At a recent house-party to support stem cell research program proposed by Jon Corzine, who is a candidate for governor of New Jersey, a family asked me about the possibility that stem cells might be useful for epilepsy for their daughter. A significant number of people who have spinal cord injury also may have seizures. So, when I saw this summary of epilepsy and seizures, I thought that I would post it.

Epilepsy and Seizures Can Occur at Any Age
(FDA Consumer)
Updated: Sep 21st 2005
Few events compare to the drama of an epileptic seizure. Ancient people once thought that those with epilepsy were being attacked by evil spirits that had to be driven from the body with magic or prayer. If that didn't work, those affected were isolated to prevent the "spread" of fits to others. It wasn't until the Greek physician Hippocrates recognized epileptic seizures as a dysfunction of the brain that the stigma attached to such superstitions began to fade.

A 27-year-old woman undergoing an EEG, or electroencephalogram, to monitor the electrical activity of her brain. An adult epilepsy diagram is shown on the screen.

Today, nearly 3 million people in the United States have been diagnosed with epilepsy in one of its many forms, according to the National Institute of Neurological Disorders and Stroke (NINDS). Fortunately, scientific discoveries about how the brain works have enabled about 80 percent of those diagnosed with epilepsy to benefit from modern medicines and an implantable device regulated by the Food and Drug Administration, and to live productive lives. The most recent anti-epileptic treatment approved by the FDA was Lyrica (pregabalin), in June 2005.

What Is Epilepsy?

Epilepsy is a neurological condition that can produce brief disturbances, called seizures, in the brain's electrical function. According to the NINDS, clusters of nerve cells, or neurons, in the brain normally generate electrochemical impulses that act on other neurons, glands, and muscles to produce human thoughts, feelings, and actions. In epilepsy, the normal pattern of neuronal activity becomes disturbed briefly when the nerves in the brain "fire" spontaneously, causing strange sensations, emotions, and behaviors, and oftentimes seizures with muscle spasms and loss of consciousness.

Brain neurons may fire as many as 500 times a second during a seizure-much faster than the normal rate of about 80 times a second. This happens occasionally in some people, according to the NINDS, but may happen up to hundreds of times a day in others.

Doctors have identified hundreds of different epilepsy syndromes- disorders characterized by a specific set of symptoms that include seizures. According to the Epilepsy Foundation, classifying epilepsy by seizure type alone leaves out other important information about the patient and the episodes themselves. Classifying epilepsy into syndromes takes a number of characteristics into account, such as the type of seizure, behavior during the seizure, and genetics.

Most seizures do not seem to have a detrimental effect on the brain. Any changes that do occur are usually subtle, and it is often unclear whether these changes are caused by the seizures themselves or by the underlying problem that caused the seizures. Epilepsy can develop at any time in life, but develops most commonly in early childhood and old age. While it might not be curable, seizures for some can eventually go away.

Epilepsy is not contagious, nor is it a mental illness. People with mental retardation may experience seizures, but according to the NINDS, seizures do not mean that the person has or will develop mental impairment. While any seizure is cause for concern, the NINDS says that having one seizure does not by itself mean that a person has epilepsy.

Paul Scribner, 38, began experiencing epileptic seizures when he was 18. Doctors told him there was no known medical cause.

In Sue Mielenhausen's case, her now 12-year-old son Mike experienced his first seizure when he was 4.

"We armed ourselves with as much information as we could, but held off with medications," she says. It wasn't until Mike had a second seizure a year later that he was diagnosed with epilepsy. Mielenhausen says that her son's seizures became sporadic and impossible to predict. He could go many months without one, but she also remembers once that "he had a stretch where he had more than one a week."

The NINDS says that a person is considered to have epilepsy only if he or she has two or more seizures. First seizures, fever-caused (febrile) seizures, those not caused by electrical disruptions in the brain (nonepileptic events), and seizures during pregnancy (eclampsia) all are examples of seizures that may not be associated with epilepsy.

Causes of Epilepsy

Epileptic syndromes can be of unknown cause (idiopathic) or can result from underlying brain damage or disease. Anything that disturbs the normal pattern of neuron activity-illness, brain damage, or abnormal brain development-can lead to seizures. According to the NINDS, research has shown that the cell membrane surrounding each neuron plays an important role in epilepsy. Cell membranes are crucial for a neuron to generate electrical impulses. For this reason, researchers are studying details of the membrane structure, how molecules move in and out of membranes, and how the cell nourishes and repairs the membrane. A disruption in any of these processes may lead to epilepsy.

In some cases, the brain's attempts to repair itself after a head injury, stroke, or other problem may generate abnormal nerve connections that lead to epilepsy. Although Mike was born with a birth defect that resolved without surgery, and also was diagnosed a few years ago with a learning disability, his mother says, "The neurologists we've worked with have been reluctant to say definitely that the birth defect caused Mike's seizures and his learning disability." But, she adds, "logic certainly suggests there must be a connection."

Paul Scribner, although not entirely certain, attributes his 20- year bout with epilepsy to three or four minor concussions he had as a child.

"If I had to guess, and knowing what I know today," he says, "it's the only thing it could be." The onset of his seizures, however, didn't begin until age 18, when he participated in a dance marathon "that involved 72 hours of perpetual motion."

According to the NINDS, about half of all seizures have no known cause. In other cases, however, seizures are clearly linked to infection, trauma, or other identifiable causes. Sometimes epilepsy is inherited.

Types of Seizures

With epilepsy, people experience different types of seizures. Some people have just one type, while others have more than one. The kind of seizure a person has depends on which part and how much of the brain is affected by the electrical disturbance that produces seizures.

Seizures are currently classified by their clinical symptoms, such as how a person acts during a seizure, or how he or she reports the experience. The classification most widely used today is based on a system introduced by the International League Against Epilepsy in 1969 that divides more than 30 types of seizures into two major categories: partial, also called focal, and generalized.

Partial seizures, the most common type experienced by people with epilepsy, occur when abnormal electrical activity involves only one area of the brain. There also are two kinds of partial seizures: simple, in which the person remains conscious; and complex, in which consciousness is lost or altered. Although the person remains aware of the environment and remembers the experience, he or she may be limited in how to interact while it is in process. Speech, for example, may be lost.

The Epilepsy Foundation says that partial seizures may progress through several stages that reflect the spread of abnormal neuronal firing to different areas of the brain. When this happens, for example, a seizure that begins in a motor area may cause twitching of the hand or face.

Generalized seizures affect both sides of the brain and cause loss or alteration of consciousness either briefly or for a longer period of time. These seizures are subcategorized into several major types including:

* tonic-clonic, formerly called grand mal

* myoclonic

* absence, formerly called petit mal

* atonic, also called drop attacks.

Generalized tonic-clonic seizures begin with stiffening limbs, the tonic phase, followed by jerking of the limbs and face, the clonic phase. During the tonic phase, breathing may decrease or cease altogether, producing blue lips, nail beds, and face. Breathing typically returns during the clonic phase, but it may be irregular. Some people experience only the tonic phase of the seizure, while others exhibit only the clonic phase, or jerking movements. Still others may have a tonic-clonic-tonic pattern.

Doctors believe that most of Mike's seizures began as complex partial and developed into generalized tonic-clonic seizures, the same type that Scribner has had. Both say that their seizures typically occur during sleep, and each is aware that he's had one because he feels bad physically afterward. "I've never had a seizure when I was fully awake," says Scribner, whose wife has witnessed his nighttime episodes.

Myoclonic seizures are rapid, brief contractions of bodily muscles, which usually occur at the same time on both sides of the body. People usually think of them as sudden jerks or clumsiness.

Absence seizures are lapses of awareness, sometimes with staring, that begin and end abruptly, lasting only a few seconds. There is no warning and no aftereffect from this type of seizure. According to the Epilepsy Foundation, absence seizures are frequently so brief that they escape anyone's notice.

Atonic seizures produce an abrupt los\s of muscle tone. They cause head drop, loss of posture, or sudden collapse. This type of seizure tends to be resistant to drug therapy, according to the Epilepsy Foundation.

Most epileptic seizures last only a minute or two and are not life-threatening. The person, however, who experiences repeated seizures (status epilepticus) and does not regain awareness between seizures needs immediate attention. And someone with prolonged seizures, those lasting at least 30 minutes, also needs immediate attention.

Contrary to popular belief, nothing should be placed in the mouth of a person experiencing a seizure. Experts say that at no time is it possible to swallow the tongue.

Controlling Seizures

Diagnosing and characterizing epilepsy in people is a multi-step process. A person first must be confirmed to have had at least two or more epileptic seizures. Once the diagnosis of epilepsy is made, the patient's seizure type is characterized. A clinician then must determine whether the patient's seizure disorder conforms to a particular type of epilepsy or epileptic syndrome, and a clinical investigation targeting the cause of the epilepsy is conducted. Based on this and other information, the most appropriate therapy is selected.

Anti-epileptic drugs best treat the symptoms of epilepsy, but they do not cure the disease. The goal of treatment, says John Feeney, M.D., neurology team leader in the FDA's Division of Neurology Products, is to decrease the number and severity of seizures and minimize drug side effects. Since 1990, a large number of new anti-epileptic drugs have been approved, increasing the treatment options for patients and their doctors. But Feeney says it's important to remember that all the drugs, even the new ones, have some side effects. "Anti-epileptic drugs are centrally active on the nervous system," he says, "so you could expect that they would be associated with such side effects as dizziness or drowsiness."

How well an epilepsy drug works may be affected by other drugs a person is taking. Known as drug interaction, this relationship may involve how the drug is absorbed, metabolized, and otherwise distributed in the body. The interaction, for example, may speed up or slow down how quickly an epilepsy drug is eliminated, either making it less effective at preventing seizures because a lower level is present in the blood, or more likely to build up to toxic levels and cause side effects.

Some of the newer treatments do not interfere with the body's metabolism when taken in combination with other epilepsy drugs. The FDA says that studies have indicated that because some newer treatments are not metabolized through the liver, they are less likely to cause interactions with other epilepsy drugs or commonly used drugs, such as oral contraceptives. This makes them an attractive alternative for those needing more than one anti-seizure medication.

When a person starts a new epilepsy drug, according to the NINDS, it's important to tailor the dosage to achieve the best results. Feeney adds that patients react to medications in different and sometimes unpredictable ways. He says that it may take some time to find the right drug at the right dose to control seizures, while minimizing any side effects. "Certain seizure types seem to respond to some drugs better than others," he says. "Why this is so isn't fully understood."

Mielenhausen says her son is such a case. "The first medication we tried made things worse for Mike," she says. Besides the seizures occurring more frequently, Mike exhibited profound mood swings. And the medication had a sedative effect on him. "It's been a roller coaster at times," Mielenhausen says, "but we also have a lot to be thankful for." Once Mike was tapered off the first medication and was prescribed one that worked, things got better. His seizures occurred less frequently with minimal side effects. "We've gotten to know many families who have a much harder time with seizure control," she says, "and it helps us to keep that in mind."

"Some people will do reasonably well on just one drug," Feeney says. In many other cases, several anti-seizure medications are required to stop the seizures. In fact, Feeney adds, "clinical trials done to support approval of new drugs are usually done on people taking more than one epilepsy drug."

Magnetic resonance imaging (MRI) is used to take pictures of the brain and provide useful information for diagnosing epilepsy.

The Epilepsy Foundation adds that people who are being treated with anti-epileptic drugs may sometimes need periodic blood tests to determine whether they are getting enough medication and to check for adverse effects on the liver or the blood. Achieving the best seizure control possible, experts say, depends on taking the same amount of the medicines every day that have been prescribed by a doctor.

Scribner hasn't had a seizure in over a year. He believes that his last one was brought on by his having forgotten to take his medication. "That's why people with epilepsy shouldn't take themselves off their medicines, even though they appear to be seizure-free," says Scribner, an epilepsy educator at the Epilepsy Foundation.

Other Treatments

When seizures cannot be adequately controlled by medications, doctors may recommend that a person be evaluated for surgery. If a person is considered a good candidate, experts generally agree that surgery should be performed as early as possible.

While surgery can significantly reduce or even halt seizures for some people, it is important to remember that any kind of surgery carries some amount of risk. The Epilepsy Foundation advises people to ask their surgeon about his or her experiences, success rates, and complication rates with the procedure they are considering.

The NINDS also says that even when surgery completely ends a person's seizures, it is important to continue taking seizure medication for a period of time to give the brain time to readjust. As always, people should talk about this with their doctors.

In children, studies have shown that certain types of seizures may respond to a strict diet high in fats and low in carbohydrates. The "ketogenic diet," which is not the same as other popular low- carbohydrate diets, causes the body to break down fats instead of carbohydrates to survive. This condition is called ketosis. Doctors recommend the ketogenic diet for children whose seizures have not responded to several different seizure medicines.

The ketogenic diet is also not easy to maintain, according to the NINDS. It requires strict adherence to an unusual and limited range of foods, usually requiring the help of a dietitian. Possible side effects include retarded growth due to nutritional deficiency and a buildup of uric acid in the blood, which can lead to kidney stones. Children who are on the ketogenic diet also need to take seizure medications.

An implanted device that delivers electrical stimulations to the brain was approved by the FDA in 1997 for use in people whose seizures are not well-controlled by medication. Manufactured by Cyberonics Inc. of Houston, the VNS Therapy system is a battery- powered vagus nerve stimulator that is surgically implanted under the skin of the chest and attached to the vagus nerve in the lower neck. This device delivers short bursts of electrical energy to the brain. Patients usually cannot stop taking epilepsy medications because of the stimulator, but they often experience fewer seizures and they may be able to reduce the dose of their medication.

The FDA reminds people that serious injury or death can occur in those with implanted neurological stimulators who undergo magnetic resonance imaging (MRI) procedures. The mechanism for these adverse events is likely to involve heating of the electrodes at the end of the leadwires, resulting in injury to the surrounding tissue. Therefore, people with implanted neurological stimulators are advised to consider other imaging options.

Epilepsy and Older People

Epilepsy is often considered a disorder of the young, or a disease that people are born with. But according to the National Council on the Aging (NCOA), people can develop epilepsy as they age, and the greatest number of newly diagnosed cases each year occurs in older people. Those older than 65 are the fastest-growing group in America to develop epilepsy.

According to the NCOA, knowing the difference between a "senior moment" and a serious disease such as epilepsy is critical. Epilepsy often develops as a result of common health problems in older people, and physicians face the challenge of simultaneously treating patients for epilepsy as well as for multiple health problems. In these cases, the potential for adverse drug interaction becomes increased.

"Epilepsy is one of the most often misdiagnosed, mistreated, or undertreated conditions affecting seniors," says NCOA President James Firman, Ed.D. The condition often is characterized by recurrent seizures affecting awareness, movement, or sensation. Epilepsy may, however, present itself differently in older people and is often confused with the normal signs of aging. Because epilepsy is more often associated with seizures causing convulsions, the more subtle but potentially dangerous symptoms, such as hearing unusual sounds, blurred vision, or sudden anxiety, are often overlooked.

The VNS Therapy system consists of an implantable battery- powered pulse generator connected by wires to two electrodes wrapped around the left cranial (vagus) nerve in the neck. Once implanted, the device is programmed by a medical professional to deliver a regular pattern of stimulation.

Although there are a number of effective therapies for treating epilepsy, treating older people poses special challenges. The older anti-epileptic drugs, called first generation, are primarily used to treat the most common type of seizures. But they are far from ideal for older people because, according to \the NCOA, these drugs can be difficult to dose accurately, they can interact with other drugs often taken by the group, and they can have side effects such as heart toxicity, weight gain, and bone loss.

Looking to the Future

Scientists continue to study how nerves fire and how non- neuronal cells in the brain contribute to seizures, and researchers are working to identify genes that may influence epilepsy. This information, according to the NINDS, may one day allow doctors to prevent epilepsy or to predict which treatments will be most beneficial. Scientists also are experimenting with several new types of therapies for epilepsy, including transplanting stem cells and using a device that could predict seizures up to three minutes before they begin. This is, however, preliminary research. Much is being done also to improve MRI and other brain scans, and, according to the NINDS, researchers hope to develop implantable devices that can deliver drugs to specific parts of the brain.

For More Information

Epilepsy Foundation

(800) 332-1000

National Institute of Neurological Disorders and Stroke

(800) 352-9424

The National Council on the Aging

(202) 479-1200

If someone is having a seizure, bring the person gently to the floor, roll them on their side, and cushion the head.

What to Do for Someone Having a Seizure

* Roll the person on the side to prevent choking on any fluids or vomit

* Cushion the head

* Loosen tight clothing around the neck

* Keep the airway open. If necessary, grip the person's jaw gently and tilt his or her head back

* Do not restrict the person from moving unless he or she is in danger

* Do not put anything into the mouth, not even medicine or liquid

* Remove sharp or solid objects that the person might hit during the seizure

* Note how long the seizure lasts and what symptoms occurred so you can tell a doctor or emergency personnel, if necessary

* Stay with the person until the seizure ends.

National Institute of Neurological Disorders and Stroke

Copyright Superintendent of Documents Sep/Oct 2005