Human immunodeficiency

virus–associated neurological disease

 Prevalence
• Almost 75 million people have been infected
with the HIV virus 
• Around 36 million people have died of HIV
• Globally, 35.3 million [32.2–38.8 million] people
were living with HIV at the end of 2012.
• An estimated 0.8% of adults aged 
15–49 years worldwide are living with HIV
• Sub-Saharan Africa remains most severely
affected, with nearly 1 in every 20 adults living
with HIV
• HIV is neuroinvasive with early involvement of
the nervous system
• There is potential to cause disease at any site
of the neuro-axis during the evolution from
seroconversion to late stage HIV.
• Disease may result from: direct viral infection,
opportunistic infections, AIDS-defining
cancers, antiretroviral therapy,
• Highly active antiretroviral therapy (HAART) is
effective in suppressing systemic human
immunodeficiency virus (HIV) viral load
• This has led to a decrease in mortality rates in patients
with HIV infection and reduced the incidence of
opportunistic infections in AIDS
• However with this the spectrum of CNS diseases has
remained relatively unchanged
• CNS diseases can result in long hospital stays, reduced
quality of life and marked disability.
 Directed HIV related disease
• Primary infection (seroconversion) may
present as a neurological illness; aseptic
meningitis, facial palsy, Guillain-Barré
syndrome and transverse myelitis
• Only 1–4% of patients will develop acute
neurological disease at this time
 Aseptic meningitis
• Aseptic meningitis is the most common and can
also occur in early disease when it can be
asymptomatic.
• It is indistinguishable from enteroviral or other
lymphocytic meningitides, but may be associated
with unilateral or bilateral facial palsy.
• HIV-RNA is positive on CSF examination.
• Its course is benign but in 1–3% may be severe
when ARV treatment is recommended.
 Guillian Barré
• GB syndrome is rare

• HIV accounts for 10% of cases and therefore

screening is essential.

• Investigation and treatment are identical to

non-HIV-related disease.
 HIV-associated neurocognitive disorders
(HAND)
• This is the umbrella term to describe
neurodegenerative disease caused by chronic HIV
infection.
• Consists of asymptomatic neurocognitive impairment
(ANI), HIV-associated mild neurocognitive disorder
(MND) and HIV-associated dementia (HAD).
• Incidences ranging from 29% to 69% in the HIV positive
population
• Associated with High viral CNS load, current nadir of
CD4 counts and co infection with Hep C
 HIV-associated dementia (HAD)
• HIV-associated dementia (HAD) is the most severe form
of HAND
• Significant decline in cognition with functional
impairment
• Patients can exhibit signs of spasticity and
extrapyramidal signs
• Imaging shows widespread atrophy and CSF levels of
HIV-RNA are high.
• The diagnosis remains clinical, it is important to exclude
other potentially reversible causes of dementia
 Vacuolar myelopathy
• Most common chronic myelopathy associated with HIV 
• It is HIV-specific and can occur at any stage but is more
likely when the CD4 is <50 c/mm3
• The impaired ability to utilize vitamin B-12 as a source
of methionine in transmethylation metabolism for
myelin maintenance in the spinal cord
• presents as a slow progression of painless leg
weakness, spastic paraperisis, sensory ataxia,
hyperreflexia and incontinence
• Treatment is Supportive
Opportunistic infections
 Cerebral toxoplasmosis
• Frequent cause of focal brain disease in HIV
infection.
• Caused by the Protozoan Tonoplasma gondii.
Primary infection occurs after the ingestion of
infected cysts
• Toxoplasmic encephalitis is almost always
caused by reactivation of Toxoplasma gondii
cysts in brain parenchyma.
 Cerebral toxoplasmosis
• Clinical disease occurs typically the CD4 count
is <100 c/mm3
• Patients present with headache, fever,
seizures, confusion and focal neurological
deficits.
• Imaging demonstrates multiple ring enhancing
lesions, with marked surrounding oedema.
Cerebral toxoplasmosis
 Cerebral toxoplasmosis – Diagnosis +
treatment
• Diagnosis of cerebral toxoplasmosis based on:
– Progressive neurological deficits
– Contrast enhancing mass on imaging
– Successful resonance to treatment within 2 weeks

• Treatment is with Pyrimethamine for at least 6

weeks combined with Sulfadiazine and Folinic
acid
• Patients are usually started on anticonvulsants
 Cryptococcal meningitis
• Infection with the yeast Cryptococcus neoformans, in
HIV-infected individuals most often leads to a
subacute meningitis
• Symptoms consist of fever, headache, visual
disturbances and confusion.
• Disease is caused by inhalation of the yeast and
dissemination throughout the body.
• Raised intracranial pressure (ICP) is common leading
to complications such as blindness, seizures and
coma.
 Cryptococcal meningitis – Diagnosis and
treatment
• A definitive diagnosis of cryptococcal meningitis is made by
using any of the following methods:
– Visualizing the fungus in the CSF using India ink (sensitivity 75–85%)
– Detecting cryptococcal antigen in the CSF
– 3 Positive CSF culture for C. neoformans

• Treatment is via reducing the pressure with repeated LP and

drainage
• First line treatment is with amphotericin and 5-flucytosine for
two weeks followed by oral high-dose fluconazole for a
further eight weeks
Progressive multifocal leukoencephalopathy
(PML)
• A viral opportunistic infection (JC virus) of
oligodendrocytes and astrocytes leading to
demyelination in the CNS.
• Occurs when CD4 is 50 c/mm3.
• Presents with speech and visual defects
• Diagnosed via white matter abnormalities
without surrounding oedema on MRI and JC
virus in the CSF
• HAART - PML arrests or remits in approximately
50%, and survival is prolonged in these patients
Progressive multifocal leukoencephalopathy
(PML)
 Non-AIDS-related disease
• The incidence of stroke is higher in the HIV
population (1–2% of patients)
– mass lesions, such as toxoplasmosis and primary
CNS lymphoma
– increased use of illicit drugs
– Vasculitis caused by several opportunistic infections
• HIV can cause vasculopathy with lipid
deregulation and increased vessel wall
inflammation
 Summary
• Despite the success of HAART, HIV individuals
are risk of a variety of neurological
complications.
• HIV should therefore be considered in acute
neurological syndromes and an HIV antibody
test performed urgently.
• In the case of primary syndromes, a prompt
diagnosis may prevent severe HIV-related
disease in the future.
 References
• Portegies, P., et al. "Guidelines for the diagnosis and
management of neurological complications of HIV
infection." European Journal of Neurology11.5 (2004): 297-
304.
• McArthur, Justin C., Bruce J. Brew, and Avi Nath.
"Neurological complications of HIV infection." The Lancet
Neurology 4.9 (2005): 543-555.
• Hogan, Celia, and Ed Wilkins. "Neurological complications in
HIV." Clinical Medicine 11.6 (2011): 571-575.
• Who.int, (2014). WHO | HIV/AIDS. [online] Available at:
http://www.who.int/gho/hiv/en/