Exploratory longitudinal studies on cerebral small vessel disease (CSVD) in apparently asymptomatic individuals with neuropsychological, neuroimaging and microparticles profiling

The prevalence of cerebral small vessel disease (CSVD) for asymptomatic (‘silent’) manifestation is typically obtained from incidental findings of white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). This study aimed to explore novel surrogate markers for the assessment of white matter integrity in CSVD among apparently asymptomatic individuals with neuropsychological, neuroimaging and microparticles (MPs) profiling. The recruited subjects with low to moderate cardiovascular risk prediction score as defined by QRISK2 underwent MRI brain scan, followed by neuropsychological indices of Weschler Adults Intelligence Scale (WAIS-IV) that measured their perceptual reasoning (PRI), working memory (WMI) and processing speed (PSI). Prior to flow cytometry MPs subpopulations enumerations, 18 ml of fasting blood was collected. Similar procedures were carried out at baseline (T0) and at 12 months follow-up (T12). At baseline, 48 asymptomatic individuals were recruited (mean age: 38.81±10.9); 24 were young adults, YA (mean age 29.7±4.33) and 24 mature adults, MA (mean age: 47.92±7.01). Fifteen (29.4%) had WMHs (WMH+) detected, of who five were YA, and 10 were MA. However, after one-year, 40 (mean age: 39.35±11.31) were able to participate; eight (20%) subjects were lost to follow up fourteen (35%) subjects were WMH+ and 26 (65%) were WMHAge influenced the presence of WMHs and WMH+ subject as having higher risk of CSVD. WMH+ subjects showed higher mean percentage of QRISK2 and MPs especially platelet derived MPs (CD41a and CD62P). In term of white matter integrity, QRISK2 score increased with reduced integrity (measured by fractional anisotropy, FA) of white matter tracts of superior corona radiata (SCR) and superior longitudinal fasciculus (SLF). White matter integrity was also reduced with advancing age. The PRI and WMI performance varied between subjects, but PSI consistently lower in WMH+ subjects. There were no significant temporal changes on cognitive and memories performances from both groups. FA of all tracts consistently and positively correlated with neuropsychological profiles. The integrity of white matter tracts such as left SLF and left anterior corona radiata were correlated with red blood cell MPs (CD235a) (r= -0.313, p=0.030) and CD62P (r=0.289, p= 0.047), respectively. Although with a relatively small sample size and one-year follow-up period, this study had established the correlations between cardio-cerebrovascular risk prediction by QRISK, neuropsychological indices performance, WMHs/white matter integrity from diffusion MRI and MPs profiling as potential surrogate markers for CSVD in apparently asymptomatic individuals

Neuroprotective Potentials of Natural Vitamin E for Cerebral Small Vessel Disease

Cerebral small vessel disease (CSVD) refers to a spectrum of clinical and neuroimaging findings resulting from pathological processes of various etiologies affecting cerebral arterioles, perforating arteries, capillaries, and venules. It is the commonest neurological problem that results in significant disability, but awareness of it remains poor. It affects over half of people over 65 years old and inflicts up to third of acute strokes, over 40% of dementia, and a significant decline in physical ability in otherwise asymptomatic, aging individuals. Moreover, the unifying theory for the pathomechanism of the disease remains elusive and hence the apparent ineffective therapeutic approaches. Given the growing literature for natural vitamin E (tocopherols and tocotrienols) as a potent antioxidant, this chapter attempts to consolidate the contemporary evidence to shed plausible insights on the neuroprotective potentials of natural vitamin E in addressing the heterogenous CSVD spectrum, in health and in disease

Neuroinflammation and COVID-19 ischemic stroke recovery—Evolving evidence for the mediating roles of the ACE2/angiotensin-(1–7)/mas receptor axis and NLRP3 inflammasome

Cerebrovascular events, notably acute ischemic strokes (AIS), have been reported in the setting of novel coronavirus disease (COVID-19) infection. Commonly regarded as cryptogenic, to date, the etiology is thought to be multifactorial and remains obscure; it is linked either to a direct viral invasion or to an indirect virus-induced prothrombotic state, with or without the presence of conventional cerebrovascular risk factors. In addition, patients are at a greater risk of developing long-term negative sequelae, i.e., long-COVID-related neurological problems, when compared to non-COVID-19 stroke patients. Central to the underlying neurobiology of stroke recovery in the context of COVID-19 infection is reduced angiotensin-converting enzyme 2 (ACE2) expression, which is known to lead to thrombo-inflammation and ACE2/angiotensin-(1–7)/mitochondrial assembly receptor (MasR) (ACE2/Ang-(1-7)/MasR) axis inhibition. Moreover, after AIS, the activated nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome may heighten the production of numerous proinflammatory cytokines, mediating neuro-glial cell dysfunction, ultimately leading to nerve-cell death. Therefore, potential neuroprotective therapies targeting the molecular mechanisms of the aforementioned mediators may help to inform rehabilitation strategies to improve brain reorganization (i.e., neuro-gliogenesis and synaptogenesis) and secondary prevention among AIS patients with or without COVID-19. Therefore, this narrative review aims to evaluate the mediating role of the ACE2/Ang-(1-7)/MasR axis and NLRP3 inflammasome in COVID-19-mediated AIS, as well as the prospects of these neuroinflammation mediators for brain repair and in secondary prevention strategies against AIS in stroke rehabilitation

Reduced cerebral vascular fractal dimension among asymptomatic individuals as a potential biomarker for cerebral small vessel disease

Cerebral small vessel disease is a neurological disease frequently found in the elderly and detected on neuroimaging, often as an incidental finding. White matter hyperintensity is one of the most commonly reported neuroimaging markers of CSVD and is linked with an increased risk of future stroke and vascular dementia. Recent attention has focused on the search of CSVD biomarkers. The objective of this study is to explore the potential of fractal dimension as a vascular neuroimaging marker in asymptomatic CSVD with low WMH burden. Df is an index that measures the complexity of a self-similar and irregular structure such as circle of Willis and its tributaries. This exploratory cross-sectional study involved 22 neurologically asymptomatic adult subjects (42 ± 12 years old; 68% female) with low to moderate 10-year cardiovascular disease risk prediction score (QRISK2 score) who underwent magnetic resonance imaging/angiography (MRI/MRA) brain scan. Based on the MRI findings, subjects were divided into two groups: subjects with low WMH burden and no WMH burden, (WMH+; n = 8) and (WMH−; n = 14) respectively. Maximum intensity projection image was constructed from the 3D time-of-flight (TOF) MRA. The complexity of the CoW and its tributaries observed in the MIP image was characterised using Df. The Df of the CoW and its tributaries, i.e., Df (w) was significantly lower in the WMH+ group (1.5172 ± 0.0248) as compared to WMH− (1.5653 ± 0.0304, p = 0.001). There was a significant inverse relationship between the QRISK2 risk score and Df (w), (rs = −.656, p = 0.001). Df (w) is a promising, non-invasive vascular neuroimaging marker for asymptomatic CSVD with WMH. Further study with multi-centre and long-term follow-up is warranted to explore its potential as a biomarker in CSVD and correlation with clinical sequalae of CSVD

The Cerebral Plasticity Prospect of Stingless Bee Honey-Polyphenols Supplementation in Rehabilitation of Post-Stroke Vascular Cognitive Impairment

The neuroprotective potential of stingless bee honey (SBH) is still to be documented from numerous studies including that of its effect on cerebrovascular event. This review should guide stroke rehabilitation specialties to a high understanding of the overall circuit changes post-stroke, the clinical relevance of this change in stroke to cognitive impairment and dementia, and SBH as a supplementation in modern stroke rehabilitation in progresses. However, the potential of SBH as a supplementation therapy and highlights treatment to induced plasticity for post-stroke vascular cognitive impairment (PSVCI) remains largely unexplored. This Chapter attempts to deliberate on recent evidence that highlight the therapeutic properties of honey and SBH, the features of PSVCI, and proposing the plausible mechanism of action for SBH as a supplementation during stroke rehabilitation that could halt the progression of PSVCI. It is hoped that such an approach could complement the existing evidence-based stroke care, and which will help in the development of future direction of brain plasticity to delay the progression of cognitive impairment post-stroke

Role of purinergic signalling in endothelial dysfunction and thrombo-inflammation in ischaemic stroke and cerebral small vessel disease

The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood–brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain

Exploring morality among orphans: a study of akhlaq and social standards in Pusat Jagaan Hembusan Kasih Sayang

This study explores the Islamic perspective on the care and treatment of orphans, focusing on their moral development within an institutional setting. Islamic teachings emphasize the holistic welfare of orphans, advocating for their physical, emotional, and spiritual well-being. This notion is grounded in the Quran and Hadith, where caring for orphans is not only a moral obligation but a means to attain spiritual reward. The study employs a quantitative cross-sectional design, using self-report questionnaires distributed among 50 children at Pusat Jagaan Hembusan Kasih Sayang, Kuantan. The questionnaire assesses various aspects of morality ('akhlaq') in relation to God, guardians, peers, and daily life. Results show a strong adherence to Islamic practices among the children, such as prayer, Quran recitation, and fasting, reflecting their spiritual upbringing. Their interactions with guardians and peers demonstrate respect, assistance, and effective conflict resolution, aligning with Islamic values of empathy and social harmony. Daily habits like tidiness and honesty are indicative of the institution's success in instilling Islamic principles of cleanliness and integrity. The study highlights the significant role of institutions like Pusat Jagaan Hembusan Kasih Sayang in shaping the moral development of orphans. These institutions provide not only physical care but also moral and spiritual guidance, crucial for children lacking familial support. The findings suggest that integrating religious teachings into the upbringing of children fosters a strong moral compass, preparing them to be responsible and ethical members of society. Overall, this research underscores the potential of religious education in promoting moral and ethical values in young individuals and calls for its replication in other childcare and educational settings. Future research could explore the long-term societal impact of such upbringing and the challenges faced by caregivers and educators in reinforcing these values

The perceived psychological well-being of LGBTQ individuals in Malaysia

This study explores the psychological well-being of lesbian, gay, bisexual, and transgender (LGBTQ) individuals in Malaysia, focusing on their experiences of identity formation, societal understanding, and the impact of prevailing attitudes on their mental health. Through qualitative methods, including in-depth interviews with nine participants from the LGBTQ community in Kuantan, Pahang, this research delves into the personal narratives of two lesbians, two gay individuals, two bisexuals, and three transgender persons, to understand the complexities of living as an LGBTQ individual in a society marked by religious and legal considerations. .The findings reveal that participants recognized their LGBTQ identity during adolescence, often navigating societal expectations discreetly to avoid backlash. Despite challenges, participants demonstrated resilience and found support within familial and community networks. Notably, the study highlights a shift towards greater understanding of LGBTQ individuals in Malaysia, potentially reducing instances of psychological distress within the community. This research underscores the importance of supportive environments and the need for culturally competent mental health care for LGBTQ individuals. It also calls for further studies to include broader societal perspectives and professional insights to enrich the discourse on LGBTQ mental well-being. This study contributes valuable insights into the evolving landscape of LGBTQ perceptions and the factors influencing the psychological health of LGBTQ individuals in Malaysia

Regional cerebral blood perfusion changes in chronic stroke survivors as potential brain correlates of the functional outcome following gamiied home-based rehabilitation (IntelliRehab)—a pilot study

Background: Hospital-based stroke rehabilitation for stroke survivors in developing countries may be limited by staffing ratios and length of stay that could hamper recovery potential. Thus, a home-based, gamified rehabilitation system (i.e., IntelliRehab) was tested for its ability to increase cerebral blood flow (CBF), and the secondary impact of changes on the upper limb motor function and functional outcomes. Objective: To explore the effect of IntelliRehab on CBF in chronic stroke patients and its correlation with the upper limb motor function. Methods: Two-dimensional pulsed Arterial Spin Labelling (2D-pASL) was used to obtain CBF images of stable, chronic stroke subjects (n = 8) over 3-months intervention period. CBF alterations were mapped, and the detected differences were marked as regions of interest. Motor functions represented by Fugl-Meyer Upper Extremity Assessment (FMA) and Stroke Impact Scale (SIS) were used to assess the primary and secondary outcomes, respectively. Results: Regional CBF were significantly increased in right inferior temporal gyrus and left superior temporal white matter after 1-month (p = 0.044) and 3-months (p = 0.01) of rehabilitation, respectively. However, regional CBF in left middle fronto-orbital gyrus significantly declined after 1-month of rehabilitation (p = 0.012). Moreover, SIS-Q7 and FMA scores significantly increased after 1-month and 3-months of rehabilitation. There were no significant correlations, however, between CBF changes and upper limb motor function. Conclusions: Participants demonstrated improved motor functions, supporting the benefit of using IntelliRehab as a tool for home-based rehabilitation. However, within-participant improvements may have limited potential that suggests the need for a timely administration of IntelliRehab to get the maximum capacity of improvement

Integrative healthcare approaches for children with special needs: a holistic study on challenges and solutions

This study delves into the intricate healthcare landscape for children with special needs, shedding light on the multifarious challenges these individuals face and evaluating the effectiveness of integrative healthcare models tailored to their unique requirements. Conducted at Sekolah Kebangsaan Pendidikan Khas Kuantan, this cross-sectional qualitative analysis involved detailed surveys with 20 teachers and engaging discussions with 24 students, aiming to unravel the complexities of providing holistic care to this vulnerable population. The investigation meticulously identifies pivotal concerns such as the prevalence of behavioral issues, particularly in autistic children, who often exhibit aggressive and self-injurious behaviors, and the struggles encountered by hearing-impaired students in communication and learning. It further explores the susceptibility of these children to frequent infections due to immune system dysfunction, exacerbated by dietary imbalances and physical inactivity. The research emphasizes the indispensable role of early detection and intervention in mitigating health risks and outlines the significance of specialized supplements, medications, and rigorous oral hygiene practices in maintaining the overall well-being of these children. Additionally, the study brings to the forefront the critical impact of socioeconomic factors on healthcare access, advocating for equitable healthcare solutions. It also highlights the transformative potential of technology, including telehealth and assistive devices, in overcoming barriers to healthcare and education. Through this analysis, the study advocates for a comprehensive, integrative care approach that encompasses medical, educational, social, and psychological services, underscoring the necessity of collaborative efforts among healthcare providers, educators, and families to significantly enhance the quality of life and well-being of children with special needs