Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders

Abstract

Importance: Functional neurological disorders (FND) are common sources of disability in medicine. Patients have often been misdiagnosed, correctly diagnosed after lengthy delays, and/or subjected to poorly delivered diagnoses that prevent diagnostic understanding and lead to inappropriate treatments, iatrogenic harm, unnecessary and costly evaluations, and poor outcomes.

Observations: Functional Neurological Symptom Disorder/Conversion Disorder was adopted by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, replacing the term psychogenic with functional and removing the criterion of psychological stress as a prerequisite for FND. A diagnosis can now be made in an inclusionary manner by identifying neurological signs that are specific to FNDs without reliance on presence or absence of psychological stressors or suggestive historical clues. The new model highlights a wider range of past sensitizing events, such as physical trauma, medical illness, or physiological/psychophysiological events. In this model, strong ideas and expectations about these events correlate with abnormal predictions of sensory data and body-focused attention. Neurobiological abnormalities include hypoactivation of the supplementary motor area and relative disconnection with areas that select or inhibit movements and are associated with a sense of agency. Promising evidence has accumulated for the benefit of specific physical rehabilitation and psychological interventions alone or in combination, but clinical trial evidence remains limited.

Conclusions and relevance: Functional neurological disorders are a neglected but potentially reversible source of disability. Further research is needed to determine the dose and duration of various interventions, the value of combination treatments and multidisciplinary therapy, and the therapeutic modality best suited for each patient.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Espay is supported by the National Institutes of Health and has received grant support from CleveMed/Great Lakes Neurotechnologies, Davis Phinney Foundation, and the Michael J Fox Foundation; personal compensation as a consultant or scientific advisory board member for Solvay, Abbott, Chelsea Therapeutics, TEVA, Impax, Merz, Lundbeck, and Eli Lilly; honoraria from TEVA, UCB, the American Academy of Neurology, and the Movement Disorders Society; and publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer. Dr Aybek is supported by a Swiss National Foundation Ambizione Grant (grant PZ00P3–147997). Dr Carson acknowledges submitting paid testimony in court actions on a range of neuropsychiatric topics and receiving payment as editor of Journal Neurology, Neurosurgery, and Psychiatry and royalties from BMJ press and Elsevier for books. Dr Edwards has received research funding from the Medical Research Council, National Institute for Health Research, and the Guarantors of Brain; honoraria from Merz Pharma, TEVA, and UCB; and publishing royalties from Oxford University Press. Dr Goldstein has received research funding from the National Institute of Health Research and publishing royalties from Wiley and Routledge. Dr Hallett serves as Chair of the Medical Advisory Board for and may receive honoraria and funding for travel from the Neurotoxin Institute. He might accrue revenue on US patent #6,780,413 B2 (issued August 24, 2004): Immunotoxin (MAB-Ricin) for the treatment of focal movement disorders, and US patent #7,407,478 (issued August 5, 2008): Coil for Magnetic Stimulation and methods for using the same (H-coil); in relation to the latter, he has received license fee payments from the National Institutes of Health (from Brainsway) for licensing of this patent. He is on the Medical Advisory Board of Cala Health. He is on the editorial board of approximately 20 journals, and received royalties and/or honoraria from publishing from Cambridge University Press, Oxford University Press, and Elsevier. Dr Hallett’s research at the National Institutes of Health is largely supported by the National Institutes of Health Intramural Program. Supplemental research funds have been granted by Merz for treatment studies of focal hand dystonia, Allergan for studies of methods to inject botulinum toxins, Medtronic Inc for a study of deep brain stimulation for dystonia, and Cala Health for studies of a device to suppress tremor. Dr LaFaver has received honoraria from Pfizer, Teva, the American Academy of Neurology, and the Movement Disorders Society and is on the medical advisory board for FND Hope, a patient organization for functional neurological disorders. Dr LaFrance has served on the editorial boards of Epilepsia, Epilepsy & Behavior, Journal of Neuropsychiatry and Clinical Neurosciences and Journal of Neurology, Neurosurgery and Psychiatry; receives editor’s royalties from the publication of Gates and Rowan’s Nonepileptic Seizures, 3rd ed. (Cambridge University Press, 2010) and 4th ed. (2018); author’s royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015); has received research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke(grant 5K23NS45902), Rhode Island Hospital, the American Epilepsy Society, the Epilepsy Foundation, Brown University, the Siravo Foundation, and the Department of Defense (grant W81XWH-17–1-0619); serves on the Epilepsy Foundation Professional Advisory Board; has received honoraria for the American Academy of Neurology Annual Course; has served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, Spectrum Health, and Emory University; and has provided medicolegal expert testimony. Dr Lang has served as an advisor for AbbVie, Allon Therapeutics, Avanir Pharmaceuticals, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Ceregene, Cipla, InteKrin, Lilly, Medtronic, Merck, Novartis, NeuroPhage Pharmaceuticals, Teva, and UCB; received honoraria from Medtronic, Teva, UCB, and AbbVie; received grants from Brain Canada, the Canadian Institutes of Health Research, the Edmond J. Safra Philanthropic Foundation, The Michael J Fox Foundation, the Ontario Brain Institute, National Parkinson Foundation, Parkinson Society Canada, Physicians Services Incorporated, Tourette Syndrome Association, W Garfield Weston Foundation; received publishing royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press; and has served as an expert witness in cases related to the welding industry. Dr Nicholson receives research funding from the National Institute for Health Research. Dr Nielsen receives research funding from the National Institute for Health Research. Dr Reuber receives payment as Editor in Chief of Seizure: European Journal of Epilepsy; royalties from Oxford University Press; an unrestricted research grant from UCB; and speaker fees from Eisai, Livanova, and UCB. Dr Voon is a Medical Research Council Senior Fellow (grant MR/P008747/1). Dr Stone receives royalties from UpToDate Inc, BMJ Publications, and Elsevier, and acknowledges paid testimony in court in relation to functional neurologic disorders. He is supported by NHS Scotland Career Fellowship and runs the free website https://www.neurosymptoms.org/ for patients with functional neurologic disorders. Dr Morgante has received honoraria as a Consultant and Advisory Board member from Medtronic, UCB, and Chiesi. She has received honoraria for speaking from UCB Pharma, Medtronic, Zambon, Chiesi, and Abbvie. She serves on the editorial boards of Movement Disorders Clinical Practice and Frontiers in Movement Disorders. She receives royalties from the publication of Disorders of Movement (Springer, 2016).

Figures

Figure.

Clinical Signs in Selected Functional Neurological Disorders A, Hoover sign in functional leg weakness is present if a weak hip extension is corrected when the patient flexes the contralateral hip against resistance. B, Drift without pronation sign in functional weakness is present when the affected outstretched arm, held in supination at the outset, fails to pronate when drifting. C, Fixed dystonia phenotypes expressed as fixed posturing of the jaw (unilateral deviation, often with ipsilateral platysma activation, resistant to passive manipulation), hand (with preservation of pincer function), and foot (ankle inversion with plantar flexion). D, Tubular vision in functional blindness is positive when the area of visual field defect remains unchanged despite moving away from the visual target