CNS Infections.txt

  1. CNS Infections: Meningitis
    • Acute purulent type
    • Chronic types: tuberculosis, syphilis, fingal
    • Viral
  2. Meningitis: clinical features
    • Fever
    • headache
    • nuchal rigidity
    • Kernig sign: thigh at 90, can't extend leg without pain
    • Brudzinski sign: neck flexion causes pain and knees to flex
  3. Normal values for CSF exam
    • clear to inspection (like water)
    • opening pressure: 80-180 mm/H2O
    • protein: 20-40 mg/dL
    • Glucose: 45-65 mg/dL (60% blood glucose)
    • Cells: 0-5 lymphocytes
  4. Bacterial meningitis: pathogenesis of brain injury
    • Proinflammatory cytokines: vasodilatation - NO, PGI2, PAF; brain edema (C3a, C5a, histamine)
    • Tissue invasion: brain and ventricles; blood vessels
  5. Acute purulent meningitis
    • Exudate in meninges
    • ploys in subarachnoid space
    • vascular dilatation part of acute inflammation
    • Brain edema
    • ventriculitis and abscess formation - if meningitis is untreated
    • Infection spread to vessels with vasculitis may lead to
    • Multiple small infarcts
  6. Tuberculous meningitis
    • Declining incidence in US except AIDS patients
    • infection begins in the lung: reinfection TV with spread via blood
    • Dx using CSF exam and/or PCR
    • Complications are those of chronic basilar fibrosing meningitis (like cryptococcus and syphilis)
  7. Tb Meningitis
    • thick exudate at base of brain leading to meningeal fibrosis
    • Tuberculoma: extension from meninges - can get a Tb infiltration of brain
  8. Tb meningitis: what are complications of fibrosing meningitis at the base of the brain?
    obstruction of Luschka, decreased reabsorption of CSF in arachnoid villi
  9. CNS Syphilis
    • Occurs in tertiary disease
    • Meningovascular syphilis: chronic fibrosing meningitis; obliterative arteritis with infarcts
    • Tabes dorsalis: dorsal root disease
  10. Meningovascular syphilis
    • Chronic fibrosing meningitis: especially over the convexities
    • Infarcts due to obliterative arteritis
  11. Tertiary syphilis destroys lumbosacral sensory roots
    tabes dorsalis
  12. Tabes dorsalis
    • dorsal root disease with loss of axons in posterior columns
    • Spirochetes seldom seen in tertiary syphilis
    • Impaired proprioception (+Romberg) and loss of sensation in lower extremities
  13. Cryptococcal meningitis
    • Caused by fungus cryptococcus: found in bird excreta, rotting vegetation
    • Underlying debilitating disease, 50% cases - but not just in the immunocompromised
    • Primary focus in the lung
    • Headache, low grade fever, cranial nerve palsies
    • CSF exam important in Dx
    • Chronic, progressive course
  14. Cryptococcal Meningitis Histo
    • Chronic fibrosing meningitis at the base of the brain
    • Meningeal fibrosis traps cranial nerves causing cranial neuropathies
    • Meningitis may etend along Virchow-Robin spaces,but organisms do not invade the brain
    • Noncommunicating hydrocephalus due to chronic meningitis
    • Meningitis obstructs foramina and restricts subarachnoid CSF flow
    • Organisms with thick unstained capsule
    • Capsule around organisms stained with mucin stain
    • CSF showing organisms outlined by India ink
  15. Aseptic Meningitis
    • Usually viral in origin, culture negative
    • Patients present with clinical findings of meningitis
    • Causes: Enterovirus 80%; HSV-2, LCM
    • Often no definite Dx is made
    • Infection is usually self-limited: no treatment is given
  16. Brain Abscess
    • Sources: local or distant infection
    • Etiology usually bacterial - mixed flora
    • Signs of mass lesion with fever: headache, seizures, elevated WBC
    • CSF exam not useful: 10% mortality; 50% morbidity
  17. Brain abscess
    • early abscess without a capsule
    • may also have an early abscess with unilateral edema
    • Early abscess without capsule; necrotic tissue with many ploys
    • Two week old abscess with early capsule formation shown in trichrome stain for collagen (blue)
    • Mature abscess: with fibrous capsule
    • Abscess with ring enhancement
    • this is the only instance ein which there's a fibrous scar forms in the brain - with an abscess
    • will get a ring-enhancing lesion and a lot of edema around the abscess
  18. Embolic infection
    • Mycotic aneurysms: involve small arteries beyond circle; due to bacteria, less often fungi - origin often endocarditis
    • Septic infarcts: infected emboli from heart; infarcts are small, multiple cortical
  19. Mycotic aneurysms
    • wall of aneurysm with inflammation
    • multiple hemorrhagic septic infarcts
    • septic infarct with numerous ploys and clusters of bacteria
  20. Aspergillosis
    • Opportunistic infection: HIV, cancer, immunosuppression
    • Invasive disease
    • May originate from pneumonia
    • Angiocentric infection: and hemorrhagic infarction
  21. Angiophilic infections: other characters in the cast
    • bacteria: meningococci, pseudomonas, leptospira
    • Rickettsiae
    • Fungi: aspergillus, mucomycosis
    • viruses: HIV, varicella/zoster
  22. Aspergillosis
    • Typical lesion deep, can have multiple lesions
    • with a deep hemorrhagic infarct
    • organisms can be seen invading vessel wall
    • Silver stain showing acute angle branching hyphae
  23. Toxoplasmosis
    • Opportunistic infection, esp. AIDS
    • Caused by parasite T gondii
    • Reactivated from dormant sites
    • Presents as massl lesion or infection
    • ring-enhancing lesion by imaging
  24. Toxoplasmosis: histo
    • toxoplasma abscess
    • abscess with necrotic cells and numerous ploys
    • cyst containing many bradyzoites
    • also looks like trypanosome cruzii
  25. Typical viral encephalitis: arbovirus infections
    • represents the typical viral encephalitis: actually CNS viral infection is meningoencephalitis
    • many agents usually in summer, warmer weather
    • sudden onset, fever, headache, drowsiness, stupor, coma
    • Course variable
  26. Viral encephalitis
    • Brain is diffusely swollen and congested
    • lymphocytic perivascular cuffing b/c started in the blood
    • death of neurons are phagocytized (not specific, can also be caused by apoptosis or be seen in Rickettsial disease
    • Glial nodules: primarily of microglial cells and lymphocytes - scattered
  27. West Nile fever
    • was confined to Middle East
    • First US case in summer of 1999
    • Reservoir in crows and other birds
    • Culex mosquito
    • Dx: based on IgM Ab in CSF
    • Sudden onset, fever, headache:rash, muscle weakness, myalgia
    • most cases are mild - 15-20% mortality with encephalitis, risk greater after age 50
  28. Rabies
    • Usually due to animal bite: rabid animal is aggressve; dogs, cats, wild carnivores
    • Contact with bats less common: spread in aerosol
    • Find the rabid animal and test it
    • Long incubation period: shorter when bite is closer to head
    • Human Dx can be made with corneal smear: show rabies antigen with IF
  29. Rabies: clinical facts
    • headache, fever, paresthesias or pain at wound site
    • Patients then become restless, develop seizures
    • Have laryngeal muscle spasm with hydrophobia - can't swallow
    • Nearly 100% mortality without Tx!!: vaccine available - can be given after bite along with human rabies Ig
    • Tx: vaccine and antibodies
  30. Rabies pathology
    • Lymphocytic perivascular cuffing: especially brainstem
    • Negri bodies=cytoplasmic viral inclusions: especially in hippocampus and Purkinjie cells
  31. Latent virus infections: Herpes Simplex Encephalitis
    • Most common sporadic encephalitis in US
    • Usually due to HSV-1: HSV-2 causes meningitis
    • 90% adult population has HSV-1 antibodies
    • primary infection occurs in childhood: often subclinical
    • Encephalitis = recurrent infection
  32. Herpes Simplex Encephalitis
    • 15% pts. have history of oral lesions
    • Sudden onset of headache, fever: may present as a mass lesion
    • CSF contains ploys and red cells early: xanthocromia later, PCR has replaced brain biopsy for diagnosis
    • Rapidly progressive; 20% mortality: Rx with antivirals such as acyclovir - inhibits viral DNA polymerase
    • Inferior frontal or temporal lobe and almost always unilateral: hemorrhagic or necrotizing
    • Tends to produce marked brain edema: patients in danger of cynic from herniation
  33. Herpes simplex encephalitis - histo
    Neutrophils - predominate early: Cowdry inclusion body, EM shows herpes virus: can see virus particles
  34. Varicella - Zoster infections
    • Varicella - worldwide, highly contagious, usually in children; ages 2-8
    • Rash begins on trunk: spreads to mouth, face, limbs
    • Usually benign course - some get encephalitis
  35. Herpes Zoster
    • nonseasonal
    • latent infection: trigeminal ganglion, posterior root ganglia especially; reactivation with lower immunity, HIV, aging, cancer
    • Worldwide, sporadic, nonseasonal
    • Usually in adults
    • Neuropathy, rash: very painful with fever; permanent nerve damage common
    • Vesicular rash following intercostal nerves, rash often unilateral
  36. Shingles: herpes zoster
    • Inflammation in nerve root and ganglia
    • Inclusions in neurons (like simplex)
    • May be necrosis or hemorrhage in ganglia
  37. Progressive multifocal leukoencephalopary (PML)
    • Cause is papovavirus, DNA virus, 40nm: three known strains; JC is major strain
    • 80% population has antibodies: no clinical disease in vast majority; virus latent in lymphoid organs, bone marrow
    • Opportunistic infection: AIDS, lymphoma, immunosuppression - after MS treatment with natalizumab , Poor cell-mediated immunity
  38. Progressive multifocal leukoencephalopathy
    • Onset 45-65 years: younger patients have AIDS
    • Gradual development of symptoms
    • Dementia, focal findings, especially loss of visual acuity
    • CSF exam often normal
    • Subacute course with 3-6mo. survival
  39. PML Histo
    • Multiple small foci of demyelination
    • many lesions located in occipital white matter
    • tiny demyelinating lesions: a lot smaller than in MS
    • Demyelination with many gitter cells
    • Bizarre atypical astrocytes: BIG
    • Intranuclear inclusions: wine-colored in oligodendroglia
    • Composed of numerous viral particles
    • infected olives dies - myelin no longer made nor maintained
  40. Cysticercosis
    • Most common in developing countries: especially Latin America
    • Caused by cestode, taenia solium
    • Eat uncooked pork -> adult tapeworm: release proglottid segments with eggs in stool
    • Fecal-oral route: eat eggs -> larvae hatch and penetrate gut: spread via blood to brain
  41. Cysticercosis
    • CNS symptoms: meningitis, seizures, focal signs
    • Intraventricular lesions may cause hydrocephalus
    • Rx: Surgery, Albendazole
  42. Cysticercosis Histology
    • Cysts in brain often multiple
    • cysts are thin-walled and contain parasites
    • thin-walled cyst with SCOLEX: organism in the middle
    • Intact cyst does not produce inflammation
    • Rx and death of parasite may induce an inflammatory response:
    • scolex have hooklets
  43. Creutzfeldt-Jakob Disease
    • Subacute spongiform encephalopathy
    • Disease both genetic and infectious
    • Agent is an abnormal protein or prion
    • PrPsc derived from normal protein PrPc
    • Results from conformational change
    • about 10% are inherited: PRNP gene on short arm of chromosome 20; point mutations in gene coding for PrPc
  44. Bovine spongiform encephalopathy
    • Human disease is a varian of CJD: vCJD
    • Most cases in britain
    • prions found in appendix in mad cow disease in animals
    • Clinical picture: young adults, longer course, behavioral symptoms
    • Pathologically extensive cortical plaques: !
  45. CJD
    • Onset in middle-aged patients
    • Severe dementia with memory loss
    • Myoclonus
    • Ataxia
    • CSF contains excessive amount of protein: ***
    • Fatal in 6-24 months: !
  46. CJD early spongiform stage
    Spongiform change with marked cellular edema in neurons and neuropil
  47. CJD late stage
    • Cerebral atrophy: large ventricles, large sulci
    • Striking fliosis (PTAH) and marked neuronal loss: brain is totally gliotic
  48. CJD amyloid formation
    • Prion protein undergoes a conformation change into a beta-pleated sheet
    • becomes insoluble amyloid: amyloid (congophilic) plaque
    • can see amyloid plaque with silver stain as well
    • EM shows amyloid as masses of filaments
Card Set
CNS Infections.txt