COVID-19—White matter and globus pallidum lesions

Brun, Gilles; Hak, Jean-François; Coze, S.; Kaphan, Elsa; Carvelli, Julien; Girard, Nadine; Stellmann, Jan‐Patrick

doi:10.1212/nxi.0000000000000777

Cited by 61 publications

(32 citation statements)

References 7 publications

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“…Small-vessel CNS vasculitis was present as a result of presumably direct viral infection of endothelial cells based on a radiological finding of gadolinium-enhanced white matter lesions. Similar findings occurred in one case in the UK-wide cohort [90,99].…”

Section: -Clinical Phenotypesupporting

confidence: 84%

Endothelial Dysfunction in COVID-19: Lessons Learned from Coronaviruses

et al. 2020

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Purpose of Review To review current literature on endothelial dysfunction with previous coronaviruses, and present available data on the role of endothelial dysfunction in coronavirus disease-2019 (COVID-19) infection in terms of pathophysiology and clinical phenotype Recent Findings Recent evidence suggests that signs and symptoms of severe COVID-19 infection resemble the clinical phenotype of endothelial dysfunction, implicating mutual pathophysiological pathways. Dysfunction of endothelial cells is believed to mediate a variety of viral infections, including those caused by previous coronaviruses. Experience from previous coronaviruses has triggered hypotheses on the role of endothelial dysfunction in the pathophysiology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which are currently being tested in preclinical and clinical studies. Summary Endothelial dysfunction is the common denominator of multiple clinical aspects of severe COVID-19 infection that have been problematic for treating physicians. Given the global impact of this pandemic, better understanding of the pathophysiology could significantly affect management of patients.

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Section: -Clinical Phenotypesupporting

confidence: 84%

Endothelial Dysfunction in COVID-19: Lessons Learned from Coronaviruses

et al. 2020

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“…SARS-COV-2 induces endothelial dysfunction [23] and infects vascular beds in multiple tissues [24]. Cerebral white matter is particularly vulnerable to changes in cerebral blood flow, as would be expected in association with diffuse small vessel dysfunction and has been reported in COVID-19 [68][69][70]. The integrity of subcortical white matter is critically important for maintenance of cognitive function [71,72], and one of the consequences of white matter damage in COVID-19 is likely to be cognitive impairment.…”

Section: The Types Of Cerebral Ischaemic Damage Seen In Covid-19 Are mentioning

confidence: 90%

Cognitive impact of COVID-19: looking beyond the short term

2020

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COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence of central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It is unclear how much of the ischaemic damage is mediated by direct or inflammatory effects of virus on the CNS vasculature and how much is secondary to extracranial cardiorespiratory disease. Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted. Several aspects of COVID-19 are likely to impact on cognition. Cerebral white matter is particularly vulnerable to ischaemic damage in COVID-19 and is also critically important for cognitive function. There is accumulating evidence that cerebral hypoperfusion accelerates amyloid-β (Aβ) accumulation and is linked to tau and TDP-43 pathology, and by inducing phosphorylation of α-synuclein at serine-129, ischaemia may also increase the risk of development of Lewy body disease. Current therapies for COVID-19 are understandably focused on supporting respiratory function, preventing thrombosis and reducing immune activation. Since angiotensin-converting enzyme (ACE)-2 is a receptor for SARS-CoV-2, and ACE inhibitors and angiotensin receptor blockers are predicted to increase ACE-2 expression, it was initially feared that their use might exacerbate COVID-19. Recent meta-analyses have instead suggested that these medications are protective. This is perhaps because SARS-CoV-2 entry may deplete ACE-2, tipping the balance towards angiotensin II-ACE-1-mediated classical RAS activation: exacerbating hypoperfusion and promoting inflammation. It may be relevant that APOE ε4 individuals, who seem to be at increased risk of COVID-19, also have lowest ACE-2 activity. COVID-19 is likely to leave an unexpected legacy of long-term neurological complications in a significant number of survivors. Cognitive follow-up of COVID-19 patients will be important, especially in patients who develop cerebrovascular and neurological complications during the acute illness.

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“…The mortality rate was 4.8%. 11 or acute necrotizing encephalopathy [12][13][14] , other nonspecific diffuse involvement of white matter 15,16 , mesio-temporal lesion 10,17 with possible frontoinsular extension, leptomeningeal abnormalities 4 and brainstem lesions 18 . Only two patients in our registry had a positive SARS-CoV-2 PCR in the CSF.…”

Section: Main Neurological Manifestations Associated With Covid-19: Amentioning

confidence: 99%

“…. The remaining patients had neurological manifestations several days after the first COVID-19 symptoms, with a median delay of 6 (IQR 3-8) and 7 (IQR 5-10) days respectively in CAE and encephalitis patients, 12 days (IQR[7][8][9][10][11][12][13][14][15][16][17][18] in AICS and 18 days (IQR 15-28) in GBS. Median age was 65 years (IQR 55-78).…”

mentioning

confidence: 99%