Treatment outcomes in functional neurological disorder: a systematic review and meta-analysis exploring the influence of symptom chronicity.

Background: Functional neurological disorder (FND) is a common cause of neurological disability with symptoms spanning motor, sensory and cognitive domains. While effective treatments exist, the impact of symptom chronicity on treatment outcomes is unclear. This systematic review and meta-analysis investigated whether longer symptom duration influences treatment outcomes across FND phenotypes: functional movement disorders, functional/dissociative seizures (FDS) and mixed presentations. Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO and grey literature were systematically searched till 29 June 2024. Studies were included if they involved adult FND participants undergoing any intervention and evaluated symptom change, function and health-related quality of life (HrQoL). Studies were excluded with <10 participants, missing symptom duration data or irrelevant outcomes. Two reviewers independently extracted data and assessed risk of bias. Meta-analyses used random effects models, subgroup analyses and univariate meta-regression to examine associations with symptom chronicity. Results: 63 studies met inclusion criteria; 27 studies (885 participants) were meta-analysed. Longer symptom duration modestly reduced improvements in motor symptoms (-3.24 points/year, scale: 0-100) and physical HrQoL (-1.2 points/year, scale: 0-100). Global improvements (mean Clinical Global Impression-Change 2.43, 95% CI: 2.28 to 2.59, scale: 1-7) and mental HrQoL gains (mean Short Form-Mental Component Summary +5.04 points, 95% CI: 1.67 to 8.41) were observed irrespective of chronicity. FDS frequency reduced after psychotherapy in eight of nine studies, even with prolonged symptoms. Conclusions: Symptom chronicity modestly reduced motor and physical HrQoL improvements, but did not negate meaningful gains across a range of outcomes. Early diagnosis and treatment are critical for better outcomes, but remain beneficial in chronic stages.