Two Paediatric Patients with Encephalopathy and Concurrent COVID-19 Infection: Two Sides of the Same Coin?

Abstract

There is increasing evidence that SARS-CoV-2 has neurotropic potential. We report on two paediatric patients who presented with encephalopathy during COVID-19 illness. Both patients had ADEM-like changes in their neuroimaging, negative SARS-CoV-2 RNA PCR in CSF, and paucity of PIMS-TS laboratory findings. However, the first patient was positive for serum MOG antibodies with normal CSF analysis, and the second had negative MOG antibodies but showed significant CSF lymphocytic pleocytosis. We concluded that the first case was a typical case of demyelination, which could have been triggered by different cofactors. In the second case, however, we postulated that the encephalopathic process was triggered by SARS-CoV-2, as no other cause was identified. With these two contrasting cases, we provide evidence that SARS-CoV-2-associated encephalitis can show ADEM-like changes, which can present during the postinfectious phase of COVID-19 illness. As ADEM is a relatively common type of postinfectious encephalitis in children, the distinguishing line between the two conditions of encephalitis and ADEM can be relatively fine. The development of more reliable diagnostic tools (e.g., anti-SARS-CoV-2 antibodies in CSF) might play an assisting role in the differentiation of these encephalopathic processes.

SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature

“…Microhemorrhage of bilateral globus pallidus ADEM NA NA 31 [ 50 ] 54/F Respiratory distress (+) RT-PCR/NPS Altered mental status without focal neurologic deficit 8 Normal CSF SARS-CoV-2 PCR negative NA Multiple supratentorial punctiform and tumefactive lesions of white matter, involving corpus callosum: hypersignal on flair and DWI with restricted diffusion. 10 day after: enhancement of all lesions (No lesion in spine MRI) ADEM Steroid treatment NA 32 [ 34 ] 13/F Fever, (+) RT-PCR/NPS Altered consciousness, seizures 3 CSF analysis showed 10/mm 3 white cells, being negative for SARS-CoV-2 RNA MOG IgG antibodies(+) Brain: bilateral widespread white matter highsignal abnormalities, including the splenium of the corpus callosum with associated diffusion restriction and high signal in the thalami and pons ADEM Steroid treatment Partial recovery Spine: normal 33 [ 34 ] 10/F Vomiting, lethargy, and pyrexia (+) RT-PCR/NPS Ageusia, headache; fluctuating sensorium and urinary incontinence 15 CSF analysis showed a markedly raised white-cell count (WCC) of 6075/mm 3 with 93% lymphocytes and CSF protein of 0.58 g/L. CSF SARS-CoV-2 RNA test was negative MOG IgG antibodies (−) Brain: asymmetric bilateral high-signal lesions in the basal ganglia and the subcortical white matter in the frontal and temporal lobes, with involvement of the left internal capsule and left hippocampus ADEM IV aciclovir and antibiotics …”

“…AQP4 antibodies were tested in 19 patients, being negative in all. MOG antibodies were searched in 19 patients, being positive in one case [ 34 ]. Furthermore, CSF SARS-CoV-2 RNA was not reported or not calculable in 23 patients.…”

A Systematic Review of Severe Neurological Manifestations in Pediatric Patients with Coexisting SARS-CoV-2 Infection

“…Three cases of encephalopathy were reported in the United States of America and the United Kingdom by Abel et al, 2020 [24] and Vraka et al, 2021 [25] respectively. The first case was reported in New York, a 33-month-old boy who met the criteria for MIS-C and developed a reversible encephalopathy.…”

“…There were seven case series [10,[13][14][15][16][48][49][50], 23 case reports [18][19][20][21][22][23][24][25][28][29][30][31][32][34][35][36][37][38][40][41][42][43]52], and the rest were letters to the editor, brief reports, and a scientific letter. Two studies were international [15,16], twenty studies were from the USA [13,[17][18][19][20]24,[28][29][30]32,33,35,[37][38][39]41,47,48,…”

“…The age of the children ranged from 24-h to 17-years old. From the 159 patients, 38 were reported with some type of cerebrovascular disease [12][13][14][15][16][17][18][19][20][21][22], 32 with different types of encephalitis [13][14][15][26][27][28][29][30][31][32], 22 with encephalopathy [10,13,24,25], and 10 patients with Guillain-Barre syndrome [13,14,[42][43][44]. Sixty-five out of 159 patients with severe neurological manifestations, were reported with Multisystem Inflammatory Syndrome (MIS-C) [10,12,[14][15][16][17]23,32,45,50,[52][53][54] (Table 1).…”