CNS infections Flashcards

1
Q

Describe the blood brain barrier

A
  • Maintains the sterile environment of the brain
  • Formed by the endothelium lining the brain capillaries
    • Intercellular tight junctions – limit paracellular flux
    • Limited pinocytotic activity – limit transcellular flux
    • Additional physical protection with the basement membrane and astrocyte foot processes
    • Specific carrier and transport systems
  • Forms a continuous barrier between the blood and brain that restricts transport of ions, molecules, cells and pathogens – note antibiotics vary in their permeability
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2
Q

List potential sites for CNS infections

A
  • Meningitis
    • inflammation of the meninges (with inflammatory cells in CSF)
  • Encephalitis
    • inflammation of the brain (with or without inflammatory cells in CSF)
  • Myelitis
    • inflammation of the spinal cord (with or without inflammatory cells in CSF)
  • Focal lesions/abscesses
    • Intracerebral/intraspinal
    • Subdural (between dura mater and arachnoid mater)
    • Extradural (between skull and dura mater)
    • Epidural (outside dura mater in spinal canal)
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3
Q

Describe mechanisms of spread of CNS infections

A
  • Haematogenous pathway
  • Physical pathway
    • Traumatic/post surgical
    • Direct extension
  • Peripheral nerve pathway
  • Olfactory nerve pathway
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4
Q

Describe haematogenous spread

A
  • Primary blood infection after entry to body (usually via upper respiratory tract) as a result of BBB breach
    • Bacteraemia – eg Neisseria meningitidis, Streptococcus pneumoniae
    • Viraemia
    • Fungaemia
    • Parasitaemia
  • Secondary blood infection from primary focus of infection elsewhere
    • Eg pneumonia – Streptococcus pneumoniae meningitis
    • Eg endocarditis – Staphylococcus aureus brain abscess
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5
Q

Describe physical pathway

A
  • The BBB/BCB may be physically compromised through
    • Congenital defect
    • Trauma or surgery
    • Extensions from bone infections resulting from
      • chronic sinus, mastoid or middle ear infections
      • vertebrodiscitis (epidural abscess)
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6
Q

List examples of other spread

A

Peripheral Nerve Pathway

  • Eg HSV 1 encephalitis
  • rare

Peripheral Nerve Pathway

  • E.g. Rabies encephalitis (lyssavirus)
  • also rare

Dissemination – Olfactory Nerve Pathway
e.g. URTIs
(Flint et al., 2000)

Naegleria fowleri - amoebic meningoencephalitis

  • Uniformly fatal ….
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7
Q

Describe clinical features of CNS infections

A

Clinical presentations

  • Meningitis
    • Headache
    • Fever
    • Neck Stiffness
    • Photophobia
  • Confusion, seizures and/or neurological deficits
    • suggests either encephalitis/myelitis or focal lesion/abscess
  • Manifestations of infection elsewhere
    • Eg rash, pneumonia, sinusitis, otitis media
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8
Q

Describe meningitis aetiology

A
  • Infectious
    • Bacterial (fatal without antibiotics, more common in children)
    • Viral (most common, usually self-limiting)
    • Fungal (uncommon, fatal without antifungals)
    • Parasitic (uncommon, high mortality)
  • Non-infectious
    • Autoimmune diseases
    • Drugs
    • Malignancy
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9
Q

List some bacterial meningitis causes, risks of acquiring it and associated conditions

A

Organism

  • Streptococcus pneumoniae (Gram-positive diplococcus)

Risks

  • Hyposplenism, <2 years, elderly, HIV infection, hypogammaglobulinaemia (multiple myeloma)

Associations

  • Mastoiditis, sinusitis, otitis media, pneumonia, bacteraemia

Neisseria meningitidis (Gram-negative diplococcus)

Bacteraemia with rash

  • Listeria monocytogenes (Gram-positive bacillus)
    • Immunosuppressed (T cell deficiency), pregnancy, neonates
    • Subacute
    • Zoonosis – unpasteurised dairy products, deli meat, raw salads

Group B Streptococcus (Gram-positive coccus in chains)

  • Neonates – early onset within the first week of life, late onset 1-4 weeks of life
  • Maternal colonisation & chorioamnionitis

Mycobacterium tuberculosis (acid-fast bacillus)

  • TB exposure in the past, reactivation, immunosuppressed
  • Subacute-chronic presentation, tuberculomas
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10
Q

Describe viral meningitis

A
  • Mostly self-limiting without treatment
  • Not all cases of suspected viral meningitis will be confirmed by identification of a viral agent - only a small subset is directly identifiable
  • Enterovirus (picornavirus) & parechovirus
  • Herpes simplex 2»1 (human herpes virus)
  • Varicella-Zoster Virus (human herpes virus)
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11
Q

Describe encephalitis and myelitis

A
  • Acute viral encephalitis/myelitis
    • direct viral infection of neuronal cells
  • Post-infectious encephalomyelitis/myelitis
    • immune-mediated
    • peri-venular inflammation and demyelination
    • eg post-viral ADEM, post-measles SSPE (rare)

Encephalitis & Myelitis

  • Viral (most common)
    • Herpes simplex 1/2
    • Enterovirus (including polio)
    • Varicella zoster
    • Cytomegalovirus
    • Arboviruses (insect transmission)
      • Australian (Murray Valley) encephalitis
      • Japanese encephalitis
      • Kunjin/West Nile virus
      • Rabies
      • Hendra/Nipah virus
  • Bacterial
    • Listeria monocytogenes
    • Mycoplasma pneumoniae
  • Parasitic
    • Naegleria fowleri
    • Acanthomoeba
    • Trypanosoma brucei (African sleeping sickness)
    • Cysticercosis (pork tapeworm)
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12
Q

Describe brain abscess

A
  • Contiguous focus
    • Otitis media, sinusitis
    • Usually polymicrobial including streptococci, anaerobes & gram negatives
  • Haematogenous spread
    • Lung abscess (Streptococcus milleri, anaerobes, Mycobacterium tuberculosis), infective endocarditis (Staphylococcus aureus), dental infection

Brain Abscess

  • Trauma or post-surgical
    • Often Staphylococcus aureus from skin or upper respiratory tract flora from sinuses, but potentially any organism
  • Immunocompromised hosts are at risk for a broad range of unusual microorganisms
    • Toxoplasmosis (HIV)
    • Nocardia
    • Fungal infections (neutropenic)

Ring enhancing lesion with oedema consistent with abscess

  • Clinically behaves the same as other mass lesions, such as neoplasms, but may also have associated fever
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13
Q

Describe spinal epidural abscess

A
  • Collection of pus between the outermost layer of meninges (dura) and the vertebral column
  • EMERGENCY
  • May cause irreversible paraplegia or quadriplegia due to cord compression or infarction
  • Haematogenous spread (50%)
  • Direct extension from osteomyelitis/discitis
  • Penetrating injury
  • Extension from a pressure ulcer
  • Post-procedure
    • e.g. surgery, lumbar puncture, epidural anesthesia
  • Fever
  • Severe local vertebral pain
  • Radicular pain
  • Neurological impairment
  • Staphylococcus aureus 60-90%
  • Mycobacterium tuberculosis (endemic regions)
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14
Q

Describe how CNS infections are diagnosed

A
  • Clinical history including exposures/risk factors
  • +/- Imaging – CT/MRI (encephalitis, brain abscess, epidural abscess)
  • +/- EEG (encephalitis esp due to HSV1)
  • Microbiological (diagnostic and definitive organism identification)
    • LP - CSF analysis
    • Abscess aspirate - culture
    • Tissue biopsy – histology & culture
    • Blood cultures
    • Immunoassay – antibody/antigen detection

note also PCR can be used to identify pathogens

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15
Q

List some additional tests

A
  • Special stains
  • Special culture
    • Mycobacterial
    • ZN/AFBs for TB
    • Giemsa for eosinophils and amoeba
  • Antigen tests
    • Cryptococcus neoformans
  • Molecular tests
    • Herpes simplex 1&2
    • Enterovirus
    • Meningococcus & pneumococcus
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16
Q

Describe herpes simplex encephalitis

A
  • Temporal and frontal lobes
    • Dysphasia and behavioral changes
    • 2/3 have seizures
  • Diagnosis
    • CSF PCR: HSV 1 > 95% sensitivity
    • EEG: temporal spike and wave pattern 84%
    • MRI: abnormal in 50-75%
  • Treat with acyclovir

HSV IgG seroconversion indicates recent HSV1 infection

HSV1 encephalitis may occur with primary or reactivation HSV infection – with or without cutaneous lesions