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HIV dementia and HIV-related brain impairment (HRBI) Jeanette Meadway FRCP Consultant Physician Mildmay Hospital UK Hackney Road, London E2 7NA What is HIV dementia? An AIDS-defining illness with WHO definition (ICD10) Objectively defined decline in recent memory Evidence of HIV infection Exclusion of opportunistic infections, tumours or other brain disorders Absence of acute brain syndrome (delirium) HIV dementia - cause HIV affecting the brain No HIV in nerve cells (neurons) HIV in macrophages and glial cells Damage due to increased cytokines? Damage due to toxic effects of HIV envelope protein gp120? Damage leads to cell apoptosis (cell death) and structural changes Diagnosis of HIV dementia Function: cognitive impairment, motor dysfunction, behavioural changes HIV disease: usually advanced with low CD4 (<200), high viral load, no ARV treatment or inadequate ARVs despite deterioration CT and MRI scans show brain shrinkage and white matter changes MRI changes Brain shrinkage – rim of CSF inside skull, flattened gyri White matter changes, most likely to affect frontal lobes as in this scan (contrast medium in ventricles) What is HIV-related brain impairment? Not a diagnosis, an assessment of function which is useful for rehabilitation Cognitive dysfunction (+- behaviour change and motor dysfunction) due to HIV-related pathology Includes HIV-related illnesses causing cognitive impairment Does not include unrelated brain impairment in an HIV+ve person eg due to alcohol The same diagnoses are not included in HRBI if there is no cognitive dysfunction Why this definition of HRBI? The conditions which lead to behavioural problems, cognitive impairment and motor problems in the context of advanced HIV offer the same challenge for rehabilitation All are likely to benefit from supervised adherence to ARVs, multidisciplinary approach to social skills and other rehabilitation HRBI diagnoses HIV dementia PML (progressive multifocal leukoencephalopathy) due to JC virus Cerebral toxoplasmosis Herpes simplex virus encephalopathy Cryptococcal meningitis Cerebral lymphoma other infections eg TB meningitis Cerebral toxoplasmosis When CD4 low toxoplasma causes a cerebral abscess When contrast is injected, there is high uptake around the abscess – a ringenhancing lesion Toxoplasma may cause cognitive impairment Cryptococcal Meningitis Cryptococcal meningitis is more insidious than bacterial meningitis Varied neurological changes occur eg cognitive impairment PML Progressive – without treatment deteriorating neurology and death Multifocal – affects separate parts of the brain, as seen with 3 in this scan Leuko – affects white matter HRBI rehab at Mildmay Patients accidentally rehabbed at first Those improving had full effective ARVs and full multidisciplinary team involvement Emphasis on self-medication programme, relearning social skills and skills to allow independent activity Some patients return to live independently Behavioural improvements allow more appropriate placements for most patients A new type of dementia A patient restarted on ARVs later deteriorated and died despite fully controlled viral load and good CD4 PM showed no HIV in brain, no other infections or tumours, and vacuolated cells This may be immune reconstitution syndrome Occurs only in a minority of patients Summary - HRBI Cognitive +- behavioural and motor impairment due to HIV disease Occurs only in advanced HIV Most improve with full regular ARVs Improvement with rehab team input Rehab allows easier placement and improved quality of life Deterioration on ARVs is uncommon