What tests are used to diagnose and rule out multiple sclerosis?

Diagnostic Tests for Multiple Sclerosis

MRI is the cornerstone diagnostic test for multiple sclerosis, with specific protocols required for brain and spinal cord imaging to demonstrate dissemination of lesions in space and time. 1

MRI Requirements for MS Diagnosis

Brain MRI

• Essential sequences:
  • T2-weighted images
  • T1 post-gadolinium images
  • T2-FLAIR (fluid-attenuated inversion recovery)
  • Minimum field strength of 1.5T (3.0T preferred for improved sensitivity) 1
  • 3D acquisitions or 2D with 3-mm thick slices and no gap between slices 1

Spinal Cord MRI

• Complete spinal cord imaging (cervical, thoracic, and lumbar) is essential 1, 2
• Characteristics of MS spinal lesions:
  • T2-hyperintense
  • At least 3mm in length but less than two vertebral segments
  • Occupy only part of the cross-section of the cord
  • Little or no swelling of the cord 1

Optic Nerve Imaging

• Fat-suppressed MRI of optic nerves should be considered, especially in atypical cases 1

MRI Diagnostic Criteria (Dissemination in Space)

To demonstrate dissemination in space, three of the following four criteria must be met 1:

1. At least one gadolinium-enhancing lesion OR nine T2-hyperintense lesions if no gadolinium enhancement
2. At least one infratentorial lesion
3. At least one juxtacortical lesion (involving subcortical U-fibers)
4. At least three periventricular lesions (abutting the lateral ventricles)

Note: One spinal cord lesion can substitute for one brain lesion in these criteria 1

Additional Diagnostic Tests

Cerebrospinal Fluid Analysis

• Indicated when MRI findings are insufficient or atypical, particularly in older patients 1
• Look for:
  • Oligoclonal IgG bands not present in serum (using isoelectric focusing)
  • Elevated IgG index
  • Lymphocytic pleocytosis (<50/mm³) 1

Visual Evoked Potentials (VEP)

• Can provide objective evidence of a second lesion when clinical examination shows only one lesion not affecting visual pathways
• Look for delayed but well-preserved waveform typical of MS 1

Special Considerations

Age-Related Factors

• Pediatric patients: Look for at least one T1 "black hole" and at least one periventricular lesion 1
• Patients >50 years or with vascular risk factors: More stringent criteria needed (higher number of periventricular lesions) 1

Differential Diagnosis

• Neuromyelitis Optica Spectrum Disorders (NMOSD): Test for aquaporin-4 antibodies (AQP4-IgG); look for longitudinally extensive transverse myelitis (LETM) spanning ≥3 vertebral segments 1
• Other conditions: Consider vascular disease, migraine, and other inflammatory or infectious disorders when MRI patterns are atypical 1

Interpretation Considerations

• Serial imaging is valuable to demonstrate dissemination in time (new lesions developing over time) 1
• Gadolinium enhancement is typically transient (2-8 weeks, usually 4 weeks) 1
• Interpretation should be performed by trained neuroradiologists or clinicians familiar with MS features 1
• A normal brain MRI does not exclude MS; approximately 20% of patients with clinically isolated syndrome and normal baseline MRI still convert to MS after 20 years 2, 3

Common Pitfalls to Avoid

1. Inadequate imaging protocols: Ensure proper sequences and coverage of all relevant CNS regions
2. Misinterpreting non-specific white matter lesions: Particularly in older patients or those with vascular risk factors
3. Failure to image the entire spinal cord: Up to 40% of spinal cord lesions are found in the thoracolumbar region 2
4. Overlooking the need for gadolinium: Essential for demonstrating active inflammation and dissemination in time
5. Applying diagnostic criteria in inappropriate clinical contexts: The McDonald criteria should only be applied when the clinical presentation is typical for MS 2

Remember that while MRI is highly sensitive for MS lesions, no single test is diagnostic of MS, and clinical correlation remains essential for accurate diagnosis.