ETD

• atypical parkinsonism
• corticobasal syndrome
• dystonia
• longitudinal analysis
• multiple system atrophy
• progressive supranuclear palsy

Atypical parkinsonian disorders (APDs) represent a group of neurodegenerative disorders,
including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal
syndrome (CBS), characterized by signs and symptoms of parkinsonism with other motor and non-
motor features. Dystonia is a frequent yet inconsistently described characteristic within the clinical
spectrum of APDs, and its different distribution and evolution across syndromes remain
substantially unexplored.

This study provides the first systematic, longitudinal comparison of dystonia across PSP, MSA, and
CBS, with the aim to explore the spatial and temporal evolution of this feature. Clinical data were
retrospectively collected from a large single-center cohort (182 patients) and analysed to determine
the topography, timing, and clinical correlates of dystonia. A subset of patients (n = 119) with at least five years of homogeneous follow-up from disease onset was examined to ensure comparability
across diagnoses and to extract both prevalence estimates and spatiotemporal trajectory of
dystonia. Complementary time-to-event analyses were used to model the evolution of dystonia
across the entire disease course. Finally, we investigated potential association between dystonia
and major clinical milestones, like dysphagia and loss of ambulation.

Dystonia was found to be highly frequent in our cohort as per prevalence estimates after 5 years
from disease onset. Distinct spatiotemporal patterns of dystonia emerged among PSP, MSA and
CBS, suggesting that each condition follows a characteristic trajectory in terms of both body
distribution and timing of onset. When comparing dystonia prevalence across body regions,
significant differences were found for cranial dystonia (p < 0.001) and upper limb dystonia (p <
0.001). Specifically, cranial dystonia was most frequent in PSP (55.6%), while upper limb dystonia
predominated in CBS (82.6%). No significant differences were observed for cervical (p = 0.075) or
truncal (p = 0.293) dystonia. Regarding the timing of onset, upper limb dystonia occurred earlier in
CBS compared to PSP (p = 0.025), whereas no significant temporal differences were found in
other regions. Dystonia-related pain was more common in CBS than in MSA and PSP (p < 0.001). Among PSP
subtypes, dystonia prevalence did not differ significantly; however, patients with MSA-P exhibited a
significantly higher prevalence of dystonia compared to those with MSA-C (p = 0.002). Dysphagia
and loss of ambulation were not significantly influenced by dystonia, although they appeared more
frequently in association with specific forms of dystonic patterns.

This work offers new insights into the natural history of dystonia in APDs and proposes a
structured approach for its longitudinal assessment. Prospective and larger studies will further
clarify the existing findings and potentially improve both diagnostic and therapeutic approaches.