Robert Dodd, MD, PhD

All Publications

• Surgical Performance Determines Functional Outcome Benefit in the Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) Procedure NEUROSURGERY Awad, I. A., Polster, S. P., Carrion-Penagos, J., Thompson, R. E., Cao, Y., Stadnik, A., Money, P., Fam, M. D., Koskimaeki, J., Girard, R., Lane, K., McBee, N., Ziai, W., Hao, Y., Dodd, R., Carlson, A. P., Camarata, P. J., Caron, J., Harrigan, M. R., Gregson, B. A., Mendelow, A., Zuccarello, M., Hanley, D. F., Abdul-Rahim, A., Abou-Hamden, A., Abraham, M., Ahmed, A., Alba, C., Aldrich, E., Ali, H., Altschul, D., Amin-Hanjani, S., Anderson, C. S., Anderson, D., Ansari, S., Antezana, D., Ardelt, A., Arikan, F., Avadhani, R., Baguena, M., Baker, A., Barrer, S. J., Barzo, P., Becker, K. J., Bergman, T., Betz, J. F., Bistran-Hall, A. J., Bostrom, A., Braun, J., Brindley, P., Broaddus, W. C., Brown, R., Buki, A., Bulters, D., Cao, B., Carhuapoma, J., Chalela, J., Chang, T., Chicoine, M. R., Chorro, I., Chowdhry, S., Cobb, C., Corral, L., Csiba, L., Davies, J., Dawson, J., Diaz, A., Dierdeyn, C. P., Diringer, M., Dlugash, R., Ecker, R., Economas, T., Enriquez, P., Ezer, E., Fan, Y., Feng, H., Franz, D., Freeman, W., Fusco, M., Galicich, W., Gandhi, D., Gelea, M., Goldstein, J., Gonzalez, A., Grabarits, C., Greenberg, S., Gregson, B., Gress, D., Gu, E., Gupta, G., Hall, C., Harnof, S., Hernandez, F., Hoesch, R., Hoh, B. L., Houser, J., Hu, R., Huang, J., Huang, Y., Hussain, M., Insinga, S., Jadhav, A., Jaffe, J., Jahromi, B. S., Jallo, J., James, M., James, R. F., Janis, S., Jankowitz, B., Jeon, E., Jichici, D., Jonczak, K., Jonker, B., Karlen, N., Kase, C. S., Keric, N., Kerz, T., Kitagawa, R., Knopman, J., Koenig, C., Krishnamurthy, S., Kumar, A., Kureshi, I., Laidlaw, J., Lakhanpal, A., Latorre, J., LeDoux, D., Lees, K. R., Leifer, D., Leiphart, J., Lenington, S., Li, Y., Lopez, G., Lovick, D., Lumenta, C., Luo, J., Maas, M. B., MacDonald, J., MacKenzie, L., Madan, V., Majkowski, R., Major, O., Malhorta, R., Malkoff, M., Mangat, H., Maswadeh, A., Matouk, C., Mayo, S. W., McArthur, K., McCaul, S., Medow, J., Mezey, G., Mighty, J., Miller, D., Mitchell, P., Mohan, K. K., Mould, W., Muir, K., Munoz, L., Nakaji, P., Nee, A., Nekoovaght-Tak, S., Nyquist, P., O'Kane, R., Okasha, M., O'Kelly, C., Ostapkovich, N., Pandey, A., Parry-Jones, A., Patel, H., Perla, K., Pollack, A., Pouratian, N., Quinn, T., Rajajee, V., Reddy, K., Rehman, M., Reimer, R., Rincon, F., Rosenblum, M., Rybinnik, I., Sanchez, B., Sansing, L., Sarabia, R., Schneck, M., Schuerer, L., Schul, D., Schweitzer, J., Seder, D. B., Seyfried, D., Sheth, K., Spiotta, A., Stechison, M., Sugar, E. A., Szabo, K., Tamayo, G., Tanczos, K., Taussky, P., Teitelbaum, J. S., Terry, J., Testai, F., Thomas, K., Thompson, C. B., Thompson, G., Torner, J. C., Huy Tran, Tucker, K., Ullman, N., Ungar, L., Unterberg, A., Varelas, P., Vargas, N., Vatter, H., Venkatasubramanian, C., Vermillion, K., Vespa, P., Vollmer, D., Wang, W., Wang, Y., Wang, Y., Wen, J., Whitworth, L., Willis, B., Wilson, A., Wolfe, S., Wrencher, M., Wright, S. E., Xu, Y., Yanase, L., Yenokyan, G., Yi, X., Yu, Z., Zomorodi, A., MISTIE III Trial Investigators 2019; 84 (6): 1157–67

  View details for DOI 10.1093/neuros/nyz077

  View details for Web of Science ID 000471247000027

• Superselective methohexital challenge prior to intracranial endovascular embolization JOURNAL OF CLINICAL NEUROSCIENCE Bican, O., Cho, C., Suarez-Roman, A., Viet Nguyen, Lee, L., Le, S., Heit, J., Dodd, R., Lopez, J. 2019; 63: 68–71

  View details for DOI 10.1016/j.jocn.2019.01.051

  View details for Web of Science ID 000466249000013

• Granular Cell Pituitary Tumor in a Patient with Multiple Endocrine Neoplasia-1 CUREUS Pendharkar, A., Lin, C., Born, D. E., Hoffman, A. R., Dodd, R. L. 2019; 11 (4)

  View details for DOI 10.7759/cureus.4541

  View details for Web of Science ID 000467810600002

• 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; 124: E649–E658

  View details for DOI 10.1016/j.wneu.2018.12.171

  View details for Web of Science ID 000463087800083

• Surgical Performance Determines Functional Outcome Benefit in the Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) Procedure. Neurosurgery Awad, I. A., Polster, S. P., Carrion-Penagos, J., Thompson, R. E., Cao, Y., Stadnik, A., Money, P. L., Fam, M. D., Koskimaki, J., Girard, R., Lane, K., McBee, N., Ziai, W., Hao, Y., Dodd, R., Carlson, A. P., Camarata, P. J., Caron, J., Harrigan, M. R., Gregson, B. A., Mendelow, A. D., Zuccarello, M., Hanley, D. F., MISTIE III Trial Investigators 2019

  Abstract

  BACKGROUND: Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr).OBJECTIVE: To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes.METHODS: Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n=242) of the MISTIE trial.RESULTS: Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of≤15 mL end of treatment ICH volume or≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at≤30 mL end of treatment ICH volume, or>53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation.CONCLUSION: This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

  View details for PubMedID 30891610

• Superselective methohexital challenge prior to intracranial endovascular embolization. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Bican, O., Cho, C., Suarez-Roman, A., Nguyen, V., Lee, L., Le, S., Heit, J., Dodd, R., Lopez, J. 2019

  Abstract

  Pharmacologic provocative testing (PT) and intraoperative neurophysiologic monitoring (IONM) both mitigate and predict risks associated with endovascular embolization procedures. We present a series of patients undergoing endovascular intracranial embolization predominantly for AVMs both under general anesthesia and awake with the use of IONM. We reviewed our database to identify all patients undergoing endovascular procedures between January 1, 2014 and January 1, 2016. Awake patients were tested with SSEP, EEG and real time neurologic examination while TcMEPs were performed in all anesthetized patients. BAEPs were performed in anesthetized patients if indicated. Methohexital was administered as an injection at a dose of 5 mg or 10 mg and repeat testing was performed if needed.Sixty-three endovascular procedures that met criteria were performed in 32 patients. 54 procedures in 28 patients were performed under general anesthesia, 9 procedures in 4 patients were performed in wakefulness. PT was negative in 61 procedures and subsequently completed embolizations without neurological sequelae. In two cases, the testing was positive and the procedure was terminated without embolization in one patient. The other patient underwent embolization at an alternative site without repeat PT. There were no new postoperative neurologic deficits after any of these procedures. Specificity of PT was 100% as none of the patients with a negative provocative test developed a new postoperative neurologic deficit after embolization. To our knowledge, this is the first review of PT with the use of neurophysiologic IONM techniques under general anesthesia. These data suggest a high specificity comparable to awake testing.

  View details for PubMedID 30772199

• Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet (London, England) Hanley, D. F., Thompson, R. E., Rosenblum, M., Yenokyan, G., Lane, K., McBee, N., Mayo, S. W., Bistran-Hall, A. J., Gandhi, D., Mould, W. A., Ullman, N., Ali, H., Carhuapoma, J. R., Kase, C. S., Lees, K. R., Dawson, J., Wilson, A., Betz, J. F., Sugar, E. A., Hao, Y., Avadhani, R., Caron, J., Harrigan, M. R., Carlson, A. P., Bulters, D., LeDoux, D., Huang, J., Cobb, C., Gupta, G., Kitagawa, R., Chicoine, M. R., Patel, H., Dodd, R., Camarata, P. J., Wolfe, S., Stadnik, A., Money, P. L., Mitchell, P., Sarabia, R., Harnof, S., Barzo, P., Unterberg, A., Teitelbaum, J. S., Wang, W., Anderson, C. S., Mendelow, A. D., Gregson, B., Janis, S., Vespa, P., Ziai, W., Zuccarello, M., Awad, I. A., MISTIE III Investigators, Abdul-Rahim, A., Abou-Hamden, A., Abraham, M., Ahmed, A., Alba, C. A., Aldrich, E. F., Altschul, D., Amin-Hanjani, S., Anderson, D., Ansari, S., Antezana, D., Ardelt, A., Arikan, F., Baguena, M., Baker, A., Barrer, S. J., Becker, K. J., Bergman, T., Bostrom, A., Braun, J., Brindley, P., Broaddus, W. C., Brown, R., Buki, A., Cao, B., Cao, Y., Carrion-Penagos, J., Chalela, J., Chang, T., Chorro, I. M., Chowdhry, S., Corral, L., Csiba, L., Davies, J., Diaz, A. T., Dierdeyn, C. P., Diringer, M., Dlugash, R., Ecker, R., Economas, T., Enriquez, P., Ezer, E., Fan, Y., Feng, H., Franz, D., Freeman, W. D., Fusco, M., Galicich, W., Gelea, M. L., Goldstein, J., Gonzalez, A. C., Grabarits, C., Greenberg, S., Gress, D., Gu, E., Hall, C., Hernandez, F. M., Hoesch, R., Hoh, B. L., Houser, J., Hu, R., Huang, Y., Hussain, M. A., Insinga, S., Jadhav, A., Jaffe, J., Jahromi, B. S., Jallo, J., James, M., James, R. F., Jankowitz, B., Jeon, E., Jichici, D., Jonczak, K., Jonker, B., Karlen, N., Keric, N., Kerz, T., Knopman, J., Koenig, C., Krishnamurthy, S., Kumar, A., Kureshi, I., Laidlaw, J., Lakhanpal, A., Latorre, J. G., Leifer, D., Leiphart, J., Lenington, S., Li, Y., Lopez, G., Lovick, D., Lumenta, C., Luo, J., Maas, M. B., MacDonald, J., MacKenzie, L., Madan, V., Majkowski, R., Major, O., Malhorta, R., Malkoff, M., Mangat, H., Maswadeh, A., Matouk, C., McArthur, K., McCaul, S., Medow, J., Mezey, G., Mighty, J., Miller, D., Mohan, K. K., Muir, K., Munoz, L., Nakaji, P., Nee, A., Nekoovaght-Tak, S., Nyquist, P., O'Kane, R., Okasha, M., O'Kelly, C., Ostapkovich, N., Pandey, A., Parry-Jones, A., Perla, K. R., Pollack, A., Polster, S., Pouratian, N., Quinn, T., Rajajee, V., Reddy, K., Rehman, M., Reimer, R., Rincon, F., Rybinnik, I., Sanchez, B., Sansing, L., Schneck, M., Schuerer, L., Schul, D., Schweitzer, J., Seder, D. B., Seyfried, D., Sheth, K., Spiotta, A., Stechison, M., Szabo, K., Tamayo, G., Tanczos, K., Taussky, P., Terry, J., Testai, F., Thomas, K., Thompson, C. B., Thompson, G., Torner, J. C., Tran, H., Tucker, K., Ungar, L., Varelas, P., Vargas, N. M., Vatter, H., Venkatasubramanian, C., Vermillion, K., Vollmer, D., Wang, Y., Wang, Y., Wen, J., Whitworth, L. T., Willis, B., Wrencher, M., Wright, S. E., Xu, Y., Yanase, L., Yi, X., Yu, Z., Zomorodi, A. 2019

  Abstract

  BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage.METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046.FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012).INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons.FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.

  View details for PubMedID 30739747

• 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

  Abstract

  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 PubMedID 30639494

• Granular Cell Pituitary Tumor in a Patient with Multiple Endocrine Neoplasia-1. Cureus Pendharkar, A. V., Lin, C. Y., Born, D. E., Hoffman, A. R., Dodd, R. L. 2019; 11 (4): e4541

  Abstract

  Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disorder characterized by parathyroid, pancreatic islet, and pituitary tumors. Approximately 40% of MEN-1 patients harbor a pituitary adenoma. Separately, granular cell tumors (GCTs) of the sellar/parasellar region are an exceedingly rare clinical entity with less than 100 reported cases in the literature. These slow-growing, often asymptomatic lesions are difficult to diagnose and may mimic pituitary adenoma, Rathke cleft cyst, or other sellar/supra-sellar pathology. There is no known association with MEN-1 or any other familial syndrome. A 36-year-old neurologically normal woman with known MEN-1 underwent a screening magnetic resonance imaging (MRI) scan which revealed a 10 mm x 6 mm x 7 mm sellar/suprasellar lesion. She underwent endoscopic endonasal transsphenoidal resection. Subsequent neuropathological analysis was consistent with GCT of the pituitary gland. Here we describe the first report to our knowledge of a GCT of the pituitary gland occurring in a patient with MEN-1.

  View details for DOI 10.7759/cureus.4541

  View details for PubMedID 31275768

  View details for PubMedCentralID PMC6592835

• Arterial Pseudoaneurysm following Radiotherapy in Patients with a History of Nasopharyngeal Carcinoma. OTO open Choby, G., Tangbumrungtham, N., Dodd, R., Patel, Z. M. 2019; 3 (1): 2473974X18823002

  View details for DOI 10.1177/2473974X18823002

  View details for PubMedID 31236534

• Arterial-Spin Labeling MRI Identifies Residual Cerebral Arteriovenous Malformation Following Stereotactic Radiosurgery Treatment. Journal of neuroradiology. Journal de neuroradiologie Heit, J. J., Thakur, N. H., Iv, M., Fischbein, N. J., Wintermark, M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. 2019

  Abstract

  Brain arteriovenous malformation (AVM) treatment by stereotactic radiosurgery (SRS) is effective, but AVM obliteration following SRS may take two years or longer. MRI with arterial spin labeling (ASL) may detect brain AVMs with high sensitivity. We determined whether brain MRI with ASL may accurately detect residual AVM following SRS treatment.We performed a retrospective cohort study of patients who underwent brain AVM evaluation by DSA between June 2010 and June 2015. Inclusion criteria were: (1) AVM treatment by SRS, (2) follow - up MRI with ASL at least 30 months after SRS, (3) DSA within 3 months of the follow-up MRI with ASL, and (4) no intervening AVM treatment between the MRI and DSA. Four neuroradiologists blindly and independently reviewed follow-up MRIs. Primary outcome measure was residual AVM indicated by abnormal venous ASL signal.15 patients (12 females, mean age 29 years) met inclusion criteria. There were three posterior fossa AVMs and 12 supratentorial AVMs. Spetzler-Martin (SM) Grades were: SM1 (8%), SM2 (33%), SM3 (17%), SM4 (25%), and SM5 (17%). DSA demonstrated residual AVM in 10 patients. The pooled sensitivity, specificity, positive predictive value, and negative predictive value of venous ASL signal for predicting residual AVM were 100% (95% CI: 0.9-1.0), 95% (95% CI: 0.7-1.0), 98% (95% CI: 0.9-1.0), and 100% (95% CI: 0.8-1.0), respectively. High inter-reader agreement as found by Fleiss' Kappa analysis (k = 0.92; 95% CI: 0.8-1.0; p < 0.0001).ASL is highly sensitive and specific in the detection of residual cerebral AVM following SRS treatment.

  View details for PubMedID 30658138

• Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience. Journal of neurointerventional surgery Lee, S., Heit, J. J., Albers, G. W., Wintermark, M., Jiang, B., Bernier, E., Fischbein, N. J., Mlynash, M., Marks, M. P., Do, H. M., Dodd, R. L. 2019

  Abstract

  The extended time window for endovascular therapy in adult stroke represents an opportunity for stroke treatment in children for whom diagnosis may be delayed. However, selection criteria for pediatric thrombectomy has not been defined.We performed a retrospective cohort study of patients aged <18 years presenting within 24 hours of acute large vessel occlusion. Patient consent was waived by our institutional IRB. Patient data derived from our institutional stroke database was compared between patients with good and poor outcome using Fisher's exact test, t-test, or Mann-Whitney U-test.Twelve children were included: 8/12 (66.7%) were female, mean age 9.7±5.0 years, median National Institutes of Health Stroke Scale (NIHSS) 11.5 (IQR 10-14). Stroke etiology was cardioembolic in 75%, dissection in 16.7%, and cryptogenic in 8.3%. For 2/5 with perfusion imaging, Tmax >4 s appeared to better correlate with NIHSS. Nine patients (75%) were treated: seven underwent thrombectomy alone; one received IV alteplase and thrombectomy, and one received IV alteplase alone. Favorable outcome was achieved in 78% of treated patients versus 0% of untreated patients (P=0.018). All untreated patients had poor outcome, with death (n=2) or severe disability (n=1) at follow-up. Among treated patients, older children (12.8±2.9 vs 4.2±5.0 years, P=0.014) and children presenting as outpatient (100% vs 0%, P=0.028) appeared to have better outcomes.Perfusion imaging is feasible in pediatric stroke and may help identify salvageable tissue in extended time windows, though penumbral thresholds may differ from adult values. Further studies are needed to define criteria for thrombectomy in this unique population.

  View details for PubMedID 31097548

• Direct targeting of the mouse optic nerve for therapeutic delivery. Journal of neuroscience methods Mesentier-Louro, L. A., Dodd, R., Domizi, P., Nobuta, H., Wernig, M., Wernig, G., Liao, Y. J. 2018

  Abstract

  BACKGROUND: Animal models of optic nerve injury are often used to study central nervous system (CNS) degeneration and regeneration, and targeting the optic nerve is a powerful approach for axon-protective or remyelination therapy. However, the experimental delivery of drugs or cells to the optic nerve is rarely performed because injections into this structure are difficult in small animals, especially in mice.NEW METHOD: We investigated and developed methods to deliver drugs or cells to the mouse optic nerve through 3 different routes: a) intraorbital, b) through the optic foramen and c) transcranial.RESULTS: The methods targeted different parts of the mouse optic nerve: intraorbital proximal (intraorbital), intracranial middle (optic-foramen) or intracranial distal (transcranial) portion.COMPARISON WITH EXISTING METHODS: Most existing methods target the optic nerve indirectly. For instance, intravitreally delivered cells often cannot cross the inner limiting membrane to reach retinal neurons and optic nerve axons. Systemic delivery, eye drops and intraventricular injections do not always successfully target the optic nerve. Intraorbital and transcranial injections into the optic nerve or chiasm have been performed but these methods have not been well described. We approached the optic nerve with more selective and precise targeting than existing methods.CONCLUSIONS: We successfully targeted the murine optic nerve intraorbitally, through the optic foramen, and transcranially. Of all methods, the injection through the optic foramen is likely the most innovative and fastest. These methods offer additional approaches for therapeutic intervention to be used by those studying white matter damage and axonal regeneration in the CNS.

  View details for PubMedID 30389488

• Stem cell therapy for treatment of ischemic optic neuropathy Mesentier-Louro, L., Yang, N., Shariati, A., Domizi, P., Dodd, R., Wernig, G., Wernig, M., Liao, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912501176

• Clinical and Immunohistochemical Analysis of Clinically Non-functional Pituitary Neuroendocrine Tumors Lavezo, J., Frankel, M., Balliu, B., Pan, J., Hoffman, A., Dodd, R., Harsh, G., Katznelson, L., Vogel, H. OXFORD UNIV PRESS INC. 2018: 518

  View details for Web of Science ID 000434064400162

• Porcine small intestine submucosal grafts improve remucosalization and progenitor cell recruitment to sites of upper airway tissue remodeling. International forum of allergy & rhinology Nayak, J. V., Rathor, A., Grayson, J. W., Bravo, D. T., Velasquez, N., Noel, J., Beswick, D. M., Riley, K. O., Patel, Z. M., Cho, D., Dodd, R. L., Thamboo, A., Choby, G. W., Walgama, E., Harsh, G. R., Hwang, P. H., Clemons, L., Lowman, D., Richman, J. S., Woodworth, B. A. 2018

  Abstract

  BACKGROUND: To better understand upper airway tissue regeneration, the exposed cartilage and bone at donor sites of tissue flaps may serve as in vivo "Petri dishes" for active wound healing. The pedicled nasoseptal flap (NSF) for skull-base reconstruction creates an exposed donor site within the nasal airway. The objective of this study is to evaluate whether grafting the donor site with a sinonasal repair cover graft is effective in promoting wound healing.METHODS: In this multicenter, prospective trial, subjects were randomized to intervention (graft) or control (no graft) intraoperatively after NSF elevation. Individuals were evaluated at 2, 6, and 12 weeks postintervention with endoscopic recordings. Videos were graded (Likert scale) by 3 otolaryngologists blinded to intervention on remucosalization, crusting, and edema. Scores were analyzed for interrater reliability and cohorts compared. Biopsy and immunohistochemistry at the leading edge of wound healing was performed in select cases.RESULTS: Twenty-one patients were randomized to intervention and 26 to control. Subjects receiving the graft had significantly greater overall remucosalization (p = 0.01) than controls over 12 weeks. Although crusting was less in the small intestine submucosa (SIS) group, this was not statistically significant (p = 0.08). There was no overall effect on nasal edema (p = 0.2). Immunohistochemistry demonstrated abundant upper airway basal cell progenitors in 2 intervention samples, suggesting that covering grafts may facilitate tissue proliferation via progenitor cell expansion.CONCLUSION: This prospective, randomized, controlled trial indicates that a porcine SIS graft placed on exposed cartilage and bone within the upper airway confers improved remucosalization compared to current practice standards.

  View details for PubMedID 29856526

• 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

  Abstract

  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

• 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

  Abstract

  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 PubMedID 28768818

• Conus Medullaris Dural Arteriovenous Fistula Arising From the Artery of the Filum Terminale: 2-Dimensional Operative Video. Operative neurosurgery (Hagerstown, Md.) Lamsam, L., Quon, J., Fischbein, N., Iv, M., Dodd, R., Ratliff, J. 2018

  View details for PubMedID 29444295

• 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

  Abstract

  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 PubMedID 29739912

• Practical Pearl: Use of MRI to Differentiate Pseudo-subarachnoid Hemorrhage from True Subarachnoid Hemorrhage. Neurocritical care Ho, A. L., Sussman, E. S., Pendharkar, A. V., Iv, M., Hirsch, K. G., Fischbein, N. J., Dodd, R. L. 2018

  View details for PubMedID 29948997

• High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations. Journal of neurosurgery. Pediatrics Iv, M., Choudhri, O., Dodd, R. L., Vasanawala, S. S., Alley, M. T., Moseley, M., Holdsworth, S. J., Grant, G., Cheshier, S., Yeom, K. W. 2018: 1–10

  Abstract

  OBJECTIVE Patients with brain arteriovenous malformations (AVMs) often require repeat imaging with MRI or MR angiography (MRA), CT angiography (CTA), and digital subtraction angiography (DSA). The ideal imaging modality provides excellent vascular visualization without incurring added risks, such as radiation exposure. The purpose of this study is to evaluate the performance of ferumoxytol-enhanced MRA using a high-resolution 3D volumetric sequence (fe-SPGR) for visualizing and grading pediatric brain AVMs in comparison with CTA and DSA, which is the current imaging gold standard. METHODS In this retrospective cohort study, 21 patients with AVMs evaluated by fe-SPGR, CTA, and DSA between April 2014 and August 2017 were included. Two experienced raters graded AVMs using Spetzler-Martin criteria on all imaging studies. Lesion conspicuity (LC) and diagnostic confidence (DC) were assessed using a 5-point Likert scale, and interrater agreement was determined. The Kruskal-Wallis test was performed to assess the raters' grades and scores of LC and DC, with subsequent post hoc pairwise comparisons to assess for statistically significant differences between pairs of groups at p < 0.05. RESULTS Assigned Spetzler-Martin grades for AVMs on DSA, fe-SPGR, and CTA were not significantly different (p = 0.991). LC and DC scores were higher with fe-SPGR than with CTA (p < 0.05). A significant difference in LC scores was found between CTA and fe-SPGR (p < 0.001) and CTA and DSA (p < 0.001) but not between fe-SPGR and DSA (p = 0.146). A significant difference in DC scores was found among DSA, fe-SPGR, and CTA (p < 0.001) and between all pairs of the groups (p < 0.05). Interrater agreement was good to very good for all image groups (κ = 0.77-1.0, p < 0.001). CONCLUSIONS Fe-SPGR performed robustly in the diagnostic evaluation of brain AVMs, with improved visual depiction of AVMs compared with CTA and comparable Spetzler-Martin grading relative to CTA and DSA.

  View details for PubMedID 29882734

• Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery Chin, A. L., Fujimoto, D., Kumar, K. A., Tupper, L., Mansour, S., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R., Li, G., Gephart, M. H., Ratliff, J. K., Tse, V., Usoz, M., Sachdev, S., Soltys, S. G. 2018

  Abstract

  Stereotactic radiosurgery (SRS) for benign intracranial tumors is an established standard of care. The widespread implementation of SRS for benign spinal tumors has been limited by lack of long-term data.To update our institutional experience of safety and efficacy outcomes after SRS for benign spinal tumors.We performed a retrospective cohort study of 120 patients with 149 benign spinal tumors (39 meningiomas, 26 neurofibromas, and 84 schwannomas) treated with SRS between 1999 and 2016, with follow-up magnetic resonance imaging available for review. The primary endpoint was the cumulative incidence of local failure (LF), with death as a competing risk. Secondary endpoints included tumor shrinkage, symptom response, toxicity, and secondary malignancy.Median follow-up was 49 mo (interquartile range: 25-103 mo, range: 3-216 mo), including 61 courses with >5 yr and 24 courses with >10 yr of follow-up. We observed 9 LF for a cumulative incidence of LF of 2%, 5%, and 12% at 3, 5, and 10 yr, respectively. Excluding 10 tumors that were previously irradiated or that arose within a previously irradiated field, the 3-, 5-, and 10-yr cumulative incidence rates of LF were 1%, 2%, and 8%, respectively. At last follow-up, 35% of all lesions had decreased in size. With a total of 776 patient-years of follow-up, no SRS-related secondary malignancies were observed.Comparable to SRS for benign intracranial tumors, SRS provides longer term local control of benign spinal tumors and is a standard-of-care alternative to surgical resection.

  View details for PubMedID 30445557

• 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

  Abstract

  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 PubMedID 29555872

• 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

  Abstract

  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 PubMedID 28735125

• 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

  Abstract

  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

• Radiosurgical ablation of spinal cord arteriovenous malformations. Handbook of clinical neurology Sussman, E. S., Adler, J. R., Dodd, R. L. 2017; 143: 175-187

  Abstract

  Spinal cord arteriovenous malformations (SCAVMs) are rare entities that account for less than 20% of spinal masses. These lesions represent a unique clinical challenge, in that surgical or endovascular treatment is often associated with devastating functional consequences. Over the past few decades, radiosurgery has become a well-established treatment modality for SCAVMs, and may be a first-line treatment in many patients afflicted with this devastating disease. This chapter summarizes the data available regarding radiosurgical treatment of SCAVMs.

  View details for DOI 10.1016/B978-0-444-63640-9.00017-5

  View details for PubMedID 28552140

• 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

  Abstract

  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 PubMedID 28758549

• Endoscopic Resection of Skull Base Teratoma in Klippel-Feil Syndrome through Use of Combined Ultrasonic and Bipolar Diathermy Platforms. Case reports in otolaryngology Edward, J. A., Psaltis, A. J., Williams, R. A., Charville, G. W., Dodd, R. L., Nayak, J. V. 2017; 2017: 6384586-?

  Abstract

  Klippel-Feil syndrome (KFS) is associated with numerous craniofacial abnormalities but rarely with skull base tumor formation. We report an unusual and dramatic case of a symptomatic, mature skull base teratoma in an adult patient with KFS, with extension through the basisphenoid to obstruct the nasopharynx. This benign lesion was associated with midline palatal and cerebral defects, most notably pituitary and vertebrobasilar arteriolar duplications. A multidisciplinary workup and a complete endoscopic, transnasal surgical approach between otolaryngology and neurosurgery were undertaken. Out of concern for vascular control of the fibrofatty dense tumor stalk at the skull base and need for complete teratoma resection, we successfully employed a tissue resection tool with combined ultrasonic and bipolar diathermy to the tumor pedicle at the sphenoid/clivus junction. No CSF leak or major hemorrhage was noted using this endonasal approach, and no concerning postoperative sequelae were encountered. The patient continues to do well now 3 years after tumor extirpation, with resolution of all preoperative symptoms and absence of teratoma recurrence. KFS, teratoma biology, endocrine gland duplication, and the complex considerations required for successfully addressing this type of advanced skull base pathology are all reviewed herein.

  View details for DOI 10.1155/2017/6384586

  View details for PubMedID 28133560

• Patient Outcomes and Cerebral Infarction after Ruptured Anterior Communicating Artery Aneurysm Treatment. AJNR. American journal of neuroradiology Heit, J. J., Ball, R. L., Telischak, N. A., Do, H. M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Wintermark, M., Marks, M. P. 2017; 38 (11): 2119–25

  Abstract

  Anterior communicating artery aneurysm rupture and treatment is associated with high rates of dependency, which are more severe after clipping compared with coiling. To determine whether ischemic injury might account for these differences, we characterized cerebral infarction burden, infarction patterns, and patient outcomes after surgical or endovascular treatment of ruptured anterior communicating artery aneurysms.We performed a retrospective cohort study of consecutive patients with ruptured anterior communicating artery aneurysms. Patient data and neuroimaging studies were reviewed. A propensity score for outcome measures was calculated to account for the nonrandom assignment to treatment. Primary outcome was the frequency of frontal lobe and striatum ischemic injury. Secondary outcomes were patient mortality and clinical outcome at discharge and at 3 months.Coiled patients were older (median, 55 versus 50 years;P= .03), presented with a worse clinical status (60% with Hunt and Hess Score >2 versus 34% in clipped patients;P= .02), had a higher modified Fisher grade (P= .01), and were more likely to present with intraventricular hemorrhage (78% versus 56%;P= .03). Ischemic frontal lobe infarction (OR, 2.9; 95% CI, 1.1-8.4;P= .03) and recurrent artery of Heubner infarction (OR, 20.9; 95% CI, 3.5-403.7;P< .001) were more common in clipped patients. Clipped patients were more likely to be functionally dependent at discharge (OR, 3.2;P= .05) compared with coiled patients. Mortality and clinical outcome at 3 months were similar between coiled and clipped patients.Frontal lobe and recurrent artery of Heubner infarctions are more common after surgical clipping of ruptured anterior communicating artery aneurysms, and are associated with poorer clinical outcomes at discharge.

  View details for PubMedID 28882863

• 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. 2016

  Abstract

  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 PubMedID 28017742

• 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

  Abstract

  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

• 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; 25 (6): 717-723

  Abstract

  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 PubMedID 27611897

• Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial LANCET NEUROLOGY Hanley, D. F., Thompson, R. E., Muschelli, J., Rosenblum, M., Mcbee, N., Lane, K., Bistran-Hall, A. J., Mayo, S. W., Keyl, P., Gandhi, D., Morgan, T. C., Ullman, N., Mould, W. A., Carhuapoma, J. R., Kase, C., Ziai, W., Thompson, C. B., Yenokyan, G., Huang, E., Broaddus, W. C., Graham, R. S., Aldrich, E. F., Dodd, R., Wijman, C., Caron, J., Huang, J., Camarata, P., Mendelow, A. D., Gregson, B., Janis, S., Vespa, P., Martin, N., Awad, I., Zuccarello, M. 2016; 15 (12): 1226-1235

  Abstract

  Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage.MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770.Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7-22.6] vs eight [14·8%, 6·6-27·1], p=0·542), 7 day mortality (zero [0%, 0-8·4] vs one [1·9%, 0·1-9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1-12·6] vs five [9·3%, 3·1-20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1-12·6] vs zero [0%, 0-6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0-35·6] vs three [7·1%; 1·5-19·5]; p=0·051).MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage.National Institute of Neurological Disorders and Stroke, Genentech, and Codman.

  View details for Web of Science ID 000386315700018

  View details for PubMedCentralID PMC5154627

• Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial. The Lancet. Neurology Hanley, D. F., Thompson, R. E., Muschelli, J., Rosenblum, M., Mcbee, N., Lane, K., Bistran-Hall, A. J., Mayo, S. W., Keyl, P., Gandhi, D., Morgan, T. C., Ullman, N., Mould, W. A., Carhuapoma, J. R., Kase, C., Ziai, W., Thompson, C. B., Yenokyan, G., Huang, E., Broaddus, W. C., Graham, R. S., Aldrich, E. F., Dodd, R., Wijman, C., Caron, J., Huang, J., Camarata, P., Mendelow, A. D., Gregson, B., Janis, S., Vespa, P., Martin, N., Awad, I., Zuccarello, M. 2016; 15 (12): 1228-1237

  Abstract

  Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage.MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770.Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7-22.6] vs eight [14·8%, 6·6-27·1], p=0·542), 7 day mortality (zero [0%, 0-8·4] vs one [1·9%, 0·1-9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1-12·6] vs five [9·3%, 3·1-20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1-12·6] vs zero [0%, 0-6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0-35·6] vs three [7·1%; 1·5-19·5]; p=0·051).MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage.National Institute of Neurological Disorders and Stroke, Genentech, and Codman.

  View details for DOI 10.1016/S1474-4422(16)30234-4

  View details for PubMedID 27751554

  View details for PubMedCentralID PMC5154627

• 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

  Abstract

  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

• UTILITY OF A GLUCOCORTICOID SPARING STRATEGY IN THE MANAGEMENT OF PATIENTS FOLLOWING TRANSSPHENOIDAL SURGERY ENDOCRINE PRACTICE Jia, X., Pendharkar, A. V., Loftus, P., Dodd, R. L., Chu, O., Fraenkel, M., Katznelson, L. 2016; 22 (9): 1033-1039

  Abstract

  Following transsphenoidal surgery (TSS), it is important to assess for and manage adrenal insufficiency (AI). The goal of this study is to assess the efficacy and safety of a glucocorticoid (GC) sparing protocol to limit GC exposure in patients undergoing TSS.Adult patients undergoing TSS (excluding Cushing disease) with adequate adrenal function prior to surgery underwent TSS without perioperative GC coverage. Following TSS, daily morning fasting serum cortisol levels were tested. GCs were administered at stress doses for serum cortisol <5 mcg/dL, between 5 and 12 mcg/dL in the presence of clinically significant symptoms of AI, or >12 mcg/dL with severe headache, nausea or vomiting, fatigue, anorexia, or hyponatremia. The primary endpoint was the use of GCs in the immediate postoperative period.Of 178 subjects, GCs were administered to 80 (45%) patients for the following indications: 31.3% for serum cortisol <5 mcg/dL; 36.3% for cortisol between 5 and 12 mcg/dL accompanied by symptoms or signs of AI; 8.8% for moderate to severe postoperative hyponatremia; and 7.5% for severe headache, nausea and vomiting, fatigue, or anorexia with cortisol >12 mcg/dL. Logistic regression analysis showed that longer length of hospital stay (odds ratio [OR] 1.22, confidence interval [CI] 1.02-1.45) and the presence of new postoperative anterior pituitary hormone deficiency (OR 3.3, CI 1.26-8.67) were associated with postoperative GC use. By 12 weeks, only 14% of subjects remained on GCs. There were no adverse events related to withholding GCs.Our protocol for managing GC replacement is both safe and effective for limiting GC exposure in patients undergoing TSS.AI = adrenal insufficiency CI = confidence interval FSH = follicle-stimulating hormone GC = glucocorticoid GH = growth hormone IGF-1 = insulin-like growth factor-1 IV = intravenous LH = luteinizing hormone LOS = length of hospital stay OR = odds ratio TSS = transsphenoidal surgery.

  View details for DOI 10.4158/EP161256.OR

  View details for Web of Science ID 000384279900001

  View details for PubMedID 27124693

• Interventional Therapy for Brain AVMs Before and After ARUBA Sussman, E., Teo, M., Iyer, A., Ho, A., Pendharkar, A., Dodd, R., Steinberg, G. LIPPINCOTT WILLIAMS & WILKINS. 2016

  View details for Web of Science ID 000399956102128

• Detection of acute femoral artery ischemia during neuroembolization by somatosensory and motor evoked potential monitoring INTERVENTIONAL NEURORADIOLOGY Purger, D., Feroze, A. H., Choudhri, O., Lee, L., Lopez, J., Dodd, R. L. 2015; 21 (3): 397-400

  Abstract

  Neuromonitoring can be used to map out particular neuroanatomical tracts, define physiologic deficits secondary to specific pathology or intervention, or predict postoperative outcome and proves essential in the detection of central and peripheral ischemic events during neurosurgical intervention. Herein, we describe an instance of elective balloon-assisted coiling of a recurrent basilar tip aneurysm in a 61-year-old woman, where intraoperative somatosensory evoked potentials (SSEPs) and transcranial motor evoked potentials (TcMEPs) were lost in the right lower extremity intraoperatively. We aim to highlight that targeted use of monitoring proves advantageous in both the open surgical and endovascular setting, even in the avoidance of potential iatrogenic peripheral nerve damage and limb ischemia as documented herein. Consideration of the increased risk for peripheral ischemia in the neurointerventional setting is especially imperative in particular populations where blood vessels might be of diminished size, such as in infants, young children, and severely deconditioned adults.

  View details for DOI 10.1177/1591019915583219

  View details for Web of Science ID 000356305000019

  View details for PubMedID 26015519

  View details for PubMedCentralID PMC4757266

• 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

  Abstract

  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

• Persistent trigeminal artery supply to an intrinsic trigeminal nerve arteriovenous malformation: A rare cause of trigeminal neuralgia. Journal of clinical neuroscience Choudhri, O., Heit, J. J., Feroze, A. H., Chang, S. D., Dodd, R. L., Steinberg, G. K. 2015; 22 (2): 409-412

  Abstract

  Infratentorial arteriovenous malformations (AVM) associated with the trigeminal nerve root entry zone are a known cause of secondary trigeminal neuralgia (TN). The treatment of both TN and AVM can be challenging, especially if the AVM is embedded within the trigeminal nerve. A persistent trigeminal artery (PTA) can rarely supply these intrinsic trigeminal nerve AVM. We present a 64-year-old man with TN from a right trigeminal nerve AVM supplied by a PTA variant. The patient underwent microvascular decompression and a partial resection of the AVM with relief of facial pain symptoms. His residual AVM was subsequently treated with CyberKnife radiosurgery (Accuray, Sunnyvale, CA, USA). A multimodality approach may be required for the treatment of trigeminal nerve associated PTA AVM and important anatomic patterns need to be recognized before any treatment. Herein, we report to our knowledge the third documented patient with a posterior fossa AVM supplied by a PTA and the first PTA AVM presenting as facial pain.

  View details for DOI 10.1016/j.jocn.2014.06.007

  View details for PubMedID 25070632

• 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

  Abstract

  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 PubMedID 24385556

• Utility of Adrenocorticotropic Hormone in Assessing the Response to Transsphenoidal Surgery for Cushing's Disease. Endocrine practice Salmon, P. M., Loftus, P. D., Dodd, R. L., Harsh, G., Chu, O. S., Katznelson, L. 2014; 20 (11): 1159-1164

  Abstract

  To compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics in subjects with Cushing's disease (CD) following transsphenoidal surgery (TSS) and to determine the value of early postoperative ACTH levels in predicting subsequent hypocortisolemia.Following TSS for CD, serum cortisol and plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid coverage.A total of 26 subjects (25 female) underwent 28 operations. Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who achieved hypocortisolemia had significantly lower ACTH levels by 19 hours postoperatively (P = .007). Plasma ACTH fell to <30 pg/mL in 86% and <20 pg/mL in 82% of subjects who subsequently achieved hypocortisolemia. Plasma ACTH declined to <30 pg/mL by a mean of 10 hours and to <20 pg/mL by 13 hours prior to hypocortisolemia. Follow-up data were available on 25 patients for a median of 23 months. Three subjects who achieved initial surgical remission had disease recurrence at 19, 24, and 36 months; all of these subjects had a postoperative nadir serum cortisol levels <3 μg/dL and plasma ACTH <20 pg/mL.Following TSS for CD, plasma ACTH declined prior to achievement of hypocortisolemia in most subjects. In the majority, the ACTH level reached a nadir of <20 pg/mL. Low early postoperative ACTH levels predict early hypocortisolemia but may not accurately predict long-term remission.

  View details for DOI 10.4158/EP14140.OR

  View details for PubMedID 24936567

• 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

  Abstract

  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

• Pre-Operative Somatostatin Analog Therapy Reduces Perioperative Risk from Obstructive Sleep Apnea in Acromegaly: A Case Report Beaver, K., Dodd, R. L., Katznelson, L. ENDOCRINE SOC. 2014

  View details for Web of Science ID 000209805101040

• Clinical characteristics and pituitary dysfunction in patients with metastatic cancer to the sella. Endocrine practice Ariel, D., Sung, H., Coghlan, N., Dodd, R., Gibbs, I. C., Katznelson, L. 2013; 19 (6): 914-919

  Abstract

  Objective: Metastatic disease to the sella is uncommon and there are limited available data regarding the clinical aspects of this disease. We sought to characterize the clinical demographics of sellar metastases.Methods: Retrospective chart review of adults at Stanford University Medical Center from 1980 to 2011 with metastatic disease to the sella.Results: 13 subjects were identified (9 F). The mean age at diagnosis was 55 years (range: 25-73 y). 6 (46%) had breast carcinoma, 3 (23%) had renal cell carcinoma, 2 (15%) had squamous cell carcinoma of the head and neck, 1 had bronchoalveolar carcinoma of the lung, and 1 had nodular sclerosing Hodgkin's lymphoma. The most common presenting signs and symptoms were headache (58%), followed by fatigue (50%), polyuria (50%), visual field defects (42%), and ophthalmoplegia (42%). 75% presented with at least one pituitary hormone insufficiency, including 6 (50%) with diabetes insipidus (DI). 8 (67%) subjects had secondary hypothyroidism, and 5 (45%) had secondary adrenal insufficiency. Of the patients with stalk involvement, 86% had DI. All patients had a prior diagnosis of malignancy for a mean duration of 95 months.Conclusion: In this retrospective review, the most common neoplastic sources to the sella were breast and renal cell carcinoma. Secondary hypothyroidism was the most common endocrine abnormality, followed by DI, and adrenal insufficiency. New onset central hypothyroidism and diabetes insipidus along with known malignancy in a patient with a sellar lesion should raise the suspicion of a metastatic source.

  View details for DOI 10.4158/EP12407.OR

  View details for PubMedID 23757610

• 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

  Abstract

  : 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

• 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

  Abstract

  : 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

• Detection of inferolateral trunk syndrome by neuromonitoring during catheter angiography with provocative testing. Journal of neurointerventional surgery Le, S., Dodd, R., López, J., Nguyen, V., Cho, S. C., Lee, L. 2013; 5 (2)

  Abstract

  It is not uncommon that endovascular balloon test occlusion (BTO) is performed to assess collateral blood flow and risk of injury of permanent occlusion of the internal carotid artery (ICA). This case is the first reported of detection and reversal of the inferolateral trunk (ILT) syndrome in an awake patient during provocative BTO; prompt recognition of the syndrome effectively prevented permanent neurologic deficits.The case of a 42-year-old woman is reported who had a left sphenoid wing meningioma with extension into the cavernous sinus and who underwent awake catheter angiography with provocative BTO of the ICA. Serial examinations by intraoperative monitoring neurologists and neurointerventionalists detected acute progressive left retro-orbital pressure followed by sudden inability to adduct the left eye, or a left medial rectus palsy, indicative of the ILT syndrome which led to immediate balloon deflation and resolution of the deficits. The hypothesis was that hypoperfusion of the ILT, an arterial branch of the ICA which provides blood supply to several cranial nerves (CN) III, CN V1 and CN V2, caused her acute symptoms.Although cerebral ischemia is a well known complication of endovascular procedures, CN ischemia is a rare potential risk. Knowledge of cerebrovascular anatomy and serial examinations prevented neurologic deficits; this case underscores the added utility of examinations by intraoperative monitoring neurologists and interdisciplinary collaboration.

  View details for DOI 10.1136/neurintsurg-2011-010236

  View details for PubMedID 22345146

• Case Series: Intraoperative Neurophysiologic Monitoring (IONM) Changes during Presumably "Non-Critical" Periods of Surgery Lee, L., Cho, S., Viet Nguyen, Ferreira, R., Taricco, L., Steinberg, G., Dodd, R., Ryu, S., Lopez, J. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332068606183

• The Stroke Interventional Radiology (SIR) Process for Rapid Transport of the Acute Stroke Patient Baumann, J. J., Barch, C., Dodd, R., Marcellus, M., Lansberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000330540201465

• Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial LANCET NEUROLOGY Hill, M. D., Martin, R. H., Mikulis, D., Wong, J. H., Silver, F. L., TerBrugge, K. G., Milot, G., Clark, W. M., Macdonald, R. L., Kelly, M. E., Boulton, M., Fleetwood, I., McDougall, C., Gunnarsson, T., Chow, M., Lum, C., Dodd, R., Poublanc, J., Krings, T., Demchuk, A. M., Goyal, M., Anderson, R., Bishop, J., Garman, D., Tymianski, M. 2012; 11 (11): 942-950

  Abstract

  Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings.For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12-95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182.Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment-12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38-0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42-0·83).Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials.NoNO Inc and Arbor Vita Corp.

  View details for DOI 10.1016/S1474-4422(12)70225-9

  View details for Web of Science ID 000310422200010

  View details for PubMedID 23051991

• Initial investigation of F-18-NaF PET/CT for identification of vertebral sites amenable to surgical revision after spinal fusion surgery EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Quon, A., Dodd, R., Iagaru, A., de Abreu, M. R., Hennemann, S., Alves Neto, J. M., Sprinz, C. 2012; 39 (11): 1737-1744

  Abstract

  A pilot study was performed in patients with recurrent back pain after spinal fusion surgery to evaluate the ability of (18)F-NaF PET/CT imaging to correctly identify those requiring surgical intervention and to locate a site amenable to surgical intervention.In this prospective study 22 patients with recurrent back pain after spinal surgery and with equivocal findings on physical examination and CT were enrolled for evaluation with (18)F-NaF PET/CT. All PET/CT images were prospectively reviewed with the primary objective of identifying or ruling out the presence of lesions amenable to surgical intervention. The PET/CT results were then validated during surgical exploration or clinical follow-up of at least 15 months.Abnormal (18)F-NaF foci were found in 16 of the 22 patients, and surgical intervention was recommended. These foci were located at various sites: screws, cages, rods, fixation hardware, and bone grafts. In 6 of the 22 patients no foci requiring surgical intervention were found. Validation of the results by surgery (15 patients) or on clinical follow-up (7 patients) showed that (18)F-NaF PET/CT correctly predicted the presence of an abnormality requiring surgical intervention in 15 of 16 patients and was falsely positive in 1 of 16.In this initial investigation, (18)F-NaF PET/CT imaging showed potential utility for evaluation of recurrent symptoms after spinal fusion surgery by identifying those patients requiring surgical management.

  View details for DOI 10.1007/s00259-012-2196-7

  View details for Web of Science ID 000309562600010

  View details for PubMedID 22895860

  View details for PubMedCentralID PMC3464378

• Sex Differences in Clinical Presentation and Treatment Outcomes in Moyamoya Disease NEUROSURGERY Khan, N., Achrol, A. S., Guzman, R., Burns, T. C., Dodd, R., Bell-Stephens, T., Steinberg, G. K. 2012; 71 (3): 587-593

  Abstract

  Moyamoya (MM) disease is an idiopathic steno-occlusive angiopathy occurring more frequently in females.To evaluate sex differences in preoperative symptoms and treatment outcomes after revascularization surgery.We analyzed 430 MM disease patients undergoing 717 revascularization procedures spanning 19 years (1991-2010) and compared gender differences in preoperative symptoms and long-term outcomes after surgical revascularization.A total of 307 female and 123 male patients (ratio, 2.5:1) with a mean age of 31.0 ± 16.7 years and adults-to-children ratio of 2.5:1 underwent 717 revascularization procedures. Female patients were more likely to experience preoperative transient ischemic attacks (odds ratio: 2.1, P = .001) and less likely to receive a diagnosis of unilateral MM disease (odds ratio: 0.6, P = .04). No association was observed between sex and risk of preoperative ischemic or hemorrhagic stroke. There was no difference in neurological outcome because both male and female patients experienced significant improvement in the modified Rankin Scale score after surgery (P < .0001). On Kaplan-Meier survival analysis, 5-year cumulative risk of adverse postoperative events despite successful revascularization was 11.4% in female vs 5.3% in male patients (P = .05). In multivariate Cox proportional hazards analysis, female sex trended toward an association with adverse postoperative events (hazard ratio: 1.9, P = .14).Female patients are more susceptible to the development of preoperative transient ischemic attack and may be at higher risk of adverse postoperative events despite successful revascularization. There is, however, no sex difference in neurological outcome because patients of both sexes experience significant improvement in neurological status with low risk of the development of future ischemic events after surgical revascularization.

  View details for DOI 10.1227/NEU.0b013e3182600b3c

  View details for Web of Science ID 000308074400016

  View details for PubMedID 22718024

• 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

  Abstract

  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 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

  Abstract

  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 PubMedID 22482792

• F18 NaF PET/CT of the spine for the pre-interventional evaluation of back pain Guo, H., Dodd, R., Huy Do, Quon, A. SOC NUCLEAR MEDICINE INC. 2012

  View details for Web of Science ID 000443680201218

• Concurrent stenoocclusive disease of intracranial and extracranial arteries in a patient with polycythemia vera. Case reports in medicine Hua, L. H., Dodd, R. L., Schwartz, N. E. 2012; 2012: 151767-?

  Abstract

  Moyamoya disease is a stenoocclusive disease involving the intracranial carotid and proximal middle cerebral arteries. There are rarely any additional extracranial stenoses occurring concurrently with moyamoya. The pathophysiology of moyamoya remains obscure, but hematologic disorders, notably sickle-cell anemia, have been associated in some cases. We describe the novel case of polycythemia vera associated with severe steno-occlusive disease of both intracranial and extracranial large arteries. A 47-year-old woman with polycythemia vera had multiple transient ischemic attacks, and noninvasive vessel imaging revealed steno-occlusive disease of bilateral supraclinoid internal carotid arteries with moyamoya-type collaterals, proximal left subclavian artery, right vertebral artery origin, bilateral renal arteries, superior mesenteric artery, and right common iliac artery. Laboratory workup for systemic vasculitis was negative. She required bilateral direct external carotid to internal carotid bypass procedures and percutaneous balloon angioplasty of her right VA origin stenosis. This case suggests that hematologic disorders can lead to vessel stenoses and occlusion. The pathophysiology may be due to a prothrombotic state leading to repeated endothelial injury, resultant intimal hyperplasia, and progressive steno-occlusion.

  View details for DOI 10.1155/2012/151767

  View details for PubMedID 22690222

  View details for PubMedCentralID PMC3368357

• The dynamics of post-operative plasma ACTH values following transsphenoidal surgery for Cushing's disease PITUITARY Srinivasan, L., Laws, E. R., Dodd, R. L., Monita, M. M., Tannenbaum, C. E., Kirkeby, K. M., Chu, O. S., Harsh, G. R., Katznelson, L. 2011; 14 (4): 312-317

  Abstract

  Rapid assessment of adrenal function is critical following transsphenoidal surgery (TSS) for Cushing's disease (CD) in order to determine surgical efficacy. We hypothesize that there may be a role for ACTH measurement as a rapid indicator of adrenal function. Following surgery for CD, glucocorticoids were withheld and paired plasma ACTH and serum cortisol levels were measured every 6 h. Post-operative hypocortisolemia was defined as serum cortisol <2 mcg/dl or a serum cortisol <5 mcg/dl with the onset of symptoms of adrenal insufficiency within 72 h. We studied 12 subjects, all female, mean age 44.6 years (range 25-55), including 13 surgeries: nine subjects attained hypocortisolemia. Plasma ACTH levels decreased more in subjects with hypocortisolemia (0.9 pg/ml/hr, P = 0.0028) versus those with persistent disease (0 0.2 pg/ml/hr, P = 0.26) within the first 48 h after surgery. In contrast to subjects with persistent disease, all subjects with hypocortisolemia achieved a plasma ACTH <20 pg/ml by 19 h (range 1-19 h). Four of the nine subjects with hypocortisolemia achieved plasma ACTH <20 pg/ml by 13 h and the remaining five subjects by 19 h. Hypocortisolemia occurred between 3-36 h following achievement of a plasma ACTH <20 pg/ml. In CD, a reduction in postoperative plasma ACTH levels differentiates subjects with surgical remission versus subjects with persistent disease. The utility of plasma ACTH measurements in the postoperative management of CD remains to be determined.

  View details for DOI 10.1007/s11102-011-0295-2

  View details for Web of Science ID 000300349800003

  View details for PubMedID 21298507

• Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spinal Tumors NEUROSURGERY Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L., Gibbs, I. C. 2011; 69 (3): 533-539

  Abstract

  The role of stereotactic radiosurgery in the treatment of benign intracranial lesions is well established. Although a growing body of evidence supports its role in the treatment of malignant spinal lesions, a much less extensive dataset exists for treatment of benign spinal tumors.To examine the safety and efficacy of stereotactic radiosurgery for treatment of benign, intradural extramedullary spinal tumors.From 1999 to 2008, 87 patients with 103 benign intradural extramedullary spinal tumors (32 meningiomas, 24 neurofibromas, and 47 schwannomas) were treated with stereotactic radiosurgery at Stanford University Medical Center. Forty-three males and 44 females had a median age of 53 years (range, 12-86). Twenty-five patients had neurofibromatosis. Treatment was delivered in 1 to 5 sessions (median, 2) with a mean prescription dose of 19.4 Gy (range, 14-30 Gy) to an average tumor volume of 5.24 cm (range, 0.049-54.52 cm).After a mean radiographic follow-up period of 33 months (range, 6-87), including 21 lesions followed for ≥ 48 months, 59% were stable, 40% decreased in size, and a single tumor (1%) increased in size. Clinically, 91%, 67%, and 86% of meningiomas, neurofibromas, and schwannomas, respectively, were symptomatically stable to improved at last follow-up. One patient with a meningioma developed a new, transient myelopathy at 9 months, although the tumor was smaller at last follow-up.As a viable alternative to microsurgical resection, stereotactic radiosurgery provides safe and efficacious long-term control of benign intradural, extramedullary spinal tumors with a low rate of complication.

  View details for DOI 10.1227/NEU.0b013e318218db23

  View details for Web of Science ID 000293586200003

  View details for PubMedID 21832967

• 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

  Abstract

  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

  Abstract

  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 PubMedID 21221025

• TECHNIQUE FOR TARGETING ARTERIOVENOUS MALFORMATIONS USING FRAMELESS IMAGE-GUIDED ROBOTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hristov, D., Liu, L., Adler, J. R., Gibbs, I. C., Moore, T., Sarmiento, M., Chang, S. D., Dodd, R., Marks, M., Do, H. M. 2011; 79 (4): 1232-1240

  Abstract

  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 PubMedID 20801584

• 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

  Abstract

  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 PubMedID 21135550

• 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

  Abstract

  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 PubMedID 21990637

• The Dynamics of Post-Operative Serum ACTH Values Following Transsphenoidal Surgery for Cushing's Disease. Srinivasan, L., Monita, M., Kirkeby, K., Laws, E. R., Dodd, R. L., Chu, O., Katznelson, L. ENDOCRINE SOC. 2010

  View details for Web of Science ID 000281989402685

• Predictors of Clinical and Angiographic Outcome Following Surgical or Endovascular Therapy of Very Large and Giant Intracranial Aneurysms 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. LIPPINCOTT WILLIAMS & WILKINS. 2010: E266

  View details for Web of Science ID 000276106100300

• Gender Differences in Clinical Presentation and Treatment Outcomes in Moyamoya Disease International Stroke Conference Khan, N., Achrol, A. S., Guzman, R., Dodd, R., Bell-Stephens, T., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2010: E264–E264

  View details for Web of Science ID 000276106100293

• Successful treatment of severe cerebral vasospasm following hemorrhage of an arteriovenous malformation JOURNAL OF NEUROSURGERY-PEDIATRICS Pendharkar, A. V., Guzman, R., Dodd, R., Cornfield, D., Edwards, M. S. 2009; 4 (3): 266-269

  Abstract

  The authors describe the case of a 13-year-old boy who presented with an intraventricular hemorrhage caused by a left trigonal arteriovenous malformation. After an initial recovery, the patient experienced complete right-sided paresis on posthemorrhage Day 6. Severe cerebral vasospasm was found on MR angiography and confirmed on conventional cerebral angiography. Intraarterial nicardipine injection and balloon angioplasty were successfully performed with improved vasospasm and subsequent neurological recovery. Cerebral vasospasm should be considered in the differential diagnosis for neurological deterioration following an arteriovenous malformation hemorrhage, and aggressive treatment can be administered to prevent ischemia and further neurological deficits.

  View details for DOI 10.3171/2009.4.PEDS09126

  View details for Web of Science ID 000269223300012

  View details for PubMedID 19772412

• Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spine Tumors 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L. A., Gibbs, I. C. ELSEVIER SCIENCE INC. 2009: S101–S101

  View details for Web of Science ID 000270573600216

• Subarachnoid hemorrhage. Handbook of clinical neurology Kelly, M. E., Dodd, R., Steinberg, G. K. 2009; 93: 791-808

  View details for DOI 10.1016/S0072-9752(08)93039-6

  View details for PubMedID 18804680

• Image-guided robotic radiosurgery for spinal metastases RADIOTHERAPY AND ONCOLOGY Gibbs, I. C., Kamnerdsupaphon, P., Ryu, M., Dodd, R., Kiernan, M., Change, S. D., Adler, J. R. 2007; 82 (2): 185-190

  Abstract

  To determine the effectiveness and safety of image-guided robotic radiosurgery for spinal metastases.From 1996 to 2005, 74 patients with 102 spinal metastases were treated using the CyberKnife at Stanford University. Sixty-two (84%) patients were symptomatic. Seventy-four percent (50/68) of previously treated patients had prior radiation. Using the CyberKnife, 16-25 Gy in 1-5 fractions was delivered. Patients were followed clinically and radiographically for at least 3 months or until death.With mean follow-up of 9 months (range 0-33 months), 36 patients were alive and 38 were dead at last follow-up. No death was treatment related. Eighty-four (84%) percent of symptomatic patients experienced improvement or resolution of symptoms after treatment. Three patients developed treatment-related spinal injury. Analysis of dose-volume parameters and clinical parameters failed to identify predictors of spinal cord injury.Robotic radiosurgery is effective and generally safe for spinal metastases even in previously irradiated patients.

  View details for DOI 10.1016/j.radonc.2006.11.023

  View details for Web of Science ID 000245151400011

  View details for PubMedID 17257702

• Cyberknife radiosurgery for benign intradural extramedullary spinal tumors NEUROSURGERY Dodd, R. L., Ryu, M. R., Kamnerdsupaphon, P., Gibbs, I. C., Chang, S. D., Adler, J. R. 2006; 58 (4): 674-684

  Abstract

  Microsurgical resection of benign intradural extramedullary spinal tumors is generally safe and successful, but patients with neurofibromatosis, recurrent tumors, multiple lesions, or medical problems that place them at higher surgical risk may benefit from alternatives to surgery. In this prospective study, we analyzed our preliminary experience with image-guided radiosurgical ablation of selected benign spinal neoplasms.Since 1999, CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery was used to manage 51 patients (median age, 46 yr; range, 12-86 yr) with 55 benign spinal tumors (30 schwannomas, nine neurofibromas, 16 meningiomas) at Stanford University Medical Center. Total treatment doses ranged from 1600 to 3000 cGy delivered in consecutive daily sessions (1-5) to tumor volumes that varied from 0.136 to 24.6 cm.Less than 1 year postradiosurgery, three of the 51 patients in this series (one meningioma, one schwannoma, and one neurofibroma) required surgical resection of their tumor because of persistent or worsening symptoms; only one of these lesions was larger radiographically. However, 28 of the 51 patients now have greater than 24 months clinical and radiographic follow-up. After a mean follow-up of 36 months, all of these later lesions were either stable (61%) or smaller (39%). Two patients died from unrelated causes. Radiation-induced myelopathy appeared 8 months postradiosurgery in one patient.Although more patients studied over an even longer follow-up period are needed to determine the long-term efficacy of spinal radiosurgery for benign extra-axial neoplasms, short-term clinical benefits were observed in this prospective analysis. The present study demonstrates that CyberKnife radiosurgical ablation of such tumors is technically feasible and associated with low morbidity.

  View details for DOI 10.1227/01.NEU.0000204128.84742.8F

  View details for Web of Science ID 000237047200026

  View details for PubMedID 16575331

• Oxidative stress and neuronal death/survival signaling in cerebral ischemia Satellite Symposium on Oxidative Mechanisms in Neurodegenerative Disorder Saito, A., Maier, C. M., Narasimhan, P., Nishi, T., Song, Y. S., Yu, F. S., Liu, L., Lee, Y. S., Nito, C., Kamada, H., Dodd, R. L., Hsieh, L. B., Hassid, B., Kim, E. E., Gonzalez, M., Chan, P. H. HUMANA PRESS INC. 2005: 105–16

  Abstract

  It has been demonstrated by numerous studies that apoptotic cell death pathways are implicated in ischemic cerebral injury in ischemia models in vivo. Experimental ischemia and reperfusion models, such as transient focal/global ischemia in rodents, have been thoroughly studied and the numerous reports suggest the involvement of cell survival/death signaling pathways in the pathogenesis of apoptotic cell death in ischemic lesions. In these models, reoxygenation during reperfusion provides oxygen as a substrate for numerous enzymatic oxidation reactions and for mitochondrial oxidative phosphorylation to produce adenosine triphosphate. Oxygen radicals, the products of these biochemical and physiological reactions, are known to damage cellular lipids, proteins, and nucleic acids and to initiate cell signaling pathways after cerebral ischemia. Genetic manipulation of intrinsic antioxidants and factors in the signaling pathways has provided substantial understanding of the mechanisms involved in cell death/survival signaling pathways and the role of oxygen radicals in ischemic cerebral injury. Future studies of these pathways could provide novel therapeutic strategies in clinical stroke.

  View details for PubMedID 15953815

• Damage to the endoplasmic reticulum and activation of apoptotic machinery by oxidative stress in ischemic neurons JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Hayashi, T., Saito, A., Okuno, S., Ferrand-Duke, M., Dodd, R. L., Chan, P. H. 2005; 25 (1): 41-53

  Abstract

  The endoplasmic reticulum (ER), which plays a role in apoptosis, is susceptible to oxidative stress. Because superoxide is produced in the brain after ischemia/reperfusion, oxidative injury to this organelle may be implicated in ischemic neuronal cell death. Activating transcription factor-4 (ATF-4) and C/EBP-homologous protein (CHOP), both of which are involved in apoptosis, are induced by severe ER stress. Using wild-type and human copper/zinc superoxide dismutase transgenic rats, we observed induction of these molecules in the brain after global cerebral ischemia and compared them with neuronal degeneration. In ischemic, wild-type brains, expression of ATF-4 and CHOP was increased in the hippocampal CA1 neurons that would later undergo apoptosis. Transgenic rats had a mild increase in ATF-4 and CHOP and minimal neuronal degeneration, indicating that superoxide was involved in ER stress-induced cell death. We further confirmed attenuation on induction of these molecules in transgenic mouse brains after focal ischemia. When superoxide was visualized with ethidium, signals for ATF-4 and superoxide overlapped in the same cells. Moreover, lipids in the ER were robustly peroxidized by ischemia but were attenuated in transgenic animals. This indicates that superoxide attacked and damaged the ER, and that oxidative ER damage is implicated in ischemic neuronal cell death.

  View details for DOI 10.1038/sj.jcbfm.9600005

  View details for Web of Science ID 000226360000004

  View details for PubMedID 15678111

• Recoverin regulates light-dependent phosphodiesterasc activity in retinal rods JOURNAL OF GENERAL PHYSIOLOGY Makino, C. L., Dodd, R. L., Chen, J., Burns, M. E., Roca, A., Simon, M. I., Baylor, D. A. 2004; 123 (6): 729-741

  Abstract

  The Ca2+-binding protein recoverin may regulate visual transduction in retinal rods and cones, but its functional role and mechanism of action remain controversial. We compared the photoresponses of rods from control mice and from mice in which the recoverin gene was knocked out. Our analysis indicates that Ca2+-recoverin prolongs the dark-adapted flash response and increases the rod's sensitivity to dim steady light. Knockout rods had faster Ca2+ dynamics, indicating that recoverin is a significant Ca2+ buffer in the outer segment, but incorporation of exogenous buffer did not restore wild-type behavior. We infer that Ca2+-recoverin potentiates light-triggered phosphodiesterase activity, probably by effectively prolonging the catalytic activity of photoexcited rhodopsin.

  View details for DOI 10.1085/jgp.200308994

  View details for Web of Science ID 000221988000009

  View details for PubMedID 15173221

• Oxidative injury to the endoplasmic reticulum in mouse brains after transient focal ischemia NEUROBIOLOGY OF DISEASE Hayashi, T., Saito, A., Okuno, S., Ferrand-Drake, M., Dodd, R. L., Chan, P. H. 2004; 15 (2): 229-239

  Abstract

  Oxidative damage to the endoplasmic reticulum (ER) could be involved in ischemic neuronal cell death because this organelle is susceptible to reactive oxygen species. Using wild-type mice and copper/zinc-superoxide dismutase (SOD1) transgenic mice, we induced focal cerebral ischemia and compared neuronal degeneration and ER stress, that is, phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) and RNA-dependent protein kinase-like ER eIF2alpha kinase (PERK). We found that neurons with severe and prolonged phosphorylation of eIF2alpha and PERK underwent later degeneration, and that this was partially prevented by SOD1 overexpression. Signals for superoxide production and phospho-PERK were colocalized, which further indicates a pivotal role for superoxide in ER damage. We investigated the molecular mechanisms of oxidative ER stress and found that detachment of glucose-regulated protein 78 from PERK was the key step. We conclude that ER damage is involved in oxidative neuronal injury in the brain after ischemia/reperfusion.

  View details for DOI 10.1016/j.nbd.2003.10.005

  View details for Web of Science ID 000220173800008

  View details for PubMedID 15006693

• Oxidative damage to the endoplasmic reticulum is implicated in ischemic neuronal cell death JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Hayashi, T., Saito, A., Okuno, S., Ferrand-Drake, M., Dodd, R. L., Nishi, T., Maier, C. M., Kinouchi, H., Chan, P. H. 2003; 23 (10): 1117-1128

  Abstract

  The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. Because reactive oxygen species (ROS) are robustly produced in the ischemic brain, ER damage by ROS may be implicated in ischemic neuronal cell death. We induced global brain ischemia on wild-type and copper/zinc superoxide dismutase (SOD1) transgenic rats and compared ER stress and neuronal damage. Phosphorylated forms of eukaryotic initiation factor 2 alpha (eIF2 alpha) and RNA-dependent protein kinase-like ER eIF2 alpha kinase (PERK), both of which play active roles in apoptosis, were increased in hippocampal CA1 neurons after ischemia but to a lesser degree in the transgenic animals. This finding, together with the finding that the transgenic animals showed decreased neuronal degeneration, indicates that oxidative ER damage is involved in ischemic neuronal cell death. To elucidate the mechanisms of ER damage by ROS, we analyzed glucose-regulated protein 78 (GRP78) binding with PERK and oxidative ER protein modification. The proteins were oxidatively modified and stagnated in the ER lumen, and GRP78 was detached from PERK by ischemia, all of which were attenuated by SOD1 overexpression. We propose that ROS attack and modify ER proteins and elicit ER stress response, which results in neuronal cell death.

  View details for DOI 10.1097/01.WCB.0000089600.87125.AD

  View details for Web of Science ID 000185755500002

  View details for PubMedID 14526222

• Spontaneous resolution of a prepontine arachnoid cyst - Case report and review of the literature PEDIATRIC NEUROSURGERY Dodd, R. L., Barnes, P. D., Huhn, S. L. 2002; 37 (3): 152-157

  Abstract

  Prepontine arachnoid cysts are rare developmental anomalies that occur almost exclusively in children. The symptomatic child typically suffers from hydrocephalus, visual impairment, endocrine dysfunction and/or cranial neuropathies. Some cysts, however, are discovered incidentally upon prenatal or postnatal imaging for other indications. While there is little doubt that surgical treatment should be initiated to help the symptomatic child, appropriate therapy for the asymptomatic patient is unclear. Although arachnoid cysts are often managed conservatively using serial imaging, the consequences of injury to surrounding structures with prepontine cysts often lowers the threshold for intervention. The natural history of asymptomatic prepontine arachnoid cysts is unknown. It has been reported that some cysts enlarge and cause symptoms, whereas others are stable for years. This report describes an index case of spontaneous resolution of a prepontine arachnoid cyst in a female infant over a 5-year period.

  View details for Web of Science ID 000177787800006

  View details for PubMedID 12187060

• Prolonged photoresponses in transgenic mouse rods lacking arrestin NATURE Xu, J., Dodd, R. L., Makino, C. L., Simon, M. I., Baylor, D. A., Chen, J. 1997; 389 (6650): 505-509

  Abstract

  Arrestins are soluble cytoplasmic proteins that bind to G-protein-coupled receptors, thus switching off activation of the G protein and terminating the signalling pathway that triggers the cellular response. Although visual arrestin has been shown to quench the catalytic activity of photoexcited, phosphorylated rhodopsin in a reconstituted system, its role in the intact rod cell remains unclear because phosphorylation alone reduces the catalytic activity of rhodopsin. Here we have recorded photocurrents of rods from transgenic mice in which one or both copies of the arrestin gene were disrupted. Photoresponses were unaffected when arrestin expression was halved, indicating that arrestin binding is not rate limiting for recovery of the rod photoresponse, as it is in Drosophila. With arrestin absent, the flash response displayed a rapid partial recovery followed by a prolonged final phase. This behaviour indicates that an arrestin-independent mechanism initiates the quench of rhodopsin's catalytic activity and that arrestin completes the quench. The intensity dependence of the photoresponse in rods lacking arrestin further suggests that, although arrestin is required for normal signal termination, it does not participate directly in light adaptation.

  View details for Web of Science ID A1997XY90900059

  View details for PubMedID 9333241

• Phospholipase C beta 4 is involved in modulating the visual response in mice PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Jiang, H. P., Lyubarsky, A., Dodd, R., Vardi, N., Pugh, E., Baylor, D., Simon, M. I., Wu, D. Q. 1996; 93 (25): 14598-14601

  Abstract

  Expression of G protein-regulated phospholipase C (PLC) beta 4 in the retina, lateral geniculate nucleus, and superior colliculus implies that PLC beta 4 may play a role in the mammalian visual process. A mouse line that lacks PLC beta 4 was generated and the physiological significance of PLC beta 4 in murine visual function was investigated. Behavioral tests using a shuttle box demonstrated that the mice lacking PLC beta 4 were impaired in their visual processing abilities, whereas they showed no deficit in their auditory abilities. In addition, the PLC beta 4-null mice showed 4-fold reduction in the maximal amplitude of the rod a- and b-wave components of their electroretinograms relative to their littermate controls. However, recording from single rod photoreceptors did not reveal any significant differences between the PLC beta 4-null and wild-type littermates, nor were there any apparent differences in retinas examined with light microscopy. While the behavioral and electroretinographic results indicate that PLC beta 4 plays a significant role in mammalian visual signal processing, isolated rod recording shows little or no apparent deficit, suggesting that the effect of PLC beta 4 deficiency on the rod signaling pathway occurs at some stage after the initial phototransduction cascade and may require cell-cell interactions between rods and other retinal cells.

  View details for Web of Science ID A1996VY44800075

  View details for PubMedID 8962098

  View details for PubMedCentralID PMC26179

• Multiple visual pigments in a photoreceptor of the salamander retina JOURNAL OF GENERAL PHYSIOLOGY Makino, C. L., Dodd, R. L. 1996; 108 (1): 27-34

  Abstract

  Although a given retina typically contains several visual pigments, each formed from a retinal chromophore bound to a specific opsin protein, single photoreceptor cells have been thought to express only one type of opsin. This design maximizes a cell's sensitivity to a particular wavelength band and facilitates wavelength discrimination in retinas that process color. We report electrophysiological evidence that the ultraviolet-sensitive cone of salamander violates this rule. This cell contains three different functional opsins. The three opsins could combine with the two different chromophores present in salamander retina to form six visual pigments. Whereas rods and other cones of salamander use both chromophores, they appear to express only one type of opsin per cell. In visual pigment absorption spectra, the bandwidth at half-maximal sensitivity increases as the pigment's wavelength maximum decreases. However, the bandwidth of the UV-absorbing pigment deviates from this trend; it is narrow like that of a red-absorbing pigment. In addition, the UV-absorbing pigment has a high apparent photosensitivity when compared with that of red- and blue-absorbing pigments and rhodopsin. These properties suggest that the mechanisms responsible for spectrally tuning visual pigments separate two absorption bands as the wavelength of maximal sensitivity shifts from UV to long wavelengths.

  View details for Web of Science ID A1996UV94000003

  View details for PubMedID 8817382

• "Phospholipase C beta-4 is involved in modulating the visual response in mice Proc. Natl. Acad. Sci. USA 93 Jiang, H., Lyubarsky, A, Dodd, RL, Vardi, N., Pugh, E., Baylor, D., Simon, M.I., Wu, D 1996; 14598-601