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Updated Criteria for Diagnosing Multiple Sclerosis

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Updated Criteria for Diagnosing Multiple Sclerosis r e v i e w a r t i c l e Updated criteria for diagnosing Multiple Sclerosis or in the case of progressive MS, a slow or step- Key take home messages wise progression of disability over a period of • The diagnostic criteria for MS have at least six months been recently updated • and objective clinical evidence of lesions in • These criteria should only be applied two or more distinct sites in the white matter to populations in whom MS is of the central nervous system common and patients who present • with no more satisfactory explanation. Peter Brex with typical symptoms for which no The Schumacher criteria were purely clinical, MB BS, MD, FRCP is a Consultant Neurologist at King’s College Hospital better explanation can be found although investigations were encouraged (blood, NHS Foundation Trust. He trained in • All patients with suspected MS should urine, chest X-ray, CSF analysis) to exclude London and was appointed to his current have an MRI brain scan; spinal cord alternative conditions. role in 2005. He specialises in multiple imaging is not mandatory Over the next few years modifications to the sclerosis, with a particular interest in early 2,3 prognostic markers and the management • Unmatched oligoclonal bands in the Schumacher criteria were published but in 1983 of MS during pregnancy. CSF can be used as a substitute for the Schumacher criteria were replaced by criteria demonstrating dissemination in time, developed by a committee chaired by Charles allowing an earlier diagnosis than was Poser (1923 – 2010).4 The Poser criteria incorpor- previously possible ated laboratory and clinical tests developed in the previous decade to support the diagnosis with ‘paraclinical evidence’ of lesions. This included Abstract evoked potentials, computed tomography (CT) The fourth update of the McDonald criteria or NMR scans (as MRI was known in its early enables an earlier diagnosis of MS in people days), as well as induced hyperthermia (the hot presenting with typical symptoms. It broadens bath test) and expert urological assessment. The Victoria Williams MRI evidence for dissemination in space to acceptable age of onset was extended to 10 to has been a Consultant Neurologist since include symptomatic and cortical lesions and 59 years of age. The criteria emphasised that 2009. She is an MS specialist at Guy's and allows dissemination in time to be demonstrated symptoms should be consistent with MS and the St Thomas' and King's College Hospitals by unmatched oligoclonal bands in the CSF diagnosis made by a ‘competent neurologist’. NHS Trusts. as well as by new or enhancing MRI lesions. The criteria divided patients into two groups Correspondence to: To avoid misdiagnosis, it should be used with – ‘Definite’ and ‘Probable’ MS – each with PA Brex, caution in patients with atypical symptoms or in two sub-groups – ‘Clinical’ and ‘Laboratory- Department of Neurology, populations in which MS is uncommon. supported’; the latter referring to the presence King’s College Hospital NHS Trust, Denmark Hill, of oligoclonal bands or raised IgG in the CSF. London The history of diagnostic criteria for Clinically Definite MS became the requirement SE5 9RS. multiple sclerosis (MS) for entry into therapeutic trials of the time and Conflict of interest statement: Dr Brex Multiple Sclerosis (MS) became widely required two attacks and objective clinical and Dr Williams have between them recognised after Jean-Martin Charcot (1825 – evidence of two lesions; or two attacks with received honoraria from Biogen, MedDay 1893) (Figure 1a) described it in his lectures in objective evidence of one lesion and paraclinical pharmacuticals, Merck, Roche, Sanofi- Genzyme & Teva. the late 18th century. Prior to this patients with MS evidence of another separate lesion. Certain would typically have been described as having historical symptoms could be substituted for clin- Provenance and peer review: Submitted a palsy, paralysis or paraplegia, without much ical evidence in some instances, e.g. Lhermitte’s and externally reviewed. understanding as to the cause. phenomenon in the absence of cervical spondyl- Date submitted: 1/4/18 In May 1960, a symposium on the ‘Evaluation osis; painful optic neuritis in an under 50-year-old, Date submitted after peer review: 4/10/18 of Drug Therapy in Neurologic and Sensory trigeminal neuralgia in an under 40-year-old. Acceptance date: 11/10/18 Diseases’ held at the University of Wisconsin In 2001, Poser’s criteria were replaced by To cite: Brex P, Williams V. concluded that criteria for MS were required McDonald’s criteria,5 developed by the ACNR 2018;18(2):14-16. to provide a common ground of terminology International Panel on MS Diagnostics, chaired amongst investigators to facilitate therapeutic at their first meeting by Ian McDonald (1933 – trials. 2006) (Figure 1b). These criteria placed a much A committee of experts chaired by George greater emphasis on the use of MRI lesions (areas Schumacher (1912 – 2008) was formed and of T2 hyperintensity at least 3mm in cross-sec- published the Schumacher criteria in 1965.1 This tion) to demonstrate dissemination of disease enabled a diagnosis of definite MS in in space and time. These criteria enabled a • a typically aged individual (defined as diagnosis of MS after a single clinical attack between 10 and 50 years) which allowed clinical trials to include patients • with a compatible history – attacks lasting at at a much earlier stage than had previously been least 24 hours, separated by at least a month; possible. Progressive MS, which had not been 14 > ACNR > VOLUME 18 NUMBER 2 > NOVEMBER-JANUARY 2019 r e v i e w a r t i c l e regions. Changes to the diagnostic criteria were evidence-based and not just based on expert opinion. The most significant change is the revital- isation of the role of CSF analysis. The finding or tfo or more oligoclonal bands was found to be more reliable than a raised IgG index and their presence has been shown to have high predictive value for conversion from clinically isolated syndromes to MS. The panel agreed the presence of unmatched oligoclonal bands in the CSF could confirm dissemination in time in place of clinical or MRI evidence. The Figure 1b: panel also stressed the importance of CSF in Ian McDonald (1933 – 2006) excluding MS mimics. Image courtesy The MRI criteria for dissemination in space of Queen Square have also been changed. Cortical lesions can Figure 1a: Jean-Martin Charcot (1825 – 1893). Archive. now be counted in place of juxtacortical ones when assessing for lesions in one of the four typical sites (the others sites are periv- Table 1. New diagnostic criteria for RR MS8 entricular, brainstem or spinal cord lesion). Number Number of lesions Additional evidence required However, cortical lesions are not well appreci- of clinical with objective ated on currently available clinical MRI scans attacks* clinical evidence conducted outside of research and so this will ≥ 2 ≥ 2 None not have a great impact on most clinicians. The panel did not increase the number of ≥ 2 1 plus good historical None evidence periventricular lesions required, as was recom- mended in a 2016 MAGNIMS MRI criteria ≥ 2 1 Dissemination in space by a further clinical episode at paper,9 but suggested this may be advisable in another site or by MRI older patients and those at high risk of having 1 ≥ 2 Dissemination in time by a further clinical episode, by MRI white matter lesions, e.g. vascular risk factors, or the presence of CSF oligoclonal bands migraine. They did allow for the inclusion of 1 1 Dissemination in space by a further clinical episode at symptomatic lesions when assessing for radio- another site or by MRI logical evidence of dissemination in space – an exception being high signal in the optic AND nerves in people with optic neuritis. Dissemination in time by a further clinical episode, by MRI As with the criteria that have predated it, the or the presence of CSF oligoclonal bands McDonald criteria do enable MS to be diagnosed without the need for any supporting investiga- *attacks should be separated by at least 30 days between onset tions, but the panel recommended all patients in whom a diagnosis of MS was being considered simplify the criteria.6,7 The number of lesions should have an MRI brain. An MRI of the cord is 8 Table 2. New diagnostic criteria for PP MS required to provide evidence of dissemination not mandatory but advisable when signs localise 1 year of disability progression (retrospectively in space have been reduced and evidence to the cord, in progressive MS and in populations or prospectively determined) independent of of dissemination of disease in time may be in whom MS is more unusual. clinical relapse. obtained from a single MRI with both enhan- Whilst the sensitivity and specificity of the cing and non-enhancing lesions. The criteria McDonald MRI criteria have been shown to be Plus two of the following criteria: for progressive MS were changed so that high when applied to patients with typically • One or more T2-hyperintense lesions insidious neurological progression became clinically isolated syndromes suggestive of characteristic of multiple sclerosis in one the main requirement and oligoclonal bands MS,10 there have been a number of papers or more of the following brain regions: or elevated IgG index in the CSF were no published demonstrating that they over-diag- periventricular, cortical or juxtacortical, or longer mandatory if there were typical MRI nose MS in a ‘real world’ setting.11-13 The infratentorial findings in the brain and spinal cord. The term McDonald criteria were not developed to • Two or more T2-hyperintense lesions in ‘possible MS’ was added for people with a diagnose MS in patients with atypical symp- the spinal cord typical clinically isolated syndrome who did toms or to distinguish it from other conditions not meet the criteria.
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