1. Clinically Isolated Syndromes
[CIS]
Dr Ashraf Abdou
Neuropsychiatry dept
Alexandria univ.

2. Is it MS?
• Mona 25 yrs old female referred from an
ophthalmologist with Rt optic neuritis
• Neurological examination; normal
• MRI:

3. Diagnosis of MS
• Dissemination in TIME
• Dissemination in SPACE
• Exclusion of others causes
McDonald’s classification
•
•
•
Definite MS
Possible MS
Not MS

4. Thrower, B. W. Neurology 200768:S12-S15

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. • 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. 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. 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. Is MS?
• Mona 25 yrs old female referred from an
ophthalmologist with Rt optic neuritis
• Neurological examination; normal
• MRI:

10. Clinically Isolated Syndromes
[CIS]

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. Classical CIS
• Optic Neuritis
• Brain stem dysfunction
• Transverse myelitis

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. Transverse Myelitis
• +ve cerebral
MRI ; 80-90%
• Sensory>motor • -ve cerebral
MRI ; 30%
• CSF;
Oligoclonal
band or ↑ IgG
index
• Partial

15. Brainstem dysfunction
• Internuclear
ophthalmoplegia
• Nystagmus
• Any eye
movement
abnormality
• Facial weakness
• Vertigo
• Loss of hearing,
taste
• Dysarthria
• Dysphagia
• Ataxia

16. Treat or Not to Treat?

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. BENEFIT
45% of placebo develop MS within 2 yrs
Thrower, B. W. Neurology 2007;68:S12-S15

19. CHAMPS
50% of placebo develop MS
within 3 yrs
CHAMPIONS
Delayed vs Immediate;
modest

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. 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.