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      Drugs & Diseases > Neurology

      Multiple Sclerosis Guidelines

      Updated: Jan 03, 2023
      • Author: Christopher Luzzio, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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      Guidelines

      Guidelines Summary

      Imaging

      The following organizations have issued guidelines for the use of imaging in the diagnosis of MS: [76, 143, 144, 145]

      • Consortium of Multiple Sclerosis Centers (CMSC)
      • MAGNIMS (Magnetic Resonance Imaging in MS) Network
      • European Academy of Neurology (EAN)

      Although MRI alone cannot be used to diagnose MS, all four guidelines (MAGNIMS has two) concur that it is the imaging procedure of choice for confirming MS and monitoring disease progression in the brain and spinal cord.

      Consortium of Multiple Sclerosis Centers (CMSC)

      CMSC revised guidelines recommend using higher-resolution three-dimensional (3D) imaging over two-dimensional (2D) imaging whenever possible. Recommended studies for patients with CIS or suspected MS include the following:

      Brain MRI protocol with gadolinium at baseline

      • Spinal cord MRI if transverse myelitis, inconclusive brain MRI, or age older than 40 with non-specific brain MRI findings
      • Cervical cord MRI performed simultaneously with brain MRI is advantageous in patients with or without transverse myelitis
      • Orbital MRI if severe optic neuritis with poor recovery

      Recommended schedules for follow-up brain MRI in patients with a CIS or suspected MS are as follows:

      • 6–12 months for high-risk CIS (≥2 ovoid lesions on first MRI)
      • 12–24 months for low-risk CIS (normal brain MRI findings) and/or uncertain clinical syndrome with suspicious brain MRI features (eg, radiologically isolated syndrome [RIS])

      Follow-up brain MRI with gadolinium is recommended for patients with an established diagnosis of MS in the following circumstances:

      • No recent prior imaging available (eg, patient with MS transferring to a new clinic)
      • Postpartum, to establish a new baseline
      • Prior to starting or switching disease-modifying therapy
      • Approximately 6 months after switching disease-modifying therapy, to establish a new baseline on the new therapy
      • Every 1–2 years while on disease-modifying therapy, to assess subclinical disease activity
      • In the event of unexpected clinical deterioration or reassessment of original diagnosis

      In addition, brain MRI is recommended to monitor for progressive multifocal leukoencephalopathy (PML) at the following intervals:

      • Every 12 months for patients negative for serum JC virus antibody
      • Every 3–6 months for patients positive for serum JC virus antibody treatment and treatment duration with natalizumab ≥18 months

      MAGNIMS (Magnetic Resonance Imaging in MS) Network

      In 2005, the MAGNIMS Network released two separate guidelines for use of MRI in MS. One covers diagnosis of suspected MS and the other covers use of MRI in disease monitoring.

      The MAGNIMS guidelines find currently available evidence insufficient to support the use of advanced MRI to establish the initial diagnosis or differential diagnosis of MS in patients with CIS. 

      Other recommendations include the following:

      • Spinal cord MRI should always be performed in patients with spinal cord symptoms at disease onset
      • Spinal cord MRI should be performed when brain MRI results are inconclusive, and for all patients with brain MRI suggestive for RIS

      The MAGNIMS guidelines recommend more frequent follow-up than the CMSC guidelines, as follows:

      • 3–6 months after baseline brain scan for patients with RIS or CIS and abnormal MRI
      • If the second brain scan is inconclusive, a third can be done 6-12 months later
      • Follow-up spinal cord MRI in patients with CIS, to demonstrate dissemination in space (DIS) and dissemination in time (DIT), has limited value and should not be done routinely

      The recommendation for monitoring of patients with established diagnosis of MS include the following:

      • T2-weighted and contrast-enhanced T1-weighted brain MRI are the modalities of choice for MS disease monitoring
      • The use of spinal cord MRI in addition to brain MRI is not recommended for routine monitoring  and should be limited to certain clinical situations (eg, unexplained and/or unexpected spinal cord symptoms)
      • Although assessment of brain volume does not have a role in the diagnosis of MS, it can be a good predictor of long-term disability
      • Rates of change in brain volume are not recommended as a marker of disease progression in individual patients, owing to the technical, biological and pharmacological factors that can influence the measurement and interpretation of atrophy rate
      • MRI should be included in drug monitoring to screen for opportunistic infections, unexpected disease activity (including paradoxical reactions), and comorbidities
      • In patients at high risk of developing opportunistic infections who are switching disease-modifying drugs (DMDs), brain MRI should be performed at the time the current treatment is discontinued and after the new treatment is started
      • Enhanced pharmacovigilance, including brain MRI every 3–4 months for up to 12 months, is required in patients who switch from natalizumab to other therapeutics (including fingolimod, alemtuzumab, and dimethyl fumarate)

      European Academy of Neurology (EAN)

      The 2011 guidelines from the European Academy of Neurology (EAN) offer no significant variance with the CMSC and MAGNIMS guidelines.

      Disease-modifying therapies

      Currently, most disease-modifying agents have been approved for use only in relapsing forms of MS. To address the need for early intervention, the Multiple Sclerosis Coalition developed a consensus document in 2014 to provide support for broader access to US Food and Drug Administration (FDA)-approved MS disease-modifying therapies. [146]  

      The guidelines recommend treatment with an FDA-approved disease-modifying agent as soon as possible after any of the following events:

      • Diagnosis of relapsing MS
      • First episode of neurologic symptoms with MRI findings consistent with MS, and other possible causes have been ruled out
      • Diagnosis of secondary-progressive MS (SPMS) but patient continues to have relapses and/or inflammatory changes on MRI

      The guidelines further recommend that treatment with any disease-modifying medication should be continued indefinitely, unless any of the following occur:

      • The patient or healthcare provider determines that the treatment is failing to adequately control the disease
      • The side effects are intolerable
      • The patient is unable to follow the recommended treatment regimen
      • A more appropriate treatment becomes available

      Additional recommendations include the following:

      • Switch from one disease-modifying treatment to another should only occur for medically appropriate reasons
      • When a medication is not providing adequate benefit, another agent with a different mechanism of action should be considered
      • Factors affecting choice of treatment are complex and should be addressed collaboratively by the patient and healthcare provider
      • Access to treatment should not be limited by frequency of relapses, level of disability, or personal characteristics such as age, gender, or ethnicity
      • Absence of relapses may indicate that the treatment is working and should not be considered a justification for discontinuing the treatment

      European Committee for Research and Treatment of Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN)

      In 2017, the ECTRIMS and EAN released the first set of guidelines on the use of disease-modifying therapies in multiple sclerosis. The European guidelines cover the treatment of adults with MS or clinically isolated syndrome (CIS), the monitoring of treatment response, the stopping and switching of treatment strategies, and treatment in special situations, such as pregnancy. There are 20 main recommendations. [147] Those with strong evidence include the following:

      • Offer interferon or glatiramer acetate to patients with CIS and abnormal MRI findings with lesions suggesting MS who do not fulfill full criteria for MS.
      • Offer early treatment with disease-modifying drugs in patients with active relapsing-remitting MS (RRMS), as defined by clinical relapses and/or MRI activity (active lesions: contrast-enhancing lesions; new or unequivocally enlarging T2 lesions assessed at least annually).
      • Offer a more efficacious drug to patients treated with interferon or glatiramer acetate who show evidence of disease activity.

      American Academy of Neurology (AAN) 

      Released in 2018, guidelines from the AAN on the use of disease-modifying therapies in patients with multiple sclerosis provide updated guidance on starting, switching, and stopping treatment and recommend an earlier start to treatment rather than later in the disease course. These guidelines are endorsed by the Multiple Sclerosis Association of America and the National Multiple Sclerosis Society. In all, 30 recommendations were developed: 17 on starting DMTs, 10 on switching from one therapy to another if breakthrough disease develops, and 3 on considerations related to stopping therapy. [148, 149, 150]

      Immunization

      In 2019, the American Academy of Neurology (AAN) issued guidelines for vaccine-preventable infections and immunization in multiple sclerosis. Recommendations include the following: [151]

      • Discuss the evidence regarding immunizations in MS with patients.
      • Recommend that MS patients follow all local vaccine standards, unless there are specific contraindications.
      • Recommend annual influenza vaccination to MS patients.
      • Counsel MS patients about infection risks associated with specific immunosuppressive/ immunomodulating (ISIM) medications and treatment-specific vaccination guidance according to prescribing information (PI).
      • Vaccinate patients with MS as needed at least 4–6 weeks before initiating ISIM therapy.
      • Screen for infections according to PI before initiating ISIM medications and treat patients testing positive for latent infections. In high-risk populations, screen for latent infections before starting ISIM therapy even when not specifically mentioned in PI.
      • Recommend against using live-attenuated vaccines in MS patients receiving ISIM therapies.
      • Delay vaccination in MS patients experiencing a relapse.
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