Epilepsy

DEFINITION: A serious neurologic disease characterized by recurrent seizures, which may involve convulsions and loss of consciousness

ALSO KNOWN AS: Seizure disorder

ANATOMY OR SYSTEM AFFECTED: Brain, head, nerves, nervous system

CAUSES: Brain injury, brain tumors, disease, possible genetic factors

SYMPTOMS: Seizures, loss of consciousness

DURATION: Typically chronic

TREATMENTS: Anticonvulsant drugs, surgery to remove tumor or causative brain tissue abnormality, vagus nerve stimulation, modified diet

Causes and Symptoms

Epilepsy is characterized by seizures, which may involve convulsions and the loss of consciousness. It was called the “falling disease” or “sacred disease” in antiquity and was mentioned in 2080 BCE. in the laws of the famous Babylonian king Hammurabi. Epilepsy is a serious neurologic disease that usually appears between the ages of two and fourteen. It does not affect intelligence, as shown by the fact that the range of intelligence quotients (IQs) for people diagnosed with epilepsy is quite similar to that of the general population.

In 400 BCE., Hippocrates of Cos proposed that epilepsy arose from physical problems in the brain. This origin of the disease is now known to be unequivocally true. Despite many centuries of exhaustive study and effort, however, only a small proportion (20 percent) of cases of epilepsy caused by brain injuries, brain tumors, and other diseases are curable. This type of epilepsy is called symptomatic epilepsy. In contrast, 80 percent of people diagnosed with epilepsy can be treated to control the occurrence of seizures but cannot be cured of the disease, which is therefore a lifelong affliction. In these cases, the basis of the epilepsy is not known, although the suspected cause is genetically programmed brain damage that still evades discovery. Most epilepsy is, therefore, an idiopathic disease (one of unknown origin), and such people are thus said to experience idiopathic epilepsy.

A common denominator in idiopathic epilepsy, and also in symptomatic epilepsy, is that it is evidenced by unusual electrical discharges, or brain waves, seen in the electroencephalograms (EEGs) of people diagnosed with epilepsy. These brain waves are called seizure discharges. They vary in both their strength and their frequency, depending on whether an individual is having a seizure and what type of seizure is occurring. Seizure discharges are almost always present and recognizable in the EEGs of people with epilepsy, even during sleep.

There are four types of common epileptic seizures. Two of these are partial (local) seizures called focal motor and temporal lobe seizures, respectively. The others, and petit mal, are generalized and may involve the entire body. A focal motor seizure is characterized by rhythmic jerking of the facial muscles, an arm, or a leg. As with other epileptic seizures, it is caused by abnormal electrical discharges in the portion of the brain that controls normal movement in the body part that is affected. This abnormal electrical activity is always seen as seizure discharges in the EEG of the affected part of the brain.

In contrast, temporal lobe seizures (also known as psychomotor epilepsy), again characterized by seizure discharges in a distinct portion of the cerebrum of the brain, are characterized by hallucinations and other types of consciousness alteration, a meaningless physical action, or even a babble of some incomprehensible language. Thus, for example, temporal lobe seizures may explain some cases of people “speaking in tongues” in religious experiences or in tales of the Delphic oracles of ancient Greece.

The term “grand mal” refers to the most severe type of epileptic seizure. Also called tonic-clonic seizures, grand mal attacks are characterized by very severe EEG seizure discharges throughout the entire brain. A grand mal seizure is usually preceded by sensory symptoms called an aura (probably related to temporal lobe seizures), which warn a patient of an impending attack. The aura is quickly followed by the grand mal seizure itself, which involves the loss of consciousness, localized or widespread jerking and convulsions, and severe body stiffness.

People with epilepsy experiencing a grand mal seizure usually fall to the ground, may foam at the mouth, and often bite their tongues or the inside of their cheeks. In a few cases, the affected person will lose bladder or bowel control. When a person with epilepsy is untreated, grand mal seizures can occur weekly. Most of these attacks last for only a minute or two, followed quickly by full recovery after a brief sense of disorientation and feelings of severe exhaustion. In some cases, however, grand mal seizures may last for up to five minutes and lead to temporary amnesia or to other mental deficits of a longer duration. In rare cases, the life-threatening condition of status epilepticus occurs, in which many sequential tonic-clonic seizures occur over several hours without recovery between them.

The fourth type of epileptic seizure is petit mal, which is often called generalized nonconvulsive seizure or, more simply, absence. A petit mal seizure consists of a brief period of loss of consciousness (ten to forty seconds) without the individual falling down. The person usually appears to be daydreaming (absent) and shows no other symptoms. Often a person affected by a petit mal seizure is not even aware that the event has occurred. In some cases, a petit mal seizure is accompanied by mild jerking of hands, head, or facial features and/or rapid blinking of the eyes. Petit mal attacks can be quite dangerous if they occur while a person is driving a motor vehicle.

Diagnosing epilepsy usually requires a patient history, a careful physical examination, blood tests, and a neurologic examination. The patient history is most valuable when it includes eyewitness accounts of the symptoms, the frequency of occurrence, and the usual duration of the seizures observed. In addition, documentation of any preceding severe trauma, infection, or episodes of addictive drug exposure provides useful information that will often differentiate between idiopathic and symptomatic epilepsy.

Evidence of trauma is quite important, as head injuries that caused unconsciousness are often the basis for later symptomatic epilepsy. Similarly, infectious diseases of the brain, including meningitis and encephalitis, can cause this type of epilepsy. Finally, excessive use of alcohol or other psychoactive drugs can also be a causative agent for symptomatic epilepsy.

Blood tests for glucose and calcium, electroencephalography, and computed tomography (CT) are also useful diagnostic tools. The EEG will nearly always show seizure discharges in people with epilepsy, and the location of the discharges in the brain may localize problem areas associated with the disease. CT scanning is most useful for identifying tumors and other serious brain damage that may cause symptomatic epilepsy. Other tests that may be used to diagnose epilepsy include magnetic resonance imaging (MRI), magnetoencephalography (MEG) imaging, and a lumbar puncture or spinal tap. When all tests are negative except for abnormal EEGs, the epilepsy is considered idiopathic.

It is thought that epileptic symptoms occur because of a malfunction in nerve impulse transport in some of the billions of nerve cells (neurons) that make up the brain and link it to the body organs that it innervates. This nerve impulse transport is an electrochemical process caused by the ability of the neurons to retain substances (including potassium) and to excrete substances (including sodium). This ability generates the weak electrical current that makes up a nerve impulse and that is registered by electroencephalography.

A nerve impulse leaves a given neuron via an outgoing extension (or axon), passes across a tiny synaptic gap that separates the axon from the next neuron in line, and enters an incoming extension (or dendrite) of that cell. The process is repeated until the impulse is transmitted to its site of action. The cell bodies of neurons make up the gray matter of the brain, and axons and dendrites (white matter) may be viewed as connecting wires.

Passage across synaptic gaps between neurons is mediated by chemicals called neurotransmitters, and it is believed that epilepsy results when unknown materials cause abnormal electrical impulses by altering production rates and/or the ability of sodium, potassium, and related substances to enter or leave neurons. The various nervous impulse abnormalities that cause epilepsy can be shown to occur in the portions of the gray matter of the cerebrum that control high-brain functions. For example, the frontal lobe—which controls speech, body movement, and eye movements—is associated with temporal lobe seizures.

Treatment and Therapy

Idiopathic epilepsy is viewed as the expression of a large group of different diseases, thought to stem from genetic abnormalities, all of which present themselves clinically as seizures. This is extrapolated from the various types of symptomatic epilepsy observed, which have causes that include faulty biochemical processes (such as inappropriate calcium levels), brain tumors or severe brain injury, infectious diseases (such as encephalitis), and the chronic overuse of addictive drugs.

Symptomatic epilepsy is treated with medication and either by the extirpation of the tumor or other causative brain tissue abnormality that was engendered by trauma or disease or by the correction of the metabolic disorder involved. The more common, incurable idiopathic disease is usually treated entirely with medication that relieves symptoms. This treatment is essential, because without it most people diagnosed with epilepsy cannot attend school successfully, maintain continued employment, or drive a motor vehicle safely.

A large number of drugs are available for epilepsy management. However, no one therapeutic drug will control all types of seizures. In addition, some patients require several such drugs for effective therapy, and the natural history of a given case of epilepsy may often require periodic changes from drug to drug as the disease evolves. Furthermore, many antiepilepsy drugs have dangerous side effects that may occur when present in the body above certain levels or after they are used beyond some given time period. Therefore, each epileptic patient must be monitored at frequent intervals to ascertain that no dangerous physical symptoms are developing and that the drug levels in the body (monitored by the measurement of drug content in blood samples) are within a tolerable range.

Dozens of antiepilepsy drugs are widely used. Phenytoin (Dilantin) is very effective for grand mal seizures. Because of its slow metabolism, phenytoin can be administered relatively infrequently, but this slow metabolism also requires seven to ten days before its anticonvulsant effects occur. Side effects include cosmetically unpleasant hair overgrowth, swelling of the gums, and skin rash. These symptoms are particularly common in epileptic children. More serious are central nervous effects including ataxia (unsteadiness in walking), drowsiness, anemia, and marked thyroid deficiency. Most such symptoms are reversed by decreasing the drug doses or by discontinuing it. Phenytoin is often given together with other antiepilepsy drugs to produce optimum seizure prevention. In those cases, great care must be taken to prevent dangerous synergistic drug effects from occurring. High phenytoin doses also produce blood levels of the drug that are very close to toxic 25 micrograms per milliliter values.

Carbamazepine (Tegretol) is another frequently used antiepilepsy drug. Chemically related to the drugs used as antidepressants, it is useful against both psychomotor epilepsy and grand mal seizures. Common carbamazepine side effects are ataxia, drowsiness, and double vision. A more dangerous, and fortunately less common, side effect is the inability of to produce blood cells. Again, very serious and unexpected complications occur in mixed-drug therapy that includes carbamazepine, and at high doses toxic blood levels of the drug may be exceeded.

Phenobarbital (Luminal), a sedative hypnotic also used as a tranquilizer by people without epilepsy, is a standby for treating epilepsy. It too can have serious side effects, including a lowered attention span, hyperactivity, and learning difficulties. In addition, when given with phenytoin, phenobarbital will speed up the excretion of that drug, lowering its effective levels.

A newer generation of antiepileptic medications that act by various mechanisms became available starting in the 1990s. These drugs, which include gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, zonisamide, oxcarbazepine, and pregabalin, are often better tolerated, safer, and faster acting than the older generation of antiepileptic medications, which have been available since the mid-twentieth century. However, the efficacy of both the newer and older drugs to prevent seizures remains highly dependent on the individual patient.

About 20 percent of people diagnosed with idiopathic epilepsy do not achieve adequate seizure control after prolonged and varied drug therapy. Another option for some—but not all—such people is brain surgery. This type of brain surgery is usually elected after two conditions are met. First, often-repeated EEGs must show that most or all of the portion of the brain in which the seizures develop is very localized. Second, these affected areas must be in a brain region that the patient can lose without significant mental loss (often in the prefrontal or temporal cerebral lobes). When such surgery is carried out, it is reported that 50 to 75 percent of the patients who are treated and given chronic, antiepilepsy drugs become able to achieve seizure control.

The most frequent antiepilepsy surgery is anterior temporal lobectomy. The brain has two temporal lobes, one of which is dominant in the control of language, memory, and thought expression. An anterior temporal lobectomy is carried out by removing a portion of the front part of the temporal lobe, when it is the site of epilepsy. About 6 percent of temporal lobectomies lead to a partial loss of temporal lobe functions, which may include impaired vision, movement, memory, and speech. However, better than 60 percent of patients become completely seizure-free following the procedure, making this surgery the standard approach for patients with temporal lobe epilepsy who are resistant to drug therapy.

Another common type of antiepilepsy surgery is called corpus callosotomy. This procedure involves partially disconnecting the two cerebral hemispheres by severing some of the nerves in the corpus callosum that links them. This surgery is performed when a person has frequent, uncontrollable grand mal attacks that cause many dangerous falls. The procedure usually results in reduced numbers of seizures and decreases in their severity.

Other treatments for epilepsy include vagus nerve stimulation (VNS), in which a device similar to a pacemaker is implanted in the patient to deliver regular electrical currents to the vagus nerve in the neck, which has been shown to reduce the number of seizures for about half of patients. In a limited number of cases, the rate of seizures may also be reduced by a special dietary regimen called a ketogenic diet, which is high in fat and low in carbohydrates.

Physicians also believe that many cases of epilepsy may be prevented by methods aimed at avoiding head injury (especially in children) and the use of techniques such as amniocentesis to identify people who will potentially have epilepsy and treat them before birth. Furthermore, the prophylactic administration of antiepilepsy drugs to nonepileptic people who have encephalitis and other diseases known to produce epilepsy is viewed as wise.

Perspective and Prospects

A great number of advances have occurred in the treatment of epilepsy via therapeutic drugs and surgical techniques. Drug therapy has been the method of choice, because it is less drastic than surgery, is easier to manage, and rarely has the potential for the irreversible damage to patients that can be caused by the removal of a portion of the brain. A tremendous variety of chemical therapies has been developed and utilized successfully.

In addition to antiepileptic drugs, alternative nonsurgical treatments that have been tried include high doses of vitamins, injections of muscle relaxants, and changes in diet. The variety is unsurprising, considering the vast number of disease states that can cause seizures. Readers are encouraged to investigate the many epilepsy treatments that have not been noted. Such an examination may be quite valuable, as there are about 2 million people diagnosed with epilepsy in the United States alone, and some estimates indicate that four of every thousand humans are likely to develop some epileptic symptoms during their lifetime.

Modern surgical treatment of epilepsy reportedly began in 1828, with the efforts of Benjamin Dudley, who removed epilepsy-causing blood clots and skull fragments from five patients, who all survived despite primitive and nonsterile operating rooms. The next landmark in such surgery was the removal of a brain tumor by the German physician R. J. Godlee, in 1884, prior to invention of imaging technology such as X-rays.

By the 1950s, EEGs were used to locate epileptic brain foci, and physicians such as the Canadians Wilder Penfield and Herbert Jasper pioneered their use to locate brain regions to remove for epilepsy remission without damaging vital functions. After considerable evolution, antiepilepsy surgery had by the 1990s become widespread, commonplace, and relatively safe.

Nevertheless, because of the imperfections of all available methodologies, 5 to 8 percent of people with epilepsy cannot achieve seizure control by any method or method combination, and even the “well-managed” epilepsy treatment regimen has its flaws. There is still much to be learned about curing epilepsy. Clinical and experimental perioperative studies may be performed during epilepsy surgery to examine the bioelectrical activity and molecular events of the affected neurons. It is hoped that the efforts of ongoing biomedical research, both in basic science and in clinical settings, will drastically reduce or eliminate epilepsy through the development of new therapeutic drugs and advances in surgery and other nondrug methods.

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