Clinical Features of MS Flashcards
Define MS
Chronic, inflammatory, multifocal, demyelinating disease of the CNS of unknown cause
Briefly describe how MS occurs
Autoimmunity -> inflammation -> neurodegeneration (irreversible axonal loss)
Describe the geographical distribution of MS
Latitude effect: the higher the latitude, the higher the incidence and the greater number of MS cases
MS epidemiology in sexes?
More in women than men
MS disease duration
40-50 mean years
Social impact of MS
Only 1 third of patients remain actively employed 15 years after MS onset
Only 1 third of patients remain in a relationship 24 years of MS onset
Describe cognitive impairment in MS
- memory
- speed of information processing
- attention
- executive functioning
Aetiology of MS?
Multifactorial
- genetically susceptible
- environmental factors (latitude, vitamin D, sunlight exposure)
- hormones
- viral infections (EBV)
Evidence of the role of Vit D in MS?
- Low 25 (OH) D serum level-> higher risk of acute attacks
- Low 25 (OH) D serum level -> higher risk of MS
- Low Vit D intake (w/ high latitude) -> higher risk of MS
Potential factors affecting MS incidence?
Latitude effect: greater MS prevalence at higher latitudes; role of Vit D; exceptions to both
Time of exposure: period of susceptibility (<15yrs- original risk & >15 new risk; month of birth effect (May births); more in Spring
Viral Hypothesis: MS triggered by e.g. EBV; more in EBV seropostitive (-ve has 0 risk); higher anti EBV titres has more MS
Genetics: 30% risk, HLA Class II has strongest effect: FHx- 10x risk
Hormones: pregnancy -> less relapses, 3 months post-part has more relapses
Confounding factors for role of Vit D in MS
Black people are more likely to have Vitamin D deficiency, but less likely to develop MS
Confounding evidence to the latitude effect?
- Norway’s North-South gradient is inverted
- Black people are more likely to have Vitamin D deficiency, but less likely to develop MS
Month of Birth effect in MS?
MS higher incidence for May born
Lower incidence for November born
Role of EBV in MS
Similarities in epidemiology:
Young pts (esp women)
High income countries
EBV has a similar latitude distribution
(EBV postive pts are 13x more likely to develop MS)
Confounding evidence to the correlation between EBV and MS
90-95% of world is EBV positive
BUT: MS is virtually absent, among EBV seronegative subjects
Relationship between titres of EBV antibodies and MS?
Higher anti-EBNA IgG titres = higher risk of MS
Relationship between infectious mononucleosis and MS
History of IM = higher risk of MS (2.3 relative risk higher in those with infectious mononucleosis)
Evidence that there are genetic factors for MS
- first degree relatives are 10-25x more likely to develop MS
(HLA-DRB1*15 seems to play a large role)- HLA-clas sII genes have the strongest effect
The role of hormones in MS (2)
- Incidence of MS in women has almost doubled in the last 50 years
- Relapse frequency decreases in pregnancy, but increases in first 3 months post partum
How MS clinically manifests (2)
- Relapses: episodic, acute neuro symptoms lasting over 24 hrs
- Progression: insidious, steady accumulation of irreversible disability for at least 1 yr- needs retrospective assessment (NB: minor/temporary improvement can happen)
Symptoms of relapses (based on lesion location)?
- optic neuritis
- spinal cord lesion: limb weakness, paraesthesia, Lhermitte’s (electric shock), urgency/incontinence, sexual dysfunction
- brainstem lesion: diplopia, paraesthesia, vertigo/nystagmus, dysarthria
- cerebellar lesion: incoordination of limbs, ataxia
- cerebral lesion: impaired conc., hemiparesis, hemisensory, SEIZURES., PSYCH DISTURBANCE
- fatigue
Most common relapse symptoms? (3)
- optic neuritis
- motor weakness
- sensory disturbances
Why are MS symptoms so varied?
Amount and location of damage to nervous system varies between each patient
Subtypes of MS? (3)
and incidence of them
- Relapsing-remitting MS (80-85%)
- Secondary progressive MS (follows RRMS)
- Primary progressive MS (15-20%)
Relationship between RR-MS and SP-MS
85% of RR-MS convert to SP-MS after 25 years from onset (10-15 median years)
How to diagnose MS?
[DIAGNOSIS OF EXCLUSION]
Lesions that are:
- Disseminated in time
- Disseminated in space
How to confirm suspicion of MS?
- MRI
- CSF analysis: increased production of Ig in CSF- oligoclonal bands in CSF only, NOT serum
- Electrophysiology- visually evoked potentials (VEP)-> for DIS criteria
How to use MRI to identify MS?
Use gadolinium contrast to identify how recent the lesion is…
Enhanced contrast at newer lesions from previous 6 weeks (due to faulty BBB)
What is McDonald’s diagnostic criteria for MS?
Uses MRI in conjunction w/ DIT and DIS criteria:
2 attacks (DIT) + neuro exam abnormal
2 attacks +MRI
MRI + 1 attack + neuro exam abn
1 attack + MRI
1 yr disease progression + MRI
Features of MRI-T2 lesions in MS
- round, ovoid
- few mm, 1 cm
- perventricular, around corpus callosum, cerebellum, brainstem
Relationship between MRI lesions and clinical attacks
Most lesions are clinically silent (asymptomatic)
How long does GAD enhancement last for?
2-6 weeks
CSF abnormalities in MS?
White cells: normal/mild increase (10-20 cells/mm3) -90% lymphocytes
IgG oligoclonal bands: +ve in CSF only, NOT serum
Oligoclonal bands in serum pathophysiology?
Inflammation of BBB, allowing Igs to move into CSF
Red flags for alternative diagnosis to MS?
- Lack of oligoclonal bands
- V. high lymphocytes (white cells >20cells/mm3)
What do visually evoked potentials (VEP) show?
Looks at evidence of delayed conduction (that might not show symptoms)
MS DDx
ADEM (Acute Disseminated Encephalomyelitis)
Acute/subacute monophasic inflammatory and demyelinated process of CNS
Single event -6months-> inflammation resolves
Mainly in paeds, low frequency oligoclonal bands, variable symptoms
NMO (Neuromyelitis Optica)
CNS demyelination w/ optic neuritis and Acute myelitis (mainly spinal cord involved)
monophasic/relapsing (more disabling than MS)
Differentiating between ADEM and MS?
MS has much smaller lesions (and lesions are in hallmark areas)
Difference in symptoms of NMO and MS?
MS has unitlateral optic neuritis, but NMO has bilateral optic neuritis
MRI for NMO shows lesion >3 vertebrae
Auto-Ab for AQP4 channel
How is disability graded in MS patients?
Expanded Disability Status Scale (EDSS)
Scale from 1-10
0: complete normal examination
10: death from MS
What is clinically isolated syndrome (CIS)?
First presentation in MS (DIS but NO DIT)
NB: this is at risk of conversion to clinically defined MS
NBII: If demyelinating attack w/ no lesions on MRI -> low probability of a new inflammatory attack
MS prognostic indicators: Good VS Bad?
GOOD Prognostic Indicators
- young onset
- female
- optic neuritis/ only sensory symptoms
- low freq of early attacks
- complete remission of symptoms
- long first inter-attack interval
BAD Prognostic Indicators [more likely to gain progressive MS] - >40yrs at onset - male insidious pyramidal tract involvement - prominent cerebellar involvement - frequent early attacks - rapid dvpmt of fixed disability
Main cause of death in MS patients?
A cause related to their MS
