(neuro) cerebral inflammation Flashcards
define meningitis
inflammation of the meninges caused by a bacterial or viral infection
define encephalitis
inflammation of the brain caused by infection or autoimmune mechanisms
define cerebral vasculitis
inflammation of the blood vessel walls, involving the brain (alternatively called angiitis)
which is more aggressive in terms of meningitis: a bacterial or viral infection?
bacterial infection of the meninges tends to be more aggressive than a viral one
define myelitis
inflammation of the spinal cord
what is an alternative term for cerebral vasculitis?
angiitis
what is angiitis?
cerebral vasculitis (i.e. inflammation of the walls of small blood vessels)
how was the existence of the blood-brain barrier discovered?
dyes/tracers were injected intravenously into various tissues
accumulated in most tissues, except CNS tissues
= suggested the existence of a BBB
describe the vascularisation of the CNS
the CNS has very dense vascularisation as no neurone is more than 100 micrometres away from a capillary
how dense is the vascularisation of the CNS?
very dense - no neurone is ever more than 100 micrometres away from a capillary
how much of the cardiac output is directed towards the brain?
approximately 20%
how is the blood-brain barrier formed?
capillaries of the BBB have very strong tight junctions between the endothelial cells = massively reducing the solute and fluid leak across the capillary wall
why does the BBB actually work?
there are very strong tight junctions between the endothelial cells that massively reduce fluid and solute leakage across the capillary wall
how does diffusion occur across the endothelial tight junctions of the BBB?
nothing can freely diffuse across as the tight junctions are extremely strong = massively reduce the solute and fluid leakage across the capillary wall
which CNS cell is involved in maintaining the BBB?
astrocytes
how does the ‘tightness’ of the BBB capillaries compare to peripheral capillaries?
solutes that would normally diffuse and be exchanged across peripheral capillaries cannot cross the BBB
= special transporters to control the influx and efflux of these solutes into/out of the CNS
how is the brain adapted to overcome the additional ‘tightness’ caused by the BBB?
= special transporters to control the influx and efflux of these solutes into/out of the CNS (that cannot diffuse normally across the capillary wall)
give one way in which the tightness of the BBB is an advantage
blood-borne infectious agents have reduced entry into the CNS tissue
what are the initial symptoms of encephalitis?
initially
- pyrexia (high body temperature)
- headache
- flu-like symptoms
what are the longer-term symptoms of encephalitis?
within hours, days, weeks
- confusion, disorientation
- seizures/fits
- changes in personality/behaviour
- difficulty speaking
- weakness/loss of movement
- loss of consciousness
what is the most common cause of encephalitis?
viral infection (herpes simplex, measles, varicella - chickenpox, Rubella)
which viruses commonly cause encephalitis?
herpes simplex, measles, varicella (chickenpox), Rubella
what are the possible causes of encephalitis?
viral infection
mosquite/tick/insect bites
bacterial/fungal infection
trauma
autoimmune
what are the treatments for encephalitis?
depend on underlying cause BUT
- antivirals
- steroids
- antibiotics/antifungals
- analgesics
- anticonvulsants
- ventilation
why are anti-convulsants used as treatment for encephalitis?
prophylactic treatment for potential seizures
what is multiple sclerosis?
autoimmune demyelinating disease of the CNS
how does multiple sclerosis occur?
autoimmune antibodies are produced against the myelin that encases the neurones of the CNS = causing demyelination and subsequent neurodegeneration
what are the types of multiple sclerosis?
relapsing-remitting (associated w inflammation)
secondary progression
what is the relapsing-remitting type of multiple sclerosis associated with?
inflammation (i.e. inflammatory demyelination)
why is myelin important?
insulation of the neurones of the CNS and to enable saltatory conduction
how does multiple sclerosis initially present?
initially presents with different neurological presentation each time
how does axonal loss progress with multiple sclerosis?
progressively worsens as MS proceeds from being relapsing-remitting to continuous (secondary progression)
what does axonal loss cause?
neurodegeneration
how does the cellular pathology of multiple sclerosis progress?
inflammation
demyelination
axonal loss
neurodegeneration
why do the symptoms vary so much between MS patients?
vary because the amount and location of damage/demyelination to the CNS is different in each person w MS
what causes the progression of disease in multiple sclerosis and why?
increased inflammation
leads to increased demyelination = increased neurodegeneration
how many people does meningitis affect yearly?
approx 5 million worldwide
what is the long-term impact of meningitis on individuals?
leaves 1 in 5 people with an impairment after the infection has been cleared
what are the main causes of meningitis?
bacterial infection (meningococcal, pneumococcal, haemophilus influnzae type B, streptococcal)
viral infection (very rarely life-threatening)
fungal infection
what are the main causes of bacterial meningitis?
meningococcal (most common cause of bacterial meningitis in the UK)
penumococcal
HiB (haemophilus influenzae type B)
streptococcal (main cause in new born babies)
what is the most common cause of bacterial meningitis in the UK?
meningococcal
what is the most common cause of bacterial meningitis in the newborns?
streptococcal
how is meningitis confirmed?
take a small sample of CSF and stain it to check for the presence of pathogens
(LUMBAR PUNCTURE)
how do desired fluid and solute molecules overcome the blood-brain barrier?
active transport mechanisms (transport pumps)
what are multiple sclerosis relapses associated with?
inflammatory (demyelination) activity
what do immune cell infiltrates contain in multiple sclerosis?
both T lymphocytes and B lymphocytes
= perivascular immune cell infiltration (CD3 T-cells and CD20 B-cells)
what happens when the blood-brain barrier is disrupted?
leakage of blood from the capillary into the cerebral tissue
= astrocytes migrate to clean up and respond to the leakage
what is the response to a blood-brain barrier disruption?
astrocytes migrate to clean up and respond to the leakage
which cells respond to a blood-brain barrier disruption?
astrocytes
what is astrogliosis?
when the astrocyte numbers increase significantly to repair damage to the CNS
(i.e. when BBB is damaged due to trauma/infection)
which cells make up the perivascular immune cell infiltrate in multiple sclerosis?
CD3 T cells
CD20 B cells
= activated and then migrate across the BBB capillary walls to cause inflammation & damage
