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.

Functional Neurological Disorder Presenting After Concussion: A Retrospective Case Series.

OBJECTIVE: Although a majority of individuals recover from a concussion within weeks of the index injury, a substantial minority of patients report persistent postconcussion symptoms. Some of these symptoms may reflect a diagnosis of functional neurological disorder (FND). The authors evaluated the relationship between persistent postconcussion symptoms and FND symptoms. METHODS: In this retrospective chart review, the authors characterized demographic and clinical information from 50 patients with a confirmed diagnosis of FND whose functional neurological symptoms started after a concussion. RESULTS: Patients who developed FND after a concussion had high rates of baseline risk factors for both persistent postconcussion symptoms and FND. After the concussive event, functional neurological symptoms presented abruptly or developed insidiously over time. Functional neurological symptoms ranged widely and included gait symptoms, seizures, speech and language symptoms, weakness, sensory symptoms, tremors, and vision and oculomotor symptoms. CONCLUSIONS: Functional neurological symptoms can arise after a concussion. FND should be considered in the differential diagnosis of individuals presenting with neurological symptoms beginning after a concussion. By failing to recognize functional symptoms, clinicians may inadvertently reinforce negative health-related beliefs regarding a patient's injured brain.

Comparing focused attention meditation to meditation with mobile neurofeedback for persistent symptoms after mild-moderate traumatic brain injury: a pilot study.

PRIMARY OBJECTIVE: This study evaluated whether a meditation practice incorporating mobile neurofeedback (mNF) offers any advantage over a more traditional form of focused attention (FA) meditation in managing persistent symptoms after traumatic brain injury (TBI) (clinicaltrials.gov NCT02615535). RESEARCH DESIGN: Pilot randomized clinical trial, exploring feasibility of mNF in TBI. METHODS AND PROCEDURES: Participants included adults with chronic mood and/or cognitive complaints following mild-moderate TBI. Subjects practiced either FA (n = 10) or mNF (n = 10) meditation 12 minutes daily for 6 weeks. Pre-post intervention difference on the Neurobehavioral Symptom Inventory (NSI) was the primary outcome variable. Secondary outcomes included the Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), amongst other scales and neurocognitive tests. MAIN OUTCOMES AND RESULTS: No significant pre-post between-group differences were found on the NSI (p = .838) nor other assessments. In an exploratory analysis combining FA and mNF data, meditation was associated with significant improvements on the NSI (p = .04), BAI (p = .012) and BDI (p = .037). CONCLUSIONS: Meditating with neurofeedback does not appear to provide an advantage over meditating on one's own for chronic post-TBI symptoms. Further research on home-based meditation following TBI, whether self-directed or technologically facilitated, is warranted.

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.

Inpatient Rehabilitation for Acute Presentations of Motor Functional Neurological Disorder: A Retrospective Cohort Study.

OBJECTIVE: Patients with functional neurological disorder involving the motor system (eg, functional weakness, functional gait) may acutely present to the hospital for new-onset symptoms. For some, symptoms may remain severe enough at the time of hospital discharge to qualify for an inpatient rehabilitation facility stay. DESIGN: Data were extracted via retrospective chart review on functional neurological disorder patients ( N = 22) admitted to an inpatient rehabilitation facility between September 2019 and May 2022. Demographic and clinical data, including admission and discharge physical and occupational therapy measurements on the Inpatient Rehabilitation Facility Patient Assessment Instrument, were recorded and analyzed. RESULTS: Symptom duration was less than 1 wk for nearly two thirds of the cohort. After an approximately 2-wk length of stay, patients showed statistically significant changes in admission to discharge measures of self-care, transfers, ambulation, and balance. More than 95% of patients were able to be discharged home. The presence or absence of comorbid depression, anxiety, or posttraumatic stress disorder did not impact outcomes. CONCLUSIONS: For a subset of patients with persistent motor symptoms after an acute hospital admission for a new diagnosis of functional neurological disorder, a relatively short inpatient rehabilitation facility stay was associated with significant clinical gains.

Setting up Functional Neurological Disorder Treatment Services: Questions and Answers.

Functional neurologic disorder (FND) is commonly encountered across outpatient and inpatient medical settings. Given the potential for a high burden of disability in some patients and mounting evidence for the efficacy of FND-specific multidisciplinary treatment services, expanding clinical services for this population is a necessity. In this perspective article, we discuss considerations for creating FND services, including the types of services that exist, how to start, how to identify appropriate referrals, and how to develop and monitor individualized treatment plans. In addition, we discuss how this effort can be done sustainably - balancing patient needs with limited healthcare resources.

Intensive rehabilitation for functional motor disorders (FMD) in the United States: A review.

BACKGROUND: Higher levels of care in the form of intensive rehabilitation may be appropriate for select patients with a diagnosis of functional motor disorder (FMD). Intensive rehabilitation, as delivered through an outpatient day program or through admission to an inpatient rehabilitation facility, can offer a greater frequency and variety of integrated clinical services than most lower levels of care. OBJECTIVE: Higher levels of rehabilitation for FMD have not yet been well characterized in the literature. In this article, we will focus on the population of FMD patients who begin receiving care in the outpatient setting. METHOD: In this review, we describe a range of options for higher levels of FMD care, evaluate the supporting literature, and weigh the pros and cons of each approach. Several specific examples of intensive rehabilitation programs in the United States will be described. Finally, we will consider existing health systems barriers to each of these outpatient and inpatient higher levels of care. RESULTS: Within a stepped model of care, intensive outpatient day-programs and inpatient rehabilitation may be considered for individuals who present with complex, refractory motor deficits from FMD. For appropriately selected patients, a growing body of literature suggests that time-limited, goal-oriented intensive rehabilitation may provide an effective treatment avenue. CONCLUSION: It remains to be determined whether treatment in intensive care settings, while more costly in the short term, could lead to greater cost savings in the long term. The prospect of telemedicine rehabilitation for FND in terms of efficacy and cost also remains to be determined.

The use of rhythmic auditory stimulation for functional gait disorder: A case report.

BACKGROUND: Functional gait disorders (FGD) are a common and disabling condition. Consensus-based rehabilitation techniques for treating FGD and other functional neurological disorder presentations at large utilize a variety of therapeutic strategies, including distraction, novel approaches to movement, entrainment, stress/hypervigilance modulation, and psychotherapy. CASE REPORT: Here we present a case of a 24-year-old woman with a complex history of anxiety, depression, left frontal astrocytoma, postural orthostatic tachycardia syndrome (POTS) and FGD. During a multidisciplinary inpatient rehabilitation stay for FGD, the patient underwent rhythmic auditory stimulation (RAS) delivered by a neurologic music therapist in conjunction with physical therapy, occupational therapy, and psychotherapy. RESULTS: The RAS intervention appeared to play a significant role in symptom resolution for this patient. Improvement in the patient's truncal displacement, foot dragging, and well as overall gait speed occurred following serial RAS trials performed over a single treatment session. Benefits persisted immediately following the intervention and upon subsequent reassessment. Although at four-year follow-up the patient's FGD symptoms remained resolved, fatigue continued to limit her ambulatory capacity and overall endurance. CONCLUSION: RAS represents a unique therapeutic approach for treating FGD, complementary to existing consensus-based rehabilitation recommendations, and may warrant further consideration by the field.

Development of an inpatient rehabilitation pathway for motor functional neurological disorders: Initial reflections.

BACKGROUND: Emerging research supports a primary role for rehabilitation therapy alongside psychoeducation and psychotherapy in the treatment of functional neurological disorder (FND). OBJECTIVE: While consensus recommendations for physical therapists, occupational therapists, and speech and language pathologists treating FND have been published, specific recommendations for multidisciplinary FND care delivered on an inpatient rehabilitation unit are yet to be established. METHODS: This report describes one inpatient rehabilitation facility's efforts to design and implement a clinical pathway for patients with acute-onset motor FND-patients recently hospitalized for work-up of new neurological symptoms subsequently deemed functional. RESULTS: Detailed descriptions on defining admission criteria and delivering consensus- and evidence-based multidisciplinary inpatient rehabilitation are provided. CONCLUSIONS: In the context of prospective research studies, considerably more work is needed to delineate the optimal duration and intensity of inpatient rehabilitation treatment for the management of patients with motor FND.

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.

Functional outcomes in the inpatient rehabilitation setting following severe COVID-19 infection.

OBJECTIVE: To characterize the functional impairments of a cohort of patients undergoing inpatient rehabilitation after surviving severe COVID-19 illness, in order to better understand the ongoing needs of this patient population. METHODS: This study consisted of a retrospective chart review of consecutive patients hospitalized for COVID-19 and admitted to a regional inpatient rehabilitation hospital from April 29th to May 22nd, 2020. Patient demographics, clinical characteristics and complications from acute hospitalization were examined. Measures of fall risk (Berg Balance Scale), endurance (6 Minute Walk Test), gait speed (10 Meter Walk Test), mobility (transfer and ambulation independence), cognition, speech and swallowing (American Speech and Hearing Association National Outcomes Measurement System Functional Communication Measures) were assessed at rehabilitation admission and discharge. RESULTS: The study population included 29 patients and was 70% male, 58.6% white and with a mean age of 59.5. The mean length of acute hospitalization was 32.2 days with a mean of 18.7 days intubated. Patients spent a mean of 16.7 days in inpatient rehabilitation and 90% were discharged home. Patients demonstrated significant improvement from admission to discharge in measures of fall risk, endurance, gait speed, mobility, cognition, speech and swallowing, (p< 0.05). At discharge, a significant portion of the population continued to deficits in cognition (attention 37%; memory 28%; problem solving 28%), balance (55%) and gait speed (97%). CONCLUSION: Patients admitted to inpatient rehabilitation after hospitalization with COVID-19 demonstrated deficits in mobility, cognition, speech and swallowing at admission and improved significantly in all of these domains by discharge. However, a significant number of patients exhibited residual deficits at discharge highlighting the post-acute care needs of this patient population.

Imaging the functional connectivity of the Periaqueductal Gray during genuine and sham electroacupuncture treatment.

BACKGROUND: Electroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA. RESULTS: Forty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels. CONCLUSIONS: Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception.

The need to act a little more 'scientific': biomedical researchers investigating complementary and alternative medicine.

The advent of scientific research on complementary and alternative medicine (CAM) has contributed to the current state of flux regarding the distinction between biomedicine and CAM. CAM research scientists play a unique role in reconfiguring this boundary by virtue of their training in biomedical sciences on the one hand and knowledge of CAM on the other. This study uses qualitative interviews to explore how CAM researchers perceive and negotiate challenges inherent in their work. Our analysis considers eight NIH-funded CAM researchers': (1) personal engagement with CAM, (2) social reactions towards perceived suspiciousness of research colleagues and (3) strategic methodological efforts to counteract perceived biases encountered during the peer review process. In response to peer suspicion, interviews showed CAM researchers adjusting their self-presentation style, highlighting their proximity to science, and carefully 'self-censoring' or reframing their unconventional beliefs. Because of what was experienced as peer reviewer bias, interviews showed CAM researchers making conciliatory efforts to adopt heightened methodological stringency. As CAM researchers navigate a broadening of biomedicine's boundaries, while still needing to maintain the identity and research methods of a biomedical scientist, this article explores the constant pressure on CAM researchers to appear and act a little more 'scientific'.

Nocebo Effects in Concussion: Is All That Is Told Beneficial?

Nocebo effects refer to new or worsening symptoms that develop in response to negative health-related information, beliefs, and/or experiences. In recent years, research on concussion pathophysiology has significantly advanced. Through health campaigns and media coverage, emerging knowledge on the risks of this injury has been quickly disseminated to the public, and nowadays, the public perceives concussions as more hazardous to health than ever before. Although advancements in concussion-related research and care are of great importance and value, we ask in this article whether the increasing negative publicity regarding concussion also carries any latent costs. Are additional nocebo effects being fostered? To do so, we will review the literature on the psychological and neurobiological processes underlying nocebo effects, present a series of clinical studies demonstrating the ways in which nocebos may impact concussion outcomes both clinically and societally, then speculate on further potential mechanisms for nocebo effects in concussion. We conclude with an outline of the specific efforts one may take to minimize nocebo effects in concussion-related care.

Outpatient Physical, Occupational, and Speech Therapy Synchronous Telemedicine: A Survey Study of Patient Satisfaction with Virtual Visits During the COVID-19 Pandemic.

The COVID-19 pandemic transformed health care delivery, including rapid expansion of telehealth. Telerehabilitation, defined as therapy provided by physical therapy, occupational therapy, and speech and language pathology, was rapidly adopted with goals to provide access to care and limit contagion. The purpose of this brief report was to describe the feasibility of and satisfaction with telerehabilitation. A total of 205 participants completed online surveys after a telerehabilitation visit. Most commonly, participants were women (53.7%), 35-64 yrs old, and completed physical therapy (53.7%) for established visits of 30-44 mins in duration for primary impairments in sports, lower limb injuries, and pediatric neurology. Overall, high ratings ("excellent" or "very good" responses) were observed for all patient-centered outcome metrics (range, 93.7%-99%) and value in future telehealth visit (86.8%) across telerehabilitation visits. Women participated more frequently and provided higher ratings than male participants did. Other benefits included eliminating travel time, incorporating other health care advocates, and convenience delivering care in familiar environment to pediatric patients. Technology and elements of hands-on aspects of care were observed limitations. Recognizing reduced indirect costs of care that telerehabilitation may provide along with high patient satisfaction are reasons policy makers should adopt these services into future health care delivery models.

A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect.

Previous studies suggest that nocebo effects, sometimes termed "negative placebo effects," can contribute appreciably to a variety of medical symptoms and adverse events in clinical trials and medical care. In this study, using a within-subject design, we combined functional magnetic resonance imaging (fMRI) and an expectation/conditioning manipulation model to investigate the neural substrates of nocebo hyperalgesia using heat pain on the right forearm. Thirteen subjects completed the study. Results showed that, after administering inert treatment, subjective pain intensity ratings increased significantly more on nocebo regions compared with the control regions in which no expectancy/conditioning manipulation was performed. fMRI analysis of hyperalgesic nocebo responses to identical calibrated noxious stimuli showed signal increases in brain regions including bilateral dorsal anterior cingulate cortex (ACC), insula, superior temporal gyrus; left frontal and parietal operculum, medial frontal gyrus, orbital prefrontal cortex, superior parietal lobule, and hippocampus; right claustrum/putamen, lateral prefrontal gyrus, and middle temporal gyrus. Functional connectivity analysis of spontaneous resting-state fMRI data from the same cohort of subjects showed a correlation between two seed regions (left frontal operculum and hippocampus) and pain network including bilateral insula, operculum, ACC, and left S1/M1. In conclusion, we found evidence that nocebo hyperalgesia may be predominantly produced through an affective-cognitive pain pathway (medial pain system), and the left hippocampus may play an important role in this process.

Expectancy and treatment interactions: a dissociation between acupuncture analgesia and expectancy evoked placebo analgesia.

Recent advances in placebo research have demonstrated the mind's power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects - including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) - interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture+high expectation and sham acupuncture+high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment).

An fMRI study on the interaction and dissociation between expectation of pain relief and acupuncture treatment.

It is well established that expectation can significantly modulate pain perception. In this study, we combined an expectancy manipulation model and fMRI to investigate how expectation can modulate acupuncture treatment. Forty-eight subjects completed the study. The analysis on two verum acupuncture groups with different expectancy levels indicates that expectancy can significantly influence acupuncture analgesia for experimental pain. Conditioning positive expectation can amplify acupuncture analgesia as detected by subjective pain sensory rating changes and objective fMRI signal changes in response to calibrated noxious stimuli. Diminished positive expectation appeared to inhibit acupuncture analgesia. This modulation effect is spatially specific, inducing analgesia exclusively in regions of the body where expectation is focused. Thus, expectation should be used as an important covariate in future studies evaluating acupuncture efficacy. In addition, we also observed dissociation between subjective reported analgesia and objective fMRI signal changes to calibrated pain in the analysis across all four groups. We hypothesize that as a peripheral-central modulation, acupuncture needle stimulation may inhibit incoming noxious stimuli; while as a top-down modulation, expectancy (placebo) may work through the emotional circuit.

Functional neuroanatomical investigation of vision-related acupuncture point specificity--a multisession fMRI study.

The concept that specific acupuncture points have salubrious effects on distant target organ systems is a salient feature of Traditional Chinese Medicine (TCM). In this study, we used a multiple-session experiment to test whether electroacupuncture stimulation at two TCM vision-related acupoints, UB 60 and GB 37, located on the leg, could produce fMRI signal changes in the occipital regions of the brain, and the specificity of this effect when compared with stimulation at an adjacent non-acupoint (NAP). Six normal, acupuncture naive subjects completed the study. Each subject participated in six identical scanning sessions. Voxelwise group analysis showed that electroacupuncture stimulation at both vision-related acupoints and the NAP produced modest, comparable fMRI signal decreases in the occipital cortex, including the bilateral cuneus, calcarine fissure and surrounding areas, lingual gyrus, and lateral occipital gyrus. Further analysis of fMRI signal changes in occipital cortex showed no significant difference among the three points, UB 60, GB 37, and NAP. Our results thus do not support the view that acupuncture stimulation at vision-related acupoints induces specific fMRI blood oxygen level dependent (BOLD) signal changes in the occipital cortex. We speculate that cross modal inhibition, produced by needling-evoked somatosensory stimulation, may account for our finding of BOLD signal decreases in the occipital cortex. Given the complexity of acupuncture systems and brain activity, additional work is required to determine whether functional neuroanatomical correlates of acupoint specificity can be validated by means of brain imaging tools.

Psychopharmacology of traumatic brain injury.

The pathophysiology of traumatic brain injury (TBI) can be highly variable, involving functional and/or structural damage to multiple neuroanatomical networks and neurotransmitter systems. This wide-ranging potential for physiologic injury is reflected in the diversity of neurobehavioral and neurocognitive symptoms following TBI. Here, we aim to provide a succinct, clinically relevant, up-to-date review on psychopharmacology for the most common sequelae of TBI in the postacute to chronic period. Specifically, treatment for neurobehavioral symptoms (depression, mania, anxiety, agitation/irritability, psychosis, pseudobulbar affect, and apathy) and neurocognitive symptoms (processing speed, attention, memory, executive dysfunction) will be discussed. Treatment recommendations will reflect general clinical practice patterns and the research literature.