Blood neurofilament light chain as a surrogate marker for dystonia

Dystonia is a heterogeneous movement disorder and whether neurodegeneration is involved remains inconsistent. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. Here, we investigated whether plasma NfL levels are elevated and associated with disease severity in patients with dystonia. We enrolled 231 unrelated dystonia patients (n=203 isolated dystonia, n=28 combined dystonia) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated by the Fahn Marsden Dystonia Rating Scale, Unified Dystonia Rating Scale, and Global Dystonia Rating Scale. Blood NfL levels were measured by single-molecule array. Plasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL, P = 0.01) or controls (P A (p.R41H) variant in THAP1 (DYT6) and the other one carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and the dystonia rating scores. Plasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.