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      Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders

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          Abstract

          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. 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. 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.

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          Most cited references49

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          Stressful life events and maltreatment in conversion (functional neurological) disorder: systematic review and meta-analysis of case-control studies

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            Emotional stimuli and motor conversion disorder.

            Conversion disorder is characterized by neurological signs and symptoms related to an underlying psychological issue. Amygdala activity to affective stimuli is well characterized in healthy volunteers with greater amygdala activity to both negative and positive stimuli relative to neutral stimuli, and greater activity to negative relative to positive stimuli. We investigated the relationship between conversion disorder and affect by assessing amygdala activity to affective stimuli. We conducted a functional magnetic resonance imaging study using a block design incidental affective task with fearful, happy and neutral face stimuli and compared valence contrasts between 16 patients with conversion disorder and 16 age- and gender-matched healthy volunteers. The patients with conversion disorder had positive movements such as tremor, dystonia or gait abnormalities. We also assessed functional connectivity between the amygdala and regions associated with motor preparation. A group by affect valence interaction was observed. Post hoc analyses revealed that whereas healthy volunteers had greater right amygdala activity to fearful versus neutral compared with happy versus neutral as expected, there were no valence differences in patients with conversion disorder. There were no group differences observed. The time course analysis also revealed greater right amygdala activity in patients with conversion disorder for happy stimuli (t = 2.96, P = 0.006) (with a trend for fearful stimuli, t = 1.81, P = 0.08) compared with healthy volunteers, with a pattern suggestive of impaired amygdala habituation even when controlling for depressive and anxiety symptoms. Using psychophysiological interaction analysis, patients with conversion disorder had greater functional connectivity between the right amygdala and the right supplementary motor area during both fearful versus neutral, and happy versus neutral 'stimuli' compared with healthy volunteers. These results were confirmed with Granger Causality Modelling analysis indicating a directional influence from the right amygdala to the right supplementary motor area to happy stimuli (P < 0.05) with a similar trend observed to fearful stimuli (P = 0.07). Our data provide a potential neural mechanism that may explain why psychological or physiological stressors can trigger or exacerbate conversion disorder symptoms in some patients. Greater functional connectivity of limbic regions influencing motor preparatory regions during states of arousal may underlie the pathophysiology of motor conversion symptoms.
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              Symptoms 'unexplained by organic disease' in 1144 new neurology out-patients: how often does the diagnosis change at follow-up?

              It has been previously reported that a substantial proportion of newly referred neurology out-patients have symptoms that are considered by the assessing neurologist as unexplained by 'organic disease'. There has however been much controversy about how often such patients subsequently develop a disease diagnosis that, with hindsight, would have explained the symptoms. We aimed to determine in a large sample of new neurology out-patients: (i) what proportion are assessed as having symptoms unexplained by disease and the diagnoses given to them; and (ii) how often a neurological disorder emerged which, with hindsight, explained the original symptoms. We carried out a prospective cohort study of patients referred from primary care to National Health Service neurology clinics in Scotland, UK. Measures were: (i) the proportion of patients with symptoms rated by the assessing neurologist as 'not at all' or only 'somewhat explained' by 'organic disease' and the neurological diagnoses recorded at initial assessment; and (ii) the frequency of unexpected new diagnoses made over the following 18 months (according to the primary-care physician). One thousand four hundred and forty-four patients (30% of all new patients) were rated as having symptoms 'not at all' or only 'somewhat explained' by 'organic disease'. The most common categories of diagnosis were: (i) organic neurological disease but with symptoms unexplained by it (26%); (ii) headache disorders (26%); and (iii) conversion symptoms (motor, sensory or non-epileptic attacks) (18%). At follow-up only 4 out of 1030 patients (0.4%) had acquired an organic disease diagnosis that was unexpected at initial assessment and plausibly the cause of the patients' original symptoms. Eight patients had died at follow-up; five of whom had initial diagnoses of non-epileptic attacks. Seven other types of diagnostic change with very different implications to a 'missed diagnosis' were found and a new classification of diagnostic revision is presented. One-third of new neurology out-patients are assessed as having symptoms 'unexplained by organic disease'. A new diagnosis, which with hindsight explained the original symptoms, rarely became apparent to the patient's primary care doctor in the 18 months following the initial hospital consultation.
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                Author and article information

                Journal
                JAMA Neurology
                JAMA Neurol
                American Medical Association (AMA)
                2168-6149
                September 01 2018
                September 01 2018
                : 75
                : 9
                : 1132
                Affiliations
                [1 ]University of Cincinnati Gardner Neuroscience Institute, Gardner Family Center for Parkinson’s Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio.
                [2 ]Department of Neurology, University Hospital Inselspital, Bern, Switzerland
                [3 ]Neuropsychiatry, Centre for Clinical Brain Studies, University of Edinburgh, Edinburgh, United Kingdom
                [4 ]Motor Control and Movement Disorders Group, Institute of Molecular and Clinical Sciences, St George's University of London, London, United Kingdom
                [5 ]Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
                [6 ]Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
                [7 ]Department of Neurology, University of Louisville, Louisville, Kentucky
                [8 ]Department of Psychiatry, Alpert Medical School of Brown University, Providence, Rhode Island
                [9 ]Department of Neurology, Alpert Medical School of Brown University, Providence, Rhode Island
                [10 ]Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital and Edmond J. Safra Program in Parkinson Disease, University of Toronto, Toronto, Ontario, Canada
                [11 ]Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
                [12 ]Academic Neurology Unit, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom
                [13 ]Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
                [14 ]Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
                [15 ]Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
                Article
                10.1001/jamaneurol.2018.1264
                7293766
                29868890
                6f3936b2-24a4-4e82-a5d6-27c1d66306aa
                © 2018
                History

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