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

Abstract

SARS-CoV-2 infection in children produces mild respiratory symptoms or no symptoms at all in most cases. Some pediatric patients develop a severe complication associated with high mortality, the multisystem inflammatory syndrome in children (MIS-C). In both scenarios, there are reports of neurological manifestations. This article aims to review the cases of pediatric patients with severe neurological issues and a coexisting positive SARS-CoV-2 test. A literature search was performed between March 2020 and May 2021. The results included the data from 41 studies, with 159 children with severe neurological manifestations, within an age range from 24 h to 17 years. The neurological disorders included 38 cases with stroke, 32 with encephalitis, 22 with encephalopathy, and 10 with Guillain–Barre syndrome. Sixty-five out of 159 cases with severe neurological manifestations were diagnosed with MIS-C. Direct neuroinvasion and the exaggerated immune response in some patients seem to be the most critical factors triggering these manifestations. Further research in the ongoing pandemic is needed to elucidate the precise mechanism.

Neurological complications of COVID-19 in pediatric patients require comprehensive evaluation

“…We do not agree with the notion that COVID-19 in pediatric patients usually takes a mild course (Krueger et al 2021). There are several reports about paediatric patients with severe COVID-19 or its complications (O'Loughlin et al 2021;Grewal et al 2021).…”

COVID-19 and neurologic manifestations: a synthesis from the child neurologist’s corner

“…Known risk factors for this cerebrovascular disease include infections and inflammatory diseases, principally causing a secondary focal cerebral arteriopathy [ 40 ]. Other viruses have been associated with an increased incidence of stroke in children, including influenza and the varicella-zoster virus [ 41 ]. An increased risk for stroke in COVID-19 patients has been demonstrated, especially in the subgroups that required intensive treatment unit admission and in patients with encephalopathy [ 6 , 40 , 42 ].…”

“…Even though most strokes secondary to COVID-19 have been reported in adults (0.9–2.0%) [ 40 ], there have also been reports of children presenting with predominantly ischemic stroke [ 7 , 40 , 44 , 45 ]. In a systematic review of severe neurologic manifestations coexisting with SARS-CoV-2 infection in children by O’Loughlin et al the most common neurologic manifestation was cerebrovascular disease (38 cases) including ischemic and hemorrhagic strokes, venous thrombosis, and cerebral arteriopathy [ 41 ]. Nonetheless, the incidence of pediatric stroke has not changed since the beginning of the pandemic, and most of the cases published so far had other risk factors for stroke.…”

“…Patients presenting with encephalopathy, especially the ones with severe COVID-19 or MIS-C had increased mortality and worse outcomes. In this regard, there have also been reports of children presenting with encephalopathy as a sign of acute, and sometimes fatal, cerebral edema associated with COVID-19 [ 19 , 41 , 66 , 67 ].…”

Neurological effects of COVID‐19 in infants and children

“…Neurological manifestations were initially thought to be quite rare; however, over time they have become increasingly recognized in both adults 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 and children. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 The reported neurological symptoms are wide‐ranging, from non‐specific to specific, across the lifespan. A meta‐analysis of COVID‐19 in children noted that 16.7% of 3707 patients reviewed had non‐specific neurological symptoms (headache, myalgia, fatigue), with other (specific) neurological deficits being much less prevalent (approximately 1% with encephalopathy, seizures, or meningeal signs).…”