MS New Diagnostic Criteria
MS's New Challenge: The McDonald Criteria
Craig H. Smith, M.D.
Director, Swedish Medical Center
Multiple Sclerosis Center
An Antiquated Paradigm
Over the past 5 years there has been a virtual explosion in the knowledge regarding the pathophysiology and immunology of MS. Practicing neurologists have been confronted with new technologies to incorporate into the diagnostic workup of the patient with presumed MS. Folded into this thicket of information and powerful technologic tools is the bewildering morass of immunomodulatory therapies with conflicting claims of efficacy. Just when we thought that there was light at the end of the long tunnel of learning, a new diagnostic criterion has thrown seemingly more confusion into an already over-burdened arena of care. In this article we will review the new diagnostic criterion and how this integrates into our neurologic care of the MS patient. The new criteria, when closely examined, assist significantly in defining an early diagnostic approach to MS.
MS remains a clinical diagnosis; dependent on a detailed history, careful neurologic examination and a review of paraclinical evidence (MRI studies, cerebrospinal fluid analysis and evoked potential testing). The classical diagnostic criterion in MS, which is still applicable, is evidence of lesions in the central nervous system (CNS) disseminated in time and space. This means that more than one lesion has to involve more than one area of the nervous system. This involvement might occur in optic nerve, brain or spinal cord. Prior to the 1980's, confusion reigned regarding the diagnosis of this condition. Virtually no guidelines existed to help clinicians, and clinical trials were virtually unknown; not forcing establishment of accepted diagnostic standards.
In 1982 a committee, established by the National MS Society, produced the Poser criteria1 for use in clinical trials involving MS. The committee proposed four categories including clinically definite MS; laboratory (CSF) supported definite MS, probable MS (either clinically or laboratory supported) and possible MS. In 1982, MRI as a technology, was in its infancy - and was included as a paraclinical element along with urodynamic testing and evoked potentials. For twenty years we have utilized the Poser criteria despite a burgeoning science of imaging technology-integrating MRI into the diagnostic paradigms of MS. As a result, neurologists have been hampered by out-dated diagnostic paradigms strangling the utilization of advancing technologic tools. Clinical trials demanded a better set of criteria.
In July 2000, the International Panel on the Diagnosis of MS, chaired by W. Ian McDonald, FRCP (Royal College of Physicians, London), met in London to review the Poser criteria and to recommend change, where appropriate-including integration of MRI into the diagnostic process because of its ability to depict disease-related damaged areas, or lesions, in the brain and spinal cord.
The panelists developed step-by-step instructions to guide physicians toward diagnosing different forms of MS, including primary-progressive MS, which involves progressive disability from onset without the distinct attacks of the more common relapsing-remitting form of MS. For the first time, the panel also outlined steps to determine an MS diagnosis in a person who has only had one attack of symptoms.
The new diagnostic criteria, published in the July 2001 issue of Annals of Neurology (published early online on April 2, 2001), were authored by Dr. McDonald and 15 other panel members. This new criteria is now also named after the committee chair; in this case it is called the "McDonald criteria" 2. This was a true international effort, and the guidelines were designed by the committee to be used anywhere, irrespective of regional differences in healthcare resources or practices.
In a Nutshell
The general conclusions of the new criteria are:
- The diagnosis of MS requires objective evidence of lesions disseminated in time and space.
- MRI may contribute to determining dissemination in time and/or space.
- 3 diagnostic categories were established: possible MS, MS, or not MS.
- Other supportive tests include CSF and VEP
- The category of probable MS had little practical value for clinicians - and has had no value in clinical trial utilization; it has therefore been eliminated.
Importance of MRI
Although the McDonald criteria retain the time-honored (and well-established) basis for diagnosing MS by clinical means, MRI now plays a much larger role in our new diagnostic guidelines. Although the gold standard thus remains a complete neurologic history and detailed neurological examination providing evidence for more than one episode involving more than one area of the CNS - and no better diagnosis present - neuroimaging now may provide evidence of dissemination in the nervous system.
If an MRI of the brain or spinal cord performed at three or more months after an initial clinical event demonstrates a new Gadolinium-enhancing lesion, this would indicate a new CNS inflammatory event. The duration of Gadolinium enhancement in MS is generally less than 6 weeks. If one does not see a new Gadolinium enhancing lesions but does see a new T2 lesion (presuming an MRI was done at the time of the initial event), then one should perform a repeat MRI scan after another three months. All events within the first 30 days after an exacerbation are considered part of the initial exacerbation; the new T2 lesion developing within the 30 days following an exacerbation would not count as a new event - the new lesions seen on the 3-month scan, however, would be a new a presumably separate demyelinating event. This is, of course, only a guideline given by the committee. Individual neurologists must make their own call on this information.
The McDonald criteria recognized the need for standardization of MR imaging; a consensus meeting organized by the Consortium of MS Centers issued recommendations regarding the requirements fro MRI. These include contiguous slices with a thickness of 3mm, standard T1, T2 and FLAIR and T1 Gadolinium enhanced sequences in at least two planes (coupled with a adequate field strength - 1.5 Tesla).
Table 2. New diagnostic criteria for MRI determination of dissemination in time
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Cerebrospinal Fluid; is it useful?
Spinal fluid immunologic markers were not felt by the international committee to be necessary for the diagnosis of relapsing forms of MS. However, CSF analysis was deemed necessary for diagnosing primary progressive MS (PPMS). PPMS is often difficult to diagnosis with this conditions' paucity of identifiable abnormalities on brain MRI. With respect to CSF testing, the presence of oligoclonal IgG bands in the CSF not present in serum - or an elevated IgG index - is considered to be supportive of a diagnosis of MS. In the presence of CSF Ig abnormalities by isoelectric focusing method, the MRI criteria for dissemination in space are relaxed, requiring only two MS lesions.
The international committee also considered that visual evoked potential responses provide diagnostically valuable data of dissemination of lesions in space - other evoked potentials do not.
The American Academy of Neurology Quality Standards Subcommittee practice parameter guidelines were taken into consideration when establishing the recommendations noted above.
How does this work in Practice?
How does one use these guidelines in a clinical neurology practice? The following guidelines are outlined in the McDonald criteria:
If a patient has had two or more attacks with objective evidence of involvement of two or more areas of the CNS, and there is no better diagnosis, then the criteria for MS has been established. This becomes important in regions where access to neuroimaging is limited. Obviously, if neuroimaging or CSF is also assessed, the findings should be consistent with the diagnosis of MS.
If your patient has had one attack and evidence of two lesions in the CNS, then the clinician will need to obtain evidence for dissemination in time - this can then be accomplished by either noting a second clinical event or a change on subsequent MRI.
If your patient has had two or more attacks but evidence on exam of involvement of only one area of the CNS, confirmation of dissemination in space must be established. A second attack, involving a new area of the CNS, or changes on subsequent MRI scans will fulfill this criterion.
When patients have had one attack and evidence of only one area of CNS involvement (optic neuritis, for example), dissemination in both space and time must be confirmed clinically or by fulfilling the MRI criteria for dissemination for each.
In primary progressive MS, the risk of confounding diagnoses is greater than for other forms of MS. For this reason, in the case of insidious onset and progression of neurologic dysfunction suggestive of MS, one needs to find positive CSF and evidence of dissemination in time by MRI or continued progression for at lease one year and dissemination in space by MRI or two or more spinal MRI abnormalities or four to eight cerebral MRI lesions and one spinal cord lesion or an abnormal VEP and four to eight cerebral lesions on MRI or an abnormal VEP and fewer than four cerebral lesions plus one spinal cord lesion. This requires a considerable amount of work on the part of the clinician, but fortunately, PPMS is a rarely seen diagnosis.
A careful review of the McDonald criteria, along with posting the elements of the new component aspects of the criteria in a place that the clinician can easily refer to it, will help considerably in clarifying what has been a confusing arena; the result of coupling new technology with a clinically based diagnostic skills.
(Table 1) New MS Diagnostic Criteria1
Clinical |
Objective |
Additional Requirements |
2 or |
1 |
|
2 or |
1 |
|
1 |
2 or |
|
0 (progression from onset)
|
1 |
· Positive CSF AND
or 2 or more cord lesions or 4-8 brain and 1 cord lesion or positive VEP with 4-8 brain and 1 cord lesion or positive VEP with 4-8 MRI lesions or positive VEP with less than 4 brain lesions plus 1 cord lesion AND
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References:
1.LublinFD. Modernize Your Approach to Multiple Sclerosis. Practical Neurology 2002; 44-47.
2.McDonald et al. Recommended Diagnostic Criteria for MS. Ann Neurol 2001; 50:121-127
3. Poser CM, Paty DW, Scheinberg L, et al. "New Diagnostic Criteria For Multiple Sclerosis: Guidelines For Research Protocols" Ann Neurol 1983; 13:227-231