The prognosis of functional limb weakness: a 14-year case-control study
Open accessAbstract
Reliable data on the prognosis of functional motor disorder are scarce, as existing studies of the prognosis of functional motor disorder are nearly all retrospective, small and uncontrolled. In this study we used a prospectively recruited, controlled cohort design to assess misdiagnosis, mortality and symptomatic and health outcome in patients with functional limb weakness compared to neurological disease and healthy control subjects. We also carried out an exploratory analysis for baseline factors predicting outcome. One hundred and seven patients with functional limb weakness, 46 neurological and 38 healthy control subjects from our previously studied prospective cohort were traced for follow-up after an average of 14 years. Misdiagnosis was determined in a consensus meeting using information from records, patients and their GPs. Numbers and causes of death were collected via death certificates. Outcome of limb weakness, physical and psychiatric symptoms, disability/quality of life and illness perception were recorded with self-rated questionnaires. Outcome measures were compared within and between groups. Seventy-six patients (71%) with functional limb weakness, 31 (67%) neurological and 23 (61%) healthy controls were included in follow-up. Misdiagnosis was found in one patient in the functional limb weakness group (1%) and in one neurological control (2%). Eleven patients with functional limb weakness, eight neurological control subjects and one healthy control subject had died. Weakness had completely remitted in 20% of patients in the functional limb weakness group and in 18% of the neurological controls (P = 0.785) and improved in a larger proportion of functional limb weakness patients (P = 0.011). Outcomes were comparable between patient groups, and worse than the healthy control group. No baseline factors were independent predictors of outcome, although somatization disorder, general health, pain and total symptoms at baseline were univariably correlated to outcome. This study is the largest and longest follow-up study of functional limb weakness. Misdiagnosis in functional limb weakness is rare after long-term follow-up. The disorder is associated with a higher mortality rate than expected, and symptoms are persistent and disabling. It appears difficult to predict outcome based on common baseline variables. These data should help inform clinicians to provide a more realistic outlook of the outcome and emphasize the importance of active and targeted therapy.
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In a 14-year prospective case-control study of 89 patients with functional limb weakness published in 2019, the only person who had a diagnosis at follow-up which in hindsight may have been a better explanation for their symptoms had been diagnosed with MS.
“In a 14-year prospective case–control study of 89 patients with functional limb weakness published in 2019, the only person who had a diagnosis at follow-up which in hindsight may have been a better explanation for their symptoms had been diagnosed with MS. This patient had comorbid FND and MS [18].”
From Functional neurological disorder and multiple sclerosis: a systematic review of misdiagnosis and clinical overlap (2022) · cites this paper as [18]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThat patient had comorbid FND and MS.
“This patient had comorbid FND and MS [18].”
From Functional neurological disorder and multiple sclerosis: a systematic review of misdiagnosis and clinical overlap (2022) · cites this paper as [18]
FND diagnoses generally remain stable in clinical practice.
“Clinical practice suggests that FND diagnoses do generally remain stable [7, 17, 18]”
From Functional neurological disorder and multiple sclerosis: a systematic review of misdiagnosis and clinical overlap (2022) · cites this paper as [18]
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“Importantly, the dual diagnosis of DSM-IV-SD and FND correlated with poor clinical outcomes in a 14-year follow-up study of 76 patients with functional limb weakness (Gelauff et al. , 2019).”
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“Misdiagnosis rates in FND are low and comparable with misdiagnosis rates of other neurologic conditions.(9,10) The neural mechanisms of FND are also increasingly understood, including emerging evidence for aberrant motor-limbic connectivity, motor planning, self-agency perceptions, and multimodal integration among oth…”
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“This search for biomarkers is needed not for diagnostic purposes as clinical signs have been found reliable and diagnostic criteria are established but because it is still difficult to predict which patient will have a favourable outcome (Gelauff et al., 2019).”
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“The prognosis is often poor (gelauff et al., 2019; Ibrahim et al., 2009; Sharpe et al., 2010), associated with worse physical and mental health outcomes and greater impact on quality of life than in people with similar symptoms that are due to structural brain changes or known disease (carson et…”
BackgroundIntegrated model of care for functional movement disorder: targeting brain, mind and body
Bhatt, H., MacGillivray, L., Gilmour, G. S., Marcelle, K., Langer, L. K., & Lidstone, S. C. (2024) · Disability and Rehabilitation · doi:10.1080/09638288.2024.2373775 · Cited by 17 · see citing works
“Earlier studies in indicated an unfavorable prognosis [1–3].”
Functional neurological disorder: A common reason for a neurology inpatient referral
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Lessons Learned in Outpatient Physical Therapy for Motor Functional Neurological Disorder
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The neuropsychology of functional neurological disorders
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“…positive signs mean that FNDs are not a diagnosis of exclusion and the determination of FND by an experienced clinician is associated with high diagnostic accuracy and stability over time (i.e., misdiagnosis is rare; Gelauff et al., 2019; Stone et al., 2005, 2009; Walzl et al., 2019).”
BackgroundCortisol in functional neurological disorders: State, trait and prognostic biomarkers
Weber, S., Bühler, J., Messmer, F., Bruckmaier, R. M., & Aybek, S. (2024) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2024.111615 · Cited by 12 · see citing works
Speech and language therapy: A treatment case series of 20 patients with functional speech disorder
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“For example, a concurrent diagnosis of somatization disorder (indicative of prominent bodily complaints including pain) correlated with poor prognosis in a 14-year prospective study of clinical outcomes in patients with functional weakness (Gelauff et al., 2019).”
Functional Neurological Disorder: Historical Trends and Urgent Directions
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Movement perception of the tonic vibration reflex is abnormal in functional limb weakness
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The role of neuropsychology in the care of patients with functional neurological symptom disorder
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“Critically, when made by experienced clinicians, diagnoses of FNSD tend to be accurate and stable across time (Stone et al., 2005, 2009), with rates of misdiagnosis being similarly low to those of other neurological conditions (Gelauff et al., 2019; Walzl et al., 2019).”
Biopsychosocial prognostic indicators in Functional Neurological Disorder: A systematic review
Sekine, E. R., Kanaan, R., McMillan, J., Oxford, S., & Iles, R. (2025) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2025.112201 · Cited by 9 · see citing works
Botulinum neurotoxin (BoNT) treatment in functional movement disorders: long-term follow-up
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“The symptoms of FND can be highly disabling and are associated with high levels of distress, reduced quality of life and high health and social care utilisation (Carson et al., 2011; Gelauff et al., 2019; Merkler et al., 2015).”
BackgroundFunctional Gait Disorders: Clinical presentations, Phenotypes and Implications for treatment
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Calma, A. D., Heffernan, J., Farrell, N., Gelauff, J., O’Connell, N., Perez, D. L., Perriman, D. M., Smyth, L. M., Stone, J., & Lueck, C. J. (2023) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2023.111513 · Cited by 9 · see citing works
Self-citationIllness perception in functional neurological disorder: low illness coherence and personal control
Joos, A. A. B., Popkirov, S., Lahmann, C., Jöbges, M., Herrmann, C., Maner, P., Schörner, K., Birke, G., & Hartmann, A. (2024) · BMJ Neurology Open · doi:10.1136/bmjno-2024-000648 · Cited by 8 · see citing works
“16 36 In clinical practice, patients often report being puzzled by explanations that there is ‘nothing wrong’ with them.”
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“…& Pen fi l, 2008), autoimmune encephalitis (Flanagan et al., 2023; Wilkinson-Smith et al., 2020), sarcoma-induced osteomalacia, cerebellar medulloblastoma, Huntington ’ s chorea, dystonia (Teasell & Shapiro, 2002), astasia-abasia (Stankovi´c et al., 2015), paresis/paralysis (Gelauff et al., 2019).”
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Lessons from a Neurologist After 25 Years of Functional Neurological Disorder Subspeciality Practice
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“Two more recent cohort studies of FNDs in Scotland (periods covering 2000– 2004) [19,20] showed lower rates of overall misdiagnosis (between 0.”
BackgroundPhenomenology and psychiatric correlates of pseudocataplexy
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Outcomes of specialist physiotherapy for functional motor disorder: the Physio4FMD RCT
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Self-citationInpatient Rehabilitation for Acute Presentations of Motor Functional Neurological Disorder
Polich, G. R., Zalanowski, S., Maney, J., Sugarman, S., Christopulos, K., Hebb, C., Perez, D. L., Baslet, G. C., Shah, P., & Herman, S. D. (2023) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000002303 · Cited by 5 · see citing works
Functional Neurological Disorder
Butler, M., & Nicholson, T. R. (2024) · Cambridge University Press eBooks · doi:10.1017/9781911623861.018 · Cited by 5 · see citing works
Funktionelle neurologische Störungen – eine häufige, aber häufig nicht erkannte Diagnose
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Self-citationTreat by Suggestion: The Potential Use of N = 1 Trials in Functional Neurological Disorders
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“Functional neurological disorders (FND) are a common cause of refractory movement disorders.(1) In FND, in addition to pro-”
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Communication Challenges in Functional Movement Disorder
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Functional Movement Disorder in Older Adults
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“Breaking the News” of a Functional Movement Disorder
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Psychogenic Neurologic Deficits
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Myasthenia Gravis, Myasthenic Syndrome, and Related Disorders
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Functional Neurological Disorder
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La prise en soins des TNF en neurologie
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Cerebellar ataxias and functional movement disorders: navigating clinical overlap
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“…also due to the dysfunction of predictive cerebellar circuit functions, as abnormal predictive processing is considered a key mechanism of FMD. Finally, functional symptoms can occur in the prodromal phases of progressive cerebellar disease, 13 much like in other neurodegenerative diseases.”
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“Evidence indicates that pain in FND is associated with poorer clinical outcomes including greater severity of weakness [13].”
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“Recent literature has revealed a misdiagnosis rate of approximately 4% for FND in the outpatient setting [36,37] and about 11% in the inpatient setting [13,38].”
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“…medical comorbidities, illness duration, and select psychosocial factors (e.g. disability payment or litigation) may have prognostic implications for the motor and seizure subtypes of FND (Gelauff et al. 2014 ; LaFrance and Syc 2009 ; Gelauff et al. 2019 ; Duncan et al. 2016 ; Glass et al. 2018 ).”
Mega-Analysis of Structural Brain Imaging in Functional Neurological Disorder
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“Functional neurological disorder (FND), previously known as conversion disorder, is a common, costly, and potentially disabling neuropsychiatric disorder (1–3).”
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Treatment of Functional Neurological Disorders
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Unmet needs in functional neurological disorder related to digital healthcare
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“Follow-up studies suggest that whatever neurologists are doing, the diagnosis of FND appears reasonably stable over time [18 ,19 ].”
Self-citation
- Authors
- Gelauff, J. M., Carson, A., Ludwig, L., Tijssen, M. A. J., & Stone, J.
- Affiliations
- University Medical Center Groningen (NL)
- University of Edinburgh (GB)
- Corresponding author
- Gelauff, Jeannette M
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-06-05
- Volume
- 142
- Issue
- 7
- Pages
- 2137-2148
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2948558558
- Cited by
- 102
- References
- 32
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 14 · 2023: 17 · 2022: 18 · 2021: 7 · 2020: 17 · 2019: 5
- FWCI
- 9.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- NHS Research Scotland Career Fellowship
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Keywords
- prognosis, misdiagnosis, mortality, disability, quality of life, illness perception, somatization disorder, long-term follow-up, prognostic factors
- MeSH terms
- Cause of Death, Diagnostic Errors, Disability Evaluation, Female, Follow-Up Studies, Humans, Male, Middle Aged, Nervous System Diseases, Prognosis, Prospective Studies, Quality of Life, Remission Induction, Time Factors, Case-Control Studies, Muscle Weakness
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