NEUROLOGICAL MANIFESTATIONS OF HIV INFECTION

AN UPDATE

Dr. Dibbendhu Khanra

HIV ENTRY – TROJAN HORSE THEORY

Presenting feature of HIV/ AIDS in 10-20%

Neurologic complications are present in more than 40% of PLHA

Autopsy - prevalence of neuro-pathologic abnormalities in 80%

NEUROLOGICAL COMPLICATIONS OF HIV/AIDS

HIV itself• HAND• HIV neuropathy• Aseptic meningitis• HIV myelopathy• HIV myopathy OI• TB• Toxoplasma• Cryptococcus• PML• CMV Lymphoma ART related

CHANGING PARADIGM

1981-1994 – OI, ADC 1995-2006 - HAART,

Decline of CNS complications

2007-2012 - DSPN, HAND, CHAIN

‘’The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART’’ - CHARTER’ 2010

‘’The association of sustained impairment with worse current immune status (low CD4 cell count) suggests that restoring immuno-competence increases the likelihood of neuro-cognitive recovery.’’ - ALLRT ‘2007

ASSESSMENT OF HAND

Cognition• Modified HIV Dementia

Scale Memory registration Motor speed Memory recall construction

Motor• Timed Gait• Paper based tapping test Neuropsychology• Trails Making Test A & B• Figural Visual Scanning Task• Digit-Symbol Task (WAIS-R)

Spectrum of HAND

Cognitive impairment

>=2 domains1.Language2.Attention3.Execution4.Memory

5.Motor skill6.Information

processing

Impairment of

everyday function1.Mental

acuity2.Efficiency in work3.Social

functioning

ANI >=1 SD below expected

no/mild

MND >=1 SD below expected

moderate

ADC >=2 SD below expected

severe

Stages of ADC

PATHOGENESIS AND CO-FACTORS

Fronto-striatal pathway injury

WM abnormality with increased volume of gray matter

Atorphy of posterior cerebellar vermis. Neuronal loss of granular/ perkinje cell layer of cerebellum.

Decreased thickness of corpus callosum.

Expansion of ventricular size

Low NAA in frontal cortex

High level of Glx in basal ganglia

Activated Kynurenine pathway

QUIN correlated with greater cell loss in striatum and limbic cortex

Increased QUIN in CSF and correlation with HAND svereity

QUIN elevates CCR5 expression and viral replication

CSF viral loadCD4

Metabolic causesElevated BMIPoor nutrition

DepressionCocaine abuseCo-infection (HCV, VZV)

MANAGING HAND

CART CPE score MME score

Thalidomite

Memantine Nimodipine Selegiline Minocyclin

e Lexipafant PDGF-BB

HIV AND CEREBRAL SOL

TOXO

PCNSL

TBCRYPTO

PML V/S HIVE

PML

HIVE

MS

STROKE IN HIV

Prevalence: 6 - 34% – 9.1 for infarction – 12.7 for ICH Young patients: 33.4

yrs v/s 64.0 yrs in HIV negative

42% of HIV+ stroke were first HIV dx

Meningitis- 28% Vasculitis – 20% Vasculopathy – 20% Coagulopathy - 19% Cardioembolic -14%

EPIDEMIOLOGY ETIOLOGY

HIV MYELOPATHY

In 55% patients dying of AIDS

In advanced immuno-suppression

Cervical> thoracic Sensory-motor deficits Brisk DTRs Associated Vit B12

deficiency Lipid-laden

macrophages Others: HTLV,VZV,CMV,

spinal Lymphoma

HIV PERIPHERAL NEUROPATHY

Distal sensory polyneuropathy(DSPN)

MC neuropathy in HIV/AIDS 33% patients of HIV/AIDS Present in 88% in autopsy With low CD4 count Stocking-glove sensory loss

Mononeuritis multiplex Inflammatory demyeliting

polyradiculopathy

Polymyositis Nemaline (rod body)

myopathy Vacuolar myopathy IBM

Peripheral neuropathy

CVA Psychiatric

manifestations Myopathy IRIS

HIV myopathy ART induced