Pediatric CNS-isolated hemophagocytic lymphohistiocytosis with brain hemorrhages: a case report

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is an inherited syndrome characterized by immune dysregulation. Central nervous system (CNS)-isolated disease is a rare presentation of familial HLH. We present a case of pediatric CNS-isolated HLH with a presentation complicated by unusual hemorrhagic intraparenchymal lesions.

Case presentation: A 15-year-old male presented with ataxia and MRI findings of multiple hemorrhagic lesions in his cerebral white matter, brainstem, and cerebellum, suggestive of vasculitis. After failing to improve with steroids and plasmapheresis, and progression to acute neurologic decompensation, new brainstem hemorrhages were noted. Further workup revealed 2 PRF1 mutations, confirming a diagnosis of familial CNS-HLH. He was later found to have a platelet granule defect, explaining his atypical neuroradiologic findings. The patient received treatment per the HLH-1994 protocol and underwent stem cell transplantation. Two years post-transplant, his perforin expression is nearly normal and his neurologic deficits have significantly improved.

Conclusions: This case illustrates the variability in presentation of isolated CNS-HLH. Although rare, it is important to include this diagnosis on the differential in patients with CNS hemorrhagic lesions. If initial diagnostic studies remain inconclusive or response to early treatments is poor, CNS-HLH should be considered, as delay in diagnosis and treatment significantly affects morbidity and mortality.

Keywords: CNS involvement; Case report; Hemophagocytic lymphohistiocytosis; Hemorrhage; Pediatric.

Fig. 1

Left – Initial MRI: Axial Susceptibility Weighted Image (SWI) at the level of the brainstem demonstrates a prominent area of susceptibility related signal loss within the left aspect of the pons compatible with hemorrhage (white arrow). Right – Follow-up MRI 2 weeks later: Axial SWI at the same level demonstrates new prominent areas of hemorrhage within the right aspect of the pons (white arrowheads)

Fig. 2

Axial contrast enhanced images of the brain demonstrate multifocal patchy areas of enhancement within the pons, cerebellum, and left greater than right cerebral hemispheres (white arrows)

Fig. 3

Left – Sagittal T2 Dixon image of the thoracic spine demonstrates multifocal spinal cord signal abnormality (white arrows). Center – Sagittal T1 contrast enhanced images of the thoracic spine demonstrates multifocal spinal cord signal abnormality (white arrowheads). Right – Axial T1 contrast enhanced image of the thoracic spine demonstrates an abnormal focus of enhancement within the spinal cord (white arrow)