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.

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.

How Sex Hormones Affect Migraine: An Interdisciplinary Preclinical Research Panel Review.

Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing. A panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin. Notably, other hormones, such as progesterone, testosterone, and vasopressin, are less well studied but are also highlighted in this review. When discussing what new therapeutic agent might be an alternative to hormone therapy and menopause replacement therapy for migraine treatment, the panel pointed to oxytocin delivered as a nasal spray. Overall, the conclusion was that progress in the preclinical study of hormones on the nervous system has been challenging and slow, that there remain substantial gaps in our understanding of the complex roles sex hormones play in migraine, and that opportunities remain for improved or novel therapeutic agents. Manipulation of sex hormones, perhaps through biochemical modifications where its positive effects are selected for and side effects are minimized, remains a theoretical goal, one that might have an impact on migraine disease and other symptoms of menopause. This review is a call to action for increased interest and funding for preclinical research on sex hormones, their metabolites, and their receptors. Interdisciplinary research, perhaps facilitated by a collaborative communication network or panel, is a possible strategy to achieve this goal.

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.

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.

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.

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.

Fluorine labelling of therapeutic human tolerogenic dendritic cells for 19F-magnetic resonance imaging.

Tolerogenic dendritic cell (tolDC) therapies aim to restore self-tolerance in patients suffering from autoimmune diseases. Phase 1 clinical trials with tolDC have shown the feasibility and safety of this approach, but have also highlighted a lack of understanding of their distribution in vivo. Fluorine-19 magnetic resonance imaging (19F-MRI) promises an attractive cell tracking method because it allows for detection of 19F-labelled cells in a non-invasive and longitudinal manner. Here, we tested the suitability of nanoparticles containing 19F (19F-NP) for labelling of therapeutic human tolDC for detection by 19F-MRI. We found that tolDC readily endocytosed 19F-NP with acceptable effects on cell viability and yield. The MRI signal-to-noise ratios obtained are more than sufficient for detection of the administered tolDC dose (10 million cells) at the injection site in vivo, depending on the tissue depth and the rate of cell dispersal. Importantly, 19F-NP labelling did not revert tolDC into immunogenic DC, as confirmed by their low expression of typical mature DC surface markers (CD83, CD86), low secretion of pro-inflammatory IL-12p70, and low capacity to induce IFN-γ in allogeneic CD4+ T cells. In addition, the capacity of tolDC to secrete anti-inflammatory IL-10 was not diminished by 19F-NP labelling. We conclude that 19F-NP is a suitable imaging agent for tolDC. With currently available technologies, this imaging approach does not yet approach the sensitivity required to detect small numbers of migrating cells, but could have important utility for determining the accuracy of injecting tolDC into the desired target tissue and their efflux rate.

Preventive Approaches in Women's Neurology: Prepartum, Pregnancy, and Postpartum.

Women's neurology is the subspecialty within neurology concerned with the distinct healthcare needs of women. In this article, we review current literature and expert management strategies regarding disease-specific neurologic concerns of women, with an emphasis on issues related to contraception, pregnancy, and lactation. Health conditions that we discuss in this article include epilepsy, headache, stroke, multiple sclerosis, and Chiari I malformation. Current findings on neurologic disease in women suggest that many women with neurologic disease can safely manage their disease during pregnancy and have healthy children, though pregnancy planning is important in many conditions to mitigate risks and effective contraceptive management is important when pregnancy prevention is desired.

UK pharmacists' experiences and perceptions of conflict between personal ethical commitments and professional obligations, as set out in professional guidance.

BACKGROUND: In 2017, the General Pharmaceutical Council (UK) issued new Standards for Pharmacy Professionals and supporting guidance, Guidance on Religion, Personal Values and Beliefs, to help pharmacists when their religion, personal values or beliefs might impact on their provision of services. OBJECTIVE: To understand how pharmacists in the UK experience and perceive conflicts between their personal ethical commitments (matters of conscience) and professional obligations in guidance from their regulator. METHODS: Twenty-four registered pharmacists were interviewed using semi-structured interviews. Interviews were transcribed verbatim and analysed using thematic analysis. KEY FINDINGS: Participants were generally aware of the Council's consultations and responded if they had something to say, or it was their role to respond. Age and stage, confidence, and workload impacted on whether participants responded to Council consultations, and, therefore, on the range of views heard. The professional obligation to provide person-centred care (PCC) was central to participants' practice, and personal ethical commitments were important to some. Conflicts between such commitments and professional obligations were rare, and it was generally believed that the former should be accommodated, as far as possible, but not imposed on others. Personal ethical commitments could affect PCC, and some suggested that the Council's Guidance was not clear on pharmacists' responsibilities in this regard. CONCLUSIONS: Clarification on the role of personal ethical commitments in professional practice, particularly in relation to providing PCC, would be useful. Clearer guidance on how pharmacists should manage perceived conflicts between their personal ethical commitments and their professional obligations would also be welcomed.

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.

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.

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.

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.

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.

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.