PGR-2: Neuropsychological Sequelae of Febrile Infection-Related Epilepsy Syndrome (FIRES) with Comorbid ASD and ADHD: A Pediatric Case Study of Surgical Candidacy and Outcome

Abstract

Objective: Febrile infection-related epilepsy syndrome (FIRES) is a rare pediatric condition marked by refractory seizures after febrile illness and persistent neurocognitive impairment, particularly involving frontal systems dysfunction. Co-occurring neurodevelopmental vulnerabilities in this cognitive function - attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) - substantially confound localization and lateralization. This case highlights these challenges when evaluating Deep Brain Stimulation (DBS) candidacy in a patient with FIRES-related medically refractory epilepsy. Method/Data Selection: A 17-year-old, right-handed, English-speaking female with a history of FIRES (onset age 7), ADHD, and ASD underwent neuropsychological evaluation. EEG and neuroimaging studies suggest seizures localize to right temporal-occipital regions with mesial temporal sclerosis and hypometabolism. She has long-standing diagnoses of neurodevelopmental disorders and academic challenges; she is currently placed in a 1:1 learning environment. Results/Data Synthesis: Neuropsychological evaluation revealed a pattern of below age-expected intellectual functioning, attenuated by attentional difficulties and neurocognitive fatigue. Weaknesses were noted in verbal and visual memory, visuospatial skills (relative to language), and left (nondominant) hand fine motor dexterity, suggesting bilateral involvement with greater nondominant contribution. The profile is consistent with Mild Neurocognitive Disorder due to multiple etiologies (FIRES, hypothyroidism, anxiety) and fronto-temporal network disruption. Conclusions: This case shows that the neuropsychological profile of FIRES-related frontal-subcortical and fronto-temporal dysfunction cannot be explained by seizure localization alone, as co-occurring ADHD and ASD also disrupt overlapping circuits, making lateralization unreliable. This neuropsychological uncertainty complicates presurgical evaluation goals (e.g., target selection, cognitive and psychiatric risk reduction, post-operative outcome prediction), highlighting the need for serial neuropsychological monitoring and network-level approaches to track neuromodulatory intervention effects and developmental trajectories.