How do you diagnose multiple sclerosis?

Diagnosing Multiple Sclerosis

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 Based on Clinical Presentation

• Two or more attacks with objective clinical evidence of two or more lesions: No additional tests required for diagnosis, though MRI, CSF, or other tests would typically be abnormal if performed 1

• Two or more attacks with objective clinical evidence of one lesion: Requires demonstration of dissemination in space through:

  • MRI showing lesions in characteristic regions (periventricular, juxtacortical, infratentorial, spinal cord) 2
  • OR two or more MRI-detected lesions consistent with MS plus positive CSF 2
  • OR await further clinical attack implicating a different site 2

• One attack with objective clinical evidence of two or more lesions: Requires demonstration of dissemination in time through:

  • MRI showing new lesions on follow-up scan 2
  • OR a second clinical attack 2

• One attack with objective clinical evidence of one lesion: Requires demonstration of both dissemination in space and time 2

• Insidious neurological progression suggestive of MS: Requires positive CSF and demonstration of dissemination in space and time or continued progression for one year 2, 1

MRI Criteria

Dissemination in Space (DIS)

• Requires at least one typical MS lesion in at least two of these characteristic regions 2:
  • Periventricular (abutting the lateral ventricles)
  • Juxtacortical
  • Infratentorial
  • Spinal cord (cervical + thoracic)

Dissemination in Time (DIT)

• If first scan occurs ≥3 months after clinical event: presence of gadolinium-enhancing lesion (not at site of original event) demonstrates DIT 2
• If first scan is <3 months after clinical event: a second scan ≥3 months after clinical event showing new gadolinium-enhancing lesion provides evidence for DIT 2
• If no enhancing lesion is seen on second scan: a further scan not less than 3 months after first scan showing new T2 lesion or enhancing lesion will suffice 2

MRI Technical Requirements

• MRI studies should be performed on scanners with minimum field strength of 1.5 T 2
• Key sequences include T2-weighted and T1 post-gadolinium images of brain and spinal cord 2
• Spinal cord MRI significantly increases diagnostic yield (found in 83% of early MS patients) 3
• Lesions should be confirmed on multiple planes to avoid false positives/negatives 2
• Serial imaging supports diagnosis as MS is characterized by accrual of lesions over time 2

CSF Analysis

• Positive CSF is defined as oligoclonal IgG bands detected by isoelectric focusing that differ 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, in atypical presentations, or in older patients 1

Additional Diagnostic Tools

• Visual Evoked Potentials (VEP): Can provide objective evidence of a second lesion, particularly when the only clinically expressed lesion did not affect visual pathways 2, 1
• Fat-suppressed MRIs of optic nerves should be considered in atypical cases 2

Important Considerations and Pitfalls

• Alternative diagnoses must always be considered - if tests are negative or atypical, extreme caution should be taken before making an MS diagnosis 2, 1
• Differential diagnosis includes cerebral ischemia, infections (Lyme disease), paraneoplastic disorders, acute disseminated encephalomyelitis, neuromyelitis optica, and leukodystrophies 1, 4
• Special care needed in patients younger than 10 or older than 50 years, those with progressive onset, or unusual presentations 2, 1
• In patients older than 50 years or with vascular risk factors, more stringent criteria should be applied (e.g., higher number of periventricular lesions) 2
• Interpretation of MRI scans should be performed by trained neuroradiologists or clinicians familiar with MS features 2
• The quality of CSF analysis varies between laboratories - ensure testing is done with state-of-the-art technology 2, 1

Diagnostic Outcomes

• If criteria are fulfilled: diagnosis is MS 2
• If criteria are not completely met: diagnosis is "possible MS" 2
• If criteria are fully explored and not met: diagnosis is "not MS" 2

The diagnosis of MS has evolved significantly with each revision of diagnostic criteria, allowing for earlier diagnosis without compromising accuracy 5, 6. The 2017 McDonald criteria incorporate MRI as a fundamental tool with high sensitivity and accuracy, but inappropriate application may increase misdiagnosis risk, particularly with atypical presentations 7.