Headache can appear at any stage of HIV infection and may be primary or secondary. Primary headaches occur in the acute illness stage associated with HIV-1 seroconversion and accompany acute, recurrent, or chronic aseptic meningitis or emerge in the late stage as late stage HIV-headache without pleocytosis. Secondary HIV-related headaches are caused by opportunistic infections and tumors resulting from medications used to treat HIV-1 infections and accompanying immune restoration inflammatory syndrome.
Headache appearing in an HIV-infected person requires the same differential diagnostic skills as with all other headaches, and opportunistic infections and neoplasms must constantly be kept in mind. In the early HIV stage, migraine and tension-type headaches predominate, while sinus infections are not uncommon in those with CD4 counts above 200/mm2. For those with counts below 200/mm2, the three most common opportunistic conditions that cause headaches are cryptococcal meningitis, toxoplasma encephalitis, and primary CNS lymphoma; less frequent infections that cause headaches include bacterial meningitis, viral encephalitis, coccidioidomycosis, histoplasmosis, tuberculosis, nocardiosis, and pyogenic brain abscesses. Failure to maintain a high index of suspicion can be fatal. In patients with a CD4+ T cell count below 200/mm3, a serum cryptococcal antigen assay should be obtained to screen for cryptococcal disease. A negative result essentially excludes cryptococcal meningitis; a positive result must be followed up with a lumbar puncture and assay for cryptococcal antigen in the CSF.
Primary HIV-related Headaches
Headaches often occur as part of the acute mononucleosis-like illness experienced as part of the primary infection with HIV-1 [1, 2]. This acute illness, occurring in 53% to 93% of individuals, develops two to four weeks after HIV-1 exposure and lasts one to two weeks. The headaches these patients develop range from febrile headaches associated with the systemic viral infection, to headaches associated with retro-orbital pain, photophobia, and meningeal signs reflecting acute viral lymphocytic meningitis. Acute aseptic meningitis has been estimated to occur in 1% to 2% of all primary HIV-1 infections. Other neurologic complications that may accompany the primary infection with HIV-1 include Bell palsy, acute encephalitis, acute demyelinating polyneuropathy, and brachial neuritis. Aseptic meningitis is often self-limited but can recur at any time following the primary infection. HIV-infected individuals can suffer from chronic headaches that last for months.
At any stage of the disease following initial infection, an acute or chronic headache can develop in the presence of an unexplained lymphocytic pleocytosis. The acute headache resembles meningitis associated with the primary infection and is associated with fever, meningeal signs, and cranial nerve palsies. The cerebrospinal fluid lymphocytic pleocytosis ranges from 20 cells/mm3 to 300 cells/mm3 and is often associated with an elevated cerebrospinal fluid protein. The chronic headaches are holocephalic, low-to-moderate in intensity, and resemble tension-type headaches. These patients may also have an unexplained cerebrospinal fluid lymphocytosis, but the increase in CSF white cells, which is rarely above 40 cells/mm3, is not as dramatic as in those patients with the acute aseptic meningitis. This finding is not specific for headache, as mild lymphocytic pleocytosis with accompanying elevated cerebrospinal fluid protein can also be seen in asymptomatic HIV-infected individuals without headaches.
Patients in late stages of the HIV disease may also present with a new-onset headache without an identifiable etiology. These patients usually complain of holocephalic pain and frequently experience photophobia. A defining feature of the headache is the absence of CSF pleocytosis and may represent “aseptic” meningitis in a lymphocyte-depleted patient.
At any stage of the disease following initial infection, an acute or chronic headache can develop in the presence of an unexplained lymphocytic pleocytosis. The acute headache resembles meningitis associated with the primary infection and is associated with fever, meningeal signs, and cranial nerve palsies. The cerebrospinal fluid lymphocytic pleocytosis ranges from 20 cells/mm3 to 300 cells/mm3 and is often associated with an elevated cerebrospinal fluid protein.
Opportunistic Infections and Tumors
Two studies analyzed headache characteristics and associated symptomatology in HIV-infected patients presenting with an opportunistic infection or tumor. Headaches secondary to an opportunistic infection causing meningitis were constant, gradual in onset, and associated with fever, nausea, vomiting, and photophobia. Headaches secondary to mass lesions were variable in onset and quality, and associated with focal neurologic deficits and confusion. However, considerable variability occurs, and a fulminant opportunistic disease can arise in patients with mild or no symptoms, including the absence of headache [3, 4].
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