Admission Hyperglycemia Predicts a Worse Outcome in Stroke Patients Treated With Intravenous Thrombolysis

OBJECTIVE: Admission hyperglycemia has been associated with worse outcomes in ischemic stroke. We hypothesized that hyperglycemia (glucose >8.0 mmol/l) in the hyperacute phase would be independently associated with increased mortality, symptomatic intracerebral hemorrhage (SICH), and poor functional status at 90 days in stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). RESEARCH DESIGN AND METHODS: Using data from the prospective, multicenter Canadian Alteplase for Stroke Effectiveness Study (CASES), the association between admission glucose >8.0 mmol/l and mortality, SICH, and poor functional status at 90 days (modified Rankin Scale >1) was examined. Similar analyses examining glucose as a continuous measure were conducted. RESULTS: Of 1,098 patients, 296 (27%) had admission hyperglycemia, including 18% of those without diabetes and 70% of those with diabetes. After multivariable logistic regression, admission hyperglycemia was found to be independently associated with increased risk of death (adjusted risk ratio 1.5 [95% CI 1.2-1.9]), SICH (1.69 [0.95-3.00]), and a decreased probability of a favorable outcome at 90 days (0.7 [0.5-0.9]). An incremental risk of death and SICH and unfavorable 90-day outcomes was observed with increasing admission glucose. This observation held true for patients with and without diabetes. CONCLUSIONS: In this cohort of IV-tPA-treated stroke patients, admission hyperglycemia was independently associated with increased risk of death, SICH, and poor functional status at 90 days. Treatment trials continue to be urgently needed to determine whether this is a modifiable risk factor for poor outcome

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration: A united approach

Item does not contain fulltextCerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE)

APOE/TOMM40 genetic loci, white matter hyperintensities and cerebral microbleeds

Background: Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease. Aim and/or hypothesis: To test for independent associations between two Alzheimer's disease-susceptibility gene loci – APOE ε and the TOMM40 ‘523’ poly-T repeat – and white matter hyperintensities/cerebral microbleed burden in community-dwelling older adults. Methods: Participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 0·7; range = 71–74). Results: No significant effects of APOE ε or TOMM40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants. Conclusions: Lack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature

Reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndromes (RCVS) are a group of disorders that have in common an acute presentation with headache, reversible vasoconstriction of cerebral arteries, with or without neurological signs and symptoms. In contrast to primary central nervous system vasculitis, they have a relatively benign course. We describe here a patient who was diagnosed with RCVS

Protocol for LASER: A Randomized Evaluation and an Associated Registry of Early Anticoagulation With Edoxaban After Ischemic Stroke in Patients With Atrial Fibrillation

Background: The optimal timing of anticoagulation after stroke in patients with atrial fibrillation (AF) is unknown. Aim and Hypothesis: Our primary aim is to demonstrate the safety of edoxaban initiation within 5 days of AF related stroke. Our secondary aim is to determine predictors of hemorrhagic transformation (HT) after AF related stroke. We hypothesize that the rate of radiological HT will not be increased in patients starting edoxaban within 5 days of AF related stroke, relative to those in whom initiation is delayed. We hypothesize that the risk of HT in patients treated with edoxaban can be predicted using RNA expressed in leukocytes at time of stroke. Methods and Design: LASER (Lixiana Acute Stroke Evaluation Registry) is a randomized controlled trial with an associated registry (clinicaltrials.gov NCT03494530). One hundred and fifty patients with ischemic stroke and AF will undergo baseline Computed Tomography (CT) scan and will be randomized 2:1 within 5 days of symptom onset to early (≤5 days, n = 100) or delayed (6–14 days, n = 50) edoxaban initiation. Participants will undergo clinical assessment and repeat CT at 7 days and clinical assessment at 90 days. Study Outcomes: The primary outcome is the rate of incident radiological HT. Secondary outcomes include symptomatic HT, recurrent ischemic stroke, recurrent sub-clinical infarcts on follow up CT, systemic hemorrhagic complication rate, National Institute of Health Stroke Scale and modified Rankin Scale at day 7 and 90, mortality within 90 days, quality of life assessments at day 90, and predictors of HT, including RNA expression by 6 pre-selected candidate genes. Discussion: Event rates for both HT and recurrent ischemic events, in patients treated with early vs. delayed edoxaban initiation are unknown. The primary study endpoint of LASER is an objective performance criterion relevant to clinical decision making in patients with AF related stroke. This study will provide data required for a definitive safety/efficacy study sample size power calculation