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

Initial Workup for Suspected Multiple Sclerosis (MS)

The initial diagnostic workup for a patient suspected of having Multiple Sclerosis should include brain and spinal cord MRI, cerebrospinal fluid analysis, and blood tests to rule out alternative diagnoses. 1

Imaging Studies

Brain MRI

• Brain MRI is the most important paraclinical tool for MS diagnosis due to its high sensitivity in detecting demyelinating plaques 1
• A standardized protocol should include:
  • 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 1
• Gadolinium contrast (0.1 mmol/kg body weight) should be administered with a minimum delay of 5 minutes after injection 1
• MRI findings should be evaluated for dissemination in space (DIS) and dissemination in time (DIT) according to the McDonald Criteria 1

Spinal Cord MRI

• Spinal cord MRI is recommended even in patients without spinal symptoms as asymptomatic cord lesions are found in 30-40% of patients with clinically isolated syndrome 1
• Indications for spinal cord MRI include:
  • 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
  • Suspected primary progressive MS 1
• The standardized protocol should include:
  • Sagittal dual-echo (proton-density and T2-weighted) conventional/fast spin-echo
  • Sagittal STIR (short-tau inversion recovery)
  • Contrast-enhanced T1-weighted spin-echo (if T2 lesions are present) 1

Laboratory Studies

Cerebrospinal Fluid Analysis

• CSF examination is primarily used to rule out other causes of neurological symptoms 1
• Key CSF findings in MS include:
  • Albumino-cytological dissociation (elevated CSF protein with normal cell count)
  • Oligoclonal bands detected by isoelectric focusing that are not present in serum
  • Elevated IgG index 1, 2
• Note that protein levels may be normal in 30-50% of patients in the first week after disease onset 1
• Marked pleocytosis (>50 cells/μl) suggests alternative diagnoses 1

Blood Tests

• Complete blood count (CBC)
• Blood chemistry including glucose, electrolytes, kidney function (BUN, creatinine), and liver enzymes
• These tests primarily help exclude other causes of neurological symptoms 1
• Additional specific tests may be ordered based on the differential diagnosis 1

Additional Diagnostic Tests

Visual Evoked Potentials (VEP)

• VEP can provide evidence of a second lesion in patients with a single clinical manifestation 1
• Abnormal VEP in MS typically shows delay with a well-preserved waveform 1

Electrodiagnostic Studies

• While not required for MS diagnosis, these studies can support the diagnosis, particularly in atypical presentations 1
• Findings may include reduced conduction velocities, reduced sensory and motor evoked amplitudes, and abnormal temporal dispersion 1
• Note that results may be normal early in the disease course (within 1 week of symptom onset) 1

Diagnostic Criteria

• The diagnosis of MS relies on demonstrating evidence of inflammatory-demyelinating injury that is disseminated in both time and space 3
• The 2017 McDonald Criteria (updated from 2010) are the standard for MS diagnosis 1, 4
• Diagnosis requires:
  • Two or more attacks with objective clinical evidence of two or more lesions, or
  • Two or more attacks with objective clinical evidence of one lesion plus dissemination in space demonstrated by MRI or positive CSF, or
  • One attack with objective clinical evidence of two or more lesions plus dissemination in time, or
  • One attack with objective clinical evidence of one lesion plus dissemination in space and time 1

Differential Diagnosis Considerations

• MRI "red flags" that suggest diagnoses other than MS should be carefully evaluated 5
• Important differential diagnoses include:
  • Neuromyelitis optica spectrum disorders (NMOSD) - characterized by aquaporin-4 antibodies and longitudinally extensive transverse myelitis 1
  • Other inflammatory/autoimmune conditions
  • Vascular disorders
  • Infectious diseases
  • Metabolic disorders 5, 3

Common Pitfalls to Avoid

• Relying solely on MRI findings without clinical correlation can lead to misdiagnosis 1, 5
• Non-standardized MRI examinations with inadequate quality may yield inaccurate results 1
• Failure to consider alternative diagnoses when "red flags" are present 5
• Interpreting MRI without consideration of relevant clinical and laboratory data 1
• Diagnosing MS based on radiologically isolated syndrome (RIS) findings alone - at least one clinical event consistent with acute demyelination remains essential for MS diagnosis 1

By following this comprehensive diagnostic approach, clinicians can accurately diagnose MS while appropriately ruling out conditions that may mimic this disease.