Characteristics of epilepsy associated with hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome frequently complicated by severe neurological manifestations, including epilepsy. This study aimed to characterize the clinical phenotype, identify risk factors, and determine outcomes specific to HLH-associated epilepsy.

We conducted a retrospective cohort study of 76 patients with HLH, comparing those with epilepsy (n = 25) and those without (n = 51). Comprehensive clinical, laboratory, genetic, electroencephalogram, and neuroimaging data were analyzed.

Patients with HLH-associated epilepsy were significantly younger and had a higher prevalence of primary HLH. They demonstrated a more severe inflammatory profile, marked by elevated ferritin, interleukin-6, and cerebrospinal fluid (CSF) pleocytosis. Multivariate analysis identified age ≤25 years, ferritin >20,000 ng/mL, CSF pleocytosis, and evolution to cortical atrophy as independent risk factors for epilepsy. Neuroimaging revealed a characteristic "enhancement-to-atrophy" sequence, where acute contrast-enhancing lesions (64.0 % vs. 29.4 %) often progressed to cortical atrophy (56.0 % vs. 19.6 %), highlighting a trajectory from acute neuroinflammation to permanent structural injury. The epilepsy group had significantly poorer survival (median 19 vs. 23 months). Although systemic HLH remission was achieved, the majority of patients (68.0 %) developed refractory epilepsy, necessitating long-term antiseizure medication.

HLH-associated epilepsy constitutes a severe clinical entity driven by intense neuroinflammation, which frequently results in irreversible brain damage. Early identification of its hallmark features, including young age, extreme hyperferritinemia, CSF pleocytosis, and the distinctive "enhancement-to-atrophy" neuroimaging sequence, is crucial for prompt intervention and long-term neurological management.