Background Huntington Disease is characterized by progressive motor and cognitive impairment. Here we explored pyramidal syndrome reflecting cortical involvement. Previous imaging studies found structural alterations of the cortico-spinal tract, myelin breakdown as well as primary motor cortex atrophy.

Aims To unravel the prevalence, prognostic value, and imaging of pyramidal syndrome in individuals with Huntington Disease.

Methods We examined 178 individuals, including 24 (13%) prodromal HTT CAG repeat expansion carriers ≥36, defined by UHDRS (Unified Huntington Disease Rating Scale) < 5/124. We compared the presence or absence of pyramidal signs with repeat size, disease burden by CAP score defined as age x ((CAG-30)/6.27)), disease duration, UHDRS and plasma neurofilament light (NfL). Cerebral MR included corticospinal microstructure using NODDI and magnetisation transfer sequences.

Results We found increased reflexes in the large majority of HD individual (n=156), representing 88%. One third (35%, n=62) had extensor plantar reflexes and/or diffused reflexes in all limbs. Comparison of this pyramidal group with those without any pyramidal signs showed significant differences in age at examination (55.5±13.5 years versus 47.7±14.4 years, p< 0.001); CAP score (114.4±22.4 versus 99.7±28.1, p<0.01) and UHDRS (43.6±23.2 versus 27.3 ±21.8 p<0.001). Despite the more severe phenotype in those with pyramidal signs, disease duration (9.5±7.2 years versus 8.1±4.5 years, ns) and plasma NfL were similar (37.1±14.0 versus 34.1±21.5, ns).

Conclusion Pyramidal syndrome in Huntington Disease is frequent and not reported, except for juvenile cases. This cortical involvement is linked to older age and faster and more severe disease. Neuroimaging correlates will follow.