T pnewlydiagnosed may_2012

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T pnewlydiagnosed may_2012

  1. 1. Multiple Sclerosis:disease, investigations,treatment Dr Trevor Pickersgill Consultant Neurologist UHW
  2. 2. Overview Summary History Pathology/causes Diagnosis and tests Range of disease Disease Modifying Treatments and new treatments quackery
  3. 3. Multiple Sclerosis is….. A nasty illness…. A benign illness…… Rapid… Slow…. Treatable…. Untreatable….. Popular: Yahoo 33.4M hits Google 67.5M hits ….a mixed bag - unpredictable
  4. 4. What we really need is amedical…..
  5. 5. St Lidwina of Schiedam1380-1433 Debilitating disease Fell skating 16 Mobility Headaches Violent tooth pains Paraplegic 19 Disturbed vision Died 53
  6. 6. Robert Carswell 1793-1857 Pathologist ‘strange lesions’ in spinal cord Jean Cruveilhier - parisian anatomist
  7. 7. Jean-Martin Charcot1825-1893 Salpetriere La sclerose en plaque First to make clinicopathological links 40 yrs after lesions described Charcot’s (housekeeper’s) Triad: Double vision Ataxia/unsteady Dysarthria/slurred
  8. 8. What Is MS? Inflammatory, Demyelinating Disease Specific to the Central Nervous System Commonest cause of chronic neurological disability in young adults in the UK 20-40 yrs RR------->SP
  9. 9. What causes MultipleSclerosis? Chance Genes Environment
  10. 10. InflammationRubor = RednessCalor = heat = painDolorTumor = swelling
  11. 11. Cardinal feature:brain/spine inflammation
  12. 12. CNS Inflammation Blood-brain barrier breached T Cell (white blood cell - fight infection) sticks to lining Migrates in Attracts more inflammation cells and cytokines (attraction chemicals) produced Inflammation causes demyelination
  13. 13. Demyelinating lesions in multiple sclerosis
  14. 14. Demyelination Disturbs nerve messages Slows conduction May cause block Interrupts normal function of nerves May be silent I.e. cause no problems
  15. 15. Putative Triggers Virus/bacterial infection EBV/glandular fever? Cross reactivity of virus coat proteins Other environmental triggers Susceptible person ….all may trigger an “autoimmune” process
  16. 16. An immune disease White cell activation Complement (destroys cells) activation Low level of immune activity normally - CNS ‘naïve’ antibodies - various or ‘oligo’- clonal in CSF F>M
  17. 17. Who Does MS Affect? Incidence 1 per 800 adult population 150/100,000 SE Wales (90-200 UK) 85,000 people in the UK Female to male 3:2 Age distribution by sex 80 70 60 50 male 40 30 femalePatient Nos 20 10 0 0-14 15-24 25-34 35-44 45-54 55-64 65-74 >75 Age group
  18. 18. What about my children? 1 parent/sib/child: 2-4% 97% risk of not getting MS Risk is over lifetime - so depends on their age If you are 50 you have lived through most of the risk 1 non-immediate relative Risk same as population
  19. 19. Diagnosis Crucial is clinical story - dissemination in time and space…. I.e. multiple sclerosis Poser criteria 1983 Definite Probable Possible Lab-supported/clinical
  20. 20. Diagnosis 2 - excludeother stuff Lupus Sarcoid Strokes Functional illness e.g. anxiety Infection How? - blood tests, chest Xray, MRI interpretation, lumbar puncture, symptoms
  21. 21. Is it MS? - case 1 F Age 14/15 tingling fingers Fatigue and weakness Ix KL and KCH Age 21 Numb feet and fingers, fatigue UCC netball team Patch of ⇓sens forearms VEP normal, OB+
  22. 22. MRI 2000 MRI 2005
  23. 23. Diagnosis? 1 attack 1 clinical lesion No paraclinical evidence of other lesions - MRI/VEP CSF + - told she had MS ‘single’ myelitis - not MS Strictly not ‘clinically isolated syndrome’
  24. 24. Multiple sclerosis: Brain MRI -changing lesions QuickTime™ and a QuickTime™ and a YUV420 codec decompressor YUV420 codec decompressor are needed to see this picture. are needed to see this picture.
  25. 25. McDonald CriteriaBasically MRI can now clinch the diagnosisaloneEven in context of single episode (CIS)>3 months intervalNew lesions appearing or any dye enhancing =Dissemination in TimeDissemination in space criteria now definedMixture of old and new lesions on singleenhanced scan
  26. 26. Case 2 - is it MS? 26F 20th August 2004 10d h/o L arm feeling heavy, foot dragging, ⇓ bladder sensation Clumsy hand - typing Vision normal No headache 4 wks previously viral illness with N+V, abdo pain Swollen optic discs
  27. 27. InvestigationsFlorid WM lesionsNo infratentorialCSF acellularSevere headacheResolved with IVMP31/8/04 no signsDIAGNOSIS = firstepisode CIS
  28. 28. Story continued 21/9/04 - foggy vision R eye Less than 1 month separation 16/17 Ishihara L nil else Resolved over 10d until 1/11/04 R periorbital pain 3/11/04 VA 1/60 Rx IVMP 16/11/04 HM - large scotoma
  29. 29. MRI Dec 2004
  30. 30. Is it MS? ….yes
  31. 31. Dynamic diseaseConstant lesion formationNot all lesions cause symptoms (10%?) QuickTime™ and a YUV420 codec decompressor are needed to see this picture.
  32. 32. Lumbar Puncture
  33. 33. CSF/lumbar punctureanalysis Raised WBC sometimes Protein normal/marginal Characteristic IgG pattern ‘Band negative’ MS
  34. 34. “Types” of MS: are you alumper or a splitter?
  35. 35. Types of MSBenign retrospective diagnosisrelapsing/remitting(RR) 80% of those initially diagnosed will follow this disease coursesecondary progressive (SP) 50-60% of PwMS will have this typeprimary progressive (PP) 10-20% of PwMS. No relapses at onset, progressive disability. Spinal disease. More severe.
  36. 36. PrognosisMean time to EDSS 6.0-18yrs
  37. 37. Relapses New neurological symptoms and/or signs persisting for more than 24h not in the context of infection Many mild, bothersome, irritating only Some more severe - may need treatment Some studies as low as 0.5/yr
  38. 38. Relapse treatment Steroid tablets (Intravenous steroids) Wait and see Do not affect outcome Outpatient Inpatient Rapid Access Clinic UHW
  39. 39. Disease ModifyingTreatments Licensed c.1999 NICE appraisal Modest usefulness 30% reduction relapses ß-ifn: Avonex Rebif Betaferon Copolymer-1 Side effects
  40. 40. Eligibility:Look for documentary evidenceof new neurological deficit>2 ‘disabling’ attacks 2yrsAssessment quite subjective
  41. 41. Eligibility 2 2+ disabling relapses /2yrs Ambulant 10m+ No/minimal background progression No contraindications Willing to inject! 30% choose to withdraw
  42. 42. Newer Treatments:Campath-1H/alemtuzumab Anti-T cell monoclonal antibody Not licensed for MS (yet) Treatment for leukaemia 80+ pts treated South Wales Relapses reduce 90% study early disease v high dose ß-ifn - 55% better than IFN Side effects - long term Single treatment annually - drip once a year
  43. 43. Newer Treatments -Tysabri/natalizumab Reduces adhesion molecules in T cell migration Prevents BBB breakdown Early studies promising MRI data 2yr RCT early RRMS 68% reduction relapses Licensed NHS: ‘highly active’ Monthly drip - 15pts Cardiff
  44. 44. Cell migration
  45. 45. PML riskJC virus40-80% of us have itSits dormant in brainReactivated when ‘normal’ immune systemis damaged (HIV)PML - untreatable - can be mild or fatalPeak after 2 yrsRisk 1:800 overall. Can test for virus If negative 1:10,000 If positive, and had other drugs 1:100150+ cases in 100,000 patients
  46. 46. New Drugs - oral[Cladribine]Fingolimod/Gilenya Daily treatment Heart and skin and eye problems Licensed recently FDA USA Licensed EU April 2011 50% reduction relapses Recently approved NICEEligibility Interferon failure 1+ relapses 1yr and active MRI
  47. 47. GilenyaOnce a day tablet£19,000/yrNICE appraisal - rejected - underappeal - now approvedFirst dose - risk of heart block‘rapidly evolving severe MS’ orinterferon failure MS.Macular oedema/bloodpressure/infections3500 Germany
  48. 48. Fampridine Oral tablet Improves walking efficiency Speed Stride Fatigue Works in 25% of pts Mechanism unsure £360/month - recently licensed Not yet approved NHS - company hasn’t applied!
  49. 49. Vitamin DSmall studies show MASSIVEdoses may reduce relapsesUK population deficientMonth of birth studies - higherrisk of MS if born spring1000 v 14,000 units/dayRisks...pregnancy, heart
  50. 50. On the horizon..... Teriflunomide Laquinimod Baclivuzumab Rituximab Daclizumab BG12
  51. 51. CCSVI....the latest wonder cure Italian doctor New technique measuring jugular vein flow ‘100%’ accurate Experimented on his wife Dozens of private clinics Few large studies - deaths?
  52. 52. CCSVI - factsHugely conflicting results‘too good to be true’MS is an immune disease.....FACT!Sluggish blood flow could not causethis....But might be an after-effectLots of money to be made.....treatingthe rich and the desperate...
  53. 53. And then there was…. Goats’ serum LDN Omega 3 Vit D??? Sativex - cannabis
  54. 54. Thank YouAcknowledgments:NI team UHWMS Society CymruAll attendees today

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