Related Terms

• Absence seizure, anticonvulsant, antiepileptic, atonic, aura, automatisms, carbohydrate, cerebral palsy, complex partial seizure, computed tomography, CT, déjà vu, EEG, electroencephalogram, electrolyte, febrile seizures, focal seizure, generalized seizure, grand mal seizure, hippocampus, hyperglycemia, hypoglycemia, hypoxia, hypsarrhythmia, ictus, idiopathic, irretractable seizure, Jacksonian epilepsy, ketogenic diet, ketone, Lennox-Gastaut syndrome, magnetic resonance imaging, motor cortex, MRI, myoclonic seizure, narcolepsy, neurodegenerative, neurofibromatosis, neurological disorder, neurotransmitter, partial seizure, PET, petit mal seizure, Phenylketonuria, PKU, positron emission tomography, postictal, pseudoseizure, simple partial seizure, single photon emission computerized tomography, SPECT, status epilepticus, stroke, Sturge-Weber syndrome, sudden unexplained death in epilepsy, SUDEP, Tay-Sachs disease, temporal lobe seizure, tonic-clonic seizure, tuberous sclerosis, tumor, vagus nerve stimulation, vertigo, video-EEG, West syndrome.

Background

• Epilepsy is a group of disorders characterized by recurrent seizures. In epilepsy, brain cells (neurons) create abnormal electricity that causes seizures or jerking movements. In some cases, seizures cause a loss of consciousness, a period of confusion, a staring spell, or muscle spasms.

• A single seizure is not considered epilepsy. Individuals with epilepsy have repeated episodes of seizures. Different forms of epilepsy are either secondary to a particular brain abnormality or neurological disorder, or are said to be idiopathic (without any clear cause).

• Normally, nerve transmission in the brain occurs in an orderly fashion, allowing a smooth flow of electrical activity. Neurons send messages using chemicals that cause an electrical signal to be produced. When a neuron is not sending a signal, it is "at rest." An action potentially occurs when a neuron sends information down an axon, away from the cell body.

• A seizure occurs when these neurons generate electrical discharges that spread throughout the brain. This can occur with both normal and abnormal nerve cells.

• Recurrent seizures or prolonged seizures can cause temporary or permanent damage to the brain and/or muscles. Seizures that last longer than 20-30 minutes can damage the brain's neurons.

• Certain areas of the brain are more likely than others to be the source of a seizure. These include the motor cortex, which is responsible for the initiation of body movement, and the temporal lobes, which include the hippocampus (involved in memory) and are found deeper in the brain. The reason these structures are more susceptible to seizures may be that nerve cells in these areas are particularly sensitive to situations that can provoke abnormal electrical transmission, such as decreased oxygen levels, metabolic changes, stress, and infection. A seizure threshold is each individual's balance (probably genetically determined) between excitatory and inhibitory forces in the brain. The relative proportions of each determine whether a person has a low threshold for seizures (because of the higher excitatory balance) or a high threshold (because of greater inhibition). According to this view, a low seizure threshold makes it easier for epilepsy to develop and easier for someone to experience a single seizure.

• A seizure is often divided into different stages. The aura is a period or warning prior to a seizure. Individuals may experience unusual smells, visual symptoms, or changes in bodily sensations. The seizure itself is known as the ictus. The period of time after the seizure is called the postictal state.

• Seizure disorders are a common neurological problem. In the United States, it has been estimated that more than four million individuals have some form of epilepsy.

• Epilepsy can affect individuals at any age.

Risk Factors and Causes

• Epilepsy is not associated with any particular disease. Many abnormalities of the nervous system can result in seizure activity. Seizures can also occur in the healthy nervous system when its metabolic balance is disturbed. The cause of epilepsy may be idiopathic (not clearly known) or related to a particular disease state, such as a brain trauma or a brain tumor. About 35% of all cases of epilepsy have no clearly definable cause.

• Age: Although epilepsy is more common in children than young adults, in seniors age 70 the incidence of epilepsy is nearly twice that of children, and in those over 80, it is more than three times that of children.

• The risk of epilepsy from birth through age 20 is approximately 1%. Within this group, the risk is highest during the first year of life and increases somewhat at the onset of puberty. From age 20-55 it decreases again, but increases after age 55. The prevalence of epilepsy in the United States has been estimated to be about five to eight in every 1,000 individuals.

• Degenerative disorders: There are several genetic, neurodegenerative (nerve damaging) disorders that are associated with seizures, including tuberous sclerosis, neurofibromatosis Tay-Sachs disease, phenylketonuria (PKU), and Sturge-Weber syndrome.

• Febrile seizures: Febrile seizures are age-associated seizures brought on by a fever in infants or small children. During a febrile seizure, a child often loses consciousness and shakes, moving limbs on both sides of the body. Less commonly, the child becomes rigid or has twitches in only a portion of the body, such as an arm or a leg, or on the right or the left side only. Most febrile seizures last a minute or two, although some can be as brief as a few seconds while others last for more than 15 minutes. Febrile seizures occur in 3-4% of children.

• Head injury: Seizures may develop at or around the time of injury or years after, usually within two years.

• Heredity: There is also an increased incidence of epilepsy in relatives of those with a seizure disorder. However, some individuals may have a genetic predisposition to the development of seizures that is not familial based.

• Infections: Infections of the nervous system may damage neurons and result in a lowered seizure threshold. Infections include meningitis (infections of the coverings of the brain and spinal fluid), encephalitis (infection of the brain itself), and human immunodeficiency virus (HIV).

• Medications: The presence of certain drugs can cause seizure activity. In addition, abrupt withdrawal of some substances can lead to seizure activity. The medications that may induce seizures include the tricyclic antidepressants (such as amitriptylline or Elavil®), lithium (Eskalith®), antipsychotic medications (such as chlorpromazine or Thorazine®), aminophylline (Theodur®), and high doses of penicillin (Pen VK®). Illicit drug use, particularly cocaine, heroin, amphetamines, and PCP, can cause seizures. Alcohol withdrawal can lead to seizure activity. Alcohol-induced seizures usually occur 12-24 hours after the last drink but can occur up to 48 hours or more after binge drinking. Withdrawal from prescription narcotics (such as morphine) can result in seizure activity.

• Metabolic disturbances: Metabolic disorders are a group of changes in various processes in the body, such as blood sugar metabolism, cardiovascular functioning (including blood flow and cellular oxygenation), and hormonal regulation. Conditions that sometimes result in seizures include: electrolyte disturbances, such as altered levels of sodium, calcium, or magnesium; hypoglycemia (low blood sugar) or hyperglycemia (elevated blood sugar); renal failure (kidney disease) with uremia (increased urea in the blood) or changes that occur around the time of kidney dialysis; liver failure leading to elevation of associated toxins; and hypoxia (lowered oxygen delivery to the brain).

• Movement disorders: Cerebral palsy (a movement disorder), secondary to lack of oxygen, infection, or trauma, is associated with epilepsy.

• Stroke: A stroke is neurological damage to the brain as a result of a lack of oxygen. Seizures can occur at the time of a stroke or many years later.

• Nutrition: The nutrient levels in young children with poorly controlled seizure disorders are often below the recommended levels. The Journal of the American Dietetic Association has reported that children with epilepsy ate statistically significant lower levels of total calories, protein, carbohydrates, fat, dietary fiber, and multiple vitamins and minerals, compared with healthy children.

• Tumors: Brain tumors, both malignant (cancerous) and benign, may be associated with seizures. The location of the tumor influences the likelihood of having seizures. Tumors can place pressure on neurons and cause irregular patterns of electrical activity, which cause a seizure.

Types of Seizures

• A well-recognized classification system for seizures is the International Classification of Epileptic Seizures. This divides seizure types by the location in the brain from which they originate. The two main categories of seizures include partial seizures and generalized seizures.

• Partial seizures:

• Partial, or focal, seizures are those that begin in a focal or discreet area of the brain. Partial seizures can be further subdivided into simple partial and complex partial.

• Simple partial seizures: In simple partial seizures, no change in consciousness occurs and seizure activity is localized in a specific portion of the brain. Individuals may experience weakness, numbness, and unusual smells or tastes. Twitching of the muscles or limbs, turning the head to the side, paralysis, visual changes, or vertigo (dizziness) may occur. If motor symptoms spread slowly from one part of the body to another, then the seizure is termed Jacksonian epilepsy.

• Complex partial seizures (temporal lobe): During complex partial seizures, consciousness is altered or lost during the event. Individuals may have some symptoms similar to those in simple partial seizures but have some change in their ability to interact with the environment. Individuals may exhibit automatisms (automatic repetitive behavior) such as walking in a circle, sitting and standing, or smacking the lips together. Often accompanying these symptoms are the presence of unusual thoughts, such as the feeling of déjà vu (having been someplace before), uncontrollable laughing, fear, visual hallucinations, and experiencing unusual unpleasant odors. These symptoms are generally thought of as being caused by abnormal electrical discharges between neurons in specific areas of the brain, such as the temporal lobe.

• Generalized seizures:

• Generalized seizures involve larger areas of the brain, often both hemispheres (sides), from the onset. They are further divided into many subtypes. The more common types include tonic-clonic (grand mal), absence (petit mal), and myoclonic seizures.

• Tonic-clonic (grand mal): Tonic-clonic seizures, also called grand mal, are the subtype that most people associate with seizures. Specific movements of the arms and legs and/or the face may occur with loss of consciousness. A yell or cry often precedes the loss of consciousness. Individuals may have an aura, or an unusual feeling that often warns the patient that they are about to have a seizure, right before the loss of consciousness. The individual will abruptly collapse and begin to have jerking movements of their body and head. Drooling, biting of the tongue, and urinary incontinence may occur. When the jerking movements stop, the individual may remain unconscious for a period of time. Tonic-clonic seizures usually last 5-20 minutes. Individuals often awaken confused and may sleep for a period of time. Todd's paralysis is a term for when the individual experiences prolonged weakness after the seizure.

• Absence (petit mal): Absence or petit mal seizures are when loss of consciousness only occurs and there are no other associated motor symptoms, such as jerking. Usually there is no aura or warning. The loss of consciousness is brief. The individual may appear to be involved with the environment and briefly stop what they are doing, stare for 5-10 seconds, and then continue their activity. No memory of the event exists. Subtle motor movements may accompany the alteration in consciousness.

• Myoclonic: Myoclonic seizures are characterized by a brief jerking movement that arises from the central nervous system, usually involving both sides of the body. The movement may be very subtle or very dramatic. There are many different syndromes associated with myoclonic seizures, including juvenile myoclonic epilepsy, West syndrome, and Lennox-Gastaut syndrome. Most cases of myoclonic epilepsy occur during the first five years of life. There is no loss of consciousness with myoclonic seizures.

• Other seizure disorders:

• West Syndrome: West syndrome, also known as infantile spasm, involves a group of symptoms including spasms in infants, retardation of psychomotor development, and a particular abnormality on the electroencephalogram (EEG) known as hypsarrhythmia. Hypsarrhythmia is the abnormally high amplitude waves and a background of irregular spikes seen in EEG. Infantile spasms are characterized by a particular posturing of the infant's body, in which the child assumes a jack-knife, or folded position. These spasms may occur frequently in the course of the day or may be continuous. Neurological problems are ultimately found in most of these children. The hypsarrhythmia pattern seen on the EEG is a grossly disorganized pattern of electrical brain activity. It is often difficult to control the seizures in this syndrome because they usually respond poorly to most anticonvulsant medications.

• Lennox-Gastaut Syndrome: Lennox-Gastaut syndrome, also known as childhood epileptic encephalopathy, is a devastating pediatric (usually before the age of four) epilepsy syndrome constituting 1-4% of childhood epilepsies. The syndrome is characterized by multiple types of seizures, mental retardation or regression, and abnormal EEG. The seizures include the myoclonic seizures, absence seizures, and atonic seizures. Absence seizures may involve staring and brief episodes of unconsciousness. They may occur in cycles and are associated with EEG findings different from those seen in typical absence seizures. Atonic seizures may be associated with sudden loss of muscle tone.

• Status Epilepticus: Status epilepticus is prolonged, repetitive seizure activity that lasts more than 20-30 minutes, during which time the patient is unconscious. Status epilepticus is a medical emergency with a significantly poor outcome. It can result in death if not treated aggressively. Its causes include improper use of certain medications, stroke, infection, trauma, cardiac arrest, illicit drug overdose (such as cocaine or methamphetamine), and brain tumor.

Signs and Symptoms

• Seizures can affect any process the brain coordinates due to abnormal activity in brain cells. A seizure can produce temporary confusion, complete loss of consciousness, a staring spell, or uncontrollable jerking movements of the arms and legs.

• Symptoms vary depending on the type of seizure. In most cases, an individual with epilepsy will tend to have the same type of seizure each time, so the symptoms will be very similar from episode to episode, but some individuals have many different types of seizures, with different symptoms each time.

• Doctors will classify seizures as either partial or generalized, based on how the abnormal brain activity begins. When seizures appear to result from abnormal activity in just one part of the brain, they are called partial or focal seizures. Seizures that seem to involve all of the brain are called generalized seizures. In some cases, seizures can begin in one part of the brain and then spread throughout the rest of the brain. Seizures may progress from partial to generalized.

• Most individuals with epilepsy can lead outwardly normal lives. Currently, epilepsy cannot be cured. However, for some individuals epilepsy does eventually go away with age. Most seizures do not cause brain damage. It is not uncommon for individuals with epilepsy, especially children, to develop behavioral and emotional problems, sometimes the consequence of embarrassment and frustration or bullying, teasing, or avoidance in school and other social settings. For many individuals with epilepsy, the risk of seizures restricts their independence (some states refuse drivers licenses to people with epilepsy) and recreational activities. Individuals with epilepsy are at special risk for two life-threatening conditions: status epilepticus and sudden unexplained death. Most women with epilepsy can become pregnant, but they should discuss their epilepsy and the medications they are taking with their doctors. Infertility in women with epilepsy is rare. Women with epilepsy have a 90% or better chance of having a normal, healthy baby.

• Partial seizures:

• Simple partial seizures: Simple partial seizures do not result in loss of consciousness. These seizures may alter emotions or change the way things look, smell, feel, taste, or sound.

• Complex partial seizures: Complex partial seizures alter consciousness, causing the individual to lose awareness for a period of time. Complex partial seizures often result in staring and non-purposeful movements, such as hand rubbing, lip smacking, arm positioning, vocalization, or swallowing.

• Generalized seizures:

• Generalized seizures involve epileptic activity in all or most of the brain.

• Absence seizures (petit mal). Absence seizures are characterized by staring, subtle body movements, and brief lapses of awareness.

• Myoclonic seizures: Myoclonic seizures usually appear as sudden jerks of the arms and legs.

• Atonic seizures: Atonic seizures are also known as drop attacks and may cause the individual to suddenly collapse or fall down.

• Tonic-clonic seizures (grand mal): Tonic-clonic seizures are the most common form of generalized seizures. They are also the most widely recognized epileptic seizure. In a tonic-clonic seizure, the person loses consciousness, the body stiffens, and then they fall to the ground. This is followed by jerking movements. After a minute or two, the jerking movements usually stop and consciousness slowly returns.

Diagnosis

• Medical history:

• Doctors will ask about the individual's history of seizures, along with other diseases, surgeries, and medications. A thorough history of recreational drug and alcohol use or abuse is equally important. It is helpful for the doctor to distinguish seizure subtypes, partial or generalized; time of day of the event, including whether the seizure occurred during wakefulness or sleep; and any known triggers, such as a flickering light, severe sleep deprivation, or dehydration.

• Physical examination:

• Doctors will perform a complete physical examination. A complete physical examination will include a neurological examination and brain function tests.

• Diagnostic testing:

• Laboratory data utilized in the diagnostic evaluation of patients with seizure disorders may include CT scan imaging, magnetic resonance imaging (MRI), and electroencephalograph (EEG). A complete blood panel, including drug-toxic screening and urinalysis are usually performed. Urine tests can determine if the individual is having a seizure due to illicit drug use, such as cocaine or methamphetamine. Blood tests will determine the basic functioning of the body, such as electrolyte (including sodium and potassium) levels and kidney and liver function.

• A blood test that measures the hormone prolactin may be used to determine if a seizure was caused by epilepsy. The test, which must be used within 10-20 minutes after a seizure, measures levels of the hormone prolactin in the blood. Prolactin is produced by the pituitary gland, but an area of the brain called the hypothalamus controls its release. Researchers think that epileptic seizures affect the hypothalamus and may alter the release of prolactin, causing levels of the hormone to rise.

• Electroencephalogram (EEG): An EEG records the electrical activity of the brain via electrodes. The electrodes are attached to the scalp. Individuals with epilepsy often have changes in the normal pattern of brain waves, even when they are not having a seizure.

• To prepare for an EEG, healthcare professionals recommended that individuals avoid elaborate hair styling, metallic hair spray, or greasy hair products. The individual should refrain from caffeine for six hours before the test. The procedure itself is painless and usually lasts about 30 minutes. However, it can take as long as an hour to place the electrodes on the scalp properly.

• Video-EEG monitoring may also be used in some individuals as a diagnostic tool while they are having a seizure. Video monitoring can be helpful because it allows the doctor to compare the behaviors that occur during a seizure with an EEG pattern from the same time. Knowing where the seizure originates in the brain helps the doctor in treating the condition. Individuals undergoing video-EEG may be required to stay in a hospital or clinic for several days. The individual is monitored on video constantly during this time. The EEG electrodes stay attached for the entire time, which may cause discomfort in some individuals.

• Computerized tomography (CT): Computerized tomography, or CT, uses special x-ray equipment to produce images of body structure. CT machines obtain images from many different angles and join them together to show cross-sectional images of the brain and skull. CT scans can reveal abnormalities in brain structure including tumors, cysts, strokes, or tangled blood vessels. This helps the doctor rule out other potential causes of the individual's seizures.

• To prepare for a CT scan of the head, individuals should remove such things as earrings, eyeglasses, dentures, and hairpins. An intravenous (IV) line may be inserted into a vein if the test requires the injection of a contrast material, which makes abnormalities easier to see. During the test, the individual will lie on a table that slides into the CT machine. Depending on the number of images needed, the scan can take between two and 20 minutes. The procedure is painless, but some individuals may experience discomfort or claustrophobia while having to sit still.

• Magnetic resonance imaging (MRI): A magnetic resonance imaging (MRI) device uses radio waves and a strong magnetic field to produce detailed images of the brain. Like CT scans, MRIs can reveal brain abnormalities that could be causing seizures. Dental fillings and braces may distort the images.

• During the test, the individual will lie on a padded table that slides into the MRI machine. The head will be immobilized in a brace to improve precision. The test is painless, but some individuals experience an uncomfortable feeling similar to claustrophobia inside the MRI device's close quarters. Sedative medications, such as alprazolam (Xanax®), can be given to sensitive individuals.

• Positron emission tomography (PET): Positron emission tomography (PET) scans use injected radioactive material to help visualize active areas of the brain. After the radioactive material is injected into a vein, it will take 3-90 minutes for the substance to accumulate in the brain tissue. During this waiting period, the individual will be asked to rest quietly and not talk or move around much. The actual scan takes 30-45 minutes. The amount of radioactive material used in the test is very small.

• Single-photon emission computerized tomography (SPECT): Single-photon emission computerized tomography (SPECT) is used primarily in individuals being evaluated for epilepsy surgery when the area of seizure onset is unclear on MRIs or EEGs. SPECT imaging requires two scans, one during a seizure and one 24 hours later. Radioactive material is injected for both scans and then the two results are compared.

• Conditions resembling seizure disorders: Seizure disorders must be differentiated from a variety of problems whose symptoms approximate or closely resemble those of epilepsy. These include cerebrovascular (stroke-related) disorders, migraine, narcolepsy (a neurological condition with uncontrollable sleep attacks and persistent daytime sleepiness), syncope (fainting), and anxiety.

• A pseudoseizure, or more properly a non-epileptogenic seizure, may also occur. These "spells" are not triggered by nerve cell discharges that cause true epilepsy, although the individual may experience muscle twitching and even apparent loss of consciousness. These spells have a psychiatric component and often coexist in persons who have epilepsy with true seizures. EEG monitoring can help distinguish disorders that mimic epilepsy from true seizures.

Complications

• Injury: If an individual falls during a seizure, they may sustain a head injury. Drowning is a risk if the individual has a seizure while swimming or bathing.

• Loss of consciousness and awareness: A seizure that causes either loss of awareness or control can be dangerous if the individual is driving a car or operating other equipment. Medications used to control seizures also can cause drowsiness, which may affect the individual's driving ability. Many states have licensing restrictions related to the individual's ability to control seizures.

• Pregnancy: Seizures during pregnancy pose dangers to both mother and baby and certain anti-epileptic medications increase the risk of birth defects. A doctor will advise an individual with epilepsy who is considering becoming pregnant. Most women with epilepsy can become pregnant and have a healthy baby, but many need to adjust their medications and be carefully monitored throughout pregnancy.

• Life-threatening complications: Life-threatening complications from epilepsy are uncommon, but do occur. Individuals who have severe, prolonged, or continuous seizures (status epilepticus) are at increased risk of permanent brain damage and death. Individuals with epilepsy, particularly those with poorly controlled epilepsy, also have a small risk of a condition called sudden unexplained death in epilepsy (SUDEP). The risk of SUDEP increases if the individual is having seizures at an early age, has frequent seizures that involve more than one area of the brain, or continues to have seizures despite treatment with medications.

Treatment

• Anticonvulsant medications:

• Anticonvulsant, or antiepileptic, medications are the treatment of choice for epilepsy and seizure disorders. Treatment options with anticonvulsants are evaluated initially based on seizure subtype, as certain anticonvulsants may be used for treating some forms of epilepsy. When making decisions about treatment with a particular agent, the doctor will take into account the patient's entire medical and medication histories, age, and gender as well as the side-effect profile of the medicine. Anticonvulsants are generally given life-long.

• Treatment with one anticonvulsant drug, called monotherapy, is the goal. Seizures can be controlled with one agent in approximately 75% of individuals with epilepsy. It is very important for individuals with epilepsy and seizure disorders to take their medications as prescribed. For medications to work effectively, a relatively constant level of medication must be maintained in the body. This is accomplished by taking medication regularly as directed, without missing doses. The consequences of missed doses may be a single seizure, more devastating multiple seizures, or status epilepticus.

• Phenytoin: Phenytoin (Dilantin®) has been used as an anticonvulsant medication for seizures since the late 1930s. Phenytoin is thought to suppress electrical activity in brain nerve cells, helping to control seizures. It can be given orally or intravenously (IV) and a newer form of the drug, fosphenytoin (Cerebyx®), can be injected into muscle.

• Phenytoin is used in treating partial and generalized tonic-clonic (grand mal) seizures. Phenytoin is used with individuals with status epilepticus, although benzodiazepine drugs, such as diazepam (Valium®), are the drugs of choice for this condition. Phenytoin drug levels are monitored closely with laboratory testing, as altered levels of phenytoin may cause side effects such as lethargy and weakness. In addition, liver function testing and a complete blood count (CBC) need to be followed. Phenytoin has many interactions with other medications, and its own level can fluctuate when other drugs are taken.

• Some of the side effects associated with phenytoin use include gingival hyperplasia (overgrowth of the gums), hirsuitism/hypertrichosis (excessive hair growth), imbalance, lethargy, anemia, and, in long-term use, peripheral neuropathy (nerve damage causing weakness).

• Carbamazepine: Carbamazepine (Tegretol® or Carbatrol®) is commonly prescribed for the treatment of partial and generalized tonic-clonic (grand mal) seizures. Carbamazepine levels are followed closely with laboratory testing. Liver function tests and complete blood count (CBC) are also checked routinely. Carbamazepine can affect the levels of a number of other drugs in the body, and its own level can fluctuate when other agents are taken.

• Side effects include drowsiness, imbalance, nausea, anemia, neutropenia (a low white blood cell count), and agranulocytosis (a lack of white blood cells).

• Phenobarbital: Phenobarbital is a barbiturate medication that is used to treat both partial and generalized seizures. Phenobarital, or phenobarb, is available in oral and intravenous forms. Blood levels are monitored closely. A complete blood analysis and liver function tests are also routinely monitored. Phenobarbital can cause changes in the metabolism of other drugs through its actions on liver enzymes. Side effects may include drowsiness, cognitive impairment, and irritability.

• Valproic acid: Valproic acid (Depakene®, Depakote®) is used for partial seizures, generalized tonic-clonic (grand mal) seizures, absence (petit mal), and myoclonic epilepsy. Valproic acid seems to affect the brain with a neurotransmitter known as GABA (gamma-aminobutyric acid). GABA inhibits the excitation of nerve cells in the brain. Drug levels are monitored closely. A complete blood analysis and liver function tests are also routinely monitored. Side effects include hepatotoxicity (liver damage), nausea, weight gain, alopecia (hair loss), and tremor.

• Topiramate: Tomipramate (Topamax®) is used with other anticonvulsant drugs in the treatment of partial seizures and generalized tonic-clonic seizures in adults and children aged 2-16. Although its precise mechanism of action is unknown, one theory suggests that its anticonvulsant activity may be due in part to increasing GABA (gamma-aminobutyric acid). Side effects include drowsiness, nausea, dizziness, and coordination problems. Children may have difficulty concentrating and may become aggressive.

• Gabapentin: Gabapentin (Neurontin®) is indicated for the treatment of partial seizures, with or without secondary generalization. The precise mechanism of action is unknown. No laboratory monitoring of liver, kidney, or hematologic (blood) function is usually necessary with gabapentin. The major side effects are drowsiness, fatigue, dizziness, and imbalance. Gabapentin has also been used successfully in individuals with neuropathic pain syndromes. When an individual begins therapy with gabapentin, it is recommended by healthcare professionals to use caution when driving or operating heavy machinery until drowsiness and fatigue subsides, which make take 2-4 weeks.

• Lamotrigine: Lamotrigine (Lamictal®) is used in the treatment of partial seizures. The precise mechanism of action is unknown. No laboratory monitoring of lamotrigine levels are usually necessary. The major side effect is the appearance of a potentially life-threatening skin rash (called Stevens-Johnson syndrome), particularly for patients who also are taking valproic acid (Depakote®). Any individuals taking lamotrigine who develops a rash should immediately report it to a doctor. Other side effects include headache, nausea, and dizziness.

• Tiagabine: Tiagabine (Gabitril®) is used in adults with partial seizures. Its mechanism of action may be related to its effect on GABA (gamma-aminobutyric acid). No laboratory monitoring of tiagabine levels are usually necessary. Some interaction likely exists when tiagabine is taken with other anticonvulsants, in that its metabolism may be altered. Side effects include dizziness and somnolence.

• Levetiracetam: Levetiracetam (Keppra®) is used in adults along with other anticonvulsants as treatment for partial seizure disorders. The side effects can include fatigue, imbalance, and behavioral changes, which often dissipate after the first month of treatment.

• Oxacarbazine: Oxcarbazepine (Trileptal®) is used alone in adults who have partial seizures and can be used in children for partial seizures. Oxacarbazine is usually taken with other anticonvulsant medications for seizure control. The most common side effects include dizziness, sleepiness, nausea, and imbalance.

• Zonisamide: Zonisamide (Zonegran®) is approved for use in adults as adjunctive therapy for partial seizures. It has been used fairly extensively in other countries for use in other seizure types including generalized seizures, myoclonic seizures, and absence seizures. Side effects can include dizziness, imbalance, and fatigue. Individuals who are allergic to sulfonamide (sulfa) drugs should not use zonisamide.

• Benzodiazepines: Benzodiazepines belong to the group of medicines called central nervous system (CNS) depressants (medicines that slow down the nervous system). Most benzodiazepines are used to relieve anxiety and insomnia (lack of sleep). Clonazepam (Klonopin®), clorazepate (Tranxene®), diazepam (Valium®), and lorazepam (Ativan®) are used in the treatment of status epilepticus. Benzodiazepines may cause drowsiness and sedation. Benzodiazepines also have the potential for abuse and may cause physical addiction.

• Other conventional treatments:

• Ketogenic diet: A ketogenic diet is a diet high in fat content and is usually reserved for epilepsy patients that have tried two anti-convulsant medications without relief from seizures. Ketogenic diets seem to alter brain function and decrease seizure activity.

• The goal of the diet is to get the body to produce ketones, which cause the body to use fat instead of glucose for energy. Ketone bodies are compounds that are produced as by-products when fatty acids are broken down for energy.

• If carbohydrates (which are composed of sugars) are eliminated from the diet, and a diet very high in fat is substituted, the body has no dietary sources of glucose. In the event of low blood glucose, most other tissues have additional energy sources besides ketone bodies (such as fatty acids) but the brain does not. After the diet has been changed to lower blood glucose for three days, the brain gets 30% of its energy from ketone bodies. After four days, this goes up to 70%.

• As a result, ketones are made from the available sources and these are used as fuel instead. Even a very small amount of sugar can cause the body to shift to glucose production and use, which it prefers to ketones. For example, this restriction is such that children on the diet have to be careful to take sugarless daily multivitamins. Some children with epilepsy have been helped by adopting a rigid diet that is high in fat and protein and low in carbohydrates.

• Elevated levels of ketones in the body of individuals with epilepsy may be associated with seizure control and seizure freedom.

• Surgery: Surgical removal of areas of the brain where partial seizures are occurring is used when seizure activity fails to respond to even the most aggressive medical anticonvulsant therapies. Patients considered for these procedures are those with intractable seizures, even when given high levels of anticonvulsant drugs. During the procedure, the surgeon makes an incision in the scalp and removes a piece of the skull bone. The area(s) responsible for seizure activity are then removed. Some individuals will be able to reduce the medications after the surgery. In some cases, surgery for epilepsy can cause complications such as permanently altering cognitive abilities. It is important to discuss all options with a doctor.

• Vagus nerve stimulation: The vagus nerve is a cranial nerve controlling muscles involved with swallowing, speaking, and coughing. The nerve is also involved with receiving input from and sending information about the heart, stomach, and lungs to the brain. A device called a vagus nerve stimulator is implanted into the chest under the collarbone. Wires from the stimulator are wrapped around the vagus nerve in the neck. The device turns on and off according to an adjustable program. The device has been reported to reduce seizures by about 20-40%. Most individuals still need to take anticonvulsant medication, but a reduction in dosage is possible.

Integrative Therapies

• Good scientific evidence:

• Yoga: Yoga is an ancient system of relaxation, exercise, and healing with origins in Indian philosophy. Several human studies report a reduction in the number of monthly seizures with the use of Sahaja yoga, when it is added to standard anti-seizure drug treatment, or a yoga meditation protocol. Research is preliminary, and more studies are needed to better determine the effects of yoga for epilepsy.

• Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, cervical spondylitis, or if at risk for blood clots. Certain yoga breathing techniques should be avoided with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction. However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

• Unclear or conflicting scientific evidence:

• Acupressure, shiatsu: Preliminary evidence suggests that acupressure may help with epileptic seizures in children. Further research is needed to confirm these results.

• With proper training, acupressure appears to be safe if self-administered or administered by an experienced therapist. Serious long-term complications have not been reported in the available literature. Hand nerve injury and herpes zoster ("shingles") cases have been reported after shiatsu massage. Forceful acupressure may cause bruising.

• Atkins Diet®: The Atkins Diet® proposes that, in order to lose weight, one should adopt an eating style that radically departs from the U.S. Food and Drug Administration's (FDA) food pyramid. It proposes the elimination of most carbohydrates as a source of energy; in the place of carbohydrates, the diet advocates the significantly increased consumption of fats, including trans fats and hydrogenated oils, and protein. The efficacy of the Atkins Diet® in individuals with epilepsy has been investigated in open label studies. Preliminary evidence suggests that seizure frequency may be reduced in some patients. Well designed controlled studies are needed. Patients should consult a qualified healthcare professional before beginning any new diet or adjusting their current regimen.

• Avoid with severe kidney disease or renal disorders. Avoid if using growth hormone. Use cautiously with mood disorders, such as depression, schizophrenia, or bipolar disorder, as well as individuals using medications for these purposes. Use cautiously in athletes due to potential for muscle cramps, negative feelings towards exercise, fatigue, and hypoglycemia. Use cautiously with osteoporosis, gout, diabetes, menstrual disorders, gastrointestinal disorders, celiac disease, skin conditions, epilepsy, and cardiovascular disease. Use cautiously in malnourished individuals, vegetarians, or individuals with absorption concerns. Use cautiously if taking diuretics, medications that alter cholesterol, medications that alter blood sugar, medications for seizures, steroids, or NSAIDS. Use cautiously in anemic individuals, individuals with thyroid concerns, and in individuals with a previous history of stroke or heart attack. Avoid if pregnant or breastfeeding.

• Bacopa: Bacopa (Bacopa monnieri) is a traditional herb used in Indian or Ayurvedic medicine. Although bacopa has been used in Ayurvedic medicine for epilepsy, high-quality clinical trials are lacking. Methodologically weak study found some evidence that bacopa reduces seizure frequency. More research is needed to confirm these results.

• Use cautiously with drugs or herbs that are metabolized by cytochrome P450 enzymes, thyroid drugs, calcium blocking drugs, and sedatives. Avoid if allergic/hypersensitive to Bacopa monnieri, its constituents or any member of the Scrophulariaceae (figwort) family. Avoid if pregnant or breastfeeding.

• Caprylic acid: Caprylic acid is an eight-carbon fatty acid naturally found in palm and coconut oil and in the milk of humans and cows. Some forms of epilepsy respond to diets that are high in fat and low in carbohydrates. Currently, the effects of caprylic acid alone to treat pediatric epilepsy are not well studied. Additional study is needed in this area.

• Avoid if allergic or hypersensitive to caprylic acid and its derivatives, such as caprylate salts. Avoid with medium-chain acyl-CoAdehydrogenase (MCAD) deficiency, kidney stones, or a tendency to developing kidney stones. Use cautiously in infants, children, pregnant women, nursing mothers, and those prone to get an upset stomach.

• Chiropractic: Chiropractic is a healthcare discipline that focuses on the relationship between musculoskeletal structure (primarily the spine) and body function (as coordinated by the nervous system), and how this relationship affects the preservation and restoration of health. Chiropractic manipulation may help decrease pressure on nerves that may be causing seizure activity. There is currently not enough reliable scientific evidence to conclude the effects of chiropractic techniques in the management of seizure disorder or epileptic seizures in children.

• Avoid with vertebrobasilar vascular insufficiency, aneurysms, arteritis, or unstable spondylolisthesis. Avoid use on post-surgical areas of para-spinal tissue. Use cautiously with acute arthritis, brittle bone disease, conditions that cause decreased bone mineralization, bleeding disorders, migraines, or if at risk of tumors or metastasis of the spine. Use extra caution during cervical adjustments. Avoid if pregnant or breastfeeding due to a lack of scientific data.

• Euphorbia: Euphorbia alkaloid, which is the active ingredient in Euphorbia fisheriana, may have anticonvulsant effects. Thus, this alkaloid may be useful in patients with epilepsy. Additional study is needed in this area.

• Avoid if allergic or hypersensitive to pollen from Euphorbia fulgens. Use cautiously with history of Epstein Barr virus infection or stomach conditions. Avoid if pregnant or breastfeeding.

• Meditation: Various forms of meditation have been practiced for thousands of years throughout the world, with many techniques originating in Eastern religious practices. In modern times, numerous meditation types are in use, often outside of their original religious and cultural contexts. Yoga meditation may help prevent seizures in epilepsy, although higher quality clinical studies are needed.

• Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.

• Melatonin: Melatonin is a neuro-hormone produced in the brain by the pineal gland from the amino acid tryptophan. The synthesis and release of melatonin are stimulated by darkness and suppressed by light, suggesting the involvement of melatonin in circadian rhythm and regulation of diverse body functions. Levels of melatonin in the blood are highest prior to bedtime. The role of melatonin in seizure disorder in children is controversial. There are several reported cases of children with intractable seizures or neurological damage who improved with regular nighttime melatonin administration. Limited animal research also suggests possible anti-seizure effects. However, there has also been a report that melatonin may actually lower seizure threshold and increase the risk of seizures. Better evidence is needed in this area before a clear conclusion can be drawn regarding the safety or effectiveness of melatonin in seizure disorder.

• Case reports raise concerns about risks of blood clotting abnormalities (particularly in patients taking warfarin), increased risk of seizure, and disorientation with melatonin overdose. Melatonin supplementation should be avoided in women who are pregnant or attempting to become pregnant. High levels of melatonin during pregnancy may increase the risk of developmental disorders.

• Selenium: It is unclear whether serum selenium levels are related to seizures in patients with epilepsy or brain tumors. More research is needed to examine whether selenium supplementation may affect the frequency or severity of seizures.

• Avoid if allergic or sensitive to products containing selenium. Avoid with a history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.

• Taurine: Taurine is a nonessential amino acid-like compound. Taurine is found in high abundance in the tissues of many animals, especially sea animals, and in much lower concentrations in plants, fungi, and some bacteria. Taurine is important in several metabolic processes of the body, including stabilizing cell membranes in electrically active tissues, such as the brain and heart. In animal studies, taurine has been suggested to have an antiepileptic action. The effect of taurine on seizures in humans has been investigated in several clinical studies. However, well-designed, randomized clinical trials need to be conducted.

• Taurine is an amino acid and it is unlikely that there are allergies related to this constituent. However, allergies may occur from multi-ingredient products that contain taurine. Use cautiously in patients with high cholesterol, low blood pressure, coagulation disorders, potential for mania, or epilepsy. Avoid alcohol or exercise after consumption of energy drinks containing taurine, caffeine, glucuronolactone, B vitamins, and other ingredients. Use cautiously if pregnant or breastfeeding; taurine is a natural component of breast milk.

• Vitamin D: Vitamin D is found in numerous dietary sources such as fish, eggs, fortified milk, and cod liver oil. The sun is also a significant contributor to daily production of vitamin D and as little as 10 minutes of exposure is thought to be enough to prevent deficiencies. Supplementation with vitamin D has been reported to reduce seizure frequency in initial research. Further study is needed to confirm the effects of vitamin D supplementation for treatment of anticonvulsant-induced osteomalacia.

• Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; doses higher than recommended may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.

• Vitamin E: Vitamin E is a fat-soluble vitamin with antioxidant properties. Vitamin E has been evaluated as an addition to other drugs used to prevent seizures, particularly in refractory epilepsy. The evidence is not conclusive at this time and more study is needed.

• Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid above the recommended daily level in pregnant or breastfeeding women.

• Fair negative scientific evidence:

• 5-HTP: 5-HTP, or 5-hydroxytryptophan, is the precursor of the neurotransmitter serotonin. It is obtained commercially from the seeds of the plant Griffonia simplicifolia. 5-HTP has been studied as a treatment for various myoclonic syndromes and epilepsy, but available research does not support this use at this time.

• Avoid 5-HTP if allergic or hypersensitive to it; signs of allergy to 5-HTP may include rash, itching or shortness of breath. Avoid with eosinophilia syndromes, Down's syndrome, and mitochondrial encephalomyopathy. Use cautiously if taking antidepressant medications such as TCAs, MAOIs, SSRIs, nefazodone, trazodone, venlafaxine, mirtazapine, bupropion; 5-HTP receptor agonists such as sumatriptan, rizatriptan, naratriptan, zolmitriptan, eletriptan, imotriptan, and frovatriptan; and carbidopa, phenobarbital, pindolol, reserpine, tramadol, or zolpidem. Use cautiously with renal (kidney) insufficiency, HIV/AIDS- particularly HIV-1 infection, epilepsy, and/or with a history of mental disorders. Avoid if pregnant or breastfeeding.

Self-Monitoring

• It is recommended by healthcare professionals for individuals with epilepsy and seizure disorders to discuss their condition with family members, friends, and co-workers in case seizures occur. Individuals should instruct the others to stay calm; do not try to keep the individual from moving; take away items that could cause injury if the person falls or bumps into them; do not move the individual to another place; and to gently turn the individual onto his or her side so any fluid in the mouth can safely come out. Do not try to force the individual's mouth open or put anything in it; understand that seizures are usually not life-threatening. A doctor or an ambulance should be called if the individual has seizures that lasts longer than 10-15 minutes; and when the seizure is over, watch the individual for signs of confusion.

• Health care providers recommend calling a doctor in the following situations: anytime seizures change, either in number or in the way the individual feels during them; anytime the individual feels ill or sick; or anytime there are changes in seizure medications or if the individual take any other medications. It is very important to take prescribed medications as directed. It is also very important for an individual to tell their doctor about herbs and other dietary supplements they may be taking. It is best to avoid taking dietary supplements without a doctor's approval.

• Although the laws vary somewhat from state to state, most states have rules regarding when seizure patients can legally resume driving. Typically, individuals must have been seizure-free six months to a year. While doctors generally are not required to report patient seizures to their state motor vehicle departments, individuals are expected to comply with the laws in their state.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Amann B, Grunze H, Vieta E, et al. Antiepileptic drugs and mood stability. Clin EEG Neurosci. 2007;38(2):116-23. View Abstract.

2. Centers for Disease Control. www.cdc.gov.

3. Duncan JS. Epilepsy surgery. Clin Med. 2007;7(2):137-42. View Abstract.

4. Epilepsy Foundation. www.epilepsyfoundation.org.

5. Epilepsy.com. www.epilepsy.com.

6. Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007;119(3):535-43. View Abstract.

7. Kang HC, Lee HS, You SJ, et al. Use of a modified Atkins diet in intractable childhood epilepsy. Epilepsia. 2007;48(1):182-6. View Abstract.

8. National Institute of Neurological Disorders and Stroke. www.ninds.nih.gov.

9. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

10. Volpe SL, Schall JI, Gallagher PR, et al. Nutrient intake of children with intractable epilepsy compared with healthy children. J Am Diet Assoc. 2007;107(6):1014-8. View Abstract.