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

TL;DR

This study examines central nervous system involvement in 22 children with hemophagocytic lymphohistiocytosis, finding that most had neurological symptoms and brain imaging abnormalities.

Contribution

The study provides new insights into the frequency and characteristics of CNS involvement in pediatric HLH patients at a single center.

Findings

CNS involvement was observed in 77.2% of pediatric HLH patients.

MRI showed abnormalities like T2 FLAIR prolongation and brain atrophy in most patients.

Patients with CNS involvement had a 75% mortality rate within the first year.

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.

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