What is Multiple Sclerosis
Multiple sclerosis is a chronic, inflammatory, 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 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 CNS. 2 The disease is characterized by:
- Demyelination: Focal destruction of the myelin sheath surrounding nerve axons 1
- Axonal injury: Variable degrees of axonal transection and neuronal damage 3
- Inflammatory process: Autoimmune-mediated attack on CNS tissue with inflammatory demyelination 3, 4
The cause remains unknown, though research strongly implicates genetic factors (particularly the HLA-DRB1*15:01 allele), environmental triggers (especially Epstein-Barr virus infection), vitamin D deficiency, and smoking. 2, 5
Clinical Forms and Natural History
MS presents in two main clinical phenotypes:
- Relapsing-Remitting MS (RRMS): Affects approximately 85% of patients, characterized by acute inflammatory relapses with periods of remission between episodes 1, 3
- Primary-Progressive MS (PPMS): Affects approximately 15% of patients, characterized by progressive neurological decline from disease onset without distinct relapses 1
During RRMS, nerve impulse conduction may be affected during acute inflammatory phases (relapses) but tends to improve during remission. Over time, relapses cause extensive myelin damage with progressive loss of neuronal function. 1 Most RRMS patients eventually transition to secondary progressive MS (SPMS), where neurological disability steadily increases. 6
Epidemiology and Demographics
- Prevalence: Affects approximately 900,000 people in the US and 2.8 million worldwide 3, 6
- Age of onset: Typically presents in young adults aged 20-30 years 3, 7
- Sex distribution: More common in females with a nearly 3:1 female-to-male ratio 3
- Geographic pattern: Prevalence ranges from 5 to 300 per 100,000 people, increasing at higher latitudes with lower sunlight exposure 3, 2
- Life expectancy: Reduced compared to general population (75.9 vs 83.4 years) 3
Clinical Presentation
MS typically presents with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes (such as internuclear ophthalmoplegia) developing over several days. 3 Common symptoms include:
- Sensory disturbances and motor weakness 7
- Visual problems (optic neuritis) 3
- Balance difficulties and coordination problems 7
- Cognitive impairment 3, 8
- Bladder and sexual dysfunction 8
Diagnostic Approach
Diagnosis requires demonstration of CNS lesions disseminated in both time and space, made by a specialist familiar with MS and its differential diagnoses. 7, 9
Key diagnostic tools include:
- MRI: The most sensitive and specific examination, showing characteristic T2 hyperintense lesions and gadolinium-enhancing lesions in brain and spinal cord 7, 9
- Cerebrospinal fluid analysis: Oligoclonal bands particularly useful when imaging is atypical or insufficient 9
- Visual evoked potentials: Provide additional diagnostic support, especially with few MRI abnormalities 9
Diagnosis applies best to individuals between 10 and 59 years of age for typical presentations. 7 In atypical presentations or progressive onset, additional evidence from CSF and visual evoked potentials helps secure the diagnosis. 7
Complications and Associated Features
Weight loss, malnutrition, and even cachexia are well-recognized features in MS patients. 1 Causes include:
- Reduced mobility and fatigue 1
- Physical difficulty eating or drinking 1
- Poor appetite and reduced cognition 1
- Dysphagia 1
Disease Course
MS is a continuous, progressive, lifelong disease with variable course. 2 The natural history involves a long latent period from initial infection to symptom onset, followed by progressive acceleration. 2 Current disease-modifying therapies primarily target the inflammatory component rather than promoting remyelination. 2