What are the symptoms and diagnostic criteria for Multiple Sclerosis (MS)?

Diagnosis and Symptoms of Multiple Sclerosis

The diagnosis of MS requires demonstrating CNS lesions disseminated in both time and space through a combination of clinical presentation and MRI findings, with at least one clinical event consistent with acute demyelination being essential—MRI alone cannot diagnose MS. 1

Core Diagnostic Principle

The fundamental requirement is objective demonstration of CNS lesions separated in both time (dissemination in time, DIT) and space (dissemination in space, DIS), while excluding alternative diagnoses. 2, 1 No single clinical feature or diagnostic test is sufficient for diagnosis. 2

Clinical Presentations and Symptoms

Relapsing-Remitting MS (85% of cases at onset)

Acute neurological symptoms develop over hours to days, with the following typical presentations: 1

• Unilateral optic neuritis (vision loss, eye pain with movement)
• Partial myelitis (weakness, sensory level, bladder dysfunction)
• Sensory disturbances (numbness, tingling in limbs or trunk)
• Diplopia and internuclear ophthalmoplegia (double vision, impaired eye coordination)
• Balance and gait dysfunction (ataxia, vertigo)

Between attacks, patients remain stable but may experience fatigue and heat sensitivity. 3

Primary Progressive MS (15% of cases)

Steadily increasing neurological disability from onset without distinct relapses, often presenting as progressive myelopathy (gradual weakness and spasticity in legs, bladder dysfunction). 1, 4

Diagnostic Criteria by Clinical Scenario

The diagnostic approach varies based on presentation, with outcomes classified as MS, "possible MS," or "not MS" (the terms "clinically definite" and "probable MS" are no longer used): 2

Two or More Attacks with Objective Evidence of Two or More Lesions

No additional testing required for diagnosis, though MRI, CSF, or VEP would be expected to be abnormal if performed. 2 Critical caveat: If these tests are undertaken and negative, extreme caution is needed before diagnosing MS—alternative diagnoses must be considered. 2

Two or More Attacks with Objective Evidence of One Lesion

Requires demonstration of dissemination in space by: 2

• MRI showing specific criteria (see below), OR
• Two or more MRI lesions consistent with MS plus positive CSF (oligoclonal bands), OR
• Awaiting another clinical attack implicating a different site

One Attack with Objective Evidence of Two or More Lesions

Requires demonstration of dissemination in time by: 2

• MRI criteria for temporal dissemination (see below), OR
• A second clinical attack

One Attack with Objective Evidence of One Lesion

Requires both: 2

• Dissemination in space (by MRI or MRI plus positive CSF), AND
• Dissemination in time (by MRI or second clinical attack)

Insidious Neurological Progression (Primary Progressive)

Requires dissemination in space demonstrated by: 2

• Nine or more T2 brain lesions, OR
• Two or more spinal cord lesions, OR
• Four to eight brain lesions plus one spinal cord lesion, OR
• Abnormal visual evoked potential with four to eight brain lesions or fewer than four brain lesions plus one spinal cord lesion

PLUS dissemination in time by: 2

• MRI criteria for temporal dissemination, OR
• Continued progression for one year

MRI Criteria Specifics

Dissemination in Space (DIS)

Classic MS lesion features include: 1

• Focal T2 hyperintense lesions with sharp edges
• Ovoid or flame-shaped orientation perpendicular to ventricles (Dawson's fingers)
• Periventricular location

Dissemination in Time (DIT)

Two pathways exist: 2

If first MRI is ≥3 months after clinical event:

• A gadolinium-enhancing lesion (not at the original clinical site) demonstrates DIT, OR
• If no enhancing lesion, a follow-up scan at 3 months showing new T2 or gadolinium-enhancing lesion suffices

If first MRI is <3 months after clinical event:

• A second scan at ≥3 months showing new gadolinium-enhancing lesion demonstrates DIT, OR
• If no enhancing lesion at second scan, a third scan ≥3 months after the first showing new T2 or enhancing lesion suffices

MRI Activity Patterns by Subtype

• RRMS: Approximately 80% of new lesions show gadolinium enhancement (high inflammatory activity) 4
• PPMS: Only about 5% of new lesions enhance (low inflammatory activity) 4

Supportive Laboratory Findings

Cerebrospinal Fluid Analysis

Oligoclonal bands specific to CSF (not present in serum) or elevated IgG index support the diagnosis. 2, 1 This is particularly useful when MRI criteria are not fully met.

Visual Evoked Potentials

Delayed conduction with well-preserved waveform is characteristic of MS-related optic nerve involvement. 2, 1

Age Considerations

Diagnostic criteria apply best to individuals aged 10-59 years with typical presentations. 1 Outside this age range, alternative diagnoses should be more carefully considered.

Critical Diagnostic Pitfalls

Misdiagnosis remains a significant issue even at MS specialty centers. 5 Key safeguards include:

• Never diagnose MS on MRI alone—at least one clinical event is mandatory 1
• Exclude MS mimics systematically: neuromyelitis optica spectrum disorders (test for aquaporin-4 antibodies), acute disseminated encephalomyelitis, CNS vasculitis, infectious diseases (Lyme, syphilis), sarcoidosis, and structural lesions 6, 3
• If standard tests are negative in a patient with typical attacks, reconsider the diagnosis entirely 2
• Sequential MRIs of brain and spine are valuable when diagnosis is uncertain 5

Monitoring Strategy

Regular MRI monitoring evaluates disease activity and treatment response by assessing new T2 lesions and gadolinium-enhancing lesions. 1 This is essential for treatment decisions and detecting subclinical disease activity.