HIV dementia and HIV-related brain impairment (HRBI)

1. HIV dementia andHIV-related brain impairment (HRBI) Jeanette Meadway FRCP Consultant Physician Mildmay Hospital UK Hackney Road, London E2 7NA

2. 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)

3. 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

5. 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

6. 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) MRI changes

7. 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

8. 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

9. 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

10. When CD4 low toxoplasma causes a cerebral abscess When contrast is injected, there is high uptake around the abscess – a ring-enhancing lesion Toxoplasma may cause cognitive impairment Cerebral toxoplasmosis

11. Cryptococcal meningitis is more insidious than bacterial meningitis Varied neurological changes occur eg cognitive impairment Cryptococcal Meningitis

12. 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 PML

13. 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

14. 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

15. 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