Neurologic Manifestations of Long COVID Differ Based on Acute COVID-19 Severity.

OBJECTIVE: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients. METHODS: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021. RESULTS: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were "brain fog" (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients. INTERPRETATION: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146-159.

Updates in Functional Movement Disorders: from Pathophysiology to Treatment Advances.

PURPOSE OF REVIEW: This review discusses advances in functional movement disorders (FMD) over the past 3 years, with a focus on risk factors, diagnosis, pathophysiology, neuroimaging studies, and treatment. RECENT FINDINGS: The past decade has brought a revived interest in functional movement disorders, with a growing number of studies exploring pathophysiological mechanisms. Here, we review recent studies demonstrating changes in attention, emotional and sensorimotor function in FMD. Through international collaborative efforts, progress has been made in defining biomarkers and outcome measures, an important prerequisite towards standardization of diagnosis and reporting of outcomes in clinical trials. Of particular interest are neuroimaging studies demonstrating functional and structural changes in motor and emotional brain circuits, deepening our understanding of FMD as a neurocircuit disorder and potentially paving the way towards new treatments. Currently available treatment modalities have shown successful outcomes via outpatient, inpatient, and virtual delivery. The last 3 years have seen tremendous efforts to better understand, diagnose, and treat FMD. The disease model has been broadened to include a biopsychosocial formulation, and insights on the pathophysiology on FMD are informing treatment efforts. Several international multidisciplinary research collaborations are underway to define biomarkers and best outcome measures, highlighting the path towards improved standardization of future treatment trials. Additionally, the rise of telemedicine during the COVID-19 pandemic has reduced geographic barriers and paved the way for virtual therapy sessions and self-guided programs.

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.

Functional movement disorder and functional seizures: What have we learned from different subtypes of functional neurological disorders?

The objective of this paper is to compare and contrast FMD and FS, and highlight important differences in etiology and the clinical approach towards these two entities. While patients with FMD often experience abnormal movements on a daily basis, FS is characterized by paroxysmal events. Both patient populations share psychiatric and environmental comorbidities, but patients with FS may have increased anxiety and neuroticism and a higher percentage of childhood trauma. Functional MRI scans have demonstrated impaired executive control over motor behavior in both groups. FMD responds well to multidisciplinary rehabilitation-oriented treatment, while psychotherapy remains the mainstay of treatment for FS. For practicing clinicians, recognizing commonalities and differences in patients with FMD and FS is important to develop the most appropriate treatment plan.

Gender disparity and abuse in functional movement disorders: a multi-center case-control study.

BACKGROUND: To determine gender differences in rates of sexual and physical abuse in functional movement disorders compared to controls and evaluate if the gender disparity of functional movement disorders is associated with abuse history. METHODS: We performed a retrospective case-control study of self-reported trauma data from 696 patients (512 women) with functional movement disorders from six clinical sites compared to 141 controls (98 women) and population data. Chi-square was used to assess gender and disorder associations; logistic regression was used to model additive effects of abuse and calculate the attributable fraction of abuse to disorder prevalence. RESULTS: Higher rates of sexual abuse were reported by women (35.3%) and men (11.5%) with functional movement disorders compared to controls (10.6% of women; 5.6% of men). History of sexual abuse increased the likelihood of functional movement disorders among women by an odds ratio of 4.57 (95% confidence interval 2.31-9.07; p < 0.0001) and physical abuse by an odds ratio of 2.80 (95% confidence interval 1.53-5.12; p = 0.0007). Population attributable fraction of childhood sexual abuse to functional movement disorders in women was 0.12 (0.05-0.19). No statistically significant associations were found in men, but our cohort of men was underpowered despite including multiple sites. CONCLUSIONS: Our study suggests that violence against women may account for some of the gender disparity in rates of functional movement disorders. Most people with functional movement disorders do not report a history of abuse, so it remains just one among many relevant risk factors to consider.

Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda.

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using "rule-in" examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

Pelvic Floor Health in Women with Parkinson's Disease.

BACKGROUND: Urinary dysfunction and constipation, manifestations of pelvic floor dysfunction are common sources of disability and impaired quality of life in women with Parkinson's disease (PD). OBJECTIVE: We sought to evaluate the pelvic floor health amongst women with PD and their reporting of bladder and bowel symptoms. METHODS: We surveyed women with PD and age-matched controls about pelvic floor health using validated questionnaires. All participants completed the Pelvic Floor Disability Index (PFDI-20), the Pelvic Floor Impact Questionnaire (PFIQ-7) and the Patient-Reported Outcomes Measurement Information System (PROMIS) short form version 2.0 Cognitive Function 8a. Additionally, PD patients underwent the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scale and the Montreal Cognition Assessment (MoCA). RESULTS: Women with PD (n = 59; age, 70.4±8.6 years, PROMIS cognitive score, 52.0±7.8) self-reported urinary symptoms to a greater extent than controls (n = 59; age, 70.2±8.7 years, PROMIS cognitive score, 51.0±10) (68% vs 43%, p < 0.01). The difference was mirrored by higher (worse) scores on both PFDI-20 (35.4 vs 15.6; p = 0.01) and PFIQ-7 (4.8 vs 0; p < 0.01) for PD women compared to controls. Only 63% of all participants with self-reported pelvic floor symptoms had previously reported these symptoms to a health care provider. There was no difference in utilization of specialty care between the two groups (30% vs 46%, p = 0.2). CONCLUSION: Pelvic floor dysfunction, more common amongst women with PD, is underreported and undertreated. Our study identifies a key gap in care of women with PD.

Treatment of functional neurological disorder: current state, future directions, and a research agenda.

Functional neurological disorder (FND) encompasses a complex and heterogeneous group of neuropsychiatric syndromes commonly encountered in clinical practice. Patients with FND may present with a myriad of neurological symptoms and frequently have comorbid medical, neurological, and psychiatric disorders. Over the past decade, important advances have been made in understanding the pathophysiology of FND within a biopsychosocial framework. Many challenges remain in addressing the stigma associated with this diagnosis, refining diagnostic criteria, and providing access to evidence-based treatments. This paper outlines FND treatment approaches, emphasizing the importance of respectful communication and comprehensive explanation of the diagnosis to patients, as critical first step to enhance engagement, adherence, self-agency, and treatment outcomes. We then focus on a brief review of evidence-based treatments for psychogenic non-epileptic seizures and functional movement disorder, a guide for designing future treatment trials for FND, and a proposal for a treatment research agenda, in order to aid in advancing the field to develop and implement treatments for patients with FND.

Initial experiences of US neurologists in practice during the COVID-19 pandemic via survey.

OBJECTIVE: To test the hypothesis that US neurologists were experiencing significant challenges with lack of personal protective equipment (PPE), rapid changes in practice, and varying institutional protocols, we conducted this survey study. The current coronavirus disease of 2019 (COVID-19) pandemic has caused widespread disease and death. Rapid increases in patient volumes have exposed weaknesses in health care systems and challenged our ability to provide optimal patient care and adequate safety measures to health care workers (HCWs). METHODS: A 36-item survey was distributed to neurologists around the United States through various media platforms. RESULTS: Over a 1-week period, 567 responses were received. Of these, 56% practiced in academia. A total of 87% had access to PPE, with 45% being asked to reuse PPE due to shortages. The pandemic caused rapid changes in practice, most notably a shift toward providing care by teleneurology, although a third experienced challenges in transitioning to this model. Wide variations were noted both in testing and in the guidance provided for the exposed, sick, or vulnerable HCWs. Notably, 59% of respondents felt that their practices were doing what they could, although 56% did not feel safe taking care of patients. CONCLUSIONS: Results from our survey demonstrate significant variability in preparedness and responsiveness to the COVID-19 pandemic in neurology, affected by region, health care setting, and practice model. Practice guidelines from professional societies and other national entities are needed to improve protection for physicians and their patients, promote recommended practice changes during a pandemic, and optimize future preparedness for public health emergencies.

Treatment of Functional Movement Disorders.

Functional movement disorders (FMD) are commonly seen in neurologic practice and frequent sources of disability. Patients may present with tremor, weakness, dystonia, jerking movements, abnormal gait and speech, often combining several movement phenomenologies. Associated symptoms include chronic pain, depression, and anxiety. Treatment of FMD begins with an explanation of the diagnosis and needs to be tailored to patients' symptoms and comorbidities. There may be benefit from multidisciplinary treatment, including physical, occupational, and speech therapy, as well as psychotherapeutic interventions, especially cognitive behavior therapy. The role for neuromodulation such as transmagnetic stimulation in FMD treatment requires further research.

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.

Gender as a Risk Factor for Functional Movement Disorders: The Role of Sexual Abuse.

BACKGROUND: The prevalence of functional movement disorders is 2 to 3 times higher in women than in men. Trauma and adverse life events are important risk factors for developing functional movement disorders. On a population level, rates of sexual abuse against women are higher when compared with the rates against men. OBJECTIVES: To determine gender differences in rates of sexual abuse in functional movement disorders compared with other neurologic disorders and evaluate if the gender prevalence is influenced by higher rates of sexual abuse against women. METHODS: We performed a case-control series including 199 patients with functional movement disorders (149 women) and 95 controls (60 women). We employed chi-squared test to assess gender and sexual abuse associations and Bayes formula to condition on sexual abuse. RESULTS: Our analysis showed an association between sexual abuse and functional movement disorders in women (odds ratio, 4.821; 95% confidence interval, 2.089-12.070; P < 0.0001), but not men. Bayesian analysis found the functional movement disorder prevalence ratio between women and men conditional on sexual abuse to be 4.87 times the unconditioned ratio. CONCLUSIONS: There is a statistically significant association between sexual abuse and functional movement disorders in women and a greater likelihood that women who are sexually abused will develop functional movement disorders than men who are sexually abused. Our findings suggest that the increased prevalence of functional movement disorders in women is associated, at least in part, with sexual abuse and its sequelae; however, further research is needed to explore the role of other traumatic and nontraumatic factors.

Internal Versus External Frame of Reference in Functional Movement Disorders.

OBJECTIVE: The purpose of this study was to determine whether patients with functional movement disorders (FMDs) differ in their internal versus external locus of control (LOC) and whether LOC in these patients affected disease severity, quality of life, and functional impairment compared with control subjects with degenerative (Parkinson's disease) and nondegenerative (focal dystonia) neurological conditions. METHODS: A total of 156 patients with FMD (N=45), Parkinson's disease (N=64), and focal dystonia (N=47) were recruited between June 2015 and August 2017. The authors administered the general Levenson Multidimensional LOC (LOC-G) and health-specific Multidimensional Health LOC (LOC-H) scales. An internal LOC was represented similarly in both scales: the external LOC included "chance" and "powerful others" in the LOC-G measure and chance, "other people," and "doctors" in the LOC-H measure. Quality of life, functional impairment, and FMD severity were assessed. One-way analysis of variance and adjusted logistic regressions were used, as well as ordinary least-squares between and within groups, respectively. RESULTS: Patients with FMD had lower external chance LOC-G scores compared with patients in the Parkinson's disease group (odds ratio=0.90, p=0.03) and higher internal (odds ratio=1.22, p=0.01) and lower external (odds ratio=0.77, p=0.02) doctors LOC-H scores compared with patients in the focal dystonia group. External powerful others LOC-G score was associated with functional impairment (regression coefficient=-0.04, p=0.02). There were no effects of LOC on quality of life or disease severity. CONCLUSIONS: Patients with FMD exhibited high "within our control" internal general and health-specific frame of reference. LOC had no influence on quality of life or disease severity in this patient population.

Impaired Action Control in Patients With Functional Movement Disorders.

OBJECTIVE: Despite being a major cause of neurological disability, the neural mechanisms of functional movement disorders (FMDs) remain poorly understood. Recent studies suggest that FMD is linked to dysfunctional motor and prefrontal regions that could lead to motor and cognitive impairments. The aim of this study was to investigate different components of action control in FMD by using choice-reaction, stop-signal, and Simon tasks. METHODS: Thirty patients with an FMD were prospectively recruited from the University of Louisville Movement Disorders Clinic and compared with 53 healthy control subjects, recruited from the Vanderbilt University Medical Center Movement Disorders Clinic. FMD motor symptom severity was rated with the Simplified Functional Movement Disorder Rating Scale (S-FMDRS). By using a computer and handheld response grips, participants completed three action-control tasks (choice-reaction task, stop-signal task, and Simon task) that tested action initiation, action cancelation, and interference control over actions. Action-control measures were compared between groups with analyses of variance. RESULTS: Patients with FMD were less proficient in suppressing incorrect response impulses on the Simon task and were slower to stop on the stop-signal task compared with healthy control subjects. No significant correlation with neuropsychological measurements, S-FMDRS scores, and action-control measurements was observed. CONCLUSIONS: These results suggest that two forms of inhibitory control, selective impulse inhibition and global action cancelation, are impaired in patients with FMD, independent of slowing on go reaction times. Improved understanding of action control in FMD may help in the development of new diagnostic and therapeutic strategies.

Experiential Learning: Transforming Theory into Practice through the Parkinson's Disease Buddy Program.

Problem: Persons over age 65 constitute a large proportion of patients presenting for healthcare services; therefore, physicians must be prepared to provide care to patients that face degenerative neurological diseases. Medical students can have difficulty identifying and caring for older patients with neurological difficulties, and often perceive neurology to be a challenging specialty. Medical education service-learning programming that engages community members and medical students, while fostering specialized neurology training, may help improve care for this patient population. Intervention: We developed the Parkinson's Disease Buddy Program for first year medical students (M1s), which involved pairing students with patients with Parkinson's disease (PD) to engage in a social relationship. Students attended monthly seminars covering a range of topics specific to PD patient care and met with their PD buddies throughout the year. A mixed-methods approach was used to evaluate the program and involved pre/post assessments, as well as focus groups with both students and patients. Context: The University of Louisville's School of Medicine and College of Education implemented this volunteer service-learning program for students by partnering with a locally based nonprofit, dedicated to serving PD patients. A total of 70 (35 M1s and 35 PD patients) participated. Outcome: Students' total correct PD knowledge scores significantly increased after participation with a large effect size (pre-test mean = 14.77, [SD = 2.57]; post-test mean = 19.69 [SD = 2.06], Cohen's d = 1.64) and a paired t-test indicated a significant change in students' Parkinson's Attitude Scale scores (t (34) = 2.22, p < .05). Ninety-one percent of students (31) indicated they would recommend the program and 82% (29) indicated they would participate again. During focus groups, students reflected on the relationships they formed with their buddies, indicating the program provided a support system while helping them learn about PD. Patients indicated the program expanded their social circle and meetings with M1s were beneficial. Lessons Learned: An experiential learning opportunity can help medical students become better acquainted with patients living with a neurological disease. We identified an impact on PD patients' self-efficacy and social behavior that was not originally expected. We learned the importance of incorporating active learning modalities such as PD buddy panels and peer-to peer group discussions. The resources required to implement programs like ours can be lightened by engaging with local community partners and collaborating within and outside departments.

Smell status in functional movement disorders: New clues for diagnosis and underlying mechanisms.

OBJECTIVE: Functional movement disorders (FMDs) mimic a range of movements, neuropsychiatric and neurodegenerative disorders known to have smell dysfunction, which has been neglected in terms of its application to FMD. We aim to determine the smell status in FMD patients tested by a non-invasive, reliable and validated olfactory test. PATIENTS AND METHODS: We quantitatively assessed in thirty-five FMD patients their smell status and compared it to that of healthy age- and sex-matched controls, and of patients with Parkinson's disease (PD). All participants were administered the Brief Smell Identification Test (B-SIT), a standardized short version of the University of Pennsylvania Smell Identification Test (UPSIT). The Picture Identification Test (PIT), a visual test analogous in content and form to the UPSIT designed to control for non-olfactory cognitive confounds, was also administered. RESULTS: The B-SIT scores of the FMD patients were higher than those from PD patients [respective means (standard deviations: SDs) = FMD, 9.54 (1.57); PD, 4.64 (1.05), p < 0.01)] but similar to the smell scores from healthy controls [9.97 (1.77), p = 0.35]. Gender, age, time of disease onset, smoking status, and phenotypic expression did not influence the test scores. Fourteen FMD patients who mentioned having olfactory dysfunction before smell testing have their test results within normal range. PIT scores from patients and healthy controls were within normal range. CONCLUSIONS: These findings indicate that FMD patients have normal olfactory function. Olfactory testing may be helpful in identifying and differentiating FMD from other movement, neurodegenerative and neuropsychiatric diseases for which smell function is altered.

Burnout and Career Satisfaction in Women Neurologists in the United States.

BACKGROUND: Professional burnout is a growing problem among physicians. Neurology has been found to be one of the specialties with the highest prevalence for burnout. However, little is known about gender-specific risk factors. The objectives of this study were (1) to determine the prevalence of burnout among a sample of women neurologists in the United States and (2) to identify predictive factors leading to burnout. MATERIALS AND METHODS: An online survey was distributed to 798 U.S. women neurologists through the closed Facebook group Women Neurologists Group. Burnout was assessed with the Mini-Z survey. Additional questions assessed current practice settings, family and childcare responsibilities, work-life balance, gender discrimination experiences, career satisfaction, and plans for career changes. RESULTS: The survey received 181 responses, yielding a 22.7% response rate. Most respondents were 1-10 years post-training and 35.4% indicated they felt neutral or dissatisfied toward their current job; 42.6% of respondents reported symptoms of burnout. Working in a high stress environment, lack of control over the work schedule, a higher number of hours at work, and self-reported gender discrimination were each independent predictive factors for burnout. Having more children was associated with decreased likelihood of becoming a physician again, and less than a third of respondents with three or more children indicated they would become a physician again. While 91.1% of respondents considered themselves effective with electronic health record use, 56.9% indicated insufficient time for documentation. CONCLUSIONS: Professional burnout and career dissatisfaction have high prevalence in women neurologists and threaten the future of the neurology workforce. There is an urgent need for interventions to alleviate stressors associated with burnout and measures to reduce gender discrimination.