What are the steps to diagnose and treat multiple sclerosis?

Diagnosing Multiple Sclerosis

Multiple sclerosis (MS) diagnosis 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

The diagnosis of MS follows a structured approach based on clinical presentation:

• Two or more attacks with objective clinical evidence of two or more lesions

  • No additional tests required for diagnosis 1
  • Though MRI, CSF analysis 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 showing characteristic lesions OR
    • Two or more MRI-detected lesions plus positive CSF OR
    • Awaiting further clinical attack implicating a different site 2, 1

• One attack with objective evidence of two or more lesions

  • Requires demonstration of dissemination in time through:
    • MRI showing new lesions OR
    • Second clinical attack 2, 1

• One attack with objective evidence of one lesion

  • Requires demonstration of both dissemination in space AND time 2, 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:

• 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 1

Dissemination in Time

Can be demonstrated by:

• Presence of gadolinium-enhancing lesion (not at site of original event) on scan performed ≥3 months after clinical event OR
• New T2 lesion on follow-up scan compared to baseline scan 2, 1

CSF Analysis

• Positive CSF defined as:

  • Oligoclonal IgG bands detected by isoelectric focusing that are different from any bands in serum, OR
  • Elevated IgG index 2, 1
  • Lymphocytic pleocytosis should be less than 50/mm³ 2

• CSF analysis is particularly helpful when:

  • Imaging criteria fall short
  • Clinical presentation is atypical
  • In older patients where MRI findings may lack specificity 2, 1

Visual Evoked Potentials (VEP)

• Abnormal VEP (delayed but with well-preserved waveform) can provide objective evidence of a second lesion
• Particularly useful when the only clinically expressed lesion did not affect visual pathways 2

Diagnostic Outcomes

After evaluation, the diagnosis will be one of:

• MS: When all criteria are fulfilled 1
• Possible MS: When criteria are not completely met 1
• Not MS: When criteria are fully explored and not met 1

Important Considerations and Pitfalls

• Alternative diagnoses must always be considered:

  • If MRI or CSF tests are negative or atypical, extreme caution should be taken before making an MS diagnosis 1
  • Key differential diagnoses include:
    • Cerebral ischemia/infarction in young adults (phospholipid antibody syndrome, lupus, CADASIL)
    • Infections (HTLV1, Lyme disease)
    • Paraneoplastic disorders
    • Acute disseminated encephalomyelitis
    • Neuromyelitis optica (Devic's syndrome)
    • Leukodystrophies 2

• Special populations require additional caution:

  • Patients younger than 10 or older than 59 years
  • Those with progressive onset
  • Unusual presentations (dementia, epilepsy, aphasia) 2

• Timing between clinical events and MRI scans is crucial for establishing dissemination in time 1

• Quality of CSF analysis varies between laboratories - ensure testing is done with state-of-the-art technology to avoid misdiagnosis 2

• Biopsy should rarely be undertaken, but can confirm inflammatory and demyelinating nature of lesions 2

• Incidental findings ("silent disease") discovered on imaging done for other purposes may require monitoring 2, 3

By following these diagnostic criteria and being mindful of potential pitfalls, clinicians can accurately diagnose MS and initiate appropriate management to reduce disability progression and improve quality of life.