What is the usual workup for a concern of multiple sclerosis (MS)?

Diagnostic Workup for Multiple Sclerosis

The standard workup for suspected multiple sclerosis includes MRI of the brain and spinal cord, cerebrospinal fluid analysis, and visual evoked potentials to demonstrate dissemination of lesions in both space and time, which is essential for diagnosis. 1, 2

Initial Assessment

When multiple sclerosis (MS) is suspected, the diagnostic approach should follow these steps:

Clinical Evaluation

• Focus on symptoms suggesting demyelinating events:
  • Visual disturbances (optic neuritis)
  • Sensory abnormalities (numbness, tingling)
  • Motor weakness
  • Coordination problems
  • Bladder/bowel dysfunction
  • Fatigue
  • Cognitive changes

Neuroimaging

• Brain MRI with and without contrast - essential first-line test 1, 2

  • Look for:
    • T2-hyperintense lesions in periventricular, juxtacortical, infratentorial, and spinal cord regions
    • Gadolinium-enhancing lesions (indicating active inflammation)
    • Lesion morphology (ovoid, perpendicular to ventricles - "Dawson's fingers")

• Spinal cord MRI with and without contrast 1, 2

  • Particularly important when brain MRI findings are minimal or equivocal
  • Helps demonstrate dissemination in space

Cerebrospinal Fluid Analysis

• Lumbar puncture to evaluate: 1, 2
  • Oligoclonal bands not present in serum (indicates intrathecal antibody production)
  • Elevated IgG index
  • Normal cell count and protein levels (mild elevation may be seen)
  • Rule out infectious causes

Evoked Potentials

• Visual Evoked Potentials (VEP) 1, 2
  • Particularly useful when MRI findings are limited
  • Helps detect subclinical optic nerve involvement
  • Delayed P100 latency suggests demyelination

Diagnostic Criteria

The McDonald criteria (with revisions) are used to establish MS diagnosis based on: 1, 2, 3

1. Dissemination in Space (DIS): Lesions in at least two of four CNS areas:

   • Periventricular
   • Juxtacortical/cortical
   • Infratentorial
   • Spinal cord

2. Dissemination in Time (DIT): Evidence that lesions developed at different times:

   • New T2 or gadolinium-enhancing lesion on follow-up MRI
   • Simultaneous presence of gadolinium-enhancing and non-enhancing lesions

Differential Diagnosis Workup

Additional tests to rule out MS mimics may include: 1, 4

• Blood tests:

  • Complete blood count
  • Comprehensive metabolic panel
  • ESR/CRP (inflammatory markers)
  • ANA, anti-dsDNA (for autoimmune conditions)
  • Vitamin B12, folate levels
  • Syphilis serology
  • HIV testing
  • Aquaporin-4 antibodies and MOG antibodies (for neuromyelitis optica spectrum disorders)

• Additional imaging:

  • MR angiography (if vascular disease suspected)
  • CT scan (if structural lesions suspected)

Special Considerations

• Primary Progressive MS: Requires more stringent criteria including: 1

  • One year of disease progression
  • Two of the following:
    • Brain lesions characteristic of MS
    • Two or more spinal cord lesions
    • Positive CSF (oligoclonal bands)

• Atypical presentations: In patients with unusual symptoms (dementia, epilepsy, aphasia) or age groups (<10 or >59 years), additional CSF and VEP analysis is recommended for diagnostic certainty 1, 2

Common Pitfalls to Avoid

1. Misinterpreting nonspecific white matter lesions - Small, nonspecific white matter lesions are common, especially in older patients with vascular risk factors 1

2. Overlooking MS mimics - Conditions like neuromyelitis optica, acute disseminated encephalomyelitis, and small vessel disease can mimic MS 1

3. Diagnosing MS based solely on MRI findings - Radiologically isolated syndrome (incidental MRI findings) should not be diagnosed as MS without clinical correlation 3, 4

4. Neglecting spinal cord imaging - Spinal cord lesions are highly specific for MS and can be crucial for diagnosis when brain MRI is equivocal 1, 2

The diagnostic workup should be performed by clinicians experienced in MS diagnosis, as interpretation of findings requires expertise to avoid misdiagnosis and inappropriate treatment initiation 1, 3.