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2020 ; 19
(9
): 767-783
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Neurological associations of COVID-19
#MMPMID32622375
Ellul MA
; Benjamin L
; Singh B
; Lant S
; Michael BD
; Easton A
; Kneen R
; Defres S
; Sejvar J
; Solomon T
Lancet Neurol
2020[Sep]; 19
(9
): 767-783
PMID32622375
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BACKGROUND: The COVID-19 pandemic, caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza
pandemic. Although the predominant clinical presentation is with respiratory
disease, neurological manifestations are being recognised increasingly. On the
basis of knowledge of other coronaviruses, especially those that caused the
severe acute respiratory syndrome and Middle East respiratory syndrome epidemics,
cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be
expected to be rare. RECENT DEVELOPMENTS: A growing number of case reports and
series describe a wide array of neurological manifestations in 901 patients, but
many have insufficient detail, reflecting the challenge of studying such
patients. Encephalopathy has been reported for 93 patients in total, including 16
(7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of
58 patients in intensive care with COVID-19 in France. Encephalitis has been
described in eight patients to date, and Guillain-Barré syndrome in 19 patients.
SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are
common, and can occur in the absence of other clinical features. Unexpectedly,
acute cerebrovascular disease is also emerging as an important complication, with
cohort studies reporting stroke in 2-6% of patients hospitalised with COVID-19.
So far, 96 patients with stroke have been described, who frequently had vascular
events in the context of a pro-inflammatory hypercoagulable state with elevated
C-reactive protein, D-dimer, and ferritin. WHERE NEXT?: Careful clinical,
diagnostic, and epidemiological studies are needed to help define the
manifestations and burden of neurological disease caused by SARS-CoV-2. Precise
case definitions must be used to distinguish non-specific complications of severe
disease (eg, hypoxic encephalopathy and critical care neuropathy) from those
caused directly or indirectly by the virus, including infectious,
para-infectious, and post-infectious encephalitis, hypercoagulable states leading
to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of
neurological disease associated with SARS-CoV-2 in patients whose respiratory
infection is mild or asymptomatic might prove challenging, especially if the
primary COVID-19 illness occurred weeks earlier. The proportion of infections
leading to neurological disease will probably remain small. However, these
patients might be left with severe neurological sequelae. With so many people
infected, the overall number of neurological patients, and their associated
health burden and social and economic costs might be large. Health-care planners
and policy makers must prepare for this eventuality, while the many ongoing
studies investigating neurological associations increase our knowledge base.
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