CLINICALLY ISOLATED SYNDROME

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CLINICALLY ISOLATED SYNDROME

  1. 1. Clinically Isolated Syndromes [CIS] Dr Ashraf Abdou Neuropsychiatry dept Alexandria univ.
  2. 2. Is it MS? • Mona 25 yrs old female referred from an ophthalmologist with Rt optic neuritis • Neurological examination; normal • MRI:
  3. 3. Diagnosis of MS • Dissemination in TIME • Dissemination in SPACE • Exclusion of others causes McDonald’s classification • • • Definite MS Possible MS Not MS
  4. 4. Thrower, B. W. Neurology 200768:S12-S15
  5. 5. CLINICAL EXAMINATION 2 ATTACKS 2 LESIONS 2 ATTACKS 1 LESION 2001 Rev 2005 INVESTIGATIONS MRI OR MRI + CSF 1 ATTACK 2 LESIONS 1 ATTACK 1 LESION MRI dissemination in time MRI dissemination in time dissemination in space OR MRI dissemination in time + CSF
  6. 6. • An attack should last at – least 24 hrs. – Two separate attacks: 1 month should separate the onset of the 1st event from the onset of the 2nd event. • CSF abnormalities : [lymphocytic pleocytosis <50] – Oligoclonal IgG bands different from any such band in the serum AND/OR – Elevated IgG index • VEP : can be used to supplement the clinical examination to provide evidence of a 2nd lesion.
  7. 7. MRI criteria for dissemination in space 3/4 are required: – 1 gadolinium-enhancing (Gd+) lesion – 1 infratentorial lesion on MRI – 1 juxtacortical lesion – 3 periventricular lesions – One spinal cord lesion OR 9 T2 lesions
  8. 8. MRI: criteria for dissemination in time: • Detection of gadolinium enhancement at least 3 months after the onset of the initial clinical event, not at the site corresponding to the initial event • Detection of a new T2 lesion if it appears at any time compared with a reference scan done at least 30 days after the onset of the initial clinical event R evised criteria 2005
  9. 9. Is MS? • Mona 25 yrs old female referred from an ophthalmologist with Rt optic neuritis • Neurological examination; normal • MRI:
  10. 10. Clinically Isolated Syndromes [CIS]
  11. 11. Definition First neurologic event suggestive of MS lasting for at least 24 hours and with symptoms and signs indicating either: – a single lesion (monofocal) – more than one lesion (multifocal) within the CNS
  12. 12. Classical CIS • Optic Neuritis • Brain stem dysfunction • Transverse myelitis
  13. 13. Optic Neuritis • Unilateral eye involvement • Retrobulbar • Eye pain • Partial vision loss, with at least some recovery • No retinal exudate, disc hges, macular star • 10 years follow-up: 38% develop MS • Normal MRI ; risk 22% • Abnormal MRI ; risk 55% – 20 yrs follow up; risk 90%
  14. 14. Transverse Myelitis • +ve cerebral MRI ; 80-90% • Sensory>motor • -ve cerebral MRI ; 30% • CSF; Oligoclonal band or ↑ IgG index • Partial
  15. 15. Brainstem dysfunction • Internuclear ophthalmoplegia • Nystagmus • Any eye movement abnormality • Facial weakness • Vertigo • Loss of hearing, taste • Dysarthria • Dysphagia • Ataxia
  16. 16. Treat or Not to Treat?
  17. 17. Trials • ETOMS : Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. The Lancet 2001. • CHAMPS : – The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS). N Engl J Med. 2000 – Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance (CHAMPIONS). NEUROLOGY 2006 • BENEFIT : – Betaferon® in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT): clinical results. Presented at ECTRIMS/ACTRIMS 2005. – BENEFIT Study Group. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet. 2007.
  18. 18. BENEFIT 45% of placebo develop MS within 2 yrs Thrower, B. W. Neurology 2007;68:S12-S15
  19. 19. CHAMPS 50% of placebo develop MS within 3 yrs CHAMPIONS Delayed vs Immediate; modest
  20. 20. ETOMS 45% of placebo develop MS within 2 yrs interferon beta-1a 22 μg or placebo subcutaneously once weekly for 2 years Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. The Lancet 2001; 357:1576-1582
  21. 21. CONCLUSIONS • CIS: 1 st attack of demyelination [CLINICAL & MRI] • Repeat MRI after 3 months looking for new lesions • 50% to develop MS • Current evidence that early treatment is beneficial. • Early treatment is modestly better than delayed treatment.

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