Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Functional neurological disorder in people with long COVID: A systematic review.

BACKGROUND AND PURPOSE: Acute health events, including infections, can trigger the onset of functional neurological disorder (FND). It was hypothesized that a proportion of people with long COVID might be experiencing functional symptoms. METHODS: A systematic review of studies containing original data on long COVID was performed. The frequency and characteristics of neurological symptoms were reviewed, looking for positive evidence suggesting an underlying functional disorder and the hypothesized causes of long COVID. RESULTS: In all, 102 studies were included in our narrative synthesis. The most consistently reported neurological symptoms were cognitive difficulties, headaches, pain, dizziness, fatigue, sleep-related symptoms and ageusia/anosmia. Overall, no evidence was found that any authors had systematically looked for positive features of FND. An exception was three studies describing temporal inconsistency. In general, the neurological symptoms were insufficiently characterized to support or refute a diagnosis of FND. Moreover, only 13 studies specifically focused on long COVID after mild infection, where the impact of confounders from the general effects of severe illness would be mitigated. Only one study hypothesized that some people with long COVID might have a functional disorder, and another eight studies a chronic-fatigue-syndrome-like response. DISCUSSION: Neurological symptoms are prevalent in long COVID, but poorly characterized. The similarities between some manifestations of long COVID and functional disorders triggered by acute illnesses are striking. Unfortunately, the current literature is plagued by confounders, including the mixing of patients with initial mild infection with those with severe acute medical complications. The hypothesis that long COVID might in part correspond to a functional disorder remains untested.

The prognosis of functional limb weakness: a 14-year case-control study.

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.

Botulinum neurotoxin treatment in jerky and tremulous functional movement disorders: a double-blind, randomised placebo-controlled trial with an open-label extension.

OBJECTIVE: To study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD). METHODS: Patients with invalidating, chronic (>1 year) symptoms were randomly assigned to two subsequent treatments with BoNT or placebo every 3 months with stratification according to symptom localisation. Improvement on the dichotomised Clinical Global Impression-Improvement scale (CGI-I) (improvement vs no change or worsening) at 4 months, assessed by investigators blinded to the allocated treatment was the primary outcome. Subsequently all patients were treated with BoNT in a ten month open-label phase. RESULTS: Between January 2011 and February 2015 a total of 239 patients were screened for eligibility of whom 48 patients were included. No difference was found on the primary outcome (BoNT 16 of 25 (64.0%) vs Placebo 13 of 23 patients (56.5%); proportional difference 0.075 (95% CI -0.189 to 0.327; p=0.77). Secondary outcomes (symptom severity, disease burden, disability, quality of life and psychiatric symptoms) showed no between-group differences. The open-label phase showed improvement on the CGI-I in 19/43 (44.2%) of remaining patients, with a total of 35/43 (81.4%) improvement compared with baseline. CONCLUSIONS: In this double-blind randomised controlled trial of BoNT for chronic jerky and tremulous FMD, we found no evidence of improved outcomes compared with placebo. Motor symptoms improved in a large proportion in both groups which was sustained in the open-label phase. This study underlines the substantial potential of chronic jerky and tremulous FMD patients to recover and may stimulate further exploration of placebo-therapies in these patients. TRIAL REGISTRATION NUMBER: NTR2478.

Self-Help for Medically Unexplained Symptoms: A Systematic Review and Meta-Analysis.

OBJECTIVE: Medically unexplained symptoms (MUS), which are highly prevalent in all fields of medicine, are considered difficult to treat. The primary objective of this systematic review and meta-analysis was to assess the efficacy of self-help for adults with MUS. METHODS: Four electronic databases were searched for relevant studies. Randomized controlled trials comparing self-help to usual care or waiting list in adults with MUS were selected. Studies were critically appraised using the Cochrane "risk of bias assessment tool." Standardized mean differences (Hedges g) were pooled using a random-effects model. Outcomes were symptom severity and quality of life (QoL) directly posttreatment and at follow-up. RESULTS: Of 582 studies identified, 18 studies met all inclusion criteria. Studies were heterogeneous with regard to patient populations, intervention characteristics, and outcome measures. Compared with usual care or waiting list, self-help was associated with lower symptom severity (17 studies, n = 1894, g = 0.58, 95% confidence interval = 0.32-0.84, p < .001) and higher QoL (16 studies, n = 1504, g = 0.66, 95% confidence interval = 0.34-0.99, p < .001) directly posttreatment. Similar effect sizes were found at follow-up. A high risk of bias was established in most of the included studies. However, sensitivity analyses suggested that this did not significantly influence study results. Funnel plot asymmetry indicated potential publication bias. CONCLUSIONS: Self-help is associated with a significant reduction in symptom severity and improvement of QoL. The methodological quality of included studies was suboptimal, and further research is needed to confirm the findings of this meta-analysis.

The prognosis of functional (psychogenic) motor symptoms: a systematic review.

BACKGROUND: The prognosis of functional (or psychogenic) motor symptoms (weakness and movement disorder) has not been systematically reviewed. METHODS: We systematically reviewed PubMed for all studies of eight or more patients with functional motor symptoms reporting follow-up data longer than 6 months (excluding studies reporting specific treatments). We recorded symptom duration, physical and psychiatric comorbidity, disability, occupational functioning at follow-up and prognostic factors. RESULTS: 24 studies were included. There was heterogeneity regarding study size (number of patients (n)=10 491), follow-up duration clinical setting and data availability. Most studies (n=15) were retrospective. Reported symptom outcome was highly variable. Mean weighted follow-up duration was 7.4 years (in 13 studies where data was extractable). The mean percentage of patients same or worse at follow-up for all studies was 39%, range 10% to 90%, n=1134. Levels of physical disability and psychological comorbidity at follow-up were high. Short duration of symptoms, early diagnosis and high satisfaction with care predicted positive outcome in two studies. Gender had no effect. Delayed diagnosis and personality disorder were negatively correlated with outcome. Prognostic factors that varied between studies included age, comorbid anxiety and depression, IQ, educational status, marital status and pending litigation. CONCLUSIONS: Existing follow-up studies of functional motor symptoms give us some insights regarding outcome and prognostic factors but are limited by their largely retrospective and selective nature. Overall, prognosis appears unfavourable. The severity and chronicity of functional motor symptoms argues for larger prospective studies including multiple prognostic factors at baseline in order to better understand their natural history.

Altered Posterior Midline Activity in Patients with Jerky and Tremulous Functional Movement Disorders.

Objective: To explore changes in resting-state networks in patients with jerky and tremulous functional movement disorders (JT-FMD). Methods: Resting-state functional magnetic resonance imaging data from seventeen patients with JT-FMD and seventeen age-, sex-, and education-matched healthy controls (HC) were investigated. Independent component analysis was used to examine the central executive network (CEN), salience network, and default mode network (DMN). Frequency distribution of network signal fluctuations and intra- and internetwork functional connectivity were investigated. Symptom severity was measured using the Clinical Global Impression-Severity scale. Beck Depression Inventory and Beck Anxiety Inventory scores were collected to measure depression and anxiety in FMD, respectively. Results: Compared with HC, patients with JT-FMD had significantly decreased power of lower range (0.01-0.10 Hz) frequency fluctuations in a precuneus and posterior cingulate cortex component of the DMN and in the dorsal attention network (DAN) component of the CEN (false discovery rate-corrected p < 0.05). No significant group differences were found for intra- and internetwork functional connectivity. In patients with JT-FMD, symptom severity was not significantly correlated with network measures. Depression scores were weakly correlated with intranetwork functional connectivity in the medial prefrontal cortex, while anxiety was not found to be related to network connectivity. Conclusions: Given the changes in the posterodorsal components of the DMN and DAN, we postulate that the JT-FMD-related functional alterations found in these regions could provide support for the concept that particularly attentional dysregulation is a fundamental disturbance in these patients. Impact statement In this study, we explored static brain network functional connectivity in patients with jerky and tremulous functional movement disorders (JT-FMD) and healthy controls. We studied network functioning by analyzing functional connectivity measures, and also time course frequency spectra, which is novel compared with previous studies. We discovered aberrations in the frequency distribution of a posterior component of the default mode network (precuneus/posterior cingulate) and the dorsal attention network in patients with JT-FMD relative to controls. Conclusively, our findings could provide support for impaired attentional control as a fundamental disturbance in JT-FMD and contribute to the growing conceptualization of this disorder.

Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda.

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using "rule-in" examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

Internet-based self-help randomized trial for motor functional neurologic disorder (SHIFT).

OBJECTIVE: To determine whether self-rated health of patients with motor functional neurologic disorder (FND) can be improved by unguided Internet-based self-help and education. METHODS: In this nonblinded randomized controlled trial, patients were allocated 1:1 unbiased to an unguided education and self-help website in addition to usual care or usual care only. Patients over 17 years of age with a functional motor symptom that caused distress or disability were included. The primary outcome was self-rated health on the Clinical Global Improvement scale at 3 and 6 months. Secondary outcomes were severity of motor symptoms, other physical and psychiatric symptoms, physical functioning, quality of life, work and social adjustment, illness beliefs, and satisfaction with care. RESULTS: A total of 186 patients were randomized, with a follow-up rate of 87% at 6 months. There was no difference in improvement of self-rated health at 3 months (44% vs 40%, p = 0.899) or 6 months (42% vs 43%, p = 0.435). Secondary outcomes did not differ between groups, with a threshold of p < 0.01. Satisfaction was high, with 86% of patients recommending the website to other patients. CONCLUSION: We found no significant effect of the intervention added to usual care on self-rated health or secondary outcome measures, despite high patient satisfaction with the intervention. These results suggest that online education and nonguided self-help could be valuable additions to stepped care for motor FND, but are not effective treatments as interventions in their own right. CLINICALTRIALSGOV IDENTIFIER: NCT02589886. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with motor FND, online education and self-help intervention does not significantly improve self-rated health.

The chronnectome as a model for Charcot's 'dynamic lesion' in functional movement disorders.

This exploratory study set out to investigate dynamic functional connectivity (dFC) in patients with jerky and tremulous functional movement disorders (JT-FMD). The focus in this work is on dynamic brain states, which represent distinct dFC patterns that reoccur in time and across subjects. Resting-state fMRI data were collected from 17 patients with JT-FMD and 17 healthy controls (HC). Symptom severity was measured using the Clinical Global Impression-Severity scale. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. Independent component analysis was used to extract functional brain components. After computing dFC, dynamic brain states were determined for every subject using k-means clustering. Compared to HC, patients with JT-FMD spent more time in a state that was characterized predominantly by increasing medial prefrontal, and decreasing posterior midline connectivity over time. They also tended to visit this state more frequently. In addition, patients with JT-FMD transitioned significantly more often between different states compared to HC, and incorporated a state with decreasing medial prefrontal, and increasing posterior midline connectivity in their attractor, i.e., the cyclic patterns of state transitions. Altogether, this is the first study that demonstrates altered functional brain network dynamics in JT-FMD that may support concepts of increased self-reflective processes and impaired sense of agency as driving factors in FMD.

Electrophysiologic testing aids diagnosis and subtyping of myoclonus.

OBJECTIVE: To determine the contribution of electrophysiologic testing in the diagnosis and anatomical classification of myoclonus. METHODS: Participants with a clinical diagnosis of myoclonus were prospectively recruited, each undergoing a videotaped clinical examination and battery of electrophysiologic tests. The diagnosis of myoclonus and its subtype was reviewed after 6 months in the context of the electrophysiologic findings and specialist review of the videotaped clinical examination. RESULTS: Seventy-two patients with myoclonus were recruited. Initial clinical anatomical classification included 25 patients with cortical myoclonus, 7 with subcortical myoclonus, 2 with spinal myoclonus, and 15 with functional myoclonic jerks. In 23 cases, clinical anatomical classification was not possible because of the complexity of the movement disorder. Electrophysiologic testing was completed in 66, with agreement of myoclonus in 60 (91%) and its subtype in 28 (47%) cases. Subsequent clinical review by a movement disorder specialist agreed with the electrophysiologic findings in 52 of 60; in the remaining 8, electrophysiologic testing was inconclusive. CONCLUSIONS: Electrophysiologic testing is an important additional tool in the diagnosis and anatomical classification of myoclonus, also aiding in decision-making regarding therapeutic management. Further development of testing criteria is necessary to optimize its use in clinical practice.

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.

BACKGROUND: North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy. RESULTS: Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients. CONCLUSIONS: This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified Atkins diet might be considered as a possible treatment in this devastating disorder.

Functional Disorders in Neurology: Case Studies.

Functional, often called psychogenic, disorders are common in neurological practice. We illustrate clinical issues and highlight some recent research findings using six case studies of functional neurological disorders. We discuss dizziness as a functional disorder, describing the relatively new consensus term Persistent Posturo-Perceptual Dizziness (PPPD), axial jerking/myoclonus as a functional movement disorder, functional speech symptoms, post-concussion disorder with functional cognitive symptoms and finally advances in treatment of dissociative seizures and functional motor disorders.

Functional neurological disorders: mechanisms and treatment.

Functional neurological disorders are common problems in neurologic practice. In the past decade there has been an increasing interest in this group of disorders both from a clinical as well as research point of view. In this review, we highlight some of the most salient and exciting publications from recent years focusing especially on new findings illuminating mechanism and studies examining treatment.

Treatment of functional motor disorders.

OPINION STATEMENT: For the treatment of functional motor disorder, we recommend a three-stage approach. Firstly, patients must be assessed and given an unambiguous diagnosis, with an explanation that helps them understand that they have a genuine disorder, with the potential for reversibility. A key ingredient is allowing the patients to describe all of their symptoms as well as their ideas about what may be wrong. The patient should clearly understand that the positive diagnosis is based on the presence of typical signs (e.g., Hoover's sign for paralysis, entrainment test for tremor) that, in and of themselves, indicate the potential for reversibility. We suggest an approach that avoids the assumption that psychological stressors in the patient's life are causing the symptoms. The symptoms themselves are often the main stressor. Insisting that there must be others often leads to a frustrated doctor and an angry patient. Rather, at this initial stage, we encourage exploration of mechanisms - e.g., triggering of symptoms by pain, injury, or dissociation - and a discussion of how symptoms manifest as "abnormal motor programs" in the nervous system.Secondly, further time spent exploring the diagnosis, treating comorbidity, and, in the context of a multidisciplinary team, experimenting with altered movements and behaviors may benefit some patients, without the need for more complex intervention.Thirdly, some patients do require more complex treatment, often with a combination of physical rehabilitation and psychological treatments. Hypnosis, sedation, and transcranial magnetic stimulation may have a role in select patients.Finally, although they have confidence in the diagnosis, many patients do not respond to treatment. Ultimately, however, patients with functional motor disorder may have much greater potential for recovery than health professionals often consider.

Jerky periods: myoclonus occurring solely during menses.

BACKGROUND: In this case report, we describe an unusual case of a patient with myoclonus only occurring during menses. CASE REPORT: A 41-year-old female, known to have neurological sequelae after a car accident 1 year earlier, presented with myoclonic movements of the right arm and hand only during menses. Brain magnetic resonance imaging is compatible with head trauma. Electromyography shows brief irregular bursts with a duration of about 20 ms. DISCUSSION: This appears to be the first description of myoclonus appearing only during menses. We suggest a cortical origin for myoclonus.