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David L. Perez - One of the best experts on this subject based on the ideXlab platform.
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autonomic endocrine and inflammation profiles in functional Neurological Disorder a systematic review and meta analysis
Journal of Neuropsychiatry and Clinical Neurosciences, 2021Co-Authors: Sara Paredesecheverri, Indrit Bègue, Julie Maggio, Susannah Pick, Timothy R Nicholson, David L. PerezAbstract:Objective: Functional Neurological Disorder (FND) is a core neuropsychiatric condition. To date, promising yet inconsistently identified neural circuit profiles have been observed in patients with ...
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the role of evidence based guidelines in the diagnosis and treatment of functional Neurological Disorder
Epilepsy & Behavior Reports, 2021Co-Authors: Benjamin Tolchin, David L. Perez, Curt W Lafrance, Alan Carson, Laura H Goldstein, Gaston Baslet, Barbara A Dworetzky, Steve Martino, Markus Reuber, Jon StoneAbstract:Abstract Evidence-based clinical practice guidelines, based on systematic reviews of existing evidence, play an important role in improving and standardizing the quality of patient care in many medical and psychiatric Disorders, and could play an important role in the diagnosis and treatment of functional seizures and other functional Neurological Disorder (FND) subtypes. There are several reasons to think that evidence-based guidelines might be especially beneficial for the management of FND. In particular, the interdisciplinary and multidisciplinary teamwork necessary for the care of people with FND, the current lack of formal clinical training in FND, and the rapidly expanding body of evidence relating to FND all make guidelines based on systematic literature reviews especially valuable. In this perspective piece, we review clinical practice guidelines, their advantages and limitations, the reasons why evidence-based guidelines might be especially beneficial in the diagnosis and treatment of FND, and the steps that must be taken to create such guidelines for FND. We propose that professional organizations such as the American Academy of Neurology and the American Psychiatric Association undertake guideline development, ideally to create a co-authored or jointly endorsed set of guidelines that can set standards for interdisciplinary care for neurologists and mental health clinicians alike.
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expanding the therapeutic toolkit in functional Neurological Disorder consensus recommendations for speech and language therapy
Journal of Neurology Neurosurgery and Psychiatry, 2021Co-Authors: David L. PerezAbstract:Our ability to communicate with one another is precious. For individuals diagnosed with functional Neurological Disorder (FND)—a prevalent, costly and potentially disabling condition at the intersection of neurology and psychiatry—patients can present with speech and swallowing difficulties in isolation or as part of a mixed symptom complex.1 Baker and colleagues have deftly addressed a previously unmet need in the field by organising a multidisciplinary, international expert panel (including 18 speech and language professionals) to detail consensus recommendations for the management of functional communication, swallowing, cough and related conditions.2 Convergent with published consensus recommendations for physiotherapy and occupational therapy in FND,3 4 this article expands the therapeutic toolkit for the management of …
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reduced limbic microstructural integrity in functional Neurological Disorder
Psychological Medicine, 2021Co-Authors: Ibai Diez, Benjamin F Williams, Marek Kubicki, Nikos Makris, David L. PerezAbstract:Background Functional Neurological Disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and correlated fiber bundle integrity with symptom severity, physical disability, and illness duration. Methods A diffusion tensor imaging (DTI) study was performed in 32 patients with mixed FND compared to 36 healthy controls. Diffusion-weighted magnetic resonance images were collected along with patient-reported symptom severity, physical disability (Short Form Health Survey-36), and illness duration data. Weighted-degree and link-level graph theory and probabilistic tractography analyses characterized fractional anisotropy (FA) values across cortico-subcortical connections. Results were corrected for multiple comparisons. Results Compared to controls, FND patients showed reduced FA in the stria terminalis/fornix, medial forebrain bundle, extreme capsule, uncinate fasciculus, cingulum bundle, corpus callosum, and striatal-postcentral gyrus projections. Except for the stria terminalis/fornix, these differences remained significant adjusting for depression and anxiety. In within-group analyses, physical disability inversely correlated with stria terminalis/fornix and medial forebrain bundle FA values; illness duration negatively correlated with stria terminalis/fornix white matter integrity. A FND symptom severity composite score did not correlate with FA in patients. Conclusions In this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.
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neuroimaging in functional Neurological Disorder state of the field and research agenda
NeuroImage: Clinical, 2021Co-Authors: David L. Perez, Ibai Diez, Indrit Bègue, Alan Carson, Timothy R Nicholson, Anthony S David, Ali A Asadipooya, Matthew Butler, Quinton Deeley, Mark J. EdwardsAbstract: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.
Timothy R Nicholson - One of the best experts on this subject based on the ideXlab platform.
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autonomic endocrine and inflammation profiles in functional Neurological Disorder a systematic review and meta analysis
Journal of Neuropsychiatry and Clinical Neurosciences, 2021Co-Authors: Sara Paredesecheverri, Indrit Bègue, Julie Maggio, Susannah Pick, Timothy R Nicholson, David L. PerezAbstract:Objective: Functional Neurological Disorder (FND) is a core neuropsychiatric condition. To date, promising yet inconsistently identified neural circuit profiles have been observed in patients with ...
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neuroimaging in functional Neurological Disorder state of the field and research agenda
NeuroImage: Clinical, 2021Co-Authors: David L. Perez, Ibai Diez, Indrit Bègue, Alan Carson, Timothy R Nicholson, Anthony S David, Ali A Asadipooya, Matthew Butler, Quinton Deeley, Mark J. EdwardsAbstract: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.
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characteristics of patients with motor functional Neurological Disorder in a large uk mental health service a case control study
Psychological Medicine, 2020Co-Authors: Nicola Oconnell, Timothy R Nicholson, Simon Wessely, Anthony S DavidAbstract:Background Functional Neurological Disorder (FND), previously known as conversion Disorder, is common and often results in substantial distress and disability. Previous research lacks large sample sizes and clinical surveys are most commonly derived from Neurological settings, limiting our understanding of the Disorder and its associations in other contexts. We sought to address this by analysing a large anonymised electronic psychiatric health record dataset. Methods Data were obtained from 322 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who had an ICD-10 diagnosis of motor FND (mFND) (limb weakness or Disorders of movement or gait) between 1 January 2006 and 31 December 2016. Data were collected on a range of socio-demographic and clinical factors and compared to 644 psychiatric control patients from the same register. Results Weakness was the most commonly occurring functional symptom. mFND patients were more likely to be female, British, married, employed pre-morbidly, to have a carer and a physical health condition, but less likely to have had an inpatient psychiatric admission or to receive benefits. No differences in self-reported sexual or physical abuse rates were observed between groups, although mFND patients were more likely to experience life events linked to inter-personal difficulties. Conclusions mFND patients have distinct demographic characteristics compared with psychiatric controls. Experiences of abuse appear to be equally prevalent across psychiatric patient groups. This study establishes the socio-demographic and life experience profile of this understudied patient group and may be used to guide future therapeutic interventions designed specifically for mFND.
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outcome measures for functional Neurological Disorder a review of the theoretical complexities
Journal of Neuropsychiatry and Clinical Neurosciences, 2020Co-Authors: Timothy R Nicholson, David L. Perez, Glenn Nielsen, Mark J. Edwards, Alan Carson, Mark Hallett, Clare Nicholson, Bridget Mildon, Laura H Goldstein, Susannah PickAbstract: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.
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emotional processing in functional Neurological Disorder a review biopsychosocial model and research agenda
Journal of Neurology Neurosurgery and Psychiatry, 2019Co-Authors: Susannah Pick, David L. Perez, Laura H Goldstein, Timothy R NicholsonAbstract:Functional Neurological Disorder (FND) is a common and highly disabling Disorder, but its aetiology remains enigmatic. Conceptually, there has been reduced emphasis on the role of psychosocial stressors in recent years, with a corresponding increase in neurobiological explanations. However, a wealth of evidence supports the role of psychosocial adversities (eg, stressful life events, interpersonal difficulties) as important risk factors for FND. Therefore, there is a need to integrate psychosocial (environmental) and neurobiological factors (eg, sensorimotor and cognitive functions) in contemporary models of FND. Altered emotional processing may represent a key link between psychosocial risk factors and core features of FND. Here, we summarise and critically appraise experimental studies of emotional processing in FND using behavioural, psychophysiological and/or neuroimaging measures in conjunction with affective processing tasks. We propose that enhanced preconscious (implicit) processing of emotionally salient stimuli, associated with elevated limbic reactivity (eg, amygdala), may contribute to the initiation of basic affective/defensive responses via hypothalamic and brainstem pathways (eg, periaqueductal grey). In parallel, affect-related brain areas may simultaneously exert a disruptive influence on neurocircuits involved in voluntary motor control, awareness and emotional regulation (eg, sensorimotor, salience, central executive networks). Limbic-paralimbic disturbances in patients with FND may represent one of several neurobiological adaptations linked to early, severe and/or prolonged psychosocial adversity. This perspective integrates neurobiological and psychosocial factors in FND and proposes a research agenda, highlighting the need for replication of existing findings, multimodal sampling across emotional response domains and further examination of emotional influences on sensorimotor and cognitive functions in FND populations.
Anthony S David - One of the best experts on this subject based on the ideXlab platform.
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neuroimaging in functional Neurological Disorder state of the field and research agenda
NeuroImage: Clinical, 2021Co-Authors: David L. Perez, Ibai Diez, Indrit Bègue, Alan Carson, Timothy R Nicholson, Anthony S David, Ali A Asadipooya, Matthew Butler, Quinton Deeley, Mark J. EdwardsAbstract: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.
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characteristics of patients with motor functional Neurological Disorder in a large uk mental health service a case control study
Psychological Medicine, 2020Co-Authors: Nicola Oconnell, Timothy R Nicholson, Simon Wessely, Anthony S DavidAbstract:Background Functional Neurological Disorder (FND), previously known as conversion Disorder, is common and often results in substantial distress and disability. Previous research lacks large sample sizes and clinical surveys are most commonly derived from Neurological settings, limiting our understanding of the Disorder and its associations in other contexts. We sought to address this by analysing a large anonymised electronic psychiatric health record dataset. Methods Data were obtained from 322 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who had an ICD-10 diagnosis of motor FND (mFND) (limb weakness or Disorders of movement or gait) between 1 January 2006 and 31 December 2016. Data were collected on a range of socio-demographic and clinical factors and compared to 644 psychiatric control patients from the same register. Results Weakness was the most commonly occurring functional symptom. mFND patients were more likely to be female, British, married, employed pre-morbidly, to have a carer and a physical health condition, but less likely to have had an inpatient psychiatric admission or to receive benefits. No differences in self-reported sexual or physical abuse rates were observed between groups, although mFND patients were more likely to experience life events linked to inter-personal difficulties. Conclusions mFND patients have distinct demographic characteristics compared with psychiatric controls. Experiences of abuse appear to be equally prevalent across psychiatric patient groups. This study establishes the socio-demographic and life experience profile of this understudied patient group and may be used to guide future therapeutic interventions designed specifically for mFND.
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medication prescriptions in 322 motor functional Neurological Disorder patients in a large uk mental health service a case control study
General Hospital Psychiatry, 2019Co-Authors: Nicola Oconnell, Timothy R Nicholson, Graham Blackman, Jennifer Tavener, Anthony S DavidAbstract:Abstract Objective This study describes medication prescribing patterns in patients with motor functional Neurological Disorder (mFND) treated in South London and Maudsley NHS Foundation Trust (SLaM), comparing outcomes to a control group of psychiatric patients from the same hospital trust. Method This is a retrospective case-control study using a psychiatric case register. Cross-sectional data were obtained from 322 mFND patients and 644 psychiatry controls who had had contact with SLaM between 1st January 2006 and 31st December 2016. Results A slightly lower proportion of mFND patients received medication compared to controls (76.6% v. 83.4%, OR: 0.59, CI: 0.39–0.89, p Conclusions This is the first study to describe medication prescriptions in a large cohort of mFND patients. Patients were prescribed a wide range of psychiatric and physical health medications, with higher rates of polypharmacy than controls. Psychotropic medication prescription is not necessarily the first line treatment for mFND, where physiotherapy and psychotherapy may be offered initially. There is limited, early-phase evidence for pharmacological therapies for mFND, and as such, the benefit-to-risk ratio of prescribing in this complex and poorly understood Disorder should be carefully assessed.
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stressful life events and maltreatment in conversion functional Neurological Disorder systematic review and meta analysis of case control studies
The Lancet Psychiatry, 2018Co-Authors: Selma Aybek, Timothy R Nicholson, Lea Ludwig, Joelle A Pasman, Anthony S David, Sharon Tuck, Richard A A Kanaan, Karin RoelofsAbstract:Summary 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 ( I 2 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.
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26 scan negative cauda equina syndrome a new functional Neurological Disorder
Journal of Neurology Neurosurgery and Psychiatry, 2017Co-Authors: Lucy Gibson, Cristina Dudau, Anthony S DavidAbstract:Objective Cauda equina syndrome (CES) is a neurosurgical emergency, identified by a range of clinical symptoms including back pain coupled with saddle anaesthesia, bladder or bowel symptoms. A high index of suspicion for CES warrants an emergency lumbar MRI. However, up to 48% of patients undergoing such scans have no radiological correlate for their symptoms but are clinically indistinguishable from those with established CES (Rooney et al, 2009, J Neurol). Relatively little is known about this scan-negative patient group. We therefore examined a cohort of “CES” patients from a single regional centre and examined radiological and referral outcomes. Method 179 patients who had a lumbar MRI at Kings College Hospital, London, after attending A and E in a 12 month period ending December 2015 were retrospectively identified. 160 patients met the inclusion criteria: over 18; had lumbar MRI performed specifically to exclude suspected CES; and had an admission entry in the medical notes detailing their history. Electronic patient records were then assessed for age, gender, presenting symptoms and follow up. Results CES was confirmed in 16% of lumbar MRI scans (n=25), 84% (n=135) were ‘scan-negative’ with no structural correlate for CES although 44% showed some evidence of root involvement. Fisher’s exact test (two-sided) was used to compare the groups’ symptomology. No significant differences were found for back pain (p=0.59), urinary incontinence (p=0.98), urinary retention (p=0.16), altered urinary sensation (p=0.57), bowel incontinence (p=0.80), leg weakness (p=0.67), sciatica (p=0.57), leg paresthesia (p=0.37). There was an observed difference in the demographics: the scan-negative group was predominantly female [71% vs 48% (p=0.023)] and significantly younger [42.7 vs 54.7 years (p Conclusion These findings replicate established difficulties in identifying CES from clinical symptoms alone. Demographic differences between scan-positive and negative patients indicate heterogeneity requiring further investigation. It is likely that a proportion of the scan negative patients have a functional Neurological Disorder although the precise figure has yet to be determined. Routine follow up was inconsistent. More detailed neuropsychiatric evaluation and longer follow-up are required to characterise this patient group which would inform a range of clinical care pathways addressing their medical and psychiatric needs.
Selma Aybek - One of the best experts on this subject based on the ideXlab platform.
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briquet syndrome revisited implications for functional Neurological Disorder
Brain Communications, 2020Co-Authors: Julie Maggio, Priyanka R. Alluri, Sara Paredesecheverri, Anna G Larson, Petr Sojka, Bruce H Price, Selma Aybek, David L. PerezAbstract: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.
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stressful life events and maltreatment in conversion functional Neurological Disorder systematic review and meta analysis of case control studies
The Lancet Psychiatry, 2018Co-Authors: Selma Aybek, Timothy R Nicholson, Lea Ludwig, Joelle A Pasman, Anthony S David, Sharon Tuck, Richard A A Kanaan, Karin RoelofsAbstract:Summary 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 ( I 2 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.
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identifying motor functional Neurological Disorder using resting state functional connectivity
NeuroImage: Clinical, 2018Co-Authors: Jennifer Wegrzyk, Selma Aybek, Valeria Kebets, Jonas Richiardi, Silvio Galli, Dimitri Van De VilleAbstract:Abstract 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.
Mark J. Edwards - One of the best experts on this subject based on the ideXlab platform.
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no increased suggestibility to placebo in functional Neurological Disorder
European Journal of Neurology, 2021Co-Authors: Annecatherine M L Huys, Brianna Beck, Patrick Haggard, Kailash P Bhatia, Mark J. EdwardsAbstract:Background On the basis of occasional strong placebo responses, increased susceptibility to placebo has been proposed as a characteristic of functional Neurological Disorder. The aim of this study was to clarify whether people with functional Neurological Disorder have a stronger placebo analgesic response than healthy controls. Methods A classic placebo paradigm, with additional conditioning and open-label components, was performed in 30 patients with a functional Neurological Disorder, and in 30 healthy controls. Ratings of mildly to moderately painful electrotactile stimuli were compared before and after the application of a placebo "anaesthetic" cream versus a control cream, after an additional conditioning exposure, and after full disclosure (open-label component). Results Pain intensity ratings at the placebo compared to the control site were similarly reduced in both groups. The conditioning exposure had no additional effect. After placebo disclosure a residual analgesic effect remained. Conclusion Functional Neurological Disorder patients did not have stronger placebo responses than healthy controls. The notion of generally increased suggestibility or increased suggestibility to placebo in FND seems mistaken. Instead, occasional dramatic placebo responses may occur because functional symptoms are inherently more changeable than those due to organic disease.
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neuroimaging in functional Neurological Disorder state of the field and research agenda
NeuroImage: Clinical, 2021Co-Authors: David L. Perez, Ibai Diez, Indrit Bègue, Alan Carson, Timothy R Nicholson, Anthony S David, Ali A Asadipooya, Matthew Butler, Quinton Deeley, Mark J. EdwardsAbstract: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.
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occupational therapy consensus recommendations for functional Neurological Disorder
Journal of Neurology Neurosurgery and Psychiatry, 2020Co-Authors: Clare Nicholson, Mark J. Edwards, Alan Carson, Paula Gardiner, Dawn Golder, Kate Hayward, Susan Humblestone, Helen Jinadu, Carrie Lumsden, Julie MacleanAbstract:Background People with functional Neurological Disorder (FND) are commonly seen by occupational therapists; however, there are limited descriptions in the literature about the type of interventions that are likely to be helpful. This document aims to address this issue by providing consensus recommendations for occupational therapy assessment and intervention. Methods The recommendations were developed in four stages. Stage 1: an invitation was sent to occupational therapists with expertise in FND in different countries to complete two surveys exploring their opinions regarding best practice for assessment and interventions for FND. Stage 2: a face-to-face meeting of multidisciplinary clinical experts in FND discussed and debated the data from stage 1, aiming to achieve consensus on each issue. Stage 3: recommendations based on the meeting were drafted. Stage 4: successive drafts of recommendations were circulated among the multidisciplinary group until consensus was achieved. Results We recommend that occupational therapy treatment for FND is based on a biopsychosocial aetiological framework. Education, rehabilitation within functional activity and the use of taught self-management strategies are central to occupational therapy intervention for FND. Several aspects of occupational therapy for FND are distinct from therapy for other Neurological conditions. Examples to illustrate the recommendations are included within this document. Conclusions Occupational therapists have an integral role in the multidisciplinary management of people with FND. This document forms a starting point for research aiming to develop evidence-based occupational therapy interventions for people with FND.
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Management of functional Neurological Disorder
Journal of Neurology, 2020Co-Authors: Gabriela S. Gilmour, Glenn Nielsen, Tiago Teodoro, Mahinda Yogarajah, Jan Adriaan Coebergh, Michael D. Dilley, Davide Martino, Mark J. EdwardsAbstract:Functional Neurological Disorder (FND) is a common cause of persistent and disabling Neurological symptoms. These symptoms are varied and include abnormal control of movement, episodes of altered awareness resembling epileptic seizures and abnormal sensation and are often comorbid with chronic pain, fatigue and cognitive symptoms. There is increasing evidence for the role of neurologists in both the assessment and management of FND. The aim of this review is to discuss strategies for the management of FND by focusing on the diagnostic discussion and general principles, as well as specific treatment strategies for various FND symptoms, highlighting the role of the neurologist and proposing a structure for an interdisciplinary FND service.
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outcome measures for functional Neurological Disorder a review of the theoretical complexities
Journal of Neuropsychiatry and Clinical Neurosciences, 2020Co-Authors: Timothy R Nicholson, David L. Perez, Glenn Nielsen, Mark J. Edwards, Alan Carson, Mark Hallett, Clare Nicholson, Bridget Mildon, Laura H Goldstein, Susannah PickAbstract: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.
