Abstract Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

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Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4–18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4–18] versus 6 [IQR, 3–14]), P =0.03; (odds ratio, 1.69 [95% CI, 1.08–2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2–6] versus 2 [IQR, 1–4], P <0.001) and death (odds ratio, 4.3 [95% CI, 2.22–8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

The higher risk of early recurrent stroke after posterior circulation transient ischaemic attack or minor stroke versus after carotid territory events could be due to a greater prevalence of large artery stenosis, but there have been few imaging studies, and the prognostic significance of such stenoses is uncertain. Reliable data are necessary to determine the feasibility of trials of angioplasty and stenting and to inform imaging strategies. In the first-ever population-based study, we determined the prevalence of > or = 50% apparently symptomatic vertebral and basilar stenosis using contrast-enhanced MRA in consecutive patients, irrespective of age, presenting with posterior circulation transient ischaemic attack or minor ischaemic stroke in the Oxford Vascular Study and related this to the 90-day risk of recurrent transient ischaemic attack and stroke. For comparison, we also determined the prevalence of > or = 50% apparently symptomatic carotid stenosis on ultrasound imaging in consecutive patients with carotid territory events. Of 538 consecutive patients, 141/151 (93%) had posterior circulation events and had vertebral and basilar imaging, of whom 37 (26.2%) had > or = 50% vertebral and basilar stenosis, compared with 41 (11.5%) patients with > or = 50% ipsilateral carotid stenosis in 357/387 (92%) patients with carotid events who had carotid imaging (OR = 2.74; 95% CI = 1.67-4.51; P = 0.002). Presence of > or = 50% vertebral and basilar stenosis was unrelated to age, sex or vascular risk factors and, in contrast to > or = 50% carotid stenosis was not associated with evidence of coronary/peripheral atherosclerosis. In patients with posterior circulation events, > or = 50% vertebral and basilar stenosis was associated multiple transient ischaemic attacks at presentation (22% versus 3%; OR = 9.29; 95% CI = 2.31-37.27; P < 0.001) and with a significantly higher 90-day risk of recurrent events (OR = 3.2; 95% CI = 1.4-7.0; P = 0.006), reaching 22% for stroke and 46% for transient ischaemic attack and stroke. The prevalence of > or = 50% vertebral and basilar stenosis in posterior circulation transient ischaemic attack or minor stroke is greater than the prevalence of > or = 50% carotid stenosis in carotid territory events, and is associated with multiple transient ischaemic attacks at presentation and a high early risk of recurrent stroke. Trials of interventional treatment are therefore likely to be feasible, but more data are required on the long-term risk of stroke on best medical treatment.

That about half of all recurrent strokes during the 7 days after a TIA occur in the first 24 hours highlights the need for emergency assessment. That the ABCD2 score is reliable in the hyperacute phase shows that appropriately triaged emergency assessment and treatment are feasible.

The effects of raised brain lactate levels on neuronal survival following hypoxia or ischemia is still a source of controversy among basic and clinical scientists. We have sought to address this controversy by studying the effects of glucose and lactate on neuronal survival in acute and cultured hippocampal slices. Following a 1-h hypoxic episode, neuronal survival in cultured hippocampal slices was significantly higher if glucose was present in the medium compared with lactate. However, when the energy substrate during the hypoxic period was glucose and then switched to lactate during the normoxic recovery period, the level of cell damage in the CA1 region of organotypic cultures was significantly improved from 64.3 ± 2.1 to 74.6 ± 2.1% compared with cultures receiving glucose during and after hypoxia. Extracellular field potentials recorded from the CA1 region of acute slices were abolished during oxygen deprivation for 20 min, but recovered almost fully to baseline levels with either glucose (82.6 ± 10.0%) or lactate present in the reperfusion medium (108.1 ± 8.3%). These results suggest that lactate alone cannot support neuronal survival during oxygen deprivation, but a combination of glucose followed by lactate provides for better neuroprotection than either substrate alone.

on behalf of the Oxford Vascular StudyBackground and Purpose-Most guidelines now recommend that patients with minor stroke or high-risk transient ischemic attack (TIA) are assessed within 24 hours of their event, but the feasibility of this depends on patients' behavior. We studied behavior immediately after TIA and minor stroke according to clinical characteristics, patients' perception of the nature of the event, and their predicted stroke risk. Methods-In a population-based study in Oxfordshire, UK, with face-to-face interview of 1000 consecutive patients with TIA and minor stroke (National Institutes of Health Stroke Scale Յ5) from 2002 to 2007 (Oxford Vascular Study), we studied delay in seeking medical attention and identified patients who did not seek attention after an initial event and only presented after a recurrent stroke. Results-Of 1000 patients (459 TIAs, 541 minor strokes), 300 (67%) with TIA and 400 (74%) with minor stroke sought medical attention within 24 hours and 208 (47%) and 234 (46%), respectively, sought attention within 3 hours. Most patients (77%) first sought attention through their primary care physician. In patients with TIA, incorrect recognition of symptoms, absence of motor or speech symptoms, shorter duration of event, lower ABCD 2 score, no history of stroke or atrial fibrillation, and weekend presentation were associated with significantly longer delays. However, age, sex, social class, and educational level were all unrelated to either correct recognition of symptoms or to delay in seeking attention. Of 129 patients with TIA or minor stroke who had a recurrent stroke within 90 days, 41 (31%) did not seek medical attention after their initial event. These patients were more likely to have had a TIA (Pϭ0.003), shorter duration of event (Pϭ0.02), and a history of TIA (Pϭ0.09) and less likely to have had motor (Pϭ0.004) or speech symptoms (Pϭ0.04) compared with those patients who sought medical attention for their initial event.Conclusion-Approximately 70% of patients do not correctly recognize their TIA or minor stroke, 30% delay seeking medical attention for Ͼ24 hours, regardless of age, sex, social class, or educational level, and approximately 30% of early recurrent strokes occur before seeking attention. Without more effective public education of all demographic groups, the full potential of acute prevention will not be realized. (Stroke. 2010;41:1108-1114.)