pyrimidinones and AIDS-Dementia-Complex

Neuro-inflammation accompanies numerous neurological disorders and conditions where it can be associated with a progressive neurodegenerative pathology. In a similar manner, alterations in sphingolipid metabolism often accompany or are causative features in degenerative neurological conditions. These include dementias, motor disorders, autoimmune conditions, inherited metabolic disorders, viral infection, traumatic brain and spinal cord injury, psychiatric conditions, and more. Sphingolipids are major regulators of cellular fate and function in addition to being important structural components of membranes. Their metabolism and signaling pathways can also be regulated by inflammatory mediators. Therefore, as certain sphingolipids exert distinct and opposing cellular roles, alterations in their metabolism can have major consequences. Recently, regulation of bioactive sphingolipids by neuro-inflammatory mediators has been shown to activate a neuronal NADPH oxidase 2 (NOX2) that can provoke damaging oxidation. Therefore, the sphingolipid-regulated neuronal NOX2 serves as a mechanistic link between neuro-inflammation and neurodegeneration. Moreover, therapeutics directed at sphingolipid metabolism or the sphingolipid-regulated NOX2 have the potential to alleviate neurodegeneration arising out of neuro-inflammation.

Topics: AIDS Dementia Complex; Animals; Biological Products; Brain Diseases, Metabolic, Inborn; Drug Discovery; Encephalitis, Viral; Enzyme Activation; Enzyme Replacement Therapy; Humans; Inflammation; NADPH Oxidase 2; Naphthalenes; Nerve Tissue Proteins; Neurodegenerative Diseases; Neurons; Oxidation-Reduction; Pyrimidinones; Reactive Oxygen Species; Sphingolipids; Zika Virus Infection

Subacute central nervous system infection must be considered in any infant presenting with progressive encephalopathy. We present the case of an 18-month-old child with normal neuromotor development until the age of 14 months admitted for spastic hypertonia of the legs and arms associated with axial hypotonia. The mother reported that she recently had been found to be HIV-seropositive. HIV antibodies were negative during the first trimester of pregnancy. On the child's blood sample, the HIV test was positive associated with a major decrease in CD4 cell count. Viral load (ARN-PCR) was 720 copies par millilitre. On brain MRI, hypersignals were found in the white matter. HIV related encephalopathy caused by maternal fetal transmission was diagnosed. After 2 months of antiretroviral treatment (azidothymidine, lamivudine, and boosted lopinavir), the child's neurological condition improved. HIV infection must be suspected in all infants with progressive encephalopathy. The HIV test in pregnant women must be proposed at the beginning of pregnancy and repeated during the last trimester.

Topics: AIDS Dementia Complex; Anti-HIV Agents; Anti-Infective Agents; Drug Therapy, Combination; Female; Fluconazole; HIV Infections; HIV Protease Inhibitors; HIV Seropositivity; HIV-1; Humans; Infant; Infectious Disease Transmission, Vertical; Lamivudine; Lopinavir; Polymerase Chain Reaction; Pyrimidinones; Reverse Transcriptase Inhibitors; RNA, Viral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine