Objective To describe neuroimaging findings and to report the epidemiological and clinical characteristics of COVID-19 patients with neurological manifestations. Methods In this retrospective multicenter study (10 Hospitals), we included 64 confirmed COVID-19 patients with neurologic manifestations who underwent a brain MRI. Results The cohort included 43 men (67%), 21 women (33%), and the median age was 66 years (range: 20-92). 36 (56%) brain MRIs were considered abnormal, possibly related to SARS-CoV-2. Ischemic strokes (27%), leptomeningeal enhancements (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurological manifestation, following by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from the other patients with abnormal brain imaging since the former had less frequently acute respiratory distress syndrome (p=0·006) and more frequently corticospinal tract signs (p=0·02). Patients with encephalitis were younger (p=0·007), whereas agitation was more frequent for patients with leptomeningeal enhancements (p=0·009). Conclusions COVID-19 patients may develop a wide range of neurological symptoms, which can be associated with severe and fatal complications, such as ischemic stroke or encephalitis. Concerning the meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology rather seems to involve an immune and/or inflammatory process given the presence of signs of inflammation in both cerebrospinal fluid and neuroimaging but the lack of virus in cerebrospinal fluid.

 

Figure e-1: Ischemic stroke. Axial diffusion (a), SWI (b), 3D TOF MR angiography (c). Man aged 71 years: right fronto-insular diffusion cortico-subcortical hyperintensity (arrow) corresponding to middle cerebral artery acute ischemic stroke.  Middle cerebral artery SWI hypointensity (star) (b) corresponding to a thrombus inducing arterial occlusion (cross)

 

Figure e-2: Radiological acute hemorrhagic necrotizing encephalopathy. Man aged 66 years: axial diffusion (a) Apparent Diffusion Coefficient (ADC) map (b), axial SWI (c,d), axial FLAIR (e), sagittal FLAIR (f). Left frontal intracerebral hematoma (cross). Corpus callosum FLAIR and diffusion signal abnormalities with ADC decrease (star) corresponding to cytotoxic edema. Peri hematoma and corpus callosum, multiple microhemorrhage on SWI weighted MR images (arrow).

 

Figure e-3: Multiple correspondence analysis: considering each clinical manifestation separately, subjects can be distinguished mainly based on a global pattern depending on their oxygen requirement, seizure, gender, headaches, history of autoimmune disease, history of seizure, age, anosmia, confusion and disturbances of consciousness.    References: 0=absence; 1=presence; HSt= history of seizures; O2= oxygen therapy; OtherH= another neurological history; Seiz= Seizures; CST= corticospinal tract involvement; HA= headaches; HAI= history of autoimmune diseases; HHM= history of hematological malignancies; HSeiz= history of seizures; Agit= agitation; Agueus= ageusia; Anos= anosmia; Conf= Confusion; Consc= disturbance of consciousness