eMedicine Specialties > Psychiatry > Psychosomatic
Dementia Due to HIV Disease: Differential Diagnoses & Workup
Updated: Jan 2, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
| Alcoholism | Schizophreniform Disorder |
| Bipolar Affective Disorder | Systemic infections |
| Cerebral lymphoma | Toxic-metabolic states (eg, alcoholism, vitamin
B-12 deficiency, thyroid disorders, adverse medication
effects, drug interaction, recreational drug
use) |
| CNS infections (eg, tuberculosis, toxoplasmosis,
cryptococcal meningitis, neurosyphilis, cytomegalovirus
encephalitis) | Toxoplasmosis |
| Depression | |
| Injecting Drug Use | |
| Progressive multifocal
leukoencephalopathy |
Other Problems to Be Considered
Medication adverse effects: Antiretroviral medications can sometimes have neurocognitive side effects (eg, efavirenz therapy can result in depression, insomnia, and decreased neuropsychological testing).21
Immune reconstitution inflammatory syndrome (IRIS): Clinical worsening may be observed in patients with HIV soon after initiation of HAART therapy due to mounting of a significant inflammatory response. This is seen even while patients’ CD4 count improves and viral load dramatically decreases. IRIS may actually worsen ADC and PML.22 ADC and IRIS can be distinguished by the speed of onset: ADC is subacute to chronic whereas IRIS can be more acute to subacute. ADC occurs in the setting of untreated progressive AIDS whereas IRIS begins with the start of treatment. Distinguishing between the 2 is important because the treatment is different. ADC requires HAART with high penetration into CNS. IRIS should be treated with steroids depending on its severity.
A 40-year-old woman presented with confusion, decline in memory without any focal findings, and dehydration. She was diagnosed with HIV 3 months prior and started on HAART medication 1 month prior when she had no cognitive symptoms. The MRI shows atrophy and white matter hyperintensity on T2 not involving U-fibers. CSF studies were negative for demyelinating disease, JC virus DNA, cryptococcal antigen, and CMV IgG and IgM. Confusion eventually improved with hydration, but on follow-up 2 months later, she still had significant cognitive deficits and needed assistance from family in instrumental activities of daily living.
Workup
Laboratory Studies
- HIV antibody and Western blot testing as well as viral load and CD4 count
- Draw peripheral blood for syphilis serology testing, vitamin B-12 and folate levels, thyroid studies, routine electrolyte levels, BUN/creatinine determination, and a drug screen to effectively exclude other metabolic and infectious etiologies.23
- TB testing/screening
Imaging Studies
- In the early stages, neuroimaging study findings may be entirely normal.
- CT scanning of the brain can reveal brain atrophy, ventricular enlargement, and increased white matter signal in later stages.
- MRI is the first-choice neuroimaging modality. An MRI of the brain must be performed to exclude other CNS causes of dementia, including toxoplasmosis, progressive multifocal leukoencephalopathy, and cerebral lymphoma. In the late stages of AIDS dementia complex (ADC), MRI findings typically show diffuse nonenhancing white matter, hyperintensity, cerebral atrophy, and ventricular enlargement. The degree of cerebral atrophy correlates with the symptoms and progression of ADC.
- Positron emission tomography (PET) scanning and functional nuclear MRI reveal decreased metabolism in the thalamus and basal ganglia in the early stages of ADC. PET scanning can be particularly useful in very difficult cases to help exclude CNS lymphoma, which shows increased uptake, whereas the lesions of AIDS dementia do not.
- Proton magnetic resonance spectroscopy (MRS) is a functional imaging technique that measures brain metabolites. In persons with ADC, neuronal injury is confirmed by finding lower N -acetyl aspartate (NA) levels (a marker of neuronal metabolism) in the frontal white matter. In the basal ganglia and white matter, where gliosis and inflammatory changes are noted, the level of choline-containing metabolites, which is a marker of glial metabolism, is increased. In the future, proton MRS could be used to follow the effectiveness of CNS-targeted therapies for ADC.
- Chang et al recently showed that even in the asymptomatic stage, metabolite changes are seen by MRS in the basal ganglia and frontal white matter. In the absence of clinically recognizable symptoms, elevated glial marker, myoinositol to creatinine ratio (MI/Cr), is seen in the white matter, indicating early HIV brain disease. Patients with ADC have elevated MI/Cr and choline to creatinine ratio (Cho/Cr) in basal ganglia and white matter, relative to the asymptomatic group. However, compared with controls, patients with ADC have decreased NA/Cr ratio, which is a neuronal marker. The decreased NA/Cr ratio in ADC is more profound in younger subjects. This indicates that in older individuals, the metabolic changes seen may be a combination of age and HIV infection.24,25
A 22-year-old woman who was infected with HIV from a perinatal blood transfusion, presented with bilateral leg weakness. Brain MRI showed atrophy and minimal white matter hyperintensity. Thoracic and lumbar MRI showed no abnormalities. The radiological diagnosis was HIV-encephalitis. The weakness in the legs did not change over the next 4 years. Despite treatment with HAART, cognitive changes developed 4 years later. The patient died of intracranial hemorrhage due to blood dyscrasia at the age of 25.
A 22-year-old woman who was infected with HIV from a perinatal blood transfusion, presented with bilateral leg weakness. Brain MRI showed atrophy and minimal white matter hyperintensity. Thoracic and lumbar MRI showed no abnormalities. The radiological diagnosis was HIV-encephalitis. The weakness in the legs did not change over the next 4 years. Despite treatment with HAART, cognitive changes developed 4 years later. The patient died of intracranial hemorrhage due to blood dyscrasia at the age of 25.
A 22-year-old woman who was infected with HIV from a perinatal blood transfusion, presented with bilateral leg weakness. Brain MRI showed atrophy and minimal white matter hyperintensity. Thoracic and lumbar MRI showed no abnormalities. The radiological diagnosis was HIV-encephalitis. The weakness in the legs did not change over the next 4 years. Despite treatment with HAART, cognitive changes developed 4 years later. The patient died of intracranial hemorrhage due to blood dyscrasia at the age of 25.
Candida, GMS stain.
Cerebritis.
Pontine hemorrhage.
Other Tests
- Electroencephalogram
- Patients with subclinical seizures may present with symptoms that mimic dementia. Consider performing an EEG to help exclude this type of pseudodementia.
- EEG findings may be normal in early dementia or may demonstrate diffuse slowing. However, this finding is nonspecific and is present in persons with dementia from any cause (even metabolic); therefore, it does not help in making an etiologic diagnosis.
- Neuropsychological testing
- This type of testing can be used for early screening of asymptomatic high-risk patients (eg, those with high viral load and low CD4 count26 ) and for follow-up evaluations of patients with ADC.
- In the early stages of the disease, MSE findings may be entirely normal. In such cases, neuropsychological testing is especially useful and can help detect mild early cognitive abnormalities. Performing this test can help quantify and determine the specific pattern of the cognitive abnormality.
- Specialists use several neuropsychiatric screening techniques; the most widely accepted is the HIV dementia scale. The scale consists of 4 subsets that target memory (eg, recall, registration), psychomotor speed, constructional ability, and concentration. A total of 12 points can be earned, and a score of fewer than 6 points is considered abnormal. The test takes 10 minutes to administer and can be given by a nonneurologist. These tests are useful diagnostic adjuncts, but the results cannot solely determine the presence of ADC.
- Combination screening: The Memorial Sloan-Kettering rating scale is used for clinical staging of ADC from 0 (normal) to 4 (end stage). It combines functional ability results with the findings from neuropsychological testing. Currently, it is used mostly as a research instrument.
Procedures
Lumbar puncture and cerebrospinal fluid (CSF)
- CSF studies, including cryptococcal antigen, CSF Venereal Disease Research Laboratory (VDRL) test, fluorescent treponemal antibody-absorption test (FTA-abs), and cytomegalovirus polymerase chain reaction (PCR) test help exclude CNS infection. Depending on the clinical picture, PCR studies may also be obtained for herpes simplex and varicella zoster viruses and JC virus (the causative agent of progressive multifocal leukoencephalopathy [PML]).
- Patients with ADC usually have a mild elevation of CSF protein levels and, in the cell count, increased total immunoglobulin fraction and intrathecal synthesis of anti-HIV immunoglobulin G, with the detection of oligoclonal bands in as many as 35% of cases.
- These CSF abnormalities are nonspecific and are often present in neurologically asymptomatic patients with HIV.
- HIV-1 virus is present in CSF in the absence of neurologic abnormalities. CSF HIV RNA levels do not correlate with neuropsychological impairment; rather, plasma levels are a better correlation.
- CSF markers are helpful in early dementia, when the diagnosis may be confusing. CSF markers, including neopterin, quinolinic acid, certain cytokines (eg, TNF-alpha, interleukin 1, interleukin 6), and antibodies to gp120 (eg, HIV viral envelope protein), correlate with the severity of dementia, but are only research tools and therefore not widely available. CSF beta-2 microglobulin, an immune activation marker, is a more specific CSF marker and has a positive predictive value of 88% if levels are higher than 3.8 mg/dL. CSF beta-2 microglobulin levels were twice as high in patients who cognitively improved with HAART than in those who did not, indicating that CNS inflammation plays a major role in reversible neurocognitive deficits.
- Some studies have shown the association of plasma TNF-alpha and CSF macrophage chemoattractant protein 1 (MCP-1) with ADC.27
- Patients with HIV dementia have elevated levels of certain matrix metalloproteins in the CSF, but the clinical significance of these metalloproteins is unclear.
Histologic Findings
Gross brain specimens show white matter pallor and microglial nodules. Microscopically, ADC is typically associated with a triad of multinucleate giant cells, microglial nodules, and perivenular inflammation. Severe ADC is characterized microscopically by microgranulomatous foci of multinucleate giant cells, initially in the white matter and later in the gray matter. Reactive gliosis is also observed, in which an increase occurs in both the number and size of astrocytes, associated with infiltration by monocytes.
More on Dementia Due to HIV Disease |
| Overview: Dementia Due to HIV Disease |
 Differential Diagnoses & Workup: Dementia Due to HIV Disease |
| Treatment & Medication: Dementia Due to HIV Disease |
| Follow-up: Dementia Due to HIV Disease |
| Multimedia: Dementia Due to HIV Disease |
| References |
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Further Reading
Keywords
AIDS dementia complex, ADC, subacute HIV encephalitis, AIDS-related dementia, HIV-related dementia, AIDS-induced dementia, HIV-induced dementia, viral dementia, virus-induced dementia, multinucleate giant cell encephalitis, HIV-1-associated cognitive/motor complex, AIDS encephalopathy, HIV dementia, HIV encephalopathy, dementia, mental illness, psychosis, subcortical dementia, depression
