Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians.

INTRODUCTION: The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses. MATERIAL AND METHODS: Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles. RESULTS: We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n=13), acute necrotizing encephalopathy (ANE, n=4), Bickerstaff's encephalitis (n=5), generalized myoclonus (n=3) and acute transverse myelitis (n=7); other encephalitis including limbic encephalitis (n=9) and miscellaneous encephalitis with variable radiologic findings (n=26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n=17), cerebral venous thrombosis (n=8) and posterior reversible encephalopathy (n=5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain-Barré syndrome (n=31) and variants including Miller Fisher syndrome (n=3), polyneuritis cranialis (n=2) and facial diplegia (n=2); isolated oculomotor neuropathy (n=6); critical illness myopathy (n=6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff's encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain-Barré Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients. CONCLUSION: The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2.

Early neurological deterioration following thrombolysis for minor stroke with isolated internal carotid artery occlusion.

BACKGROUND AND PURPOSE: Better understanding the incidence, predictors and mechanisms of early neurological deterioration (END) following intravenous thrombolysis (IVT) for acute stroke with mild symptoms and isolated internal carotid artery occlusion (iICAo) may inform therapeutic decisions. METHODS: From a multicenter retrospective database, we extracted all patients with both National Institutes of Health Stroke Scale (NIHSS) score <6 and iICAo (i.e. not involving the Willis circle) on admission imaging, intended for IVT alone. END was defined as ≥4 NIHSS points increase within 24 h. END and no-END patients were compared for (i) pre-treatment clinical and imaging variables and (ii) occurrence of intracranial occlusion, carotid recanalization and parenchymal hemorrhage on follow-up imaging. RESULTS: Seventy-four patients were included, amongst whom 22 (30%) patients experienced END. Amongst pre-treatment variables, suprabulbar carotid occlusion was the only admission predictor of END following stepwise variable selection (odds ratio = 4.0, 95% confidence interval: 1.3-12.2; P = 0.015). On follow-up imaging, there was no instance of parenchymal hemorrhage, but an intracranial occlusion was now present in 76% vs. 0% of END and no-END patients, respectively (P < 0.001), and there was a trend toward higher carotid recanalization rate in END patients (29% vs. 9%, P = 0.07). As compared to no-END, END was strongly associated with a poor 3-month outcome. CONCLUSIONS: Early neurological deterioration is a frequent and highly deleterious event after IVT for minor stroke with iICAo, and is of thromboembolic origin in three out of four patients. The strong association with iICAo site-largely a function of underlying stroke etiology-may point to a different response of the thrombus to IVT. These findings suggest END may be preventable in this setting.

Large vessel stroke in six patients following SARS-CoV-2 infection: a retrospective case study series of acute thrombotic complications on stable underlying atherosclerotic disease.

BACKGROUND AND PURPOSE: Ischaemic stroke has been described in association with COVID-19. Several pathophysiological mechanisms have been suggested, i.e. prothrombotic state, cardiac injury etc. It was sought to assess the potential association between ischaemic stroke associated with SARS-CoV-2 infection and underlying atherosclerotic lesions. METHODS: A retrospective analysis of stroke related to large vessel occlusion was conducted amongst patients with SARS-CoV-2 infection and underlying mild atherosclerotic disease, between 19 March and 19 April 2020 in six different stroke centers in the Île-de France area, France. RESULTS: The median age was 52 years, median body mass index was 29.5 kg/m2 . All patients displayed previous vascular risk factors such as high blood pressure, diabetes, dyslipidemia or body mass index > 25. The delay between the first respiratory symptoms of COVID-19 and stroke was 11.5 days. At baseline, all had tandem occlusions, i.e. intracerebral and extracerebral thrombus assessed with computed tomography or magnetic resonance imaging. Cases displayed a large thrombus in the cervical carotid artery with underlying mild non-stenosing atheroma, after an etiological workup based on angio-computed tomography or magnetic resonance imaging and/or cervical echography. CONCLUSION: Our study should alert clinicians to scrutinize any new onset of ischaemic stroke during COVID-19 infection, mainly in patients with vascular risk factors or underlying atherosclerotic lesions.