eMedicine Specialties > Neurology > Neurological Infections

HIV-1 Associated CNS Conditions - Meningitis

Author: Niranjan N Singh, MD, DNB, Assistant Professor of Neurology, University of Missouri Columbia
Coauthor(s): Florian P Thomas, MD, MA, PhD, Drmed,, Director, Spinal Cord Injury Service, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Contributor Information and Disclosures

Updated: Feb 23, 2010

Introduction

Background

Different forms of meningitis are associated with HIV infection. They may be classified according to the etiologic agent as cryptococcal, tuberculous, syphilitic, or Listeria species; others are lymphomatous or aseptic.

Pathophysiology

Meningitis is multifactorial in patients with HIV/AIDS. Besides specific pathogens, autoimmune processes and HIV itself have been implicated.

Although HIV-seropositive individuals are at increased risk of certain types of meningitis, evidence suggests that they are also more likely than the general population to develop community-acquired bacterial or viral meningitides. An early form of aseptic, HIV-associated meningitis develops within days to weeks after HIV infection. It appears as a mononucleosis-like illness and is rarely associated with encephalitis. Meningitides due to cryptococcosis, coccidioidomycosis, histoplasmosis, or other fungal infection are AIDS-defining events and occur typically with very low CD4⁺ lymphocyte counts.

Chronic meningitis or episodes of acute meningitis for which no cause is found can occur anytime during the disease course.

An asymptomatic form is found in one third of patients in whom CSF is examined for other reasons (eg, headache).

Cytomegaloviral (CMV) infection usually presents as an encephaloventriculitis with possible meningeal involvement.

Medications as causes are often overlooked including nonsteroidal anti-inflammatory drugs (NSAIDs), trimethoprim/sulfamethoxazole, and intravenous immunoglobulin (IVIG).

In patients receiving highly active anti-retroviral therapy (HAART) and a syndrome of relapsing remitting meningitis with negative cultures and atypical signs and symptoms, consider immune reconstitution inflammatory syndrome (IRIS). This is regarded as an overactive response of a newly reconstituted immune system to infectious agents already present in the patient when the therapy is started. Symptoms that are consistent with an infectious and/or inflammatory condition appear while the patient is on antiretroviral therapy and the symptoms cannot be explained by a new or a previous infection or by the side effects of the therapy. It has been proposed that IRIS is due to an imbalance of CD8⁺/CD4⁺ cells.

Frequency

United States

Cryptococcal meningitis is the most common opportunistic infection of the CNS, affecting 5-7% of patients with AIDS. The second most common type of meningitis is aseptic meningitis, which may be caused by HIV-1 itself.

Rarer CNS infections are due to Listeria monocytogenes, coccidioidomycosis, histoplasmosis, syphilis, and tuberculosis. CNS syphilis may occur earlier and more frequently in HIV-seropositive individuals than in HIV-seronegative individuals.

Bacterial meningitis often occurs in conjunction with sepsis due to the same organism.

In rare cases, metastatic CNS lymphoma can appear as meningitis.

Mortality/Morbidity

Mortality rates and morbidity vary by the etiology of meningitis. A previously reported mortality rate of 20% for cryptococcal meningitis, for example, may now be as low as 6% owing to more aggressive therapy. Higher mortality rates correlate with poor mental status, high CSF opening pressure at presentation, positive India ink test, extra-CNS manifestations, and higher fungal burdens.

Clinical

History

In general, symptoms and signs typically associated with meningitis are less likely to occur in HIV-seropositive individuals than in the general population. This probably reflects the different organisms involved and the differences in immune responses.

One meta-analysis showed that stiff neck occurred in 50% of cases of non-AIDS meningitis; four studies shoed rates of 22%, 31%, 37%, and 44% for AIDS meningitis. Similarly, the frequency of papilledema was 28% in that same study of non-AIDS meningitis, whereas frequencies of 6% and 8% were reported in 2 studies of AIDS meningitis.

Characteristics of HIV-seropositive patients with meningitis are the following:

• Patients present with malaise, fever, stiff neck, photophobia, and headache.
• Less common findings are confusion, somnolence, and personality changes.
• The time course is variable. Patients with aseptic meningitis, a diagnosis of exclusion, have a good prognosis and do not require any specific treatment.
• Cryptococcal meningitis can occur acutely, with severe headache, change in mental status, fever, nuchal rigidity, and focal signs, or with a subacute course of malaise and headache without stiff neck over several weeks. Sometimes Cryptococcus neoformans is incidentally found in the CSF.
• CMV ventriculoencephalitis often causes death within weeks to months. It usually results in a change in mental status evolving over several weeks and can be misdiagnosed as HIV-associated dementia

Physical

• Examination can reveal nuchal rigidity, fever, and cranial neuropathies.
• In rare cases, the patient is somnolent or confused.

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