What laboratory tests and procedures are recommended for the diagnosis and management of Multiple Sclerosis (MS)?

Laboratory Tests for Multiple Sclerosis Diagnosis

Order brain and spinal cord MRI as the primary diagnostic test, supplemented by CSF analysis for oligoclonal bands when imaging is insufficient or the presentation is atypical. 1

Essential Laboratory Tests

MRI (First-Line Imaging)

• Brain and spinal cord MRI is the most sensitive and specific paraclinical test for MS diagnosis and should be performed in all suspected cases 1, 2
• For dissemination in space, look for lesions in at least two of these locations: periventricular (≥3 lesions), juxtacortical (≥1 lesion), infratentorial (≥1 lesion), or spinal cord 1, 2
• For dissemination in time, identify either: gadolinium-enhancing and non-enhancing lesions simultaneously on one scan, OR new T2/gadolinium-enhancing lesions on follow-up MRI (≥3 months after initial clinical event) 1, 2
• One gadolinium-enhancing lesion or nine T2-hyperintense lesions (if no enhancement) can substitute for multiple lesions in space criteria 1

CSF Analysis (Second-Line, Situational)

• Perform CSF analysis when MRI criteria are incomplete, clinical presentation is atypical, or in patients over 59 years where MRI specificity decreases 1, 2
• Test for oligoclonal IgG bands using isoelectric focusing (must be present in CSF but absent in serum) OR elevated IgG index 1, 2
• Verify lymphocytic pleocytosis is <50/mm³ (higher counts suggest alternative diagnoses) 1
• Ensure testing is performed with state-of-the-art technology, as quality varies significantly between laboratories 1

Visual Evoked Potentials (Supplementary)

• Order VEPs when MRI abnormalities are few or lack specificity, particularly in older patients with vascular risk factors 3, 2
• VEPs showing delayed latency with preserved waveform can provide objective evidence of a second lesion when only one clinical lesion is apparent 1, 2

Monitoring Laboratory Tests During Treatment

Baseline and Periodic Monitoring

• Obtain complete blood count with differential, platelet count, and comprehensive metabolic panel including liver function tests at baseline 4
• Repeat these tests at 1,3, and 6 months after starting disease-modifying therapy, then periodically thereafter 4
• Monitor more intensively if myelosuppression develops 4

Critical Differential Diagnosis Testing

Rule Out MS Mimics

• Test for aquaporin-4 (AQP4) antibodies to exclude neuromyelitis optica spectrum disorders, which require completely different treatment 5
• Test for myelin oligodendrocyte glycoprotein (MOG) antibodies to identify MOG-antibody disease, another distinct entity 5
• Consider antiphospholipid antibodies, lupus serologies, HTLV-1, Lyme serology, and syphilis testing based on clinical context 3, 1
• In children and teenagers, consider genetic testing for leukodystrophies 3, 1

Important Caveats and Pitfalls

When to Exercise Extreme Caution

• If MRI and CSF tests are negative or atypical, do not diagnose MS - alternative diagnoses must be vigorously pursued 1
• In patients <10 or >59 years old, progressive onset without relapses, or unusual presentations (dementia, epilepsy, aphasia), require additional scrutiny before diagnosis 1, 2
• MRI findings in older patients may reflect microvascular ischemic disease rather than MS, reducing specificity 2

Quality Control Considerations

• Poor quality paraclinical testing (MRI, CSF, evoked potentials) leads to misdiagnosis - ensure high-quality imaging and laboratory standards 1
• Biopsy is rarely indicated but can confirm inflammatory demyelination when diagnosis remains uncertain despite comprehensive workup 3, 2

Timing Requirements

• Clinical attacks must last ≥24 hours and be separated by ≥30 days from onset to onset 2
• Single paroxysmal episodes do not constitute relapses; multiple episodes over 24 hours do 2
• Wait at least 3 months after initial clinical event before using new MRI lesions to establish dissemination in time 1, 2