Multiple Sclerosis: Enhancing Botulinum Toxin Effects in Spasticity Management, a Systematic Review
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Eligibility Criteria
2.3. Selection Process
3. Results
3.1. Physical Exercise
3.2. Extracorporeal Shock Wave Therapy (ESWT)
3.2.1. Radial ESWT
3.2.2. Focused ESWT
3.3. Vibration
3.3.1. Whole Body Vibration
3.3.2. Segmental Muscle Vibration
3.4. Transcranial Direct Current Stimulation
3.5. Transcutaneous Electrical Nerve Stimulation
4. Discussion
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type | Intervention | Outcomes | Moments | Results | Adverse Effects | |
---|---|---|---|---|---|---|
Frasson [7], 2005 | Prospective, randomized, double blind, 12 pts spastic paraparesis (5 with SM) | Group I: BoNT + transcutaneous NS * (4 Hz) Group II: BoNT + transcutaneous NS (25 Hz) 5 days of 30 min/day | EMG * parameters (CMAP *), clinical assessment of spasticity | Baseline Days 2, 3, 4, 10, 15, 30 | Better blockade for group I Both groups decreased spasticity, significantly better for group I | No adverse effects |
Giovanelli [9], 2007 | Prospective, single-blind, randomized controlled trial, 40 pts | Group I: BoNT + physical exercise (15 daily sessions, passive or active exercise and stretching) versus Group II: BoNT alone | EDSS * MAS * Self-evaluation of spasticity on a VAS | Baseline, Weeks 2, 4, 12 | Significant improvement in objective and subjective spasticity at all moments Group I significantly better results | No adverse effects |
Paoloni [8], 2013 | Prospective, controlled, single blind, randomized, 42 pts | Group A: vibration (30 min, 120 Hz, three times a week for four weeks) Group B: vibration + BoNT Group C: BoNT Rectus femoris muscle Gastrocnemius medialis and lateralis muscles | MAS * Fatigue severity scale Barthel Index | Baseline, weeks 10 and 22 | Spasticity significantly reduced in all groups, Group B longer-lasting effects, up to week 22. Fatigability improved across all groups, with a significant reduction observed in Group B. | No adverse effects |
Marinaro [13], 2021 | Prospective, non-randomized, single blind, controlled trial, 16 pts | BoNT, 4 months later rESWT (500 impulses, energy density flux 1.8 barr, frequency 4 Hz), 4 weekly sessions, Triceps surae muscle | MAS * MTS * ROM * active, passive | Baseline, 30 days, 90 days after BoNT injection and after rESWT administration | After BoNT, all parameters improved significantly by day 30, peaked at day 90, and then gradually declined by day 120. Following radial ESWT, all parameters showed significant improvement on day 30. | No adverse effects |
Facciorusso [14], 2021 | Case report, one patient | SM with upper limb tremor BoNT Week 15: transcranial direct current stimulation (tDCS) | sEMG * ADL self-questionnaire 9 HPT * BBT * | Baseline Week 15 Week 30 | Functional parameters improved after BoNT and continued to improve after tDCS | Mild weakness in the extension of the fourth and fifth finger of the hand |
Hefter [10], 2024 | Prospective, controlled, pilot, 14 pts | Group 1: vibration ergometry training + BoNT Group 2: BoNT Leg muscles Arm muscles (according to evaluation) | Gait analysis (ground reaction forces, foot contact parameters) | Baseline Vibration protocol Control protocol | Gait parameters improved in patients with mild spasticity in both groups, no significant difference. Moderate spasticity: no functional benefit. | No adverse effects |
Déniz [11], 2025 | Phase 1, observational Phase 2, prospective, interventional, 8 pts (out of 18) | Phase I: BoNT alone Phase II: BoNT + fESWT, (EFD of 0.1 mJ/mm2, 1500 impulses at a frequency of 5 Hz) 3 weekly sessions, pectoralis major or subscapularis, the upper limb (elbow or wrist or finger flexors) and the lower limbs (rectus femoris quadriceps or triceps surae or tibialis posterior | Ashworth scale (AS) 10 MWT * | Baseline 6 months | Phase I: AS decreased with 1 point at week 5 and maintained at week 17 Phase II: AS decreased with 2 points at week 1, maintained in week 25 and significantly faster times on 10 MWT | Transient discomfort when applied in the proximity of bony surfaces, no skin reactions |
Déniz [12], 2025 | Prospective, randomized, controlled trial, 13 pts | BoNT + focused ESWT (3 weekly sessions) versus BoNT + unfocused ESWT (3 weekly sessions) Upper and lower limbs spastic muscles | Ashworth scale 10 MWT * Patient satisfaction | Baseline, 6 months | Both groups improved in spasticity and function (maintained from week 2 to week 26) Patient satisfaction significantly higher in unfocused group | No adverse effects |
Therapy Added to BoNT | Moment of Application, Number of Sessions | Results/Taking into Consideration the Limited Evidence |
---|---|---|
Physical exercise | After injection, 15 daily sessions | Spasticity reduction, functional improvement |
Radial ESWT | Four months after the injection, four weekly sessions | Spasticity reduction, functional improvement |
Focused/unfocused ESWT | After injection, four weekly sessions | Spasticity reduction, functional improvement |
Whole body vibration | After injection, five weekly sessions | Inconsistent results |
Segmental body vibration | After injection, three weekly session, four weeks | Spasticity reduction, functional improvement |
Transcranial direct current stimulation | After injection, five weekly sessions | Still under research |
Electrical stimulation (low frequency) | After injection, five daily sessions | Spasticity reduction, functional improvement |
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Poenaru, D.; Sandulescu, M.I.; Furculescu, C.; Potcovaru, C.G. Multiple Sclerosis: Enhancing Botulinum Toxin Effects in Spasticity Management, a Systematic Review. J. Clin. Med. 2025, 14, 5252. https://doi.org/10.3390/jcm14155252
Poenaru D, Sandulescu MI, Furculescu C, Potcovaru CG. Multiple Sclerosis: Enhancing Botulinum Toxin Effects in Spasticity Management, a Systematic Review. Journal of Clinical Medicine. 2025; 14(15):5252. https://doi.org/10.3390/jcm14155252
Chicago/Turabian StylePoenaru, Daniela, Miruna Ioana Sandulescu, Catalin Furculescu, and Claudia Gabriela Potcovaru. 2025. "Multiple Sclerosis: Enhancing Botulinum Toxin Effects in Spasticity Management, a Systematic Review" Journal of Clinical Medicine 14, no. 15: 5252. https://doi.org/10.3390/jcm14155252
APA StylePoenaru, D., Sandulescu, M. I., Furculescu, C., & Potcovaru, C. G. (2025). Multiple Sclerosis: Enhancing Botulinum Toxin Effects in Spasticity Management, a Systematic Review. Journal of Clinical Medicine, 14(15), 5252. https://doi.org/10.3390/jcm14155252