/min, p less than .01). The larger AVMs (greater than 8 cm3) were associated with a more marked decrease with a mean difference of 12.22 ml/100 g/min (p less than .02). Regions of interest were also chosen on the basis of angiographic findings, which suggested areas of decreased flow. Comparison of these areas with analogous contralateral areas also showed a significant decline in cerebral blood flow (mean difference = 8.86 ml/100 g/min); this decline was greater with larger AVMs (volume greater than 8 cm3), which had a mean difference of 11.38 ml/100 g/min (p less than .01). Our correlative study enabled us to pinpoint the regions most likely to have reduced flow from an AVM.

    View details for Web of Science ID A1988Q748200020

    View details for PubMedID 3143241



    Seven of 24 patients with intracranial vascular malformations who were treated with helium-ion Bragg-peak radiosurgery had complications of therapy. New symptoms and corresponding radiologic abnormalities developed 4-28 months after therapy. Five patients had similar patterns of white matter changes and mass effect on computed tomographic scans and magnetic resonance images. The abnormalities were centered in the radiation field. Gray matter changes and abnormal enhancement in the thalamus and hypothalamus outside the radiation field developed in one patient. This patient also had vasculopathic changes on angiograms. Rapidly progressive large vessel vasculopathy developed in another patient and caused occlusion of major vessels. Thus, different mechanisms may be involved in the complications of heavy-ion radiosurgery.

    View details for Web of Science ID A1988P303300029

    View details for PubMedID 3293113



    Twenty-four patients with intracranial vascular malformations were examined before and after helium ion radiosurgical treatment with angiography, computed tomography (CT), and magnetic resonance (MR) imaging. Twenty patients had high-flow arteriovenous malformations (AVMs). After treatment 18 of 20 AVMs (90%) showed a significant reduction in size on angiograms or MR images. Eleven of 20 (55%) had complete resolution on angiograms or MR images, 35% had partial resolution, and 10% showed no size change. Before treatment, the size range of the AVMs was 0.86-383 cm3 (median, 21.7 cm3). Smaller AVMs (less than 8 cm3) were more likely to resolve completely than medium-sized AVMs (8-64 cm3) or larger AVMs (greater than 64 cm3). Four additional patients had slow-flow vascular malformations: One had a venous angioma; one, a probable cavernous hemangioma; and two, malformations that were not seen on angiograms. CT proved inaccurate in demonstrating the boundaries of the AVM after treatment because it showed persistent contrast enhancement even when the AVM was completely obliterated on angiograms. MR imaging and angiography were complementary in the evaluation of therapeutic results and should be the primary modalities in the examination of patients with AVMs.

    View details for Web of Science ID A1988P303300028

    View details for PubMedID 3293112

  • CASE REPORT-420 - PAROSTEAL OSTEOSARCOMA SKELETAL RADIOLOGY Marks, M. P., MARKS, S. C., Segall, H. D., SCHWINN, C. P., Forrester, D. M. 1987; 16 (3): 246-251

    View details for Web of Science ID A1987H061800013

    View details for PubMedID 3473691



    Four previously healthy children presented in a 6-week period with marked hypoproteinemia without liver disease, malnutrition, or significant proteinuria. They all had strikingly similar radiographic findings consisting of enlarged folds confined to the fundus and body of the stomach. Three of the children had prodromal symptoms suggesting a viral illness. Cytomegalovirus was cultured from the urine in all cases and from the gastric biopsy specimens in three patients. Two of these patients also showed intranuclear inclusions in their biopsy specimens compatible with cytomegalovirus. It is not certain if cytomegalovirus was the cause of the illness.

    View details for Web of Science ID A1986E499600032

    View details for PubMedID 3020954