Severe pediatric acute encephalopathy syndromes related to SARS-CoV-2

Abstract

Background and objectivesTo clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes.MethodsA nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge.ResultsOf the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P < 0.01).DiscussionAcute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.

Recurrent infection triggered encephalopathy syndrome in a pediatric patient with RANBP2 mutation and severe acute respiratory syndrome coronavirus 2 infection

“…Eleven patients (11/16, recovery, four patients (4/18, 22.2%) died, and 11 patients (11/18, 61.1%) had a neurologic disability. Sakuma et al 21 reported 31 pediatric patients with COVID-19-related ITES (including two ANE cases) and nine patients (29%) had severe neurological sequelae or died. Levine et al 22 summarized 87 cases of non-SARS-CoV-2-induced ANE with a 30% mortality rate and a full recovery rate of less than 10%.…”

“…After excluding one case without a prognosis report, only 3 patients (3/18, 16.7%) made a full recovery, four patients (4/18, 22.2%) died, and 11 patients (11/18, 61.1%) had a neurologic disability. Sakuma et al 21 . reported 31 pediatric patients with COVID‐19‐related ITES (including two ANE cases) and nine patients (29%) had severe neurological sequelae or died.…”

Predicting factors for acute encephalopathy in febrile seizure children with SARS-CoV-2 omicron variant: a retrospective study

“…Among these, acute encephalopathy constitutes 49% of the neurological symptoms and signs [ 1 ]. Various encephalopathy/encephalitis may arise, including infection-triggered encephalopathy syndrome (ITES), such as acute necrotizing encephalopathy (ANE), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), encephalopathy with acute fulminant cerebral edema, mild encephalopathy with reversible splenial lesions (MERS), hemorrhagic shock and encephalopathy syndrome (HSES), as well as acute encephalopathy of unknown cause or unclassified, typically occurring during acute febrile illness [ 2 ]. Additionally, demyelination disorders like acute disseminated encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (AHLE) may manifest during both acute and post-infection periods [ 3 – 5 ].…”

CSF neopterin and quinolinic acid are biomarkers of neuroinflammation and neurotoxicity in FIRES and other infection‐triggered encephalopathy syndromes

“…1 A genetic vulnerability is presumed and can be demonstrated in some patients (such as RANBP2 in acute necrotising encephalopathy), but the majority of patients with ITES do not harbour genetic variants that are measurable in current clinical practise. 2 ITES can occur as a recognisable 'clinico-radiological phenotype', such as acute encephalopathy with biphasic seizures and late restricted diffusion (AESD), febrile infection-related epilepsy syndrome (FIRES), acute necrotising encephalopathy of childhood (ANE), acute fulminant cerebral oedema 3 (AFCE) and mild encephalopathy with reversible splenial lesion (MERS). 1,4 Less common ITES syndromes are acute infantile encephalopathy predominantly affecting the frontal lobes (AIEF) which is a variant of AESD, 5 and hemiplegia hemiconvulsion epilepsy syndrome (HHE).…”