HIV ASSOCIATED NEUROLOGICAL

MANIFESTATIONS
OBJECTIVES

• Understand the effects of HIV on the

neurological system
• The spectrum of neurological disease in the
context of HIV (neuropathogenesis)
• Common central nervous system conditions –
infections, malignancies, HAND
• HIV- related pathology of the peripheral nervous
system
Case study: Mr TN

28 year old man

History
• 2 year history of skin rashes, Herpes Zoster and
numbness of lower limbs – treated at local clinic
• 3 months ago HIV test positive
• CD4 count 265
• Commenced on CMZ prophylaxis
• Now comes with 10 day history of ‘flu’ & headaches
not responding to Pynstop
Mr TN

• Nausea and occasional vomiting for past 3 days

• No cough
• Some weight loss, trousers loose & belt tightened
• Progressive weakness in legs, blurred vision
Examination
• Unwell, T 37, not pale, no thrush, no LN, ‘wet towel
sign’ +ve
• RS, CVS, ABD all normal
• CNS – mild neck stiffness, generalised ↓ tone
 Mr TN

Assessment ??
• Differential diagnosis?
• WHO Stage?

Plan??
• Investigations
• Treatment
NEUROLOGICAL COMPLICATIONS OF
HIV OVERVIEW
• Can happen at the time of seroconversion
• Occur in 30-50% during the course of the
disease
• Are detected in >90% at autopsy
• Affect central and peripheral nervous system
• Side effects of antiretroviral medications on
the nervous system
WIDE SPECTRUM OF NEUROLOGICAL DISEASES

• Opportunistic
infections
• Opportunistic
tumors
• Neurotoxicity of HIV
itself
• Complications of
ART
• Co-morbidities

www.ruedi-luethy-
foundation.ch
NEUROLOGICAL MANIFESTATIONS OF
THE CNS ASSOCIATED WITH HIV
• Meningitis: fungal (Cryptococci), bacterial (TB,
Meningococci, Pneumococci), viral (HSV, CMV)
• Space occupying lesion: Toxoplasmosis,
lymphoma, tuberculoma, neurosyphilis, brain
abscess
• Degenerative: HIV-Associated Neuro-cognitive
Disorders (HAND), AIDS Dementia Complex
(ADC), progressive multifocal
leukoencephalopathy (PML)
• Vascular accidents: Stroke
CRYPTOCOCCAL MENINGITIS (CM)

• Cryptococcal disease is one of the most important

OIs, and a major contributor to early mortality of
patients infected with HIV, accounting for 13% to
44% of deaths in resource-limited countries
• CM is the leading cause of community-acquired
meningitis in sub-Saharan Africa and is estimated
to cause more than 600,000 deaths per year which
may exceed those attributed to tuberculosis
• CM is the cause of death in as many as 20%–30%
of patients with AIDS and the case fatality rate is
between 35%-65%
SYMPTOMS AND SIGNS OF
CRYPTOCOCCAL MENINGITIS
• Clinical signs and symptoms very subtle, may
evolve over weeks to months.
• Headache often insidious, may be severe
• Impaired consciousness in later stages
– Confusion, depressed level of
consciousness, seizures, psychosis
• Cranial nerve palsies (including decreased
vision or hearing), localizing lesions, blindness
DIAGNOSIS OF CRYPTOCOCCAL
MENINGITIS
• Lumbar puncture is essential:
– CSF microscopy
• India ink
• Gram stain
– Biochemistry (glucose, protein)
– (Fungal culture)
– Cryptococcal antigen test (CrAg)
– Measure CSF pressure if possible
DIAGNOSIS OF CRYPTOCOCCAL
MENINGITIS
• India ink positive in 75%
• Gram stain may show yeasts
• CrAg positive 99% on CSF (98% in serum)
• Culture almost always positive within 48 hours
TREATMENT OF CRYPTOCOCCAL
MENINGITIS
• Amphotericin B: 1.0 mg / kg given as an infusion
over 24 hrs, daily for 14 days, continue with
fluconazole to complete 6 weeks of initial treatment
• Fluconazole 800-1200mg daily for 6-10 weeks,
watch out for hepatotoxicity!
• Maintenance-Therapy: Fluconazole 200 mg OD
Adults: discontinue if CD4 has remained > 100
for > 6 months and no signs and symptoms of
cryptococcosis and suppressed VL
Children: continue, until more data available
ANCILLARY TREATMENT

• Pain Control:
– Paracetamol
– Opiates
• Raised CSF Pressure Management:
– Consider when headache severe or when there
is clinical deterioration
– Therapeutic LP tap till pressure below 20cm
• can require removal of 20 - 25 ml
• many require multiple LP taps
CM Disease Screening

• Screen all HIV infected persons with CD4 <100

using serum CrAg before commencing ART
• Patients who have had CM previously do not
need to be screened
• CrAg Negative: Initiate ART, no need for
fluconazole
• CrAg Positive: Manage according to algorithm
 CrAg Positive

Screen for symptoms of meningitis

Symptomatic Asymptomatic

Start Fluconazole 1200mg daily and

LP
LP negative for CM

LP positive for CM
Fluconazole 800mg daily
Treat for Cryptococcal Meningitis x 2 weeks then 400mg
daily for 2 months then
200mg daily. Start ART
after 2/52
Start ART after 4 – 6 weeks
 TB-MENINGITIS
• Symptoms: Headache, meningism, fever (low grade),
reduced alertness, focal deficits (20%) especially
cranial nerve lesions
• Sometimes seizures and loss of consciousness
• Cranial nerve palsies result from exudates around
base of the brain
• Up to 40% have an abnormal chest X-ray
• 10% of AIDS patients who present with TB will show
involvement of the meninges
• 1% of all TB cases involve the central nervous
system
 DIAGNOSIS OF TB-MENINGITIS
• Lumbar puncture: lymphocytosis, high lactate,
high protein, low glucose, AFB (seldom
positive), culture
• Clinically suspect if:
– Slow onset neuro symptoms (+/- 2 weeks)
– Presence of abdominal lymph nodes
– Presence of abnormal chest X-ray
• CT scan: enhancement of meninges, single
lesion (tuberculoma)
• Mantoux pos in 20-30% only because of
immune suppression
TREATMENT OF TB MENINGITIS

• TB treatment according to national protocol for

12 months
• In case of severe neurological signs (cranial
nerve lesions, drowsiness, coma), use
prednisolone 1 mg/kg for 2-4 weeks, then taper
off over 4-6 weeks
HIV ASSOCIATED NEUROCOGNITIVE
DISORDERS (HAND)
• One of the common manifestations of HIV/AIDS
is neurocognitive impairments – changes in how
fast a person can process information, pay
attention, multi-task and remember things
• There is a lack of adequate screening tests
• The severe form of HAND has ↓ significantly
with the availability of ART
• The prevalence of the minor form of HAND has
slightly ↑, affecting 50 to 60% of PLWH
HIV ASSOCIATED NEUROCOGNITIVE
DISORDERS (HAND)
• Identifying patients with mild HAND is important
• The condition can have a significant impact on
a patient’s everyday functioning, affecting their
ability to adhere to medications, perform at
work, it may lead to social withdrawal and
isolation
• The 2 tests (HIV Dementia Scale & International
Dementia Scale) were shown to be ineffective in
identifying the mild form of HAND
AIDS Dementia Complex (ADC) or HIV-
associated Dementia
• Subcortical dementia
• Progressive disabling disorder manifested as ↑ in loss of
attention & concentration
• Motor slowing
• Various behavioural components
• Generally → death within 1 year.
• Associated with pathological changes in the brain
including generalised atrophy, changes in white matter
→ leuco-encephalopathy, microglial nodules typical of
viral encephalitis, multinucleated giant cells
EARLY SYMPTOMS OF HAND

• Forgetfulness
• Loss of concentration
• Deterioration in handwriting
• Loss of balance
DIAGNOSIS OF HAND

• Diagnosis of exclusion
• Cerebro-spinal fluid commonly normal
• Diagnostic tool: HIV Dementia Scale
– Internationally validated but only detects more
advanced HAND
– Sensitivity: 80%, specificity: 60%
– 3 items are tested: memory (recall 4 words),
motor (finger-tapping with non-dominant hand),
psychomotor (sequence of movements with
non-dominant hand)
 CT-SCAN OF PATIENT WITH HAND

Brain atrophy
TREATMENT OF HAND

• Use ARVs with good penetration of the blood-

brain barrier:
• NRTIs: choose AZT or abacavir
• NNRTIs: choose nevirapine
• PIs: choose lopinavir/ritonavir
SPINAL CORD AND PERIPHERAL
NERVOUS SYSTEM DISEASES
Myelopathy
Progressive polyradiculopathy
Mononeuritis multiplex
Distal symmetrical sensory polyneuropathy

Can occur at all stages of the HIV-infection!

Most important differential diagnosis:
ART-associated toxicity (Zidovudine/Stavudine)
HIV SENSORY NEUROPATHIES
• HIV sensory neuropathies are common, prevalence
30%
• Aetiology variable:
– HIV
– Neurotoxic ART (‘d’ drugs) – mitochondrial
toxicity
– Other drugs (Isoniazid)
– Vitamin deficiency (vitamin B6)
– Alcohol, diabetes mellitus
• Primary symptoms: pain, dysaesthesia,
paraesthesia
– Symmetrical, starts in feet
• Few proven restorative or symptomatic treatments
 Pain management: paracetamol, NSAID’s, may
need morphine, amitryptyline, carbamazepine of
limited benefit, unless high doses are used,
frequently under-treated !
Thank you!