Articles on Medical Diseases and Conditions

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  • Blood Tests

    Beyond routine blood tests that are done to assess a variety of condi- tions, some blood tests are speci?c to the diagnosis of cardiovascular disease. Blood tests can indicate the levels of lipids (cholesterol and triglycerides), cardiac enzymes (markers of cardiac damage), the oxygen content, and the amount of time it takes for your blood to clot (pro- thrombin time). Some newer blood tests detect injury to the heart muscle in a person who has had a symptom such as chest pain, shortness of breath, or light-headedness. These tests can be done quickly in an emergency setting for immediate detection of a heart attack.
    For some types of blood tests, such as the lipid pro?le, you will be asked to fast overnight. For many heart-related blood tests, blood will be drawn from a vein or sometimes from an artery, rather than from a ?ngertip.

    Lipid ProfileMeasuring the cholesterol circulating in your blood is a common, rou- tine test . Called a lipoprotein pro?le, or sometimes a lipid panel, the test measures the levels of your total cholesterol, low-density lipoproteins (LDL, the “bad” cholesterol), high-density lipoproteins (HDL, the “good” cholesterol), and triglycerides (the most common form of fat in the blood). This is to determine whether you need treat- ment or to check if a treatment is working.
    If these measurements are not precise enough, a more sophisticated test, called a nuclear magnetic resonance lipid test, can be done to more precisely measure and classify subparticles of HDL and LDL. Other new tests, which may help to further assess risk, include measuring apoprotein levels such as apoprotein B, a component of LDL, and apoprotein A-1, a component of HDL. The usefulness of these tests is uncertain; currently, they are used mainly to decide if people with bor- derline high LDL and HDL levels need drug treatment.

    Cardiac Enzymes

    Testing your blood for certain cardiac enzymes (proteins), which are sometimes called cardiac markers because they indicate heart muscle injury, can be a way to detect damage to your heart from a heart attack very early in the course of the attack. If you are having chest pains, your doctor may order these tests to see if damage is being done to your heart. If you go to an emergency room because of warning signs of a heart attack , the doctor will probably do this analysis.
    Small amounts of cardiac enzymes are found in the blood of healthy people. However, the heart muscle is rich in these enzymes, and they can leak into your blood in larger amounts if your heart is damaged by a heart attack. They may enter your bloodstream very early in an attack, before you realize you are having one, or before much heart tissue has been damaged.
    One enzyme commonly measured to con?rm the existence of heart muscle damage is creatine kinase (CK). Different types of CK are found in heart muscles and in the skeleton. The enzyme type that most accu- rately con?rms heart damage is the form of CK known as CK-MB. The level of CK-MB found in the blood increases about 6 hours after the start of a heart attack and reaches its peak in about 18 hours. If you have had a symptom such as pain, testing for these markers can con?rm whether a heart attack has occurred.
    Other cardiac markers called troponins (including troponin I and troponin T) have a role in heart muscle contraction and are very sensitive indicators of heart muscle damage. Their presence in your blood can indicate very mild damage to your heart that tests for creatine kinase don’t detect. Troponins increase in as little as 4 hours after the beginning of an attack and can remain elevated in your blood for 2 weeks.
    Myoglobin is still another marker used to detect heart damage. It is a less speci?c marker of cardiac damage than one type of CK but has the advantage of being the very ?rst of the cardiac markers to rise after a heart attack, as early as a couple of hours after the heart damage occurs. This makes a blood test for myoglobin useful in determining whether someone who is having chest pain is having a heart attack.

    Homocysteine

    Homocysteine is an amino acid in your blood. Doctors have studied homocysteine closely because high levels of it appear to place you at higher risk of cardiovascular disease, regardless of your age or other risk factors. Some evidence suggests that homocysteine might damage the lining of your arteries and promote blood clots, but no direct cause- and-effect relationship has been established. Although homocysteine levels were at first strongly linked to heart disease, more recently researchers have found that link not as strong as they ?rst thought. The level of homocysteine in your blood may be partly hereditary, but it is also related to your diet. In some cases, an elevated level of homocys- teine results from a vitamin B12 de?ciency, so it is important that your doctor measure your level of vitamin B12 through a blood test.
    Your doctor may test your homocysteine levels if you have a strong history of heart disease but you don’t have the obvious risk factors such as high cholesterol, high blood pressure, diabetes, and others. Eating a diet rich in folic acid and B vitamins helps reduce homocys- teine. Many doctors routinely recommend that those at risk for heart disease take folic acid and vitamin B complex. Other doctors rec- ommend the supplements only if homocysteine levels are elevated; however, recent research suggests folate supplements may block the action of naturally occurring folates and vitamin B that you eat in your diet.

    Creactive Protein

    Although high cholesterol is most often considered the major risk fac- tor for heart attack because of its role in the accumulation of plaque in the arteries, not all people who have heart attacks have arteries that are blocked in this way. Doctors have been studying the role of in?amma- tion within the arteries as a separate process that may contribute to the development of coronary artery disease. In?ammation may also explain why in some people, an artery recloses after a balloon angioplasty has been performed to open it.
    In?ammation anywhere in your body causes swelling. If it occurs in your arteries, this swelling can reduce the blood ?ow to your heart. When in?ammation occurs, your body produces a substance called C-reactive protein. The level of C-reactive protein in your blood (detected by a blood test) is a strong predictor of heart disease, espe- cially in people who have had prior heart attacks.
    No one is sure yet what causes the in?ammation in the arteries. It may be a bacterial agent such as Helicobacter pylori (which also causes stomach ulcers) or a viral agent such as the herpes simplex virus. Chlamydia pneumoniae, another type of bacteria, has been studied as a possible predictor of heart disease but with no clear evidence that the bacteria is involved. Some research suggests that in?ammation may damage the arterial wall in a speci?c way that increases the chance of blood clots that block the artery. Obesity and diabetes may also cause an increase in C-reactive protein levels. In fact, visceral or belly fat is the best predictor of an individual’s high level of C-reactive protein. If you are at a moderate or high risk for cardiovascular disease, measur- ing your C-reactive protein may help guide your treatment. You can lower your C-reactive protein with a heart-healthy diet and exercise to lose the belly fat, and also by quitting smoking.

  • Chest X-ray

    Even though far more sophisticated imaging techniques have been developed, the basic chest X-ray can occasionally be a useful tool to assess your cardiovascular system. The X-ray technique works by pass- ing a small, relatively safe amount of radiation through your body and onto a piece of ?lm. The chest X-ray gives your doctor an image of your heart and lungs that reveals the size and shape of your heart, the pres- ence of calcium deposits within your heart, and the presence of congestion in your lungs. If your heart is enlarged, the shape of the enlargement may offer clues to the cause. For example, a narrowed

    heart valve causes a different shape than the enlargement due to conges- tive heart failure.
    Calcium, which shows clearly on an X-ray, sometimes builds up in diseased or injured tissue. In the heart, calcium deposits may accumu- late on a valve, an artery, or the heart muscle itself. The presence of these deposits will direct further testing.
    X-rays also make a picture of your lungs and help your doctor deter- mine whether your symptoms are caused by heart disease or lung dis- ease. The presence of ?uid in lung tissue (a sign called pulmonary edema) means that a weakened heart may have caused ?uid to back up, thereby congesting the lungs (congestive heart failure).
    Having an X-ray done is easy and painless. You will be asked to remove your clothes above your waist and to take off any jewelry that might interfere with the image. You will stand against the X-ray machine, hold your arms out, and hold your breath while the X-ray is being taken (to make your heart and lungs show up more clearly, and to help you hold still).

  • Exercise Echocardiography

    As with other stress tests, an exercise echocardiogram shows how your heart functions when it is working harder. It is most often done to con- ?rm or rule out coronary artery disease. The moving image enables your doctor to see where blockages are occurring.
    A stress echocardiogram may be done in a doctor’s of?ce or a hospi- tal. The test has two parts. First, the technician does a resting echocar- diogram (ultrasound of the heart) while you lie on a table. Then you get on a treadmill or a stationary bicycle and exercise until your heart is working to maximum. A second echocardiogram is done while your heart rate is still high. The test will show if there are any exer- cise-induced changes in your heart in the results of the echocardiogram. For example, in areas of the heart where the blood supply is limited because of obstructions of the blood vessels to the heart muscle, that area may not contract as well as it should. In another example, an exercise- induced abnormality not present when the heart is at rest suggests reversible blood ?ow abnormalities and the need for treatment to prevent a heart attack.

    Chemical Stress Testing

    If a disability (for example, arthritis, back trouble, or a stroke) prevents you from exercising for a stress test, your doctor can use intravenous medication to increase your heart rate combined with an imaging tech- nique such as echocardiography to see how your heart functions when it’s working harder. This method is called chemical or pharmacologic stress testing. The medications most commonly used are dobutamine, dipyridamole, or adenosine.
    The drugs are administered so that your heart rate increases gradu- ally. If you are able to do some exercise, you may be asked to walk on a treadmill for a minute or so after the drug is injected. Trained medical assistants will monitor you throughout the test, and you should report any unusual symptoms. Dobutamine may cause a marked increase in blood pressure or an arrhythmia. Adenosine may cause a brief, passing slowing of the heart rate. Both adenosine and dipyridamole can cause wheezing and should be used cautiously, if at all, in people with asthma or chronic obstructive pulmonary disease. The drugs can be stopped at any time.
    Preparation for a chemical stress test is similar to regular stress test- ing. You will be asked not to eat or drink anything for at least 3 hours before the test, in order to avoid nausea. If you take medications, be sure to talk to your doctor about what to do; you may need to stop tak- ing them for an interval before the test. If you have diabetes and take insulin, you will need speci?c instructions. If you have any history of asthma, bronchitis, or emphysema, tell your doctor, because some stress-inducing medications may be harmful to you.

  • Electrocardiography

    Electrocardiography is a technique to study your heart’s electrical activ- ity by recording the path of an electrical impulse from its origin in the sinoatrial node through your heart as it causes the heart to contract (see page 11). The printout of this activity, an electrocardiogram, is a graph of the electrical activity of each heartbeat over time and the rhythm of successive beats.

    Electrocardiogram

    The electrocardiogram (ECG) is a safe, inexpensive way to get a wealth of information: it tells your doctor about your heart rate and heart rhythm. The ECG may also suggest whether a heart attack has occurred and whether there are potential problems with blood supply to the heart. It is a routine, painless test.

    What to Expect

    You do not have to prepare in any special way to have an ECG, except perhaps to wear clothes that you can take off easily. The ECG may be done in your doctor’s of?ce or in a hospital. For the test, you may be asked to change into a hospital gown and sit or lie on an examina- tion table. In order to conduct the electrical impulse, electrodes will be attached to various parts of your body: your chest, back, wrists, and ankles. To ensure a good connection between your skin and each elec- trode, which is mounted on a sticky patch, the technician will clean these areas, perhaps shave areas of the chest on a man, and apply a conducting gel. Then he or she will hook up the electrodes and enter

    some data into the electrocardiograph machine. You will not feel anything during the testing, which usually lasts a minute or less. There is no electrical energy being passed into your body, and there is no danger of electrical shock. The ECG simply records your heart’s activity.

    What the Results Mean

    In a healthy person, the electrical impulse during a heartbeat follows a regular, sequential path. The electrodes over different parts of your heart follow the path of the impulse and record it on the ECG. The most basic piece of information it gives is your heart rate, which is usu- ally measured by your pulse, but the ECG can give a more accurate rate if your pulse is unusually irregular or hard to feel. Normal heart rates range between 60 and 100 beats per minute.
    The ECG also indicates your heart rhythm, which should be regu- lar. The test may reveal either an abnormally fast beat (tachycardia) or an abnormally slow one (bradycardia). It can also demonstrate an elec- trical blockage in the heart that alters the rhythm and causes an irregu- lar ECG tracing. Each type of arrhythmia causes a distinctive type of tracing pattern.
    In addition, the ECG may tell whether you have had a heart attack, because damaged muscle or scar tissue doesn’t transmit the electrical impulse the same way as healthy tissue would. It can indicate approxi- mately where the damage is in the heart ventricle. Often the ECG reveals evidence of a past heart attack that you didn’t even know occurred. It can also indicate if you are having an attack during the test.
    A component of the wave on the ECG can be affected by an inade- quate supply of blood or oxygen to your heart, particularly if the test is obtained during chest pain symptoms. Further tests may be necessary to determine why this is happening and under what circumstances.
    The ECG can provide information about structural abnormalities, the effects of medications on the heart rhythm and electrical conduc- tion, hypertension, kidney problems, or hormonal problems that affect the wave pattern in speci?c ways. Although a normal ECG does not always exclude heart disease, it still is a reassuring ?nding. Also, if there is a heart problem, the ECG may give clues that indicate what type of testing is needed to further isolate and identify the problem.

    Holter Monitoring

    Because a conventional ECG records only a brief period (6 seconds) of your heart activity, a continual recording over a period of 24 hours or longer may be useful to identify changes in your heart’s rate or rhythm. To accomplish this form of ambulatory ECG, you will wear a battery-powered recording device called a Holter monitor. About the size of a small paperback book, the Holter monitor is portable enough to wear around your waist or on your belt. The monitor connects to electrodes placed on your chest via wires (leads) that pass under your clothes.
    Being ?tted for a Holter monitor is a painless procedure. It is a good idea to bathe or shower before you go to your doctor’s of?ce, because you cannot get the monitor wet once you are wearing it. The technician will prepare your skin just as for an of?ce ECG. At least one electrode and lead may be taped down to secure it as you move around. You will wear the device usually for 24 hours, including while you sleep. You will also be asked to keep a log as you go about your usual day: what you were doing and whether you experienced any symptoms, and at what times. Every heartbeat will be recorded and analyzed for information.
    After the designated monitoring period, you will return to your doc- tor’s of?ce to turn in the device. Having the electrodes removed might be uncomfortable, like tearing off a bandage. The tracings for the mon- itoring period will be analyzed, and correlations will be made between the Holter recording and the times of unusual symptoms or events in your log.

    Event Monitoring

    If you are having symptoms that are unpredictable or infrequent, you may have to use another ECG device called an event monitor or transtelephonic monitor, which records your heart rhythm. You are usu- ally asked to use this monitor for one month. You can take it off to bathe, or for other brief periods, but it’s best to wear it as often as possible. A small recorder is attached to a bracelet or ?nger clip. If you experience a symptom, such as light-headedness, you attach the recorder (if you are not wearing it) and push a button on the monitor that triggers a memory of what was recorded for several minutes before and after you pushed the button. This data can be transmitted over the telephone, or you can bring the monitor to the of?ce. This helps identify any rhythm disturbances that occur while you have symptoms. If a dangerous rhythm problem is identi?ed, you may be instructed to seek medical attention urgently.
    Another type of event monitor, this one implantable, has been devel- oped to capture your heart’s activity during infrequent symptoms that occur only a few times a year. Called an implantable loop recorder, it is inserted in your chest, and you wear it for as long as 18 months.

    Exercise Stress Testing

    An exercise stress test is a continuous ECG that shows how your heart performs during exercise, when the body is demanding more blood and oxygen. It shows the adequacy of the blood sup- ply to the coronary arteries and how well the heart muscle functions. You also might hear it called a treadmill test, an exercise tolerance test, or an exercise ECG. It is a common diagnostic tool for detecting coronary artery disease and the origin of symptoms such as chest pain, because it shows whether the blood supply in the coronary arteries is reduced. It can identify a safe level of exercise for any heart patient, checks the effectiveness of medications, helps predict the risk of heart attack, and checks the effectiveness of procedures done to improve circulation in a person with coronary artery disease.
    The test is designed to place stress on your heart—about as much as a fast walk or a jog up a hill in a carefully controlled environment with trained staff close at hand. During the test, the technician will carefully monitor your heart rate, breathing, blood pressure, heart rhythm, and how tired you feel.

    Having an exercise stress test
    An exercise stress test is a type of ECG that shows how the heart performs when you exercise. Usually the test is done while you walk on a treadmill, and then the speed or slope are gradually increased to make your heart work harder. The test is like a carefully supervised workout, with a warm-up, a gradual increase in the level of exercise, and a cool-down period. A doctor or technician will watch you closely throughout the test.

    The most typical stress test is done by having you walk on a treadmill or ride a stationary bicycle. If the test shows that your heart doesn’t function normally during exercise, you may need to repeat the treadmill test combined with echocardiography  or nuclear tech- nology  to better identify the problem. Often these tests are done with the initial exercise stress test to improve the accuracy of diagnosis, especially in women. If you are unable to exercise because of illness, you may undergo a chemical stress test (see page 128), for which you will be given a drug that mimics some of the effects of exercise on your heart rate while ECG tracings or nuclear images are made.

    What to Expect

    You will be asked not to eat for 12 hours before the test, because a meal can make you uncomfortable or nauseous. You can drink a small amount of liquid such as water, but no beverage such as coffee, tea, soda, or chocolate that contains caffeine. Be sure to ask your doctor about any medications you take and whether you should stop taking them before the test. If you have diabetes, you will be given speci?c instructions about taking insulin.
    A technician will prepare your skin for the placement of electrodes, similar to the preparation for a regular ECG. You will also be ?tted with a blood pressure cuff. A resting ECG will be taken before you start exercising, and then you will get on a treadmill or a bicycle. The ?rst 2 or 3 minutes you will exercise at a slow, warm-up pace. Then every 2 or 3 minutes, the speed or slope will be increased gradually to simulate going uphill. The doctor will probably encourage you to continue until you are too tired to go on, or until you have a symptom such as pain, dizziness, or shortness of breath. After this pro- cedure, you lie down or sit quietly for about 10 minutes. Your doctor or technician will monitor your heart and blood pressure throughout this period. He or she will ask you questions about how tired or out of breath you feel. If the ECG reveals any potential problems, the doctor or technician will ask you to stop exercising. After the test is complete, you can return to your normal day.

    What the Results Mean

    The doctor reading the ECG may be able to tell you preliminary results immediately, but a complete analysis will probably take several days. If the test shows that your heart functions normally during exer- cise, the results can be used to help you plan a ?tness program. If the results indicate that your heart functions abnormally during exercise, you may need to have more tests, such as an echocardiographic stress test  or a nuclear stress test, to determine more precisely where the blood supply is being blocked. On occasion, you may go straight to having an angiography . If you already have coronary artery disease, the test can reveal a new blockage or one that is worsening.
    The choice of stress testing will depend in part on your medical history and your doctor’s preferences. Exercise stress testing is less specific—and therefore, less helpful—than thallium or echocardio- graphic stress testing; however, exercise stress testing is much less expensive and thus is often used as a ?rst step in screening for heart dis- ease. Those who already have heart conditions that may in?uence the ECG result may need nuclear stress testing. Echocardiographic stress testing may be better for women because women, especially young women, are prone to false positives on ECGs.

  • Evaluating a Heart Problem

    If you experience any symptoms that might be indicators of a heart problem—such as chest pain, shortness of breath, or a pounding heart—see your doctor immediately. He or she will interview you thoroughly about your medical history and symptoms and then do a physical examination to try to detect what might be causing the symptoms. Depending on what the examination reveals, he or she may order further testing to diagnose the problem. If you know what to expect, you will probably feel more relaxed about the exam, and you can be better prepared to answer questions. It will be very helpful if you can bring in notes with speci?c details about when you experienced a symptom, how often it recurred, and how long it lasted.

    Medical History

    If you are seeing a doctor for the ?rst time, he or she will ask some gen- eral questions about your medical history. If you are reporting a speci?c event, the questions will focus on that event. Here is a general outline of what to expect:
    • Questions about your chief complaint. Your doctor will want to know what brought you into the of?ce. He or she will ask speci?c questions such as how it felt, when it occurred, what you were doing when it occurred, or what seemed to relieve it. Be as thor- ough and speci?c as you can be. Do not hesitate to volunteer information beyond the questions.
    • Questions about your medical history. Information about other medical conditions you have or have had can help indicate possi- ble causes for your symptoms and rule out unnecessary tests or inappropriate treatments. Again, written notes may help you remember illnesses, tests, or surgery that you have had. If you are seeing a specialist, your other doctor or doctors may be able to send medical records and test results in advance of your appoint- ment. If you are referred to a spe- cialist, ask the referring doctor for pertinent test results to take with you to the appointment.
    • Medications. Your doctor will want to review all the medications you are taking; bring a list that includes dosages to the appointment. It is important to include herbal prepa- rations and nonprescription med- ications, because they may interact with other drugs. Also, know and remember your drug allergies.
    • Family history. Be prepared to answer questions about the medical history of your parents, siblings, and children. This information gives the doctor clues about hereditary aspects of some conditions and your overall risk.
    • Lifestyle. Information about habits such as smoking or drinking, diet, and exercise are important. Some of these factors may help explain a symptom; for instance, caffeine can cause an irregular heartbeat in some people. Do not worry about looking bad or being embarrassed by your habits. This information can help a great deal with diagnosis and treatment. You may also be asked questions about your workplace and about stress.
    • Other organ systems. Your doctor may systematically review other body systems to make sure nothing is overlooked.

    A Physical Examination in Detail

    A cardiovascular physical examination will include taking your blood pressure (see page 43), measuring your heart rate and rhythm by check- ing your pulses, inspecting the veins in your neck, checking your body for swellings, and listening to the sounds of your breath, heart, and

    blood vessels. You will probably be asked to change out of your clothes into a hospital gown and sit or lie on an examining table.
    • Measuring your heart rate and rhythm. Your doctor will check the pulse at your wrist, in the carotid arteries in your neck, or in the femoral arteries in your groin. The pulses enable him or her to measure your heart rate and to determine if your heart- beat is regular, skips beats, or has extra beats. An absent or reduced pulse at one of the sites may indicate a blockage in a blood vessel.
    • Veins in your neck. The doctor will look at (not feel) the jugular vein in your neck to observe the pulse. The location and size of the pulse indicates the pressure on the right side of the heart and the possible presence of excess ?uid in your system.
    • Swelling. Swellings in parts of your body such as your legs and ankles can indicate excess ?uid or a blockage in a vein.
    • Listening to your breath. Listening to your breath sounds by placing a stethoscope on your chest can reveal ?uid building up in your lungs (which makes a crackling sound) or scarred tissue in your lungs. Thumping on your chest can help locate where the ?uid is; a ?uid-?lled area sounds dull instead of hollow.
    • Listening to your heart. Putting the stethoscope on four distinct sites over your heart, your doctor can listen to blood ?owing through your heart and heart valves. A heart murmur is the sound of turbulence caused by a problem with a valve or another heart structure. You may be asked to stand up, squat, or lie back, because murmurs change when you are in different positions. Extra sounds, called gallops, or other types of sounds may indicate vari- ous types of heart problems. Some unusual sounds are completely harmless.
    • Listening to blood vessels. Your doctor can evaluate blood ?ow in large blood vessels by listening at different points in your neck, abdomen, and groin. Turbulence in these vessels makes a sound called a bruit, which may indicate blockage.
    Depending on what the doctor learns from this basic examination, or “cardiac workup,” he or she may order blood tests, imaging procedures, or other tests of cardiac function in order to diagnose more speci?cally and plan treatment.

    After a physical examination including listening to your heart and lungs with a stethoscope—your doctor will need more detailed infor- mation about your heart. The doctor will ask questions about diseases you have been diagnosed with, any persistent symptoms you have noticed, and your family medical history. A variety of tests are available to examine the structure of your heart, how well it functions, whether it is damaged or diseased, and the nature or extent of the disease.
    Which tests you take depend on your symptoms, your medical history, your general cardiac condition, and your doctor’s assessment. Usually you will have some simple tests ?rst, such as an ECG (an electrocardiogram, which records your heart’s electrical activity), and then additional tests as needed to assess your particular problem. In addition to electrocardiography, other means of testing include blood tests; echocardiography (which uses sound waves to examine the heart valves and chambers); different types of stress tests (to study the heart while it is working harder); nuclear imaging (using safe amounts of radioactive materials to study heart function); other imaging tech- niques; and in some cases, more invasive tests that are done in a hospi- tal setting.
    The tests can reveal useful information speci?c to your heart symp- tom or problem that will help guide your treatment. Many of the tests are noninvasive, meaning that they do not involve a needle stick or the introduction of any catheters (tubes) into your body. Knowing how and why a test is performed will help you feel more comfortable, and under- standing something about the possible results will help you learn about your heart along with your doctor. Don’t hesitate to ask questions before or after any test. Many tests require your permission or informed consent, and your doctor should fully explain beforehand any risks from the tests.

  • Physical Examinations and Diagnostic Tests

    The best way to monitor your health is to see your doctor and work together as a team for your health. Many of the major risk factors (such as blood pressure and cholesterol) are apparent only with a med- ical examination. The earlier you can identify a problem area and start to work on it, the more likely you will be able to prevent the develop- ment of more serious disease. For instance, an evaluation of prehyper- tension (see page 43) or prediabetes (see page 106) gives you a head start on these risk factors. As you work on one risk factor (for instance, exer- cising more to lower cholesterol) you will very likely be improving oth- ers as well. Know all your risk factors from your medical history—not only high blood pressure, diabetes, and smoking, but also risks from
    menopause, aging, and lifestyle choices regarding food and exercise.

  • Stress

    In addition to the major risk factors for heart disease (high cholesterol, high blood pressure, physical inactivity, smoking, and diabetes), stress can be a contributing factor. The effects of stress on your heart health are dif?cult to study and quantify in part because people not only expe- rience different levels of stress, but they also respond differently. Researchers have identi?ed several ways that stress may adversely affect some people’s hearts:
    • Under stress, your body releases extra hormones (epinephrine and norepinephrine) that raise your blood pressure, which may over time injure the lining of your arteries. As the arteries repair them- selves, they may thicken, which promotes the buildup of plaque.
    • A stressful situation tends to raise your heart rate and blood pres- sure, so your heart requires more oxygen. In someone who already has heart disease, this oxygen shortage can bring on chest pain (angina).
    • Stress increases the clotting factors in your blood, which increases the chances that a blood clot will form and block an artery, espe- cially one already partially closed by plaque.
    Then, of course, there are the ways that many people may choose to deal with stress—overeating, smoking, drinking excessively—that are damaging to the cardiovascular system.

    The fact is that everyone is under stress of some kind at least intermittently and perhaps much of the time. You can usually recognize symptoms of your own stress in the form of aches and pains, dif?culty ?ghting off mild infections like colds, sleeplessness, or feelings of anxiety or irritability. You also probably know when some of your less healthy coping mecha- nisms are escalating—as, for example, when you put on weight during a tough time, or start smoking more.
    Learning to manage stress makes good sense for your overall health. But more research is needed before experts can reliably recommend specific methods of stress reduction as treatments for cardio- vascular diseases. Generally, if you or your doctor believes that stress is having a harmful effect on your health, you can work on several strategies to manage its impact:

    • Communicate with family and friends about the things that trou- ble you. Their support and love will help reduce your response to stressful situations.
    • If you feel a sense of urgency because of competing demands on your time, consider time management techniques that will help you prioritize and set realistic expectations. Your workplace, library, or the Internet may offer speci?c methods. Also, be cau- tious about agreeing to take on new projects.
    • Choose a relaxation technique, such as yoga, meditation, or biofeedback, and make time to master it and practice it regularly. Although there is no conclusive medical proof these techniques can lower blood pressure, there are some promising studies point- ing in that direction.
    • When you know that a speci?c problem is causing you anxiety, talk to your doctor or other health-care provider about a support group that focuses on that problem. These resources may be avail- able through a community center, hospital, religious organization, or YMCA.
    • Professional counseling or psychotherapy may help you through certain dif?cult periods. Your doctor can help refer you to an     appropriate professional. If medications such as antidepressants are appropriate, your doctor or a psychiatrist can prescribe them and help you get essential counseling as well.
    • Use commonsense therapy: eat a healthy diet, exercise regularly (see the box on page 80), limit alcohol and caffeine, and do not smoke.
    Managing stress, or preventing stress in the ?rst place, is especially important to people who have already had a heart attack or a stroke. Preventing another heart attack or stroke called secondary prevention by doctors is a key goal for the doctor-patient team. As noted repeat- edly in this book, lifestyle changes are crucial to prevention or second- ary prevention, and stress management should be a key focus of lifestyle changes that also include controlling your cholesterol level, controlling your blood pressure, losing weight if needed, exercising regularly, and stopping smoking.
    Depression may be related to stress but is a disorder that needs treat- ment. It is natural to a certain degree to feel “blue” or be upset after a heart attack or a stroke. However, if you have persistent depression, it is important to note that it is treatable—that is, not just “something to live with” (see also “Depression after a Stroke,” page 232). Depression symptoms include prolonged periods of feeling sad or unable to cope, strong feelings of guilt, strong feelings of pessimism or loss of hope, a loss of interest in normal pleasures (including sex), unusual weight changes (unintentional losses or gains), and dif?culty relating to loved ones or coworkers. If you or a loved one has depression, seek treatment from your primary care doctor; he or she will make treatment sugges- tions, possibly including medications or talking therapy, or refer you to a psychiatrist or other mental health professional.

  • Research: Finding out more

    There is a variety of sources about new research on MS. Which you use depends on your own inclinations, and indeed your own resources! The most important source of reliable and accurate scientific research on MS is that contained in the peer-reviewed scientific, and especially neurological, journals. Usually these are not obtainable directly except in specialist medical libraries, but recent key issues and findings on MS from the journals can be obtained through computer searches, often through ordinary libraries, using one of the major medical databases such as ‘Medline’. Increasingly the MS Society in Britain, and the MS Society in the United States are putting out press statements and information on major current research issues, often highlighting advances in their regular Newsletters.
    If you have access to the World Wide Web, there are now all sorts of possibilities of keeping track of new research. These include:

    • the websites of the MS Society in Britain and the United States;
    • the website of MS Trust, which is fast, efficient and up to date;
    • using one of the ‘search engines’ on the Web to trawl for updates on MS, and other sources of information;
    • joining ones of the growing number of Newsgroups in which people exchange information about new developments and other issues about MS. These latter groups are particularly important in terms of contact with other people with MS, and are often likely to be amongst the first sources of information about all kinds of developments, both scientific and non-scientific.

    Web addresses are currently changing too fast to permit any sensible listing here, but one source which is likely to be with us for sometime is the Usenet News Group at news://alt.support.mult-sclerosis. This group hosts 50–100 messages per day and includes announcements about new web pages and updates about existing pages.
    The next stage beyond these publications is to go to a good public library (a regional centre rather than a local library) and search for books on MS. Most libraries, including most local public libraries now have computer terminals for keyword and title searches. Library staff are usually keen to help with difficult searches and to help locate specific information.

  • Research: New lines of research

    Genetic research

    Chapter 1 discusses the possible causal relationship between MS, genetics and the environment. The most striking thing now is the speed at which research on possible underlying genetic factors is being undertaken. Of course, this research is part of the massive international research effort which has now ‘mapped’ human genetic makeup – in other words which has unravelled the human ‘genome’. In the course of this research more and more genetic associations with particular diseases are being uncovered. Of particular interest is the fact that genes control the human immune system, and so, if it turns out that people with MS have a clearly different genetic makeup to other people, ultimately the most effective way to manage immune system malfunctions may be to try and deal with those genetic differences. This will not be a simple process because several genes are already known to be implicated in MS, unlike some other conditions where only one gene is involved.
    Currently genetic research on MS is based on two main lines of inquiry:

    • Genes that allow the body to recognize which are its own tissues and which are those of an ‘invader’ bacteria or virus are being studied. If this recognition process goes wrong, then an
    ‘autoimmune’ attack of the body’s own tissue is likely to occur, as in MS. The genes under investigation here that perform this recognition function – ‘histocompatibility genes’ – are usually either HLA (human leukocyte antigen) genes, or MHC (major histocompatibility) genes.
    • The genetic control of ‘lymphocytes’ (T cells), which are one important class of cells responding to insults to the immune system, is the second line of study. Although there is much detailed research still to be undertaken, it appears likely that a combination of genes controlling these lymphocytes and related immune
    activity produces a susceptibility in people with MS to the disease, although other triggering factors, perhaps environmentally determined, may be necessary for the onset of the disease.

    Research on viruses and Multiple Sclerosis

    The relationship of viruses to MS has been the subject of much research over the past two decades, and causes an equal amount of controversy. Almost every year, it has been claimed that a virus specific to the cause of MS has been discovered. However, none of these claims has been sustained after further extensive investigation. The basic issue is really one of cause or ef fect. Does a virus cause Multiple Sclerosis, or does a weakened immune system have the effect of making the body more susceptible to attack by viruses? Most researchers believe the latter to be the case, but an existing faulty recognition process in the immune system may either also fail to recognize (and thus attack) an invading virus, or such a virus may, through the same process, accelerate the body’s own attack on itself. In this respect recent work on viruses is being linked to other research on malfunctioning immune systems, and genetic research is also continuing.

    Regeneration of myelin

    This research area – trying to regenerate myelin – has been significant over the past few years. The cells that produce myelin are called
    ‘oligodendrocytes’, one of a family of what are described as ‘glial cells’. If the life of oligodendrocytes could be fully understood, as well as their role in the formation and repair of myelin, then an attempt to encourage their revitalization in MS could be made. This research process has also involved investigating exactly how the nervous system responds to myelin damage and how scar tissue is formed, as well as estimating what effects regeneration of myelin might have.
    Research on myelin damage and possible regeneration is yet another story of an initially hopeful scientific development followed by major disappointment. For some time it was thought that myelin could not be regenerated at all, and then more sophisticated techniques indicated that myelin repair did occur in Multiple Sclerosis, although it was very slow and weak – and was not enough to compensate for the original damage. Now scientists are concentrating on seeing whether and how this process of repair might be made more effective. The importance of this research is the knowledge that, even if myelin has been lost (and thus messages along the nerves are malfunctioning), the underlying nervous tissue is almost certainly still intact, at least in the early stages of MS; thus, if it was reinsulated (remyelinated), it may well be able to function normally. Once demyelination has occurred for some time this may be less likely.
    Animal models have suggested that remyelination is possible in such a way as to restore some functions originally lost. Strategies have included:

    • using substances called growth factors to enhance the actions of myelin-producing cells;
    • trying to inhibit other processes that weaken the actions of those cells, or
    • in a more adventurous way, investigating the possibility of transplanting cells to produce myelin.

    There are a number of substances being tested on humans to assist remyelination, although the lessons of the disappointments of equally promising possibilities arising from animal work with EAE (see above) are important to bear in mind. It is also important to say that most of the remyelinating strategies are essentially compensatory ones, i.e. they do not address the underlying disease process that is still going on – whilst some remyelination may be assisted, other demyelination may be occurring or about to occur. In addition for those with long-standing Multiple Sclerosis, the underlying nervous tissue will probably have been damaged, as well as the myelin coating of that tissue. In such a situation, remyelination may have little or no effect on symptoms.

  • Research: Types of research

    People sometimes use the term ‘research’ in a very loose way for almost any kind of information-gathering about a topic of interest – finding out information about your Multiple Sclerosis, by reading this book for example. However,
    ‘scientific research’ involves a very particular way of acquiring information, where a specific question – called a hypothesis – is devised and tested, to find out whether, under particular conditions, that question is answered negatively or positively. To be treated as scientifically correct (valid), the same answer must be repeated under exactly the same conditions by other researchers.
    There are broadly five kinds of scientific research being undertaken in relation to MS:

    • The systematic study of the distribution and patterns of MS in different communities and countries – usually known as epidemiological research – might involve asking questions about whether Multiple Sclerosis is more common in one geographical area than another, or is decreasing or increasing in a particular population over time, and what factors might explain these differences.
    • Laboratory-based research focuses on questions related to the development of MS, for example why and how it affects specific nervous system tissue, where researchers often work at the level of individual cells; or what are the possible genetic differences between people with and without MS where blood or tissue types are examined.
    • Clinical research on patients seeks to answer questions about what is often called the ‘natural development’ of Multiple Sclerosis in individuals, through the investigation of particular symptoms and signs that develop in those individuals over time, and what consequences these have for people’s ability to function in everyday life.
    • Other research concentrates on questions about the effectiveness of potential therapies for MS, commonly undertaken through clinical trials – often after extensive safety testing in the laboratory. People with MS may be asked if they wish to participate in a clinical trial, for example to test a new drug.
    • More research is increasingly taking place in what is called applied science in relation to MS. In the absence of a cure, much of this research is investigating how, for example, physiotherapy or speech therapy can reduce the impact of symptoms, or how far psychological support or counselling can help people to manage their symptoms better.

    Each of these approaches uses scientific methods to understand Multiple Sclerosis, and assist people with the disease. However, the most common form of scientific method you are likely to come across personally is the clinical trial.

    Epidemiological research

    As we have said, epidemiological research primarily focuses on the distribution of MS in specific populations and countries. In Chapter 1 we talked about some distribution patterns that had led to important lines of inquiry about possible causes of the disease. Thus the facts that MS is found largely in temperate regions of the world and more amongst women, and that there appear to be geographical ‘hotspots’ of the disease, all seem to explain something about Multiple Sclerosis. The problem with epidemiological research is that there are many, many reasons why such patterns could occur. Most patterns are misleading in that they either disappear when subjected to detailed investigation, or are explained by another factor not related to MS. Quite a number of people with MS have found several others with the condition in their area, or have had some job or other life experience in common. It is tempting to jump immediately to the conclusion that there must be some link that has caused the MS. Usually such patterns occur just by chance – even when very odd things happen, such as two or three unrelated people with MS living in the same street. In such cases the findings of epidemiological research are primarily suggestive, and must be supported by other kinds of research.
    At present two of the most interesting, although very time-consuming, types of epidemiological research, are those trying to detect and assess all people with MS in a particular area, and those measuring the distribution in the population of certain genetic ‘markers’ linked with MS. In the former studies, findings are indicating that there are more people with MS than we had previously thought, and the latter findings are suggesting increasingly firm associations between particular genetic markers and types of Multiple Sclerosis.

    Laboratory research

    There is a very wide spectrum of research in this area; it is usually undertaken on individual cells or cellular processes, often in animals. Much of this research is linked to understanding how the body’s immune system in Multiple Sclerosis seems to attack itself. Many scientists believe that the body’s failure to distinguish between ‘foreign invaders’ in the form of bacteria, viruses and so on (which it should attack), and its own tissue (which it should not attack), is the root explanation of why MS occurs. This kind of research has identified many of the different types of cell in the immune system, how they work, and what happens when they fail or become disrupted. Studying how immune systems work both in animals and in people with MS, who also have other diseases thought to be immune related (such as rheumatoid arthritis), gives a clearer idea of what is happening in people with MS. However, such work is not always directly transferable to MS. For example, in the late 1980s, research on a disease model in animals (called EAE – experimental allergic encephalomyelitis), thought to be similar to Multiple Sclerosis in humans, revealed promising clues to therapies that might prevent EAE in animals, and thus possibly prevent MS in humans. However, it turned out that the human immune system was far more complicated than that of laboratory animals. As a parallel development a number of fierce immunosuppressant therapies were devised, in the hope that, by suppression of the activities of the immune system, then at least no further ‘autoimmune’ attacks would occur on the body’s own tissue. However, many of these therapies suppressed all immune system activity, and so led to major infections and complications, in which often the intended ‘cures’ produced worse symptoms than those of the disease they were supposed to help.
    Nevertheless, from these studies have come some interesting develop- ments – and one of these developments is work on what are called
    ‘cytokines’. These are chemical messengers associated with the regula- tion of immune system activity; understanding these cytokines has already proved rewarding. For example ‘interferons’ are one kind of cytokine and, of course, ‘beta-interferons’ have proved to give consider- able therapeutic benefit in MS. However, the position is still complicated, for some cytokines seem to make MS worse and some seem to help con- trol it; whilst beta-interferons seem to help MS, other types of interferon do not. The lesson from this particular kind of research, just as in much scientific research, is that there are many disappointments as well as new developments, and often the disappointments lead to new approaches to Multiple Sclerosis.

    Clinical research

    Clinical research directly involves studying people with Multiple Sclerosis and their symptoms on an individual basis. Although it may sound strange after many years of research on MS, what is called the ‘natural history’ of the disease is still not entirely clear, although major studies in Canada have revealed much about the long-term outcome of MS. As we discussed in Chapter 1, it is still not really possible to give anyone a clear idea of how their disease will develop over time, so much clinical research is still devoted to assessing people with MS over long periods of time – several decades – to chart as carefully as possible how their disease develops, especially in relation to early symptoms and signs. Such information is very important, in order to judge, for example, whether early inter- vention will af fect the later course of the disease. As people with the condition know, the effects of MS appear to be very fickle on a day-to-day basis, let alone a longer term one, so it is one of the most difficult research tasks to determine the specific effects of MS, as against those occurring from other, perhaps unrelated, conditions, and the effects of natural ageing processes. Other clinical research is focused on improving and developing diagnostic techniques to try and ensure that such techniques are both accurate and available as early as possible.

    Applied research

    The traditional kind of research on MS has focused on the causes and cures of the disease, and indeed this kind of research is still the most important in terms of size and funding. However, this research generally does not tackle all the everyday problems that people with MS have of living with the condition. To put it another way, whilst waiting for a cure, people with Multiple Sclerosis have had to live for years with many difficult and annoying problems, and indeed may have to wait many more years before MS and its problems are banished. Thus an area of ‘applied research’ has arisen where the focus is on researching the best ways in which people with MS can live with or manage their current and future symptoms, and their consequences. This research might include:

    • clinical trial research on drugs and other means of managing everyday symptoms;
    • the most appropriate forms of equipment that people may need, to live as comfortably as possible;
    • the most effective ways in which physiotherapy, occupational therapy and speech therapy can help people with MS;
    • the most appropriate ways in which issues of employment, housing and insurance can be dealt with;
    • the psychological and social consequences of MS, especially in relation to concerns about the quality of life, and
    • issues about counselling and support for the family consequences of the condition.

    In practice, this broad area of ‘applied research’ is one of the most significant of current research areas, and is one which – on reflection – many people with MS find extremely valuable and relevant. Although everyone wishes to find a cure for MS, a realistic view is that this will take some time, and meanwhile research on how people with MS can make the best of their everyday lives is very important.

    Clinical trials

    Much of the hugely expensive development work on new (drug) therapies is undertaken by pharmaceutical companies. The commercial return on their investment in these costs, including clinical trials, has to come from patenting and protecting the rights to the therapy involved. Potential medicines that may be freely available, or are not patentable, offer very little incentive for such companies to invest in them, unless they can in some way lay claim to a variant of the medicine concerned or a particular way of administering it. In such cases, other funding agencies, such as the Medical Research Council (MRC), step in to support formal trials on drugs or other substances that are considered promising therapies for MS.

    What is a clinical trial?
    A clinical trial is actually a formal scientific means of testing the safety or the effectiveness of a drug or other treatment, either against another drug or treatment, or against what is called a ‘placebo’, i.e. an inactive substance that cannot be distinguished from the ‘real’ or active drug by people who are taking part in a trial nor the doctors who are administering it. This way the drug can be tested for efficacy compared to the other drug or substance.
    In a clinical trial of a potential therapy for Multiple Sclerosis, usually one group of patients (the experimental group) receives the active drug or the drug being tested, and another group (the control group) receives the drug against which it is to be compared, or the placebo, the inactive substance.
    The two groups of patients should be as similar as possible at the outset of the trial, so that the drug alone will make the dif ference between the groups. Various characteristics of the two groups of people will be measured before, during and after the trial – typically these will include measures of disability, the number of MS ‘attacks’ or ‘relapses’ people have had, and other things such as blood cell counts or hormone levels. It is always hoped, of course, that the trial will show that the group who has received the active drug will do better. Thus, for the active drug to be shown to be ef fective, the trial must finally result in a statistically significant difference between the characteristics of the two groups. However, many trials are relatively inconclusive and, because MS is a complicated condition, statistically significant differences will be observed for some characteristics but not others, or indeed only for certain types of participant.

    Blinded and randomised clinical trials
    ‘Blinded’ in this sense means that you do not know which drug – active or inactive – you are taking, and thus you will not be able to exert any psychological impact on the results, or be tempted to take supplements if you know that you are in the control rather than the experimental group. People are also usually ‘randomized’, meaning that they are allocated to either the experimental or control groups randomly, i.e. they cannot choose which group they join. If people are allowed to choose which group they go into, biases may arise in the trial, as certain people, for example with milder or more serious forms of Multiple Sclerosis, may elect to join one of the groups and not the other. ‘Double-blinded’ means that the researchers also do not know which people receive which substance. The placebo and the active substance must therefore look and taste identical, so they are often provided in coded containers to each person. Only at the end of the trial is the code broken to reveal who received which compound, when the trial is ‘unblinded’. This minimizes the possibility of researchers influencing the outcome, for instance by paying more attention, or giving additional and dif ferential care, to people in the treatment group during the trial.

    The placebo effect
    The ‘placebo ef fect’, i.e. feeling better as a result of taking any
    ‘medication’ that people believe may have a beneficial effect whatever its real and unique (physiological) effects, has been shown to operate even when coloured water is drunk. Therefore there is a danger that any real effects of a drug being tested could be mixed up with this ‘placebo effect’, which is why comparing treatments in identical ways is so important. Indeed, the problem caused by the placebo ef fect is one reason why rigorous clinical trials must be performed before a new drug or other therapy can be scientifically accepted.

    Clinical trial phases
    Before a drug can be licensed for normal clinical use, there are three essential sets of information that have to be researched: its safety (a Phase 1 trial), its appropriate dose levels and the medical conditions or symptoms for which it is best suited (a Phase II trial), and its effectiveness (a Phase III trial).

    • A Phase I clinical trial is a test of safety, or toxicity, and is aimed primarily at determining whether the substance has any adverse effects on humans. Of course, before the drug is given to humans, toxicity will also have been tested in animals, cell cultures or computer simulation tests.
    • A Phase II clinical trial is usually only undertaken on a small scale and determines whether a larger scale trial is worth undertaking. Phase II trials also help to clarify which groups of people and, for example, which types of MS are most likely to benefit, and how that benefit might be measured. However, Phase II trials may not test for effectiveness, which often requires large numbers of subjects.
    • So a Phase III trial is necessary to prove the effectiveness of a drug to enable it to be licensed for clinical practice. Phase III trials are usually very large, very expensive and very lengthy, but show to a high degree of statistical certainty how effective a substance is in treating the chosen people and conditions.
    • Sometimes Phase IV trials are undertaken. These are conducted after the drug has been licensed, and thus may be described as the
    ‘post-marketing phase’ of trials. In such trials, longer term side effects may be assessed; the drug may be tested in different types of MS; or its use may be tested in other conditions – perhaps not associated with MS.

    Of course it is important to say that, even when a drug has been tested in all three Phases (I,II and III) and is licensed for clinical use, it may still not become widely available owing to its cost, practical problems in administering it, or its generally unacceptable side effects.

    Which drugs are tested in clinical trials?
    As we have implied, in order for a drug to be licensed for clinical use, it has to go through the complicated process of clinical trials, and such a process is very expensive. Increasingly, international pharmaceutical companies sponsor the majority of such trials, with additional support from national Multiple Sclerosis Societies, and government-funded Medical Research Councils. Whilst pharmaceutical companies necessarily use scientific methods to evaluate the drugs that they themselves have developed, the choices as to which are subjected to the most expensive Phase III trials, or indeed the initial choices as to which drugs are developed, must – in their terms – be subject to a commercial judgement on their part. This would involve making a judgement about the size of the market for such a drug, and its likely profitability, as well as, of course, making a judgement about its likely efficacy.
    It would be reassuring to believe that only a scientific basis was used to decide which drugs were subject to Phase III trials, but generally there are far more drugs that could be subject to such trials than the funding available, and it is clear that commercial as well as scientific factors must intrude in the selection process. Such a process, at least from a commercial point of view, is likely to relegate drugs with a potentially low profitability, or which cannot be patented. The history of therapeutic possibilities in Multiple Sclerosis is littered with the hopes of people often for non- patentable substances in relation to the disease – such as evening primrose oil, hyperbaric oxygen and, most recently, cannabis. It is very unlikely that pharmaceutical companies would be involved in testing such substances unless they can patent a variant of the substance concerned, and thus usually – as in the case of all three substances mentioned – medical charities and/or the government-funded Medical Research Councils themselves would need to fund such trials. Such funding may occur in response to the continuous and widely expressed concerns of people with MS, although decisions for this kind of funding are not normally justified on this basis.
    Finally, it is worth saying that, although some major potential therapeutic advances will remain untested because of the particular focus of the pharmaceutical companies, this is unlikely because of the significant number of checks and balances made by the Multiple Sclerosis Society and the Medical Research Council.

    Participating in a clinical trial
    First of all it is important to say that, if you participate in a clinical trial (especially a Phase III trial) for MS, it will generally not be guaranteed that you will receive the new drug – but you will indeed have a chance to take it, probably on the basis of being randomized to the ‘treatment group’. You will probably have a 50–50 chance of receiving the new drug or being randomized into the ‘control’ group, who will use either a placebo or another comparison drug.
    However, there are several reasons why it is still worth your while joining a clinical trial, even if you are not given the new drug by being randomized to a comparison group:

    • To be frank, it is likely that you will receive more careful clinical assessment and support, than you otherwise would do, if you participate in a clinical trial, whether you receive the new drug or not. This is because all those participating have to be meticulously and regularly monitored.
    • You will almost certainly gain from the placebo effect, whatever you are taking in the trial.
    • You would have the altruistic satisfaction of participating in a trial that would benefit others, even if you do not have the new drug yourself.
    • Often trial procedures allow standard tried and tested therapies to continue to be used if, for example, you have an attack or exacerbation during the trial.
    • More frequently now, trials compare one drug with another, not just with a placebo substance. In these trials you would receive an active drug, whichever group you were in. Indeed the comparison drug will already have been shown to effective in managing some aspects of MS, and often the new drug is one in which only a marginal additional assistance for MS is hoped for – but not yet known.

    Depending on the type of clinical trial concerned, people are used from many different sources, but the largest sources of all are people with MS already under the care of neurologists, or those who are attending hospital clinics. In Britain the major means of recruitment is usually directly through your neurologist. When they are notified of a particular trial, they will investigate their own lists of people with MS to see whether any are suitable for the trial. You would then be contacted and asked if you would be prepared to participate. Of course, you can make your neurologist aware of your interest in clinical trials at one of your assessment meetings or by letter. Increasingly, in the United States, trials are more widely advertised through specialist centres and publications, and people can apply directly to participate, but in Britain this more open process of recruitment is still in its infancy.

    Eligibility
    One of the things about clinical trials is that they all have what are called eligibility criteria. These are often very specific, and relate to the particular types of people and the particular types of MS that they feel would most benefit from the new drug. These criteria could mean that your type of MS is not considered to be the type that could gain most from the new drug. There is also another consideration here. In order to be able to test for the effectiveness of a drug over a reasonable period of time, people whose Multiple Sclerosis is currently changing relatively rapidly, or who are having attacks, or in whom progression is more measurable (for example in relation to changes in the ability to walk) may well be chosen, in preference to people whose MS is worse overall but is relatively stable. Thus it is often frustrating for people with long-standing MS to be excluded from some trials, on the grounds that they cannot walk, or that their MS is too advanced. However, more recently, for such people who wish to participate in clinical trials, some of the newer interferon family of drugs, and indeed others, are now being tested on people with longer term and progressive MS. Do not to get too disheartened if you are not eligible for one clinical trial, because there may be others you can join in due course.

    Payment for drugs
    You should not be asked to pay for any drugs you receive in clinical trials in which you participate. As a matter of principle, either pharmaceutical companies or other funding bodies of trials pay for these drugs. Indeed your travelling expenses will usually be reimbursed if, for example, you need to attend for assessment at a hospital more frequently for the trial than you would otherwise have done.
    There is one issue of payment, however, that sometimes arises, and that is at the conclusion of a trial, when a new drug may be found to be ef fective, and participants wish to continue taking it. Usually trial funding bodies will not pay for any continuing administration of the drug beyond the end of trial, and you would have to negotiate any such administration through your usual doctor. In many cases this may be difficult, not only because new drugs may be very expensive but also because they may not yet be licensed for clinical use outside a trial.

    Patient consent
    It is a requirement for participation in all properly conducted trials that you – as a potential participant – give your ‘informed consent’. You will have received a form and almost certainly have had a discussion with your doctor, and this form states the nature, benefits and risks of the trial, and asks you formally to give your consent to participation in the trial. You are also agreeing to follow the procedures that the trial requires. The form should be written in clear and plain English, and usually Ethics Committees, who give necessary ethical approval for such trials, try and make sure that such forms are not written in medical or legal jargon. If there is anything, anything at all, that is not clear in the document, then it is essential that you ask for clarification before agreeing to participate.

    Some recent trials on beta-interferon
    The results of some recent clinical trials have shown that the beta- interferons may slow down the course of the disease over a 3–4-year period. We must remember that the criteria for ‘relapsing-remitting MS’ in trials are drawn very tightly and many people have types of MS that were not covered by previous trial findings. New trials are underway to test whether these other people might benefit as well. However, because it is more difficult to test the effects of such drugs in people with more complicated relapsing-remitting, or progressive types of MS, the findings are taking some time, although initial results are promising. The difficulty is turning out to be not just the effectiveness of interferons in these cases but their cost effectiveness. Although it has been shown that interferons may slow down the disease in some people, the number in which this occurs is not large, and the costs of the drugs are very expensive. A number of clinicians and also, importantly, other bodies regulating the extent to which the drugs can be used on the NHS for such types of MS were reluctant to see it made available for all categories. Now there is agreement with the pharmaceutical industry to share expenses of the treatment.

    Previous trials on steroids
    One trial on steroid therapy has indicated that the steroids reduced the risk of developing clinically definite MS by half over a 2-year period. There have been serious criticisms of some aspects of the trial, and further trials are needed on this issue. However, further trials to test whether this was an abnormal result or not are very difficult to organize. It is almost impossible to identify and ensure that enough people participate in such a trial with very early, and especially the first, symptoms of Multiple Sclerosis, i.e. within a month or so of those symptoms appearing
    – and also to ensure that they have an MRI scan within this phase. Because the beta-interferons and other drugs have shown more overall promise in MS, there is now some reluctance to conduct large-scale and expensive trials on steroids.