In preparation for the meetings, the Panel conducted literature searches (completed April 15, 2017) in PubMed (English language, using search terms “multiple sclerosis” and “diagnosis” with a focus on publications since 2010 but also including earlier publications as appropriate). It reviewed papers on topics including, but not limited to: the role in diagnosis of MRI, optical coherence tomography, evoked potentials, and CSF analysis; diagnosis in diverse populations (paediatric, Asian, and
Position PaperDiagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria
Introduction
Diagnostic criteria for multiple sclerosis combining clinical, imaging, and laboratory evidence have evolved over time, with the most recent being the 2010 McDonald criteria from the International Panel on Diagnosis of Multiple Sclerosis (referred to as the Panel from here on).1, 2, 3, 4, 5 The increasing incorporation of paraclinical assessments, especially imaging, to supplement clinical findings has allowed earlier, more sensitive, and more specific diagnosis.6 New data, emerging technology, and evolving consensus necessitate a periodic re-examination of diagnostic criteria and their usefulness. The Panel reconvened under the auspices of the International Advisory Committee on Clinical Trials in Multiple Sclerosis (sponsored by the US National Multiple Sclerosis Society and the European Committee for Treatment and Research in Multiple Sclerosis) for two meetings (Nov 2–5, 2016, in Philadelphia, PA, USA, and May 20–21, 2017, in Berlin, Germany). In this Position Paper, we discuss issues related to misdiagnosis, differential diagnosis, and appropriate application of the McDonald criteria, with a particular emphasis on diagnosis in diverse populations and in patients with atypical presentations. With the 2017 McDonald criteria, we present recommendations concerning the diagnostic process for multiple sclerosis, make specific revisions to the 2010 McDonald criteria, and outline research that should be done to inform future refinements of the criteria.
Section snippets
Rationale and methods for the 2017 revisions
The Panel meetings to consider revisions to the 2010 McDonald criteria were motivated by new data in several areas: the performance of the 2010 McDonald criteria in diverse populations; the distinction between multiple sclerosis and other diseases with potentially overlapping clinical and imaging features, such as neuromyelitis optica spectrum disorders (NMOSDs); challenges in making the diagnosis in individuals with presentations other than a typical clinically isolated syndrome; the frequency
Misdiagnosis and differential diagnosis
Before considering potential revisions of the 2010 McDonald criteria, the Panel reviewed issues related to the diagnosis of multiple sclerosis, appropriate use of the McDonald criteria, and performance of the criteria across patient populations.
Misdiagnosis of multiple sclerosis remains an issue in clinical practice,15, 16, 17, 18 and the Panel identified several factors that potentially increase this risk. Multiple sclerosis has heterogeneous clinical and imaging manifestations, which differ
Role of MRI in diagnosis of multiple sclerosis
MRI has been increasingly used to support the diagnosis of multiple sclerosis and to look for atypical radiological features arguing against this diagnosis. MAGNIMS and the Consortium of Multiple Sclerosis Centers recently proposed standardised MRI protocols for the diagnostic process, to determine prognosis, and for follow-up.14, 59, 60 Brain and spinal cord MRI remain the most useful paraclinical tests to aid the diagnosis of multiple sclerosis and can substitute for clinical findings in the
Role of CSF examination in diagnosis of multiple sclerosis
Although CSF examination has been de-emphasised in successive iterations of the McDonald criteria, it remains a valuable diagnostic test.61 In the appropriate clinical setting, evidence of intrathecal antibody synthesis, although not specific for multiple sclerosis, supports the diagnosis.62 Conversely, CSF findings atypical of multiple sclerosis (eg, an elevated protein concentration of >100 mg/dL, pleocytosis with >50 cells per mm3, or the presence of neutrophils, eosinophils, or atypical
CSF oligoclonal bands
Numerous studies65, 66, 67, 68, 69, 70, 71, 72, 73 have provided evidence that, in adult patients with a clinically isolated syndrome, CSF oligoclonal bands are an independent predictor of the risk of a second attack when controlling for demographic, clinical, treatment, and MRI variables. After considering these data, the Panel recommended that with a typical clinically isolated syndrome, fulfilment of clinical or MRI criteria for DIS, and no better explanation for the clinical presentation,
Number of periventricular lesions
The 20013 and 20054 McDonald criteria required three or more periventricular lesions as one of the anatomical locations that could fulfil MRI criteria for DIS. In the 2010 McDonald criteria,5 this requirement was changed to one or more periventricular lesions as one of the four anatomical locations (periventricular, juxtacortical, and infratentorial brain regions, and the spinal cord). However, non-specific white matter lesions are common in older individuals and in those with vascular risk
Conclusions
Early diagnostic criteria for multiple sclerosis were based primarily on clinical evidence.1 Subsequent criteria incorporated imaging and other paraclinical markers in response to technological advances and new data.2, 3, 4, 5 The 2017 revisions to the well established 2010 McDonald criteria revitalise the role of CSF analysis, reconsider the value of imaging findings previously not included (symptomatic and cortical lesions), and articulate more clearly cautions about misdiagnosis and
Search strategy and selection criteria
References (99)
- et al.
MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines
Lancet Neurol
(2016) - et al.
Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis
Lancet Neurol
(2005) - et al.
MRI mimics of multiple sclerosis
Handb Clin Neurol
(2014) Misdiagnosis of multiple sclerosis and β-interferon
Lancet
(1997)- et al.
MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation”
Lancet Neurol
(2006) - et al.
Comparison of the 2010 and 2005 versions of the McDonald MRI criteria for dissemination-in-time in Taiwanese patients with classic multiple sclerosis
J Neurol Sci
(2013) - et al.
Use of the 2010 McDonald criteria can facilitate early diagnosis in pediatric multiple sclerosis in a predominantly black cohort
Pediatr Neurol
(2014) - et al.
A serum antibody marker of neuromyelitis optica: distinction from multiple sclerosis
Lancet
(2004) - et al.
Treatment of neuromyelitis optica: review and recommendations
Mult Scler Relat Disord
(2012) - et al.
Prevalence of cerebrospinal fluid oligoclonal IgG bands in Greek patients with clinically isolated syndrome and multiple sclerosis
Clin Neurol Neurosurg
(2013)
Gray matter pathology in multiple sclerosis
Lancet Neurol
Evaluation of quality of life and fatigue in radiologically isolated syndrome
Rev Neurol (Paris)
Problems of experimental trials of therapy in multiple sclerosis: report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis
Ann NY Acad Sci
New diagnostic criteria for multiple sclerosis: guidelines for research protocols
Ann Neurol
Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis
Ann Neurol
Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”
Ann Neurol
Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald Criteria
Ann Neurol
Multiple Sclerosis 1. Diagnosis of multiple sclerosis: progress and challenges
Lancet
Differential diagnosis of suspected multiple sclerosis: a consensus approach
Mult Scler
Defining the clinical course of multiple sclerosis: the 2013 revisions
Neurology
Intracortical lesions. Relevance for new MRI diagnostic criteria for multiple sclerosis
Neurology
Diagnosis of multiple sclerosis: a multicentre study to compare revised McDonald-2010 and Filippi-2010 criteria
J Neurol Neurosurg Psychiatry
MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—clinical implementation in the diagnostic process
Nat Rev Neurol
Characteristics of patients found not to have multiple sclerosis
Can Med Assoc J
Initial evaluations for multiple sclerosis in a university multiple sclerosis center
Arch Neurol
The contemporary spectrum of multiple sclerosis misdiagnosis: a multicenter study
Neurology
The tension between early diagnosis and misdiagnosis in multiple sclerosis
Nat Rev Neurol
Multiple sclerosis. The problem of incorrect diagnosis
Arch Neurol
Application and a proposed modification of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Canadian cohort of patients with clinically isolated syndromes
Mult Scler J
Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study
J Neurol
Application of the 2010 revised criteria for the diagnosis of multiple sclerosis to patients with clinically isolated syndromes
Eur J Neurol
Application of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Spanish cohort of patients with clinicaly isolated syndromes
Mult Scler J
Revised McDonald criteria for multiple sclerosis diagnostics in central Russia: sensitivity and specificity
Mult Scler J
Evaluation of McDonald MRI criteria for dissemination in space in Korean patients with clinically isolated syndromes
Mult Scler J
Multiple sclerosis in Japan appears to be a milder disease compared to the UK
J Neurol
Predictors of conversion to multiple sclerosis in patients with clinically isolated syndrome using the 2010 revised McDonald criteria
ISRN Neurol
Consensus guidelines for the diagnosis and treatment of multiple sclerosis
Curr Med Res Opin
Application of the McDonald 2010 criteria for the diagnosis of multiple sclerosis in an Argentinean cohort of patients with clinically isolated syndromes
Mult Scler J
Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI
Arq Neuropsiquiatr
Evaluation of the 2010 McDonald multiple sclerosis criteria in children with a clinically isolated syndrome
Mult Scler J
2010 McDonald Criteria for diagnosing pediatric multiple sclerosis
Ann Neurol
Paediatric multiple sclerosis: examining utility of the McDonald 2010 criteria
Mult Scler J
2010 McDonald criteria in a pediatric cohort: is positivity at onset associated with a more aggressive multiple sclerosis course?
Mult Scler J
Predicting multiple sclerosis following isolated optic neuritis in children
Eur J Neurol
Pediatric onset multiple sclerosis: McDonald criteria 2010 and the contribution of spinal cord MRI
Mult Scler J
Risk of multiple sclerosis after a first demyelinating syndrome in an Australian paediatric cohort: clinical, radiological features and application of the McDonald 2010 MRI criteria
Mult Scler J
Acute disseminated encephalomyelitis. Updates on an inflammatory CNS syndrome
Neurology
International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions
Mult Scler J
Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis
Arch Neurol
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