Infectious Diseases of the Nervous System Pathology Flashcards Preview

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Flashcards in Infectious Diseases of the Nervous System Pathology Deck (59):
1

How does infection manifest in the brain?

  • Hematogeneous spread
    • Arterial spread
    • Retrograde venous spread
      • Anastomotic connections between face veins & cerebral circulation
      • Paravertebral venous plexus, Batson
  • Local extension – air sinuses, infected tooth
  • Neural Route (Extension from PNS to CNS)
  • Direct implantation – trauma, iatrogenic

2

What is neurotropism?

A special affinity for nervous tissue

3

What are the mechanisms for neurotropism?

  • Viral specific receptors on brain cells
    • Poliovirus for motor neurons of anterior horns of spinal cord
    • Mumps virus for ependymal cells lining ventricles
  • Capsule proteins that adhere to meninges and possess antiphagocytic properties
    • Group B streptococci, E. coli subtypes
  • Viral spread along nerves
    • Herpes simplex virus
    • Rabies
    • Varicella zoster virus

4

Meningitis

Clinical signs/symptoms

  • headache
  • photophobia
  • stiff neck (nuchal rigidity)
  • clouded consciousness
  • fever

5

Meningitis

Clinical subtypes (4)

  • Hyperacute (<24 hrs)
    • Meningococcal meningitis
    • Sparse inflammation, numerous organisms, congestion
  • Acute (2-7 days) -most common infection in CNS
    • Usually bacterial
    • Usually results from hematogeneous spread
  • Subacute/chronic (> 1 week)
    • Tuberculosis, syphilis (often brain parenchyma also affected)
    • Lymphocytes, plasma cells, macrophages appear in exudate
  • “Aseptic” (usually viral) - much less fulminant than bacterial meningitis & less severe symptoms
    • Summer & early fall
    • Lymphocytic infiltrate in meninges

6

What can be seen grossly if there is acute meningitis?

layer of exudate under the meninges

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7

What will be seen micropscopically in acute bacterial meningitis?

Exudate present, numerous polymorphonuclear
leukocytes
, in subarachnoid space

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8

What are complications of bacterial meningitis?

  • Brain infarcts
  • Phlebitis
    • may cause infarction of underlying brain tissue
  • 2° vasculitis

9

What causes aseptic meningitis?

  • Arboviruses
  • Enterovirus (most common)
    • Echovirus
    • Coxsackie

10

Parenchymal infections: Brain Abscesses

  • Definition:
  • Clinical Signs & Symptoms:

  • Definition: Circumscribed focus of infection
  • Clinical S/S:
    • focal deficits
    • raised intracranial pressure

11

What are the usual causes of brain abscesses?

Bacterial or fungal

  • Immunocompetent host:
    1. Strep
    2. Staph
  • Immunocompromised host:
    1. Toxoplasma
    2. Nocardia
    3. Listeria
    4. Gram neg bacilli
    5. Mycobacteria
  • •Fungi

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12

  • What is encephalitis?
  • What are the causes?

  • Inflammation of brain
    • Spinal cord-myelitis
    • Meninges and brain-meningoencephalitis
  • Causes: 
    • Bacterial meningoencephalitis
      • Tuberculosis
      • Syphilis
      • Lyme disease
    • Viral meningoencephalitis
    • Fungal meningoencephalitis

13

What is the most common form of tuberculosis in the brain?

Meningoencephalitis

14

What is a risk factor for TB in the brain?

HIV

15

Menigoencephalitis

  • CSF:
  • S/S:
  • Meninges contain:

  • CSF: elevated pressure & protein, decreased glucose, lymphocytic pleocytosis
    • Cultures for AFB are positive in 50%
    • PCR for TB now always performed
  • S/S: headache, lethargy, confusion, vomiting
  • Meninges contain:
    • lymphocytes
    • macrophages
    • granulomas with extension into underlying brain

16

Where is TB of the brain usually found?

Exudate, primarily over the base of brain

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17

What is a tuberculoma?

  • Mass lesion with central necrotic core of caseation, surrounded by fibroblasts, epithelioid histiocytes, giant cells & lymphocytes
  • Acid-fast bacilli (AFB) are present in necrosis

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18

What is the result of TB osteomyelitis?

Spondylitis (Pott’s disease)

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

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19

What stage of Syphilis affects the CNS?

Tertiary

20

  • When does the tertiary stage of Syphilis manifest?
  • How does it manifest?

  • Typically manifests months/yrs after inital infection
    • 10% of patients
  • Major forms:
    • General paresis (paretic neurosyphilis)
    • Meningovascular
    • Tabes dorsalis

21

Describe general paresis (paretic syphilis):

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

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22

Describe the menigovascular type of syphilis:

Chronic meningitis & multifocal arteritis

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

23

Tabes Dorsalis

  • Definition
  • Clinical S/S

  • Chronic inflammation in dorsal roots & ganglia with loss of neurons and associated degeneration of posterior columns (axons & myelin)
  • Clinical S/S:
    • "lightening pains" or paraesthesias in affected roots
    • eventual loss of position/vibration sense
    • shuffling broad-based gait

24

Viral (menigo)encephalitis

  • General Features: 
  • Specific Organisms:

  • General features: perivascular lymphocytes, microglial nodules, neuronophagia
  • Specific organisms
    • Arboviral encephalitis
    • Herpes virus infections (Herpes simplex 1, Herpes simplex 2, Cytomegalovirus, Varicella-zoster)
    • HIV
    • Progressive multifocal leukoencephalopathy (PML)

25

What is the characterstic microscopic pathology of viral encephalitis?

  • Perivascular and parenchymal lymphocytic infiltrate
  • Microglial nodules

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26

What happened if you see:

  • Remnant of a neuronal cell body w/inflammatory cells

Neuronophagia

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27

What is the most common cause of sporadic acute viral encephalitis in temperate climates?

HSV-1

28

HSV-1 in the CNS

  • Clinical S/S: 
  • MRI: 
  • CSF:

  • Clinical S/S:
    • 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 DNA

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29

What are the gross & microscopic changes in acute herpes simplex encephalitis?

  • Gross:
    • congestion
    • swelling
    • hemorrhagic necrosis of temporal lobes, insula, cingulate gyri, orbital cortex
  • Microscopic:
    • Necrotizing hemorrhagic inflammation
    • Intranuclear viral inclusion
      • Cowdry type A

30

When will HSV-2 be seen in the CNS?

Meningitis in neonates passing through birth canal in mother with active HSV2 infection

31

When will CMV be seen in the CNS?

  • Commonest opportunist viral infection in AIDS patients
  • Subacute encephalitis
    • Microglial nodules
    • Cytomegalic cells contain viral inclusions
      • intranuclear or intracytoplasmic

32

When will Varicella Zoster virus be seen in the CNS?

  • Reactivation of latent virus residing in sensory ganglia
  • Vesicles in dermatome distribution
  • Followed by scar and pain
  • Dorsal root ganglia or sensory cranial nerve ganglia have lymphocytes, sometimes necrosis

33

What is an important cause of epidemic encephalitis?

Arbovirus

34

Arboviral meningoencephalitis

  • What are the clinical s/s?
  • What are the specific types important in the US? 
  • What is important for identification of the virus?

  • Generalized neurological deficits (seizures, confusion, stupor, delirium, coma) & focal signs
  • Specific types important in U.S.
    • West Nile
    • Eastern, western equine
    • Venezuelan
    • St. Louis
    • California
  • PCR important for id of specific virus

35

HIV in the CNS

  • What type of virus is HIV?
  • What is the most commonly affected cell?
  • What is a major target of HIV infection?
  • What are the different types of involvement of HIV?

  • RNA virus, retrovirus
  • Microglia are most common cell infected in CNS by HIV
  • CNS is a major target of HIV infection
  • Types of involvement
    • HIV meningitis
    • HIV encephalitis/leukoencephalopathy
    • Vacuolar myelopathy

36

When does HIV meningitis present?

Presents during acute flu-like illness at time of seroconversion

37

What is the presentation of HIV encephalitis/leukoencephalopathy?

  • Present in > 75% of autopsied HIV patients
  • Clinical S/S (AIDS dementia complex):
    • Cognitive and behavioral deterioration
    • eventually dementia
    • ataxia & tremor
  • Slight diffuse atrophy
  • Classic lesion – microglial nodule containing multinucleated microglial cells (contain HIV virus)
    • Also perivascular lymphocytes, patchy demyelination and astrocytosis

38

Progressive Multifocal Leukoencephalopathy (PML)

  • Which patients are vunerable? 
  • What are the causative organisms? 
  • Which virus is most common?

  • Occurs in immunosuppressed hosts (often AIDS patients)
  • Caused by JC virus, polyomavirus, infects oligodendrocytes
  • Most have serologic evidence of prior JC virus infection by adolescence
    • JC virus is re-activated with immunosuppression

39

What are the pathological changes of PML?

  • Small foci of gray discoloration in white matter
  • Irregular poorly defined areas of demyelination
  • Elarged oligodendrocyte nuclei
  • Oligodendrocyte inclusion

40

  • In which patient population does fungi (menigo)encephalitis usually occur?
  • What are the patterns of damage?

  • Commonly occur in immunocompromised hosts (and occasionally in immunocompetent hosts):
    • Candida, Mucor, Aspergillus, Cryptococcus, Histoplasma, Coccidiodes, Blastomyces
  • Patterns of damage
    • Chronic meningitis
    • Parenchymal invasion (encephalitis)
    • Vasculitis (especially Aspergillus and Mucor)
      • Cause hemorrhagic infarcts

41

What are the pathological changes seen with Aspergillus brain infection?

  • Multiple foci of hemorrhagic necrosis
  • Brain necrosis with inflammation

42

Cryptococcosis

  • Causative organism: 
  • Site of infection: 
  • Who usually gets infected?
  • Source: 

  • Cryptococcus neoformans
  • Affects lungs first usually & spreads hematogeneously to brain
  • Most often in immunosuppressed patients
    • may occur in immunocompetenthosts
  • Organism found in soil and bird excreta

43

Cyptococcosis

  • Main forms: 
  • CSF: 

  • Main forms:
    • Meningitis with or without brain parenchymal cysts (encephalitis)
    • Abscesses (Cryptococcomas)
  • CSF: lymphocytes, high protein, normal or reduced glucose
    • India ink stains allows identification of organism (by negative staining of capsule)
    • Assay for presence of Cryptococcal antigen is more sensitive

44

What is the gross change in cryptococcal meninges?

thickened meninges particularly over the sulci

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45

What are the pathological changes seen in cryptococcal menigoencephalitis?

  • Multiple intraparenchymal “cysts”
    • Also called “soap bubbles” (secondary to gelatinous capsular material)
  • Occur in 50% of cases in addition to meningeal involvement

46

What can be seen on microscopy in cryptococcal meningitis?

  • Organisms are single round yeast forms surrounded by capsule (clear space around organism)
  • Usually minimal inflammatory reaction

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47

Parasites of the CNS

  • Single or multicellular? 
  • Who is the typical patient population? 
  • What can they cause?

  • Single-cell organisms
  • Infection occurs in immunocompetent and immunosuppressed (where the infection is more severe)
  • Cause meningoencephalitis or abscesses

48

List the parasites of the CNS (5):

  1. Amoeba
  2. Plasmodium (Malaria)
  3. Toxoplasma
  4. Trypanosoma (Sleeping sickness)
  5. Cysticercus (Taenia solium)

49

What is the most common cause of mass lesions in CNS in AIDS patients?

Toxoplasma gondii

50

Toxoplasma gondii

  • Man is ________ host
    • Cat is ________ host 
  • Infection is secondary to ingestion of ___________ ____ or _____________ _____ from another intermediate host
  • What can happen if there is tranfer to the fetus during pregancy?
  • Which population is at risk for this infection?

  • Man is intermediate host
    • Cat is definitive host
  • Infection secondary to ingestion of contaminated food (cat feces) or raw/undercooked meat from another intermediate host (sheep, pig)
  • Tranfer during pregnancy ⇒ Congenital disease
  • Important infection in immunocompromised hosts, esp. AIDS patients
    • Uncommon in healthy adults

51

What can be seen in cerebral toxoplasmosis?

Multiple localized necrotic lesions

52

Epidural and subdural empyemas

  • Are usually caused by ....
  • What are they an extension of?

  • Usually bacterial (staph or strep commonly)
  • Local extension of infectious process
    • Frontal or mastoid sinusitis
    • Otitis media
    • Trauma
    • Osteomyelitis
    • Surgical procedure

53

What is transmissible spongiform encephalopathy caused by?

Prions

54

What are the types of Prion disease?

  1. Idiopathic
    • Sporadic Creutzfeldt-Jakob disease (CJD) –most common form
    • Inherited (15%): several forms of familial disease
  2. Acquired
    • Iatrogenic CJD (growth hormone, corneal transplant, etc.)
    • Dietary
      • Kuru (Papua, New Guinea)
      • New-variant CJD (vCJD) - linked to “mad-cow” disease

55

Describe how a defective prion protein leads to prion disease:

  • Infectious agent is abnormal form of prion protein
  • PrPsc = abnormal disease causing form of protein, has an abnormal ß-pleated sheet conformation
    • a type of amyloid
    • Does not contain nucleic acid
    • Resistant to usual methods of denaturation (i.e., formalin fixation)

56

Describe the role of the normal prion protein:

  • PrPc = normal prion protein
    • Physiological function uncertain but likely participates in signaling pathways
    • Membrane sialoglycoprotein
    • Gene (PRNP) on chr. 20
    • Normal prion protein is normally found in brain (neurons) and selected other organs

57

What is the BSE epidemic and what did it result in?

  • BSE epidemic
    • Diets contained feed from scrapie infected sheep
    • Spread by addition of infected cow tissues to cattle feed
    • Ban on feeding ruminant-derived protein to ruminants (1988)
  • Ban on cattle offal in human food (1989)
  • Coincidence of vCJD and BSE in time and space
    • Similarity in biological strain phenotypes of vCJD and BSE

58

What is the most common clinical presentation of prion disease?

Creutzfeldt-Jakob disease (CJD)

59

Creutzfeldt-Jakob Disease (CJD)

  • Clinical Features 
  • EEG 
  • MRI 
  • CSF 
  • Treatment 
  • Prognosis

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  • Clinical features
    • Rapidly progressive dementia
    • Often cerebellar signs (ataxia)
    • Myoclonic jerking
    • Mean survival is 7 mos.
  • EEG – triphasicwaves at 1-2 sec intervals
  • MRI – often increased signal in basal ganglia
  • CSF usually normal
  • No effective treatment at present
  • Death occurs w/in one year

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