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Zarontin

Ethosuximide is a succinimide anticonvulsant, used mainly in absence seizures. It is sold by Pfizer under the name Zarontin®. more...

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Adverse Effects

Central Nervous System

Common

  • drowsiness
  • mental confusion
  • insomnia
  • nervousness
  • headache
  • euphoria
  • ataxia
  • hiccups
  • impaired concentration
  • irritability
  • hyperactivity
  • loss of taste
  • night terrors

Rare

  • paranoid psychosis
  • increased libido
  • exacerbation of depression

Gastrointestinal

  • dyspepsia
  • vomiting
  • nausea
  • cramps
  • constipation
  • diarrhea
  • stomach pain
  • loss of appetite
  • weight loss
  • gingival hyperplasia
  • swelling of tongue

Genitourinary

  • microscopic hematuria
  • vaginal bleeding

Hematopoietic

The following can occur with or without bone marrow loss:

  • pancytopenia
  • agranulocytosis
  • leukopenia
  • eosinophilia

Integumentary

  • urticaria
  • systemic lupus erythematosus
  • Stevens-Johnson syndrome
  • hirsutism
  • pruritic erythematous rashes

Ocular

  • myopia

Complications

  • abnormal liver function

Drug Interactions

Valproates can either decrease or increase the levels of ethosuximide; However, combinations of valproates and ethosuximide had a greater Protective Index than either drug alone.

It may elevate serum phenytoin levels.

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Seizure disorder
From Gale Encyclopedia of Medicine, 4/6/01 by Maureen Haggerty

Definition

A seizure is a sudden disruption of the brain's normal electrical activity accompanied by altered consciousness and/or other neurological and behavioral manifestations. Epilepsy is a condition characterized by recurrent seizures that may include repetitive muscle jerking called convulsions.

Description

There are more than 20 different seizure disorders. One in ten Americans will have a seizure at some time, and at least 200,000 have at least one seizure a month.

Epilepsy affects 1-2% of the population of the United States. Although epilepsy is as common in adults over 60 as in children under 10, 25% of all cases develop before the age of five. One in every two cases develops before the age of 25. About 125,000 new cases of epilepsy are diagnosed each year, and a significant number of children and adults that have not been diagnosed or treated have epilepsy.

Most seizures are benign, but a seizure that lasts a long time can lead to status epilepticus, a life-threatening condition characterized by continuous seizures, sustained loss of consciousness, and respiratory distress. Non-convulsive epilepsy can impair physical coordination, vision, and other senses. Undiagnosed seizures can lead to conditions that are more serious and more difficult to manage.

Types of seizures

Generalized epileptic seizures occur when electrical abnormalities exist throughout the brain. A partial seizure does not involve the entire brain. A partial seizure begins in an area called an epileptic focus, but may spread to other parts of the brain and cause a generalized seizure. Some people who have epilepsy have more than one type of seizure.

Motor attacks cause parts of the body to jerk repeatedly. A motor attack usually lasts less than an hour and may last only a few minutes. Sensory seizures begin with numbness or tingling in one area. The sensation may move along one side of the body or the back before subsiding.

Visual seizures, which affect the area of the brain that controls sight, cause people to see things that are not there. Auditory seizures affect the part of the brain that controls hearing and cause the patient to imagine voices, music, and other sounds. Other types of seizures can cause confusion, upset stomach, or emotional distress.

Generalized seizures

A generalized tonic-clonic (grand-mal) seizure begins with a loud cry before the person having the seizure loses consciousness and falls to the ground. The muscles become rigid for about 30 seconds during the tonic phase of the seizure and alternately contract and relax during the clonic phase, which lasts 30-60 seconds. The skin sometimes acquires a bluish tint and the person may bite his tongue, lose bowel or bladder control, or have trouble breathing.

A grand mal seizure lasts between two and five minutes, and the person may be confused or have trouble talking when he regains consciousness (post-ictal state). He may complain of head or muscle aches, or weakness in his arms or legs before falling into a deep sleep.

Primary generalized seizures

A primary generalized seizure occurs when electrical discharges begin in both halves (hemispheres) of the brain at the same time. Primary generalized seizures are more likely to be major motor attacks than to be absence seizures.

Absence seizures

Absence (petit mal) seizures generally begin at about the age of four and stop by the time the child becomes an adolescent.

Absence seizures usually begin with a brief loss of consciousness and last between one and 10 seconds. A person having a petit mal seizure becomes very quiet and may blink, stare blankly, roll his eyes, or move his lips. A petit mal seizure lasts 15-20 seconds. When it ends, the person who had the seizure resumes whatever he was doing before the seizure began. He will not remember the seizure and may not realize that anything unusual has happened. Untreated, petit mal seizures can recur as many as 100 times a day and may progress to grand mal seizures.

Myoclonic seizures

Myoclonic seizures are characterized by brief, involuntary spasms of the tongue or muscles of the face, arms, or legs. Myoclonic seizures are most apt to occur when waking after a night's sleep.

A jacksonian seizure is a partial seizure characterized by tingling, stiffening, or jerking of an arm or leg. Loss of consciousness is rare. The seizure may progress in characteristic fashion along the limb.

Limp posture and a brief period of unconsciousness are features of akinetic seizures, which occur in young children. Akinetic seizures, which cause the child to fall, are also called drop attacks.

Partial seizures

Simple partial seizures do not spread from the focal area where they arise. Symptoms are determined by what part of the brain is affected. The patient usually remains conscious during the seizure and can later describe it in detail.

Complex partial seizures

A distinctive smell, taste, or other unusual sensation (aura) may signal the start of a complex partial seizure.

Complex partial seizures start as simple partial seizures, but move beyond the focal area and cause loss of consciousness. Complex partial seizures can become major motor seizures. Although a person having a complex partial seizure may not seem to be unconscious, he does not know what is happening and may behave inappropriately. He will not remember the seizure, but may seem confused or intoxicated for a few minutes after it ends.

Causes & symptoms

The origin of 50-70% of all cases of epilepsy is unknown. Epilepsy is sometimes the result of trauma at the time of birth. Such causes include insufficient oxygen to the brain; head injury; heavy bleeding or incompatibility between a woman's blood and the blood of her newborn baby; and infection immediately before, after, or at the time of birth.

Other causes of epilepsy include:

  • Head trauma resulting from a car accident, gunshot wound, or other injury.
  • Alcoholism.
  • Brain abscess or inflammation of membranes covering the brain or spinal cord.
  • Phenylketonuria (PKU, a disease that is present at birth, is often characterized by seizures, and can result in mental retardation) and other inherited disorders.
  • Infectious diseases like measles, mumps, and diphtheria.
  • Degenerative disease.
  • Lead poisoning, mercury poisoning, carbon monoxide poisoning, or ingestion of some other poisonous substance.
  • Genetic factors.

Status epilepticus, a condition in which a person suffers from continuous seizures and may have trouble breathing, can be caused by:

  • Suddenly discontinuing anti-seizure medication.
  • Hypoxic or metabolic encephalopathy (brain disease resulting from lack of oxygen or malfunctioning of other physical or chemical processes).
  • Acute head injury.
  • Blood infection caused by inflammation of the brain or the membranes that cover it.

Diagnosis

Personal and family medical history, description of seizure activity, and physical and neurological examinations help primary care physicians, neurologists, and epileptologists diagnose this disorder. Doctors rule out conditions that cause symptoms that resemble epilepsy, including small strokes (transient ischemic attacks, or TIAs), fainting (syncope), pseudoseizures, and sleep attacks (narcolepsy).

Neuropsychological testing uncovers learning or memory problems. Neuro-imaging provides views of brain areas involved in seizure activity.

The electroencephalogram (EEG) is the main test used to diagnose epilepsy. EEGs use electrodes placed on or within the skull to record the brain's electrical activity and pinpoint the exact location of abnormal discharges.

The patient may be asked to remain motionless during a short-term EEG or to go about his normal activities during extended monitoring. Some patients are deprived of sleep or exposed to seizure triggers, such as rapid, deep breathing (hyperventilation) or flashing lights (photic stimulation). In some cases, people may be hospitalized for EEG monitorings that can last as long as two weeks. Video EEGs also document what the patient was doing when the seizure occurred and how the seizure changed his behavior.

Other techniques used to diagnose epilepsy include:

  • Magnetic resonance imaging (MRI), which provides clear, detailed images of the brain. Functional MRI (fMRI), performed while the patient does various tasks, can measure shifts in electrical intensity and blood flow and indicate which brain region each activity affects.
  • Positron emission tomography (PET) and single photon emission tomography (SPECT) monitor blood flow and chemical activity in the brain area being tested. PET and SPECT are very effective in locating the brain region where metabolic changes take place between seizures.

Treatment

The goal of epilepsy treatment is to eliminate seizures or make the symptoms less frequent and less severe. Long-term anticonvulsant drug therapy is the most common form of epilepsy treatment.

Medication

A combination of drugs may be needed to control some symptoms, but most patients who have epilepsy take one of the following medications:

  • Dilantin (phenytoin)
  • Tegretol (carbamazepine)
  • Barbita (phenobarbital)
  • Mysoline (primidone)
  • Depakene (valproic acid, sodium valproate)
  • Klonopin (clonazepam)
  • Zarontin (ethosuximide).

Dilantin, Tegretol, Barbita, and Mysoline are used to manage or control generalized tonic-clonic and complex partial seizures. Depakene, Klonopin, and Zarontin are prescribed for patients who have absence seizures.

Neurontonin (gabapentin) and Lamictal (lamotrigine) are medications recently approved in the United States to treat adults who have partial seizures or partial and grand mal seizures.

Even a patient whose seizures are well controlled should have regular blood tests to measure levels of anti-seizure medication in his system and to check to see if the medication is causing any changes in his blood or liver. A doctor should be notified if any signs of drug toxicity appear, including uncontrolled eye movements; sluggishness, dizziness, or hyperactivity; inability to see clearly or speak distinctly; nausea or vomiting; or sleep problems.

Status epilepticus requires emergency treatment, usually with Valium (Ativan), Dilantin, or Barbita. An intravenous dextrose (sugar) solution is given to patients whose condition is due to low blood sugar, and a vitamin B1 preparation is administered intravenously when status epilepticus results from chronic alcohol withdrawal. Because dextrose and thiamine are essentially harmless and because delay in treatment can be disastrous, these medications are given routinely, as it is usually difficult to obtain an adequate history from a patient suffering from status epilepticus.

Intractable seizures are seizures that cannot be controlled with medication or without sedation or other unacceptable side effects. Surgery may be used to eliminate or control intractable seizures.

Surgery

Surgery can be used to treat patients whose intractable seizures stem from small focal lesions that can be removed without endangering the patient, changing the patient's personality, dulling the patient's senses, or reducing the patient's ability to function.

Each year, as many as 5,000 new patients may become suitable candidates for surgery, which is most often performed at a comprehensive epilepsy center. Potential surgical candidates include patients with:

  • Partial seizures and secondarily generalized seizures (attacks that begin in one area and spread to both sides of the brain).
  • Seizures and childhood paralysis on one side of the body (hemiplegia).
  • Complex partial seizures originating in the temporal lobe (the part of the brain associated with speech, hearing, and smell) or other focal seizures. However, the risk of surgery involving the speech centers is that the patient will lose speech function.
  • Generalized myoclonic seizures or generalized seizures featuring temporary paralysis (akinetic) or loss of muscle tone (atonal).

A physical examination is conducted to verify that a patient's seizures are caused by epilepsy, and surgery is not used to treat patients with severe psychiatric disturbances or medical problems that raise risk factors to unacceptable levels.

Surgery is never indicated unless:

  • The best available anti-seizure medications have failed to control the patient's symptoms satisfactorily.
  • The origin of the patient's seizures has been precisely located.
  • There is good reason to believe that surgery will significantly improve the patient's health and quality of life.

Every patient considering epilepsy surgery is carefully evaluated by one or more neurologists, neurosurgeons, neuropsychologists, and/or social workers. A psychiatrist, chaplain, or other spiritual advisor may help the patient and his family cope with the stresses that occur during and after the selection process.

Types of surgery

Surgical techniques used to treat intractable epilepsy include:

  • Lesionectomy. Removing the lesion (diseased brain tissue) and some surrounding brain tissue is very effective in controlling seizures. Lesionectomy is generally more successful than surgery performed on patients whose seizures are not caused by clearly defined lesions, but removing only part of the lesion lessens the effectiveness of the procedure.
  • Temporal resections. Removing part of the temporal lobe and the part of the brain associated with feelings, memory, and emotions (the hippocampus) provides good or excellent seizure control in 75-80% of properly selected patients with appropriate types of temporal lobe epilepsy. Some patients experience post-operative speech and memory problems.
  • Extra-temporal resection. This procedure involves removing some or all of the frontal lobe, the part of the brain directly behind the forehead. The frontal lobe helps regulate movement, planning, judgment, and personality, and special care must be taken to prevent post-operative problems with movement and speech. Extra-temporal resection is most successful in patients whose seizures are not widespread.
  • Hemispherectomy. This method of removing brain tissue is restricted to patients with severe epilepsy and abnormal discharges that often extend from one side of the brain to the other. Hemispherectomies are most often performed on infants or young children who have had an extensive brain disease or disorder since birth or from a very young age.
  • Corpus callosotomy. This procedure, an alternative to hemispherectomy in patients with congenital hemiplegia, removes some or all of the white matter that separates the two halves of the brain. Corpus callosotomy is performed almost exclusively on children who are frequently injured during falls caused by seizures. If removing two-thirds of the corpus callosum doesn't produce lasting improvement in the patient's condition, the remaining one-third will be removed during another operation.
  • Multiple subpial transection. This procedure is used to control the spread of seizures that originate in or affect the "eloquent" cortex, the area of the brain responsible for complex thought and reasoning.

Other forms of treatment

Ketogenic diet

A special high-fat, low-protein, low-carbohydrate diet is sometimes used to treat patients whose severe seizures have not responded to other treatment. Calculated according to age, height, and weight, the ketogenic diet induces mild starvation and dehydration. This forces the body to create an excessive supply of ketones, natural chemicals with seizure-suppressing properties.

The goal of this controversial approach is to maintain or improve seizure control while reducing medication. The ketogenic diet works best with children between the ages of one and 10. It is introduced over a period of several days, and most children are hospitalized during the early stages of treatment.

If a child following this diet remains seizure-free for at least six months, increased amounts of carbohydrates and protein are gradually added. If the child shows no improvement after three months, the diet is gradually discontinued.

Introduced in the 1920s, the ketogenic diet has had limited, short-term success in controlling seizure activity. Its use exposes patients to such potentially harmful side effects as:

  • Staphylococcal infections
  • Stunted or delayed growth
  • Low blood sugar (hypoglycemia)
  • Excess fat in the blood (hyperlipidemia)
  • Disease resulting from calcium deposits in the urinary tract (urolithiasis)
  • Disease of the optic nerve (optic neuropathy).
Vagus nerve stimulation

The United States Food and Drug Administration (FDA) has approved the use of vagus nerve stimulation (VNS) in patients over the age of 16 who have intractable partial seizures. This non-surgical procedure uses a pacemaker-like device implanted under the skin in the upper left chest, to provide intermittent stimulation to the vagus nerve. Stretching from the side of the neck into the brain, the vagus nerve affects swallowing, speech, breathing, and many other functions, and VNS may prevent or shorten some seizures.

First aid for seizures

A person having a seizure should not be restrained, but sharp or dangerous objects should be moved out of reach. Anyone having a complex partial seizure can be warned away from danger by someone calling his/her name in a clear, calm voice.

A person having a grand mal seizure should be helped to lie down. Tight clothing should be loosened. A soft, flat object like a towel or the palm of a hand should be placed under the person's head. Forcing a hard object into the mouth of someone having a grand mal seizure could cause injuries or breathing problems. If the person's mouth is open, placing a folded cloth or other soft object between his teeth will protect his tongue. Turning his head to the side will help him breathe. After a grand mal seizure has ended, the person who had the seizure should be told what has happened and reminded of where he is.

Alternative treatment

Stress increases seizure activity in 30% of people who have epilepsy. Relaxation techniques can provide some sense of control over the disorder, but they should never be used instead of anti-seizure medication or used without the approval of the patient's doctor. Yoga, meditation, and favorite pastimes help some people relax and manage stress more successfully. Biofeedback can teach adults and older adolescents how to recognize an aura and what to do to stop its spread. Children under 14 are not usually able to understand and apply principles of biofeedback. Acupuncture treatments (acupuncture needles inserted for a few minutes or left in place for as long as half an hour) make some people feel pleasantly relaxed. Acupressure can have the same effect on children or on adults who dislike needles.

Aromatherapy involves mixing aromatic plant oils into water or other oils and massaging them into the skin or using a special burner to waft their fragrance throughout the room. Aromatherapy oils affect the body and the brain, and undiluted oils should never be applied directly to the skin. Ylang ylang, chamomile, or lavender can create a soothing mood. People who have epilepsy should not use rosemary, hyssop, sage or sweet fennel, which seem to make the brain more alert.

Dietary changes that emphasize whole foods and eliminate processed foods may be helpful. Homeopathic therapy also can work for people with seizures, especially constitutional homeopathic treatment that acts at the deepest levels to address the needs of the individual person.

Prognosis

People who have epilepsy have a higher-than-average rate of suicide; sudden, unexplained death; and drowning and other accidental fatalities.

Benign focal epilepsy of childhood and some absence seizures may disappear in time, but remission is unlikely if seizures occur several times a day, several times in a 48-hour period, or more frequently than in the past.

Seizures that occur repeatedly over time and always involve the same symptoms are called stereotypic seizures. The probability that stereotypic seizures will abate is poor.

About 85% of all seizure disorders can be partially or completely controlled if the patient takes anti-seizure medication according to directions; avoids seizure-inducing sights, sounds, and other triggers; gets enough sleep; and eats regular, balanced meals.

Anyone who has epilepsy should wear a bracelet or necklace identifying his seizure disorder and listing the medication he takes.

Prevention

Eating properly, getting enough sleep, and controlling stress and fevers can help prevent seizures. A person who has epilepsy should be careful not to hyperventilate. A person who experiences an aura should find a safe place to lie down and stay there until the seizure passes. Anticonvulsant medications should not be stopped suddenly and, if other medications are prescribed or discontinued, the doctor treating the seizures should be notified. In some conditions, such as severe head injury, brain surgery, or subarachnoid hemorrhage, anticonvulsant medications may be given to the patient to prevent seizures.

Key Terms

Acupressure
Needleless acupuncture.
Acupuncture
An ancient Chinese method of relieving pain or treating illness by piercing specific areas of the body with fine needles.
Biofeedback
A learning technique that helps individuals influence automatic body functions.
Epileptologist
A physician who specializes in the treatment of epilepsy.

Further Reading

For Your Information

    Books

  • Shaw, Michael, ed. Everything You Need to Know about Diseases. Springhouse, PA: Springhouse Corporation, 1996.

    Periodicals

  • Batchelor, Lori, et al. "An Interdisciplinary Approach to Implementing the Ketogenic Diet for the Treatment of Seizures." Pediatric Nursing (September-October 1997): 465-471.
  • Dichter, M.A., and M.J. Brodie. "Drug Therapy: New Antiepileptic Drugs." The New England Journal of Medicine (15 June 1996): 1583-1588.
  • Lannox, Susan L. "Epilepsy Surgery for Partial Seizures." Pediatric Nursing (September-October 1997): 453-458.
  • McDonald, Melori E. "Use of the Ketogenic Diet in Treating Children with Seizures." Pediatric Nursing (September-October 1997): 461-463.

    Organizations

  • American Epilepsy Society. 638 Prospect Avenue, Hartford, CT 06105-4298. (205) 232-4825.
  • Epilepsy Concern International Service Group. 1282 Wynnewood Drive, West Palm Beach, FL 33417. (407) 683-0044.
  • Epilepsy Foundation of America. 4251 Garden City Drive, Landover, MD 20875-2267. (800) 532-1000.
  • Epilepsy Information Service. (800) 642-0500.

    Other

  • Bourgeois, Blaise F.D. Epilepsy Surgery in Children. http://www.neuro.wustl.edu/epilepsy/21children.html (3 March 1998).
  • Cosgrove, G. Rees, and Andrew J. Cole. Surgical Treatment of Epilepsy. http://neurosurgery.mgh.harvard.edu/ep-sxtre.htm (3 March 1998).
  • Epilepsy. http://www.ninds.nih.gov/healinfo/disorder/epilepsy/epilepfs.htm (28 February 1998).
  • Epilepsy and Dental Health. http://www.epinet.org.au/efvdent.html (3 March 1998).
  • Epilepsy Facts and Figures. http://www.efa.org/what/education/FACTS.html (28 February 1998).
  • Frequently Asked Questions (FAQs) About the Ketogenic Diet. http://www-leland.Stanford.edu/group/ketodiet/FAQ.html (28 February 1998).
  • Surgery for Epilepsy: NIH Consensus Statement Online. http://neurosurgery.mgh.harvard.edu/epil-nih.htm (3 March 1998).
  • The USC Vagus Nerve Stimulator Program. http://www.usc.edu/hsc/medicine/neurology/VNS.html (3 March 1998).

Gale Encyclopedia of Medicine. Gale Research, 1999.

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