eMedicine Specialties > Physical Medicine and Rehabilitation > Medical Diseases

Multiple Sclerosis

Author: Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers
Coauthor(s): Timothy Lee Vollmer, MD, Van Denburgh Chair, Barrow Neurological Institute, Division of Neurology, Director of Neuroimmunology Program, St Joseph's Hospital and Medical Center; Fu-Dong Shi, MD, PhD, Director of Neuroimmunology Laboratory, Barrow Neurological Institute, St Joseph's Hospital and Medical Center; Daniel D Scott, MD, MA, BS, Associate Professor, Department of Physical Medicine and Rehabilitation, University of Colorado at Denver and Health Sciences Center; Sandra F Williamson, MS, ANP-C, CRRN, Clinic Coordinator, Department of Rehabilitation Medicine, Denver Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Jul 17, 2009

Introduction

Background

Multiple sclerosis (MS) is a progressive disease that attacks the central nervous system (CNS) and affects multiple systems of the body through attacks on the nervous system. MS affects individuals of all races and socioeconomic groups and is seen all over the world. It is most common in white women of northern European descent. The initiating event is unknown, but a great deal of progress has been made in understanding the pathophysiology and treatment of the disease. This article discusses the epidemiology, pathophysiology, signs and symptoms, diagnosis, treatments, and outlook for the future for patients with MS. (See image below and Image 1.)

Pathophysiology

Multiple sclerosis (MS) is an immune-mediated inflammatory disease that attacks myelinated axons in the CNS, destroying the myelin and the axon in variable degrees. The disease is characterized initially by episodes of reversible neurologic deficits, which, in most patients, are followed by progressive neurologic deterioration over time. The cause of the disease is not known, but it likely involves a combination of genetic susceptibility and an environmental trigger, resulting in a self-sustaining autoimmune disorder that leads to recurrent immune attacks on the CNS.

MS is currently believed to be an immune-mediated disorder with an initial trigger, which may have a viral etiology, although this concept has been debated for years. Identification of a single virus has not been successful to date, despite ongoing efforts worldwide. In fact, no evidence exists that MS is contagious. Multiple viruses may initiate an immune reaction that cross-reacts with a neural antigen (eg, myelin antigens), which Talbot has called molecular mimicry. This cross-reaction may then lead to injury of the myelinated CNS axons and oligodendrocytes and neurons. The oligodendrocyte is responsible for producing the protective myelin sheath surrounding the axon in the CNS and may be particularly susceptible to the immune attack. CNS infections may also lead to the transmigration of activated T lymphocytes into the CNS, which may be sufficient to initiate the autoimmune process in genetically susceptible individuals. However, the pathogenesis remains incompletely understood.¹

Examination of the demyelinating lesions, called plaques, in the spinal cord and brain of patients with MS shows myelin loss, destruction of oligodendrocytes, and reactive astrogliosis, often with relative sparing of the axon cylinder.² However, in some MS patients, the axon is also aggressively destroyed. These active lesions show breakdown of the blood-brain barrier with penetration of leukocytes. A combination of T cells, B cells, and macrophages is believed to be responsible for the attack on the myelin antigens. (See image below and Image 2.) The location of lesions in the CNS dictates the type of deficit that results. As the inflammation resolves, some remyelination occurs, but most recovery of function that occurs in a patient may be due to cortical reorganization.

The initial phase of the disease is characterized by relapsing attacks of neurologic disability believed to be caused by demyelination with some axonal injury, followed by partial or complete neurologic recovery. This stage of the disease is called relapsing-remitting MS. As the lesion burden increases with continued relapses, patients tend to enter a phase in which relapses become less common but a slow, progressive loss of neurologic function ensues. This is referred to as the secondary progressive phase of the disease and does not seem to be responsive to currently available disease-modifying agents, unlike the earlier relapsing phase. The exact mechanism of the secondary progressive phase of the disease is not known but is suggested to be due to ongoing neural degeneration. Among MS patients, 10-15% have no relapsing phase, with the symptoms instead being slowly progressive from the beginning. This form of MS is called primary progressive MS.

Frequency

United States

According to the National Multiple Sclerosis Society, 250,000-300,000 individuals in the United States are affected by MS. Approximately 1 person per 1000 population in the United States is believed to have the disease.

International

Worldwide, approximately 1.1 million people are affected by multiple sclerosis.

Mortality/Morbidity

Life expectancy is shortened only slightly with multiple sclerosis (MS), and the survival rate is linked to disability. Usually, death is due to secondary complications (50-66%), such as pulmonary or renal causes, suicide, primary complications, and causes other than MS seen in the general population.

Race

Multiple sclerosis is seen in all parts of the world and in all races, but whites of northern European descent have the highest incidence.

Sex

The female-to-male ratio for multiple sclerosis is 2:1.

Age

Multiple sclerosis disease is usually diagnosed in persons aged 15-45 years; however, it can occur in persons of any age. The average age at diagnosis is 29 years in women and 31 years in men.

Clinical

History

Patients with multiple sclerosis (MS) initially have a difficult time describing their symptoms because, in the most common form of the disease (relapsing-remitting MS), the symptoms appear and subsequently resolve. The sine qua non of MS is that the symptoms are separated in time and space. These symptoms affect different parts of the body at different times. As an example, a patient may present with paresthesias of a hand that resolves, followed in a couple of months by weakness in a leg or visual disturbances (eg, diplopia).

In the early phase of the disease, patients frequently do not bring these symptoms to the attention of their doctors because the problems resolve. Ultimately, the disease is recognized by the patient, which leads to a medical evaluation. Because, early in the disease course, the primary symptoms (eg, sensory disturbance, fatigue, pain) may be invisible to the examiner, patients are often initially misdiagnosed. However, the chronically recurring nature of the disease eventually leads to a correct diagnosis in most patients.

Physical

Patients with multiple sclerosis (MS) may demonstrate various physical findings. These findings may change from examination to examination, depending on the pattern of disease and whether or not the patient is having an exacerbation or relapse.

• A thorough physical examination, including neurologic assessment, is critical to determine deficits. All systems must be addressed, including motor, sensory, and musculoskeletal, as well as reflexes, tone, coordination, bulbar, vision, gait, and skin.
  • Some of the findings may include localized weakness, focal sensory disturbances (with persistent decrease of proprioception and vibration), hyperreactive reflexes with clonus in the ankles and upgoing toes, and increased tone or stiffness in the extremities with velocity-dependent passive range of motion.
  • Additional signs may include the following: nystagmus, internuclear ophthalmoplegia, visual disturbances, pallor of the optic disc, poor coordination of upper and lower extremity movements, the Lhermitte sign, and wide-based gait with inability to tandem walk.
  • Secondary problems may include infections, urinary problems, skin breakdown, and musculoskeletal complaints. Skin should be examined in all nonambulatory patients, and the musculoskeletal system must be addressed as appropriate.
• Based on the findings, a patient may be rated according to several clinical scales. The most widely accepted clinical rating scale is the 10-point Kurtzke Expanded Disability Status Scale,³ developed originally in 1955 as the Disability Status Scale, which is as follows:
  • Grade 0 - Normal neurologic examination (all grade 0 in functional systems [FS], cerebral grade 1 acceptable)
  • Grade 1.0 - No disability, minimal signs in 1 FS (ie, grade 1 excluding cerebral grade 1)
  • Grade 1.5 - No disability, minimal signs in more than 1 FS (more than 1 grade 1 excluding cerebral grade 1)
  • Grade 2.0 - Minimal disability in 1 FS (1 FS grade 2, others 0 or 1)
  • Grade 2.5 - Minimal disability in 2 FS (2 FS grade 2, others 0 or 1)
  • Grade 3.0 - Moderate disability in 1 FS (1 FS grade 3, others 0 or 1) or mild disability in 3 or 4 FS (3/4 FS grade 2, others 0 or 1) though fully ambulatory
  • Grade 3.5 - Fully ambulatory but with moderate disability in 1 FS (1 grade 3) and 1 or 2 FS grade 2, or 2 FS grade 3, or 5 FS grade 2 (others 0 or 1)
  • Grade 4.0 - Fully ambulatory without aid; self-sufficient; up and about some 12 h/d despite relatively severe disability, consisting of 1 FS grade 4 (others 0 or 1) or combinations of lesser grades exceeding limits of previous steps; able to walk without aid or rest approximately 500 m
  • Grade 4.5 - Fully ambulatory without aid; up and about much of the day; able to work a full day; may otherwise have some limitation of full activity or require minimal assistance; characterized by relatively severe disability, usually consisting of 1 FS grade 4 (others 0 or 1) or combinations of lesser grades exceeding limits of previous steps; able to walk without aid or rest for approximately 300 m
  • Grade 5.0 - Ambulatory without aid or rest for approximately 200 m; disability severe enough to impair full daily activities (eg, to work full day without special provisions; usual FS equivalents are 1 grade 5 alone, others 0 or 1; or combinations of lesser grades usually exceeding specifications for step 4.0)
  • Grade 5.5 - Ambulatory without aid or rest for approximately 100 m; disability severe enough to preclude full daily activities (usual FS equivalents are 1 grade 5 alone; others 0 or 1; or combinations of lesser grades usually exceeding those for step 4.0)
  • Grade 6.0 - Intermittent or unilateral constant assistance (cane, crutch, or brace) required to walk approximately 100 m with or without resting (usual FS equivalents are combinations with more than 2 FS grade 3+)
  • Grade 6.5 - Constant bilateral assistance (canes, crutches, or braces) required to walk approximately 20 m without resting (usual FS equivalents are combinations with more than 2 FS grade 3+)
  • Grade 7.0 - Unable to walk beyond approximately 5 m even with aid; essentially restricted to wheelchair; wheels self in standard wheelchair and transfers alone; up and about approximately 12 h/d (usual FS equivalents are combinations with more than 1 FS grade 4+; very rarely, pyramidal grade 5 alone)
  • Grade 7.5 - Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair (usual FS equivalents are combinations with more than 1 FS grade 4+)
  • Grade 8.0 - Essentially restricted to bed or chair or perambulated in wheelchair but may be out of bed itself much of the day, retains many self-care functions; generally has effective use of arms (usual FS equivalents are combinations, generally grade 4+ in several systems)
  • Grade 8.5 - Essentially restricted to bed much of the day; has some effective use of arms; retains some self-care functions (usual FS equivalents are combinations, generally 4+ in several systems)
  • Grade 9.0 - Helpless bed patient; can communicate and eat (usual FS equivalents are combinations, mostly grade 4+)
  • Grade 9.5 - Totally helpless bed patient; unable to communicate effectively or eat/swallow (usual FS equivalents are combinations, almost all grade 4+)
  • Grade 10.0 - Death due to MS
• These criteria have been revised over the years and remain the standard scale by which patients may be compared. The scale ranges from 0-10 in 0.5 increments. The scores from grades 0-4 are derived from FS scales that evaluate dysfunction in 8 neurologic systems, including pyramidal, cerebellar, brainstem, sensory, bladder and bowel, vision, cerebral, and "other."
  • Advantages of this scale are that it is widely used clinically, is easy to administer, and requires no special equipment.
  • Limitations of the Expanded Disability Status Scale are that it (1) is heavily dependent on mobility; (2) is somewhat subjective in certain areas (eg, bowel and bladder function); (3) is insensitive to small changes; and (4) does not present an accurate picture of the patient's cognitive abilities and functional abilities in performing activities of daily living (ADL).
• Additional useful scales include the Ambulation Index, which is based solely on the ability to walk 25 feet, and the Scripps Neurologic Rating Scale, developed by Sipe in 1984. This scale has a finer incremental scale than the Kurtzke scale, but it is not widely accepted and does not consider cognitive involvement.

Causes

The cause of multiple sclerosis (MS) is not known. Environmental factors and a genetic predisposition, which affect an individual's chance of acquiring the disease, appear to play a role.

• Identical twin studies have shown up to a 60% risk of one twin's developing MS if the other is affected. The first-degree family members (children or siblings) of people affected with MS have a 3-5% risk of developing MS.
• Geography is clearly an important factor in the equation. Persons from the equatorial regions of the world have a much lower incidence than those in the southernmost and northernmost regions. If an individual lives in an area with low incidence of MS until age 15 years, that person's risk is low; however, if an individual lives in an area with a high incidence until age 15 years, the risk of developing MS is high.
  
  The interesting point is that if that person moves to an area of high incidence from an area of low incidence after age 15 years, the person does not have increased risk beyond the area from which he or she moved. It appears that whatever environmental factor is involved, it must exert its effect in early childhood. Certain ethnic groups (eg, Eskimos), despite living in areas of higher incidence, do not have high incidence of MS. Therefore, the exact role played by geography versus genetics in incidence of the disease is not clear.

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