Table 1
Eligibility criteria for including studies in systematic review based on PICO.
| DOMAIN | DETERMINED CRITERIA |
|---|---|
| Population/participants | Patients with a family history or clinically diagnosed idiopathic Parkinson’s disease (stage 1 to 3 according to H&Y scale) and hand tremor (uni/bilateral),which one year passed from the definitive diagnosis of their illness and are under pharmacotherapy. There was no restriction on age and sex. |
| Interventions | Guided Botulinum toxin injection with no restriction on dosage (e.g., high, low) and injection intervals (e.g., daily, weekly) |
| Control/comparison | Placebo/No treatment |
| Outcomes | Any beneficial effect of Botulinum toxin on the symptoms of the disease |
| Study design | Case report, case series, cohort studies, and trials published in English between 1990 and September 2021 with full text available regardless of location |
[i] Abbreviation H&Y: Hoehn and Yahr.
Table 2
Characteristics of double-blind and open-label studies to evaluate botulinum toxin injection in the treatment of Parkinson’s disease tremor.
| REF NO. | STUDY | YEAR | COUNTRY | STUDY TYPE | POPULATION (DIAGNOSIS) | NUMBER OF PATIENTS WITH PARKINSON | NUMBER OF DROPPED OUTPATIENTS | NUMBER OF INCLUDED PATIENTS | AGE (MEAN ± SD) | SEX | DURATION (YEAR) | PD SEVERITY (H & Y) | MAXIMUM FOLLOW UP (WEEK) | ASSESSMENTS TIME POINTS (WEEK) | OCEBM LEVEL OF EVIDENCE |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 20 | Samotus et al. | 2017 | England | Open label | 24 ET, 28 PD | 28 | 14 | 14 | 65.5 ± 11.5 | 21 F7 M | 7.5 ± 3.1 | UC | 96 | 0, 6, 16, 22, 32, 38, 48, 54, 64, 70, 80, 86, 96 | III |
| 21 | Pullman | 1996 | USA | Open label | 91 FD, 28 SD, 17 GD, 107 UED, 29 LED, 17 ET, 15 PD, 5 CBLT, 2 CTS, 6 CIS, 5 DDS, 1 PLSS | 15 | UC | 15 | 63.9 | UC | UC | 1 to 2.5 | 384 | 6 to 8 | III |
| 22 | Rahimi et al. | 2013 | England | Open label | 7 PD | 7 | 0 | 7 | 59 ± 7.7 | 5 F2 M | 5.6 ± 3.1 | UC | 12 | 4, 8, 12 | III |
| 23 | Rahimi et al. | 2015 | England | Open label | 28 PD | 28 | Week 6: 3Week 32: 3After week 32: 4 | 18 | 65.5 ± 11.5 | 21 F7 M | 7.5 ± 3.1 | 2 to 3 | 32 | 0, 6, 16, 22, 32 | III |
| 24 | Mittal et al. | 2017 | USA | Cross over double blind RCT with placebo control | 30 PD | 34:IncoA-Placebo: 16Placebo-IncoA: 18 | 4:IncoA-Placebo: 2 (moved)Placebo-IncoA: 2 (health problem) | 30:IncoA-Placebo: 14Placebo-IncoA: 16 | 67.12 | 23 F7 M | 3.12 | UC | 8 | 0, 4, 8 | I |
| 25 | Jankovic & Schwartz | 1991 | USA | Open label | 14 DysT, 12 ET, 22 Dyst+ET, 1PD, 1 PI, 1 MB | 1 | 0 | 1 | UC | UC | UC | 1 to 3 | UC | 1 | IV |
| 26 | Trosch & Pullman | 1994 | USA | Open label | 14 ET, 12 PD | 12 | 0 | 12 | 66.3 | UC | UC | 1 to 3 | 6 | 3, 6 | III |
| 27 | Henderson | 1996 | Sweden | Open label with placebo control | 17 non-DysT: 3 PD, 2 PD+ET, 3 MSA, 1 MD, 4ET, 2 ET + mild EPS, 1 HT, 1 EPT | 3 | 0 | 3 | 76.3 ± 9.46 | 2 F1 M | 5 | Moderate to severe | 6 | 0, 4, 8 | III |
| 28 | Niemann & Jankovic | 2018 | USA | Retrospective cohort | 99 ET, 6 PD, 37 DysT, 1 COT | 6 | 0 | 6 | UC | UC | UC | UC | 120 | 0, 120 | III |
| 29 | Kreiser | 2019 | France | Retrospective cohort | 21 ET, 8HTFbl, 4 Dyst, 4 Pwt, 1 PD | 1 | 0 | 1 | UC | UC | UC | UC | 4 | 0, 4 | IV |
[i] Abbreviation PD: Parkinson’s disease; H&Y: Hoehn and Yahr; OCEBM: Oxford center for evidence-based medicine; DysT: Dystonic tremor; ET: Essential tremor; PI: peripherally included; MB: midbrain; FD: focal dystonia, SD: segmental dystonia, GD: generalized dystonia, UED: upper extremity dystonia, LED: lower extremity dystonia, CBLT: Cerebellar tremor; CTS: cerebral trauma spasticity, CIS: cerebral infarct spasticity, DDS: dermyelinating disease spasticity, PLSS: primary lateral sclerosis spasticity, MSA: Multiple system atrophy; EPS: Extrapyramidal symptoms; HT: Head titubation; EPT: exaggerated physiological tremor; COT: Cerebellar outflow tremor; HTFbl: Holmes tremor secondary to a focal brain lesion; Pwt: Primary writing tremor; IncoA: Incobotulinumtoxin A; F; female; M; Male; IncoA: Incobotulinumtoxin A; UPDRS: Unified Parkinson’s disease rating scale; NIHCGC tremor severity: National Institutes of Health Collaborative Genetic Criteria; PGIC: Patient Global Impression of Change Scale; PDQL: Parkinson disease quality-of-life questionnaire; FTM: Fahan-Tolosa-Martin tremor scale; UC: unclear.
Figure 1
PRISMA flow chart summary of the systematic search process.
Table 3
A review of the approach of the first injection of botulinum toxin in the treatment of Parkinson’s tremor.
| AUTHOR, YEAR | INDEX | ECR | ECU | EDC | EPL | EIP | FCR | FCU | FDL | FPL | FDP | FDS | FPB | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Jankovic & Schwartz, 1991 | ✓ | ✓ | ✓ | ✓ | ||||||||||
| Trosch. R.M, et al., 1994 | No. | 9 | 5 | 2 | 10 | 9 | ||||||||
| Dose | 11.92 ± 3.84 | 11.67 ± 3.54 | 26.67 ± 22.55 | 18.21 ± 6.68 | 17.31 ± 6.96 | |||||||||
| Pullman, 1996 | 20.4 ± 14.2 | 15.8 ± 7.0 | 16.3 ± 5.5 | 6.5 ± 5.8 | 5.8 ± 2.8 | 25.6 ± 13.2 | 26.0 ± 16.7 | 53.3 ± 15.3 | 19.6 ± 7.2 | 30.6 ± 8.7 | 17.6 ± 9.4 | |||
| Henderson, 1996 | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||
| Rahimi. F. et al., 2013 | No. | 5 | 5 | 4 | 4 | 1 | 1 | |||||||
| Dose | 22 ± 3 | 22 ± 3 | 22 ± 3 | 22 ± 3 | 10 | 15 | ||||||||
| Rahimi. F. et al., 2015 | No. | 24 | 28 | 24 | 28 | |||||||||
| Dose | 18.5 ± 8.2 | 16.8 ± 6.7 | 16.3 ± 7.0 | 16.8 ± 6.7 | ||||||||||
| Samotus. O, et al., 2017 | ✓ | ✓ | ✓ | ✓ | ||||||||||
| Mittal, S. O., et al., 2017 | No. | 19 | 10 | 18 | 27 | 25 | 7 | 6 | 11 | |||||
| Dose | 5–10 | 5–10 | 5–10 | 10–15 | 10–20 | 10 | 10–20 | 5–10 | ||||||
| Niemann & Jankovic, 2018 | 6 | 6 | ||||||||||||
| Kreiser, 2019 | ||||||||||||||
| AUTHOR, YEAR | INDEX | PT | PQ | BICEPS | TRICEPS | SUP | BRACHORADIALIS | PECTORALIS MAJOR | TERES MAJOR | DELTOLID | SUPRASPINATUS | APB | OPPONENS POLLICIS | TOTAL |
| Jankovic & Schwartz, 1991 | 1 | |||||||||||||
| Trosch. R.M, et al., 1994 | No. | 1 | 2 | 2 | 12 | |||||||||
| Dose | 35.00 ± 7.07 | 63.23 ± 15.28 | 52.50 ± 23.98 | 107.50 ± 50.56 | ||||||||||
| Pullman, 1996 | 22.3 ± 6.2 | 17.9 ± 4.3 | 96.7 ± 32.7 | 58.6 ± 15.7 | 32.5 ± 14.7 | 51.4 ± 9.0 | 67.0 ± 27.3 | 65.2 ± 18.0 | 108.1 ± 24.6 | 3.1 ± 1.3 | 4.4 ± 1.3 | |||
| Henderson, 1996 | ||||||||||||||
| Rahimi. F. et al., 2013 | No. | 4 | 1 | 1 | 4 | 7 | ||||||||
| Dose | 21 ± 3 | 50 | 50 | 19 ± 3 | 97 ± 52 | |||||||||
| Rahimi. F. et al., 2015 | No. | 25 | 25 | 23 | 10 | 22 | 1 | 9 | 6 | 4 | 5 | 28 | ||
| Dose | 17.4 ± 5.1 | 16.0 ± 4.9 | 33.9 ± 10.3 | 29.5 ± 10.1 | 17.3 ± 4.5 | 20.0 ± 0.0 | 33.3 ± 8.7 | 25.8 ± 6.7 | 30.0 ± 9.4 | 28.0 ± 2.4 | 174.1 ± 66.8 | |||
| Samotus. O, et al., 2017 | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||
| Mittal, S. O., et al., 2017 | No. | 25 | 23 | 3 | 5 | 6 | 1 | |||||||
| Dose | 10–20 | 10–15 | 10 | 10 | 5–10 | 5 | ||||||||
| Niemann & Jankovic, 2018 | 47.9 ± 11.5 | |||||||||||||
| Kreiser, 2019 | ||||||||||||||
[i] Note All values are presented as mean ± standard deviation.
A tick sign indicates that the injection has been given in that muscle.
The results are related to the main injection and Booster injection, so in cases where even one person was injected, the indicators could be calculated.
Abbreviations No: the number of injected people; ECU: extensor carpi ulnaris; ECR: extensor carpi radialis; EDC: extensor digitrorum communis; FCU: flexor carpi ulnaris; FCR: flexor carpi radialis; FDL: flexor digitorum longus; FPL: flexor pollicis longus; EIP: extensor indicisproprius; EPL: extensor pollicis longus; FDP: flexor digitorum profunds; FDS: Flexor digitorum subllmis; FPB: Flexor pollicis brevis; PT: Pronator teres; PQ: Pronator quadratus; SUP: supinator; APB: Abductor pollicis brevis.
Table 4
The reported indicators related to the outcomes in the articles included in the review.
| AUTHOR, YEAR | PRIMARY OUTCOME: CLINICAL SEVERITY OF HAND TREMOR | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (CLINICAL SCALES/NON KINEMATIC MEASUREMENT METHOD) | ||||||||||||||||||
| FTM | SPINAL DRAWING | LINE DRAWING | NIHCGC | UPDRS QUESTIONNAIRE HAND ONLY (SCORE 0–4) | ||||||||||||||
| ITEM 16 | ITEM 20 | ITEM 21 | ||||||||||||||||
| PRE. INJ. | POST. INJ (4–6W) | POST. INJ (16 W) | POST. INJ (96 W) | PRE. INJ. | POST. INJ (4–6W) | PRE. INJ. | POST. INJ (16W) | PRE. INJ. | POST. INJ | PRE. INJ. | POST. INJ | PRE. INJ. | POST. INJ (16 W) | POST. INJ (96 W) | PRE. INJ. | POST. INJ (16 W) | POST. INJ (96 W) | |
| Trosch. R. M., et al., 1994 | ||||||||||||||||||
| Rahimi. F. et al., 2013 | 1.4 ± 1.5 | 0.7 ± 1.5 | 1.0 ± 1.5 | 0.7 ± 1.5 | (20 & 21 item from 8): baseline: 4.8 ± 1.5; post score: 2.1 ± 1.4 | |||||||||||||
| Rahimi. F. et al., 2015 | 9.6 ± 5.9 | 1.5 ± 1.5 | 1.2 ± 1.5 | 2.7 ± 0.6 | 2.0 ± 0.8 | 1.6 ± 0.9 | 0.9 ± 1.0 | |||||||||||
| Samotus. O, et al., 2017 | 9.6 ± 5.9 | 9 ± 5.7 | 9.1 ± 4.8 | 8.6 ± 3.3 | 2.7 ± 0.6 | 2.0 ± 0.8 | 1.3 ± 0.9 | 1.6 ± 0.9 | 0.9 ± 1.0 | 0.8 ± 0.7 | ||||||||
| Mittal, S. O., et al. (Placebo/IncoA), 2017 | 3 (2–4) | 0 (–2 to 2) | 2 (1–4) | 0 (–3 to 1) | 3 ± 0.64 | 0 ± 0.63* | 1.73 ± 0.98 | 0 ± 1.93* | ||||||||||
| Mittal, S. O., et al. (IncoA/Placebo), 2017 | 3 (2–4) | 1 (–1 to 2) | 3 (1–4) | 0 (0 to 2) | 3.27 ± 0.36 | 1.53 ± 1.31* | 2.47 ± 1.31 | 1.27 ± 0.97* | ||||||||||
| AUTHOR, YEAR | SECONDARY OUTCOME: KINEMATIC EVALUATION OF HAND TREMOR | |||||||||||||||||
| KINEMATIC EVALUATION | ||||||||||||||||||
| TREMOR COMPOSITION (TORSIOMETER)/INCLINOMETER (DEGREE) | ACCELEROMETER (M/S2) | |||||||||||||||||
| REST | POSTURE | REST | POSTURE | |||||||||||||||
| PRE. INJ. | POST. INJ | PRE. INJ. | POST. INJ | PRE. INJ. | POST. INJ | PRE. INJ. | POST. INJ | |||||||||||
| Trosch.R.M., et al., 1994 | 30.3 ± 15.7 | 23.1 ± 13.6 | 20.9 ± 14.7 | 16.5 ± 11.2 | ||||||||||||||
| Rahimi. F. et al., 2013 | 0.9 ± 1.2 | 1.2 ± 1.8 | 1.5 ± 2.1 | 2.3 ± 2.7 | ||||||||||||||
| Rahimi. F. et al., 2015 | ||||||||||||||||||
| Samotus. O, et al, 2017 | ||||||||||||||||||
| Mittal, S. O., et al. (Placebo/IncoA), 2017 | ||||||||||||||||||
| Mittal, S. O., et al. (IncoA/Placebo), 2017 | ||||||||||||||||||
[i] Abbreviations FTM: Fahan-Tolosa-Martin tremor scale; NIHCGC tremor severity: National Institutes of Health Collaborative Genetic Criteria; UPDRS: Unified Parkinson’s disease rating scale; Inj.: injection.
Figure 2
The therapeutic efficacy of local injection of botulinum toxin. The columns represent the changes on Unified Parkinson’s Disease rating scale-20, Unified Parkinson’s Disease rating scale-21, and grip strength before and after the injection.