Spectrum of neuroradiological manifestations in primary hemophagocytic lymphohistiocytosis: a comparative study of EBV-induced versus non-EBV-induced forms in 75 genetically confirmed pediatric cases

Objectives Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition affecting young children. It is potentially triggered by Epstein-Barr virus (EBV). This study describes the neuroradiological features observed in 75 children with genetically confirmed primary HLH, comparing EBV-induced with non-EBV-induced HLH forms. Methods Brain MRIs between 2007 and 2021 from 75 children with HLH according to the 2004 Histiocyte Society criteria and with a confirmed HLH-related mutation, were retrospectively reviewed by two pediatric neuroradiologists blinded to EBV status and to mutation status. At diagnosis, 17 children with EBV viremia above a threshold of 1000 copies/mL were included in the EBV-induced HLH group. The remaining 58 patients were included in the non-EBV-induced HLH group. Results Of the 75 children initially included, 21 had abnormal MRI (21/75 (28%); 9/17 in the EBV-induced HLH group and 12/58 in the non-EBV-induced HLH group). All patients with abnormal MRI had neurological symptoms. Abnormal MRIs showed white matter lesions; the posterior fossa was affected in all but one case. There was no significant difference between groups regarding the localization or morphology of white matter lesions. The striatum was more frequently affected in the EBV-induced HLH group (8/9 (89%) versus 1/12 (8%), p = 0.00037). All lesions, whether in the white matter or in the basal ganglia, presented increased ADC values on diffusion weighted imaging (DWI). Conclusion In this study of 75 children with genetically confirmed HLH, only children with neurological signs had abnormal brain MRI. Bilateral striatum involvement suggested an EBV-induced form of HLH. Key Points • In children with genetically proven HLH, only those with neurological signs did have brain abnormalities at MRI. • All patients with abnormal brain MRI had multiple white matter lesions with increased ADC values, including in the posterior fossa in almost all cases. • Basal ganglia and in particular the striatum were bilaterally and symmetrically affected in almost all EBV-induced HLH patients, in contrast to the non-EBV-induced HLH patients.