All have animal hosts (wild birds, forest rodents)

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Central Nervous System4. Infections
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BRAIN ABSCESS space occupying lesion

• MCC Streptoc. Staphyloc.
• Predisposing conditions
• Acute bacterial endocarditis.
• Cyanotic Congenital Heart Diseases (right to left
  shunt).
• Blood bypassing filtering action of lung and go
  directly to brain
• Chronic pulmonary suppurations. Lung abscess,
  cystic fibrosis
• Direct spread otitis media, mastoiditis or
  sinusitis.
• Clinical picture
• Focal neurologic deficits
• ?ICP, ?CSF protein ?cell count, but normal
  glucose.
• Morphology
• Central focus of suppuration, surrounded by edema
• Later a fibrous capsule reactive gliosis.
• Fibroblasts from larger vessels of brain try to
  wall of infection to form fibrous cap
• Brain has no fibroblasts however in an abscess
  fibroblasts from the BV form fibrosis. Other
  damage has liquefaction necrosis

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BRAIN ABSCESS space occupying lesion

• Complications
• Herniation of fibrous capsule
• Abscess rupture ventriculitis, meningitis
• Rupture into left temporal horn of lateral
  ventricle causing ventriculitis ? usually a fatal
  complication
• Prognosis
• With surgery antibiotics mortality rate is lt
  10

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VIRAL ENCEPHALITIS (VE)

• life-threatening infection of the brain
• Characterized by
• Perivascular parenchymal mononuclear cellular
  infiltrate lymphocyte infiltrate
• Microglial nodules
• Focal proliferations of microglia, try to
  phagocyte
• Neuronophagia
• Individual neurons undergoing necrosis surrounded
  by phagocytic cells PMNs and microglia
• In some VE, inclusion bodies are diagnostic e.g.
  
• Intranuclear Cowdry type A, pink in colour in
  HSV1 present in the temporal lobe
• Cytoplasmic Negri bodies in Rabies hippocampus

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VIRAL ENCEPHALITIS (VE)

• Lesions of VE tend to localize in specific areas
  (viral tropism) e.g.
• HSV -- temporal lobe with hemorrhagic necrosis
• JC virus -- cerebral white matter.
  (oligodendrocytes disease is PML progressive
  multifocal leukoencephalopathy )
• Rabies brain stem
• Present with focal or diffuse neurologic symptoms
  signs and altered level of consciousness.
• CSF profile is similar to viral meningitis.
• Clear, glucose is normal and some lymphocytes in
  CSF

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VIRAL ENCEPHALITIS (VE)
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ARTHROPOD-BORNE VE

• Outbreaks of epidemic viral encephalitis.
• All have animal hosts (wild birds, forest
  rodents) mosquito or tick vectors (zoonoses)
• Clinical course varies widely
• Characterized by
• Perivascular infiltrates
• Foci of necrosis with Neuronophagia
• Necrotizing vasculitis
• No inclusion bodies
• Major types in USA
• Eastern Equine (EEE). Seen in Atlantic, Gulf
  areas.
• Most serious fulminant form of encephalitis ?
  death in 4-5 days
• Western Equine (WEE), seen in West, Midwest.
• Venezuelan Equine (VEE), seen in South.
• St. Louis (SLE), seen in all regions of USA.
• California (CE), seen in East, North-Central
  regions.

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Herpes Simplex (HSV) Encephalitis

• HSV-1 (Labialis) Encephalitis
• MCC of sporadic Viral Encephalitis in USA
• Seen in children young adults
• Causes a hemorrhagic, necrotizing encephalitis
• Localized in the Temporal lobes.
• HSV-1 resides in the Gasserian ganglion in
  patients with labial herpes
• Sensory ganglion on the 5th CN that sends out
  sensory nerve fibers in the lip
• Also has sensory fibers that go out over the
  temporal lobe virus can get to the brain via
  these fibers
• Only 10 have a Hx of recurrent labial herpes

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Herpes Simplex (HSV) Encephalitis

• Cowdry type A intranuclear inclusion bodies
• Eosinophilic intranuclear inclusions with poorly
  defined halo
• Found in both neurons Glia.
• Presents with classic temporal signs
• Alterations in mood, behavior memory.
• HSV-2 (Genitalis) Encephalitis
• Causes generalized severe encephalitis ( not
  limited to temporal lobe) in up to 50 of
  neonates born by vaginal delivery to women with
  active HSV-2 infection.
• Prevent with C section delivery

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Herpes Simplex (HSV) Encephalitis
Cowdry type A intranuclear inclusion bodies

• Causes a hemorrhagic, necrotizing encephalitis
• Localized in the temporal lobes.

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POLIOMYELITIS

• Clinical
• Mild gastroenteritis ? meningitis ? paralysis
• May have paralysis of respiratory muscles
• Fecoroal infection
• Morphology
• Virus attacks the anterior horn motor neurons
  sometimes cranial nerve motor nuclei ? lower
  motor neuron paralysis (flaccid paralysis).
• Process
• Early perivascular infiltrates, Chromatolysis
  Neuronophagia
• Late loss of motor neurons gliosis
• Vaccines Sabin (live virus) Salk (killed
  virus).
• Chromatosis nucleus pushed to the side

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POLIOMYELITIS

• Entero-viruses that enter via oral-fecal route
• 3 strains of poliovirus
• Live vaccines (sabin) must not be given to
  immuno-compromised children!
• Post-polio Syndrome
• Progressive weakness, ? muscle mass (especially
  calf), pain this is only in a few cases
• Dont know why this occurs

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POLIOMYELITIS
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HIV-1 CNS

• 1. HIV-1 aseptic meningitis
• Seen in 10 of patients, 1-2 weeks after
  seroconversion
• Virus can be isolated from CSF
• Usually self limited infection
• 2. HIV-1 encephalitis
• After AIDS develop
• Occurs late
• Presents with AIDS dementia motor complex
• Insidious onset of dementia, apathy, motor
  abnormalities, ataxia, bladder bowel
  incontinence
• Brain shows
• Mild cerebral atrophy, mainly involving
  subcortical gray white matter
• Virus-containing microglial nodules with
  multinucleated giant cells (CLASSIC FINDING)
  fusion of microglial cells
• Demyelination reactive gliosis

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HIV-1 CNS

• 3. Vacuolar myelopathy
• Involvement of the spinal cord
• Demyelination of posterior column
• Results in ataxia
• Demyelination of lateral columns
• Results in spastic paraparesis UMN signs in
  lower extremities
• This is not due to direct HIV virus Virus NOT
  identified in spinal cord (It looks like subacute
  demyelination of the cord due to vitamin
  deficiency, Probably due to impaired utilization
  of vitamin B12 )
• HIV enters the CNS via monocytes/macrophages
• Have CD4 markers which interact with the envelope
  protein of the virus. Microglia and protoplasmic
  astrocytes are vehicles for HIV entry into the
  brain ie the have markers

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HIV-1 CNS

• Microglia astrocytes also have CD4 markers
• They become infected destroyed by the virus
• Fusion of macrophages produces
• Multi-nucleated giant cells, which are
  characteristic of AIDS (AIDS Dementia Complex)
• Inflammatory reaction causes damage
• Cytokines, viral products (e.g. gp 120)
  cross-reacting antibodies may cause damage to
• Oligodendrocytes (demyelination)
• Neurons (neurologic deficit)
• Opportunistic infections of the CNS further
  complicate the clinical picture
• Toxoplasmosis, Cryptococcosis, CMV, JC virus
• (PML), Herpes, Varicella-Zoster, Tuberculosis.

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PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

• Infection of Oligodendrocytes by a Polyoma virus
  (JC virus).
• This virus infects the vast majority of normal
  individuals before the age of puberty, without
  causing symptomatic disease.
• In immunocompromised persons (AIDS) it causes
• Diseases is very aggressive
• Multifocal demyelinating disease
• Most probably represents reactivation.
• Insidious onset of
• Weakness, visual loss, ataxia, dementia ? death
  within 6 months.
• Myelin stain
• Normally should be all blue (luxol fast blue)
  also used to stain axons
• De-myelinated punched out pink areas throughout
  the entire brain

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PML

• Morphology
• Lesions consist of patches of demyelination
• Oligodendrocytes show large nuclei with
  intranuclear viral inclusions
• Astrocytes show atypical nuclei
• Polyoma viruses are
• Oncogenic the nuclear atypia may be an
  expression of ? risk for Gliomas (esp.
  Astrocytomas)

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PML

• Myelin stain stains myelin BLUE
• Normally should be all blue but see completely
  demyelinated punched out pink areas throughout
  the entire brain

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FUNGAL INFECTIONS OF THE CNS

• Seen in immunocompromised patients
• As a terminal event in a more disseminated
  systemic infection.
• MCC
• Candida albicans, Mucor, Aspergillus fumigatus
• Cryptococcus neoformans (true in AIDS patients)
  involves the basal meninges ( negatively staining
  capsule with India ink) Cryptococcus in the CNS
  is AIDS defining diagnoses
• Histoplasma capsulatum, Coccidioides immitis,
  Blastomyces dermatitidis.

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• Patterns of CNS disease include
• Chronic Meningitis
• MCC Cryptococcus neoformans
• Affects the basal Leptomeninges ? may cause
  non-communicating hydrocephalus.
• ? Fibrosis block flow to 4th ventricle
• Vasculitis
• MCC Mucor Aspergillus fumigatus ?
• Invade walls of vessels, intravascular thrombosis
  infarction.
• Focal Encephalitis with granulomas abscesses
• MCC Candida, Cryptococcus

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Cryptococcal Meningitis

• Cryptococcal meningitis India ink preparation
• quick and easy diagnosis
• note the big thick mucoid capsule that doesnt
  pick up the stain