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Título

Susceptibility to Infection-Induced Acute Encephalopathy (IIAE1/ANE1) triggerd by COVID-19

RESUMO

CASE PRESENTATION:
A 3-year-old male patient had a first episode of epileptic seizure at the age of 1 year, 2 days after the onset of fever. After this episode, he had several hospitalizations for epileptic seizures, always preceded by fever, and in the last one he had status epilepticus and required sedation. His cerebrospinal fluid showed increased proteinorrachia (122), 6 red blood cells and 10 cells (69% macrophages) and MRI of the Skull showed hypersignal on T2 FLAIR temporal poles, external capsule, insula and posterior trigone, bilaterally. Normal interictal electroencephalogram. In 1 year, when he had COVID, he started with severe epileptic encephalopathy, requiring ICU admission. New new MRI showed extensive white matter lesions on T2 FLAIR. After treatment with pulse therapy with corticosteroids and tocilizumab, he had a response. When he started with fever again, he made early use of steroids, preventing further deterioration. His father was diagnosed with encephalitis at age 4. After Exome sequencing, found a probably pathogenic variant in heterozygosis in the RANBP2 gene c.1754C>T: p. (Thr585Met), suggesting the diagnosis of Susceptibility to Infection-Induced Acute Encephalopathy (IIAE1/ANE1), an autosomal dominant disease. Segregation analysis showed that her father is also a carrier of the variant.
DISCUSSION:
The most frequent clinical presentation of IIAE1/ANE1 is characterized by three stages: prodromal (febrile viral infection), acute (encephalopathy, on average 3 days after the beginning of the prodromal phase, which may be accompanied by epileptic seizures and focal neurological signs). and recovery. Episodes can be recurring. MRI findings are characterized by T2/FLAIR hypersignal in the thalamus and brainstem. The outcome ranges from complete recovery to persistent deficits and death. Several infectious triggers have already been reported, but here we report one of the first triggered by COVID-19. Early high doses of corticosteroids seem to be the best treatment. IL6 (tocilizumab) and TNF alpha inhibitors appear to play a role, but there are very few studies to date.
FINAL COMMENTS
Although rare, the investigation of genes associated with susceptibility to Acute Encephalopathy should be investigated in recurrent cases triggered by infectious triggers, as early treatment with corticosteroids or immunomodulators seems to change the outcome of patients.

Palavras Chave

RANBP2; Susceptibility to Infection-Induced Acute Encephalopathy; COVID-19