Para and Post-COVID-19 CNS Acute Demyelinating Disorders in Children: A Case Series on Expanding the Spectrum of Clinical and Radiological Characteristics

Abstract

Viral infections can serve as a trigger for variable autoimmune, antibody-mediated demyelinating disorders. There is accumulating evidence that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, causing coronavirus disease 2019 (COVID-19) infection and responsible for the current worldwide pandemic, can lead to a cascade of immune-mediated brain and spinal cord demyelinating injuries. However, such observation in the pediatric age group was only reported in very few patients. Thus, the heterogeneous spectrum of this phenomenon in children is still unfolding. We are reporting a case series of five pediatric patients with a variety of acute central nervous system (CNS) demyelinating disorders in the context of acute or recent COVID-19 infection. A 16-year-old female with anti-myelin oligodendrocyte glycoprotein (MOG) disorder, an eight-year-old male with acute disseminated encephalomyelitis (ADEM), a 13-year-old female with neuromyelitis optica spectrum disorder (NMOSD), and two 14 and 13-year-old females with new-onset multiple sclerosis (MS) are reported, all of whom presented acutely following COVID-19 infection. We propose that para and post-infectious CNS demyelinating disorders can potentially follow acute COVID-19 infection in children. Considering SARS-CoV-2 testing as a part of diagnostic workup is possibly useful. Awareness of the presence of this phenomenon can help in the recognition and management of those patients.

COVID-19 and the risk of CNS demyelinating diseases: A systematic review

“…In 10 case reports, AQP4-IgG Abs were positive ( 22 – 27 , 29 , 31 , 86 , 87 ). In two case reports the AQP4 abs were negative ( 30 , 32 ) and each fulfilled the diagnostic criteria for seronegative NMOSD.…”

“…Twelve articles describe post-COVID-19 NMOSD ( 21 – 32 ), 25 describe post-COVID-19 MOGAD ( 33 – 56 ), and 29 describe post-COVID-19 MS ( 57 – 85 ). One paper describes three patients with post-COVID-19 demyelinating events, of which one is NMOSD, one- MOGAD, and one- clinically isolated syndrome (CIS) ( 86 ). Another paper describes various CNS inflammatory diseases, of which three were MOGAD and one—NMOSD ( 87 ).…”

“…Collectively, 13 case reports and one case series describe the occurrence of 18 NMOSD-related clinical events in the context of COVID-19 ( 21 – 32 , 86 , 87 ). Eight patients were females, four were males, and in six cases the patients' sex was not reported.…”

“…Ten case reports describe the onset of newly diagnosed NMOSD in people without previous neurological disease ( 22 – 26 , 28 – 30 , 32 , 87 ). Two case reports describe people with previously undiagnosed neurological disease who then presented with a second clinical manifestation in temporal association to COVID-19, leading to an NMOSD diagnosis ( 27 , 86 ). In one case, the aquaporin-4 antibodies (AQP4 Abs) were retrospectively found to be positive in a stored serum sample drawn 11 months before SARS-CoV-2 infection and more than a year before the clinical onset of NMOSD ( 31 ).…”

“…Treatment consisted of corticosteroid (CS) monotherapy in seven cases ( 21 , 22 , 28 , 87 ), CS + rituximab in two cases ( 26 , 32 ), intravenous methylprednisolone (IVMP)+ intravenous immunoglobulin (IVIG)+plasma exchange (PLEX) in one case ( 23 ), CS +IVIG+ rituximab in one case ( 30 ), and CS + PLEX in one case ( 25 ). In the remaining six cases, the treatment regimen was not reported ( 21 , 24 , 27 , 29 , 86 ). A favorable outcome (i.e., improvement of neurological symptoms) was reported in eight patients ( 21 , 25 , 26 , 30 , 32 , 87 ), while poor neurological outcome (i.e., worsening of neurological disability) was reported in four patients ( 21 – 23 ).…”