Complication*		Signs and symptoms	Typical CD4 lymphocyte count	Diagnostic evaluation
				Imaging	Serology	Microbiology/other
Cerebral toxoplasmosis		Focal neurologic deficits, confusion, occasional fever or headache; seizure or coma with progressive disease	< 50 per mm3 (0.05 × 109 per L)	Contrast MRI or CT usually shows one or more ring-enhancing lesions with edema, with or without mass effect	Serum toxoplasma immunoglobulin G is often positive (absence makes diagnosis less likely)	Brain biopsy is recommended if patients do not improve with empiric therapy
						CSF analysis is rarely performed
Cryptococcal meningoencephalitis (or cryptococcoma)		Headache, fever, confusion, altered mental status	< 50 per mm3	—	Serum cryptococcal antigen is almost always positive	Fungal cultures and CSF or blood staining may yield organism
					CSF antigen may be elevated
Viral meningoencephalitis		In general: fever, headache, confusion, delirium, lethargy, focal deficits, occasionally seizure (virus-specific symptoms listed below)	—	—	—	PCR of CSF (or brain tissue), special staining, viral culture
	Cytomegalovirus	Worsening focal deficits	< 50 per mm3	Periventricular enhancement on MRI
	Herpes simplex virus	Behavioral, personality, or memory changes	< 200 per mm3 (0.20 × 109 per L)	Diffuse edema, occasionally shows necrosis of frontal and temporal lobes (MRI more sensitive than CT)
				Electroencephalography often shows characteristic focal temporal abnormalities
	Varicella zoster virus	Vasculitis, leading to stroke syndromes	Risk increases with lower CD4 count	Diffuse edema with demyelination, possible focal infarcts (MRI more sensitive than CT)
Progressive multifocal leukoencephalopathy		Progressive focal deficits (e.g., cognitive decline, cranial nerve palsy, aphasia, ataxia, weakness or sensory loss, seizure); may progress to coma	< 200 per mm3	Single or multiple white matter lesions with little to no enhancement and no edema or mass effect (MRI more sensitive than CT)	—	Brain biopsy is definitive but rarely performed
						PCR detection of JC virus in CSF helps confirm diagnosis
Neurosyphilis		Wide range of symptoms (e.g., behavioral and psychological abnormalities, delirium, dementia, focal deficits, stroke syndromes related to arteritis, ocular and auditory changes, meningitis, myelitis)	< 350 per mm3 (0.35 × 109 per L)	—	CSF VDRL test is specific but not sensitive; reactive test confirms diagnosis (nonreactive test does not exclude diagnosis) CSF treponemal tests (e.g., FTA-ABS) are sensitive but not specific; nonreactive test excludes diagnosis†	CSF typically shows elevated protein level and mononuclear pleocytosis (white blood cell count > 10 to 20 per μL [.01 to .02 × 109 per L])
		Risk increases when serum rapid plasma reagin titer ≥ 1:32
Primary central nervous system lymphoma		Focal neurologic deficits, headache, blurred vision, seizure, motor difficulty, personality or cognitive changes, confusion	Risk increases with lower CD4 count	Solitary white matter lesions on CT or MRI, often with mild edema and mass effect	—	Brain biopsy is definitive, although CSF examination for cytology, flow cytometry, and PCR testing may also be useful
				Multicentric lymphoma occurs less frequently
				PET/SPECT is occasionally useful to differentiate from cerebral toxoplasmosis