Central nervous system involvement in pediatric hemophagocytic lymphohistiocytosis: A single-center descriptive study of clinical features, neurodiagnostic findings, and outcomes.

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperimmune condition triggered by the pathological activation of T-cells, natural killer cells, and macrophages leading to a cytokine storm with widespread hyperinflammation affecting multiple organ systems, including the brain. This retrospective chart review characterizes the central nervous system (CNS) features in 22 pediatric HLH patients at a single center. CNS involvement was determined based on symptoms, exam, abnormal cerebrospinal fluid (CSF) studies, neuroimaging, and electroencephalogram (EEG) findings. Twenty-two children with HLH were analyzed, classifying them into primary HLH (pHLH) and secondary HLH (sHLH) based on genetic testing. Of 20 patients who underwent genetic testing, 6 (30%) had pathogenic pHLH mutations, while 14 were sHLH (8 with variants of unknown significance, 6 with no variants). CNS involvement was noted in 17 (77.2%) patients. Symptoms included generalized weakness, altered sensorium, seizures, and headaches. MRI abnormalities included patchy T2 FLAIR prolongation (85%) with and without contrast enhancement and subdural collection, diffuse brain atrophy (40%), microhemorrhages (15%) and diffusion restriction (15%) patients. CSF studies showed higher WBC counts in pHLH . Therapies amongst this cohort varied, with 47% receiving dexamethasone, etoposide and cyclosporine, and 29% undergoing HSCT. Mortality in the first year was 18%, with 75% of deaths involving patients with CNS involvement of HLH. Mean survival at six months was 167 days, with no further deaths in the 12-year follow-up. We conclude that frequent neurological abnormalities are noted in children with HLH highlighting the role for active surveillance of CNS involvement in this group of patients.