Bio

Clinical Focus


  • Stroke
  • Intracerebral Hemorrhage
  • Traumatic Brain Injury
  • Neurocritical Care
  • Neurology

Academic Appointments


Honors & Awards


  • Fellowship Award for Clinical Research, Neurocritical Care Society (2005)
  • Gold Medal in Cardiology, Cardiological and Electrophysiological Society of India (1999)
  • Gold Medal for "Best Outgoing Student in M.B.B.S", Indian Medical Association (1996)
  • Gold Medal in Pathology, Indian Association of Pathologists and Microbiologists (1993)

Professional Education


  • Fellowship:London School of Health and Tropical Medicine (09/31/2013) UK
  • Internship:Kaiser Permanente/Santa Clara (2002) CA
  • Fellowship:Stanford University Medical Center (2006) CA
  • Residency:Coimbatore Medical College (1999) India
  • Board Certification, American Society of Neuroimaging, Neurosonology (2010)
  • Board Certification: Vascular Neurology, American Board of Psychiatry and Neurology (2008)
  • Board Certification, United Council of Neurologic Subspecialties, Neurocritical Care (2007)
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2007)
  • Residency:Stanford University Medical Center (2005) CA
  • Medical Education:Coimbatore Medical College (1999) India
  • M.B.B.S., Dr MGR Medical University India, Medicine (1996)

Research & Scholarship

Current Research and Scholarly Interests


I care for neurologically critically ill patients in the intensive care unit and patients with acute stroke and TIA in the inpatient stroke unit. I also see outpatients in a stroke clinic and conduct follow-up of patients discharged from the neurological ICU, in the “Outcomes clinic”.
I am interested in the study of the radiological characteristics and temporal profile of edema/ tissue injury in the perihematomal area around spontaneous intracerebral hemorrhage. I am also interested in developing protocols for emergent reversal of anticoagulation in a life-threatening hemorrhage situation.

Clinical Trials


  • Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-4) Recruiting

    The purpose of the study is to determine whether desmoteplase is effective and safe in the treatment of patients with acute ischaemic stroke when given within 3 to 9 hours from onset of stroke symptoms.

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  • Transient Ischemic Attack (TIA) Triage and Evaluation of Stroke Risk Recruiting

    Transient ischemic attack (TIA) is a transient neurological deficit (speech disturbance, weakness…), caused by temporary occlusion of a brain vessel by a blood clot that leaves no lasting effect. TIA diagnosis can be challenging and an expert stroke evaluation combined with magnetic resonance imaging (MRI) could improve the diagnosis accuracy. The risk of a debilitating stroke can be as high as 5% during the first 72 hrs after TIA. TIA characteristics (duration, type of symptoms, age of the patient), the presence of a significant narrowing of the neck vessels responsible for the patient's symptoms (symptomatic stenosis), and an abnormal MRI are associated with an increased risk of stroke. An emergent evaluation and treatment of TIA patients by a stroke specialist could reduce the risk of stroke to 2%. Stanford has implemented an expedited triage pathway for TIA patients combining a clinical evaluation by a stroke neurologist, an acute MRI of the brain and the vessels and a sampling of biomarkers (Lp-PLA2). The investigators are investigating the yield of this unique approach to improve TIA diagnosis, prognosis and secondary stroke prevention. The objective of this prospective cohort study is to determine which factors will help the physician to confirm the diagnosis of TIA and to define the risk of stroke after a TIA.

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  • Insulin Resistance Intervention After Stroke Trial Recruiting

    The purpose of this study is to determine if pioglitazone is effective in preventing future strokes or heart attacks among non-diabetic persons who have had a recent ischemic stroke.

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  • High-Dose Deferoxamine in Intracerebral Hemorrhage Recruiting

    The main purpose of this study is to determine whether treatment with deferoxamine mesylate is of sufficient promise to improve outcome before pursuing a larger clinical trial to examine its effectiveness as a treatment for brain hemorrhage.

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  • Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III Recruiting

    The overall objective of this Phase III clinical trial is to obtain information from a population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of current clinical practice and national demographics of ICH regarding the benefit (or lack thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS). This application requests funding for five years to initiate a Phase III randomized clinical trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA and Boehringer Ingelheim, Inc., Ingelheim, Germany) with EVD+ placebo in the management and treatment of subjects with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH defined as ICH < 30 cc and obstruction of the 3rd or 4th ventricles by intraventricular blood clot).

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  • Efficacy and Safety Trial of Transcranial Laser Therapy Within 24 Hours From Stroke Onset (NEST-3) Recruiting

    The purpose of this pivotal study is to demonstrate safety and efficacy of transcranial laser therapy (TLT) with the NeuroThera® Laser System in the treatment of subjects diagnosed with acute ischemic stroke. The initiation of the TLT procedure must be feasible for each subject between 4.5 and 24 hours of stroke onset.

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  • Computed Tomography Perfusion (CTP) to Predict Response to Recanalization in Ischemic Stroke Project (CRISP) Recruiting

    The overall goal of the CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is to develop a practical tool to identify acute stroke patients who are likely to benefit from endovascular therapy. The project has two main parts. During the first part, the investigators propose to develop a fully automated system (RAPID) for processing of CT Perfusion (CTP) images that will generate brain maps of the ischemic core and penumbra. There will be no patient enrollment in part one of this project. During the second part, the investigators aim to demonstrate that physicians in the emergency setting, with the aid of a fully automated CTP analysis program (RAPID), can accurately predict response to recanalization in stroke patients undergoing revascularization. To achieve this aim the investigators will conduct a prospective cohort study of 240 consecutive stroke patients who will undergo a CTP scan prior to endovascular therapy. The study will be conducted at four sites (Stanford University, St Luke's Hospital, University of Pittsburgh Medical Center, and Emory University/Grady Hospital). Patients will have an early follow-up MRI scan within 12+/-6 hours to assess reperfusion and a late follow-up MRI scan at day 5 to determine the final infarct.

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  • Progesterone for the Treatment of Traumatic Brain Injury Recruiting

    The ProTECT study will determine if intravenous (IV) progesterone (started within 4 hours of injury and given for a total of 96 hours), is more effective than placebo for treating victims of moderate to severe acute traumatic brain injury.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Serum Neuron-Specific Enolase Levels from the Same Patients Differ Between Laboratories: Assessment of a Prospective Post-cardiac Arrest Cohort. Neurocritical care Mlynash, M., Buckwalter, M. S., Okada, A., Caulfield, A. F., Venkatasubramanian, C., Eyngorn, I., Verbeek, M. M., Wijman, C. A. 2013; 19 (2): 161-166

    Abstract

    In comatose post-cardiac arrest patients, a serum neuron-specific enolase (NSE) level of >33 μg/L within 72 h was identified as a reliable marker for poor outcome in a large Dutch study (PROPAC), and this level was subsequently adopted in an American Academy of Neurology practice parameter. Later studies reported that NSE >33 μg/L is not a reliable predictor of poor prognosis. To test whether different clinical laboratories contribute to this variability, we compared NSE levels from the laboratory used in the PROPAC study (DLM-Nijmegen) with those of our hospital's laboratory (ARUP) using paired blood samples.We prospectively enrolled cardiac arrest patients who remained comatose after resuscitation. During the first 3 days, paired blood samples for serum NSE were drawn at a median of 10 min apart. After standard preparation for each lab, one sample was sent to ARUP laboratories and the other to DLM-Nijmegen.Fifty-four paired serum samples from 33 patients were included. Although the serum NSE measurements correlated well between laboratories (R = 0.91), the results from ARUP were approximately 30 % lower than those from DLM-Nijmegen. Therapeutic hypothermia did not affect this relationship. Two patients had favorable outcomes after hypothermia despite NSE levels measured by DLM-Nijmegen as >33 μg/L.Absolute serum NSE levels of comatose cardiac arrest patients differ between laboratories. Any specific absolute cut-off levels proposed to prognosticate poor outcome should not be used without detailed data on how neurologic outcomes correspond to a particular laboratory's method, and even then only in conjunction with other prognostic variables.

    View details for DOI 10.1007/s12028-013-9867-5

    View details for PubMedID 23839710

  • Christine Anne Cunegonde Wijman, MD, PhD (1965-2013). Neurocritical care Finley Caulfield, A., Venkatasubramanian, C. 2013; 19 (1): 135-136

    View details for DOI 10.1007/s12028-013-9855-9

    View details for PubMedID 23690248

  • Magnetic resonance imaging profile of blood-brain barrier injury in patients with acute intracerebral hemorrhage. Journal of the American Heart Association Aksoy, D., Bammer, R., Mlynash, M., Venkatasubramanian, C., Eyngorn, I., Snider, R. W., Gupta, S. N., Narayana, R., Fischbein, N., Wijman, C. A. 2013; 2 (3)

    Abstract

    Spontaneous intracerebral hemorrhage (ICH) is associated with blood-brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage.Twenty-five prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (K(trans)) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror-image locations (control ROI). In all patients BBB permeability was significantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI (P<0.0001). Large hematomas (>30 mL) had higher K(trans) values than small hematomas (P<0.005). K(trans) values of lobar hemorrhages were significantly higher than the K(trans) values of deep hemorrhages (P<0.005), independent of hematoma volume. Higher K(trans) values were associated with larger edema volumes.BBB leakage in the brain tissue immediately bordering the hematoma can be measured and quantified by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes.

    View details for DOI 10.1161/JAHA.113.000161

    View details for PubMedID 23709564

  • A comparison of cooling techniques to treat cardiac arrest patients with hypothermia. Stroke research and treatment Finley Caulfield, A., Rachabattula, S., Eyngorn, I., Hamilton, S. A., Kalimuthu, R., Hsia, A. W., Lansberg, M. G., Venkatasubramanian, C., BAUMANN, J. J., Buckwalter, M. S., Kumar, M. A., Castle, J. S., Wijman, C. A. 2011; 2011: 690506-?

    Abstract

    Introduction. We sought to compare the performance of endovascular cooling to conventional surface cooling after cardiac arrest. Methods. Patients in coma following cardiopulmonary resuscitation were cooled with an endovascular cooling catheter or with ice bags and cold-water-circulating cooling blankets to a target temperature of 32.0-34.0°C for 24 hours. Performance of cooling techniques was compared by (1) number of hourly recordings in target temperature range, (2) time elapsed from the written order to initiate cooling and target temperature, and (3) adverse events during the first week. Results. Median time in target temperature range was 19 hours (interquartile range (IQR), 16-20) in the endovascular group versus. 10 hours (IQR, 7-15) in the surface group (P = .001). Median time to target temperature was 4 (IQR, 2.8-6.2) and 4.5 (IQR, 3-6.5) hours, respectively (P = .67). Adverse events were similar. Conclusion. Endovascular cooling maintains target temperatures better than conventional surface cooling.

    View details for DOI 10.4061/2011/690506

    View details for PubMedID 21822470

  • Natural History of Perihematomal Edema After Intracerebral Hemorrhage Measured by Serial Magnetic Resonance Imaging STROKE Venkatasubramanian, C., Mlynash, M., Finley-Caulfield, A., Eyngorn, I., Kalimuthu, R., Snider, R. W., Wijman, C. A. 2011; 42 (1): 73-80

    Abstract

    knowledge on the natural history and clinical impact of perihematomal edema (PHE) associated with intracerebral hemorrhage is limited. We aimed to define the time course, predictors, and clinical significance of PHE measured by serial magnetic resonance imaging.patients with primary supratentorial intracerebral hemorrhage ? 5 cm(3) underwent serial MRIs at prespecified intervals during the first month. Hematoma (H(v)) and PHE (E(v)) volumes were measured on fluid-attenuated inversion recovery images. Relative PHE was defined as E(v)/H(v). Neurologic assessments were performed at admission and with each MRI. Barthel Index, modified Rankin scale, and extended Glasgow Outcome scale scores were assigned at 3 months.twenty-seven patients with 88 MRIs were prospectively included. Median H(v) and E(v) on the first MRI were 39 and 46 cm(3), respectively. Median peak absolute E(v) was 88 cm(3). Larger hematomas produced a larger absolute E(v) (r(2)=0.6) and a smaller relative PHE (r(2)=0.7). Edema volume growth was fastest in the first 2 days but continued until 12 ± 3 days. In multivariate analysis, a higher admission hematocrit was associated with a greater delay in peak PHE (P=0.06). Higher admission partial thromboplastin time was associated with higher peak rPHE (P=0.02). Edema volume growth was correlated with a decline in neurologic status at 48 hours (81 vs 43 cm(3), P=0.03) but not with 3-month functional outcome.PHE volume measured by MRI increases most rapidly in the first 2 days after symptom onset and peaks toward the end of the second week. The timing and magnitude of PHE volume are associated with hematologic factors. Its clinical significance deserves further study.

    View details for DOI 10.1161/STROKEAHA.110.590646

    View details for Web of Science ID 000285636400019

    View details for PubMedID 21164136

  • MRI Profile of the Perihematomal Region in Acute Intracerebral Hemorrhage STROKE Olivot, J., Mlynash, M., Kleinman, J. T., Straka, M., Venkatasubramanian, C., Bammer, R., Moseley, M. E., Albers, G. W., Wijman, C. A. 2010; 41 (11): 2681-2683

    Abstract

    The pathophysiology of the presumed perihematomal edema immediately surrounding an acute intracerebral hemorrhage is poorly understood, and its composition may influence clinical outcome. Method-Twenty-three patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were prospectively enrolled and studied with MRI. Perfusion-weighted imaging, diffusion-weighted imaging, and fluid-attenuated inversion recovery sequences were coregistered. TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient values in the presumed perihematomal edema regions of interest were compared with contralateral mirror and remote ipsilateral hemispheric regions of interest.Compared with mirror and ipsilateral hemispheric regions of interest, TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient were consistently increased in the presumed perihematomal edema. Two thirds of the patients also exhibited patchy regions of restricted diffusion in the presumed perihematomal edema.The MRI profile of the presumed perihematomal edema in acute intracerebral hemorrhage exhibits delayed perfusion and increased diffusivity mixed with areas of reduced diffusion.

    View details for DOI 10.1161/STROKEAHA.110.590638

    View details for Web of Science ID 000283443500058

    View details for PubMedID 20947849

  • MIGRAINE-LIKE HEADACHE WITH VISUAL DEFICIT AND PERFUSION ABNORMALITY ON MRI NEUROLOGY Kapinos, G., Fischbein, N. J., Zaharchuk, G., Venkatasubramanian, C. 2010; 74 (21): 1743-1745

    View details for Web of Science ID 000278018400014

    View details for PubMedID 20498443

  • Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists NEUROLOGY Caulfield, A. F., GABLER, L., Lansberg, M. G., Eyngorn, I., Mlynash, M., Buckwalter, M. S., Venkatasubramanian, C., Wijman, C. A. 2010; 74 (14): 1096-1101

    Abstract

    Physician prediction of outcome in critically ill neurologic patients impacts treatment decisions and goals of care. In this observational study, we prospectively compared predictions by neurointensivists to patient outcomes at 6 months.Consecutive neurologic patients requiring mechanical ventilation for 72 hours or more were enrolled. The attending neurointensivist was asked to predict 6-month 1) functional outcome (modified Rankin scale [mRS]), 2) quality of life (QOL), and 3) whether supportive care should be withdrawn. Six-month functional outcome was determined by telephone interviews and dichotomized to good (mRS 0-3) and poor outcome (mRS 4-6).Of 187 eligible patients, 144 were enrolled. Neurointensivists correctly predicted 6-month functional outcome in 80% (95% confidence interval [CI], 72%-86%) of patients. Accuracy for a predicted good outcome was 63% (95% CI, 50%-74%) and for poor outcome 94% (95% CI, 85%-98%). Excluding patients who had life support withdrawn, accuracy for good outcome was 73% (95% CI, 60%-84%) and for poor outcome 87% (95% CI, 74%-94%). Accuracy for exact agreement between neurointensivists' mRS predictions and actual 6-month mRS was only 43% (95% CI, 35%-52%). Predicted accuracy for QOL was 58% (95% CI, 39%-74%) for good/excellent and 67% (95% CI, 46%-83%) for poor/fair. Of 27 patients for whom withdrawal of care was recommended, 1 patient survived in a vegetative state.Prediction of long-term functional outcomes in critically ill neurologic patients is challenging. Our neurointensivists were more accurate in predicting poor outcome than good outcome in patients requiring mechanical ventilation >or=72 hours.

    View details for Web of Science ID 000276354400005

    View details for PubMedID 20368630

  • Utility of Early MRI in the Diagnosis and Management of Acute Spontaneous Intracerebral Hemorrhage CEREBROVASCULAR DISEASES Wijman, C. A., Venkatasubramanian, C., Bruins, S., Fischbein, N., Schwartz, N. 2010; 30 (5): 456-463

    Abstract

    The optimal diagnostic evaluation for spontaneous intracerebral hemorrhage (ICH) remains controversial. In this retrospective study, we assessed the utility of early magnetic resonance imaging (MRI) in ICH diagnosis and management.Eighty-nine (72%) of 123 patients with spontaneous ICH underwent a brain CT and MRI within 30 days of ICH onset. Seventy patients with a mean age of 62 ± 15 years were included. A stroke neurologist and a general neurologist, each blinded to the final diagnosis, independently reviewed the admission data and the initial head CT and then assigned a presumed ICH cause under 1 of 9 categories. ICH cause was potentially modified after subsequent MRI review. The final 'gold standard' ICH etiology was determined after review of the complete medical record by an independent investigator. Change in diagnostic category and confidence and the potential impact on patient management were systematically recorded.Mean time to MRI was 3 ± 5 days. Final ICH diagnosis was hypertension or cerebral amyloid angiopathy (CAA) in 50% of patients. After MRI review the stroke neurologist changed diagnostic category in 14%, diagnostic confidence in an additional 23% and management in 20%, and the general neurologist did so in 19, 21 and 21% of patients, respectively. MRI yield was highest in ICH secondary to ischemic stroke, CAA, vascular malformations and neoplasms, and did not differ by age, history of hypertension, hematoma location or the presence of intraventricular hemorrhage.The results of this study suggest potential additive clinical benefit of early MRI in patients with spontaneous ICH.

    View details for DOI 10.1159/000316892

    View details for Web of Science ID 000282752200004

    View details for PubMedID 20733299

  • Favorable Outcome From A Locked-In State Despite Extensive Pontine Infarction By MRI NEUROCRITICAL CARE Samaniego, E. A., Lansberg, M. G., DeGeorgia, M., Venkatasubramanian, C., Wijman, C. A. 2009; 11 (3): 369-371

    Abstract

    Outcome prediction of patients who are in a locked-in state is challenging. Extensive pontine infarction on diffusion weighted imaging MRI (DWI) has been proposed as a poor prognosticator. We report on three patients with a locked-in state with unexpected favorable recoveries despite DWI evidence of widespread pontine ischemia.Report of three cases.Three young patients (32-, 30-, and 16-years-old) presented with a locked-in state caused by pontine infarction. The first patient did not receive any acute stroke therapies, the second patient underwent endovascular therapy 20 h after symptom onset resulting in partial recanalization of the basilar artery, and the third patient progressed to a locked-in state despite having received intravenous tissue plasminogen activator. The DWI of all three patients demonstrated acute and widespread pontine infarction involving more than two-thirds of the pons. Two patients regained full independence in their activities of daily living. The third patient remained wheelchair bound, but lives with her family, eats independently, uses a typewriter and wrote a book.Patients who are in a locked-in state may have substantial functional recovery despite DWI evidence of extensive pontine infarction.

    View details for DOI 10.1007/s12028-009-9268-y

    View details for Web of Science ID 000271943800011

    View details for PubMedID 19707888

  • Transient Isolated Vertigo Secondary to an Acute Stroke of the Cerebellar Nodulus Arch Neurol Schwartz N, V. A. 2007
  • Natural history and clinical significance of perihematomal edema after spontaneous intracerebral hemorrhage (abstract) Stroke Venkatasubramanian C, M. K. 2007
  • The effect of blood pressure on hematoma and perihematomal area in acute intracerebral hemorrhage. Neurosurgery clinics of North America Wijman, C. A., Venkatasubramanian, C. 2006; 17: 11-24

    View details for PubMedID 17967690

  • Myocarditis following scorpion sting The Antiseptic S. Dandapani, Subbiah, Chitra V. 1998: 303-304
  • Privatization of medical services in India Indian Journal of Clinical Practice Chitra V. 1997: 81-82

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