eMedicine Specialties > Neurology > Neurological Infections

HIV-1 Encephalopathy and AIDS Dementia Complex: Differential Diagnoses & Workup

Author: Niranjan N Singh, MD, DNB, Fellow in Neurophysiology, Department of Neurology, St Louis University School of Medicine
Coauthor(s): Sofia Yahya, MD, Staff Physician, Department of Psychiatry, Barnes-Jewish Hospital, Washington University School of Medicine; Mandeep Garewal, MD, Staff Physician, Department of Neurology, Saint Louis University School of Medicine; Florian P Thomas, MD, MA, PhD, DrMed, Associate Chief of Staff, St Louis VA Medical Center; Associate Director, Neurology Residency Program; Professor, Departments of Neurology, Molecular Virology, and Molecular Microbiology and Immunology, Saint Louis University School of Medicine
Contributor Information and Disclosures

Updated: May 8, 2007

Differential Diagnoses

Alzheimer Disease
Parkinson Disease
EEG in Dementia and Encephalopathy
Parkinson-Plus Syndromes
Frontal and Temporal Lobe Dementia
Pick Disease
Frontal Lobe Syndromes
Uremic Encephalopathy
HIV-1 Associated Opportunistic Infections: Cytomegalovirus Encephalitis
Viral Encephalitis
HIV-1 Associated Opportunistic Infections: PML
Vitamin B-12 Associated Neurological Diseases
Multiple Sclerosis
Multiple System Atrophy
Neurosyphilis

Other Problems to Be Considered

Metabolic encephalopathies
Depression
Psychoactive drugs
Attention deficit hyperactivity disorder

Workup

Laboratory Studies

  • Cerebrospinal fluid (CSF) is rarely completely normal and helps to exclude other etiologies of altered mental status.
    • CSF shows elevated protein (60%) and immunoglobulin G (80%).
    • Oligoclonal bands are sometimes present.
    • CSF is usually acellular, but a mononuclear pleocytosis is found in 25%.
    • HIV antibodies are present.
    • HIV frequently is cultured from CSF or detected by means of polymerase chain reaction (PCR). CSF testing of HIV PCR may be the best correlate of ADC.
    • Several cytokines, chemokines, and other soluble factors are increased, including beta-2 microglobulin, neopterin, and quinolinic acid.
    • Dopamine levels are reduced.
  • Serum studies
    • Vitamin B-12 and folic acid levels should be determined and, if necessary, corrected (see Vitamin B-12 Associated Neurological Diseases.
    • In cases of borderline low B-12 levels, homocysteine and methylmalonic acid levels are better indicators of a deficiency.
    • An assay for anti-parietal cell or anti-intrinsic factor antibodies and a Schilling test may be indicated.

Imaging Studies

  • These can support a diagnosis of ADC and rule out other neurologic opportunistic infections or neoplasms.
  • Diffuse cortical atrophy is the most common finding on CT and MRI. Basal ganglia calcifications are seen in adults but are more common in children. Neuroimaging results may be normal in MCMD.
  • MRI
    • Hyperintense lesions are noted in the periventricular white matter and centrum semiovale on T2-weighted images.
    • These lesions tend to be patchy in the early stages and diffuse as the disease progresses.
    • Differential diagnosis includes multiple sclerosis (MS) and small-vessel disease.
  • Position emission tomography (PET) may reveal abnormalities in cortical metabolism. This method is not widely available and is most useful as a research tool.
  • Single photon emission computed tomography (SPECT) may reveal abnormalities in cerebral blood flow. This method is most useful for research rather than as a routine diagnostic tool.
  • Functional MRI studies are not yet widely available, but they may demonstrate abnormalities in regional brain activation during working memory tasks before mild dementia can be detected by clinical or neuropsychological evaluation.

Other Tests

  • EEG reveals generalized slowing in the later stages of ADC.
  • Neuropsychological testing has a place in diagnosis, management, and monitoring in both clinical settings and research settings.
    • Early in disease, impairment of working memory is noted in bedside testing such as digit and word reversals and serial sevens.
    • In advancing disease, tests that explore motor ability (ie, Finger Tapping Test, Grooved Pegboard Test), concentration (ie, Continuous Performance Test, Trail Making Test A and B), processing (ie, Trail Making Test A and B, Choice Reaction Time), memory/learning (ie, Weschler Memory Scale, California Verbal Learning Test), abstraction (ie, Wisconsin Card-Sorting Test), and speech/language (ie, Boston Naming Test, Verbal Fluency Test) may be helpful.
    • Formal neuropsychological testing results may be normal in MCMD.

Procedures

  • Brain biopsy is not recommended for corroboration, but biopsy material obtained for other reasons may confirm this diagnosis.

Histologic Findings

The hallmark is HIV encephalitis in the white and subcortical gray matter. These changes are noted in 20-90% of patients. Some patients with ADC show only minimal changes. Atrophy is typically in a frontotemporal distribution. Diffuse myelin pallor may be present but is more commonly due to changes in the blood-brain barrier than to demyelination. Vacuolation may be observed.

Cortical neuronal loss is noted in 18-50% of patients. Subcortical neuronal loss (substantia nigra) is noted in 25%. Reduced synaptic density and dendritic arborization may be observed. Some neurons and astrocytes appear to die by apoptosis. Brain tissue may be infiltrated by microglia, macrophages, lymphocytes, and multinucleated giant cells. Activated glial cells are twice as numerous in brains of patients with AIDS as in brains of controls. Microgliosis may be diffuse or form clumps or nodules, often in a perivascular pattern in the white and subcortical gray matter. Infected cells are associated consistently with macrophages/microglia and endothelial cells. Less commonly observed are astrocytes and neurons with restricted expression of HIV genes.

More on HIV-1 Encephalopathy and AIDS Dementia Complex

Overview: HIV-1 Encephalopathy and AIDS Dementia Complex
Differential Diagnoses & Workup: HIV-1 Encephalopathy and AIDS Dementia Complex
Treatment & Medication: HIV-1 Encephalopathy and AIDS Dementia Complex
Follow-up: HIV-1 Encephalopathy and AIDS Dementia Complex
Multimedia: HIV-1 Encephalopathy and AIDS Dementia Complex
References
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References

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Further Reading

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Keywords

AIDS dementia complex, ADC, HIV-1–associated cognitive/motor complex, AIDS encephalopathy, HIV encephalopathy, subacute HIV encephalitis, HIV-associated dementia complex, AIDS-related dementia, HIV dementia, acquired immunodeficiency syndrome, AIDS, human immunodeficiency virus, HIV, minor cognitive motor disorder, MCMD, highly active antiretroviral therapy, HAART

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Contributor Information and Disclosures

Author

Niranjan N Singh, MD, DNB, Fellow in Neurophysiology, Department of Neurology, St Louis University School of Medicine
Niranjan N Singh, MD, DNB is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Coauthor(s)

Sofia Yahya, MD, Staff Physician, Department of Psychiatry, Barnes-Jewish Hospital, Washington University School of Medicine
Sofia Yahya, MD is a member of the following medical societies: American Psychiatric Association
Disclosure: Nothing to disclose.

Mandeep Garewal, MD, Staff Physician, Department of Neurology, Saint Louis University School of Medicine
Mandeep Garewal, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, and American Society of Neuroimaging
Disclosure: Nothing to disclose.

Florian P Thomas, MD, MA, PhD, DrMed, Associate Chief of Staff, St Louis VA Medical Center; Associate Director, Neurology Residency Program; Professor, Departments of Neurology, Molecular Virology, and Molecular Microbiology and Immunology, Saint Louis University School of Medicine
Florian P Thomas, MD, MA, PhD, DrMed is a member of the following medical societies: American Academy of Neurology and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

Medical Editor

Michael J Schneck, MD, Associate Professor, Department of Neurology and Neurosurgery, Loyola University Chicago, Stritch School of Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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