What are the typical presentation and treatment options for Multiple Sclerosis (MS)?

Presentation and Treatment of Multiple Sclerosis (MS)

Typical Presentation of MS

Multiple sclerosis typically presents in young adults (ages 20-30) with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. 1 The disease disproportionately affects women with a female-to-male ratio of approximately 3:1.

The clinical presentation varies based on MS subtype:

• Relapsing-Remitting MS (RRMS): Most common initial presentation (80-85% of cases)

  • Characterized by clearly defined attacks (relapses) followed by partial or complete recovery (remissions)
  • High asymptomatic disease activity on MRI
  • 80% of new lesions show gadolinium enhancement 2

• Secondary Progressive MS (SPMS):

  • Follows an initially relapsing-remitting course
  • Progressive deterioration for at least six months, with or without superimposed relapses 3
  • Moderate asymptomatic disease activity on MRI

• Primary Progressive MS (PPMS):

  • Deterioration from disease onset without relapses or remissions
  • Accounts for only 5-10% of MS patients
  • Minimal asymptomatic disease activity with only 5% of new lesions showing gadolinium enhancement 3, 2

• Clinically Isolated Syndrome (CIS):

  • First clinical episode with features suggestive of MS
  • Requires evidence of dissemination in space and time for MS diagnosis 3

Diagnostic Criteria

Diagnosis of MS requires:

1. Dissemination of lesions in space and time 3
2. No better explanation for clinical presentation

The 2017 McDonald Criteria incorporate:

• Clinical evidence of attacks/progression
• MRI findings:
  • T2-weighted sequences (more sensitive than T1 for lesion detection)
  • Gadolinium enhancement (indicates active inflammation)
  • Specific protocols for demonstrating dissemination in space and time 3, 2
• Laboratory findings:
  • CSF analysis for oligoclonal bands
  • Evoked potentials (particularly in cases with progressive onset)

For monosymptomatic presentations, diagnosis requires:

1. Evidence of dissemination in space through MRI or at least two brain lesions plus positive CSF
2. Evidence of dissemination in time through MRI or a second clinical attack 3

Treatment Options

Disease-Modifying Therapies (DMTs)

Early treatment with high-efficacy therapies should be initiated within the first 2-10 years of symptom onset to prevent long-term disability and improve outcomes. 2, 4

DMTs are approved for:

• Relapsing forms of MS (including CIS, RRMS, and active SPMS)
• Primary progressive MS (limited options)

FDA-approved options include:

1. Interferons:

   • Interferon beta-1a (IM) 5
   • Interferon beta-1b (IM) 6
   • Reduce annual relapse rates by 29-68% compared to placebo 1

2. High-Efficacy Therapies:

   • Natalizumab: Indicated as monotherapy for relapsing forms of MS 7
     • Caution: Increases risk of PML; requires JCV antibody testing every 6 months 2
   • Ocrelizumab: Only FDA-approved option for primary progressive MS 2
   • Ofatumumab: Approved for relapsing forms of MS 2

3. Other DMTs:

   • Glatiramer acetate
   • Teriflunomide
   • Sphingosine 1-phosphate receptor modulators
   • Fumarates
   • Cladribine (Mavenclad): Effective for highly active relapsing MS 2

4. Advanced Therapies:

   • Autologous hematopoietic stem cell transplantation (AHSCT): Consider for patients who have failed ≥1 high-efficacy DMT with poor prognostic factors 2

Symptomatic Management

• Acute relapses: Intravenous methylprednisolone for 3 days 8
• Adjunctive therapies:
  • Plasma exchange for severe cases
  • Intravenous immunoglobulin (IVIg) as part of combination therapy 2
• Symptom-specific treatments for:
  • Spasticity
  • Paresthesias
  • Tremor
  • Erectile dysfunction
  • Depression and anxiety
  • Fatigue
  • Pain 8

Monitoring and Assessment

• Annual MRI monitoring is recommended even in the absence of clinical symptoms 2

  • Protocol should include:
    • T2-weighted FLAIR sequences
    • T2-weighted fast/turbo spin echo sequences
    • Gadolinium-enhanced T1-weighted sequences
    • Diffusion-weighted imaging (for patients at risk of PML)

• Regular clinical assessment using:

  • Expanded Disability Status Scale (EDSS)
  • Multiple Sclerosis Functional Composite (MSFC) for better sensitivity
  • Cognitive assessments
  • Patient-reported outcomes including fatigue and quality of life measures 2

Important Considerations

• Vaccination: Complete hepatitis B vaccination before starting potent MS therapy; avoid live vaccines 2

• JCV antibody testing: Required for patients on natalizumab; negative status indicates lower risk of PML 2

• Pregnancy: Reduces disease activity during gestation, but higher risk of relapse in the postpartum period 8

• Life expectancy: Overall reduced compared to general population (75.9 vs 83.4 years) 1