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.

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.