What are the updated guidelines for diagnosing and treating a patient suspected of having Multiple Sclerosis (MS) using the McDonald criteria?

McDonald Criteria for Multiple Sclerosis Diagnosis

Apply the 2017 McDonald Criteria as the current diagnostic standard for MS, which allows earlier diagnosis than previous versions by incorporating MRI findings, CSF analysis, and clinical presentation in a unified algorithmic approach. 1, 2, 3

Diagnostic Framework for Relapsing-Remitting MS

The diagnosis requires demonstrating dissemination in space (DIS) and dissemination in time (DIT) through the following algorithm: 1, 4

Dissemination in Space Requirements

One or more lesions in at least two of four characteristic CNS locations: 5

• Periventricular regions
• Juxtacortical regions (including cortical lesions, which are now equivalent to juxtacortical foci per 2017 revisions) 3
• Infratentorial/posterior fossa regions
• Spinal cord (≥2 lesions) 5

Critical caveat: Exclude symptomatic lesions in brainstem and spinal cord syndromes from the DIS count. 5

Dissemination in Time Requirements

DIT can be established by any of the following: 5

• New T2 or gadolinium-enhancing lesions on follow-up MRI (optimal interval 3-6 months from baseline) 5
• Simultaneous presence of gadolinium-enhancing AND non-enhancing lesions on a single MRI at any time (allows diagnosis after just one scan) 5
• CSF-specific oligoclonal IgG bands not present in serum (2017 revision reintroduced this for DIT in relapsing forms) 1, 3

Clinical Scenarios

Two or more clinical attacks with objective evidence of two lesions: No additional testing required if presentation is typical. 1

Two or more attacks with objective evidence of one lesion: Demonstrate DIS using MRI or abnormal CSF with oligoclonal bands. 1

One attack with objective evidence of two lesions: Demonstrate DIT using follow-up MRI, simultaneous enhancing/non-enhancing lesions, or CSF oligoclonal bands. 1, 3

Primary Progressive MS Diagnostic Criteria

PPMS diagnosis requires all three components: 5

1. One year of disease progression (determined retrospectively or prospectively) 5

2. Two of the following three criteria:

   • One or more T2 lesions in characteristic MS locations (periventricular, juxtacortical, or infratentorial—excluding spinal cord) 5
   • Two or more T2 lesions in the spinal cord 5
   • CSF oligoclonal IgG bands and/or elevated IgG index 5

3. Mandatory CSF evidence of inflammation (oligoclonal bands or elevated IgG index) 1, 4

Important note: Recent evidence suggests the 2017 RRMS DIS criteria perform well in PPMS diagnosis (sensitivity 92.9-95.4%, specificity 95%) when combined with DIT/positive CSF, supporting movement toward unified diagnostic criteria. 6

Essential Diagnostic Workup

MRI Requirements

Brain and spinal cord MRI with gadolinium is mandatory and must use high-quality, state-of-the-art technology. 1, 4 MRI is the most sensitive and specific paraclinical test for MS diagnosis. 1, 4, 2

CSF Analysis Indications

Perform lumbar puncture when: 1, 4

• Clinical presentation is atypical or unusual
• MRI findings don't satisfy diagnostic criteria
• Diagnosing PPMS (mandatory component)
• Patient has vascular risk factors making MRI findings less specific 4
• Seeking to establish DIT without waiting for follow-up MRI 3

CSF provides critical information about inflammation and immunological disturbance that differs from what MRI provides. 4

Visual Evoked Potentials

Consider VEP in specific scenarios: 1, 4

• Few MRI abnormalities, particularly in PPMS with progressive myelopathy
• Older patients with vascular risk factors where MRI has lower specificity
• Radiological findings don't satisfy MRI specificity criteria

Critical Interpretation Requirements

MRI scans must be interpreted by experienced readers who: 5

• Are aware of complete clinical and laboratory information
• Can fully assess evidence both for AND against MS diagnosis
• Recognize the full range of brain and spinal cord abnormalities that support or refute MS

Major pitfall: The simplified 2010/2017 criteria risk overdiagnosis when MRI is interpreted without clinical context or by inexperienced readers. 5

Mandatory Differential Diagnosis Exclusion

Before diagnosing MS, systematically exclude: 1, 4

Mimicking conditions requiring specific testing:

• Neuromyelitis optica spectrum disorders (NMO/NMOSD)—test for aquaporin-4 antibodies 1, 3
• MOG antibody disease 1, 3
• Acute disseminated encephalomyelitis (ADEM) 5, 1
• Vascular disorders 1
• Infections (Lyme disease, HTLV-1, syphilis) 4

Recommended blood work panel: 4

• Complete blood count and metabolic panel
• Vitamin B12 levels
• Thyroid function tests
• ANA and antiphospholipid antibodies
• Lyme serology
• HTLV-1 testing
• Syphilis serology

Special Population Considerations

Exercise particular caution in atypical presentations: 4

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

Pediatric patients: The 2010/2017 criteria can be applied in children >11 years if they lack ADEM-like symptoms (high sensitivity and specificity demonstrated). 5

Asian populations: Apply criteria after excluding NMO/NMOSD, as accuracy is similar to European populations once these are ruled out. 5

Key Advantages of Current Criteria

The 2017 McDonald criteria allow: 5, 3

• Earlier diagnosis than previous versions
• Diagnosis potentially after a single MRI (if simultaneous enhancing/non-enhancing lesions present)
• Diagnosis at first clinical attack when CSF oligoclonal bands are present with typical MRI lesion distribution
• No mandatory time interval between clinical attack and baseline MRI

Clinical impact: Earlier diagnosis enables timely initiation of disease-modifying therapy, which reduces annual relapse rates by 29-68% compared to placebo and slows disability progression. 2, 7