Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists' Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

RéSUMé: Ces Lignes directrices de pratique clinique 2023 Lignes directrices de pratique clinique dicale du décès basée sur l'arrêt permanent de la fonction cérébrale qui s'applique à toute personne, ainsi que des recommandations pour la détermination du décès par des critères circulatoires pour des donneurs d'organes potentiels et des recommandations pour la détermination du décès par des critères neurologiques pour tous les patients sous ventilation mécanique, indépendamment de leur potentiel de donneur d'organes. Les présentes Lignes directrices sont approuvées par la Société canadienne de soins intensifs, l'Association médicale canadienne, l'Association canadienne des infirmiers/infirmières en soins intensifs, la Société canadienne des anesthésiologistes, la Fédération des sciences neurologiques du Canada (représentant la Société canadienne de neurologie, la Société canadienne de neurochirurgie, la Société canadienne de neurophysiologie clinique, l'Association canadienne de neurologie pédiatrique, la Société canadienne de neuroradiologie et le Consortium neurovasculaire canadien), la Société canadienne du sang, le Programme de recherche en don et transplantation du Canada, l'Association canadienne des médecins d'urgence, l'Association des infirmières et infirmiers praticiens du Canada, et la Société canadienne de soins intensifs cardiovasculaires (CANCARE) et la Société canadienne de pédiatrie.

Neuroprognostication in the Post Cardiac Arrest Patient: A Canadian Cardiovascular Society Position Statement.

Cardiac arrest (CA) is associated with a low rate of survival with favourable neurologic recovery. The most common mechanism of death after successful resuscitation from CA is withdrawal of life-sustaining measures on the basis of perceived poor neurologic prognosis due to underlying hypoxic-ischemic brain injury. Neuroprognostication is an important component of the care pathway for CA patients admitted to hospital but is complex, challenging, and often guided by limited evidence. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the evidence underlying factors or diagnostic modalities available to determine prognosis, recommendations were generated in the following domains: (1) circumstances immediately after CA; (2) focused neurologic exam; (3) myoclonus and seizures; (4) serum biomarkers; (5) neuroimaging; (6) neurophysiologic testing; and (7) multimodal neuroprognostication. This position statement aims to serve as a practical guide to enhance in-hospital care of CA patients and emphasizes the adoption of a systematic, multimodal approach to neuroprognostication. It also highlights evidence gaps.

Functional Outcomes and Mortality in Patients With Intracerebral Hemorrhage After Intensive Medical and Surgical Support.

BACKGROUND AND OBJECTIVES: Despite decades of increasingly sophisticated neurocritical care, patient outcomes after spontaneous intracerebral hemorrhage (ICH) remain dismal. Whether this reflects therapeutic nihilism or the effects of the primary injury has been questioned. In this contemporary cohort, we determined the 30- and 90-day mortality, cause-specific mortality, functional outcome, and the effect of surgical intervention in a culture of aggressive medical and surgical support. METHODS: This was a retrospective cohort study of consecutive adult patients with spontaneous ICH admitted to a tertiary neurocritical care unit. Patients with secondary ICH and those subject to limitation of care before 72 hours were excluded. For each ICH score, mortality at 30- and 90-days, and the modified Rankin Scale (mRS) within 1-year were examined. The effect of craniotomy/craniectomy ± hematoma evacuation on the outcome of supratentorial ICH was determined using propensity score matching. Median patient follow-up after discharge was 2.2 (interquartile range [IQR] 0.4-4.4) years. RESULTS: Among 319 patients with spontaneous ICH (median age was 69 [IQR 60-77] years, 60% male), 30- and 90-day mortality were 16% and 22%, respectively, and unfavorable functional outcome (mRS score 4-6) was 50% at a median 3.1 months after ICH. Admission predictors of mortality mirrored those of the original ICH score. Unfavorable outcomes for ICH scores 3 and 4 were 73% and 86%, respectively. The most common adjudicated primary causes of mortality were direct effect or progression of ICH (54%), refractory cerebral edema (21%), and medical complications (11%). In matched analyses, lifesaving surgery for supratentorial ICH did not significantly alter mortality or unfavorable functional outcome in patients overall. In subgroup analyses restricted to (1) surgery with hematoma evacuation and (2) ICH score 3 and 4 patients, the odds of 30-day mortality were reduced by 71% (odds ratio [OR] 0.29, 95% CI 0.09-0.9, p = 0.032) and 80% (OR 0.2, 95% CI 0.04-0.91, p = 0.038), respectively, but no difference was observed for 90-day mortality or unfavorable functional outcome. DISCUSSION: This study demonstrates that poor outcomes after ICH prevail despite aggressive treatment. Unfavorable outcomes appear related to direct effects of the primary injury and not to premature care limitations. Lifesaving surgery for supratentorial lesions delayed mortality but did not alter functional outcomes.

Prospective Validation of Computed Tomography to Identify Patients at High Risk for Stroke After Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Computed tomography (CT) findings of acute and chronic ischemia are associated with subsequent stroke risk in patients with transient ischemic attack. We sought to validate these associations in a large prospective cohort of patients with transient ischemic attack or minor stroke. METHODS: This prospective cohort study enrolled emergency department patients from 13 hospitals with transient ischemic attack who had CT imaging. Primary outcome was stroke within 90 days. Secondary outcomes were stroke within 2 or 7 days. CT findings were abstracted from radiology reports and classified for the presence of acute ischemia, chronic ischemia, or microangiopathy. Multivariable logistic regression was used to test associations with primary and secondary end points. RESULTS: From 8670 prospectively enrolled patients between May 2010 and May 2017, 8382 had a CT within 24 hours. From this total population, 4547 (54%) patients had evidence of acute ischemia, chronic ischemia, or microangiopathy on CT, of whom 175 had a subsequent stroke within 90 days (3.8% subsequent stroke rate; adjusted odds ratio [aOR], 2.33 [95% CI, 1.62-3.36]). This was in comparison to those with CT imaging without ischemia. Findings associated with an increased risk of stroke at 90 days were isolated acute ischemia (6.0%; aOR, 2.42 [95% CI, 1.03-5.66]), acute ischemia with microangiopathy (10.7%; aOR, 3.34 [95% CI, 1.57-7.14]), chronic ischemia with microangiopathy (5.2%; aOR, 1.83 [95% CI, 1.34-2.50]), and acute ischemia with chronic ischemia and microangiopathy (10.9%; aOR, 3.49 [95% CI, 1.54-7.91]). Acute ischemia with chronic ischemia and microangiopathy were most strongly associated with subsequent stroke within 2 days (aOR, 4.36 [95% CI, 1.31-14.54]) and 7 days (aOR, 4.50 [95% CI, 1.73-11.69]). CONCLUSIONS: In patients with transient ischemic attack or minor stroke, CT evidence of acute ischemia with chronic ischemia or microangiopathy significantly increases the risk of subsequent stroke within 90 days of index visit. The combination of all 3 findings results in the greatest early risk.

Subarachnoid Hemorrhage, Delayed Cerebral Ischemia, and Milrinone Use in Canada.

INTRODUCTION: Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. There is little high-quality evidence available to guide the management of DCI. The Canadian Neurosurgery Research Collaborative (CNRC) is comprised of resident physicians who are positioned to capture national, multi-site data. The objective of this study was to evaluate practice patterns of Canadian physicians regarding the management of aSAH and DCI. METHODS: We performed a cross-sectional survey of Canadian neurosurgeons, intensivists, and neurologists who manage aSAH. A 19-question electronic survey (Survey Monkey) was developed and validated by the CNRC following a DCI-related literature review (PubMed, Embase). The survey was distributed to members of the Canadian Neurosurgical Society and to Canadian members of the Neurocritical Care Society. Responses were analyzed using quantitative and qualitative methods. RESULTS: The response rate was 129/340 (38%). Agreement among respondents was limited to the need for intensive care unit admission, use of clinical and radiographic monitoring, and prophylaxis for the prevention of DCI. Several inconsistencies were identified. Indications for starting hyperdynamic therapy varied. There was discrepancy in the proportion of patients who felt to require IV milrinone, IA vasodilators, or physical angioplasty for treatment of DCI. Most respondents reported their facility does not utilize a standardized definition for DCI. CONCLUSION: DCI is an important clinical entity for which no homogeneity and standardization exists in management among Canadian practitioners. The CNRC calls for the development of national standards in the definition, identification, and treatment of DCI.

Risk of stroke is low after transient ischemic attack presentation with isolated dizziness.

OBJECTIVE: Stroke presenting as dizziness is a diagnostic challenge in frontline settings, given the multitude of benign conditions that present similarly. The risk of stroke after episodic dizziness is unknown, leading to divergent guidance on optimal workup and management. Prior TIA risk scores have shown a history of dizziness is a negative predictor of subsequent stroke. Our objective was to assess the subsequent stroke risk within 90 days following emergency department assessment (ED) for isolated dizziness diagnosed as TIA during the index visit. METHODS: We conducted prospective, multicenter cohort studies at 13 Canadian EDs over 11 years. We enrolled patients diagnosed with TIA and compared patients with isolated dizziness to those with other neurological deficits. Our primary outcome was subsequent stroke within 90 days. Secondary outcomes were subsequent stroke within 2, 7, and 30 days, respectively, as well as subsequent TIA within 90 days. RESULTS: Only 4/483 (0.8%) patients with isolated dizziness had a stroke within 90 days compared to 320/11024 (2.9%) of those with any focal neurological sign or symptom (RR 0.29, 95% CI 0.11-0.76). Over the first 90 days, the two groups differ significantly in their probability of stroke (p = 0.007). Subsequent TIA was also significantly less common in the isolated dizziness group (1.7% vs. 5.6%, p = 0.001) with a relative risk of 0.30 (95% CI 0.15-0.60). CONCLUSION: The risk of subsequent stroke following ED presentation for TIA is low when the presenting symptoms are isolated dizziness.

RéSUMé: OBJECTIF: Les accidents vasculaires cérébraux (AVC) se présentant sous forme de vertiges constituent un défi diagnostique en première ligne, étant donné la multitude d'affections bénignes qui se présentent de la même manière. Le risque d'accident vasculaire cérébral (AVC) après des vertiges épisodiques est inconnu, ce qui donne lieu à des conseils divergents sur le bilan et la prise en charge optimaux. Des scores de risque d'AIT antérieurs ont montré que des antécédents de vertiges sont un facteur prédictif négatif d'accident vasculaire cérébral ultérieur. Notre objectif était d'évaluer le risque ultérieur d'accident vasculaire cérébral (AVC) dans les 90 jours suivant l'évaluation aux urgences d'un étourdissement isolé diagnostiqué comme un AIT lors de la visite de référence. MéTHODES: Nous avons mené des études de cohorte prospectives multicentriques dans 13 services d'urgence canadiens pendant 11 ans. Nous avons recruté des patients ayant reçu un diagnostic d'AIT et avons comparé les patients présentant des vertiges isolés à ceux présentant d'autres déficits neurologiques. Nous avons inscrit des patients ayant reçu un diagnostic d'AIT et comparé des patients ayant des étourdissements isolés à ceux présentant d'autres déficits neurologiques. Notre résultat primaire était l'AVC subséquent dans les 90 jours. Les résultats secondaires étaient l'AVC subséquent dans les 2, 7 et 30 jours, respectivement, ainsi que l'AIT subséquent dans les 90 jours. RéSULTATS: Seuls 4/483 (0,8 %) des patients présentant des vertiges isolés ont eu un AVC dans les 90 jours, contre 320/11 024 (2,9 %) de ceux présentant un signe ou symptôme neurologique focal (RR 0,29, IC 95 % 0,11-0,76). Au cours des 90 premiers jours, les deux groupes diffèrent significativement en termes de probabilité d'AVC (p = 0,007). L'AIT ultérieur était également significativement moins fréquent dans le groupe des vertiges isolés (1,7 % contre 5,6 %, p = 0,001) avec un risque relatif de 0,30 (IC 95 % 0,15-0,60). CONCLUSIONS: Le risque d'AVC ultérieur après une présentation aux urgences pour un AIT est faible lorsque les symptômes présentés sont des étourdissements isolés.

Predictors of neurologists confirming or overturning emergency physicians' diagnosis of TIA or stroke.

BACKGROUND: Transient ischemic attack (TIA) and non-disabling stroke are common emergency department (ED) presentations. Currently, there are no prospective multicenter studies determining predictors of neurologists confirming a diagnosis of cerebral ischemia in patients discharged with a diagnosis of TIA or stroke. The objectives were to (1) calculate the concordance between emergency physicians and neurologists for the outcome of diagnosing TIA or stroke, and (2) identify characteristics associated with neurologists diagnosing a stroke mimic. METHODS: This was a planned sub-study of a prospective cohort study at 14 Canadian EDs enrolling patients diagnosed with TIA or non-disabling stroke from 2006 to 2017. Logistic regression was used to identify factors associated with neurologists' diagnosis of cerebral ischemia. Our primary outcome was the composite outcome of cerebral ischemia (TIA or non-disabling stroke) based on the neurologists' assessment. RESULTS: The diagnosis of cerebral ischemia was confirmed by neurologists in 5794 patients (55.4%). The most common identified stroke mimics were migraine (18%), peripheral vertigo (7%), syncope (4%), and seizure (3%). Over a third of patients (38.4%) ultimately had an undetermined aetiology for their symptoms. The strongest predictors of cerebral ischemia confirmation were infarct on CT (OR 1.83, 95% CI 1.65-2.02), advanced age (OR comparing 75th-25th percentiles 1.67, 1.55-1.80), language disturbance (OR 1.92, 1.75-2.10), and smoking (OR 1.67, 1.46-1.91). The strongest predictors of stroke mimics were syncope (OR 0.59, 0.48-0.72), vertigo (OR 0.52, 0.45-0.59), bilateral symptoms (OR 0.60, 0.50-0.72), and confusion (OR 0.50, 0.44-0.57). CONCLUSION: Physicians should have a high index of suspicion of cerebral ischemia in patients with advanced age, smoking history, language disturbance, or infarcts on CT. Physicians should discriminate in which patients to pursue stroke investigations on when deemed at minimal risk of cerebral ischemia, including those with isolated vertigo, syncope, or bilateral symptoms.

RéSUMé: CONTEXTE: L'accident ischémique transitoire (AIT) et l'accident vasculaire cérébral (AVC) non invalidant sont des présentations courantes dans les services d'urgence. Actuellement, il n'existe pas d'études prospectives multicentriques déterminant les facteurs prédictifs de la confirmation par les neurologues d'un diagnostic d'ischémie cérébrale chez les patients sortis de l'hôpital avec un diagnostic d'AIT ou d'AVC. Les objectifs étaient de (1) calculer la concordance entre les urgentistes et les neurologues pour le résultat du diagnostic de l'AIT ou de l'AVC, et (2) identifier les caractéristiques associées au diagnostic par les neurologues d'une imitation d'AVC. MéTHODES: Il s'agissait d'une sous-étude planifiée d'une étude de cohorte prospective dans 14 services d'urgence canadiens recrutant des patients diagnostiqués avec un AIT ou un AVC non invalidant de 2006 à 2017. Une régression logistique a été utilisée pour identifier les facteurs associés au diagnostic d'ischémie cérébrale par les neurologues. Notre résultat principal était le résultat composite de l'ischémie cérébrale (AIT ou accident vasculaire cérébral non invalidant) selon l'évaluation des neurologues. RéSULTATS: Le diagnostic d'ischémie cérébrale a été confirmé par des neurologues chez 5 794 patients (55,4 %). Les imitateurs d'AVC identifiés les plus courants étaient la migraine (18 %), le vertige périphérique (7 %), la syncope (4 %) et les convulsions (3 %). Plus d'un tiers des patients (38,4 %) avaient finalement une étiologie indéterminée pour leurs symptômes. Les prédicteurs les plus forts de la confirmation de l'ischémie cérébrale étaient l'infarctus au scanner (OR 1.83, IC 95 % 1.65­2.02), l'âge avancé (OR comparant les 75e et 25e percentiles 1.67, 1.55­1.80), les troubles du langage (OR 1.92, 1.75­2.10) et le tabagisme (OR 1.67, 1.46­1.91). Les prédicteurs les plus forts d'imitateurs d'AVC étaient la syncope (OR 0.59, 0.48­0.72), le vertige (OR 0.52, 0.45­0.59), les symptômes bilatéraux (OR 0.60, 0.50­0.72) et la confusion (OR 0.50, 0.44­0.57). CONCLUSION: Les médecins devraient avoir un indice élevé de suspicion d'ischémie cérébrale chez les patients ayant un âge avancé, des antécédents de tabagisme, des troubles du langage ou des infarctus au scanner. Les médecins doivent distinguer les patients sur lesquels poursuivre des investigations sur un AVC lorsqu'ils sont jugés à risque minimal d'ischémie cérébrale, y compris ceux présentant des vertiges isolés, une syncope ou des symptômes bilatéraux.

Heart donation and transplantation after circulatory determination of death: expert guidance from a Canadian consensus building process.

Controlled donation after circulatory determination of death (DCD), where death is determined after cardiac arrest, has been responsible for the largest quantitative increase in Canadian organ donation and transplants, but not for heart transplants. Innovative international advances in DCD heart transplantation include direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). After death is determined, DPP involves removal and reanimation of the arrested heart on an ex situ organ perfusion system. Normothermic regional perfusion involves surgically interrupting (ligating the aortic arch vessels) brain blood flow after death determination, followed by restarting the heart and circulation in situ using extracorporeal membrane oxygenation. The objectives of this Canadian consensus building process by a multidisciplinary group of Canadian stakeholders were to review current evidence and international DCD heart experience, comparatively evaluate international protocols with existing Canadian medical, legal, and ethical practices, and to discuss implementation barriers. Review of current evidence and international experience of DCD heart donation (DPP and NRP) determined that DCD heart donation could be used to provide opportunities for more heart transplants in Canada, saving additional lives. Although candid discussion identified a number of potential barriers and challenges for implementing DCD heart donation in Canada, it was determined that DPP implementation is feasible (pending regulatory approval for the use of an ex situ perfusion device in humans) and in alignment with current medical guidelines for DCD. Nevertheless, further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

RéSUMé: Le don contrôlé après un décès circulatoire (DDC), cas dans lequel le décès est déterminé après un arrêt cardiaque, est à l'origine de la plus forte augmentation quantitative des dons et des transplantations d'organes au Canada, sauf pour les transplantations cardiaques. Parmi les progrès internationaux novateurs dans la transplantation cardiaque après DDC, citons l'obtention directe et perfusion (ODP) et la circulation régionale normothermique (CRN). Une fois le décès déterminé, l'ODP consiste à retirer et réanimer le cœur arrêté sur un système de perfusion ex situ. La circulation régionale normothermique consiste à interrompre de manière chirurgicale (en ligaturant les vaisseaux de l'arc aortique) le flux sanguin au cerveau après la détermination du décès, puis à redémarrer le cœur et la circulation in situ utilisant l'oxygénation par membrane extracorporelle (ECMO). Les objectifs de ce processus canadien d'établissement de consensus par un groupe multidisciplinaire d'intervenants canadiens étaient d'examiner les données probantes et les expériences internationales actuelles en matière de DDC, d'évaluer comparativement les protocoles internationaux par rapport aux pratiques médicales, juridiques et éthiques canadiennes existantes, et de discuter des obstacles à la mise en œuvre de tels protocoles. L'examen des données probantes et des expériences internationales actuelles en matière de don de cœur après DDC (ODP et CRN) a permis de déterminer que le don de cœur après DDC pourrait être utilisé afin de faire de plus nombreuses transplantations cardiaques au Canada, sauvant ainsi des vies supplémentaires. Bien que des discussions aient permis d'identifier plusieurs obstacles et défis potentiels à la mise en œuvre du don cardiaque après DDC au Canada, il a été déterminé que la mise en œuvre de l'ODP est réalisable (en attente de l'approbation réglementaire pour l'utilisation d'un dispositif de perfusion ex situ chez l'humain) et en accord avec les directives médicales actuelles concernant le DDC. Néanmoins, d'autres travaux sont nécessaires pour évaluer la conformité de la CRN aux politiques canadiennes actuelles de détermination de la mort et pour garantir l'absence de perfusion cérébrale au cours de ce processus.

Canadian stroke best practice recommendations: Management of Spontaneous Intracerebral Hemorrhage, 7th Edition Update 2020.

Spontaneous intracerebral hemorrhage is a particularly devastating type of stroke with greater morbidity and mortality compared with ischemic stroke and can account for half or more of all deaths from stroke. The seventh update of the Canadian Stroke Best Practice Recommendations includes a new stand-alone module on intracerebral hemorrhage, with a focus on elements of care that are unique or affect persons disproportionately relative to ischemic stroke. Prior to this edition, intracerebral hemorrhage was included in the Acute Stroke Management module and was limited to its management during the first 12 h. With the growing evidence on intracerebral hemorrhage, a separate module focused on this topic across the care continuum was added. In addition to topics related to initial clinical management, neuroimaging, blood pressure management, and surgical management, new sections have been introduced addressing topics surrounding inpatient complications such as venous thromboembolism, seizure management, and increased intracranial pressure, rehabilitation as well as issues related to secondary management including lifestyle management, maintaining a normal blood pressure and antithrombotic therapy, are addressed. The Canadian Stroke Best Practice Recommendations (CSBPR) are intended to provide up-to-date evidence-based guidelines for the prevention and management of stroke and to promote optimal recovery and reintegration for people who have experienced stroke, including patients, families, and informal caregivers.

Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project.

IMPORTANCE: There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries. OBJECTIVE: To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel. PROCESS: Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery. EVIDENCE SYNTHESIS: Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed. RECOMMENDATIONS: Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing. Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability. CONCLUSIONS AND RELEVANCE: This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.

CAEP Position Statement - Management of devastating brain injuries in the emergency department: Enhancing neuroprognostication and maintaining the opportunity for organ and tissue donation.

The primary purpose of this statement is to improve neuroprognostication after devastating brain injury (DBI), with a secondary benefit of potential organ and tissue donation.

Milrinone for refractory cerebral vasospasm with delayed cerebral ischemia.

OBJECTIVE: Intravenous (IV) milrinone is a promising option for the treatment of cerebral vasospasm with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, data remain limited on the efficacy of treating cases that are refractory to standard therapy with IV milrinone. The aim of this study was to determine predictors of refractory vasospasm/DCI despite treatment with IV milrinone, and to analyze the outcome of rescue therapy with intraarterial (IA) milrinone and/or mechanical angioplasty. METHODS: The authors conducted a retrospective cohort study of all patients with aSAH admitted between 2010 and 2016 to the Montreal Neurological Institute and Hospital. Patients were stratified into 3 groups: no DCI, standard therapy, and rescue therapy. The primary outcome was frequency of DCI-related cerebral infarction identified on neuroimaging before hospital discharge. Secondary outcomes included functional outcome reported as modified Rankin Scale (mRS) score, and segment reversal of refractory vasospasm. RESULTS: The cohort included 322 patients: 212 in the no DCI group, 89 in the standard therapy group, and 21 in the rescue therapy group. Approximately half (52%, 168/322) were admitted with poor-grade aSAH at treatment decision (World Federation of Neurosurgical Societies grade III-V). Among patients with DCI and imaging assessing severity of vasospasm, 62% (68/109) had moderate/severe radiological vasospasm on DCI presentation. Nineteen percent (21/110) of patients had refractory vasospasm/DCI and were treated with rescue therapy. Targeted rescue therapy with IA milrinone reversed 32% (29/91) of the refractory vasospastic vessels, and 76% (16/21) of those patients experienced significant improvement in their neurological status within 24 hours of initiating therapy. Moderate/severe radiological vasospasm independently predicted the need for rescue therapy (OR 27, 95% CI 8.01-112). Of patients with neuroimaging before discharge, 40% (112/277) had developed new cerebral infarcts, and only 21% (23/112) of these were vasospasm-related. Overall, 65% (204/314) of patients had a favorable functional outcome (mRS score 0-2) assessed at a median of 4 months (interquartile range 2-8 months) after aSAH, and there was no difference in functional outcome between the 3 groups (p = 0.512). CONCLUSIONS: The aggressive use of milrinone was safe and effective based on this retrospective study cohort and is a promising therapy for the treatment of vasospasm/DCI after aSAH.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: A United Kingdom and Canadian proposal.

There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere.