Seizures / Epilepsy
Overview
Epilepsy is a recurrent seizure disorder caused by abnormal electrical discharges from brain cells, often in the cerebral cortex. It is not a distinct disease, it is a group of disorders for which recurrent seizures are the main symptom. 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 way, allowing a smooth flow of electrical activity. A seizure occurs when these neurons generate uncoordinated electrical discharges that spread throughout the brain. This can occur with both normal and abnormal nerve cells.
The Physiology of a Seizure
In order to understand the process of electrical transmission within nerve cells, it is important to review the structure and function of a nerve. A nerve cell can be thought of as a tube, having an inner section, and bounded by a cell wall (membrane). Importantly, the chemical composition of the inside of the cell and the outside of the cell are very different. Specifically, there is a difference in the concentration of sodium and potassium salts, with sodium being much higher on the outside, and potassium being much higher on the inside. In a normal resting state, special pumps (called membrane pumps) are continually at work to maintain each salt in its proper location.
When a nerve is called upon to transmit an electrical signal, a sudden movement of these salts from one side of the cell's membrane to the other occurs. This movement spreads like a wave from one end of the nerve to the other, until it reaches the end. At this point, the nerve's signal may be transmitted to the next nerve cell either by a direct extension of this process, or, more commonly, by releasing a special chemical called a neurotransmitter. Neurotransmitters generally have one of two special functions. One type is responsible for encouraging cell-to-cell communication and is referred to as an "excitatory" neurotransmitter. The second type is able to slow down, or even stop cell-to-cell communication and is called an "inhibitory" neurotransmitter. In some cases, overactivity of excitatory neurotransmitters or underactivity of inhibitory neurotransmitters may lead to seizure activity by allowing an uncoordinated flow of electrical activity in the brain.
Interestingly, certain areas of the brain are more likely than others to be the source of a seizure. These include the motor cortex (responsible for the initiation of body movement) and the temporal lobes (including a special deep area called the hippocampus, which is involved in memory). The reason for this likelihood may be that nerve cells in these areas are particularly sensitive to certain situations that can provoke abnormal electrical transmission. Examples include sensitivity to decreased oxygen levels, metabolic changes, and infection, any of which may lead to a seizure.
Many types of brain abnormalities can be responsible for producing seizure activity. Abnormal discharges may spread to other cells in a local area or to remote areas of the brain, resulting in intermittent disturbance in the brain's normal functions. Changes in brain biochemistry and communication between brain cells occur. These basic neurofunctional abnormalities that lead to epilepsy produce the clinical symptoms that are seen. In turn, recurrent seizures or prolonged seizures can cause injury to the brain. Seizures that last longer than 20 to 30 minutes can damage the brain's neurons.
A seizure is often divided into different parts. The aura is a period or warning prior to a seizure. Patients may experience unusual smells, visual symptoms, or feelings. The seizure itself is known as the ictus. The period of time after the seizure is called the postictal state.
Seizures were depicted by prehistoric man in cave paintings. Hippocrates wrote of epilepsy and of its relationship to the brain. Epilepsy also is described in the Bible. Writings from 4000 years ago depict epileptics as possessed by demons. Julius Caesar, the great Russian novelist Dostoyevsky, and King Charles II all are said to have had seizures.
Incidence
Seizure disorders are a common neurological problem. In the United States alone, it has been estimated that more than 4 million people have some form of epilepsy.
The incidence of epilepsy, that is the number of newly diagnosed cases over a specific period of time (e.g., one year), depends somewhat on the age of the individual. The risk of epilepsy from birth through age 20 is approximately 1 percent. Within this group, the risk is highest during the first year of life and increases somewhat at the onset of puberty. From age 20 to 55 it decreases again, but increases after age 55. The prevalence of epilepsy (defined as the total of the population suffering from a disorder at a particular time) has been estimated to be about 5 to 8 in every 1000 people.
Types
There have been many attempts to categorize seizures, based on both the causes of seizures as well as the different seizure subtypes. A well-recognized classification system is the International Classification of Epileptic Seizure. This divides seizure types by the location in the brain that they originate from.
The two main categories of seizures include partial seizures and generalized seizures.
Partial seizures are those that begin in a focal or discreet area of the brain. This type can be further subdivided into:
- Simple partial: No change in consciousness occurs. Patients 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 may occur. When motor symptoms spread slowly from one part of the body to another, this "epileptic march" has been termed jacksonian epilepsy (first described by Hughlings Jackson).
- Complex partial seizures (temporal lobe): Consciousness is altered during the event. Patients may have some symptoms similar to those in simple partial seizures but have some change in their ability to interact with the environment. Patients may exhibit automatisms (automatic repetitive behavior) such as walking in a circle, sitting and standing, or smacking their lips together. Often accompanying these symptoms are the presence of unusual thoughts, such as the feeling of deja vu (having been someplace before), uncontrollable laughing, fear, visual hallucinations, and experiencing unusual unpleasant odors. These interesting symptoms are thought to be caused by abnormal discharges in the temporal lobe.
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 include:
- Tonic-clonic (grand mal): This subtype is what 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. Prior to this, patients may have an aura (an unusual feeling that often warns the patient that they are about to have a seizure). The person will abruptly fall and begin to have jerking movements of their body and head. Drooling, biting of the tongue, and incontinence of urine may occur. When the jerking movements stop, the patient may remain unconscious for a period of time. The seizure usually lasts 5 to 20 minutes. They often awaken confused and may sleep for a period of time. The patients may experience prolonged weakness after the event; this is termed Todds paralysis.
- Absence (petit mal): Loss of consciousness only occurs, without associated motor symptoms. Usually there is no aura, or warning. The loss of consciousness is brief; the patient may appear to be involved with the environment and briefly stop what they are doing, stare for 5 to 10 seconds, and then continue their activity. No memory of the event exits. 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 5 years of life.
West Syndrome
West syndrome involves a group of symptoms including infantile spasms, retardation of psychomotor development, and a particular abnormality on the electroencephalogram (EEG) known as hypsarrhythmia. 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 is characterized by the early onset of a common seizure type called minor motor seizures. These seizures include the aforementioned myoclonic seizures, atypical absence seizures, and atonic seizures. Atypical 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 to 30 minutes, during time which 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, drug overdose, and brain tumor.
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 normal nervous system when its metabolic balance is disturbed. The etiology (cause) of epilepsy may be idiopathic (not clearly known) or related to a particular disease state. About 35% of all cases of epilepsy have no clearly definable cause.
The following summarizes some of the more common factors leading to seizure activity.
Genetic factors: It is now accepted that some persons may have a genetic predisposition to the development of seizures. There is also an increased incidence of epilepsy in relatives of those with a seizure disorder.
Head injury: Seizures may develop at or around the time of injury or years after (usually not more than two years later). They may occur with either an "open" or "closed" head injury.
Stroke/cerebrovascular disorders: Seizures can occur at the time of a stroke or many years later. They may occur with strokes that result in lack of blood flow to the brain or with those that involve bleeding into or around the brain.
Metabolic disturbances: This group of disorders changes levels of various metabolic substances in the body. These disease states sometimes result in seizures.
- Electrolyte disturbances (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
- Hepatic failure (severe liver disease) and elevation of associated toxins
- Hypoxia (lowered oxygen delivery to the brain)
Toxic causes: The presence of certain drugs can cause seizure activity. In addition, abrupt withdrawal of some substances can lead to seizure activity. These substances that may induce seizures include the tricyclic antidepressants, lithium, antipsychotic medications, aminophylline, and high doses of penicillin.
Illicit drug use, particularly cocaine, heroine, amphetamines, and PCP, can cause seizures. Alcohol withdrawal can be associated with seizure activity. These seizures usually occur 12-24 hours after the last drink but can occur up until 48 hours or more after binge drinking.
Withdrawal from prescription drugs and agents such as barbiturates and narcotics can result in seizure activity.
Infections: Infections of the nervous system may result in a lowered seizure threshold. These may include meningitis (infections of the coverings of the brain and spinal fluid), encephalitis (infection of the brain itself), and HIV (human immunodeficiency virus), and related infections.
Tumors and space-occupying lesions: Brain tumors, both malignant (cancerous) and benign, may be associated with seizures. The anatomic location of the abnormality influences the likelihood of having seizures.
Degenerative disorders: There are many neurodegenerative disorders that are accompanied by seizures. These include tuberous sclerosis, neurofibromatosis, Tay-Sachs disease, phenylketonuria (PKU), and Sturge-Weber syndrome.
Brain damage in infancy: Cerebral palsy secondary to lack of oxygen, infection, or trauma is associated with epilepsy.
Febrile seizures: These are an age-associated form of epilepsy that may present as a single seizure or may be recurring. They are associated with a high fever in children 3 months to 4 years of age and occur in 3%-4% of children.
Disorders That Mimic Seizure Disorders
True 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, syncope (fainting), and anxiety and other psychiatric disorders.
Another type of spell well known to physicians is the so-called pseudoseizure, or more properly nonepileptogenic seizure. These spells are not triggered by nerve cell discharges that cause true epilepsy, although the patient may experience muscle twitching and even apparent loss of consciousness. These spells have a psychiatric component and often coexist in persons who have true epilepsy. EEG monitoring can help distinguish disorders that mimic epilepsy from true seizures.
Diagnosis
Patients should be evaluated thoroughly after an initial seizure. It is imperative that the clinician take a complete and detailed patient history, including details of birth, childhood, family history, and medication regimen; and a thorough medical history, including any illnesses of the nervous system. In some cases, other conditions (e.g., irregular heartbeat) must be ruled out. A thorough history of drug and alcohol use is equally important.
It also is helpful 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.
Thorough general physical and detailed neurological examinations also should be performed.
Diagnostic Testing
Laboratory data utilized in the diagnostic evaluation of patients with seizure disorders may include CAT scan imaging, magnetic resonance imaging (MRI), and electroencephalography (EEG). A complete blood laboratory panel, including drug-toxic screening, and urinalysis are usually performed.
CAT scan brain imaging is often the first radiological study obtained, especially in the emergency room setting. It can indicate pathology such as a brain tumor, stroke, brain hemorrhage, acute or remote trauma, and infection. Limitations include inability to evaluate certain structures in the brain in detail, particularly the temporal lobes of the brain, often the first sites of seizure activity.
MRI brain imaging is performed for many patients with seizure disorders. It has the ability to visualize in great detail much of our brain anatomy. Subtle asymmetries in relevant structures, as well as undetected mass lesions, small strokes, and evidence of trauma may be uncovered. The use of a contrast agent (injected into the vein) can enhance the ability to show underlying abnormalities.
EEG (also known as "brain wave") provides information about the electrical activity in the brain. Unlike CAT or MRI, it does not produce an image of the brain, but supplies information about the function or dysfunction of parts of the brain. Multiple small electrodes are placed at specific points on the scalp on both sides of the head to record activity generated mainly by the cerebral cortex. Brain wave activity is usually recorded for 30-45 minutes.
Many patients will also be tested while hyperventilating (breathing rapidly and deeply), when flashing lights are flashing, while sleeping, or when sleep deprived. The brain normally exhibits particular patterns on the EEG during wakefulness, drowsiness, and sleep. The duration and character of normal brain-wave activity can be used as a baseline for comparison with abnormal waves on an EEG.
Some of the findings on EEG are specific to particular disorders and subtypes of epilepsy. Activity during a seizure can be identified by a pattern on the graph indicating epilepsy called epileptiform. Correlating this type of data with clinical symptoms of seizures often helps make an accurate diagnosis. The EEG recording between seizures is often abnormal in patients with epilepsy, and so can be helpful in this setting. EEG can be combined with video monitoring to record activity both electrically and visually. EEG can also be performed in a long-term care setting with a portable ambulatory unit, to monitor patients for up to many days at a time.
Other uses of the EEG include evaluation of altered states of consciousness, brain damage, metabolic-toxic injury, and suspected brain death.
EEG can be combined with video monitoring to record activity both electrically and visually. EEG can also be performed in a long-term care setting with a portable ambulatory unit, to monitor patients for up to many days at a time.
Other uses of the EEG include evaluation of altered states of consciousness, brain damage, metabolic-toxic injury, and suspected brain death.
Treatment
The medications used to treat patients with epilepsy are called anticonvulsants. Many of these drugs are available and each has a different mechanism of action, but all serve to reduce the frequency of epileptic seizures. These medications can be given for long periods of time.
Treatment options are evaluated initially based on seizure subtype, as certain anticonvulsants may be indicated for treating some forms of epilepsy and contraindicated for others. When making decisions about treatment with a particular agent, the physician should always take into account the patient's entire medical and medication histories, age and gender, and side-effect profile. It is important to evaluate the risks and benefits of treatment for each individual. That said, some general principles apply to treatment.
Monotherapy, treatment with a single agent, is the goal. Seizures can be controlled with one agent in approximately 75% of patients. Management becomes complicated when patients are given medications in combinations. This also risks increasing the number and frequency of side effects, making it less likely that patients will take their medication appropriately.
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.
Divided doses may be preferable with some medications, ensuring a more constant level of medication in the bloodstream.
Appropriate dosing levels depend on many factors, including the patient's body weight, concomitant medications, and reaction to treatment.
Many neurologists believe brand-name medications are preferable to generic products. Generic medications may be produced by different companies without rigorous standards regarding adequate drug level at a particular dose. Patients who use these medications may therefore be exposed to fluctuating levels of medication. For some people with epilepsy, this can result in loss of seizure control. Brand-name anticonvulsants, meeting stringent standards, provide more confidence in the dose-blood level relationship.
Any medication can cause an allergic reaction. Dermatological problems, including rashes, are not uncommon. Life-threatening reactions, such as the Stevens-Johnson syndrome, can occur. It is essential that patients report any suspected reactions to their physician.
When medications are to be discontinued, it is almost always recommended that they be slowly tapered down in dosage strength because abrupt withdrawal can produce seizures.
Kidney and liver function testing should be performed to evaluate the ability of these organs to metabolize the medication; some drugs will require changing the dosage if function is impaired.
There is still some controversy over whether to treat a patient who has had only a single seizure. Approximately 75% of seizure sufferers have only one seizure and no reoccurrence. In making treatment decisions, it is helpful to look at risk factors that may predict a second seizure. These include lesions of the brain, an abnormal EEG, or a family history of seizure disorders.
Anticonvulsants can reduce the risk of further seizure activity. People who have had more than one seizure should probably be treated with anticonvulsants.
It is convenient to divide some of the existing medications into first-generation anticonvulsants-older medications-and second-generation-more recently developed-drugs. Pharmaceutical research of new drugs is ongoing, with exciting developments in progress. The following medications are commonly prescribed for epilepsy.
First-Generation Anticonvulsants
Phenytoin (Dilantin®) was first used in the late 1930s. It has become one of the more commonly used agents and often is considered the first-line drug to treat seizures. It is thought to work by suppressing electrical activity in brain nerve cells. It can be given orally or intravenously (IV), and a newer form of the drug, fosphenytoin (Cerebryx®) can be injected into muscle. The oral form has the benefit of once-a-day dosing.
Phenytoin is a first-line agent for treating partial and generalized tonic-clonic (grand mal) seizures. It is also one of the main agents used with patients who present with status epilepticus. Phenytoin drug levels need to be monitored with laboratory testing. The therapeutic concentration recommended is between 10-20mg/L. 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 its use include gingival hyperplasia (overgrowth of the gums), hirsuitism/hypertrichosis (excessive hair growth), imbalance, lethargy, anemia, and, in long-term use, peripheral neuropathy (weakness).
Carbamazepine (Tegretol®/Carbatrol®) has been in use for over 30 years. It is commonly prescribed for the treatment of partial and generalized tonic-clonic (grand mal) seizures. The mechanism by which it works is not well understood. In oral form, it can be taken 2 to 3 times a day; a recent development of the drug in sustained-release form allows for twice-a-day dosing.
Carbamazepine levels need to be followed with laboratory testing. The recommended therapeutic level is between 8-12mg/L. Liver function tests and CBC also need to be 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.
Recognized side effects include drowsiness, imbalance, nausea, anemia, and neutropenia (low, white blood cell count). Carbamazepine is also used to treat trigeminal neuralgia, or tic douloureux, a painful nerve disorder of the face, and other neuropathic pain syndromes.
Phenobarbital is the oldest of this group of anticonvulsants. It can be used to treat both partial and generalized seizures. It also is used as part of the protocol after phenytoin use in status epilepticus as well as in neonatal epilepsy. It is available in oral and intravenous forms.
Levels need to be monitored. The recommended therapeutic level is 15-40mg/L. A complete blood analysis also should be routinely conducted. 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.
Valproate (Depakote®) has been in use for more than 20 years. It can be prescribed for a broad spectrum of anticonvulsant needs, including partial seizures, generalized tonic-clonic (grand mal) seizures, absence (petit mal), and myoclonic epilepsy. Its mechanism of action is thought to be related to the effect of a brain substance known as GABA (gamma-aminobutyric acid). It is available in oral form and must be taken 2 to 3 times per day for adequate dosing.
Drug levels must be monitored, as well as liver function, and blood count. The drug's suggested therapeutic window is 50-100mg/L. Side effects include hepatotoxicity (liver damage), nausea, weight gain, allopecia (hair loss), and tremor.
Second-Generation Anticonvulsants
Topiramate (Topamax®) is used with other anticonvulsant drugs in the treatment of partial seizures and generalized tonic-clonic seizures in adults and children aged 2 to 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), a neurotransmitter that inhibits excitation of nerve cells in the brain. It is available in oral form, including sprinkles for children, and should be taken twice daily.
Major side effects include drowsiness, nausea, dizziness, and coordination problems. Children may have difficulty concentrating and may become agressive. Acute glaucoma and visual abnormality, a potentially very serious complication, has been reported in a small number of patients. If any abnormal visual symptoms occur, patients should notify their physician immediately. There are few drug interactions between Topamax® and other medications or other anticonvulsants.
Gabapentin (Neurontin®) is indicated for the adjunctive treatment of partial seizures, with or without secondary generalization. Although it is structurally related to the substance GABA (gamma-aminobutyric acid), it does not interact with GABA receptors in the brain, and its mechanism of action is unknown. It is available in oral form and should be taken three times daily.
No laboratory monitoring of liver, kidney, or hematologic (blood) function is necessary with Neurontin®. Its major side effects are fatigue, dizziness, and imbalance. Neurontin® also has been used successfully in patients with neuropathic pain syndromes.
Lamotrigine (Lamictal®) is used for the adjunctive treatment of partial seizures. Its precise mechanism of action is unknown. It is presently available in oral form. Lamictal® should be taken twice daily. No laboratory monitoring of Lamictal levels are necessary. Its major side effect is the appearance of a potentially life-threatening skin rash, particularly for patients who also are taking valproate (Depakote®). Any patient taking Lamictal who develops a rash should immediately report it to his or her physician. Other side effects include headache, nausea, and dizziness.
Tiagabine (Gabitril®) is indicated for adjunctive therapy in adults with partial seizures. Its mechanism of action may be related to its effect on the brain substance GABA (gamma-aminobutyric acid). It is available in oral form and should be given in divided doses two to four times daily. No laboratory monitoring of Gabitril levels are necessary. Some interaction likely exists when Gabitril is taken with other anticonvulsants, in that its metabolism may be altered. Side effects include dizziness and somnolence.
Keppra® (levetiracetam) Keppra is approved for use in adults as adjunctive therapy for the treatment of partial seizure disorders. The side effects can include fatigue, imbalance and behavioral changes, which often dissipate after the first month of treatment.
Trileptal® (oxcarbazepine) is indicated for monotherapy (used alone) in adults who have partial seizures and can be used in children as add-on therapy for partial seizures. The most common side effects include dizziness, sleepiness, nausea, and imbalance, but these do not warrant clinical observation.
Zonegram (Zonisamide) is approved for use in adults as adjunctive therapy for partial seizures. It has however, 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 drugs should not use Zonisamide since it is a derivative of this class of drug.
Surgery
Surgical resection of epileptogenic areas of the brain in patients with partial seizures sometimes is considered when seizure activity fails to respond to even the most aggressive medical management. Patients considered for these procedures are those with intractable seizures, even when given high levels of anticonvulsant drugs. Video-EEG monitoring on a long-term basis is used to determine where in the brain the seizures occur.
In some patients, placing electrodes beneath the scalp may help to define epileptogenic areas of the brain. Specialized centers throughout the country have multidisciplinary teams to aid in the evaluation of potential candidates for these procedures.
Precautions
The word epilepsy is used when more than one seizure has occurred, and, if someone has a single seizure, they usually are not said to have epilepsy. Unfortunately, epilepsy connotes something very negative to many people. The terms epilepsy and seizure disorders are often used interchangeably.
Psychosocial Aspects of Seizure Disorders
Seizure disorders can have a profound effect on many aspects of normal daily living. An individual's perception of his or her own health or illness may be dramatically changed when they have a seizure disorder. For some patients, epilepsy carries a stigma that may cause them to alter plans regarding their future educational, employment, or social opportunities. Awareness of these issues is key to developing a treatment and counseling plan for patients and their families. Important issues to address and include when educating patients about managing epilepsy are:
- what seizures are, and what symptoms may warn of their onset
- when to notify a physician about any change in symptoms
- details of medication dosing, side effects, and importance of medication compliance (taking medications exactly as they are directed and not missing doses)
- importance of laboratory monitoring tests with some drugs
- advice on living a healthy lifestyle and avoiding things that may trigger seizure activity (sleep deprivation, increased stress, alcohol and drug abuse)
- counseling women of childbearing age about epilepsy, medications, and pregnancy
Driving and Seizure Disorders
Although the laws vary somewhat from state to state, most states have rules regarding when seizure patients can legally resume driving. Typically, patients must have been seizure-free 6 months to a year. While physicians generally are not required to report patient seizures to their state motor vehicle departments, patients usually are expected to comply with the laws in their state.
Pregnancy
Approximately 1,000,000 women of childbearing age in the United States suffer from epilepsy. Complications arise during conception and pregnancy that involve the choice and use of medication, dosing schedules, and seizure management. These complications have social as well as medical ramifications for pregnant women and their families.
During pregnancy, factors such as antiepileptic drug (AED) treatment, hormonal changes, and vitamin deficiency can influence seizure patterns, even for women who have had excellent seizure control in the past.
These complications combined with genetic factors also lead to a greater risk for major and minor birth defects for babies born to epileptic mothers. Although this risk is not typically significant enough for neurologists and epileptologists (epilepsy specialists) to advise their patients against pregnancy, health care specialists advocate a conscientious and careful pregnancy for all prospective mothers who suffer, or have suffered, from epilepsy.
Incidence
For most epileptic women, seizure frequency remains unchanged during pregnancy. However, approximately 20% will experience an increase in seizure frequency during pregnancy. And some women experience seizures only during birth.
The physiological changes that may play a role in the increased incidence of seizures for some women include changes in hormone production, metabolism, stress, and alteration in sleeping patterns.
Hormones such as estrogen and progesterone increase naturally and steadily during normal pregnancy. Estrogen has been shown to be epileptogenic (increases seizure activity) for epileptics, while progesterone is thought to have an antiseizure effect. Fluctuations in the levels of these hormones can make it more difficult for epileptic mothers to predict and control their seizures.
Generally, sleep deprivation influences seizure frequency for those who suffer from epilepsy. A significant increase in seizure occurrence may result during pregnancy when sleep patterns change. Stress, and the associated changes in eating and sleeping habits, may also contribute to an increase in seizures in some cases.
AEDs like phenobarbital, valporate (Depakene®), and carbamazepine (Tegretol®) are used to treat epilepsy. In most cases, the level of AEDs in the blood decreases during pregnancy, despite adherence to the proper dosage. For many women, this does not translate into an increased seizure frequency. However, in most cases, where seizures are seen to increase, the levels of AED in the blood are found to be lower than the recommended therapeutic range. It is therefore very important to monitor levels closely during pregnancy and to adhere to a physician-prescribed treatment.
Should I Continue AED Medication While Pregnant?
Many women are concerned about the effects of AED therapy on the health of their developing fetus. Although many medications, including antiepileptic drugs, have teratogenetic potential (causing abnormal embryo development), most women continue to need treatment to prevent seizures during this period of time. In order to maintain optimum seizure control and minimize risk to the fetus, women should educate themselves about medication and pregnancy prior to conception.
It is necessary for women who are treated with AEDs to continue medication when they learn they are pregnant. A physician may decide to discontinue drug therapy if a patient has not experienced seizures for several months. But this decision should be made at the discretion of the physician only. Often, patients who are not having seizures wrongly decide on their own to minimize dosage or to discontinue taking their medication entirely. This is unsafe because seizures can adversely affect a developing baby by decreasing vital oxygen or blood supply to the womb. Changes in treatment can immediately alter the balance of medication in the body, which could lead to sudden changes in condition, especially when pregnancy is involved.
For example, a period known as status epilepticus may occur, during which a series of seizures can result in intermittent consciousness or an indefinite period of unconsciousness. Considering that epilepsy symptoms can include collapse during loss of consciousness, the risk to a mother and a developing baby is high. So negligent discontinuation of medication is perhaps less safe than continuing medication until counseling and re-evaluation can begin. The reality is that epileptic women find themselves in a double bind concerning pregnancy. On one hand, it is broadly known that taking various medications while pregnant poses certain risks to the fetus. However, for women with epilepsy, it is usually necessary to take this otherwise avoidable risk, because discontinuing medication might result in uncontrollable symptoms and permanent damage to both mother and child. In fact, while it is generally understood that medication is necessary for epileptics to function safely in life, complications that can affect fetal development deter many epileptic mothers from conceiving.
Risks for Mother and Child
It is generally thought that women with epilepsy have at least a 90% chance of having a normal, healthy baby. All women have roughly a 2% to 3% chance of giving birth to a baby with some type of malformation. Although the exact causes for an increased incidence of abnormality are not fully known, a number of factors are thought to increase congenital malformations in the children of women with epilepsy.
These factors include genetic predisposition, seizures that occur during pregnancy, and the effects of AEDs. It is estimated that mothers with epilepsy have approximately twice the risk of having a baby born with a malformation than women in the general population, an approximately 4% to 6% risk.
The most common malformations include neural tube defects such as spinal bifida (characterized by the protrusion of spinal cord membranes through abnormal gaps between vertebrae), cleft palate, cleft lip, and congenital defects that affect the heart.
Some minor abnormalities, including developmental delay, speech abnormalities, widened eye set, flattened nasal bridge, small fingernails, and other structural features have also been described in association with AED treatment. These minor abnormalities have no long-term medical ramifications. Also, fertility rates (giving birth to live offspring) are lower in persons with epilepsy. This may be related partially to hormonal changes and menstrual irregularities associated with the disease.
For many years, researchers of epilepsy have hypothesized that a main mechanism of abnormal fetal development is an AED-based folate disturbance. Folate (folic acid, a B vitamin) is an important component in many chemical reactions in the body. It is necessary in the transfer of carbon, which is used to make the amino acids that form proteins in the body. Many AEDs can decrease the level of folate in the blood, which might lead to metabolic dysfunction, abnormal fetal developmental, and malformations.
More Medications, More Risk Involved
Other evidence also suggests that the risk of giving birth to a child with major malformations increases with the number of medications used simultaneously to treat seizure disorders, including epilepsy. The extent to which AED combination influences such a risk is not specifically known at this time. Epilepsy patients, whether pregnant or not, are usually treated with as few medications as possible. Combinations of Tridione® and Paradione®, as well as those drugs mentioned above, are thought to cause more frequent and extensive congenital birth defects.
Some of these drugs are being prescribed less and less by physicians because of their association with such defects. Also, AED use is restricted for patients who have a family history of neural tube defects. Again, pregnant women should consult with their physician prior to adjusting dosage of any or all AEDs.
Management
In addition to the traditional means of promoting healthy pregnancy, such as proper nutrition, exercise, good sleep, and substance avoidance, there is a disease-specific regimen often prescribed to mothers afflicted with epilepsy.
Early planning, management, and education is especially essential for all women of childbearing age who suffer from epilepsy. It is best if prior to conception, when pregnancy is being planned, that a woman see her physician, and that a full evaluation is performed. A thorough neurological exam is necessary to teach women all the major issues of potential concern. Women might consider involving an epileptologist or a neurologist who has experience treating issues and complications surrounding pregnancy, as well as an obstetrician. Ultimately, an epileptic woman must have the right to make an educated decision regarding conception. Indeed, the risks often deter couples from having children. However, should an epileptic woman decide to conceive a child, she can utilize several management strategies to reduce the risk of abnormal pregnancy and birth.
For example, a major component to healthy pregnancy for sufferers of epilepsy is multivitamin therapy with folate (folic acid). Research has indicated that the use of folate can help minimize the risk of some of the major congenital malformations, specifically those involving the spinal cord.
Even women with a seizure disorder who are not using AEDs (which diminish folic acid levels) during pregnancy should take daily folate supplements. In fact, it is suggested that women should begin folic acid supplementation before conception. Specialists recommend that a minimal dose of 2 mg a day is sufficient to maintain proper folate balance before and during pregnancy.
Compliance with medication is essential. Many clinicians also believe that even before becoming pregnant, if at all possible, women should switch to monotherapy (treatment with just one AED). Doing so, and using the lowest possible dose, can help minimize risks. Again, seizures can potentially affect a developing baby by decreasing oxygen or blood supply to the womb. So the decision to reduce dosage should only be made at the discretion of a physician who understands the biological and physiological patterns of epilepsy.
Many clinicians suggest a thorough ultrasonography examination at 16-18 weeks of gestation. This exam, which produces internal sonographic photos of the fetus, can help rule out spina bifida, limb abnormalities, and heart abnormalities. Amniocentesis, with testing for alpha-fetoprotein (a protein that is elevated in spina bifida), is often suggested for epileptic mothers.
Furthermore, an increase in vaginal hemorrhaging, early labor, and eclampsia (toxemia of pregnancy with postpartum convulsions) has been reported in epilepsy-related pregnancies.
Postpartum Management, Effects, and Incidence
Treatment for epileptic mothers does not stop after birth. Careful monitoring of AED levels should be performed throughout pregnancy and after delivery postpartum. The risk of seizure while attending to a newborn is significant enough for most epileptic parents to create alternative ways of care. For example, parents are often advised to change and feed their babies while sitting in secure, protective areas. Continued medication after pregnancy is especially important, as the effects of proper care now influence a baby who requires it.
Also, there is a chance that a baby born to a woman who has been treated with AEDs will be affected by the medication. Sometimes, newborns experience sedation as well as withdrawal symptoms for the first few weeks of life. Although alarming, these symptoms are usually temporary. They pose no significant medical problem, unless they prohibit the baby from eating properly.
Does AED Treatment Affect Breastfeeding?
Antiepileptic drugs do show up in fairly low levels in breast milk, some higher than others, but pose no serious health threat to a nursing baby. However, physicians often advise caution for mothers who have been treated with certain AEDs that tend to remain at higher levels in breast milk. Generally, mothers with epilepsy can expect to breastfeed their babies without complication, though counseling with an obstetrician is advised.
What Are the Chances that My Baby Will Have Epilepsy?
Because the causes for most types of seizure disorder are varied, the occurrence of epilepsy in children born to epileptic parents varies. Children whose mothers have epilepsy have about a 3% chance of getting the disease. If just the father is affected by epilepsy, the risk is the same as it is for anyone in the general public. If both parents are epileptic, the risk rises to approximately 5%.
Often, those who suffer from epilepsy gain an advanced knowledge of their disease as a result of planning a pregnancy. Certainly, preconception planning is just as important as the 9 months that follow. With the assistance of a physician, women with epilepsy can experience a healthy pregnancy and childbirth.