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The role of MRI in the diagnosis of Multiple Sclerosis

LH is a 34 yo female with a history of relapsing remitting MS presents to the multiple sclerosis clinic for MRI follow up of disease progression.

Brice Gaudilliere, PhD (Harvard Medical School year IV)

Gillian Lieberman, MD

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–Briefly review the pathogenesis of multiple sclerosis (MS).

–Introduce the McDonald's MRI criteria for diagnosis of MS.

–Describe the typical MRI findings and disease- progression of MS.

–Discuss limits and future prospects of MRI diagnosis of MS.

Objectives

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Multiple Sclerosis1868: Jean-Martin Charcot describes the “Sclérose en Plaque” as a new disease linking clinical and postmortem findings.

MRI Pathology Luxol Fast BlueN Engl J Med. 2000 Sep 28;343(13):938-52.

4Pathogenesis of MS

Extravasating T-cells

Demyelination

N Engl J Med. 2006 Mar 2;354(9):942-55

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Disease Patterns • Relapsing remitting (RRMS)

• Secondary progressive: initial RRMS then progression.

• Primary progressive: Progression from onset with occasional plateau.

• Progressive relapsing: Progression from onset with acute relapse.

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Diagnostic criteria for MS

• POSER criteria (1980s)

Two attacks + Two separate clinical lesions=

Clinically definite MS

Two attacks + one clinical lesion + Labs findings (CSF,OCB, IgG) =

Laboratory definite MS

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Diagnostic criteria for MS• McDonald’s criteria (2001 and 2005)

• Demonstrate dissemination of clinical events in space and time.

• Demonstrate dissemination of MRI findings in space and time.

• Assigns confidence for MS vs Possible MS vs. Not MS based on clinical and MRI findings

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MRI modality of choice for MS• Conventional MRI is the most sensitive way to detect

MS lesions.

• Typical MRI lesions correlate well with histopathology: Found in periventricular region, corpus callosum, subcortical region, brainstem, optic nerve and visual pathways.

• Lesions usually not seen on CT.

• Use of contrast allows early detection of acute lesions.

• Specificity 90%, sensitivity 80%, ppv 65%. (<50yo)

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Ant. Horn of lateral ventricules

Head of Caudate nucleus

ThalamusPutamen

Ant. And post.Limb of internalcapsule

Genu of Corpus Callosum

Visual Cortex

Neuroanatomy

http://www.imaios.com/en/e-Anatomy/Brain-neuroanatomy-MR

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companion patient 1: MS lesions on MRI

N Engl J Med. 2000 Sep 28;343(13):938-52.

Hypointense lesions on T1WI Hyperintense lesions on T2WI

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Companion patient 2: Fluid attenuated Inversion Recovery (vFLAIR) allows for better visualization

of periventricular lesionsHyperintense lesions on T2WI Hyperintense lesions on T2 FLAIR

AJNR Am J Neuroradiol 2006; 27: 1165–76.

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DDx of white matter lesion

• Ischemia• Systemic lupus

erythematosus• HTLV-I• Sarcoidosis• Behcet's disease• Vasculitides

Companion patient 3: axial FLAIR

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Specific MRI findings to narrow the differential

• Review specific lesions found in MS.

• Apply McDonald’s criteria for dissemination in space and time.

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Classical MS lesions: Dawson’s fingers (Patient LH)

Sagital FLAIR (PACS, BIDMC) Axial FLAIR (PACS, BIDMC)

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Classical MS lesions : Black holes (patient LH)

T2 (PACS, BIDMC) T1 (PACS, BIDMC)

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McDonald’s MRI criteria: Three of the following are required:

At least one gadolinium-enhancing lesion or nine T2 hyperintense lesions

• At least one infratentorial lesion• At least one juxtacortical lesion• At least three periventricular lesions

Dissemination in Space

Polman CH et al. Ann Neurol. 20 Dec; 58(6): 840-6.

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Dissemination in space (Patient LH)

Sagital FLAIR (PACS, BIDMC) Sagital T2 (PACS, BIDMC)

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Detection of gadolinium enhancement at least 3 months after the onset of the initial clinical event.

Detection of a new T2 lesion

Dissemination in Time:

Polman CH et al. Ann Neurol. 20 Dec; 58(6): 840-6.

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Detection of recent MS lesions • Acute MS lesions disrupt the Blood Brain

Barrier.

• Can be seen as Gadolinium-enhancing lesions on T1-Post.

• Remain for days to months

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Detection of recent MS lesions: T1 post-contrast (Patient LH)

05/10/08 05/10/08

(PACS, BIDMC) (PACS, BIDMC)

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Dissemination in time (Patient LH)

Sagital T2 (PACS, BIDMC)

AXIALFLAIR (PACS, BIDMC)

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Limitation of traditional MRI• Many lesions seen on histopathology are missed

on MRI.

• Conversely the number and size of lesions seen is dependent on field strength and amount of contrast given.

• Although useful in following the disease, poor correlation between T1, T2, T1-post findings and clinical evolution.

AJNR Am J Neuroradiol 1998; 19: 1489-93

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Companion patient 7: Volumetric analysis

• New uses of conventional MRI: subtraction measures for disease follow up.

AJNR Am J Neuroradiol 2008; 29: 340–46.

Companion patient 7:Axial FLAIR

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Companion patient 8: Volumetric analysis

• Measures of diffuse cortical atrophy, some evidence correlating grey matter atrophy and functional impairment

Lancet Neurol 2006; 5: 158–70. Companion patient 8

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Companion patient 9: Diffuse Tensor imaging

• Diffusion MRI allowing reconstruction of axonal tracts and may provide correlation between circuitry damage and functional impairment.

NeuroImage 2005;26: 258–65.

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Acknowledgments

• Rafeeque Bhadelia, MD• Rich Rana, MD• Maria Levantakis• Larry Barbaras• Gillian Liberman, MD

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Reference• Noseworthy JH et al. N Engl J Med. 2000 Sep 28;343(13):938-52. • Frohman EM et al. N Engl J Med. 2006 Mar 2;354(9):942-55. • Islam T et al. Neurology. 2007 Jul 24;69(4):381-8.• Ge Y., AJNR Am J Neuroradiol 2006; 27: 1165–76.• Offenbacher H et al. Neurology 1993 May;43(5):905-9. • Bakshi R et al. Lancet Neurol. 2008 Jul;7(7):615-25. • Polman CH et al. Ann Neurol. 20 Dec; 58(6): 840-6.• Geurts JG et al. Lancet Neurol. 2008 Sep;7(9):841-51.• Pagani E et al. NeuroImage 2005;26: 258–65.• Duan Y et al. AJNR Am J Neuroradiol 2008; 29: 340–46• http://www.imaios.com/en/e-Anatomy/Brain-neuroanatomy-MR• http://www.nationalmssociety.org