The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good practice point) are defined at the end of the "Major Recommendations" field.
Magnetic Resonance Imaging (MRI) Assessment of Patients at Presentation with Clinically Isolated Syndromes Suggestive of Multiple Sclerosis (MS)
In patients at presentation with clinically isolated syndrome (CIS) suggestive of MS (i.e. neurological findings typically seen in the setting of MS) (Frohman et al., 2003) after appropriate exclusion of alternative diagnostic considerations that can mimic MS, the following recommendations should be considered:
- Conventional MRI (cMRI) of the brain (dual-echo, pre- and post-contrast T1-weighted scans) should be obtained as soon as possible in all patients presenting with an isolated demyelinating syndrome involving the central nervous system (CNS), not only to collect additional evidence for lesion dissemination in space, but also to exclude other possible neurological conditions. As suggested by recent guidelines from the American Academy of Neurology (Frohman et al., 2003) the finding in these patients of three or more T2-hyperintense lesions with the imaging characteristics underlined by the International Panel (IP) guidelines (McDonald et al., 2001) (Type A recommendation) and the presence of two or more gadolinium (Gd)-enhancing lesions at baseline are sensitive predictors of the subsequent development of clinically definite MS (CDMS) within the next 7 to 10 years (Type B recommendation).
- The presence of three or more white matter lesions on brain T2-weighted MRI in patients suspected of having MS is not diagnostic, especially when their location and appearance is non-characteristic for demyelination. In this context the IP criteria (McDonald et al., 2001) should be applied. Incidental white matter lesions are not an infrequent observation even in the young normal population. Note that with ageing (at least >50 years) incidental white matter lesions may also show progression (Schmidt et al., 2003; Longstreth et al., 2005) (good practice point).
- In the case of steroids treatment, which is known to dramatically suppress Gd enhancement, one of the possible markers of inflammation, cMRI should be performed before treatment or, at least, 1 month after treatment termination (good practice point).
- cMRI of the spinal cord is useful in those circumstances when brain MRI is normal or equivocal, and in patients with non-specific brain T2-abnormalities (especially when older than 50 years), because, contrary to what happens for the brain, cord lesions rarely develop with ageing per se (Kidd et al., 1993). In patients presenting with a spinal cord syndrome, spinal cord MRI is highly recommended to rule out other conditions that may mimic MS, such as compressive lesions (good practice point).
- In patients with acute optic neuritis (ON), MRI of the optic nerve can be useful in ruling out alternative diagnosis. In this case, short-tau inversion recovery (STIR) sequences should be used (good practice point).
- Follow-up MRIs are required to demonstrate disease dissemination in time. In this perspective, the appearance of Gd-enhancing lesions 3 months after the clinical episode (and after a baseline MRI assessment) or new T2- or Gd-enhancing lesions 6 months after the clinical episode (and after a baseline MRI assessment) is highly predictive of the subsequent development of definite MS in the near term (Frohman et al., 2003) (Type A recommendation). Follow-up scans need to be performed with the same machinery and scanning parameters and identical slice positions are required for exact comparison.
- Repeat scanning beyond the two initial studies need to be considered by individual neurologists considering the clinical circumstances that are appropriate for each patient (is not routinely recommended as the disease becomes more likely to manifest clinically in the longer term (Dalton et al., 2002; Miller et al., 2004) (good practice point).
- Even though non-conventional MRI techniques may provide essential and critical information in patients with CIS and their application for monitoring treatment might provide a more accurate assessment of efficacy on inflammation, axonal protection and demyelination/remyelination, their use in clinical practice is, currently, not recommended. All these techniques are yet to be adequately compared with cMRI for sensitivity and specificity in detecting tissue damage in MS and for predicting the development of MS and disability. At present, these quantitative techniques show differences at a group level, but do not allow inferences at an individual level.
- In patients with insidious neurological progression suggestive of MS, according to published criteria (Thompson et al., 2000) an abnormal cerebrospinal (CSF) finding with evidence of inflammation and immune abnormality is another important finding to corroborate the diagnostic suspicious.
MRI in Patients with Established MS
In patients with established MS, the following recommendations should be considered:
- cMRI scans (dual-echo and post-contrast T1-weighted images) should be obtained using standardized protocols and accurate procedures for patients' repositioning in order to facilitate the interpretation of follow-up studies. Post-contrast T1-weighted scans should be acquired after an interval of 5 to 7 min from the injection of contrast material (Fazekas et al., 1999). Considering the weak correlation with clinical finding and the low predictive value of cMRI metrics for the subsequent worsening of clinical disability, the use of surveillance MRI for the purpose of making treatment decisions cannot be generally recommended (Fazekas et al., 1999). Serial MRI scans should be considered when diagnostic issues arise.
- Repetition of MRI of the spinal cord is advisable only if suspicion arises concerning the evolution of an alternate process (e.g. mechanical compression) or atypical symptoms develop.
- Although preliminary work based on clinical trial data has suggested that presence (Giugni et al., 2003) and amount (Rudick et al., 2004) of MRI-detected disease activity may identify interferon (IFN)-beta response status in terms of relapse rate and accumulated disability (Rudick et al., 2004) in MS patients at a group level, there are no validated methods for monitoring disease-modifying therapy in individual patients.
- Metrics derived from cMRI are not enough to provide a complete picture of the MS pathological process. Although cMRI has undoubtedly improved our ability to assess the efficacy of experimental MS therapies and, at least partially, our understanding of MS evolution, it provides only limited information on MS pathology in terms of accuracy and specificity and it has limited correlations with clinical metrics. This implies that the ability of a given treatment to modify metrics derived from cMRI does not mean that the treatment will necessarily be able to prevent the progressive accumulation of clinical disability, especially at an individual patient level.
- Measurements of T1-hypointense lesions loads and brain and cord atrophy in clinical practice continue to be considered at a preliminary stage of development, as they need to be standardized in terms of acquisition and post-processing. Conversely, these metrics should be included as an end-point in disease-modifying agents trials (Miller et al., 2002) in order to further elucidate the mechanisms responsible for disability.
- The application of non-conventional MRI techniques in monitoring patients with established MS in clinical practice is, at the moment, not advisable. All these techniques still need to be evaluated for sensitivity and specificity in detecting tissue damage in MS and its changes over time.
- Magnetization transfer (MT) MT-MRI should be incorporated into new clinical trials to gain additional insights into disease pathophysiology and into the value of this technique in the assessment of MS. The performance and contribution of diffusion tensor MRI (DT-MRI) and MR spectroscopy (1H-MRS) in multicenter trials still have to be evaluated.
Definitions:
Evidence Classification Scheme for a Diagnostic Measure
Class I: A prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where the test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class II: A prospective study of a narrow spectrum of persons with the suspected condition, or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation
Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls)
Rating of Recommendations
Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.
Good practice point Where there was lack of evidence but consensus was clear the Task Force members have stated their opinion as good practice points.
