Making Sense of MS Terminology

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Making Sense of MS Terminology: A guide to understanding medical terms and procedures for individuals with MS

Written by Christine Norris
Co-written and edited by Susan Wells Courtney
Reviewed by Dr. Jack Burks

Whether you've been diagnosed with multiple sclerosis (MS) or if you know someone with this disorder, becoming familiar with its medical terms and procedures is extremely helpful for understanding the symptoms and treatments. While many long-time readers of The Motivator have a strong vocabulary of MS-related terms, others – such as family members, friends, or individuals who are newly diagnosed – may benefit from an explanation of common MS terminology.

To follow is a description of terms frequently used when discussing MS. Topics include an overview of MS, an explanation of how the nerves are affected, tools used to evaluate disease activity, a description of the different clinical trial phases, and drugs presently approved for the treatment of MS. Terms are defined within the text and have been bolded for easy reference.


What is MS?

Multiple sclerosis is a neurological disorder affecting the nerves of the central nervous system (CNS), which consists of the brain, optic nerves, and spinal cord. Individuals with MS commonly experience their first symptoms as a young adult, and most individuals are diagnosed with the disease at this prime time in their life, when going to school, starting a career, or starting a family. For 80 percent of people with early MS, symptoms may come and go – or "relapse" and "remit," making the diagnosis difficult. While treatments are available to slow disease activity, researchers have yet to find a cure. MS is not contagious, and in most cases, does not shorten one's expected lifespan.

Symptoms of MS include a wide range of physical, mental, and emotional difficulties. Examples include: visual problems, spasticity (tightening of muscles and spasms), weakness, tremor, numbness, and dizziness; bladder, bowel, and sexual dysfunction; chronic, aching pain; fatigue, depression, and memory problems. Some individuals may experience L'hermitte's sign. This is an electrical sensation that runs down the spine to the legs when the neck is flexed forward.

Fortunately, treatments are available for most symptoms. Additionally, at least in early stages of the disease, symptoms may come and go with disease activity. Anyone experiencing these types of symptoms should be referred to a neurologist. This is a physician who specializes in diagnosing and treating disorders of the nervous system, including MS.


What are the types of MS?

On average, 80 percent of people with MS begin with the relapsing-remitting form of MS (RRMS). What distinguishes this type of MS from other types are the temporary symptom flare-ups or "exacerbations" (also referred to as relapses, attacks, or bouts), which typically last for one to three months. These are followed by a complete or partial recovery ("remission"). Women are two or three times more likely to be diagnosed with RRMS than men.

Between relapses, many people may go into remission for a year or more. During this time, they may remain symptom free, or only experience mild changes with symptoms that did not fully remit following the exacerbation. While symptoms may not appear or worsen between MS attacks, changes do continue within the CNS. Six disease-modifying treatments are presently approved by the Food and Drug Administration (FDA), each shown to help slow disease activity. These are described in a later section.

If untreated, more than 90 percent of individuals with RRMS may eventually enter a second phase of RRMS, known as secondary-progressive MS (SPMS), within 25 years. This phase is reached when the patient experiences a progressive worsening of symptoms. SPMS may occur with or without superimposed relapses.

While approximately 80 percent of individuals with MS are initially diagnosed with RRMS, the majority of the other 20 percent are diagnosed with primary-progressive MS (PPMS). This form of MS presents a gradual but steady accumulation of neurological problems from the onset, without the presence of relapses and remissions. Unlike RRMS, PPMS is equally divided between the genders.

Other types of MS exist, but these are not as common. These include benign MS (with little or no change after 20 years), progressive-relapsing MS (PRMS) (a progressive course from the onset with acute relapses), and malignant or fulminant MS (a rapidly progressive disease course).


What causes the symptoms of MS?

In a healthy body, nerve fibers (also referred to as "axons") have a protective, fatty-rich protein covering known as myelin. This covering insulates the nerve fibers, similar to the insulating rubber covering of an electric wire. Myelin allows for the smooth and uninterrupted flow of nerve impulses, which in turn enables the body to send vital instructions from the brain to the different parts of the body.

With MS, the body's own system of defense, known as the immune system, malfunctions. It sends disease-fighting cells into the CNS to destroy the body's own myelin. This occurs because the immune system is incorrectly identifying the myelin in the CNS as a foreign body. When the body's own immune system attacks its own tissue, this is referred to as an autoimmune disease. Most researchers believe that MS is an autoimmune disease. Examples of other autoimmune diseases include lupus and rheumatoid arthritis.

Lymphocytes are a type of white blood cell and play a strong role in the body's defense system. Lymphocytes can be "B-cells," which produce antibodies to fight against "foreign invaders" (such as bacteria or viruses) within the body. They may also be "T-cells," which help to regulate the immune response; "helper" T-cells can increase an immune response, while "suppressor" T-cells can suppress an immune response. Another type of white blood cell is the macrophage, and this works to ingest and destroy foreign substances. All of these lymphocytes appear to be involved with the destruction of myelin, with the exception of suppressor T-cells, which aid in stopping the attack.

White blood cells circulate in the blood and are produced when the immune system perceives a foreign body and instructs the cells to eliminate it, thereby "protecting" the body. In order to reach the nerves within the CNS, the immune system cells and molecules must cross a protective barrier that surrounds the blood vessels. Known as the blood-brain barrier (BBB), this layer of cells is designed to prevent damaging cells and other substances in the blood (including those that could cause disease) from entering the brain, optic nerves, and spinal cord of the CNS.

With MS, damaging immune-system cells are able to breakthrough the BBB and enter the CNS, where they begin their attack on the myelin. This break in the BBB is facilitated through adhesion molecules, which attach to the lining of the blood vessels and bind to the immune-system cells. The adhesion molecules work like a gate and key, enabling damaging cells to pass through this cell membrane.

Once the damaging cells enter the CNS, macrophages and other lymphocytes begin their attack on the myelin. This creates inflammation along the nerves where the myelin is being damaged. Areas of activity are known as lesions (or plaques). Lesions vary in activity levels, ranging from very active (acute), to chronic, to inactive. Often myelin that is damaged may be restored through a process called "remyelination," particularly early in the disease. Oligodendrocytes are cells which produce and maintain myelin. Over time, however, oligodendrocytes may be lost and fail to repair the damaged myelin.

Areas of damaged myelin become scarred and can no longer fully insulate the nerve – leaving unprotected areas, where the flow of nerve impulses is interrupted. Additionally, nerves (or axons) eventually experience damage as well, and these damaged nerves are unable to efficiently conduct impulse flow. This interruption in the communication between the brain and other parts of the body results in the symptoms experienced by individuals with MS.


What tools are used to evaluate MS activity?

Lesions may be viewed by a magnetic resonance imaging (MRI) scan of the brain and/or spine. The MRI uses a computer, radiofrequency stimulator, and a large electromagnet to provide a picture of the brain. For those with MS, the MRI is used to evaluate the size and location of lesions. Inflammation can be better evaluated with gadolinium-enhancement – a type of dye given to the patient via injection prior to the procedure.

Magnetic resonance spectroscopy (MRS) is a procedure used to provide an anatomical picture of lesions. MRS also provides important information about the biochemistry of the brain in MS, indicating the types of immune-system cells and other substances found in and around a lesion. Presently, the MRS is primarily used as a research tool.

A lumbar puncture (also known as a spinal tap) is a procedure where a very thin needle is inserted at the base of the spine and a small amount of cerebrospinal fluid (CSF) is collected. CSF is the liquid that surrounds the brain and spinal cord. By collecting a small amount of this fluid, laboratory testing may be performed to evaluate cellular and chemical abnormalities. The neurologist will particularly be looking for oligoclonal bands, which are abnormal immune proteins called immunoglobulins. These are present in the CSF of roughly 90 percent of individuals with MS, however, they can occur with several other neurological disorders. Since the introduction of the MRI, CSF analysis is used less often, but it can be helpful in supporting an MS diagnosis if the MRI results are normal or inconclusive.

Evoked potential (EP) tests may also be used to help diagnose MS. These tests are especially useful when findings on the MRI scan are normal or inconclusive. Evoked potentials measure the speed of the brain's response to visual, auditory (sound), or sensory (feeling) stimuli, using electrodes taped to the patient's head. Delayed responses can indicate possible damage to the nerve pathways.

In addition to the procedures listed, doctors have several evaluative tools available to help assess a patient's condition. Through these universally accepted systems of measurement, physicians can record their patients' presenting condition and subsequent improvements, relapses, or disease progression. These systems are particularly valuable to clinical trials.

The most widely known scale among the MS community is the Kurtzke Expanded Disability Status Scale (EDSS). Kurtzke, a physician, first introduced this system in 1955 as the Disability Status Scale (DSS). It used whole numbers from one to 10 to measure degree of disability, largely in terms of mobility.

To make the measurements more sensitive, Kurtzke "expanded" the scale by adding half-points between the numbers. The EDSS is used in conjunction with Kurtzke's Functional System (FS). This measures the function of seven major systems in the CNS (plus a section for "other"), each relating to the different areas of functioning that can be affected by MS (such as movement, sensory, bowel and bladder, vision, cognition, etc.). These are each graded on a scale of zero (normal) to six (severe).

A newer measurement system designed to be even more sensitive is the MS Functional Composite (MSFC) scale. This measures lower extremity function with a Timed 25-Foot Walk, upper extremity function through the 9-Hole Peg Test (9-HPT), and cognitive function, using the Paced Auditory Serial Additions Test (PASAT).


How are drugs and treatments developed?

Clinical trials are conducted to ensure the safety and efficacy of potential treatments for a multitude of diseases and conditions, including MS. Studies conducted in the United States need to be reviewed and approved by the FDA. More drugs to treat MS are being tested than ever before, but prior to their approval, various phases of clinical trials must be successfully completed.

A Phase I trial tests for safety in humans and its sampling is small, with typically less than 100 "healthy" volunteers. Investigators may observe how the human body responds to the medication (how the drug is absorbed, metabolized, and excreted). The researchers also will determine safe doses and related side effects. Phase I trials are referred to as "open label" and "unblinded," because everyone – the patient, medical staff, and investigators, knows the drug and dose that each participant is receiving. Phase I trials can take several months to one year to complete. Sometimes a few individuals who have the disorder (such as MS) will be given the drug to study its effects before going on to the next phase. About 30 percent of medications being studied for MS do not continue beyond Phase I testing.

The next phase of study for experimental drugs is the Phase II clinical trials, which typically run for several months to two years. In this phase, approximately 100 to 300 people with the disorder (in this case, MS) are given either the active drug or a placebo (a medication that looks the same as the drug being tested but has no active ingredients or physical value of any kind). Phase II studies are often "double-blinded." This means that neither the participants nor the medical staff administering or evaluating the new treatment are told who is receiving the drug and who is receiving the placebo. These studies are also "randomized," so that participants are assigned to treatment groups (or "treatment arms") based on chance. Examples of treatment groups include active drug versus placebo, or high-dose versus low-dose, etc.

Roughly one-third of experimental medications for MS reach the Phase III clinical trial level. These trials can take several years to complete and involve 1,000 to 3,000 participants receiving treatment and evaluation at many different medical locations. These studies are randomized, placebo-controlled, and double-blinded. They are designed to provide more information on a potential drug's safety and efficacy (effectiveness), as well as additional benefits, side effects, and adverse reactions.

More than two-thirds of the drugs that enter Phase III studies successfully complete this phase. Upon completion, a data analysis is performed to determine the overall effectiveness and safety of the drug or therapy. If the results are favorable, an application for approval of the drug is submitted to the FDA, whose panel reviews the results and recommends approval if it finds the treatment to be beneficial and safe.

Phase IV clinical trials are conducted after a drug has been approved. Participants are enrolled to further monitor safety and side effects, while evaluating long-term efficacy. What drugs are presently approved for the long-term treatment of MS?

Six FDA-approved, long-term treatments for MS are available. Many experts now recommend treatment as early as possible with one of these approved, disease-modifying agents. Research has shown that treating after the first attack can significantly delay the amount of time to the second attack. Early treatment is also thought to possibly limit axonal (nerve) injury, which may be irreversible, and later lead to a progressive form of MS.

The FDA-approved long-terms treatments for MS are: Avonex® (interferon beta-1a); Betaseron® (interferon beta-1b), Copaxone® (glatiramer acetate); Rebif® (interferon beta-1a); Novantrone® (mitoxantrone), and Tysabri® (natalizumab). All but Novantrone have been approved to treat RRMS (relapsing-remitting MS). Novantrone is the first drug approved to treat worsening RRMS, PRMS, and SPMS (secondary-progressive MS). Patients may only be given one of these drugs during any one time period, although trials with combinations of these drugs are being conducted.

Results from several large clinical trials have found that all of these drugs reduce the number and severity of relapses, as well as the development of new areas of inflammation as seen on MRI. These studies also showed some evidence of delaying disease progression on a short-term basis.

Avonex, Betaseron, Copaxone, and Rebif are all long-term treatments that may be given via self-injections at home – ranging from weekly to daily doses. These four drugs have long-term data supporting safety as well as efficacy, and are usually the first-line of treatment prescribed by the treating physician.

Novantrone and Tysabri are administered via intravenous infusions (injected directly into the blood stream) at hospitals or infusion centers. Novantrone is given once every three months for a maximum of two-to-three years (to avoid damage to the heart). Tysabri is given once every four weeks, and as the newest drug approved, it does not have a set time limit or maximum number of doses. Either of these drugs may provide stronger results, but they also carry bigger risks. Physicians typically reserve these stronger treatments for patients who do not respond to any of the first four medications mentioned.


For more information

Readers may refer to the cover story in this issue titled, "MS Research Update." This provides updates on study findings, approved medications, and experimental treatments for MS. The terminology given in this Health and Wellness article should be helpful while reading the more in-depth cover story.

For additional information about MS and to learn about MSAA's programs and services, please visit MSAA's website at www.msassociation.org, or call MSAA's Helpline at (800) 532-7667. MSAA also has many related publications available on MS and its treatments, including articles appearing in past issues of The Motivator; brochures; and specifically, a monograph titled, Understanding Clinical Trials. These are all available through the website and phone number listed above.