MS Treatment and the prevention of end organ damage

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1.MS treatment and preservation of end-organ damage in MS Gavin Giovannoni Barts and The London2. . 3. Thomas Blizard Curling 1811 – 1888 • Assistant-surgeon to The Royal…
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  • 1.MS treatment and preservation of end-organ damage in MS Gavin Giovannoni Barts and The London
2. . 3. Thomas Blizard Curling 1811 – 1888 • Assistant-surgeon to The Royal London Hospital in 1883 and full surgeon in 1849 • President of the Royal College of Surgeons • Seminal work on tetanus, winning the Jacksonian prize for his work • Famous for his skill in treating diseases of the testes and rectum 4. ESRF end-stage renal failure 5. Does the brain fail in MS? 6. Should multiple sclerosis be redefined as a dementia? 7. www.multiple-sclerosis-research.org 8. Definition of dementia Dementia is a loss of mental ability severe enough to interfere with normal activities of daily living, lasting more than six months, not present since birth, and not associated with a loss or alteration of consciousness.• Normal activities of daily living • • • •Physical  Mental  Social Occupational• Lasting more than six months  • Not present since birth  • Not associated with a loss or alteration of consciousness  9. Occupational functioningPfleger et al. Multiple Sclerosis 2010; 16(1) 121–126. 10. At what level of physical disability does unemployment occur?Kobelt et al. Neurol Neurosurg Psychiatry 2006;77:918–926. 11. Cognition in early multiple sclerosis 60%57% 40%MSers failing ≥ 2 cognitive tests20%p < 0.00010%7%-20%CISers n = 40Healthy Controls n = 30Deficits were found mainly in memory, speed of information processing, attention and executive functioning.Feuillet et al. Mult Scler. 2007. 12. Definition of dementia Dementia is a loss of mental ability severe enough to interfere with normal activities of daily living, lasting more than six months, not present since birth, and not associated with a loss or alteration of consciousness.• Normal activities of daily living • • • •Physical  Mental  Social  Occupational • Lasting more than six months  • Not present since birth  • Not associated with a loss or alteration of consciousness “Multiple sclerosis is therefore a dementia.” 13. What is the pathological substrate of MS dementia? 14. 11,000 to 1Trapp, et al. NEJM 1998;338:278-85 15. ControlMultiple sclerosis 16. Brain atrophy occurs across all stages of the disease n= 963 MSersDe Stefano, et al. Neurology 2010 17. Hypothetical treatment effectsBrain Volume (mL)Brain atrophy curves 1500 1450 1400 1350 1300 1250 1200 1150 1100 1050 1000 950 900 850 800 750Lower limit of normal Average Upper limit of normal303540455055 Age (years)6065707580 18. Hypothetical treatment effectsBrain Volume (mL)Brain atrophy curves 1500 1450 1400 1350 1300 1250 1200 1150 1100 1050 1000 950 900 850 800 750-5%-30%MS lower limitMS Average MS Upper limit 303540455055 Age (years)6065707580 19. Laquinimod: Percent of brain volume change from baseline to month 24 Placebo (n = 1006) Laquinimod 0.6 mg (n = 984)POOLED% Change From Baseline0-0.4-0.8-0.834 -1.188-1.230% P