Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria

Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria Chris H. Polman Stephen C. Reingold Brenda Banwell M. Clanet Jeffrey A. Cohen Massimo Filippi Kazuo Fujihara Eva Havrdová Michael Hutchinson Ludwig Kappos Fred Lublin Xavier Montalbán Paul O’Connor Magnhild Sandberg‐Wollheim Alan J. Thompson Emmanuelle Waubant Brian G. Weinshenker Jerry S. Wolinsky

Tag layer of the DHSS Meta-Tagging Project. The article text is reproduced from the staged copy named in sourceDesc and is not altered; the tags are held separately in standOff so that overlapping and nested spans are preserved.

Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria 2011 Annals of Neurology 10.1002/ana.22366 polman2011-diagnostic-criteria-for-multiple-s polman2011-diagnostic-criteria-for-multiple-s.txt, the project's staged copy c69755bf00f1de5875dc04f66a857c69cb57d959 cc-by medicine

the paper's own words

the tag layer; a sentence written by the tagger about the paper, always anchored to a quotation but not itself a quotation

0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them A DIAGNOSTIC DEFINITION ON ITS THIRD REVISION BY THE SAME PANEL, LOOSENED EACH TIME ON PURPOSE - the McDonald Criteria of 2001, revised 2005 and again here, each round making the diagnosis of multiple sclerosis earlier and the procedure simpler Quotation withheld because this record is not cleared for redistribution. how far the imaging requirements for demonstrating dissemination in space and time can be simplified without losing specificity, and whether the criteria hold outside the population they were derived from Quotation withheld because this record is not cleared for redistribution. MAGNIMS-based imaging criteria for dissemination in space, a rule letting enhancing and non-enhancing lesions on ONE scan establish dissemination in time, and recommendations for pediatric, Asian and Latin American populations Quotation withheld because this record is not cleared for redistribution. method Quotation withheld because this record is not cleared for redistribution. a disease with no confirmatory biomarker, diagnosed by a rule that has been rewritten three times, whose rewriting changes which past trial subjects would have qualified Quotation withheld because this record is not cleared for redistribution. expert-consensus expert-consensus Quotation withheld because this record is not cleared for redistribution. A DEFINITION DELIBERATELY LOOSENED, THREE TIMES, BY THE SAME PANEL: `These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.` The corpus holds definitions tightened, abolished and kept for continuity. This one has been relaxed on purpose in 2001, 2005 and 2010, each time with the sensitivity/specificity claim attached Quotation withheld because this record is not cleared for redistribution. AND DISSEMINATION IN TIME IS NOW DEMONSTRABLE AT A SINGLE MOMENT: `in some circumstances dissemination in space and time can be established by a single scan` - because `a single brain MRI study that demonstrates DIS and both asymptomatic gadolinium-enhancing and non-enhancing lesions is highly specific for predicting early development of clinically definite MS`. A criterion whose name is TIME, satisfied without the passage of any - the two lesion types imply different ages, so one image carries a history Quotation withheld because this record is not cleared for redistribution. AND A WAITING REQUIREMENT WAS DROPPED BECAUSE IT COST A SCAN: `The 2005 revision ... based [DIT] on the appearance of a new T2 lesion on a scan compared to a reference or baseline scan performed AT LEAST 30 days after the onset ... In clinical practice, however, there is reason NOT TO POSTPONE A FIRST MRI until after 30 days, which would result in an extra MRI scan to confirm a diagnosis. ABANDONING THE REQUIREMENT ... does not compromise specificity.` A criterion removed on cost, with the specificity claim cited beside it Quotation withheld because this record is not cleared for redistribution. AND A FURTHER LIBERALISATION WAS REFUSED, FOR A REASON ABOUT THE EVIDENCE BASE: `In the 2001 and 2005 McDonald Criteria, a positive CSF finding could be used to reduce the MRI requirements ... However, when applying the simplified MAGNIMS imaging criteria, the Panel believes that even further liberalizing MRI requirements in CSF-positive patients is not appropriate, as CSF status was not evaluated for its contribution to the MAGNIMS criteria.` A relaxation declined because the variable was not in the study the new rule came from - and an existing allowance withdrawn by the same reasoning Quotation withheld because this record is not cleared for redistribution. AND THE PANEL SAYS THE REVISION CHANGES WHAT THE EARLIER TRIALS WERE ABOUT: `Quotation withheld` The clearest statement in the corpus that a definitional change reaches backwards into evidence already collected Quotation withheld because this record is not cleared for redistribution. AND THE VALIDITY DOMAIN IS PRINTED TWICE, ONCE AT EACH END: `the McDonald Criteria should only be applied in those patients who present with a typical clinically isolated syndrome ... because the development and validation of the Criteria have been limited to patients with such presentations`, and in the Conclusions `These revised McDonald Criteria ... should therefore be applied only when patients have experienced a typical CIS`. A rule that states where it does not apply, twice Quotation withheld because this record is not cleared for redistribution. AND AN INSTRUMENT MAY REPLACE THE OBSERVATION THE DEFINITION WAS BUILT ON: `Although the diagnosis can be made on clinical grounds alone, MAGNETIC RESONANCE IMAGING ... can support, supplement, or even replace some clinical criteria ... The McDonald Criteria have resulted in earlier diagnosis of MS with a high degree of both specificity and sensitivity, allowing for better counseling of patients and earlier treatment.` The scan does not merely support the clinical judgement - it stands in for it Quotation withheld because this record is not cleared for redistribution. AND `ATTACK` IS DEFINED WITH A DURATION FLOOR AND A CONFOUND EXCLUDED: `patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the CNS, current or historical, with duration of at least 24 hours, in the absence of fever or infection ... Reports of paroxysmal symptoms should, however, consist of multiple episodes occurring over not less than 24 HOURS.` A unit of disease activity given a minimum length, and a historical report admitted as evidence Quotation withheld because this record is not cleared for redistribution. AND A PHENOTYPE WAS SPLIT OFF PARTLY BECAUSE THE TREATMENT FAILS ON IT: `There was agreement that this phenotype should be separated from typical MS because of different clinical course, prognosis, and underlying pathophysiology and poor response to some available MS disease-modifying therapies.` Neuromyelitis optica leaves the class on four grounds, and one of them is that the drugs for the parent class do not work Quotation withheld because this record is not cleared for redistribution. AND A TERM IS DIAGNOSED AS AN ADMIXTURE OF TWO OTHERS: `there is some uncertainty, especially in Asia, about whether MS and NMO are distinct and if so, how they should be distinguished. As currently applied, the term opticospinal MS appears to be an admixture of conventional MS and NMO.` A name in regional use that turns out to cover two classes the rest of the field separates Quotation withheld because this record is not cleared for redistribution. AND THE TEST THAT SEPARATES THEM IS ASYMMETRIC: `Quotation withheld` A marker that rules in better than it rules out, used to decide which disease a patient is treated for Quotation withheld because this record is not cleared for redistribution. AND THE IMAGING-ONLY CASE IS REFUSED A DIAGNOSIS: `occasional individuals investigated by MRI for indications unrelated to MS have incidental findings of brain lesions with appearance and topography consistent with MS ... the Panel concluded that a firm diagnosis of MS based on incidental findings on MRI alone, even with additional supportive findings ... in the absence of MS-relevant clinical symptoms, is problematic.` The same images that can replace a clinical criterion cannot, alone, make the diagnosis - a boundary drawn between supporting and constituting Quotation withheld because this record is not cleared for redistribution. THERE IS STILL NO CONFIRMATORY BIOMARKER: `Although increased IgG index or the presence of oligoclonal bands in the CSF support an MS diagnosis, and AQP4 antibody assays can help in the differential diagnosis process, there are still no specific biomarkers to confirm the diagnosis.` Every criterion in this document is a proxy, and the document says so Quotation withheld because this record is not cleared for redistribution. AND THE CRITERIA ARE NOT VALIDATED IN THE POPULATIONS THE PAPER EXTENDS THEM TO: `These 2010 revisions ... are likely to be applicable in pediatric, Asian, and Latin American populations ... The predictive validity of DIS and DIT based on a single first scan in children with CIS needs to be confirmed in prospective studies. The McDonald Criteria have not yet been validated in Asian and Latin American populations.` Extended and unvalidated in the same paragraph, with `likely` carrying the weight Quotation withheld because this record is not cleared for redistribution. AND THE POPULATION THE RULE IS USED ON IS NOT THE ONE IT WAS TESTED ON: `A proportion of patients with nonspecific symptoms (eg, fatigue, weakness, or dizziness) and nonspecific MRI findings are referred to secondary and tertiary MS centers ... for a second opinion and do not in fact have MS`, and the Panel notes `only limited research and practical experience in general neurology practice populations`. The criteria are validated in MS centres and applied in clinics Quotation withheld because this record is not cleared for redistribution. AND AT LEAST ONE ATTACK MUST BE OBJECTIVELY CORROBORATED, WHICH IMPORTS THE INSTRUMENT INTO THE DEFINITION: `before a definite diagnosis of MS can be made, AT LEAST 1 ATTACK MUST BE CORROBORATED BY FINDINGS ON NEUROLOGICAL EXAMINATION, VISUAL EVOKED POTENTIAL RESPONSE ..., or MRI consistent with demyelination in the area of the CNS implicated in the historical report.` A patient's history counts only where an instrument agrees with it Quotation withheld because this record is not cleared for redistribution. refusing to liberalise the MRI requirement for CSF-positive patients, because CSF status was not a variable in the studies the new imaging rule came from eliminates: carrying an allowance from the old criteria into a rule set whose evidence base never tested it · outcome: held Quotation withheld because this record is not cleared for redistribution. restricting the criteria to patients presenting with a typical clinically isolated syndrome, stated in the Considerations and again in the Conclusions eliminates: application to the nonspecific-symptom referrals who 'do not in fact have MS' · outcome: partial Quotation withheld because this record is not cleared for redistribution. requiring at least one attack to be corroborated by examination, evoked potentials or MRI in the implicated CNS area eliminates: a diagnosis resting entirely on undocumented patient history · outcome: held Quotation withheld because this record is not cleared for redistribution. NMO NMO Quotation withheld because this record is not cleared for redistribution. typical MS typical MS Quotation withheld because this record is not cleared for redistribution. opticospinal MS opticospinal MS Quotation withheld because this record is not cleared for redistribution. conventional MS conventional MS Quotation withheld because this record is not cleared for redistribution. The McDonald Criteria The McDonald Criteria Quotation withheld because this record is not cleared for redistribution. earlier diagnosis of MS earlier diagnosis of MS Quotation withheld because this record is not cleared for redistribution. a first MRI a first MRI Quotation withheld because this record is not cleared for redistribution. an extra MRI scan an extra MRI scan Quotation withheld because this record is not cleared for redistribution. `attack` (relapse, exacerbation) - `patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the CNS, current or historical, with duration of at least 24 hours, in the absence of fever or infection` Quotation withheld because this record is not cleared for redistribution. `dissemination in time` (2010 sense) - satisfied EITHER by a new lesion on a later scan OR by enhancing and non-enhancing lesions coexisting on ONE baseline scan; the 2005 sense required a reference scan at least 30 days after onset Quotation withheld because this record is not cleared for redistribution. `opticospinal MS` - a regionally used term that `appears to be an admixture of conventional MS and NMO` rather than a class of its own Quotation withheld because this record is not cleared for redistribution. `radiologically isolated syndrome` - MS-appearing lesions found incidentally, for which `a firm diagnosis of MS based on incidental findings on MRI alone ... is problematic`; the imaging is present and the diagnosis is withheld Quotation withheld because this record is not cleared for redistribution. extends → the original (2001) and revised (2005) McDonald Criteria, whose 'underlying concepts ... are still valid' and whose imaging requirements this revision replaces Quotation withheld because this record is not cleared for redistribution. extends → the MAGNIMS network's comparison of the Barkhof/Tintore DIS criteria against Swanton's simplified criteria in 282 CIS patients, adopted here wholesale Quotation withheld because this record is not cleared for redistribution. critiques → the term 'opticospinal MS' as used in Asia, which 'appears to be an admixture of conventional MS and NMO' Quotation withheld because this record is not cleared for redistribution. NMO —distinct-from→ typical MS NMO typical MS the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'There was agreement…' One of the four grounds is that the parent class's drugs do not work - a boundary drawn partly by what happens when you treat across it, which is arain2010's treatment-response boundary in a different field · the relation stated: separated on four grounds - clinical course, prognosis, pathophysiology, and poor response to MS disease-modifying therapies Quotation withheld because this record is not cleared for redistribution. The McDonald Criteria —causes→ earlier diagnosis of MS The McDonald Criteria earlier diagnosis of MS the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'THE McDONALD CRITERIA HAVE RESULTED…' Read against the paper's own acknowledgement that the revised criteria 'MAY CHANGE SOME…': the same change that brings treatment forward also moves the denominator of every study that used an earlier version · the relation stated: the criteria are credited with moving the diagnosis earlier at high sensitivity and specificity, which is also the stated aim of each revision Quotation withheld because this record is not cleared for redistribution. a first MRI —causes→ an extra MRI scan a first MRI an extra MRI scan the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'In clinical practice…' A definitional requirement removed because of what it costs to satisfy, with the specificity claim - 'DOES NOT COMPROMISE…' - supplied by a single cited study · the relation stated: postponing the baseline scan past 30 days, as the 2005 rule required, forces an additional scan to confirm the diagnosis - which is why the requirement was abandoned Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says POSTPONING a first MRI would result in an extra scan; causes is loose. Quotation withheld because this record is not cleared for redistribution. the revised McDonald criteria simplify diagnosis and may allow earlier diagnosis while preserving sensitivity and specificity the revised McDonald criteria simplify diagnosis and may allow earlier diagnosis while preserving sensitivity and specificity Quotation withheld because this record is not cleared for redistribution. AND DISSEMINATION IN TIME IS NOW DEMONSTRABLE AT A SINGLE MOMENT: `in some circumstances dissemination in space and time can be established by a single scan` AND DISSEMINATION IN TIME IS NOW DEMONSTRABLE AT A SINGLE MOMENT: `in some circumstances dissemination in space and time can be established by a single scan` Quotation withheld because this record is not cleared for redistribution. AND THE REVISION CHANGES WHAT EARLIER TRIALS WERE ABOUT: `using these refined diagnostic criteria may change some of the outcomes of patients in natural history studies and clinical trials` AND THE REVISION CHANGES WHAT EARLIER TRIALS WERE ABOUT: `using these refined diagnostic criteria may change some of the outcomes of patients in natural history studies and clinical trials` Quotation withheld because this record is not cleared for redistribution. AND A LIBERALISATION WAS REFUSED FOR A REASON ABOUT THE EVIDENCE BASE: `even further liberalizing MRI requirements in CSF-positive patients is not appropriate, as CSF status was not evaluated for its contribution` AND A LIBERALISATION WAS REFUSED FOR A REASON ABOUT THE EVIDENCE BASE: `even further liberalizing MRI requirements in CSF-positive patients is not appropriate, as CSF status was not evaluated for its contribution` Quotation withheld because this record is not cleared for redistribution. AND A PHENOTYPE WAS SPLIT OFF PARTLY BECAUSE THE DRUGS FAIL ON IT: NMO separated from typical MS on `poor response to some available MS disease-modifying therapies` AND A PHENOTYPE WAS SPLIT OFF PARTLY BECAUSE THE DRUGS FAIL ON IT: NMO separated from typical MS on `poor response to some available MS disease-modifying therapies` Quotation withheld because this record is not cleared for redistribution. AND A REGIONAL TERM COVERS TWO CLASSES: `the term opticospinal MS appears to be an admixture of conventional MS and NMO` AND A REGIONAL TERM COVERS TWO CLASSES: `the term opticospinal MS appears to be an admixture of conventional MS and NMO` Quotation withheld because this record is not cleared for redistribution. a firm diagnosis of MS from incidental MRI findings alone, without MS-relevant symptoms, is judged problematic a firm diagnosis of MS from incidental MRI findings alone, without MS-relevant symptoms, is judged problematic Quotation withheld because this record is not cleared for redistribution. `patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the CNS, current or historical, with duration of at least 24 hours, in the absence of fever or infection` attack (relapse, exacerbation) Quotation withheld because this record is not cleared for redistribution. a new T2 lesion `irrespective of the timing of the baseline MRI`, or enhancing and non-enhancing lesions together on one baseline scan - against the 2005 rule's reference scan `at least 30 days after the onset` DIT Quotation withheld because this record is not cleared for redistribution. the Panel `met for a third time` in Dublin in May 2010 revisions of the criteria Quotation withheld because this record is not cleared for redistribution. `in the absence of fever or infection` the minimum duration of an attack Quotation withheld because this record is not cleared for redistribution. `Abandoning the requirement for an extra reference MRI after 30 days does not compromise specificity` the waiting period abandoned Quotation withheld because this record is not cleared for redistribution. the abstract claims the revisions `preserve their diagnostic sensitivity and specificity`; the DIS change is `simpler and slightly more sensitive ... without compromising specificity and accuracy`; the DIT change `does not compromise specificity`. Every relaxation is licensed by the same pair of numbers, and none of them is reported for the criteria AS A WHOLE in this paper sensitivity and specificity as the currency of every revision Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1002/ana.22366.