Cerebrovascular disease in children with HIV-1 infection.

An estimated 3.2 million children worldwide have human immunodeficiency virus (HIV) infection. Antiretroviral therapy (ART) has resulted in prolonged survival, leading to an increase in complications previously recognized in adults. Children with HIV infection have increased risk of cerebrovascular disease from multiple aetiologies including HIV-associated vasculopathy, opportunistic vasculitis, cardioembolism or coagulopathy, all of which may be secondary to the infection. Prevalence of cerebrovascular disease in HIV-infected children is underestimated because of limited neuroimaging in low and middle income countries, silent events without overt motor manifestations, and mislabeling as HIV encephalopathy for non-motor manifestations such as behavioural and cognitive difficulties. No management guidelines for cerebrovascular disease in HIV-infected children exist but common practices target risk factors for stroke in low and middle income countries. Where capacity permits, screening for opportunistic infections, vasculitis, coagulopathy and cardioembolism is important. Optimising virological suppression, correction of anaemia, control of seizures and aspirin prophylaxis are management priorities. Neurosurgical interventions may have a role.

Growing Up Can Be Hard to Do: Reimagining 1 Structurally Supportive Pediatric-to-Adult Transitions of Care from a Rights-Based Perspective.

Extended life expectancies and shifting dynamics in chronic disease have changed the landscape of public health interventions worldwide, with an increasing emphasis on chronic care. As a result, transition from pediatric to adult care for medically complex adolescents and young adults is a growing area of intervention. Transition medicine is a nascent field whose current emphasis is on middle- and high-income countries, and thus far its methods and discourse have reflected those origins. Through several case-based examples, this paper aims to highlight the possibilities of an analytic approach grounded in structural competency for transforming transition medicine through a human rights-based framework, with an emphasis on imagining a more global framework for transition medicine. Our cases highlight the disparities between patients navigating pediatric to adult-based care, illuminating social stigma, stratification between public and private insurances, engagement in risk-taking behaviors, family conflict, and challenges with transition readiness. To reimagine transition medicine so that it is based on human rights, we must prioritize structural solutions that embrace multisectoral integration and holistic mental health support rather than oppress and marginalize these critical systemic adaptations. We aim to reconfigure this scaffolding to center structures that integrate holistic well-being and imagine alternate realities to healing. Our work contributes to the literature bringing structural competency to new spaces of clinical practice, contextualizing new frontiers for the exploration of chronic diseases across diverse clinical contexts worldwide.

Management of Pediatric Stroke - Challenges and Perspectives from Resource-limited Settings.

Childhood stroke is not as common as adult stroke, but it is underrecognized the world over. Diagnosis is often delayed due to lack of awareness not only by the lay public but also by emergency and front-line health care workers. Despite the relative rarity of childhood stroke, the impact on morbidity, mortality and the economic burden for families and society is high, especially in poorly resourced settings. The risk factors for stroke in children differ from the adult population where lifestyle factors play a more important role. The developmental aspects of the pediatric cerebral vasculature and hematological maturational biology affects the clinical presentation, investigation, management and outcomes of childhood stroke in a different way compared to adults. The management of childhood stroke is currently based on expert guidelines and evidence extrapolated from adult studies. Hyperacute therapies that have revolutionized the treatment of stroke in adults cannot be easily applied to children at this stage due to the diagnostic delays, diverse risk factors and developmental considerations mentioned above. Much has been achieved in the understanding of genetic, acquired, preventable and recurrent stroke risk factors in the past decade through international collaborative efforts like the International Pediatric Stroke Study. Evidence for the prevention and treatment of childhood stroke remains elusive. Even more elusive are relevant and achievable management guidelines for pediatric stroke in resource-limited settings. This narrative review focusses on the current management practices globally, emphasizing the challenges, and gaps in knowledge of pediatric stroke in low- and middle-income countries and other areas with limited resources. Priorities and some potential solutions at national and local level are suggested for these settings.

Neuropsychiatric and Neurocognitive Manifestations in HIV-Infected Children Treated With Efavirenz in South Africa-A Retrospective Case Series.

Background: Efavirenz is associated with transient neuropsychiatric manifestations but the impact on neurocognition in children is unknown. Genetically slow metabolizers of efavirenz may be at risk of toxicity. This study describes neuropsychiatric and neurocognitive manifestations of South African children with suspected efavirenz neurotoxicity. Method: This retrospective study describes clinical features of 12 children with features consistent with efavirenz neurotoxicity between 2008 and 2014. Results: Twelve children (4 males, 8 females) aged 3-12 years (median 8.4 years) were referred to a dedicated pediatric neuroHIV service. Eight were of indigenous African (black) ancestry and 4 were of mixed ancestry. The total duration on efavirenz-containing ART at the time of referral was 6-72 (mean 31) months. Two children (both of black ancestry) were phenotypically slow metabolizers and presented with acute manifestations and high plasma efavirenz concentrations above normal range resulting in discontinuation of efavirenz. Ten other children had clinical presentations compatible with efavirenz neurotoxicity but had normal or sub-therapeutic plasma efavirenz concentrations and continued treatment with efavirenz. The acute neuropsychiatric manifestations reported included drowsiness, seizures, sleep disturbances, personality changes, ataxia, and slurred speech. These were noticed 2-8 weeks (mean 5 weeks) after commencing efavirenz and resolved over a few weeks. Nine children had neurocognitive deficits and showed poor performance in all neurocognitive domains that were tested. Interpretation: Efavirenz causes transient neuropsychiatric adverse effects and may contribute to poor long-term neurocognitive outcomes in HIV-infected children. Prospective studies comparing efavirenz-treated and efavirenz-naïve children are needed to further elucidate the manifestations of efavirenz toxicity.

NeuroAIDS in children.

The human immunodeficiency virus-1 (HIV-1) enters the central nervous system compartment within the first few weeks of systemic HIV infection and may cause a spectrum of neurologic complications. Without combination antiretroviral therapy (cART), 50-90% of all HIV-infected infants and children develop some form of neuroAIDS. Of the estimated 2.3 million children less than 15 years of age who were living in sub-Saharan Africa at the end of 2014, only 30% were receiving cART, suggesting that there is a large burden of neuroAIDS among HIV-infected children in sub-Saharan Africa. There is complex interplay between the disease process itself, the child's immune reaction to the disease, the secondary complications, the side-effects of antiretroviral drugs, and inadequate antiretroviral drug uptake into the central nervous system. In addition there is the layering effect from the multiple socioeconomic challenges for children living in low- and middle-income countries. Adolescents may manifest with a range of neurocognitive sequelae from mild neurocognitive disorder through to severe neurocognitive impairment. Neuroimaging studies on white-matter tracts have identified dysfunction, especially in the frontostriatal networks needed for executive function. Psychiatric symptoms of depression, attention deficit hyperactivity disorder, and behavioral problems are also commonly reported in this age group. Antiretroviral drugs may cause treatment-limiting neurologic and neuropsychiatric adverse reactions. The following chapter addresses the neurologic complications known to be, and suspected of being, associated with HIV infection in children and adolescents.

Moyamoya Syndrome in South African Children With HIV-1 Infection.

A national multicenter study identified 17 South African children with vertically acquired HIV-1 infection and HIV-associated vasculopathy. Five of the children (all indigenous African ancestry) had progressive vascular disease, consistent with moyamoya syndrome. Median presentation age 5.8 years (range 2.2-11). The children with moyamoya syndrome presented with abnormal CD4 counts and raised viral loads. Clinical features included motor deficits, neuroregression, and intellectual disability. Neuroimaging supported progressive vascular disease with preceding clinically silent disease course. Neurologic recovery occurred in 1 patient with improved CD4 counts. Four of the 5 children presented during the era when access to antiretroviral therapy was limited, suggesting that with improved management of HIV-1, progressive vasculopathy is less prevalent. However the insidious disease course illustrated indicates that the syndrome can progress "silently," and manifest with misleading phenotypes such as cognitive delay or regression. Sub-Saharan Africa has limited access to neuroimaging and affected children may be underdiagnosed.