Decade of progress in motor functional neurological disorder: continuing the momentum

Abstract

Functional neurological disorder (FND) is a prevalent, disabling and costly condition at the neurology-psychiatry intersection. After being marginalised in the late 20th century, there has been renewed interest in this field. In this article, we review advances that have occurred over the past decade (2011-2020) across diagnosis, mechanisms, aetiologies, treatments and stigma in patients with motor FND (mFND, that is, functional movement disorder and functional limb weakness). In each content area, we also discuss the implications of recent advances and suggest future directions that will help continue the momentum of the past decade. In diagnosis, a major advance has been the emphasis on rule-in physical signs that are specific for hyperkinetic and hypokinetic functional motor symptoms. Mechanistically, greater importance has been given to determining 'how' functional neurological symptoms develop, highlighting roles for misdirected attention, expectation and self-agency, as well as abnormal influences of emotion/threat processing brain areas on motor control circuits. Aetiologically, while roles for adverse life experiences remain of interest in mFND, there is recognition of other aetiologic contributors, and efforts are needed to investigate links between aetiological factors and mechanisms. This decade has seen the first randomised controlled trials for physiotherapy, multidisciplinary rehabilitation and psychotherapy performed in the field, with consensus recommendations for physiotherapy, occupational therapy and outcome measures also published. Across patients, clinicians, healthcare systems and society, stigma remains a major concern. While challenges persist, a patient-centred integrated clinical neuroscience approach is primed to carry forward the momentum of the past decade into the future.

Keywords: conversion disorder; functional neurological disorder; neuropsychiatry.

Conflict of interest statement

Competing interests: DLP has received honoraria for continuing medical education lectures in functional neurological disorder and is on the editorial board of Epilepsy & Behavior. MH is an inventor of patents held by National Institutes of Health (NIH) for an immunotoxin for the treatment of focal movement disorders and the H-coil for magnetic stimulation; in relation to the latter, he has received license fee payments from the NIH (from Brainsway). He is on the medical advisory boards of Cala Health and Brainsway. He has research grants from Allergan for studies of methods to inject botulinum toxins, Medtronic, Inc. for a study of deep brain stimulation (DBS) for dystonia and Cala Health for studies of a device to suppress tremor. WCL receives editor’s royalties from the publication of Gates and Rowan’s Nonepileptic Seizures, 3rd edition (Cambridge University Press, 2010) and 4th edition (2018) and author’s royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015) and receives research support from the Department of Defense (DoD W81XWH-17-0169).

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1.. Model and evidence supporting the role for sensorimotor expectations and mis-directed attention in the pathophysiology of motor functional neurological disorder (mFND).

Based on Edwards et al., Panel A shows the hierarchical anatomy that is theorized to underlie false inference in patients with functional motor symptoms. Within this model, abnormal prior expectation is formed within prediction units of intermediate motor areas (here the supplementary motor area (SMA)) (black triangles). This prior is afforded abnormal precision by attentional processes (blue arrow) that cause intermediate level motor predictions (thick black arrows) to elicit movement, and prediction errors (thick red arrows) from prediction error units (red triangles) to report the unpredicted content of the movement to higher cortical areas (here, pre-SMA (pSMA)). The secondary consequence of these prediction errors is that prefrontal regions try to explain them in terms of symptomatic interpretation or misattribution of agency to external causes. Based on findings of Lin et al., Panel B (top portion) displays the broken escalator phenomenon. Following a series of initial ‘BEFORE’ tasks where participants step onto and off of a stationary platform (not shown), participants then go on to step onto a moving sled performed 10 times (‘MOVING’). In the ‘AFTER’ trials, participants once again step onto a stationary sled 5 times. The ‘broken escalator’ phenomenon, also called the locomotor after-effect, occurs when the learned motor response during the ‘MOVING’ phase is carried forward in the ‘AFTER’ trials. In Panel B (lower panel), linear trunk displacement measurements show that only patients with a functional gait displayed persistence of the locomotor after-effect across repeated ‘AFTER’ trials. Lin and colleagues suggested this reflected evidence of failed de-adaptation (failure to update expectations).

Figure 2.. Examples of two recent functional neuroimaging studies bridging neural mechanisms and etiological factors in motor functional neurological disorder (mFND).

Based on the findings of Diez et al., Panel A shows connectograms and scatterplots illustrating that resting-state functional connectivity strength between emotion processing brain areas (amygdala, insula) and primary motor cortex (precentral gyrus) positively correlated with the magnitude of previously experienced childhood physical abuse in patients with mixed mFND. Note: findings are bilateral but for ease of viewing only left hemisphere findings are displayed. Similar childhood physical abuse – functional brain architecture relationships were not observed in psychiatric controls. Based on the findings of Spagnolo et al., Panel B shows that childhood abuse burden correlated with functional movement disorder symptom severity only in the subset of patients carrying the G-703T polymorphism (rs4570625) in the tryptophan hydroxylase-2 (TPH2) gene; Panel C illustrates that T carriers with mFND exhibited reduced right amygdala-middle frontal gyrus resting-state functional connectivity compared to GG homozygotes with mFND and healthy controls.