Central Nervous System Infections

what are the 2 integral parts of infections for rabies

1. needs to get from bite site to salivary glands

2. needs to change behavior of animal

what is some general information about CNS homeostasis

non-renewable cells → highly metabolically active

• solutes & waste products

CNS is physically separated from the body by

• blood-brain barrier → selective regulated exchange

• blood cerebrospinal fluid barrier

• prevents effects of the body spreading to brain

what can CNS infections result in

meningitis → inflammation of meninges

• e.g. bacterial, fungal

encephalitis → inflammation of brain tissue/parenchyma

• e.g. viral, parasite

what is mechanical protection of the brain

bone & CSF

• meninges - containing CSF

• vertebral column protects spinal cord

what kind of contents can cross the BBB & BCSFB

signaling, nutrients, metabolites, blood vessels & nerves

what are the major routes for infection

blood vessels → major route of CNS infection

peripheral nerves

invasion via ears/sinuses & olfactory tract

penetrating injury/surgery

what are some layer protecting the CNS

hair, skin, bone, meninge (3 layers), brain tissue

• subarachnoid space → contains CSF

• located between arachnoid & pia mater

• CSF → produced by choroid plexus

describe the BBB

tight junctions between capillary endothelial cells

• thick basement membrane

• astrocytes surrounding capillaries

• no fenestrations (pores)

• infection = encephalitis

describe the BCSFB

endothelial cells of capillary

• basement membrane → thinner than BBB

• tight junctions between choroid plexus ependymal (epithelium) cells → looser junction than BBB

• infection = meningitis

how can microorganisms cross the BBB/BCSFB

transcellular

• infection → growing across ECs

• passive transport via endocytosis

pericellular

• transport between cells (if junctions weaken by inflammation)

trojan horse

• inflammation allows infected WBCs to enter CNS

describe how microorganisms infect via peripheral nerves

enter via muscle or directly from peripheral nerves

• travels towards CNS then to brain

• facilitated by cytoskeleton & dynein (moves cargo towards CNS)

describe other methods of CNS invasion

via olfactory tract

• nasal tract → olfactory tract → meningitis/encephalitis

via sinuses or middle/inner ear

• infection tissue damage

direct inoculation

• shunts, head wounds

describe the normal CNS immunity

protected by macrophages (meninges) & microglia (brain parenchyma)

• fewer immune cells than other tissues

• small number of T cells for surveillance

describe CNS during invasion

macrophages activate T cells

• pro-inflammatory cytokines released

• loosen tight junctions, recruit more immune cells

• loose junction can compromise BBB/BCSFB

what are some side effects of immune response in CNS

• swelling in brain

• damage to nerves (irreparable)

• low blood pressure

• potential autoimmunity

how is the CNS monitored for infection

lumbar puncture → testing CSF for microbes

why might CSF appear cloudy

due to the presence of fungi or bacteria

• fungi = rare

what are the clinical presentations of acute bacterial meningitis

1. fever

2. stiff neck

3. altered mental status

4. headache

how is acute meningitis diagnosed

history of patient

• knowledge of current illness, vaccines

physical examination

blood culture

CSF EXAMINATION

what are the 3 main bacteria responsible for bacterial meningitis

• Hemophilus influenzae

• Streptococcus pneumoniae

• Neisseria meningitidis

what is some information about Neisseria meningitidis

-gram (CSF) diplococcus bacterium

• expresses lipopolysaccharides → inflam. response

• thick capsule → prevent phagocytosis (blood survival)

• untreated = septic shock

• transmission = droplets

• vaccines don’t protect against every serogroup

what is some information about Streptococcus pneumoniae

+gram coccus shaped bacterium

• thick capsule → prevent phagocytosis (blood survival)

• carried in throats of many healthy patients

• invasion of blood & meninges is rare

what is some information about hemophilus influenzae

-gram non/capsulated coccobacillus bacteria

• expresses LPS → large inflammatory response

• healthy people may carry non-capsule type in throat

• rarely enters blood & meninges

describe the treatment for bacterial meningitis

3rd generation [broad spectrum] cephalosporin

• often dexamethasone for reduced inflam. response

• switch following species identification & testing

describe TB meningitis

gradual onset → develops over several weeks

• symptoms: malaise, anorexia, neck stiffness

• always a focus of infection elsewhere (e.g. lungs)

• CSF = clear but ↑protein, ↓glucose, ↑WBCs

• treatment needs to be fast to prevent serious issues

describe fungal meningitis

primary infection site = lungs → blood → meningitis

• low birth weight babies → suppressed cell-mediated immunity

• major cause: cryptococcus neoformans

describe protozoal meningitis/encephalitis

rapid onset, usually fatal

• amoeba enters nose, olfactory tract → meningitis

• can infect healthy individuals

describe viral meningitis

milder disease than bacterial meningitis

• symptoms: headache, fever, photophobia

• CSF = aseptic (non-bacterial meningitis)

• PCT testing

• usually recover without drugs (rest & support)

what are some common effects of encephalitis

cerebral dysfunction - abnormal behavior, seizures

focal neurological effects - loss of sensation, muscle weakness, partial paralysis

altered consciousness - hallucinations

describe the general pathogenesis of bloodborne viruses

viruses commonly access the CNS via the blood

• leaves blood via BBB → infects glial cells

• causes damage/dysfunction

immune response

• monocytes & lymphocytes go from blood to brain

• can clear infection but also cause immune pathology

what are some clinical features of viral encephalitis

fever & headache

• seizures depending on region of brain

alter conscious state - “acting funny” to coma

focal neurological signs - depends on affected brain regions

describe the management for viral encephalitis

immediate treatment

• HSV therapy

• restricting fluids to lower pressure in brain

• anti-seizure medication

describe herpes simplex virus

primary infection → lesions or cold sores

• enters sensory nerves, travels to dorsal root ganglion or trigeminal ganglion

• can be reactivated by stress or illness

• ganglion typically returns to lesions, can travel to CNS leading to encephalitis

describe diagnosis & treatment of HSV using CSF

CSF may have ↑lymphocytes, RBCs

• medical imaging can also find evidence of HSV

• PCR of CSF can help identify HSV

treatment

• prompt treatment with acyclovir before diagnosis confirmed

what are some clinical features of rabies

bite/scratch from animal

• slow incubation → virus must reach peripheral nerves

• no immunological response → hidden in nerves

• virus spreads from peripheral nerves → CNS

what are the main symptoms of rabies

• behavioral changes

• flu-like symptoms

• spasms, fits, hallucinations

• coma, respiratory failure

• death

how is rabies diagnosed

detect viral antigen by immunofluorescence/RT-PCR

• skin biopsies, saliva or CSF

what is some information on HIV

retrovirus, may invade CNS after initial infection

• ↑WBCs in CSF

as disease progresses → subacute encephalitis with dementia may occur

describe post vaccinal/post infectious encephalitis

• infection of CNS by “slow virus” years after infection

• incomplete replication due to partial control by host

• usually triggered by immune response to host & virus

what is spongiform encephalopathy

common pathology of prion diseases

• appearance of gaps in brain tissue

• misfolding of proteins

describe the parasite toxoplasma gondii

parasite ingested from sources like uncooked meat, contaminated water

• can localize to brain → eye damage

what is clostridium tetani (tetanus)

bacteria that secrete a toxin that causes damage to CNS

• toxin travels to CNS via retrograde transportation up motor neurons to CNS

• overactive moto neurons → stimulate contraction pathway

• rigid paralysis