A human immunodeficiency virus type 1 (HIV)—seropositive, antiretroviral-naive patient presented with significant cognitive dysfunction. Neuropsychologic, neuroradiologic, immunologic, and virologic studies confirmed HIV-associated dementia (HAD). After 12 weeks of highly active antiretroviral therapy (HAART) with ibuprofen, dramatic improvements were demonstrated in neurologic function and were sustained for >1 year. HIV-1 RNA in cerebrospinal fluid (CSF) decreased from 105 to 104 copies/mL after 4 weeks. After 20 weeks of therapy, plasma viremia decreased from 106 copies/mL to undetectable (<96 copies/mL). Assays of neurotoxins (tumor necrosis factor-α, quinolinic acid, and nitric oxide) in plasma and CSF were considerably elevated at presentation and significantly decreased after therapy. Baseline plasma and CSF demonstrated neurotoxic activities in vitro, which also reduced markedly. These data, taken together, support the notion that HAD is a reversible metabolic encephalopathy fueled by viral replication. HAART used with nonsteroidal antiinflammatory agents leads to the suppression of inflammatory neurotoxins and can markedly improve neurologic function in HAD.
—Neuropathologic evaluation was performed on an infant with fetal alcohol effects.
Design.
—Coronal brain sections and representative tissue blocks stained with hematoxylin-eosin, silver stain, and immunocytochemical stains for hypothalamic and pituitary hormones were evaluated for neuropathologic abnormalities.
Patient.
—A 2.5-month-old American Indian girl who had been exposed to first-trimester maternal binge alcohol abuse died after persistent problems of growth failure, sodium imbalance, aberrant temperature regulation, respiratory distress, and seizures.
Results.
—Autopsy revealed severe microcephaly, hypertelorism, midfacial hypoplasia, a high-arched palate, shortened palpebral fissures, and a small brain. The frontal lobes were fused anteriorly; olfactory bulbs and tracts were absent; and optic nerves were hypoplastic. An enlarged and bulbous hypothalamus obscured the pituitary gland. The thalamus and caudate nuclei were fused across the midline. Posteriorly, the single ventricle split to form rudimentary lateral horns. The anterior corpus callosum, septum pellucidum, fimbria, and fornices could not be identified. The anterior commissure and supraoptic nuclei were microscopically present. Many Purkinje cells were horizontally positioned, with abnormal dendritic structure. The posterior pituitary lobe was absent, and the infundibulum was flanked by a hypoplastic adenohypophysis and a large subarachnoid heterotopia. Immunocytochemical studies identified only vasopressin and neurophysin in the hypothalamus and only growth hormone and prolactin in the pituitary gland.
Conclusion.
—To our knowledge, an association between fetal alcohol effects and a complex cerebral anomaly with features of incomplete holoprosencephaly and septo-optic dysplasia has not previously been reported and suggests a possible common pathogenesis needing further study.
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