Brain Sci., Volume 8, Issue 10 (October 2018) – 13 articles

Neurocognitive impairment remains an important HIV-associated comorbidity despite combination antiretroviral therapy (ART). Since the advent of ART, the spectrum of HIV-associated neurocognitive disorder (HAND) has shifted from the most severe form to milder forms. Independent replication of HIV in the central nervous system despite ART, so-called cerebrospinal fluid (CSF) escape is now recognised in the context of individuals with a reconstituted immune system. This review describes the global prevalence and clinical spectrum of CSF escape, it role in the pathogenesis of HAND and current advances in the diagnosis and management. It highlights gaps in knowledge in sub-Saharan Africa where the HIV burden is greatest and discusses the implications for this region in the context of the global HIV treatment scale up. Full article

The convenience of referring to dyslexia as a neurodevelopmental disorder has been repeatedly brought into question. In this opinion article, we argue in favor of the current diagnosis of dyslexia based on the criteria of harm and dysfunction. We discuss the favorable clinical and educational outcomes of a neuroscience-informed approach of dyslexia as a disorder. Furthermore, we discuss insights derived from neuroimaging studies and their importance to address problems related to developmental dyslexia. Full article

Schizophrenia is a severe, chronic mental disorder characterized by delusions and hallucinations. Several evidences support the link of schizophrenia with accelerated telomeres shortening and accelerated aging. Thus, schizophrenia patients show higher mortality compared to age-matched healthy donors. The etiology of schizophrenia is multifactorial, involving genetic and environmental factors. Telomere erosion has been shown to be accelerated by different factors including environmental factors such as cigarette smoking and chronic alcohol consumption or by psychosocial stress such as childhood maltreatment. In humans, telomere studies have mainly relied on measurements of leukocyte telomere length and it is generally accepted that individuals with short leukocyte telomere length are considered biologically older than those with longer ones. A dysregulation of both innate and adaptive immune systems has been described in schizophrenia patients and other mental diseases supporting the contribution of the immune system to disease symptoms. Thus, it has been suggested that abnormal immune activation with high pro-inflammatory cytokine production in response to still undefined environmental agents such as herpesviruses infections can be involved in the pathogenesis and pathophysiology of schizophrenia. It has been proposed that chronic inflammation and oxidative stress are involved in the course of schizophrenia illness, early onset of cardiovascular disease, accelerated aging, and premature mortality in schizophrenia. Prenatal or neonatal exposures to neurotropic pathogens such as Cytomegalovirus or Toxoplasma gondii have been proposed as environmental risk factors for schizophrenia in individuals with a risk genetic background. Thus, pro-inflammatory cytokines and microglia activation, together with genetic vulnerability, are considered etiological factors for schizophrenia, and support that inflammation status is involved in the course of illness in schizophrenia. Full article

Down syndrome (DS) caused by a trisomy of chromosome 21 (HSA21), is the most common genetic developmental disorder, with an incidence of 1 in 800 live births. Its phenotypic characteristics include intellectual impairment, early onset of Alzheimer’s disease, congenital heart disease, hypotonia, muscle weakness and several other developmental abnormalities, for the majority of which the pathogenetic mechanisms remain unknown. Among the numerous protein coding genes of HSA21, dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (DYRK1A) encodes a proline-directed serine/threonine and tyrosine kinase that plays pleiotropic roles in neurodevelopment in both physiological and pathological conditions. Numerous studies point to a crucial role of DYRK1A protein for brain defects in patients with DS. Thus, DYRK1A inhibition has shown benefits in several mouse models of DS, including improvement of cognitive behaviour. Lastly, a recent clinical trial has shown that epigallocatechine gallate (EGCG), a DYRK1A inhibitor, given to young patients with DS improved visual recognition memory, working memory performance and adaptive behaviour. Full article

Delivery of highly sophisticated, and subspecialised, management protocols for glioblastoma in low volume rural and regional areas creates potential issues for equivalent quality of care. This study aims to demonstrate the impact on clinical quality indicators through the development of a novel model of care delivering an outsourced subspecialised neuro-oncology service in a regional centre compared with the large volume metropolitan centre. Three hundred and fifty-two patients with glioblastoma were managed under the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) Protocol, and survival outcome was assessed in relation to potential prognostic factors and the geographical site of treatment, before and after opening of a regional cancer centre. The median overall survival was 17 months (95% CI: 15.5–18.5), with more favourable outcome with age less than 50 years (p < 0.001), near-total resection (p < 0.001), Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1 (p < 0.001), and presence of O-6 methylguanine DNA methyltransferase (MGMT) methylation (p = 0.001). There was no difference in survival outcome for patients managed at the regional centre, compared with metropolitan centre (p = 0.35). Similarly, no difference was seen with clinical quality process indicators of clinical trial involvement, rates of repeat craniotomy, use of bevacizumab and re-irradiation. This model of neuro-oncology subspecialisation allowed equivalent outcomes to be achieved within a regional cancer centre compared to large volume metropolitan centre. Full article

Alzheimer’s disease (AD) is characterized by the accumulation of neurofibrillary tangles (NFT), deposition of beta amyloid plaques, and consequent neuronal loss in the brain tissue. Oxidative stress to the neurons is often attributed to AD, but its link to NFT and β-amyloid protein (BAP) still remains unclear. In an animal model of AD, we boosted the oxidative defense by N-Acetyl cysteine (NAC), a precursor of glutathione, a powerful antioxidant and free radical scavenger, to understand the link between oxidative stress and NFT. In mimicking AD, intracerebroventricular (ICV) colchicine, a microtubule disrupting agent also known to cause oxidative stress was administered to the rats. The animal groups consisted of an age-matched control, sham operated, AD, and NAC treated in AD models of rats. Cognitive function was evaluated in a passive avoidance test; neuronal degeneration was quantified using Nissl staining. NFT in the form of abnormal tau expression in different regions of the brain were evaluated through immunohistochemistry using rabbit anti-tau antibody. ICV has resulted in significant cognitive and neuronal loss in medial prefrontal cortex (MFC) and all the regions of the hippocampus. It has also resulted in increased accumulation of intraneuronal tau in the hippocampus and MFC. NAC treatment in AD model rats has reversed the cognitive loss and neuronal degeneration. The intraneuronal tau expression also minimized with NAC treatment in AD model rats. Thus, our findings suggest that an antioxidant supplement during the progression of AD is likely to prevent neuronal degeneration by minimizing the neurofibrillary degeneration in the form of tau accumulation. Full article

Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands. To study this, we challenged female control and SLE mice with lipopolysaccharide (LPS) and measured c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic hormone (ACTH) as an index of anterior pituitary function, and plasma corticosterone as an index of adrenal function. We found that c-Fos expression in the PVN, and plasma ACTH and corticosterone were comparable between unchallenged SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice three hours after LPS challenge; however, there were no changes in plasma ACTH amongst any experimental groups post inflammatory challenge. Plasma corticosterone was markedly increased in LPS-challenged SLE mice compared to their vehicle-treated counterparts, but not in controls. Paradoxically, following LPS challenge, brain and spleen TNF-α were elevated in LPS-challenged SLE mice despite heightened plasma corticosterone. This suggests that, despite normal c-Fos expression in the PVN and activation of the HPA axis following LPS challenge, this cumulative response may not adequately defend SLE mice against inflammatory stimuli, leading to abnormally heightened innate immune responses and peripheral inflammation. Full article

Background: Gender may alter African Americans’ vulnerability to discrimination. The type of outcomes that follow exposure to discrimination may also be gender-specific. Although teacher discrimination is known to deteriorate school performance, it is yet unknown whether male and female African American youth differ in the effect of teacher discrimination on school performance. Objective: This cross-sectional study explored the moderating role of gender on the effect of teacher discrimination on school performance in a national sample of African American youth. Methods: The National Survey of American Life-Adolescent Supplement (NSAL-A) enrolled a nationally representative sample (n = 810) of 13–17-year-old African American youth. Demographic factors, socioeconomic status, teacher discrimination, and school performance (grade point average, GPA) were measured. Linear multivariable regression models were applied for data analysis. Results: Males and females reported similar levels of perceived teacher discrimination. In the pooled sample, higher teacher discrimination was associated with lower school performance among African American youth (b = −0.35; 95% confidence interval (CI) = −0.49 to −0.22). Gender interacted with perceived teacher discrimination (b = 12; 95% CI = 0.24–2.02), suggesting a significant difference between males and females in the magnitude of the association between perceived teacher discrimination and GPA. In stratified models, perceived teacher discrimination was associated with worse school performance of females (b = −12; 95% CI = −0.03 to −2.78) but not males (b = 0.01; 95% CI = −0.07 to 0.08). Conclusion: In line with previous studies, gender was found to alter the vulnerability of African American youth to perceived discrimination. African American boys and girls may differ in their sensitivity to the effects of teacher discrimination on school performance. Full article

Background: Recent research has shown smaller health effects of socioeconomic status (SES) indicators such as education attainment for African Americans as compared to whites. However, less is known about diminished returns based on gender within African Americans. Aim: To test whether among African American men are at a relative disadvantage compared to women in terms of having improved mental health as a result of their education attainment. This study thus explored gender differences in the association between education attainment and mental health, using a representative sample of American adults. Methods: The National Survey of American Life (NSAL; 2003) recruited 3570 African American adults (2299 females and 1271 males). The dependent variables were depressive symptoms and psychological distress. The independent variable was education attainment. Race was the focal moderator. Age, employment status, and marital status were covariates. Linear regressions were used for data analysis. Results: In the pooled sample that included both male and female African American adults, high education attainment was associated with lower depressive symptoms and psychological distress, net of covariates. Significant interactions were found between gender and education attainment with effects on depressive symptoms and psychological distress, suggesting stronger protective effects of high education attainment against depressive symptoms and psychological distress for female as compared to male African Americans. Conclusion: A smaller gain in mental health with respect to educational attainment for male African American males as compared to African American females is in line with studies showing high risk of depression in African American men of high-socioeconomic status. High-SES African American men need screening for depression and psychological distress. Full article

In literature nothing is known about the clinical significance of Ultra High Risk (UHR) symptoms in children and adolescents with diagnosis of obsessive–compulsive disorder (OCD). In this study, we examined the prevalence of UHR symptoms and their relationship with severity of obsessive–compulsive symptomatology, global, social, and role functioning, and level of associated depressive symptoms in a clinical sample (n = 51) of children and adolescents aged between 8 and 17 years with a diagnosis of OCD. The prevalence of UHR symptoms in this sample was 43.1%. We divided the whole sample into two groups: children and adolescents with OCD and UHR symptoms (n = 22) and children and adolescents with OCD without UHR symptoms (n = 29). Our findings suggest that the group with OCD and UHR symptoms shows worse global, social, and role functioning than the group with OCD without UHR symptoms. No differences were found on the severity of obsessive–compulsive symptomatology, the number of psychiatric diagnoses associated, and the level of depressive symptoms. The presence of UHR symptoms in children and adolescents with OCD could cause significant functional impairment and should be considered in order to plan specific and targeted therapeutic interventions. Full article

Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. However, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. The aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. Our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. However, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes. Full article

Recent work found that experimental pain appeared to negate alterations in cortical somatosensory evoked potentials (SEPs) that occurred in response to motor learning acquisition of a novel tracing task. The goal of this experiment was to further investigate the interactive effects of pain stimulus location on motor learning acquisition, retention, and sensorimotor processing. Three groups of twelve participants (n = 36) were randomly assigned to either a local capsaicin group, remote capsaicin group or contralateral capsaicin group. SEPs were collected at baseline, post-application of capsaicin cream, and following a motor learning task. Participants performed a motor tracing acquisition task followed by a pain-free retention task 24–48 h later while accuracy data was recorded. The P25 (p < 0.001) SEP peak significantly decreased following capsaicin application for all groups. Following motor learning acquisition, the N18 SEP peak decreased for the remote capsaicin group (p = 0.02) while the N30 (p = 0.002) SEP peaks increased significantly following motor learning acquisition for all groups. The local, remote and contralateral capsaicin groups improved in accuracy following motor learning (p < 0.001) with no significant differences between the groups. Early SEP alterations are markers of the neuroplasticity that accompanies acute pain and motor learning acquisition. Improved motor learning while in acute pain may be due to an increase in arousal, as opposed to increased attention to the limb performing the task. Full article