Functional Neurological Disorder Research Articles

Autoimmune astrocytopathy double negative for AQP4-IgG and GFAP-IgG: Retrospective research of clinical practice, biomarkers, and pathology.

The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.

An essay on the Charcot and Richer hysteria: from charcoal drawings to cell phones.

Hysteria, previously also known as the disease of the womb, has moved from being a woman's illness through the medieval times' stigma of demonic possession, to the modern concept of a functional neurological disorder. Interestingly to the present assay, Charcot (1825-1893) and Richer (1849-1933) described, in their 1887 work Les Démoniaques dans l'art, by means of iconography, semiological aspects of the so-called Grande Attaque Hystérique, which resembles features of psychogenic nonepileptic seizures emulating grand mal epileptic seizures. The aim of the present assay is to describe how those charcoal iconographic representations evolved through history and are nowadays portrayed in videos recorded at epilepsy monitoring units and patients' cell phones.

The impact of genetic variations in the serotonergic system on symptom severity and clinical outcome in functional neurological disorders

ObjectiveWe studied gene-environment, as well as gene-gene interaction to elucidate their effects on symptom severity and predict clinical outcomes in functional neurological disorders (FND). MethodsEighty-five patients with mixed FND were genotyped for ten single-nucleotide polymorphisms (SNP) from seven different stress-related genes. We tested cross-sectionally the association between genotype and the symptomatology of FND (symptom severity assessed with the examiner-based clinical global impression score [CGI] and age of onset). Clinical outcome was assessed in 52 patients who participated in a follow-up clinical visit after eight months (following their individual therapies as usual). We tested longitudinally the association between genotype and clinical outcome in FND. We examined the contribution of each SNP and their interaction between them to FND symptomatology and outcome. ResultsWe identified a nominal association between tryptophan hydroxylase 1 (TPH1) rs1800532 and symptom severity (CGI1) in FND under a codominant model (T/T: ßT/T = 2.31, seT/T = 0.57; G/T: ßG/T = -0.18, seG/T = 0.29, P = 0.035), with minor allele (T) carriers presenting more severe symptoms. An association was identified between TPH1 and clinical outcome, suggesting that major allele (G) carriers were more likely to have an improved outcome under a codominant model (G/T: ORG/T = 0.18, CIG/T = [0.02–1.34]; T/T: ORT/T = 2.08, CIT/T = [0.30–14.53], P = 0.041). Our analyses suggested a significant gene-gene interaction for TPH2 (rs4570625) and OXTR (rs2254298) on symptom severity, and a significant gene-gene interaction for TPH1, TPH2 and BDNF (rs1491850) on clinical outcome. ConclusionFND might arise from a complex interplay between individual predisposing risk genes involved in the serotonergic pathway and their gene-gene interactions.

Opinions and experience of neurologists and neurology trainees in Saudi Arabia on functional neurological disorders: a survey based study

BackgroundFunctional Neurological Disorder (FND) is commonly encountered in clinical practice, causing functional impairment and poor quality of life. As there is limited data from Saudi Arabia, our study aims to explore the experience and opinions of Saudi neurologists and neurology trainees regarding FND.MethodsIn our cross-sectional observational study, we included 100 neurology consultants and trainees. Data was collected using an online questionnaire from March to August 2023.ResultsA total of one hundred neurologists participated in the survey. Although 41% of physicians encountered FND patients on a weekly basis or more frequently, only 41.7% of trainees reported receiving dedicated lectures on FND. Furthermore, only 46% of respondents felt comfortable providing a clear explanation of the FND diagnosis to their patients. While the majority (64%) used the term “Functional Neurological Disorder” in medical documentation, only 43% used this term when communicating the diagnosis to patients, with the terminology varying widely. Clinicians emphasized that inconsistent and variable neurological examinations were key indicators raising diagnostic suspicion, which aligns with the recommended reliance on detailed clinical history and neurological examination. Lastly, 61% of physicians stated that their approach to patients with FND lacked a structured management plan.ConclusionOur study findings emphasize that FND is commonly encountered in clinical practice and reveal a significant lack of targeted education on FND for neurology trainees. Enhancing educational programs for both trainees and practicing neurologists on this prevalent neurological condition is essential for improving patient care and outcomes.

Performance of ChatGPT 3.5 and 4 as a tool for patient support before and after DBS surgery for Parkinson's disease.

Deep brain stimulation (DBS) is a neurosurgical procedure that involves implanting electrodes into specific areas of the brain to treat a variety of medical conditions, including Parkinson's disease. Doubts and questions from patients prior to or following surgery should be addressed in line with the most recent scientific and clinical practice. ChatGPT emerges as an example of how artificial intelligence can be used, with its ability to comprehend and answer medical questions in an understandable way, accessible to everyone. However, the risks of these resources still need to be fully understood.ChatGPT models 3.5 and 4 responses to 40 questions in English and Portuguese were independently graded by two experienced specialists in functional neurosurgery and neurological movement disorders and resolved by a third reviewer. ChatGPT 3.5 and 4 demonstrated a good level of accuracy in responding to 80 questions in both English and Portuguese, related to DBS surgery for Parkinson's disease. The proportion of responses graded as correct was 57.5% and 83.8% for GPT 3.5 and GPT 4, respectively. GPT 3.5 provided potentially harmful answers for 6.3% (5/80) of its responses. No responses from GPT 4 were graded as harmful. In general, ChatGPT 3.5 and 4 demonstrated good performance in terms of quality and reliability across two different languages. Nonetheless, harmful responses should not be scorned, and it's crucial to consider this aspect when addressing patients using these resources. Considering the current safety concerns, it's not advisable for patients to use such models for DBS surgery guidance. Performance of ChatGPT 3.5 and 4 as a tool for patient support before and after DBS surgery for Parkinson's disease.

Functional neurological disorder: A rule-in diagnosis.

Functional neurological disorder: A rule-in diagnosis.

Tales of functional neurological disorder from the ED.

Tales of functional neurological disorder from the ED.

Prehospital management of functional neurological disorder.

Prehospital management of functional neurological disorder.

Comorbidity rates of autism spectrum disorder and functional neurological disorders: A systematic review, meta-analysis of proportions and qualitative synthesis.

Autism spectrum disorder (ASD) and functional neurological disorders (FND) are relatively common conditions, and there has been recent interest in the overlap between them. Both conditions share core features of alexithymia, impaired interoception and deficits in attentional focus. To date, relatively little is known about the comorbidity rates between ASD and FND. This is the first meta-analysis and qualitative synthesis on the subject. We found that around 10% of children presenting with functional seizures have a comorbid ASD diagnosis. People with ASD are more likely than the neurotypical population to have functional somatic disorders, and there is also evidence that ASD rates are higher for other FNDs such as functional motor disorders. Since FND comes with risks of unnecessary medical procedures and investigations, it is important to recognize the potential for people with ASD to have an FND comorbidity.

Prevalence of autoimmune diseases in functional neurological disorder: influence of psychiatric comorbidities and biological sex

BackgroundFunctional neurological disorder (FND) is a common and disabling neuropsychiatric condition, which disproportionally affects women compared with men. While the etiopathogenesis of this disorder remains elusive, immune dysregulation is emerging...

"Virtual reality fixed me": A case report of the use of virtual reality during intensive interdisciplinary pain treatment.

Virtual reality (VR) is an innovative technology with the potential to enhance treatment for children with chronic pain and functional symptoms. Currently, little is known about patients' experiences of VR in the setting of intensive interdisciplinary pain treatment (IIPT). This study aimed to better understand how patients engage with and benefit from VR. This case report focuses on a 12-year-old female with amplified musculoskeletal pain syndrome and comorbid functional neurological disorder receiving treatment in inpatient IIPT. VR was incorporated into physical/occupational and recreational therapy sessions. A semi-structured interview was completed one-month post-discharge. Qualitative analysis revealed three major themes: Process of Change (VR was unique/immersive, reduced pain focus, challenged skepticism, and changed pain perception), Efficacy (VR increased movement, supported transitioning from a wheelchair to walking independently, and increased confidence, excitement, and surprise), and Engagement (VR aided in acknowledging progress, increased camaraderie, was fun, and challenged patient to extend treatment goals made in VR to real life). Therapist observations of the benefits and barriers to using VR in treatment are described. Overall, this report indicates that VR may be a helpful tool to use with existing IIPT interventions to enhance patient engagement in treatment and improve functionaloutcomes.

Functional neurological disorder in Europe: regional differences in education and health policy.

Functional neurological disorder (FND) is a common cause of neurological disability. Despite recent advances in pathophysiological understanding and treatments, application of this knowledge to clinical practice is variable and limited. Our aim was to provide an expert overview of the state of affairs of FND practice across Europe, focusing on education and training, access to specialized care, reimbursement and disability policies, and academic and patient-led representation of people with FND. We conducted a survey across Europe, featuring one expert per country. We asked experts to compare training and services for people with FND to those provided to people with multiple sclerosis (MS). Responses from 25 countries revealed that only five included FND as a mandatory part of neurological training, while teaching about MS was uniformly included. FND was part of final neurology examinations in 3/17 countries, unlike MS that was included in all 17. Seventeen countries reported neurologists with an interest in FND but the estimated mean ratio of FND-interested neurologists to MS neurologists was 1:20. FND coding varied, with psychiatric coding for FND impacting treatment access and disability benefits in the majority of countries. Twenty countries reported services refusing to see FND patients. Eight countries reported an FND special interest group or network; 11 reported patient-led organizations. FND is largely a marginal topic within European neurology training and there is limited access to specialized care and disability benefits for people with FND across Europe. We discuss how this issue can be addressed at an academic, healthcare and patient organization level.

Treatment of functional neurological disorders by example of a patient with cardiac neurosis, tension headache, musculoskeletal pain and insomnia

Treatment of functional neurological disorders by example of a patient with cardiac neurosis, tension headache, musculoskeletal pain and insomnia

Functional Movement Disorder as a Prodromal Symptom of Parkinson's Disease-Clinical and Pathophysiological Insights.

Functional movement disorder (FMD) is a common manifestation of functional neurological disorder. FMD can occur alongside other neurological conditions, but especially in patients with established Parkinson's disease (PD). An interesting observation emerging across cohort studies and case series is that FMD can precede the diagnosis of PD, suggesting that FMD may itself be a prodromal symptom of neurodegeneration. Such a notion would have significant clinical implications for the assessment and management of people with FMD, particularly with respect to decisions around the use of auxiliary investigations, counselling, and follow-up. In this Viewpoint we review the evidence concerning the temporal relationship between FMD and PD. We discuss the potential explanations and mechanisms for FMD as a prodromal symptom of PD, and highlight clinical considerations and important outstanding questions in the field. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Spectrum Between Catatonia and Functional Neurologic Disorder Superimposed on Post-Infectious Encephalitis in a Marine Recruit.

Catatonia, a neuropsychiatric condition characterized by abnormal speech, volition, and movement, is primarily thought of as a symptom of a primary psychiatric pathology, but there are a variety of non-psychiatric medical conditions that must be considered. As a result of symptomatic complexity and the wide range of differential diagnoses, catatonia-like symptoms can cloud the clinical evaluation and complicate treatment regimens. Within the realm of catatonic-like diagnoses is functional neurological disorder because of its vast range of potential presentations. Functional neurologic disorder can be diagnosed by evidence of incompatibility between neurologic symptoms and recognized neurological or medical conditions. Clinical uncertainty is further intensified in the presence of co-morbid medical etiologies because of inability to neatly delegate symptoms to a specific diagnosis. The blurred spectrum between catatonia and functional neurologic disorder is highlighted in this patient's complex clinical presentation while being further obscured in the setting of a possible overlying encephalitis exacerbating the presentation. This case report presents a unique case of a Marine recruit whose inconsistent catatonic symptoms caused diagnostic uncertainty and were ultimately decided to have neurologic and psychiatric contributions, highlighting that diagnoses are not mutually exclusive and should be continually re-assessed as new data become available. This report also showcases the distinctiveness of U.S. Marine culture and possible physical manifestations because of imposed psychological stress.

'Positive' inter-ictal clinical signs of functional neurological disorders are found in patients with functional dissociative seizures.

Prior studies highlighted the high diagnostic specificity (ranging from 92% to 100%) of clinical signs observed in functional neurological disorders (FNDs). However, these signs are rarely looked for by epileptologists when trying to distinguish between functional dissociative seizure (FDS) and epileptic seizure. The aim of this study was to determine the prevalence of inter-ictal clinical signs of FND in a cohort of patients with probable FDS. The secondary objective was to compare the prevalence of inter-ictal FND clinical signs in FDS patients with age- and gender-matched epileptic patients without FDS. Patients diagnosed with FDS seen at two tertiary care centres and epileptic outpatients were included in the study. Each patient underwent a physical examination, searching for inter-ictal clinical signs of FND. In the FDS group, 79% of patients presented at least one sign of FND, compared to 16.6% of patients with epilepsy (p < 0.001). Moreover, 66.6% of FDS patients presented three or more FND signs, whereas only 4.1% of epileptic patients did (p < 0.001). The median number of FND clinical signs in the FDS group was four (SD 1.7; 5.5). Using the threshold of three signs or more, the specificity of detecting three or more FND signs was 83.3%, with a sensitivity of 79.2%. Inter-ictal clinical signs of FND are present in patients with FDS and should be looked for during neurological examination.

The role of neuropsychology in the care of patients with functional neurological symptom disorder.

Functional neurological symptom disorder (FNSD) is a neuropsychiatric condition characterized by signs/symptoms associated with brain network dysfunction. FNSDs are common and are associated with high healthcare costs. FNSDs are relevant to neuropsychologists, as they frequently present with chronic neuropsychiatric symptoms, subjective cognitive concerns, and/or low neuropsychological test scores, with associated disability and reduced quality of life. However, neuropsychologists in some settings are not involved in care of patients with FNSDs. This review summarizes relevant FNSD literature with a focus on the role of neuropsychologists. A brief review of the literature is provided with respect to epidemiology, public health impact, symptomatology, pathophysiology, and treatment. Two primary areas of focus for this review are the following: (1) increasing neuropsychologists' training in FNSDs, and (2) increasing neuropsychologists' role in assessment and treatment of FNSD patients. Patients with FNSD would benefit from increased involvement of neuropsychologists in their care.

Lived experience of driving in individuals with functional neurological disorder.

Functional neurological disorder (FND) is a common neurological diagnosis that encapsulates a range of incapacitating clinical presentations. These include functional seizures, movement disorders, and sensory disturbances. Safe driving requires both cognitive skills and physical abilities, which may be impacted by FND symptoms. The primary objective of this study was to gain deeper insights into the challenges faced by people with FND when driving. A qualitative study and interpretative phenomenological analysis were conducted. Individuals experiencing functional seizures and/or movement disorders completed both questionnaires and semi-structured interviews about FND symptoms, driving behavior, and crashes. A total of 26 patients with FND participated in this study. Based on the interviews, four key themes were identified: (1) driving difficulties experienced by individuals with FND; (2) strategies utilized by people with FND to overcome difficulties experienced while driving; (3) barriers preventing driving challenges being addressed in this population; and (4) crashes and perceived dangerous driving events experienced by individuals with FND. All participants reported that driving a car provoked FND symptoms and this affected their driving ability. FND sufferers reported using a number of strategies such as limiting how far they drive and relying on advanced driver assistance system features to help manage their associated symptoms, such as fatigue and/or pain. Several participants reported crashes and perceived dangerous driving events since developing FND. Individuals experiencing FND often employ self-regulation techniques, yet the extent to which these methods enhance driving safety remains uncertain. The variable nature of the disorder makes judging an individual's driving risk particularly difficult. The themes emerging from the interviews highlighted the need for further empirical research to inform guidelines and best practice when determining the impact of FND on an individual's driving safety .

Stiff Person Syndrome and GAD Antibody-Spectrum Disorders.

Antibodies against glutamic acid decarboxylase (GAD), originally associated with stiff person syndrome (SPS), define the GAD antibody-spectrum disorders that also include cerebellar ataxia, autoimmune epilepsy, limbic encephalitis, progressive encephalomyelitis with rigidity and myoclonus (PERM), and eye movement disorders, all of which are characterized by autoimmune neuronal excitability. This article elaborates on the diagnostic criteria for SPS and SPS spectrum disorders, highlights disease mimics and misdiagnoses, describes the electrophysiologic mechanisms and underlying autoimmunity of stiffness and spasms, and provides a step-by-step therapeutic scheme. Very-high serum GAD antibody titers are diagnostic for GAD antibody-spectrum disorders and also predict the presence of GAD antibodies in the CSF, increased intrathecal synthesis, and reduced CSF γ-aminobutyric acid (GABA) levels. Low serum GAD antibody titers or the absence of antibodies generates diagnostic challenges that require careful distinction in patients with a variety of painful spasms and stiffness, including functional neurologic disorders. Antibodies against glycine receptors, first found in patients with PERM, are seen in 13% to 15% of patients with SPS, whereas amphiphysin and gephyrin antibodies, seen in 5% of patients with SPS spectrum disorders, predict a paraneoplastic association. GAD-IgG from different SPS spectrum disorders recognizes the same dominant GAD intracellular epitope and, although the pathogenicity is unclear, is an excellent diagnostic marker. The biological basis of muscle stiffness and spasms is related to autoimmune neuronal hyperexcitability caused by impaired reciprocal γ-aminobutyric acid-mediated (GABA-ergic) inhibition, which explains the therapeutic response to GABA-enhancing agents and immunotherapies. It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses, considering that SPS is treatable if managed correctly from the outset to prevent disease progression. A step-by-step, combination therapy of GABA-enhancing medications along with immunotherapies ensures prolonged clinical benefits.

Making meaning: The experience of Shared Individual Formulation Therapy in adults with functional neurological disorder

Making meaning: The experience of Shared Individual Formulation Therapy in adults with functional neurological disorder