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Coronavirus disease 2019 (COVID-19) has been associated with Acute Ischemic Stroke (AIS). Here, we characterize our institutional experience with management of COVID-19 and AIS. Baseline demographics, clinical, imaging, and outcomes data were determined in patients with COVID-19 and AIS presenting within March 2020 to October 2020, and November 2020 to August 2021, based on institutional COVID-19 hospitalization volume. Of 2512 COVID-19 patients, 35 (1.39%, mean age 63.3 years, 54% women) had AIS. AIS recognition was frequently delayed after COVID-19 symptoms (median 19.5 days). Four patients (11%) were on therapeutic anticoagulation at AIS recognition. AIS mechanism was undetermined or due to multiple etiologies in most cases (n = 20, 57%). Three patients underwent IV TPA, and three underwent mechanical thrombectomy, of which two suffered re-occlusion. Three patients had incomplete mRNA vaccination course. Fourteen (40%) died, with 26 (74%) having poor outcomes. Critical COVID-19 severity was associated with worsened mortality (p = 0.02). More patients (12/16; 75%) had either worsened or similar 3-month functional outcomes, than those with improvement, indicating the devastating impact of co-existing AIS and COVID-19. Comparative analysis showed that patients in the later cohort had earlier AIS presentation, fewer stroke risk factors, more comprehensive workup, more defined stroke mechanisms, less instance of critical COVID-19 severity, more utilization of IV TPA, and a trend towards worse outcomes for the sub-group of mild-to-moderate COVID-19 severity. AIS incidence, NIHSS, and overall outcomes were similar. Further studies should investigate outcomes beyond 3 months and their predictive factors, impact of completed vaccination course, and access to neurologic care.

Introduction: Little is known about racial differences in inpatient outcomes following hospitalizations for myasthenia gravis (MG). In this study, we used a claims-based database to assess racial differences in outcomes in hospitalized myasthenics. Methods: The 2006–2014 National Inpatient Sample database was queried using the International Classification of Diseases 9th Edition diagnosis code (358.01) to identify adult patients (age >17 years) undergoing hospitalization for MG. Race was categorized into – white, black/African American (AA), Asian or Pacific Islander, Hispanic, Native American, and other. Complications assessed included urinary tract infections, acute renal failure, cardiac complications, systemic infection, deep venous thrombosis, and pulmonary embolism. Multivariate logistic regression analyses were used to assess whether race was associated with a difference in outcomes, after controlling for baseline demographics, hospital characteristics, and treatment factors. Results: A total of 56,189 patient admissions, using a weighted sample, underwent hospitalization for MG between 2006 and 2014. Black/AA patients had significantly higher odds of experiencing systemic infections (odds ratio [OR] 1.35 [95% confidence intervals [CI] 1.16–1.58]; p < 0.001), deep venous thrombosis (OR 2.11 [95% CI 1.36–3.27]; p = 0.001), and renal failure (OR 1.19 [95% CI 1.05–1.35]; p = 0.005). Black/AA patients were more likely to be intubated (OR 1.09 [95% CI 1.01–1.19]; p = 0.028) and receive noninvasive mechanical ventilation (OR 1.62 [95% CI 1.46–1.79]; p < 0.001), however, were less likely to receive intravenous immunoglobulin (OR 0.77 [95% CI 0.73–0.82]; p < 0.001) and plasmapheresis (OR 0.77 [95% CI 0.72–0.82]; p < 0.001). Black/AA and Hispanic patients had lower mortality (OR 0.74 [95% CI 0.59–0.94; p = 0.012]. Conclusions: Significant racial differences exist in both treatment utilization and inpatient outcomes for patients hospitalized for MG.

OBJECTIVE Venous thromboembolism (VTE) can cause significant morbidity and mortality in hospitalized patients, and may disproportionately occur in patients with limited mobility following spinal trauma. The authors aimed to characterize the epidemiology and clinical predictors of VTE in pediatric patients following traumatic spinal injuries (TSIs). METHODS The authors conducted a retrospective cohort analysis of children who experienced TSI, including spinal fractures and spinal cord injuries, encoded within the National Trauma Data Bank from 2011 to 2014. RESULTS Of the 22,752 pediatric patients with TSI, 192 (0.8%) experienced VTE during initial hospitalization. Proportionally, more patients in the VTE group (77%) than in the non-VTE group (68%) presented following a motor vehicle accident. Patients developing VTE had greater odds of presenting with moderate (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.4–4.8) or severe Glasgow Coma Scale scores (aOR 4.3, 95% CI 3.0–6.1), epidural hematoma (aOR 2.8, 95% CI 1.4–5.7), and concomitant abdominal (aOR 2.4, 95% CI 1.8–3.3) and/or lower extremity (aOR 1.5, 95% CI 1.1–2.0) injuries. They also had greater odds of being obese (aOR 2.9, 95% CI 1.6–5.5). Neither cervical, thoracic, nor lumbar spine injuries were significantly associated with VTE. However, involvement of more than one spinal level was predictive of VTE (aOR 1.3, 95% CI 1.0–1.7). Spinal cord injury at any level was also significantly associated with developing VTE (aOR 2.5, 95% CI 1.8–3.5). Patients with VTE stayed in the hospital an adjusted average of 19 days longer than non-VTE patients. They also had greater odds of discharge to a rehabilitative facility or home with rehabilitative services (aOR 2.6, 95% CI 1.8–3.6). CONCLUSIONS VTE occurs in a low percentage of hospitalized pediatric patients with TSI. Injury severity is broadly associated with increased odds of developing VTE; specific risk factors include concomitant injuries such as cranial epidural hematoma, spinal cord injury, and lower extremity injury. Patients with VTE also require hospital-based and rehabilitative care at greater rates than other patients with TSI.

BackgroundStudies on tenecteplase have been yielding mixed results on several important variables at different doses, thus hampering objective guideline recommendations in acute ischemic stroke management. This meta-analysis stratifies doses in order to refine our interpretation of outcomes and quantify the benefits and harms of tenecteplase at different doses.MethodsPubMed/MEDLINE, the Cochrane Library, and reference lists of the included articles were systematically searched. Several efficacy and safety outcomes were pooled and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Network meta-analysis was used to find the optimal dose of tenecteplase. Meta-regression was run to investigate the impact of baseline NIHSS scores on functional outcomes and mortality.ResultsTen randomized controlled trials with a total of 4140 patients were included. 2166 (52.32%) patients were enrolled in the tenecteplase group and 1974 (47.68%) in the alteplase group. Tenecteplase at 0.25 mg/kg dose demonstrated significant improvement in excellent functional outcome at 3 months (RR 1.14, 95% CI 1.04-1.26), and early neurological improvement (RR 1.53, 95% CI 1.03-2.26). There was no statistically significant difference between tenecteplase and alteplase in terms of good functional outcome, intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality at any dose. Meta-regression demonstrated superior tenecteplase efficacy with increasing stroke severity, however, the results were statistically nonsignificant.ConclusionsTenecteplase at 0.25 mg/kg dose is more efficacious and at least as safe as alteplase for stroke thrombolysis. Newer analyses need to focus on direct comparison of tenecteplase doses and whether tenecteplase is efficacious at longer needle times.

BACKGROUND Growing evidence associates traumatic brain injury (TBI) with increased risk of dementia, but few studies have evaluated associations in patients younger than 55 yr using non-TBI orthopedic trauma (NTOT) patients as controls to investigate the influence of age and TBI severity, and to identify predictors of dementia after trauma. OBJECTIVE To investigate the relationship between TBI and dementia in an institutional group. METHODS Retrospective cohort study (2000-2018) of TBI patients aged 45 to 100 yr vs NTOT controls. Primary outcome was dementia after TBI (followed ≤10 yr). Cox proportional hazards models were used to assess risk of dementia; logistic regression models assessed predictors of dementia. RESULTS Among 24 846 patients, TBI patients developed dementia (7.5% vs 4.6%) at a younger age (78.6 vs 82.7 yr) and demonstrated higher 10-yr mortality than controls (27% vs 14%; P

OBJECTIVE Sports injuries are known to present a high risk of spinal trauma. The authors hypothesized that different sports predispose participants to different injuries and injury severities. METHODS The authors conducted a retrospective cohort analysis of adult patients who experienced a sports-related traumatic spinal injury (TSI), including spinal fractures and spinal cord injuries (SCIs), encoded within the National Trauma Data Bank from 2011 through 2014. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were estimated. RESULTS The authors included 12,031 cases of TSI, which represented 15% of all sports-related trauma. The majority of patients with TSI were male (82%), and the median age was 48 years (interquartile range 32–57 years). The most frequent mechanisms of injury in this database were cycling injuries (81%), skiing and snowboarding accidents (12%), aquatic sports injuries (3%), and contact sports (3%). Spinal surgery was required during initial hospitalization for 9.1% of patients with TSI. Compared to non-TSI sports-related trauma, TSIs were associated with an average 2.3-day increase in length of stay (95% CI 2.1–2.4; p < 0.001) and discharge to or with rehabilitative services (adjusted OR 2.6, 95% CI 2.4–2.7; p < 0.001). Among sports injuries, TSIs were the cause of discharge to or with rehabilitative services in 32% of cases. SCI was present in 15% of cases with TSI. Within sports-related TSIs, the rate of SCI was 13% for cycling injuries compared to 41% and 49% for contact sports and aquatic sports injuries, respectively. Patients experiencing SCI had a longer length of stay (7.0 days longer; 95% CI 6.7–7.3) and a higher likelihood of adverse discharge disposition (adjusted OR 9.69, 95% CI 8.72–10.77) compared to patients with TSI but without SCI. CONCLUSIONS Of patients with sports-related trauma discharged to rehabilitation, one-third had TSIs. Cycling injuries were the most common cause, suggesting that policies to make cycling safer may reduce TSI.

OBJECTIVESports injuries present a considerable risk of debilitating spinal injury. Here, the authors sought to profile the epidemiology and clinical risk of traumatic spinal injuries (TSIs) in pediatric sports injuries.METHODSThe authors conducted a retrospective cohort analysis of pediatric patients who had experienced a sports-related TSI, including spinal fractures and spinal cord injuries, encoded in the National Trauma Data Bank in the period from 2011 to 2014.RESULTSIncluded in the analysis were 1723 cases of pediatric sports-related TSI, which represented 3.7% of all pediatric sports-related trauma. The majority of patients with TSI were male (81%), and the median age was 15 years (IQR 13–16 years). TSIs arose most often from cycling accidents (47%) and contact sports (28%). The most frequently fractured regions were the thoracic (30%) and cervical (27%) spine. Among patients with spinal cord involvement (SCI), the cervical spine was involved in 60% of cases.The average length of stay for TSIs was 2 days (IQR 1–5 days), and 32% of the patients required ICU-level care. Relative to other sports-related trauma, TSIs without SCI were associated with an increased adjusted mean length of stay by 1.8 days (95% CI 1.6–2.0 days), as well as the need for ICU-level care (adjusted odds ratio [aOR] 1.6, 95% CI 1.3–1.9). Also relative to other sports-related trauma, TSIs with SCI had an increased length of stay by 2.1 days (95% CI 1.8–2.6 days) and the need for ICU-level care (aOR 3.6, 95% CI 2.6–4.8).TSIs without SCI were associated with discharge to or with rehabilitative services (aOR 1.7, 95% CI 1.5–2.0), as were TSIs with SCI (aOR 4.0, 95% CI 3.2–4.9), both relative to other sports-related trauma. Among the patients with TSIs, predictors of the need for rehabilitation at discharge were having a laminectomy or fusion, concomitant lower-extremity injury, head injury, and thoracic injury. Although TSIs affected 4% of the study cohort, these injuries were present in 8% of patients discharged to or with rehabilitation services and in 17% of those who died in the hospital.CONCLUSIONSTraumatic sports-related spinal injuries cause significant morbidity in the pediatric population, especially if the spinal cord is involved. The majority of TSI cases arose from cycling and contact sports accidents, underscoring the need for improving education and safety in these activities.

OBJECTIVEThere is variability and uncertainty about the optimal approach to the management and discontinuation of an external ventricular drain (EVD) after subarachnoid hemorrhage (SAH). Evidence from single-center randomized trials suggests that intermittent CSF drainage and rapid EVD weans are safe and associated with shorter ICU length of stay (LOS) and fewer EVD complications. However, a recent survey revealed that most neurocritical care units across the United States employ continuous CSF drainage with a gradual wean strategy. Therefore, the authors sought to determine the optimal EVD management approach at their institution.METHODSThe authors reviewed records of 200 patients admitted to their institution from 2010 to 2016 with aneurysmal SAH requiring an EVD. In 2014, the neurocritical care unit of the authors’ institution revised the internal EVD management guidelines from a continuous CSF drainage with gradual wean approach (continuous/gradual) to an intermittent CSF drainage with rapid EVD wean approach (intermittent/rapid). The authors performed a retrospective multivariable analysis to compare outcomes before and after the guideline change.RESULTSThe authors observed a significant reduction in ventriculoperitoneal (VP) shunt rates after changing to an intermittent CSF drainage with rapid EVD wean approach (13% intermittent/rapid vs 35% continuous/gradual, OR 0.21, p = 0.001). There was no increase in delayed VP shunt placement at 3 months (9.3% vs 8.6%, univariate p = 0.41). The intermittent/rapid EVD approach was also associated with a shorter mean EVD duration (10.2 vs 15.6 days, p < 0.001), shorter ICU LOS (14.2 vs 16.9 days, p = 0.001), shorter hospital LOS (18.2 vs 23.7 days, p < 0.0001), and lower incidence of a nonfunctioning EVD (15% vs 30%, OR 0.29, p = 0.006). The authors found no significant differences in the rates of symptomatic vasospasm (24.6% vs 20.2%, p = 0.52) or ventriculostomy-associated infections (1.3% vs 8.8%, OR 0.30, p = 0.315) between the 2 groups.CONCLUSIONSAn intermittent CSF drainage with rapid EVD wean approach is associated with fewer VP shunt placements, fewer complications, and shorter LOS compared to a continuous CSF drainage with gradual EVD wean approach. There is a critical need for prospective multicenter studies to determine if the authors’ experience is generalizable to other centers.

Background and Purpose— We aimed to determine if microemboli after endovascular thrombectomy correlate with unfavorable outcomes despite successful recanalization. Methods— This is a prospective multicenter study of consecutive patients with ischemic stroke and occlusion of anterior circulation vessels (terminal internal carotid or main trunk of the middle cerebral artery/first-order branch of the main trunk of the middle cerebral artery segments of middle cerebral artery) after successful thrombectomy (modified Treatment In Cerebral Ischemia grades 2b-3). Microembolic signals (MES) were assessed by 30 minutes of transcranial Doppler monitoring within 72 hours of the last-seen-well time. Major outcomes included modified Rankin Scale at 90 days and infarct volume on head computed tomography at 24 hours. We also assessed early outcomes based on National Institutes of Health Stroke Scale variation and recurrence of stroke, transient ischemic attack, or systemic embolism within 90 days. Results— Among 111 patients, MES were detected in 43 (39%), with a median rate of 4 counts/h (interquartile range 2–12). The occurrence of MES was not associated with a significant difference in modified Rankin Scale (ordinal shift analysis, adjusted odds ratio, 1.06 [95% CI, 0.48–2.34] P =0.85) nor in functional independence (modified Rankin Scale, 0–2: adjusted odds ratio, 0.52 [95% CI, 0.19–1.39] P =0.19). Patients with and without MES had similar infarct volumes (adjusted beta, 11.2 [95% CI, −46.6 to +22.9] P =0.51) on 24-hour computed tomography. MES did predict new embolic events (adjusted Cox hazard ratio, 6.78 [95% CI, 1.63–27.8] P =0.01). Conclusions— MES detected by transcranial Doppler following endovascular treatment of anterior circulation occlusions do not predict clinical or radiological outcome. However, such emboli are an independent marker of recurrent embolic events within 90 days.

Carotid artery stenting (CAS) for carotid stenosis (CS) is widely performed. Randomized trials may not be reflective of real-world outcomes. We used the 2012-19 ACS-NSQIP CAS Procedure Targeted Dataset to identify the incidence and risk factors associated with periprocedural 30-day adverse events (AE). AE were categorized as follows: vascular (embolization - proximal and distal thrombosis, myocardial infarction [MI], stroke, restenosis, and TIA) , stroke/TIA alone, major (organ-space surgical site infection [SSI]), pneumonia, intubation, pulmonary embolism, post-operative ventilator use, blood transfusion, deep venous thrombosis, sepsis), minor (urinary tract infections, acute renal failure, superficial SSI). Other outcome variables were readmissions, reoperations, mortality, and non-home discharges. Multivariate logistic regression analysis, using backward stepwise model with entry and removal probabilities of p=0.05 and p=0.1. 1552 patients (median age=70 IQR 62-76) were included. 64% were male. 49% of CAS procedures were in asymptomatic patients, whereas 24% were following stroke, 16% to TIA and 8% for amaurosis fugax. 2.1% were mild (21 (OR 1.68; p=0.043), hypoalbuminemia (OR 3.00; p=0.002), and operative time >77mins (OR 1.92; p=0.013). Pre-procedural aspirin lowered odds of experiencing major AE (OR 0.43; p=0.035). Risk factors of 30-day readmissions were contralateral severe (OR 2.73; p=0.002) or complete (OR 3.07; p=0.001) stenosis, COPD (OR 2.01; p=0.003) and congestive heart failure (OR 2.85; p=0.004). In conclusion, almost half of CAS procedures were performed in asymptomatic patients. Periprocedural complications were higher than those reported in randomized trials. Physicians should use the findings for risk stratification.

Author(s): Parikh, Anuraag S; Khawaja, Ayaz; Puram, Sidharth V; Srikanth, Priya; Tjoa, Tjoson; Lee, Hang; Sethi, Rosh KV; Bulbul, Mustafa; Varvares, Mark A; Rocco, James W; Emerick, Kevin S; Deschler, Daniel G; Lin, Derrick T | Abstract: Objectives:To describe a 10-year single center experience with parotid gland malignancies and to determine factors affecting outcomes. Study Design:Retrospective review. Methods:The institutional cancer registry was used to identify patients treated surgically for malignancies of the parotid gland between January 2005 and December 2014. Clinical and pathologic data were collected retrospectively from patient charts and analyzed for their association with overall survival (OS) and disease-free survival (DFS). Results:Two hundred patients were identified. Mean age at surgery was 57.8 years, and mean follow-up time was 52 months. One hundred two patients underwent total parotidectomy, while 77 underwent superficial parotidectomy, and 21 underwent deep lobe resection. Seventy patients (35%) required facial nerve (FN) sacrifice. Acinic cell carcinoma was the most common histologic type (22%), followed by mucoepidermoid carcinoma (21.5%) and adenoid cystic carcinoma (12.5%). Twenty-nine patients (14.5%) experienced recurrences, with mean time to recurrence of 23.6 months (range: 1-82 months). Five- and 10-year OS were 81% and 73%, respectively. Five- and 10-year DFS were 80% and 73%, respectively. In univariate analyses, age g 60, histologic type, positive margins, high grade, T-stage, node positivity, perineural invasion, and FN involvement were predictors of OS and DFS. In the multivariate analysis, histology, positive margins, node positivity, and FN involvement were independent predictors of OS and DFS. Conclusions:Our single-center experience of 200 patients suggests that histology, positive margins, node positivity, and FN involvement are independently associated with outcomes in parotid malignancies. Level of Evidence:4.

Prior studies show hospital admission volume to be associated with poor outcomes following elective procedures and inpatient medical hospitalizations. However, it is unknown whether hospital volume impacts Inpatient outcomes for status epilepticus (SE) hospitalizations. In this study, we aimed to assess the impact of hospital volume on the outcome of patients with SE and related inpatient medical complications.The 2005 to 2013 National Inpatient Sample database was queried using International Classification of Diseases 9th Edition diagnosis code 345.3 to identify patients undergoing acute hospitalization for SE. The National Inpatient Sample hospital identifier was used as a unique facility identifier to calculate the average volume of patients with SE seen in a year. The study cohort was divided into three groups: low volume (0-7 patients with SE per year), medium volume (8-22 patients with SE per year), and high volume ( 22 patients with SE per year). Multivariate logistic regression analyses were used to assess whether medium or high hospital volume had lower rates of inpatient medical complications compared with low-volume hospitals.A total of 137,410 patients with SE were included in the analysis. Most patients (n = 50,939; 37%) were treated in a low-volume hospital, 31% (n = 42,724) were treated in a medium-volume facility, and 18% (n = 25,207) were treated in a high-volume hospital. Patients undergoing treatment at medium-volume hospitals (vs. low-volume hospitals) had higher odds of pulmonary complications (odds ratio [OR] 1.18 [95% confidence interval {CI} 1.12-1.25]; p 0.001), sepsis (OR 1.24 [95% CI 1.08-1.43] p = 0.002), and length of stay (OR 1.13 [95% CI 1.0 -1.19] p 0.001). High-volume hospitals had significantly higher odds of urinary tract infections (OR 1.21 [95% CI 1.11-1.33] p 0.001), pulmonary complications (OR 1.19 [95% CI 1.10-1.28], p 0.001), thrombosis (OR 2.13 [95% CI 1.44-3.14], p 0.001), and renal complications (OR 1.21 [95% CI 1.07-1.37], p = 0.002). In addition, high-volume hospitals had lower odds of metabolic (OR 0.81 [95% CI 0.72-0.91], p 0.001), neurological complications (OR 0.80 [95% CI 0.69-0.93], p = 0.004), and disposition to a facility (OR 0.89 [95% CI 0.82-0.96], p 0.001) compared with lower-volume hospitals.Our study demonstrates certain associations between hospital volume and outcomes for SE hospitalizations. Further studies using more granular data about the type, severity, and duration of SE and types of treatment are warranted to better understand how hospital volume may impact care and prognosis of patients.

Background and Purpose— Digital subtraction angiography has been used as the gold standard to confirm successful aneurysmal obliteration after aneurysm clipping procedures using titanium or cobalt alloy clips. Computed tomographic angiography is a newer, less invasive imaging technique also used to confirm successful aneurysmal obliteration; however, its use compared with digital subtraction angiography remains controversial. Methods— A comprehensive literature search was conducted on Pubmed, EMBASE, and Cochrane databases through November 6, 2017, for studies that evaluated postclipping aneurysm obliteration with both computed tomographic angiography and digital subtraction angiography. Pooled sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR−) were calculated using the bivariate random-effects model. Results— Out of 6916 studies, 13 studies met inclusion criteria for this meta-analysis. A total of 510 patients with 613 aneurysms were included. Compared with digital subtraction angiography, which detected 87 residual aneurysms, computed tomographic angiography detected 58 resulting in a pooled sensitivity of 69% (95% CI, 54%–81%) and a pooled specificity of 99% (95% CI, 97%–99%). This corresponded to LR+ of 55.5 (95% CI, 23.6–130.9) and LR− of 0.31 (95% CI, 0.20–0.48). Univariate meta-regression revealed that the pooled sensitivity was worse in prospective designs ( P interaction P interaction Conclusions— This meta-analysis revealed that computed tomographic angiography had a favorable LR+ but not a favorable LR−. Thus, this imaging modality may be applicable to rule in, but not rule out, residual aneurysms after clipping.

Background: Neurological COVID-19 disease has been reported widely, but often without using standard case definitions or detailed diagnostic work up. Several meta-analyses, based on such reports, describe the neurological diagnoses but give little information on outcomes and risk factors. Methods: We conducted an individual patient data meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute, and extracted aggregate data from published reports. We analysed features associated with poor outcome (moderate to severe sequelae or death, 3-6, on the modified Rankin scale) using multivariable models. Findings: We identified 381 studies (31 unpublished) describing 4443 patients with COVID-19 and neurological disease: 83 of these provided IPD for 1979 (45%) patients. Encephalopathy (978 [49%]) and cerebrovascular events (506 [26%]), were the most common diagnoses in the IPD database and aggregate data. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41] overall), and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-Dimer. Overall, 30-day mortality was 30% (27-32). The hazard of death was reduced for patients in the WHO European region, but increased in low- and lower-middle-income countries. Interpretation: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission. Funding This study was funded by the UK Medical Research Council’s Global Effort on COVID-19 Programme (MR/V033441/1); UK National Institute for Health Research (NIHR)-funded Global Health Research Group on Acute Brain Infections (17/63/110); and the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907), at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant Nos. IS-HPU-1112-10117 and NIHR200907). Declaration of Interests: BS reports a grant from UKRI/DHSC Global Effort on COVID-19 Research (Medical Research Council) and non-financial support from UK National Institute for Health Research Global Health Research Group on Brain Infections. SL and TS are supported by a grant from the EU Zika Preparedness Latin American Network consortium (ZikaPLAN). ZikaPLAN has received funding from the EU's Horizon 2020 research and innovation programme under grant agreement number 734584. LCG reports non-financial support from Pfizer, non-financial support from Gilead. LB reports grants from GlaxoSmithKline, Research England and Wellcome Trust. AMBM reports grants from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico CNPq/Brazil, and Sao Paulo Research Foundation FAPESP/Brazil. AP reports personal fees from ZAMBON, UCB , BIOMARIN, and ABBvie pharma. TS was an adviser to the GlaxoSmithKline Ebola Vaccine programme, chaired a Siemens Diagnostics clinical advisory board, and advises the WHO Brain Health Unit Forum on Neurology and COVID-19; TS has also previously filed a patent for a test for bacterial meningitis based on a blood test (GB 1606537.7, April 14, 2016), and has grants from the UK Medical Research Council and National Institute for Health Research. All other authors declare no conflict of interest

Extra-axial fluid collections (EACs) frequently develop after decompressive craniectomy. Management of EACs remains poorly understood, and information on how to predict their clinical course is inadequate. We aimed to better characterize EACs, understand predictors of their resolution, and delineate the best treatment paradigm for patients.We reviewed patients who developed EACs after undergoing decompressive craniectomy for treatment of refractory intracranial pressure elevations. We excluded patients who had an ischemic stroke, as EACs in these patients have a different clinical course. We performed univariate analysis and multiple linear regression to find variables associated with earlier resolution of EACs and stratified our analyses by EAC phenotype (complicated vs. uncomplicated). We conducted a systematic review to compare our findings with the literature.Of 96 included patients, 73% were male, and median age was 42.5 years. EACs resolved after a median of 60 days. Complicated EACs were common (62.5%) and required multiple drainage methods before cranioplasty. These were not associated with a protracted course or increased risk of death (P0.05). Early bone flap restoration with simultaneous drainage was independently associated with earlier resolution of EACs (β = 0.56, P 0.001). Systematic review confirmed lack of standardized direction with respect to EAC management.Our analyses reveal 2 clinically relevant phenotypes of EAC: complicated and uncomplicated. Our proposed treatment algorithm involves replacing the bone flap as soon as it is safe to do so and draining refractory EACs aggressively. Further studies to assess long-term clinical outcomes of EACs are warranted.

Objective: Cervical spine injury screening is common practice for traumatic brain injury (TBI) patients. However, risk factors for concomitant thoracolumbar trauma remain unknown. We characterized epidemiology and clinical risk for concomitant thoracolumbar trauma in TBI. Methods: We conducted a multi-center, retrospective cohort analysis of TBI patients in the National Trauma Data Bank from 2011-2014 using multivariable logistic regression. Results: Out of 768,718 TBIs, 46,654 (6.1%) and 42,810 (5.6%) patients were diagnosed with thoracic and lumbar spine fractures, respectively. Only 11% of thoracic and 7% of lumbar spine fracture patients had an accompanying spinal cord injury at any level. The most common mechanism of injury was motor vehicle accident (67% of thoracic and 71% and lumbar fractures). Predictors for both thoracic and lumbar fractures included moderate (thoracic: OR 1.26, 95%CI 1.21-1.31; lumbar: OR 1.13, 95%CI 1.08-1.18) and severe Glasgow Coma Scale (GCS) score (OR 1.71, 95%CI 1.67-1.75; OR 1.17, 95%CI 1.13-1.20) compared to mild; epidural hematoma (OR 1.36, 95%CI 1.28-1.44; OR 1.1, 95%CI 1.04-1.19); lower extremity injury (OR 1.38, 95%CI 1.35-1.41; OR 2.50, 95%CI 2.45-2.55); upper extremity injury (OR 2.19, 95%CI 2.14-2.23; OR 1.15, 95%CI 1.13-1.18); smoking (OR 1.09, 95%CI 1.06-1.12; OR 1.12, 95%CI 1.09-1.15); and obesity (OR 1.39, 95%CI 1.34-1.45; OR 1.29, 95%CI 1.24-1.35). Thoracic injuries (OR 4.45; 95% CI 4.35-4.55) predicted lumbar fractures, while abdominal injuries (OR 2.02; 95% CI 1.97-2.07) predicted thoracic fractures. Conclusions: We identified GCS, smoking, upper and lower extremity injuries, and obesity as common risk factors for thoracic and lumbar spinal fractures in TBI.

The development of the endovascular thrombectomy (EVT) technique has revolutionized acute stroke management for patients with large vessel occlusions (LVOs). The impact of successful recanalization using an EVT on autoregulatory profiles is unknown. A more complete understanding of cerebral autoregulation in the context of EVT may assist with post-procedure hemodynamic optimization to prevent complications. We examined cerebral autoregulation in 107 patients with an LVO in the anterior circulation (proximal middle cerebral artery (M1/2) and internal cerebral artery (ICA) terminus) who had been treated using an EVT. Dynamic cerebral autoregulation was assessed at multiple time points, ranging from less than 24 hours to 5 days following last seen well (LSW) time, using transcranial Doppler ultrasound recordings and transfer function analysis. Complete (Thrombolysis in Cerebral Infarction (TICI) 3) recanalization was associated with a more favorable autoregulation profile compared with TICI 2b or poorer recanalization (p < 0.05), which is an effect that was present after accounting for differences in the infarct volumes. Less effective autoregulation in the first 24 h following the LSW time was associated with increased rates of parenchymal hematoma types 1 and 2 hemorrhagic transformations (PH1–PH2). These data suggest that patients with incomplete recanalization and poor autoregulation (especially within the first 24 h post-LSW time) may warrant closer blood pressure monitoring and control in the first few days post ictus.

INTRODUCTION: Surgical outcomes and healthcare utilization have been shown to vary based on patient insurance status. We analyzed whether patients’ insurance affects case urgency for and readmission after craniotomy for meningioma resection, using benign meningioma as a model system to minimize confounding from the disease-related characteristics of other neurosurgical pathologies. METHODS: We analyzed 90-day readmission for patients who underwent resection of a benign meningioma in the Nationwide Readmission Database from 2014–2015. RESULTS: A total of 9783 meningioma patients with private insurance (46%), Medicare (39%), Medicaid (10%), self-pay (2%), or another scheme (3%) were analyzed. 72% of all cases were elective; with 78% of cases in privately insured patients being elective compared to 71% of Medicare (p>0.05), 59% of Medicaid patients (OR 2.3, p

A hypothalamic hamartoma consists of hyperplastic heterotopic tissue growing in a disorganized fashion. These lesions occur in about one per 50,000 to 100,000 people. Hypothalamic hamartomas can cause intrinsic epileptogenesis leading to gelastic seizures. Surrounding cortical structures may also develop secondary epileptogenesis. Persistent seizures caused by hypothalamic hamartomas can be debilitating and result in significant cognitive and behavioral impairment. Early recognition and treatment is important in controlling seizures and in preventing further cognitive deterioration. Some patients experience improved cognition and behavior following early treatment, suggesting that hypothalamic hamartomas represent a reversible epileptic encephalopathy. The outcome of epilepsy associated with these lesions has significantly evolved with the availability of new treatment techniques and an improved understanding of its pathogenesis. Increasing evidence supporting the role of hypothalamic hamartomas as a cause of gelastic seizures and secondary epileptogenesis has led to more frequent use of surgery as the definitive treatment. Several minimally invasive procedures have been devised, including neuroendoscopic approaches and different stereotactic radio and laser ablation techniques. Each of these techniques can lead to unique adverse events. We review the various classification schemes used to characterize hypothalamic hamartomas and the recommended surgical approaches for each subtype. We also review the literature for currently available treatment modalities and compare their efficacy in controlling seizures and their safety profiles.

ObjectiveThe efficacy of intra-arterial vasodilators (IADs) for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains debatable. The objective of this meta-analysis was to pool estimates of angiographic and neurological response, clinical outcome, and mortality following treatment of vasospasm with IADs.MethodsWe searched PubMed, Embase, Scopus, Clinicaltrials.gov, Cochrane database, and CINAHL in December 2015 and August 2016. Studies reporting angiographic and neurological response, clinical outcome, and mortality following IAD treatment of vasospasm in 10 or more adults with aSAH were included. All established IADs were allowed. Two authors independently selected studies and abstracted the data. Mean weighted probabilities (MWP) were calculated using random effects model.ResultsInclusion criteria were met by 55 studies (n=1571). MWP for immediate angiographic response to IAD treatment was 89% (95% CI 83% to 94%), post-IAD neurological improvement 57% (95% CI 49% to 65%), good outcome 66% (95% CI 60% to 71%), and mortality was 9% (95% CI 7% to 12%). After adjusting for publication bias, MWP for mortality was 5% (95% CI 4% to 7%). When transcranial Doppler (TCD) was used along with clinical deterioration for patient selection, rates of neurological response (64%) and good outcome (72%) were better. IADs were not superior to controls (balloon angioplasty or medical management).ConclusionIAD treatment leads to a robust angiographic response and fair (but lower) rates of neurological response and good clinical outcome. Mortality was lower than the average reported in the literature. Rates of neurological response and good outcome were better when TCD was used for patient selection. Carefully designed studies are needed to compare IADs against medical management and balloon angioplasty.

Introduction The Centers for Disease Control and Prevention (CDC) reports that there were 2.87 million cases of traumatic brain injury (TBI) in the United States in 2014, 69 million worldwide. Some studies suggest a connection between TBI and increased risk of dementia, but it remains unclear whether the risk increases with age and TBI severity. Given our aging population, it is essential to better characterize the link between TBI and dementia. Methods We conducted a retrospective cohort study of two major academic medical centers for years 2000-2015. We identified all patients with TBI, aged 45 and older. Variables included age, TBI severity, pre-existing dementia, dementia diagnosed after TBI, years to dementia, and follow-up time. TBI severity was determined by head/neck AIS score, using ICD-PIC software. Mild TBI was defined as AIS 0-2, and Moderate/Severe as AIS 3-6. Analysis was done in R.v.3.0.1 software. Results Overall, there were 14,199 patients with TBI, of which 9,938 (70%) were mild and 4,261 (30%) were moderate/severe. Mean age was 70.5 (±14.0). There were 1,422 cases (10%) of pre-existing dementia, and 850 (6%) cases of dementia diagnosed after TBI. The mean follow-up time was 1,129 (±1,474) days. The 75-84 age group had the highest incidence of TBI (28%). When compared by age group and TBI severity, the proportion of moderate/severe TBI increased with increasing age. The proportion of pre-existing dementia increased with age, as expected. Notably, there is increased incidence of dementia after TBI in patients aged 65 and older (7-10%, p < 0.001). There was no observed effect of TBI severity on the risk of dementia after TBI. Conclusions Our results indicate that TBI is a risk factor for the development of dementia, especially in patients aged 65 and older. Given the global public health burden of these two diseases it is critical to develop effective TBI primary prevention strategies. Key messages TBI is a risk factor for the development of dementia. Need for public health measures to mitigate the risk of TBI in the patient population 65 and older.

Objective: To survey US-trained graduating neurology residents who are American Academy of Neurology members, in an effort to trend perceived quality and completeness of graduate neurology education. Methods: An electronic survey was sent to all American Academy of Neurology members graduating from US neurology residency programs in the Spring of 2014. Results: Of 805 eligible respondents, 24% completed the survey. Ninety-three percent of adult neurology residents and 56% of child neurology residents reported plans to pursue fellowship training after residency. Respondents reported a desire for additional training in neurocritical care, neuro-oncology, neuromuscular diseases, botulinum toxin injection, and nerve blocks. There remains a clear deficit in business training of neurology residents, although there was notable improvement in knowledge of coding and office management compared to previous surveys. Discussion: Although there are still areas of perceived weakness in neurology training, graduating neurology residents feel generally well prepared for their chosen careers. However, most still pursue fellowship training for reasons that are little understood. In addition to certain subspecialties and procedures, practice management remains deficient in neurology training and is a point of future insecurity for most residents. Future curriculum changes should consider resident-reported gaps in knowledge, with careful consideration of improving business training.

The carbohydrate binding molecule Galectin-3 has been the focus of recent study in a variety of disease processes, and there is evidence that it plays a role in diseases of the cerebrovascular system. In this review, we summarize the relevant clinical literature on the role of Galectin-3 in ischemic stroke, intracranial hemorrhage and subarachnoid hemorrhage. We also provide a brief overview of the cellular and molecular mechanisms behind the role played by Galectin-3 following ischemic brain injury. Our review is aimed at clinicians who manage these conditions, and neuroscientists who study the role of biomarkers in cerebrovascular disease.

BACKGROUND Control of systolic blood pressure (SBP) after primary intracerebral hemorrhage improves outcomes. Factors determining the number of blood pressure medications (BPM) required for goal SBP

New-onset refractory status epilepticus (NORSE) is defined as a state of persistent seizures with no identifiable etiology in patients without preexisting epilepsy that lasts longer than 24h despite optimal therapy. Management of NORSE is challenging, and the role of immunotherapy (IT) is unclear. We identified patients fulfilling the criteria for NORSE at a single institution. These patients were described, analyzed, and compared with NORSE cases available from the literature. Finally, a pooled analysis of available case series was conducted to compare the outcomes in patients who received IT with those not treated with IT during the course of NORSE in order to generate hypotheses for further research. In our case series, NORSE was diagnosed in 11 patients (9 females) with a mean age of 48 years and a mean duration of 54.4 days. Autoantibodies were identified in 7 patients, of which anti-GAD (glutamic acid decarboxylase) and anti-NMDAR (N-methyl-D-aspartate receptor) were most frequent. Of the 11 patients, 8 were treated with IT (intravenous steroids, immunoglobulins, plasmapheresis, or a combination), and 4 received chemotherapy. Of the 8 patients treated with IT, 6 had favorable outcomes (defined as any outcome other than death, vegetative state, or inability to take care of oneself) compared with 0 out of 3 patients who did not receive IT. Difference in outcomes was significant (p=0.026). Pooled analysis of all identified case series, including ours, showed a statistically significant effect (p=0.022), with favorable outcomes in 42% of the patients who received any IT compared with 20% in those who did not. In all patients with refractory SE and negative comprehensive investigations, a diagnosis of NORSE should be considered. This would aid planning for early immunotherapy. Currently, only Class IV evidence for the use of immunotherapy in NORSE is available. Prospective multicenter studies are necessary to assess the true efficacy of IT in NORSE.

We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids.

Objectives: This case report describes two cases of high-dose methotrexate–induced nephrotoxicity: death in the case of conventional supportive care and successful renal function recovery in a patient treated with glucarpidase and continuous dialysis. Methods: High dose methotrexate is widely used for management of adult and pediatric malignancies. However, high-dose methotrexate–induced renal nephrotoxicity may cause severe, even lethal complications. Here we present examples of such outcomes. Results: We present one case of lethal high-dose methotrexate nephrotoxicity in a patient treated with conventional rescue therapy. We contrast this outcome with another patient with high-dose methotrexate–induced anuric acute kidney injury, who has recovered renal function following therapy with glucarpidase and continuous dialysis. Conclusions: This is only the second reported case of high-dose methotrexate–induced anuric acute kidney injury, and the only one with a reported clinical outcome. This first report of recovery from high-dose methotrexate–induced anuric acute kidney injury after glucarpidase administration supports available evidence pointing to the effectiveness of this therapy.

BACKGROUND It is not clear whether performing continuous EEG (cEEG) in critically ill patients during intensive care unit (ICU) treatment affects outcomes at discharge. MATERIAL AND METHODS We prospectively matched 234 patients who received cEEG (cases) by admission diagnosis and sex to 234 patients who did not receive cEEG (controls) and followed them until discharge. Patients admitted due to seizures were excluded. The primary measures of outcome were Glasgow Coma Scale at Discharge (GCSD) and disposition at discharge, and the secondary measures of outcome were AED modifications, Glasgow Outcomes Scale, and Modified-Rankin Scale. These outcomes were compared between the cases and controls. RESULTS Some differences in primary outcome measures between the groups emerged on univariate analyses, but these differences were small and not significant after controlling for covariates. Cases had longer ICU stays (p=0.002) and lower admission GCS (p=0.01) but similar GCSD (p=0.10). Of the secondary outcome measures, the mean (SD) number of AED modifications for cases was 2.2±3.1 compared to 0.4±0.8 for controls (p

Background: Patients with primary intracerebral hemorrhage (pICH) are at risk of airway compromise and commonly undergo intubation. Poor outcomes have been reported for these patients. Factors predicting intubation prior to admission (PTA), and after admission are unknown. These factors may be helpful in predicting which pICH patients require intubation, and its optimal timing. Methods: Patients with pICH directly admitted or transferred from another facility to our center were included. Patients with SAH, SDH, epidural hemorrhage, underlying lesions, or infarct with hemorrhagic transformation were excluded. Intubation note from medical chart was used to determine the timing of intubation. Demographic and clinical data were recorded. The primary outcome was a discharge mRS (dmRS) of 4-6. Results: A total of 370 patients were included. Patients intubated PTA had a lower average GCS (6 vs. 9; p=0.0003) and a higher average NIHSS (26 vs. 18; p=0.0007) than those intubated after admission. Higher incidences of hematoma expansion (30.9% vs. 16.3%; p=0.0253), tracheostomies performed (17.5% vs. 4.8%; p=0.0004), ICH volumes > 30cc (40% vs. 25.5%; p=0.0352), and pneumonia (35.1% vs. 5.4%; p Conclusions: Lower GCS and higher NIHSS significantly predict intubation in pICH patients PTA. ICH volumes > 30cc, hematoma expansion and pneumonia significantly predict intubation after admission. Intubation is significantly associated with poor functional outcomes independent of ICH score and pneumonia. Location of ICH does not predict intubation.

Summary Chordomas are rare tumors that can develop anywhere along the craniospinal axis. These tumors present challenges with respect to diagnosis and treatment due to a high rate of recurrence, even after multiple surgeries, and the propensity to involve any region within the craniospinal axis. New developments in radiation therapy have improved recurrence-free survival in patients with chordomas. Different regimens of chemotherapy and molecularly-targeted therapies, as adjuvants to surgery, have been described in individual case reports and case series. The purpose of this paper is to describe a case of clival chordoma and review recent developments in diagnostic and therapeutic options. A 77-year-old female was referred because of diplopia and progressively worsening headaches. Head imaging revealed a large expansile and erosive mass in the skull base. The patient underwent a successful endoscopic endonasal trans-sphenoidal resection of the mass, with biopsy confirming the diagnosis of chordoma. Postoperatively, the patient experienced an improvement in neurological symptoms. Chordomas can present a diagnostic challenge due to the rare occurrence and a tendency to involve any region within the craniospinal axis.

Summary: Lateralized periodic discharges (LPDs) are commonly seen on EEG in critically ill patients. They are often associated with seizures, but some patients may have them without seizures. Therefore, they are considered to lie in the ictal–interictal continuum. When ictal, they require multiple antiepileptic drugs to treat effectively, which can expose the patient to iatrogenic complications. Therefore, optimal management is controversial. We present here two cases where perfusion-weighted MRI was useful in distinguishing ictal from interictal LPDs. In the first patient, hyperperfusion in the area showing LPDs was considered an indication that the LPDs were ictal, and aggressive treatment led to clinical improvement. The second patient had no asymmetry on perfusion-weighted MRI, and therefore, we did not escalate antiepileptic therapy, and the LPDs resolved spontaneously over the next few days. Perfusion-weighted MRI offers several advantages over other techniques, such as single-photon emission computerized tomography that have been used for this purpose before. It does not expose the patient to radiation, and newer techniques like arterial spin labeling can even obviate the need for intravenous contrast. Larger scale studies using perfusion-weighted MRI will be of great value to clinical practice.

Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal

Objective: Previous meta-analyses have not reported pooled estimates of response to the treatment of vasospasm with intra-arterial vasodilators (IADs) in aneurysmal subarachnoid hemorrhage (aSAH). The objective of this meta-analysis was to pool estimates of angiographic & clinical response, good outcome, & mortality rates following treatment of vasospasm with IADs. Methods: We searched PubMed using MeSH terms for “Subarachnoid Hemorrhage" AND ("Endovascular Procedures" OR "Infusions, Intra-Arterial") AND "Vasodilator Agents". Bibliographies of retrieved articles were also searched. Studies reporting clinical and angiographic response, mortality, and outcome, following IAD treatment of vasospasm in adult humans with aSAH were included. All IADs were allowed. Two authors independently selected studies & abstracted data. Mean weighted probabilities (MWP) were calculated using random effects model. Results: Inclusion criteria were met by 48 studies (n=1264). Heterogeneity was significant in all syntheses (I2 ≥50%; P< 0.5) and studies were of poor quality. Publication bias was significant for the synthesis of mortality. MWP for immediate angiographic response to IAD treatment was 90% (95% CI 84-95%), post-IAD neurological improvement 59% (95% CI 47-71%), good outcome 56% (95% CI 49-63%), and Mortality rate was 9% (95% CI 6-12%). Subgroup analysis is shown in the table. Conclusion: IAD treatment leads to a fair angiographic and neurologic response but the impact on outcome is unknown. Studies were of poor quality and bias was significant. Current evidence does not support the use of IADs for the treatment of cerebral vasospasm in aSAH. Randomized/pragmatic trials are needed to elucidate the role of IADs in vasospasm in aSAH.