MRI Patterns in Pediatric CNS Hemophagocytic Lymphohistiocytosis
P Malik1, L Antonini2, P Mannam1
1From the Departments of Diagnostic Imaging (P. Malik, P. Mannam, S.E.M.).
Insights
Neuroimaging reveals distinct patterns in pediatric CNS hemophagocytic lymphohistiocytosis (HLH). These patterns correlate with age, clinical presentation, and genetic factors, aiding diagnosis in children with HLH.
Area of Science:
- Pediatric Neurology
- Neuroradiology
- Genetics
Background:
- Neuroimaging is crucial for identifying central nervous system (CNS) involvement in pediatric hemophagocytic lymphohistiocytosis (HLH).
- Characterizing neuroradiologic features in pediatric CNS HLH is essential for understanding disease presentation and progression.
Purpose of the Study:
- To characterize neuroradiologic features in pediatric patients with CNS HLH.
- To identify distinct MR imaging patterns and their correlation with clinical phenotypes and genotypes.
Main Methods:
- Retrospective analysis of clinical and MR imaging data from pediatric patients with CNS HLH.
- Assessment of 123 MR imaging studies from 57 children treated between 2010 and 2018.
Main Results:
- Two broad MR imaging patterns were identified: significant parenchymal disease (Pattern 1) in older children and an attenuated phenotype (Pattern 2) in younger children.
- Pattern 1 included multifocal white matter lesions, brainstem predominant disease, or cerebellitis.
- Pattern 2 was associated with younger age.
Conclusions:
- Distinct MR imaging patterns in pediatric CNS HLH correlate with clinical phenotypes and potential genetic factors.
- Specific imaging patterns, particularly brainstem and cerebellitis, warrant further investigation for CNS HLH in children with negative etiologic work-ups.
- Genetic mutations correlate with younger onset age in pediatric CNS HLH.
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.
