Figure 1
Study protocol and timeline. After enrollment, all participants underwent baseline assessment (T0) and were then allocated to one of two treatment sequences according to clinical scheduling: Group 1 (active ESWT + BoNT followed by sham ESWT + BoNT) or Group 2 (sham ESWT + BoNT followed by active ESWT + BoNT). Each treatment period included an immediate post-treatment assessment (T0*), followed by follow-up evaluations at 1 month (T1) and 3 months (T2). A washout period of at least 3 months separated the two treatment periods, after which participants crossed over to the alternate intervention. This design allowed within-subject comparisons between active and sham conditions. ESWT = extracorporeal shock wave therapy. BoNT= Botulinum toxin.
Figure 2
Schematic representation of focused ESWT applied prior to BoNT injection, illustrating active stimulation of the paraspinal muscles in the treatment condition (see Figure 3 for a real image example), and sham stimulation with minimal energy and no direct tissue contact in the placebo condition.
Figure 3
ESWT application to paraspinal muscles.
Table 1
Patients’ characteristics.
| GROUP 1 (ESWT → sham) n = 9 | GROUP 2 (sham → ESWT) n = 6 | p | |
|---|---|---|---|
| Sex, F | 3 (33.3%) | 2 (33.3%) | 1.000a |
| Age, y | 78.0 ± 4.3 | 74.3 ± 2.7 | 0.058b |
| Height, m | 1.70 ± 0.07 | 1.71 ± 0.06 | 0.783b |
| Weight, kg | 70 (56–97) | 74.2 (60–102) | 0.906c |
| BMI | 24.3 ± 3.1 | 25.4 ± 4.1 | 0.585b |
| PD age onset, y | 68.8 ± 7.5 | 67.2 ± 3.0 | 0.575b |
| Disease duration, y | 9.2 ± 4.6 | 6.5 ± 2.8 | 0.218b |
| PD latency, y | 5.4 ± 3.6 | 3.8 ± 3.1 | 0.383b |
| Treatment latency, y | 1 (0.8–2) | 1.25 (0.5–3) | 0.671c |
| PS duration, y | 3.67 ± 1.66 | 3.17 ± 2.56 | 0.652b |
| Phenotype | 0.460d | ||
| Tremor dominant | 1 (6.7%) | 1 (16.7%) | |
| Rigid-akinetic | 2 (22.2%) | 0 | |
| Mixed | 6 (66.7%) | 5 (83.3%) | |
| Side of symptoms | 0.329a | ||
| Right | 7 (77.8%) | 3 (50%) | |
| Left | 2 (22.2%) | 3 (50%) | |
| Falls | 1 (11.1%) | 0 (0%) | 1.000a |
| Comorbidity (n = 9, n = 5) | 9 (100%) | 5 (100%) | na |
| Rehabilitation within last 3 months | 2 (22.2%) | 2 (33.3%) | 1.000a |
| PS direction at baseline | 0.608a | ||
| Right | 5 (55.6%) | 2 (33.3%) | |
| Left | 4 (44.4%) | 4 (66.7%) | |
| Metronome phenomenon | 1 (11.1%) | 0 (0%) | 1.000a |
| PS pattern at onset | 1.000a | ||
| Chronic | 8 (88.9%) | 6 (100%) | |
| Subacute | 1 (11.1%) | 0 (0%) | |
| PS side at onset | 0.580a | ||
| Ipsilateral | 4 (44.4%) | 1 (16.7%) | |
| Contralateral | 5 (55.5%) | 5 (83.3%) | |
| Awareness | 7 (77.8%) | 5 (83.3%) | 1.000a |
| Head compensation | 2 (22.2%) | 4 (66.7%) | 0.136a |
| Sensory trick | 0 (0%) | 0 (0%) | na |
[i] aFisher’s Exact Test; bIndependent samples T-test; cMann Whitney U; dChi square Test; na = not applicable.
Table 2
Clinical scores at baseline.
| GROUP 1 (ESWT → sham) n = 9 | GROUP 2 (sham → ESWT) n = 6 | p | |
|---|---|---|---|
| Pisa syndrome degrees | 8.33 ± 4.31 | 8.85 ± 4.65 | 0.829b |
| LEDD | 666.7 ± 222.1 | 568.7 ± 196.40 | 0.398b |
| FOG, n (%) | 5 (55.6%) | 1 (16.7%) | 0.287a |
| FOG severity | 5.44 ± 6.37 | 1 ± 2.45 | 0.085b |
| PDQ8 | 4.22 ± 2.11 | 5.17 ± 5.12 | 0.625b |
| H&Y | 2 (2–3) | 2 (2–3) | 0.776c |
| Pain, n (%) | 4 (44.4%) | 3 (50%) | 1.000a |
| NRS other than back | 0 (0–7) | 0 (0–0) | 0.776c |
| NRS back | 0 (0–7) | 1 (0–4) | 1.000c |
| UPDRS-III | 31.89 ± 8.21 | 36.67 ± 17.72 | 0.558b |
[i] aFisher’s Exact Test, bIndependent samples T-test, cMann Whitney U.
Figure 4
Angular measurements across the different study time points. Treatment 1 = sham; Treatment 2 = ESWT; Error Bars: 95% CI.
Figure 5
Representative image of a study patient illustrating the angular variation at T0, T0’, T1, and T2.
Figure 6
FOG severity score, PDQ-8, PGI-I (5-point), PGI-I total score, and NRS pain scores across time. Repeated-measures GLM showed no significant effects of Time, Treatment, or Time × Treatment interaction. No significant post-treatment vs baseline differences were observed in either group (panels a–d). Treatment 1 = sham; Treatment 2 = ESWT; Error Bars: 95% CI.
Figure 7
UPDRS-III scores across time and treatment conditions. Treatment 1 = sham; Treatment 2 = ESWT; Error Bars: 95% CI.