Serial FDG-PET in probable seronegative autoimmune encephalitis presenting as severe behavioral regression in a child with autism.

Abstract

Background: Autoimmune encephalitis in children may present with predominant psychiatric and behavioral symptoms, creating diagnostic challenges, particularly in patients with pre-existing autism spectrum disorder. Seronegative forms are especially difficult to recognize because neuronal autoantibodies are not detected, and diagnostic overshadowing may delay consideration of immune-mediated etiologies.

Case presentation: We report the case of an 11-year-old boy of Turkish background living in France, with autism and normal intelligence, who developed severe subacute behavioral and cognitive regression. Symptoms included explosive aggression, self-injurious behavior, obsessive-compulsive-like behavioral loops, psychotic-like features, agitated catatonic deterioration from baseline, loss of adaptive skills, and marked functional decline. The condition was resistant to intensive psychiatric care and multiple psychotropic treatments. Etiological assessment revealed focal epilepsy, cerebrospinal fluid abnormalities, and abnormal brain fluorodeoxyglucose positron emission tomography (FDG-PET) findings, while extensive work-up excluded infectious, metabolic, genetic, systemic autoimmune, and oncological causes. Neuronal autoantibodies were negative in serum and cerebrospinal fluid. A cautious diagnosis of probable seronegative autoimmune encephalitis was retained based on the clinical course, focal epilepsy, serial FDG-PET abnormalities, follow-up cerebrospinal fluid findings, exclusion of alternative etiologies, and expert consensus. Intravenous immunoglobulin therapy was associated with progressive but partial clinical improvement, and rituximab was introduced after a response plateau.

Conclusion: This case highlights the risk of diagnostic overshadowing in children with autism presenting with severe, treatment-resistant behavioral or catatonic regression. Immune-mediated etiologies should be considered even in the absence of detectable autoantibodies. Serial FDG-PET may support diagnostic reasoning and follow-up, while remaining nonspecific and insufficient as diagnostic proof in isolation.