What is the diagnostic workup for a patient with suspected multiple sclerosis (MS)?

Diagnostic Workup for Multiple Sclerosis

The diagnostic workup for suspected multiple sclerosis (MS) should include brain and spinal cord MRI, cerebrospinal fluid analysis, and evoked potential testing, with emphasis on demonstrating dissemination of lesions in both time and space according to the 2017 McDonald criteria. 1

Core Diagnostic Approach

Clinical Assessment

• Evaluate for typical MS presentations:
  • Optic neuritis (20-31% of initial presentations)
  • Sensory disturbances
  • Motor weakness
  • Brainstem syndromes (e.g., internuclear ophthalmoplegia)
  • Symptoms typically develop over several days

Neuroimaging

• Brain MRI (mandatory sequences):

  • Axial T1-weighted sequences
  • Axial T2-weighted and proton-density sequences
  • Sagittal 2D or isotropic 3D T2-FLAIR sequences
  • Single dose gadolinium-based contrast with minimum 5-minute delay
  • Look for characteristic lesions: periventricular, juxtacortical, or infratentorial 1

• Spinal Cord MRI:

  • Essential for complete evaluation
  • Look for focal lesions with clearly demarcated borders, typically small and located in the periphery 1

• Optic Nerve Imaging (when appropriate):

  • May show T2 hyperintensity, optic nerve swelling, and contrast enhancement in acute lesions 1

Laboratory Testing

• Lumbar Puncture (particularly important when diagnosis is uncertain):

  • Test for oligoclonal bands (absence is a strong predictor of alternative diagnosis)
  • Evaluate IgG index
  • Check cell count and protein levels 1, 2

• Basic Laboratory Tests to rule out alternative diagnoses:

  • Complete blood count
  • Comprehensive metabolic panel
  • Erythrocyte sedimentation rate
  • C-reactive protein
  • Urinalysis 1

• Additional Testing when clinically indicated:

  • AQP4-IgG antibody (for neuromyelitis optica)
  • MOG-IgG antibody (for MOG-associated encephalomyelitis) 1

Evoked Potentials

• Visual evoked potentials (normal VEPs suggest alternative diagnosis) 1, 2
• Somatosensory evoked potentials
• Brainstem auditory evoked potentials

Diagnostic Criteria Application

The 2017 McDonald criteria should be applied, focusing on:

1. Dissemination in Space (DIS): Evidence of damage in different parts of the nervous system
2. Dissemination in Time (DIT): Evidence of damage occurring at different times
3. No better explanation for the clinical presentation 1

Red Flags Suggesting Alternative Diagnoses

Be alert to features that suggest conditions other than MS:

• Absence of CSF oligoclonal bands (strongest predictor of alternative diagnosis) 2
• Presence of atypical MRI lesions 2
• Absence of dissemination in space 2
• Normal visual evoked potentials 2
• Atypical presentations:
  • Isolated cranial nerve dysfunction
  • Pure sensory or motor variants
  • Posterior optic nerve involvement
  • Simultaneous bilateral optic neuritis
  • Long optic nerve lesions
  • Leptomeningeal enhancement 1

Common MS Mimics to Consider

The most frequent alternative diagnoses (accounting for approximately 24% of suspected MS cases) include:

• Nonspecific neurologic symptoms with atypical MRI lesions of suspected vascular origin
• Migraine with atypical MRI lesions
• Neuromyelitis optica spectrum disorders 2

Clinical Pitfalls to Avoid

1. Overreliance on MRI: The diagnosis of MS must remain clinical, supported by MRI but not exclusively based on it. Reliance on MRI alone can lead to misdiagnosis in up to one-third of cases 3

2. Inadequate exclusion of alternatives: Always consider other conditions that can mimic MS, particularly when atypical features are present 2, 4

3. Failure to apply diagnostic criteria properly: Ensure proper application of the 2017 McDonald criteria, which have improved sensitivity while maintaining specificity 1

4. Neglecting cervical spine imaging: An MRI of the cervical spine is recommended in all patients suspected of having MS who have symptoms suggestive of spinal cord involvement 3

Early and accurate diagnosis is crucial as disease-modifying therapies can reduce relapse rates by 29-68% compared to placebo or active comparators, potentially improving long-term outcomes and quality of life 1, 5.