What are the diagnostic criteria for multiple sclerosis?

Diagnostic Criteria for Multiple Sclerosis

The diagnosis of Multiple Sclerosis (MS) is based on the McDonald criteria, which require demonstration of lesions in the central nervous system with dissemination in space (DIS) and time (DIT), with no better explanation for the clinical presentation. 1

Core Diagnostic Requirements

The diagnosis relies on three fundamental principles:

1. Objective evidence of dissemination in space and time
2. Exclusion of alternative diagnoses
3. Integration of clinical and paraclinical findings

Clinical Presentation-Based Diagnostic Requirements

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 [1]

Criteria for Dissemination in Space (DIS)

DIS requires at least three of the following:

• 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 1

Additionally:

• A lesion in the optic nerve is now considered an additional CNS area for DIS criteria
• Spinal cord lesions can replace brain lesions for DIS criteria 1

Criteria for Dissemination in Time (DIT)

DIT can be demonstrated by either:

• A 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 1

Imaging and Laboratory Support

MRI Requirements

• Imaging of the entire spinal cord is recommended when brain MRI criteria for DIS are not met
• Spinal cord lesions should be clearly hyperintense on T2-weighted images, at least 3mm but less than two vertebral segments long, and occupy only a portion of the cord cross-section 1

Cerebrospinal Fluid Analysis

CSF analysis provides supportive evidence when:

• 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 1

Visual Evoked Potentials (VEP)

VEPs may provide additional support when:

• MRI abnormalities are few (e.g., in primary progressive MS with progressive myelopathy)
• MRI abnormalities have lesser specificity (e.g., in older individuals with risk factors for microvascular ischemic disease) 2

Diagnostic Process

1. Evaluate clinical presentation for typical MS symptoms
2. Perform MRI of brain and spinal cord
3. Consider CSF analysis when MRI findings are insufficient or atypical
4. Perform VEP if necessary
5. Exclude alternative diagnoses 1

Important Considerations

• No distinction is made between symptomatic and asymptomatic MRI lesions for DIS and DIT 1
• Identical DIS criteria are used for primary-progressive MS and relapsing-remitting MS 1
• The diagnosis should be made by a neurologist with expertise in MS 1
• Biopsy is rarely needed but can confirm inflammatory demyelination when diagnosis remains uncertain 1

Differential Diagnosis

MS must be distinguished from conditions that can mimic its clinical or radiological features, including:

• Hypoxic-ischemic vasculopathy
• Inflammatory diseases and vasculitis
• Non-MS idiopathic inflammatory diseases
• Toxic, metabolic, and infectious diseases
• Neuromyelitis optica spectrum disorders 1

Diagnostic Pitfalls to Avoid

• Misdiagnosis remains a significant issue even at MS specialty centers 3
• A positive test for a putative MS "mimic" does not automatically exclude MS 4
• Diagnostic criteria should be applied cautiously in atypical presentations 3
• The McDonald criteria should result in a diagnosis of MS, possible MS, or not MS, avoiding older terms like "clinically definite" or "probable MS" 2

The diagnosis of MS remains partly subjective and partly objective, requiring careful clinical evaluation and judgment along with thorough differential diagnosis 1.