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

Multiple Sclerosis Diagnostic Criteria

MS diagnosis requires demonstration of dissemination in space (DIS) and dissemination in time (DIT) of CNS inflammatory-demyelinating lesions, with exclusion of alternative diagnoses that better explain the clinical presentation. 1, 2

Core Diagnostic Framework

The diagnostic approach depends on the clinical presentation pattern, with MRI serving as the primary paraclinical tool integrated with clinical findings 1:

Clinical Presentation Categories

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

• MS diagnosis can be made on clinical grounds alone 1
• No additional testing required if clinical evidence is clear
• MRI, CSF, or visual evoked potentials should be performed to confirm typical MS findings and exclude alternative diagnoses 1

Two or More Attacks with Objective Clinical Evidence of One Lesion

• Requires demonstration of DIS through MRI or alternative paraclinical evidence 1
• MRI must show lesions meeting specific spatial distribution criteria (see DIS criteria below) 1
• Alternatively, ≥2 brain lesions or 1 brain + 1 spinal cord lesion consistent with MS plus abnormal CSF can document DIS 1

One Attack with Objective Clinical Evidence of Two or More Lesions

• Requires demonstration of DIT 1
• Can be fulfilled by MRI showing simultaneous gadolinium-enhancing and non-enhancing lesions, or new T2/enhancing lesions on follow-up MRI 2
• Minimum 3-month interval required between clinical event and new lesion detection to avoid misdiagnosing acute disseminated encephalomyelitis 1

One Attack with Objective Clinical Evidence of One Lesion (Clinically Isolated Syndrome)

• Requires demonstration of both DIS and DIT 1
• Most challenging diagnostic scenario requiring comprehensive MRI evaluation 1
• CSF-specific oligoclonal bands can substitute for DIT criterion in presence of typical MRI lesion distribution per 2017 McDonald criteria 2, 3

Insidious Neurological Progression (Primary Progressive MS)

• Requires abnormal CSF showing inflammation/immune abnormality, plus evidence of DIS and DIT 1
• DIT can be demonstrated by MRI or continued progression of disability for 1 year 1
• Recent data suggest 2017 McDonald RRMS DIS criteria perform well for PPMS diagnosis (sensitivity 92.9-95.4%, specificity 95%) 4

MRI Criteria for Dissemination in Space (DIS)

DIS requires lesions in ≥2 of 5 characteristic CNS regions 1:

The Five CNS Regions (MAGNIMS 2016 Modifications)

1. Periventricular: ≥3 lesions required (not just 1) 1
2. Cortical/Juxtacortical: Combines intracortical, leukocortical, and juxtacortical lesions into single category since conventional MRI cannot reliably distinguish them 1
3. Infratentorial: Brainstem or cerebellar lesions 1
4. Spinal cord: Whole spinal cord imaging recommended, particularly when brain MRI doesn't fulfill DIS 1
5. Optic nerve: Added as fifth region (increased from 4 to 5 total regions) 1

Key DIS Clarifications

• No distinction between symptomatic and asymptomatic MRI lesions 1, 3
• Spinal cord lesions present in 30-40% of clinically isolated syndrome patients without spinal symptoms 2
• One spinal cord lesion can substitute for one brain lesion 1

MRI Criteria for Dissemination in Time (DIT)

DIT can be demonstrated by 1, 2:

• Simultaneous presence of gadolinium-enhancing and non-enhancing lesions on single MRI (most efficient method) 2
• New T2 or gadolinium-enhancing lesions on follow-up MRI compared to baseline 2
• CSF-specific oligoclonal bands can substitute for DIT requirement per 2017 McDonald criteria 2, 3

Important DIT Considerations

• Non-enhancing black holes are not useful for demonstrating DIT in adults 1
• Minimum 3-month interval between clinical event and new lesion detection recommended 1

Essential Complementary Evaluations

Complete spinal cord MRI is recommended even without spinal symptoms, as 30-40% of CIS patients have asymptomatic cord lesions 2

Lumbar puncture should be performed when 2:

• MRI criteria are borderline or limited
• Differential diagnosis requires exclusion
• Seeking to establish DIT through oligoclonal bands (per 2017 McDonald criteria) 3
• Look for oligoclonal bands and elevated IgG index 2

Anti-aquaporin-4 antibody testing is mandatory to exclude neuromyelitis optica spectrum disorders (NMOSD), which requires different treatment 2, 3

Critical Diagnostic Pitfalls

Never diagnose MS based solely on MRI findings without clinical correlation 2:

• Non-specific white matter lesions can be vascular or metabolic in origin 2
• Radiologically isolated syndrome (incidental MRI findings) requires at least one clinical event compatible with acute demyelination before MS diagnosis 2, 3

Always exclude important differential diagnoses 1, 2:

• NMOSD (anti-aquaporin-4 antibodies) 2, 3
• MOG antibody-associated disease 3
• Vascular disorders (especially in older patients with vascular risk factors) 2
• Infectious diseases (Lyme, HIV, syphilis)
• Metabolic disorders (B12 deficiency, mitochondrial disorders)
• Other inflammatory CNS diseases (sarcoidosis, Behçet's)

Exercise extreme caution when 1:

• Clinical presentation is atypical for MS
• MRI findings are not typical in distribution or morphology 1
• Patient age <11 years (use serial clinical and MRI evaluation rather than relying solely on baseline criteria) 1

Special Populations

Pediatric patients ≥11 years with non-ADEM presentation: Use identical DIS and DIT criteria as adults 1

Pediatric patients <11 years: Exercise caution with 2010 criteria at baseline; serial clinical and MRI evaluation over time is particularly important 1

Asian and Latin American populations: Identical DIS and DIT criteria apply once alternative conditions (especially NMOSD) are carefully excluded 1