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Apr 23, 2009

Differential Diagnosis of Multiple Sclerosis: National MS Society International Task Force Develops Consensus-Driven Guidelines and Invites Their Validation

An international task force convened by the National MS Society’s International Advisory Committee on Clinical Trials has published a landmark paper to guide neurologists through the complex process of distinguishing multiple sclerosis from other disorders. The consensus-based guidelines for the differential diagnosis of MS should greatly enhance the accuracy of diagnosing MS and its look-alikes, and speed the delivery of appropriate therapies. David Miller, MD, FRCP (University College London), Chris Polman, MD, PhD (Free University Medical Centre, Amsterdam) and colleagues present these guidelines in Multiple Sclerosis 2008 Nov;14[9]:1157-74, inviting feedback and research to validate them. Because of its potential impact, the National MS Society provided funds to make this paper available to all at no charge. 

Background: At this time, there are no symptoms, physical findings or laboratory tests that can, by themselves, determine if a person has MS. In order to make a diagnosis of MS, the physician must find evidence of damage in at least two separate areas of the central nervous system (CNS, which includes the brain, spinal cord and optic nerves) AND find evidence that the episodes of damage occurred at least one month apart AND rule out all other possible diagnoses.

In efforts to improve care for people with MS, the National MS Society and its advisors have vigorously pursued ways to refine and speed the diagnosis of MS – especially in light of evidence suggesting benefits when treatment is started early in the course of the disease. The efforts of the Society’s International Panel on the Diagnosis of MS in 2001 and 2005 led to the “McDonald Criteria” for diagnosing MS.

The McDonald Criteria (Polman et al. Diagnostic Criteria for Multiple Sclerosis: 2005 Revisions to the “McDonald Criteria.” Annals of Neurology (2005) 58: 840-846) specify that other possible disorders must be ruled out before MS is diagnosed. To address this critical need, in 2006 the Society’s International Advisory Committee on Clinical Trials convened the International Task Force on Differential Diagnosis in MS. Using available literature, and achieving a consensus through conference calls and meetings, the group developed a series of guidelines that can serve as a practical tool to help physicians diagnose MS more speedily, or to rule it out.

Task Force Guidelines: The task force identified 79 major and minor ‘red flags’ that would point away from an MS diagnosis in individuals with central nervous system involvement. Detailed in a comprehensive table, these include major, intermediate and minor red flags and alternative disorders to consider.

(Here is a small sample adapted from the publication. Please see the published paper for the complete table, flowcharts and other helpful tools. The final, definitive version of this paper has been published in Multiple Sclerosis, Vol. 14/No. 9, November 2008 by SAGE Publications Ltd, All rights reserved.)

• The paper provides algorithmic flowcharts that offer stepwise differential diagnostic considerations when an initial clinical presentation occurs as demyelinating optic neuritis, demyelinating brain stem syndrome, or isolated spinal cord syndrome.
• The task force also offers a more precise definition of CIS (clinically-isolated syndrome), in which a patient experiences one attack of suggestive neurological symptoms that can sometimes lead to the development of definite MS), agreeing that this term comprises five types of isolated syndrome. These types of CIS are differentiated by where symptoms occur (e.g., vision problems, foot numbness) and whether disease activity is apparent on MRI scans.
• The task force describes distinguishing features of NMO (neuromyelitis optica, a demyelinating disease commonly mistaken for MS), including severe episodes of myelitis (inflammation of myelin) usually accompanied by a spinal cord lesion; severe episodes of optic neuritis (often with incomplete recovery); often normal brain MRI scans; and a high expression of the protein aquaporin 4. In this paper, the task force also proposes criteria for distinguishing acute disseminated encephalomyelitis (ADEM) from MS.

Additional Research Needed: The authors acknowledge that additional research will be needed to confirm these consensus-driven guidelines, and that having sensitive disease biomarkers – the subject of intense, ongoing investigation – will greatly improve differential diagnosis. In an accompanying editorial, the editors of Multiple Sclerosis invite readers who are expert in some of the MS-mimicking disorders to offer their own views to help shape these guidelines in the future.

Task Force on Differential Diagnosis in MS
• Chair: C.H. Polman, Department of Neurology, VU Medical Centre Amsterdam, Amsterdam NL.
• Subgroup Leader: D.H. Miller, Institute of Neurology, NMR Research Unit, Department of Inflammation, Queen Square, London UK
• Subgroup Leader: B.G. Weinshenker, Department of Neurology, Mayo Clinic College of Medicine, Rochester MN, USA
• Subgroup Leader: M. Filippi, Neuroimaging Research Unit, Department of Neurology, Ospedale San Rafaele, Milan IT

Members:
• B.L. Banwell, The Hospital for Sick Children, Toronto, CA;
• J.A. Cohen, The Mellen Center, Cleveland Clinic, Cleveland, USA;
• M.S. Freedman, MS Research Unit, University of Ottawa, The Ottawa Hospital – General Campus, Ottawa, CA;
• S.L. Galetta, Department of Neurology, University of Pennsylvania Hospital, Philadelphia USA;
• M. Hutchinson, St Vincent’s University Hospital, Dublin, IR;
• R.T. Johnson, The Johns Hopkins Hospital, Baltimore USA;
• L. Kappos, Department of Neurology, University Hospitals, Basel, CH;
• J. Kira, Department of Neurology, Kyushu University, Kyushu, JP;
• F.D. Lublin, Corrine Goldsmith Dickinson Center for Multiple Sclerosis, Mt. Sinai School of Medicine, New York City USA;
• H.F. McFarland, Neuroimmunology Branch, NINDS, National Institutes of Health, Bethesda, MD USA;
• X. Montalban, Unitat de Neuroimmunologia Clinica, Hospital Universitari Vall d’Hebron, Barcelona SP;
• H. Panitch, Neurology Service, University of Vermont College of Medicine, Burlington USA;
• J. Richert, Research and Clinical Programs Department, National Multiple Sclerosis Society, New York City USA;
• S.C. Reingold, Research and Clinical Programs Department, National Multiple Sclerosis Society, New York City USA and Scientific and Clinical Review Associates, LLC, New York City USA.

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