Multiple Sclerosis

SOURCE

Source: Bainbridge JL, Miravalle A, Wong P. Multiple sclerosis. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. https://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146062622. Accessed September 10, 2018.

DEFINITION

• Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal damage.

• Two main characteristics of the disease

  • Multiple neurologic symptoms accruing over time

  • Characteristic plaques or sclerosed areas

EPIDEMIOLOGY

• Affects approximately 2.3 million people worldwide

• Usually diagnosed between the ages of 15 and 45; peak incidence occurs in the fourth decade

• Women are afflicted more than men by a ratio of 2:1

ETIOLOGY

• Exact cause of MS is still unknown, but disease is thought to develop in genetically susceptible individuals that are exposed to random events and environmental factors.

• Genetic variation accounts for approximately 30% of the overall disease risk.

• Nongenetic factors have a proportionately larger contribution than genetic factors to immunological heterogeneity.

• Certain viral or bacterial infections may also participate in the pathogenesis of MS by initiating or activating autoreactive immune cells.

• The familial recurrence rate of MS is approximately 5%, with siblings being the most commonly reported relationship, and a concordance rate among monozygotic twins of approximately 25%.

PATHOPHYSIOLOGY

• Infiltration of peripheral immune cells into the CNS and promote neurodegeneration by stripping of the myelin sheath surrounding CNS axons.

  • Demyelination causes axonal damage, which correlates with disability.

    • Damage should be visualized as hypointense lesions, or “black holes,” on T1-weighted MRI.

• T cells recognize and become activated against myelin.

  • Activated T cells release inflammatory cytokines and activate other immune cells.

• Loss of myelin slows and disrupts signal transmission.

• MS lesions are heterogeneous.

  • Acute lesions show demyelination and axonal destruction with lymphocytic activity consistent with an inflammatory state.

  • Chronic lesions display less inflammatory lymphocytes with active remyelination.

• Repeated damage leads to axonal destruction and permanent loss of function.

RISK FACTORS

• Sex (female > male)

• Geographical location

• Genetic factors

• Low vitamin D₃ levels

• Smoking

• Infections

CLINICAL PRESENTATION

• Primary symptoms/signs

  • Direct consequence of conduction disturbances produced by demyelination and axonal damage, and reflect the area of the CNS that is damaged.

    • Visual complaints/optic neuritis

    • Gait problems and falls

    • Paresthesias

    • Pain

    • Spasticity

    • Weakness

    • Ataxia

    • Speech difficulty

    • Psychological changes

    • Cognitive changes

    • Fatigue

    • Bowel/bladder dysfunction

    • Sexual dysfunction

    • Tremor

• Secondary symptoms

  • Complications resulting from primary symptoms

    • Recurrent UTIs

    • Urinary calculi

    • Decubiti and osteomyelitis

    • Osteoporosis

    • Respiratory infections

    • Poor nutrition

    • Depression

• Tertiary symptoms

  • Relate to the effect of the disease on the patient’s everyday life

    • Financial problems

    • Personal/social problems

    • Vocational problems

    • Emotional problems

COURSE OF ILLNESS

• Clinically isolated syndrome (CIS)

  • First clinical presentation of MS

• Relapsing remitting MS (RRMS)

  • Characterized by new ...