Multiple sclerosis secondary prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D., Julinka Auta Fernandes

There is no single secondary-prevention intervention appropriate for every person at risk of multiple sclerosis. Secondary prevention focuses on people who already have objective evidence suggesting early central nervous system demyelination but remain asymptomatic or have experienced only a first clinical demyelinating event.

The principal strategies are risk assessment, structured clinical and magnetic resonance imaging surveillance, and timely consideration of disease-modifying treatment in appropriately selected patients. The goals are to delay a first or subsequent clinical demyelinating event and to reduce new MRI disease activity.^[1]

Secondary-prevention strategies may be considered for:

• People with incidental MRI lesions compatible with inflammatory demyelination but without a previous MS-typical clinical event.
• People following a first clinical demyelinating event when MRI findings suggest an increased likelihood of further inflammatory disease activity.
• People with suggestive clinical or MRI findings who do not currently meet the diagnostic criteria for MS and therefore require structured surveillance.

Some people previously classified as having radiologically isolated syndrome (RIS) may satisfy the 2024 revised McDonald criteria for MS. Their diagnostic status should therefore be reassessed under the current criteria before preventive treatment or surveillance is selected.^[2]

Factors associated with a greater risk of a near-term clinical manifestation or additional inflammatory disease activity include:^[1][3]

• Younger age
• A high burden of characteristic demyelinating lesions
• Gadolinium-enhancing lesions
• Spinal cord or infratentorial lesions
• New or unequivocally enlarging lesions on follow-up MRI
• Intrathecal immunoglobulin synthesis demonstrated by cerebrospinal fluid-restricted oligoclonal bands or an elevated cerebrospinal-fluid kappa free-light-chain index

These factors should be considered together rather than used individually to determine whether preventive intervention is appropriate.^[1]

For people with incidental MRI abnormalities suggestive of demyelination, or suggestive symptoms in whom MS cannot be diagnosed and immunotherapy is not initiated, the Deutsche Gesellschaft für Neurologie (DGN; German Neurological Society) living guideline recommends clinical assessment together with brain and spinal-cord MRI after approximately 6 months and, when appropriate, subsequently every 12 months.^[1]

The interval should be individualized according to the initial findings and estimated risk. A new clinical demyelinating event, a new or enlarging lesion on transverse relaxation time–weighted (T2-weighted) imaging, or a contrast-enhancing lesion should prompt earlier reassessment.^[1]

Following a first clinical demyelinating event, American and European guidelines support timely consideration of disease-modifying treatment when MRI demonstrates lesions characteristic of MS and the anticipated benefit outweighs the treatment risks.

The American Academy of Neurology recommends discussing the benefits and risks of disease-modifying treatment with people who have experienced a single clinical demyelinating event and have two or more characteristic brain lesions. Treatment should be offered when the patient elects to begin therapy following shared decision-making.^[4]

The joint European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/European Academy of Neurology (EAN) guideline similarly supports early disease-modifying treatment following a clinically isolated syndrome when MRI abnormalities are suggestive of MS.^[5]

The Assessment of Tecfidera in Radiologically Isolated Syndrome (ARISE) and Teriflunomide in Radiologically Isolated Syndrome (TERIS) randomized trials demonstrated that selected disease-modifying treatments can delay a first clinical demyelinating event in participants meeting earlier RIS definitions.^[6][7]

These trial results do not support routine immunotherapy for every person with incidental demyelinating-appearing lesions. The DGN living guideline states that treatment may be considered when incidental lesions satisfy the 2024 McDonald criteria, the person desires treatment, and high-risk features suggest a near-term clinical manifestation. When the 2024 criteria are not fulfilled, immediate immunotherapy should not be initiated solely for the incidental lesions; structured clinical and MRI surveillance is recommended instead.^[1]

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