MRI Patterns in Pediatric CNS Hemophagocytic Lymphohistiocytosis

Abstract

Background and purpose: Neuroimaging has an important role in detecting CNS involvement in children with systemic or CNS isolated hemophagocytic lymphohistiocytosis. We characterized a cohort of pediatric patients with CNS hemophagocytic lymphohistiocytosis focusing on neuroradiologic features and assessed whether distinct MR imaging patterns and genotype correlations can be recognized.

Materials and methods: We retrospectively enrolled consecutive pediatric patients diagnosed with hemophagocytic lymphohistiocytosis with CNS involvement treated at 2 pediatric neurology centers between 2010 and 2018. Clinical and MR imaging data were analyzed.

Results: Fifty-seven children (40 primary, 70%) with a median age of 36 months (interquartile range, 5.5-80.8 months) were included. One hundred twenty-three MR imaging studies were assessed, and 2 broad imaging patterns were identified. Pattern 1 (significant parenchymal disease, 32/57, 56%) was seen in older children (P = .004) with worse clinical profiles. It had 3 onset subpatterns: multifocal white matter lesions (21/32, 66%), brainstem predominant disease (5, 15%), and cerebellitis (6, 19%). All patients with the brainstem pattern failed to meet the radiologic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. An attenuated imaging phenotype (pattern 2) was seen in 25 patients (44%, 30 studies) and was associated with younger age.

Conclusions: Distinct MR imaging patterns correlating with clinical phenotypes and possible genetic underpinnings were recognized in this cohort of pediatric CNS hemophagocytic lymphohistiocytosis. Disruptive mutations and missense mutations with absent protein expression correlate with a younger onset age. Children with brainstem and cerebellitis patterns and a negative etiologic work-up require directed assessment for CNS hemophagocytic lymphohistiocytosis.

FIG 1.

Findings of 4 patients with subpattern 1.2 (brainstem–predominant pattern). Axial T2WI (A1–D1) and axial postcontrast T1WI (A2–D2) at the level of the pons show multiple punctate (dashed white arrow, B2, D2) to nodular (solid white arrow, A2 and C2), enhancing foci and extension of the T2 signal abnormality (black arrow, A1–D1) beyond the enhancement in all cases.

FIG 2.

Findings of subpattern 1.3 (cerebellitis). Axial T2WI at the level of the fourth ventricle (A1–C1), lateral ventricles (A3–C3), and midline sagittal T1WI (A2–C2). Onset MR imaging (December 2016) shows severe cerebellar edema and expansion (white arrow, A1) with mass effect on the brainstem, effacement of the prepontine cistern (dashed white arrow, A2), and foramen magnum crowding (white arrow, A2). Lateral ventricular dilation (asterisk, A3) and transependymal CSF seepage (dashed black arrow, A3) are also noted. Mild reduction in cerebellar edema and mass effect (dashed arrow, B2) with new cerebellar (white arrow, B1), parieto-occipital (dashed arrow, B3), and deep gray nuclei (black arrow, B3) hyperintensities were found in June 2017. Last MR imaging in November 2017 shows cerebral (white arrow, C3) and cerebellar (white arrows, C1–2) atrophy, diffuse white matter hyperintensities, and ventriculomegaly (asterisk, C3).