What are the diagnostic criteria and treatment options for an adult presenting with a first clinical demyelinating event suspected to be multiple sclerosis (MS) according to the McDonald criteria 2024?

McDonald Criteria 2024 for Multiple Sclerosis Diagnosis

Key Updates in the 2024 McDonald Criteria

The 2024 McDonald criteria introduce three major changes: the optic nerve is now recognized as a fifth topographic site for dissemination in space (DIS), CSF-specific oligoclonal IgG bands can substitute for dissemination in time (DIT), and radiologically isolated syndrome (RIS) can be classified as MS when specific conditions are met. 1

Dissemination in Space (DIS) Requirements

To demonstrate DIS, you need at least one T2 lesion in at least 2 of 5 characteristic CNS locations: 2, 3

• Periventricular (≥3 lesions required, not just 1) 4
• Juxtacortical/cortical (includes cortical involvement, expanding beyond the 2010 definition) 4
• Infratentorial/posterior fossa 2
• Spinal cord (≥2 lesions) 2
• Optic nerve (NEW in 2024) 1

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

Dissemination in Time (DIT) Requirements

DIT can be established through any one of the following: 2, 3

• New T2 or gadolinium-enhancing lesions on follow-up MRI compared to baseline
• Simultaneous presence of gadolinium-enhancing AND non-enhancing lesions on a single MRI
• CSF-specific oligoclonal IgG bands not present in serum (NEW as standalone criterion in 2024) 2, 1

Optional High-Specificity MRI Markers (2024 Addition)

The 2024 criteria incorporate two advanced imaging markers on susceptibility-sensitive sequences as optional diagnostic tools: 1

• Central vein sign (CVS)
• Paramagnetic rim lesion (PRL)

These markers enhance specificity but are not mandatory for diagnosis. 1

Diagnostic Algorithm for First Clinical Demyelinating Event

Step 1: Confirm Clinical Presentation

Look for typical MS symptoms developing over several days: 5

• Unilateral optic neuritis
• Partial myelitis
• Sensory disturbances
• Brainstem syndromes (e.g., internuclear ophthalmoplegia)
• Motor weakness, gait impairment, incoordination
• Bladder dysfunction

Age consideration: Criteria apply best to ages 10-59 years. 6

Step 2: Obtain Brain AND Spinal Cord MRI

• Whole spinal cord imaging is recommended, as approximately 40% of spinal cord lesions occur in the thoracolumbar region 3
• Spinal cord MRI is particularly valuable when brain MRI doesn't fulfill DIS criteria 4
• MRI must be interpreted by experienced readers aware of complete clinical and laboratory information 2

Step 3: Apply DIS and DIT Criteria

If the patient has DIS (≥1 lesion in ≥2 of 5 locations) AND DIT (by any of the three methods above), diagnose MS. 2, 3

Step 4: When Criteria Are Not Fully Met

If DIS is met but DIT is not: 2

• Perform follow-up MRI to detect new T2 or enhancing lesions
• Consider lumbar puncture for CSF oligoclonal bands (can substitute for DIT) 2, 1

If neither DIS nor DIT is met: 6

• Classify as clinically isolated syndrome (CIS)
• Monitor with serial clinical and MRI evaluations
• Consider CSF analysis and visual evoked potentials (VEP) in atypical cases 6, 2

Step 5: Exclude Alternative Diagnoses

Always exclude these MS mimics before finalizing diagnosis: 6, 2

• Neuromyelitis optica spectrum disorder (NMOSD) - particularly critical in Asian populations 6, 2
• Cerebrovascular disease (multifocal ischemia/infarction in young adults) 6
• Infectious diseases (HTLV-1, Lyme disease, syphilis) 6, 2
• Autoimmune conditions (check ANA, antiphospholipid antibodies if clinically indicated) 6
• Functional neurological disorders 3

Essential principle: A diagnosis of MS cannot be made if there is a better explanation for the clinical and paraclinical abnormalities. 6

Special Populations Requiring Stricter Criteria

Age >50 Years or Vascular Risk Factors

Apply more stringent diagnostic criteria (e.g., higher number of periventricular lesions required) to avoid misdiagnosis of vascular disease as MS. 6, 2

Children <11 Years

• Use caution when applying 2010/2017 criteria solely at baseline 4, 2
• Serial clinical and MRI evaluation to confirm new lesions over time is particularly important 4
• At least one black hole (T1 hypointense lesion) and at least one periventricular lesion help distinguish MS from monophasic demyelination 6

Children ≥11 Years (Non-ADEM Presentation)

Use identical DIS and DIT criteria as in adults. 4, 2, 3

Patients with Headache Disorders

Apply stricter diagnostic thresholds to mitigate misdiagnosis risk. 1

Primary Progressive MS (PPMS) Criteria

All three components are required for PPMS diagnosis: 2

1. One year of disease progression (retrospective or prospective)
2. Two of the following three:
   • ≥1 T2 lesion in characteristic MS locations (periventricular, juxtacortical, or infratentorial)
   • ≥2 T2 lesions in spinal cord
   • CSF oligoclonal IgG bands and/or elevated IgG index
3. Mandatory CSF evidence of inflammation (oligoclonal bands or elevated IgG index) 2

Radiologically Isolated Syndrome (RIS) - 2024 Update

Major change: When a clinical attack occurs in RIS patients who have DIT (and by definition already have DIS), a diagnosis of MS can now be made. 4, 2

However: Persons should not be diagnosed with MS on the basis of MRI findings alone - at least one clinical event consistent with acute demyelination remains essential. 4, 6, 3

Role of Ancillary Testing

CSF Analysis

Obtain lumbar puncture when: 6, 2

• Clinical picture is unusual or atypical
• Imaging criteria for diagnosis are not fulfilled
• Progressive onset without clear relapses
• Age <10 or >59 years at onset
• Diagnosis is uncertain

CSF provides critical information about inflammation and immunological disturbance that differs from MRI. 2

Visual Evoked Potentials (VEP)

Consider VEP when: 6, 2

• MRI abnormalities are few
• Primary progressive MS with progressive myelopathy
• Older individuals with vascular risk factors (where MRI has lesser specificity)
• Suspected optic nerve involvement or limited MRI access
• Radiological findings don't satisfy MRI specificity criteria

Treatment Initiation After Diagnosis

Acute Relapse Management

Steroids are the mainstay of treatment for initial presentation and relapses. 7

• Patients who do not adequately respond to steroids may benefit from plasmapheresis 7

Disease-Modifying Therapy (DMT)

Nine classes of DMTs are available for relapsing-remitting MS and secondary progressive MS with activity: 5

• Interferons
• Glatiramer acetate
• Teriflunomide
• Sphingosine 1-phosphate receptor modulators
• Fumarates
• Cladribine
• Three types of monoclonal antibodies

Efficacy: DMTs reduce annualized relapse rates by 29-68% compared with placebo or active comparators. 5

For PPMS: Ocrelizumab is the approved DMT. 5

Monitoring

Regular MRI monitoring is recommended to assess disease activity and treatment response. 6

Critical Diagnostic Pitfalls to Avoid

• Never diagnose MS on MRI alone - at least one clinical event is mandatory 4, 6, 3
• Symptomatic and asymptomatic MRI lesions are treated equally for DIS and DIT 4
• A positive test for an MS mimic does not automatically exclude MS - clinical judgment is essential 8
• Bilateral sudden hearing loss suggests a condition other than MS 6
• Sudden focal neurologic symptoms (headache, confusion, diplopia, dysarthria, focal weakness) may indicate stroke rather than MS 6
• Diagnosis must be made by a specialist familiar with MS, its differential diagnoses, and interpretation of paraclinical assessments 6, 2