Multiple Sclerosis Flashcards
WHAT IS MS
i) what is it?
ii) which area is targeted?
iii) what causes the damage?
iv) what may be seen in the form of lesions? where can these form?
v) what is the most common age of onset? is it more common in men or women? how many people are affected worldwide
i) MS is an autoimmune, inflammatory, demyelinating & degenerative condition of the central nervous system.
ii) The immune trigger is unknown but the targets are myelinated Central Nervous System (CNS) Tracts.
iii) In regions of inflammation, breakdown of the blood–brain barrier occurs and destruction of myelin ensues, with axonal damage, gliosis and the formation of sclerotic plaques.
iv) Plaques (MS lesions) may form in the CNS white matter in any location (and also in grey matter); thus, clinical presentations may be diverse
v) onset 20-40yrs
- x2 more common in women than men
- 2.5 million people worldwide
CURRENT DOGMA
i) which two cells are thought to be involved in MS physiol? where do these cells go? what does this cause?
ii) does most damage occur initially when there is a clinical attack or at a later stage? name two things that happen
iii) name two symptoms a patient may present with if there has been demylination of the optic nerve? (2) what is this called?
iv) what happens after a demyelination event? how does this change through disease progression?
v) what is seen on MRI when there are lesions? what can also be seen?
vi) what may be seen in CSF?
i) T cells and B cells > enter CNS > cause inflam and demylination
- T cells activate B cells > recruit more cells
- B cells prod ABs > more damage to CNS
ii) most occures at a later stage > get delayed neuroaxonal loss and gliosis > disease progression
iii) pain on eyemovement, loss of colour vision > optic neuritis
iv) get remylination > clinical recovery
- initially this recovery is complete but gradually has increased disability
v) enhacing lesions (also have breakdown of BBB due to inflam) and can also see brain atrophy
vi) oligoclonal bands > biomarker of MS
GENETIC FACTORS
i) what is the most common gene associated? which chromosome is it found on?
ii) what is the familial recurrence rate?
iii) what can modify the risk of MS?
iv) is there a strong link in monozygotic twins?
i) HLA DRB1 > chromo 6p21
ii) 20%
iii) migration > age of migration affects risk
iv) no - 20-30% > not just a genetic disorder (also enviro)
NON GENETIC FACTORS
i) how is prevalence linked to position from equator? why?
ii) what are 40% of new clinical symptoms associated with?
iii) having what as a young adult increases risk of 8x
i) more cases further from equator > less sun > vitamin D defic
ii) viral infection
iii) EBV as a young adult = 8x increase
DEFINITIONS
i) what is clinically isolated syndrome (CIS)? what is radiologically isol syndrome? (RIS)
ii) what % of patients will relapse/remit after first clinical or radiol dx? what may patients that are not treated with disease mod drugs go on to develop?
iii) what is primary progressive MS?
i) CIS = first presentation of MS
RIS - just radiol change but asymp > a large percent will also become clinically present
ii) 85% will recover then have another attack
- not tx > secondary progressive MS (gradually worse after relapse/remit)
iii) primary progressive is those who get gradually worse after dx and dont have sudden relapses
CLINICALLY ISOLATED SYNDROME
i) what % of cases present like this? what is it?
ii) name four symptoms that are charac of MS
iii) what are Lhermitte and Uthoff features?
i) 85% > acute/subacute neurol sundrome - other differentials as CIS refers to a demyelinating syndrome
ii) painful optic neuritis, partial acute TV myelitis (inflam of sp cord), Lhermitte symptom, bilat interuclear opthalmoparesis, paroxysmal dysarthria, tonic seizures
iii) Lhermitte > electric shock sensation on bending neck (indic cervical spine problem, can be seen in other things eg cervical spondylosis, B12 defic)
Uhtoff - symptoms getting worse after increase in body core temperature eg after a hot shower
- due to impaired but still functioning myelin > bdown in elec impulse transmission when it heats up
OPTIC NEURITIS
i) name three typical features that present with MS? what investigation can be done and what is seen?
ii) name three presenations that are not typical of MS and may be due to another dx?
iii) what imaging should be done? what is seen in MS? what is the risk of MS if this is normal?
i) unilat vis loss, pain on eye movement, afferent pupil defect
- do fundoscopy and see mild swelling
ii) no pain, retinal exudate, retinal haemmorhage, severe disk swelling, no visual recovery after a month or bilateral vis loss
iii) brain MRI > see abnormal lesions consistent with demyelination
- if normal > risk of MS is low (20%)
- if there is one lesion > risk is 80% to be MS
ISOLATED BRAIN STEM SYNDROME
i) name three presenting features that are typically seen in MS?
ii) name three features that make it unlikely to be due to MS?
iii) what makes a MS dx likely on MRI? what criteria can be used
iv) what type of dx if favoured if MRI is normal but symptoms of MS?
i) typical - internuc opthalmoplegia, 6th nerve palsy (one eye in), multifocal signs eg facial sensory loss, vertigo, hearing loss
ii) atypical - hyperacute onset, vasc territory signs, age >50, isol trigeminal neuralgia, non remitting, fever, meningism
iii) lesions consis with demyelination > high risk (60-90%) > use McDOnald criteria
iv) inflammatory condition
ISOLATED SPINAL CORD SYNDROME
i) name four features typical for MS
ii) name four features that make it less likely to be MS? name three differentials
iii) is partial or complete myelitis more common in MS?
i) evolution over hours or days, partial myelitis, purley sensory, Lherrmite, partial brown sequard, spont remission
ii) hyperacute onset, complete TV myelitis, sharp sensory level, radicular pain, fail to remit
- DD > compression eg disk, ischaemia/infarction, inflamm conditions, infection, toxic/nutrition/metabolic, guillian barre/MG
iii) partial eg one leg or arm
DIAGNOSING MS
i) what is dissemination in time? what is dissemination in space? what is needed for a MS dx?
ii) which criteria can be used to confirm DIT and DIS?
iii) name four areas which DIS can be used? how many are needed for a dx?
iv) how can DIT be confirmed? how new is an enhancing lesion
v) what can be seen in the CSF that can confirm DIT?
i) DIT - two demyelinating events at different time points
DIS - two different parts of NS affected eg brain, spine, optic nerve
- need both for an MS dx
ii) MRI > mcdonald criteria
iii) in CNS - periventricular, juxtacortical, infratentorial or spinal cord - need two of these
iv) do a repeat MRI scan > need to see at least one lesions or simultan enhancing lesions
- if lesion is enhancing - its occured in last 6-8 wks and if not enhancing it is older than 2 months (can use enhance/non enhance lesions simultan = dissem in time)
v) pres of oligoclonal bands in CSF
PROGRESSION IN MS
i) which scale is used?
ii) what is a result of 3 likely to correlate with clinically?
iii) what score correlates with a perosn using a walking stick to mobilise? using two walking stick to mobilise?
iv) after which score will the patient do nothing but progress?
v) what is the aim of treatment? how can risk of progression be estimated?
i) EDSS
ii) one sided weakness - mild to mod disability
ii) one stick = 6, two stick = 6.5, wheelchair = 7
iii) EDSS of 3 = irreversible
iv) want to delay patient reaching EDSS of 3 (start tx early to prevent progression) - reduce number of relapses
- estimate progress by how many relapses a patient has (low is 0-1 attach in 2 yrs, intermed in 2-4 in 2 years, high is >5 in 2 yrs)
PREDICTORS OF OUTCOME
i) what is used as an indicator of likelyhood to progress?
ii) what is another predictor of outcome? how is this related to EDSS
iii) how is recovery from relapse associated with outcomes
iv) what can be assessed on MRI in relation to likelihood to progress to MS?
v) lesions in which three brain areas are linked to worse outcomes for patients
vi) increased lesion volume in what time period is assoc with higher risk of converting to secondary relapse/remit MS
i) number of relapses
ii) first inter attack interval - how long between attacks
- patients with shorter intervals reach a higher EDSS quicker
- 6+ years between relapses > EDSS 6 in 20 yrs avg
iii) recover quicker > better outcomes
iv) 0 lesions on MRI > reduced risk of converting to MS
- 0 lesions = unlikely
- 1 lesion > 80% likely
- more lesions = more likely to progress
v) lesions in bs, cerebellum, spinal cord (infratentorial) > patients do worse
vi) high lesions growth/volume in first 5 years
GREY MATTER LESIONS
i) how is grey matter atrophy linked to disease stage?
ii) what do GM lesions it correlate with
i) increased atrophy rate > increased with stage
ii) correlate with disability
MS TREATMENT
i) which injectable treatments be used?
ii) name two side effects of highly effective medications
iii) what two main treatment appraoches are taken
iv) does MRI presentation correlate with EDSS/progression?
i) beta interferon
ii) risk of hepatic infection and malignancy - need surveillance
iii) induction or escalation (start low and only increase if relapse etc)
iv) no - can have lots of WM lesions and low EDSS
