S. Bachiller, Itzia Jimenez-Ferrer, A. Paulus
et al.
Microglia represent a specialized population of macrophages-like cells in the central nervous system (CNS) considered immune sentinels that are capable of orchestrating a potent inflammatory response. Microglia are also involved in synaptic organization, trophic neuronal support during development, phagocytosis of apoptotic cells in the developing brain, myelin turnover, control of neuronal excitability, phagocytic debris removal as well as brain protection and repair. Microglial response is pathology dependent and affects to immune, metabolic. In this review, we will shed light on microglial activation depending on the disease context and the influence of factors such as aging, environment or cell-to-cell interaction.
Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood–brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial‐based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease‐targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial‐mediated treatment of neurological diseases.
Astrocytes are the most abundant glial cells in the central nervous system (CNS) and participate in synaptic, circuit, and behavioral functions. The well‐developed protoplasmic astrocytes contain numerous processes forming well‐delineated bushy territories that overlap by as little as 5% at their boundaries. This highly complex morphology, with up to approximately 80% of the cell's membrane constituted by fine processes with dimensions on the tens of nanometer scale and high surface area to volume ratios, comes in contact with synapses, blood vessels, and other glial cells. Recent progress is challenging the conventional view that astrocytes are morphologically homogeneous throughout the brain; instead, they display circuit‐ and region‐specific morphological diversity that may contribute to the heterogeneous astrocyte‐neuron spatiotemporal interplay in different brain areas. Further, the fine structure of astrocytes is found to be highly plastic and activity‐dependent. We are beginning to understand how astrocyte structural plasticity contributes to brain functions. The change/loss of astrocyte morphology, traditionally known as a hallmark for reactive astrogliosis, is a common pathological feature in many neurological disorders. However, recent data suggest the fine structural deficits preceding reactive astrogliosis may drive disease progression. This review summarizes recent advances in astrocyte morphological diversity, plasticity, and disease‐related deficits.
Brain is a vital organ of the human body which performs very important functions such as analysis, processing, coordination, and execution of electrical signals. For this purpose, it depends on a complex network of nerves which are ensheathed in lipids tailored myelin; an abundant source of lipids in the body. The nervous system is enriched with important classes of lipids; sphingolipids and cholesterol which compose the major portion of the brain particularly in the form of myelin. Both cholesterol and sphingolipids are embedded in the microdomains of membrane rafts and are functional units of the neuronal cell membrane. These molecules serve as the signaling molecules; hold important roles in the neuronal differentiation, synaptogenesis, and many others. Thus, their adequate provision and active metabolism are of crucial importance in the maintenance of physiological functions of brain and body of an individual. In the present review, we have highlighted the physiological roles of cholesterol and sphingolipids in the development of the nervous system as well as the association of their altered metabolism to neurological and neurodegenerative diseases.
IntroductionIn addition to anxiety disorders and depressive symptoms, transgender people are also shown to have pathological personality profiles. These patterns are due to functioning under chronic stress, exposure to discrimination, victimization, the inability to affirm gender identity, and insufficient social support. The internalized transphobia predisposes transgender individuals to psychological decompensation. The study aims to assess Dark Personality Trait among transgender individuals and to establish the relationships between Dark Tetrad traits and resilience.Materials and MethodsThe Dark Tetrad (narcissism, psychopathy, Machiavellianism, sadism) was assessed using The Short Dark Tetrad Scale (SD4-PL). Resilience was measured using The Resilience Measurement Scale (SPP-25) questionnaire. The dimensions of psychological resilience were also evaluated, including perseverance, determination in action, openness to new experiences, sense of humor, personal competence in coping, tolerance of negative emotions, tolerance for failure, viewing life as a challenge, optimism, and the ability to mobilize in difficult situations. In the statistical analysis, a Multivariate Analysis of Covariance (MANCOVA) was conducted. Correlations between dark personality traits in the transgender and cisgender groups were compared using Fisher’s z-test.ResultsThe study results indicate a slightly lower level of narcissism and Machiavellianism in transgender women compared with cisgender women, and a slightly increased level of sadism in all men, regardless of whether they are transgender or cisgender. No differences were observed between the transgender and cisgender groups in terms of dark personality traits. Transgender individuals exhibited significantly lower level of general resilience than cisgender individuals.ConclusionsThe results of participants from the transgender group indicate lower level of dark personality traits. Observed differences in dark personality traits are related to gender and are independent of transgenderism. Psychological resilience provides a subtle protective function against the development of dark personality traits.
Andrew Zillgitt, David E Burdette, Atheel Yako
et al.
Clobazam (CLB) and cenobamate (CNB) are commonly used antiseizure medications (ASMs) in the treatment of patients with drug-resistant epilepsy (DRE). However, concomitant use of these two ASMs may lead to significant treatment-related adverse events (TRAE). Furthermore, these TRAE may be exacerbated in individuals with genetic polymorphisms involving the P450 system. In patients with DRE, epilepsy surgery, including neuromodulation, may lead to improved seizure control and a reduction in systemic TRAE from ASMs. This case report describes a patient with drug-resistant idiopathic generalized epilepsy (IGE) who experienced persistent excessive somnolence correlated with elevated N-desmethylclobazam (N-CLB) levels. Pharmacogenetic testing revealed poor metabolism of CYP2C19, and N-CLB levels remained elevated and detectable for nearly one year after the discontinuation of treatment with CLB and CNB. Responsive neurostimulator (RNS) implantation within the bilateral centromedian nuclei (CMN) of the thalamus resulted in seizure freedom until N-CLB levels fell, after which there was an 83–93 % reduction in the frequency of generalized tonic-clonic seizures (GTC).
Neurology. Diseases of the nervous system, Neurophysiology and neuropsychology
ObjectiveThis study aimed to examine the psychological mechanisms of depression in both bariatric surgery candidates and post-bariatric surgery patients and to explore the roles of resilience and anxiety in these relationships.MethodsA total of 431 candidates for bariatric surgery were recruited from a hospital. One month after the bariatric surgery, 228 patients continued to participate in the study. All participants completed the Insomnia Severity Index (ISI), Connor and Davidson Resilience Scale (CD-RISC), Generalized Anxiety Disorder 7-item scale (GAD-7), and Patient Health Questionnaire Depression Scale (PHQ-9). A mediation model analysis was used to investigate the mediating role of resilience, the mediating role of anxiety, and the chain mediating role of resilience and anxiety in the relationship between insomnia and depression.ResultsInsomnia positively correlated with depression through the mediating role of resilience, the mediating role of anxiety, and the serial mediating effect of resilience and anxiety among bariatric surgery candidates. However, only a direct effect of insomnia on depression and the mediating role of anxiety were found in post-bariatric surgery patients.ConclusionThe findings demonstrated that insomnia leads to an increase in depression among bariatric surgery patients, with resilience and anxiety playing significant mediating roles. This also highlights the need for targeted resilience-enhancing interventions in obese patients who are about to undergo bariatric surgery.
Jerry John Nutor, Robert Kaba Alhassan, Rachel G A Thompson
et al.
Depression among people living with HIV/AIDS in higher-income countries is associated with suboptimal adherence to antiretroviral therapy and though counterintuitive. Yet, less is known regarding how depression, social support, and other sociodemographic factors influence outcomes among people living with HIV, particularly in resource-limited settings like Ghana. In view of this gap, this study investigated factors associated with depressive symptoms among people living with HIV in the Volta region of Ghana. A total of 181 people living with HIV from a local antiretroviral clinic was purposively sampled for the study. The questionnaire included the Center for Epidemiologic Studies Depression Scale, the Internalized Stigma of HIV/AIDS Tool, and the Interpersonal Support Evaluation List-12. An independent student t-test, one-way analysis of variance, and chi-square test were conducted to ascertain the associations among the variables of interest. The magnitude of association was evaluated with multiple linear regression. The average depression score among the participants was 9.1±8.8 and 20.4% reported signs of depression. Majority (78%) of participants who were depressed were male compared to females (p = 0.031). In the multiple linear regression, every one-year increase in age was significantly associated with an estimated 0.012 standard deviation increase in depression scores (95% CI: 0.002-0.021) after adjusting for all other variables in the model. Every unit standard deviation increase in social support was significantly associated with an estimated 0.659 standard deviation increase in depression scores (95% CI:0.187-1.132), after adjusting for all other variables in the model. We found a high prevalence of depressive symptoms among people living with HIV especially among males. An increase in age and social support was associated with an increase in depressive symptoms among people living with HIV in this study. We recommend further study using longitudinal approach to understand this unexpected association between depression and social support among people living with HIV in Ghana.
Vitamin D may have multiple effects on the nervous system and its deficiency can represent a possible risk factor for the development of many neurological diseases. Recent studies are also trying to clarify the different effects of vitamin D supplementation over the course of progressive neurological diseases. In this narrative review, we summarise vitamin D chemistry, metabolism, mechanisms of action, and the recommended daily intake. The role of vitamin D on gene transcription and the immune response is also reviewed. Finally, we discuss the scientific evidence that links low 25-hydroxyvitamin D concentrations to the onset and progression of severe neurological diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, migraine, diabetic neuropathy and amyotrophic lateral sclerosis. Completed and ongoing clinical trials on vitamin D supplementation in neurological diseases are listed.
Swati Saroha, Dipasri Bhattacharya, Prashant Arya
et al.
Background: Pain originating in the facet joint accounts for an estimated 15%–45% of cases of low back pain. Radiofrequency ablation (RFA) of the medial branch nerves (MBN) is used in refractory cases. However, very few studies have compared the clinical outcomes of cooled versus conventional/traditional RFA (T-RFA) for the treatment of lumbar facet joint pain. Objective: To determine the clinical outcomes of MBN cooled RFA (C-RFA) compared with T-RFA, as measured by improvements in pain and physical function. Methodology: Forty patients with positive diagnostic MBN blocks were allocated to C-RFA or T-RFA group. Reduction in pain (NRS “Numerical Rating Scale” score), improvement in quality of life (Oswestry Disability Index [ODI]), proportion of responders/successful treatment (≥50% NRS reduction, and or ≥30% or ≥15 point reduction in ODI at 6 months follow up) in the two groups were recorded. Results: Total 34 patients were analysed, C-RFA (n = 18) and T-RFA (n = 16). There was significant reduction in pain scores as well as improvement in quality of life in both the groups, but the difference between the two groups was not significant. NRS reduction of ≥50% was observed in 72.22% and 68.5% of participants in the C-RFA and T-RFA groups, respectively (P = 0.824). A ≥15-point or ≥30% reduction in ODI score was observed in 77.77% and 75% of participants in the C-RFA and T-RFA groups, respectively (P = 0.849). Conclusions: Both the groups showed significant improvement in pain scores and quality of life. C-RFA resulted in greater treatment success rate than conventional RFA, but the difference was not significant.
Peter J. Lawrence, Simona Skripkauskaite, Adrienne Shum
et al.
Abstract Background The COVID‐19 pandemic caused significant disruption to the lives of children and their families. Pre‐school children may have been particularly vulnerable to the effects of the pandemic, with the closure of childcare facilities, playgrounds, playcentres and parent and toddler groups limiting their opportunities for social interaction at a crucial stage of development. Additionally, for parents working from home, caring for pre‐school aged children who require high levels of support and care, was likely challenging. We conducted an intensive longitudinal, but not nationally representative, study to examine trajectories of pre‐schoolers’ mental symptoms in the United Kingdom during the first year of the COVID‐19 pandemic. Methods UK‐based parents and carers (n = 1520) of pre‐school‐aged children (2–4 years) completed monthly online surveys about their pre‐schoolers’ mental health between April 2020 and March 2021. The survey examined changes in children's emotional symptoms, conduct problems and hyperactivity/inattention. Results In our final mixed‐effects models, our predictors (fixed effects) accounted for 5% of the variance in each of conduct problems, emotional symptoms and hyperactivity/inattention symptoms scores, and the combined random and fixed effects accounted for between 64% and 73% of the variance. Pre‐schoolers’ emotional problems and hyperactivity/inattention symptoms declined from April through summer 2020 and then increased again during the autumn and winter 2020/2021 as lockdowns were re‐introduced. Pre‐schoolers who attended childcare showed greater decline in symptom severity than those who did not. Older children, compared to younger, showed greater lability of emotion symptom severity. Attending childcare predicted lower symptom severity across all three domains of conduct problems, emotional symptoms, and hyperactivity/inattention, while the opposite pattern was observed for children whose parent had a mental health problem. Conclusions Our findings reinforce the importance of examining pre‐schoolers’ mental health in the context of micro and macro‐level factors. Interventions focussing on family factors such as parent mental health, as well as continued provision of childcare, may have most potential to mitigate the impact of COVID‐19 on young children's mental health.
IntroductionSymptoms induced by arachnoid cysts in the fallopian canal are uncommon, and facial nerve paralysis without cerebrospinal fluid otorrhea is comparatively rarer.MethodsHerein, we present two cases of arachnoid cysts in the fallopian canal with acute severe facial nerve paralysis and review the relevant literature.ResultsThe symptoms and imaging findings of these two cases resembled those of facial nerve schwannomas. Cerebrospinal fluid otorrhea occurred upon removal of the arachnoid cyst, and the facial nerve was observed to be separated into multiple filaments or compressed and atrophied. Facial-hypoglossal nerve anastomosis and decompression were conducted after packing the dehiscence of cerebrospinal fluid otorrhea for the two cases.ConclusionArachnoid cysts of the fallopian canal rarely cause facial nerve paralysis. Enhanced magnetic resonance imaging is vital for differentiating schwannomas. Different treatment strategies should be adopted for patients with different degrees of facial nerve paralysis; however, concurrent repair of cerebrospinal fluid otorrhea and facial nerves during surgery can occasionally be challenging.
Abstract Background Using traditional pharmacotherapy to treat Borderline Personality Disorder (BPD) such as mood stabilizers and second-generation antipsychotics has a lack of supporting evidence. Buprenorphine/Naloxone (BUP/N), a combination medication consisting of a partial opioid agonist, and a full opioid antagonist, is an effective treatment for opioid use disorder. It has also been found effective for treatment-resistant mood disorders. Previous studies suggest a relationship between BPD and endogenous opioids, therefore our case report investigates the effect of BUP/N on a patient diagnosed with BPD. Case presentation A 26-year-old female diagnosed with BPD, having recurrent visits to the emergency department (ED) for self-harm/suicidality was treated with BUP/N. Usage of crisis services, ED visits, and hospital admissions were tracked from 15 months prior to BUP/N to 15 months after using BUP/N. Since starting BUP/N, the length and frequency of mental health-related hospital admissions decreased drastically, as did the number of times that she reached out to community crisis services. Since the dosing adjustment to 6 mg in Oct 2020, there have been no calls to the community crisis lines. Conclusions We suggest pharmacological treatment targeting BPD as a disorder of distress tolerance and self-soothing mediated by the opioid system is an effective individual healing attempt. An important note is that this patient did not use opioids prior to BUP/N and had never been diagnosed with an opioid use disorder. However, she exhausted multiple other pharmacologic therapies and was open to trying whatever was available to improve her quality of life.
Objective: There has become a consensus for detecting intellectual disability in its early stages and implementing effective intervention. However, there are many difficulties and limitations in the evaluation of intelligence-related scales in low-age children. Eye-tracking technology may effectively solve some of the pain points in the evaluation.Method: We used an eye-tracking technology for cognitive assessment. The subjects looked at a series of task pictures and short videos, the fixation points of which were recorded by the eye-movement analyzer, and the data were statistically analyzed. A total of 120 children aged between 1.5 and 4 years participated in the study, including 60 typically developing children and 60 children with global development delay, all of whom were assessed via the Bayley scale, Peabody Picture Vocabulary Test (PPVT), and Gesell scale.Results: Cognitive scores from eye-tracking technology are closely related to the scores of neuropsychological tests, which shows that the technique performs well as an early diagnostic test of children's intelligence.Conclusions: The results show that children's cognitive development can be quickly screened using eye-tracking technology and that it can track quantitative intelligence scores and sensitively detect intellectual impairment.