Objective. To analyze the spectrum and characteristics of neurological manifestations associated with SARS-CoV-2 infection. Methods. We conducted a nationwide, multicentric, retrospective study during the French COVID-19 epidemic in March-April 2020. All COVID-19 patients with de novo neurological manifestations were eligible. Results. We included 222 COVID-19 patients with neurological manifestations from 46 centers throughout the country. Median age was 65 years (IQR 53-72), and 136 patients (61.3%) were male. COVID-19 was severe or critical in almost half of the patients (102, 45.2%). Brain imaging was performed in 192 patients (86.5%), including 157 MRI (70.7%). Cerebrospinal fluid was analyzed in 97 patients (43.7%), with positive SARS-CoV-2 PCR in 2 out of 75 tested (2.7%). The most common neurological diseases were COVID-19 associated encephalopathy (CAE, 67/222, 30.2%), acute ischemic cerebrovascular syndrome (AICS, 57/222, 25.7%), encephalitis (21/222, 9.5%), and Guillain-Barre Syndrome (GBS, 15/222, 6.8%). Neurological manifestations appeared after first COVID-19 symptoms with a median delay of 6 days in CAE, 7 days in encephalitis, 12 days in AICS and 18 days in GBS. Around 25% of CAE and AICS were inaugural and 30% of CAE and encephalitis were diagnosed after discontinuation of sedation. Less common manifestations were also described, including meningitis and cranial neuropathy. The median follow-up of the patients was 24 days, with a particularly high short-term mortality rate in patients with CAE and AICS (19/124, 15.3%). Interpretation. Neurological manifestations associated with COVID-19 mainly included CAE, AICS, encephalitis and GBS. Clinical spectrum and outcomes were broad and heterogeneous, suggesting different underlying pathogenic processes.
Background Hyperintense Acute Reperfusion Marker (HARM) is a hyperintense subarachnoid signal on FLAIR MRI sequence caused by gadolinium contrast leakage into the subpial space. While, on FLAIR, HARM may mimic subarachnoid hemorrhage, it is differentiated from it on computed tomography (CT) and SWAN MRI sequences. Cerebral microbleeds are black, rounded spots on SWAN caused by blood-products deposition following red blood cell leakage from small cerebral vessels brain. Both microbleeds and HARM carry important prognostic implication as they are associated with blood-brain barrier disruption and an increased risk of intracerebral hemorrhage. Case presentation A 79-year-old man presented with aphasia and right hemiparesis due to ischemic stroke with left middle cerebral artery occlusion. Admission NIHSS score was 7, and he was successfully treated by intravenous thrombolysis and mechanical thrombectomy. On day 1, his clinical condition worsened, and he had an urgent gadolinium-enhanced MRI. There was no evidence of early recurrence, nor of hemorrhage on SWAN or on FLAIR. Left middle cerebral artery was permeable. The patient was anticoagulated for newly diagnosed atrial fibrillation, and a second MRI following a generalized tonic-clonic seizure showed multiple left hemispheric diffusion-weighted imaging (DWI) hyperintense spots and a left hemispheric sub-arachnoid hyperintensity on FLAIR, compatible with a subarachnoid hemorrhage. This diagnosis was excluded by SWAN MRI sequence and a normal cerebral CT the same day. The diagnosis of HARM was retained. At day 9, patient’s condition improved, and a control MRI did not show evidence of HARM. However, numerous microbleeds were detected in the left hemisphere only (ipsilateral with HARM and stroke). Conclusions This case highlights first of all the importance of differentiating HARM and subarachnoid hemorrhage, especially in an anticoagulated patient with clinical aggravation. Secondly, it is crucial to identify microbleeds and understand their pathophysiology, as they are associated with higher risk of hemorrhage and stroke recurrence in ischemic stroke patients. Finally, the mono-hemispheric appearance of microbleeds in this case suggests for the first time that, in some acute ischemic stroke patients, a relationship between HARM and cerebral microbleeds may exist.
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