Neuropathic Pain in Neuromyelitis Optica Spectrum Disorders: Prevalence and Management Strategies-A Systematic Review...

Introduction: Neuropathic pain (NP) in neuromyelitis optica spectrum disorder (NMOSD) represents a significant and often under-recognized complication arising from central nervous system (CNS) lesions. Unlike other demyelinating disorders, NMOSD involves a distinct immunopathogenesis primarily driven by aquaporin-4 antibodies (AQP4-IgG), leading to severe inflammatory damage. NP is typically the consequence of inflammatory damage to the spinothalamic tract or dorsal columns, resulting in both acute and chronic pain syndromes. Methods: A systematic review and meta-analysis were conducted following a comprehensive search of Medline and Scopus, identifying nine eligible studies reporting on NP in NMOSD. Results: Pooled prevalence was estimated using a random-effects metaprop meta-analysis with Freeman-Tukey transformation and REML-based heterogeneity estimation. The pooled prevalence of NP among patients with NMOSD was 56.2% (95% CI: 41.7-70.1%; I² = 95.3%, p < 0.001). Sensitivity analysis including only AQP4-IgG⁺ cohorts revealed a prevalence of 63.2% (95% CI: 23.4-94.7%; I² = 98.1%, p < 0.001). No significant difference was found between mixed and AQP4-IgG⁺-only populations (53.05% vs. 63.27%, p = 0.63). Meta-regression showed no significant associations between NP prevalence and age (β = 0.01, p = 0.33) or disability (β = 0.08, p = 0.18). Qualitative synthesis demonstrated an association between thoracic spinal cord lesions and NP, and also indicated that NP was often resistant and refractory to standard pharmacologic therapies. Conclusions: NP affects one in two NMOSD patients, and is associated with thoracic spinal cord lesions. In comparison with multiple sclerosis, NP in NMOSD is primarily structural and immunopathological in origin. Treatment strategies remain inadequate, emphasizing the need for early recognition and a disease-specific therapeutic approach.