Multiple Sclerosis Management

Diagnosis and Assessment

• The 2017 McDonald Criteria, endorsed by the American Academy of Neurology, are used to diagnose MS, incorporating clinical evidence of attacks/progression, MRI findings, and laboratory findings, including CSF analysis for oligoclonal bands and evoked potentials 1
• Diagnosis of MS requires evidence of dissemination in space and time, which can be demonstrated through MRI or clinical attacks, as recommended by the National Institute of Neurological Disorders and Stroke 2
• Monosymptomatic presentations require evidence of dissemination in space through MRI or at least two brain lesions plus positive CSF, and evidence of dissemination in time through MRI or a second clinical attack, according to the Multiple Sclerosis International Federation 2
• The prevalence of Primary Progressive MS (PPMS) is approximately 5-10% of MS patients, with minimal asymptomatic disease activity, according to the Multiple Sclerosis Association of America 1

Imaging and Monitoring

• The American Academy of Neurology recommends conducting an MRI to assess new or enlarging lesions using T2-weighted FLAIR sequences, T2-weighted fast/turbo spin echo sequences, and Gadolinium-enhanced T1-weighted sequences (minimum 5-minute delay after contrast) 3
• Annual MRI monitoring is recommended to assess disease activity, even in the absence of clinical symptoms, with a protocol that includes T2-weighted FLAIR sequences, T2-weighted fast/turbo spin echo sequences, Gadolinium-enhanced T1-weighted sequences, and diffusion-weighted imaging (for patients at risk of PML) 3
• MRI follow-up should be conducted at least annually, more frequently (every 3-4 months) for patients at risk of serious treatment-related adverse events 3
• The following table summarizes MS subtypes and their characteristics:

1

Therapy and Treatment

• High-efficacy therapies such as natalizumab, ocrelizumab, and ofatumumab may be considered for highly active multiple sclerosis, reducing annual relapse rates by 29-68% compared to placebo, as recommended by the National Multiple Sclerosis Society, American Academy of Neurology, and other organizations 4, 5, 6
• Ocrelizumab is the only FDA-approved option for primary progressive MS, reducing clinical relapses and MRI lesions, as approved by the US Food and Drug Administration 5, 1
• Mavenclad (cladribine) is a deoxyadenosine analogue prodrug that preferentially depletes lymphocytes, demonstrating efficacy in highly active relapsing MS, as recommended by the National Multiple Sclerosis Society 4
• Autologous hematopoietic stem cell transplantation (AHSCT) can be considered for patients who have failed ≥1 high-efficacy disease-modifying therapy with poor prognostic factors, as suggested by the National Institute of Neurological Disorders and Stroke 4

Safety Monitoring and Adverse Effects

• Enhanced pharmacovigilance, including brain MRI every 3-4 months for up to 12 months, is required when switching from natalizumab to other therapeutics (fingolimod, alemtuzumab, dimethyl fumarate) 3
• For patients on natalizumab, JCV antibody status should guide monitoring frequency, with JCV positive patients requiring MRI every 3-4 months and JCV negative patients requiring annual MRI 3
• The risk of progressive multifocal leukoencephalopathy (PML) with natalizumab is stratified by anti-JCV antibody status, with negative status indicating lower risk and positive status indicating higher risk, as outlined by the Journal of Neurology, Neurosurgery and Psychiatry 5
• When switching therapies, healthcare providers should be aware of potential drug-related adverse effects that can occur at discontinuation or several months after starting a new treatment 3

Vaccinations and Infections

• Complete hepatitis B vaccination is recommended before starting potent MS therapy, with vaccines administered 4-6 weeks before starting or 4-6 months after ending certain treatments, as advised by the Centers for Disease Control and Prevention and American College of Neurology 1, 7, 8, 6
• Patients should have no concurrent use of live vaccines, having received appropriate vaccinations including COVID-19, shingles, flu, and RSV vaccines, as recommended by the American Academy of Neurology 8

Outcome Assessment and Follow-up

• Regular assessment using Expanded Disability Status Scale (EDSS) is recommended, and consider combining EDSS with Multiple Sclerosis Functional Composite (MSFC) for better sensitivity, according to the Nature Reviews Neurology 4
• Cognitive outcomes and patient-reported outcomes, including fatigue and quality of life measures, should be systematically assessed, as recommended by the Nature Reviews Neurology 4
• Early identification and treatment during the first 2-10 years of symptom onset is critical to prevent long-term disability and improve patient outcomes in multiple sclerosis, as suggested by the National Multiple Sclerosis Society 4
• Delaying treatment or underestimating subclinical disease activity can lead to worse outcomes, highlighting the importance of early intervention and regular monitoring in multiple sclerosis, as recommended by the National Institute of Neurological Disorders and Stroke 3