Genetic determinants play important role in the complex processes of inflammation and immune response in stroke and could be studied in different ways. Inflammation and immunomodulation are ...associated with repair processes in ischemic stroke, and together with the concept of preconditioning are promising modes of stroke treatment. One of the important aspects to be considered in the recovery of patients after the stroke is a genetic predisposition, which has been studied extensively. Polymorphisms in a number of
, such as
,
,
,
, and
could be associated with stroke outcome and recovery. Recent GWAS studies pointed to the variant in
and
as new genetic markers of long term outcome. Epigenetic regulation of immune response in stroke is also important, with mechanisms of histone modifications, DNA methylation, and activity of non-coding RNAs. These complex processes are changing from acute phase over the repair to establishing homeostasis or to provoke exaggerated reaction and death. Pharmacogenetics and pharmacogenomics of stroke cures might also be evaluated in the context of immuno-inflammation and brain plasticity. Potential novel genetic treatment modalities are challenged but still in the early phase of the investigation.
Strokes within pediatric populations are considered to be the 10th leading cause of death in the United States of America, with over half of such events occurring in children younger than one year of ...life. The multifactorial etiopathology that has an influence on stroke development and occurrence signify the importance of the timely recognition of both modifiable and non-modifiable factors for adequate diagnostic and treatment approaches. The early recognition of a stroke and stroke risk in children has the potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after the onset of a stroke, improving the outcomes and quality of life for affected children and their families. The recent development of molecular genetic methods has greatly facilitated the analysis and diagnosis of single-gene disorders. In this review, the most significant single gene disorders associated with pediatric stroke are presented, along with specific therapeutic options whenever they exist. Besides monogenic disorders that may present with stroke as a first symptom, genetic polymorphisms may contribute to the risk of pediatric and perinatal stroke. The most frequently studied genetic risk factors are several common polymorphisms in genes associated with thrombophilia; these genes code for proteins that are part of the coagulation cascade, fibrolysis, homocystein metabolism, lipid metabolism, or platelets. Single polymorphism frequencies may not be sufficient to completely explain the stroke causality and an analysis of several genotype combinations is a more promising approach. The recent steps forward in our understanding of the disorders underlying strokes has given us a next generation of therapeutics and therapeutic targets by which to improve stroke survival, protect or rebuild neuronal connections in the brain, and enhance neural function. Advances in DNA sequencing and the development of new tools to correct human gene mutations have brought genetic analysis and gene therapy into the focus of investigations for new therapeutic options for stroke patients.
Stroke during pregnancy and preeclampsia are two distinct but interrelated medical conditions, sharing a common denominator—blood control failure. Along with cardiovascular diseases, diabetes, ...dyslipidemia, and hypercoagulability, hypertension is undoubtedly a major risk factor associated with stroke. Even though men have higher age-specific stroke rates, women are facing higher life-long stroke risk, primarily due to longer life expectancy. Sex hormones, especially estrogen and testosterone, seem to play a key link in the chain of blood pressure control differences between the genders. Women affected with stroke are more susceptible to experience some atypical stroke manifestations, which might eventually lead to delayed diagnosis establishment, and result in higher morbidity and mortality rates in the population of women. Preeclampsia is a part of hypertensive disorder of pregnancy spectrum, and it is common knowledge that women with a positive history of preeclampsia are at increased stroke risk during their lifetime. Preeclampsia and stroke display similar pathophysiological patterns, including hypertension, endothelial dysfunction, dyslipidemia, hypercoagulability, and cerebral vasomotor reactivity abnormalities. High-risk pregnancies carrying the burden of hypertensive disorder of pregnancy have up to a six-fold higher chance of suffering from stroke. Resemblance shared between placental and cerebral vascular changes, adaptations, and sophisticated auto-regulatory mechanisms are not merely coincidental, but they reflect distinctive and complex cardiovascular performances occurring in the maternal circulatory system during pregnancy. Placental and cerebral malperfusion appears to be in the midline of both of these conditions; placental malperfusion eventually leads to preeclampsia, and cerebral to stoke. Suboptimal performances of the cardiovascular system are proposed as a primary cause of uteroplacental malperfusion. Placental dysfunction is therefore designated as a secondary condition, initiated by the primary disturbances of the cardiovascular system, rather than an immunological disorder associated with abnormal trophoblast invasion. In most cases, with properly and timely applied measures of prevention, stroke is predictable, and preeclampsia is a controllable condition. Understanding the differences between preeclampsia and stroke in pregnancy is vital for healthcare providers to enhance their clinical decision-making strategies, improve patient care, and promote positive maternal and pregnancy outcomes. Management approaches for preeclampsia and stroke require a multidisciplinary approach involving obstetricians, neurologists, and other healthcare professionals.
Migraine is a prevalent neurological disorder that significantly impacts the quality of life for affected individuals. The pathogenesis behind migraines is not yet fully understood, but hormonal ...changes, especially fluctuations in, estrogen and progesterone levels, have a significant role in the susceptibility of women to migraines. Pregnancy introduces a unique set of challenges for women who experience migraines, as they must navigate the complexities of managing their condition while safeguarding the health of both them and their unborn child. Pharmacological options for treating migraines during pregnancy are limited, and, therefore, there is a growing interest in exploring alternative approaches to migraine symptom relief and management. Physical activity during pregnancy provides a range of benefits, and it has gained attention as a potentially valuable tool for alleviating migraine symptoms in pregnant patients. This review explores the intricate relationship between migraines and pregnancy, emphasizing how physical activity and other alternative approaches may influence the frequency, severity, and overall experience of migraines during pregnancy. Through collaboration with healthcare providers and the adoption of personalized management strategies, women can strike a balance that supports both their own well-being and the healthy development of their unborn child. By examining existing research and emerging insights, we aim to provide a comprehensive understanding of the potential benefits and considerations of incorporating physical activity and other treatment options into migraine management strategies for pregnant women. Further research is needed to elucidate the specific mechanisms linking migraines, pregnancy, and physical activity, enabling the development of more targeted interventions and guidelines.
Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not ...fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein aggregation and miss-folding, oxidative stress, glutamate excitotoxicity, inflammation and epigenetic dysregulation. Additionally, as mitochondria plays a leading role in cellular homeostasis maintenance, a rising amount of evidence indicates mitochondrial dysfunction as a substantial contributor to disease onset and progression. The aim of this review is to summarize most relevant findings that link genetic factors in ALS pathogenesis with different mechanisms with mitochondrial involvement (respiratory chain, OXPHOS control, calcium buffering, axonal transport, inflammation, mitophagy, etc.). We highlight the importance of a widening perspective for better understanding overlapping pathophysiological pathways in ALS and neurodegeneration in general. Finally, current and potentially novel therapies, especially gene specific therapies, targeting mitochondrial dysfunction are discussed briefly.
Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, ...clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.
During the last three years, since the emergence of the COVID-19 pandemic, a significant number of scientific publications have focused on resolving susceptibility to the infection, as well as the ...course of the disease and potential long-term complications. COVID-19 is widely considered as a multisystem disease and a variety of socioeconomic, medical, and genetic/epigenetic factors may contribute to the disease severity and outcome. Furthermore, the SARS-COV-2 infection may trigger pathological processes and accelerate underlying conditions to clinical entities. The development of specific and sensitive biomarkers that are easy to obtain will allow for patient stratification, prevention, prognosis, and more individualized treatments for COVID-19. miRNAs are proposed as promising biomarkers for different aspects of COVID-19 disease (susceptibility, severity, complication course, outcome, and therapeutic possibilities). This review summarizes the most relevant findings concerning miRNA involvement in COVID-19 pathology. Additionally, the role of miRNAs in wide range of complications due to accompanied and/or underlying health conditions is discussed. The importance of understanding the functional relationships between different conditions, such as pregnancy, obesity, or neurological diseases, with COVID-19 is also highlighted.
Maternal obesity influences pregnancy course in several different manners, and imbalanced nutrition during pregnancy may lead to various adverse pregnancy outcomes. Additionally, nutritional status ...during pregnancy may have implications for the health of the offspring and may possibly influence early motor development in children. The aim of this study was to assess the impact of excessive gestational weight gain (EGWG) on pregnancy outcomes and infant's motor development within the first twelve months of life.
The study included 200 participants divided in two groups based on their gestational weight gain. Maternal, perinatal, and neonatal factors were analyzed, and early motor development was assessed using the Alberta infant motor scale (AIMS).
EGWG was significantly associated with: pre-pregnancy BMI (
< 0.001), family history for cardiovascular diseases (
= 0.013) and diabetes mellitus (
= 0.045), hypertensive disorder of pregnancy (
= 0.003), gestational diabetes mellitus (
< 0.001), gestational anemia (
= 0.001), vitamin D deficiency (
= 0.001), metformin use (
= 0.045), pre-labor premature rupture of membranes (
= 0.031), amniotic fluid index (
= 0.047), and APGAR score in the first five min of life (
= 0.007). Scored by AIMS, EGWG was significantly associated with parameters of early motor development at the age of three AIMS total (
< 0.001), six AIMS total (
< 0.001), nine AIMS total (
< 0.001), and twelve AIMS total (
< 0.001) months of infant's life.
The link between EGWG and adverse neurodevelopmental outcomes in offspring is a complex and multifaceted issue. Our results imply significant alterations in early motor development in the group of infants born from mothers who gained weight excessively during pregnancy. Further studies are needed to unravel the intricacies of this relationship and inform strategies for preventive interventions and supportive care during pregnancy and infancy.
Background: Recognized as one of the most serious musculoskeletal deformities, occurring in 1–2 per 1000 newborns, 80% of clubfeet are idiopathic while 20% present with associated malformations. The ...etiopathogenesis of clubfoot is described as multifactorial, including both genetic and environmental risk factors. The aim of this study was to analyze possible genetic causes of isolated and syndromic clubfoot in Serbian children, as well as to correlate clinical and genetic characteristics that would provide insight into clubfoot etiopathogenesis and possibly contribute to global knowledge about clinical features of different genetically defined disorders. Methods: We evaluated 50 randomly selected, eligible children with clubfoot aged 3 to 16 years that were initially hospitalized and treated at University Children’s Hospital between November 2006 and November 2022. The tested parameters were gender, age, dominant foot, affected foot, degree of deformity, treatment, neuromuscular disorders, positive family history, and maternal smoking. According to the presence of defined genetic mutation/s by whole exome sequencing (WES), patients were separated into two groups: positive (with genetic mutation/s) and negative (without genetic mutation/s). Results: Seven patients were found to be positive, i.e., with genetic mutation/s. A statistically significant difference between categorical variables was found for families with a history of clubfoot, where more than half (57.14%) of patients with confirmed genetic mutation/s also had a family history of genetic mutation/s (p = 0.023). Conclusions: The results from this study further expand the genetic epidemiology of clubfoot. This study contributes to the establishment of genetic diagnostic strategies in pediatric patients with this condition, which can lead to more efficient genetic diagnosis.
Background
Only several studies analyzed the characteristics of neuropathic pain (NeP) more extensively in patients with Charcot-Marie-Tooth type 1A (CMT1A). Therefore, we sought to determine the ...frequency and features of NeP in CMT1A patients and to assess the association between NeP and sociodemographic and clinical characteristics of patients with CMT1A.
Methods
Our research included 51 genetically diagnosed CMT1A patients. The International Association for the Study of Pain (IASP) criteria were used for diagnosis of NeP. PainDETECT questionnaire (PD-Q) was used to assess NeP features. The Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale (ONLS) score, and Beck Depression Inventory were also used.
Results
NeP was present in 15 (29.4%) patients with CMT1A. The average intensity of pain was 5.7 ± 2.2 out of 10. The most sensitive neuropathic symptoms were numbness, then tingling, and burning sensations, while the most specific symptom was allodynia. Patients with NeP more frequently reported pain in the back (
p
< 0.01) and the trunk (
p
< 0.05). Patients with NeP had more pronounced disability of the upper extremities and overall disability, as assessed by the ONLS score (
p
< 0.05). Depression was more frequent in patients with NeP compared with patients without NeP (66.7 to 13.9%,
p
< 0.01).
Conclusion
NeP was present in almost one-third of the patients with CMT1A and it was moderate on average. Presence of NeP was associated with worse functional disability and depression.
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