What are the diagnostic criteria and treatment options for a patient suspected of having multiple sclerosis?

Multiple Sclerosis Diagnosis and Treatment

The diagnosis of multiple sclerosis (MS) requires evidence of inflammatory-demyelinating injury within the central nervous system that is disseminated in both time and space, with no better explanation for the clinical presentation. 1

Diagnostic Criteria

Clinical Presentations

• Two or more attacks with objective clinical evidence of two or more lesions does not require additional tests for MS diagnosis, though MRI, CSF, or other tests would typically be abnormal if performed 1
• Two or more attacks with objective evidence of one lesion requires demonstration of dissemination in space through MRI or CSF analysis 1
• One attack with objective evidence of two or more lesions requires demonstration of dissemination in time through MRI or a second clinical attack 1
• One attack with objective evidence of one lesion requires demonstration of both dissemination in space and time 1
• Insidious neurological progression suggestive of MS requires demonstration of dissemination in space and time or continued progression for one year 1

MRI Criteria

• Dissemination in space requires three of four of the following 1:

  • One gadolinium-enhancing lesion or nine T2-hyperintense lesions if no gadolinium enhancement
  • At least one infratentorial lesion
  • At least one juxtacortical lesion
  • At least three periventricular lesions
  • Note: One spinal cord lesion can substitute for one brain lesion

• Dissemination in time can be demonstrated by 1:

  • If first scan is ≥3 months after clinical event: presence of gadolinium-enhancing lesion (not at site of original event) or new T2 lesion on follow-up scan
  • If first scan is <3 months after clinical event: new gadolinium-enhancing lesion on second scan (≥3 months after event) or new T2 lesion on a third scan (≥3 months after first scan)

CSF Analysis

• Positive CSF is defined as oligoclonal IgG bands detected by isoelectric focusing that are different from any bands in serum, or elevated IgG index 1
• Lymphocytic pleocytosis should be less than 50/mm³ 1
• CSF analysis is particularly helpful when imaging criteria fall short or in atypical presentations 1

Visual Evoked Potentials (VEP)

• Abnormal VEP showing delayed but well-preserved waveform can provide evidence of a second lesion if the clinically expressed lesion did not affect visual pathways 1

Spinal Cord Imaging

• Spinal cord lesions should be 1:
  • Hyperintense on T2-weighted images
  • At least 3mm but less than two vertebral segments in length
  • Occupy only part of the cross-section of the cord
  • Have little or no swelling
• Spinal cord MRI increases diagnostic sensitivity in suspected MS cases 2
• Asymptomatic spinal cord lesions may occur and can help establish dissemination in space 2

Diagnostic Outcomes

• If criteria are fulfilled: diagnosis is MS 1
• If criteria are not completely met: diagnosis is "possible MS" 1
• If criteria are fully explored and not met: diagnosis is "not MS" 1

Treatment Options

Disease-Modifying Therapies (DMTs)

• Nine classes of DMTs are available for relapsing-remitting MS and secondary progressive MS with activity 3:
  • Interferons (e.g., interferon beta-1b) - reduce annual relapse rate and MRI lesions 4
  • Glatiramer acetate
  • Teriflunomide
  • Sphingosine 1-phosphate receptor modulators
  • Fumarates
  • Cladribine
  • Monoclonal antibodies (including natalizumab)
  • Ocrelizumab (also approved for primary progressive MS)

Monitoring for Treatment Complications

• For natalizumab treatment, patients must be monitored for Progressive Multifocal Leukoencephalopathy (PML) 5:
  • Anti-JCV antibody testing is recommended
  • MRI monitoring, especially for high-risk patients
  • Immediate discontinuation of treatment if PML is suspected
  • Symptoms of PML include progressive weakness, visual disturbances, and cognitive changes

Important Considerations and Pitfalls

• Alternative diagnoses must always be considered - if tests (MRI, CSF) are negative or atypical, extreme caution should be taken before making an MS diagnosis 1
• Reliance on MRI as the principal basis for diagnosis without appropriate clinical correlation can lead to error in up to one-third of cases 6
• The diagnosis of MS remains fundamentally clinical, supported by paraclinical tests 6
• Spinal cord imaging is particularly valuable in patients with primary progressive MS and those with isolated spinal cord syndromes 2
• Careful consideration of timing between clinical events and MRI scans is crucial for establishing dissemination in time 1