Elsevier

The Lancet Neurology

Volume 5, Issue 10, October 2006, Pages 841-852
The Lancet Neurology

Review
MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation”

https://doi.org/10.1016/S1474-4422(06)70572-5Get rights and content

Summary

Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features “not suggestive” of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of “no better explanation”, and inform future diagnostic criteria for multiple sclerosis.

Introduction

A diagnosis of multiple sclerosis is based on showing disease dissemination in space and time and excluding other neurological disorders that can clinically and radiologically mimic multiple sclerosis. Although the international scientific community has made a substantial effort to establish firm criteria to define what constitutes disease dissemination in space,1, 2, 3, 4, 5, 6 not as much has been done to define a corresponding set of “exclusion” criteria.

Given the increased availability of MRI scanners and the sensitivity of this technique in showing asymptomatic lesions of multiple sclerosis, recent consensus criteria for the diagnosis of the disorder4, 6 have defined a set of MRI criteria to complement clinical and other paraclinical data to fulfil disease dissemination in space and time in patients suspected of having multiple sclerosis. These criteria have been successfully applied in clinical practice and have a high specificity for the subsequent development of clinically defined multiple sclerosis1 in patients who present with a well characterised first clinical episode (eg, unilateral optic neuritis) suggestive of disease onset.7, 8 In a recent study,9 MRI criteria for disease dissemination in space was characterised by a good specificity (89%) when applied to patients with a subsequently confirmed diagnosis of other neurological disorders. Nevertheless, the common and incidental presence of non-specific white-matter abnormalities on MRI scans and the large number of disorders (in addition to multiple sclerosis) that are associated with such abnormalities continue to pose diagnostic difficulties that may not be reliably resolved by the application of existing MRI criteria. In this context, the presence of MRI features that are not suggestive of multiple sclerosis—or indeed suggestive of a different disorder—might also contribute substantially to the work-up of patients suspected of having multiple sclerosis. The presently available diagnostic criteria for multiple sclerosis do not consider this additional potential of MRI. Avoiding misdiagnoses is particularly compelling now that there are partially effective treatments for multiple sclerosis as well as different therapies for other disorders that can mimic multiple sclerosis.

Against this background, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held in Amsterdam in January 2005. The aim of the workshop was not to review all the possible disorders that can enter a differential diagnosis with multiple sclerosis, but rather to define a set of MRI red flags, derived from evidence-based findings and educated guesses. These MRI signs should alert clinicians and lead them to extensively assess patients with such MRI abnormalities, which is typically not done routinely. For example, T1-hypointense lesions in the spinal cord more than three vertebral segments in length should prompt the search for serum autoantibodies of neuromyelitis optica, and the preferential involvement of the external capsules and temporal poles should initiate genetic testing for cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Such MRI red flags (ie, features atypical for multiple sclerosis but instead suggestive of an alternative diagnosis) are summarised in the table in a way that resembles everyday clinical practice, which indicates the everyday clinical practice more closely than a disease-centred approach. For a more systematic approach, we will discuss the MRI red flags in the context of those diseases that can mimic multiple sclerosis to give a more complete clinical and paraclinical background. We will only discuss disorders in which MRI can give important diagnostic hints. We will not consider disorders in which clinical presentation is highly suggestive of an alternative specific diagnosis (eg, neurological syndromes in the context of head trauma, chronic alcoholism, or carbon monoxide intoxication). Although the incidence of the various differential diagnostic possibilities represents an additional guidance to the clinician, this issue is beyond the scope of this review because the relative risks for the different diagnostic possibilities vary widely according to local or individual factors (eg, geographic location, patient demographics, genetic background, type of clinical presentation, overall neurological and laboratory picture). When translating the present contribution into clinical practice one should always consider that small-vessel disease is much more common than multiple sclerosis. By contrast, multiple sclerosis is more common than any type of vasculitis, which in turn have a higher incidence than the disorders discussed under the heading of Other disorders, with the exception of sarcoidosis.

In this review we will report on the conclusions of this international consensus and discuss additional pieces of information presented in the time elapsed between the workshop and the final drafting of this review, which should represent a first step beyond the concept of “no better explanation” and inform future diagnostic criteria for multiple sclerosis.

Section snippets

Variants of multiple sclerosis

The variants of multiple sclerosis include neuromyelitis optica, Balo's concentric sclerosis, acute multiple sclerosis (Marburg type), Schilder's disease, and tumefactive demyelinating lesions (diagnosed at biopsy), which overlap substantially with multiple sclerosis by clinical, laboratory, and imaging measures.10 As a result, diagnostic uncertainty is typical and misdiagnosis can occur; the latter is increasingly important because optimal treatment for neuromyelitis optica in particular can

General considerations

An important, and the most common, differential diagnosis of white-matter lesions in patients suspected of having multiple sclerosis is the possibility that these lesions can also be caused by hypoxic-ischaemic cerebral small-vessel disorders, which are usually asymptomatic but can also present with migraine, transient ischaemic attacks, stroke, or subcortical arteriosclerotic encephalopathy.

The prevalence of multiple sclerosis is 1 per 1000 people, whereas MRI white-matter lesions attributable

Meningitis

The most characteristic feature of meningitis on MRI is meningeal enhancement after injection of a contrast agent. Although meningeal inflammation has been recently reported in a neuropathological study of multiple sclerosis,73 only one patient with multiple sclerosis has been described with meningeal enhancement,74 and the presence of such enhancement for practical purposes excludes a diagnosis of multiple sclerosis or implies double pathology.

There is sometimes parenchymal involvement in

Adult forms of leucoencephalopathies

Classical leucodystrophies, such as adrenoleucodystrophy, metachromatic leucodystrophy, and Krabbe disease can have adult onset. These patients may not show a classical presentation of the disease and can have variable neurological involvement and MRI patterns, sometimes very close to those seen in multiple sclerosis.89 In all these cases, however, white-matter lesions tend to be bilateral and symmetric, which is an important feature against the diagnosis of multiple sclerosis.40, 90 Other,

Additional considerations

Although none of the following additional considerations constitute a definitive diagnostic finding, the lack of these additional features of multiple sclerosis should also alert the clinician.

Conclusions

There has been a major effort in the past few decades to develop and implement criteria to demonstrate disease dissemination in space and time in multiple sclerosis.1, 4, 6 However, although such criteria do recognise the importance of careful exclusion of other disorders that can mimic multiple sclerosis, there has been no detailed attention to how this might be done. Findings from clinical history, physical examination, MRI, and other laboratory tests are usually combined to establish a firm

Search strategy and selection criteria

Data for this review were identified by searches of MEDLINE, Current Contents, and references from relevant articles. The search terms “multiple sclerosis”, “diagnosis” and “magnetic-resonance imaging” were used. The final search strategy was done in June 2006. Only papers published in English were reviewed. The final reference list was generated based on the originality and relevance to the topics covered in the review.

References (104)

  • M Tintoré et al.

    Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis

    AJNR Am J Neuroradiol

    (2000)
  • WI McDonald et al.

    Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis

    Ann Neurol

    (2001)
  • CM Dalton et al.

    New T2 lesions enable an earlier diagnosis of multiple sclerosis in clinically isolated syndromes

    Ann Neurol

    (2003)
  • CH Polman et al.

    Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”

    Ann Neurol

    (2005)
  • CM Dalton et al.

    Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis

    Ann Neurol

    (2002)
  • M Tintoré et al.

    New diagnostic criteria for multiple sclerosis: application in first demyelinating episode

    Neurology

    (2003)
  • JM Nielsen et al.

    Overdiagnosis of multiple sclerosis and magnetic resonance criteria

    Ann Neurol

    (2005)
  • JH Simon et al.

    Variants of Multiple Sclerosis

  • DA Wingerchuk et al.

    Revised diagnostic criteria for neuromyelitis optica

    Neurology

    (2006)
  • BA Cree et al.

    An open label study of the effects of rituximab in neuromyelitis optica

    Neurology

    (2005)
  • RN Mandler et al.

    Devic's neuromyelitis optica: a clinicopathological study of 8 patients

    Ann Neurol

    (1993)
  • JI O'Riordan et al.

    Clinical, CSF, and MRI findings in Devic's neuromyelitis optica

    J Neurol Neurosurg Psychiatry

    (1996)
  • M Filippi et al.

    MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic's neuromyelitis optica

    Neurology

    (1999)
  • DM Wingerchuk et al.

    The clinical course of neuromyelitis optica (Devic's syndrome)

    Neurology

    (1999)
  • A Ghezzi et al.

    Clinical characteristics, course and prognosis of relapsing Devic's Neuromyelitis Optica

    J Neurol

    (2004)
  • SJ Pittock et al.

    Brain abnormalities in neuromyelitis optica

    Arch Neurol

    (2006)
  • MA Rocca et al.

    Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica

    Neurology

    (2004)
  • DL Yao et al.

    Concentric sclerosis (Balo): morphometric and in situ hybridization study of lesions in six patients

    Ann Neurol

    (1994)
  • JJ Kepes

    Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients

    Ann Neurol

    (1993)
  • E Capello et al.

    Marburg type and Balo's concentric sclerosis: rare and acute variants of multiple sclerosis

    Neurol Sci

    (2004)
  • T Menge et al.

    Acute disseminated encephalomyelitis: an update

    Arch Neurol

    (2005)
  • RC Dale et al.

    Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children

    Brain

    (2000)
  • JL Hynson et al.

    Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children

    Neurology

    (2001)
  • RC Dale et al.

    Acute disseminated encephalomyelitis or multiple sclerosis: can the initial presentation help in establishing a correct diagnosis?

    Arch Dis Child

    (2005)
  • S Schwarz et al.

    Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients

    Neurology

    (2001)
  • S Tenembaum et al.

    Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients

    Neurology

    (2002)
  • J Kesselring et al.

    Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis

    Brain

    (1990)
  • T Seifert et al.

    Relapsing acute transverse myelitis: a specific entity

    Eur J Neurol

    (2005)
  • Proposed diagnostic criteria and nosology of acute transverse myelitis

    Neurology

    (2002)
  • F Fazekas et al.

    The spectrum of age-associated brain abnormalities: their measurement and histopathological correlates

    J Neural Transm Suppl

    (1998)
  • N Badjatia et al.

    Intracerebral hemorrhage

    Neurologist

    (2005)
  • M Dichgans et al.

    Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study

    Stroke

    (2002)
  • F Barkhof et al.

    Imaging of white matter lesions

    Cerebrovasc Dis

    (2002)
  • C Enzinger et al.

    Lesion probability maps of white matter hyperintensities in elderly individuals: results of the Austrian stroke prevention study

    J Neurol

    (2006)
  • VI Kwa et al.

    T2-weighted hyperintense MRI lesions in the pons in patients with atherosclerosis. Amsterdam Vascular Medicine Group

    Stroke

    (1997)
  • A Joutel et al.

    Notch3 mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a mendelian condition causing stroke and vascular dementia

    Ann N Y Acad Sci

    (1997)
  • M O'Sullivan et al.

    MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL

    Neurology

    (2001)
  • H Chabriat et al.

    CADASIL. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

    Adv Neurol

    (2003)
  • S Singhal et al.

    The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features

    AJNR Am J Neuroradiol

    (2005)
  • R Diaz-Arrastia

    Homocysteine and neurologic disease

    Arch Neurol

    (2000)
  • Cited by (198)

    • Imaging characteristics of neuroimmunological disorders

      2023, Translational Neuroimmunology: Neuroinflammation: Volume 7
    View all citing articles on Scopus
    View full text