HIV Involving Nervous System

CNS INVOLVEMENT OF HIV:

  • Cerebral involvement: AIDS dementia complex
  • Multinucleate giant cells
  • Vacuolar myelopathy
  • HIV -1 associated neuronopathy is characterized by infiltration of macrophages into the CNS, formation of microglial nodule and multinucleated giant cell which result possibly from virus induced fusion of microglia and/macrophages in central white or gray matter
  • Astrocyte activation and damage, neuronal loss particularly in Hippocampus, Basal ganglia, Caudate nucleus.
PATHOLOGICAL FEATURES OF BRAINS IN AIDS :
 Gross:
  •  Encephalitis: frontal /temporal cortical atrophy 
Histology:
  • Meningitis with mild lymphocytic infiltrates and scanty perivascular inflammation
Features of giant cell (HIV) encephalitis are:
  • Presence of microglial nodules
  • Pericapillary aggregates of multinucleated giant cells having generous or scanty neoplasm 
  • Perivascular lymphocytic cuffing
  • In leukoencephalopathy: there is diffuse demyelination and infiltration of macrophages and multinucleated giant cells.
  • Microscopic findings of HIV encephalitis are :
  1. Diffuse white matter pallor
  2. Perivascular infiltrates of lymphocytes and macrophages
  3. Foci of necrosis, gliosis and / or demyelination
  4. Microglial nodules, macrophages and multinucleated cells
MENINGITIS IN AIDS:
  • Opportunistic infections of the CNS generally occur in HIV infected patients with CD4 counts below 200.
  • Most common organism that causes acute meningitis in an AIDS patients is Cyptococcus neoformans.
Creutzfeldt-Jakob Disease
  • Caused By prion Protein 
  • Prions are proteins. 
  • They are infectious. 
  • Most common infectious prion disease in humans
  • On light microscopy, the pathologic hallmarks of CJD are spongiform degeneration and astrogliosis.
  • The lack of an inflammatory response in CJD and other prion diseases is an important pathologic feature of these degenerative disorders.
  • Spongiform degeneration is characterized by many 1- to 5-um vacuoles in the neuropil between nerve cell bodies
  • In (New variant ) nvCJD, a characteristic feature is the presence of "florid plaques." These are composed of a central core of PrP amyloid surrounded by vacuoles in a pattern suggesting petals on a flower.
 CJD can Occur Following These Procedures
  • Corneal transplants
  • EEG electrodes
  • Dura mater grafts
  • Human growth hormones from human pituitaries
Diffuse Axonal Injury
  • Deep white matter lesion consists of widespread acute disruption, or "shearing," of axons at the time of impact.
  • Pathologically there are small areas of tissue disruption in the corpus callosum and dorsolateral pons. The presence of widespread axonal damage of both hemispheres, a state called Diffuse axonal injury, has been proposed as the explanation of persistent coma or vegetative state, but small ischemic-hemorrhagic lesions in the midbrain and low diencephalon are as often the cause.
  • Only severe shearing lesions that contain blood are visualized by CT, usually in the corpus callosum and centrum semiovale however, within days of the injury,
  • MRI scan demonstrates such lesions throughout the white matter, especially with the use of gradient echo MRI sequences.
CNS

Astrocytoma Oligodendroglioma Ependymoma
Origin from astrocytes
Most common primary brain tumor in adults
GFAP Positive Origin From oligodendrocytes Usually in ventricular system
Glioblastoma multiforme is grade IV astrocytoma Fried Egg Appearance Ependymal rosettes
Crosses midline Chicken wire pattern of capillaries Perivascular pseudorossettes
(Butterfly Glioma) Slow growing Often causes hydrocephalus
Pseudopallisading Necrosis
CNS LYMPHOMA:
  • Primary CNS lymphoma is relatively common type of lymphoma in AIDS patients shows multicentric mass lesions in the brain and meninges derived from B-lymphocytes
  • Presenting symptoms include seizures, headache, and cranial nerve deficits (e.g., the abducens nerve palsy in this patient). The lesions are often multicentric, and may involve the leptomeninges in a significant number of cases.
  • Primary CNS lymphoma is typically a late manifestation of AIDS (median CD4 count 40/μl).
  • This lymphoma is usually an intermediate-to-high-grade B cell lymphoma; evidence of Epstein- Barr virus infection is commonly present.Astrocytoma is a neoplasm derived from cells in the astrocyte lineage. 
  • Ependymal cells line the ventricles. Tumors derived from ependymal cells, called ependymomas, characteristically produce rosettes or perivascular pseudorosettes, microscopically. The incidence of ependymoma is not increased in AIDS patients.
  • Melanoma is a neoplasm arising from transformation of melanocytic cells. Whereas the brain is a favorite site for metastatic melanoma, the incidence of melanoma is not particularly increased in AIDS patients.
SEIZURES IN AIDS:
  • It may be due to:
  • HIV encephalopathy(24-47%)
  • Cerebral Toxoplasmosis(28%)
  • Cerebral lymphoma(4%)
  • Cryptococcal meningitis(13%)
  • Progressive multifocal leukoencephalopathy(1%)
  1. It is due to Polyoma JC Virus
  2. It is mostly due to immunocompromised states.
  3. Demyelination and Astrogliosis are a feature
  4. These are B cell malignancies that present within the neuraxis without evidence of systemic lymphoma.
  5. They occur most frequently in immunocompromised individuals, specifically organ transplant recipients or patients with AIDS.
  • In immunocompromised patients CNS lymphomas are invariably associated with Epstein - Barr virus (EBV) infection of the tumor cells.
  • Treatment :> The mainstay of definitive therapy is chemotherapy including high-dose methotrexate. This is followed in patients < 60 years with radiotherapy. A single dose of rituximab is generally administered prior to cytotoxic chemotherapy
  • Chemotherapy includes high-dose methotrexate, but multiagent chemotherapy, usually adding vincristine and procarbazine, appears to be more effective than methotrexate alone. Chemotherapy is followed in patients90% of patients develop recurrent CNS disease.
Exam Question

  • Progressive multifocal leukoencephalopathy is the least common cause of seizures in AIDS
  • Pathologic features of brain in AIDS includes microglial nodule, Pericapillary aggregates of multinucleated giant cells having generous or scanty neoplasm , Perivascular lymphocytic cuffing, demyelination and infiltration of macrophages and multinucleated giant cells.
  • Cryptococcus neoformans is the most common cause of acute meningitis in an AIDS patient
  • Primary CNS lymphoma shows multicentric mass lesions in the brain and meninges derived from B-lymphocytes
  • Diffuse white matter pallor, Perivascular infiltrates of lymphocytes and macrophages, Foci of necrosis, gliosis and / or demyelination, Microglial nodules, macrophages and multinucleated cells e the Histopathological features of HIV encephalitis
  • Perivascular lymphocytes & microglial nodules are seen in HIV encephalitis
  • Primary CNS lymphoma is the Most common CNS neoplasm in HIV patient
  • HIV associated neuronal loss occurs particularly in Hippocampus, Basal ganglia, Caudate nucleus.
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