Bio

Bio


Dr Appelboom is Clinical Instructor of Neurosurgery at Stanford. Dr Appelboom is focused on advancing minimally invasive surgical techniques for diseases of the brain and spine.

Dr Appelboom is a surgeon scientist. He spent 3 years of integrated PhD research at Columbia University Medical Center to study genetic predictors of vascular fragility. Dr Appelboom has authored over 60 peer reviewed publications in international journals including Stroke, Translational Stroke Research, Current Atherosclerosis Reports, and Journal of Neurology, Neurosurgery & Psychiatry. He has also completed a master in stereotactic neurosurgery at La Sorbonne University in Paris. Dr Appelboom’s research efforts include utilization of MR guided technologies such as stereotactic radiosurgery and focused ultrasound.

Dr Appelboom is a Stanford faculty with an entrepreneurial spirit. He was selected to be a 2017 Faculty Fellow at the Byers Center for Biodesign. The program provides the most in-depth training experience in health technology innovation with a multidisciplinary experience that involve hands-on health technology projects with the help of Biodesign faculty and industry experts.

Clinical Focus


  • Neurosurgery

Academic Appointments


Administrative Appointments


  • Clinical Instructor, Stanford University (2016 - Present)
  • Senior Research Scientist, Columbia University (2012 - 2013)
  • Post Doctoral Scientist, Columbia University (2009 - 2011)
  • Post Doctoral Scientist, The Rockefeller University (2007 - 2007)

Honors & Awards


  • Faculty Innovation Fellow, Stanford Byers Center for Biodesign (2016-2017)
  • Hoover Fellow For Medical Research, BAEF (2010)

Boards, Advisory Committees, Professional Organizations


  • Active Member, American Association of Neurological Surgeons (2014 - Present)
  • Active Member, The Congress of Neurological Surgeon (2014 - Present)
  • Active Member, American Society for Stereotactic and Functional Neurosurgery (2015 - Present)

Professional Education


  • Fellowship:Columbia University Vagelos College of Physicians and Surgeons Registrar (2011) NY
  • Board Certification: NeurosurgeryN/A
  • Residency:Free University of BrusselsBelgium
  • Medical Education:Free University of Brussels (2007) Belgium

Patents


  • Geoffrey Appelboom. "United States Patent US 20150102208 A1 Wearable system and method to measure and monitor ultraviolet, visible light, and infrared radiations in order to provide personalized medical recommendations, prevent diseases, and improve disease management"

Publications

All Publications


  • Brainstem Dose Constraints in Nonisometric Radiosurgical Treatment Planning of Trigeminal Neuralgia: A Single-Institution Experience WORLD NEUROSURGERY Zhang, M., Lamsam, L. A., Schoen, M. K., Mehta, S. S., Appelboom, G., Adler, J. K., Soltys, S. G., Chang, S. D. 2018; 113: E399–E407

    Abstract

    CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) administers nonisometric, conformational high-dose radiation to the trigeminal nerve with risk of subsequent hypoesthesia.We performed a retrospective, single-institution review of 66 patients with TGN treated with CyberKnife SRS to compare outcomes from 2 distinct treatment periods: standard dosing (n = 38) and reduced dosing (n = 28). Standard and reduced dosing permitted a maximum brainstem dose of 45 Gy and 25 Gy, respectively, each with a prescription dose of 60 Gy. Primary and secondary outcomes were Barrow Neurologic Institute pain and numbness scores. Maximum brainstem dose, prepontine nerve length, and treatment history were recorded for their predictive contributions by logistic regression.After matching, patients in the standard dosing and reduced dosing groups were followed for a median of 25 months and 19.5 months, respectively. Mean trigeminal nerve length was 8.55 mm in the standard dosing group and 9.46 mm in the reduced dosing group. Baseline rates of poorly controlled pain were 97% and 88%, respectively, which improved to 23.4% and 8.3%, respectively (P < 0.001 for both). The baseline rates of bothersome numbness were null in both groups, and increased to 25% in the standard group (P = 0.006) and to 21% in the reduced group (P = 0.07). Regression analyses suggested that reduced brainstem exposure (P = 0.01), as well as a longer trigeminal nerve (P = 0.01), were predictive of durable pain control.These outcomes demonstrate that a lower maximum brainstem dose can provide excellent pain control without affecting facial numbness. Longer nerves may achieve better long-term outcomes and help optimize individual plans.

    View details for DOI 10.1016/j.wneu.2018.02.042

    View details for Web of Science ID 000432942700047

    View details for PubMedID 29454124

  • Relationship between ambulatory physical activity assessed by activity trackers and physical frailty among nursing home residents. Gait & posture Buckinx, F., Mouton, A., Reginster, J. Y., Croisier, J. L., Dardenne, N., Beaudart, C., NELIS, J., Lambert, E., Appelboom, G., Bruyère, O. 2017; 54: 56-61

    Abstract

    The aim of this study was to assess the relationship between the level of ambulatory physical activity, measured by physical activity tracker, and the clinical components of physical frailty, among nursing home residents.We proceeded in 3 steps: (1) Validation of the physical activity tracker (i.e. the Pebble): 24 volunteer adults walked on a treadmill. The number of steps recorded by the Pebble worn by the subjects was compared with the number of steps counted by the investigators, by means of the Intra-class correlation coefficients (ICC). (2) Measurement of ambulatory physical activity, using the Pebble trackers, over a 7-day period. (3) Relationship between the results obtained with the Pebble trackers (step 2) and subjects' clinical characteristics, linked to physical frailty.ICC data, showed that the reliability of the Pebble was better when it was worn at the foot level (ICC ranged from 0.60 to 0.93 depending on the tested speed). Gait speed is also an important determinant of the reliability, which is better for low gait speed. On average, the 27 nursing home residents included in the second step of this study walked 1678.4±1621 (median=1300) steps per day. Most physical components of frailty measured in this study were significantly different between subjects who walked less than 1300 steps per day and those who were more active.This study showed that nursing home residents have a poor ambulatory physical activity, assessed using a physical activity tracker, which is associated with poorer physical performances and higher disability.

    View details for DOI 10.1016/j.gaitpost.2017.02.010

    View details for PubMedID 28259040

  • Stereotactic modulation of blood-brain barrier permeability to enhance drug delivery NEURO-ONCOLOGY Appelboom, G., Detappe, A., Lopresti, M., Kunjachan, S., Mitrasinovic, S., Goldman, S., Chang, S. D., Tillement, O. 2016; 18 (12): 1601-1609

    Abstract

    Drug delivery in the CNS is limited by endothelial tight junctions forming the impermeable blood-brain barrier. The development of new treatment paradigms has previously been hampered by the restrictiveness of the blood-brain barrier to systemically administered therapeutics. With recent advances in stereotactic localization and noninvasive imaging, we have honed the ability to modulate, ablate, and rewire millimetric brain structures to precisely permeate the impregnable barrier. The wide range of focused radiations offers endless possibilities to disrupt endothelial permeability with different patterns and intensity following 3-dimensional coordinates offering a new world of possibilities to access the CNS, as well as to target therapies. We propose a review of the current state of knowledge in targeted drug delivery using noninvasive image-guided approaches. To this end, we focus on strategies currently used in clinics or in clinical trials such as targeted radiotherapy and magnetic resonance guided focused ultrasound, but also on more experimental approaches such as magnetically heated nanoparticles, electric fields, and lasers, techniques which demonstrated remarkable results both in vitro and in vivo. We envision that biodistribution and efficacy of systemically administered drugs will be enhanced with further developments of these promising strategies. Besides therapeutic applications, stereotactic platforms can be highly valuable in clinical applications for interventional strategies that can improve the targetability and efficacy of drugs and macromolecules. It is our hope that by showcasing and reviewing the current state of this field, we can lay the groundwork to guide future research in this realm.

    View details for DOI 10.1093/neuonc/now137

    View details for Web of Science ID 000387331500004

    View details for PubMedID 27407134

  • Causes and Timing of Unplanned Early Readmission After Neurosurgery NEUROSURGERY Taylor, B. E., Youngerman, B. E., Goldstein, H., Kabat, D. H., Appelboom, G., Gold, W. E., Connolly, E. S. 2016; 79 (3): 356-369

    Abstract

    Reducing the rate of 30-day hospital readmission has become a priority in healthcare quality improvement policy, with a focus on better characterizing the reasons for unplanned readmission. In neurosurgery, however, peer-reviewed analyses describing the patterns of readmission have been limited in their number and generalizability.To determine the incidence, timing, and causes of 30-day readmission after neurosurgical procedures.We conducted a retrospective longitudinal study from 2009 to 2012 using the Statewide Planning And Research Cooperative System, which collects patient-level details for all admissions and discharges within New York. We identified patients readmitted within 30 days of initial discharge. The rate of, reasons for, and time to readmission were determined overall and within 4 subgroups: craniotomies, cranial surgery without craniotomy, spine, and neuroendovascular procedures.There were 163 743 index admissions, of whom 14 791 (9.03%) were readmitted. The most common reasons for unplanned readmission were infection (29.52%) and medical complications (19.22%). Median time to readmission was 11 days, with hemorrhagic strokes and seizures occurring earlier, and medical complications and infections occurring later. Readmission rates were highest among patients undergoing cerebrospinal fluid shunt revision and malignant tumor resection (15.57%-22.60%). Spinal decompressions, however, accounted for the largest volume of readmissions (33.13%).Many readmissions may be preventable and occur at predictable time intervals. The causes and timing of readmission vary significantly across neurosurgical subgroups. Future studies should focus on detecting specific complications in select cohorts at predefined time points, which may allow for interventions to lower costs and reduce patient morbidity.CSF, cerebrospinal fluidIQR, interquartile rangeSPARCS, Statewide Planning And Research Cooperative System.

    View details for DOI 10.1227/NEU.0000000000001110

    View details for Web of Science ID 000383274400011

    View details for PubMedID 26562821

  • Preoperative chemotherapy and corticosteroids: independent predictors of cranial surgical-site infections JOURNAL OF NEUROSURGERY Lieber, B. A., Appelboom, G., Taylor, B. E., Lowy, F. D., Bruce, E. M., Sonabend, A. M., Kellner, C., Connolly, E. S., Bruce, J. N. 2016; 125 (1): 187-195

    Abstract

    OBJECT Preoperative corticosteroids and chemotherapy are frequently prescribed for patients undergoing cranial neurosurgery but may pose a risk of postoperative infection. Postoperative surgical-site infections (SSIs) have significant morbidity and mortality, dramatically increase the length and cost of hospitalization, and are a major cause of 30-day readmission. In patients undergoing cranial neurosurgery, there is a lack of data on the role of patient-specific risk factors in the development of SSIs. The authors of this study sought to determine whether chemotherapy and prolonged steroid use before surgery increase the risk of an SSI at postoperative Day 30. METHODS Using the national prospectively collected American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for 2006-2012, the authors calculated the rates of superficial, deep-incisional, and organ-space SSIs at postoperative Day 30 for neurosurgery patients who had undergone chemotherapy or had significant steroid use within 30 days before undergoing cranial surgery. Trauma patients, patients younger than 18 years, and patients with a preoperative infection were excluded. Univariate analysis was performed for 25 variables considered risk factors for superficial and organ-space SSIs. To identify independent predictors of SSIs, the authors then conducted a multivariate analysis in which they controlled for duration of operation, wound class, white blood cell count, and other potential confounders that were significant on the univariate analysis. RESULTS A total of 8215 patients who had undergone cranial surgery were identified. There were 158 SSIs at 30 days (frequency 1.92%), of which 52 were superficial, 27 were deep-incisional, and 79 were organ-space infections. Preoperative chemotherapy was an independent predictor of organ-space SSIs in the multivariate model (OR 5.20, 95% CI 2.33-11.62, p < 0.0001), as was corticosteroid use (OR 1.86, 95% CI 1.03-3.37, p = 0.04), but neither was a predictor of superficial or deep-incisional SSIs. Other independent predictors of organ-space SSIs were longer duration of operation (OR 1.16), wound class of ≥ 2 (clean-contaminated and further contaminated) (OR 3.17), and morbid obesity (body mass index ≥ 40 kg/m(2)) (OR 3.05). Among superficial SSIs, wound class of 3 (contaminated) (OR 6.89), operative duration (OR 1.13), and infratentorial surgical approach (OR 2.20) were predictors. CONCLUSIONS Preoperative chemotherapy and corticosteroid use are independent predictors of organ-space SSIs, even when data are controlled for leukopenia. This indicates that the disease process in organ-space SSIs may differ from that in superficial SSIs. In effect, this study provides one of the largest analyses of risk factors for SSIs after cranial surgery. The results suggest that, in certain circumstances, modulation of preoperative chemotherapy or steroid regimens may reduce the risk of organ-space SSIs and should be considered in the preoperative care of this population. Future studies are needed to determine optimal timing and dosing of these medications.

    View details for DOI 10.3171/2015.4.JNS142719

    View details for Web of Science ID 000378980100026

    View details for PubMedID 26544775

  • Assessment of the "July Effect": outcomes after early resident transition in adult neurosurgery JOURNAL OF NEUROSURGERY Lieber, B. A., Appelboom, G., Taylor, B. E., Malone, H., Agarwal, N., Connolly, E. S. 2016; 125 (1): 213-221

    Abstract

    OBJECT Each July, 4th-year medical students become 1st-year resident physicians and have much greater responsibility in making management decisions. In addition, incumbent residents and fellows advance to their next postgraduate year and face greater challenges. It has been suggested that among patients who have resident physicians as members of their neurosurgical team, this transition may be associated with increased rates of morbidity and mortality, a phenomenon known as the "July Effect." In this study, the authors compared morbidity and mortality rates between the initial and later months of the academic year to determine whether there is truly a July Effect that has an impact on this patient population. METHODS The authors compared 30-day postoperative outcomes of neurosurgery performed by surgical teams that included resident physicians in training during the first academic quarter (Q1, July through September) with outcomes of neurosurgery performed with resident participation during the final academic quarter (Q4, April through June), using 2006-2012 data from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Regression analyses were performed on outcome data that included mortality, surgical complications, and medical complications, which were graded as mild or severe. To determine whether a July Effect was present in subgroups, secondary analyses were performed to analyze the association of outcomes with each major neurosurgical subspecialty, the postgraduate year of the operating resident, and the academic quarter during which the surgery was performed. To control for possible seasonal trends in certain diseases, the authors compared patient outcomes at academic medical centers to those at community-based hospitals, where procedures were not performed by residents. In addition, the efficiency of academic centers was compared to that of community centers in terms of operative duration and total length of hospital stay. RESULTS Overall, there were no statistically significant differences in mortality, morbidity, or efficiency between the earlier and later quarters of the academic year, a finding that also held true among neurosurgical subspecialties and among postgraduate levels of training. There was, however, a slight increase in intraoperative transfusions associated with the transitional period in July (6.41% of procedures in Q4 compared to 7.99% in Q1 of the prior calendar year; p = 0.0005), which primarily occurred in cases involving junior (2nd- to 4th-year) residents. In addition, there was an increased rate of reoperation (1.73% in Q4 to 2.19% in Q1; p < 0.0001) observed mainly among senior (5th- to 7th-year) residents in the early academic months and not paralleled in our community cohort. CONCLUSIONS There is minimal evidence for a significant July Effect in adult neurosurgery. Our results suggest that, overall, the current resident training system provides enough guidance and support during this challenging transition period.

    View details for DOI 10.3171/2015.4.JNS142149

    View details for Web of Science ID 000378980100029

    View details for PubMedID 26666349

  • Focused ultrasound to transiently disrupt the blood brain barrier JOURNAL OF CLINICAL NEUROSCIENCE Mitrasinovic, S., Appelboom, G., Detappe, A., Connolly, E. S. 2016; 28: 187-189

    View details for DOI 10.1016/j.jocn.2015.12.011

    View details for Web of Science ID 000376714500041

    View details for PubMedID 26883350

  • Association of Steroid Use with Deep Venous Thrombosis and Pulmonary Embolism in Neurosurgical Patients: A National Database Analysis WORLD NEUROSURGERY Lieber, B. A., Han, J., Appelboom, G., Taylor, B. E., Han, B., Agarwal, N., Connolly, E. S. 2016; 89: 126-132

    Abstract

    Venous thromboembolism (VTE) is a major preventable cause of morbidity and mortality in hospitalized patients and is a widely accepted measure for quality of care. Prolonged corticosteroid therapy, which is common in neurosurgical patients, has been associated with VTE. Using a national database, we sought to determine whether corticosteroid use for >10 days was an independent risk factor for deep venous thrombosis (DVT) and pulmonary embolism (PE).The well-validated American College of Surgeons National Surgical Quality Improvement Program database was queried to evaluate the rates of VTE during the period 2006-2013 in patients undergoing neurosurgical procedures. A multivariate regression model was constructed to assess the effect of prolonged corticosteroid use on the occurrence of PE and DVT by postoperative day 30.Of 94,620 patients identified, 565 (0.60%) developed PE and 1057 (1.12%) developed DVT within 30 days after surgery. In the multivariate model, patients receiving corticosteroids were significantly more likely to have PE (odds ratio = 1.47, 95% confidence interval = 1.13-1.90, P = 0.004) and DVT (odds ratio = 1.55, 95% confidence interval = 1.28-1.87, P < 0.001). Other factors independently associated with development of PE and DVT included the presence of malignancy, longer hospitalization, certain infections (including pneumonia and urinary tract infections), and stroke with a neurologic deficit.In the neurosurgical population, prolonged courses of corticosteroids are associated with an increased risk of developing postoperative DVT and PE, even when controlling for potential confounders.

    View details for DOI 10.1016/j.wneu.2016.01.033

    View details for Web of Science ID 000376448700020

    View details for PubMedID 26805689

  • Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia AGING CLINICAL AND EXPERIMENTAL RESEARCH Reginster, J., Cooper, C., Rizzoli, R., Kanis, J. A., Appelboom, G., Bautmans, I., Bischoff-Ferrari, H. A., Boers, M., Brandi, M. L., Bruyere, O., Cherubini, A., Flamion, B., Fielding, R. A., Gasparik, A. I., van Loon, L., McCloskey, E., Mitlak, B. H., Pilotto, A., Reiter-Niesert, S., Rolland, Y., Tsouderos, Y., Visser, M., Cruz-Jentoft, A. J. 2016; 28 (1): 47-58

    Abstract

    Sarcopenia is an age-related muscle condition which is frequently a precursor of frailty, mobility disability and premature death. It has a high prevalence in older populations and presents a considerable social and economic burden. Potential treatments are under development but, as yet, no guidelines support regulatory studies for new drugs to manage sarcopenia. The objective of this position paper is therefore to suggest a set of potential endpoints and target population definitions to stimulate debate and progress within the medico-scientific and regulatory communities.A multidisciplinary expert working group was hosted by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, which reviewed and discussed the recent literature from a perspective of clinical experience and guideline development. Relevant parallels were drawn from the development of definition of osteoporosis as a disease and clinical assessment of pharmaceutical treatments for that indication.A case-finding decision tree is briefly reviewed with a discussion of recent prevalence estimations of different relevant threshold values. The selection criteria for patients in regulatory studies are discussed according to the aims of the investigation (sarcopenia prevention or treatment) and the stage of project development. The possible endpoints of such studies are reviewed and a plea is made for the establishment of a core outcome set to be used in all clinical trials of sarcopenia.The current lack of guidelines for the assessment of new therapeutic treatments for sarcopenia could potentially hinder the delivery of effective medicines to patients at risk.

    View details for DOI 10.1007/s40520-015-0517-y

    View details for Web of Science ID 000371249700005

    View details for PubMedID 26717937

  • Impact of Hyponatremia on Morbidity, Mortality, and Complications After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review WORLD NEUROSURGERY Mapa, B., Taylor, B. E., Appelboom, G., Bruce, E. M., Claassen, J., Connolly, E. S. 2016; 85: 305-314

    Abstract

    Hyponatremia is a common metabolic disturbance after aneurysmal subarachnoid hemorrhage (SAH), and it may worsen outcomes. This review aims to characterize the effect of hyponatremia on morbidity and mortality after SAH.We sought to determine the prevalence of hyponatremia after SAH, including in subgroups, as well as its effect on mortality and certain outcome measures, including degree of disability and duration of hospitalization.A search of terms "hyponatremia" and "subarachnoid hemorrhage" was performed on PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Studies were included if they reported prevalence of hyponatremia and if they discussed outcomes such as mortality, duration of stay, functional outcomes (e.g., Glasgow Outcomes Scale), or incidence of complications in patients with aneurysmal SAH. Two independent researchers assessed the titles and abstracts and reviewed articles for inclusion.Thirteen studies met inclusion criteria. The prevalence of at least mild hyponatremia was 859 of 2387 (36%) of patients. Hyponatremia was associated with vasospasm and duration of hospitalization, but it did not influence mortality.Hyponatremia is common after SAH, and there is evidence that it is associated with certain poorer outcomes. Larger, prospective studies are needed to assess these findings and provide further evidence.

    View details for DOI 10.1016/j.WNUE.2015.08.054

    View details for Web of Science ID 000368229700045

    View details for PubMedID 26361321

  • The role of age in intracerebral hemorrhages. Journal of clinical neuroscience Camacho, E., LoPresti, M. A., Bruce, S., Lin, D., Abraham, M., Appelboom, G., Taylor, B., McDowell, M., DuBois, B., Sathe, M., Sander Connolly, E. 2015; 22 (12): 1867-1870

    Abstract

    We aimed to identify the role of age in intracerebral hemorrhage (ICH), as well as characterize the most commonly used age cut off points in the literature, with the hope of understanding and guiding treatment. Strokes are one of the leading causes of death in the USA, and ICH is the deadliest type. Age is a strong risk factor, but it also affects the body in numerous ways, including changes to the cardiovascular and central nervous systems that interplay with the multiple risk factors for ICH. Understanding the role of age in risk and outcomes of ICH can guide treatment and future clinical trials. A current review of the literature suggests that the age cut offs for increased rates of mortality and morbidity vary from 60-80 years of age, with the most common age cut offs being at 65 or 70 years of age. In addition to age as a determinant of ICH outcomes, age has its own effects on the maturing body in terms of changes in physiology, while also increasing the risk of multiple chronic health conditions and comorbidities, including hypertension, diabetes, and anticoagulant treatment for atrial fibrillation, all of which contribute to the pathology of ICH. The interaction of these chronic conditions, changes in physiology, age, and ICH is evident. However, the exact mechanism and extent of the impacts remains unclear. The ambiguity of these connections may be further obscured by individual patient preferences, and there are limitations in the literature which guides the current recommendations for aging patients.

    View details for DOI 10.1016/j.jocn.2015.04.020

    View details for PubMedID 26375325

  • The role of age in intracerebral hemorrhages JOURNAL OF CLINICAL NEUROSCIENCE Camacho, E., LoPresti, M. A., Bruce, S., Lin, D., Abraham, M., Appelboom, G., Taylor, B., McDowell, M., DuBois, B., Sathe, M., Connolly, E. S. 2015; 22 (12): 1867-1870
  • Aquaporin-4 gene variant independently associated with oedema after intracerebral haemorrhage NEUROLOGICAL RESEARCH Appelboom, G., Bruce, S., Duren, A., Piazza, M., Monahan, A., Christophe, B., Zoller, S., Lopresti, M., Connolly, E. S. 2015; 37 (8): 657-661

    Abstract

    Aquaporin-4 (AQP4) is the prominent water-channel protein in the brain playing a critical role in controlling cell water content. After intracerebral haemorrhage (ICH), perihematomal oedema (PHE) formation leads to a rapid increase in intracranial pressure (ICP) after the initial bleed. We sought to investigate the effect of a common genomic variant in the AQP4 gene on PHE formation after ICH.We reviewed the literature and identified a candidate polymorphism in AQP4 genes previously reported in Genome Wide Association Studies (GWAS). Between February 2009 and March 2011, 128 patients consented to genetic testing and were genotyped for single nucleotide polymorphism (SNP) on the AQP4 gene. Genomic DNA was extracted from buccal swabs using MasterAmp extraction kits (Epicentre, Madison, WI, USA). DNA extracted from buffy coats of whole blood samples was amplified via PCR. Linear regression with log-transformed ICH + PHE volume as the response variable was used to determine the association of SNP controlled for admission variables age, GCS, infratentorial location, hypertension, systolic blood pressure (SBP), blood urea nitrogen (BUN), glucose and alkaline phosphatase.Nine of 128 patients had the minor allele for SNP rs1058427. Presence of the minor allele was significant in the model (P = 0.021), and associated with an increase of 88% in ICH + PHE volume (β = 0.632, exp(β) = 1.88) after controlling for admission variables. The only other significant variables included in the model was GCS (P < 0.001).The establishment of an independent association between rs1054827 and ICH + PHE volume provides evidence implicating the AQP4 gene in haematoma and oedema formation after ICH. Further investigation is needed to characterise this link.

    View details for DOI 10.1179/1743132815Y.0000000047

    View details for Web of Science ID 000356891600001

    View details for PubMedID 26000774

  • Motion Sensors to Assess and Monitor Medical and Surgical Management of Parkinson Disease WORLD NEUROSURGERY Lieber, B., Taylor, B. E., Appelboom, G., McKhann, G., Connolly, E. S. 2015; 84 (2): 561-566

    Abstract

    Patients with Parkinson disease (PD) often suffer from a resting tremor, bradykinesia, rigidity, postural instability, and gait difficulty. Determining a patient's candidacy for deep-brain stimulation (DBS) surgery and tracking their clinical response postoperatively requires that the frequency, duration, and severity of these symptoms be characterized in detail. Conventional means of assessing these symptoms, however, rely heavily on patient self-reporting, which often fails to provide the necessary level of detail. Wearable accelerometers are a novel tool that can detect and objectively characterize these movement abnormalities in both the clinical setting and the patient's home environment. In this article, we review the role of accelerometers in surgical candidate selection, recording and predicting falls, recording and predicting freezing of gait, evaluating surgical outcomes, and evaluating postoperative recovery and in altering DBS settings. Although accelerometry has yet to make it into the mainstream clinic, there is great promise for this technology in monitoring Parkinson patients.

    View details for DOI 10.1016/j.wneu.2015.03.024

    View details for Web of Science ID 000359324900061

    View details for PubMedID 25827041

  • Mobile Phone-Connected Wearable Motion Sensors to Assess Postoperative Mobilization JMIR MHEALTH AND UHEALTH Appelboom, G., Taylor, B. E., Bruce, E., Bassile, C. C., Malakidis, C., Yang, A., Youngerman, B., D'Amico, R., Bruce, S., Bruyere, O., Reginster, J., Dumont, E. P., Connolly, E. S. 2015; 3 (3)

    Abstract

    Early mobilization after surgery reduces the incidence of a wide range of complications. Wearable motion sensors measure movements over time and transmit this data wirelessly, which has the potential to monitor patient recovery and encourages patients to engage in their own rehabilitation.We sought to determine the ability of off-the-shelf activity sensors to remotely monitor patient postoperative mobility.Consecutive subjects were recruited under the Department of Neurosurgery at Columbia University. Patients were enrolled during physical therapy sessions. The total number of steps counted by the two blinded researchers was compared to the steps recorded on four activity sensors positioned at different body locations.A total of 148 motion data points were generated. The start time, end time, and duration of each walking session were accurately recorded by the devices and were remotely available for the researchers to analyze. The sensor accuracy was significantly greater when placed over the ankles than over the hips (P<.001). Our multivariate analysis showed that step length was an independent predictor of sensor accuracy. On linear regression, there was a modest positive correlation between increasing step length and increased ankle sensor accuracy (r=.640, r(2)=.397) that reached statistical significance on the multivariate model (P=.03). Increased gait speed also correlated with increased ankle sensor accuracy, although less strongly (r=.444, r(2)=.197). We did not note an effect of unilateral weakness on the accuracy of left- versus right-sided sensors. Accuracy was also affected by several specific measures of a patient's level of physical assistance, for which we generated a model to mathematically adjust for systematic underestimation as well as disease severity.We provide one of the first assessments of the accuracy and utility of widely available and wirelessly connected activity sensors in a postoperative patient population. Our results show that activity sensors are able to provide invaluable information about a patient's mobility status and can transmit this data wirelessly, although there is a systematic underestimation bias in more debilitated patients.

    View details for DOI 10.2196/mhealth.3785

    View details for Web of Science ID 000359792200005

    View details for PubMedID 26220691

  • Influence on morbidity and mortality of neoadjuvant radiation and chemotherapy among cranial malignancy patients in the postoperative setting JOURNAL OF CLINICAL NEUROSCIENCE Hein, P. N., Lieber, B., Bruce, E., Taylor, B., Appelboom, G., Abraham, M., Connolly, E. S. 2015; 22 (6): 998-1001

    Abstract

    We sought to assess the impact of neoadjuvant therapy on 30 day mortality and morbidity using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Chemotherapy and radiotherapy are both often indicated for treatment of cranial or systemic malignancy but can have significant adverse effects in the postsurgical setting. Data from 2006 to 2012 were obtained from the national ACS-NSQIP database. A total of 1044 patients were identified who obtained surgery for removal of metastatic brain tumors, of whom 127 received neoadjuvant chemotherapy and 65 neoadjuvant radiotherapy. Our primary outcome was 30 day mortality and secondary outcomes were 30 day surgical and medical morbidities. We selected previously reported preoperative variables to build a univariate and a multivariate model to determine preoperative characteristics most associated with neurosurgical mortality and morbidity. Our study found that neoadjuvant chemotherapy was associated with a 2.4-fold increase in the risk of 30 day mortality compared to the patient cohort who did not receive chemotherapy (p=0.023). Interestingly, there was no statistically significant increase in overall 30 day surgical or medical morbidity for the chemotherapy group. Neoadjuvant radiotherapy was not associated with an increase in 30 day morbidity or mortality. The significant increase in mortality associated with chemotherapy warrants further investigation, particularly to determine how to best personalize neoadjuvant chemotherapy treatment options to improve surgical outcomes. Neoadjuvant radiotherapy may be safer in terms of short-term postoperative morbidity and mortality.

    View details for DOI 10.1016/j.jocn.2015.01.005

    View details for Web of Science ID 000355050300016

    View details for PubMedID 25769250

  • Unilateral Craniofacial Microsomia: Unrecognized Cause of Pediatric Obstructive Sleep Apnea JOURNAL OF CRANIOFACIAL SURGERY Szpalski, C., Vandegrift, M., Patel, P. A., Appelboom, G., Fisher, M., Marcus, J., McCarthy, J. G., Shetye, P. R., Warren, S. M. 2015; 26 (4): 1277-1282

    Abstract

    Bilateral craniofacial microsomia causes obstructive sleep apnea (OSA). We hypothesize that unilateral craniofacial microsomia (UCFM) is an underappreciated cause of OSA. The records of all pediatric UCFM patients from 1990 to 2010 were reviewed; only complete records were included in the study. UCFM patients with OSA (apnea hypopnea index >1/hr) were compared to UCFM patients without OSA. Univariate and multivariate Fisher and χ(2) tests were performed. Of the 62 UCFM patients, 7 (11.3%) had OSA. All OSA patients had Pruzansky IIB or III mandibles. OSA patients presented with snoring (71.4%), failure to thrive (FTT) (57.1%), and chronic respiratory infections (42.8%). Snoring (P < 0.001), Goldenhar syndrome (P = 0.001), and FTT (P = 0.004) were significantly associated with OSA, but race, obesity, clefts, respiratory anomalies, adenotonsillar hypertrophy, and laterality were not. The prevalence of OSA in UCFM patients is up to 10 times greater than in the general population. Snoring, Goldenhar syndrome, and FTT are significantly associated with the presence of OSA.

    View details for DOI 10.1097/SCS.0000000000001551

    View details for Web of Science ID 000357569600114

    View details for PubMedID 26080175

  • Exploring the Interest in and the Usage of the Internet Among Patients Eligible for Osteoporosis Screening CALCIFIED TISSUE INTERNATIONAL Slomian, J., Reginster, J. Y., Gaspard, U., Streel, S., Beaudart, C., Appelboom, G., Buckinx, F., Bruyere, O. 2015; 96 (6): 518-526

    Abstract

    The aim of this study was to evaluate the interest in the Internet and its usage for health-related issues among people eligible for osteoporosis screening. Self-administered questionnaires have been distributed to subjects who were screened for osteoporosis and to menopausal women. 177 patients have responded to the survey (64.5 ± 10.1 years, 88.1% of women). There are 78.5% of Internet users. Among them, 67.2% said searching information about their health and 74.5% said using the Internet for this purpose. All respondents attributed an average score, out of 10, of 5.7 ± 2.3 regarding the reliability of information that they could find on the Internet. The use of the Internet differs significantly depending on age: those who use the Internet are younger (62.1 ± 8.91 years) than those who do not use it (73.3 ± 9.42 years). The socioeconomic status also has an impact on the Internet use: Internet users have a higher education, are more professionally active and have a higher net monthly household income compared to the group of non-users. Even if age and socioeconomic status appear to be determining factors in the use of the Internet for the search of health information in patients eligible for osteoporosis screening, almost 75% of the study population use the Internet for this purpose. Action to promote health through an Internet platform must therefore take these parameters into account.

    View details for DOI 10.1007/s00223-015-9987-3

    View details for Web of Science ID 000354704100005

    View details for PubMedID 25837844

  • Meta-analysis of telemonitoring to improve HbA1c levels: Promise for stroke survivors JOURNAL OF CLINICAL NEUROSCIENCE Lieber, B. A., Taylor, B., Appelboom, G., Prasad, K., Bruce, S., Yang, A., Bruce, E., Christophe, B., Connolly, E. S. 2015; 22 (5): 807-811

    Abstract

    Monitoring glycemic control is useful not only in the primary prevention of stroke in diabetics, but also in the rehabilitation from and secondary prevention of stroke. In an often functionally and neurocognitively impaired population, however, poor compliance with treatment regimens is a major problem. Wireless, telemonitoring glucometers - often integrated into the patient's healthcare system - offer a solution to the compliance issue. We sought to evaluate the effectiveness of telemonitoring technologies in improving long-term glycemic control. A search on www.clinicaltrials.gov, using keywords such as "telemonitoring" and "self-care device" was performed, and five trials were identified that compared hemoglobin A1c (HbA1c) levels of a group receiving standard care (controls) to a group receiving a telemonitoring intervention. Four of the five studies showed a greater reduction in HbA1c in the intervention group compared to controls at 6 months, although only one was statistically significant. There was considerable heterogeneity between studies (I(2)=69.5%, p=0.02), and the random effects model estimated the aggregate effect size for mean difference in reduction of HbA1c levels to be 0.08% (95% confidence interval -0.12% to 0.28%), which was not statistically significant (p=0.42). The varying results may be due to specific factors in the trials that contributed to their large heterogeneity, and further trials are needed to support the role of telemonitoring in improving diabetes management in this population. Nonetheless, in the future telemonitoring may substantially help patients at risk of ischemic stroke and those who require close glucose monitoring.

    View details for DOI 10.1016/j.jocn.2014.11.009

    View details for Web of Science ID 000353929500005

    View details for PubMedID 25791996

  • Underlying effect of age on outcome differences in arteriovenous malformation-associated intracerebral hemorrhage JOURNAL OF CLINICAL NEUROSCIENCE Taylor, B., Appelboom, G., Yang, A., Bruce, E., Lopresti, M., Bruce, S., Christophe, B., Claassen, J., Connolly, E. S. 2015; 22 (3): 526-529

    Abstract

    Brain arteriovenous malformations (AVM) are the most common cause of intracerebral hemorrhage (ICH) in young adults. Although previous studies have found that the mortality and morbidity of ICH due to AVM (AVM-ICH) is lower than in spontaneous ICH, it is unclear whether the more favorable prognosis is directly related to the presence of the vascular malformation. We included 34 patients with AVM-ICH and 187 with spontaneous intracerebral hemorrhage (sICH) due to either hypertension or cerebral amyloid angiopathy. Patient data were obtained from the prospective Intracerebral Hemorrhage Outcomes Project, which enrolls ICH patients admitted to Columbia University Medical Center. Using ICH etiology (AVM-ICH or sICH) and previously verified predictors of ICH outcome, two multivariate analyses were performed with and without age to compare the odds of death at 3 months and the functional outcome. Although mortality in AVM-ICH group was lower than the sICH group (20.6% versus 43.3%, respectively), this value was only significant when age was excluded (p=0.017) and lost its significance when we controlled for age (p=0.157). There was an analogous loss of significance with functional outcome using the modified Rankin Scale. In conclusion, our data suggests that the previously observed lower case fatality rate and more favorable functional outcomes in the AVM-ICH group compared to the sICH group may largely be the result of age.

    View details for DOI 10.1016/j.jocn.2014.09.009

    View details for Web of Science ID 000350515000017

    View details for PubMedID 25510539

  • Hemicraniectomy for malignant middle cerebral artery territory infarction: an updated review JOURNAL OF NEUROSURGICAL SCIENCES Taylor, B., LoPresti, M., Appelboom, G., Connolly, E. S. 2015; 59 (1): 73-78

    Abstract

    A decompressive hemicraniectomy is frequently performed for patients with malignant middle cerebral artery territory infarction (MMI) to reduce the intracranial hypertension, which may otherwise result in transtentorial herniation. However, certain clinically significant issues ‑ diagnostic criteria, predictors of the MMI clinical course, benefit of surgery in certain populations, timing of surgery ‑ are unresolved. In this article, we provide an updated review on the diagnosis and management of MMI. An extensive search of the PubMed, EMBASE, and Cochrane was conducted using varying combinations of the search terms, "hemicraniectomy," "decompressive craniectomy," "malignant middle cerebral artery territory infarction," "massive middle cerebral artery territory infarction," "massive ischemic stroke," "decompressive surgery," and "neurosurgery for ischemic stroke." Several large, randomized trials within the past decade have firmly established the benefit of decompressive hemicraniectomy (DHC) as a treatment of MMI. Further studies since then have not only better characterized the diagnosis and predictors of MMI, but have also shown that this benefit extends to patients with additional clinical and demographic characteristics. Future randomized studies should continue to evaluate the benefit of a DHC in other subgroups, and assess neurocognitive and psychosocial secondary outcomes.

    View details for Web of Science ID 000353077900008

    View details for PubMedID 25423133

  • Age Selection for Decompressive Craniectomy in Malignant Middle Cerebral Artery Infarction WORLD NEUROSURGERY Taylor, B., Appelboom, G., Connolly, E. S. 2015; 83 (3): 301-302

    View details for DOI 10.1016/j.wneu.2014.06.012

    View details for Web of Science ID 000353036900013

    View details for PubMedID 24831105

  • Clinical and surgical applications of smart glasses TECHNOLOGY AND HEALTH CARE Mitrasinovic, S., Camacho, E., Trivedi, N., Logan, J., Campbell, C., Zilinyi, R., Lieber, B., Bruce, E., Taylor, B., Martineau, D., Dumont, E. L., Appelboom, G., Connolly, E. S. 2015; 23 (4): 381-401

    Abstract

    With the increased efforts to adopt health information technology in the healthcare field, many innovative devices have emerged to improve patient care, increase efficiency, and decrease healthcare costs. A recent addition is smart glasses: web-connected glasses that can present data onto the lenses and record images or videos through a front-facing camera.In this article, we review the most salient uses of smart glasses in healthcare, while also denoting their limitations including practical capabilities and patient confidentiality.Using keywords including, but not limited to, ``smart glasses'', ``healthcare'', ``evaluation'', ``privacy'', and ``development'', we conducted a search on Ovid-MEDLINE, PubMed, and Google Scholar. A total of 71 studies were included in this review.Smart glasses have been adopted into the healthcare setting with several useful applications including, hands-free photo and video documentation, telemedicine, Electronic Health Record retrieval and input, rapid diagnostic test analysis, education, and live broadcasting.In order for the device to gain acceptance by medical professionals, smart glasses will need to be tailored to fit the needs of medical and surgical sub-specialties. Future studies will need to qualitatively assess the benefits of smart glasses as an adjunct to the current health information technology infrastructure.

    View details for DOI 10.3233/THC-150910

    View details for Web of Science ID 000358797600001

    View details for PubMedID 26409906

  • The quantified patient: a patient participatory culture CURRENT MEDICAL RESEARCH AND OPINION Appelboom, G., Lopresti, M., Reginster, J., Connolly, E. S., Dumont, E. P. 2014; 30 (12): 2585-2587

    Abstract

    The Quantified Self Movement, which aims to improve various aspects of life and health through recording and reviewing daily activities and biometrics, is a new and upcoming practice of self monitoring that holds much promise. Now, the most underutilized resource in ambulatory health care, the patient, can participate like never before, and the patient's Quantified Self can be directly monitored and remotely accessed by health care professionals.

    View details for DOI 10.1185/03007995.2014.954032

    View details for Web of Science ID 000345602300022

    View details for PubMedID 25118077

  • Hematoma volume as the major determinant of outcomes after intracerebral hemorrhage JOURNAL OF THE NEUROLOGICAL SCIENCES LoPresti, M. A., Bruce, S. S., Camacho, E., Kunchala, S., Dubois, B. G., Bruce, E., Appelboom, G., Connolly, E. S. 2014; 345 (1-2): 3-7

    Abstract

    Intracerebral hemorrhage (ICH) is a leading cause of morbidity and mortality, greatly linked to hematoma volume. Understanding the characteristics and size of hematoma is integral to evaluating severity and prognosis after ICH. Examination of the literature suggests that markers for hematoma size vary, but the key range between 20-30 mL is most widely used as the cut-off for classification of hematoma volume. The role of hematoma volume in episodes of hematoma expansion and re-bleeding further impact outcomes, with increased growth associated with larger hematoma volume. Additionally, many commonly used predictors of ICH outcomes are directly related to hematoma volume, implicating it as an important variable when determining outcomes. In conclusion, hematoma volume is likely the most significant determinant of outcomes in intracerebral hemorrhage.

    View details for DOI 10.1016/j.jns.2014.06.057

    View details for Web of Science ID 000343689600002

    View details for PubMedID 25034055

  • The promise of wearable activity sensors to define patient recovery JOURNAL OF CLINICAL NEUROSCIENCE Appelboom, G., Yang, A. H., Christophe, B. R., Bruce, E. M., Slomian, J., Bruyere, O., Bruce, S. S., Zacharia, B. E., Reginster, J., Connolly, E. S. 2014; 21 (7): 1089-1093

    Abstract

    The recent emergence of mobile health--the use of mobile telecommunication and wireless devices to improve health outcomes, services, and research--has inspired a patient-centric approach to monitor health metrics. Sensors embedded in wearable devices are utilized to acquire greater self-knowledge by tracking basic parameters such as blood pressure, heart rate, and body temperature as well as data related to exercise, diet, and psychological state. To that end, recent studies on utilizing wireless fitness activity trackers to monitor and promote functional recovery in patients suggest that collecting up-to-date performance data could help patients regain functional independence and help hospitals determine the appropriate length of stay for a patient. This manuscript examines existing functional assessment scales, discusses the use of activity tracking sensors in evaluating functional independence, and explores the growing application of wireless technology in measuring and promoting functional recovery.

    View details for DOI 10.1016/j.jocn.2013.12.003

    View details for Web of Science ID 000337120400002

    View details for PubMedID 24534628

  • A critical assessment of approaches to outpatient monitoring CURRENT MEDICAL RESEARCH AND OPINION Appelboom, G., Sussman, E. S., Raphael, P., Juilliere, Y., Reginster, J., Connolly, E. S. 2014; 30 (7): 1383-1384

    View details for DOI 10.1185/03007995.2014.904774

    View details for Web of Science ID 000338516700021

    View details for PubMedID 24627950

  • Can new information and communication technologies help in the management of osteoporosis? Women's health (London, England) Slomian, J., Appelboom, G., Ethgen, O., Reginster, J., Bruyère, O. 2014; 10 (3): 229-232

    View details for DOI 10.2217/whe.14.15

    View details for PubMedID 24956289

  • Variability in Outcome After Elective Cerebral Aneurysm Repair in High-Volume Academic Medical Centers STROKE Zacharia, B. E., Bruce, S. S., Carpenter, A. M., Hickman, Z. L., Vaughan, K. A., Richards, C., Gold, W. E., Lu, J., Appelboom, G., Solomon, R. A., Connolly, E. S. 2014; 45 (5): 1447-1452

    Abstract

    Unruptured intracranial aneurysm repair is the most commonly performed procedure for the prevention of hemorrhagic stroke. Despite efforts to regionalize care in high-volume centers, overall results have improved little. This study aims to determine the effectiveness in improving outcomes of previous efforts to regionalize unruptured intracranial aneurysm repair to high-volume centers and to recommend future steps toward that goal.Using data obtained via the New York Statewide Planning and Research Cooperative System, this study included all patients admitted to any of the 10 highest volume centers in New York state between 2005 and 2010 with a principal diagnosis of unruptured intracranial aneurysm who were treated either by microsurgical or endovascular repair. Mixed-effects logistic regression was used to determine the degree to which hospital-level and patient-level variables contributed to observed variation in good outcome, defined as discharge to home, between hospitals.Of 3499 patients treated during the study period, 2692 (76.9%) were treated at the 10 highest volume centers, with 2198 (81.6%) experiencing a good outcome. Good outcomes varied widely between centers, with 44.6% to 91.1% of clipped patients and 75.4% to 92.1% of coiled patients discharged home. Mixed-effects logistic regression revealed that procedural volume accounts for 85.8% of the between-hospital variation in outcome.There is notable interhospital heterogeneity in outcomes among even the largest volume unruptured intracranial aneurysm referral centers. Although further regionalization may be needed, mandatory participation in prospective, adjudicated registries will be necessary to reliably identify factors associated with superior outcomes.

    View details for DOI 10.1161/STROKEAHA.113.004412

    View details for Web of Science ID 000335578100053

    View details for PubMedID 24668204

  • Smart wearable body sensors for patient self-assessment and monitoring. Archives of public health = Archives belges de sante publique Appelboom, G., Camacho, E., Abraham, M. E., Bruce, S. S., Dumont, E. L., Zacharia, B. E., D'Amico, R., Slomian, J., Reginster, J. Y., Bruyère, O., Connolly, E. S. 2014; 72 (1): 28-?

    Abstract

    Innovations in mobile and electronic healthcare are revolutionizing the involvement of both doctors and patients in the modern healthcare system by extending the capabilities of physiological monitoring devices. Despite significant progress within the monitoring device industry, the widespread integration of this technology into medical practice remains limited. The purpose of this review is to summarize the developments and clinical utility of smart wearable body sensors.We reviewed the literature for connected device, sensor, trackers, telemonitoring, wireless technology and real time home tracking devices and their application for clinicians.Smart wearable sensors are effective and reliable for preventative methods in many different facets of medicine such as, cardiopulmonary, vascular, endocrine, neurological function and rehabilitation medicine. These sensors have also been shown to be accurate and useful for perioperative monitoring and rehabilitation medicine.Although these devices have been shown to be accurate and have clinical utility, they continue to be underutilized in the healthcare industry. Incorporating smart wearable sensors into routine care of patients could augment physician-patient relationships, increase the autonomy and involvement of patients in regards to their healthcare and will provide for novel remote monitoring techniques which will revolutionize healthcare management and spending.

    View details for DOI 10.1186/2049-3258-72-28

    View details for PubMedID 25232478

  • Clinical Trials in Decompressive Craniectomy After Severe Diffuse Traumatic Brain Injury WORLD NEUROSURGERY Appelboom, G., Piazza, M., Zoller, S. D., Connolly, E. S. 2013; 80 (5): E153-E155

    View details for DOI 10.1016/j.wneu.2011.05.013

    View details for Web of Science ID 000329729400029

    View details for PubMedID 22120384

  • von Willebrand Factor Genetic Variant Associated With Hematoma Expansion After Intracerebral Hemorrhage JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Appelboom, G., Piazza, M., Han, J. E., Bruce, S. S., Hwang, B., Monahan, A., Hwang, R. Y., Kisslev, S., Mayer, S., Meyers, P. M., Badjatia, N., Connolly, E. S. 2013; 22 (6): 713-717

    Abstract

    Hematoma expansion, the leading cause of neurologic deterioration after intracerebral hemorrhage (ICH), remains one of the few modifiable risk factors for poor outcome. In the present study, we explored whether common genetic variants within the hemostasis pathway were related to hematoma expansion during the acute period after ICH.Patients with spontaneous ICH who were admitted to the institutional Neuro-ICU between 2009 and 2011 were enrolled in the study, and clinical data were collected prospectively. Hematoma size was measured in patients admitted on or before postbleed day 2. Baseline models for hematoma growth were constructed using backwards stepwise logistic regression. Genotyping of single-nucleotide polymorphisms for 13 genes involved in hemostasis was performed, and the results were individually included in the above baseline models to test for independent association of hematoma expansion.During the study period, 82 patients were enrolled in the study and had complete data. The mean age was 65.9 ± 14.9 years, and 38% were female. Only von Willebrand factor was associated with absolute and relative hematoma growth in univariate analysis (P < .001 and P = .007, respectively); von Willebrand factor genotype was independently predictive of relative hematoma growth but only approached significance for absolute hematoma growth (P = .002 and P = .097, respectively).Our genomic analysis of various hemostatic factors identified von Willebrand factor as a potential predictor of hematoma expansion in patients with ICH. The identification of von Willebrand factor single-nucleotide polymorphisms may allow us to better identify patients who are at risk for hematoma enlargement and will benefit the most from treatment. The relationship of von Willebrand factor with regard to hematoma enlargement in a larger population warrants further study.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2011.10.018

    View details for Web of Science ID 000323497700003

    View details for PubMedID 22244714

  • Volume-dependent effect of perihaematomal oedema on outcome for spontaneous intracerebral haemorrhages JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Appelboom, G., Bruce, S. S., Hickman, Z. L., Zacharia, B. E., Carpenter, A. M., Vaughan, K. A., Duren, A., Hwang, R. Y., Piazza, M., Lee, K., Claassen, J., Mayer, S., Badjatia, N., Connolly, E. S. 2013; 84 (5): 488-493

    Abstract

    It is still unknown whether subsequent perihaematomal oedema (PHE) formation further increases the odds of an unfavourable outcome.Demographic, clinical, radiographic and outcome data were prospectively collected in a single large academic centre. A multiple logistic regression model was then developed to determine the effect of admission oedema volume on outcome.133 patients were analysed in this study. While there was no significant association between relative PHE volume and discharge outcome (p=0.713), a strong relationship was observed between absolute PHE volume and discharge outcome (p=0.009). In a multivariate model incorporating known predictors of outcome, as well as other factors found to be significant in our univariate analysis, absolute PHE volume remained a significant predictor of poor outcome only in patients with intracerebral haemorrhage (ICH) volumes ≤30 cm(3) (OR 1.123, 95% CI 1.021 to 1.273, p=0.034). An increase in absolute PHE volume of 10 cm(3) in these patients was found to increase the odds of poor outcome on discharge by a factor of 3.19.Our findings suggest that the effect of absolute PHE volume on functional outcome following ICH is dependent on haematoma size, with only patients with smaller haemorrhages exhibiting poorer outcome with worse PHE. Further studies are needed to define the precise role of PHE in driving outcome following ICH.

    View details for DOI 10.1136/jnnp-2012-303160

    View details for Web of Science ID 000317388800006

    View details for PubMedID 23345281

  • Endoscope-integrated ICG technology: first application during intracranial aneurysm surgery NEUROSURGICAL REVIEW Bruneau, M., Appelboom, G., Rynkowski, M., Van Cutsem, N., Mine, B., De Witte, O. 2013; 36 (1): 77-84

    Abstract

    Microscopic indocyanine green videoangiography (mICG-VA) has gained wide acceptance during intracranial aneurysm surgery by lowering rates of incomplete clipping and occlusion of surrounding vessels. However, mICG-VA images are limited to the microscopic view and some deeper areas, including the aneurysm sac/neck posterior side, cannot be efficiently assessed as they are hidden by the aneurysm, clips, or surrounding structures. Contrarily, endoscopes allow a wider area of visualization, but neurosurgical endoscopes to date only provided visual data. We describe the first application of endoscope ICG-integrated technology (eICG) applied in an initial case of anterior communicating artery aneurysm clipping. This new technique provided also relevant information regarding aneurysm occlusion and patency of parent and branching vessels and small perforating arteries. eICG-VA provided additional information compared to mICG-VA by magnifying areas of interest and improving the ability to view less accessible regions, especially posterior to the aneurysm clip. Obtaining eICG sequences required currently the microscope to be moved away from the operating field. eICG-VA was only recorded under infrared illumination which prevented tissue handling, but white-infrared light views could be interchanged instantaneously. Further development of angled endoscopes integrating the ICG technology and dedicated filters blocking the microscopic light could improve visualization capacities even further. In conclusion, as a result of its ability to reveal structures around corners, the eICG-VA technology could be beneficial when used in combination with mICG-VA to visualize and confirm vessel patency in areas that were previously hidden from the microscope.

    View details for DOI 10.1007/s10143-012-0419-9

    View details for Web of Science ID 000313093900017

    View details for PubMedID 22918545

  • Predicting Outcome After Arteriovenous Malformation-Associated Intracerebral Hemorrhage with the Original ICH Score WORLD NEUROSURGERY Appelboom, G., Hwang, B. Y., Bruce, S. S., Piazza, M. A., Kellner, C. P., Meyers, P. M., Connolly, E. S. 2012; 78 (6): 646-650

    Abstract

    To evaluate the predictive ability of the original ICH Score (oICH) in a large independent cohort of patients with arteriovenous malformation-associated intracerebral hemorrhage (AVM-ICH), an important cause of intracerebral hemorrhage (ICH) that is associated with significantly different epidemiology, clinical course, and outcome compared with primary ICH.During the period 1997-2009, 91 patients were admitted to Columbia Medical Center with acute AVM-ICH. Demographic and admission clinical and radiographic variables were obtained for 84 patients through retrospective chart review. Admission oICH and Spetzler-Martin grading scale (SMGS) were calculated. Outcome was assessed at 3 months using the modified Rankin Scale (mRS). Maximum Youden Indices were used to identify cutoffs for age and ICH volume that are associated with optimal predictive accuracy for an unfavorable outcome (mRS ≥ 3). Receiver operating characteristic (ROC) analysis was used to evaluate the predictive performance of oICH, and oICH with new age and ICH cutoff points (new AVM-ICH score based on original ICH Score [AVM-oICH]).The mean age was 35 years ± 14, and mean ICH volume was 22 mL ± 20. At 3-month follow-up, 3 (4%) patients were dead, and 15 (18%) had an unfavorable outcome. Two of the patients who died had oICH of 3, and one had oICH of 5. ICH volume of 37 mL and age of 41 years were identified as optimal cutoffs for predicting an unfavorable outcome. oICH and AVM-oICH showed good predictive accuracies with area under the curve of 0.914 and 0.891 (P = 0.422). AVM-oICH and oICH had similarly high sensitivities (0.889 and 0.944; P = 1.00), but the former had significantly greater specificity (0.879 vs. 0.682; P < 0.001).oICH is a valid clinical grading scale with high predictive accuracy for functional outcome after AVM-ICH. It is unclear whether the score is appropriate for risk stratification with regard to mortality because of the low risk of death associated with AVM-ICH. Simple adjustments of the age and ICH volume cutoff points improve performance of the score and reduce the probability of overestimating a patient's risk of an unfavorable outcome after AVM-ICH.

    View details for DOI 10.1016/j.wneu.2011.12.001

    View details for Web of Science ID 000312950100029

    View details for PubMedID 22381312

  • Clinical Trials for Neuroprotective Therapies in Intracerebral Hemorrhage: A New Roadmap from Bench to Bedside TRANSLATIONAL STROKE RESEARCH Ayer, A., Hwang, B. Y., Appelboom, G., Connolly, E. S. 2012; 3 (4): 409-417

    Abstract

    The most deadly form of stroke, intracerebral hemorrhage (ICH) continues to puzzle researchers and produce substantial decrements in the quality of patients' lives. Intensive basic research has devised many agents with putative benefit in mitigating the devastating effects of ICH, but these therapies have been largely ineffective in the transition to clinical trials. However, a steady translational pipeline continues to provide new avenues of treatment that may be effective in the management of this condition. In this review, we aim to summarize the array of neuroprotective clinical trials and techniques used in the history of ICH, and delineate the progression of relevant research to date. Furthermore, we provide insight into methods that may allow for better translation of basic science advances into productive clinical trials.

    View details for DOI 10.1007/s12975-012-0207-4

    View details for Web of Science ID 000311407000001

    View details for PubMedID 24323830

  • Serum biomarkers of spontaneous intracerebral hemorrhage induced secondary brain injury JOURNAL OF THE NEUROLOGICAL SCIENCES Brunswick, A. S., Hwang, B. Y., Appelboom, G., Hwang, R. Y., Piazza, M. A., Connolly, E. S. 2012; 321 (1-2): 1-10

    Abstract

    Intracerebral hemorrhage (ICH) is a devastating form of stroke associated with a high rate of morbidity and mortality. It is now believed that much of this damage occurs in the subacute period following the initial insult via a cascade of complex pathophysiologic pathways that continues to be investigated. Increased levels of certain serum proteins have been identified as biomarkers that may reflect or directly participate in the inflammation, blood brain barrier disruption, endothelial dysfunction, and neuronal and glial toxicity that occur during this secondary period of cerebral injury. Some of these biomarkers have the potential to serve as therapeutic targets or surrogate endpoints for future research or clinical trials. Others may someday augment current clinical techniques in diagnosis, risk-stratification, prognostication, treatment decision and measurement of therapeutic efficacy. While much work remains to be done, biomarkers show significant potential to expand clinical options and improve clinical management, thereby reducing mortality and improving functional outcomes in ICH patients.

    View details for DOI 10.1016/j.jns.2012.06.008

    View details for Web of Science ID 000309570000001

    View details for PubMedID 22857988

  • Functional outcome prediction following intracerebral hemorrhage JOURNAL OF CLINICAL NEUROSCIENCE Appelboom, G., Bruce, S. S., Han, J., Piazza, M., Hwang, B., Hickman, Z. L., Zacharia, B. E., Carpenter, A., Monahan, A. S., Vaughan, K., Badjatia, N., Connolly, E. S. 2012; 19 (6): 795-798

    Abstract

    The ICH score is a validated method of assessing the risk of mortality and morbidity after intracerebral hemorrhage (ICH). We sought to compare the ability of the ICH score to predict outcome assessed with three of the most widely used scales: the Barthel Index (BI), modified Rankin Scale (mRS), and Glasgow Outcome Score (GOS). All patients with ICH treated at our institution between February 2009 and March 2011 were followed-up at three months using the mRS, GOS, and BI. The ICH score was highly correlated with the three-month mRS (ρ=0.59, p<0.001), BI (ρ=-0.57, p<0.001) and GOS (ρ=0.61, p<0.001). The ICH score also predicted dependency for each measure well, with areas under the curve falling between 0.826 and 0.833. Our results suggest that future clinical studies that use the ICH score to stratify patients may employ any of the three outcome scales and expect good discrimination of disability.

    View details for DOI 10.1016/j.jocn.2011.11.005

    View details for Web of Science ID 000305040700004

    View details for PubMedID 22516544

  • Variation in a locus linked to platelet aggregation phenotype predicts intraparenchymal hemorrhagic volume NEUROLOGICAL RESEARCH Appelboom, G., Piazza, M., Bruce, S. S., Zoller, S. D., Hwang, B., Monahan, A., Hwang, R. Y., Kisslev, S., Mayer, S., Meyers, P. M., Badjatia, N., Connolly, E. S. 2012; 34 (3): 232-237

    Abstract

    Alteration in platelet aggregation has been shown to promote bleeding and affect outcome after intracerebral hemorrhage (ICH).We investigated the influence of genetic variants of platelet aggregation, and their effects on admission ICH volume and clinical outcome.Our prospective study analyzed selected candidate single-nucleotide polymorphisms (SNPs) previously associated with platelet aggregation phenotype in previous genome-wide association studies, with regards to outcome and ICH volume. Patients were assessed at the Columbia University Medical Center Neuro-Intensive Care Unit. Exclusion criteria included age <18 years, ICH following trauma, hemorrhagic transformation, or tumor, no consent for genetic analysis, or incomplete data. Radiological variables (location and volume of acute ICH, presence of intraventricular extension, midline shift, and hydrocephalus) and clinical variables (mortality and modified Rankin score at discharge) were prospectively recorded.One hundred and twenty-two patients with spontaneous ICH between February 2009 and May 2011 diagnosed via clinical assessment and admission computed tomography scan were included. The median admission Glasgow coma scale score (GCS) was 11·5. Univariate predictors of mortality at discharge included systolic blood pressure, presence of intraventricular hemorrhage, anticoagulant use, and GCS, the only independent predictor of discharge mortality (P<0·001). Age, intraventricular hemorrhage, and GCS were associated with poor functional outcome; age (P = 0·001) and GCS (P<0·001) were significant in the multivariate model. Admission GCS (P<0·01), antiplatelet use, and rs342286 (PIK3CG; P = 0·04; R(2) = 0·247) had univariate associations with hematoma volume.We identified SNP rs342286 as an independent predictor of admission hematoma volume. Our findings suggest that PIK3CG function, which is previously linked to this SNP and affects platelet aggregation, impacts the severity of the intraparenchymal bleed.

    View details for DOI 10.1179/1743132811Y.0000000080

    View details for Web of Science ID 000302582500003

    View details for PubMedID 22449554

  • Glioblastoma biomarkers from bench to bedside: advances and challenges BRITISH JOURNAL OF NEUROSURGERY Farias-Eisner, G., Bank, A. M., Hwang, B. Y., Appelboom, G. R., Piazza, M. A., Bruce, S. S., Connolly, E. S. 2012; 26 (2): 189-194

    Abstract

    Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, with few available therapies providing significant improvements in mortality. Biomarkers, which are defined by the National Institutes of Health as 'characteristics that are objectively measured and evaluated as indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention', have the potential to play valuable roles in the diagnosis and treatment of GBM. Although GBM biomarker research is still in its early stages because of the tumour's complex pathophysiology, a number of potential markers have been identified which can be measured in either brain tissue or blood serum. In conjunction with other clinical data, particularly neuroimaging modalities such as MRI, these proteins could contribute to the clinical management of GBM by helping to classify tumours, predict prognosis and assess treatment response. In this article, we review the current understanding of GBM pathophysiology and recent advances in GBM biomarker research, and discuss the potential clinical implications of promising biomarkers. A better understanding of GBM pathophysiology will allow researchers and clinicians to identify optimal biomarkers and methods of interpretation, leading to advances in tumour classification, prognosis prediction and treatment assessment.

    View details for DOI 10.3109/02688697.2011.629698

    View details for Web of Science ID 000301835000005

    View details for PubMedID 22176646

  • Evaluation of intraventricular hemorrhage assessment methods for predicting outcome following intracerebral hemorrhage Clinical article JOURNAL OF NEUROSURGERY Hwang, B. Y., Bruce, S. S., Appelboom, G., Piazza, M. A., Carpenter, A. M., Gigante, P. R., Kellner, C. P., Ducruet, A. F., Kellner, M. A., Deb-Sen, R., Vaughan, K. A., Meyers, P. M., Connolly, E. S. 2012; 116 (1): 185-192

    Abstract

    Intraventricular hemorrhage (IVH) associated with intracerebral hemorrhage (ICH) is an independent predictor of poor outcome. Clinical methods for evaluating IVH, however, are not well established. This study sought to determine the best IVH grading scale by evaluating the predictive accuracies of IVH, Graeb, and LeRoux scores in an independent cohort of ICH patients with IVH. Subacute IVH dynamics as well as the impact of external ventricular drain (EVD) placement on IVH and outcome were also investigated.A consecutive cohort of 142 primary ICH patients with IVH was admitted to Columbia University Medical Center between February 2009 and February 2011. Baseline demographics, clinical presentation, and hospital course were prospectively recorded. Admission CT scans performed within 24 hours of onset were reviewed for ICH location, hematoma volume, and presence of IVH. Intraventricular hemorrhage was categorized according to IVH, Graeb, and LeRoux scores. For each patient, the last scan performed within 6 days of ictus was similarly evaluated. Outcomes at discharge were assessed using the modified Rankin Scale (mRS). Receiver operating characteristic analysis was used to determine the predictive accuracies of the grading scales for poor outcome (mRS score ≥ 3).Seventy-three primary ICH patients (51%) had IVH. Median admission IVH, Graeb, and LeRoux scores were 13, 6, and 8, respectively. Median IVH, Graeb and LeRoux scores decreased to 9 (p = 0.005), 4 (p = 0.002), and 4 (p = 0.003), respectively, within 6 days of ictus. Poor outcome was noted in 55 patients (75%). Areas under the receiver operating characteristic curve were similar among the IVH, Graeb, and LeRoux scores (0.745, 0.743, and 0.744, respectively) and within 6 days postictus (0.765, 0.722, 0.723, respectively). Moreover, the IVH, Graeb, and LeRoux scores had similar maximum Youden Indices both at admission (0.515 vs 0.477 vs 0.440, respectively) and within 6 days postictus (0.515 vs 0.339 vs 0.365, respectively). Patients who received EVDs had higher mean IVH volumes (23 ± 26 ml vs 9 ± 11 ml, p = 0.003) and increased incidence of Glasgow Coma Scale scores < 8 (67% vs 38%, p = 0.015) and hydrocephalus (82% vs 50%, p = 0.004) at admission but had similar outcome as those who did not receive an EVD.The IVH, Graeb, and LeRoux scores predict outcome well with similarly good accuracy in ICH patients with IVH when assessed at admission and within 6 days after hemorrhage. Therefore, any of one of the scores would be equally useful for assessing IVH severity and risk-stratifying ICH patients with regard to outcome. These results suggest that EVD placement may be beneficial for patients with severe IVH, who have particularly poor prognosis at admission, but a randomized clinical trial is needed to conclusively demonstrate its therapeutic value.

    View details for DOI 10.3171/2011.9.JNS10850

    View details for Web of Science ID 000298632500031

    View details for PubMedID 21999319

  • Clinical relevance of blast-related traumatic brain injury ACTA NEUROCHIRURGICA Appelboom, G., Han, J., Bruce, S., Szpalski, C., Connolly, E. S. 2012; 154 (1): 131-134

    View details for DOI 10.1007/s00701-011-1210-3

    View details for Web of Science ID 000298643300021

    View details for PubMedID 22037982

  • Minimally invasive spinal arthrodesis in osteoporotic population using a cannulated and fenestrated augmented screw: technical description and clinical experience. Minimally invasive surgery Lubansu, A., Rynkowski, M., Abeloos, L., Appelboom, G., Dewitte, O. 2012; 2012: 507826-?

    Abstract

    We describe a percutaneous or minimally invasive approach to apply an augmentation of pedicle fenestrated screws by injection of the PMMA bone cement through the implant and determine the safety and efficiency of this technique in a clinical series of 15 elderly osteoporotic patients. Clinical outcome and the function were assessed using respectively the Visual Analogue Scale (VAS) score and the Oswestry Disability Index (ODI). Peri- and post-operative complications were monitored during a minimum of 2 years of follow-up. Radiographic follow-up was based on plain fluoroscopic control at 3, 6 and 12 months and every year. In this approach, four steps were considered with care: optimal positioning of the screws, correct alignment of the screw heads, waiting time before the injection of cement, fluoroscopic control of the cement injection. Using these precautions, only 2 minor complications occurred. VAS scores and ODI questionnaires showed a statistically significant improvement up to 13.3 months postoperatively. No radiological complications were observed. Based on this experience, PMMA augmentation technique through the novel fenestrated screws provided an effective and long lasting fixation in osteoporotic patients. Applying this procedure through percutaneous or minimally invasive approach under fluoroscopic control seems to be safe.

    View details for DOI 10.1155/2012/507826

    View details for PubMedID 22970360

  • Arteriovenous malformation-associated aneurysms in the pediatric population JOURNAL OF NEUROSURGERY-PEDIATRICS Anderson, R. C., McDowell, M. M., Kellner, C. P., Appelboom, G., Bruce, S. S., Kotchetkov, I. S., Haque, R., Feldstein, N. A., Connolly, E. S., Solomon, R. T., Meyers, P. M., Lavine, S. D. 2012; 9 (1): 11-16

    Abstract

    Conventional cerebral angiography and treatment for ruptured arteriovenous malformations (AVMs) in children are often performed in a delayed fashion. In adults, current literature suggests that AVM-associated aneurysms may be more likely to hemorrhage than isolated AVMs, which often leads to earlier angiography and endovascular treatment of associated aneurysms. The nature of AVM-associated aneurysms in the pediatric population is virtually unknown. In this report, the authors investigate the relationship of associated aneurysms in a large group of children with AVMs.Seventy-seven pediatric patients (≤ 21 years old) with AVMs were treated at the Columbia University Medical Center between 1991 and 2010. Medical records and imaging studies were retrospectively reviewed, and associated aneurysms were classified as arterial, intranidal, or venous in location. Clinical presentation and outcome variables were compared between children with and without AVM-associated aneurysms.A total of 30 AVM-associated aneurysms were found in 22 children (29% incidence). Eleven were arterial, 9 intranidal, and 10 were venous in location. There was no significant difference in the rate of hemorrhage (p = 0.91) between children with isolated AVMs (35 of 55 [64%]) and children with AVM-associated aneurysms (13 of 22 [59%]). However, of the 11 children with AVM-associated aneurysms in an arterial location, 10 presented with hemorrhage (91%). An association with hemorrhage was significant in univariate analysis (p = 0.045) but not in multivariate analysis (p = 0.37).Associated aneurysms are present in nearly a third of children with AVMs, and when arterially located, are more likely to present with hemorrhage. These data suggest that early angiography with endovascular treatment of arterial-based aneurysms in children with AVMs may be indicated.

    View details for DOI 10.3171/2011.10.PEDS11181

    View details for Web of Science ID 000298630700002

    View details for PubMedID 22208314

  • Occlusive Hyperemia Versus Normal Perfusion Pressure Breakthrough after Treatment of Cranial Arteriovenous Malformations NEUROSURGERY CLINICS OF NORTH AMERICA Zacharia, B. E., Bruce, S., Appelboom, G., Connolly, E. S. 2012; 23 (1): 147-?

    Abstract

    Arteriovenous malformations (AVMs) are vascular lesions characterized by direct connections between feeding arteries and draining veins without an intervening capillary network. Two hypotheses, normal perfusion pressure breakthrough (NPPB) and occlusive hyperemia, prevail in the literature regarding the occasional development of hemorrhage and edema following AVM resection. The NPPB hypothesis was introduced in 1978. Since the occlusive hyperemia hypothesis was first postulated in 1993, however, a debate has persisted within the cerebrovascular community concerning which hypothesis better explains the complications of edema and hemorrhage seen after AVM resection. Recent advances in cerebrovascular imaging and hemodynamic analysis have allowed a better evaluation of intracerebral changes following AVM resection. It is likely that these 2 hypotheses are not mutually exclusive and perhaps exist in a spectrum of hemodynamic alteration following AVM resection.

    View details for DOI 10.1016/j.nec.2011.09.005

    View details for Web of Science ID 000298312000014

    View details for PubMedID 22107865

  • A Comparative Evaluation of Existing Grading Scales in Intracerebral Hemorrhage NEUROCRITICAL CARE Bruce, S. S., Appelboom, G., Piazza, M., Hwang, B. Y., Kellner, C., Carpenter, A. M., Bagiella, E., Mayer, S., Connolly, E. S. 2011; 15 (3): 498-505

    Abstract

    In recent years, a multitude of clinical grading scales have been created to help identify patients at greater risk of poor outcome following ICH. We sought to validate and compare eight of the most frequently used ICH grading scales in a prospective cohort.Eight grading scales were calculated for 67 patients with non-traumatic ICH enrolled in the prospective intracerebral hemorrhage outcomes project (ICHOP) database. Receiver operating characteristic (ROC) analysis, including area under the curve (AUC) and maximum Youden Index were used to assess the ability of each score to predict in-hospital mortality, long-term (3 months) mortality, and functional outcome at 3 months (mRS ≥ 3).All scales demonstrated excellent to outstanding discrimination for in-hospital and long-term mortality, with no significant differences between them after controlling for the false discovery rate. All scales demonstrated acceptable to outstanding discrimination for functional outcome at 3 months, with the new ICH score demonstrating significantly lower AUC than 6 of the 8 scores. Essen ICH score was the only score to demonstrate outstanding discrimination for each outcome measure.Though significant differences were minimal in our cohort, we showed the existing selection of ICH grading scales to be useful in stratifying patients according to risk of mortality and poor functional outcome. Continued validation and comparison in large prospective cohorts will bring the goal of a singular prognostic model for ICH closer to fruition.

    View details for DOI 10.1007/s12028-011-9518-7

    View details for Web of Science ID 000297365400021

    View details for PubMedID 21394545

  • Complement Factor H Y402H polymorphism is associated with an increased risk of mortality after intracerebral hemorrhage JOURNAL OF CLINICAL NEUROSCIENCE Appelboom, G., Piazza, M., Hwang, B. Y., Bruce, S., Smith, S., Bratt, A., Bagiella, E., Badjatia, N., Mayer, S., Connolly, E. S. 2011; 18 (11): 1439-1443

    Abstract

    Intracerebral hemorrhage (ICH) accounts for 10% to 15% of all strokes and is a major cause of morbidity and mortality. Despite advances in management, numerous clinical trials have failed to demonstrate significant benefit of medical and surgical interventions, underscoring the need for the identification of novel therapeutic targets based on improved understanding of ICH pathophysiology and optimal risk stratification based on reliable and effective prognosticators. The alternative complement cascade has been implicated as an important contributor to neurological injury after ICH. Therefore, common, functionally relevant genetic variants in the key components of this pathway have been associated with greater inflammation post-ictus, further cerebral damage, and ultimately, a worse outcome. We investigated the affects of single-nucleotide polymorphisms (SNP) on mortality in complement component 3 C3 (rs2230199), complement component 5 C5 (rs17611), and Complement Factor H (CFH; rs1061170) genes, which are associated with the onset and progression of several neurological diseases, in a prospective cohort of patients with spontaneous ICH. From February 2009 through May 2010, adult patients with spontaneous ICH were admitted to the Columbia University Neurological Intensive Care Unit and enrolled in the Intracerebral Hemorrhage Outcomes Project. Demographic, clinical, radiographic, and treatment data were prospectively collected. Buccal swabs were obtained, and isolated cells were sequenced for the aforementioned SNP. A total of 103 patients were admitted with ICH, and of these, 82 consented for genetic testing and were included in the analysis. The median age was 61 years and 39% were females. The median Glasgow Coma Scale score on admission was 11.5. The CFH SNP was significantly associated with both discharge (p = 0.01) and 6-month mortality (p = 0.02), while no such association was observed for C3 (p = 0.545 and p = 0.830) or C5 (p = 0.983 and p = 0.536) SNP. Additionally, after controlling for pertinent variables identified in the univariate analysis, the CFH genotype independently predicted mortality at discharge (p = 0.019, odds ratio [OR] 7.62, 95% confidence interval [CI] 1.40-41.6) and at 6 months (p = 0.041, OR 1.822, 95% CI 1.025-3.239). The CFH genotype was also independently predictive of survival duration (p = 0.041, OR 1.822, 95% CI 1.025-3.239). We concluded that CFH Y402H polymorphism independently predicts mortality at discharge and 6-months and survival duration after spontaneous ICH.

    View details for DOI 10.1016/j.jocn.2011.04.001

    View details for Web of Science ID 000296402800003

    View details for PubMedID 21871809

  • Traumatic brain injury in pediatric patients: evidence for the effectiveness of decompressive surgery NEUROSURGICAL FOCUS Appelboom, G., Zoller, S. D., Piazza, M. A., Szpalski, C., Bruce, S. S., McDowell, M. M., Vaughan, K. A., Zacharia, B. E., Hickman, Z., D'Ambrosio, A., Feldstein, N. A., Anderson, R. C. 2011; 31 (5)

    Abstract

    Traumatic brain injury (TBI) is the current leading cause of death in children over 1 year of age. Adequate management and care of pediatric patients is critical to ensure the best functional outcome in this population. In their controversial trial, Cooper et al. concluded that decompressive craniectomy following TBI did not improve clinical outcome of the analyzed adult population. While the study did not target pediatric populations, the results do raise important and timely clinical questions regarding the effectiveness of decompressive surgery in pediatric patients. There is still a paucity of evidence regarding the effectiveness of this therapy in a pediatric population, and there is an especially noticeable knowledge gap surrounding age-stratified interventions in pediatric trauma. The purposes of this review are to first explore the anatomical variations between pediatric and adult populations in the setting of TBI. Second, the authors assess how these differences between adult and pediatric populations could translate into differences in the impact of decompressive surgery following TBI.

    View details for DOI 10.3171/2011.8.FOCUS11177

    View details for Web of Science ID 000296762300006

    View details for PubMedID 22044104

  • Alterations in systemic complement component 3a and 5a levels in patients with cerebral arteriovenous malformations JOURNAL OF CLINICAL NEUROSCIENCE Haque, R., Hwang, B. Y., Appelboom, G., Piazza, M. A., Guo, K., Connolly, E. S. 2011; 18 (9): 1235-1239

    Abstract

    The role of the complement cascade in the pathophysiology of cerebral arteriovenous malformation (AVM) is largely undefined. Complement subcomponents, C3a and C5a, are potent anaphylatoxins and key mediators of immuno-inflammatory response. Complement activation may contribute to the pro-inflammatory state observed in AVM. Thus, we sought to determine the systemic levels of C3a and C5a and their response to treatments in patients with AVM. Blood samples of 18 patients undergoing treatment for unruptured AVM, and from 30 healthy control participants, were obtained at four times: (i) pre-treatment, (ii) 24-hours post-embolization, (iii) 24-hours post-resection, and at 1-month follow-up. Plasma concentrations of C3a and C5a were measured using enzyme-linked immunosorbent assay. The pre-treatment mean plasma C3a level was significantly higher in patients with AVM (1817±168 ng/mL) compared to controls (1126±151 ng/mL). The mean C3a level decreased 24-hours after embolization (1482±170 ng/mL) and remained at statistically similar levels 24-hours after resection (1511±149 ng/mL) and at 1-month follow-up (1535±133 ng/mL). Mean C3a levels at the three time points were higher than control levels.The baseline mean plasma C5a level was significantly elevated in patients with AVM (13.1±2.2 ng/mL) compared to controls (3.9±1.5 ng/mL).Mean C5a level decreasedpost-embolization (8.2±2.3 ng/mL) and remained at similar levels post-resection (8.5±3.0 ng/mL) and at 1-month follow-up (7.7±2.9 ng/mL). Mean C5a levels at the three time points were significantly higher than the control levels. We conclude that systemic C3a and C5a levels in patients with AVM are elevated at baseline, decrease significantly after embolization, and remain at the new baseline levels after surgery and 1-month follow-up.

    View details for DOI 10.1016/j.jocn.2011.02.015

    View details for Web of Science ID 000294320000021

    View details for PubMedID 21742500

  • Severity of Intraventricular Extension Correlates With Level of Admission Glucose After Intracerebral Hemorrhage STROKE Appelboom, G., Piazza, M. A., Hwang, B. Y., Carpenter, A., Bruce, S. S., Mayer, S., Connolly, E. S. 2011; 42 (7): 1883-1888

    Abstract

    Hyperglycemia after spontaneous intracerebral hemorrhage (ICH) is associated with poor outcome, but the pathophysiology of ICH-induced glucose dysregulation remains unclear. We sought to identify clinical and radiographic parameters of ICH that are associated with admission hyperglycemia.Patients admitted to the Columbia University Medical Center Neurological Intensive Care Unit with spontaneous ICH between January 2009 and September 2010 were prospectively enrolled in the ICH Outcomes Project. Clinical, radiographic, and laboratory data were collected prospectively. Receiver operating characteristic analysis was used to identify the glucose level with optimal sensitivity and specificity for in-hospital mortality. Logistic and linear regression analyses were used to identify independent predictors of outcome measures where appropriate.One hundred four patients admitted during the study period were included in the analysis. Mean admission glucose level was 8.23 ± 3.15 mmol/L (3.83 to 18.89 mmol/L) and 23.2% had a history of diabetes mellitus. Admission glucose was significantly associated with discharge (P=0.003) and 3-month mortality (P=0.002). Critical hyperglycemia defined at 10 mmol/L independently predicted discharge mortality (P=0.027; OR, 4.381; 95% CI, 1.186 to 16.174) and 3-month mortality (P=0.011; OR, 10.95; 95% CI, 1.886 to 62.41). Admission intraventricular extension score (P=0.038; OR, 1.117; 95% CI, 1.043 to 1.197) and diabetes mellitus (P=0.002; OR, 5.530; 95% CI, 1.833 to 16.689) were independent predictors of critical hyperglycemia. The intraventricular extension score (B=0.115, P=0.001) linearly correlated with admission glucose level (R=0.612, P=0.001) after adjusting for other clinical variables.Admission hyperglycemia after spontaneous ICH is associated with poor outcome and potentially related to the presence and severity of intraventricular extension.

    View details for DOI 10.1161/STROKEAHA.110.608166

    View details for Web of Science ID 000292090900027

    View details for PubMedID 21636822

  • Improving patient selection for endovascular treatment of acute cerebral ischemia: a review of the literature and an external validation of the Houston IAT and THRIVE predictive scoring systems NEUROSURGICAL FOCUS Ishkanian, A. A., McCullough-Hicks, M. E., Appelboom, G., Piazza, M. A., Hwang, B. Y., Bruce, S. S., Hannan, L. M., Connolly, S. R., Lavine, S. D., Meyers, P. M. 2011; 30 (6)

    Abstract

    Outcome after intraarterial therapy (IAT) for acute ischemic stroke remains variable, suggesting that improved patient selection is needed to better identify patients likely to benefit from treatment. The authors evaluate the predictive accuracies of the Houston IAT (HIAT) and the Totaled Health Risks in Vascular Events (THRIVE) scores in an independent cohort and review the existing literature detailing additional predictive factors to be used in patient selection for IAT. They reviewed their center's endovascular records from January 2004 to July 2010 and identified patients who had acute ischemic stroke and underwent IAT. They calculated individual HIAT and THRIVE scores using patient age, admission National Institutes of Health Stroke Scale (NIHSS) score, admission glucose level, and medical history. The scores' predictive accuracies for good outcome (discharge modified Rankin Scale score ≤ 3) were analyzed using receiver operating characteristics analysis. The THRIVE score predicts poor outcome after IAT with reasonable accuracy and may perform better than the HIAT score. Nevertheless, both measures may have significant clinical utility; further validation in larger cohorts that accounts for differences in patient demographic characteristics, variation in time-to-treatment, and center preferences with respect to IAT modalities is needed. Additional patient predictive factors have been reported but not yet incorporated into predictive scales; the authors suggest the need for additional data analysis to determine the independent predictive value of patient admission NIHSS score, age, admission hyperglycemia, patient comorbidities, thrombus burden, collateral flow, time to treatment, and baseline neuroimaging findings.

    View details for DOI 10.3171/2011.3.FOCUS1144

    View details for Web of Science ID 000291165100008

    View details for PubMedID 21631231

  • Isoflurane preconditioning affords functional neuroprotection in a murine model of intracerebral hemorrhage. Acta neurochirurgica. Supplement Gigante, P. R., Appelboom, G., Hwang, B. Y., Haque, R. M., Yeh, M. L., Ducruet, A. F., Kellner, C. P., Gorski, J., Keesecker, S. E., Connolly, E. S. 2011; 111: 141-144

    Abstract

    Exposure to isoflurane gas prior to neurological injury, known as anesthetic preconditioning, has been shown to provide neuroprotective benefits in animal models of ischemic stroke. Given the common mediators of cellular injury in ischemic and hemorrhagic stroke, we hypothesize that isoflurane preconditioning will provide neurological protection in intracerebral hemorrhage (ICH).24 h prior to intracerebral hemorrhage, C57BL/6J mice were preconditioned with a 4-h exposure to 1% isoflurane gas or room air. Intracerebral hemorrhage was performed using a double infusion of 30-μL autologous whole blood. Neurological function was evaluated at 24, 48 and 72 h using the 28-point test. Mice were sacrificed at 72 h, and brain edema was measured.Mice preconditioned with isoflurane performed better than control mice on 28-point testing at 24 h, but not at 48 or 72 h. There was no significant difference in ipsilateral hemispheric edema between mice preconditioned with isoflurane and control mice.These results demonstrate the early functional neuroprotective effects of anesthetic preconditioning in ICH and suggest that methods of preconditioning that afford protection in ischemia may also provide protection in ICH.

    View details for DOI 10.1007/978-3-7091-0693-8_23

    View details for PubMedID 21725745

  • Advances in Neuroprotective Strategies: Potential Therapies for Intracerebral Hemorrhage CEREBROVASCULAR DISEASES Hwang, B. Y., Appelboom, G., Ayer, A., Kellner, C. P., Kotchetkov, I. S., Gigante, P. R., Haque, R., Kellner, M., Connolly, E. S. 2011; 31 (3): 211-222

    Abstract

    Intracerebral hemorrhage (ICH) is associated with higher mortality and morbidity than any other form of stroke. However, there currently are no treatments proven to improve outcomes after ICH, and therefore, new effective therapies are urgently needed. Growing insight into ICH pathophysiology has led to the development of neuroprotective strategies that aim to improve the outcome through reduction of secondary pathologic processes. Many neuroprotectants target molecules or pathways involved in hematoma degradation, inflammation or apoptosis, and have demonstrated potential clinical benefits in experimental settings. We extensively reviewed the current understanding of ICH pathophysiology as well as promising experimental neuroprotective agents with particular focus on their mechanisms of action. Continued advances in ICH knowledge, increased understanding of neuroprotective mechanisms, and improvement in the ability to modulate molecular and pathologic events with multitargeting agents will lead to successful clinical trials and bench-to-bedside translation of neuroprotective strategies.

    View details for DOI 10.1159/000321870

    View details for Web of Science ID 000291816300001

    View details for PubMedID 21178344

  • External ventricular drainage following aneurysmal subarachnoid haemorrhage BRITISH JOURNAL OF NEUROSURGERY Gigante, P., Hwang, B. Y., Appelboom, G., Kellner, C. P., Kellner, M. A., Connolly, E. S. 2010; 24 (6): 625-632

    Abstract

    External ventricular drain (EVD) placement is standard of care in the management of aneurysmal subarachnoid haemorrhage-associated hydrocephalus (aSAH). However, there are no guidelines for EVD placement and management after aSAH. Optimal EVD insertion conditions, techniques to reduce the risk of EVD-associated infection and aneurysmal rebleeding, and methods of EVD removal are critical, yet incompletely answered management variables. The present literature consists primarily of small studies with heterogeneous populations and variable outcome measures, and suggests the following: EVDs may increase the risk of rebleeding; EVDs are increasingly placed by non-neurosurgeons with unclear results; intraparenchymal ICP monitors may be safely considered (with or without spinal drainage) in the setting of difficult EVD placement; the optimal timing and manner of EVD removal has yet to be defined; and the efficacy of prophylactic systemic antibiotics and antibiotic-coated EVDs needs further investigation. Nevertheless, there are no definitive practice guidelines for EVD placement and management techniques in aSAH patients. Large prospective randomised trials are needed to definitively address important gaps in our understanding of EVD management principles in the neurocritical care setting.

    View details for DOI 10.3109/02688697.2010.505989

    View details for Web of Science ID 000284118100005

    View details for PubMedID 20854058

  • Bedside Use of a Dual Aortic Balloon Occlusion for the Treatment of Cerebral Vasospasm NEUROCRITICAL CARE Appelboom, G., Strozyk, D., Hwang, B. Y., Prowda, J., Badjatia, N., Helbok, R., Meyers, P. M. 2010; 13 (3): 385-388

    Abstract

    Delayed ischemic neurological deficits (DIND) due to cerebral vasospasm remains a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Methods to prevent DIND remain limited both in safety and efficacy. A novel intra-aortic dual balloon catheter (NeuroFlo™: CoAxia, Maple Grove, MN) is under investigation for treatment of ischemic stroke, including DIND. Because this technique does not require cerebral artery navigation, it may be useful as a bedside procedure, outside of the conventional angiography suite. We report the first case of ultrasound-guided application of the NeuroFlo™ system at bedside in the Neurological Intensive Care Unit.A 52-year-old woman presented with Hunt Hess IV aSAH complicated by medically refractory cerebral vasospasm. Despite surgical clipping of her aneurysm, the patient remained critically ill, failing maximal conventional medical therapy. For that reason, the NeuroFlo™ system was deployed using two-dimensional, spectral and color-flow Doppler ultrasound guidance at the patient's bedside while maintaining all forms of cerebral blood flow monitoring.The procedure was well tolerated and there was no complication.Bedside application of the NeuroFlo™ system may be safely performed in critically ill patients. The NeuroFlo™ system is under investigation for treatment of refractory cerebral vasospasm to prevent delayed ischemic neurological disease.

    View details for DOI 10.1007/s12028-010-9442-2

    View details for Web of Science ID 000284653800015

    View details for PubMedID 20859705

  • The sociopolitical history and physiological underpinnings of skull deformation NEUROSURGICAL FOCUS Ayer, A., Campbell, A., Appelboom, G., Hwang, B. Y., McDowell, M., Piazza, M., Feldstein, N. A., Anderson, R. C. 2010; 29 (6)

    Abstract

    In this report, the evidence, mechanisms, and rationale for the practice of artificial cranial deformation (ACD) in ancient Peru and during Akhenaten's reign in the 18th dynasty in Egypt (1375-1358 BCE) are reviewed. The authors argue that insufficient attention has been given to the sociopolitical implications of the practice in both regions. While evidence from ancient Peru is widespread and complex, there are comparatively fewer examples of deformed crania from the period of Akhenaten's rule. Nevertheless, Akhenaten's own deformity, the skull of the so-called "Younger Lady" mummy, and Tutankhamen's skull all evince some degree of plagiocephaly, suggesting the need for further research using evidence from depictions of the royal family in reliefs and busts. Following the anthropological review, a neurosurgical focus is directed to instances of plagiocephaly in modern medicine, with special attention to the conditions' etiology, consequences, and treatment. Novel clinical studies on varying modes of treatment will also be studied, together forming a comprehensive review of ACD, both in the past and present.

    View details for DOI 10.3171/2010.9.FOCUS10202

    View details for Web of Science ID 000285648900002

    View details for PubMedID 21121715

  • Response to the Letter to the Editor from Gustavo Cartaxo Patriota, M.D., M.Sc., on "Clinical Grading Scales in Intracerebral Hemorrhage" Neurocritical care Hwang, B. Y., Appelboom, G., Kellner, C. P., Connolly, E. S. 2010: -?

    View details for PubMedID 20811961

  • Clinical Grading Scales in Intracerebral Hemorrhage NEUROCRITICAL CARE Hwang, B. Y., Appelboom, G., Kellner, C. P., Carpenter, A. M., Kellner, M. A., Gigante, P. R., Connolly, E. S. 2010; 13 (1): 141-151

    Abstract

    Intracerebral hemorrhage (ICH) carries higher risk of long-term disability and mortality than any other form of stroke. Despite greater understanding of ICH pathophysiology, treatment options for this devastating condition remain limited. Moreover, a lack of a standard, universally accepted clinical grading scale for ICH has contributed to variations in management protocols and clinical trial designs. Grading scales are essential for standardized assessment and communication among physicians, selecting optimized treatment regiments, and designing effective clinical trials. There currently exist a number of ICH grading scales and prognostic models that have been developed for mortality and/or functional outcome, particularly 30 days after the ICH onset. Numerous reliable scales have been externally validated in heterogeneous populations. We extensively reviewed the inherent strengths and limitations of all the existing clinical ICH grading scales based on their development and validation methodology. For all ICH grading scales, we carefully observed study design and the definition and timing of outcome assessment to elucidate inconsistencies in grading scale derivation and application. Ultimately, we call for an expansive, prospective, multi-center clinical outcome study to clearly define all aspects of ICH, establish ideal grading scales, and standardized management protocols to enable the identification of novel and effective therapies in ICH.

    View details for DOI 10.1007/s12028-010-9382-x

    View details for Web of Science ID 000279505900023

    View details for PubMedID 20490715

  • Current Recommendations for Endovascular Interventions in the Treatment of Ischemic Stroke CURRENT ATHEROSCLEROSIS REPORTS Appelboom, G., Strozyk, D., Meyers, P. M., Higashida, R. T. 2010; 12 (4): 244-250

    Abstract

    Ischemic stroke remains one of the leading cause of adult death and disability in the United States. Reperfusion of the occluded vessel is the standard of care in the setting of acute ischemic stroke according to established guidelines. Since the introduction of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in the late 1990s, significant advances have been made in methods to deliver thrombolytic agents and in devices for mechanical recanalization of occluded vessels. Furthermore, improvements in patient selection contribute to achievement of good clinical outcomes after endovascular therapy. This article summarizes findings from recent clinical trials and presents evidence-based guidelines for endovascular interventions in the treatment of ischemic stroke.

    View details for DOI 10.1007/s11883-010-0115-6

    View details for Web of Science ID 000278179300005

    View details for PubMedID 20461559

  • Brain-computer interfaces: military, neurosurgical, and ethical perspective NEUROSURGICAL FOCUS Kotchetkov, I. S., Hwang, B. Y., Appelboom, G., Kellner, C. P., Connolly, E. S. 2010; 28 (5)

    Abstract

    Brain-computer interfaces (BCIs) are devices that acquire and transform neural signals into actions intended by the user. These devices have been a rapidly developing area of research over the past 2 decades, and the military has made significant contributions to these efforts. Presently, BCIs can provide humans with rudimentary control over computer systems and robotic devices. Continued advances in BCI technology are especially pertinent in the military setting, given the potential for therapeutic applications to restore function after combat injury, and for the evolving use of BCI devices in military operations and performance enhancement. Neurosurgeons will play a central role in the further development and implementation of BCIs, but they will also have to navigate important ethical questions in the translation of this highly promising technology. In the following commentary the authors discuss realistic expectations for BCI use in the military and underscore the intersection of the neurosurgeon's civic and clinical duty to care for those who serve their country.

    View details for DOI 10.3171/2010.2.FOCUS1027

    View details for Web of Science ID 000277193600025

    View details for PubMedID 20568942

  • Infectious Aneurysm of the Cavernous Carotid Artery in a Child Treated With a New-Generation of Flow-Diverting Stent Graft: Case Report NEUROSURGERY Appelboom, G., Kadri, K., Hassan, F., Leclerc, X. 2010; 66 (3): E623-U214

    Abstract

    To report a unique case of wide-necked mycotic cerebral aneurysm treated with a new generation of intracranial stent.A 10-year-old girl presented with meningitis complicated by an infectious intracavernous large aneurysm revealed by cranial nerve palsy.The aneurysm was treated by a new-generation, flow-diverting, endoluminal implant (SILK; BALT EXTRUSION, Montmorency, France) placed across the aneurysm neck without coiling. Angiographic controls showed complete thrombosis of the aneurysmal sac with dramatic improvement of symptoms a couple of weeks after the procedure. Follow-up magnetic resonance imaging and digital subtraction angiography 3 months after the procedure, confirmed total occlusion of the aneurysm with normal circulation in the parent vesselThis is a simple and highly effective way to exclude an aneurysm from the parent vessel without the difficulties observed with the semi-rigid stents. Flow-disrupting stent grafting may be a safe and effective alternative treatment for large intracranial aneurysms.

    View details for DOI 10.1227/01.NEU.0000365370.82554.08

    View details for Web of Science ID 000274795800049

    View details for PubMedID 20173536