6 - multiple sclerosis and inflammation Flashcards
fill this in for the action potential in neurones
describe the Node of Ranvier
- no myelin sheath
- where Na+ channels are located
what is the composition of the myelin sheath?
lipids
> galactocerebroside
glycoproteins
> myelin basic protein (MBP)
> myelin oligodendrocyte glycoprotein (MOG)
> myelin associated glycoprotein (MAG)
how does conduction speed differ in unmyelinated vs myelinated axons?
0.5-10 m/s for unmyelinated vs 150 m/s for myelinated
what is multiple sclerosis?
slow progressive CNS disease characterised by destruction of the myelin sheath around the axons in the brain and spinal cord
multiple sclerosis is an immune attack against what?
oligodendrocyte (and/or Schwann cells)
what does the immune attack in MS lead to?
several neurological symptoms, including loss of sensations (touch, taste), motor coordination impairment, vision impairment (involuntary eye movement)
where can pathology occur in MS?
white AND grey matter — lesions occur all over the CNS
what is the clinical-radiological paradox?
- some have few lesions but lots of disability
- some have lots of lesions but not as much disability
new lesions are not always linked to relapses
what are some symptoms and signs of lesions in the cerebrum?
symptoms:
- cognitive impairment (decreased processing speed, decreased memory)
- sensory and motor deficit
- depression
- seizures (rare)
- focal cortical deficit
signs:
deficit in attention, reasoning and executive function (early), dementia (late), upper motor neurone signs
what are some signs and symptoms of lesions in the optic nerve?
symptoms:
- loss of vision
- delayed VEP (visual evoked potential)
signs:
- scotoma
- reduced visual acuity
- colour vision
- pupillary defect
what are some signs and symptoms of lesions in the cerebellum and cerebellar pathways?
symptoms:
- tremor
- clumsiness, poor balance
signs:
- postural and action tremor
- dysarthria
- limb in coordination
- gait ataxia
what are some signs and symptoms of lesions in the brainstem?
symptoms:
- vertigo
- impaired speech
- impaired swallowing
signs:
- dysarthria (difficulty speaking)
what are some signs and symptoms of lesions in the spinal cord?
symptoms:
- weakness
- stiffness and spasms
signs:
- upper motor signs
- spasticity
what is spasticity?
an abnormal increase in muscle tone or stiffness of muscle
lesions in where is a bad prognostic marker?
spinal cord
describe benign MS
- 10-20% of all MS patients
- very short episodes of mild neurological symptoms
- symptoms do not worsen during subsequent attacks
- return to normal between attacks
describe relapsing remitting / relapsing persistent MS
- 85-90% of all MS patients
- unpredictable attacks (relapses) lasting 24 hours or more followed by periods of months to years of improvement (remission) with no new signs of disease activity
- the period between attacks may decrease
- symptoms become more severe
describe relapsing-remitting followed by secondary progression MS
- after 20 years, roughly 50% of those with initial relapsing-remitting MS will have developed secondary progression MS (SPMS)
- this decline may include more severe neurological symptoms, worsening cognitive function, or other deficits
- gradient of slope can differ between people
describe primary chronic progression MS
- describe the approx 10% of individuals who never have remission after their initial MS symptoms
- decline occurs continuously without clear attacks
- affects people who are older at disease onset
disability is most commonly measured using what?
the expanded disease severity scale, EDSS
when is MS typically diagnosed?
between the ages of 20-40
men : woman MS prevalence
1 : 3.5
where are prevalence rates of MS higher geographically?
- further away from the equator
- in northern parts of european countries
what is the chance of both twins developing MS if one twin does for monozygotic and dizygotic twins?
- monozygotic — 25% chance
- dizygotic — 3% chance
in MS, there is a genetic association with which chromosome? what does this also contain?
- chromosome 6
- also contains MHC class genes and myelin proteins
what viruses have been implicated in MS pathogenesis?
hepatitis B, Epstein Barr virus
what is the blood brain barrier?
- membrane that controls the passage of substances from the blood into the CNS
- physical barrier (tight junctions of endothelial cells) between the local blood vessels and smooth parts of the CNS
what is the CNS normally inaccessible to and why?
T cells due to BBB
on an MRI, what do white lesions indicate?
areas of inflammation and open BBB
what can be seen on MRI apart from lesions?
brain atrophy with widened lateral ventricles and cortical sulci
why can diagnosis be harder for primary progressive MS?
few lesions, no clinical relapses
what can lesions represent on T2-weighed MRI scan?
- demyelination
- inflammation
- axonal loss (particularly when visible as “black holes” on T1-weighted imaging)
- gliosis
- remyelination
- oedema
what can lesions represent in T1-weighted MRI scans?
axonal loss and demyelination
cerebrospinal fluid protein electrophoresis shows what in mroe than 90% of MS cases? what is this particularly useful for?
- oligoclonal IgG (gamma-globulin) bands — underlying inflammatory pathology
- particularly useful for primary progressive MS where there are few lesions and relapses
what are visual evoked potentials (VEPs) like in patients with MS?
delayed and reduced
what us a common cause of delayed VEP in MS?
optic neuritis (lesions in optic nerve/tract)
what is the prognosis for those with fewer lesions on MRI at clinically isolated stage (CIS)?
lower risk of developing disability
lesions in where predict greater disability in greater stages?
infratentorial lesions
there are worst cognitive outcomes in MS in who?
men
worst EDSS outcomes in who?
those with primary progressive MS and those who present with high EDSS
