Presentation of Neuro-COVID is Broad and Pathogenesis Diverse

Abstract

To the Editor: With interest we read the review article by Valiuddin et al. about the neurological implications of coronavirus disease 2019 (COVID-19) (neuro-COVID).1 The authors listed ischemic stroke, transverse myelitis, seizures, acute hemorrhaghic necrotising encephalopathy (AHNE), acute disseminated encephalo-myelitis (ADEM), posterior reversible encephalopathy syndrome (PRES), myasthenia, and sinus venous thrombosis as central nervous system (CNS) manifestations, and hyposmia/hypogeusia, Guillain-Barré syndrome, facial palsy, ophthalmoparesis, and neuropathy, as peripheral nervous system (PNS) manifestations of COVID-19.1 We have the following comments and concerns. The review is comprehensive but does not include the entire spectrum of neuro-COVID-19. Several neurological manifestations of COVID-19 in the CNS and PNS were not discussed. CNS disorders not included in the review were intracerebral bleeding,2 cerebral vasculitis,3 acute cerebral demyelination,4 headache,5 myoclonus-ataxia syndrome,6 limbic encephalitis,7 cytokine release syndrome,8 delirium,9 and psychosis.10 Peripheral nervous system disorders not included in the review were isolated oculomotor, trochlear, facial, or hypoglossal nerve palsy,11 myositis/ dermatomyositis,12 myopathy,13 and rhabdomyolysis.14 There was no discussion about the putative delineation between neurological disorders due to direct attack of the virus (primary manifestations), secondary CNS/PNS disorders due to the immune response (secondary manifestations), and those occurring as a side effect of the treatment or involvement of other organs than the CNS (tertiary manifestations). Whether such a distinction is truly permissible is under debate. Limited data from animal and basic science research are currently available. Disregarding this debate, there are indications that the virus enters the CNS via the blood brain barrier (BBB) or via retrograde invasion along peripheral nerves, as mentioned in the review.1,15 There are even indications that the virus disrupts the BBB.16 Interestingly, in most of the CNS disorders claimed to have been triggered by direct contact of the virus Klinik Landstrasse, Messerli Institute, Department of Neurology, Vienna, Austria