3-2-2015 CNS Infections

Question 1

Tuberculosis

Answer 1

• CNS involvement in 10-15%
• HIV infection is risk factor
• Meningoencephalitis
  o Most common form of TB in CNS
  o CSF = elevated pressure/protein, decreased glucose, lymphocytic pleocytosis
   AFB+ (acid fast bacilli) cultures, PCR for TB always performed
  o S/S = headache, lethargy, confusion, vomiting
  o Meninges contain lymphocytes, macrophages, granulomas with extension into brain

Question 2

Tuberculoma

Answer 2

o Mass lesion with central necrotic core of caseation, surrounded by fibroblasts, epithelioid histiocytes, giant cells & lymphocytes
o AFB present in necrosis

Question 3

TB Osteomyelitis (Spondylitis aka Pott’s Disease)

Answer 3

o Granulomatous process involves vertebral bodies & discs
o Causes epidural abscess
o Cord compression, vertebral collapse
o Epidural extension of the granulomatous inflammation

Question 4

Neurosyphilis (tertiary stage)

Answer 4

• Months/years after initial infection…10% of untreated patients
  3 Types:
  1. General paresis (paretic neurosyphilis)
  2. meningovascular
  3. Tabes dorsalis

Question 5

General paresis (paretic neurosyphilis)

Answer 5

o Gradual impairment of cognition/attention
o Meningo-encephalitis
 Thickened meninges and atrophic brain
 Meningeal & parenchymal perivascular lymphocytes, plasma cells, and microglia

Question 6

Meningovascular

Answer 6

o Severe at base of brain
o Causes infarcts & hydrocephalus
o Meningeal & arterial/arteriolar lymphocytes & plasma cells with collagenous thickening of wall and eventual occlusion
o Often focal neurologic deficits due to vascular compromise secondary to arteritis

Question 7

Tabes dorsalis

Answer 7

o Chronic inflammation in dorsal roots & ganglia with loss of neurons and associated degeneration of posterior columns (axons & myelin)
o ‘Lightning pains’ or paresthesia in affected roots, eventual loss of position/vibration sense; shuffling broad-based gait

Question 8

Viral meningoencephalitis

Answer 8

• Perivascular lymphocytes, microglial nodules, neuronophagia
• Arboviral encephalitis
  o Important cause of epidemic encephalitis
  o West Nile, Venezuelan, St. Louis, California, etc
  o PCR important to ID specific virus

Also HSV/CMV/VZV/HIV/PML

Question 9

HSV-1

Answer 9

 Most common cause of sporadic acute viral encephalitis in temperate climates
 Headache, fever, mood, memory, behavior abnormalities, drowsiness, coma
 MRI-focal abnormalities in frontal or temporal lobes
 CSF – increased pressure, lymphocytic pleocytosis, elevated protein, PCR for HSV1

Question 10

HSV-2

Answer 10

Meningitis in neonates passing through birth canal in mother with active infection

Question 11

CMV

Answer 11

 Commonest opportunistic viral infection in AIDS patients

 Subacute encephalitis (microglial nodules and intranuclear or intracytoplasmic viral inclusioins)

Question 12

Varicella Zoster

Answer 12

 Reactivation of latent virus residing in sensory ganglia
 Dermatomal distribution
 Scarring and pain

Question 13

HIV

Answer 13

o RNA retrovirus
o Microglia most common cell infected in CNS by HIV
o HIV meningitis
 Presents during acute flu-like illness at time of seroconversion
o HIV encephalitis/leukoencephalopathy
 >75% autopsied HIV patients
 AIDS dementia complex = cognitive and behavioral deterioration, dementia, ataxia, tremor
 Slight diffuse atrophy
 Classic lesion = microglial nodule containing multinucleated microglial cells
o Vacuolar myelopathy

Question 14

Primary multifocal leukoencephalopathy (PML)

Answer 14

o Occurs in immunosuppressed hosts (AIDS)
o Caused by JC virus, polyomavirus, infects oligodendrocytes
o Most have serologic evidence of prior JC virus infection by adolescence…reactivated with immunosuppression

Question 15

Fungal meningoencephalitis

Answer 15

• Commonly in immunocompromised hosts
  o Candida, Mucor, Aspergillus, Cryptococcus, Histoplasma, Coccidiodies, Blastomyces
• Patterns of damage = chronic meningitis, parenchymal invasion, vasculitis

Question 16

Cryptococcosis

Answer 16

o Lungs first, spreads hematogenously to brain
o Often in immunospressed but some in immunocompetent hosts
o Soil and bird feces
o Meningitis with/without brain parenchymal cysts OR abscesses
o CSF: lymphycytes, high protein, nl/low glucose
 India ink stain allows identification of organism (negative staining of capsule)

Question 17

Epidural and subdural Empyemas

Answer 17

• Usually bacterial (staph/strep)
• Local extension of infectious process
  o Frontal/mastoid sinusitis, otitis media, trauma, osteomyelitis, surgical procedure

Question 18

Prion Disease (transmissible spongiform encephalopathy)

Answer 18

• Inherited or idiopathic but also transmissible
  o Ideopathic
   Sporadic Creutzfeldt-Jakob disease (CJD) – most common form
  o Inherited (15%) several forms of familial
  o Acquired
   Iatrogenic CJD (GH, corneal transplant, etc.)
   Dietary
• Infectious agent is abnormal form of prion protein
  o PrPsc = abnormal disease causing form of protein (abnormal B-sheet)
  o PrPc = normal prion protein
   Normally found in brain and selected other organs

Question 19

Creutzfeldt-Jakob disease

Answer 19

o Most common clinical presentation of prion disease
o Rapidly progressive dementia, cerebellar signs (ataxia), myoclonic jerking, 7month survival
o MRI – increased signal in basal ganglia
o CSF = usually normal
o No effective treatment….death within one year
o Spongiform change = neurons with vacuoles (prion protein in vacuole)