Purpose: Despite recent advances in diagnosis, the etiology of 30-60% of suspected cases of infectious encephalitis remain unclear. This number is even larger in adults who had encephalitis in childhood and were investigated 20 or more years ago. In this study, we retrospectively explored possible genetic explanations for adults with epilepsy who had a childhood diagnoses of infectious encephalitis and post-vaccination encephalopathy

Method: A database search was carried out to identify adult patients with a childhood diagnosis of infectious encephalitis, meningitis or post-vaccine encephalopathy at the Toronto Western Hospital's Adult Genetic Epilepsy (AGE) Clinic. Clinical history was reviewed and only patients with symptoms suggestive of those diagnoses but no microorganism growth on their CSF were included.

Results: -68 patients were identified but 44 of them were excluded due to incomplete/missing data, a confirmed or suspected case of Rasmussen's encephalitis /autoimmune encephalitis, or other causes of acquired epilepsy.

-58% (14/24) of our cohort, who were initially diagnosed with infectious encephalitis, were later found to have a genetic diagnosis of developmental and epileptic encephalopathy (DEE) in adulthood. This included pathogenic variants impacting genes such as SCN1A, SPATA5, YWHAG, DEPDC5 and KCNA1. We also found a tandem repeat expansion that fell into the reported disease-causing range in DIP2B gene.

-57% had a diagnosis of DS, 29% had monogenic DEE, 7% had EHLMRS, and the remaining 7% were diagnosed with Jacobsen Syndrome

-67% (16/24) had medically refractory epilepsy with intellectual disability and 21% (5/24) had a formal diagnosis of autism spectrum disorder

Conclusion: Our study shows the importance of re-evaluation of childhood diagnosis. Comorbidities such as intellectual disability, autism spectrum disorder, and other complex phenotypic clues should alert the adult neurologists to reinvestigate and explore a possible genetic diagnosis.