Types of MS

1. Types of MS Relapsing Remitting Secondary Progressive Primary Progressive

2. Types of disease Main groups • Relapsing remitting 85% (Thompson et al 2000) • Secondary progressive 75% 10-15 years after RRMS (Weinshenker et al 1989) • Primary progressive 10 - 15% Sub groups • “Benign” (Sub-set of RRMS)≈10 - 20% • Progressive relapsing < 5%

3. Patterns of disease

4. Relapsing Remitting (RRMS)

5. Key points (RRMS) • 80 - 85% of new cases will present with RRMS • 40 - 75% RRMS will go on to develop SPMS • Most widely recognised type of MS • RRMS varies greatly in severity in individuals • Frequent relapses at the onset of disease are associated with poorer prognosis (Weinshenker 1995)

6. Clinical course of RRMS • Variable, intermittent disease course • ‘Attacks’ or exacerbation of symptoms (relapses) • Followed by full or partial recovery (remission) • Disability accumulation due to incomplete recovery from relapses

7. Relapses • Episodes of acute or sub-acute neurological symptoms of variable severity • Rapid appearance of new symptoms or reappearance of old over 1-2 weeks • In relapse symptoms last more than 24 hours in the context of normal body temperature • Typically 2 - 6 weeks • May persist for 6 months or longer • Annual relapse rate initially averages 2-2.5 (Barnes 2000) gradually falling as the years progress

8. Remissions • Can last any length of time • Spontaneous recovery generally within 8 -12 weeks • Degree of recovery unpredictable and variable • May be complete (early in disease) or incomplete with residual disability

9. Relapse trigger factors • Stress • Stress includes emotional stress, trauma, and medical interventions • NICE recommend that if a person with MS needs surgery for any reason then it should go ahead • Injury / trauma - Studies indicate that relapse is no more likely to happen (Thompson 2002)

10. Relapse trigger factors • Hormonal changes following child birth • No evidence that pregnancy itself influences the overall course of MS over time • Risk of relapse decreases during pregnancy, in the third trimester relapse is reduced by 60% (Thompson 2002) with same increase in relapse 3 months postpartum • Vaccinations A number of studies are inconclusive but Flu vaccine is now confirmed safe (NICE 2003)

11. Confirmation of new relapse • Establish: • presence of new symptoms • re-occurrence of old symptoms for longer than 24hours • Exclude pseudo-exacerbating factors: • infection • menstrual cycle • stress • Confirm a period of 30 days from end of any previous relapse

12. Disease progression • Specifically refers to increasing damage to the nervous system • Progression of clinical disability • Disability progresses even in between relapses which may only become apparent over time • Some episodes of worsening due to another illness (eg UTI) and not CNS damage

13. Signs of Progression • Increase in polyregional relapses: causing multiple neurological symptoms • Decreased response to steroids • Increase in accumulation of disability- clear evidence of sustained deterioration for at least 6 months • MRI: Axonal loss = cerebral atrophy

14. Progression of MS:axonal integrity and disability

15. Neuroaxonal loss Trapp et al., N Engl J Med 1998;338:278-85.

16. 0 6 0 6 12 18 12 18 Progressive cerebral atrophy Patient 2: Gd-volume = 0.4 ml Patient 1: Gd-volume = 34 ml Losseff et al. Brain 1996;119:2009-19.

17. Brain atrophy in MS

18. Secondary Progressive MS (SPMS)

19. Key points SPMS • Most RRMS will eventually develop SSMS • About 65% of RRMS becomes SPMS by 15 years • Must have clear history of initial RRMS • The rate of deterioration is variable

20. SPMS RRMS Progression to SPMS

21. Clinical course of SPMS • Relapse / recovery may still occur • usually less common and may stop • recovery may be full or incomplete • Disability progression independent of relapses

22. Pathology of SPMS • Main pathology now scarring and further gradual axonal loss • Lesions are large and confluent • Increased risk of cortical atrophy

23. Primary Progressive MS (PPMS)

24. Key points PPMS • About 10% of all cases • Typically older age (40+) & male dominance (Cotterell et al 1999) • Progressive from outset with no discernible relapses or remissions • Typically presents with an increasing spastic gait • Disease modifying therapy ineffective • Management primarily symptomatic

25. Clinical course of PPMS • No relapses / remissions • Prognosis worse • Progressive disability / paraparesis from onset • Symptoms gradually worsen • Often spinal in origin - 85% develop walking problems

26. Primary progressive MS

27. Pathology of PPMS • Inflammation and MRI changes much less marked than in RRMS or SPMS • Inflammation mainly in spinal cord • Fewer lesions on T2 weighted images & in the periventricular area • Lesions that are present are small (85% are less than 5mm in diameter) • Less cortical atrophy • Similar lesions seen in other neurological conditions

28. Spinal MS

29. Spinal MS

30. “Sub-groups” Progressive Relapsing MS Benign MS

31. Benign MS • Really a subgroup of RRMS • Estimated at 10-20% of MS cases • % falls with increasing length of disease • Can develop into full-blown RRMS or progress to SPMS • Accurate diagnosis only possible with retrospect analysis of medical history/ examination over a course of 10-15years

32. Clinical course of Benign MS • Few very mild relapses • Long & complete remissions • Little/no accumulating disability EDSS less than 3 • Very benign cases may be diagnosed only at autopsy

33. Progressive relapsing MS • < 5% of cases and very rare • Progressive from outset with clearly defined relapses superimposed • Possibly may not represent a type of MS but more extreme form of PPMS or SPMS? (Burgess 2002)

34. Progressive relapsing MS Clinical course of P-RMS • Continued progression with acute relapses • There may be recovery from relapses Lublin et al (1996)