1. PM6 Assignment  Preparation time  Discussion time  Demonstration time  All based on cases in PM6

2. Multiple Sclerosis Janet Rooney 2006

3. Definition  “A common idiopathic inflammatory demyelinating disease of the central nervous system (brain and spinal cord) characterised by discrete lesions (plaques) scattered throughout the CNS with symptoms resulting from impaired conduction through the demyelinated and transected axons” (Giovannoni and Miller, 1999; Ko Ko, 1999; Schwid, 2003; Lazoff, 2005; Dangond, 2006; Multiple Sclerosis Society, 2006)

4. Prevalence  Most common cause of progressive neurological disability in the United Kingdom Giovannoni and Miller, 1999  Lifetime risk = 1:400 Compston and Coles, 2002  350,000 cases in the United States, more than 2.5 million worldwide Dangond, 2006

5. Prevalence  100-130/100,000 in the United Kingdom Craig et al, 2003; NICE, 2003  52-85,000 people in the United Kingdom NICE, 2003; Multiple Sclerosis Society, 2006

6. Incidence  25,000 persons newly diagnosed with MS in the United States, more than 1 million worldwide Lazoff, 2005  3-7/100,000 diagnosed with MS each year in the United Kingdom NICE, 2003

7.  Early adulthood with a peak onset between the ages of 20 and 45 Ko Ko, 1999  Female to male ratio 2:1  Predominantly northern Europeans  Familial recurrence rate of about 15% Compston and Coles, 2002

8. Diagnosis  Expert panel McDonald et al, 2001  An ‘attack’ Exacerbation/relapse Episode of neurological disturbance Lasts at least 24 hours Not ‘pseudo-attack’

9. Diagnosis  Magnetic resonance imaging  Cerebro-spinal fluid examination Oligoclonal bands on electrophoresis Presence of an elevated I g G  Visual Evoked Potentials Slow but with well-preserved wave form

10. Clinical subtypes  Relapsing remitting 65-75% evolve into secondary progressive ) Dangond, 2006; Multiple Sclerosis Society, 2006  Chronic progressive Primary progressive Relapsing progressive Secondary progressive  Acute fulminant/Malignant  Benign Lazoff, 2005; Multiple Sclerosis Society, 2006

11. Symptoms  Primary Neurological  Secondary Consequence of immobility Consequence of impairment Consequence of Disability  Tertiary Consequence of Handicap

12. Pathophysiology Giovannoni and Miller, 1999

13. Demyelination

14. MRI scan - plaques

15. Impact  Career and aspirations, social and family life  Muscle weakness  Spasticity  Altered or reduced sensation  Visual loss  Dysarthria/dysphagia  Respiratory dysfunction

16. Impact  Loss of coordination/ataxia  Cognitive impairment  Anxiety and depression  Fatigue,  Heat intolerance  Pain/sensory disturbance  Loss of bladder and bowel control Ko Ko, 1999; Thompson, 2001

17. Fatigue  75%-95% of individuals with MS experience variable degrees of fatigue  50%- 60% report fatigue as one of their worst problems Multiple Sclerosis Council for Clinical Guidelines, 1998; Dangond, 2006

18. Fatigue  Contractile force 30-70% lower than controls  Reduced muscle oxidative capacity  Decreased ability to activate their muscle/failure of muscle activation  A portion of the weakness in MS can be attributed to disuse Lambert et al, 2001, Surakka et al, 2004

19. Spasticity  Contributes to poor hygiene  Pressure sores  Difficulty in sexual activity  Painful spasm  Contractures of limbs  Can be a good thing

20. Urinary tract dysfunction  Causes distress, disability and handicap  Urgency, frequency and incontinence combined with poor mobility Disturbance of sleep Tissue breakdown Pressure sores Spasticity Ko Ko, 1999

21. EDSS  Kurtzke Expanded Disability Status Scale  Measure of disease progression Dangond, 2006  Severity scored on a scale of 1-10  Reliable, valid but not responsive Sharrack et al, 1999

22. Heat sensitivity  Uthoff’s phenomenon  Conduction block through partially demyelinated nerves increases steadily as temperature increases  Cooling demyelinated nerves can reduce conduction block  Patients in Schwid et al study reported less fatigue during cooling Schwid, 2003

23. Morbidity/Mortality  Life expectancy of someone with MS is reduced on average by 6 – 11 years Multiple Sclerosis Society, 2006  Live 25 years from diagnosis Compston and Coles, 2002  Will manage without walking aids for 15 years from diagnosis

24. Autonomic Disturbance  Bladder dysfunction  Bowel dysfunction  Sexual dysfunction  Cardiovascular autonomic dysfunction  Thermoregulation  Sweating  Pupillary function Merkelbach et al, 2006

25. Neuroplasticity  Evidence of potentially adaptive cortical plasticity that increases with brain injury in patients with multiple sclerosis Reddy et al, 2002; Reddy et al, 2000  Training dependent changes in the brain can be demonstrated using MRI scanning technology  Limited task specific reductions in activation in the brain following training in patients vs. normals Morgen et al, 2004

26. Interventions for MS  Evolves and changes as disease progresses Education Therapy input  Neurorehabilitation to minimize disability and handicap and to maintain the role of each individual in the family, workplace and community  Alleviation of symptoms Drug treatment  Treatments that modify the course of the disease by changing its natural history Ko Ko, 1999; Thompson, 2001

27. Which intervention  Pills and potions Steroids Beta interferon Glatiramer acetate  Group exercise Freeman and Allison, 2004  Home exercise Surakka et al, 2004

28. Which intervention  Bobath concept Facilitation approach  Motor relearning approach (Carr & Shepherd) Task-oriented approach Lord et al, 1998

29. Which intervention  Yoga Oken et al, 2004  ‘Rehabilitation’ Craig et al, 2003  Supportive technologies Cattaneo et al, 2002

30. Effectiveness  Depends what you mean 65% of patients made functional gains Only 18% improved neurologically Reduction in distress  Ko Ko 1999  The more the merrier  Slade et al 2002

31. Guidelines  National Institute for Clinical Excellence (2003) Multiple Sclerosis: national clinical guideline for diagnosis and management in primary and secondary care [online] available from http://www.rcplondon.ac.uk/pubs/books/ MS/MSfulldocument.pdf [accessed 16/10/2006] http://www.rcplondon.ac.uk/pubs/books/ MS/MSfulldocument.pdf

32. Guidelines  National Institute for Clinical Excellence (2002), Multiple sclerosis – beta interferon and glatiramer acetate for the treatment of multiple sclerosis, NICE Technology Appraisal Guidance No. 51. London, National Institute for Clinical Excellence [online] available from the World Wide Web at http://www.nice.org.uk http://www.nice.org.uk

33. Guidance  Multiple Sclerosis Society (2006), A guide to MS for GPs and primary care teams, London, Multiple Sclerosis Society [online] available from the World Wide Web at http://www.mssociety.org.uk/document.r m?id=1077 [accessed 16/10/2006] http://www.mssociety.org.uk/document.r m?id=1077