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Background:There is international variability in whether neurological determination of death (NDD) is conceptually defined based on permanent loss of brainstem function or “whole brain death.” Canadian guidelines are not definitive. Patients with infratentorial stroke may meet clinical criteria for NDD despite persistent cerebral blood flow (CBF) and relative absence of supratentorial injury.Methods:We performed a multicenter cohort study involving patients that died from ischemic or hemorrhagic stroke in Alberta intensive care units from 2013 to 2019, focusing on those with infratentorial involvement. Medical records were reviewed to determine the incidence and proportion of patients that met clinical criteria for NDD; whether ancillary testing was performed; and if so, whether this demonstrated the absence of CBF.Results:There were 95 (27%) deaths from infratentorial and 263 (73%) from supratentorial stroke. Sixteen patients (17%) with infratentorial stroke had neurological examination consistent with NDD (0.55 cases per million per year). Among patients that underwent confirmatory evaluation for NDD with an apnea test, ancillary test (radionuclide scan), or both, ancillary testing was more common with infratentorial compared with supratentorial stroke (10/12 (85%) vs. 25/47 (53%), p = 0.04). Persistent CBF was detected in 6/10 (60%) patients with infratentorial compared with 0/25 with supratentorial stroke (p = 0.0001).Conclusions:Infratentorial stroke leading to clinical criteria for NDD occurs with an annual incidence of about 0.55 per million. There is variability in clinicians’ use of ancillary testing. Persistent CBF was detected in more than half of patients that underwent radionuclide scans. Canadian consensus is needed to guide clinical practice.

To qualitatively and quantitatively summarize curricula, teaching methods, and effectiveness of educational programs for training bedside care providers (non-experts) in the performance and screening of adult electroencephalography (EEG) for nonconvulsive seizures and other patterns. PRISMA methodological standards were followed. MEDLINE, EMBASE, Cochrane, CINAHL, WOS, Scopus, and MedEdPORTAL databases were searched from inception until February 26, 2020 with no restrictions. Abstract and full-text review was completed in duplicate. Studies were included if they were original research; involved non-experts performing, troubleshooting, or screening adult EEG; and provided qualitative descriptions of curricula and teaching methods and/or quantitative assessment of non-experts (vs gold standard EEG performance by neurodiagnostic technologists or interpretation by neurophysiologists). Data were extracted in duplicate. A content analysis and a meta-narrative review were performed. Of 2430 abstracts, 35 studies were included. Sensitivity and specificity of seizure identification varied from 38 to 100% and 65 to 100% for raw EEG; 40 to 93% and 38 to 95% for quantitative EEG, and 95 to 100% and 65 to 85% for sonified EEG, respectively. Non-expert performance of EEG resulted in statistically significant reduced delay (86 min, p

Background: Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to “self-fulfilling prophecy,” where withdrawal of life-sustaining measures (WLSM) is invariably followed by death. Methods: We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM. Results: Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score = 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02). Conclusions: We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from “self-fulfilling prophecy.” Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.

Traumatic brain injury (TBI) is common and potentially devastating. Traditional examination-based patient monitoring following TBI may be inadequate for frontline clinicians to reduce secondary brain injury through individualized therapy. Multimodal neurologic monitoring (MMM) offers great potential for detecting early injury and improving outcomes. By assessing cerebral oxygenation, autoregulation and metabolism, clinicians may be able to understand neurophysiology during acute brain injury, and offer therapies better suited to each patient and each stage of injury. Hence, we offer this primer on brain tissue oxygen monitoring, pressure reactivity index monitoring and cerebral microdialysis. This narrative review serves as an introductory guide to the latest clinically-relevant evidence regarding key neuromonitoring techniques.

A health care crisis such as the coronavirus disease 2019 (COVID-19) pandemic requires allocation of hospital staff and resources on short notice. Thus, new and sometimes less experienced team members might join the team to fill in the gaps. This scenario can be particularly challenging in endovascular stroke treatment, which is a highly specialized task that requires seamless cooperation of numerous health care workers across various specialties and professions. This document is intended for stroke teams who face the challenge of integrating new team members into endovascular stroke-treatment workflows during the COVID-19 pandemic or any other global health care emergency. It discusses the key strategies for smooth integration of new stroke-team members in a crisis situation: 1) transfer of key knowledge (simple take-home messages), 2) open communication and a nonjudgmental atmosphere, 3) strategic task assignment, and 4) graded learning and responsibility. While these 4 key principles should generally be followed in endovascular stroke treatment, they become even more important during health care emergencies such as the COVID-19 pandemic, when health care professionals have to take on new and additional roles and responsibilities in challenging working environments for which they were not specifically trained.

Background The objective of this study was to evaluate the accuracy of seizure burden in patients with super-refractory status epilepticus (SRSE) by using quantitative electroencephalography (qEEG). Methods EEG recordings from 69 patients with SRSE (2009-2019) were reviewed and annotated for seizures by three groups of reviewers: two board-certified neurophysiologists using only raw EEG (gold standard), two neurocritical care providers with substantial experience in qEEG analysis (qEEG experts), and two inexperienced qEEG readers (qEEG novices) using only a qEEG trend panel. Results Raw EEG experts identified 35 (51%) patients with seizures, accounting for 2950 seizures (3,126 min). qEEG experts had a sensitivity of 93%, a specificity of 61%, a false positive rate of 6.5 per day, and good agreement (κ = 0.64) between both qEEG experts. qEEG novices had a sensitivity of 98.5%, a specificity of 13%, a false positive rate of 15 per day, and fair agreement (κ = 0.4) between both qEEG novices. Seizure burden was not different between the qEEG experts and the gold standard (3,257 vs. 3,126 min), whereas qEEG novices reported higher burden (6066 vs. 3126 min). Conclusions Both qEEG experts and novices had a high sensitivity but a low specificity for seizure detection in patients with SRSE. qEEG could be a useful tool for qEEG experts to estimate seizure burden in patients with SRSE.

Electroencephalography (EEG) is used to prognosticate recovery in comatose patients with hypoxic ischemic brain injury (HIBI) secondary to cardiac arrest. We sought to determine the prognostic use of specific EEG patterns for predicting disability and death following HIBI secondary to cardiac arrest. This systematic review searched Medline, Embase, and Cochrane Central up to January 2020. We included original research involving prospective and retrospective cohort studies relating specific EEG patterns to disability and death in comatose adult patients suffering HIBI post cardiac arrest requiring admission to an intensive care setting. We evaluated study quality using the Quality of Diagnostic Accuracy Studies 2 tool. Descriptive statistics were used to summarize study, patient, and EEG characteristics. We pooled study-level estimates of sensitivity and specificity for EEG patterns defined a priori using a random effect bivariate and univariate meta-analysis when appropriate. Funnel plots were used to assess publication bias. Of 5191 abstracts, 333 were reviewed in full text, of which 57 were included in the systematic review and 32 in meta-analyses. No reported EEG pattern was found to be invariably associated with death or disability across all studies. Pooled specificities of status epilepticus, burst suppression, and electrocerebral silence were high (92-99%), but sensitivities were low (6-39%) when predicting a composite outcome of disability and death. Study quality varied depending on domain; patient flow and timing performed was well conducted in all, whereas EEG interpretation was retrospective in 17 of 39 studies. Accounting for variable study quality, EEG demonstrates high specificity with a low risk of false negative outcome attribution for disability and death when status epilepticus, burst suppression, or electrocerebral silence is detected. Increased use of standardized cross-study protocols and definitions of EEG patterns are required to better evaluate the prognostic use of EEG for comatose patients with HIBI following cardiac arrest.

Background: Cerebral venous thrombosis is a rare cause of stroke, with a number of well-defined risk factors. However, there exist few studies that describe trends in the prognosis of this disease over time. Methods: A retrospective study was performed on patients diagnosed with cerebral venous thrombosis at the University of Alberta Hospital during two time periods: 1988-1998 (21 patients) and 1999-2009 (40 patients). Signs and symptoms, risk factors, imaging findings, etiologies, treatment modalities, and status at discharge were examined. Results: Headache, nausea and vomiting, focal motor deficit, and seizure were the most common signs and symptoms, and active hormonal contraception was the most commonly identified risk factor between the two cohorts. Hematoma and hyperdense sinuses were the most commonly identified CT findings between groups. Thrombophilia and the use of hormonal contraception were the most frequently identified etiologies between the two cohorts. Treatment was similar, with the majority of patients in both cohorts receiving unfractionated heparin as first-line therapy. Patients in the 1999-2009 cohort were significantly less likely to have a severe deficit or be dead at discharge (odds ratio [OR]=0.178; 95% confidence interval [CI95%]=0.051, 0.625) and were more likely to have a favorable modified Rankin Scale score of 0 or 1 at discharge (OR=7.98; CI95%=1.79, 35.71). Conclusions: Our data indicate a reduction in severe residual symptoms at discharge and improved functional status at discharge for patients presenting with cerebral venous thrombosis from 1999 to 2009, as compared with 1988-1998.

ObjectiveTo test ketamine infusion efficacy in the treatment of super-refractory status epilepticus (SRSE), we studied patients with SRSE who were treated with ketamine retrospectively. We also studied the effect of high doses of ketamine on brain physiology as reflected by invasive multimodality monitoring (MMM).MethodsWe studied a consecutive series of 68 patients with SRSE who were admitted between 2009 and 2018, treated with ketamine, and monitored with scalp EEG. Eleven of these patients underwent MMM at the time of ketamine administration. We compared patients who had seizure cessation after ketamine initiation to those who did not.ResultsMean age was 53 ± 18 years and 46% of patients were female. Seizure burden decreased by at least 50% within 24 hours of starting ketamine in 55 (81%) patients, with complete cessation in 43 (63%). Average dose of ketamine infusion was 2.2 ± 1.8 mg/kg/h, with median duration of 2 (1–4) days. Average dose of midazolam was 1.0 ± 0.8 mg/kg/h at the time of ketamine initiation and was started at a median of 0.4 (0.1–1.0) days before ketamine. Using a generalized linear mixed effect model, ketamine was associated with stable mean arterial pressure (odds ratio 1.39, 95% confidence interval 1.38–1.40) and with decreased vasopressor requirements over time. We found no effect on intracranial pressure, cerebral blood flow, or cerebral perfusion pressure.ConclusionKetamine treatment was associated with a decrease in seizure burden in patients with SRSE. Our data support the notion that high-dose ketamine infusions are associated with decreased vasopressor requirements without increased intracranial pressure.Classification of evidenceThis study provides Class IV evidence that ketamine decreases seizures in patients with SRSE.

Disorder of consciousness (DOC) is common in patients with acute brain injury (ABI) and it weighs heavily in goals of care discussion.1 Dopaminergic agents to support recovery have shown encouraging results in chronic DOC following traumatic brain injury (TBI) and are currently the most promising candidates to also support recovery during the acute post injury phase.2 Amantadine is a neurohormonal modulator that increases the concentration of dopamine at the synaptic cleft. Behavioural assessments of consciousness alone are often operator dependent, time consuming to obtain and may miss patients with covert consciousness.3 Our hypothesis is that resting Electroencephalogram (EEG) features follow a predictable course preceding behavioural recovery in patients with acute non-hypoxic-ischaemic brain injury receiving amantadine and may serve as biomarkers for recovery of consciousness. We studied 44 patients with ABI that were not following commands and were on EEG monitoring before and after the start of amantadine. A full description of the methods is available in the online supplementary file. ### Supplementary data [jnnp-2019-322645supp001.pdf] ### Study cohort From a cohort of 44 patients, 30 (68%) recovered consciousness prior to hospital discharge (online supplementary tables S1, S2). ### Baseline predictors of recovery Age, focal versus diffuse brain injury and admission Glasgow Coma Score were not associated with recovery of command following. Presence of sleep structures in the EEG (spindles and K-complexes) prior to starting amantadine was independently associated with recovery of command following (online supplementary table S3). Average spectrogram plots for each EEG recording classified according to the ‘ABCD’ model representing thalamocortical integrity were generated (figure 1A, online supplementary figure).4 The percent of patients that recovered command following did not increase hierarchically with higher ‘ABCD’ levels (figure 1B). Power spectral density analysis …

A 23-year-old healthy fitness instructor was prescribed Diane-35 (cyproterone acetate–ethinyl estradiol) for acne. Three weeks later, she suddenly lost the ability to speak. She arrived at the hospital 2 hours and 45 minutes after symptom onset. Stroke causing nonfluent aphasia was diagnosed.

Although the common carotid artery is the second most common site for extracranial carotid artery stenosis, complete symptomatic occlusion in the absence of devastating stroke is rare. We present a case of complete common carotid artery occlusion failing medical management and requiring endovascular intervention. The clinical presentation, diagnostic investigations, and management of complete carotid artery occlusions are discussed.

OBJECTIVE Intracranial pressure (ICP) is an important and established clinical measurement that is used in the management of severe acute brain injury. ICP waveforms are usually triphasic and are susceptible to artifact because of transient catheter malfunction or routine patient care. Existing methods for artifact detection include threshold-based, stability-based, or template matching, and result in higher false positives (when there is variability in the ICP waveforms) or higher false negatives (when the ICP waveforms lack complete triphasic components but are valid). APPROACH We hypothesized that artifact labeling of ICP waveforms can be optimized by an active learning approach which includes interactive querying of domain experts to identify a manageable number of informative training examples. MAIN RESULTS The resulting active learning based framework identified non-artifactual ICP pulses with a superior AUC of 0.96 + 0.012, compared to existing methods: template matching (AUC: 0.71 + 0.04), ICP stability (AUC: 0.51 + 0.036) and threshold-based (AUC: 0.5 + 0.02). SIGNIFICANCE The proposed active learning framework will support real-time ICP-derived analytics by improving precision of artifact-labelling.

A man in his early 70s with a diagnosis of chronic lymphocytic leukemia and being treated with prednisone, fludarabine, cyclophosphamide, and rituximab presented with progressive multifocal neurologic decline. The patient died 2 months after the onset of this decline despite extensive clinical and laboratory investigation and a trial of methylprednisolone therapy. The approach to the immunosuppressed patient with progressive neurologic decline, neuropathologic findings, and final diagnosis are discussed.