How is Multiple Sclerosis (MS) diagnosed?

Diagnosing Multiple Sclerosis (MS)

The diagnosis of Multiple Sclerosis requires demonstrating lesions in the central nervous system with dissemination in space (DIS) and time (DIT), with no better explanation for the clinical presentation, following the McDonald criteria. 1

Diagnostic Criteria (McDonald Criteria)

The diagnostic approach depends on the 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

Key Definitions

• Attack (exacerbation, relapse): Episode of neurological disturbance lasting at least 24 hours 2
• Separation between attacks: At least 30 days between onset of first event and onset of second event 2

MRI Criteria

Dissemination in Space (DIS)

At least three of the following must be met 1:

• One or more gadolinium-enhancing lesions or nine T2-hyperintense lesions
• One or more infratentorial lesions
• One or more cortical/juxtacortical lesions
• Three or more periventricular lesions
• Lesion in the optic nerve (counts as an additional CNS area)

Dissemination in Time (DIT)

Can be demonstrated by 1:

• 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 point

Cerebrospinal Fluid Analysis

CSF analysis provides supportive evidence when 1:

• MRI criteria are insufficient
• MRI findings are non-specific
• Clinical presentation is atypical

A positive CSF finding is defined by:

• Oligoclonal IgG bands that differ from those in serum
• Elevated IgG index
• Lymphocytic pleocytosis of less than 50/mm³

Additional Diagnostic Tests

Visual Evoked Potentials (VEPs)

• Highly valuable for detecting demyelinating lesions in the optic pathways
• Delayed P100 latency is a sensitive indicator of demyelination
• Can detect subclinical optic nerve involvement even when routine ophthalmological examinations are normal 1

Spinal Cord Imaging

• Imaging of the entire spinal cord is recommended to define DIS, especially when brain MRI criteria are not met
• Spinal cord lesions should be 1:
  • Clearly hyperintense on T2-weighted images
  • At least 3 mm but less than two vertebral segments long
  • Occupy only a portion of the spinal cord cross-section

Differential Diagnosis

Consider these conditions that can mimic MS 2, 1:

• Vascular: Phospholipid antibody syndrome, lupus erythematosus, CADASIL, Takayasu's disease, meningovascular syphilis, carotid dissection
• Infectious: HTLV1, Lyme disease
• Inflammatory: Neuromyelitis optica spectrum disorders (test for NMO-IgG)
• Monophasic demyelinating diseases: Acute disseminated encephalomyelitis, postviral Devic's syndrome, acute transverse myelitis
• Other: Paraneoplastic disorders, leukodystrophies (especially in children and teenagers)

Important Considerations

1. No distinction is made between symptomatic and asymptomatic MRI lesions for DIS and DIT 1
2. The diagnosis remains partly subjective and partly objective, best made by a neurologist with expertise in MS 2, 1
3. Biopsy is rarely needed but can confirm inflammatory demyelination when diagnosis remains uncertain 1
4. MS typically presents in young adults (20-30 years) with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes 3
5. MS more commonly affects women (female to male ratio nearly 3:1) 3

Diagnostic Algorithm

1. Evaluate clinical presentation for typical MS symptoms
2. Perform brain and spinal cord MRI to assess DIS and DIT criteria
3. If MRI findings are insufficient or atypical, perform CSF analysis
4. Consider VEP if additional evidence is needed, particularly for optic pathway involvement
5. Rule out conditions that mimic MS
6. Apply McDonald criteria to determine if diagnosis is MS, possible MS, or not MS

The diagnosis of MS has significant implications for treatment and prognosis, with overall life expectancy less than the general population, so thoroughness in the diagnostic process is essential 1, 3.