DOI: 10.3390/sclerosis4030025 ISSN: 2813-3064

Cryoneurolysis in Neurological Spasticity: Current Evidence with Emerging Applications in Multiple Sclerosis

Luigi Di Lorenzo

Background: Spasticity is one of the most disabling manifestations of multiple sclerosis (MS), contributing to limitations in walking and transfers, pain, progressive functional limitation, and reduced quality of life. Despite advances in rehabilitation, pharmacological therapies, botulinum toxin injections, and intrathecal baclofen, many patients continue to experience refractory focal or multifocal spasticity requiring alternative therapeutic approaches. Percutaneous cryoneurolysis has recently emerged as a minimally invasive peripheral neuromodulation technique capable of selectively reducing pathological muscle overactivity through reversible axonotmesis while preserving the structural framework necessary for nerve regeneration. Growing clinical experience has expanded its application across several neurological disorders; however, its role in MS has not yet been comprehensively defined. Methods: A structured narrative review was conducted through comprehensive searches of PubMed/MEDLINE, Scopus, and Web of Science. Original clinical studies evaluating percutaneous cryoneurolysis for neurological spasticity were identified and critically synthesized. Because disease-specific evidence in MS remains limited, studies involving other upper motor neuron disorders, including stroke, cerebral palsy, traumatic brain injury, and spinal cord injury, were also considered to provide a broader overview of current clinical applications, procedural techniques, safety, and functional outcomes. Results: The available evidence includes case reports, case series, and prospective and retrospective observational studies, together with recent evidence syntheses. Across different neurological conditions, ultrasound-guided cryoneurolysis has consistently demonstrated technical feasibility and a favorable safety profile, with reported reductions in spasticity, improvements in passive range of motion, pain reduction, facilitation of positioning and nursing care, and, in selected studies, improved functional performance. Recent observational cohorts and prospective studies have expanded the evidence base by providing larger patient populations and longer follow-up, while systematic evidence syntheses have confirmed the growing clinical interest in this technique. Nevertheless, substantial heterogeneity persists regarding patient selection, target nerves, procedural protocols, outcome measures, and duration of follow-up. Evidence specifically addressing patients with MS remains limited and is currently derived primarily from individual case reports and small clinical series. Conclusions: Current evidence suggests that percutaneous cryoneurolysis represents a promising minimally invasive adjunctive treatment for selected patients with focal or multifocal neurological spasticity, including those with multiple sclerosis. However, the available evidence remains predominantly observational, and randomized controlled trials comparing cryoneurolysis with established therapies are still lacking. Future multicenter prospective studies, standardized treatment protocols, and disease-specific investigations are required to better define patient selection, long-term efficacy, safety, and the role of cryoneurolysis within contemporary multidisciplinary spasticity management.

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