Artificial Intelligence in Managing Spasticity with Botulinum Toxin Type A—Insights from an Exploratory Pilot Investigation: The AIMS Study
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Description of the GPT-o1 Algorithm (Self-Generated by AI)
4.2. Consensus Among Rehabilitation Physicians
4.3. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| AI | Artificial Intelligence |
| BoNT/A | Botulinum toxin type A |
References
- Topol, E.J. High-performance medicine: The convergence of human and artificial intelligence. Nat. Med. 2019, 25, 44–56. [Google Scholar] [CrossRef]
- Dorr, D.A.; Adams, L.; Embí, P. Harnessing the promise of artificial intelligence responsibly. JAMA 2023, 329, 1347–1348. [Google Scholar] [CrossRef] [PubMed]
- Esteva, A.; Robicquet, A.; Ramsundar, B.; Kuleshov, V.; DePristo, M.; Chou, K.; Cui, C.; Corrado, G.; Thrun, S.; Dean, J. A guide to deep learning in healthcare. Nat. Med. 2019, 25, 24–29. [Google Scholar] [CrossRef] [PubMed]
- Fritz, P.; Kleinhans, A.; Raoufi, R.; Sediqi, A.; Schmid, N.; Schricker, S.; Schanz, M.; Fritz-Kuisle, C.; Dalquen, P.; Firooz, H.; et al. Evaluation of medical decision support systems (DDX generators) using real medical cases of varying complexity and origin. BMC Med. Inform. Decis. Mak. 2022, 22, 254. [Google Scholar] [CrossRef]
- Egger, J.; Gsaxner, C.; Pepe, A.; Pomykala, K.L.; Jonske, F.; Kurz, M.; Li, J.; Kleesiek, J. Medical deep learning—A systematic meta-review. Comput. Methods Programs Biomed. 2022, 221, 106874. [Google Scholar] [CrossRef]
- Kanjee, Z.; Crowe, B.; Rodman, A. Accuracy of a generative artificial intelligence model in a complex diagnostic challenge. JAMA 2023, 330, 78–80. [Google Scholar] [CrossRef]
- Reinkensmeyer, D.J.; Burdet, E.; Casadio, M.; Krakauer, J.W.; Kwakkel, G.; Lang, C.E.; Swinnen, S.P.; Ward, N.S.; Schweighofer, N. Computational neurorehabilitation: Modeling plasticity and learning to predict recovery. J. Neuroeng. Rehabil. 2016, 13, 42. [Google Scholar] [CrossRef]
- Lance, J.W. The control of muscle tone, reflexes, and movement: Robert Wartenberg Lecture. Neurology 1980, 30, 1303–1313. [Google Scholar] [CrossRef]
- Kuo, C.L.; Hu, G.C. Post-stroke spasticity: A review of epidemiology, pathophysiology, and treatments. Int. J. Gerontol. 2018, 12, 280–284. [Google Scholar] [CrossRef]
- Wissel, J.; Manack, A.; Brainin, M. Toward an epidemiology of poststroke spasticity. Neurology 2013, 80, S13–S19. [Google Scholar] [CrossRef]
- Francisco, G.E.; McGuire, J.R. Poststroke spasticity management. Stroke 2012, 43, 3132–3136. [Google Scholar] [CrossRef]
- Biering-Soerensen, B.; Stevenson, V.; Bensmail, D.; Grabljevec, K.; Martínez Moreno, M.; Pucks-Faes, E.; Wissel, J.; Zampolini, M. European expert consensus on improving patient selection for the management of disabling spasticity with intrathecal baclofen and/or botulinum toxin type A. J. Rehabil. Med. 2022, 54, jrm00241. [Google Scholar] [CrossRef]
- Simpson, D.M.; Hallett, M.; Ashman, E.J.; Comella, C.L.; Green, M.W.; Gronseth, G.S.; Armstrong, M.J.; Gloss, D.; Potrebic, S.; Jankovic, J.; et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. Neurology 2016, 86, 1818–1826. [Google Scholar] [CrossRef] [PubMed]
- Baude, M.; Nielsen, J.B.; Gracies, J.M. The neurophysiology of deforming spastic paresis: A revised taxonomy. Ann. Phys. Rehabil. Med. 2019, 62, 426–430. [Google Scholar] [CrossRef] [PubMed]
- Tamburin, S.; Filippetti, M.; Mantovani, E.; Smania, N.; Picelli, A. Spasticity following brain and spinal cord injury: Assessment and treatment. Curr. Opin. Neurol. 2022, 35, 728–740. [Google Scholar] [CrossRef] [PubMed]
- Baricich, A.; Battaglia, M.; Cuneo, D.; Cosenza, L.; Millevolte, M.; Cosma, M.; Filippetti, M.; Dalise, S.; Azzollini, V.; Chisari, C.; et al. Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study. Front. Neurol. 2023, 14, 1133390. [Google Scholar] [CrossRef]
- Boissonnault, È.; Jeon, A.; Munin, M.C.; Filippetti, M.; Picelli, A.; Haldane, C.; Reebye, R. Assessing muscle architecture with ultrasound: Implications for spasticity. Eur. J. Transl. Myol. 2024, 34, 12397. [Google Scholar] [CrossRef]
- Calderone, A.; Latella, D.; Bonanno, M.; Quartarone, A.; Mojdehdehbaher, S.; Celesti, A.; Calabrò, R.S. Towards Transforming Neurorehabilitation: The Impact of Artificial Intelligence on Diagnosis and Treatment of Neurological Disorders. Biomedicines 2024, 12, 2415. [Google Scholar] [CrossRef]
- Lee, M.H.; Siewiorek, D.P.; Smailagic, A.; Bernardino, A.; Bermúdez i Badia, S. Opportunities of a machine learning-based decision support system for stroke rehabilitation assessment. arXiv 2020, arXiv:2002.12261. [Google Scholar] [CrossRef]
- Alshami, A.; Nashwan, A.; AlDardour, A.; Qusini, A. Artificial Intelligence in rehabilitation: A narrative review on advancing patient care. Rehabilitacion 2025, 59, 100911. [Google Scholar] [CrossRef]
- Mennella, C.; Maniscalco, U.; De Pietro, G.; Esposito, M. The Role of Artificial Intelligence in Future Rehabilitation Services: A Systematic Literature Review. IEEE Access 2023, 11, 1024–1043. [Google Scholar] [CrossRef]
- Filippetti, M.; Lugoboni, L.; Di Censo, R.; Degli Esposti, L.; Facciorusso, S.; Varalta, V.; Santamato, A.; Calabrese, M.; Smania, N.; Picelli, A. Classification of upper limb spasticity patterns in patients with multiple sclerosis: A pilot observational study. J. Rehabil. Med. 2024, 56, jrm40548. [Google Scholar] [CrossRef]
- Hefter, H.; Jost, W.H.; Reissig, A.; Zakine, B.; Bakheit, A.M.; Wissel, J. Classification of posture in poststroke upper limb spasticity: A potential decision tool for botulinum toxin A treatment? Int. J. Rehabil. Res. 2012, 35, 227–233. [Google Scholar] [CrossRef] [PubMed]
- Esquenazi, A.; Alfaro, A.; Ayyoub, Z.; Charles, D.; Dashtipour, K.; Graham, G.D.; McGuire, J.R.; Odderson, I.R.; Patel, A.T.; Simpson, D.M. OnabotulinumtoxinA for lower limb spasticity: Guidance from a Delphi panel approach. PM&R 2017, 9, 960–968. [Google Scholar] [CrossRef] [PubMed]
- Simpson, D.M.; Patel, A.T.; Alfaro, A.; Ayyoub, Z.; Charles, D.; Dashtipour, K.; Esquenazi, A.; Graham, G.D.; McGuire, J.R.; Odderson, I.R. OnabotulinumtoxinA injection for poststroke upper-limb spasticity: Guidance for early injectors from a Delphi panel process. PM&R 2017, 9, 136–148. [Google Scholar]
- Harb, A.; Kishner, S. Modified Ashworth Scale. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. [Google Scholar]
- Meseguer-Henarejos, A.B.; Sánchez-Meca, J.; López-Pina, J.A.; Carles-Hernández, R. Inter- and intra-rater reliability of the Modified Ashworth Scale: A systematic review and meta-analysis. Eur. J. Phys. Rehabil. Med. 2018, 54, 576–590. [Google Scholar] [CrossRef]
- Ansari, N.N.; Naghdi, S.; Hasson, S.; Azarsa, M.H.; Azarnia, S. The Modified Tardieu Scale for the measurement of elbow flexor spasticity in adult patients with hemiplegia. Brain Inj. 2008, 22, 1007–1012. [Google Scholar] [CrossRef]
- Metz, C.; The New York Times. OpenAI Unveils New ChatGPT That Can Reason Through Math and Science. Available online: https://www.deccanherald.com/business/companies/openai-unveils-new-chatgpt-that-can-reason-through-math-and-science-6-3197173 (accessed on 12 September 2024).
- OpenAI. Introducing OpenAI o1. 2024. Available online: https://openai.com (accessed on 26 July 2025).
- Scaglione, F. Conversion ratio between Botox®, Dysport®, and Xeomin® in clinical practice. Toxins 2016, 8, 65. [Google Scholar] [CrossRef]
| Pattern | n | Physician 1 | Physician 2 | Physician 3 | Physician 4 | Physician 5 | All | n | Artificial Intelligence |
|---|---|---|---|---|---|---|---|---|---|
| Adducted shoulder | 8 | 81.21 ± 39.82 | 80.83 ± 25.49 | 70.21 ± 16.58 | 73.74 ± 38.69 | 68.74 ± 23.22 | 74.98 ± 5.84 | 1 | 40.00 ± n.c. |
| Flexed elbow | 11 | 80.29 ± 59.67 | 67.58 ± 28.44 | 76.51 ± 34.72 | 81.47 ± 43.05 | 61.51 ± 29.86 | 70.90 ± 8.62 | 7 | 62.86 ± 29.84 |
| Flexed wrist | 6 | 66.63 ± 29.83 | 56.67 ± 8.16 | 83.33 ± 25.82 | 64.13 ± 16.84 | 73.88 ± 31.17 | 64.98 ± 9.94 | 6 | 41.67 ± 17.22 |
| Flexed fingers | 9 | 77.78 ± 38.44 | 76.67 ± 37.16 | 51.36 ± 34.07 | 50.90 ± 19.65 | 70.00 ± 31.22 | 73.89 ± 13.31 | 7 | 52.14 ± 28.85 |
| Thumb in palm | 5 | 43.32 ± 9.15 | 46.00 ± 8.94 | 26.32 ± 6.69 | 37.98 ± 8.37 | 22.00 ± 4.47 | 32.66 ± 10.53 | 4 | 21.25 ± 2.50 |
| Adducted thigh | 12 | 65.96 ± 10.33 | 87.48 ± 7.55 | 88.18 ± 11.50 | 55.53 ± 27.73 | 84.83 ± 28.34 | 75.40 ± 14.81 | 13 | 36.41 ± 13.76 |
| Flexed knee | 4 | 75.03 ± 16.65 | 86.65 ± 9.03 | 75.00 ± 20.41 | 137.45 ± 79.81 | 75.84 ± 30.47 | 75.44 ± 5.69 | 1 | 140.00 ± n.c. |
| Extended knee | 4 | 68.73 ± 27.55 | 88.33 ± 14.53 | 95.83 ± 8.35 | 101,65 ± 25.20 | 76.67 ± 25.17 | 72.70 ± 13.53 | 6 | 70.83 ± 24.58 |
| Equinovarus foot | 35 | 189.85 ± 68.77 | 176.75 ± 63.48 | 164.00 ± 56.79 | 179.80 ± 64.89 | 169.30 ± 84.13 | 179.58 ± 9.95 | 39 | 145.64 ± 48.71 |
| Flexed toes | 9 | 45.33 ± 17.22 | 72.50 ± 27.12 | 63.89 ± 22.05 | 56.26 ± 26.21 | 53.81 ± 15.29 | 49.57 ± 8.04 | 6 | 45.83 ± 18.82 |
| Striatal toe | 4 | 37.48 ± 8.35 | 31.65 ± 1.91 | 28.75 ± 2.50 | 37.48 ± 8.35 | 29.15 ± 9.60 | 33.32 ± 4.32 | 5 | 18.99 ± 6.94 |
| Pattern | n | Physician 1 | Physician 2 | Physician 3 | Physician 4 | Physician 5 | All | n | Artificial Intelligence |
|---|---|---|---|---|---|---|---|---|---|
| Adducted shoulder | 8 | 75.00 (54.17; 75.00) | 73.33 (66.67; 83.30) | 68.33 (54.16; 81.22) | 56.65 (50.00; 91.65) | 60.00 (52.50; 79.12) | 68.33 (60.00; 73.33) | 1 | 40.00 (40.00; 40.00) |
| Flexed elbow | 11 | 75.00 (33.30; 75.00) | 66.67 (50.00; 66.67) | 75.00 (50.00; 75.00) | 66.60 (66.60; 80.00) | 50.00 (50.00; 60.00) | 66.67 (66.60; 75.00) | 7 | 50.00 (40.00; 100.00) |
| Flexed wrist | 6 | 66.60 (33.30; 100.00) | 55.00 (50.00; 62.50) | 100.00 (50.00; 100.00) | 66.60 (47.50; 77.90) | 80.00 (38.32; 102.50) | 66.60 (66.60; 80.00) | 6 | 50.00 (20.00; 52.50) |
| Flexed fingers | 9 | 75.00 (41.65; 112.50) | 66.67 (50.00; 116.67) | 50.00 (25.00; 80.00) | 43.30 (36.65; 72.50) | 60.00 (45.00; 105.00) | 60.00 (50.00; 66.67) | 7 | 40.00 (30.00; 80.00) |
| Thumb in palm | 5 | 50.00 (33.30; 50.00) | 50.00 (40.00; 50.00) | 25.00 (20.00; 33.30) | 33.30 (31.65; 46.65) | 20.00 (20.00; 25.00) | 33.30 (25.00; 50.00) | 4 | 20.00 (20.00; 23.75) |
| Adducted thigh | 12 | 66.65 (54.15; 75.00) | 83.30 (83.30; 95.82) | 83.30 (83.30; 100.00) | 48.30 (33.30; 63.27) | 83.30 (66.60; 100.00) | 83.30 (66.65; 83.30) | 13 | 30.00 (25.00; 50.00) |
| Flexed knee | 4 | 66.70 (66.70; 91.67) | 83.30 (80.82; 95.82) | 75.00 (56.25; 93.75) | 116.60 (74.95; 220.80) | 66.67 (54,16; 106.66) | 75.00 (66.70; 83.30) | 1 | 140.00 (140.00; 140.00) |
| Extended knee | 4 | 70.80 (41.62; 93.75) | 91.65 (73.32; 100.00) | 100.00 (87.47; 100.00) | 110.00 (74.95; 120.00) | 73.30 (54,15; 95.00) | 91.65 (73.30; 100.00) | 6 | 62.50 (50.00; 100.00) |
| Equinovarus foot | 35 | 200.00 (133.30; 233.30) | 150.00 (133.30; 216.67) | 166.67 (125.00; 200.00) | 170.00 (133.30; 240.30) | 166.60 (100,00; 217.45) | 166.67 (166.60; 170.00) | 39 | 150.00 (100.00; 200.00) |
| Flexed toes | 9 | 33.30 (33.30; 66.60) | 66.67 (50.00; 95.00) | 50.00 (50.00; 87.50) | 50.00 (33.30; 69.90) | 50.00 (45,00; 70.00) | 50.00 (50,00; 50.00) | 6 | 50.00 (25.00; 56.25) |
| Striatal toe | 4 | 33.30 (33.30; 45.82) | 31.65 (30.00; 33.30) | 30.00 (26.25; 30.00) | 33.30 (33.30; 45.82) | 30.00 (19,95; 37.50) | 31.65 (30,00; 33.30) | 5 | 20.00 (12,48; 25.00) |
| Pattern | n | Physician 1 Versus All | Physician 2 Versus All | Physician 3 Versus All | Physician 4 Versus All | Physician 5 Versus All |
|---|---|---|---|---|---|---|
| Adducted shoulder | 8 | 0.570 | 0.260 | 0.779 | 0.673 | 0.481 |
| Flexed elbow | 11 | 0.586 | 0.332 | 0.857 | 0.784 | 0.041 |
| Flexed wrist | 6 | 0.458 | 0.043 | 0.105 | 0.715 | 0.462 |
| Flexed fingers | 9 | 0.212 | 0.399 | 0.776 | 0.138 | 0.497 |
| Thumb in palm | 5 | 0.083 | 0.066 | 0.102 | 0.285 | 0.034 |
| Adducted thigh | 12 | 0.003 | 0.083 | 0.054 | 0.029 | 0.943 |
| Flexed knee | 4 | 0.705 | 0.066 | 1.000 | 0.144 | 0.713 |
| Extended knee | 4 | 0.144 | 0.705 | 0.317 | 0.269 | 0.144 |
| Equinovarus foot | 35 | 0.143 | 0.851 | 0.750 | 0.351 | 0.950 |
| Flexed toes | 9 | 0.087 | 0.046 | 0.102 | 0.733 | 0.223 |
| Striatal toe | 4 | 0.059 | 1.000 | 0.059 | 0.059 | 0.461 |
| Pattern | n | Artificial Intelligence Versus Physician 1 | Artificial Intelligence Versus Physician 2 | Artificial Intelligence Versus Physician 3 | Artificial Intelligence Versus Physician 4 | Artificial Intelligence Versus Physician 5 | Artificial Intelligence Versus All |
|---|---|---|---|---|---|---|---|
| Adducted shoulder | 8 | n.c. | n.c. | n.c. | n.c. | n.c. | n.c. |
| Flexed elbow | 11 | 0.553 | 0.866 | 0.866 | 0.735 | 0.752 | 0.734 |
| Flexed wrist | 6 | 0.066 | 0.102 | 0.066 | 0.068 | 0.068 | 0.041 |
| Flexed fingers | 9 | 0.068 | 0.068 | 0.500 | 0.345 | 0.068 | 0.498 |
| Thumb in palm | 5 | 0.066 | 0.066 | 0.180 | 0.068 | 0.655 | 0.059 |
| Adducted thigh | 12 | 0.026 | 0.010 | 0.011 | 0.246 | 0.017 | 0.016 |
| Flexed knee | 4 | n.c. | n.c. | n.c. | n.c. | n.c. | n.c. |
| Extended knee | 4 | 0.593 | 0.285 | 0.180 | 0.109 | 0.655 | 0.458 |
| Equinovarus foot | 35 | 0.002 | 0.026 | 0.180 | 0.009 | 0.215 | 0.030 |
| Flexed toes | 9 | 0.892 | 0.043 | 0.063 | 0.080 | 0.080 | 0.564 |
| Striatal toe | 4 | 0.066 | 0.066 | 0.066 | 0.068 | 0.144 | 0.066 |
| Type of Discrepancy | Frequency | Percentage |
|---|---|---|
| Treatment of more muscles of the same pattern | 17 | 20.48 |
| Omission of clinically relevant muscles | 14 | 16.87 |
| Ignoring clinical context (e.g., pain, functionality) | 13 | 15.67 |
| Substitution of target muscles | 9 | 10.84 |
| Symmetrical treatment despite asymmetry | 8 | 9.64 |
| Under-treatment of upper limb | 8 | 9.64 |
| Overtreatment of functionally preserved areas | 7 | 8.43 |
| Omission of shoulder muscles | 7 | 8.43 |
| Total | 83 | 100 |
| Number of Specialists Selecting Muscle | Decision |
|---|---|
| First round | |
| 1 out of 5 | Discarded |
| 2 or 3 out of 5 | Discussed in the second round |
| 4 or 5 out of 5 | Definitive muscle target |
| Second round | |
| 2 out of 5 | If no additional support, discarded |
| If only one additional support, sixth specialist was consulted; if yes, definitive muscle target; if not, discarded | |
| 3 out of 5 | If fourth preference obtained, definitive muscle target |
| If no further preference obtained, sixth specialist was consulted. If yes, definitive muscle target; if no, discarded | |
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Filippetti, M.; Di Censo, R.; Arcari, L.; Schiavariello, M.C.; Battaglia, M.; Facciorusso, S.; Spina, S.; Antonucci, L.; Santamato, A.; Baricich, A.; et al. Artificial Intelligence in Managing Spasticity with Botulinum Toxin Type A—Insights from an Exploratory Pilot Investigation: The AIMS Study. Toxins 2025, 17, 573. https://doi.org/10.3390/toxins17120573
Filippetti M, Di Censo R, Arcari L, Schiavariello MC, Battaglia M, Facciorusso S, Spina S, Antonucci L, Santamato A, Baricich A, et al. Artificial Intelligence in Managing Spasticity with Botulinum Toxin Type A—Insights from an Exploratory Pilot Investigation: The AIMS Study. Toxins. 2025; 17(12):573. https://doi.org/10.3390/toxins17120573
Chicago/Turabian StyleFilippetti, Mirko, Rita Di Censo, Lyria Arcari, Maria Concetta Schiavariello, Marco Battaglia, Salvatore Facciorusso, Stefania Spina, Laura Antonucci, Andrea Santamato, Alessio Baricich, and et al. 2025. "Artificial Intelligence in Managing Spasticity with Botulinum Toxin Type A—Insights from an Exploratory Pilot Investigation: The AIMS Study" Toxins 17, no. 12: 573. https://doi.org/10.3390/toxins17120573
APA StyleFilippetti, M., Di Censo, R., Arcari, L., Schiavariello, M. C., Battaglia, M., Facciorusso, S., Spina, S., Antonucci, L., Santamato, A., Baricich, A., Smania, N., & Picelli, A. (2025). Artificial Intelligence in Managing Spasticity with Botulinum Toxin Type A—Insights from an Exploratory Pilot Investigation: The AIMS Study. Toxins, 17(12), 573. https://doi.org/10.3390/toxins17120573

