This is the current release of the guideline.

Multiple sclerosis

Diagnosis
Education
Risk Assessment
Technology Assessment

Family Practice
Neurology
Radiology

Physicians

• To consider the evidence that magnetic resonance imaging (MRI) can prospectively predict the future conversion to clinically definite multiple sclerosis (CDMS) in patients presenting with a syndrome consistent with inflammatory demyelination
• To consider the evidence for the use of baseline and follow-up magnetic resonance imaging in the diagnosis of patients with suspected multiple sclerosis

• Patients with symptoms suggestive of multiple sclerosis (MS)
• Patients presenting with a syndrome consistent with inflammatory demyelination

Magnetic resonance imaging (MRI)

Specificity, sensitivity, positive predictive value, and diagnostic accuracy of magnetic resonance imaging (MRI) in multiple sclerosis (MS)

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

A search was undertaken using the following terms: clinically isolated syndromes, multiple sclerosis, and magnetic resonance imaging. Guideline developers used the Medline database from 1966 to 2003. In addition, the reference lists of the articles identified were also reviewed to identify articles not found by the computer search. They reviewed the abstracts of these articles and further limited their assessment to English language studies that were prospective and utilized a well-defined gold standard for the development of clinically definite multiple sclerosis (CDMS).

Inclusion/Exclusion

The guideline developers only reviewed articles that studied at least 20 patients. There were 22 such studies identified. All of these articles considered the risk of developing clinically definite multiple sclerosis in patients with clinically isolated syndrome (CIS), based on the presence or absence of magnetic resonance imaging (MRI) lesions within the brain or spinal cord.

46 articles were originally identified

22 studies met inclusion criteria

Weighting According to a Rating Scheme (Scheme Given)

Rating of Diagnostic Article

Class I: Evidence provided by a prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy. In addition, there must be adequate accounting for dropouts with numbers sufficiently low to have minimal potential for bias.

Class II: Evidence provided by 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).

Systematic Review

Not stated

Not stated

Translation of Evidence to Recommendations

Level A rating requires at least one convincing Class I study or at least two consistent, convincing Class II studies.

Level B rating requires at least one convincing Class II study or at least three consistent Class III studies.

Level C rating requires at least two convincing and consistent Class III studies.

Rating of Recommendation

A = established as useful/predictive or not useful/predictive for the given condition in the specified population.

B = probably useful/predictive or not useful/predictive for the given condition in the specified population.

C = possibly useful/predictive or not useful/predictive for the given condition in the specified population.

U = data inadequate or conflicting. Given current knowledge, test/predictor is unproven.

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

Draft guidelines were reviewed for accuracy, quality, and thoroughness by the American Academy of Neurology (AAN) members, topic experts, and pertinent physician organizations.

Final guidelines were approved by the American Academy of Neurology Therapeutics and Technology Assessment Subcommittee on April 16, 2002, the American Academy of Neurology Practice Committee on April 2, 2003, and the American Academy of Neurology Board of Directors on June 22, 2003. They were published in Neurology 2003:61:602-611.

Definitions of the strength of the recommendations (A, B, C, U) and classification of the evidence (Class I through Class IV) are provided at the end of the "Major Recommendations" field.

Recommendations

1. Magnetic resonance imaging (MRI) changes seen in multiple sclerosis (MS) are known to be nonspecific (refer to Table 2, entitled "Diagnostic Consideration in Patients with Suspected MS and/or MRI White Matter Abnormalities" in the original guideline document). Therefore, the information derived from imaging investigations must always be considered in the context of the specific clinical situation presented by an individual patient. As a result, the following recommendations are predicated on the exclusion, at baseline, of appropriate alternative conditions that can mimic MS or can mimic the radiographic findings seen in MS.
2. On the basis of consistent Class I, II, and III evidence, in patients with clinically isolated syndrome (CIS), the finding of three or more white matter lesions on a T2-weighted MRI scan is a very sensitive predictor (>80%) of the subsequent development of clinically definite MS (CDMS) within the next 7 to 10 years (Type A recommendation). It is possible that the presence of even a smaller number of white matter lesions (e.g., one to three) may be equally predictive of future MS although this relationship requires better clarification.
3. The presence of two or more gadolinium (Gd)-enhancing lesions at baseline is highly predictive of the future development of clinically definite MS (Type B recommendation).
4. The appearance of new T2 lesions or new gadolinium enhancement 3 or more months after a clinically isolated demyelinating episode (and after a baseline MRI assessment) is highly predictive of the subsequent development of clinically definite MS in the near term (Type A recommendation).
5. The probability of making a diagnosis other than MS in patients with clinically isolated syndrome with any of the above MRI abnormalities is quite low, once alternative diagnoses that can mimic MS or can mimic the radiographic findings of MS have been excluded (Type A recommendation).
6. The MRI features helpful in the diagnosis of primary progressive MS (PPMS) cannot be determined from the existing evidence (Type U recommendation).

Definitions:

Rating of Recommendation

A = Established as useful/predictive or not useful/predictive for the given condition in the specified population.

B = Probably useful/predictive or not useful/predictive for the given condition in the specified population.

C = Possibly useful/predictive or not useful/predictive for the given condition in the specified population.

U = Data inadequate or conflicting. Given current knowledge, test/predictor is unproven

Rating of Diagnostic Article

Class I: Evidence provided by a prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy. In addition, there must be adequate accounting for dropouts with numbers sufficiently low to have minimal potential for bias.

Class II: Evidence provided by 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).

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

• These guidelines may assist physicians in making appropriate clinical decisions regarding the clinical utility of magnetic resonance imaging (MRI) in suspected multiple sclerosis (MS).
• With MRI techniques, occult disease activity can be demonstrated in 50 to 80% of patients at the time of the first clinical presentation. Prospective studies have shown that the presence of such lesions predicts the future conversion to clinically definite MS (CDMS). Indeed, in a young to middle-aged adult with a clinically isolated syndrome (CIS), once alternative diagnoses are excluded at baseline, the finding of three or more white matter lesions on a T2-weighted MRI scan (especially if one of these lesions is located in the periventricular region) is a very sensitive predictor (>80%) of the subsequent development of clinically definite MS within the next 7 to 10 years. Moreover, the presence of two or more gadolinium (Gd)-enhancing lesions at baseline and the appearance of either new T2 lesions or new gadolinium enhancement on follow-up scans are also highly predictive of the subsequent development of clinically definite MS in the near term.

Not stated

• The guideline developers acknowledge inherent limitations of the literature. Any study of the predictive validity of magnetic resonance imaging (MRI) is dependant upon the gold standard used to establish the diagnosis of multiple sclerosis (MS). Generally, this standard is the development of clinically definite MS (CDMS) by some criteria, after some period of follow-up. Nevertheless, in a disease like MS (where the development of clinically definite MS can be delayed by decades from the onset of clinical symptoms) such a design has serious limitations, especially when the follow-up is either too short or too variable. Most studies of the predictive validity of MRI in MS are confounded by this limitation.
• This statement is provided as an educational service of the American Academy of Neurology. It is based on an assessment of current scientific and clinical information. It is not intended to include all possible proper methods of care for a particular neurologic problem or all legitimate criteria for choosing to use a specific procedure. Neither is it intended to exclude any reasonable alternative methodologies. The American Academy of Neurology recognizes that specific patient-care decisions are the prerogative of the patient and the physician caring for the patient, based on all of the circumstances involved.

An implementation strategy was not provided.

Living with Illness

Effectiveness

Not applicable: The guideline was not adapted from another source.

2003 Sep 9

American Academy of Neurology - Medical Specialty Society
Child Neurology Society - Medical Specialty Society

American Academy of Neurology (AAN)

Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
Practice Committee of the Child Neurology Society

Members of the Therapeutics and Technology Assessment Subcommittee: Douglas S. Goodin, MD (chair); Carmel Armon, MD; Elliot M. Frohman, MD, PhD; Robert S. Goldman, MD; David Hammond, MD; Chung Y. Hsu, MD, PhD; Andres M. Kanner, MD; David S. Lefkowitz, MD; Isaac E. Silverman, MD; Michael A. Sloan, MD; Yuen T. So, MD, PhD; Edgar J. Kenton III, MD; Wendy Edlund, AAN Staff Liaison

Not stated

This is the current release of the guideline.

This summary was completed by ECRI on February 12, 2004. This summary was updated by ECRI Institute on May 17, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Gadolinium-based contrast agents. This summary was updated by ECRI Institute on June 20, 2007 following the U.S. Food and Drug Administration (FDA) advisory on gadolinium-based contrast agents.

This NGC summary is based on the original guideline, which is copyrighted by the American Academy of Neurology.