Temporal Sequence of Onset: ME/CFS-like Fatigue and Functional Neurological Disorder

Background Fatigue is the most prevalent and one of the most disabling symptoms of Functional Neurological Disorder (FND), yet its causal relationship to the condition remains poorly understood. Emerging evidence suggests that chronic fatigue may precede rather than follow the onset of functional neurological symptoms. We hypothesised that a specific phenotype of chronic fatigue, resembling that seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), may act as a precipitating factor in FND. Methods We conducted a retrospective review of clinical records from 89 patients assessed through an integrated ME/CFS and FND community service in Wigan, UK, between March 2022 and March 2025. Complete data were available for 76 patients. Fatigue prevalence, phenotype, and its temporal relationship to the onset of FND symptoms were extracted and analysed descriptively. Results Fatigue was reported by 62 of 76 patients (81.5%). In 39 patients (51% of the cohort), fatigue predated the onset of FND symptoms by months to years and exhibited features resembling ME/CFS, including post-exertional malaise, cognitive dysfunction, pain, and immune-like symptoms unrelieved by rest. In all 39, fatigue onset followed one or more stressful life events. A further 23 patients (30%) reported fatigue emerging concurrently with or following FND onset, also with post-exertional exacerbation. The remaining 14 patients (18.5%) without significant fatigue tended to present with isolated focal symptoms and minimal fluctuation, or with primary psychiatric or pain co-morbidities. Conclusions These findings suggest that ME/CFS-like fatigue may play a previously underappreciated precipitating and perpetuating role in a substantial subgroup of FND patients. One possible interpretation is that persistent fatigue and post-exertional symptom exacerbation may constrain the brain’s capacity to process and integrate information, potentially contributing to the emergence or persistence of functional neurological symptoms. These observations are preliminary and require prospective validation, but they raise important questions about FND phenotypic heterogeneity and the appropriateness of exercise-based interventions in fatigue-predominant presentations.