Large and Small Cerebral Vessel Involvement in Severe COVID-19

Abstract

Background and Purpose: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. Methods: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. Results: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. Conclusions: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Neuropathologic findings of patients with COVID-19: a systematic review

“…Out of the total 165 cases in the literature included in this review, only 146 patients were included in the synthesis; 19 of these cases did not undergo a pathological study of the brain and were excluded in the final analysis [ 14 , 24 ]. The demographic data are summarized in Table 1 .…”

“…SARS-CoV-2 reactivity in brain sections of these patients was positive in only 15.1% ( n =22) [ 13 , 18 ]. Most patients tested negative in SARS-CoV-2 immunohistochemistry ( n =70, 47.9%) [ 11 , 13 , 15 , 16 , 18 , 24 ], while the rest was unreported ( n =54, 37%) [ 11 , 12 , 14 , 17 , 19 – 23 ]. No pathologic findings concerning the peripheral nervous system (PNS) were reported.…”

“…These infarctions were demonstrated in the cortical and deep-seated areas like the basal ganglia and the brainstem, and even in watershed areas. There was evidence of intracranial bleeding localized in the cerebellum ( n =3, 2.1%) [ 14 , 16 ]. Uncal and tonsillar herniation was seen in one patient (0.7%) [ 23 ].…”

SARS-CoV-2/COVID-19 in multiple sclerosis patients receiving disease-modifying therapy

“…According to Mahammedi's observations in patients with COVID-19, brain MRI also shows posterior reversible encephalopathy syndrome (PRES), hypoxic ischaemic encephalopathy, cerebral venous thrombosis, Guillian-Barre syndrome, and Miller-Fisher syndrome [ 51 ]. Initially, ischaemic and haemorrhagic complications were reported in COVID-19 patients [ 52 , 53 ]. At present, there are also described the uneven demyelinating lesions in the brain and spinal cord, which are considered complications of SARS-CoV-2 infection [ 54 , 55 ].…”

Neurological infections in 2020: COVID-19 takes centre stage

“…Nevertheless, it has become clear that there is a striking incidence of neurological involvement in this disease, the symptoms of which span reversible anosmia, stroke-related disability, and death. 1 , 2 , 3 …”