Is HIV infection associated with optic neuromyelitis (neuromyelitis optica spectrum disorder) in adults, particularly those with uncontrolled disease or low CD4 counts?

HIV and Neuromyelitis Optica: Established but Uncommon Association

HIV infection can be associated with neuromyelitis optica spectrum disorder (NMOSD), though this represents a rare clinical entity that requires high clinical suspicion and careful diagnostic evaluation. 1

Evidence for HIV-NMOSD Association

The relationship between HIV and NMOSD is documented in the medical literature as a distinct clinical entity termed "HIV-associated NMOSD" (HIV-NMOSD). 1

Key Clinical Characteristics

• Presentation patterns: Optic neuritis followed by myelitis is the most common presentation, occurring in approximately 71% (5 of 7) of reported cases. 1

• Demographics: The condition affects both males and females across a wide age range (8-49 years), with HIV infection duration ranging from newly detected to 15 years at NMOSD presentation. 1

• Antibody status: Only 43% (3 of 7) of HIV-NMOSD patients test positive for anti-aquaporin-4 antibodies, meaning seronegative status does not exclude the diagnosis. 1

Differential Diagnosis Considerations

When evaluating neurological symptoms in HIV-infected patients, clinicians must distinguish NMOSD from other HIV-associated conditions:

• Infectious causes: HIV is associated with acute transverse myelitis from direct viral effects, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, syphilis, tuberculosis, or diphtheria. 2

• HIV-specific complications: Polyradiculoneuritis and myositis can occur directly from HIV infection. 2

• True inflammatory NMOSD: This represents a separate autoimmune process that can coexist with HIV infection, listed among inflammatory causes of myelitis distinct from infectious etiologies. 2

Diagnostic Approach

Essential Testing

• Screen all HIV patients presenting with optic neuritis and/or myelitis for anti-aquaporin-4 antibody status, as this combination should trigger NMOSD evaluation. 1

• Conversely, test all NMOSD patients for HIV infection to rule out this association. 1

• Perform lumbar puncture in immunocompromised HIV patients with suspected CNS inflammation, even if CSF white cell count appears normal, as these patients may have acellular CSF despite active infection. 2

• Obtain MRI imaging as soon as possible in all immunocompromised patients with suspected encephalitis or myelitis. 2

Expanded Microbiological Workup for HIV Patients

In HIV-infected individuals with myelitis or optic neuritis, comprehensive CSF testing should include:

• CSF PCR for HSV 1 & 2, VZV, enteroviruses, EBV, and CMV 2
• Acid-fast bacillus staining and culture for M. tuberculosis 2
• CSF and blood culture for Listeria monocytogenes 2
• Cryptococcal antigen testing 2
• Syphilis antibody testing of serum and CSF if positive 2

Treatment Considerations

Acute Management

• All HIV-NMOSD patients should receive immunomodulatory treatment for acute attacks, though recovery may be incomplete (5 of 7 patients had poor recovery from acute attacks in reported cases). 1

• Aggressive treatment of relapses with high-dose steroids and often plasma exchange is crucial to prevent residual disability, as untreated NMOSD leads to wheelchair dependence and blindness in 50% of patients within 5 years. 3

Long-term Management

• Dual therapy approach: Patients require both antiretroviral therapy (ART) for HIV and long-term immunosuppression for NMOSD relapse prevention. 1

• Relapse prevention is critical: No patient in the reported series experienced further relapses while maintained on combined immunomodulatory treatment and antiretroviral therapy. 1

• Disability accrual in NMOSD is related to relapses rather than progressive disease, making relapse prevention the cornerstone of management. 3

Clinical Pitfalls

• Do not dismiss NMOSD based on negative anti-aquaporin-4 antibodies in HIV patients, as more than half may be seronegative. 1

• Avoid delaying diagnosis by attributing all neurological symptoms to direct HIV effects or opportunistic infections without considering autoimmune demyelination. 1, 4

• Consider brain biopsy in diagnostically challenging cases where initial testing is inconclusive and the patient fails to respond to empiric treatment, as demonstrated in complex HIV-associated demyelinating cases. 4

• Recognize geographic variation: HIV-associated transverse myelitis and polyradiculoneuritis are more frequently reported in low- and middle-income countries where HIV prevalence is higher. 2