Abstract
BACKGROUND: The role of neuroinflammation and autoimmune processes in neurodegenerative diseases is not fully understood. Activation of microglia with expression of proinflammatory cytokines supports the hypothesis that immune processes may play an important role in the pathophysiology of Huntington's disease (HD) and thus, immunomodulating therapies might have potential neuroprotective properties. Until now, no disease-modifying therapy (DMT) is available for HD. OBJECTIVE: The aim of this research was to characterize a cohort of patients suffering from both HD and autoimmune demyelinating diseases of the central nervous system (classified as G35-37 in ICD-10; ADD-CNS) in comparison to HD cases without ADD-CNS. In particular, we were interested to investigate potential modulating effects on disease manifestation and progression of HD over time of prescribed immunomodulating medications (DMT). METHODS: We analyzed the course of HD regarding motoric, functional, and cognitive aspects, using longitudinal data of up to 2 years from the worldwide registry study ENROLL-HD. Additional cross-sectional data in the largest cohort worldwide of HD patients was analyzed using demographic and molecular genetic parameters. Data were analyzed using analysis of variance (ANOVA) for cross-sectional and repeated-measures ANOVA for longitudinal parameters in IBM SPSS Statistics V.27. RESULTS: Within the ENROLL-HD database, we investigated N = 21,116 participants and identified n = 60 participants suffering from ADD-CNS. Molecular, genetic, and demographic data did not differ between groups. The subgroup of n = 32 participants with motor-manifest HD revealed better cognitive performance in five out of eight cognitive tests at baseline with less progression over time in two tests (all p < 0.05). Differentiation between DMT-treated and untreated patients revealed better cognitive and motor performance in the DMT group; those patients, however, tended to be younger. Pre-manifest HD patients simultaneously diagnosed with ADD-CNS (n = 12) showed lower functional scores and more decline over time when compared with other pre-manifest HD (p < 0.05). CONCLUSION: Patients suffering from motor-manifest HD and simultaneously from ADD-CNS have better cognitive capacities compared with other motor-manifest HD patients. Moreover, DMTs might have beneficial effects on progression of neurodegeneration including the motor phenotype. However, this effect might have been biased by younger age in DMT-treated patients. Pre-manifest HD patients showed more functional impairment as expected due to their additional ADD-CNS disease.