What is Multiple Sclerosis (MS)?
Multiple sclerosis is a chronic, inflammatory, and autoimmune disease of the central nervous system that causes widespread focal degradation of the myelin sheath, variable axonal and neuronal injury, and progressive disability in young adults. 1
Disease Mechanism and Pathophysiology
MS originates from complex interactions between genetic susceptibility, environmental factors, and immunological mechanisms that lead to activation and migration of pro-inflammatory B cells and T cells into the central nervous system. 2 The disease is characterized by:
- Autoimmune-mediated inflammatory demyelination with axonal transection throughout the CNS 3
- Dysregulation of T-cells (Th1 and Th17 subsets) and B-cells that mount an autoimmune attack on myelin 4
- Progressive neurodegeneration and axonal damage that occurs alongside the inflammatory process 4
- Strong evidence implicating Epstein-Barr virus (EBV) as a key environmental trigger leading to immune dysregulation 2
Clinical Forms and Natural History
MS presents in two main clinical patterns that determine prognosis and treatment approach:
Relapsing-Remitting MS (RRMS)
- Affects approximately 85% of patients at disease onset 1
- Characterized by acute episodes of neurological dysfunction developing over hours to days, followed by spontaneous stabilization and resolution 5
- Nerve impulse conduction is affected during acute inflammatory phases (relapses) but tends to improve with healing during remission 1
- Over time, relapses cause extensive myelin damage and scarring with progressive loss of neuronal function 1
- The majority of RRMS patients eventually progress to secondary progressive MS (SPMS) 6
Primary Progressive MS (PPMS)
- Affects approximately 15% of patients 1
- Presents with steadily increasing neurological disability from onset, often as progressive myelopathy 5
- No distinct relapses or remissions occur 5
- Characterized by progressive neurological damage rather than relapsing-remitting pattern 1
Epidemiology and Demographics
- Affects an estimated 900,000 people in the United States and approximately 2.8 million people worldwide 3, 6
- Typically presents in young adults with mean age of onset 20-30 years 3
- More commonly affects women with a female-to-male ratio of nearly 3:1 3
- Prevalence worldwide ranges from 5 to 300 per 100,000 people, increasing at higher latitudes 3
- Overall life expectancy is reduced compared to the general population (75.9 vs 83.4 years) 3
Typical Clinical Presentations
MS typically presents with:
- Unilateral optic neuritis (inflammation of the optic nerve causing vision loss) 3
- Partial myelitis (spinal cord inflammation) 3
- Sensory disturbances including numbness and tingling 3
- Brainstem syndromes such as internuclear ophthalmoplegia (eye movement abnormality) 3
- Motor weakness, balance difficulties, and visual problems 7
These symptoms develop over several days during acute relapses. 3
Associated Complications
Weight loss, malnutrition, and even cachexia are well-recognized features of MS patients. 1 The causes include:
- Reduced mobility and fatigue 1
- Inappropriate diet and physical difficulty eating or drinking 1
- Poor appetite, poor sight, and reduced cognition 1
- Dysphagia (swallowing difficulties) 1
Etiology and Risk Factors
The cause of MS is unknown, but research suggests genetic, immunological, and environmental factors are all involved in a complex etiology. 1 Key risk factors include:
- HLA-DRB1*15:01 allele and other non-HLA genetic loci conferring genetic susceptibility 4
- Epstein-Barr virus infection as a key environmental trigger 2, 4
- Vitamin D deficiency and low sunlight exposure 2
- Smoking 4
- Geographic variability with higher incidence in regions with lower sunlight exposure 2
Disease Course
MS is a continuous, progressive, lifelong disease with a variable course. 2 The natural history involves: