Causes and Symptoms
Seizures can be divided into two fundamental groups—partial and generalized. In partial seizures, the abnormal discharge of neurons usually arises in a portion of one hemisphere and may spread to other parts of the brain during a seizure. Generalized seizures, however, have no evidence of localized onset; the clinical manifestations and abnormal electrical discharge give no indication of the locus of onset of the abnormality, if such a locus exists.
Partial seizures are divided into three groups: simple partial seizures, complex partial seizures, and partial seizures secondarily generalized. Simple partial seizures are associated with the preservation of consciousness and unilateral hemispheric involvement. The area of seizure may spread until the entire side is involved. This type of seizure, with motor, sensory, or autonomic signs, was originally called Jacksonian epilepsy. Complex partial seizures are associated with alteration or loss of consciousness and bilateral hemispheric involvement. A partial seizure secondarily generalized is a generalized tonic-clonic seizure that proceeds directly from either a simple partial seizure or a complex partial seizure. The distinction between simple partial seizures and complex partial seizures is clarified by the observation that neurologic problems that are confined to one hemisphere, such as a unilateral cerebral stroke, generally spare consciousness, whereas bilateral cerebral (or brain stem) involvement causes alteration of consciousness.
If there is no evidence of localized onset, then the attack is a generalized seizure. Generalized seizures are more heterogeneous than partial seizures. The generalized seizures include generalized tonic-clonic (grand mal), absence (petit mal), atonic, myoclonic, clonic, and tonic seizures.
Tonic-clonic seizure is a common seizure pattern with sudden loss of consciousness, tonic contraction of muscles, loss of postural control, and a cry caused by contraction of respiratory muscles forcing exhalation. This is followed by a generalized contraction of the muscles of the four extremities. After two to five minutes of unconsciousness and the cessation of clonic contractions, the individual gradually regains consciousness. Fecal and urinary incontinence, as well as biting of the tongue, may occur. The individual does not remember the event and may not be completely functional for several days.
The absence seizure usually begins in childhood or early adolescence, and in many cases individuals outgrow the condition. Although unresponsiveness is the rule, motionlessness occurs in less than 10 percent of absence attacks; in fact, phenomena such as mild clonic motion and increased or decreased postural tone may accompany such attacks. Absence seizures are generally brief, usually lasting less than ten seconds and very rarely longer than forty-five seconds. The attacks are not associated with auras, hallucinations, or other symptoms characteristic of partial seizures, generalized tonic-clonic seizures, or infantile spasms. Individuals exhibiting these seizures are normal except for the seizures, but the seizures may occur as frequently as one hundred times a day.
Atonic seizures are characterized by a sudden loss of muscle tone. Myoclonic seizures are sudden and brief contractions of a single group of muscles or of the entire body. The patients fall but do not lose consciousness. Clonic and tonic seizures are characterized by alternation of contraction and relaxation and by contraction, respectively.
Infantile spasms are generalized seizures occurring in the first year of life. These are synchronous contractions of the muscles of the neck, trunk, and arms. About 90 percent of infants experiencing these attacks are intellectually disabled.
Seizures may be further subdivided into epileptic (those involving recurrent seizures) and nonepileptic. The term “nonepileptic seizure,” however, is somewhat problematic. For example, a seizure caused by
hypoglycemia (low blood sugar) may not be considered an epileptic attack by some because it is a transient event easily corrected by metabolic manipulation. Of the organic nonepileptic seizures, the most common are of cardiovascular origin; others are caused by transient cerebral ischemia, movement disorders, toxic or metabolic problems, sleep disorders, and even headaches. Nonepileptic attacks may also be of nonorganic or psychiatric origin, such as with hysteria and schizophrenia, in which case they are called psychogenic seizures or pseudoseizures.
Attempts to find a cause for the sudden abnormal discharge of cerebral neurons has not been possible in all types of seizure activity. In some cases, a brain tumor, scar tissue remaining from trauma to the brain, or a progressive neurological disease may be responsible. In the great majority of cases, however, no pathologic basis for the seizures is evident, either during life or at autopsy. The latter type of seizure has been classified as “idiopathic.” In certain circumstances, for example, fever, infection, or hyperglycemia, the response may include seizure. In many instances, these events are isolated and do not recur, and for this reason they are not categorized as epilepsy.
The cause of a seizure is related to the age of onset of the first attack. When seizures begin in the neonatal and infant period, the most likely causes are perinatal
anoxia (a deficiency of oxygen), congenital brain defects, meningitis, birth injuries, or other metabolic problems, such as hypoglycemia or hypercalcemia (excessive calcium). Less common causes of seizures in young children include toxins such as
lead poisoning, as well as rare degenerative diseases. In older children or adults, although metabolic or degenerative processes must be considered, other causes become more probable.
Head trauma accounts for the origin of many partial epileptic seizures in young adults, whereas brain tumors and vascular diseases are the major cause of such seizures in later life. Brain tumor is not a common cause of epilepsy in children, since 60 to 70 percent of brain tumors in children are located in the posterior fossa. Arteriosclerotic cerebrovascular disease is the most common cause of seizures in patients over the age of fifty. In about 4 percent of patients with brain infarction and 10 percent of those with intracerebral hemorrhage, seizures accompany the stroke; an additional 3 percent of patients who experience a stroke have recurrent seizures in later life, presumably generated by the cerebral
scar.
Most idiopathic seizure activity appears to have its origin in an inherited propensity to cerebral dysrhythmia. Although there is a high incidence of electroencephalographic (EEG) abnormalities in close relatives of persons with recurrent seizures, not all family members have clinical seizures. In general, genetic factors are particularly important when recurrent seizures begin in childhood and decrease in importance with age.
In most studies of early seizures predicting future epilepsy, the conditions that are associated with high risk include a depressed skull fracture, an acute intracerebral hematoma, post-traumatic amnesia lasting more than twenty-four hours, and the presence of tears in the dura mater of the brain or focal neurologic signs.
Generalized tonic-clonic seizures sometimes develop during the course of chronic
intoxication with
alcohol or barbiturates, almost always in association with withdrawal or reduction of the drugs. How long a period of chronic drug intoxication or abuse must last to produce seizures upon withdrawal is uncertain, but such patients often give a history of many years (sometimes decades) of drug dependence. Usually, the patients experience one or more seizures or short bursts of two to six seizures over a period of hours. An episode of alcohol withdrawal rarely precipitates more than a single burst of convulsions, while convulsions may recur for several days after barbiturate withdrawal. Studies have shown that among those who have had withdrawal seizures without other evidence of neurological damage, seizures almost always occurred during the seven-hour to forty-eight-hour period following the cessation of drinking. With alcohol withdrawal seizures, tremor, anorexia, and insomnia follow the seizure in perhaps 20 to 30 percent of cases. Delirium tremens is a less frequent event.
Treatment and Therapy Prior to treatment, it is necessary for the physician to conduct a thorough investigation of the patient to identify any remediable cause of the seizures. This investigation would include metabolic diseases, endocrine system disturbances, cerebral tumors, abscess of the brain, or meningitis.
Persons who have recurrent convulsions controlled by medications can participate in sports and lead a relatively normal life; most countries will permit a person to drive an automobile if he or she has experienced no seizures for six months to one year. If seizures are uncontrolled, however, then automobile driving, swimming, the operation of unguarded machinery, and ladder climbing are not advised.
Drug therapy varies with the type of seizure presented. In the case of recurrent seizures, it generally consists of at least two to four years of daily medication. Careful neurologic examinations every four to six months, monitoring of seizure frequency correlated with drug blood level, and serial EEGs about once a year are also required. If there is a change in seizure frequency despite adequate drug blood levels, if there are focal neurologic signs or signs of increased intracranial pressure, or if evidence of focal changes on EEGs develop, further evaluation, including a computed tomography (CT) scan, is necessary. A small brain tumor may not be apparent even on a CT scan at the time of the initial evaluation, particularly in a patient with adult-onset epilepsy or in an older child or adolescent with partial seizures without a documented specific cause.
Absence seizures present less urgency. The patient rarely seeks medical advice until repeated episodes have occurred. Early treatment and prevention or reduction of repeated seizures can be beneficial. The drugs of choice for absence epilepsy are ethosuximide or valproate sodium. Medication is generally discontinued after two to four seizure-free years, depending on the presence or absence of generalized tonic-clonic seizures and the results of the EEGs. After the medication is discontinued, and after follow-up for fifteen to twenty-three years, there is about a 12 percent incidence of recurrence.
If the seizure process is strong enough to require more than one drug, multiple drug administration needs to be maintained. The aim of the treatment is to achieve the best possible seizure control with the least amount of side effects. This goal may necessitate a compromise in patients with resistant seizures; such patients may prefer having an occasional seizure to being continuously sedated or unsteady. This is particularly true with patients who experience partial seizures that are not excessively disruptive.
The side effects of drugs may cause impairment of liver function in susceptible individuals. Thus, periodic monitoring of the patient’s complete blood count and platelet count is necessary, as are liver function tests. This monitoring is done more frequently at the onset of therapy or after an upward adjustment of dosage.
The selection of specific drugs to be used for the prevention and control of seizures depends on the type of seizure. The most commonly used drugs include phenytoin, carbamazepine, phenobarbital, primidone, ethosuximide, methsuximide, clonazepam, valproate sodium, and trimethadione.
The pharmacokinetics and side effects of these drugs in infants and children differ somewhat from those observed in older children and adults. Absorption, plasma-protein binding, and metabolism are subject to age-specific variations. Younger children usually require a higher dose per kilogram to maintain a therapeutic blood level than do adults. Some of the classic signs of toxicity to the medications that are seen in adults may not be obvious in children.
If the seizures are related to a lesion in the brain, neurosurgical treatment is indicated. Surgery is the obvious form of treatment for demonstrable structural lesions such as cysts lying in accessible areas of the cerebral hemispheres. In a more restricted sense, surgical therapy is considered in patients without a mass lesion when the seizures are unresponsive to drug treatment and the patient has a consistent, electrophysiologically demonstrable focus emanating from, for example, a scar. Specific surgical treatments vary from case to case.
Up to 80 percent of properly selected patients have been found to benefit to some extent from surgical removal of the focal lesion. In some cases of intractable seizures associated with behavior disorders and hemiplegia of childhood, removal of a damaged cerebral hemisphere has been found to control the intractable seizures and to improve the behavior disorder without causing further neurological deficit.
Perspective and Prospects In the twentieth century, major developments were made in diagnosis and therapy. In 1929, Hans Berger recorded the first human electroencephalogram. Descriptions of EEG patterns and their correlation with clinical absences, partial seizures, and generalized tonic-clonic seizures led to important developments in classification and treatment. Special EEG recordings with activation techniques, depth recordings, and long-term recordings for patients with intractable seizures became available to aid in the diagnosis and medical management of patients and in the selection of candidates for possible neurosurgical treatment.
Prolonged EEG recording by telemetry (the transmission of data electronically to a distant location) and ambulatory monitoring became helpful in making a diagnosis in patients who have brief spells of uncertain type. Electrical activity at the time of the attack can be documented. Videotaping with split-screen EEG recording and patient observation allows excellent correlation between the clinical and EEG manifestations, which aids in the classification and determination of appropriate therapy in difficult clinical problems. In those patients with intractable epilepsy, prolonged recording can document the frequency of seizures and correlation with anticonvulsive drug blood levels.
Radiological advances and CT scans in the 1970s, and later positron emission tomography (PET) scans, improved diagnostic skill in delineating potentially remediable lesions in patients with seizures.
During the twentieth century, many other medications became available for patients with seizures. The use of the operating microscope and technical advances in microsurgical techniques refined surgical treatments and improved the outlook for patients with structural lesions such as brain tumors, vascular malformations, and scars.
Bibliography
Bloom, Floyd E., M. Flint Beal, and David J. Kupfer, eds. The Dana Guide to Brain Health. New York: Dana Press, 2006.
Carson-DeWitt, Rosalyn, and Rimas Lukas. "Seizure Disorder—Adult." Health Library, Sept. 30, 2012.
Delanty, Norman, ed. Seizures: Medical Causes and Management. Totowa, N.J.: Humana Press, 2002.
Freeman, John M., Eileen P. G. Vining, and Diana J. Pillas. Seizures and Epilepsy in Childhood: A Guide. 3d ed. Baltimore: Johns Hopkins University Press, 2002.
Kohnle, Diana, and Michael Woods. "Seizure—Child." Health Library, Sept. 12, 2012.
Kohnle, Diana, Rebecca J. Stahl, and Kari Kassir. "Seizure Disorder—Child." Health Library, June 6, 2012.
Levy, René H., et al., eds. Antiepileptic Drugs. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2002.
Rowan, A. James, and John R. Gates, eds. Non-epileptic Seizures. 2d ed. Boston: Butterworth-Heinemann, 2000.
"Seizures." Epilepsy Foundation, 2012.
"Seizures." MedlinePlus, May 20, 2013.
"Seizures and Epilepsy: Hope through Research." National Institute of Neurological Disorders and Stroke, Apr. 8, 2013.
Solomon, Gail, Henn Kutt, and Fred Plum. Clinical Management of Seizures. 2d ed. Philadelphia: W. B. Saunders, 1983.
Weaver, Donald F. Epilepsy and Seizures: Everything You Need to Know. Toronto, Ont.: Firefly Books, 2001.
