HIV dementia andHIV dementia andHIV-related brain HIV-related brain

impairment (HRBI)impairment (HRBI)Jeanette Meadway FRCPJeanette Meadway FRCP

Consultant PhysicianConsultant PhysicianMildmay Hospital UKMildmay Hospital UK

Hackney Road, London E2 7NAHackney Road, London E2 7NA

What is HIV dementia?What is HIV dementia?

An AIDS-defining illness with WHO An AIDS-defining illness with WHO definition (ICD10)definition (ICD10)

Objectively defined decline in recent Objectively defined decline in recent memorymemory

Evidence of HIV infectionEvidence of HIV infection Exclusion of opportunistic infections, Exclusion of opportunistic infections,

tumours or other brain disorderstumours or other brain disorders Absence of acute brain syndrome Absence of acute brain syndrome

(delirium) (delirium)

HIV dementia - causeHIV dementia - cause

HIV affecting the brainHIV affecting the brain No HIV in nerve cells (neurons)No HIV in nerve cells (neurons) HIV in macrophages and glial cellsHIV in macrophages and glial cells Damage due to increased cytokines?Damage due to increased cytokines? Damage due to toxic effects of HIV Damage due to toxic effects of HIV

envelope protein gp120?envelope protein gp120? Damage leads to cell apoptosis (cell Damage leads to cell apoptosis (cell

death) and structural changesdeath) and structural changes

Diagnosis of HIV dementiaDiagnosis of HIV dementia

Function: cognitive impairment, Function: cognitive impairment, motor dysfunction, behavioural motor dysfunction, behavioural changeschanges

HIV disease: usually advanced with HIV disease: usually advanced with low CD4 (<200), high viral load, no low CD4 (<200), high viral load, no ARV treatment or inadequate ARVs ARV treatment or inadequate ARVs despite deteriorationdespite deterioration

CT and MRI scans show brain CT and MRI scans show brain shrinkage and white matter changesshrinkage and white matter changes

MRI changesMRI changes

Brain shrinkage – Brain shrinkage – rim of CSF inside rim of CSF inside skull, flattened gyriskull, flattened gyri

White matter White matter changes, most changes, most likely to affect likely to affect frontal lobes as in frontal lobes as in this scanthis scan

(contrast medium (contrast medium in ventricles) in ventricles)

What is HIV-related brain What is HIV-related brain impairment?impairment?

Not a diagnosis, an assessment of function Not a diagnosis, an assessment of function which is useful for rehabilitationwhich is useful for rehabilitation

Cognitive dysfunction (+- behaviour Cognitive dysfunction (+- behaviour change and motor dysfunction) due to HIV-change and motor dysfunction) due to HIV-related pathologyrelated pathology

Includes HIV-related illnesses causing Includes HIV-related illnesses causing cognitive impairmentcognitive impairment

Does not include unrelated brain Does not include unrelated brain impairment in an HIV+ve person eg due to impairment in an HIV+ve person eg due to alcohol alcohol

The same diagnoses are not included in The same diagnoses are not included in HRBI if there is no cognitive dysfunctionHRBI if there is no cognitive dysfunction

Why this definition of HRBI?Why this definition of HRBI?

The conditions which lead to The conditions which lead to behavioural problems, cognitive behavioural problems, cognitive impairment and motor problems in impairment and motor problems in the context of advanced HIV offer the the context of advanced HIV offer the same challenge for rehabilitationsame challenge for rehabilitation

All are likely to benefit from All are likely to benefit from supervised adherence to ARVs, supervised adherence to ARVs, multidisciplinary approach to social multidisciplinary approach to social skills and other rehabilitation skills and other rehabilitation

HRBI diagnosesHRBI diagnoses

HIV dementia HIV dementia PML (progressive multifocal PML (progressive multifocal

leukoencephalopathy) due to JC virusleukoencephalopathy) due to JC virus Cerebral toxoplasmosisCerebral toxoplasmosis Herpes simplex virus encephalopathyHerpes simplex virus encephalopathy Cryptococcal meningitisCryptococcal meningitis Cerebral lymphomaCerebral lymphoma other infections eg TB meningitisother infections eg TB meningitis

Cerebral toxoplasmosisCerebral toxoplasmosis When CD4 low When CD4 low

toxoplasma causes toxoplasma causes a cerebral abscessa cerebral abscess

When contrast is When contrast is injected, there is injected, there is high uptake high uptake around the around the abscess – a ring-abscess – a ring-enhancing lesionenhancing lesion

Toxoplasma may Toxoplasma may cause cognitive cause cognitive impairmentimpairment

Cryptococcal MeningitisCryptococcal Meningitis

Cryptococcal Cryptococcal meningitis is meningitis is more insidious more insidious than bacterial than bacterial meningitismeningitis

Varied Varied neurological neurological changes occur eg changes occur eg cognitive cognitive impairmentimpairment

PMLPML

Progressive – Progressive – without treatment without treatment deteriorating deteriorating neurology and neurology and deathdeath

Multifocal – affects Multifocal – affects separate parts of separate parts of the brain, as seen the brain, as seen with 3 in this scanwith 3 in this scan

Leuko – affects Leuko – affects white matterwhite matter

HRBI rehab at MildmayHRBI rehab at Mildmay

Patients accidentally rehabbed at firstPatients accidentally rehabbed at first Those improving had full effective ARVs Those improving had full effective ARVs

and full multidisciplinary team and full multidisciplinary team involvementinvolvement

Emphasis on self-medication programme, Emphasis on self-medication programme, relearning social skills and skills to allow relearning social skills and skills to allow independent activityindependent activity

Some patients return to live independentlySome patients return to live independently Behavioural improvements allow more Behavioural improvements allow more

appropriate placements for most patients appropriate placements for most patients

A new type of dementiaA new type of dementia

A patient restarted on ARVs later A patient restarted on ARVs later deteriorated and died despite fully deteriorated and died despite fully controlled viral load and good CD4controlled viral load and good CD4

PM showed no HIV in brain, no other PM showed no HIV in brain, no other infections or tumours, and infections or tumours, and vacuolated cellsvacuolated cells

This may be immune reconstitution This may be immune reconstitution syndromesyndrome

Occurs only in a minority of patientsOccurs only in a minority of patients

Summary - HRBISummary - HRBI

Cognitive +- behavioural and motor Cognitive +- behavioural and motor impairment due to HIV disease impairment due to HIV disease

Occurs only in advanced HIVOccurs only in advanced HIV Most improve with full regular ARVsMost improve with full regular ARVs Improvement with rehab team inputImprovement with rehab team input Rehab allows easier placement and Rehab allows easier placement and

improved quality of lifeimproved quality of life Deterioration on ARVs is uncommonDeterioration on ARVs is uncommon