Biomarkers, Neurophysiological and Clinical Correlates Following Botulinum Toxin Treatment in Various Clinical Presentations of Cervical Dystonia: A Controlled Study Across Peak and Waning Response Phases

Cervical dystonia (CD) is a focal dystonia typically treated with botulinum toxin type A (BoNT-A), but objective biomarkers of disease state and treatment response are limited. In a prospective controlled observational study with within-subject phase comparison, we evaluated clinical, neurophysiological, and biochemical markers at two time points (waning and peak response phases) within the BoNT-A injection interval in 30 CD individuals (with caput, collis and mixed patterns) and 25 healthy controls. We measured clinical status (TWSTRS and VAS pain), neurophysiology (F-wave minimal latency (F-min) and cutaneous silent period (CSP) indices) and plasma biochemical markers (neurofilament light chain (NfL) and zonulin). Compared with controls, CD patients showed lower NfL levels, higher zonulin, shorter CSP end duration and shorter CSP-derived central conduction time (CSP-CCT); nerve conduction velocity and CSP onset were similar. From waning to peak, TWSTRS (all subscales) and VAS improved, zonulin decreased, NfL increased, CSP end duration and CSP-CCT increased, and Fmin slightly prolonged. Changes in CSP measures correlated with pain (VAS and TWSTRS pain), while zonulin changes showed no significant correlations and NfL changes correlated weakly/negatively with CSP end time. Phase-dependent changes in biochemical and neurophysiological markers were observed alongside clinical measures across the BoNT-A treatment cycle in CD, suggesting potential associations between peripheral biochemical markers, central inhibitory measures, and treatment phase. These findings may warrant further investigation of multimodal biomarker approaches in CD.