What is multiple sclerosis (MS)?

Multiple Sclerosis (MS): An Overview

Multiple sclerosis is a chronic autoimmune disease of the central nervous system characterized by inflammatory demyelination, resulting in focal lesions in both cerebral white and grey matter, with substantial brain volume loss occurring even in early stages. 1

Disease Characteristics

Pathophysiology

• MS is characterized by active inflammation evidenced by contrast-enhancing lesions on MRI and persistent inflammatory processes in the central nervous system 1
• The primary pathological hallmark is inflammatory demyelination with subsequent axonal damage 2
• Both T cells and B cells play crucial roles in disease pathology, with myeloid cells also contributing significantly 3

Epidemiology

• MS affects approximately 900,000 people in the United States 2
• Typically presents in young adults (ages 20-30 years) 2
• More common in women with a female-to-male ratio of nearly 3:1 2
• Prevalence ranges from 5 to 300 per 100,000 people, increasing at higher latitudes 2
• Overall life expectancy is reduced compared to the general population (75.9 vs 83.4 years) 2

Risk Factors

• Complex etiology involving:
  • Genetic susceptibility
  • Hormonal factors
  • Geographic location
  • Vitamin D deficiency (associated with increased MS risk) 1
  • Viral exposure 4

Clinical Presentation

Common Symptoms

• Symptoms vary based on the site of inflammation but commonly include:
  • Weakness
  • Sensory impairment
  • Vision loss (often unilateral optic neuritis)
  • Brainstem dysfunction including internuclear ophthalmoplegia
  • Back pain and leg tingling 1, 4

Disease Course

• Relapsing-Remitting MS (RRMS): Most common initial presentation, characterized by relapses with stable neurological disability between episodes 2
• Secondary Progressive MS (SPMS): Many RRMS patients transition to this phase with gradual disability accrual affecting gait, coordination, and bladder function 4
• Primary Progressive MS (PPMS): Affects approximately 10% of patients, progressive from onset 4

Diagnostic Evaluation

McDonald Criteria

• Diagnosis requires evidence of:
  1. Dissemination in space (damage in different parts of the nervous system)
  2. Dissemination in time (damage occurring at different times)
  3. No better explanation for the clinical presentation 1

Key Diagnostic Tests

• Brain MRI with and without contrast: To assess for T2 lesions, gadolinium-enhancing lesions, and rule out other pathologies 1
• Spine MRI with and without contrast: Particularly important with back pain and leg tingling 1
• Lumbar puncture: For cerebrospinal fluid analysis including oligoclonal bands 1, 2
• Laboratory tests: Complete blood count, comprehensive metabolic panel, and inflammatory markers 1

Treatment Approaches

Disease-Modifying Therapies (DMTs)

• Nine classes of DMTs are available for RRMS and SPMS with activity 1, 2:

  1. Interferons
  2. Glatiramer acetate
  3. Teriflunomide
  4. Sphingosine 1-phosphate receptor modulators
  5. Fumarates
  6. Cladribine
  7. Monoclonal antibodies (three types)
  8. Ocrelizumab (also approved for PPMS)

• DMTs reduce clinical relapses by 29-68% compared to placebo or active comparators 1, 2

Relapse Management

• High-dose corticosteroids (methylprednisolone 1g IV daily for 3-5 days) for acute relapses 1

Symptomatic Treatment

• Rehabilitation and energy conservation strategies for fatigue and weakness
• Physical therapy and medications for spasticity and gait problems
• Prophylactic antimicrobials for patients at high risk of infection 1

Complications and Comorbidities

• Increased infection risk: Particularly pneumococcal disease 1
• Neuroinflammatory complications: Including ME/CFS-like syndrome and dysautonomia 1
• Endocrine dysfunction: Hypothalamus-pituitary-adrenal axis abnormalities 1
• Ophthalmological complications: Including corneal small nerve fiber loss and retinal abnormalities 1
• Metabolic issues: Vitamin D deficiency associated with increased disease activity 1
• Exercise intolerance: Due to impaired oxygen consumption, reduced anaerobic threshold, and mitochondrial dysfunction 1

Follow-up and Disease Management

• Neurology follow-up within 1-2 weeks after relapse
• Repeat MRI in 3-6 months to assess for new lesions and treatment response
• Consider adjustment of disease-modifying therapy if relapse is confirmed 1
• Special vaccination considerations, particularly after treatments like autologous hematopoietic stem cell transplantation 1

Common Pitfalls

• Misattribution of symptoms: Not all neurological symptoms in MS patients are due to MS 1
• Delayed imaging: Prompt MRI with contrast is essential for accurate diagnosis 1
• Missing cerebral venous thrombosis: Can be life-threatening and requires prompt diagnosis 1
• Overlooking medication-related adverse events: Can lead to delayed diagnosis and treatment 1