Functional neurological disorder, physical activity and exercise: What we know and what we can learn from comorbid disorders.

Functional neurological disorder (FND) is a common neurologic disorder associated with many comorbid symptoms including fatigue, pain, headache, and orthostasis. These concurrent symptoms lead patients to accumulate multiple diagnoses comorbid with FND, including fibromyalgia, chronic fatigue syndrome, postural orthostatic tachycardia syndrome, persistent post-concussive symptoms, and chronic pain. The role of physical activity and exercise has not been evaluated in FND populations, though has been studied in certain comorbid conditions. In this traditional narrative literature review, we highlight some existing literature on physical activity in FND, then look to comorbid disorders to highlight the therapeutic potential of physical activity. We then consider abnormalities in the autonomic nervous system (ANS) as a potential pathophysiological explanation for symptoms in FND and comorbid disorders and postulate how physical activity and exercise may provide benefit via autonomic regulation.

Postictal psychiatric symptoms: A neurophysiological study.

OBJECTIVE: Postictal psychiatric symptoms (PPS) are a relatively common but understudied phenomenon in epilepsy. The mechanisms by which seizures contribute to worsening in psychiatric symptoms are unclear. We aimed to identify PPS prospectively during and after admission to the epilepsy monitoring unit (EMU) in order to characterize the postictal physiologic changes leading to PPS. METHODS: We prospectively enrolled patients admitted to the EMU and administered repeat psychometric questionnaires during and after their hospital stay in order to assess for postictal exacerbations in four symptom complexes: anger/hostility, anxiety, depression, and paranoia. Electroclinical and electrographic seizures were identified from the EEG recordings, and seizure durations were measured. The severity of postictal slowing was calculated as the proportion of postictal theta/delta activity in the postictal EEG relative to the preictal EEG using the Hilbert transform. RESULTS: Among 33 participants, 8 demonstrated significant increases in at least one of the four symptoms (the PPS+ group) within three days following the first seizure. The most common PPS was anger/hostility, experienced by 7/8 participants with PPS. Among the 8 PPS+ participants, four experienced more than one PPS. As compared to those without PPS (the PPS- group), the PPS+ group demonstrated a greater degree of postictal EEG slowing at 10 min (p = 0.022) and 20 min (p = 0.05) following seizure termination. They also experienced significantly more seizures during the study period (p = 0.005). There was no difference in seizure duration between groups. SIGNIFICANCE: Postictal psychiatric symptoms including anger/hostility, anxiety, depression, and paranoia may be more common than recognized. In particular, postictal increases in anger and irritability may be particularly common. We provide physiological evidence of a biological mechanism as well as a demonstration of the use of quantitative electroencephalography toward a better understanding of postictal neurophysiology.

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

BACKGROUND: Functional 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 as one potential mechanism. To begin to understand the role of immune dysfunctions in FND, we assessed the prevalence of several common autoimmune diseases (ADs) in a large cohort of patients with FND and examined the influence of psychiatric comorbidities and biological sex. METHODS: Using a large biorepository database (Mass General Brigham Biobank), we obtained demographic and clinical data of a cohort of 643 patients diagnosed with FND between January 2015 and December 2021. The proportion of ADs was calculated overall, by sex and by the presence of psychiatric comorbidities. RESULTS: The overall prevalence of ADs in our sample was 41.9%, with connective tissue and autoimmune endocrine diseases being the most commonly observed ADs. Among patients with FND and ADs, 27.7% had ≥2 ADs and 8% met criteria for multiple autoimmune syndrome. Rates of ADs were significantly higher in subjects with comorbid major depressive disorder and post-traumatic stress disorder (p= 0.02). Women represented the largest proportion of patients with concurrent ADs, both in the overall sample and in the subgroups of interest (p's < 0.05). CONCLUSIONS: This study is unique in providing evidence of an association between FND and ADs. Future studies are needed to investigate the mechanisms underlying this association and to understand whether FND is characterised by distinct dysregulations in immune response.

Developing a Curriculum for Functional Neurological Disorder in Neurology Training: Questions and Answers.

Functional neurologic disorder (FND) is a common condition for which neurology residents often receive little to no formal teaching. Using a question-and-answer format, this article puts forward a case for why an FND curriculum is needed and aims to provide guidance on possible curricular content including medical knowledge, clinical skills, communication, and team-based collaboration. The authors also discuss methods for teaching and evaluating this knowledge and associated clinical skills, linking this to current Accreditation Council for Graduate Medical Education neurology milestones. Finally, the authors consider how to better engage and energize neurology trainees around this underserved yet challenging patient population.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Initial case series of a novel sensing deep brain stimulation device in drug-resistant epilepsy and consistent identification of alpha/beta oscillatory activity: A feasibility study.

OBJECTIVE: Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. METHODS: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software. Local field potentials recorded over 12-18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in-clinic broadband LFP recordings, real-time LFP response to stimulation, and chronic recordings to guide DBS programming. RESULTS: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose-dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button-presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. SIGNIFICANCE: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real-time and chronic LFP recording.

Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

The Potential of Wearable Devices and Mobile Health Applications in the Evaluation and Treatment of Epilepsy.

Wearable devices and mobile health software applications have a great potential for improving epilepsy-related health outcomes and contributing to personalized medical care for persons with epilepsy. With limitations and challenges, they can be used for tracking seizure occurrence and for seizure detection, prediction, and forecasting in hospital and ambulatory settings. They can also help promote self-monitoring and self-management and thereby contribute to patient empowerment. In this review, we provide an overview of current wearable devices and mobile health software applications for epilepsy. We focus on clinically validated devices, their clinical applications, the challenges faced when using these devices in real-world settings, and how these devices may be optimized in the future.

Functional neurological disorder: new subtypes and shared mechanisms.

Functional neurological disorder is common in neurological practice. A new approach to the positive diagnosis of this disorder focuses on recognisable patterns of genuinely experienced symptoms and signs that show variability within the same task and between different tasks over time. Psychological stressors are common risk factors for functional neurological disorder, but are often absent. Four entities-functional seizures, functional movement disorders, persistent perceptual postural dizziness, and functional cognitive disorder-show similarities in aetiology and pathophysiology and are variants of a disorder at the interface between neurology and psychiatry. All four entities have distinctive features and can be diagnosed with the support of clinical neurophysiological studies and other biomarkers. The pathophysiology of functional neurological disorder includes overactivity of the limbic system, the development of an internal symptom model as part of a predictive coding framework, and dysfunction of brain networks that gives movement the sense of voluntariness. Evidence supports tailored multidisciplinary treatment that can involve physical and psychological therapy approaches.

Sustained improvement with mindfulness-based therapy for psychogenic nonepileptic seizures.

BACKGROUND: We previously reported on the efficacy of a manualized 12-session mindfulness-based therapy (MBT) for psychogenic nonepileptic seizures (PNES). Completion of MBT provided improvements in weekly PNES frequency and self-rated intensity. OBJECTIVES: In this study, we aimed to determine sustainability of improvement of seizure-related measures at 3- to 6-month follow-up after treatment completion. We also examined changes at treatment end and at follow-up on therapeutic targets of the MBT program. METHODS: Patients with documented PNES were recruited from 2014 to 2018. Baseline measures were collected at time of diagnosis (T0) and at first follow-up post-diagnosis (T1). Outcomes are reported at MBT treatment completion (T3) and 3- to 6-month follow-up (T4). The Wilcoxon signed-rank test was used for pair-wise comparisons of PNES frequency; linear mixed models were used for other outcomes. RESULTS: Fourteen of the 26 MBT completers (54%) attended follow-up (median 147.5 days between T3 and T4). PNES frequency, intensity, and number of days/week with PNES remained reduced at T4 (p < 0.01 for all; median frequency reduction 1.3/week from T1). Illness perception and feeling understood remained improved at T4 (p < 0.001 for both) as did worry about PNES (p < 0.05). Illness attribution (physical, mental or both) changed from T0 to T3 (p < 0.01), but not to T4. Psychological flexibility did not change over time. CONCLUSION: Previously reported improvements in seizure-related measures with MBT at treatment conclusion were maintained at 3- to 6-month follow-up. There were sustained improvements in some underlying processes (illness perception, feeling understood, and symptom worry) over the course of treatment and at follow-up. Long-term benefits of MBT need to be established with randomized controlled trials.

The role of evidence-based guidelines in the diagnosis and treatment of functional neurological disorder.

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.

Functional neurological disorder: Engaging patients in treatment.

Patients with a functional neurological disorder can be difficult to engage in treatment. The reasons for this are complex and may be related to physician, patient and health care system issues. Providers contribute to difficulties in treatment engagement by giving confusing explanations for the patient symptoms, stigmatizing patients, and not allowing patients time to voice their questions and concerns. Patient factors include a lack of engagement after an explanation of the diagnosis, resistance to treatment, family/work dynamics and prior negative experiences with the health care system. The scarcity of providers skilled in the treatment of functional neurological disorder is yet another hurdle. This article will define these barriers and discuss good clinical practices to help improve outcomes by tackling those challenges and discuss why for many patients an integrated care team approach is needed.

How to do things with words: Two seminars on the naming of functional (psychogenic, non-epileptic, dissociative, conversion, ) seizures.

Amongst the most important conditions in the differential diagnosis of epilepsy is the one that manifests as paroxysms of altered behaviour, awareness, sensation or sense of bodily control in ways that often resemble epileptic seizures, but without the abnormal excessive or synchronous electrical activity in the brain that defines these. Despite this importance, there remains little agreement - and frequent debate - on what to call this condition, known inter alia as psychogenic non-epileptic seizures (PNES), dissociative seizures (DS), functional seizures (FS), non-epileptic attack disorder (NEAD), pseudoseizures, conversion disorder with seizures, and by many other labels besides. This choice of terminology is not merely academic - it affects patients' response to and understanding of their diagnosis, and their ability to navigate health care systems.This paper summarises two recent discussions hosted by the American Epilepsy Society and Functional Neurological Disorders Society on the naming of this condition. These discussions are conceptualised as the initial step of an exploration of whether it might be possible to build consensus for a new diagnostic label.

Functional Neurologic Disorders: The Need for a Model of Care.

Neurologists are commonly consulted for patients with a functional neurologic disorder. Best practices as to their diagnosis and treatment have been established, and multiple academic centers have programs in place for their treatment. However, given the number of patients suffering from this condition, a comprehensive model of care that can be broadly implemented needs to be developed and applied beyond specialized academic programs.

The probability of sudden unexpected death in epilepsy given postictal prone position.

Sudden Unexpected Death in Epilepsy (SUDEP) is strongly linked to prone position in the immediate aftermath of a generalized tonic-clonic seizure (GTCS). The risk of SUDEP after a GTCS resulting in prone position has not yet been estimated. We calculated the probability of SUDEP given prone position after a GTCS using Bayesian analysis with inputs obtained from known risk of SUDEP and probability of prone position after a GTCS. The risk for SUDEP given the prone position is estimated to be 0.41% (95% Credible Interval 0.13-0.69%). The relative risk of SUDEP in prone vs. non-prone position following a GTCS is estimated to be 63 (95% Credible Interval 30-96). Sudden Unexpected Death in Epilepsy might be prevented by repositioning the patient after a seizure to avoid the prone position.

Pediatric and adult neurologist perspectives on the challenges of sustaining a transfer clinic.

We present a novel epilepsy fellow-driven transfer clinic model and discuss the challenges experienced in finding sustainability; this is timely as many pioneering transition clinics are dissolving across North America. The goal of this clinic was to improve patient care and satisfaction, as measured by a post-visit telephone survey. Unfortunately, our transfer clinic model proved unsustainable due to several factors, broadly categorized as (1) cultural-societal differences between the pediatric and adult health care environments, (2) staffing issues, (3) lack of an established standardized process for transfer of care, and (4) financial and administrative barriers. We suggest potential solutions to these challenges, but the fate of transition and transfer of care clinics may ultimately depend on implementation of practice, policy, and/or financial guidelines.

Association of epileptiform abnormalities and seizures in Alzheimer disease.

OBJECTIVE: To examine the relationship between scalp EEG biomarkers of hyperexcitability in Alzheimer disease (AD) and to determine how these electric biomarkers relate to the clinical expression of seizures in AD. METHODS: In this cross-sectional study, we performed 24-hour ambulatory scalp EEGs on 43 cognitively normal elderly healthy controls (HC), 41 participants with early-stage AD with no history or risk factors for epilepsy (AD-NoEp), and 15 participants with early-stage AD with late-onset epilepsy related to AD (AD-Ep). Two epileptologists blinded to diagnosis visually reviewed all EEGs and annotated all potential epileptiform abnormalities. A panel of 9 epileptologists blinded to diagnosis was then surveyed to generate a consensus interpretation of epileptiform abnormalities in each EEG. RESULTS: Epileptiform abnormalities were seen in 53% of AD-Ep, 22% of AD-NoEp, and 4.7% of HC. Specific features of epileptiform discharges, including high frequency, robust morphology, right temporal location, and occurrence during wakefulness and REM, were associated with clinical seizures in AD. Multiple EEG biomarkers concordantly demonstrated a pattern of left temporal lobe hyperexcitability in early stages of AD, whereas clinical seizures in AD were often associated with bitemporal hyperexcitability. Frequent small sharp spikes were specifically associated with epileptiform EEGs and thus identified as a potential biomarker of hyperexcitability in AD. CONCLUSION: Epileptiform abnormalities are common in AD but not all equivalent. Specific features of epileptiform discharges are associated with clinical seizures in AD. Given the difficulty recognizing clinical seizures in AD, these EEG features could provide guidance on which patients with AD are at high risk for clinical seizures.

Motivational Interviewing Techniques to Improve Psychotherapy Adherence and Outcomes for Patients With Psychogenic Nonepileptic Seizures.

Psychogenic nonepileptic seizures (PNES) are a highly disabling disorder frequently encountered by neurologists, psychiatrists, and emergency medicine physicians. There is accumulating evidence for the efficacy of psychological therapies, yet the majority of patients do not complete treatment. A range of health care system-based, clinician-based, and patient-based barriers to treatment exists, including stigma, poor clinician-patient communication, and patient ambivalence about the diagnosis and treatment of PNES. These barriers frequently lead to treatment nonadherence. Motivational interviewing (MI) is a patient-centered counseling style targeting ambivalence about behavior change, which has been shown to be effective in improving psychotherapy adherence and outcomes among patients with PNES. The authors review MI processes and techniques that may be useful to health care providers helping patients with PNES and other functional neurological disorders to engage in psychotherapy. The authors examine common challenges arising during MI for patients with PNES, including somatic symptoms distracting from clinician-patient communication, ambivalence about making concrete plans for treatment, and psychiatric comorbidities. Strategies for overcoming these obstacles are reviewed, including the use of complex reflections to enhance patient engagement; the use of an ask-tell-ask format and specific, measurable, achievable, relevant, and time-limited (SMART) goals to facilitate treatment planning; and close collaboration between the neurology and psychotherapy teams.

Mindfulness-based therapy for psychogenic nonepileptic seizures.

BACKGROUND: Mindfulness-based therapies (MBTs) are effective in many neuropsychiatric disorders, and represent a potential therapeutic strategy for psychogenic nonepileptic seizures (PNES). OBJECTIVE: The objective of this study was to investigate the clinical effect of a manualized 12-session MBT for PNES in an uncontrolled trial. We hypothesized reductions in PNES frequency, intensity, and duration, and improvements in quality of life and psychiatric symptom severity at treatment completion. METHODS: Between August 2014 and February 2018, 49 patients with documented PNES (with video electroencephalography [EEG]) were recruited at Brigham and Women's Hospital to participate in the MBT for PNES treatment study. Baseline demographic and clinical information and self-rating scales were obtained during the diagnostic evaluation (T0). Baseline PNES frequency, intensity, and duration were collected at the first follow-up postdiagnosis (T1). Frequency was obtained at each subsequent MBT session and analyzed over time with median regression analysis. Outcomes for other measures were collected at the last MBT session (T3), and compared to baseline measures using linear mixed models. RESULTS: Twenty-six patients completed the 12-session MBT program and were included in the analysis. Median PNES frequency decreased by 0.12 events/week on average with each successive MBT session (p = 0.002). At session 12, 70% of participants endorsed a reduction in PNES frequency of at least 50%. Freedom from PNES was reported by 50% of participants by treatment conclusion. Seventy percent reported a 50% reduction in frequency from baseline and 50% reported remission at session 12. By treatment end, PNES intensity decreased (p = 0.012) and quality of life improved (p = 0.002). Event duration and psychiatric symptom severity were lower after treatment, but reductions were not statistically significant. CONCLUSIONS: Completion of a manualized 12-session MBT for PNES provides improvement in PNES frequency, intensity, and quality of life. The high dropout rate is consistent with adherence studies in PNES. Possible reasons for dropout are discussed. Randomized controlled trials and longer-term outcomes are needed to demonstrate the efficacy of MBT in PNES.