NEUROPATHOLOGY OF AIDS

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I. SUMMARY
II. INTRODUCTION
III. OPPORTUNISTIC INFECTIONS
IV. CEREBRAL TUMORS
V. DIRECT INVOLVEMENT OF CNS BY HIV
VI. PERIPHERAL NERVOUS SYSTEM INVOLVEMENT

VOCABULARY TERMS
Terms you should be familiar with:

AIDS
Primary brain lymphoma
Kaposi sarcoma
Human immune deficiency virus
Tropism
Toxoplasma gondii
Cryptococcus
Candidiasis
Coccidioidomycosis
Histoplasmosis
Escherichia coli
Mycobacterium tuberculosis
M. avium intracellulare
Cytomegalovirus
Progressive Multifocal Leukoencephalopathy
Herpes Simplex Virus
Varicella Zoster Virus
AIDS dementia complex
Vacuolar myelopathy


OBJECTIVES: The objectives of this hour are to recognize the central and peripheral nervous systems as primary targets of the infectious agent of AIDS, to be aware of some of the opportunistic infections and neoplasms of the CNS that affect AIDS patients, and to become familiar with the most frequent neuropathologic lesion of AIDS, the AIDS Dementia Complex.

I. SUMMARY

The nervous system is involved in 75% of cases of AIDS examined postmortem. The most significant pathologic processes are related to direct infection by HIV. Other lesions include primary brain lymphoma, opportunistic infections, and a variety of peripheral neuropathies and myopathies.


II. INTRODUCTION

• AIDS is caused by lymphadenopathy associated virus (LAV) or human T cell lymphotrophic retrovirus type III (HTLV III). The virus is now referred to as human immune deficiency virus, or HIV.
  
  
• HIV has a particular tropism for the protein CD4 found on the surface of T4 lymphocytes. T4 lymphocytes are destroyed with consequent loss of cell mediated immunity.
  
  
• HIV at-risk groups have been well defined.
  
  
• 40 to 50% of AIDS patients have neurologic symptoms that in 10% of cases may represent the first manifestation of the disease.

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III. OPPORTUNISTIC INFECTIONS

• Toxoplasma gondii is the most common cause of focal mass brain lesions in AIDS. It was present in 10% of cases in one large study. The characteristic lesion is focal with a necrotic center surrounded by a granulomatous reaction. A biopsy may be necessary to distinguish it from primary brain lymphoma.
  
  
• Mycoses occur in relatively low frequency. Cryptococcus is the most common fungal brain infection in AIDS. Cryptococcus usually presents as meningitis or meningoencephalitis. Cryptococcus can be identified by India ink stain done on CSF. Other mycoses reported (rarely) include candidiasis, coccidiomycosis, and histoplasmosis.
  
  
• Bacterial Infections are relatively rare.
  
  
  • Escherichia coli
  • Mycobacterium tuberculosis
  • Mycobacterium avium intracellulare
  • Syphilis (may be making a comeback in relationship to AIDS.)
    
    
• Viral Infections
  
  
  • Cytomegalovirus (CMV) is found in 26% of brains examined in one large study. CMV may present as acute or subacute encephalitis. Pathologic features include microglial nodules, giant cells containing CMV inclusions, and a typical periventricular location.
  • Progressive Multifocal Leukoencephalopathy occurs in up to 2% of cases; the pathologic features are the same as described for CMV.
  • Herpes Simplex Virus (type I and II) Encephalitis.
  • Varicella Zoster Virus is rarely reported. It tends to occur as white matter lesions.

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IV. CEREBRAL TUMORS

• Primary brain lymphoma is usually of the large B cell type, is often multicentric, and tends to be much more aggressive than when found in the normal population. It may be difficult on clinical and CT grounds to distinguish a primary lymphoma from toxoplasmosis; so brain biopsy may be necessary. It is the second most common cause of a mass brain lesion in AIDS patients.
  
  
• Secondary spread from systemic lymphoma is much less common and occurs as lymphomatous leptomeningitis or as an epidural spinal cord mass.
  
  
• Metastatic Kaposi sarcoma is rare, particularly compared with high incidence of systemic disease.

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V. DIRECT INVOLVEMENT OF CNS BY HIV

• AIDS Dementia Complex (ADC) is the most frequent neuropathologic lesion of AIDS. It was originally thought to be due to CMV and to be a form of subacute encephalitis; but ultrastructural and immunocytochemical evidence strongly supports direct HIV infection of the brain. It commonly presents as a rapidly progressive dementia leading to death within six months. It predominantly involves hemispheric white matter with myelin destruction, bizarre reactive astrocytes, perivascular macrophages, and giant cells. HIV is most often identified in the macrophages.
  
  
• Vacuolar myelopathy lesions are symmetric and most severe in the lateral and posterior columns of the thoracic cord. Pathologic changes resemble subacute combined degeneration, but B12 levels are normal.

VI. PERIPHERAL NERVOUS SYSTEM INVOLVEMENT

• Painful Sensory Polyneuropathy
  
  
• Inflammatory Demyelinating Peripheral Neuropathy
  
  
• Myopathy- Takes the form of polymyositis or shows nonspecific changes

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Go Back to Course Outline

Go Back to Neuropathology

[ Introduction and Objectives | Basic Reactions of the CNS | Vascular Disease | Trauma to the CNS | Alcohol and the CNS | Infections of the CNS | Tumors of the CNS | Diseases of the Myelin Sheath | Spinal Cord Disease | Muscle Disease | Congenital Anomalies of the CNS | Neuropathology of AIDS | Degenerative Diseases of the CNS | Dementia and Related Issues | Unconventional Transmissible Agent (Prion) Diseases ]

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[ CATS Home | About CATS | CATS Teaching Modules | UVM Department of Pathology | Other Pathology Sites | UVM College of Medicine | UVM ]

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Questions? Comments? Send a message to the CATS guru: jkessler@salus.uvm.edu