Article

Even prior to the introduction of criteria defining the radiologically isolated
syndrome (RIS), longitudinal clinical data from individuals with incidentally
identified T2 lesions suggestive of multiple sclerosis (MS) were described.
Healthy individuals who do not exhibit signs of neurological dysfunction may have
a brain MRI performed for a reason other than suspicion of MS that reveals
unexpected anomalies highly suggestive of demyelinating plaques given their size,
location, and morphology. These healthy subjects lack a history or symptomatology
suggestive of MS and fulfill formal criteria for RIS, a recently described MS
subtype that shares the phenotype of at-risk individuals for future demyelinating
events. A formal description of RIS was first introduced in 2009 by Okuda et al.,
and defines a cohort of individuals who are at risk for future demyelinating
events. European or North American observational studies have found that up to
30-45% of patients presenting with RIS will present with neurological symptoms,
either acute or progressive. The median time to clinical conversion differs
between studies. It was 2.3 years for a series of French patients and 5.4 years
for an American cohort. Most patients who developed clinical symptoms had prior
radiological progression. The presence of asymptomatic lesions in the cervical
cord indicated an increased risk of progression, either to relapsing or to
progressive MS. The consortium studying the epidemiology of RIS worldwide (RISC)
presented their first retrospective cohort last year. Data were available for 451
RIS subjects (F: 354 [78.5%]). The mean age at RIS diagnosis was 37.2 years with
a mean clinical follow-up time of 4.4 years. The observed 5-year conversion rate
to the first clinical event was 34%. Of the converters within this time period,
9.6% fulfilled criteria for primary progressive MS. In the multivariate model,
age, sex (male), and lesions within the cervical or thoracic spinal cord were
identified as significant predictors for the development of a first clinical
event. Cognitive impairment is observed in RIS patients, and two studies
demonstrated a significant proportion of patients with cognitive decline compared
with healthy controls. Despite progress into the characterization of RIS subjects
and into our understanding of risk factors for initial symptom development, the
natural course of such cases and risk-profiles for a seminal neurological event,
from prospectively acquired data, remain unclear. A prospective study is
mandatory to increase our knowledge about these asymptomatic patients and
individual therapeutic initiatives cannot be undertaken until a prospective
clinical study demonstrates the benefit of introducing a disease modifying
treatment for this very early stage of a chronic demyelinating disease.
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