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The development and selection of optimal outcome measures is increasingly recognized as a key component of evidence-based medicine, particularly the need for the development of a standardized set of measures for use in clinical trials. This process is particularly complex for functional neurological disorder (FND) for several reasons. FND can present with a wide range of symptoms that resemble the full spectrum of other neurological disorders. Additional physical (e.g., pain, fatigue) and psychological (e.g., depression, anxiety) symptoms are commonly associated with FND, which also can be highly disabling with implications for prognosis, and warrant concurrent assessment, despite an unclear etiological relationship with FND. Furthermore, several unique clinical aspects of FND make it likely that the usual prioritization of "objective" (or clinician-rated) over "subjective" (or patient-rated) measures might not be appropriate. Self-report measures may be more clinically meaningful in this patient population. Despite being a common and disabling disorder, there has been little research into outcome measures in FND, and to date trials have largely used measures designed for the assessment of other disorders. An international FND Core Outcome Measure group (FND-COM) has been established to develop a consensus battery of outcomes for FND: a "core outcome set." In this perspective article, the authors reviewed the process of outcome measure development and selection before considering the specific features of FND affecting the development of a core outcome set, as well as a research agenda to optimize outcome measurement in this complex neuropsychiatric disorder.

Functional neurological disorders (FND) are complex and prevalent neuropsychiatric conditions. Importantly, some patients with FND develop acute onset symptoms requiring emergency department (ED) evaluations. Historically, FND was a "rule-out" diagnosis, making assessment and management in the ED difficult. While the rapid triage of potential neurological emergencies remains the initial task, advancements have altered the approach to FND. FND is now a "rule-in" diagnosis based on validated neurological examination signs and semiological features. In this perspective article, we review signs and semiological features that can help guide the initial assessment of FND in the acute setting. Thereafter, we outline potential approaches to introduce a suspected diagnosis of FND to patients in the ED, while emphasizing the need for a comprehensive neurological evaluation. Physical and occupational therapy may be useful adjunct assessments in some individuals. Notably, clinicians in the ED setting are important members of the interdisciplinary approach to FND., Competing Interests: D.L.P. has received honorarium for lectures from the American Academy of Neurology, Movement Disorder Society, and Harvard Medical School Continuing Education programs. All other authors do not have any conflicts of interests/disclosures., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas., Methods: This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects., Results: Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume., Conclusions: This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Disturbances of the autonomic nervous system (ANS) are common in neuropsychiatric disorders. Disease specific alterations of both sympathetic and parasympathetic activity can be assessed by heart rate variability (HRV), whereas electrodermal activity (EDA) can assess sympathetic activity. In posttraumatic stress disorder (PTSD), parasympathetic HRV parameters are typically decreased and EDA is increased, whereas in major depressive disorder (MDD) and dissociation, both parasympathetic and sympathetic markers are decreased. ANS abnormalities have also been identified in psychogenic nonepileptic seizures (PNES) by using HRV, indicating lower parasympathetic activity at baseline. In addition to reviewing the current literature on ANS abnormalities in PTSD, MDD, and disorders with prominent dissociation, including borderline personality disorder (BPD), this article also presents data from a pilot study on EDA in patients with PNES. Eleven patients with PNES, during an admission to our epilepsy monitoring unit (EMU), were compared with 9 with generalized tonic-clonic seizures (GTCS). The area under the EDA curve, the number of EDA responses lasting longer than 2 seconds, and the number of EDA surges during sleep (sympathetic sleep storms) were calculated on ictal and interictal days by an automated algorithm. EDA changes in PNES patients did not follow a systematic pattern of sympathetic hyperarousal (like EDA after GTCS) but were more variable. How specific PNES semiologies, and/or underlying neuropsychiatric disorders, may influence ictal and interictal EDA patterns, and lead to a novel diagnostic biomarker remains to be evaluated in future larger studies., (© EEG and Clinical Neuroscience Society (ECNS) 2015.)

Functional neurological disorder (conversion disorder) is a neurobehavioral condition frequently encountered by neurologists. Psychogenic nonepileptic seizure (PNES) and functional movement disorder (FMD) patients present to epileptologists and movement disorder specialists respectively, yet neurologists lack a neurobiological perspective through which to understand these enigmatic groups. Observational research studies suggest that PNES and FMD may represent variants of similar (or the same) conditions given that both groups exhibit a female predominance, have increased prevalence of mood-anxiety disorders, frequently endorse prior abuse, and share phenotypic characteristics. In this perspective article, neuroimaging studies in PNES and FMD are reviewed, and discussed using studies of emotional dysregulation, dissociation and psychological trauma in the context of motor control. Convergent neuroimaging findings implicate alterations in brain circuits mediating emotional expression, regulation and awareness (anterior cingulate and ventromedial prefrontal cortices, insula, amygdala, vermis), cognitive control and motor inhibition (dorsal anterior cingulate, dorsolateral prefrontal, inferior frontal cortices), self-referential processing and perceptual awareness (posterior parietal cortex, temporoparietal junction), and motor planning and coordination (supplementary motor area, cerebellum). Striatal-thalamic components of prefrontal-parietal networks may also play a role in pathophysiology. Aberrant medial prefrontal and amygdalar neuroplastic changes mediated by chronic stress may facilitate the development of functional neurological symptoms in a subset of patients. Improved biological understanding of PNES and FMD will likely reduce stigma and aid the identification of neuroimaging biomarkers guiding treatment development, selection, and prognosis. Additional research should investigate neurocircuit abnormalities within and across functional neurological disorder subtypes, as well as compare PNES and FMD with mood-anxiety-dissociative disorders., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

Psychogenic nonepileptic seizures (PNES) were first described in the medical literature in the 19th century, as seizure-like attacks not related to an identified central nervous system lesion, and are currently classified as a conversion disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). While a universally accepted and unifying etiological model does not yet exist, several risk factors have been identified. Management of PNES should be based on interdisciplinary collaboration, targeting modifiable risk factors. The first treatment phase in PNES is patient engagement, which is challenging given the demonstrated low rates of treatment retention. Acute interventions constitute the next phase in treatment, and most research studies focus on short-term evidence-based interventions. Randomized controlled pilot trials support cognitive-behavioral therapy. Other psychotherapeutic and psychopharmacological interventions have been less well-studied using controlled and uncontrolled trials. Within the discussion of acute interventions, we present a preliminary evaluation for feasibility of a mindfulness-based psychotherapy protocol in a very small sample of PNES patients. We demonstrated in 6 subjects that this intervention is feasible in real-life clinical scenarios and warrants further investigation in larger scale studies. The final treatment phase is long-term follow-up. Long-term outcome studies in PNES show that a significant proportion of patients remains symptomatic and experiences continued impairments in quality of life and functionality. We believe that PNES should be understood as a disease that requires different types of intervention during the various phases of treatment., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)