Functional Neurologic Symptoms in Multiple Sclerosis: Estimated Prevalence and Associated Comorbidities

Functional neurologic disorder is a common cause of neurologic symptoms and disability in clinical practice, characterized by motor, sensory, or cognitive difficulties that show internal inconsistency and cannot be explained by structural nervous system damage. Despite growing recognition, research exploring functional neurologic symptoms (FNS) in people with multiple sclerosis (PwMS) remains limited. We aimed to estimate the prevalence of FNS in PwMS and characterize associated clinical features and comorbidities.

We conducted a retrospective convenience cohort study of all adult patients attending an Australian tertiary MS outpatient clinic over 12 months (January-December 2024). Inclusion criteria comprised a confirmed diagnosis of multiple sclerosis, clinically or radiologically isolated syndrome, age 18-64 years, and at least 1 in-person clinic visit. FNS were operationally defined to include (1) neurologist-documented functional neurologic disorder (FND), (2) patients with positive rule-in examination signs, (3) persistent postural-perceptual dizziness, and/or (4) cognitive symptoms inconsistent with MS that demonstrated features of functional cognitive disorder on neuropsychological or clinical assessment. Clinical data were extracted from the electronic medical record. Differences between patients with and without FNS were analyzed.

FNS were identified in 62 of 411 PwMS (15.1%, 95% CI 11.8%-18.9%), comprising 20 patients (4.9%) with a chart-documented FND diagnosis, 11 (2.7%) with "functional overlay," and 31 (7.5%) with rule-in signs alone. Overall, 55 PwMS (13.4%) demonstrated at least 1 FND sign in physical examination. PwMS with FNS were more likely to be female (96.8% vs 76.2%, p < 0.001) and to experience cognitive symptoms, fatigue impairing function, chronic pain, migraine, and polypharmacy (all p < 0.001). Psychiatric comorbidities were more prevalent, including anxiety or depression (p < 0.001), post-traumatic stress disorder (p = 0.012), and 3 or more psychiatric diagnoses (p = 0.003). Emergency department use was higher among those with FNS (p = 0.035). Multivariable logistic regression identified female sex, fatigue impairing function, cognitive symptoms, chronic pain, and migraine as factors most strongly associated with FNS.

FNS affected 1 in 7 PwMS in a tertiary outpatient clinic and were associated with a high burden of medical and psychiatric comorbidity, nonmotor symptoms, and greater emergency department use. More research is needed to further characterize and contextualize the clinical occurrence and impact of FNS in PwMS.