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.

Reproducibility of 19 F-MR ventilation imaging in healthy volunteers.

PURPOSE: To assess the reproducibility of percentage ventilated lung volume (%VV) measurements in healthy volunteers acquired by fluorine (19 F)-MRI of inhaled perfluoropropane, implemented at two research sites. METHODS: In this prospective, ethically approved study, 40 healthy participants were recruited (May 2018-June 2019) to one of two research sites. Participants underwent a single MRI scan session on a 3T scanner, involving periodic inhalation of a 79% perfluoropropane/21% oxygen gas mixture. Each gas inhalation session lasted about 30 seconds, consisting of three deep breaths of gas followed by a breath-hold. Four 19 F-MR ventilation images were acquired per participant, each separated by approximately 6 minutes. The value of %VV was determined by registering separately acquired 1 H images to ventilation images before semi-automated image segmentation, performed independently by two observers. Reproducibility of %VV measurements was assessed by components of variance, intraclass correlation coefficients, coefficients of variation (CoV), and the Dice similarity coefficient. RESULTS: The MRI scans were well tolerated throughout, with no adverse events. There was a high degree of consistency in %VV measurements for each participant (CoVobserver1 = 0.43%; CoVobserver2 = 0.63%), with overall precision of %VV measurements determined to be within ± 1.7% (95% confidence interval). Interobserver agreement in %VV measurements revealed a high mean Dice similarity coefficient (SD) of 0.97 (0.02), with only minor discrepancies between observers. CONCLUSION: We demonstrate good reproducibility of %VV measurements in a group of healthy participants using 19 F-MRI of inhaled perfluoropropane. Our methods have been successfully implemented across two different study sites, supporting the feasibility of performing larger multicenter clinical studies.

Dynamic susceptibility contrast 19 F-MRI of inhaled perfluoropropane: a novel approach to combined pulmonary ventilation and perfusion imaging.

PURPOSE: To assess alveolar perfusion by applying dynamic susceptibility contrast MRI to 19 F-MRI of inhaled perfluoropropane (PFP). We hypothesized that passage of gadolinium-based contrast agent (GBCA) through the pulmonary microvasculature would reduce magnetic susceptibility differences between water and gas components of the lung, elevating the T2∗ of PFP. METHODS: Lung-representative phantoms were constructed of aqueous PFP-filled foams to characterize the impact of aqueous/gas phase magnetic susceptibility differences on PFP T2∗ . Aqueous phase magnetic susceptibility was modulated by addition of different concentrations of GBCA. In vivo studies were performed to measure the impact of intravenously administered GBCA on the T2∗ of inhaled PFP in mice (7.0 Tesla) and in healthy volunteers (3.0 Tesla). RESULTS: Perfluoropropane T2∗ was sensitive to modulation of magnetic susceptibility difference between gas and water components of the lung, both in phantom models and in vivo. Negation of aqueous/gas phase magnetic susceptibility difference was achieved in lung-representative phantoms and in mice, resulting in a ~2 to 3× elevation in PFP T2∗ (3.7 to 8.5 ms and 0.7 to 2.6 ms, respectively). Human studies demonstrated a transient elevation of inhaled PFP T2∗ (1.50 to 1.64 ms) during passage of GBCA bolus through the lung circulation, demonstrating sensitivity to lung perfusion. CONCLUSION: We demonstrate indirect detection of a GBCA in the pulmonary microvasculature via changes to the T2∗ of gas phase PFP within directly adjacent alveoli. This approach holds potential for assessing alveolar perfusion by dynamic susceptibility contrast 19 F-MRI of inhaled PFP, with concurrent assessment of lung ventilation properties, relevant to lung physiology and disease.

Optimized and accelerated 19 F-MRI of inhaled perfluoropropane to assess regional pulmonary ventilation.

PURPOSE: To accelerate 19 F-MR imaging of inhaled perfluoropropane using compressed sensing methods, and to optimize critical scan acquisition parameters for assessment of lung ventilation properties. METHODS: Simulations were performed to determine optimal acquisition parameters for maximal perfluoropropane signal-to-noise ratio (SNR) in human lungs for a spoiled gradient echo sequence. Optimized parameters were subsequently employed for 19 F-MRI of inhaled perfluoropropane in a cohort of 11 healthy participants using a 3.0 T scanner. The impact of 1.8×, 2.4×, and 3.0× undersampling ratios on 19 F-MRI acquisitions was evaluated, using both retrospective and prospective compressed sensing methods. RESULTS: 3D spoiled gradient echo 19 F-MR ventilation images were acquired at 1-cm isotropic resolution within a single breath hold. Mean SNR was 11.7 ± 4.1 for scans acquired within a single breath hold (duration = 18 s). Acquisition of 19 F-MRI scans at shorter scan durations (4.5 s) was also demonstrated as feasible. Application of both retrospective (n = 8) and prospective (n = 3) compressed sensing methods demonstrated that 1.8× acceleration had negligible impact on qualitative image appearance, with no statistically significant change in measured lung ventilated volume. Acceleration factors of 2.4× and 3.0× resulted in increasing differences between fully sampled and undersampled datasets. CONCLUSION: This study demonstrates methods for determining optimal acquisition parameters for 19 F-MRI of inhaled perfluoropropane and shows significant reduction in scan acquisition times (and thus participant breath hold duration) by use of compressed sensing.

Human brain 7Li-MRI following low-dose lithium dietary supplementation in healthy participants.

BACKGROUND: Lithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (7Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose. METHODS: Lithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2-7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional 7Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout. RESULTS: 7Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher 7Li-signal intensities (approximately 2-4×) compared to other study participants. LIMITATIONS: Lithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of 7Li exhibits imperfect spatial separation of signal from adjacent pixels. CONCLUSIONS: 7Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10-60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field.

Emerging Subspecialties in Neurology: Women's Neurology.

The influence of sex and gender on neurologic disease has become increasingly recognized in science and medicine. This is evident across a woman's lifespan especially during periods of hormonal transitions. Leaders in neurology have advocated for the importance of sex and gender-enriched clinical care, education, and research. The scope of women's neurology spans across a woman's life including puberty, adolescence, peripartum care, menopause, and aging. Women's neurology is a new subspecialty that aligns with a specific patient population and intersects with established neurology subspecialties and other specialties such as obstetrics, maternal fetal medicine, endocrinology, and psychiatry. Its establishment and collaboration with existing and emerging fields enables a more comprehensive approach to neurologic illness through the lens of sex and gender. Women's neurology is rapidly evolving through increased focus at academic centers, including expanded women's neurology curricula, dedicated women's neurology fellowship programs, improved understanding of sex and gender issues in neurosciences, and expansion of therapeutic options. Herein, we describe the history of the women's neurology field, emerging need for women's neurology specialists, information about training and career opportunities, and future directions.

Women and the risk of Alzheimer's disease.

Purpose of the review: This review will elucidate reasons to explain why women may be at greater risk for Alzheimer's disease. Recent findings: Potential mechanisms to explain sex and gender differences in Alzheimer dementia include: differences in risk associated with the apolipoprotein E 4 allele; telomere shortening- which is linked with neurodegeneration, higher incidence of depression and insomnia in women as psychiatric co-morbidities which are linked with an increased Alzheimer disease risk, disorders of pregnancy including gestational hypertension and preeclampsia and psychosocial factors such as educational level which may contribute to differences in cognitive reserve. Summary: The sex and gender differences in Alzheimer's disease can be explained by biological and psychosocial factors.

Opinion and Special Article: The Need for Specialized Training in Women's Neurology.

Women's Neurology is an emerging subspecialty that focuses on neurologic disorders across a woman's lifetime. This new domain recognizes that both health and disease are directly affected by hormonal and reproductive changes throughout the life span. This field includes neurologic diseases with a higher prevalence in women and diseases that require specialized management during pregnancy, postpartum period, lactation, and menopause. A survey was sent to US neurology residency program directors to understand the state of training in the area. Their responses highlighted an urgent need for additional education in this field for neurology residents. In this study, we discuss the educational gaps in this area, the clinical benefits of a women's neurology discipline, and the instructional gaps in this area and provide practical recommendations for training programs in women's neurology using 2 innovative fellowship programs.

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 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.

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.

Integrating Advanced Practice Providers in an Academic Department of Neurology.

BACKGROUND AND OBJECTIVES: Integrating advanced practice providers (APPs) into neurologic practice can improve access, promote patient education, and reduce health care costs. APPs receive limited formal education in neurology, so on-the-job training is essential. We set out to identify common challenges and best practices for onboarding, training, and integrating APPs into neurologic practice. METHODS: We conducted a survey and focus group with 8 APPs currently practicing within an academic neurology department as part of a clinical quality improvement initiative. We explored their roles in multidisciplinary teams, challenges faced during onboarding and training, and strategies for success. Qualitative thematic analysis was performed. RESULTS: Neurology APPs serve diverse roles including caring for hospitalized and ambulatory patients, performing procedures, assisting trainees, and performing research. Participants reported limited formal neurologic education before their job and a need for educational sessions and resources tailored to APPs. Neuroanatomy, neuroimaging, and generating a neurologic differential diagnosis were key knowledge gaps identified. We identified 7 informal strategies for on-the-job training, 7 challenges to on-the-job training, and factors promoting or threatening job satisfaction. Graded responsibility and clinical mentorship were essential for successful onboarding. APPs desired peer-to-peer mentorship and structured educational opportunities. DISCUSSION: Common challenges and success strategies identified can inform the design of a formal curriculum for onboarding neurology APPs. Our findings suggest that an optimal APP training process involves graded responsibility and support for self-directed learning, employs peer mentors, and targets education of the multidisciplinary team including physicians and patients. Our results may inform other institutions recruiting, hiring, and training APPs.

Effects of Fragmentation and the Case for Greater Cohesion in Neurologic Care Delivery.

GOALS: To define fragmentation in neurological care delivery; explain the positive and negative drivers in neurologic practice that contribute to fragmentation; illustrate situations that increase fragmentation risk; emphasize the costs and impact on both patients and providers; propose solutions that allow for more cohesive care. WORK GROUP: The Transforming Leaders Program (TLP) class of 2020 was tasked by American Academy of Neurology (AAN) leadership to identify the leading trends in inpatient and outpatient neurology and to predict their effects on future neurologic practice. METHODS: Research material included AAN data bases, PubMed searches, discussion with topic experts and AAN leadership. RESULTS: Trends in care delivery are driven by changes in the work force, shifts in health care delivery, care costs, changes in evidence-based care and patient factors. These trends can contribute to care fragmentation. Potential solutions to these problems are proposed based on care models developed in oncology and medicine. LIMITATIONS: This paper shares our opinions as there is a lack of evidence-based guidelines as to optimal neurological care delivery.

Neurologic complications of medical conditions in pregnancy.

This chapter discusses some of the neurologic complications of medical diseases that may occur in pregnancy. It reviews both the effects of pregnancy on the underlying disorder and how the medical condition may influence pregnancy outcomes. The most up-to-date information about risk stratification and disease management is presented. The specific disorders reviewed include sickle cell disease, antiphospholipid antibody syndrome, cardiac valve diseases, HIV infection, systemic lupus erythematosus, and fibromuscular dysplasia.

Migraine and menopause - a narrative review.

IMPORTANCE AND OBJECTIVES: This narrative review addresses common clinical questions and concerns of both physicians and patients about migraine during and after the perimenopausal transition, specifically (1) How does the perimenopausal transition affect migraine prevalence and does this vary by migraine type? (2) Does the magnitude of stroke risk associated with migraine increase with hormone therapy (HT)?, and (3) What are best practices as regards migraine treatment in perimenopausal women? METHODS: We searched PubMed from 2010 through the present. Search terms included migraine, menopause, and HT. Articles were included if they were in English and had full text availability. In addition, key references identified in the search articles were included. DISCUSSION AND CONCLUSION: Many women are informed that their migraines will disappear postmenopause; there are some data to support this, but a specific time frame has not been evidenced. Stroke risk in women with migraine with aura is small in absolute terms, but important at the population level, because migraine is so prevalent. The risk becomes clinically important in the context of additional stroke risk factors, which increase with aging such as hypertension. Estrogen in combined hormonal contraception increases the risk of an ischemic stroke, however, the lower amount of estrogen in HT may not contribute to a meaningful increase in stroke risk. HT is a preventative sex-specific treatment for female migraineurs for the menopausal transition. Sex differences for other conventional treatments outside their use in menstrual and menstrually related migraine have not been studied specifically in the menopausal transition.

Video Summary:http://links.lww.com/MENO/A636.

Caring for Patients With Functional Neurological Disorders: A Case-oriented Review.

Patients with functional neurological symptoms are commonly seen in neurological practice. They have significant disability that may not improve and their care is costly. This article will use case histories to underline the important aspects of caring for patients with functional neurological disorders, including important features of the history, examination, neurobiology, appropriate investigations, and an approach to treatment.