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Weber et al. provide evidence in support of a stress-diathesis model of functional neurological disorders. They identify trauma history in the form of emotional neglect as a psychological risk factor, and reduced hippocampus and amygdala volume as a predisposing biological trait marker., Stress is a well-known risk factor to develop a functional neurological disorder, a frequent neuropsychiatric medical condition in which patients experience a variety of disabling neurological symptoms. Only little is known about biological stress regulation, and how it interacts with predisposing biological and psychosocial risk factors. Dysregulation of the hypothalamic-pituitary-adrenal axis in patients with functional neurological disorders has been postulated, but its relationship to preceding psychological trauma and brain anatomical changes remains to be elucidated. We set out to study the hypothalamic-pituitary-adrenal axis analysing the cortisol awakening response and diurnal baseline cortisol in 86 patients with mixed functional neurological symptoms compared to 76 healthy controls. We then examined the association between cortisol regulation and the severity and duration of traumatic life events. Finally, we analysed volumetric brain alterations in brain regions particularly sensitive to psychosocial stress, acting on the assumption of the neurotoxic effect of prolonged cortisol exposure. Overall, patients had a significantly flatter cortisol awakening response (P < 0.001) and reported longer (P = 0.01) and more severe (P < 0.001) emotional neglect as compared to healthy controls. Moreover, volumes of the bilateral amygdala and hippocampus were found to be reduced in patients. Using a partial least squares correlation, we found that in patients, emotional neglect plays a role in the multivariate pattern between trauma history and hypothalamic-pituitary-adrenal axis dysfunction, while cortisol did not relate to reduced brain volumes. This suggests that psychological stress acts as a precipitating psychosocial risk factor, whereas a reduced brain volume rather represents a biological predisposing trait marker for the disorder. Contrarily, an inverse relationship between brain volume and cortisol was found in healthy controls, representing a potential neurotoxic effect of cortisol. These findings support the theory of reduced subcortical volumes representing a predisposing trait factor in functional neurological disorders, rather than a state effect of the illness. In summary, this study supports a stress-diathesis model for functional neurological disorders and showed an association between different attributes of trauma history and abnormalities in hypothalamus-pituitary-adrenal axis function. Moreover, we suggest that reduced hippocampal and amygdalar volumes represent a biological 'trait marker' for functional neurological disorder patients, which might contribute to a reduced resilience to stress.

BACKGROUND Functional neurological disorders have attracted a lot of attention of the neurological medical community over the last decades as new development in neurosciences has reduced stigma around it by showing brain network dysfunctions. An overlap with other neurological condition such as Multiple sclerosis is well known by clinicians but there is a lack of clinical and fundamental research in this field to better define diagnosis and therapeutic decisions as well as deep understanding of underlying pathophysiolopgy. AIM We set out to write a critical commentary on the state of knowledge in the borderland between FND and MS METHODS: We based our commentary on a joint point of view between an FND specialist and MS expert. RESULTS A brief review of previous literature and relevant new studies covering the overlap between FND and MS is presented along suggestions for future research directions CONCLUSION: There are clear diagnostic criteria for both FND and MS and a strict application of them will help better diagnosis and prevent unnecessary treatment escalation in MS or absence of referaal to multimodal therapy in FND. Better teaching of younger neurologist is needed as well as prospective research focusing on pathophysiology.

Contains fulltext : 289359.pdf (Publisher’s version ) (Closed access) 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.Data are available upon reasonable request. 8 p.

We set out to replicate findings of significant (a) reductions in pain, psychological distress, and motivational incongruence (i.e., insufficient motive satisfaction) after interdisciplinary multimodal pain treatment and (b) associations between reductions in motivational incongruence (i.e., improved motive satisfaction) and decreases in psychological distress (Vincent et al., Journal of Clinical Psychology in Medical Settings 28:331–343, 2021). 475 Patients with chronic primary pain completed standardized self-reported questionnaires assessing motivational incongruence, psychological distress, pain intensity, and pain interference at intake and discharge from a tertiary psychosomatic university clinic. We used hierarchical linear models to analyze motivational incongruence’s effects on psychological distress. We partially replicated Vincent et al.’s findings. Significant reductions in pain, psychological distress, and motivational incongruence after treatment were found. Reductions in motivational incongruence were associated with reductions in psychological distress. Similarly, a better motive satisfaction mediated the relationship between pain interference and psychological distress. Our findings show that reducing motivational incongruence may be a key component of treating chronic primary pain; we recommend to assess and target motivational incongruence to improve interdisciplinary multimodal pain treatment.

Functional neurological disorder (FND), previously regarded as a diagnosis of exclusion, is now a rule-in diagnosis with available treatments. This represents a major step toward destigmatizing the disorder, which was often doubted and deemed untreatable. FND is prevalent, generally affecting young and middle aged adults, and can cause severe disability in some individuals. An early diagnosis, with subsequent access to evidence based rehabilitative and/or psychological treatments, can promote recovery—albeit not all patients respond to currently available treatments. This review presents the latest advances in the use of validated rule-in examination signs to guide diagnosis, and the range of therapeutic approaches available to care for patients with FND. The article focuses on the two most frequently identified subtypes of FND: motor (weakness and/or movement disorders) and seizure type symptoms. Twenty two studies on motor and 27 studies on seizure type symptoms report high specificities of clinical signs (64-100%), and individual signs are reviewed. Rehabilitative interventions (physical and occupational therapy) are treatments of choice for functional motor symptoms, while psychotherapy is an emerging evidence based treatment across FND subtypes. The literature to date highlights heterogeneity in responses to treatment, underscoring that more research is needed to individualize treatments and develop novel interventions.

Functional neurological disorder is common in neurological practice. A new approach to the positive diagnosis of this disorder focuses on recognisable patterns of genuinely experienced symptoms and signs that show variability within the same task and between different tasks over time. Psychological stressors are common risk factors for functional neurological disorder, but are often absent. Four entities-functional seizures, functional movement disorders, persistent perceptual postural dizziness, and functional cognitive disorder-show similarities in aetiology and pathophysiology and are variants of a disorder at the interface between neurology and psychiatry. All four entities have distinctive features and can be diagnosed with the support of clinical neurophysiological studies and other biomarkers. The pathophysiology of functional neurological disorder includes overactivity of the limbic system, the development of an internal symptom model as part of a predictive coding framework, and dysfunction of brain networks that gives movement the sense of voluntariness. Evidence supports tailored multidisciplinary treatment that can involve physical and psychological therapy approaches.

Adverse life events precede the onset of functional neurological disorder (FND, also known as conversion disorder) more commonly than other neuropsychiatric conditions, but their aetiological role is unclear. We conducted a systematic review and quantitative analysis of the type, timing and number of life events preceding the onset of FND in adults, and a meta-analysis of the proportions of types of events in controlled studies. Fifty-one studies of different designs, covering 4247 patients, were eligible for inclusion. There was no clear majority of any type of preceding event. Family problems were the most common category of events, followed by relationship problems. Females were more likely to experience preceding family/relationship problems than males, who reported more work problems. Family problems were the commonest type of preceding event in studies in developing countries, whereas family and health problems were equally common in developed countries. Abuse was associated with early symptom onset, while patients with later onset were more likely to report family problems. The median number of events was one, and the events occurred closer to onset than in controls. Meta-analysis found that family, relationship and work events were all relatively more common in patients than pathological controls, as were events where symptoms might provide a solution to the stressor. In conclusion, although a range of events precede the onset of FND, they do not appear to do so uniformly. This may support a different aetiological role for stressors than in other disorders, although the support is indirect and the quality generally low.

Functional seizures (FS) known also as psychogenic non-epileptic seizures or dissociative seizures, present with ictal semiological manifestations, along with various comorbid neurological and psychological disorders. Terminology inconsistencies and discrepancies in nomenclatures of FS may reflect limitations in understanding the neuropsychiatric intricacies of this disorder. Psychological and neurobiological processes of FS are incompletely understood. Nevertheless, important advances have been made on underlying neuropsychopathophysiological mechanisms of FS. These advances provide valuable information about the underlying mechanisms of mind–body interactions. From this perspective, this narrative review summarises recent studies about aetiopathogenesis of FS at two levels: possible risk factors (why) and different aetiopathogenic models of FS (how). We divided possible risk factors for FS into three categories, namely neurobiological, psychological and cognitive risk factors. We also presented different models of FS based on psychological and neuroanatomical understanding, multilevel models and integrative understanding of FS. This work should help professionals to better understand current views on the multifactorial mechanisms involved in the development of FS. Shedding light on the different FS profiles in terms of aetiopathogenesis will help guide how best to direct therapy, based on these different underlying mechanisms.

Highlights • 1st Neuroimaging Workgroup Meeting in Functional Neurological Disorder (FND). • Underscores the importance of FND cohort characterization in brain imaging research. • Details methodological approaches taken in FND neuroimaging research to date. • Research agenda proposed to definitely elucidate the neural circuitry of FND. • Discussions underway regarding having FND researchers join the ENIGMA consortium., 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.

Background: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. Summary: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

BackgroundTourette disorder (TD), hallmarks of which are motor and vocal tics, has been related to functional abnormalities in large-scale brain networks. Using a fully data driven approach in a prospective, case–control study, we tested the hypothesis that functional connectivity of these networks carries a neural signature of TD. Our aim was to investigate (i) the brain networks that distinguish adult patients with TD from controls, and (ii) the effects of antipsychotic medication on these networks.MethodsUsing a multivariate analysis based on support vector machine (SVM), we developed a predictive model of resting state functional connectivity in 48 patients and 51 controls, and identified brain networks that were most affected by disease and pharmacological treatments. We also performed standard univariate analyses to identify differences in specific connections across groups.ResultsSVM was able to identify TD with 67% accuracy (p = 0.004), based on the connectivity in widespread networks involving the striatum, fronto-parietal cortical areas and the cerebellum. Medicated and unmedicated patients were discriminated with 69% accuracy (p = 0.019), based on the connectivity among striatum, insular and cerebellar networks. Univariate approaches revealed differences in functional connectivity within the striatum in patients v. controls, and between the caudate and insular cortex in medicated v. unmedicated TD.ConclusionsSVM was able to identify a neuronal network that distinguishes patients with TD from control, as well as medicated and unmedicated patients with TD, holding a promise to identify imaging-based biomarkers of TD for clinical use and evaluation of the effects of treatment.

Functional neurological (conversion) disorder (FND) is a prevalent and disabling condition at the intersection of neurology and psychiatry. Advances have been made in elucidating an emerging pathophysiology for motor FND, as well as in identifying evidenced-based physiotherapy and psychotherapy treatments. Despite these gains, important elements of the initial neuropsychiatric assessment of functional movement disorders (FND-movt) and functional limb weakness/paresis (FND-par) have yet to be established. This is an important gap from both diagnostic and treatment planning perspectives. In this article, the authors performed a narrative review to characterize clinically relevant variables across FND-movt and FND-par cohorts, including time course and symptom evolution, precipitating factors, medical and family histories, psychiatric comorbidities, psychosocial factors, physical examination signs, and adjunctive diagnostic tests. Thereafter, the authors propose a preliminary set of clinical content that should be assessed during early-phase patient encounters, in addition to identifying physical signs informing diagnosis and potential use of adjunctive tests for challenging cases. Although clinical history should not be used to make a FND diagnosis, characteristics such as acute onset, precipitating events (e.g., injury and surgery), and a waxing and waning course (including spontaneous remissions) are commonly reported. Active psychiatric symptoms (e.g., depression and anxiety) and ongoing psychosocial stressors also warrant evaluation. Positive physical examination signs (e.g., Hoover's sign and tremor entrainment) are key findings, as one of the DSM-5 diagnostic criteria. The neuropsychiatric assessment proposed emphasizes diagnosing FND by using "rule-in" physical signs while also considering psychiatric and psychosocial factors to aid in the development of a patient-centered treatment plan.

With the creation of the Somatic Symptom and Related Disorders category of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition in 2013, the functional neurological (symptom) disorder diagnostic criteria underwent transformative changes. These included an emphasis on ‘rule-in’ physical examination signs/semiological features guiding diagnosis and the removal of a required proximal psychological stressor to be linked to symptoms. In addition, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder, somatoform pain disorder and undifferentiated somatoform disorder conditions were eliminated and collapsed into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder diagnosis. With somatic symptom disorder, emphasis was placed on a cognitive-behavioural (psychological) formulation as the basis for diagnosis in individuals reporting distressing bodily symptoms such as pain and/or fatigue; the need for bodily symptoms to be ‘medically unexplained’ was removed, and the overall utility of this diagnostic criteria remains debated. A consequence of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition restructuring is that the diagnosis of somatization disorder that encompassed individuals with functional neurological (sensorimotor) symptoms and prominent other bodily symptoms, including pain, was eliminated. This change negatively impacts clinical and research efforts because many patients with functional neurological disorder experience pain, supporting that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition would benefit from an integrated diagnosis at this intersection. We seek to revisit this with modifications, particularly since pain (and a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder comorbidity, more specifically) is associated with poor clinical prognosis in functional neurological disorder. As a first step, we systematically reviewed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder literature to detail epidemiologic, healthcare utilization, demographic, diagnostic, medical and psychiatric comorbidity, psychosocial, neurobiological and treatment data. Thereafter, we propose a preliminary revision to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition allowing for the specifier functional neurological disorder ‘with prominent pain’. To meet this criterion, core functional neurological symptoms (e.g. limb weakness, gait difficulties, seizures, non-dermatomal sensory loss and/or blindness) would have ‘rule-in’ signs and pain (>6 months) impairing social and/or occupational functioning would also be present. Two optional secondary specifiers assist in characterizing individuals with cognitive-behavioural (psychological) features recognized to amplify or perpetuate pain and documenting if there is a pain-related comorbidity. The specifier of ‘with prominent pain’ is etiologically neutral, while secondary specifiers provide additional clarification. We advocate for a similar approach to contextualize fatigue and mixed somatic symptoms in functional neurological disorder. While this preliminary proposal requires prospective data and additional discussion, these revisions offer the potential benefit to readily identify important functional neurological disorder subgroups—resulting in diagnostic, treatment and pathophysiology implications., This article revisits the functional neurological disorder – pain intersection by systematically reviewing the somatization disorder literature. We propose a preliminary diagnostic criteria revision denoting the etiologically neutral specifier functional neurological disorder “with prominent pain”. Proposals are also suggested to characterize individuals “with prominent fatigue” and “with prominent mixed somatic symptoms”., Graphical Abstract Graphical Abstract

Background The sense of agency is an important aspect of motor control. Impaired sense of agency has been linked to several medical conditions, including schizophrenia and functional neurological disorders. A complex brain network subserves the sense of agency, and the right temporoparietal junction is one of its main nodes. In this paper, we tested whether transcranial magnetic stimulation over the right temporoparietal junction elicited behavioural changes in the sense of agency. Methods In experiment 1, 15 healthy participants performed a behavioural task during functional MRI, with the goal of localizing the area relevant for the sense of agency in the right temporoparietal junction. In the task, the movement of a cursor (controlled by the participants) was artificially manipulated, and the sense of agency was either diminished (turbulence) or enhanced (magic). In experiment 2, we applied transcranial magnetic stimulation in 20 healthy participants in a sham-controlled, crossover trial with excitatory, inhibitory or sham (vertex) stimulation. We measured the summary agency score, an indicator of the sense of agency (lower values correspond to diminished sense of agency). Results Experiment 1 revealed a peak of activation during agency manipulation in the right temporoparietal junction (Montreal Neurological Institute coordinates x, y, z: 68, -26, 34). Experiment 2 showed that inhibition of the right temporoparietal junction significantly reduced the summary agency score in both turbulence (from -14.4 ± 11.4% to -22.5 ± 8.9%), and magic (from -0.7 ± 5.8% to -4.4 ± 4.4%). Limitations We found no excitatory effects, possibly because of a ceiling effect (because healthy participants have a normal sense of agency) or noneffectiveness of the excitatory protocol. Conclusion Our experiments showed that the network subserving the sense of agency was amenable to neuromodulation in healthy participants. This sets the ground for further research in patients with impaired sense of agency. Clinical trial identification: DRKS00012992 (German clinical trials registry).

A dualistic mind-body understanding of functional neurological disorders (FNDs), also known as conversion disorders, has led to the view that the cause of the symptom should be either psychological (psychogenic) or physical (neurogenic-"organic"). One of the most influential psychological approaches is the Freudian model of conversion, which suggests that FNDs arise from a defense process in which emotional stress is converted into physical symptoms. This conversion theory has been challenged in recent years, accompanied by a shift in emphasis toward neuropathophysiological models of FND and away from historical psychological concepts. In this review, the authors consider the contemporary relevance of the conversion model from the neuroscientific perspective to reconcile the role of both psychological and biological factors in FND. A narrative review of recent neuroscientific findings pertaining to the conversion model of FND, encompassing neuroimaging, cognitive psychology, biological markers, and epigenetic studies, was performed. Research on the role of psychological stressors is discussed. Neurobiological mechanisms of repression of traumatic memories and their translation into physical symptoms are then explored. Finally, the role of physical symptoms as a potential protective defense mechanism against social stressors is considered. The authors argue that the conversion concept is consistent with recent neuroscientific research findings, and the model allows psychological and neurobiological concepts to be reconciled within a single account of FND that begins to resolve the dualistic mind-body dichotomy.

ObjectivesWe aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes.MethodsA systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group.ResultsFive FND-specific measures were identified—three clinician-rated and two patient-rated—but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost–utility (eg, healthcare resource use and quality-adjusted life years).ConclusionsThere are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.

The American Neuropsychiatric Association’s Committee on Research assigned the task of defining the most helpful clinical factors and tests in establishing the diagnosis of psychogenic nonepileptic seizures (PNES) during a neuro-psychiatric assessment. A systematic review of the literature was conducted using three search engines and specified search terms for PNES and the predetermined clinical factors and diagnostic tests, followed by a selection process with specific criteria. Data extraction results from selected articles are presented for clinical factors (semiology, psychiatric comorbidities, medical comorbidities, psychological traits) and diagnostic tests (EEG, psychometric and neuropsychological measures, prolactin level, clinical neu-roimaging, autonomic testing). Semiology with video EEG (vEEG) remains the most valuable tool to determine the diagnosis of PNES. With the exception of semiology, very few studies revealed the predictive value of a clinical factor for PNES, and such findings were isolated and not replicated in most cases. Induction techniques, especially when coupled with vEEG, can lead to a captured event, which then con-firms the diagnosis. In the absence of a captured event, postevent prolactin level and personality assessment can support the diagnosis but need to be carefully contextual-ized with other clinical factors. A comprehensive clinical assessment in patients with suspected PNES can identify several clinical factors and may include a number of tests that can support the diagnosis of PNES. This is especially relevant when the gold standard of a captured event with typical semiology on vEEG cannot be obtained.

Background Functional parkinsonism (FP) is considered rare but no studies have looked at its frequency. Case series have described high rates of comorbidity with Parkinson's disease (PD), suggesting a possible association between these conditions. Objectives To study the prevalence, epidemiology and clinical features of FP and its association with PD. Methods We conducted a cross-sectional population-based prevalence study as well as a chart review of cases who received a diagnosis of FP over a 10-year-period in two movement disorder clinics in Switzerland. Epidemiological data regarding FP features were collected. The co-occurrence of PD, psychiatric disorders and other functional disorders were recorded. Clinical differences between FP and FP + PD groups are presented and discussed in light of a literature review. Results The crude prevalence of FP was 0.64 per 100,000 in our population. FP represented 0.24% of patients with parkinsonism. Among 12 FP cases, female gender predominance (87%), mean age of onset of 45.5(± 13.3 Standard deviation SD) years and prolonged diagnostic delay (mean 59 ± 75 SD months) was found. Six patients had an additional diagnosis of PD, 83% of depression and 66% of other functional neurological disorder. In four patients with FP + PD, FP preceded PD by 6 to 56 months. Conclusions These results suggest that FP should be considered in the differential diagnosis of patients presenting with parkinsonism. The high rate of co-occurrence with PD emphasizes the importance of long-term follow up of these patients. The observation that FP often precedes PD should be verified in prospective studies.

Background Motor functional neurological disorder (mFND) is a clinical diagnosis with reliable features; however, patients are reluctant to accept the diagnosis and physicians themselves bear doubts on potential misdiagnoses. The identification of a positive biomarker could help limiting unnecessary costs of multiple referrals and investigations, thus promoting early diagnosis and allowing early engagement in appropriate therapy. Objectives To test whether resting-state (RS) functional magnetic resonance imaging could discriminate patients suffering from mFND from healthy controls. Methods We classified 23 mFND patients and 25 age- and gender-matched healthy controls based on whole-brain RS functional connectivity (FC) data, using a support vector machine classifier and the standard Automated Anatomic Labeling (AAL) atlas, as well as two additional atlases for validation. Results Accuracy, specificity and sensitivity were over 68% (p = 0.004) to discriminate between mFND patients and controls, with consistent findings between the three tested atlases. The most discriminative connections comprised the right caudate, amygdala, prefrontal and sensorimotor regions. Post-hoc seed connectivity analyses showed that these regions were hyperconnected in patients compared to controls. Conclusions The good accuracy to discriminate patients from controls suggests that RS FC could be used as a biomarker with high diagnostic value in future clinical practice to identify mFND patients at the individual level., Highlights • We classified FND patients from controls with 68% accuracy using resting-state fMRI. • Right caudate-amygdala connectivity best discriminated patients with FND from controls. • Future additional steps are needed before translation to clinical use. • This could be used in complement of clinical signs for the diagnosis of FND.

Contexte: Les symptomes neurologiques fonctionnels (non expliques par une cause structurelle ou pathologique) s'observent dans environ 30% des consultations ambulatoires en neurologie. Anciennement designes par le terme d'Hysterie et classiquement associes a des stress d'ordre psychologique, ces troubles se definissent actuellement par une incompatibilite avec une affection neurologique mise en evidence a l'examen clinique. En effet, la nouvelle classification du DSM-5 insiste sur cet aspect du diagnostic qui necessite la mise en evidence de signes dit « positifs » lors de l'examen clinique. Dans ce contexte, il est important de pouvoir etablir la validite de ces signes. Objectif: Le but de cette etude prospective est de valider les signes du sternocleidomastoidien et du peaucier, des signes peu etudies et dont la valeur scientifique n’est pas encore solide, en determinant leur specificite et sensibilite, seuls et combines. Methode: 30 patients presentant un diagnostic avere de troubles neurologiques fonctionnels (base sur les criteres du DSM-5) et 40 patients souffrant d’une lesion organique etablie ont ete inclus de maniere prospective. Les patients presentaient tous une paresie d’un membre mesuree sur l’echelle de cotation de la force (Medical Research Council Scale for muscle strength) a

Background In the nineteenth century, Jean Martin Charcot explained functional neurological disorder (formerly called conversion disorder) as a “psychodynamic” lesion. Numerous advances in neuroimaging have permitted identification of the neural underpinnings of this disorder. Case presentation Herein we describe a case of functional neurological disorder (FND) with initial left sensorimotor deficit, in-coordinated limb movements, neglect, clouded consciousness, slurred speech and a semiology of visual impairment. A single photon emission computed tomography (SPECT) showed a right thalamic hypoperfusion, which is rather concordant with the initial semiology. Later, the semiology changed, presenting with a predominantly neurovisual complex presentation. The second SPECT showed no more thalamic abnormalities but an hypoperfusion in the right temporo-occipital junction, right inferior parietal lobe and left superior frontal lobe, which is also rather concordant with the changing semiology. Conclusions This case illustrates the evolving neuroimaging patterns of FND but also the concordance between semiology and neuroimaging findings in FND supporting Charcot's theory of “dynamic lesion”.

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.

Functional movement disorders (FMD) represent a complex and disabling entity characterized by a broad range of clinical symptoms not explained by a classical neurological disease. In 2013, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) added a clinical criterion based on incongruence and inconsistency, supported by recent literature highlighting the role of "positive clinical signs". These clinical signs allow a "rule-in" procedure in making a diagnosis of FMD so that the diagnosis is no longer a "rule-out" or "by default" diagnosis made after exclusion of other neurological conditions. This review summarizes current evidence on common clinical features and highlights bedside signs in FMD, such as tremor, dystonia, myoclonus and parkinsonism. Tics, chorea and hemiballism are also briefly discussed.

Background Patients affected by functional (psychogenic) movement disorders (FMD) have abnormal processing of stress responses. However, little is known about the influence of this abnormal stress processing on automatic motor defense behavior, such as freeze response. Our aim was thus to investigate stress-induced postural motor responses in FMD. Methods Nine FMD patients and thirteen healthy controls were engaged in the Trier Social Stress Test, while we measured the movement of their body by means of accelerometers and gyroscopes attached to the thorax. Standard deviation of thorax acceleration, reflecting the variability of movement amplitude (body sway), was compared across groups over time in a 2 × 2 ANOVA design. Higuchi’s fractal dimension (HFD), reflecting the complexity of movement pattern over time, was also analyzed. Salivary cortisol and α-amylase samples were collected before and after the experiment, as stress biomarkers. Pearson’s correlation coefficients were calculated between these biomarkers and movement parameters. Results A significant interaction effect was found, showing that healthy controls reduced their thorax sway over time during exposure to stress (from 0.027 ± 0.010 m/s2 to 0.023 ± 0.008 m/s2, effect size of Cohen’s d = 0.95), whereas patients with FMD did not. This change in body sway in controls over time negatively correlated with salivary cortisol values (ρ = –0.67, p = 0.012). A significant group effect revealed that FMD patients had an overall larger body sway (0.038 ± 0.013 m/s2) compared to controls (0.025 ± 0.009 m/s2 – effect size of Cohen’s d = 1.29) and a lower HFD (1.602 ± 0.071) than controls (1.710 ± 0.078 – Cohen’s d = 1.43). Conclusions Patients with FMD failed to show a reduction of body sway over time, i.e., freeze response observed in the controls, thus suggesting an impairment in the automatic defense behavior. Moreover, our analysis found a lower complexity of movement (HFD) in FMD, which deserves future research in order to verify whether this could represent a characteristic trait of the disorder.

Purpose To compare the clinical and demographic characteristics of adult patients with nonorganic or medically unexplained visual loss (MUVL) to those with other common conditions presenting to a neuro-ophthalmology clinic. Methods Case–control design: a retrospective review of medical notes on a consecutive case series of 49 patients assessed at the King's College Hospital neuro-ophthalmology clinic with unexplained visual loss and matched with the next assessed patient identified from clinic records. Patients presented post-symptom onset with a mean clinical course of 30 months (SD = 67 months) and standard clinical examination used to confirm diagnoses, alongside ancillary investigations if required. Results Seventy-two percent (n = 36) of MUVL patients were female. In comparison with patients with organic visual disorders, MUVL cases presented with significantly higher rates of bilateral (cf. unilateral) visual impairment (41%, n = 20), premorbid psychiatric (27%, n = 13) as well as functional (24%, n = 12) diagnoses and psychotropic medication usage (22%, n = 11). Medically unexplained cases were significantly more likely to report preceding psychological stress (n = 9; 18%). Conclusions Medically unexplained visual impairment may be regarded as part of the spectrum of medically unexplained disorders seen in the general hospital setting. Research is needed to determine long-term outcomes and effective tailored interventions.

Functional neurological disorder (FND) represents a paradigmatic neuropsychiatric disorder; patients present neurological physical symptoms but associated psychosocial stressors play a role as predisposing and precipitating factors.1 Recent neuroscience research has shed light on how the physical symptoms arise in terms of aberrant brain mechanisms2 but little is known in terms of why certain individual develop the disorder. Childhood abuse and life adversities have been linked to FND but cannot be viewed solely/exclusively as causal,3 as this association is partially non-specific. A multifactorial causal model has to be considered and a gene–environment interaction is plausible, as it could theoretically integrate life stressors as precipitating factors in a subset of susceptible individuals. There is to date no evidence for genetic risks of FND with only one study reporting familial cases suggesting disease modelling in families rather than genetic transmission.4 Twin studies in other functional symptoms (chronic fatigue, irritable bowel syndrome, etc)5 have found potential, even if weak, genetic influences but no studies looked specifically at neurological functional symptoms. In order to explore potential gene–environment interaction, epigenetics offers promising new routes. In particular, epigenetics in stress research and related psychopathologies has generated novel findings that remain to be replicated in large-scale datasets.6 Methylation of …

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.

Item does not contain fulltext Background: Stressful life events and maltreatment have traditionally been considered crucial in the development of conversion (functional neurological) disorder, but the evidence underpinning this association is not clear. We aimed to assess the association between stressors and functional neurological disorder. Methods: We systematically reviewed controlled studies reporting stressors occurring in childhood or adulthood, such as stressful life events and maltreatment (including sexual, physical abuse, and emotional neglect) and functional neurological disorder. We did a meta-analysis, with assessments of methodology, sources of bias, and sensitivity analyses. Findings: 34 case-control studies, with 1405 patients, were eligible. Studies were of moderate-to-low quality. The frequency of childhood and adulthood stressors was increased in cases compared with controls. Odds ratios (OR) were higher for emotional neglect in childhood (49% for cases vs 20% for controls; OR 5·6, 95% CI 2·4-13·1) compared with sexual abuse (24% vs 10%; 3·3, 2·2-4·8) or physical abuse (30% vs 12%; 3·9, 2·2-7·2). An association with stressful life events preceding onset (OR 2·8, 95% CI 1·4-6·0) was stronger in studies with better methods (interviews; 4·3, 1·4-13·2). Heterogeneity was significant between studies (I2 21·1-90·7%). 13 studies that specifically ascertained that the participants had not had either severe life events or any subtype of maltreatment all found a proportion of patients with functional neurological disorder reporting no stressor. Interpretation: Stressful life events and maltreatment are substantially more common in people with functional neurological disorder than in healthy controls and patient controls. Emotional neglect had a higher risk than traditionally emphasised sexual and physical abuse, but many cases report no stressors. This outcome supports changes to diagnostic criteria in DSM-5; stressors, although relevant to the cause in many patients, are not a core diagnostic feature. This result has implications for ICD-11. Funding: None. 14 p.

Motor conversion disorder (CD) entails genuine disturbances in the subjective experience of patients who maintain they are unable to perform a motor function, despite lack of apparent neurological damage. Abilities by which individuals assess their own capacities during performance in a task are called metacognitive, and distinctive impairment of such abilities is observed in several disorders of self-awareness such as blindsight and anosognosia. In CD, previous research has focused on the recruitment of motor and emotional brain systems, generally linking symptoms to altered limbic-motor interactions; however, metacognitive function has not been studied to our knowledge. Here we tested ten CD patients and ten age-gender matched controls during a visually-guided motor paradigm, previously employed in healthy controls (HC), allowing us to probe for motor awareness and metacognition. Participants had to draw straight trajectories towards a visual target while, unbeknownst to them, deviations were occasionally introduced in the reaching trajectory seen on the screen. Participants then reported both awareness of deviations and confidence in their response. Activity in premotor and cingulate cortex distinguished between conscious and unconscious movement corrections in controls better than patients. Critically, whereas controls engaged the left superior precuneus and middle temporal region during confidence judgments, CD patients recruited bilateral parahippocampal and amygdalo-hippocampal regions instead. These results reveal that distinct brain regions subserve metacognitive monitoring for HC and CD, pointing to different mechanisms and sources of information used to monitor and form confidence judgments of motor performance. While brain systems involved in sensory-motor integration and vision are more engaged in controls, CD patients may preferentially rely on memory and contextual associative processing, possibly accounting for how affect and memories can imbue current motor experience in these patients.