MULTIPLE SCLEROSIS SAADIA AKHTAR, MD DEPARTMENT OF  EMERGENCY MEDICINE BIMC
DEMYLINATION <ul><li>“ A disease process whose prominent feature is the loss of myelin sheath surrounding axons in the cen...
EPIDEMIOLOGY <ul><li>Prevalence is >50 per 100,000 in US </li></ul><ul><li>Age range- 10 to 60 years </li></ul><ul><li>Pea...
 
ETIOLOGY <ul><li>Cause is still unknown </li></ul><ul><li>Identified factors: </li></ul><ul><ul><li>Autoimmune causes </li...
 
 
PATHOPHYSIOLOGY <ul><li>Scattered areas of demyelination=  </li></ul><ul><ul><li>“ Plaques” </li></ul></ul><ul><li>Plaques...
PATHOPHYSIOLOGY <ul><li>Demyelinated axons </li></ul><ul><ul><li>Do not conduct normal action potentials </li></ul></ul><u...
 
 
CLASSIFICATION <ul><li>TYPE OF MS </li></ul><ul><li>Benign MS- 10% </li></ul><ul><li>Relapsing-remitting MS- 40% </li></ul...
CLINICAL PRESENTATION <ul><li>A relapsing-remitting pattern is characteristic for this disease .  </li></ul><ul><li>EARLY ...
CLINICAL PRESENTATION <ul><li>MOTOR SYMPTOMS </li></ul><ul><ul><li>Upper motor neuron signs </li></ul></ul><ul><ul><ul><li...
CLINICAL PRESENTATION <ul><li>SENSORY SYMPTOMS </li></ul><ul><ul><li>Ascending numbness starting in the feet  </li></ul></...
CLINICAL PRESENTATION <ul><li>OCULAR SYMPTOMS </li></ul><ul><ul><li>Optic Neuritis </li></ul></ul><ul><ul><ul><li>Frequent...
 
CLINICAL PRESENTATION <ul><li>OCULAR SYMPTOMS </li></ul><ul><ul><li>Optic neuritis </li></ul></ul><ul><ul><ul><li>Change i...
CLINICAL PRESENTATION <ul><li>OCULAR SYMPTOMS </li></ul><ul><ul><li>Internuclear opthalmoplegia (INO) </li></ul></ul><ul><...
CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>Motor system </li></ul></ul><ul><ul><ul><li...
CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>Cerebellar signs </li></ul></ul><ul><ul><ul...
CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>Sensory systems </li></ul></ul><ul><ul><ul>...
CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>GU </li></ul></ul><ul><ul><ul><li>urinary i...
CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>Cognitive and emotional abnormalities  </li...
RELAPSING/REMITTING
SECONDARY PROGRESSIVE
PROGRESSIVE RELAPSING
PRIMARY PROGRESSIVE
DIFFERENTIAL DIAGNOSIS <ul><li>Postinfectious Encephalomyelitis </li></ul><ul><li>Primary CNS Vasculitis </li></ul><ul><li...
DIFFERENTIAL DIAGNOSIS <ul><li>Behçet Syndrome </li></ul><ul><li>Sarcoidosis  </li></ul><ul><li>Vitamin B-12 deficiency </...
DIAGNOSIS <ul><li>History </li></ul><ul><li>Physical Exam </li></ul><ul><li>Laboratory tests </li></ul><ul><li>Lumbar punc...
 
CRITERIA FOR DIAGNOSIS <ul><li>Probable MS with laboratory support </li></ul><ul><ul><li>History of two attacks </li></ul>...
CRITERIA FOR DIAGNOSIS <ul><li>Laboratory-supported definite MS </li></ul><ul><ul><li>History of two attacks </li></ul></u...
 
ED PRESENTATONS <ul><li>Exacerbation of previous deficits </li></ul><ul><li>Development of new deficits </li></ul><ul><li>...
TREATMENT <ul><li>General </li></ul><ul><li>Specific therapy </li></ul><ul><li>Preventive therapy for relapses </li></ul><...
TREATMENT <ul><li>GENERAL </li></ul><ul><ul><li>Exercise </li></ul></ul><ul><ul><li>Physical therapy </li></ul></ul><ul><u...
TREATMENT <ul><li>SPECIFIC THERAPY </li></ul><ul><ul><li>Steroids </li></ul></ul><ul><ul><ul><li>Mild to moderate exacerba...
TREATMENT <ul><li>PREVENTIVE THERAPY FOR RELAPSES </li></ul><ul><ul><li>Immunosuppressive agents </li></ul></ul><ul><ul><u...
TREATMENT <ul><li>SUPPORTIVE THERAPY </li></ul><ul><ul><li>Fatigue </li></ul></ul><ul><ul><li>Vertigo </li></ul></ul><ul><...
PROGNOSIS <ul><li>FAVORABLE FACTORS: </li></ul><ul><li>Females  </li></ul><ul><li>Low rate of relapses per year  </li></ul...
PROGNOSIS <ul><li>FAVORABLE FACTORS: </li></ul><ul><li>Low disability at 2 to 5 years from the disease onset  </li></ul><u...
PROGNOSIS <ul><li>UNFAVORABLE FACTORS: </li></ul><ul><li>Males  </li></ul><ul><li>High rate of relapses per year  </li></u...
PROGNOSIS <ul><li>UNFAVORABLE FACTORS: </li></ul><ul><li>Significant disability at 2 to 5 years from the onset acute onset...
PROGNOSIS <ul><li>Average life span after diagnosis is 25 to 35 years </li></ul><ul><li>Suicide rate is 7.5 times higher  ...
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MULTIPLE SCLEROSIS

  1. 1. MULTIPLE SCLEROSIS SAADIA AKHTAR, MD DEPARTMENT OF EMERGENCY MEDICINE BIMC
  2. 2. DEMYLINATION <ul><li>“ A disease process whose prominent feature is the loss of myelin sheath surrounding axons in the central nervous system ” </li></ul><ul><li>Multiple sclerosis is the most common example </li></ul>
  3. 3. EPIDEMIOLOGY <ul><li>Prevalence is >50 per 100,000 in US </li></ul><ul><li>Age range- 10 to 60 years </li></ul><ul><li>Peak incidence- 20 to 30 years </li></ul><ul><li>Female predominance </li></ul><ul><li>Genetic predisposition </li></ul><ul><ul><li>20 times higher in first-degree relatives </li></ul></ul><ul><li>Prevalence directly proportional to distance from equator </li></ul>
  4. 5. ETIOLOGY <ul><li>Cause is still unknown </li></ul><ul><li>Identified factors: </li></ul><ul><ul><li>Autoimmune causes </li></ul></ul><ul><ul><ul><li>Human Leukocyte Antigens </li></ul></ul></ul><ul><ul><li>Viral causes </li></ul></ul><ul><ul><ul><li>Roseola virus </li></ul></ul></ul>
  5. 8. PATHOPHYSIOLOGY <ul><li>Scattered areas of demyelination= </li></ul><ul><ul><li>“ Plaques” </li></ul></ul><ul><li>Plaques are more common in: </li></ul><ul><ul><li>Optic tracts </li></ul></ul><ul><ul><li>Spinal cord </li></ul></ul><ul><ul><li>Brain stem </li></ul></ul><ul><ul><li>Basal Ganglia </li></ul></ul>
  6. 9. PATHOPHYSIOLOGY <ul><li>Demyelinated axons </li></ul><ul><ul><li>Do not conduct normal action potentials </li></ul></ul><ul><ul><li>Hyperexcitable (generate action potentials with minimal stimuli) </li></ul></ul><ul><li>Lesions are “scattered in space and time” </li></ul>
  7. 12. CLASSIFICATION <ul><li>TYPE OF MS </li></ul><ul><li>Benign MS- 10% </li></ul><ul><li>Relapsing-remitting MS- 40% </li></ul><ul><li>Secondary chronic progressive- 40% of patients with original relapsing-remitting MS </li></ul><ul><li>Primary progressive MS- 10% </li></ul>
  8. 13. CLINICAL PRESENTATION <ul><li>A relapsing-remitting pattern is characteristic for this disease . </li></ul><ul><li>EARLY STAGE: </li></ul><ul><ul><li>Double or blurred vision </li></ul></ul><ul><ul><li>Numbness </li></ul></ul><ul><ul><li>Weakness in one or two extremities </li></ul></ul><ul><ul><li>Instability in walking </li></ul></ul><ul><ul><li>Tremors </li></ul></ul><ul><ul><li>Problems with bladder control </li></ul></ul><ul><ul><li>Heat intolerance. </li></ul></ul>
  9. 14. CLINICAL PRESENTATION <ul><li>MOTOR SYMPTOMS </li></ul><ul><ul><li>Upper motor neuron signs </li></ul></ul><ul><ul><ul><li>Mild spasticity </li></ul></ul></ul><ul><ul><ul><li>Hyperreflexia </li></ul></ul></ul><ul><ul><ul><li>Monoparesis (one extremity) </li></ul></ul></ul><ul><ul><ul><li>Quadriparesis (all four extremities) </li></ul></ul></ul>
  10. 15. CLINICAL PRESENTATION <ul><li>SENSORY SYMPTOMS </li></ul><ul><ul><li>Ascending numbness starting in the feet </li></ul></ul><ul><ul><li>Bilateral hand numbness </li></ul></ul><ul><ul><li>Hemiparesthesia </li></ul></ul><ul><ul><li>Reduction of vibration </li></ul></ul><ul><ul><li>Reduction of proprioception </li></ul></ul>
  11. 16. CLINICAL PRESENTATION <ul><li>OCULAR SYMPTOMS </li></ul><ul><ul><li>Optic Neuritis </li></ul></ul><ul><ul><ul><li>Frequent presenting symptom of MS (30%) </li></ul></ul></ul><ul><ul><ul><li>Inflammation of the optic nerve head </li></ul></ul></ul><ul><ul><ul><li>Fundus exam- swelling, edema, preservation of venous pulsations </li></ul></ul></ul><ul><ul><ul><li>Blurred vision </li></ul></ul></ul>
  12. 18. CLINICAL PRESENTATION <ul><li>OCULAR SYMPTOMS </li></ul><ul><ul><li>Optic neuritis </li></ul></ul><ul><ul><ul><li>Change in color perception </li></ul></ul></ul><ul><ul><ul><li>Visual field defect (central scotoma) </li></ul></ul></ul><ul><ul><ul><li>Headaches and retro-orbital pain precipitated by eye movements </li></ul></ul></ul><ul><ul><ul><li>“ Uhthoff’s phenomenon”= visual acuity worsens with increase in body temperature </li></ul></ul></ul>
  13. 19. CLINICAL PRESENTATION <ul><li>OCULAR SYMPTOMS </li></ul><ul><ul><li>Internuclear opthalmoplegia (INO) </li></ul></ul><ul><ul><ul><li>Interruption of fibers in the medial longitudinal fasciculus that connect III and VI nuclei </li></ul></ul></ul><ul><ul><ul><li>Abnormal adduction of involved eye </li></ul></ul></ul><ul><ul><ul><li>Horizontal nystagmus on abduction of contralateral eye </li></ul></ul></ul><ul><ul><ul><li>Usually bilateral </li></ul></ul></ul><ul><ul><ul><li>Healthy young person with INO= think of MS </li></ul></ul></ul><ul><ul><li>VI nerve paresis and palsy </li></ul></ul><ul><ul><li>III and IV nerves palsy (uncommon) </li></ul></ul>
  14. 20. CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>Motor system </li></ul></ul><ul><ul><ul><li>Weakness (variable severity mono- and paraparesis, hemiparesis, quadriparesis) </li></ul></ul></ul><ul><ul><ul><li>Increased spasticity resulting in spastic gait </li></ul></ul></ul><ul><ul><ul><li>Pathologic signs (Babinski's, Chaddock's, Hoffmann, Oppenheim's) </li></ul></ul></ul><ul><ul><ul><li>Dysarthria </li></ul></ul></ul>
  15. 21. CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>Cerebellar signs </li></ul></ul><ul><ul><ul><li>Incoordination (dysdiadochokinesia, problems with heel-to-shin test) </li></ul></ul></ul><ul><ul><ul><li>Slowing of rapid repeating movements </li></ul></ul></ul><ul><ul><ul><li>Ataxic gait </li></ul></ul></ul><ul><ul><ul><li>Abnormal speech </li></ul></ul></ul><ul><ul><ul><li>Loss of balance </li></ul></ul></ul>
  16. 22. CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>Sensory systems </li></ul></ul><ul><ul><ul><li>Lhermitte's sign </li></ul></ul></ul><ul><ul><ul><li>Paresthesia </li></ul></ul></ul><ul><ul><ul><li>Numbness </li></ul></ul></ul><ul><ul><ul><li>Dorsal column signs (severe decrease or loss of vibratory sense and proprioception, positive Romberg's test) </li></ul></ul></ul>
  17. 23. CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>GU </li></ul></ul><ul><ul><ul><li>urinary incontinence </li></ul></ul></ul><ul><ul><ul><li>incomplete emptying </li></ul></ul></ul><ul><ul><ul><li>increased frequency of urination </li></ul></ul></ul><ul><ul><ul><li>urinary tract infections </li></ul></ul></ul><ul><ul><li>Ocular </li></ul></ul><ul><ul><ul><li>optic disc pallor and atrophy </li></ul></ul></ul><ul><ul><ul><li>blurred vision </li></ul></ul></ul><ul><ul><ul><li>diplopia </li></ul></ul></ul><ul><ul><ul><li>nystagmus </li></ul></ul></ul><ul><ul><ul><li>intranuclear ophthalmoplegia </li></ul></ul></ul><ul><ul><ul><li>central scotomas/ visual field defects </li></ul></ul></ul>
  18. 24. CLINICAL PRESENTATION <ul><li>Ongoing symptoms and signs </li></ul><ul><ul><li>Cognitive and emotional abnormalities </li></ul></ul><ul><ul><ul><li>Emotional lability </li></ul></ul></ul><ul><ul><ul><li>Depression </li></ul></ul></ul><ul><ul><ul><li>Anxiety </li></ul></ul></ul><ul><ul><li>Fatigue </li></ul></ul>
  19. 25. RELAPSING/REMITTING
  20. 26. SECONDARY PROGRESSIVE
  21. 27. PROGRESSIVE RELAPSING
  22. 28. PRIMARY PROGRESSIVE
  23. 29. DIFFERENTIAL DIAGNOSIS <ul><li>Postinfectious Encephalomyelitis </li></ul><ul><li>Primary CNS Vasculitis </li></ul><ul><li>Lyme Disease </li></ul><ul><li>Systemic Lupus Erythematosus </li></ul><ul><li>Tropical Spastic Paraparesis </li></ul>
  24. 30. DIFFERENTIAL DIAGNOSIS <ul><li>Behçet Syndrome </li></ul><ul><li>Sarcoidosis </li></ul><ul><li>Vitamin B-12 deficiency </li></ul><ul><li>Tertiary Syphilis </li></ul><ul><li>Progressive Multifocal Leukoencephalopathy </li></ul>
  25. 31. DIAGNOSIS <ul><li>History </li></ul><ul><li>Physical Exam </li></ul><ul><li>Laboratory tests </li></ul><ul><li>Lumbar puncture </li></ul><ul><li>MRI </li></ul><ul><li>Electrophysiological tests (visual- evoked potentials) </li></ul>
  26. 33. CRITERIA FOR DIAGNOSIS <ul><li>Probable MS with laboratory support </li></ul><ul><ul><li>History of two attacks </li></ul></ul><ul><ul><li>Positive oligoclonal bands or Increased IgG in CSF </li></ul></ul><ul><ul><li>No clinical evidence of a disease </li></ul></ul><ul><li>Clinically Probable MS </li></ul><ul><ul><li>History of two attacks without laboratory abnormalities </li></ul></ul>
  27. 34. CRITERIA FOR DIAGNOSIS <ul><li>Laboratory-supported definite MS </li></ul><ul><ul><li>History of two attacks </li></ul></ul><ul><ul><li>Clinical evidence of one lesion </li></ul></ul><ul><ul><li>Oligoclonal bands or increased IgG present in CSF </li></ul></ul><ul><li>Clinically-definite MS </li></ul><ul><ul><li>History of at least two attacks </li></ul></ul><ul><ul><li>Clinical evidence of at least one lesion </li></ul></ul>
  28. 36. ED PRESENTATONS <ul><li>Exacerbation of previous deficits </li></ul><ul><li>Development of new deficits </li></ul><ul><li>Development of complications </li></ul><ul><li>Initial presentation </li></ul>
  29. 37. TREATMENT <ul><li>General </li></ul><ul><li>Specific therapy </li></ul><ul><li>Preventive therapy for relapses </li></ul><ul><li>Supportive therapy </li></ul>
  30. 38. TREATMENT <ul><li>GENERAL </li></ul><ul><ul><li>Exercise </li></ul></ul><ul><ul><li>Physical therapy </li></ul></ul><ul><ul><li>Nutrition </li></ul></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Treatment for fever/infections </li></ul></ul>
  31. 39. TREATMENT <ul><li>SPECIFIC THERAPY </li></ul><ul><ul><li>Steroids </li></ul></ul><ul><ul><ul><li>Mild to moderate exacerbations </li></ul></ul></ul><ul><ul><ul><ul><li>Oral prednisone1mg/kg/day </li></ul></ul></ul></ul><ul><ul><ul><li>Severe exacerbations </li></ul></ul></ul><ul><ul><ul><ul><li>IV methylprednisone 500 to 1000 mg/day for 3 to 5 days with taper </li></ul></ul></ul></ul>
  32. 40. TREATMENT <ul><li>PREVENTIVE THERAPY FOR RELAPSES </li></ul><ul><ul><li>Immunosuppressive agents </li></ul></ul><ul><ul><ul><li>Interferon </li></ul></ul></ul>
  33. 41. TREATMENT <ul><li>SUPPORTIVE THERAPY </li></ul><ul><ul><li>Fatigue </li></ul></ul><ul><ul><li>Vertigo </li></ul></ul><ul><ul><li>Muscle spasms </li></ul></ul><ul><ul><li>Tremors </li></ul></ul><ul><ul><li>Pain </li></ul></ul><ul><ul><li>Cognitive Dysfunction </li></ul></ul><ul><ul><li>Urinary dysfunction </li></ul></ul><ul><ul><li>Psychological problems </li></ul></ul>
  34. 42. PROGNOSIS <ul><li>FAVORABLE FACTORS: </li></ul><ul><li>Females </li></ul><ul><li>Low rate of relapses per year </li></ul><ul><li>Complete recovery from the first attack </li></ul><ul><li>Long interval between first and second attack </li></ul><ul><li>Symptoms predominantly from afferent systems (i.e. sensory symptoms) </li></ul><ul><li>Younger age of onset </li></ul>
  35. 43. PROGNOSIS <ul><li>FAVORABLE FACTORS: </li></ul><ul><li>Low disability at 2 to 5 years from the disease onset </li></ul><ul><li>Later cerebellar involvement </li></ul><ul><li>Involvement of only one CNS system at the time of onset </li></ul>
  36. 44. PROGNOSIS <ul><li>UNFAVORABLE FACTORS: </li></ul><ul><li>Males </li></ul><ul><li>High rate of relapses per year </li></ul><ul><li>Incomplete recovery from the first attack </li></ul><ul><li>Short interval between first and second attack </li></ul><ul><li>Symptoms predominantly from efferent systems (i.e. symptoms of motor tract involvement) </li></ul><ul><li>Older age of onset </li></ul>
  37. 45. PROGNOSIS <ul><li>UNFAVORABLE FACTORS: </li></ul><ul><li>Significant disability at 2 to 5 years from the onset acute onset </li></ul><ul><li>Early cerebellar involvement </li></ul><ul><li>Involvement of more than one CNS system at the time of onset </li></ul>
  38. 46. PROGNOSIS <ul><li>Average life span after diagnosis is 25 to 35 years </li></ul><ul><li>Suicide rate is 7.5 times higher </li></ul><ul><li>Common causes of death </li></ul><ul><ul><li>Compromised swallowing and breathing </li></ul></ul><ul><ul><li>Severe infections (e.g. Urosepsis, Aspiration pneumonia) </li></ul></ul>
  39. 47. QUESTIONS?
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