What are the diagnostic criteria and treatment options for multiple sclerosis (MS)?

Diagnostic Criteria for Multiple Sclerosis

Core Diagnostic Principle

The diagnosis of multiple sclerosis requires objective demonstration of CNS lesions disseminated in both space (DIS) and time (DIT), using a combination of clinical assessment and MRI findings, with exclusion of alternative diagnoses. 1

Clinical Presentations That Trigger Diagnostic Evaluation

MS typically presents in young adults aged 20-30 years with specific neurological syndromes developing over several days: 2

• Unilateral optic neuritis (vision loss, eye pain with movement)
• Partial myelitis (weakness, sensory level, bladder dysfunction)
• Brainstem syndromes (internuclear ophthalmoplegia, diplopia, vertigo)
• Sensory disturbances (numbness, tingling in limbs or trunk)
• Cerebellar symptoms (ataxia, tremor, dysmetria) 2, 3

MRI Criteria for Dissemination in Space (DIS)

Lesions must be detected in at least 2 of the following 5 CNS locations: 1

• Periventricular region (≥3 lesions required) 4
• Cortical/juxtacortical (white matter adjacent to cortex and/or cortical involvement) 4
• Infratentorial (brainstem, cerebellum)
• Spinal cord (whole cord imaging recommended)
• Optic nerve (added as fifth location in 2016 MAGNIMS guidelines) 4

Key MRI technical points: 4

• No distinction between symptomatic and asymptomatic lesions for DIS
• Cortical, leukocortical, and juxtacortical lesions combined into single category
• Spinal cord imaging particularly valuable when brain MRI insufficient

MRI Criteria for Dissemination in Time (DIT)

DIT can be demonstrated by either: 1

• Simultaneous presence of gadolinium-enhancing AND non-enhancing lesions on a single MRI scan, OR
• New T2 or gadolinium-enhancing lesion on follow-up MRI compared to baseline

This allows diagnosis from a single baseline MRI if both enhancing and non-enhancing lesions are present. 1

Cerebrospinal Fluid Analysis

CSF analysis showing oligoclonal bands (detected by isoelectric focusing) that differ from serum bands, or elevated IgG index, provides supportive evidence. 1

CSF is particularly valuable when: 1

• Clinical presentation is atypical
• MRI findings don't fully meet diagnostic criteria
• Patient has risk factors for microvascular disease that complicate MRI interpretation

Visual Evoked Potentials

VEPs showing delayed latency with preserved waveform provide additional diagnostic support, especially when: 1

• Few MRI abnormalities present
• MRI findings have reduced specificity (older patients with vascular risk factors)
• Optic nerve involvement suspected but not clearly demonstrated

Diagnostic Classification System

After evaluation, patients are classified as: 4, 1

• MS (criteria fully met)
• Possible MS (at risk but equivocal findings)
• Not MS (alternative diagnosis or insufficient evidence)

The outdated terms "clinically definite MS," "probable MS," "laboratory-supported definite MS," and "laboratory-supported probable MS" are no longer used. 4, 1

Clinical Phenotypes

Once MS is diagnosed, classify by disease course: 5

• Relapsing-Remitting MS (RRMS): Clearly defined relapses with recovery periods, no progression between attacks; ~80% show gadolinium enhancement on new lesions 5
• Secondary Progressive MS (SPMS): Initial relapsing-remitting course followed by progressive deterioration for ≥6 months 5
• Primary Progressive MS (PPMS): Progressive deterioration from onset without relapses; affects 10-15% of patients; only ~5% of new lesions enhance 5
• Clinically Isolated Syndrome (CIS): First episode suggestive of MS but not yet meeting full diagnostic criteria 5

Critical Diagnostic Caveats

Apply diagnostic criteria with caution in: 1, 3

• Atypical presentations (dementia, epilepsy, aphasia as presenting features)
• Patients with vascular risk factors where MRI white matter changes may be non-specific
• Older age at presentation (>50 years)
• Absence of typical MS symptoms

Common pitfalls to avoid: 2, 3

• Misdiagnosis remains significant even at MS specialty centers
• A positive test for an MS "mimic" does not exclude MS
• Biopsy can confirm inflammatory demyelination but cannot alone diagnose MS 1
• Sequential MRIs and laboratory tests help minimize misdiagnosis 6

Differential Diagnosis Considerations

The diagnosis requires exclusion of conditions that can mimic MS clinically and radiologically, though few conditions truly mimic MS on both fronts. 3 Thorough clinical evaluation remains fundamental despite advances in paraclinical testing. 7