How is Multiple Sclerosis (MS) diagnosed?

Diagnosis of Multiple Sclerosis

Multiple sclerosis (MS) is diagnosed based on demonstrating evidence of inflammatory-demyelinating lesions within the central nervous system that are disseminated in both time and space, with no better explanation for the clinical presentation. 1 This diagnostic approach relies on a combination of clinical presentation, neuroimaging findings, and sometimes laboratory tests.

Diagnostic Criteria

The diagnosis follows the McDonald criteria, which focus on:

1. Dissemination in Space (DIS) - Lesions in multiple areas of the CNS
2. Dissemination in Time (DIT) - Evidence that lesions occurred at different times
3. No better explanation for the clinical presentation

Clinical Presentations and Required Evidence

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 Diagnostic Tools

MRI (Primary Diagnostic Tool)

MRI evidence must show at least three of the following 1:

• One or more gadolinium-enhancing lesions or nine T2 hyperintense lesions
• One or more infratentorial lesions
• One or more juxtacortical lesions
• Three or more periventricular lesions

For demonstrating DIT by MRI:

• If the first scan occurs 3+ months after clinical onset, the presence of a gadolinium-enhancing lesion (not at the site of the original clinical event) is sufficient
• If the first scan is within 3 months of clinical onset, a follow-up scan showing a new T2 or gadolinium-enhancing lesion is required

Cerebrospinal Fluid (CSF) Analysis

CSF analysis is particularly important when clinical and MRI evidence is insufficient or atypical 1. Positive CSF findings include:

• Oligoclonal bands detected by established methods (preferably isoelectric focusing) that differ from any bands in serum
• Raised IgG index

Visual Evoked Potentials (VEP)

VEP can provide additional support, particularly in situations where 2:

• MRI abnormalities are few (e.g., in patients with primary progressive MS with progressive myelopathy)
• MRI abnormalities have lesser specificity (e.g., in older individuals with risk factors for microvascular ischemic disease)

Definition of an "Attack"

An "attack" (exacerbation, relapse) refers to 2:

• An episode of neurological disturbance typical of MS
• Duration of at least 24 hours
• Objective clinical findings of a lesion are required (not just subjective reports)
• Separate attacks should be at least 30 days apart (from onset to onset)

Common Pitfalls and Caveats

1. Misdiagnosis risk: Despite improved criteria, misdiagnosis remains a significant issue even at MS specialty centers 3. Careful application of diagnostic criteria is essential.

2. Differential diagnosis: Many conditions can mimic MS clinically or radiologically, but few truly mimic both aspects 4. A positive test for a putative MS "mimic" does not automatically exclude MS.

3. Clinical judgment: The diagnosis of MS remains partly subjective and partly objective, and is best made by a neurologist with expertise in MS 1.

4. Biopsy: Rarely needed but can confirm inflammatory demyelination when diagnosis remains uncertain despite thorough evaluation 1.

5. Pseudoattacks: Clinical assessment must rule out pseudoattacks caused by changes in core body temperature or infection 2.

6. Paroxysmal episodes: Single paroxysmal episodes (e.g., a tonic spasm) do not constitute a relapse, but multiple episodes occurring over not less than 24 hours do 2.

Diagnostic Process Algorithm

1. Evaluate clinical presentation for typical MS symptoms:

   • Unilateral optic neuritis
   • Partial myelitis
   • Sensory disturbances
   • Brainstem syndromes
   • Typical age of onset (20-30 years)

2. Perform MRI of brain and spinal cord to look for characteristic lesions and assess for gadolinium enhancement

3. Consider CSF analysis if:

   • Clinical presentation is atypical
   • MRI findings are insufficient or equivocal
   • Alternative diagnoses are strongly considered

4. Perform VEP if:

   • Clinical history suggests optic nerve involvement
   • Need to demonstrate additional evidence of dissemination

5. Apply McDonald criteria to determine if diagnosis is:

   • MS (criteria fully met)
   • Possible MS (criteria not completely met)
   • Not MS (criteria fully explored and not met)

The diagnostic process should be thorough, as MS is a diagnosis with significant implications for treatment and prognosis, with an overall life expectancy less than the general population (75.9 vs 83.4 years) 5.