Publications by authors named "Nicholas A Morris"

45 Publications

Andexanet Alfa for Factor Xa Inhibitor-Associated Intracerebral Hemorrhage: Does a Specific Reversal Agent Justify Its Cost?

Neurology 2021 Sep 23. Epub 2021 Sep 23.

Department of Neurology, Program in Trauma, University of Maryland School of Medicine, Baltimore, MD USA.

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http://dx.doi.org/10.1212/WNL.0000000000012857DOI Listing
September 2021

Seven-Year Follow-Up of an Online Critical Care Curriculum.

ATS Sch 2021 Jun 24;2(2):224-235. Epub 2021 Feb 24.

Division of Pulmonary and Critical Care Medicine, Department of Medicine.

In July of 2013, the University of Maryland launched MarylandCCProject.com. This free-access educational website delivers asynchronous high-quality multidisciplinary critical care education targeted at critical care trainees. The lectures, presented in real time on-site, are recorded and available on the website or as a podcast on iTunes or Android. Thus, the curriculum can be easily accessed around the world.

We sought to identify the impact this website has on current and former University of Maryland critical care trainees.

A 32-question survey was generated using a standard survey generation tool. The survey was e-mailed in the fall of 2019 to the University of Maryland Multi-Departmental Critical Care current and graduated trainees from the prior 7 years. Survey data were collected through December 2019. The questions focused on user demographics, overall experience with the website, scope of website use, and clinical application of the content. Anonymous responses were electronically gathered.

A total of 186 current trainees and graduates were surveyed, with a 39% ( = 72) response rate. Of responders, 76% (55) use the website for ongoing medical education. The majority use the website at least monthly. Most users (63%,  = 35) access the lectures directly through the website. All 55 current users agree that the website has improved their medical knowledge and is a useful education resource. Platform use has increased and includes users from around the world.

Based on our current data, the MarylandCCProject remains a valuable and highly used educational resource, impacting patient care both during and after critical care fellowship training.
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http://dx.doi.org/10.34197/ats-scholar.2020-0114OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362725PMC
June 2021

Verticalization for Refractory Intracranial Hypertension: A Case Series.

Neurocrit Care 2021 Aug 17. Epub 2021 Aug 17.

Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Background: Severe intracranial hypertension is strongly associated with mortality. Guidelines recommend medical management involving sedation, hyperosmotic agents, barbiturates, hypothermia, and surgical intervention. When these interventions are maximized or are contraindicated, refractory intracranial hypertension poses risk for herniation and death. We describe a novel intervention of verticalization for treating intracranial hypertension refractory to aggressive medical treatment.

Methods: This study was a single-center retrospective review of six cases of refractory intracranial hypertension in a tertiary care center. All patients were treated with a standard-of-care algorithm for lowering intracranial pressure (ICP) yet maintained an ICP greater than 20 mmHg. They were then treated with verticalization for at least 24 h. We compared the median ICP, the number of ICP spikes greater than 20 mmHg, and the percentage of ICP values greater than 20 mmHg in the 24 h before verticalization vs. after verticalization. We assessed the use of hyperosmotic therapies and any changes in the mean arterial pressure and cerebral perfusion pressure related with the intervention.

Results: Five patients were admitted with subarachnoid hemorrhage and one with intracerebral hemorrhage. All patients had ICP monitoring by external ventricular drain. The median opening pressure was 30 mmHg (25th-75th interquartile range 22.5-30 mmHg). All patients demonstrated a reduction in ICP after verticalization, with a significant decrease in the median ICP (12 vs. 8 mmHg; p < 0.001), the number of ICP spikes (12 vs. 2; p < 0.01), and the percentage of ICP values greater than 20 mmHg (50% vs. 8.3%; p < 0.01). There was a decrease in total medical interventions after verticalization (79 vs. 41; p = 0.05) and a lower total therapy intensity level score after verticalization. The most common adverse effects included asymptomatic bradycardia (n = 3) and pressure wounds (n = 4).

Conclusions: Verticalization is an effective noninvasive intervention for lowering ICP in intracranial hypertension that is refractory to aggressive standard management and warrants further study.
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http://dx.doi.org/10.1007/s12028-021-01323-zDOI Listing
August 2021

Pain Trajectories Following Subarachnoid Hemorrhage are Associated with Continued Opioid Use at Outpatient Follow-up.

Neurocrit Care 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurology, School of Medicine, University of Maryland, Baltimore, MD, USA.

Background: Subarachnoid hemorrhage (SAH) is characterized by the worst headache of life and associated with long-term opioid use. Discrete pain trajectories predict chronic opioid use following other etiologies of acute pain, but it is unknown whether they exist following SAH. If discrete pain trajectories following SAH exist, it is uncertain whether they predict long-term opioid use. We sought to characterize pain trajectories after SAH and determine whether they are associated with persistent opioid use.

Methods: We reviewed pain scores from patients admitted to a single tertiary care center for SAH from November 2015 to September 2019. Group-based trajectory modeling identified discrete pain trajectories during hospitalization. We compared outcomes across trajectory groups using χ and Kruskal-Wallis tests. Multivariable regression determined whether trajectory group membership was an independent predictor of long-term opioid use, defined as continued use at outpatient follow-up.

Results: We identified five discrete pain trajectories among 305 patients. Group 1 remained pain free. Group 2 reported low scores with intermittent spikes and slight increase over time. Group 3 noted increasing pain severity through day 7 with mild improvement until day 14. Group 4 experienced maximum pain with steady decrement over time. Group 5 reported moderate pain with subtle improvement. In multivariable analysis, trajectory groups 3 (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5-8.3) and 5 (OR 8.0; 95% CI 3.1-21.1), history of depression (OR 3.6; 95% CI 1.3-10.0) and racial/ethnic minority (OR 2.3; 95% CI 1.3-4.1) were associated with continued opioid use at follow-up (median 62 days following admission, interquartile range 48-96).

Conclusions: Discrete pain trajectories following SAH exist. Recognition of pain trajectories may help identify those at risk for long-term opioid use.
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http://dx.doi.org/10.1007/s12028-021-01282-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189709PMC
June 2021

"Broken-hearted" carbon bowl electron shuttle reaction: energetics and electron coupling.

Chem Sci 2021 Apr 8;12(19):6600-6606. Epub 2021 Apr 8.

Department of Chemistry and Biochemistry, University of South Carolina Columbia South Carolina 29208 USA

Unprecedented one-step C[double bond, length as m-dash]C bond cleavage leading to opening of the buckybowl (π-bowl), that could provide access to carbon-rich structures with previously inaccessible topologies, is reported; highlighting the possibility to implement drastically different synthetic routes to π-bowls in contrast to conventional ones applied for polycyclic aromatic hydrocarbons. Through theoretical modeling, we evaluated the mechanistic pathways feasible for π-bowl planarization and factors that could affect such a transformation including strain and released energies. Through employment of Marcus theory, optical spectroscopy, and crystallographic analysis, we estimated the possibility of charge transfer and electron coupling between "open" corannulene and a strong electron acceptor such as 7,7,8,8-tetracyanoquinodimethane. Alternative to a one-pot solid-state corannulene "unzipping" route, we reported a nine-step solution-based approach for preparation of novel planar "open" corannulene-based derivatives in which electronic structures and photophysical profiles were estimated through the energies and isosurfaces of the frontier natural transition orbitals.
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http://dx.doi.org/10.1039/d0sc06755eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132954PMC
April 2021

Neurologic Outcomes After Extracorporeal Cardiopulmonary Resuscitation: Recent Experience at a Single High-Volume Center.

ASAIO J 2021 Apr 21. Epub 2021 Apr 21.

From the Section of Neurocritical Care and Emergency Neurology, Department of Neurology, Program in Trauma, University of Maryland School of Medicine, Baltimore, Maryland Division of Thoracic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland University of Maryland School of Medicine, Baltimore, Maryland Division of Surgical Critical Care, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.

Extracorporeal cardiopulmonary resuscitation (ECPR)-veno-arterial extracorporeal membrane oxygenation (ECMO) for refractory cardiac arrest-has grown rapidly, but its widespread adoption has been limited by frequent neurologic complications. With individual centers developing best practices, utilization may be increasing with an uncertain effect on outcomes. This study describes the recent ECPR experience at the University of Maryland Medical Center from 2016 through 2018, with attention to neurologic outcomes and predictors thereof. The primary outcome was dichotomized Cerebral Performance Category (≤2) at hospital discharge; secondary outcomes included rates of specific neurologic complications. From 429 ECMO runs over 3 years, 57 ECPR patients were identified, representing an increase in ECPR utilization compared with 41 cases over the previous 6 years. Fifty-two (91%) suffered in-hospital cardiac arrest, and 36 (63%) had an initial nonshockable rhythm. Median low-flow time was 31 minutes. Overall, 26 (46%) survived hospitalization and 23 (88% of survivors, 40% overall) had a favorable discharge outcome. Factors independently associated with good neurologic outcome included lower peak lactate, initial shockable rhythm, and higher initial ECMO mean arterial pressure. Neurologic complications occurred in 18 patients (32%), including brain death in 6 (11%), hypoxic-ischemic brain injury in 11 (19%), ischemic stroke in 6 (11%), intracerebral hemorrhage in 1 (2%), and seizure in 4 (7%). We conclude that good neurologic outcomes are possible for well-selected ECPR patients in a high-volume program with increasing utilization and evolving practices. Markers of adequate peri-resuscitation tissue perfusion were associated with better outcomes, suggesting their importance in neuroprognostication.
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http://dx.doi.org/10.1097/MAT.0000000000001448DOI Listing
April 2021

Association of Refractory Pain in the Acute Phase After Subarachnoid Hemorrhage With Continued Outpatient Opioid Use.

Neurology 2021 05 25;96(19):e2355-e2362. Epub 2021 Mar 25.

From the Departments of Neurology (M.N.J., J.E.P., A.K., W.-T.W.C., M.M., G.Y.P., N.B., N.A.M.), Emergency Medicine (W.-T.W.C.), Pharmacy Services (M.J.A.), Neurosurgery (J.M.S.), Pathology (J.M.S.), and Physiology (J.M.S.), and Program in Trauma, R. Adams Cowley Shock Trauma Center (M.N.J., J.E.P., W.-T.W.C., M.M., G.Y.P., N.B., N.A.M.), University of Maryland School of Medicine (M.C.S., A.F., A.K.), Baltimore; and Department of Neurology, Division of Neurocritical Care and Emergency Neurology (K.N.S.), Yale School of Medicine, New Haven, CT.

Objective: Little is known about the prevalence of continued opioid use following aneurysmal subarachnoid hemorrhage (aSAH) despite guidelines recommending their use during the acute phase of disease. We sought to determine prevalence of opioid use following aSAH and test the hypothesis that acute pain and higher inpatient opioid dose increased outpatient opioid use.

Methods: We reviewed consecutively admitted patients with aSAH from November 2015 through September 2019. We retrospectively collected pain scores and daily doses of analgesics. Pain burden was calculated as area under the pain-time curve. Univariate and multivariable regression models determined risk factors for continued opioid use at discharge and outpatient follow-up.

Results: We identified 234 patients with aSAH with outpatient follow-up. Continued opioid use was common at discharge (55% of patients) and follow-up (47% of patients, median 63 [interquartile range 49-96] days from admission). Pain burden, craniotomy, and racial or ethnic minority status were associated with discharge opioid prescription in multivariable analysis. At outpatient follow-up, pain burden (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.5-2.4), depression (OR 3.1, 95% CI 1.1-8.8), and racial or ethnic minority status (OR 2.1, 95% CI 1.1-4.0) were independently associated with continued opioid use; inpatient opioid dose was not.

Conclusion: Continued opioid use following aSAH is prevalent and related to refractory pain during acute illness, but not inpatient opioid dose. More efficacious analgesic strategies are needed to reduce continued opioid use in patients following aSAH.

Classification Of Evidence: This study provides Class II evidence that continued opioid use following aSAH is associated with refractory pain during acute illness but not hospital opioid exposure.
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http://dx.doi.org/10.1212/WNL.0000000000011906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166442PMC
May 2021

Triage of Patients with Intracerebral Hemorrhage to Comprehensive Versus Primary Stroke Centers.

J Stroke Cerebrovasc Dis 2021 May 14;30(5):105672. Epub 2021 Mar 14.

Department of Neurology, Program in Trauma, University of Maryland School of Medicine, Baltimore, MD USA.

Objectives: The management of patients admitted with intracerebral hemorrhage (ICH) mostly occurs in an ICU. While guidelines recommend initial treatment of these patients in a neurocritical care or stroke unit, there is limited data on which patients would benefit most from transfer to a comprehensive stroke center where on-site neurosurgical coverage is available 24/7. As neurocritical units become more common in primary stroke centers, it is important to determine which patients are most likely to require neurosurgical intervention and transfer to comprehensive stroke centers.

Materials And Methods: This is a retrospective observational cohort study conducted at an academic comprehensive stroke center in the United States. Four-hundred-fifty-nine consecutive patients transferred or directly admitted to the neurocritical care unit from 2016-2018 with the primary diagnosis of ICH were included. Univariate statistics and multivariate regression were used to identify clinical characteristics associated with neurosurgical intervention, defined as undergoing craniotomy, ventriculostomy, or endovascular embolization of an arteriovenous malformation (AVM).

Results: The following variables were associated with neurosurgical intervention in multivariate analysis: age (OR 0.38, 95% CI 0.27-0.55), admission Glasgow Coma Scale (OR 0.29, 95% CI 0.18-0.48), the presence of intraventricular hemorrhage (OR 2.82, CI 1.71-4.65), infratentorial location of ICH (OR 2.28, 95% CI 1.20-4.31), previous antiplatelet use (OR 2.04, 95% CI 1.24-3.34), and an AVM indicated on CT Angiogram (OR 2.59, 95% CI 1.19-5.63) were independently associated with the need for neurosurgical intervention. This was translated into a scoring system to help make quick triage decisions, with high sensitivity (99%, 95% CI 97-99%) and negative predictive value (98%, 95% CI 89-99%).

Conclusions: Using previously well described predictors of severity in ICH patients, we were able to develop a scoring system to predict the need for neurosurgical intervention with high sensitivity and negative predictive value.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105672DOI Listing
May 2021

A Severe Course of Relapsing-Remitting Acute-Onset Chronic Inflammatory Demyelinating Polyneuropathy in a Young Man.

Case Rep Neurol 2021 Jan-Apr;13(1):73-77. Epub 2021 Feb 4.

Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is an immune mediated neuropathy characterized by progressive weakness and sensory impairment lasting over 2 months. Guillain-Barré-Strohl syndrome (GBS) is an immune mediated polyneuropathy with a similar presentation often over less than 4 weeks. While some have argued for the existence of recurrent GBS, most classify the syndrome as a form of relapsing-remitting CIDP. However, there are cases of GBS with treatment-related fluctuations that must be distinguished from A-CIDP as patients with A-CIDP require long-term immunotherapy. In this case report, we discuss a patient with multiple relapses over 3 years, who is more likely to have A-CIDP. His ganglioside profile, which has rarely been reported in A-CIDP, included high concentrations of anti-GM1, anti-GD1a, and anti-GD1b antibodies, which may account for his severe disease course.
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http://dx.doi.org/10.1159/000511956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923717PMC
February 2021

Teleneurology for Determination of Death by Neurologic Criteria: Adapting to the Times.

Neurology 2021 04 26;96(15):691-692. Epub 2021 Feb 26.

From the Department of Neurology (B.B.L., N.A.M.), Program in Trauma, University of Maryland School of Medicine, Baltimore; and Department of Neurology (J.C.M.B.), Columbia University College of Physicians and Surgeons, New York Neurological Institute, NY.

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http://dx.doi.org/10.1212/WNL.0000000000011740DOI Listing
April 2021

Intraoperative hypotension and perioperative acute ischemic stroke in patients having major elective non-cardiovascular non-neurological surgery.

J Anesth 2021 04 9;35(2):246-253. Epub 2021 Feb 9.

Department of Anesthesiology, University of Maryland School of Medicine, 22 South Greene Street, S11C00, Baltimore, MD, 21201, USA.

Purpose: The association between intraoperative hypotension and perioperative acute ischemic stroke is not well described. We hypothesized that intraoperative hypotension would be associated with perioperative acute ischemic stroke.

Methods: Four-year retrospective cohort study of elective non-cardiovascular, non-neurological surgical patients. Characteristics of patients who had perioperative acute ischemic stroke were compared against those of patients who did not have acute ischemic stroke. Multivariable logistic regression was used to determine whether hypotension was independently associated with increased odds of perioperative acute ischemic stroke.

Results: Thirty-four of 9816 patients (0.3%) who met study inclusion criteria had perioperative acute ischemic stroke. Stroke patients were older and had more comorbidities including hypertension, coronary artery disease, diabetes mellitus, active tobacco use, chronic obstructive pulmonary disease, cerebral vascular disease, atrial fibrillation, and peripheral vascular disease (all P < 0.05). MAP < 65 mmHg was not associated with increased odds of acute ischemic stroke when modeled as a continuous or categorical variable. MAP < 60 mmHg for more than 20 min was independently associated with increased odds of acute ischemic stroke, OR = 2.67 [95% CI = 1.21 to 5.88, P = 0.02].

Conclusion: Our analysis suggests that when MAP is less than 60 mmHg for more than 20 min, there is increased odds of acute ischemic stroke. Further studies are needed to determine what MAP should be targeted during surgery to optimize cerebral perfusion and limit ischemic stroke risk.
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http://dx.doi.org/10.1007/s00540-021-02901-3DOI Listing
April 2021

Development of Neurological Emergency Simulations for Assessment: Content Evidence and Response Process.

Neurocrit Care 2021 Jan 21. Epub 2021 Jan 21.

Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.

Objective: To document two sources of validity evidence for simulation-based assessment in neurological emergencies.

Background: A critical aspect of education is development of evaluation techniques that assess learner's performance in settings that reflect actual clinical practice. Simulation-based evaluation affords the opportunity to standardize evaluations but requires validation.

Methods: We identified topics from the Neurocritical Care Society's Emergency Neurological Life Support (ENLS) training, cross-referenced with the American Academy of Neurology's core clerkship curriculum. We used a modified Delphi method to develop simulations for assessment in neurocritical care. We constructed checklists of action items and communication skills, merging ENLS checklists with relevant clinical guidelines. We also utilized global rating scales, rated one (novice) through five (expert) for each case. Participants included neurology sub-interns, neurology residents, neurosurgery interns, non-neurology critical care fellows, neurocritical care fellows, and neurology attending physicians.

Results: Ten evaluative simulation cases were developed. To date, 64 participants have taken part in 274 evaluative simulation scenarios. The participants were very satisfied with the cases (Likert scale 1-7, not at all satisfied-very satisfied, median 7, interquartile range (IQR) 7-7), found them to be very realistic (Likert scale 1-7, not at all realistic-very realistic, median 6, IQR 6-7), and appropriately difficult (Likert scale 1-7, much too easy-much too difficult, median 4, IQR 4-5). Interrater reliability was acceptable for both checklist action items (kappa = 0.64) and global rating scales (Pearson correlation r = .70).

Conclusions: We demonstrated two sources of validity in ten simulation cases for assessment in neurological emergencies.
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http://dx.doi.org/10.1007/s12028-020-01176-yDOI Listing
January 2021

Risk Factors for Hypoglycemia with the Use of Enteral Glyburide in Neurocritical Care Patients.

World Neurosurg 2021 03 27;147:e63-e68. Epub 2020 Nov 27.

Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA. Electronic address:

Objective: Intravenous glyburide has demonstrated safety when used for attenuation of cerebral edema, although safety data are lacking for enteral glyburide when used for this indication. We aimed to determine the prevalence of and risk factors for hypoglycemia in neurocritical care patients receiving enteral glyburide.

Methods: We performed a retrospective case-control chart review (hypoglycemia vs. no hypoglycemia) of adult patients who received enteral glyburide for prevention or treatment of cerebral or spinal cord edema. Hypoglycemia was defined as a blood glucose <55.8 mg/dL. Descriptive statistics were used, with multivariate analysis to measure the association of risk factors and outcomes. Logistic regression was applied to outcomes with an exposure. Potential confounders were evaluated using the t-test or the Wilcoxon rank-sum test for continuous variables, and the χ test or the Fisher exact test for categorical variables.

Results: Seventy-one patients (60.6% men, median age 60 years) were included. The majority received 2.5 mg of enteral glyburide twice daily. Diagnoses included tumors (35.2%), intracerebral hemorrhage (28.2%), postspinal surgery (12.7%), and ischemic stroke (12.7%). Hypoglycemia occurred in 17 (23.9%) patients. Multivariate analysis identified admission serum creatinine (odds ratio, 27.2; [1.661, 445.3]; P < 0.05) as a risk factor for hypoglycemia, whereas body mass index >30 (odds ratio, 0.085; [0.008, 0.921]; P < 0.05) was protective.

Conclusions: Hypoglycemic episodes are common following enteral glyburide in neurocritical care patients. Both patients with and without diabetes mellitus are at risk of hypoglycemia. Elevated admission serum creatinine may increase the risk of hypoglycemia when utilizing glyburide for prevention or treatment of cerebral or spinal cord edema.
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http://dx.doi.org/10.1016/j.wneu.2020.11.107DOI Listing
March 2021

The Modified Fisher Scale Lacks Interrater Reliability.

Neurocrit Care 2021 08 16;35(1):72-78. Epub 2020 Nov 16.

Department of Neurology, Program in Trauma, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: The modified Fisher scale (mFS) is a critical clinical and research tool for risk stratification of cerebral vasospasm. As such, the mFS is included as a common data element by the National Institute of Neurological Disorders and Stroke SAH Working Group. There are few studies assessing the interrater reliability of the mFS.

Methods: We distributed a survey to a convenience sample with snowball sampling of practicing neurointensivists and through the research survey portion of the Neurocritical Care Society Web site. The survey consisted of 15 scrollable CT scans of patients with SAH for mFS grading, two questions regarding the definitions of the scale criteria and demographics of the responding physician. Kendall's coefficient of concordance was used to determine the interrater reliability of mFS grading.

Results: Forty-six participants (97.8% neurocritical care fellowship trained, 78% UCNS-certified in neurocritical care, median 5 years (IQR 3-6.3) in practice, treating median of 80 patients (IQR 50-100) with SAH annually from 32 institutions) completed the survey. By mFS criteria, 30% correctly identified that there is no clear measurement of thin versus thick blood, and 42% correctly identified that blood in any ventricle is scored as "intraventricular blood." The overall interrater reliability by Kendall's coefficient of concordance for the mFS was moderate (W = 0.586, p < 0.0005).

Conclusions: Agreement among raters in grading the mFS is only moderate. Online training tools could be developed to improve mFS reliability and standardize research in SAH.
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http://dx.doi.org/10.1007/s12028-020-01142-8DOI Listing
August 2021

Brain Death Determination: An Interprofessional Simulation to Determine Brain Death and Communicate with Families Focused on Neurology Residents.

MedEdPORTAL 2020 09 25;16:10978. Epub 2020 Sep 25.

Assistant Professor, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School.

Introduction: Significant variation exists in determining brain death despite an expectation of competence for all neurology residents. In addition, family discussions regarding brain death are challenging and may influence organ donation.

Methods: We developed two simulations of increasing complexity for PGY 2 and PGY 3 neurology residents. High-fidelity mannequins were used to simulate patients; standardized actors portrayed family members. In the first simulation, residents determined brain death and shared this information with a grieving family. In the second simulation, residents determined brain death in a more complicated scenario, requiring ancillary testing and accurate result interpretation. Following the determination, residents met with a challenging family. The residents worked with an interdisciplinary team and responded to the family's emotions, used active listening skills, and supported the family through next steps.

Results: Twelve residents completed the simulations. Prior to the simulation, three (25%) residents felt comfortable discussing a brain death diagnosis; following the simulation, eight (67%) residents felt comfortable/very comfortable discussing brain death. Prior to the simulation, eight (67%) residents stated they knew prerequisites for performing a brain death examination and seven (58%) agreed they knew indications for ancillary testing; these numbers increased to 100% following the simulation. The number of residents who felt comfortable performing the brain death exam increased from five (42%) to 10 (83%).

Discussion: This simulation of determining brain death and leading difficult family meetings was well-received by neurology residents. Further work should focus on the effects of simulation-based education on practice variation and organ donation consent rates.
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http://dx.doi.org/10.15766/mep_2374-8265.10978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521065PMC
September 2020

Stroke Risk Following Takotsubo Cardiomyopathy.

Neurohospitalist 2020 Oct 8;10(4):277-280. Epub 2020 Jun 8.

Clinical and Translational Neuroscience Unit, Division of Cardiology, Department of Neurology, Feil Family Brain and Mind Research Institute, and Weill Cornell Medicine, New York, NY, USA.

Background And Purpose: Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is an increasingly recognized cause of left ventricular dysfunction. Previously considered a benign disease, Takotsubo cardiomyopathy may be a risk factor of ischemic stroke based on recent small, single-center case series. The strength and temporal profile of this association remains uncertain.

Methods: We performed a cohort-crossover study using administrative claims data on all emergency department visits and acute care hospitalizations from 2005 to 2015 in California, New York, and Florida. We identified patients with Takotsubo cardiomyopathy, excluding those with a prior or concomitant stroke diagnosis. We compared the risk of ischemic stroke in the first year after Takotsubo cardiomyopathy to the risk of ischemic stroke in the second year after Takotsubo cardiomyopathy. Takotsubo cardiomyopathy and ischemic stroke were ascertained using previously validated codes. Absolute risks and odds ratios (OR) were calculated using McNemar test for matched data.

Results: Among 5283 patients with Takotsubo cardiomyopathy (mean age, 67 years; 92% female), we identified 49 ischemic strokes during the first year after Takotsubo cardiomyopathy versus 19 ischemic strokes during the second year after. The risk of stroke was significantly higher in the year after Takotsubo cardiomyopathy (absolute increase, 0.6%; 95% CI: 0.2-0.9; OR: 2.6; 95% CI: 1.5-4.6) as compared to the control period.

Conclusion: We found a heightened risk of ischemic stroke in the year after a diagnosis of Takotsubo cardiomyopathy, although the absolute risk increase was small.
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http://dx.doi.org/10.1177/1941874420931230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495697PMC
October 2020

The effect of platelet transfusion on functional independence and mortality after antiplatelet therapy associated spontaneous intracerebral hemorrhage: A systematic review and meta-analysis.

J Neurol Sci 2020 Oct 1;417:117075. Epub 2020 Aug 1.

Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America; Program in Trauma, The R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, United States of America.

Introduction: The practice of platelet transfusion to mitigate the deleterious effects of antiplatelet agents on spontaneous intracerebral hemorrhage (ICH) remains common. However, the effect of antiplatelet agents on patients with ICH is still controversial and transfusing platelets is not without risk. We performed a meta-analysis in order to determine the effect of platelet transfusion on antiplatelet agent associated ICH.

Methods: We queried PubMed, Embase, and Scopus databases to identify cohort studies, case-control studies, and randomized control trials. Study quality was graded by the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool, as appropriate. Outcomes of interest included functional independence as measured by the modified Rankin Scale and mortality. We compared patients with antiplatelet agent associated ICH who received platelet transfusion to those that did not.

Results: We identified 625 articles. After reviewing 44 full text articles, 5 were deemed appropriate for meta-analysis, including 4 cohort studies and one randomized control trial. Considerable heterogeneity was present among the studies (I > 81% for all analyses). We did not find a significant effect of platelet transfusions on functional independence (Odds Ratio [OR] 1.3, 95% CI.0.45-3.9) or mortality (OR 0.58, 95% Confidence Interval [CI] 0.12-2.6).

Conclusion: We found no evidence for an effect of platelet transfusions on functional independence or mortality following antiplatelet associated ICH. More randomized trials are needed to evaluate platelet transfusion in patients with ICH and proven reduced platelet activity or those requiring neurosurgical intervention.
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http://dx.doi.org/10.1016/j.jns.2020.117075DOI Listing
October 2020

Factors associated with tracheostomy decannulation in patients with severe traumatic brain injury.

Brain Inj 2020 07 2;34(8):1106-1111. Epub 2020 Jul 2.

Section of Neurocritical Care and Emergency Neurology, Program in Trauma, Department of Neurology, University of Maryland School of Medicine , Baltimore, MD, USA.

Objective: To assess variables associated with decannulation in patients with traumatic brain injury (TBI).

Participants: 79 patients with TBI requiring tracheostomy and ICU admission from January 1 to December 31, 2014.

Design: Retrospective analysis.

Measures: Patients decannulated prior to 90 days were compared with patients who remained cannulated. Two Cox Proportional Hazards models were used to predict decannulation using variables prior to tracheostomy and throughout hospitalization.

Results: Median time to decannulation was 37 days (Interquartile Range [IQR] 29-67). Variables prior to tracheostomy associated with decannulation included diabetes (HR, 0.15; 95% CI, 0.03-0.84; =.03), craniotomy (HR, 0.25; 95% CI, 0.06-1.02; =.05) and acute kidney injury (AKI) (HR, 0.06; 95% CI, 0.01-0.48; =.01). Variables present throughout hospitalization included age (HR, 1.12; 95% CI, 1.01-1.21; =.03), ventilator days (HR, 0.74; 95% CI, 0.57-0.95; =.02), reintubation (HR, 0.07; 95% CI, 0.01-0.64; =.02), aspiration (HR, 0.01; 95% CI, 0.0-0.29, =.01), craniotomy (HR, 0.004; 95% CI, 0.0-0.39; =.02) and AKI (HR, 0.0; 95% CI, 0.0-0.21; =.01).

Conclusion: The presence of diabetes, craniotomy and acute kidney injury may inform the conversation surrounding chances for decannulation prior to tracheostomy.
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http://dx.doi.org/10.1080/02699052.2020.1786601DOI Listing
July 2020

Diffuse large B cell lymphoma secondary to JC virus in progressive multifocal leukoencephalopathy.

J Neurovirol 2019 12 28;25(6):883-886. Epub 2019 May 28.

Division of Neurocritical Care and Emergency Neurology, University of Maryland, School of Medicine, 22 South Greene Street, Baltimore, MD, 20201, USA.

We present the case of a 43-year-old-man with a past medical history of HIV with recently initiated HAART and existing PML that presented with altered mental status. The initial diagnosis was deemed to be PML-IRIS; however, neuroimaging brought into question this diagnosis. Flow cytometry performed from the cerebrospinal fluid revealed diffuse large B cell lymphoma. JC virus may act in an oncogenic role similarly to EBV and predispose to CNS lymphomas. Patients with PML caused by JC virus may develop secondary malignancies.
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http://dx.doi.org/10.1007/s13365-019-00760-zDOI Listing
December 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

Inpatient Complications Predict Tracheostomy Better than Admission Variables After Traumatic Brain Injury.

Neurocrit Care 2019 04;30(2):387-393

R. Adams Cowley Shock Trauma Center, Program in Trauma, University of Maryland School of Medicine, 22 S. Greene Street, Gudelsky Bldg., Room G7K18, Baltimore, MD, 21201, USA.

Background: Data regarding who will require tracheostomy are lacking which may limit investigations into therapeutic effects of early tracheostomy.

Methods: We performed an observational study of adult traumatic brain injury (TBI) patients requiring intensive care unit (ICU) admission for ≥ 72 h and mechanical ventilation for ≥ 24 h between January 2014 and December 2014 at a level 1 trauma center. Patients who had life-sustaining measures withdrawn were excluded. Multivariable logistic regression analyses were used to assess admission and inpatient factors associated with receiving a tracheostomy and to develop predictive models. Inpatient complications prior to day 7 were used to standardize data collection for patients with and without tracheostomy. Patients who received tracheostomy prior to day 7 were excluded from analysis.

Results: In total, 209 patients (78% men, mean 48 years old, median Glasgow Coma Scale score (GCS) 8) met study criteria with tracheostomy performed in 94 (45%). Admission predictors of tracheostomy included GCS, chest tube, Injury Severity Score, and Marshall score. Inpatient factors associated with tracheostomy included the requirement for an external ventricular drain (EVD), number of operations, inpatient dialysis, aspiration, GCS on day 5, and reintubation. Multiple logistic regression analysis demonstrated that the number of operation room trips (adjusted odds ratio [AOR], 1.75; 95% CI, 1.04-2.97; P = 0.036), reintubation (AOR, 8.45; 95% CI, 1.91-37.44; P = .005), and placement of an EVD (AOR, 3.48; 95% CI, 1.27-9.58; P = .016) were independently associated with patients undergoing tracheostomy. Higher GCS on hospital day 5 (AOR, 0.52; 95% CI, 0.40-0.68; P < 0.001) was protective against tracheostomy. A model of inpatient variables only had a stronger association with tracheostomy than one with admission variables only (ROC AUC 0.93 vs 0.72, P < 0.001) and did not benefit from the addition of admission variables (ROC AUC 0.93 vs 0.92, P = 0.78).

Conclusion: Potentially modifiable inpatient factors have a stronger association with tracheostomy than do admission characteristics. Multicenter studies are needed to validate the results.
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http://dx.doi.org/10.1007/s12028-018-0624-7DOI Listing
April 2019

Response Letter: Neurological Disease Triggering Takotsubo Syndrome.

Neurocrit Care 2018 12;29(3):526-527

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, New York, NY, USA.

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http://dx.doi.org/10.1007/s12028-018-0618-5DOI Listing
December 2018

Multimodality Monitoring in Neurocritical Care: Decision-Making Utilizing Direct And Indirect Surrogate Markers.

J Intensive Care Med 2019 Jun 11;34(6):449-463. Epub 2018 Sep 11.

1 Division of Neuroendovascular Surgery and Neurocritical Care, Department of Neurology, Rutgers University, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Substantial progress has been made to create innovative technology that can monitor the different physiological characteristics that precede the onset of secondary brain injury, with the ultimate goal of intervening prior to the onset of irreversible neurological damage. One of the goals of neurocritical care is to recognize and preemptively manage secondary neurological injury by analyzing physiologic markers of ischemia and brain injury prior to the development of irreversible damage. This is helpful in a multitude of neurological conditions, whereby secondary neurological injury could present including but not limited to traumatic intracranial hemorrhage and, specifically, subarachnoid hemorrhage, which has the potential of progressing to delayed cerebral ischemia and monitoring postneurosurgical interventions. In this study, we examine the utilization of direct and indirect surrogate physiologic markers of ongoing neurologic injury, including intracranial pressure, cerebral blood flow, and brain metabolism.
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http://dx.doi.org/10.1177/0885066618788022DOI Listing
June 2019

Specialty Classifications of Physicians Who Provide Neurocritical Care in the United States.

Neurocrit Care 2019 02;30(1):177-184

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61 St, New York, NY, 10065, USA.

Background: We sought to characterize the specialty classification of US physicians who provide critical care for neurological/neurosurgical disease.

Methods: Using inpatient claims between 2009 and 2015 from a nationally representative 5% sample of Medicare beneficiaries, we selected hospitalizations for neurological/neurosurgical diseases with potential to result in life-threatening manifestations requiring critical care. Using Current Procedural Terminology codes, we determined the medical specialty of providers submitting critical care claims, and, using National Provider Identifier numbers, we merged in data from the United Council for Neurologic Subspecialties (UCNS) to determine whether the provider was a UCNS diplomate in neurocritical care. We defined providers with a clinical neuroscience background as neurologists, neurosurgeons, and/or UCNS diplomates in neurocritical care. We defined neurocritical care service as a critical care claim with a qualifying neurological/neurosurgical diagnosis in patients with a relevant primary hospital discharge diagnosis and ≥ 3 total critical care claims, excluding claims from the first day of hospitalization since these were mostly emergency-department claims. Our findings were reported using descriptive statistics with exact confidence intervals (CI).

Results: Among 1,952,305 Medicare beneficiaries, we identified 99,937 hospitalizations with at least one claim for neurocritical care. In our primary analysis, neurologists accounted for 28.0% (95% CI, 27.5-28.5%) of claims, neurosurgeons for 3.7% (95% CI, 3.5-3.9%), UCNS-certified neurointensivists for 25.8% (95% CI, 25.3-26.3%), and providers with any clinical neuroscience background for 42.8% (95% CI, 42.2-43.3%). The likelihood of management by physicians with a clinical neuroscience background increased proportionally with patients' county-level socioeconomic status and such providers were 3 times more likely to be based at an academic medical center than other physicians who billed for critical care in our sample (odds ratio, 2.9; 95% CI, 1.1-8.1).

Conclusions: Physicians with a dedicated clinical neuroscience background accounted for less than half of neurocritical care service in US Medicare beneficiaries.
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http://dx.doi.org/10.1007/s12028-018-0598-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347487PMC
February 2019

The Risk of Takotsubo Cardiomyopathy in Acute Neurological Disease.

Neurocrit Care 2019 02;30(1):171-176

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA.

Background: Case series have reported reversible left ventricular dysfunction, also known as stress cardiomyopathy or Takotsubo cardiomyopathy (TCM), in the setting of acute neurological diseases such as subarachnoid hemorrhage. The relative associations between various neurological diseases and Takotsubo remain incompletely understood.

Methods: We performed a cross-sectional study of all adults in the National Inpatient Sample, a nationally representative sample of US hospitalizations, from 2006 to 2014. Our exposures of interest were primary diagnoses of acute neurological disease, defined by ICD-9-CM diagnosis codes. Our outcome was a diagnosis of TCM. Binary logistic regression models were used to examine the associations between our pre-specified neurological diagnoses and TCM after adjustment for demographics.

Results: Among acute neurological diagnoses, the strongest associations were seen with subarachnoid hemorrhage (odds ratio [OR] 11.7; 95% confidence interval [CI] 10.2-13.4), status epilepticus (OR 4.9; 95% CI 3.7-6.3), and seizures (OR 1.3; 95% CI 1.1-1.5). In a sensitivity analysis including secondary diagnoses of acute neurological diagnoses, associations were also seen with transient global amnesia (OR 2.3; 95% CI 1.5-3.6), meningoencephalitis (OR 2.1; 95% CI 1.7-2.5), migraine (OR 1.7; 95% CI 1.5-1.8), intracerebral hemorrhage (OR 1.3; 95% CI 1.1-1.5), and ischemic stroke (OR 1.2; 95% CI 1.1-1.3). In addition, female sex was strongly associated with Takotsubo (OR 5.1; 95% CI 4.9-5.4).

Conclusion: TCM appears to be associated with varying degrees with several acute neurological diseases besides subarachnoid hemorrhage.
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http://dx.doi.org/10.1007/s12028-018-0591-zDOI Listing
February 2019

Long-term risk of seizures among cardiac arrest survivors.

Resuscitation 2018 08 19;129:94-96. Epub 2018 Jun 19.

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, United States; Department of Neurology, Weill Cornell Medicine, New York, NY, United States. Electronic address:

Introduction: The long-term risk of seizures in cardiac arrest survivors is not established. We hypothesized that survivors of cardiac arrest face an increased long-term risk for seizures.

Methods: We performed a retrospective cohort study using 2008-2015 claims data from a nationally representative 5% sample of Medicare beneficiaries ≥66 years-old. Our exposure of interest was a hospital diagnosis code of cardiac arrest, defined by previously validated ICD-9-CM codes. Since we were interested in long-term risk, we excluded patients with a history of seizure, and those who were diagnosed with a seizure during hospitalization or died during the index hospitalization. Our outcome was a diagnosis of seizure. Survival statistics were used to calculate seizure incidence and Cox proportional hazards models were used to determine the association between cardiac arrest and long-term seizures after adjustment for demographics and Charlson comorbidities.

Results: Among 1,764,508 beneficiaries with a mean 4.5 years of follow-up, we identified 57,437 patients with cardiac arrest who survived to discharge without a seizure. The annual incidence of seizures was 1.26% (95% confidence interval [CI], 1.20-1.33%) compared to 0.61% (95% CI, 0.61-0.62%) in other Medicare patients. In unadjusted analysis, cardiac arrest was associated with an increased risk of post-discharge seizures (hazard ratio [HR], 1.8; 95% CI, 1.7-1.9), but the association was lost after adjustment for demographics and comorbidities (HR 0.9; 95% CI, 0.9-1.0; P = 0.12).

Conclusion: The long-term risk of seizures was not elevated in patients with cardiac arrest who survived to hospital discharge without a seizure.
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http://dx.doi.org/10.1016/j.resuscitation.2018.06.019DOI Listing
August 2018

Novel management strategies for medically-refractory vasospasm following aneurysmal subarachnoid hemorrhage.

J Neurol Sci 2018 07 23;390:44-51. Epub 2018 Feb 23.

Department of Neurology, Henry Ford Health System, Detroit, MI, United States.

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is an important cause of further morbidity and mortality after an already devastating condition. Though traditionally attributed to vasospasm of large capacitance arteries and the resulting down-stream disruption of cerebral blood flow, the pathogenesis of DCI has proven to be more complex with early brain injury, blood-brain barrier disruption, microthrombosis, cortical spreading depolarizations, and the failure of cerebral autoregulation as newly elucidated factors. Vasospasm is a known consequence of SAH. The standard of care includes close monitoring for neurological deterioration, most often with serial clinical examinations, transcranial Doppler ultrasonography, and vascular imaging (crucial for early detection of DCI and allows for prompt intervention). Nimodipine continues to remain an important pharmacological strategy to improve functional outcomes in patients with SAH at risk for developing vasospasm. The paradigm for first line therapy in patients with vasospasm of induced hypertension, hypervolemia, and hemodilution has recently been challenged. Current American Heart Association guidelines recommend targeting euvolemia and judicious use of the pharmacologically induced hypertension component. Symptomatic vasospasm patients who do not improve with this first line therapy require rescue intervention with mechanical or chemical angioplasty and optimization of cardiac output and hemoglobin levels. This can be escalated in a step-wise fashion to include adjunct treatments such as intrathecal administration of vasodilators and sympatholytic or thrombolytic therapies. This review provides a general overview of the treatment modalities for DCI with a focus on novel management strategies that show promising results for treating vasospasm to prevent DCI.
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http://dx.doi.org/10.1016/j.jns.2018.02.039DOI Listing
July 2018

Prolonged Post-Traumatic Vasospasm Resulting in Delayed Cerebral Ischemia After Mild Traumatic Brain Injury.

Neurocrit Care 2018 Dec;29(3):512-518

Department of Neurology, Program in Trauma, University of Maryland School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1007/s12028-018-0542-8DOI Listing
December 2018

Population-Based Assessment of the Long-Term Risk of Seizures in Survivors of Stroke.

Stroke 2018 06 25;49(6):1319-1324. Epub 2018 Apr 25.

From the Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute (A.E.M., G.G., M.P.L., N.S.P., B.K., M.E.R., S.B.M., B.B.N., C.I., H.K.).

Background And Purpose: We sought to determine the long-term risk of seizures after stroke according to age, sex, race, and stroke subtype.

Methods: We performed a retrospective cohort study using administrative claims from 2 complementary patient data sets. First, we analyzed data from all emergency department visits and hospitalizations in California, Florida, and New York from 2005 to 2013. Second, we evaluated inpatient and outpatient claims from a nationally representative 5% random sample of Medicare beneficiaries. Our cohort consisted of all adults at the time of acute stroke hospitalization without a prior history of seizures. Our outcome was seizure occurring after hospital discharge for stroke. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR).

Results: Among 777 276 patients in the multistate cohort, the annual incidence of seizures was 1.68% (95% confidence interval [CI], 1.67%-1.70%) after stroke versus 0.15% (95% CI, 0.15%-0.15%) among the general population (IRR, 7.3; 95% CI, 7.3-7.4). By 8 years, the cumulative rate of any emergency department visit or hospitalization for seizure was 9.27% (95% CI, 9.16%-9.38%) after stroke versus 1.21% (95% CI, 1.21%-1.22%) in the general population. Stroke was more strongly associated with a subsequent seizure among patients <65 years of age (IRR, 12.0; 95% CI, 11.9-12.2) than in patients ≥65 years of age (IRR, 5.5; 95% CI, 5.4-5.5) and in the multistate analysis, the association between stroke and seizure was stronger among nonwhite patients (IRR, 11.0; 95% CI, 10.8-11.2) than among white patients (IRR, 7.3; 95% CI, 7.2-7.4). Risks were especially elevated after intracerebral hemorrhage (IRR, 13.3; 95% CI, 13.0-13.6) and subarachnoid hemorrhage (IRR, 13.2; 95% CI, 12.8-13.7). Our study of Medicare beneficiaries confirmed these findings.

Conclusions: Almost 10% of patients with stroke will develop seizures within a decade. Hemorrhagic stroke, nonwhite race, and younger age seem to confer the greatest risk of developing seizures.
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http://dx.doi.org/10.1161/STROKEAHA.117.020178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093303PMC
June 2018
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