What are the McDonald criteria for diagnosing multiple sclerosis?

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McDonald Criteria for Multiple Sclerosis

Core Diagnostic Principle

The McDonald criteria require objective demonstration of CNS inflammatory-demyelinating lesions disseminated in both space (DIS) and time (DIT), with no better alternative explanation for the clinical presentation. 1, 2, 3

Diagnostic Algorithm Based on Clinical Presentation

Two or More Attacks + Two or More Objective Lesions

  • No additional testing required for MS diagnosis 1
  • MRI, CSF, or other paraclinical tests would typically be abnormal if performed, but are not necessary 1

Two or More Attacks + One Objective Lesion

  • Requires demonstration of DIS through either: 1, 2
    • MRI showing lesions in ≥2 of 5 CNS locations (periventricular, cortical/juxtacortical, infratentorial, spinal cord, optic nerve) 1, 2
    • Positive CSF (oligoclonal IgG bands not in serum, or elevated IgG index) 1, 2

One Attack + Two or More Objective Lesions

  • Requires demonstration of DIT through: 1, 2, 3
    • Simultaneous gadolinium-enhancing AND non-enhancing lesions on single MRI 1, 2
    • New T2 or gadolinium-enhancing lesions on follow-up MRI (≥3 months after baseline) 1, 2
    • Second clinical attack 1
    • CSF-specific oligoclonal bands can substitute for DIT 2, 3

One Attack + One Objective Lesion

  • Requires demonstration of both DIS and DIT 1, 2
  • Apply criteria from above sections for both requirements 1, 2

Insidious Neurological Progression (Primary Progressive MS)

  • Requires all three components: 2
    • One year of disease progression (retrospective or prospective) 2
    • Two of three: (1) ≥1 T2 lesion in periventricular, cortical/juxtacortical, or infratentorial regions; (2) ≥2 T2 spinal cord lesions; (3) CSF oligoclonal bands and/or elevated IgG index 2
    • Mandatory CSF evidence of inflammation 2

MRI Criteria for Dissemination in Space (DIS)

DIS requires lesions in ≥2 of 5 CNS locations: 4, 1, 2

  • Periventricular: ≥3 lesions required (not just any periventricular lesion) 4, 1
  • Cortical/juxtacortical: Combines cortical and juxtacortical lesions into single category 4, 2
  • Infratentorial: ≥1 lesion 1, 2
  • Spinal cord: ≥2 lesions 2, 5
  • Optic nerve: Added as fifth CNS location in recent revisions 4, 1, 2

Critical caveat: Exclude symptomatic lesions in brainstem and spinal cord syndromes from the DIS count 2

MRI Criteria for Dissemination in Time (DIT)

DIT can be demonstrated by: 1, 2

  • Simultaneous presence of gadolinium-enhancing AND non-enhancing lesions on a single MRI 1, 2
  • New T2-hyperintense or gadolinium-enhancing lesions on follow-up MRI compared to baseline (≥3 months after initial clinical event) 1, 2
  • CSF-specific oligoclonal IgG bands not present in serum can substitute for MRI evidence of DIT 2, 3

No distinction is made between symptomatic and asymptomatic MRI lesions for both DIS and DIT 4, 2

CSF Analysis Criteria

Positive CSF is defined as: 1, 2

  • Oligoclonal IgG bands detected by isoelectric focusing that are different from any bands in serum 1, 2
  • Elevated IgG index 1, 2
  • Lymphocytic pleocytosis should be <50/mm³ 1

CSF analysis is particularly valuable when: 1, 2

  • Imaging criteria fall short of diagnostic thresholds 1, 2
  • Clinical presentation is atypical 1, 2
  • Patient is older with vascular risk factors where MRI specificity is reduced 1

Essential MRI Technical Requirements

Minimum technical standards: 1

  • Field strength: ≥1.5 Tesla 1
  • Maximum slice thickness: 3mm 1
  • In-plane spatial resolution: 1×1mm 1
  • Total scan time: 25-30 minutes 1

Required sequences for brain imaging: 1

  • Axial T2-weighted and proton-density (or T2-FLAIR) 1
  • Sagittal T2-FLAIR to evaluate corpus callosum 1
  • Gadolinium-enhanced T1-weighted sequences 1

Spinal cord imaging is mandatory when: 1, 2

  • Patient presents with spinal cord symptoms at disease onset 1
  • Brain MRI shows only 1-2 lesions or results are equivocal 1
  • Whole spinal cord imaging is recommended to define DIS 4, 2

Diagnostic Outcomes

Three possible diagnostic conclusions: 4, 1

  • MS: All criteria are fulfilled 4, 1
  • Possible MS: Criteria are not completely met, but patient remains at risk 4, 1
  • Not MS: Criteria are fully explored and not met, or alternative diagnosis is identified 4, 1

Critical Diagnostic Pitfalls and How to Avoid Them

Never Diagnose MS on MRI Alone

  • At least one clinical event consistent with acute demyelination is essential 2, 6
  • Historical symptoms alone are insufficient; objective neurological findings are mandatory 1, 2

High-Risk Populations Requiring Extra Caution

Exercise particular care in: 1, 2, 6

  • Age <10 years or >59 years at onset 1, 2, 6
  • Progressive onset without clear relapses 1, 2
  • Unusual features (dementia, epilepsy, aphasia) 1, 2
  • Patients with multiple vascular risk factors 1, 2

Mandatory Exclusion of MS Mimics

Always exclude these conditions before diagnosing MS: 1, 2

  • Neuromyelitis optica spectrum disorder (NMOSD): Check AQP4-IgG antibodies; look for longitudinally extensive transverse myelitis 2
  • MOG-antibody disease: Test for MOG antibodies 1
  • Vascular disorders: Antiphospholipid antibodies, lupus serologies in young adults with stroke-like presentations 1, 2
  • Infections: HTLV-1, Lyme disease, syphilis based on clinical context 1, 2
  • Leukodystrophies: Consider genetic testing in children and teenagers 1

Lesion Characteristics That Support MS Diagnosis

Highly specific imaging features: 1

  • Perivenular orientation of lesions (central vein sign) 1
  • Asymmetric involvement of inferior corpus callosum 1
  • Paramagnetic rim lesions indicating chronic active inflammation 1

Red flags suggesting non-MS diagnosis: 1, 6

  • Lesions not following typical MS distribution patterns 1
  • Bilateral sudden hearing loss 1
  • Isolated cranial nerve involvement (rare in MS, <10%) 1
  • Isolated eighth nerve palsy (extremely rare, <1%) 1

Quality Control Measures

Essential safeguards against misdiagnosis: 1, 2

  • MRI must be interpreted by experienced readers aware of complete clinical context 2
  • Confirm lesions on multiple imaging planes 1
  • Both individual lesion characteristics AND overall lesion patterns must be evaluated 1
  • Ensure state-of-the-art technology for MRI, CSF analysis, and evoked potentials 1, 2

Special Population Considerations

Pediatric Patients (Age <11 Years)

  • Use caution when applying 2010 criteria solely at baseline 4
  • At least one T1 hypointense lesion ("black hole") and at least one periventricular lesion help distinguish MS from monophasic demyelination 1, 6
  • Clinical and MRI serial evaluation to confirm new lesions over time is particularly important 4

Pediatric Patients (Age ≥11 Years)

  • Apply identical DIS and DIT criteria as in adults if presentation is non-ADEM-like 4, 2

Asian and Latin American Populations

  • Identical MRI criteria apply once NMOSD and other alternative conditions are carefully excluded 4, 2

Supportive Paraclinical Tests

Visual Evoked Potentials (VEP)

VEP provides additional diagnostic support when: 1, 2

  • MRI abnormalities are few 1, 2
  • Patient has primary progressive MS with progressive myelopathy 1, 2
  • Older individuals with vascular risk factors where MRI has lesser specificity 1, 2
  • Radiological findings don't satisfy MRI specificity criteria 2

Follow-Up Imaging Strategy

If baseline MRI shows lesions but doesn't fulfill DIS/DIT criteria: 1

  • Repeat brain MRI at 3-6 months 1
  • If second scan is inconclusive, obtain third scan at 6-12 months 1

Recent Advances and Emerging Criteria

Simplified Diagnostic Approach Based on High DIS Fulfillment

Recent research suggests that DIS in ≥4 of 4 regions (or ≥4 of 5 including optic nerve) is highly specific for MS (100% specificity), potentially eliminating the need for DIT demonstration in some cases 7. However, this approach has low sensitivity (26-30%) and is not yet incorporated into official guidelines 7. Current standard practice still requires both DIS and DIT 1, 2, 3.

Unified Criteria for All MS Subtypes

Emerging evidence supports using identical DIS criteria for both relapsing-remitting and primary progressive MS, rather than maintaining separate diagnostic pathways 4, 2, 5. The 2017 McDonald criteria already moved toward this unification 3, 5.

References

1
Guideline

Multiple Sclerosis Diagnosis and Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Guideline

Diagnostic Criteria for Multiple Sclerosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

4
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

6
Guideline

Recognizing Early Multiple Sclerosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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