1. Multiple Sclerosis

2. Multiple Sclerosis Definition Classification Etiology Pathophysiology
Epidemiology
Signs + symptoms
Investigations
Treatment
Prognosis

3. Multiple Sclerosis Definition
Demyelinating and inflammatory disease of the CNS
Characterised by multiple and varied neurological signs and symptoms over time
Lesions/attacks must be separated in both space and time
If signs/symptoms can be accounted for by a single lesion then an MS diagnosis cannot be made

4. Classification 1. Relapsing-remitting
Clearly defined attacks/relapses with complete recovery or some residual defect on recovery
No progression of disease between relapses
80% of patients early in course of illness
F>M

5. Classification 2. Primary progressive
Progressive clinical course from onset
F=M

6. Classification 3. Secondary progressive
Initial relapsing-remitting course which becomes progressive
+/- occasional relapses

7. Etiology Controversial Thought to be immune related
Triggering of the immune system by an agent (virus, bacteria, chemicals) in genetically pre- disposed people

8. Pathophysiology
Multiple discrete lesions of myelin destruction (plaques)
Common plague site include optic nerve, periventricular areas, corpus callosum, brainstem, spinal cord

9. Epidemiology Onset usually age 17-35 but can be older or younger
F:M ratio 3:2
Incidence rate per 100,000
Prevalence per 100,000 – higher prevalence in higher altitudes
Genetic predisposition – 3% risk for first degree relatives, 30% concordance for identical twins
HLA-DR2 and DW2 association

10. Signs/symptoms
Correspond to involvement of cerebral hemispheres, brainstem, cerebellum and spinal cord
1. Optic neuritis
2. Motor weakness
3. Sensory loss
4. Brain stem involvement
5. Spinal cord damage

11. Signs and symptoms Optic neuritis – acute phase
Central visual field defect
Scotoma
Pain on eye movement
Often normal fundoscopy
Recovers days
Optic neuritis – chronic phase
Optic atrophy/pale disc on fundoscopy
Visual loss often minor
In women 75% of those with optic neuritis will go on to develop MS

12. Signs/symptoms Motor weakness
Due to pyramidal tract damage (SC or higher)
Weakness – arm extension, leg flexion
Spasticity – increased tone
Hyper-reflexive, clonus, upgoing plantars

13. Signs/symptoms Sensory loss Altered sensation – para/anaesthesia
Anywhere on body

14. Signs/symptoms Brain stem involvement
Dysconjugate eye gaze - slow abduction in the ipsilateral eye with contralateral nystagmus. Due to internuclear opthalmoplegia – disruption by MS plaques of the nuclei and nerve tracts which control the extraocular muscles
Trigeminal neuralgia
Recurrent facial nerve palsy

15. Signs/symptoms Spinal cord damage Para or quadriplegia – gradual onset
Acute transverse myelitis - inflammation of spinal cord producing weakness and sensory loss (dermatomal levels)
Dorsal column damage – ataxic gait (also due to cerebellar plaques)
Lhermitte phenomena

16. Investigations MRI Test of choice to support a clinical diagnosis
Demyelinating plaques appear as hyperintense lesions on T2 weighted images usually around ventricle sor in brain stem
Contrast (gadolinium) identifies active plaque
Classic finding of periventricular lesions in corpus callosum

17. Investigations CSF Oligoclonal Ig bands in > 90% of patients
Increased IgG concentration
Mild lymphocytosis and increased protein
LP much less frequently performed these days

18. Investigations Visual evoked potentials
Useful for documenting slowing of optic nerve conduction
Can also do auditory and somatosensory evoked response testing as well
Good for revealing subclinical conduction defects

19. Treatment 1. Patient education and counselling 2. Acute treatment
3. Disease modifying therapy
4. Symptomatic treatment

20. Treatment 1. Patient education and counselling
Disclosure, future expectations, prognosis
MS society, support groups
Psychosocial issues – depression, relationship distress, suicidality
Psychologists, psychiatrists, social workers

21. Treatment 2. Acute treatment Corticosteroids
Shown to reduce severity and duration of acute relapses
No effect on relapse rate or long term disability
Probably become less effective after repeated attacks
Usual regimen – IV steroids for 3-7 days +/- short oral prednisone taper

22. Treatment 3. Disease modifying therapy
Interferon B (Betaseron, Avonex, Rebif) and glatiramer acetate (Copaxone)
Natalizumab (Tysabri)
Debate about effectiveness
Appears to reduce the number of clinical relapses in selected patients and number of new lesions on MRI
No apparent effect on disability

23. Disease modifying therapy cont
Relapsing remitting – interferon and glatiramer equally effective in reducing relapse rate by 30%, attacks are shorter and less disabling
Primary progressive –
Secondary progressive – interferon may slow progression of disability

24. Treatment 4. Symptomatic
Spacticity – baclofenBladder dysfunction – oxybutynin
Pain – TCA’s, anticonvulsants
Fatigue – amantadine, modafinil, methylphenidate
Depression – antidepressants
Allied health – physio, OT, speech, dietician

25. Prognosis
Good prognostic indicators – female, young, R-R disease, presenting with optic neuritis, low disease burden on MRI at presentation, low rates of relapses early in course of illness
Primary progressive – poorest prognosis, highest rates of disability, poor response to therapy