CNS infections Flashcards
Describe the blood brain barrier
- 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
List potential sites for CNS infections
- 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)
Describe mechanisms of spread of CNS infections
- Haematogenous pathway
- Physical pathway
- Traumatic/post surgical
- Direct extension
- Peripheral nerve pathway
- Olfactory nerve pathway
Describe haematogenous spread
- 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
Describe physical pathway
- 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)
List examples of other spread
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 ….
Describe clinical features of CNS infections
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
Describe meningitis aetiology
- 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
List some bacterial meningitis causes, risks of acquiring it and associated conditions
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
Describe viral meningitis
- 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)
Describe encephalitis and myelitis
- 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)
Describe brain abscess
- 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
Describe spinal epidural abscess
- 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)
Describe how CNS infections are diagnosed
- 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
List some additional tests
- 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