Unmet Need in Early-Onset Parkinson's Disease: Deep Brain Stimulation and Pregnancy.

Pregnancy in women with early-onset Parkinson's disease (PD) is likely to have a higher frequency given the trend toward increasing maternal age, thus resulting in a greater overlap time between childbearing age and PD risk. Deep brain stimulation (DBS) therapy is nowadays offered to PD patients at earlier stage of the disease, when women can still be pre-menopausal. However, few data are available about DBS safety during pregnancy. From a review of the available literature, only one article was published on this topic so far. Therefore, we have developed a clinical consensus on the safety of DBS during pregnancy in PD patients.

Unmet Needs of Women Living with Parkinson's Disease: Gaps and Controversies.

Personalized medicine considering sex, gender, and cultural context has become the vanguard of delivery of care. However, women's issues in Parkinson disease (PD), especially from a psychosocial standpoint, have been an overlooked field. The key research areas include women-inclusive drug and device studies and genetic and hormonal considerations. Moreover, women with PD need to be educated and empowered on how to communicate their symptoms and needs, get engaged in research, get organized as a community, and support one another. Women with PD need tools to help track and convey their unique motor and nonmotor symptoms and psychological and social support needs. The management of PD needs to be customized to include the unique stages of women's lives, including menstrual cycles, pregnancy, perimenopause, menopause, and postmenopause. Specific guidelines for the use of hormonal treatments and customized dopamine replacement dosing need to be developed. Women need guidance on culturally sensitive wellness and self-care strategies that are customized for them. Basic core competencies in knowledge for all clinicians treating women with PD need to be established, including how to accurately diagnose, proactively identify, and treat the symptoms of PD in women and to ensure timely referral for specialty care, advanced therapies, and research studies. Caregivers and families need guidance on holistically supporting women with PD. The voices of women living with PD must be amplified to catalyze real change in this neglected field. This paper provides an overview of the current knowledge, gaps, and possible strategies to deal with the unmet needs of women living with PD with a focus on the clinical and psychosocial aspects. © 2022 International Parkinson and Movement Disorder Society.

Homocysteine exposure affects early hemodynamic parameters of embryonic chicken heart function.

Maternal hyperhomocysteinemia has been associated with an increased risk of newborns with a congenital heart defect. This has been substantiated in the chicken embryo, as congenital heart defects have been induced after homocysteine treatment. Comparable heart defects are observed in venous clipping studies, a model of altered embryonic blood flow. Because of this overlap in heart defects, our aim was to test the hypothesis that homocysteine would cause alterations in embryonic heart function that precede the structural malformations previously described. Therefore, Doppler flow velocity waveforms were recorded in both primitive ventricles and the outflow tract of the embryonic heart of homocysteine treated and control chicken embryos at embryonic day 3.5. Homocysteine treatment consisted of 50 µL 0.05 M L-homocysteine thiolactone at 24, 48, and 72 hr. Homocysteine-treated embryos displayed significantly lower mean heart rates of 134 (SD 22) bpm, compared to 150 (14) bpm in control embryos. Homocysteine treatment caused an inhibiting effect on hemodynamic parameters, and altered heart function was presented by a shift in the proportions of the different wave times in percentage of total cycle time. Homocysteine induces changes in hemodynamic parameters of early embryonic chicken heart function. These changes may precede morphological changes and contribute to the development of CHD defects through alterations in shear stress and shear stress related genes, as seen before in venous clipping studies.

The effects of homocysteine and folic acid on angiogenesis and VEGF expression during chicken vascular development.

Homocysteine (Hcy) has been implicated in the development of cardiovascular developmental defects. Additionally, in experimental studies, vasculotoxic properties of Hcy have been described. Although Hcy has been identified as a vascular pathogen, little is known about the direct effects Hcy exerts during early embryonic vascular development. Angiogenesis is a critical process involved in embryo survival and development. There are limited studies on the effects of Hcy on early embryonic vasculogenesis and angiogenesis. Folic acid (FA) is a B vitamin essential in embryo development, and FA supplementation may lead to reduced Hcy levels. Therefore, the purpose of our study was to explore the effects of Hcy and FA on early embryonic vascular development. Embryonic day (E) 3.5 chicken embryos were treated with a sham, Hcy or FA solution. We developed a computational program for systematic analysis of microscopic images obtained from the extra embryonic vascular beds. These results were combined with real-time PCR data on the expression of VEGF-A and its receptor in these vascular beds. Our data show that Hcy exposure inhibits early vascular development, displayed by a significant reduction of vessel area and altered composition of the vascular beds. Vascular beds of Hcy embryos for the greater part consisted of vessels of the smallest diameters, compared to middle size vessels in control and FA embryos. Hcy also reduced expression of VEGF-A and VEGFR-2. No significant effects of FA were found. We conclude that Hcy exposure causes impaired early extra embryonic vascular development, shown by altered composition of the vascular beds as well as reduced expression of VEGF-A and VEGFR-2. These effects of Hcy, and the consecutive cascade of events, may be involved in the development of cardiovascular developmental defects.

[Acute abdominal symptoms in patients with a gastric band]. / Acute buikklachten bij patiënten met een maagband.

Three women aged 32, 35 and 37 years, respectively, presented with upper abdominal symptoms such as pain, nausea and vomiting. Their history revealed that an adjustable silicone gastric band had been implanted for the treatment of obesity one, four and seven years previously. Their symptoms were not immediately recognised as being possible complications of the gastric band and this caused treatment delay. In the first two patients ischaemic lesions were found at laparotomy. Their surgical treatment was successful. The third patient, however, was referred to the surgeon who had placed the gastric band, but she died in the mean time. Lack of recognition of symptoms caused by gastric banding and delay in diagnostic and therapeutic intervention may lead to very serious complications, or even death. Good diagnostic imaging and prompt therapeutic intervention can prevent the progression from herniation of the stomach through the silicone gastric band to irreversible ischaemia and eventually necrosis and perforation.

Teratogenicity and underlying mechanisms of homocysteine in animal models: a review.

BACKGROUND: Hyperhomocysteinemia in humans is a risk factor for adverse pregnancy outcome, especially congenital malformations. This review summarizes the studies directed on the teratogenicity of homocysteine carried out in animal studies, and elaborates on the underlying mechanisms. METHODS: Literature was searched in Pubmed (NCBI) through January 2010 and selected manually. Keywords comprised homocysteine, congenital abnormalities and animals. RESULTS: Increased frequencies of a wide range of congenital malformations are reported especially in the chicken embryo after exposure to homocysteine (Hcy) in various dosages and forms. Reduced embryonic growth and abnormalities of the vascularization of the yolk sac are described in mouse studies. A study in rats revealed a reduced development of blastocysts. The congenital malformations observed in the chicken embryo model share the mutual involvement of Hcy sensitive neural crest cells. Derangements in the behavior of these cells by interactions between Hcy and pathways involved in vascularization, growth, metabolism, signaling, and DNA synthesis and methylation may explain the wide range of effects on embryonic organs, the yolk sac and placental tissues. CONCLUSIONS: The associations between human hyperhomocysteinemia and congenital malformations are substantiated by chicken and rodent studies. Moreover, derangements of several pathways induced by Hcy are demonstrated with adverse effects on both reproduction and long term health. Because of the high prevalence of hyperhomocysteinemia in both the reproductive and general population, research on underlying epigenetic mechanisms is warranted.