Multiple sclerosis (MS) is the most common
inflammatory demyelinating disease of the
CNS and the most frequent cause of nontraumatic
neurological disability in young and
middle-aged adults.1 Women are twice as likely
to be affected as men, and onset typically
occurs between the ages of 20 and 40 years.
Variability and diversity characterize MS. Deficits in sensory, motor, cerebellar, brain stem, and autonomic functions are the most common clinical manifestations. Most patients (85%) experience a relapsing-remitting course characterized by the episodic onset of symptoms followed by residual deficits or by a full recovery within a few weeks, especially in the early stages of the disease.2
Approximately 15% of patients with relapsing-remitting MS (RRMS) will remain clinically stable or nearly stable for 2 or more decades (benign MS). However, within 25 years, RRMS in most untreated patients will evolve into secondary progressive MS, characterized by a chronic and steady increase of physical symptoms and disability.
Approximately 10% to 15% of patients with MS experience a primary progressive course. Primary progressive MS (PPMS) differs from RRMS in that it affects both men and women equally, occurs in older persons, exhibits lower levels of inflammatory markers and myelopathological features, and is unresponsive to immunomodulatory agents.3 Progressive relapsing MS is uncommon and is progressive from the onset with clear, acute relapses with or without recovery, and with periods between relapses characterized by continuing progression.4
DIAGNOSIS OF MS
MS is a clinical diagnosis, dependent on a detailed history; careful neurological examination; and supportive paraclinical investigations, including MRI, analysis of both cerebrospinal fluid (CSF) and evoked potentials, and blood tests to exclude confounding diagnoses. The classic MS diagnostic criteria are evidence of lesions in the CNS disseminated in space and time (ie, more than 1 clinical episode involving more than 1 area of the CNS [brain, spinal cord, and optic nerves]).
The use of MRI, since its introduction by Young and colleagues,5 has had a major impact on allowing early and more precise diagnosis of the disease. In patients with clinically definite MS, brain MRI reveals multifocal cerebral white matter lesions in more than 95% of patients and focal spinal cord lesions in 75% to 85% of them. Cerebral white matter lesions that are indistinguishable from those seen in definite MS are observed in about two thirds of patients who have a single episode of suspected demyelination or clinically isolated syndrome (CIS).6 Because the presence of such lesions increases the likelihood of developing clinically definite MS, it is not surprising that standard MRI features suggesting dissemination of pathologic lesions in space and time were incorporated into the diagnostic criteria for MS by the International Panel on the Diagnosis of Multiple Sclerosis in 2001.7
THE ROLE OF MRI
The previous diagnostic criteria for MS, authored by Poser8 in 1987, were established for use in clinical trials of MS and included clinically definite MS, laboratory supported (ie, evoked potentials and CSF analysis, including IgG index and oligoclonal bands) definite MS, probable MS (either clinically or laboratory supported), and possible MS. Because MRI was relatively new at the time these criteria were presented, the technology was included as a paraclinical element but was not further defined.
According to the new McDonald criteria, the diagnosis of MS requires objective evidence of lesions disseminated in space and time.
- MRI findings may contribute to the determination of dissemination in time or space.
- Other supportive investigations include evaluation of CSF and the visual evoked potential (VEP).
- Diagnostic categories include possible MS, MS, or not MS.
For dissemination in space, 3 of the following 4 features are required, based on criteria established by Barkhof and colleagues6 and Tintore and colleagues9:
- At least 1 gadolinium-enhancing lesion or 9 T2-weighted hyperintense lesions.
- At least 1 infratentorial lesion.
- At least 1 juxtacortical lesion.
- At least 3 periventricular lesions.
A spinal cord lesion can substitute for any of the above brain lesions. If immunoglobulin abnormalities are detected in the CSF, then the MRI criteria are relaxed to require that only 2 T2-weighted lesions typical of MS be present.
For dissemination in time, a new gadolinium-enhancing lesion appearing 3 or more months after the initial clinical event indicates a new CNS inflammatory event (the duration of gadolinium enhancement in MS is usually less than 6 weeks). If no gadolinium- enhancing lesions are detected but a new T2-weighted lesion is, then MRI should be repeated after another 3 months to detect the presence of a new T2-weighted lesion or a gadolinium-enhancing lesion.
Application of these criteria in several natural history and treatment trial cohorts indicated that they were more robust in facilitating an earlier diagnosis of MS than could be achieved through other diagnostic methods.10-12 The criteria also proved robust in predicting the likelihood of conversion to clinically definite MS in patients with a CIS in whom MRI ultimately showed evidence of dissemination in space and time.10-12 Specificity was high, in particular when dissemination in time was present; dissemination in space per se was less specific.
The requirement that a gadolinium-enhancing lesion be present 3 months after the initial event to fulfill dissemination in time had poor sensitivity. This was ameliorated by requiring that either a new gadolinium-enhancing or T2-weighted lesion be present instead.13
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