What is Multiple Sclerosis (MS)?

Multiple Sclerosis (MS): Definition and Characteristics

Multiple sclerosis (MS) is a chronic, inflammatory, and autoimmune disease of the central nervous system that leads to widespread focal degradation of the myelin sheath, variable axonal and neuronal injury, and disability in young adults. 1

Types of MS

• Relapsing-remitting MS (RRMS) - affects approximately 85% of clinical cases, characterized by periods of acute inflammatory phases (relapses) followed by periods of healing (remission) 1
• Primary-progressive MS (PPMS) - affects approximately 15% of clinical cases, characterized by progressive neurological damage rather than relapses and remissions 1
• Secondary progressive MS (SPMS) - develops in patients who initially had RRMS, with steadily increasing neurological disability following the relapsing course 2

Pathophysiology

• MS involves inflammatory demyelination with axonal transection in the central nervous system 2
• The disease process includes immune-mediated damage to myelin sheaths surrounding nerve fibers 3
• Over time, relapses cause extensive damage and scarring of the myelin sheath with progressive loss of neuronal function 1
• Recent evidence suggests B cells play a key role in pathogenesis, shifting from the traditional purely T-cell-mediated model 4

Epidemiology

• MS typically presents in young adults (mean age of onset 20-30 years) 2
• Affects approximately 900,000 people in the US and 2.8 million people worldwide 2, 3
• More commonly affects women with a female to male ratio of nearly 3:1 2
• Overall life expectancy is reduced compared to the general population (75.9 vs 83.4 years) 2
• Prevalence ranges from 5 to 300 per 100,000 people and increases at higher latitudes 2

Diagnostic Criteria

MS diagnosis requires evidence of:

• Dissemination in space (DIS) - lesions in different areas of the central nervous system 1, 5
• Dissemination in time (DIT) - new lesions developing over time 1, 5
• No better explanation for the clinical presentation 1, 5

MRI Criteria

• Dissemination in space requires three of four of the following: one gadolinium-enhancing lesion or nine T2-hyperintense lesions if no gadolinium enhancement, at least one infratentorial lesion, at least one juxtacortical lesion, or at least three periventricular lesions 5
• Dissemination in time can be demonstrated by the presence of gadolinium-enhancing lesion (not at site of original event) or new T2 lesion on follow-up scan 5

CSF Analysis

• Positive CSF is defined as oligoclonal IgG bands detected by isoelectric focusing that are different from any bands in serum, or elevated IgG index 5
• Lymphocytic pleocytosis should be less than 50/mm³ 5
• CSF analysis is particularly helpful when imaging criteria fall short or in atypical presentations 5

Clinical Presentation

• Common initial presentations include unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes 2
• Symptoms typically develop over several days 2
• Weight loss, malnutrition, and even cachexia are well-recognized features of patients with MS 1
• Possible causes of weight loss include reduced mobility, fatigue, inappropriate diet, physical difficulty eating or drinking, poor appetite, poor sight, reduced cognition, and dysphagia 1

Differential Diagnosis

Several conditions may be confused with MS and should be considered:

• Multifocal areas of cerebral ischemia or infarction in young adults (phospholipid antibody syndrome, acute disseminated lupus erythematosis, CADASIL, Takayasu's disease, meningovascular syphilis) 1
• Infections such as HTLV1 and Lyme disease 1
• Paraneoplastic disorders presenting as cerebellar ataxia 1
• Monophasic demyelinating diseases (acute disseminated encephalomyelitis, postviral Devic's syndrome, acute transverse myelitis) 1
• Neuromyelitis optica (Devic's syndrome) and recurrent longitudinally extensive transverse myelitis 1
• Genetic disorders of myelin such as leukodystrophies, particularly in children and teenagers 1

Treatment Options

• Nine classes of disease-modifying therapies (DMTs) are available for RRMS and SPMS with activity 2
• These include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and monoclonal antibodies 2
• Ocrelizumab is approved for primary progressive MS 2
• Efficacy rates of DMTs range from 29%-68% reduction in annualized relapse rates 2
• Autologous hematopoietic stem cell transplantation (AHSCT) may be considered for highly active RRMS that does not respond to DMTs 3, 1

Preventive Strategies

• A diet lower in saturated fat and higher in polyunsaturated fatty acids from food sources is suggested for the prevention of MS 1
• Supplementation of n-3 fatty acids is not recommended for the prevention of MS and other demyelinating diseases 1

Prognosis and Complications

• MS can lead to physical disability, cognitive impairment, and decreased quality of life 2
• The presence of comorbid autoimmune diseases does not appear to significantly affect the progression of RRMS 6
• Treatment with DMTs can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator 2