Clinical
and epidemiological features
Prediction
of Disability/Prognosis
· First clinical episode in which the patient has symptoms and signs suggestive of inflammatory demyelinating disorder of the CNS.
· By definition isolated in time
· Similar sex ratio to MS M:F 1:2.5
· Similar age group as MS – 70% between 20-40years
·
· Typically acute/subacute – reaches peak within 2-3 weeks
· Should generally last longer than 24hours
· Should occur in absence of other clinical features such as fever, infection, encephalopathy
· Usually isolated in space (i.e. monofocal), however occasionally multifocal presentation
Optic neuritis
· 10-85%
Spinal Cord syndromes
· 41-61%
Brainstem syndromes
· 53-60%
· A history of a previous, non-investigated, clinical event strong predictor
Predictors of increased risk:
· Younger age
· Non-white ethnicity
· Female
· Greater number of functional systems affected at onset
· HLA-DRB1
· Sun exposure and skin type
· Vitamin D
· Smoking (significant effect)
· 50-70% of patients presenting with CIS will have multiple asymptomatic white matter lesions suggestive of demyelination
Stratification on the basis of MRI with lesions other than the symptomatic one:
|
|
7yr |
15ys |
20yrs |
|
Abnormal MRI |
65% |
72% |
80% |
|
Normal MRI |
8% |
20% |
25% |
· Number of lesions and number meeting Barkhof criteria also increase risk (Neurology 2006; 67:968-72)
· Brain atrophy may also be a predictor however requires further validation
· If the MRI is positive then OCBs only add an extra 5% increased risk if positive
· If the MRI is negative – one study showed positive OCBs increased risk from 4% to 23%.
Poor predictive features
· Pyramidal deficits
· Cerebellar deficits
· Incomplete recovery
· Short interval to second relapse
· High relapse rate in first 2 years
· Multisystem involvement
· Lesion load at diagnosis - weak association
· Brainstem lesion at diagnosis
Good predictive features
· Purely afferent CIS – sensory or optic neuritis
Trials have been done looking at treating patients with CIS to ‘prevent’ conversion to MS:
· ~35% vs 50% conversion at 2 years (IFN vs Placebo) – similar results for all three interferons and glatiramir
· Once second event occurred patients were all switched to active treatment
· At 3 years there was reduced disability in the early treatment arm, this effect has disappeared by 5years.
·
Clinically isolated syndromes (2012) Lancet Neurology 11:157-69