To the Editor We read with interest the article by Mitsutake et al. about a 59-year-old man with severe acute respiratory syndrome coronavirus-2 infection (SC2I) who shortly afterwards suffered an acute disseminated supra- and infratentorial ischemic stroke (1). Because the patient carried a NOTCH-3 mutation, the stroke was attributed to the genetic defect induced by SC2I (1). Several points have been discussed.
First, we do not agree with the view that middle peduncle infarction is due to cerebral autosomal-dominant arteriopathy with subcortical infarctions and leucoencephalopathy (CADASIL) (1). Even if a patient with acute multifocal ischemic stroke carries a NOTCH3 mutation and their medical history does not show any atherosclerosis risk factors, it is imperative to exclude all other possible causes of ischemic stroke. These include embolic stroke, coagulopathy, and hematological diseases. Was systolic dysfunction excluded in the index patient, was the pro-brain natriuretic peptide value normal, was there a history of cardiac arrhythmias, especially atrial fibrillation, myocarditis, endocarditis, non-compaction, or heart failure?
Second, SC2I is not considered to be a primary cause of acute stroke (1). SC2I is known to be complicated by stroke through various secondary mechanisms. SC2I can be complicated by venous sinus thrombosis and secondary ischemic stroke (2). SC2I can cause multiinflammatory syndrome with a tendency for coagulopathy (3). SC2I has also been reported to cause cerebral vasculitis (4) and myocarditis, which can be complicated by intracardiac thrombus formation or atrial fibrillation. SC2I can also be complicated by endocarditis, which can cause cardioembolic stroke.
Third, the causes of cognitive impairment have not been specified (1). The patient had no apparent dementia or mild cognitive impairment before SC2I but had an IQ of 70, an minimental state examination of 24/30, and a Frontal Assessment Battery score of 9/18 after SC2I (1). Was SC2I responsible for the acute cognitive decline?
Fourth, the cerebrospinal fluid (CSF) has not been extensively studied. Patients with SC2I and central nervous system involvement can have highly upregulated cytokines, chemokines, glial parameters, 14-3-3, neurofilaments, and other factors. To confirm SC2I as the cause of stroke, it would have been useful to examine the CSF for all of these immunological parameters.
In summary, it is conceivable that the stroke in the index patient occurred independently of the NOTCH3 mutation and the stroke was only due to SC2I. Before attributing an acute ischemic stroke in a patient with CADASIL to genetic microangiopathy, all alternative causes must be thoroughly excluded.
The author states that he has no Conflict of Interest (COI).
References
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