Unravelling the Inflammatory and Metabolic Insights in Subacute Sclerosing Panencephalitis: A Prospective Multimodal Evaluation.

BACKGROUND

This study discusses results of multimodal evaluation of biomarkers of neuroinflammation and neurodegeneration in cerebrospinal fluid (CSF) and Fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) findings in Subacute sclerosing panencephalitis (SSPE).

METHODS

Consecutive children (3-14 years) with SSPE fulfilling the Dyken criteria during the study period (2020-2022) were enrolled. Clinical profile, radiological and electroencephalography data were chronicled. CSF interleukins (ILs) IL-4, IL-6, and IL-10; interferon-gamma; and neurofilament heavy chain (NFH) levels were analysed and compared with age matched pseudo-controls. 18F-FDG-PET imaging was performed in a subset of children who consented for the same.

RESULTS

Thirty-three children with SSPE were enrolled [mean age 8.06 ± 2.67 years; males: 82%; Jabbour Stage I-6%, Stage II-67%, Stage III-27%]. Two forms of presentation were seen: short/absent stage I with early onset myoclonic jerks (N = 22; mean age of onset 7.85 ± 2.45) and prolonged stage I with late onset epilepsy (N = 11; mean age 6 ± 1.9 years, P = 0.03). CSF NFH was significantly elevated in SSPE [132.62 (53.6-388.9) vs 0.0 (0-16.9) pg/ml; P = 0.0001] compared to the pseudo-controls. CSF IL-6 (pg/ml) in 21/22 SSPE [1.72 (0.85-3.04)] children and 16/17 pseudo-controls [2.60 (1.72-3.83); P = 0.17] were similar. IL-4, IL-10, and interferon-gammas were undetectable in both the groups. 18F-FDG-PET showed putaminal hypermetabolism in 7/9 (78%) and thalamo-cerebellar hypometabolism in 8/9 (88%) with variable foci of cortical hypometabolism.

CONCLUSIONS

Elevated CSF NFH levels suggest ongoing neuronal loss in SSPE. Cell mediated immunity is altered, and active neuroinflammation (T-cell mediated) may not be contributing to the ongoing neurodegeneration. 18F-FDG-PET imaging consistently reveals putaminal hypermetabolism alongside thalamo-cerebellar hypometabolism, which may prove valuable in diagnosing challenging SSPE cases.