Factors Influencing Triage to Rehabilitation in Functional Movement Disorder.

BACKGROUND: Treatment of functional movement disorder (FMD) should be individualized, yet factors determining rehabilitation engagement have not been evaluated. Subspecialty FMD clinics are uniquely poised to explore factors influencing treatment suitability and triage. OBJECTIVES: To describe our approach and explore factors associated with triage to FMD rehabilitation. METHODS: We conducted a retrospective chart review of 158 consecutive patients with FMD seen for integrated assessment by movement disorders neurology and psychiatry, with the purpose of triage to rehabilitation. Demographic and clinical variables were compared between patients triaged to therapy versus no therapy, and logistic regression was used to explore factors predictive of triage outcome. Change in primary outcome scores were analyzed. RESULTS: Sixty-six patients (42%) were triaged to FMD therapy from July 2019 to December 2021. Patients triaged to therapy were more likely to have a constant movement disorder, gait disorder and/or tremor, hyperarousal, readiness for change, and people pleasing traits. Patients triaged to no therapy demonstrated persistent diagnostic disagreement, an inability to appreciate motor symptom inconsistency, low self-agency, a propensity to dissociate, and cluster B traits. 90% of patients triaged to rehabilitation had improved outcomes. CONCLUSIONS: The ability to "opt-in" to FMD rehabilitation relies on different factors than those relevant to establishing a diagnosis. Unlike many other neurological disorders, a triage and treatment planning step is recommended to identify those likely to meaningfully engage at that time. Holistic assessment through a transdisciplinary lens, and working collaboratively with the patient is essential to prioritize symptoms, determine engagement, and identify treatment targets.

Setting up Functional Neurological Disorder Treatment Services: Questions and Answers.

Functional neurologic disorder (FND) is commonly encountered across outpatient and inpatient medical settings. Given the potential for a high burden of disability in some patients and mounting evidence for the efficacy of FND-specific multidisciplinary treatment services, expanding clinical services for this population is a necessity. In this perspective article, we discuss considerations for creating FND services, including the types of services that exist, how to start, how to identify appropriate referrals, and how to develop and monitor individualized treatment plans. In addition, we discuss how this effort can be done sustainably - balancing patient needs with limited healthcare resources.

Neuropsychiatric phenotypes in functional movement disorder.

OBJECTIVE: Functional movement disorder (FMD), the motor-dominant subtype of functional neurological disorder, is a complex neuropsychiatric condition. Patients with FMD also manifest non-motor symptoms. Given that patients with FMD are diagnosed based on motor phenotype, the contribution of non-motor features to the neuropsychiatric syndrome is not well characterized. The objective of this hypothesis-generating study was to explore potential novel, neuropsychiatric FMD phenotypes by combining movement disorder presentations with non-motor comorbidities including somatic symptoms, psychiatric diagnoses, and psychological traits. METHODS: This retrospective chart review evaluated 158 consecutive patients with a diagnosis of FMD who underwent deep phenotyping across neurological and psychiatric domains. Demographic, clinical, and self-report features were analyzed. A data-driven approach using cluster analysis was performed to detect patterns when combining the movement disorder presentation with somatic symptoms, psychiatric diagnoses, and psychological factors. These new neuropsychiatric FMD phenotypes were then tested using logistic regression models. RESULTS: Distinct neuropsychiatric FMD phenotypes emerged when stratifying by episodic vs. constant motor symptoms. Episodic FMD was associated with hyperkinetic movements, hyperarousal, anxiety, and history of trauma. In contrast, constant FMD was associated with weakness, gait disorders, fixed dystonia, activity avoidance, and low self-agency. Pain, fatigue, somatic preoccupation, and health anxiety were common across all phenotypes. CONCLUSION: This study found patterns spanning the neurological-psychiatric interface that indicate that FMD is part of a broader neuropsychiatric syndrome. Adopting a transdisciplinary view of illness reveals readily identifiable clinical factors that are relevant for the development and maintenance of FMD.

Moving Beyond Movement: Diagnosing Functional Movement Disorder.

Functional movement disorder (FMD) is a complex neuropsychiatric syndrome, encompassing abnormal movements and weakness, and is a common cause of potentially disabling neurological symptoms. It is vital to recognize that FMD is a syndrome, with nonmotor manifestations negatively affecting a patient's quality of life. This review highlights a diagnostic algorithm, where a history suggestive of FMD is combined with the presence of positive signs on examination and appropriate investigations to make the diagnosis. Positive signs indicate internal inconsistency such as variability and distractibility, and clinical findings that are incongruent with other known neurological disease. Importantly, the clinical assessment acts as the first opportunity to allow patients to understand FMD as the cause for their symptoms. Accurate and early diagnosis of FMD is necessary given that it is a treatable and potentially reversible cause of disability, with significant risk of iatrogenic harm associated with misdiagnosis.

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 movement disorder gender, age and phenotype study: a systematic review and individual patient meta-analysis of 4905 cases.

Functional movement disorder (FMD) is a common manifestation of functional neurological disorder presenting with diverse phenotypes such as tremor, weakness and gait disorder. Our current understanding of the basic epidemiological features of this condition is unclear. We aimed to describe and examine the relationship between age at onset, phenotype and gender in FMD in a large meta-analysis of published and unpublished individual patient cases. An electronic search of PubMed was conducted for studies from 1968 to 2019 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Individual patient data were collected through a research network. We described the distribution of age of onset and how this varied by gender and motor phenotype. A one-stage meta-analysis was performed using multilevel mixed-effects linear regression, including random intercepts for country and data source. A total of 4905 individual cases were analysed (72.6% woman). The mean age at onset was 39.6 years (SD 16.1). Women had a significantly earlier age of onset than men (39.1 years vs 41.0 years). Mixed FMD (23.1%), tremor (21.6%) and weakness (18.1%) were the most common phenotypes. Compared with tremor (40.7 years), the mean ages at onset of dystonia (34.5 years) and weakness (36.4 years) were significantly younger, while gait disorders (43.2 years) had a significantly later age at onset. The interaction between gender and phenotype was not significant. FMD peaks in midlife with varying effects of gender on age at onset and phenotype. The data gives some support to 'lumping' FMD as a unitary disorder but also highlights the value in 'splitting' into individual phenotypes where relevant.

Neuropsychiatric Treatments for Parkinson's Disease: Nonpharmacological Approaches.

Although diagnosed by characteristic motor features, Parkinson's disease and other movement disorders are frequently accompanied by a wide range of neuropsychiatric symptoms that require a multidisciplinary approach for treatment. Neuropsychiatric symptoms such as depression, anxiety and cognitive symptoms strongly influence quality of life, motor symptoms, and non-motor bodily symptoms. This review summarizes our current understanding of the neuropsychiatric symptoms in movement disorders and discusses the evidence base for treatments focusing on rehabilitation and nonpharmacological approaches. A practical approach is then proposed for patient selection for specific treatments based on disease stage. The article focuses mostly on Parkinson's disease as a prototypical movement disorder with the largest evidence base but the principles discussed herein are applicable to a range of other movement disorders.

Gender disparity and abuse in functional movement disorders: a multi-center case-control study.

BACKGROUND: To determine gender differences in rates of sexual and physical abuse in functional movement disorders compared to controls and evaluate if the gender disparity of functional movement disorders is associated with abuse history. METHODS: We performed a retrospective case-control study of self-reported trauma data from 696 patients (512 women) with functional movement disorders from six clinical sites compared to 141 controls (98 women) and population data. Chi-square was used to assess gender and disorder associations; logistic regression was used to model additive effects of abuse and calculate the attributable fraction of abuse to disorder prevalence. RESULTS: Higher rates of sexual abuse were reported by women (35.3%) and men (11.5%) with functional movement disorders compared to controls (10.6% of women; 5.6% of men). History of sexual abuse increased the likelihood of functional movement disorders among women by an odds ratio of 4.57 (95% confidence interval 2.31-9.07; p < 0.0001) and physical abuse by an odds ratio of 2.80 (95% confidence interval 1.53-5.12; p = 0.0007). Population attributable fraction of childhood sexual abuse to functional movement disorders in women was 0.12 (0.05-0.19). No statistically significant associations were found in men, but our cohort of men was underpowered despite including multiple sites. CONCLUSIONS: Our study suggests that violence against women may account for some of the gender disparity in rates of functional movement disorders. Most people with functional movement disorders do not report a history of abuse, so it remains just one among many relevant risk factors to consider.

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.

Diagnosing functional neurological disorder: seeing the whole picture.

Functional neurological disorder (FND) is a complex neuropsychiatric syndrome with many phenotypes that are commonly encountered in clinical practice. Despite the heterogeneity of FND, the rate of misidentification is consistently low. For the more common motor subtypes, there are clear positive clinical, electrophysiological, and rarely imaging criteria that can establish the diagnosis in the traditional sense. For nonmotor subtypes, the characterization may be less clear. Here, we argue that the current diagnostic criteria are not reflective of the current shared neuropsychiatric understanding of FND, and, as a result, provide an incomplete picture of the diagnosis. We propose a three-step diagnostic triad for FND, in which the traditional neurological diagnosis is only the first element. Other steps include psychiatric/psychological formulation, integration, and follow-up. We advocate that this diagnostic approach should be the shared responsibility of neurology and mental health professionals. Finally, a research agenda is proposed to address the missing factors in the field.

How Do I Examine Patients With Functional Tremor?

Functional tremor is the most common presentation of functional movement disorders and can occur in isolation or together with other functional symptoms, including other abnormal movements. The diagnosis of functional tremor is based on positive features on history, examination, and, if necessary, neurophysiological studies. Historical features include: sudden onset, a preceding physical event or injury, variability in severity with or without remission, variability in affected body parts, the presence of other somatic symptoms, and a history of failed therapeutic trials. Positive signs on examination include: variability in the frequency, direction, and distribution of the tremor; clear coherence in the different body parts affected; reduction or elimination of the tremor with distraction; and tremor amplification with attention, entrainability, suggestibility, and the presence of co-contraction. Neurophysiological studies include electromyography and accelerometry and can be helpful to make a laboratory-supported diagnosis when the clinical picture is less clear.

The evidence for multidisciplinary care in Parkinson's disease.

INTRODUCTION: Parkinson's Disease (PD) is a chronic and slowly progressive neurodegenerative disease. Team-based care is required to address and manage the diverse array of motor and non-motor symptoms in PD and related conditions. As the evidence base for the efficacy of non-pharmacological treatment of PD is expanding, many different centers are implementing interdisciplinary models of care with allied health professionals trained in PD. AREAS COVERED: In this review, the authors outline these various models and review the evidence for multidisciplinary approaches to care in PD. They begin by defining the terms used to describe the spectrum of multidisciplinary and integrated care models, followed by synthesizing the evidence for these models in PD. The authors then highlight some representative models to illustrate the variety of multidisciplinary care interventions: a community network-based model, a day-hospital model, an academic clinic-based model, and an intensive inpatient rehabilitation model. The authors synthesize these results and suggest directions for team-based PD care for the future. EXPERT OPINION: The future of medicine is team-based care that is decentralized and integrated vertically and horizontally across health systems. Building an evidence base for these complex interventions will require alternative models of evaluation other than randomized controlled trials.

What Is the Role of a Specialist Assessment Clinic for FND? Lessons From Three National Referral Centers.

OBJECTIVE: A growing interest in functional neurological disorders (FND) has led to the development of specialized clinics. This study aimed to better understand the structure and role of such clinics. METHODS: Data were retrospectively collected from clinical records at three national referral centers, two specifically for motor FND and one for FND in general. Data were for 492 consecutive patients referred over a 9- to 15-month period: 100 from the United Kingdom clinic, 302 from the Swiss clinic, and 90 from the Canadian clinic. Data included symptom subtype and duration, comorbid pain and fatigue, disability, and treatment recommendations. RESULTS: The mean age of the 492 patients was 44 years, and most (73%) were female. Most had a prolonged motor FND (mean symptom duration of 6 years); 35% were not working because of ill health, 26% received disability benefits, and up to 38% required a care giver for personal care. In the Swiss cohort, 39% were given a diagnosis of another somatic symptom disorder rather than an FND diagnosis. Pain was common in the United Kingdom (79%) and Canada (56%), as was fatigue (48% and 47%, respectively). Most patients (61%) were offered physiotherapy; referral to neuropsychiatry or psychology differed across centers (32%-100%). CONCLUSIONS: FND specialty clinics have an important role in ensuring correct diagnosis and appropriate treatment. Most patients with motor FND require specialized neurophysiotherapy. Patients readily accepted an integrated neuropsychiatric approach. Close collaboration between FND clinics and acute neurology facilities might improve early detection of FND and could improve outcomes.

Effects of expectation on placebo-induced dopamine release in Parkinson disease.

CONTEXT: Expectations play a central role in the mechanism of the placebo effect. In Parkinson disease (PD), the placebo effect is associated with release of endogenous dopamine in both nigrostriatal and mesoaccumbens projections, yet the factors that control this dopamine release are undetermined. OBJECTIVE: To determine how the strength of expectation of clinical improvement influences the degree of striatal dopamine release in response to placebo in patients with moderate PD. DESIGN: Randomized, repeated-measures study with perceived expectation as the independent between-subjects variable. SETTING: University of British Columbia Hospital, Vancouver, British Columbia, Canada. Patients Thirty-five patients with mild to moderate PD undergoing levodopa treatment. Intervention Verbal manipulation was used to modulate the expectations of patients, who were told that they had a particular probability (25%, 50%, 75%, or 100%) of receiving active medication when they in fact received placebo. MAIN OUTCOME MEASURES: The dopaminergic response to placebo was measured using [11C]raclopride positron emission tomography. The clinical response was also measured (Unified Parkinson Disease Rating Scale) and subjective responses were ascertained using patient self-report. RESULTS: Significant dopamine release occurred when the declared probability of receiving active medication was 75%, but not at other probabilities. Placebo-induced dopamine release in all regions of the striatum was also highly correlated with the dopaminergic response to open administration of active medication. Whereas response to prior medication was the major determinant of placebo-induced dopamine release in the motor striatum, expectation of clinical improvement was additionally required to drive dopamine release in the ventral striatum. CONCLUSIONS: The strength of belief of improvement can directly modulate dopamine release in patients with PD. Our findings demonstrate the importance of uncertainty and/or salience over and above a patient's prior treatment response in regulating the placebo effect and have important implications for the interpretation and design of clinical trials.

Accurate event-driven motion compensation in high-resolution PET incorporating scattered and random events.

With continuing improvements in spatial resolution of positron emission tomography (PET) scanners, small patient movements during PET imaging become a significant source of resolution degradation. This work develops and investigates a comprehensive formalism for accurate motion-compensated reconstruction which at the same time is very feasible in the context of high-resolution PET. In particular, this paper proposes an effective method to incorporate presence of scattered and random coincidences in the context of motion (which is similarly applicable to various other motion correction schemes). The overall reconstruction framework takes into consideration missing projection data which are not detected due to motion, and additionally, incorporates information from all detected events, including those which fall outside the field-of-view following motion correction. The proposed approach has been extensively validated using phantom experiments as well as realistic simulations of a new mathematical brain phantom developed in this work, and the results for a dynamic patient study are also presented.

Psychosocial issues in young-onset Parkinson's disease: current research and challenges.

Young-onset Parkinson's disease (YOPD) patients have psychosocial issues that create more challenges than for older patients. They are diagnosed during the most productive years of their lives, live longer with the disease, and are at increased risk for non-motor symptoms of PD. This article describes issues that health care professionals may need to address, including anxiety, depression, cognitive disturbances, breakdown of relationships, and employment. These psychosocial problems require as much attention as the medical problems; they negatively impact the emotional stability of both the patient and family, interfering with all relationships. YOPD patients can benefit from a team approach to their treatment.

Understanding the placebo effect: contributions from neuroimaging.

Neuroimaging studies have provided a major contribution to our understanding of the mechanisms of the placebo effect in neurological and psychiatric disorders. Expectation of symptom improvement has long been believed to play a critical role in the placebo effect, and is associated with increased endogenous striatal dopamine release in Parkinson's disease and increased endogenous opioid transmission in placebo analgesia. Evidence from positron emission tomography and functional magnetic resonance imaging studies suggests that expectations of symptom improvement are driven by frontal cortical areas, particularly the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortices. The ventral striatum is involved in the expectation of rewarding stimuli and, together with the prefrontal cortex, has also been shown to play an important role in the placebo-induced expectation of therapeutic benefit. Understanding the mechanisms of the placebo effect has important implications for treatment of several medical conditions, including depression, pain, and Parkinson's disease.