Meningitis | C. neoformans | Often headache, fever, and vomiting; sometimes confusion, seizure, meningismus, cranial nerve palsies; occasionally meningitis symptoms are minimal and presentation is fever, fungemia and/or extrameningeal lesion (e.g., skin, pneumonia). | CSF white blood count usually <20/μL; CSF, glucose and protein often normal; cryptococcal antigen positive in CSF (>90%) and serum (99%); positive India ink smear 50% – 90%; fungal cultures (blood, CSF, urine). |
| Aseptic (?HIV) | Headache, meningismus, and fever (all less common in chronic cases), with/without cranial neuropathies (V, VII, VIII); may occur with seroconversion, but more common later in HIV disease. | CSF examination: mild mononuclear pleocytosis, protein elevated, glucose normal (differential diagnosis also includes syphilis and lymphomatous meningitis). |
| M. tuberculosis | Usually subacute-chronic meningitis. Clinical manifestations similar to those in HIV-negative patients. Fever (89%), headache (59%), meningeal signs (65%), altered mentation (43%), focal deficits (19%), and clinical or radiologic evidence of extrameningeal tuberculosis (65%).a | CSF exam: lymphocytic pleocytosis, low glucose, and increased protein; smear for acid-fast-bacilli insensitive; cultures for M. tuberculosis. Rapid CSF diagnosis by polymerase chain reaction (PCR) appears promising,b but remains investigational. Detection of extrameningeal MTB facilitates early diagnosis.a Prior to obtaining positive CSF smears or culture, empiric therapy is indicated if clinical and spinal fluid profile are compatible with MTB. |
| Coccidioides immitis | Fever, lethargy, headache, with/without meningismus, confusion (consider if travel/residence history for endemic zone, e.g., southwestern United States). | Serum tube precipitin or complement-fixing (CF) antibody titer positive in 83% of patients with AIDS-related coccidioidomycosis.c Any positive CSF titer of CF antibodies is usually diagnostic of meningitis. CSF profile: lymphocytic pleocytosis usually >50 cells/μL, elevated protein, low glucose. Fungal cultures of blood and CSF. |
| Bacterial (pneumococcus, meningococcus, Listeria, H. influenzae) | Fever, headache with/without meningeal signs, confusion, seizures. Bacterial meningitis rare in HIV-infected patients. | CSF exam: polymorphonuclear pleocytosis, high protein, low glucose, with/without positive Gram stain and/or bacterial antigens (pneumococcus, meningococcus, H. influenzae); bacterial cultures of blood and CSF. |
Diffuse brain disease | | | |
AIDS dementia complex | HIV | Usually alert, but impaired cognition (usually concentration and memory), behavior (apathy, personality change), and motor function (slowing and reduced coordination); sometimes organic psychosis or mania. | Abnormalities on neuropsychologic testing. Other findings may include hyperreflexia, ataxia, release signs, leg weakness, incontinence and mutism. Nonspecific CSF abnormalities may include elevated protein, IgG, β2-microglobulin, neopterin, and positive HIV-1 p24 core antigen. CT or MRI: atrophy ± patchy or diffuse abnormalities of hemispheric white matter seen on MRI (T2-weighted).d |
Diffuse encephalopathies | Toxic metabolic disorders (e.g., hypoxia, sepsis, drugs), CNS toxoplasmosis, CNS lymphoma, occasionally viral infection (CMV, HSV). | Impaired alertness and cognition, with/without focal neurologic deficits. | Blood chemistry to exclude metabolic causes, with/without drug levels, serology for toxoplasmosis. MRI or contrast-enhanced CT head scan: focal lesions may be seen in toxoplasmosis, lymphoma, Herpes simplex encephalitis. |
Focal brain disease | | | |
Toxoplasmosis | Toxoplasma gondii | Headache (55%), confusion (52%), fever (47%), seizures (29%), reduced level of consciousness (42%), and focal deficits (69%) usually progressing over days. | MRI or contrast-enhanced CT scan: spherical ring-enhancing lesions in cortex, thalamus, or basal ganglia, but may have atypical appearances. Toxoplasma serum serology (IgG) usually positive (84%); possible brain biopsy (see Fig. 48-9). |
Lymphoma | Strong association with Epstein-Barr virus (EBV) | Confusion, lethargy, memory loss, progressive focal deficit(s), headache, seizure; more slowly progressive than toxoplasmosis. CD4 count usually <50 cells/μL. | MRI or contrast-enhanced CT scan: usually 1–2 lesions in white matter (often periventricular), may mimic toxoplasmosis but enhancement usually weaker and homogenous; possible brain biopsy. Spinal fluid PCR for EBV DNA has sensitivity and specificity of 80–90% and almost 100%, respectively. Combined sensitivity of positive PCR for EBV DNA or increased uptake on thallium SPECT scan almost 100%. |
Progressive multifocal leukoencephalopathy (PML) | JC virus (papovavirus) | Slowly progressive focal deficits (over weeks), but no systemic toxicity or reduced level of consciousness in the early stage. | MRI or contrast-enhanced CT scan: non-enhancing white matter lesions without mass effect. Definitive diagnosis requires brain biopsy. Spinal fluid PCR for JCV 60–100% sensitive depending on case definitions and methodology. Compatible clinical presentation plus positive PCR supports diagnosis; negative PCR does not exclude PML. |
Neurosyphilis | Treponema pallidum | Focal neurologic deficits (meningovascular involvement) with prodromal symptoms for weeks–months such as headache and behavioral changes. Syphilitic meningitis may include cranial nerve palsies. Ocular syphilis (e.g., optic neuritis) often associated with CNS involvement. | Positive serum VDRL, and FTA-ABS; CSF exam: mononuclear pleocytosis, elevated protein, with/without positive VDRL; CSF profile (if VDRL negative) may be indistinguishable from CSF abnormalities caused by HIV. |
Myelopathy | | | |
a) Subacute, chronic (diffuse) | HIV (vacuolar), HTLV-1 | Slowly progressive, painless ataxia and spasticity; bowel-bladder dysfunction occurs late; often coexistent with dementia. Usually no distinct sensory/motor level. | MRI or CT scan, with/without myelography are negative and are not indicated in typical cases (best reserved for patients with atypical findings where segmental lesions are to be excluded). Consider HTLV-1 serology. |
b) Acute, subacute (transverse myelitis, segmental) | Varicella zoster, lymphoma, cytomegalovirus | More rapid onset of myelopathy than for HIV. | CT scan or MRI, myelography. |
Peripheral neuropathy | | | |
a) Axonal neuropathy | ?HIV | Distal, mainly sensory, painful (“burning feet”), symptoms more prominent than signs. | With/without nerve conduction studies. |
b) Toxic axonal neuropathy | ddI, ddC, d4T, others | As for axonal neuropathy. Neuropathy may progress for a few weeks after stopping the offending drug. | With/without nerve conduction studies. |
Acute-chronic demyelinating neuropathy | ?Autoimmune response to HIV | Similar to Guillain-Barré syndrome; usually occurs during the early period (CD4 >500/μL) of HIV infection, or at the time of seroconversion. | Nerve conduction studies. CSF abnormalities: elevated protein, and mild pleocytosis. |
Radiculopathies | Varicella zoster virus | Herpes zoster dermatomal vesicular lesions. | Clinical diagnosis, with/without viral antigen detection in smears prepared from skin lesions. Tzanck smear is rapid but insensitive. Viral culture is slow for demonstration of cytopathic effect. |
| Cytomegalovirus | Subacute and progressive ascending polyradiculopathy with sensory loss, urinary retention, and flaccid paraparesis. | CSF: polymorphonuclear pleocytosis, elevated protein, low glucose, with/without CSF culture positive for CMV; rule out bacterial and tuberculous meningitis. |
Mononeuritis multiplex | Autoimmune vascular lesion in early HIV (CD4 200–500/μL). Multifocal CMV infection later in HIV disease (CD4 <200 μL) | Findings compatible with involvement of multiple distinct peripheral nerves. More severe in advanced HIV disease. | Nerve conduction studies. |
Myopathy | AZT | Ranges from asymptomatic elevation of CPK to progressive myalgia, atrophy, and weakness (especially proximal leg muscles). | Consider muscle biopsy (mitochondrial abnormalities with/without inflammatory cell infiltrates) if persists after stopping AZT. |
| HIV? | As for AZT-induced myopathy. | Consider muscle biopsy: myopathic changes (variable fiber size, vacuolar change and fiber destruction), with/without inflammatory infiltrates; ultrasound if localized inflammation to rule out pyomyositis. |