1. HIV dementia and HIV-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. 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)

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. Cerebral toxoplasmosis  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

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

12. 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

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