Multiple Sclerosis (MS)
Introduction
Just days after seeing her family doctor for a routine physical, Hillary, a college student, began tripping over objects and slurring her speech. Her coursework suffered because she could no longer write due to a lack of muscle control. After a battery of medical tests, she learned she had multiple sclerosis (MS). Over the next few days, her left arm became paralyzed, her left leg dragged when she tried to walk, the left side of her mouth was numb, and her left eyelid drooped. She could walk only with the help of a walker. "I couldn't believe it," she says. "One day, I was a healthy 21-year-old. Within five days I was paralyzed."
What is it?
MS is characterized by damage to the myelin sheath, or covering, surrounding nerves in multiple areas of the central nervous system (brain, spinal cord, and the optic nerves). Nerves with damaged myelin become scarred (called plaques, lesions, or sclerosis) and no longer function normally because it is more difficult to send electrical signals to the rest of the body without myelin to "grease" the way.
Examples of areas that may be attacked include the blood-brain barrier (a membrane that helps to keep harmful substances out of the brain) and the optic nerves, which are responsible for eyesight. Depending on which nerves are affected and how extensive the damage is, the patient may develop symptoms of impaired body function such as movement, speech and vision.
Hillary's case is an extreme example; MS is an extremely unpredictable and variable disease. The four main types of MS are described in the following table.
Four Types of Multiple Sclerosis (MS)
| Relapsing/Remitting MS | Secondary Progressive MS |
| The most common form of MS, affecting about 85 percent of people with the condition. Relapsing/remitting MS is characterized by sporadic attacks of degeneration (relapses) intermingled with remissions, periods of near-normal health that can last for months or years. Some people even go into permanent remission, but most experience a slow increase in permanent nerve damage. | A later stage of the relapsing/remitting form of MS where attack rate is reduced and the condition changes to a gradual but steady deterioration of body functions unrelated to acute attacks. Within 10 years, 50 percent of all patients with relapsing/remitting MS will move into the secondary progressive type. |
| Primary Progressive MS | Progressive/Relapsing MS |
| After onset of symptoms, there is a gradual but steady deterioration of body functions without acute attacks in about 10 percent of people. In the very worst cases, primary progressive MS can accelerate, leading to complete disability or death within just a few months. | The most severe form of MS, affecting about 5 percent of people with the condition. Progressive/ relapsing MS begins with a progressive course although these people also experience acute attacks. |
What causes it?
MS is an autoimmune disorder in which the body's natural defenses (the immune system) suddenly attack the central nervous system. Several types of white blood cells are involved in the process in which the myelin sheath is mistaken for a harmful substance. Although the exact cause of MS remains unknown, a combination of factors is probably involved in its development.
Genetic susceptibility has been established and is a result of an unlikely combination of several genes (US citizens have a 1 in 750 chance of developing MS whereas children of a parent with MS have a 1 in 40 chance of getting the disease). It is recognized, however, that the development of MS is not solely determined genetically, since identical twin studies reveal only a 1 in 3 chance of getting MS.
Several theories have been proposed to explain how MS begins. One is that unidentified environmental factors trigger a genetically expressed immune response. A second theory is that a virus or bacteria, possibly acquired during childhood, either attacks the cells that make myelin, attacks the myelin itself, or changes cells in the immune system.
MS is usually diagnosed with a magnetic resonance imaging scan (an MRI). An MRI is a type of x-ray that looks for problems in the body that cannot be found by other means. In MS, an MRI is useful in locating plaques.
Who has it?
In the United States, approximately 400,000 people have MS, with roughly 200 new cases diagnosed each week. Worldwide, MS may affect 2.5 million individuals. These numbers are estimates because MS is not contagious so U.S. physicians are not required to report new cases, and because symptoms can be completely invisible. Women are affected two times as often as men. The average age of onset is between 20 and 45 years, and is rarely seen before age 14 or after age 60. MS occurs more frequently in whites of Anglo-Scandanavian ancestry than in other ethnic groups. The cost of MS in the United States is estimated to exceed $2.5 billion annually.
What are the risk factors?
- Female
- Age 20-45
- Family history of MS
- Caucasians of Anglo-Scandinavian or North Sea ancestry
- Living in a geographical area with increased incidence of the disease: above the 37th parallel (in general, the further away from the equator you live, the greater your risk)
What are the symptoms?
MS has three distinct types of symptoms. Primary symptoms are caused directly by myelin destruction. Often, they can be controlled with therapy and medication, but they can also lead to secondary symptoms. For instance, bladder spasms, a primary symptom, can cause the secondary symptoms of urinary tract infections and kidney stones. Treating primary symptoms is the best way to avoid secondary ones. The third type - called tertiary symptoms - represents the effects the disease has on individual quality of life. Since it strikes a relatively young population, MS is associated with significant emotional and social impact.
Symptoms of Multiple Sclerosis
| Primary Symptoms | Secondary Symptoms | Tertiary Symptoms |
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How is it treated?
The treatment of MS focuses mainly on decreasing the rate and severity of relapse, reducing the number of MS lesions, delaying the progression of the disease, and providing symptomatic relief for the patient. Several different drugs have been developed to treat the symptoms of MS. However, in patients with the relapsing-remitting type, it is often difficult to determine if symptomatic improvements are the result of drug therapy or if it is just the natural course of the disease. The following summary of the most recent treatment guidelines outlines medications for each type of MS, describes the ways they work, and discusses their benefits for MS patients.
Relapsing/Remitting Multiple Sclerosis Treatment
| Drug Therapy | How It Works | Benefits |
| Interferon beta-1b (Betaseron) Injected under the skin every other day. |
Interferons are substances produced by the body to regulate the immune system. In this case, diminishing the activity of the specific white blood cells causing disease. |
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| Interferon beta-1a (Avonex) Injected into the muscle once a week |
Interferons are substances produced by the body to regulate the immune system. In this case, diminishing the activity of the specific white blood cells causing disease |
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High-dose/frequency Interferon beta-1a (Rebif) Injected under the skin three times a week |
Interferons are substances produced by the body to regulate the immune system. In this case, diminishing the activity of the specific white blood cells causing disease |
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| Glatiramer (Copaxone) Injected under the skin daily |
Exactly how glatiramer works is unknown, but it is believed to modify the immune process that causes MS. |
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Secondary Progressive Multiple Sclerosis Treatment
| Drug Therapy | How It Works | Benefits |
| Interferon beta (Betaseron, Avonex, Rebif) | Interferons are substances produced by the body to regulate the immune system. In this case, diminishing the activity of the disease causing white blood cells. |
|
| Mitoxantrone (Novantrone) | Mitoxantrone inhibits specific cells of the body's defense system that destroy myelin in the central nervous system. |
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Primary Progressive and Progressive/Relapsing Multiple Sclerosis Treatment
No treatment is currently approved, however, those disease modifying therapies that reduce progression of MS may be beneficial.
Short-term treatment (3-5 days) with corticosteroids (like prednisone, methylprednisolone, dexamethasone, others) can aid during periods of acute relapse. The proposed mechanism by which corticosteroids work and the possible benefits they can provide are listed in the table below.
For Acute Relapse of Multiple Sclerosis
| Drug Therapy | How It Works | Benefits |
| Corticosteroids (methylprednisolone, prednisone, dexamethasone) | Corticosteroids work by decreasing the intensity of the body defense system's reaction to the myelin in the central nervous system. |
|
Not only do healthcare practitioners treat the disease itself, but also the accompanying symptoms. The chart below details drugs used to help relieve common symptoms associated with MS.
For Relief of Symptoms, Regardless of MS Type
| Drug Class | How It Works | Symptom Relieved |
| Muscle Relaxants (Baclofen, Dantrolene, Tizanidine, Cyclobenzaprine, Clonazepam, Diazepam) | Muscle relaxants (also used for a number of other conditions), help to relieve spasms and stiffness for people with MS. |
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| Anticholinergics (Propantheline, Tolterodine Dicyclomine) | Anticholinergic drugs reduce the frequency and intensity of spasms of the bladder and bowel. |
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| Urinary Tract Antispasmodics (Oxybutynin) | By relaxing muscles in the bladder, antispasmodics increase the bladder's ability to hold urine. It also reduces bladder spasms, limits the urge to pass urine, and lessens the frequency of involuntary urination. |
|
| Tricyclic Antidepressants (Amitriptyline, Imipramine) | Tricyclic antidepressants rebalance chemicals in the central nervous system, which helps to relieve MS-associated sensory symptoms. Some of their side effects (dry mouth and urine retention, for example) make them effective for treating bowel and bladder spasm. |
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| Antidiuretic Hormone (Desmopressin, DDAVP) | Antidiuretic hormone decreases urine flow through the kidneys. |
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| Anticonvulsants (Carbamazepine, Phenytoin, Acetazolamide, Lamotrigine) | Usually used to prevent or relieve seizures, anticonvulsants rebalance chemical levels in the brain, relieving sensory symptoms caused by MS. |
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| Central Nervous System Stimulants (Pemoline) | Through an unknown process, pemoline stimulates the central nervous system, helping to relieve the tiredness that frequently accompanies MS. |
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| Selective Serotonin Reuptake Inhibitors (SSRIs) (Citalopram, Fluoxetine, Paroxetine,Sertraline) |
The ability of SSRIs to alter the levels of certain chemicals in the brain creates a stimulation effect. |
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Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) (Ibuprofen, Naproxen, Ketoprofen) |
Good for relieving minor aches and pains, NSAIDs can also reduce fever in patients taking Interferons. |
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Phosphodiesterase-5 Inhibitors (Sildenafil, Tadalafil, Vardenafil) |
These drugs alter the body's response to sexual stimulation in order to correct sexual dysfunction. |
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Helping Yourself
Remaining as active as possible is very important for MS patients. Health professionals, such as occupational, speech, and physical therapists can be extremely beneficial, not only by helping patients adapt to the symptoms of the disease, but also by providing emotional support. In addition, several national organizations provide formal emotional and social support for caregivers as well as for patients. Both on-line and local organizations can also be helpful in teaching patients about MS.
- The National Multiple Sclerosis Society
- The Multiple Sclerosis Foundation
- Multiple Sclerosis Association of America
- The Multiple Sclerosis International Federation
What is on the horizon?
- The National MS Society is currently spending $45 million on clinical trials and has a cumulative investment of over $550 million since its first grants back in 1947. They are pursuing not only better treatments, but are also seeking prevention options and a cure.
- Scientists are currently researching a way to possibly restore function to individuals affected by MS. In November 2006, investigators supported by the National MS Society reported progress in their research to discover a way to repair the nerve tissue that is damaged when a person has MS.
- Some research has linked low Vitamin D levels in the blood to Multiple Sclerosis. However, it is still unclear whether or not low levels of Vitamin D can be considered a causative factor of MS.
- Promising results were published from an early-phase clinical trial of the monoclonal antibody, natalizumab (Tysabri) in relapsing forms of MS. It was approved by the FDA in November of 2004 and removed from the market in February 2005 due to severe adverse events including death. It is currently being reviewed by the FDA for possible re-release if these adverse events are found to be false.
- FTY720 (fingolimod) an oral medication derived from a Chinese herb is currently undergoing clinical trials. Initial trials show a decrease in relapse rates and development of new lesions after six months of treatment. FTY20 decreases activity of specific white blood cells that cause MS. Novartis Pharma is currently developing the drug and enrolling patients in a large, one-year trial.
- Combination therapy (CombiRx) of interferon beta-1a (Avonex) and glatiramer acetate (Copaxone) is currently being studied in patients with relapsing/remitting MS. Investigators are studying whether the combination will reduce relapse rates more than either therapy used alone.
- Alemtuzumab (Campath-1H), a potent anti-cancer drug, given by infusion for five days once annually has shown promise at reducing relapse and progression in MS. Alemtuzumab binds to and destroys specific white blood cells responsible for myelin destruction.
- MBP8298 (myelin basic protein) is the protein in myelin that is attacked by the immune system in MS patients. High doses of antigen delivered periodically by the intravenous route are expected to suppress immune responses to the administered substance. MBP8298 is currently undergoing late stage clinical trials for Secondary Progressive MS.
- Small studies found that the cholesterol lowering medication simvastatin (Zocor) safely reduced the number of new brain lesions in people with relapsing-remitting MS. Larger studies are planned to determine the effectiveness of using this medication and other similar drugs.
Much time and effort is being devoted to learning more about MS and to find better treatment options, and someday a cure.
References
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Multiple Sclerosis (MS) Health Condition Last Updated: August 2007
Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.