Painful foot dystonia is a common and disabling complication in Parkinson disease (PD), often occurring during OFF periods and frequently resistant to medication optimization. Evidence for treatments specifically addressing dystonia-related pain in PD is limited. This randomized trial evaluated the efficacy and safety of onabotulinumtoxinA (BTXA) as a targeted treatment for pain associated with foot dystonia in adults with unilateral PD.
This was a single-center, randomized, double-blind, placebo-controlled trial with outcome assessments at 6 and 12 weeks and a subsequent 12-week open-label extension. Thirty-three adults with unilateral PD and painful foot dystonia refractory to medication optimization were randomized in a 1:1 ratio to BTXA or placebo. Randomized group sizes were BTXA n = 16 and placebo n = 17.
Participants randomized to active treatment received 100 units of onabotulinumtoxinA delivered using a guided injection protocol. Injection targets included the tibialis posterior, extensor hallucis longus, and flexor digitorum brevis. Placebo injections followed the same guided protocol. The trial evaluated a single administration with follow-up assessments at prespecified timepoints.
The primary outcome was the change from baseline in dystonia-related pain as measured by Item 5 of the King's Parkinson's Disease Pain Scale (KPPS) at 6 and 12 weeks. Secondary outcomes comprised responder rates defined as ≥30% pain reduction, KPPS Domain 3 total score, KPPS Item 5 pain severity and frequency subitems, Visual Analogue Scale (VAS) pain, Clinical Global Impression, motor outcomes using the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts III and IV, quality of life measures, and safety assessments. The trial also included a 12-week open-label extension phase.
At 6 weeks, BTXA produced a significantly greater reduction in dystonia-related pain assessed by KPPS Item 5 total score compared with placebo, with a reported mean difference of -3.60. This effect was sustained at 12 weeks (p < 0.001). The between-group effect size for the primary outcome was large (Hedges' g -1.33; 95% CI -2.13 to -0.53), indicating a clinically meaningful benefit of BTXA over placebo on the KPPS Item 5 score in this cohort.
Responder rates (≥30% pain reduction) favored BTXA at both 6 and 12 weeks, with 75.0% of BTXA-treated participants meeting the responder threshold versus ≤ 11.8% and 5.6% in the placebo group at the respective timepoints (p < 0.001). Improvements were reported in KPPS Item 5 pain severity and frequency subitems and in KPPS Domain 3 total scores at 6 and 12 weeks.
VAS pain scores decreased at 6 weeks in the BTXA group; however, there was no significant between-group difference in VAS at 12 weeks. Motor outcomes assessed by MDS-UPDRS parts III and IV did not differ between groups, and quality of life measures showed no between-group differences in this trial.
Adverse events were reported as mild, and there were no significant differences in adverse event rates between BTXA and placebo groups. Crucially, use of BTXA did not adversely affect motor outcomes in this participant cohort, supporting an acceptable safety and tolerability profile for the targeted injection protocol used in the study.
In this randomized, double-blind, placebo-controlled trial of adults with unilateral PD and medication-refractory painful foot dystonia, a single guided injection of onabotulinumtoxinA (100 units) produced significant and sustained reductions in dystonia-related pain measured by KPPS Item 5 at 6 and 12 weeks. The large between-group effect size and higher responder rates with BTXA indicate a clinically meaningful analgesic benefit specific to dystonia-related pain.
Improvements were also seen in KPPS domain and subitem scores, while global VAS pain differences were limited to the 6-week timepoint. Importantly, BTXA did not worsen motor function as measured by the MDS-UPDRS, and adverse events were mild, supporting the intervention’s tolerability.
These results support the role of targeted BTXA injections for patients with PD who have focal, painful foot dystonia not responsive to medication adjustments. Clinicians should consider guided injection protocols that target dystonic muscles identified in this study (tibialis posterior, extensor hallucis longus, flexor digitorum brevis) when contemplating BTXA for symptom-specific pain relief in PD.
The trial is registered at ClinicalTrials.gov under identifier NCT04277247. Full results are reported in Neurology: Clinical Practice (2026 Dec;16(6):e200659) with DOI 10.1212/CPJ.0000000000200659. The published abstract reports the sample size, dosing, muscle targets, primary and secondary outcomes, effect sizes, responder rates, and safety findings summarized above.