Multiple Sclerosis and the McDonald Diagnostic Criteria:

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 A Focused Review with Clinicoradiologic Correlation

Abstract

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disorder of the central nervous system characterized by multifocal inflammation, demyelination, and axonal injury. The McDonald diagnostic criteria integrate clinical, radiologic, and laboratory findings to facilitate early diagnosis and treatment initiation. Magnetic resonance imaging (MRI) plays a central role by demonstrating dissemination in space and time. This focused review summarizes the pathophysiology, epidemiology, clinical manifestations, and imaging characteristics of MS, with particular emphasis on MRI-based diagnosis using the McDonald criteria. A representative clinical case involving optic nerve, brain, and spinal cord lesions is used to illustrate practical application of the criteria and common differential diagnostic considerations.

Keywords

Multiple sclerosis; McDonald criteria; Magnetic resonance imaging; Optic neuritis; Spinal cord lesions; Demyelinating disease

1. Introduction

Multiple sclerosis (MS) is one of the most common inflammatory demyelinating diseases of the central nervous system (CNS) and a leading cause of neurological disability in young adults. The disease is characterized by immune-mediated destruction of myelin, subsequent axonal damage, and progressive neurodegeneration.

The McDonald diagnostic criteria, first introduced in 2001 and subsequently revised, have transformed the diagnostic approach to MS by incorporating MRI and cerebrospinal fluid (CSF) findings alongside clinical assessment. The 2017 revision further emphasized MRI-based demonstration of dissemination in space (DIS) and dissemination in time (DIT), enabling earlier diagnosis even after a single clinical event.

This review provides an updated overview of MS with an emphasis on MRI features relevant to the McDonald criteria, illustrated through a representative clinical case.

2. Pathophysiology

MS is driven by an aberrant immune response against CNS myelin. Autoreactive T lymphocytes, particularly CD4+ and CD8+ cells, cross the blood–brain barrier and initiate an inflammatory cascade involving cytokines such as interferon-γ, tumor necrosis factor-α, and interleukin-17.

The resulting inflammatory milieu leads to focal demyelination, oligodendrocyte injury, and variable degrees of axonal damage. While partial remyelination may occur in early disease, chronic lesions are characterized by gliosis and irreversible neuroaxonal loss. These pathological processes correspond to the hyperintense lesions observed on T2-weighted and FLAIR MRI sequences.

3. Epidemiology

MS most commonly presents between 20 and 40 years of age and shows a strong female predominance, with a female-to-male ratio of approximately 2–3:1. The disease exhibits a distinct geographic distribution, with higher prevalence in Northern Europe, North America, and Australia.

In East Asian populations, including Korea, MS was historically considered rare; however, improved access to MRI and evolving diagnostic criteria have led to increased recognition and diagnosis in recent decades.

4. Clinical Manifestations

The clinical presentation of MS is heterogeneous and depends on the location and extent of CNS involvement. Common manifestations include optic neuritis, sensory disturbances, motor weakness, cerebellar dysfunction, brainstem symptoms, fatigue, and cognitive impairment.

In the illustrative case, a 40-year-old woman presented with progressive blurring of vision in the left eye and numbness of the right lower limb, suggesting multifocal involvement of the optic nerve and spinal cord. Such a pattern is typical of early MS and frequently prompts neuroimaging evaluation.

5. MRI Features of Multiple Sclerosis

5.1 Brain MRI

T2-Weighted Imaging


[Figure 1] Axial T2-weighted image


[Figure 2] Axial T2-weighted image

[Figure 3] Sagittal T2-weighted image

[Figure 4] Axial T2-weighted image

Multiple hyperintense lesions are identified involving:

  • Juxtacortical white matter
  • Periventricular regions, with lesions directly abutting the lateral ventricles without intervening normal white matter, forming the classic appearance of Dawson’s fingers
  • Corpus callosum
  • Infratentorial regions, including small foci in the left midbrain and right anterior pons

These lesion distributions are typical of multiple sclerosis.


Post-Contrast T1-Weighted Imaging



[Figure 5] T1-weighted contrast-enhanced images

(A) Axial, (B–D) Coronal, (E) Sagittal

Several lesions demonstrate gadolinium enhancement, while others remain non-enhancing.
The simultaneous presence of enhancing and non-enhancing lesions provides radiologic evidence of dissemination in time (DIT).


Additional Brain MRI Sequences


[Figure 6] Coronal image

  • Lesions involving the corpus callosum, a highly characteristic location for MS plaques.

[Figure 7] Axial FLAIR image


[Figure 8] Sagittal FLAIR image

  • Improved visualization of periventricular and juxtacortical lesions.



[Figure 9] Axial diffusion-weighted imaging (DWI)

No diffusion restriction is observed, helping to exclude acute ischemic pathology.


Typical MS lesions are hyperintense on T2-weighted and FLAIR images and are distributed in characteristic locations, including periventricular, juxtacortical, infratentorial, and deep white matter regions.

In the presented case, brain MRI demonstrated multiple T2- and FLAIR-hyperintense lesions involving the juxtacortical white matter, periventricular regions abutting the lateral ventricles (consistent with Dawson’s fingers), the corpus callosum, and infratentorial structures such as the pons and midbrain. These findings fulfill the radiologic requirements for dissemination in space.

Post-contrast T1-weighted imaging revealed both gadolinium-enhancing and non-enhancing lesions, reflecting lesions of different ages and providing evidence of dissemination in time. Diffusion-weighted imaging showed no restricted diffusion, helping to exclude acute ischemic pathology.

5.2 Optic Nerve Involvement

Optic neuritis is a common presenting feature of MS. MRI typically demonstrates T2 hyperintensity and contrast enhancement of the affected optic nerve.

In this case, focal T2 hyperintensity and enhancement of the left optic nerve near the orbital apex correlated with the patient’s visual symptoms, further supporting the diagnosis of MS.

5.3 Spinal Cord MRI

Cervical Spine


[Figure 10] T2-weighted image

  • A faint, short-segment intramedullary lesion is seen at the C2–3 vertebral level
  • Located dorsally, slightly left of the midline
  • Involves less than 50% of the spinal cord cross-sectional area
  • Shows faint contrast enhancement

Thoracic Spine


[Figure 11] T2-weighted image

  • An intramedullary lesion at the T2–3 level
  • Right anterior location
  • Occupies less than half of the cord cross-sectional area
  • Demonstrates intense nodular contrast enhancement
These spinal cord lesions are typical of MS, which characteristically shows short-segment, eccentrically located intramedullary plaques.

Spinal cord involvement is frequent in MS and often manifests as short-segment intramedullary lesions that occupy less than 50% of the cord cross-sectional area and are eccentrically located.

The cervical spine MRI in this case revealed a faint, short-segment lesion at the C2–3 level with mild enhancement. Thoracic spine imaging demonstrated a right anterior intramedullary lesion at the T2–3 level with nodular contrast enhancement. These features are characteristic of MS and help distinguish it from other inflammatory myelopathies, such as neuromyelitis optica spectrum disorder.

6. Application of the McDonald Diagnostic Criteria

The McDonald criteria require demonstration of dissemination in space and time, supported by clinical, radiologic, and laboratory findings.

In this case, dissemination in space was established by lesions in multiple characteristic locations, including periventricular, juxtacortical, infratentorial, spinal cord, and optic nerve regions. Dissemination in time was demonstrated by the coexistence of enhancing and non-enhancing lesions on MRI, as well as the presence of oligoclonal bands in the CSF.

Together, these findings fulfill the 2017 McDonald criteria for the diagnosis of multiple sclerosis.

7. Differential Diagnosis

The differential diagnosis of MS includes other inflammatory, infectious, and vascular conditions affecting the CNS. Neuromyelitis optica spectrum disorder typically presents with longitudinally extensive spinal cord lesions and bilateral optic neuritis. Acute disseminated encephalomyelitis is more common in children and follows a monophasic course. CNS vasculitis, neurosarcoidosis, and ischemic disease may be distinguished based on lesion distribution, enhancement patterns, and diffusion characteristics.

8. Treatment and Prognosis

Acute relapses are typically treated with high-dose intravenous corticosteroids. Long-term disease-modifying therapies, including interferon beta, glatiramer acetate, fingolimod, natalizumab, and anti-CD20 monoclonal antibodies such as ocrelizumab, reduce relapse frequency and delay disability progression.

Prognosis varies according to disease subtype, relapse frequency, and lesion burden. Early diagnosis and timely initiation of therapy are key determinants of long-term outcome.

9. Conclusion

Multiple sclerosis is a complex demyelinating disease in which MRI plays a pivotal role in diagnosis and disease monitoring. The McDonald diagnostic criteria provide a robust framework for integrating clinical and radiologic findings. Case-based MRI review, as demonstrated here, remains essential for accurate diagnosis, differentiation from mimics, and optimal patient management.

References

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  7. Hauser SL, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017.

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