Doctors Talk about Epilepsy (Geigy Pharmaceuticals,1965)

[Sound of ambulance doors being opened.] [Paramedic:] Ready? [Clanking of wheels as gurney is removed from rear of ambulance.] [Dave Gilbert:] This little girl is suffering from one of the true medical emergencies, status epilepticus. [Doctor:] Hello. [Paramedic:] Hi Doc. [Paramedic:] Hi. We’ve got a 13-year-old girl here that has a history of seizure disorder since she was 10 months old. She takes Dilantin and phenobarb, and for some reason, she didn’t take her medicine today and went into generalized status… [Dave Gilbert:] Fortunately, status is comparatively rare, but if you’re a physician, especially if you’re in family practice, chances are you will run into epilepsy many hundreds of times in the course of your career. Who gets epilepsy? [Dr. Richard D. Walker:] It’s not really a function of sex. It can be, occur just as readily in males as in females. It’s not necessarily a function of age. It can occur very early in life or very late in life. It’s not necessarily a function of social-economic position in life. Who gets it, it can be anybody. [Dave Gilbert:] It can be anybody. In fact, there may be as many as four to six million persons with epilepsy in the United States. To help you keep abreast of the latest developments in the diagnosis and treatment of this important disorder, we have assembled some of the most distinguished epileptologists in the world as Doctors Talk about Epilepsy. [Dr. David D. Daly:] The essence of epilepsy is the occasional excessive discharge of nerve cells in the brain. Whenever we see a patient for the first time, we ask ourselves two questions. First, do the nerve cells in the brain discharge only in a single area, creating a focal seizure, or do the nerve cells in the brain discharge at once over the entire brain, creating a generalized seizure? This is important to decide, because it helps us in seeking the underlying cause and also in the selection of the appropriate medication. The second question that we ask is, and this is already partly answered by having decided the type of seizure, is what is the underlying disease in the brain causing the seizures? There are many diseases. Some of these are related to the age of the patient. And therefore, the variety of investigations undertaken may be only a few, or it may be many. When we talk about focal or partial seizures, we refer to seizures which may arise, for example, in the primary motor cortex, or they may arise in the temporal lobe of the brain. The type of seizure in each of these is quite different. [Dave Gilbert:] Here, the various types of seizures are grouped using the international classification of epileptic seizures, which is based on the site of origin, as determined clinically and by the EEG. They include partial seizures; that is, seizures which begin locally, and general seizures, those which are bilaterally symmetrical and without any local onset. Of the partial seizures, those in which there is no loss of consciousness are called simple. These include motor seizures, like the Jacksonian, as well as sensory, autonomic, and compound forms. The complex-partial seizures, those in which there is an impairment of consciousness, take several forms. Impairment of consciousness only, and those with cognitive symptomology, affective symptomology, psychosensory symptomology, psychomotor symptomology, and compound forms. The generalized seizures include the familiar “absence” or “petit mal,” bilateral myoclonus, infantile spasms, clonic seizures, tonic seizures, tonic-clonic or grand mal seizures, atonic seizures, and akinetic seizures. [Dr. David D. Daly:] The focal seizure signifies the existence of a focal disease in the brain. On the other hand, certain seizures begin without warning and may involve the entire brain at once. An example of the latter is the so-called absence or petit mal attack, in which the nerve cells discharge over the entire brain at one time. [Dr. J. Kiffin Penry:] Well, of the many interesting things about epilepsy that are important to the practicing physician, the two most important things, of course, are diagnosis and treatment, and diagnosis, in itself, is difficult, because many patients go for a period of one to two years before they reach a definitive diagnosis so that definitive treatment can begin. [Dr. Robert S. Dow:] It may be a tumor. It might be trauma. It might be any of the diseases that affect the brain, can have convulsions or epilepsy as one of their manifestations, but when it starts in childhood, oftentimes, there are no gross brain abnormalities other than the hyperirritability of the brain, which is the characteristic feature of epilepsy. [Dr. J. Kiffin Penry:] The difficulty is that the doctor should recognize there are many other minor forms of epilepsy, and he should be aware of the broad number of manifestations that may appear, anything from a very brief, blank stare, such as that, or hesitation in speech, to many symptoms the patient may complain of. But once he has an index of suspicion that the patient could have epilepsy, that he thinks of this, then a definitive workup is necessary. [Dave Gilbert:] And so the diagnostic process begins. [Dr. Fritz Dreifuss:] The only reliable way of making a diagnosis of epilepsy is by the history that the patient gives of the events which occur in relation to an attack, and the history, which is given in corroboration by those who have seen the seizures occurring. [Dr. Robert S. Dow:] This usually requires the cooperation of the family or some member of the community who has seen the patient in a convulsion, or whatever the patient is having, and is able to give you a very detailed description of exactly the course of events throughout the time the patient goes into the seizure and loses consciousness and recovers. This is, by far, the most important part of the examination and the identification of the patient with epilepsy. Then we go into the past history of possible things that could have happened to that patient that would be the, uh, as a possible cause. We take into consideration the age of the patient. All of these factors are taken into the history. Then a physical examination and a neurological examination is conducted. You check the function of muscles, the sensation of different parts of the body. You check the deep tendon reflexes. You check the patient’s gait and coordination and all of these features, and it’s done in a systematic way, so that you get a survey of all of the function of all the parts of the nervous system. [Dr. J. Kiffin Penry:] And of course, if abnormalities are found there, then these must be pursued also with appropriate diagnostic methods, such as examination of the head with the skull film, a lumbar spinal puncture, and electroencephalogram. Depending upon what these show, of course, the patient then has to be referred to a specialist. But let us go on and assume that he’s been able, with his own workup and by requesting these studies, or with the help of a consultation by a neurologist or some other specialist who is interested in epilepsy, to make a definitive diagnosis. The next most important area is to realize that now we have already at least 13 marketed anti-epileptic drugs, and that there are two more about to become available widely for use in practice. And now you can see the importance of the diagnosis, because these drugs should be prescribed on the basis of which type of seizure the patient has been having. For the grand mal seizure, the most commonly used medication, of course, is phenobarbital and diphenylhydantoin. For the complex-partial seizure, which has been called psychomotor or temporal-lobe type seizures, if the phenobarbital and diphenylhydantoin have not been helpful here, primidone has been helpful in some of these patients. So you can see, then, that the definitive diagnosis becomes very important for the practicing doctor to decide which drug to prescribe. He may get this information with his consultation, or he may be skilled enough and interested enough in treating epilepsy, of course, to know about these medications. [Dave Gilbert:] Here are the most frequently used drugs. For partial simple seizures: diphenylhydantoin, or Dilantin, phenobarbital, or Luminal, and primidone, or Mysoline. For partial-complex seizures: diphenylhydantoin, phenobarbital, carbamazepine, or Tegretol, and primidone. For partial-complex seizures, which have become secondarily generalized: tonic-clonic convulsions, diphenylhydantoin, phenobarbital, carbamazepine, and primidone. Automatism, diphenylhydantoin, phenobarbital, carbamazepine, and primidone. For generalized seizures: tonic-clonic convulsions, diphenylhydantoin, phenobarbital, carbamazepine, and primidone. For absence, or petit mal: ethosuximide, or Zarontin, and clonazepam. For myoclonus: ethosuximide and clonazepam. [Dr. Donald Tower:] Any patient with epilepsy has to look forward to the possibility of taking drugs all his life, and this creates a special problem in drug therapy, because the long-term effects of drugs are really not very well understood. There are not very many areas in medical therapy, where therapy has to be carried on as long as in epilepsy and some of the other neurological disorders. [Dr. Fritz Dreifuss:] Each one seems to have its own particular side effects. Diphenylhydantoin, or Dilantin, as it’s commonly known, produces unsteadiness, or ataxia, in large overdose. Prolonged administration of diphenylhydantoin may affect the gums. It may possibly affect blood-forming organs. It may cause skin rash. It may cause excessive hair growth. It may have effects on folic acid metabolism, or vitamin D metabolism. These are relatively rare side effects but are things that we, who administer these drugs, very frequently, do have to be on mind as we follow patients over long periods of time. Phenobarbital, apart from its soporific effects, appears to have an exciting effect on children, particularly children who already have a tendency to hyperactivity. Primidone, or Mysoline, as it’s commonly known, occasionally has effects on the patient’s personality. Some children have personality changes for the worse while on that medication. Carbamazepine, or Tegretol, is a drug which has been recently introduced for the treatment of complex partial seizures. Its main side effects are those of bone marrow depletion, and this requires frequent blood counts to try to avoid the development thereof. Liver function studies are also frequently monitored. [Dr. David D. Daly:] Like all drugs, anti-epileptic drugs are a two-edged sword. In addition to their therapeutic effect, they may have toxic effects. We classify toxicity into three types: dose-related, idiosyncratic, and long-term toxicity. By dose-related, we mean symptoms of toxicity that are specifically related to the amount of medication that the patient takes. Most of the dose-related toxicities involve the central nervous system and can be readily detected by measuring the serum levels of the drugs by a technique such as gas-liquid chromatography or GLC. Dose-related toxicities may appear at any time. In contrast, idiosyncratic toxicities are peculiar to the patient, are unpredictable, and may appear within a very short time after the initiation of the drug. These cannot be detected by measuring serum levels and usually involve organs outside the central nervous system; for example, the bone marrow or the skin. [Dr. Donald Tower:] There can be a buildup of effects due to other changes in the patient’s environment or any current infections or other diseases. The toxicity of the drug may suddenly become manifest, even though the patient has gone along quite well for many years before that. This is a constant problem. In addition to that, we have had, in the past, very little knowledge of exactly how individuals handled the various drugs that they were taking. I’m talking about how well they absorb them, how well they maintain a blood level, how rapidly they dispose of them. All these things that are related to therapy, and it’s only in the last decade, and in fact, more properly in the last five years, that we’ve had techniques readily available, so that we can measure the blood levels, not only of the drugs themselves, but of the major forms in which they’re metabolized by the body, so that we can have a good guide to the relationship between dose, blood level, and therapeutic response. [Dave Gilbert:] One relatively new technique is gas-liquid chromatography. [Dr. James MacDonald Watson:] Do you know why this is being done? Remember those pills you’re taking? We’re going to find out whether the pills are in the blood, how much of the medicine is in you. [Doctor:] You can tell if a patient is taking the drugs. You can tell if the patient is reacting properly to the drug or the way you would expect them to react to the drug. You can tell if a patient is getting too much drug, if the patient’s becoming toxic on a particular drug, and you can differentiate between which drug is toxic and which drugs are being effective in the treatment of epilepsy. [Dr. James MacDonald Watson:] Patients come to the laboratory here and submit the blood sample directly, or at least, in this laboratory, we have the availability of services by mail, so to speak, in which a similar specimen might arrive from a physician somewhere, who has already been supplied with a preprinted mailer, and the blood specimen arrives in a small tube, having already been reduced to serum. [Dave Gilbert:] Doctors can obtain information about gas-liquid chromatography services by contacting the Epilepsy Foundation of America, Washington D.C., or through the foundation chapter in their area. For those who can’t be helped by drugs, surgery is sometimes a possibility. For this patient, there was no other choice. [Woman:] Oh, I was, I couldn’t bear to continue with the life I was living. I was scared to death. I was depressed. I was unhappy. I was actually quite suicidal, too. [Dr. Theodore Rasmussen:] With certain limitations, no brain is better than bad brain. For example, a patient whose frontal lobe is very epileptogenic, it’s generating high-amplitude seizure discharges that spread throughout the rest of the brain. These sometimes interfere with the normal function of the rest of the brain, and that removal of this frontal lobe, even though you are taking away a large area of the frontal lobe, if it results in eradication of these big seizure discharges, the rest of the brain can function more effectively than it could when it was being bombarded by the epileptic discharges. [Woman:] I had a portion of the medial portion of the right temporal lobe removed. It was decided that the focus was located in the hippocampal gyrus. So a small section of that was taken out. I believe it was two centimeters. [Dave Gilbert:] Surgery is an increasingly important weapon in the medical arsenal against epilepsy. [Woman:] I’m studying much better. [Dave Gilbert:] Still, there seems little question that drugs will remain the major method of treatment. But there may soon be other ways of fighting epilepsy. [Dr. David D. Daly:] There are always questions about what new advances are on the horizon. One, of course, is the continued development of new anti-epileptic drugs. We do have clues to the development of new drugs, which are unrelated chemically to any of the existing drugs. Another surgical treatment, which has been proposed recently, differs from the prior types of surgical treatment, which consisted of attempting to remove the epileptic focus. Stimulation of the cerebellum has been proposed as such a technique. Another technique has been referred to as biofeedback and would be more properly described as a form of operant conditioning, in which the patient’s own brain waves are used to signal him as to whether his brain cells are acting in an appropriate fashion. Both of these are highly experimental. Their usefulness remains to be established. [Clicking, static sound] [Dr. Arthur Ward:] In the monkeys, the activity of single cells on the surface of the brain can be recorded, and the monkeys can be trained in such a fashion that they can, in ways that are not entirely clear, change the rate of firing of these cells. We know what nerve cells do is send out signals. These signals can be recorded electrically with a fine electrode. The monkey is told how fast his cells are discharging by a meter, which is placed in front of him. He knows when the meter goes to the right, that the cell discharge is going up, and when it goes to the left, the cell discharge is decreasing. On the basis of this training, he has learned that when a given light goes on, he will be rewarded if he can increase the rate of discharge of that cell. Thus, when the meter goes to the right, he now, and when it goes all the way to the right, he gets this little reward of applesauce, and goes back to work and gets the cell firing fast again and is rewarded with applesauce every few seconds. How a monkey can, how with the 10 billion cells he has in his brain, increase the rate of firing of a single cell of this kind, is obviously an amazing phenomenon. Whether the human can do this, we don’t know, but we may be able to train both monkeys and, subsequently, if that is the case, man, to control signals in such a fashion so that the number of times the seizures are precipitated will be decreased by conditioning associated with this, if you want to call it biofeedback. There’s some evidence in the monkeys, that the monkeys who have been in these conditioning experiments, which you’ve seen, epileptic monkeys who have been in these conditioning experiments, although no attempt was made in the conditioning to actually suppress their seizures, nevertheless, just the act of trying to modify the activity of single cells in the area of irritation has resulted, in several of the animals, in a very dramatic decrease in the number of seizures. One of them, in fact, has become seizure-free. [Dr. David D. Daly:] Another aspect of what is ahead is can we prevent the epileptic process from occurring at all? There are reasons to think that we may prevent the development of seizures, for example, in the person who has suffered a head injury, by administering antiepileptic drugs immediately after the head injury, whether or not seizures have occurred. Other areas of prevention also may hold promise. [Dr. J. Preston Robb:] I think the outlook is very hopeful. Indeed, in the last 10 years, we’ve seen real advances, and the patients lives have improved a great deal, in every area. [Dr. David D. Daly:] To sum this up, and to pull together the thoughts of all of us, the approach to every patient with epilepsy should be a logical one. Description of the type of seizures, a search for the underlying cause, a decision on which drugs to use, based on a knowledge of the types of seizures, assurance that adequate amounts of drug are used, particularly by measuring blood levels of the antiepileptic drugs, and a willingness to be patient, to strive for complete seizure control, knowing that this takes time and is often difficult. And finally, an understanding that these problems that beset the patient may lead to other disturbances in adjustment, and in the patient’s way of life, and a willingness of the physician to understand and help resolve these. [Dr. Richard D. Walker:] Epilepsy is a very difficult thing to treat, in that there are many drugs, and they require adjusting, and they require adjusting regularly, and most physicians are not prepared to do this. And very often, what happens is the patient starts on a drug, and it doesn’t work, so they throw up their hands and say, look, it’s no good. Now whenever a patient leaves here, I always tell them or their relatives, look, the medicine we’re giving you now may be no good. If it isn’t any good, don’t chuck it. Get on the phone. Telephone me and tell me it isn’t any good. You won’t hurt my feelings. Tell me it isn’t any good and we’ll change it. And in this way, we work together with the parents or the patient and work out a regime that is effective. I think the point I would like to make most strongly is that patients with recurring epileptic seizures can be helped. It requires hard work, in many instances, but they can be helped. [Dave Gilbert:] They can be helped, and chances are, Doctor, that their most important source of help will be you. This has been a professional education service of the Epilepsy Foundation of America, whose primary mission is to interpret the needs of the person with epilepsy to the society in which he lives. [End of film]


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