What is the recommended workup for a patient suspected of having Multiple Sclerosis (MS)?

Recommended Diagnostic Workup for Multiple Sclerosis

The recommended workup for a patient suspected of having Multiple Sclerosis (MS) should include brain and spinal cord MRI, cerebrospinal fluid analysis, and visual evoked potentials, with the goal of demonstrating lesions disseminated in both space and time with no better explanation for the clinical presentation. 1

Initial Diagnostic Evaluation

MRI Protocol

• Brain MRI (mandatory):

  • Standardized protocol including:
    • Axial T1-weighted sequences before and after contrast
    • Axial T2-weighted and proton-density (or T2-FLAIR) sequences
    • Sagittal 2D or isotropic 3D T2-FLAIR sequences 2
  • Single dose (0.1 mmol/kg) of gadolinium-based contrast with minimum 5-minute delay after injection 2
  • 1.5T or 3.0T scanner with 3D acquisitions or 2D with 3-mm thick slices and no gap 2

• Spinal Cord MRI (mandatory):

  • Sagittal imaging:
    • Dual-echo (proton-density and T2-weighted) conventional/fast spin-echo
    • STIR (alternative to proton-density-weighted)
    • Contrast-enhanced T1-weighted spin-echo (if T2 lesions present) 2
  • Axial imaging (optional):
    • 2D and/or 3D T2-weighted fast spin-echo
    • Contrast-enhanced T1-weighted spin-echo 2
  • Should include cervical, thoracic, and lumbar regions 2

Cerebrospinal Fluid Analysis

• Perform when:
  • MRI findings are insufficient or atypical
  • Clinical presentation is unusual 1
• Look for:
  • Oligoclonal IgG bands (absence strongly suggests alternative diagnosis, OR 18.113) 3
  • Elevated IgG index
  • Mild pleocytosis

Visual Evoked Potentials (VEPs)

• Particularly valuable when:
  • MRI abnormalities are few
  • MRI findings have lesser specificity (e.g., in older individuals with vascular risk factors) 2, 1
• Normal VEPs suggest alternative diagnosis (OR 3.550) 3

Diagnostic Criteria (McDonald Criteria)

Dissemination in Space (DIS)

Requires at least 3 of the following 4 criteria:

1. One or more gadolinium-enhancing lesions or nine T2-hyperintense lesions
2. One or more infratentorial lesions
3. One or more juxtacortical lesions
4. Three or more periventricular lesions 2, 1

Dissemination in Time (DIT)

Can be demonstrated by:

• New T2 or gadolinium-enhancing lesion on follow-up MRI compared to baseline
• Simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time 1

Indications for Spinal Cord MRI

• Clinically isolated syndrome with spinal cord symptoms
• Clinically isolated syndrome without spinal cord symptoms but with inconclusive brain MRI
• Strong clinical suspicion of MS but no findings on brain MRI
• Nonspecific brain MRI findings
• Radiologically isolated syndrome
• Primary progressive MS 2

Differential Diagnosis Considerations

Red Flags for Alternative Diagnoses

• Absence of CSF oligoclonal IgG bands
• Presence of atypical MRI lesions
• Absence of dissemination in space
• Normal visual evoked potentials 3

Common MS Mimics to Rule Out

1. Nonspecific neurologic symptoms with atypical MRI lesions of vascular origin
2. Migraine with atypical lesions
3. Neuromyelitis optica spectrum disorders
4. Inflammatory diseases and vasculitis
5. Toxic, metabolic, and infectious diseases 1, 3

Special Considerations

• For patients aged >50 years or with vascular risk factors, consider more stringent criteria (e.g., higher number of periventricular lesions) 2
• In pediatric cases (especially <11 years), special care is needed in interpretation 2
• No distinction between symptomatic and asymptomatic MRI lesions for DIS and DIT criteria 1

Diagnostic Algorithm Based on Clinical Presentation

Clinical Presentation	Additional Data Needed for MS Diagnosis
Two or more attacks; objective clinical evidence of 2+ lesions	No additional tests required
Two or more attacks; objective clinical evidence of 1 lesion	DIS by MRI or 2+ MRI lesions consistent with MS plus positive CSF
One attack; objective clinical evidence of 2+ lesions	DIT by MRI or second clinical attack
One attack; objective clinical evidence of 1 lesion	DIS by MRI or 2+ MRI lesions plus positive CSF AND DIT by MRI or second attack
Insidious neurological progression suggestive of MS	DIS by specific MRI criteria AND DIT by MRI or continued progression for 1 year [1]

Remember that the diagnosis of MS remains partly subjective and partly objective, and is best made by a neurologist with expertise in MS who is familiar with the disease, its differential diagnoses, and the interpretation of paraclinical assessments 1.