Clinically Isolated SyndromesClinically Isolated Syndromes[CIS][CIS]

Dr Ashraf AbdouNeuropsychiatry dept

Alexandria univ.

Is it MS?• Mona 25 yrs old female referred from

an ophthalmologist with Rt optic neuritis

• Neurological examination; normal• MRI:

Diagnosis of MSDiagnosis of MS• Dissemination in TIME

• Dissemination in SPACE

• Exclusion of others causes

McDonald’s classificationMcDonald’s classification• Definite MS• Possible MS• Not MS

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

CLINICAL EXAMINATION INVESTIGATIONS

2 ATTACKS 2 LESIONS

2 ATTACKS 1 LESION MRIOR

MRI + CSF

1 ATTACK 2 LESIONS MRI dissemination in time

1 ATTACK 1 LESION MRI dissemination in time dissemination in space

ORMRI dissemination in time

+ CSF

2001Rev 2005

• 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 serumAND/OR

– Elevated IgG index

•VEP: can be used to supplement the clinical examination to provide evidence of a 2nd lesion.

MRI criteria for dissemination in space

3/4 are required: – 1 gadolinium-enhancing (Gd+) lesion OR 9 T2 lesions

– 1 infratentorial lesion on MRI

– 1 juxtacortical lesion

– 3 periventricular lesions

– One spinal cord lesion

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

Revised criteria 2005

Is MS?• Mona 25 yrs old female referred from

an ophthalmologist with Rt optic neuritis

• Neurological examination; normal• MRI:

Clinically Isolated SyndromesClinically Isolated Syndromes[CIS][CIS]

DefinitionDefinition

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

Classical CIS

•Optic Neuritis

•Brain stem dysfunction

•Transverse myelitis

Optic NeuritisOptic 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%

Transverse MyelitisTransverse Myelitis

• Partial

• Sensory>motor

• CSF; Oligoclonal band or ↑ IgG index

•+ve cerebral MRI; 80-90%

• -ve cerebral MRI; 30%

Brainstem dysfunctionBrainstem dysfunction

• Internuclear ophthalmoplegia

•Nystagmus

•Any eye movement abnormality

• Facial weakness• Vertigo• Loss of hearing,

taste• Dysarthria• Dysphagia• Ataxia

Treat or Not to Treat?

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.

Thrower, B. W. Neurology 2007;68:S12-S15

45% of placebo develop MS within 2 yrs

BENEFIT

50% of placebo develop MS within 3 yrs

CHAMPS

Delayed vs Immediate; modest

CHAMPIONS

Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. The Lancet 2001; 357:1576-1582

45% of placebo develop MS within 2 yrs

interferon beta-1a 22 μg or placebo subcutaneously once weekly for 2 years

ETOMS

CONCLUSIONS• CIS: 1st 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.