Objective: Case series with different clinical presentations indicating central nervous system (CNS) involvement in coronavirus disease 2019 (COVID-19) have been published. Comprehensive work-ups including clinical characteristics, laboratory, electroencephalography (EEG), neuroimaging and cerebrospinal fluid (CSF) findings are needed to understand the mechanisms. Design: We evaluated 32 consecutive patients with severe SARS-CoV-2 infection treated at a tertiary care centre from March 09 to April 03, 2020 for concomitant severe central nervous system (CNS) symptoms occurring during their critical disease state. Those with CNS disorders were examined in detail regarding clinical characteristics and undergoing additional examinations, e.g. computed tomography (CT), magnetic resonance imaging (MRI), (EEG), (CSF) analysis and autopsy if they had died. Results: Of 32 critically ill patients with COVID-19 eight (18%) had severe CNS involvement (mean [SD] age, 67.6 [6.8] years;seven men;two patients died). All eight patients had cardiovascular risk factors, most frequently arterial hypertension. Two patients presented with lacunar ischemic stroke and one with status epilepticus in the early phase. As most common presentation, six patients presented with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in three of them with additional subarachnoid haemorrhage and in another two with additional small ischemic lesions. In three patients intracranial vessel wall sequence MRI was performed, for the first time to our knowledge. All cases showed contrast-enhancement of vessel walls in large and middle-sized cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. CSF analysis showed normal cells counts and chemistry. RT-PCRs for SARS-CoV-2 in CSF were all negative, and no intrathecal SARS-CoV-2 specific IgG synthesis was detectable. Conclusions: CNS disorders are common in patients with severe COVID-19. Different mechanisms might be involved. Besides unspecific encephalopathy and encephalitic syndromes, large vessel strokes might occur early after disease onset. In a later phase, microbleeds and microinfarctions indicate potential CNS small vessel disease. MRI vessel wall contrast enhancement suggests cerebral vascular wall pathologies with an inflammatory component. CNS disorders associated with COVID-19 may lead to long-term disabilities aggravating socio-economic damage. The mechanisms have to be investigated urgently in order to develop preventive and therapeutic neuroprotective strategies.
Central Nervous System Disorders in Severe SARS-CoV-2 Infection: detailed clinical work-up of eight cases