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Updated criteria for diagnosing Multiple Sclerosis

Posted in Clinical Review Article on 18th Jan 2019

Peter Brex MB BS, MD, FRCP is a Consultant Neurologist at King’s College Hospital NHS Foundation Trust. He trained in London and was appointed to his current role in 2005. He specialises in multiple sclerosis, with a particular interest in early prognostic markers and the management of MS during pregnancy.



Victoria Williams has been a Consultant Neurologist since 2009. She is an MS specialist at Guy’s and St Thomas’ and King’s College Hospitals NHS Trusts.




Correspondence to: PA Brex, Department of Neurology, King’s College Hospital NHS Trust, Denmark Hill, SE5 9RS.
Conflict of interest statement: Dr Brex and Dr Williams have between them received honoraria from Biogen, MedDay pharmacuticals, Merck, Roche, Sanofi-Genzyme & Teva.
Provenance and peer review: Submitted and externally reviewed.
Date submitted: 1/4/18
Date submitted after peer review: 4/10/18
Acceptance date: 11/10/18
To cite: Brex P, Williams V. ACNR 2018;18(2):14-16.
Published online: 18/01/19

Key take home messages

  • The diagnostic criteria for MS have been recently updated
  • These criteria should only be applied to populations in whom MS is common and patients who present with typical symptoms for which no better explanation can be found
  •  All patients with suspected MS should have an MRI brain scan; spinal cord imaging is not mandatory
  • Unmatched oligoclonal bands in the CSF can be used as a substitute for demonstrating dissemination in time, allowing an earlier diagnosis than was previously possible


The fourth update of the McDonald criteria enables an earlier diagnosis of MS in people presenting with typical symptoms. It broadens MRI evidence for dissemination in space to include symptomatic and cortical lesions and allows dissemination in time to be demonstrated by unmatched oligoclonal bands in the CSF as well as by new or enhancing MRI lesions. To avoid misdiagnosis, it should be used with caution in patients with atypical symptoms or in populations in which MS is uncommon.

The history of diagnostic criteria for multiple sclerosis (MS)

Multiple Sclerosis (MS) became widely recognised after Jean-Martin Charcot (1825 – 1893) (Figure 1a) described it in his lectures in the late 18th century. Prior to this patients with MS would typically have been described as having a palsy, paralysis or paraplegia, without much understanding as to the cause.

In May 1960, a symposium on the ‘Evaluation of Drug Therapy in Neurologic and Sensory Diseases’ held at the University of Wisconsin concluded that criteria for MS were required to provide a common ground of terminology amongst investigators to facilitate therapeutic trials.

A committee of experts chaired by George Schumacher (1912 – 2008) was formed and published the Schumacher criteria in 1965.1   This enabled a diagnosis of definite MS in

  •   a typically aged individual (defined as between 10 and 50 years)
  • with a compatible history – attacks lasting at least 24 hours, separated by at least a month; or in the case of progressive MS, a slow or step-wise progression of disability over a period of at least six months
  • and objective clinical evidence of lesions in two or more distinct sites in the white matter of the central nervous system
  • with no more satisfactory explanation.

The Schumacher criteria were purely clinical, although investigations were encouraged (blood, urine, chest X-ray, CSF analysis) to exclude alternative conditions.

Over the next few years modifications to the Schumacher criteria were published2,3 but in 1983 the Schumacher criteria were replaced by criteria developed by a committee chaired by Charles Poser (1923 – 2010).4  The Poser criteria incorporated laboratory and clinical tests developed in the previous decade to support the diagnosis with ‘paraclinical evidence’ of lesions. This included evoked potentials, computed tomography (CT) or NMR scans (as MRI was known in its early days), as well as induced hyperthermia (the hot bath test) and expert urological assessment. The acceptable age of onset was extended to 10 to 59 years of age. The criteria emphasised that symptoms should be consistent with MS and the diagnosis made by a ‘competent neurologist’.

The criteria divided patients into two groups – ‘Definite’ and ‘Probable’ MS – each with two sub-groups – ‘Clinical’ and ‘Laboratory-supported’; the latter referring to the presence of oligoclonal bands or raised IgG in the CSF. Clinically Definite MS became the requirement for entry into therapeutic trials of the time and required two attacks and objective clinical evidence of two lesions; or two attacks with objective evidence of one lesion and paraclinical evidence of another separate lesion. Certain historical symptoms could be substituted for clinical evidence in some instances, e.g. Lhermitte’s phenomenon in the absence of cervical spondylosis; painful optic neuritis in an under 50-year-old, trigeminal neuralgia in an under 40-year-old.

In 2001, Poser’s criteria were replaced by McDonald’s criteria,5 developed by the International Panel on MS Diagnostics, chaired at their first meeting by Ian McDonald (1933 – 2006) (Figure 1b, below right).

These criteria placed a much greater emphasis on the use of MRI lesions (areas of T2 hyperintensity at least 3mm in cross-section) to demonstrate dissemination of disease in space and time. These criteria enabled a diagnosis of MS after a single clinical attack which allowed clinical trials to include patients at a much earlier stage than had previously been possible. Progressive MS, which had not been addressed by the Poser criteria, was defined in McDonald’s criteria and required the presence of oligoclonal bands or raised IgG index in the CSF supported by typical MRI findings +/- delayed visual evoked potentials (VEPs) and dissemination in time demonstrated either by progression of disability over a year or new MRI lesions.

The McDonald panel have subsequently met approximately every 5-years to refine and simplify the criteria.6,7  The number of lesions required to provide evidence of dissemination in space have been reduced and evidence of dissemination of disease in time may be obtained from a single MRI with both enhancing and non-enhancing lesions. The criteria for progressive MS were changed so that insidious neurological progression became the main requirement and oligoclonal bands or elevated IgG index in the CSF were no longer mandatory if there were typical MRI findings in the brain and spinal cord. The term ‘possible MS’ was added for people with a typical clinically isolated syndrome who did not meet the criteria.

The 2017 revisions to the McDonald criteria

Following meetings in November 2016 and May 2017 the fourth version of the McDonald criteria was published in Lancet Neurology in January 2018.8 This panel was expanded to include additional expertise in clinical, imaging and laboratory aspects of MS diagnosis, and to address criticisms that they were only applicable to European and North American populations, included a broader representation from different geographical regions. Changes to the diagnostic criteria were evidence-based and not just based on expert opinion.

The most significant change is the revitalisation of the role of CSF analysis. The finding of two 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 panel also stressed the importance of CSF in excluding MS mimics.

The MRI criteria for dissemination in space have also been changed. Cortical lesions can now be counted in place of juxtacortical ones when assessing for lesions in one of the four typical sites (the others sites are periventricular, brainstem or spinal cord lesion). However, cortical lesions are not well appreciated on currently available clinical MRI scans conducted outside of research and so this will not have a great impact on most clinicians.  The panel did not increase the number of periventricular lesions required, as was recommended in a 2016 MAGNIMS MRI criteria paper,9 but suggested this may be advisable in older patients and those at high risk of having white matter lesions, e.g. vascular risk factors, migraine. They did allow for the inclusion of symptomatic lesions when assessing for radiological evidence of dissemination in space – an exception being high signal in the optic nerves in people with optic neuritis.

As with the criteria that have predated it, the McDonald criteria do enable MS to be diagnosed without the need for any supporting investigations, but the panel recommended all patients in whom a diagnosis of MS was being considered should have an MRI brain. An MRI of the cord is not mandatory but advisable when signs localise to the cord, in progressive MS and in populations in whom MS is more unusual.

Whilst the sensitivity and specificity of the McDonald MRI criteria have been shown to be high when applied to patients with typically clinically isolated syndromes suggestive of MS,10 there have been a number of papers published demonstrating that they over-diagnose MS in a ‘real world’ setting.11-13 The McDonald criteria were not developed to diagnose MS in patients with atypical symptoms or to distinguish it from other conditions which can cause high signal in the white matter lesions on MRI, e.g. acute disseminated encephalitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), vascular disease, migraine and even normal ageing. Caution should be exercised in people outside the typical presenting age for MS (although MS can present in childhood and in individuals over 60 years) and in ethnic groups in whom MS is uncommon. The benefits of expert neuro-radiological input cannot be over-emphasised.

A diagnosis of multiple sclerosis should never be made based on MRI appearances alone, although some patients with these so-called Radiologically Isolated Syndromes will develop typical symptoms of MS in time14 and may require counselling and follow-up.

Application of the 2017 revised McDonald criteria in patients with typical clinically isolated syndromes followed up for five years has been demonstrated to have greater sensitivity but less specificity for a second attack than the 2010 criteria with similar accuracy. 15 This means it will diagnose more patients with less active MS.

In conclusion, the McDonald Criteria are helpful in providing an accurate and earlier diagnosis of MS in patients following a single attack with typical symptoms, however when the presentation is atypical, or in populations in which MS is uncommon, investigation should be extended beyond MRI, with a low threshold for further investigation, particularly examination of the CSF.


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