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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?


- 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?


Lesions that are:
- Disseminated in time

- Disseminated in space


How to confirm suspicion of MS?


- 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