A Prospective Multimodal Evaluation of Subacute Sclerosing Panencephalitis In Children

OBJECTIVES: This study describes the clinical presentation; CSF cytokine profile (Interleukin-4,6and10, interferon-gamma) and neurofilament heavy chain (NFL); and fluorodeoxyglucose-positron emission tomography (FDG-PET) findings in Subacute Sclerosing Panencephalitis (SSPE).

METHODS: Consecutive children(3-14 years) diagnosed as SSPE (Dyken criteria) during the study period (2020 -2022) were enrolled. Their clinical data; EEG; brain MRI; CSF interleukin 4,6,10, interferon-gamma and NFL levels were analyzed and compared with a pseudocontrol group (children with haematological malignancies without any CNS spread). FDG-PET was performed in children in whom consent was obtained.

RESULTS: A total of 33 children with SSPE were enrolled (8.06±2.67) years; males:82%; youngest child:3.6 years; Stage I:6%, Stage II: 67% and stage III:27%. Clinical details are provided in table 1. Two forms of presentation were noted - Group A: rapidly progressive form with early drop attacks (n=22), and group B: gradually progressive form with behavioral and cognitive decline (n = 11)(Table 1). Children in group B presented late (median duration of symptoms: 12(6-72) months [P= 0.01]). In CSF (done in 22/33 SSPE and 17 pseudocontrols) interleukin 4, 10 and interferon-gamma were undetectable while interleukin-6 values were similar in both the groups. CSF NFL levels were significantly elevated in SSPE (median(IQR): 132.62(53.6-388.9) vs 0(0-16.9); P<0.0001). FDG-PET (performed in seven) showed a unique pattern of putaminal hypermetabolism and fronto-temporal or temporo-parietal hypometabolism. Conclusion: SSPE has two clinical forms. Active neuroinflammation may not be the cause of rapid neuronal loss seen in SSPE. FDG-PET imaging can indicate affected brain regions in SSPE providing new insights into its pathogenesis.