27th June 2023

Neurological complications in HIV/ AIDS

Cerebral toxoplasmosis

Toxoplasma gondii is a parasite spread through oocysts shed by infected cats. It is usually asymptomatic in people with a functioning immune system. Cerebral toxoplasmosis causes a multifocal necrotising encephalitis in people with HIV (usually CD4+ T-cell count is <200/μL), with subacute onset. Presenting features include:

• Subacute headache
• Focal neurological deficit
• Fever
• Confusion
• Seizures
• Ataxia

Radiology demonstrates ring-enhancing focal brain lesions. Contact is confirmed using an enzyme-linked immunosorbent assay (ELISA) which detects IgG and IgM antibodies against Toxoplasma gondii in the serum. This is sensitive but not specific, as many uninfected people have positive IgG titres for Toxoplasma gondii. Lumbar puncture (LP) can be used for PCR of Toxoplasma gondii DNA, however, this does not have a high sensitivity and patients with toxoplasma encephalitis may have mass effect, increasing the risk of brain herniation with an LP. Management of cerebral toxoplasmosis involves pyrimethamine and sulfadiazine with folinic acid. Second-line treatment and primary prophylaxis is with co-trimoxazole.

Primary CNS lymphoma

CNS lymphoma is a rare, aggressive non-Hodgkin lymphoma and is an AIDS-defining malignancy. It is confined to the CNS and is usually associated with low CD4+ T-cells (<50 cells/ μL). It is strongly associated with Epstein-Barr virus infection in the context of HIV.

Presentations include:

• Focal neurological deficit
• Seizures
• Altered mental state/ behavioural change
• Features of raised intracranial pressure

Imaging is key to identifying primary CNS lymphoma. MRI with gadolinium contrast is the imaging technique of choice, which demonstrates multifocal necrotic lesions. This contrasts with primary CNS lymphoma in patients without HIV, which typically demonstrates a single lesion. Management typically involves antiretroviral therapy in addition to methotrexate. Rituximab is given on induction. CNS lymphoma with HIV has the worst prognosis of all HIV-related lymphomas.

Cerebral abscesses in HIV

Brain abscesses in patients with HIV can be caused by tuberculomas and tuberculous abscesses. Tuberculous abscesses are larger, often solitary, and demonstrate ring enhancement. Pyogenic brain abscesses are less common than lymphoma and opportunistic infections. Patients with HIV are more likely to have multiple abscesses and infection caused by several bacteria, including:

• Listeria
• Cryptococcus
• Nocardia

Presentation includes:

• Headache
• Fevers
• Meningism
• Altered mental state
• Nausea and vomiting
• Seizures
• Papilloedema
• Focal neurological deficit

Cerebral aspergillosis has a very high mortality. Management typically involves both surgery (CT-guided stereotactic drainage) and medication. Medications for HIV patients need to cover for toxoplasmosis, frequently with pyrimethamine and sulfadiazine, or clindamycin. Oedema associated with abscesses causing significant mass effect is managed with corticosteroids.

Progressive multifocal leukoencephalopathy (PML)

PML is a CNS disease caused by JC virus. JC virus is a small ubiquitous DNA virus. PML is extremely rare in immunocompetent individuals; ~80% of cases are associated with HIV. Most patients with HIV have a CD4 count of <200 cells/μL, however, over 10% of cases have a greater CD4 count. JC virus transforms in PML to cause lysis of oligodendrocytes, causing demyelination. Presenting features include:

• Seizures
• Focal neurological deficits
• Gait disturbance
• Speech disturbance
• Ataxia
• Aphasia
• Visual changes

Imaging can aid diagnosis. CT shows hypodense lesions in the white matter, while MRI is more sensitive to white matter changes. There are often multifocal lesions. CSF is useful to exclude other diagnoses, and JC virus PCR can be conducted on CSF samples. Restoration of immunity with HAART in the treatment of PML may result in immune reconstitution inflammatory syndrome (IRIS). The newly reconstituted immune system targets oligodendritic cells, causing inflammatory demyelination. The most effective treatment for PML is immune reconstitution with antiretroviral therapy. In cases of IRIS, steroids are given alongside antiretroviral medications to control inflammation.

Cryptococcal meningitis

Cryptococcus is a genus of fungi. Cryptococcal infection is caused by either Cryptococcus neoformans or Cryptococcus gattii, with C. neoformans being found in pigeon droppings and is more widespread; it is found in tropical and subtropical areas. Cryptococcal meningitis chiefly affects patients with impaired cell-mediated immunity and, therefore, primarily affects patients with HIV- and a CD4+ T-cell count <100 cells/μL.

Presentations include:

• Head pain
• Neck stiffness
• Altered mental state
• Seizures
• Stroke
• Photophobia
• Nausea and vomiting
• Speech errors
• Focal neurological features
• Skin lesions

Imaging is not always positive in cryptococcal meningitis, however, MRI is more sensitive than CT. Common findings include:

• Leptomeningeal (e.g. pia/arachnoid mater) or dura mater thickening
• Focal parenchymal oedema
• Cryptococcoma
• Pseudocysts
• Dilation of the Virchow-Robin Space (VRS)

Diagnosis usually needs identification of Cryptococcus, involving:

• CSF sampling
  • India ink staining and microscopy
  • Culture
  • Cryptococcal antigen – detected with immunoassay, latex agglutination, or lateral flow assay
  • Beta-D-glucan – may be raised
• Serum
  • Cryptococcal antigen testing has comparable sensitivity to CSF

Management usually includes IV amphotericin V deoxycholate with oral flucytosine, followed by oral fluconazole. HAART should be postponed for around four weeks.

HIV associated neurocognitive disorder (HAND)

HAND is caused by HIV in the brain and inflammation of the brain caused by immunosuppression, and results in neuropsychiatric decline. Clinical features include:

• Loss of attention/ concentration
• Motor slowing
• Altered behaviour

These may be subtle and may require repeated neuropsychiatric testing in cases of mild neurocognitive disorder to be picked up. Risk factors for HAND include: age >50; hypertension; diabetes; hypercholesterolaemia; Hepatitis C infection; recreational drug abuse and low cognitive reserve.

The most important aspect of the treatment of HAND is antiretroviral therapy and management of comorbidities.