Real-world practices in reproductive health and counselling for women with epilepsy: A Canadian perspective.

Canadian women of reproductive potential living with epilepsy present unique care challenges due to the complex interplay of hormones, seizures, and medications. This study explores reproductive health practices and counselling for women with epilepsy. Through a questionnaire developed by the Canadian League Against Epilepsy women with epilepsy (WWE) workgroup, we are the first to report demographic and real-world practice characteristics of Canadian healthcare professionals providing care for WWE with specific focus on family planning, birth plans, and postpartum care counselling. Among respondents, 76.9% routinely reviewed contraception with patients and an intrauterine device (IUD) was the most popular recommended method (85.3%). With regards to preconception planning, 50% of respondents routinely had a preconception drug level prior to pregnancy. A significant proportion, 44.9%, reported not communicating a neurology-informed birth plan to obstetrical health practitioners. The majority recommended breastfeeding for WWE on anti-seizure medications (92.3%) and regularly provided safety counselling for women in the postpartum period (84.6%). Overall, our study demonstrates that Canadian practice patterns conform reasonably well to existing evidence and guidelines, although important gaps in care exist.

Real-world practices for the care of women with epilepsy during pregnancy: A Canadian perspective.

OBJECTIVE: Approximately 150,000 Canadian women live with epilepsy, a population that presents with unique challenges. Our objective was to capture demographic and real-world practice characteristics of Canadian healthcare professionals providing care for women with epilepsy (WWE) with specific focus on reproductive considerations to identify potential gaps in knowledge and care. METHODS: A questionnaire developed by the Canadian League Against Epilepsy WWE workgroup was distributed to Canadian healthcare professionals from February 2021 to October 2022 to capture participant demographic characteristics and practice patterns in key areas of the reproductive cycle in WWE. RESULTS: A total of 156 participants completed the questionnaire, most being physicians (81.4%), epilepsy specialists (69.0%), and those who cared for adult patients (86.5%), with a significant proportion based at an academic center (65.4%). The majority of participants counselled on folic acid supplementation (89.7%). Participants selected lamotrigine and levetiracetam most frequently for either focal or generalized epilepsies during pregnancy. Additionally, 85.9% performed therapeutic drug monitoring during pregnancy. Almost all practitioners always or often counseled WWE on valproic acid on the benefits of switching to a less teratogenic medication (96.2%). Some geographic variability in practice patterns was noted with valproic acid being one of the top three medications selected for patients with generalized epilepsies in Western regions, although participants in Eastern regions had brivaracetam more commonly included as one of their top three agents for this population. SIGNIFICANCE: This is the first report of real-world Canadian practices in epilepsy care for women in pregnancy. Overall, our study reports that Canadian practice patterns conform well to current evidence and best-practice guidelines. Important variations in antiseizure medication selection across different regions were identified.

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.

An Efficient Method for Generating Murine Hypothalamic Neurospheres for the Study of Regional Neural Progenitor Biology.

The hypothalamus is a key homeostatic brain region and the primary effector of neuroendocrine signaling. Recent studies show that early embryonic developmental disruption of this region can lead to neuroendocrine conditions later in life, suggesting that hypothalamic progenitors might be sensitive to exogenous challenges. To study the behavior of hypothalamic neural progenitors, we developed a novel dissection methodology to isolate murine hypothalamic neural stem and progenitor cells at the early timepoint of embryonic day 12.5, which coincides with peak hypothalamic neurogenesis. Additionally, we established and optimized a culturing protocol to maintain multipotent hypothalamic neurospheres that are capable of sustained proliferation or differentiation into neurons, oligodendrocytes, and astrocytes. We characterized media requirements, appropriate cell seeding density, and the role of growth factors and sonic hedgehog (Shh) supplementation. Finally, we validated the use of fluorescence activated cell sorting of either Sox2GFPKI or Nkx2.1GFPKI transgenic mice as an alternate cellular isolation approach to enable enriched selection of hypothalamic progenitors for growth into neurospheres. Combined, we present a new technique that yields reliable culturing of hypothalamic neural stem and progenitor cells that can be used to study hypothalamic development in a controlled environment.

Oligodendrocyte development in the embryonic tuberal hypothalamus and the influence of Ascl1.

BACKGROUND: Although the vast majority of cells in our brains are glia, we are only beginning to understand programs governing their development, especially within the embryonic hypothalamus. In mice, gliogenesis is a protracted process that begins during embryonic stages and continues into the early postnatal period, with glial progenitors first producing oligodendrocyte precursor cells, which then differentiate into pro-oligodendrocytes, pro-myelinating oligodendrocytes, and finally, mature myelinating oligodendrocytes. The exact timing of the transition from neurogenesis to gliogenesis and the subsequent differentiation of glial lineages remains unknown for most of the Central Nervous System (CNS), and is especially true for the hypothalamus. METHODS: Here we used mouse embryonic brain samples to determine the onset of gliogenesis and expansion of glial populations in the tuberal hypothalamus using glial markers Sox9, Sox10, Olig2, PdgfRα, Aldh1L1, and MBP. We further employed Ascl1 and Neurog2 mutant mice to probe the influence of these proneual genes on developing embryonic gliogenic populations. RESULTS: Using marker analyses for glial precursors, we found that gliogenesis commences just prior to E13.5 in the tuberal hypothalamus, beginning with the detection of glioblast and oligodendrocyte precursor cell markers in a restricted domain adjacent to the third ventricle. Sox9+ and Olig2+ glioblasts are also observed in the mantle region from E13.5 onwards, many of which are Ki67+ proliferating cells, and peaks at E17.5. Using Ascl1 and Neurog2 mutant mice to investigate the influence of these bHLH transcription factors on the progression of gliogenesis in the tuberal hypothalamus, we found that the elimination of Ascl1 resulted in an increase in oligodendrocyte cells throughout the expansive period of oligodendrogenesis. CONCLUSION: Our results are the first to define the timing of gliogenesis in the tuberal hypothalamus and indicate that Ascl1 is required to repress oligodendrocyte differentiation within this brain region.