Recent advances in understanding the neurobiology of pediatric functional neurological disorder.

INTRODUCTION: Functional neurological disorder (FND) is a neuropsychiatric disorder that manifests in a broad array of functional motor, sensory, or cognitive symptoms, which arise from complex interactions between brain, mind, body, and context. Children with FND make up 10%-20% of presentations to neurology services in children's hospitals and up to 20% of adolescents admitted to hospital for the management of intractable seizures. AREAS COVERED: The current review focuses on the neurobiology of pediatric FND. The authors present an overview of the small but growing body of research pertaining to the biological, emotion-processing, cognitive, mental health, physical health, and social system levels. EXPERT OPINION: Emerging research suggests that pediatric FND is underpinned by aberrant changes within and between neuron-glial (brain) networks, with a variety of factors - on multiple system levels - contributing to brain network changes. In pediatric practice, adverse childhood experiences (ACEs) are commonly reported, and activation or dysregulation of stress-system components is a frequent finding. Our growing understanding of the neurobiology of pediatric FND has yielded important flow-on effects for assessing and diagnosing FND, for developing targeted treatment interventions, and for improving the treatment outcomes of children and adolescents with FND.

Healthcare employment as a risk factor for functional neurological disorder: A case-control study.

BACKGROUND AND PURPOSE: Female gender, younger age and stressful life events are known predisposing factors for functional neurological disorders (FNDs). Employment in a healthcare profession has also been suggested to be a predisposing factor. We set out to conduct a large-scale case-control study to estimate the rate employment in a healthcare profession among people with FND. METHODS: We included 200 consecutive patients with a confirmed diagnosis of FND, referred to our clinic at University Hospital Bern Switzerland between October 1, 2016, and August 1, 2019. In addition, we included a control group of 200 patients with a confirmed neurological disorder, matched for age and gender, seen during the same period. The primary endpoint was to compare the prevalence of healthcare professionals between the groups. We also describe the clinical manifestations and concomitant psychiatric diagnoses in the FND cohort. RESULTS: Female gender was predominant (70%), and the participants' mean age was 37 years. The proportion of healthcare professionals in the FND patients was 18% (33/186), which was significantly higher than in the control group, in which it was 10.6% (17/189; p = 0.019, 95% confidence interval odds ratio 1.168-4.074). Most healthcare professionals in both cohorts were nurses (21/33 among FND patients, 10/17 among controls). Among FND patients, 140 (70%) had motor symptoms and 65 (32.5%) had a concomitant psychiatric diagnosis. CONCLUSION: This case-control study confirmed a higher rate of employment in healthcare professions in patients with FND, suggesting two potential mechanisms of FND: exposure to models/specific knowledge about neurological symptoms or stress-related professional factors. This warrants further studies on underlying mechanisms and prevention.

[Conversion disorder, caring for body, mind]. / Le trouble de conversion, prendre soin du corps et de l'esprit.

Conversion disorder is a psychiatric disorder whose clinic and management lie at the crossroads between body and mind. It challenges healthcare professionals in terms of diagnosis, further investigation, referral and care. A number of questions arise, such as how caregivers perceive the relationship between body and mind, the place of the psychiatric hypothesis among the initial diagnostic hypotheses, and the temporality of care.

Long-term course of psychogenic nonepileptic seizures: Who gets seizure-free, has better functional level and higher health-related quality of life?

BACKGROUND: The disease course of psychogenic nonepileptic seizures (PNES) over a prolonged period of time remains unclear. The aims of the study were: 1. to describe the course of illness with a median follow-up time of 4 years and a range of 2-15 years; and 2. to identify distinguishing features between participants regarding seizure cessation, functional level and health-related quality of life. METHODS: Formerly, inpatients of an epileptic ward diagnosed with PNES between 2000 and 2013 were contacted via mail. They were asked by questionnaire about illness characteristics, i.e., age at onset, PNES status at onset and in the course, treatments, psychosocial situation, and quality of life status. RESULTS: Two-thirds of the N = 63 formerly inpatients were female, their age at onset was 26.7 years. Seizure frequency decreased significantly over time, 31.7% were currently seizure-free, but still only 37% were regularly employed. Only 48% had a satisfying health-related quality of life. The remitted participants had a shorter duration of illness and higher health-related quality of life. Participants with a good level of functioning were more likely to be male, took fewer medications, and had a higher health-related quality of life. Those participants with higher quality of life were more frequently employed and had fewer seizures. CONCLUSIONS: As participants continue to be severely limited in their functional level and quality of life over the period under review, enhanced treatment approaches that address experiential avoidance seem to be needed.

[Understanding functional neurological disorders: From biological markers to pathophysiological models]. / Étiopathogénie des troubles neurologiques fonctionnels : marqueurs biologiques et modèles théoriques.

OBJECTIVES: Functional neurological disorders have witnessed intense research activity in the fields of structural and functional neuroimaging for more than twenty years. Thus, we propose a synthesis of recent research findings and etiological hypotheses that have been proposed so far. This work should help clinicians to better understand the nature of the mechanisms involved, but also help patients to increase their knowledge about the biological features underlying their functional symptoms. METHODS: We carried out a narrative review of international publications dealing with neuroimaging and biology of functional neurological disorders, from 1997 to 2023. RESULTS: Several brain networks underlie functional neurological symptoms. These networks play a role in the management of cognitive resources, in attentional control, emotion regulation, in agency and in the processing of interoceptive signals. The mechanisms of the stress response are also associated with the symptoms. The biopsychosocial model helps to better understand predisposing, precipitating, and perpetuating factors involved. The functional neurological phenotype results from the interaction between: i) a specific pre-existing vulnerability resulting from biological background and epigenetic modifications, and ii) exposure to stress factors, according to the stress-diathesis model. This interaction causes emotional disturbances including hypervigilance, lack of integration of sensations and affects, and emotional dysregulation. These characteristics in turn impact the cognitive, motor and affective control processes related with the functional neurological symptoms. CONCLUSIONS: A better knowledge of the biopsychosocial determinants of brain network dysfunctions is necessary. Understanding them would help developing targeted treatments, but is also critical for patients care.

[Overview of care management principles in functional neurological disorders]. / Synthèse des principes et schémas de prise en charge dans les troubles neurologiques fonctionnels.

After more than twenty years of academic research on functional neurological disorders (FND) throughout the world, a standardized care management strategy has emerged to allow a more adapted care offer to patients with FND, as close as possible to their experience and their needs. With regard to this special issue on FND in collaboration with L'Encéphale and at the initiative of the Neuropsychiatry section of the AFPBN (French Association of Biological Psychiatry and Neuropsychopharmacology), we would like to suggest a summary of all topics discussed in more detail in each article of this special issue, in order to facilitate its reading. We therefore cover the following themes: the initial contact with a patient with FND, the diagnostic process in favor of a positive diagnosis, the physiological, neural and psychological basis of FND, the diagnostic announcement (and its intangibles), the therapeutic patient education in FND, the general principles of therapeutic management through a personalized and multidisciplinary care program, and the validated therapeutic tools available according to the symptoms identified. This article is designed to be of broad interest on FND, supported by tables and figures showing the key points of all these steps, to keep an educational purpose at most. We hope that through this special issue, each health professional will be able to grasp this knowledge and this framework of care as easily and quickly as possible, in order to participate in the standardization of the care offer.

[Diagnostic criteria, epidemiology and assessment of patients with functional neurological disorders]. / Définitions, épidémiologie et démarche diagnostique clinique dans les troubles neurologiques fonctionnels.

Functional neurological disorders (FND) are symptoms that can affect a variety of functions including motor, sensory and cognitive. These symptoms are genuinely experienced by the patient and are related to a functional disorder rather than a structural one. There is little epidemiological data on these disorders, but their frequency is well established in clinical practice, it is the second most frequent reason for consultation in Neurology. Despite of the frequency of the disorder, general practitioners and specialists are insufficiently trained in the disease, and patients often suffer from stigmatization and/or unnecessary investigations. It is therefore important to be aware of the diagnostic approach to FND, which mostly relies on positive clinical signs. Psychiatric evaluation can help with the characterization of predisposing, precipitating and perpetuating factors of the symptoms (according to the 3P biopsychosocial model related to FND), and guide their management. Finally, diagnosis explanation is a crucial step in the management of the disease, which can in itself have a therapeutic effect, and allow the patient to adhere to the treatments.

Psychiatric and psychological assessment of Spanish patients with drug-resistant epilepsy and psychogenic nonepileptic seizures (PNES) with no response to previous treatments.

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are common imitators of epileptic seizures. Refractoriness to antiseizure medication hinders the differential diagnosis between ES and PNES, carrying deleterious consequences in patients with PNES. Psychiatric and psychological characteristics may assist in the differential diagnosis between drug-resistant epilepsy (DRE) and PNES. Nevertheless, current comprehensive psychiatric and psychological descriptive studies on both patient groups are scarce and with several study limitations. This study provides a comprehensive psychiatric and psychological characterization of Spanish patients with DRE and PNES. METHOD: A cross-sectional and comparative study was completed with 104 patients with DRE and 21 with PNES. Psychiatric and psychological characteristics were assessed with the HADS, SCL-90-R, NEO-FFI-R, PDQ-4+, COPE, and QOLIE-31 tests. Parametric and non-parametric tests were used, and regression models were fit to further explore factors affecting patients' life quality. RESULTS: Patients with PNES had greater levels of somatization and extraversion and were associated with benzodiazepine intake. Patients with DRE showed greater narcissistic personality disorder symptoms than those with PNES. In patients with DRE, difficulty in performing basic needs-related tasks and greater psychological distress severity and seizure frequency were associated with poorer life quality. In contrast, being a woman, having a psychiatric disorder history, and greater psychiatric symptoms' intensity were associated with poorer life quality in patients with PNES. CONCLUSION: Patients with DRE and PNES share similar psychiatric and psychological characteristics, with only very few being significantly different.

A suggestive seizure induction technique protocol in a short EEG in children and adolescents.

The use of a suggestive seizure induction procedure (SSI) in medicine, particularly in the differential diagnosis of psychogenic nonepileptic epileptic seizures (PNES), is well documented. However, there is no description of standardized suggestion procedures used in children and adolescents. The research presents a standardized method of SSI with a cotton swab soaked in water. The protocol was developed based on of 544 placebo trials over ten years in a center for the differential diagnosis of children and adolescents. The protocol is a safe tool that allows inducing specific behavior in children and adolescents in whom there is a well-founded suspicion of PNES.

Improving the treatment of functional seizures through a public specialist outpatient clinic.

OBJECTIVES: We performed an audit of the first 12 months of clinical operations to assess the feasibility of a newly established public outpatient clinic for the assessment and treatment of functional (psychogenic nonepileptic) seizures (FS). METHOD: Clinical notes for the first 12 months of the FSclinic weresystematicallyreviewed with data compiled onreferral pathways, clinic attendance, clinical features, treatments, and outcomes. RESULTS: Of eighty-two new FS patients referred to the clinic, over 90% attended. Patients were diagnosed with FS after comprehensive epileptological and neuropsychiatric review, mostly with typical seizure-like episodes captured during video-EEG monitoring, and most accepted the diagnosis. Most had FS at least weekly, with little sense of control and significant impairment. The majority of individuals had significant psychiatric and medical comorbidity. Predisposing, precipitating, and perpetuating factors were readily identified in >90% of cases. Of 52 patients with follow-up data within12 months, 88% were either stable or improved in terms of the control of their FS. CONCLUSION: The Alfred functional seizure clinic model, the first dedicated public outpatient clinic for FS in Australia, provides a feasible and potentially effective treatment pathway for this underserved and disabled patient group.

[Functional Neurological Disorders - A Common but Often Unrecognized Diagnosis]. / Funktionelle neurologische Störungen ­ eine häufige, aber häufig nicht erkannte Diagnose.

Functional Neurological Disorders - A Common but Often Unrecognized Diagnosis Abstract: Functional neurological disorders are frequent and diverse in the clinical presentation. Psychological factors are part of the development and perpetuation of symptoms; psychiatric comorbidities may be present, but are not an obligatory diagnostic criterion. The diagnosis is primarily made on the basis of anamnesis and positive clinical signs. The commonness and reversibility of the symptoms should be emphasised in the clinical consultation, and the positive clinical signs should be demonstrated. Science-based explanations as well as the bio-psycho-social model can help patients to understand their diagnosis, which is relevant for a successful therapeutic outcome. It is recommended to use the neutral and descriptive term "functional neurological disorder". Treatment of the potentially reversible disease will be interdisciplinary and multimodal.

Does explaining psychogenic nonepileptic seizures using either a biomedical or biopsychosocial framework affect young people's illness representations? An experimental vignette study.

Lay representations of psychogenic nonepileptic seizures (PNES) are important both for understanding public stigma and anticipating patient responses to PNES diagnosis. The current study presents the first evidence of the general public's representations of PNES and the malleability of these understandings to different ways of explaining PNES. An online experimental study exposed participants (n = 193, aged 18-25 years) to a vignette describing a case of PNES in biomedical terms, PNES in biopsychosocial terms, or epilepsy. Subsequent questionnaires assessed participants' illness representations, causal attributions, and stigmatising attitudes regarding the case about which they read. Results suggest that compared with biomedical framings, biopsychosocial explanations increased perceptions of PNES as threatening. While epilepsy was attributed to significantly more biological and less social causes than either of the PNES vignettes, causal attributions did not differ between biomedically- vs. biopsychosocially-framed PNES. Neither were there any differences between the three conditions in stigmatising attitudes towards people who experience seizures. These findings are useful for clinicians delivering a PNES diagnosis and patients disclosing a PNES diagnosis, in helping anticipate responses to these communications. Further research is required to confirm the clinical and societal significance of the study's first insights into the dynamics of lay responses to PNES.

Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder.

There have been suggestions that Long COVID might be purely functional (meaning psychological) in origin. Labelling patients with neurological dysfunction in Long COVID as having functional neurological disorder (FND) in the absence of proper testing may be symptomatic of that line of thought. This practice is problematic for Long COVID patients, as motor and balance symptoms have been reported to occur in Long COVID frequently. FND is characterized by the presentation of symptoms that seem neurological but lack compatibility of the symptom with a neurological substrate. Although diagnostic classification according to the ICD-11 and DSM-5-TR is dependent predominantly on the exclusion of any other medical condition that could account for the symptoms, current neurological practice of FND classification allows for such comorbidity. As a consequence, Long COVID patients with motor and balance symptoms mislabeled as FND have no longer access to Long COVID care, whereas treatment for FND is seldom provided and is ineffective. Research into underlying mechanisms and diagnostic methods should explore how to determine whether motor and balance symptoms currently diagnosed as FND should be considered one part of Long COVID symptoms, in other words, one component of symptomatology, and in which cases they correctly represent FND. Research into rehabilitation models, treatment and integrated care are needed, which should take into account biological underpinnings as well as possible psychological mechanisms and the patient perspective.

Prevalence of autistic traits in functional neurological disorder and relationship to alexithymia and psychiatric comorbidity.

INTRODUCTION: In a cohort of adults with Functional Neurological Disorder (FND), we aim to: METHODS: 91 patients participating in a FND 5-week outpatient program completed baseline self-report questionnaires for total phobia, somatic symptom severity, attention deficit hyperactivity disorder (ADHD) and dyslexia. Patients were grouped by Autism Spectrum Quotient (AQ-10) score of <6 or ≥ 6 and compared for significant differences in tested variables. This analysis was repeated with patients grouped by alexithymia status. Simple effects were tested using pairwise comparisons. Multistep regression models tested direct relationships between autistic traits and psychiatric comorbidity scores, and mediation by alexithymia. RESULTS: 36 patients (40%) were AQ-10 positive (scoring ≥6 on AQ-10). A further 36 patients (across AQ-10 positive and AQ-10 negative groups) (40%) screened positive for alexithymia. AQ-10 positive patients scored significantly higher for alexithymia, depression, generalised anxiety, social phobia, ADHD, and dyslexia. Alexithymia positive patients scored significantly higher for generalised anxiety, depression, somatic symptoms severity, social phobia, and dyslexia. Alexithymia score was found to mediate the relationship between autistic trait and depression scores. CONCLUSION: We demonstrate a high proportion of autistic and alexithymic traits, in adults with FND. A higher prevalence of autistic traits may highlight a need for specialised communication approaches in FND management. Mechanistic conclusions are limited. Future research could explore links with interoceptive data.

Functional neurological disorder in children and young people: Incidence, clinical features, and prognosis.

AIM: To report incidence, demographic and clinical characteristics, and symptom outcome of functional neurological disorder (FND) in children. METHOD: Children diagnosed with FND at a regional children's hospital were prospectively recruited by weekly active surveillance for 36 months. Demographic, clinical, and follow-up data were retrospectively extracted by review of electronic records. Descriptive statistical analyses were used. RESULTS: Ninety-seven children (age range 5-15 years) met the case definition of FND (annual incidence 18.3 per 100 000 children). Children with FND were likely to be female (n = 68 [70%]) and older (median 13 years) with no difference in the Scottish Index of Multiple Deprivation (marker of socioeconomic status) compared with the general childhood population. Functional motor (41%) and sensory (41%) symptoms were most common; other somatic symptoms such as headache (31%) and pain (27%) were frequent. Self-reported psychiatric symptoms and infection/inflammation were the most common predisposing and precipitating factors respectively. At a median of 15 months follow-up, 49% of 75 children reported improvement or resolution of FND symptoms with no prognostic factors found. INTERPRETATION: At this regional centre, FND in children had a higher incidence than previously reported and a less optimistic outcome than in some other studies.

Post-Operative Conversion Aphonia in a Pediatric Patient: A Case Report.

We describe an unusual case of post-operative conversion aphonia in a pediatric patient. It indicates the importance of discussing its presentation, and amplifies the need for emotional support in the immediate post-operative period for young patients with heightened anxiety. Laryngoscope, 133:1737-1738, 2023.

Functional Neurological Disorder-Old Problem New Perspective.

Functional neurological disorder (FND) is a common issue in the pediatric population. The concept and our understanding of functional neurological disorders have changed over the past years, and new etiologic models and treatment plans have been explored. Knowledge about FND in the pediatric population, however, is lacking. The aim of this review is to provide an update on pediatric functional neurological disorder. We conducted a literature search of PubMed and SCOPUS databases and reviewed a total of 85 articles to gain insight into the current understanding of FND etiology, diagnosis, treatment, and prognosis in children and adolescents. Functional and high resolution MRI revealed abnormal connectivity and structural changes in patients with functional symptoms. The diagnostic criteria no longer require the presence of a psychological factor and instead focus on a rule-in diagnosis. Treatment of FND includes a clear communication of the diagnosis and the support of a multidisciplinary team. Although FND typically has a poor prognosis, better outcomes appear to have been achieved in children and young adults. We conclude that pediatric functional neurological disorder is a prevalent pathology and that this patient population has additional specific needs compared to the adult population.

Compassion-Focused Therapy for an Older Adult with Motor Functional Neurological Disorder: A Case Study.

OBJECTIVES: Motor functional neurological disorder (mFND) is a condition where individuals may experience difficulties such as tremors, gait impairments, and paralysis which are not explained by identified structural damage to the brain. Studies on chronic conditions have suggested that psychological interventions such as compassion-focused therapy (CFT) may be effective in improving well-being in people with mFND. However, no evidence is currently available on psychotherapy for older people with mFND. METHODS: A 12-session CFT intervention was delivered to an 81-year-old British male with mFND. Standardized measures were administered at baseline and post-intervention. RESULTS: At post-intervention, a 30% decrease in perceived psychological impact of mFND was found, along with clinically significant changes in anxiety and depression. Good levels of feasibility and acceptability were also observed. CONCLUSIONS: To our knowledge, this is the first evidence of the feasibility, acceptability, and potential effectiveness of CFT for psychological difficulties linked with mFND, as well as the first evidence for any psychotherapy with an older adult with mFND. CLINICAL IMPLICATIONS: CFT shows the potential to be effective, feasible, and acceptable for treating difficulties linked with mFND in older people. However, further high-quality investigations based on experimental designs are needed to build on the present preliminary findings.

Longitudinal outcome of Functional Neurological Disorder in Children and Adolescents in a Tertiary Care centre from Northern India.

FND is common in Indian children and adolescents. Outcome related factors are not well known. With objective to study short-term outcome of FND, prospective, longitudinal, nine months follow-up study of 6-16 years was planned. Socioeconomic, clinical variables, I.Q. and personality traits at baseline and new psychiatric/physical illness, psychosocial factors and comorbidities during follow-up were assessed. Out of 68 children, scholastic (64.7%) and family problems (23.5%) were common psychosocial factors. After nine months,73% achieved remission. Reasons for non-remission were persistence of psychosocial factors and psychiatric comorbidities. A need arises for increasing awareness among general practitioners for early identification and management.

Motor and somatosensory symptoms determine cognitive error levels in functional neurological symptom disorder/conversion disorder.

INTRODUCTION: The level of cognitive error in functional neurological symptom disorder (FNSD, conversion disorder) subtypes [psychogenic non-epileptic seizure (PNES), motor (M), PNES plus motor (PM), motor plus somatosensory (MS)] have not yet been investigated. AIM: We aimed to qualify the level of cognitive error in FNSD subtypes. MATERIALS AND METHODS: The disorder symptoms were assessed via the somatoform dissociation questionnaire (SDQ), the symptom check list-90-revised (SCL-90-R), and the global assessment scale (GAS). The cognitive distortions scale (CDS) was used to evaluate cognitive errors. RESULTS: Mean ages of groups were 28.37±6.99 years (PNES, n=24), 27.90±6.22 years (M, n=21), 30.36±7.86 years (PM, n=19), 31.38±9.02 years (MS, n=21), and 30.87±7.17 years (control, n=48) (p=0.377). In terms of the global severity index of SCL-90-R, there were significant differences between PNES and PM (p=0.003); PNES and MS (p0.999); PM and MS (p=0.172). There was no significant difference between the CDS-PA scores of the patient groups (p>0.05). CONCLUSIONS: Our study demonstrated that in FNSD, the somatosensory symptoms were more associated with cognitive errors related to interpersonal relationships than the motor symptoms and the motor symptoms were more than PNES.