Multiple sclerosis

Reviewed by: Jean-Raphael Schneider, M.D., Stanley J. Swierzewski, III, M.D.


Overview

Multiple sclerosis (MS) is an inflammatory, chronic, degenerative disorder that affects nerves in the brain and spinal cord. Myelin, the fatty substance that surrounds and insulates nerves and facilitates the conduction of nerve impulses is the initial target of inflammatory destruction in multiple sclerosis.

MS is characterized by intermittent damage to myelin , called demyelination. Demyelination causes scarring and hardening (sclerosis) of nerve tissue in the spinal cord, brain, and optic nerves. Demyelination slows conduction of nerve impulses, which results in weakness, numbness, pain, and vision loss.

Because different nerves are affected at different times, MS symptoms often worsen (exacerbate), improve, and develop in different areas of the body. Early symptoms of the disorder may include vision changes (e.g., blurred vision, blind spots), numbness, dizziness, and muscle weakness.

MS can progress steadily or cause acute attacks (exacerbations) followed by partial or complete reduction in symptoms (remission). Most patients with the disease have a normal lifespan.

Incidence and Prevalence

MS is the most common neurological cause of debilitation in young people and affects about 500,000 people in the United States. Worldwide, the incidence is approximately 0.1%. Northern Europe and the northern United States have the highest prevalence, with more than 30 cases per 100,000 people.

MS is more common in women and in Caucasians. The average age of onset is between 18 and 35, but the disorder may develop at any age. Children of parents with MS have a higher rate of incidence (30–50%).

Types

Multiple sclerosis is classified according to frequency and severity of neurological symptoms, the ability of the CNS to recover, and the accumulation of damage.

Primary progressive MS causes steady progression of symptoms with few periods of remission.

Relapsing-Remitting MS causes worsening of symptoms (exacerbations) that occur with increasing frequency, along with periods of reduced symptoms (remission).

Secondary progressive MS is initially similar to relapsing-remitting MS but eventually follows a progressive course without remissions.

Relapsing-Progressive MS causes cumulative damage during exacerbations and remissions.


Risk Factors and Causes

The specific cause of MS is not fully understood. Symptoms are caused by an abnormal inflammatory attack on the nerves of the brain or spinal cord. This inflammatory response may be triggered by genetic, environmental, and viral factors that initiate demyelination.

Demyelination is associated with an abnormal immune system response that causes a type of white blood cell (called T cells) to attack myelin. Damage to the myelin then leads to sclerosis of nerve fibers in the central nervous system (CNS). The CNS has the ability to repair some of the damage but may not be able to achieve complete restoration. Exacerbations and remissions (common in multiple sclerosis) result from the intermittent damage and restoration.

A higher incidence of MS in certain geographical areas, such as the northern United States, suggests that environmental factors may be involved, but none have been confirmed.

A specific viral risk factor has not been indentified, but exposure to a virus that causes demyelination (especially prior to adolescence) may be a risk factor.

Signs and Symptoms


The hallmark of multiple sclerosis is unpredictable periods of exacerbation, remission, and progression. Initial symptoms of MS may be brief and mild. The first serious attack usually lasts weeks or months and occurs between the ages of 20 and 40.

The most common early symptoms include sensory abnormalities (e.g., tingling, numbness, itching, tightness, burning, shooting pain in the back and limbs [Lhermitte's sign]) difficulty walking, eye pain, and vision loss.

Symptoms of the disease vary, depending on where the damage occurs, and range from minor physical annoyances to major disabilities. Common symptoms include the following:

* Balance and equilibrium abnormalities (e.g., dizziness, vertigo, uncoordinated movements, tremor)
* Bladder and bowel dysfunction (e.g., urgency, incontinence, nocturia, constipation)
* Behavioral changes (e.g., mood swings, depression)
* Cognitive dysfunction (e.g., impaired memory, reasoning, concentration)
* Facial numbness
* Motor abnormalities (e.g., muscle weakness, spasticity, spasm)
* Sexual dysfunction (e.g., erectile dysfunction, sexual inactivity)
* Vision abnormalities (e.g., eye pain, vision loss in one eye, double vision [diplopia], involuntary eye movement [nystagmus])


Muscle weakness can involve the extremities (arms and legs) on one side of the body (hemiparesis), both legs (paraparesis), or all four extremities (quadraparesis). Muscles in the affected area may tighten (spasticity) and contract spontaneously (spasm or clonus).

Many people with MS experience fatigue and need to rest and sleep during the day in order to continue their activities. The degree of fatigue may not be related to the severity of other symptoms.

An increase in body temperature (e.g., caused by hot weather, hot bath and showers, or fever) can worsen symptoms or produce new ones. This occurs because elevated body temperature slows nerve impulse conduction, especially in demyelinated nerves.

Diagnosis


Diagnosis of MS is based on a detailed history, physical and neurological examination, blood tests, magnetic resonance imaging (MRI scan), spinal tap, and neurological tests.

Blood tests

Blood tests may be used to help rule out other conditions that cause similar symptoms.

Magnetic resonance imaging (MRI scan)

MRI scan uses a magnetic field to create detailed images of the brain and spinal cord. This imaging test can be used to detect lesions in the white matter of the brain.

Spinal Tap

A spinal tap, also known as a lumbar puncture, is performed to detect oligoclonal bands in cerebrospinal fluid. Oligoclonal bands result from elevated levels of the antibody immunoglobulin G (IgG) and myelin basic protein, which is a byproduct of demyelination, and are present in more than 85% of MS cases. In this procedure, a needle is inserted between two lower spine (lumbar) vertebrae and cerebrospinal fluid is collected and analyzed.


Evoked Potential Tests

Evoked potentials are electrical signals generated by the nervous system in response to stimuli. Evoked potential tests (i.e., somatosensory evoked potentials, visual evoked potentials, brainstem auditory evoked potentials) are performed to evaluate sensory, visual, and auditory functions and detect slowed nerve impulse conduction caused by demyelination.

In these tests, nerves responsible for each type of function are stimulated electronically and responses are recorded using electrodes placed over the CNS (brain and spine) and peripheral nerves (e.g., median nerve in the wrist, peroneal nerve in the knee).

Differential Diagnosis

Early signs of MS are often mistaken for other disorders, including the following:

* Cerebrovascular disease (e.g., stroke, transient ischemic attack [TIA])
* Epilepsy
* Degenerative disc disease
* Osteoarthritis
* Tumor
* Vitamin B-12 deficiency
* Weakening of the nerves (neuropathy)

Conditions that may appear similar to MS on MRI scan include the following:

* Congenital biochemical disorders (e.g., adrenaleukodystrophy, metachromatic leukodystrophy)
* Inflammation of blood vessels (vasculitis)
* Lyme disease
* Lupus (an autoimmune disorder)
* Progressive multifocal leukencephalopathy (HIV-related disorder)
* Viral infection (may produce a response that causes demyelination)

Treatment


Treatment for multiple sclerosis varies. The goals of treatment are to improve the quality of life by relieving symptoms caused by exacerbations (called palliative treatment), slowing the course of the disease as much as possible, and providing psychological support.

In general, starting treatment early in the course of the disease and continuing treatment indefinitely is thought to provide the most benefit. Health care providers and patients should make treatment decisions together.

Palliative Treatment

Corticosteroids are typically prescribed to treat exacerbations of MS. Methylprednisolone (Solu-Medrol®) is be administered through an IV (intravenously) for 2–7 days, followed by a course of prednisone. Prednisone (Deltasone®) may be given for 10 days then the dosage is gradually reduced over 3 weeks and stopped.

Corticosteroids are usually well tolerated. Side effects include the following:

* Heart failure
* High blood pressure (hypertension)
* High blood sugar levels (hyperglycemia)
* High or low levels of sodium in the blood (hyper- or hyponatremia)
* Increased risk for infection
* Low level of potassium in the blood (hypokalemia)
* Personality changes (e.g., mood swings)
* Stomach ulcer
* Swelling (edema) caused by fluid retention


Treatment for Specific MS Symptoms


Treatment for specific symptoms of multiple sclerosis may include the following:

Muscle weakness, numbness, and stiffness (spasticity) may be treated using medication taken regularly or as needed. These drugs include muscle relaxants, such as tizanidine (Zanaflex®) and baclofen (Loresal®), benzodiazepines, such as diazepam (Valium®), and anticonvulsants, such as carbamazepine (Tegretol®).

Side effects of baclofen and tizanidine include drowsiness, dizziness, and fatigue. These drugs should not be discontinued abruptly. Carbamazepine may cause severe side effects including aplastic anemia, low white blood cell count (leukopenia), cancer that develops in cells found in blood and lymph (lymphoma), heart failure, and seizures.

Fatigue may be treated using amantadine hydrochloride (Symmetrel®) or modafinil (Provigil®) when frequent napping, adequate sleep at night, and daily exercise do not help. Side effects include nausea, dizziness, and headache.

Balance and equilibrium abnormalities (e.g., difficulty walking, uncoordinated movements, tremor) may be treated using medications such as benzodiazepines (Valium®), clonazepam (Klonopin®), propranolol (Inderal®), and mysoline (Primidone®). Side effects include drowsiness, confusion, and depression.

Bladder dysfunction (e.g., incontinence, nocturia) may be treated using medications such as oxybutynin (Ditropan®), tolterodine (Detrol®), and hyosciarnine (Levsin®). Bladder-emptying regimen, intermittent catheterization, and surgery may also be used. Side effects of medication include headache, dry mouth, constipation, and dizziness.

Constipation may be worsened by inactivity. Treatment includes eating a high-fiber diet, increasing fluid intake, daily exercise, and stool softeners. Rectal suppositories or enemas occasionally may be required.

Sexual dysfunction may occur in men and women with MS. Treatment is available for erectile dysfunction and female sexual dysfunction.

Immune Therapy

These treatments involve the use of medications that modify (change) the immune system's attack on the central nervous system. Immune therapy may reduce the frequency of exacerbations and the accumulation of damage.

These disease-modifying therapies include the following medications:

* Interferon beta-1a (Avonex®, Rebif®)
* Interferon beta-1b (Betaseron®)
* Glatiramer acetate (Copaxone®)

Interferon beta-1a (Avonex®) is given into muscle (intramuscular injection) once per week and has been shown to reduce exacerbations and physical disability. Side effects include flu-like symptoms (e.g., malaise, muscle aches, fever) and inflammation (i.e., pain, redness, infection) at the injection site.

Rebif® is an interferon beta-1a that has been shown to delay progression of MS and reduce the frequency of exacerbations. It is administered subcutaneously (under the skin), 3 times per week at a dose of 22 or 44 mcg and dosing frequency maintains a constant concentration of drug in the body.

Rebif is packaged in pre-measured, pre-filled syringes, which may be helpful for patients who have difficulty preparing medication for injection. Side effects include fatigue, inflammation at the injection site, headache, and flu-like symptoms.

Interferon beta-1b (Betaseron®) is given by subcutaneous (under the skin) injection, every other day. It has been shown to reduce the frequency and severity of exacerbations. Side effects include flu-like symptoms (most common during the first few months of use) and inflammation at the injection site.

Glatiramer acetate (Copaxone®) is an amino acid that modifies actions of the immune system that may affect the progression of MS. It has been shown to reduce the frequency of exacerbations and the level of disability. It is given by subcutaneous injection every day and usually is well tolerated. Side effects include chest tightness and palpitations (rapid heart beat).

Other MS Treatments


Psychotherapy

The central nervous system abnormalities associated with MS and the psychological and social impact of the disorder often result in mood swings and depression. MS support groups, counseling, and/or antidepressants (e.g., amitriptyline, clomipramine, nortriptyline) may be helpful.

Rehabilitation

Treatment for MS may also include physical therapy, occupational therapy, and speech therapy. Physical therapy uses exercises to help strengthen muscles, reduce pain and spasticity, and improve balance and walking. Assistive devices (e.g., canes, braces, walkers) may be used to help patients remain as independent as possible.

Occupational therapy increases independent function in activities of daily living that focus on grooming, dressing, eating, driving, and handwriting. Adaptations in the work and home environment (e.g., shower chairs, hand rails, ramps) are based on patient needs.

Speech therapy may be helpful if slurred speech (dysarthria) or difficulty swallowing (dysphagia) develops.


Prognosis


Most people with MS have a relatively normal life span and life expectancy is about 35 years after onset. After 25 years, approximately two-thirds of patients remain mobile.The disorder eventually results in physical limitations in about 70% of patients.

Prevention

There is no established prevention for multiple sclerosis.