Abstract:This study evaluated the degree of neurological compromise in HIV-infected children accompanied by the outpatient clinic of infectious diseases and pediatric neurology of the Clinical Hospital of the Federal University of Paraná (UFPR) starting in 1995. Long-term progressive prospective and cross sectional study of 88 children infected by HIV and 84 seroreverter children, using data from general neurological examinations, neuroimaging procedures (brain CT scan) and neurodevelopmental tests (CAT/CLAMS and DENVE… Show more
“…This is not surprising, since much of CNS development occurs after birth, and the immature brains of children or adolescents exposed to HIV are highly vulnerable to pathologic agents. CNS disease in pediatric HIV patients manifested as static or progressive encephalopathy, with classic symptoms including delay or loss of major motor and mental milestones, and atrophy of cortical/subcortical regions and other abnormalities on CT scans (Drotar et al 1997; Epstein et al 1988; Schwartz and Major 2006; Tahan et al 2006; Ultmann et al 1985; Van Rie et al 2007). In developed countries, rates of HIV-1 vertical transmission have been reduced to 1–2%, from 40% in 1995 (Buchholz et al 2010; Van Dyke 2011).…”
HIV-associated neurocognitive disorders (HAND) are common sequelae of HIV infection, even when viral titers are well controlled by anti-retroviral therapy. Evidence in patients and animal models suggests that neurologic deficits are increased during chronic opiate exposure. We have hypothesized that CNS progenitor cells in both adult and developing CNS are affected by HIV infection, and that opiates exacerbate these effects. To examine this question, neural progenitors were exposed to HIV-1 Tat1-86 in the developing brain of inducible transgenic mice and in vitro. We examined whether Tat affected the proliferation or balance of progenitor populations expressing nestin, Sox2, and Olig2. Disease relevance was further tested by exposing human-derived progenitors to supernatant from HIV-1 infected monocytes. Studies concentrated on striatum, a region preferentially targeted by HIV and opiates. Results were similar among experimental paradigms. Tat or HIV exposure reduced the proliferation of undifferentiated (Sox2+) progenitors and oligodendroglial (Olig2+) progenitors. Co-exposure to morphine exacerbated the effects of Tat or HIV-1SF162 supernatant, but partially reversed HIV-1IIIB supernatant effects. Populations of Sox2+ and Olig2+ cells were also reduced by Tat exposure, although progenitor survival was unaffected. In rare instances, p24 immunolabeling was detected in viable human progenitors by confocal imaging. The vulnerability of progenitors is likely to distort the dynamic balance among neuron/glial populations as the brain matures, perhaps contributing to reports that neurologic disease is especially prevalent in pediatric HIV patients. Pediatric disease is atypical in developed regions, but remains a serious concern in resource-limited areas where infection occurs commonly at birth and through breast-feeding.
“…This is not surprising, since much of CNS development occurs after birth, and the immature brains of children or adolescents exposed to HIV are highly vulnerable to pathologic agents. CNS disease in pediatric HIV patients manifested as static or progressive encephalopathy, with classic symptoms including delay or loss of major motor and mental milestones, and atrophy of cortical/subcortical regions and other abnormalities on CT scans (Drotar et al 1997; Epstein et al 1988; Schwartz and Major 2006; Tahan et al 2006; Ultmann et al 1985; Van Rie et al 2007). In developed countries, rates of HIV-1 vertical transmission have been reduced to 1–2%, from 40% in 1995 (Buchholz et al 2010; Van Dyke 2011).…”
HIV-associated neurocognitive disorders (HAND) are common sequelae of HIV infection, even when viral titers are well controlled by anti-retroviral therapy. Evidence in patients and animal models suggests that neurologic deficits are increased during chronic opiate exposure. We have hypothesized that CNS progenitor cells in both adult and developing CNS are affected by HIV infection, and that opiates exacerbate these effects. To examine this question, neural progenitors were exposed to HIV-1 Tat1-86 in the developing brain of inducible transgenic mice and in vitro. We examined whether Tat affected the proliferation or balance of progenitor populations expressing nestin, Sox2, and Olig2. Disease relevance was further tested by exposing human-derived progenitors to supernatant from HIV-1 infected monocytes. Studies concentrated on striatum, a region preferentially targeted by HIV and opiates. Results were similar among experimental paradigms. Tat or HIV exposure reduced the proliferation of undifferentiated (Sox2+) progenitors and oligodendroglial (Olig2+) progenitors. Co-exposure to morphine exacerbated the effects of Tat or HIV-1SF162 supernatant, but partially reversed HIV-1IIIB supernatant effects. Populations of Sox2+ and Olig2+ cells were also reduced by Tat exposure, although progenitor survival was unaffected. In rare instances, p24 immunolabeling was detected in viable human progenitors by confocal imaging. The vulnerability of progenitors is likely to distort the dynamic balance among neuron/glial populations as the brain matures, perhaps contributing to reports that neurologic disease is especially prevalent in pediatric HIV patients. Pediatric disease is atypical in developed regions, but remains a serious concern in resource-limited areas where infection occurs commonly at birth and through breast-feeding.
“…In HIV-infected children, basal ganglia calcification is a common finding among patients with abnormal imaging. 25 These patients almost uniformly have developmental delay.…”
“…3 The prevalence of these specific neurologic complications in children with HIV-1 is limited to a few studies (Table 1). [4][5][6][7][8][9][10][11][12][13] A systematic review of 6 studies in Sub-Saharan Africa reported severe motor impairment and moderate cognitive impairment at 18 months of age in HIV-1 infected children. 14 A study from the Democratic Republic of Congo showed that environmental factors contribute to developmental dysfunction.…”
The range and extent of neurologic and neurobehavioral complications of human immunodeficiency virus (HIV-1) infection in children are under-described. Seventy-eight children with HIV-1 infection (32 females) were assessed for neurologic complications. Forty-six children had abnormal neurology examinations. Thirty-three children had global pyramidal tract signs, 5 had a hemiparesis, 4 had peripheral neuropathy, 18 had visual impairment, and 5 had hearing impairment. Thirty-nine of 63 children over 1 year of age had neurobehavioral problems. Of 24 children with HIV encephalopathy, 74% had severe immunosuppression and 45% were not receiving antiretroviral therapy. Twelve children had prior opportunistic central nervous system infections, and 9 had epilepsy. Diverse neurologic and neurobehavioral deficits are common in children with HIV-1 infection. Children with severe immunosuppression, who were not receiving antiretroviral therapy, were growth impaired and less than 1 year of age, were at greatest risk for developing neurologic complications.
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