Lower urinary tract dysfunction (LUTD) in multiple sclerosis (MS) is highly prevalent and characterised by marked clinical and pathophysiological heterogeneity. Outcomes of sacral neuromodulation (SNM) in this population are frequently perceived as inconsistent, limiting its utilisation in clinical practice. We hypothesised that treatment response is determined by underlying neuro-urological phenotype rather than intrinsic variability of the therapy. This study aimed to identify key determinants of response to SNM in MS and to develop a clinically applicable, risk-stratified model to guide patient selection.

A systematically informed narrative review was conducted using MEDLINE, Embase, and Cochrane databases. Studies evaluating the efficacy, safety, and durability of SNM in patients with MS were included. Data were analysed with emphasis on clinical phenotype (storage vs voiding symptoms), urodynamic characteristics (detrusor overactivity, compliance, contractility, post-void residual), and disease trajectory (stable vs progressive disease). Findings were synthesised using a pathophysiological framework to identify consistent determinants of response and inform a structured, risk-stratified model for patient selection.

SNM provides clinically meaningful improvement in carefully selected patients with MS; however, outcomes vary considerably across studies. When interpreted in relation to underlying pathophysiology, a consistent pattern emerges. Patients with stable disease, predominant storage symptoms, and preserved detrusor contractility demonstrate higher response rates, sustained symptom improvement, and greater treatment durability. In contrast, patients with progressive disease, detrusor underactivity, elevated post-void residual volumes, and significant voiding dysfunction show reduced efficacy and higher likelihood of treatment failure or need for revision. Across studies, detrusor contractility consistently emerges as a key determinant of response. These findings suggest that reported variability reflects heterogeneity in patient selection rather than intrinsic inconsistency of the therapy.

SNM outcomes in MS appear predictable when interpreted within a pathophysiological framework. Variability across studies likely reflects differences in neuro-urological phenotype and disease stage rather than treatment effect. Integrating clinical phenotype, urodynamic findings, and disease trajectory enables more accurate identification of patients most likely to benefit and supports a shift from empirical to mechanism-based clinical decision-making.

A risk-stratified approach provides a clinically relevant and actionable framework to guide patient selection, optimise outcomes, and reduce inappropriate intervention in patients with MS. This model supports a transition towards mechanism-informed, precision neuromodulation and may improve both clinical outcomes and healthcare resource utilisation in neuro-urological practice.