Multiple Sclerosis

1. Multiple Sclerosis Short synopsis Ross Bills 11/2/06

2. Pathology • Demyelination (loss of white matter) within CNS/Spinal Cord • Myelin sheath degenerates, fat-granule cells and lymphocytes in perivascular spaces, sclerotic plaque later (shrunken, greyish to naked eye) • Single/multiple lesions • Multiple sites present confusing clinical picture • Clinical findings dependant on sites

3. Aetiology • Complex • Geography - temperate climates more than tropical, but if people move regardless of genetic background they carry the risk of where they grow up • Familial - familial - 5% • Precipitants - complex, infection including influenza, pregnancy puerperium and lactation, allergy, surgery, trauma • Biochemical - Myelin 75% lipids, 25% proteins, enzymes that break down the protein have been found at edges of plaques, low dietary intake of polyunsaturated fats in areas where incidence is higher? • Immunological - demyelinating antibody found in plaque which acts on glial cells? • Viral - increased incidence of high antibody titres to measles, mumps, vaccinia and herpes simplex • Allergic - some animal studies showed similar pathology.

4. Presentation • Age 20-40 years at onset (12-60 not unheard of) • 1:2000 in England and Wales • 19,000+ patients in Australia • No sex bias • One of the commonest neurological conditions

5. Types of MS • Relapsing Remitting • Progressive Relapsing • Secondary Progressive • These terms describe the pattern of the disease over time.

6. Clinical • Two presentations • Single or several focal lesions worsening over a short time - settling over 1 to 2 weeks • Visual changes (optic neuritis) • Numbness or weakness of a limb, face • Bladder symptoms • Insidious onset slowly progressive, classically weakness of one or both lower limbs • Remission may see signs improve or vanish

7. Symptoms • There is no set pattern to MS and everyone with MS has a different set of symptoms, which vary from time to time and can change in severity and duration, even in the same person. • The systems commonly affected include: • vision • co-ordination • Strength • sensation • speech and swallowing • bladder control • sexuality • cognitive function • Fatigue • http://www.msif.org/en/symptoms_treatments/index.html

8. Value of the history • Because of the variability of signs and symptoms the history is all important - there may be NO clinical signs • Only later after several attacks may the signs become more permanent • More acute onset: • Pallor of the optic disc (unilateral) • Slight unilateral nystagmus • Slight intention tremor • Changes in abdominal or tendon reflexes, extensor plantar response (Babinski) • Insidious onset: • Predominantly spinal signs • Spastic paraplegia • Sensory including vibration sense changes, position sense changes • Spastic or ataxic gait

9. Investigation 1 • Investigate to exclude other causes: • Differential Diagnosis • Spinal Cord Compression • Cervical Spondylosis • Hereditary Ataxias • Tabes Dorsalis • Vitamin Deficiency (B12) • Psychological/Psychiatric Disorders • Others

10. Investigation 2 • Old: Lumbar puncture looking for abnormal proteins, monoclonal bands (oligoclonal IgG) • Ongoing: Visual evoked responses, (2/3 of people with clinical MS and no visual symptoms had abnormal VER) Auditory evoked responses, (May show changes in brainstem lesions) • Best: MRI Scan defines demyelinated lesions very well

11. Prognosis • Such a variable course • The prognosis becomes clear only after observing the patient over time • Rapidly Progressive versus Exacerbations with remissions of variable time (up to 20 years and more)

12. Treatment 1 • In the absence of curative treatment patient education and support is vital • Bladder disorders are common • Probanthine improves bladder control • Fatigue and tiredness are common • Exercise and activity within achievable levels has been shown to be beneficial • Muscle spasm and spasticity • Baclofen may help, physiotherapy, exercise • Specific Dietary Measures may be of little value • Avoidance of animal fat led to reduction in polyunsaturated fatty acids, B12 injections only useful if there is a deficiency

13. Treatment 2 • Does anything help? • In the past IV methylprednisolone infusions over five days showed some benefits in reducing length of exacerbations and severity - still used. • Dexamethasone also used • Oral steroids may also be useful (Prednisolone) • No real benefits with long term steroids • Azothioprine and other immunosuppressants showed little value in relatively benign cases, where side effects outweighed benefits • Psychological Support may be beneficial in terms of CBT to assist in coping strategies, and also in the treatment of the often present co-morbid depression of chronic disease

14. Treatment 3 • Newer Options: • Interferon has been shown to reduce recurrences and degree of disability in people who have the exacerbation/remission pattern of MS • Side effects can be severe - injection site reactions, flu like symptoms, fatigue, headache, muscle and joint pains • Interferon beta-1a (Avonex) • Interferon beta-1b (Rebif) • Interferon beta-1b (Betaferon)

15. Treatment 4 • Newer Options: • Methotrexate may have some benefits, but these need to be weighed against the serious side effects • The benefits found were not statistically significant. • This raises an obvious evidence based medicine question? Refer to Cochrane database.

16. Treatment 5 • Newest: • Mitoxantrone (MX) [Immunosupressive drug] • Has shown benefits in short term treatment of MS • Side effects are significant, and limit its use to those with evidence for significantly worsening disability • Amennorhea, nausea, vomiting, alopecia, UTI’s, transitory leucopenia in the short term • Cardiotoxicity, therapy related acute leukaemias in the longer term • Copaxone (glatiramer acetate) • Hippocrates: “First do no harm!” • Bills: “If the cure is worse than the disease, then let the patient decide to have the disease!”

17. Treatment 6 • Alternative Therapies • Supplements and vitamins - no scientific support • Fatty Acids - may have a modest effect in slowing progression, reducing severity and duration of exacerbations • Diets - a balanced diet may do no good, but will do no harm. No evidence for value of “fad diets” • Removal of old “mercury amalgam” fillings - no evidence • Acupuncture - may have psychological benefits, no influence on course of disease. Relief of pain and muscle spasm nay be a real benefit though. • Yoga/Meditation - again, psychological benefits, no influence on course of disease • Hyperbaric Oxygen - no effect on course of disease

18. Limitations • We don’t understand the cause, we have limited treatment options, and the things we do have an enormous potential to make the patient’s life worse • More than ever this is the sort of case where we should educate and involve the patient in the clinical decision making process • In general practice it is necessary to remember the need to consider all the other aspects of the patient’s life about which we can do things. • If there is a teaching point in this sort of case, it is that Humility is far better than Hubris