What is the management plan for multiple sclerosis (MS) manifestations?

Management of Multiple Sclerosis Manifestations

Initial Disease Classification and Risk Stratification

All patients with MS must be classified into one of four clinical phenotypes to guide treatment decisions: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), or clinically isolated syndrome (CIS). 1 RRMS accounts for approximately 85-90% of initial presentations and is characterized by clearly defined relapses with full or partial recovery between attacks. 2, 1 SPMS follows an initial relapsing-remitting course with progressive deterioration for at least six months, while PPMS (10-15% of cases) shows deterioration from onset without relapses. 2, 1

Baseline Diagnostic Evaluation

Before initiating treatment, obtain:

• Brain MRI with T2-weighted and gadolinium-enhanced T1-weighted sequences to establish baseline lesion burden and active inflammation 2
• Spinal cord MRI only if unexplained spinal symptoms are present, not for routine monitoring 2
• CSF analysis for oligoclonal bands and elevated IgG index to support diagnosis 2
• Visual evoked potentials if optic nerve involvement is suspected 2

Disease-Modifying Therapy Selection

For Relapsing-Remitting MS (First-Line Treatment)

Initiate disease-modifying therapy immediately upon diagnosis to reduce relapse rates and slow disability progression. 3, 4 The platform therapies include:

• Interferon beta preparations (IFNβ-1a or IFNβ-1b) are optimal first-line choices based on randomized controlled trial data 5
• Glatiramer acetate as an alternative platform therapy 5, 3
• Dimethyl fumarate 240 mg twice daily (after 7-day starter dose of 120 mg twice daily) reduces annualized relapse rate and new MRI lesions 6
• Teriflunomide or fingolimod as additional oral options 3

Escalation Strategy for Breakthrough Disease

If patients experience frequent or severe relapses (≥2 per year) or new MRI activity despite platform therapy, escalate to higher-efficacy agents rather than switching between platform therapies. 5, 3

Stage II (Acute Breakthrough):

• Add pulse corticosteroids (methylprednisolone 1000 mg IV daily for 3-5 days) to platform therapy 5, 4
• Continue platform disease-modifying therapy 5

Stage III (Continued Breakthrough):

• Natalizumab (monthly infusion) for highly active disease 3
• Alemtuzumab (induction therapy with annual courses) 3
• Ocrelizumab (twice-yearly infusion) 3
• Add immunosuppressants (cyclophosphamide or mitoxantrone) to platform therapy if biologics unavailable 5

For Primary Progressive MS

Ocrelizumab is the only FDA-approved therapy shown to slow disability progression in PPMS. 3 Other disease-modifying therapies have not demonstrated efficacy in this phenotype. 2

MRI Monitoring Protocol

Frequency Based on Disease Activity

For early RRMS and SPMS with active inflammation (80% of new lesions show gadolinium enhancement), perform MRI every 6-12 months. 2, 7

For PPMS with minimal inflammatory activity (only 5% of new lesions enhance), annual MRI is sufficient if clinically stable. 2, 7

For patients with breakthrough disease or on escalation therapy, increase MRI frequency to every 3-4 months. 7

Essential MRI Sequences

• T2-weighted sequences to detect new or enlarging lesions 2, 7
• Gadolinium-enhanced T1-weighted sequences to identify active inflammation (scan at least 5 minutes post-injection) 2, 7
• Use 5mm slice thickness with <25% interslice gap and 256x256 matrix 2
• Ensure identical positioning and coregistration between serial scans to accurately detect new lesions 2

Laboratory Monitoring for Safety

Dimethyl Fumarate Monitoring

• Obtain complete blood count before starting therapy 6
• Repeat CBC at 6 months, then every 6-12 months to monitor for lymphopenia 6
• Obtain liver function tests before therapy and as clinically indicated 6
• Discontinue if absolute lymphocyte count remains <0.5 x 10⁹/L for >6 months 6

Natalizumab Monitoring

• Test for JC virus antibody status before initiating and every 6 months during therapy 3
• Obtain brain MRI every 3-4 months for patients at high risk of progressive multifocal leukoencephalopathy (PML) - those who are JC virus positive, on therapy >2 years, or with prior immunosuppressant use 7, 6

Acute Relapse Management

Treat relapses with high-dose IV methylprednisolone 1000 mg daily for 3-5 days. 5, 4 Do not consider annual relapse rates of 0.59-0.84 on platform therapy as treatment failure - these are expected breakthrough events. 5

For patients who fail to respond to corticosteroids, consider plasmapheresis (5-7 exchanges over 10-14 days). 4

Symptomatic Management

Address specific manifestations:

• Spasticity: baclofen, tizanidine, or gabapentin 4
• Neuropathic pain: gabapentin, pregabalin, or duloxetine 4
• Fatigue: amantadine or modafinil 4
• Bladder dysfunction: anticholinergics for urgency, intermittent catheterization for retention 4
• Depression: SSRIs and cognitive behavioral therapy 4

Critical Safety Warnings

Discontinue dimethyl fumarate immediately if signs of anaphylaxis, angioedema, or PML develop (progressive weakness, vision changes, cognitive decline). 6

Permanently discontinue therapy and increase monitoring frequency to every 3 months if herpes zoster or other serious opportunistic infections occur. 7, 6

Monitor for liver injury symptoms (fatigue, anorexia, right upper quadrant pain, dark urine, jaundice) and check liver enzymes if suspected. 6

Common Pitfalls to Avoid

• Do not delay disease-modifying therapy initiation - early treatment improves long-term outcomes 3, 4
• Do not switch between platform therapies for mild breakthrough disease - escalate to higher-efficacy agents instead 5, 3
• Do not rely solely on MRI findings - always correlate with clinical assessment and disability measures 2
• Do not use inconsistent MRI protocols between follow-up scans as this makes comparison unreliable 7
• Do not restart stopped devices without guidance - this applies to any interrupted therapy requiring specialist consultation 7