Publications by authors named "Barry Czeisler"

28 Publications

  • Page 1 of 1

Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19.

Neurocrit Care 2021 Mar 16. Epub 2021 Mar 16.

Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA.

Background: Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients.

Methods: We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission.

Results: Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001).

Conclusions: TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.
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http://dx.doi.org/10.1007/s12028-021-01220-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962078PMC
March 2021

Intra-arterial thrombolytic therapy for acute anterior spinal artery stroke.

J Clin Neurosci 2021 Feb 24;84:102-105. Epub 2020 Dec 24.

Department of Neurosurgery, NYU Langone Health, New York, NY, USA. Electronic address:

Background And Importance: Spinal cord infarction is rare but can be extremely disabling. Prompt diagnosis and treatment of these infarcts is important for patient outcomes. While intravenous thrombolytic therapy is a well-established form of treatment in circumstances of cerebral stroke, it has only recently been successfully used in a few incidents of spinal cord ischemia. We present a case of anterior spinal artery (ASA) territory ischemia treated with ASA intra-arterial thrombolytic therapy.

Clinical Presentation: A 52-year-old male presented with acute onset of severe lumbar pain, rapidly progressing paraplegia and loss of pain and temperature sensation, with preservation of proprioception and vibratory sensation at the L1 level and below on the right and at the L3 level and below on the left. MRI showed restricted diffusion involving the cord at and below L1 level, with normal cord T2 signal. Digital subtraction spinal angiography showed ASA cutoff in the descending limb at the level of L1. Intra-arterial tissue plasminogen activator (t-PA) combined with verapamil and eptifibatide was administered within the ASA and the patient had significant neurological improvement immediately postoperatively and at 8-month clinical follow-up.

Conclusion: Direct ASA intra-arterial thrombolysis is feasible, and this drug combination might be an effective therapy for spinal stroke.
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http://dx.doi.org/10.1016/j.jocn.2020.11.035DOI Listing
February 2021

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

Neurology 2021 01 5;96(4):e575-e586. Epub 2020 Oct 5.

From the New York University Grossman School of Medicine (J.A.F., S.S., R.L., T.F., B.F., P.M.-V., T.S., S.B., D.Y., A.G., N.M., P.P., J.G., K.M., S.A., M.B., A.A., E.V., M.O., A.K., K.L., Daniel Friedman, David Friedman, M.H., J.H., S.T., J.H., N.A.-F., P.K., A.L., A.S.L., T.Z., D.E.K., B.M.C., J.T., S.Y., K.I., E.S., D.P., M.L., T.W., A.B.T., L.B., S.G.), New YorkUniversity of Pittsburgh School of Medicine (S.H.-Y.C., E.L.F.), PAThe Ohio State University (M.M., S.M.), ColumbusMedical University of Innsbruck (R.H.), AustriaThe Johns Hopkins University School of Medicine (C.R., J.I.S., W.Z.), Baltimore, MDUniversity of Utah School of Medicine (M.S., A.d.H.), Salt Lake CityUniversity of Cambridge (D.M.), UK.

Objective: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes.

Methods: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.

Results: Of 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17-1.62, < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, < 0.001).

Conclusions: Neurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.
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http://dx.doi.org/10.1212/WNL.0000000000010979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905791PMC
January 2021

Risk factors for intracerebral hemorrhage in patients with COVID-19.

J Thromb Thrombolysis 2021 May 24;51(4):953-960. Epub 2020 Sep 24.

Department of Neurology, New York University Langone Health, New York, NY, USA.

Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19). We aimed to assess risk factors associated with ICH in this population. We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.
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http://dx.doi.org/10.1007/s11239-020-02288-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511245PMC
May 2021

Post-COVID-19 inflammatory syndrome manifesting as refractory status epilepticus.

Epilepsia 2020 10 18;61(10):e135-e139. Epub 2020 Sep 18.

Department of Neurology, NYU Langone Medical Center, New York, New York.

There have been multiple descriptions of seizures during the acute infectious period in patients with COVID-19. However, there have been no reports of status epilepticus after recovery from COVID-19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID-19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS-CoV-2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID-19.
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http://dx.doi.org/10.1111/epi.16683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537028PMC
October 2020

Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System.

Neurocrit Care 2020 Aug 24. Epub 2020 Aug 24.

Department of Neurology, NYU Langone Medical Center, New York, NY, 10016, USA.

Background And Purpose: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19.

Methods: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method.

Results: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results.

Conclusion: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.
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http://dx.doi.org/10.1007/s12028-020-01077-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444897PMC
August 2020

Prevalence and Impact of Hyponatremia in Patients With Coronavirus Disease 2019 in New York City.

Crit Care Med 2020 12;48(12):e1211-e1217

Department of Medicine, NYU Grossman School of Medicine, New York, NY.

Objectives: Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients.

Design: Retrospective, multicenter, observational cohort study.

Setting: Four New York City hospitals that are part of the same health network.

Patients: Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020.

Interventions: None.

Measurements And Main Results: Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08-1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017).

Conclusions: Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.
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http://dx.doi.org/10.1097/CCM.0000000000004605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467047PMC
December 2020

Special considerations in the assessment of catastrophic brain injury and determination of brain death in patients with SARS-CoV-2.

J Neurol Sci 2020 10 8;417:117087. Epub 2020 Aug 8.

NYU Langone Medical Center, Department of Neurology, New York, NY 10016, United States of America; NYU Langone Medical Center, Department of Neurosurgery, New York, NY 10016, United States of America.

Introduction: The coronavirus disease 2019 (Covid-19) pandemic has led to challenges in provision of care, clinical assessment and communication with families. The unique considerations associated with evaluation of catastrophic brain injury and death by neurologic criteria in patients with Covid-19 infection have not been examined.

Methods: We describe the evaluation of six patients hospitalized at a health network in New York City in April 2020 who had Covid-19, were comatose and had absent brainstem reflexes.

Results: Four males and two females with a median age of 58.5 (IQR 47-68) were evaluated for catastrophic brain injury due to stroke and/or global anoxic injury at a median of 14 days (IQR 13-18) after admission for acute respiratory failure due to Covid-19. All patients had hypotension requiring vasopressors and had been treated with sedative/narcotic drips for ventilator dyssynchrony. Among these patients, 5 had received paralytics. Apnea testing was performed for 1 patient due to the decision to withdraw treatment (n = 2), concern for inability to tolerate testing (n = 2) and observation of spontaneous respirations (n = 1). The apnea test was aborted due to hypoxia and hypotension. After ancillary testing, death was declared in three patients based on neurologic criteria and in three patients based on cardiopulmonary criteria (after withdrawal of support (n = 2) or cardiopulmonary arrest (n = 1)). A family member was able to visit 5/6 patients prior to cardiopulmonary arrest/discontinuation of organ support.

Conclusion: It is feasible to evaluate patients with catastrophic brain injury and declare brain death despite the Covid-19 pandemic, but this requires unique considerations.
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http://dx.doi.org/10.1016/j.jns.2020.117087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414304PMC
October 2020

Factors Associated With DNR Status After Nontraumatic Intracranial Hemorrhage.

Neurohospitalist 2020 Jul 22;10(3):168-175. Epub 2019 Sep 22.

Department of Neurology, NYU Langone Medical Center, New York, NY, USA.

Background: We explored factors associated with admission and discharge code status after nontraumatic intracranial hemorrhage.

Methods: We extracted data from patients admitted to our institution between January 1, 2013, and March 1, 2016 with nontraumatic intracerebral hemorrhage or subarachnoid hemorrhage who had a discharge modified Rankin Scale (mRS) of 4 to 6. We reviewed data based on admission and discharge code status.

Results: Of 88 patients who met inclusion criteria, 6 (7%) were do not resuscitate (DNR) on admission (aDNR). Do not resuscitate on admission patients were significantly older than those who were full code on admission ( 0.04). There was no significant difference between admission code status and sex, marital status, active cancer, premorbid mRS, admission Glasgow Coma scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, or bleed severity. At discharge, 66 (75%) patients were full code (dFULL), 11 (13%) were DNR (dDNR), and 11 (13%) were comfort care. African American and Hispanic patients were significantly more likely to be dFULL than Asian or white patients ( .01) and less likely to be seen by palliative care ( .004). Patients with less aggressive code status had higher median APACHE II scores ( .008) and were more likely to have active cancer ( .06). There was no significant difference between discharge code status and sex, age, marital status, premorbid mRS, discharge GCS, or bleed severity.

Conclusions: Limitation of code status after nontraumatic intracranial hemorrhage appears to be associated with older age, white race, worse APACHE II score, and active cancer. The role of palliative care after intracranial hemorrhage and the racial disparity in limitation and de-escalation of treatment deserves further exploration.
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http://dx.doi.org/10.1177/1941874419873812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271616PMC
July 2020

Attracting neurology's next generation: A qualitative study of specialty choice and perceptions.

Neurology 2020 08 24;95(8):e1080-e1090. Epub 2020 Apr 24.

From the Department of Neurology (J.T.J.), Massachusetts General Hospital and Harvard Medical School, Boston; Member Insights Department (C.C., T.O.), American Academy of Neurology, Minneapolis, MN; Department of Neurology (L.G.), University of Iowa, Iowa City; School of Medicine (A.N.) and Department of Neurology (A.G.S.), Virginia Commonwealth University, Richmond; Department of Neurology (C.E.G.), Johns Hopkins University, Baltimore, MD; Department of Neurology (V.S.), Stanford University, Palo Alto, CA; Department of Neurology (I.A.), University of Toledo, OH; Department of Neurological Sciences (M.S.), Rush University Medical Center, Chicago, IL; Department of Pediatrics & Psychiatry (R.B.W.), University of California, Los Angeles, David Geffen School of Medicine; Department of Pediatrics (R.R.S.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (B.M.C.), New York University, New York; and American Academy of Neurology (M.R.), Minneapolis, MN.

Objectives: To better understand the reasons medical students select or avoid a career in neurology by using a qualitative methodology to explore these factors, with the long-term objective of attracting more graduates to the field.

Methods: In 2017, 27 medical students and 15 residents participated in 5 focus groups, and 33 fourth-year medical students participated in semistructured individual interviews. Participants were asked predefined open-ended questions about specialty choice, experiences in their basic neuroscience course and neurology clerkship, and perceptions about the field. Interviews were audio recorded and transcribed. We used a flexible coding methodology to generate themes across groups and interviews.

Results: Four main analytical themes emerged: (1) early and broad clinical exposure allows students to "try on" neurology and experience the variety of career options; (2) preclerkship experiences and a strong neuroscience curriculum lay the foundation for interest in the field; (3) personal interactions with neurology providers may attract or deter students from considering the specialty; and (4) persistent stereotypes about neurologists, neurology patients, and treatment options harm student perceptions of neurology.

Conclusion: Efforts to draw more students to neurology may benefit from focusing on clinical correlations during preclerkship neuroscience courses and offering earlier and more diverse clinical experiences, including hands-on responsibilities whenever possible. Finally, optimizing student interactions with faculty and residents and reinforcing the many positive aspects of neurology are likely to favorably affect student perceptions.
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http://dx.doi.org/10.1212/WNL.0000000000009461DOI Listing
August 2020

Modafinil in Recovery after Stroke (MIRAS): A Retrospective Study.

J Stroke Cerebrovasc Dis 2020 Apr;29(4):104645

NYU Langone Health, Department of Neurology, New York, New York. Electronic address:

Background And Purpose: Acute rehabilitation is known to enhance stroke recovery. However, poststroke lethargy and fatigue can hinder participation in rehabilitation therapies. We hypothesized that in patients with moderate to severe stroke complicated by poststroke fatigue and lethargy early stimulant therapy with modafinil increases favorable discharge disposition defined as transfer to acute inpatient rehabilitation or home.

Methods: We retrospectively reviewed a cohort of patients with acute stroke admitted to the stroke service over a 3-year period. All patients 18 years or older with confirmed ischemic or hemorrhagic stroke, an NIHSS greater than or equal to 5 and documentation of fatigue/lethargy in clinical documentation were included. We compared patients that were treated with modafinil 50-200 mg to those managed with standard care. The primary outcome measure was discharge disposition. Secondary outcome was 90 day modified Rankin score (mRS). Statistical significance was determined using chi-square test for association and logistic regression models. Logistic regression models were derived in 2 ways with both raw data and an adjusted model that accounted for age, sex, and NIHSS score to account for the lack of randomization.

Results: This study included 199 stroke patients (145 ischemic, 54 hemorrhagic). Seventy-two (36.2%) were treated with modafinil and 129 (64.8%) were discharged to acute inpatient rehabilitation, while none were recommended for discharge home. Median NIHSS for modafinil patients was 13.5 versus 11 for standard care patients (P = .059). In adjusted models, modafinil was associated with higher odds of favorable discharge disposition (OR 2.00, 95% CI 1.01-3.95). Favorable outcome at 90 days defined as mRS less than or equal to 2 occurred more frequently with modafinil (5.6% versus 3.3%) but this did not achieve statistical significance (P > .1). These results occurred despite the modafinil group requiring longer ICU stays and having more in-hospital complications such as infections and need for percutaneous gastrostomy tubes. The benefit of modafinil was seen across all subgroups except those with severe stroke (NIHSS ≥ 15). There were no significant adverse events associated with modafinil administration.

Conclusions: Modafinil use in acute in-hospital stroke patients with moderate stroke complicated by lethargy and fatigue was associated with improved discharge disposition. Randomized controlled trials are needed to further study the safety, efficacy, and long-term effects of modafinil in this patient population.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104645DOI Listing
April 2020

Management of Elevated Intracranial Pressure: a Review.

Curr Neurol Neurosci Rep 2019 11 26;19(12):99. Epub 2019 Nov 26.

Department of Neurology, NYU Langone, 222 East 41st Street, 9th Floor, New York, NY, 10017, USA.

Purpose Of Review: Principles of intracranial pressure (ICP) management continue to be an essential part of the neurointensivist's skillset as appropriate treatment decisions can prevent secondary injury to the central nervous system. This review of the literature aims to: discuss commonly encountered pathologies associated with increased ICP, summarize diagnostic approaches used in evaluating ICP, and present evidence-based treatment paradigms that drive clinical care in intensive care units.

Recent Findings: Recent topics of discussion include invasive and non-invasive modalities of diagnosis and monitoring, recent developments in hypothermia, hyperosmolar therapy, pharmacological interventions, and surgical therapies. The authors also present an example of an algorithm used within our system of hospitals for managing patients with elevated ICP. Recent advances have shown the mortality benefits in appropriately recognizing and treating increased ICP. Multiple modalities of treatment have been explored, and evidence has shown benefit in some. Further work continues to provide clarity in the appropriate management of intracranial hypertension.
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http://dx.doi.org/10.1007/s11910-019-1010-3DOI Listing
November 2019

Teaching NeuroImages: Hippocampal sclerosis in cerebral malaria.

Neurology 2019 07;93(1):e112-e113

From the Departments of Neurology (K.L., D.B., A. Lord, B.C., A. Lewis, A.K.) and Neurosurgery (A. Lord, B.C., A. Lewis), NYU Langone Medical Center, New York.

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http://dx.doi.org/10.1212/WNL.0000000000007725DOI Listing
July 2019

Characteristics of graduating US allopathic medical students pursuing a career in neurology.

Neurology 2019 04 29;92(17):e2051-e2063. Epub 2019 Mar 29.

From the Department of Neurology (L.G.), University of Iowa, Iowa City; Member Insights Department (C.C.), American Academy of Neurology, Minneapolis, MN; Department of Neurology (J.T.J.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (C.E.G.), Johns Hopkins University, Baltimore, MD; Department of Neurology (V.S.), Stanford University, CA; Department of Neurology (I.A.), University of Toledo, OH; Department of Neurological Sciences (M.S.), Rush University Medical Center, Chicago, IL; Department of Pediatrics & Psychiatry (R.B.W.), UCLA, Los Angeles, CA; Department of Pediatrics (R.S.), UT Southwestern, Dallas, TX; Department of Neurology (B.M.C.), New York University, New York; and Department of Neurology (A.G.S.), Virginia Commonwealth University, Richmond.

Objectives: To identify factors associated with medical students becoming neurologists because, despite the increasing burden of neurologic disorders, there is a growing neurologist shortage.

Methods: Deidentified data from the Association of American Medical Colleges Matriculating Student Questionnaire (MSQ) and Graduation Questionnaire (GQ) were obtained for the graduation years 2013 to 2014 through 2016 to 2017. Logistic regression was used to assess demographic characteristics and responses to training and career-related questions in association with specialty choice (intent to enter neurology).

Results: Of the 51,816 students with complete data, 1,456 (2.8%) indicated an intent to enter a neurology residency. Factors associated with an increased likelihood of entering neurology were a student's rating of excellent for their basic neuroscience course and neurology clerkship, participation in an MD/PhD program, majoring in neuroscience or psychology as an undergraduate, a selection response of "content of the specialty was a strong influence on career choice," and indicating interest in neurology on the MSQ. Factors associated with a decreased likelihood of entering neurology were a higher-priority response on the GQ for salary, work/life balance, and personal fit of the specialty.

Conclusion: Data from surveys at the entry into and graduation from medical school suggest several approaches to increase the number of medical students entering neurology, including a focus on the student-reported quality of the basic neuroscience course and neurology clerkships, targeted engagement with MD/PhD students, and mentoring programs for students interested in neurology. Efforts to improve salaries for neurologists, to reduce medical school debt, and to improve work/life balance may also help to attract more students.
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http://dx.doi.org/10.1212/WNL.0000000000007369DOI Listing
April 2019

How Does Preexisting Hypertension Affect Patients with Intracerebral Hemorrhage?

J Stroke Cerebrovasc Dis 2019 Mar 13;28(3):782-788. Epub 2018 Dec 13.

Department of Neurology, New York University School of Medicine, New York, New York; Department of Neurosurgery, New York University School of Medicine, New York, New York.

Background And Purpose: Patients with intracerebral hemorrhage (ICH) frequently present with hypertension, but it is unclear if this is due to pre-existing hypertension (prHTN) or to the bleed itself or associated pain. We sought to assess the relationship between prHTN and admission systolic blood pressure (aBP) and bleed severity.

Methods: We retrospectively assessed the relationship between prHTN and aBP and NIHSS in patients with ICH at 3 institutions.

Results: Of 251 patients, 170 (68%) had prHTN based on history of hypertension/antihypertensive use. Median aBP was significantly higher in those with prHTN (155 mm Hg (IQR 135-181) versus 139 mm Hg (IQR 124-158), P < .001). Patients with left ventricular hypertrophy (LVH) on electrocardiogram (ECG) or transthoracic echocardiogram (TTE) had significantly higher aBP than those without LVH (median aBP 195 mm Hg (IQR 155-216) for patients with LVH on ECG versus 147 mm Hg (IQR 129-163) for patients with no LVH on ECG, P < .001; median aBP 181 mm Hg (IQR 153-214) for patients with LVH on TTE versus 152 mm Hg (IQR 137-169) for patients with no LVH on TTE, P = .01). prHTN was associated with a higher median NIHSS (11 (IQR 3-20) for patients with history of hypertension/antihypertensive use versus 6 (IQR 1-14) for patients without this history (P = .02); 9 (IQR 3-19) versus 5 (IQR 2-13) for patients with/without LVH on ECG (P = .085); and 10 (IQR 5-18) versus 5 (IQR 1-13) for patients with/without LVH on TTE (P = .046).

Conclusions: Patients with ICH who have prHTN have higher aBP and NIHSS, suggesting that prHTN may worsen reactive hypertension in the setting of ICH.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.11.023DOI Listing
March 2019

Simulation in Neurocritical Care: Past, Present, and Future.

Neurocrit Care 2019 06;30(3):522-533

Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Simulation-based medical education is a technique that leverages adult learning theory to train healthcare professionals by recreating real-world scenarios in an interactive way. It allows learners to emotionally engage in the assessment and management of critically ill patients without putting patients at risk. Learners are encouraged to work at the edge of their expertise to promote growth and are provided with feedback to nurture development. Thus, the training is targeted to the learner, not the patient. Despite its origins as a teaching tool for neurological diseases, simulation-based medical education has been historically abandoned by neurocritical care educators. In contrast, other critical care educators have embraced the technique and built an impressive foundation of literature supporting its use. Slowly, neurocritical care educators have started experimenting with simulation-based medical education and sharing their results. In this review, we will investigate the historical origins of simulation in the neurosciences, the conceptual framework supporting the technique, current applications, and future directions.
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http://dx.doi.org/10.1007/s12028-018-0629-2DOI Listing
June 2019

Highest In-Hospital Glucose Measurements are Associated With Neurological Outcomes After Intracerebral Hemorrhage.

J Stroke Cerebrovasc Dis 2018 Oct 22;27(10):2662-2668. Epub 2018 Jul 22.

Department of Neurology, New York University School of Medicine, New York, New York; Department of Neurosurgery, New York University School of Medicine, New York, New York. Electronic address:

Background And Purpose: The relationship between in-hospital hyperglycemia and neurological outcome after intracerebral hemorrhage (ICH) is not well studied.

Methods: We analyzed the relationships between pre-hospital and hospital variables including highest in-hospital glucose (HIHGLC) and discharge Glasgow Coma Scale (GCS), discharge Modified Rankin Scale (MRS) and 3-month MRS using a single-institution cohort of ICH patients between 2013 and 2015.

Results: There were 106 patients in our sample. Mean HIHGLC was 154 ± 58 mg/dL for patients with discharge GCS of 15 and 180 ± 57 mg/dL for patients with GCS < 15; 146 ± 55 mg/dL for patients with discharge MRS 0-3 and 175 ± 58 mg/dL for patients with discharge MRS 4-6; and 149 ± 52 mg/dL for patients with 3-month MRS of 0-3 and 166 ± 61 mg/dL for patients with 3-month MRS of 4-6. On univariate analysis, discharge GCS was associated with HIHGLC (P = .01), age (P = .006), ICH volume (P = .008), and length of stay (LOS) (P = .01); discharge MRS was associated with HIHGLC (P < .001), age (P < .001), premorbid MRS (P = .046), ICH volume (P < .001), and LOS (P < .001); and 3-month MRS was associated with HIHGLC (P = .006), discharge MRS (P < .001), age (P = .001), sex (P = .002), ICH volume (P = .03), and length of stay (P = .004). On multivariate analysis, discharge GCS only had a significant relationship with ICH volume (odds ratio [OR] .949, .927-.971); discharge MRS had a significant relationship with age (OR 1.043, 1.009-1.079), premorbid MRS (OR 2.622, 1.144-6.011), and ICH volume (OR 1.047, 1.003-1.093); and 3-month MRS only had a significant relationship with age (OR 1.039, 1.010-1.069).

Conclusions: The relationship between in-hospital hyperglycemia and neurological outcomes in ICH patients was meaningful on univariate, but not multivariate, analysis. Glucose control after ICH is important.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.030DOI Listing
October 2018

A Novel Clinical Score to Assess Seizure Risk.

JAMA Neurol 2017 12;74(12):1395-1396

Columbia University College of Physicians and Surgeons, New York, New York.

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http://dx.doi.org/10.1001/jamaneurol.2017.1922DOI Listing
December 2017

Variations in Strategies to Prevent Ventriculostomy-Related Infections: A Practice Survey.

Neurohospitalist 2017 Jan 11;7(1):15-23. Epub 2016 Aug 11.

Division of Neurocritical Care, Department of Neurology, NYU Langone Medical Center, NY, USA; Department of Neurosurgery, NYU Langone Medical Center, NY, USA.

Background And Purpose: The ideal strategy to prevent infections in patients with external ventricular drains (EVDs) is unclear.

Methods: We conducted a cross-sectional survey of members of the Neurocritical Care Society on infection prevention practices for patients with EVDs between April and July 2015.

Results: The survey was completed by 52 individuals (5% response rate). Catheter selection, use of prolonged prophylactic systemic antibiotics (PPSAs), cerebrospinal fluid (CSF) collection policies, location of EVD placement, and performance of routine EVD exchanges varied. Antibiotic-impregnated catheters (AICs) and conventional catheters (CCs) were used with similar frequency, but no respondents reported routine use of silver-impregnated catheters (SICs). The majority of respondents were either neutral or disagreed with the need for PPSA with all catheter types (CC: 75%, AIC: 85%, and SIC: 87%). Despite this, 55% of the respondents reported PPSAs were routinely administered to patients with EVDs at their institutions. The majority (80%) of the respondents reported CSF collection only on an as-needed basis. The EVD placement was restricted to the operating room at 27% of the respondents' institutions. Only 2 respondents (4%) reported that routine EVD exchanges were performed at their institution.

Conclusion: Practice patterns demonstrate that institutions use varying strategies to prevent ventriculostomy-related infections. Identification and further study of optimum care for these patients are essential to decrease the risk of complications and to aid development of practice standards.
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http://dx.doi.org/10.1177/1941874416663281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167094PMC
January 2017

Prolonged prophylactic antibiotics with neurosurgical drains and devices: Are we using them? Do we need them?

Am J Infect Control 2016 12 6;44(12):1757-1758. Epub 2016 Oct 6.

Departments of Neurology and Neurosurgery, Division of Neurocritical Care NYU Langone Medical Center, New York, NY.

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http://dx.doi.org/10.1016/j.ajic.2016.06.039DOI Listing
December 2016

Public education and misinformation on brain death in mainstream media.

Clin Transplant 2016 09 25;30(9):1082-9. Epub 2016 Jul 25.

Division of Medical Ethics, Department of Population Health, NYU Langone Medical Center, New York, NY, USA.

Introduction: We sought to evaluate the caliber of education mainstream media provides the public about brain death.

Methods: We reviewed articles published prior to July 31, 2015, on the most shared/heavily trafficked mainstream media websites of 2014 using the names of patients from two highly publicized brain death cases, "Jahi McMath" and "Marlise Muñoz."

Results: We reviewed 208 unique articles. The subject was referred to as being "alive" or on "life support" in 72% (149) of the articles, 97% (144) of which also described the subject as being brain dead. A definition of brain death was provided in 4% (9) of the articles. Only 7% (14) of the articles noted that organ support should be discontinued after brain death declaration unless a family has agreed to organ donation. Reference was made to well-known cases of patients in persistent vegetative states in 16% (34) of articles and 47% (16) of these implied both patients were in the same clinical state.

Conclusions: Mainstream media provides poor education to the public on brain death. Because public understanding of brain death impacts organ and tissue donation, it is important for physicians, organ procurement organizations, and transplant coordinators to improve public education on this topic.
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http://dx.doi.org/10.1111/ctr.12791DOI Listing
September 2016

Majority of 30-Day Readmissions After Intracerebral Hemorrhage Are Related to Infections.

Stroke 2016 07 14;47(7):1768-71. Epub 2016 Jun 14.

From the Department of Neurology, New York University School of Medicine (A.S.L., A.L., B.C., K.I., J.T., B.B.-A.); Department of Neurology, Weill Cornell Medical College, New York, NY (H.K.); Department of Neurology and Rehabilitation, University of Cincinnati College of Medicine, OH (D.W.); Departments of Neurology and Epidemiology, Columbia University, New York, NY (M.S.V.E.); and Division of Epidemiology, College of Global Public Health, New York University (B.B.-A.).

Background And Purpose: Infections are common after intracerebral hemorrhage, but little is known about the risk of serious infection requiring readmission after hospital discharge.

Methods: To determine if infections are prevalent in patients readmitted within 30 days of discharge, we performed a retrospective cohort study of patients discharged from nonfederal acute care hospitals in California with a primary diagnosis of intracerebral hemorrhage between 2006 and 2010. We excluded patients who died during the index admission, were discharged against medical advice, or were not California residents. Our main outcome was 30-day unplanned readmission with primary infection-related International Classification of Diseases, Ninth Revision, Clinical Modification code.

Results: There were 24 540 index intracerebral hemorrhage visits from 2006 to 2010. Unplanned readmissions occurred in 14.5% (n=3550) of index patients. Of 3550 readmissions, 777 (22%) had an infection-related primary diagnosis code. When evaluating primary and all secondary diagnosis codes, infection was associated with 1826 (51%) of readmissions. Other common diagnoses associated with readmission included stroke-related codes (n=840, 23.7%) and aspiration pneumonitis (n=154, 4.3%). The most common infection-related primary diagnosis codes were septicemia (n=420, 11.8%), pneumonia (n=124, 3.5%), urinary tract infection (n=141, 4.0%), and gastrointestinal infection (n=42, 1.2%). Patients with a primary infection-related International Classification of Diseases, Ninth Revision, Clinical Modification code on readmission had higher in-hospital mortality compared with other types of readmission (15.6% versus 8.0%, P<0.001). After controlling for other predictors of mortality, primary infection-related readmissions remained associated with in-hospital mortality (relative risk, 1.7; 95% confidence interval, 1.3-2.2).

Conclusions: Infections are associated with a majority of 30-day readmissions after intracerebral hemorrhage and increased mortality. Efforts should be made to reduce infection-related complications after hospital discharge.
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http://dx.doi.org/10.1161/STROKEAHA.116.013229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927367PMC
July 2016

Predicting Large Vessel Occlusion in Acute Ischemic Stroke: Less is More.

Crit Care Med 2016 06;44(6):1251-2

Departments of Neurology and Neurosurgery, NYU Langone Medical Center (BMC); and Departments of Neurology and Neurosurgery, Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai (SAM), New York, NY.

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http://dx.doi.org/10.1097/CCM.0000000000001791DOI Listing
June 2016

Establishment of an External Ventricular Drain Best Practice Guideline: The Quest for a Comprehensive, Universal Standard for External Ventricular Drain Care.

J Neurosci Nurs 2016 Feb;48(1):54-65

Questions or comments about this article may be directed to Millie Hepburn-Smith, RN MSN MPhil SCRN ACNS-BC, at She is a Neuroscience, Rehabilitation and Inpatient Psychiatry Nurse Educator, NYU Langone Medical Center, New York, NY. Irina Dynkevich, RN MSN CNRN, is a Staff RN, Department of Neurosciences, NYU Langone Medical Center, New York, NY. Marina Spektor, RN CNRN CSRN, is a Staff RN, Department of Neurosciences, NYU Langone Medical Center, New York, NY. Aaron Lord, MD, is Assistant Professor, Division of Neurocritical Care, Department of Neurology, NYU Langone Medical Center, New York, NY. Barry Czeisler, MD MS, is Assistant Professor, Division of Neurocritical Care, Department of Neurology, NYU Langone Medical Center, New York, NY. Ariane Lewis, MD, is Assistant Professor, Division of Neurocritical Care, Department of Neurology, NYU Langone Medical Center, New York, NY.

External ventricular drains (EVDs) are commonly used to facilitate removal of cerebrospinal fluid in patients with neurologic dysfunction. Despite a high risk for infection (upward of 45%), many hospitals lack strict protocols for EVD placement and maintenance. In addition, EVD infections are typically not tracked with the same diligence as central-line catheter infections, because there are no widely accepted standards for routine management of EVDs. The purpose of this review is to provide a guide for the development of a standardized, best practice EVD protocol for catheter insertion, care, and maintenance to reduce ventriculostomy-related infections. A secondary goal of this review is to provide support for the future development of guidelines for the consistent tracking of EVD insertion and maintenance practices.At an academic medical center, an interdisciplinary team of nurses, advanced practice nurses, and neurointensivists reviewed recent medical and nursing literature as well as research-based institutional protocols on EVD insertion and maintenance from the United States and abroad to determine global best practices. The goal of this literature review was to identify key areas of focus in EVD insertion and maintenance as well as to identify recent studies that have shown success in managing EVDs with low rates of infection. The following terms were used in this search: EVD, externalized ventricular drains, EVD infections, EVD insertion, EVD Care and Maintenance, Nursing and EVDS. The following databases were utilized by each member of the interdisciplinary team to establish a state of the science on EVD management: American Association of Neurosurgical Surgeons, CINAHL, Cochrane, National Guidelines Clearinghouse, and PubMed. The following common EVD themes were identified: preinsertion hair removal and skin preparation, aseptic technique, catheter selection, monitoring of EVD insertion technique using a "bundle" approach, postinsertion dressing type and frequency of dressing changes, techniques for maintenance and cerebrospinal fluid sampling, duration of catheter placement, staff education/competence, and surveillance.
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http://dx.doi.org/10.1097/JNN.0000000000000174DOI Listing
February 2016

Ventriculostomy-related infections: The performance of different definitions for diagnosing infection.

Br J Neurosurg 2016 15;30(1):49-56. Epub 2015 Sep 15.

a Division of Neurocritical Care, Department of Neurology , NYU Langone Medical Center , New York , NY , USA.

Introduction: Comparison of rates of ventriculostomy-related infections (VRIs) across institutions is difficult due to the lack of a standard definition. We sought to review published definitions of VRI and apply them to a test cohort to determine the degree of variability in VRI diagnosis.

Materials And Methods: We conducted a PubMed search for definitions of VRI using the search strings "ventriculostomy-related infection" and "ventriculostomy-associated infection." We applied these definitions to a test cohort of 18 positive cerebrospinal fluid (CSF) cultures taken from ventriculostomies at two institutions to compare the frequency of infection using each definition.

Results: We found 16 unique definitions of VRI. When the definitions were applied to the test cohort, the frequency of infection ranged from 22 to 94% (median 61% with interquartile range (IQR) 56-74%). The concordance between VRI diagnosis and treatment with VRI-directed antibiotics for at least seven days ranged from 56 to 89% (median: 72%, IQR: 71-78%).

Conclusions: The myriad of definitions in the literature produce widely different frequencies of infection. In order to compare rates of VRI between institutions for the purposes of qualitative metrics and research, a consistent definition of VRI is needed.
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http://dx.doi.org/10.3109/02688697.2015.1080222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870889PMC
January 2017

Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study.

Crit Care 2014 May 21;18(3):R103. Epub 2014 May 21.

Introduction: Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE.

Methods: We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year.

Results: Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5) severely disabled, and 10% (N = 3) had no or minimal disability. Death or unresponsive wakefulness was associated with catastrophic etiology (p = 0.03), but none of the other collected variables.

Conclusions: cIV-PTB effectively aborts SRSE and complications are infrequent; outcome in this highly refractory cohort of patients with devastating underlying etiologies remains poor. Phenobarbital may be particularly helpful when weaning cIV-PTB.
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http://dx.doi.org/10.1186/cc13883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095579PMC
May 2014

Reading and writing the blood-brain barrier: relevance to therapeutics.

Recent Pat CNS Drug Discov 2006 Jun;1(2):157-73

Case Western Reserve University School of Medicine, Cleveland, OH, USA.

The blood-brain barrier (BBB) serves to protect the central nervous system (CNS) from damage by exogenous molecules. In doing so, it also can prevent some drugs from reaching their sites of action. Accordingly, a variety of methods for bypassing the BBB have been developed. Ekwuribe et al. recently patented a method for drug conjugation in order to increase lipophilicity, and therefore BBB permeability. Shalev developed a device for opening the barrier via parasympathetic nerve fiber stimulation and Gudkov et al. produced compounds that modulate the activity of multidrug transporter proteins, by either increasing or decreasing the selective permeability of the BBB. A variety of CNS disorders contribute to barrier disruption, and detection of this opening can be used for both diagnostic purposes and for determining time periods when drugs can more easily enter the CNS. While expensive and time-consuming imaging techniques are currently used for this purpose, Janigro et al. have devised a method for detecting plasma levels of S100beta, a peripheral protein marker for BBB disruption. These techniques for both "reading" and "writing" the BBB will help new and old medications to reach their pharmacological targets in the CNS.
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http://dx.doi.org/10.2174/157488906777452712DOI Listing
June 2006

Neuroprotective effects of olanzapine in a rat model of neurodevelopmental injury.

Pharmacol Biochem Behav 2006 Feb 9;83(2):208-13. Epub 2006 Mar 9.

Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Recent clinical studies have suggested that treatment with atypical antipsychotic drugs, such as olanzapine, may slow progressive changes in brain structure in patients with schizophrenia. To investigate the possible neural basis of this effect, we sought to determine whether treatment with olanzapine would inhibit the loss of hippocampal neurons associated with the administration of the excitotoxin, kainic acid, in neonatal rats. At post-natal day 7 (P7), rats were exposed to kainic acid via intracerebroventricular administration. Neuronal loss within the CA2 and CA3 subfields of the hippocampus and neurogenesis within the dentate gyrus of the hippocampus were then assessed at P14 by Fluoro-Jade B and BrdU labeling, respectively. Daily doses of olanzapine (2, 6, or 12 mg/day), haloperidol (1.2 mg/kg), melatonin (10 mg/kg), or saline were administered between P7 and P14. Melatonin is an anti-oxidant drug and was included in this study as a positive control, since it has been observed to have neuroprotective effects in a variety of animal models. The highest dose of olanzapine and melatonin, but not haloperidol, ameliorated the hippocampal neuronal loss triggered by kainic acid administration. However, drug administration did not have a significant effect on the rate of neurogenesis. These results suggest that olanzapine has neuroprotective effects in a rat model of neurodevelopmental insult, and may be relevant to the observed effects of atypical antipsychotic drugs on brain structure in patients with schizophrenia.
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http://dx.doi.org/10.1016/j.pbb.2006.01.009DOI Listing
February 2006