When should a patient be tested for Multiple Sclerosis (MS)?

When to Test for Multiple Sclerosis

Test for MS immediately when a patient aged 10-59 years presents with a first subacute or acute neurological episode (clinically isolated syndrome) suggesting inflammatory demyelination—specifically optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes—and obtain brain MRI with gadolinium to assess for dissemination in space and time. 1, 2

Primary Clinical Triggers for MS Testing

Relapsing-Remitting Presentation

• Optic neuritis: Painful unilateral vision loss with color vision impairment developing over several days 2
• Partial myelitis: Incomplete transverse myelitis with sensory level, weakness, or bladder dysfunction 2
• Brainstem syndromes: Diplopia and internuclear ophthalmoplegia 2
• Sensory disturbances: Numbness or tingling in discrete episodes lasting at least 24 hours 3
• Motor symptoms: Weakness or gait impairment that develops subacutely 3

These symptoms must develop over hours to days, stabilize, and represent new inflammatory demyelinating activity lasting at least 24 hours. 3

Primary Progressive Presentation

• Insidious progressive neurological decline over at least 1 year without distinct relapses, combined with MRI findings showing features consistent with MS lesions 1
• This presentation requires more extensive workup including spinal cord imaging and often CSF analysis 1

Age-Specific Testing Thresholds

Standard Age Range (10-59 years)

• Apply the 2010 McDonald criteria directly for patients in this age range presenting with typical symptoms 1, 3
• These criteria have been validated with high sensitivity and specificity in this population 1

Pediatric Patients (Under 11 years)

• Require special diagnostic care to distinguish MS from acute disseminated encephalomyelitis (ADEM) 1
• Look for at least one T1-hypointense lesion (black hole) and at least one periventricular lesion to distinguish MS from monophasic demyelination 2, 4
• The 2010 McDonald criteria can be applied in children older than 11 years if they do not show ADEM-like symptoms 1

Older Patients (Over 50 years)

• Apply more stringent criteria, requiring a higher number of periventricular lesions 3, 4
• Carefully exclude cerebrovascular disease and other age-related conditions that can mimic MS 3, 4

Initial Diagnostic Workup

Brain MRI Requirements

Obtain brain MRI with gadolinium at symptom onset to assess for: 1

Dissemination in Space (DIS) requires one or more lesions in at least two of four characteristic locations: 1, 2

• Periventricular regions
• Juxtacortical regions
• Infratentorial (posterior fossa)
• Spinal cord

Dissemination in Time (DIT) can be demonstrated by: 1

• Simultaneous presence of gadolinium-enhancing and non-enhancing lesions on a single scan at any time, OR
• New T2 or gadolinium-enhancing lesions on follow-up MRI compared to baseline

Spinal Cord Imaging Indications

Order whole spinal cord MRI in two specific scenarios: 1

1. Patients with spinal cord symptoms: To rule out compression, tumor, neuromyelitis optica (NMO), or vasculitides 1
2. Patients with non-spinal symptoms not fulfilling brain MRI criteria for DIS: To identify additional lesions that may establish dissemination in space 1

Use at least two MR sequences (T2 and STIR, T2 and DIR, or T2 and post-contrast T1) to increase confidence in lesion identification, as approximately 40% of spinal cord lesions occur in the thoracolumbar region. 1

Follow-Up Testing Strategy

For Patients Not Meeting Initial Diagnostic Criteria

• Obtain follow-up brain MRI 3-6 months after baseline scan in patients with abnormal baseline MRI but not fulfilling McDonald criteria 1
• If the second scan is inconclusive, obtain a third scan 6-12 months later 1
• This timing is based on evidence that 80% of CIS patients with at least three white matter lesions at baseline develop new T2 lesions within 3 months 1

For Radiologically Isolated Syndrome (RIS)

• Obtain follow-up brain MRI 3-6 months after initial imaging in patients with incidental MRI findings suggestive of MS but no clinical symptoms 1
• New active lesions substantially increase the risk of subsequent MS-related clinical events, though definite MS diagnosis requires clinical manifestations 1

Critical Red Flags Against MS Diagnosis

Do not pursue MS testing when patients present with: 3, 4

• Subacute onset over weeks with progressive evolution without stabilization 3
• Dementia, epilepsy, or aphasia as presenting features 3
• Bilateral sudden hearing loss 4
• Sudden onset of focal neurologic symptoms suggesting stroke (headache, confusion, focal weakness) 4

These features suggest alternative diagnoses requiring different diagnostic pathways. 3, 4

Supportive Paraclinical Tests

CSF Analysis

• Obtain CSF for oligoclonal bands and IgG index when: 1, 3
  • MRI is not entirely diagnostic
  • MRI reveals features unusual for MS
  • Patient presents with atypical features or progressive onset 1, 4
  • Diagnosing primary progressive MS (required as one of three supportive criteria) 1

CSF oligoclonal bands specific to CSF (not present in serum) support the MS diagnosis. 2

Visual Evoked Potentials

• Consider in suspected optic nerve involvement, particularly when MRI findings are equivocal 2
• Delayed conduction supports demyelination 2

Essential Diagnostic Principles

Clinical Event Requirement

Never diagnose MS on MRI findings alone—at least one clinical event consistent with acute demyelination remains essential for diagnosis. 2, 4 This is a critical pitfall: applying criteria to MRI abnormalities without corresponding clinical symptoms increases misdiagnosis risk. 2

Exclusion of Mimics

Before confirming MS, systematically exclude: 3, 4, 5

• Neuromyelitis optica spectrum disorder (NMOSD): Test for aquaporin-4 antibodies, especially in Asian populations 1, 3
• Acute disseminated encephalomyelitis (ADEM): Particularly in pediatric cases 1, 5
• Cerebrovascular disease: Especially in older patients with vascular risk factors 3, 4
• Infectious diseases: HTLV-1, Lyme disease 4
• Systemic inflammatory conditions: Sjögren's syndrome, systemic lupus erythematosus, Behçet's disease 5

Specialist Interpretation

MRI scans must be interpreted by experienced readers who: 1

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

The risk of overdiagnosis is particularly high when MRI findings are interpreted without clinical context or by clinicians lacking expertise in demyelinating diseases. 1

Population-Specific Considerations

Asian Populations

• Apply the 2010 McDonald criteria after excluding NMO and NMO spectrum disorders 1
• The accuracy of criteria is similar between Asian and European populations once NMO is excluded 1

Latin American Patients

• The 2010 McDonald criteria show high accuracy even in subpopulations without European ancestry 1

African and Middle Eastern Populations

• Validation studies are lacking; exercise additional caution and consider supportive paraclinical tests 1