HIV-Associated Dementia
This patient's cognitive decline is most likely caused by HIV-associated dementia (HAD), given the constellation of severe immunosuppression (CD4+ <200/mm³), detectable CSF HIV RNA, subcortical neurological findings, and characteristic MRI changes in the absence of focal lesions suggesting opportunistic infections. 1
Clinical Presentation Confirms HAD
The clinical triad presented here is pathognomonic for HIV-associated dementia:
- Cognitive dysfunction: Progressive apathy and forgetfulness represent the subcortical pattern typical of HAD 2, 3
- Motor abnormalities: Impaired saccadic eye movements, diffuse hyperreflexia, and dysdiadochokinesia indicate the motor component of this subcortical dementia syndrome 2, 3
- Frontal release signs: These indicate frontal lobe involvement consistent with HIV encephalopathy 1
Key Diagnostic Features Supporting HAD
CSF findings are critical: The elevated CSF HIV RNA (>detectable copies/ml) with elevated protein and IgG indicates active HIV replication within the CNS compartment, representing what current guidelines term "active HIV-associated brain injury (HABI)" 1, 4. This CSF HIV RNA escape occurs due to inadequate antiretroviral penetration into the CNS, resistance, or poor adherence 4.
Severe immunosuppression: The CD4+ count and history of recurrent Pneumocystis jiroveci pneumonia indicate advanced AIDS, which is when HIV-associated dementia typically manifests as an AIDS-defining condition 1, 3.
MRI characteristics: Global cerebral atrophy with ill-defined T2 hyperintensities in white matter is the classic neuroimaging pattern for HAD, distinct from the focal lesions seen in opportunistic infections 4, 5.
Why Other Diagnoses Are Less Likely
- Toxoplasmosis: Would present with focal, ring-enhancing lesions on MRI, not diffuse white matter changes 4
- Primary CNS lymphoma: Would show focal mass lesions with enhancement, typically periventricular, not diffuse atrophy 4
- CMV encephalitis: Would present with periventricular enhancement and more acute progression, often with cranial nerve involvement 4
- Disseminated MAC: Primarily causes systemic symptoms and does not typically cause this pattern of CNS involvement 4
Pathophysiology
HIV-associated dementia represents direct HIV-mediated neurotoxicity through multiple mechanisms including persistent immune activation, blood-brain barrier dysfunction, and virus-induced neurotoxicity mediated by HIV proteins (particularly Tat and gp120), oxidative stress, and glutamate dysregulation 1, 6. The multinucleated giant cells and microglial nodules characteristic of HIV encephalitis may be present histopathologically 1.
Critical Management Implications
Never interrupt antiretroviral therapy - continued viral suppression is essential for immune recovery and preventing further neurological deterioration 4. The management priority is optimizing ART with agents that have good CNS penetration to suppress CSF viral replication 4, 5.
Common Pitfall to Avoid
Do not assume all demyelinating lesions in HIV patients are Progressive Multifocal Leukoencephalopathy (PML) - while PML is the most common opportunistic infection causing demyelination in HIV, this patient's presentation with detectable CSF HIV RNA, subcortical motor findings, and diffuse (not focal asymmetric) white matter changes is more consistent with direct HIV-mediated brain injury 4.