CNS Infection in HIV / AIDS - Differential Diagnosis Framework



Principles of HIV-Associated CNS Opportunistic Infections:

 • Most CNS opportunistic infections result from reactivation of latent pathogens, including PML, toxoplasmic encephalitis, and primary CNS lymphoma.

 • IRIS might unmask previously unsuspected CNS opportunistic infections when  cART is started.

 • CNS opportunistic infections typically occur when the CD4-cell count is less than 200 cells per μL

 • Diagnosis should be based on clinical presentation, temporal evolution, CSF, and radiographic features

 • Multiple infections are present in 15% of cases and some infections might be revealed only after combination antiretroviral therapy is started

 • Combination antiretroviral therapy should be started, modified, or continued with appropriate antimicrobial therapy

 • Antimicrobial treatment is generally required until immune recovery (CD4-cell count more than 200 cells per μL) is achieved with antiretroviral therapy



Herpes Simplex Virus (HSV):

 • CD4 Variable

 • Symptoms: Fever, headache, neck stiffness, vomiting, disorientation, memory loss, dysphasia, depression, confusion, personality change, seizures, visual hallucinations and photophobia

 • Imaging: Enhancement- Inferomedial temporal lobes, brainstem, cerebellum, diencephalon, and Periventricular regions; associated intracranial hemorrhage

 • CSF PCR sensitivity 100%, specificity 99-6%



Toxoplasmic Encephalitis:

 • CD4 < 200

 • Suspect in movement disorders

 • Symptoms: Fever, headache, altered mental status, and focal neurologic complaints or seizures

 • Imaging: 

	- MRI - ring enhancing, Frontal, basal ganglia, parietal

	- Size lesions < 4cm + mass effect/Edema

 • Toxoplasma gondii PCR nearly 100% specific and 50-80% sensitive



Tuberculous Meningitis:

 • Variable, but usually CD4 < 200

 • Imaging:

	- Hemorrhage, tuberculomas, or abscesses

	- <50% show basilar enhancement on CT

	- Hydrocephalus possible



PML:

 • CD4 < 100

 • Demyelinating disease caused by the JC virus

 • Symptoms: AMS, motor deficits (hemiparesis or monoparesis), limb ataxia, gait ataxia, and visual symptoms such as hemianopia and diplopia

 • Imaging: periventricular areas and the subcortical white matter.

 • JC-virus PCR sensitivity variable at 50–90%, but specificity 90–100%



Primary CNS Lymphoma:

 • CD4 < 100

 • Symptoms: Confusion, lethargy, memory loss, hemiparesis, aphasia, and/or seizures

 • Imaging: 

	- Enhancement: multifocal lesions - Periventricular, frontal, cerebellum, temporal

	- Generally >3 cm diameter

	- +mass effect/Edema

 • EBV analysis has a sensitivity of 80–90%, and a specificity approaching 100% for primary CNS lymphoma



Cytomegalovirus Encephalitis:

 • CD4 < 50

 • Symptoms: Delirium, confusion, and focal neurologic abnormalities, rapidly progressive encephalopathy.

 • Imaging: Periventricular Enhancement 

 • PCR >90% sensitive and specific and <25% culture positive



Cryptococcal Meningitis:

 • CD4 <50

 • Symptoms: Headache, vomiting, visual changes, hearing loss, palsy of the abducens nerve, and impaired consciousness

 • Imaging: 

	- Leptomeningeal enhancement, especially in patients with IRIS

	- Frequently "punched-out" cystic lesions

 • CSF cryptococcal antigen sensitivity 92% and specificity 83% - sensitivity of serum CrAg testing is comparable to CSF testing



Others CNS Infections in HIV:

 • CNS Syphilis

 • Aspergillosis

 • Coccidioidomycosis

 • Histoplasmosis

 • VZV

 • HIV encephalopathy



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