2.14 - Cerebral inflammation Flashcards
What is meningitis?
- inflammation of the meninges caused by viral or bacterial infection
- usually subarachnoid - milky white exudate on autopsy over surface of brain
What is encephalitis?
Inflammation of the brain caused by infection or autoimmune mechanisms
What is cerebral vasculitis?
Inflammation of blood vessel walls (sometimes called angiitis) - can cause small blockages/haemorrhages
What is myelitis?
Inflammation of the spinal cord
How was the blood-brain barrier (BBB) found?
If you inject dye intravenously into organs removed from an animal, it will accumulate in most tissues except the brain (unless brain is compromised)
What is the vascularisation like of the brain?
- very densely vascularised (20% of cardiac output is to brain)
- no neuron is >100um from a capillary
What is the BBB formed from?
BBB capillaries have extensive tight junctions at the endothelial cell-cell contacts, massively reducing solute and fluid leak across the capillary wall
What is the function of the BBB?
- because of the ‘tightness’ of the BBB capillaries, solutes that can exchange across peripheral capillaries cannot cross the BBB
- allows BBB to control the exchange of these substances using specific membrane transporters to transport into and out of the CNS (influx and efflux transporters)
- blood-borne infectious agents have reduced entry into brain tissue
What defines the vasculature?
Astrocyte endfeet
What happens when the BBB gets compromised?
- BBB compromised through stroke / physical trauma etc
- blood components including fibrinogen leak into brain
- over time, the astrocytes react to the fibrinogen leakage by withdrawing their endfeet from the walls of the vessel, compromising BBB even more
- BBB compromise also leads to build up of collagen in basement membrane which hardens the vessel leading to small vessel disease in brain
What are the symptoms of encephalitis?
- initially flu-like with pyrexia and headaches
- subsequently within hours, days or weeks:
- confusion or disorientation
- seizures or fits
- changes in personality and behaviour (frontal lobe)
- difficulty speaking (left hemisphere)
- weakness or loss of movement (motor cortices)
- loss of consciousness (brainstem)
What are the causes of encephalitis?
- in most cases, encephalitis is caused by viral infection
- mosquito, tick and other insect bites
- bacterial and fungal infections
- trauma
- autoimmune
What are the commonest viruses which cause encephalitis?
- Herpes simplex virus
- measles
- varicella (chickenpox)
- rubella (German measles)
What are the treatments for encephalitis?
- depends on underlying cause but may include:
- antivirals e.g. acyclovir
- steroids
- antibiotics/antifungals
- analgesics
- anti-convulsants (prophylactic)
- ventilation
What is multiple sclerosis?
An autoimmune demyelinating disease of the CNS
How can MS present clinically?
- most commonly in a relapsing-remitting form of disease - someone has focal neurological symptoms which resolve quickly, but a few months later come in with a different neurological symptom
- different symptoms occur depending on where demyelination happens
- earliest manifestation often (unilateral) optic neuritis
- eventually you stop going into remission and go into secondary progression, where you accumulate neurological deficits
What are the initial relapses in MS linked to?
Inflammatory activity
What is the progression of MS linked to?
Neurodegeneration - can get some remyelination and regain some activity but ultimately neurones start dying
What are the four main pathological traits of MS?
- inflammation
- demyelination
- axonal loss
- neurodegeneration
What does a stained brain/spinal cord section show about MS?
- dark staining is white matter
- loss of dark staining (and therefore white matter) in the deep white matter on left side of brain
- spots of demyelination on right side near lateral ventricle
- in SC section we can see near dorsal horns (top of image) that there are white spots = demyelination
What do we see at a cellular level in MS?
Perivascular immune cell infiltration (CD3 T cells and CD20 B cells) surrounding blood vessels aka perivascular cuffing
What do the symptoms of MS
depend on?
- symptoms vary because amount and location of damage to the nervous system is different in each person with MS
- demyelination is random and can be subtle in some cases and extensive in others
What is meningitis and its’ epidemiology?
- irritation, inflammation and swelling of the meninges
- 6th most common infectious disease killer
- affects >5 million people per annum worldwide
- leaves 1/5 of the infected people with an impairment
What are the bacterial causes of meningitis?
- meningococcal - most common cause of bacterial meningitis in the UK
- pneumococcal
- haemophilus influenza type b (Hib)
- streptococcal - main cause in new-born babies
- (bacteria initially cause upper respiratory tract infection then travel by blood to brain)
What are some other causes of meningitis?
- viral - very rarely life-threatening (e.g. enteroviruses, HSV)
- fungal (e.g. cryptococci)
What are some symptoms of meningitis?
- initially common symptoms of bacterial/viral infection e.g. fever, cold, flu, rash, stiff neck
- sudden fever
- severe headache
- nausea/vomiting
- double vision
- drowsiness
- severity to bright light
- stiff neck
- rash (not always)
Compare meningitis vs encephalitis.
- fever, leukocytosis: often vs often
- meningeal irritation (nuchal rigidity, photophobia): often vs sometimes
- mental status alteration: often vs nearly always
- seizure: uncommon vs often
- focal neurologic findings (e.g. weakness, visual disturbance, aphasia, cerebellar findings, behaviour change): half of patients develop focal findings at some point during disease course (usually later on) vs hallmark feature
What diagnostic tests can be done for meningitis?
- neurological examination
- CT
- MRI
- lumbar puncture (CSF usually clear and colourless; low glucose in bacterial meningitis; raised WBC counts are a sign of inflammation)
- blood
- urine analysis
What are the treatment options for meningitis?
- antibiotics
- antivirals
- corticosteroids (reduce inflammation)
- immune suppressors
What are some of the long-term effects of meningitis?
- long-term learning disabilities
- memory loss
- poor concentration
- clumsiness/coordination problems
- headaches
- deafness/hearing problems/tinnitus/dizziness/loss of balance
- epilepsy
- weakness/paralysis/spasms
- speech problems
- visual problems
What is the pathophysiology of meningitis? (Not taught)
- (most pathogens that cause meningitis colonise the nasopharynx or upper airways —> entry into CNS)
- bacteria can release toxins causing neuronal damage and cell death
- foreign antigens/bacterial toxins trigger an immune response, immune cell infiltration can directly damage nerves
- inflammatory cascade activated will also lead to cerebral oedema
- will raise intracranial pressure
What is the classic triad of meningitis (present in 50% patients)?
Fever, headache, neck stiffness
What are some hallmark features of meningitis? (4)
- distinctive rashes
- kidney and adrenal failure (meningococcal)
- sensitive to bright light
- stiff leg
