Seizures
There are two kinds of seizure disorders: an isolated, nonrecurrent attack, such as may occur
during a febrile illness or after head trauma, and epilepsy--a recurrent, paroxysmal disorder of
cerebral function characterized by sudden, brief attacks of altered consciousness, motor activity,
sensory phenomena, or inappropriate behavior caused by excessive discharge of cerebral
neurons.
If given a sufficient stimulus (eg, convulsant drugs, hypoxia, hypoglycemia), even the normal
brain can discharge excessively, producing a seizure. In epileptics, seizures are rarely
precipitated by exogenous factors, such as sound, light, and touch.
Etiology and Incidence
Seizures result from a focal or generalized disturbance of cortical function, which may be due to
various cerebral or systemic disorders (See Table 172-1). Seizures may also occur as a
withdrawal symptom after long-term use of alcohol, hypnotics, or tranquilizers. Hysterical patients
occasionally simulate seizures. In many disorders, single seizures occur. However, seizures may
recur at intervals for years or indefinitely, in which case epilepsy is diagnosed.
Epilepsy is classified etiologically as symptomatic or idiopathic. Symptomatic indicates that a
probable cause exists and a specific course of therapy to eliminate that cause may be tried.
Idiopathic indicates that no obvious cause can be found. Unexplained genetic factors probably
underlie most idiopathic cases.
The risk of developing epilepsy is 1% from birth to age 20 yr and 3% at age 75 yr. Most persons
have only one type of seizure; about 30% have two or more types. About 90% have generalized
tonic-clonic seizures (alone in 60%; with other seizures in 30%). Absence seizures occur in about
25% (alone in 4%; with others in 21%). Complex partial seizures occur in 18% (alone in 6%; with
others in 12%).
Idiopathic epilepsy generally begins between ages 2 and 14. Seizures before age 2 are usually
caused by developmental defects, birth injuries, or a metabolic disease. Those beginning after
age 25 may be secondary to cerebral trauma, tumors, or cerebrovascular disease, but 50% are of
unknown etiology.
Symptoms and Signs
Manifestations depend on the type of seizure, which may be classified as partial or generalized.
In partial seizures, the excess neuronal discharge is contained within one region of the cerebral
cortex. In generalized seizures, the discharge bilaterally and diffusely involves the entire cortex.
Sometimes a focal lesion of one part of a hemisphere activates the entire cerebrum bilaterally so
rapidly that it produces a generalized tonic-clonic seizure before a focal sign appears.
Auras are sensory or psychic manifestations that immediately precede complex partial or
generalized tonic-clonic seizures and represent seizure onset. A postictal state may follow a
seizure (most commonly a generalized seizure) and is characterized by deep sleep, headache,
confusion, and muscle soreness.
Simple partial seizures consist of motor, sensory, or psychomotor phenomena without loss of
consciousness. The specific phenomenon reflects the affected area of the brain (see Table 1722). In jacksonian seizures, focal motor symptoms begin in one hand and then "march" up the
extremity. Other focal attacks can first affect the face area, then spread down the body to involve
an arm and sometimes a leg. Some partial motor seizures begin with raising the arm and turning
the head toward the moving part. Some proceed to generalized convulsions.
In complex partial seizures, the patient loses contact with the surroundings for 1 to 2 min. At
first, the patient may stare, perform automatic purposeless movements, utter unintelligible sounds
without understanding what is said, and resist aid. Mental confusion continues another 1 or 2 min
after motor components of the attack subside. These seizures may develop at any age, and
structural pathology (eg, mesial temporal sclerosis, low-grade astrocytomas) should be ruled out.
Complex partial seizures most commonly originate in the temporal lobe but may originate in any
lobe of the brain.
Complex partial seizures are not characterized by unprovoked aggressive behavior. However, if
restrained during a complex partial seizure, a patient may lash out at the person restraining him,
as may a patient in a postictal confused state after a generalized seizure. Between seizures,
patients with temporal lobe epilepsy have a higher incidence of psychiatric disorders than does
the general population; 33% may have psychologic difficulties, and 10% may have symptoms of
schizophreniform or depressive psychoses.
Generalized seizures cause loss of consciousness and motor function from the onset. Such
attacks often have a genetic or metabolic cause. They may be primarily generalized (bilateral
cerebral cortical involvement at onset) or secondarily generalized (local cortical onset with
subsequent bilateral spread). Types of generalized seizures include infantile spasms and
absence, tonic-clonic, atonic, and myoclonic seizures.
Infantile spasms are primarily generalized seizures characterized by sudden flexion of the arms,
forward flexion of the trunk, and extension of the legs. Seizures last a few seconds and are
repeated many times a day. They occur only in the first 3 yr of life and then are replaced by other
types of seizures. Developmental abnormalities are usually apparent.
Absence seizures (formerly called petit mal) consist of brief, primarily generalized attacks
manifested by a 10- to 30-sec loss of consciousness and eyelid flutterings at a rate of 3/sec, with
or without loss of axial muscle tone. Affected patients do not fall or convulse; they abruptly stop
activity and resume it just as abruptly after the seizure, with no postictal symptoms or even
knowledge that an attack has occurred. Absence seizures are genetic and occur predominantly in
children. Without treatment, such seizures are likely to occur many times a day. Seizures often
occur when the patient is sitting quietly and can be precipitated by hyperventilation. They rarely
occur during exercise.
Generalized tonic-clonic seizures typically begin with an outcry; they continue with loss of
consciousness and falling, followed by tonic, then clonic contractions of the muscles of the
extremities, trunk, and head. Urinary and fecal incontinence may occur. Seizures usually last 1 to
2 min. Secondarily generalized tonic-clonic seizures begin with a simple partial or complex partial
seizure.
Atonic seizures are brief, primarily generalized seizures in children. They are characterized by
complete loss of muscle tone and consciousness. The child falls or pitches to the ground, so that
seizures pose the risk of serious trauma, particularly head injury.
Myoclonic seizures are brief, lightning-like jerks of a limb, several limbs, or the trunk. They may
be repetitive, leading to a tonic-clonic seizure. There is no loss of consciousness.
Febrile seizures are associated with fever without evidence of intracranial infection. They affect
about 4% of children between the ages of 3 mo and 5 yr. Benign febrile seizures are brief,
solitary, and generalized tonic-clonic in form; complicated febrile seizures are either focal, last >
15 min, or recur >= 2 times in < 24 h. Overall, the occurrence of febrile seizures is associated
with a 2% incidence of subsequent epilepsy; the incidence of epilepsy and the risk of recurrent
febrile seizures are much greater among children with complicated febrile seizures, preexisting
neurologic abnormalities, onset before age 1 yr, or a family history of epilepsy.
In status epilepticus, seizures follow one another with no intervening periods of normal
neurologic function. Generalized convulsive status epilepticus may be fatal. It may result from
too-rapid withdrawal of anticonvulsants. Confusion may be the only manifestation of complex
partial or absence status epilepticus, and an EEG may be needed to diagnose seizure activity.
Epilepsia partialis continua is a rare form of focal (usually hand or face) motor seizures that
recur at intervals of a few seconds or minutes for days to years at a time. In adults, it is usually
due to a structural lesion, such as a stroke. In children, it is usually due to a focal cerebral cortical
inflammatory process (Rasmussen's encephalitis), possibly caused by a chronic viral infection or
autoimmune processes.
Diagnosis
Idiopathic epilepsy must be distinguished from symptomatic epilepsy. Focal seizures or focal
postictal symptoms imply a focal structural lesion in the brain; generalized seizures are more
likely to have a metabolic cause. In newborns, the type of seizure does not help distinguish
between structural and metabolic causes.
An eyewitness account of a typical seizure, the frequency of seizures, and the longest and
shortest intervals between them should be recorded. A history of prior head trauma, infection, or
toxic episodes must be sought and evaluated. A family history of seizures or neurologic disorders
is significant.
Fever and stiff neck accompanying new-onset seizures suggest meningitis, subarachnoid
hemorrhage, or encephalitis. Lumbar puncture is indicated. Focal cerebral symptoms and signs
accompanying seizures suggest brain tumor, cerebrovascular disease, or residual traumatic
abnormalities. In an adult, even generalized seizures should stimulate a search for an
unsuspected focal lesion.
Appropriate studies include EEG and serum glucose, sodium, magnesium, and calcium. When
the EEG or serum is focally abnormal or when seizures begin in adulthood, MRI is indicated. A
lumbar puncture should be performed if infection is suspected.
The EEG between seizures (interictal) in primarily generalized tonic-clonic seizures is
characterized by symmetric bursts of sharp and slow, 4- to 7-Hz activity. Focal epileptiform
discharges occur in secondarily generalized seizures. In absence seizures, spikes and slow
waves appear at a rate of 3/sec. Interictal temporal lobe foci (spikes or slow waves) occur with
complex partial seizures of temporal lobe origin. Because an EEG taken during a seizure-free
interval is normal in 30% of patients, one normal EEG does not exclude epilepsy. A second EEG
performed during sleep in sleep-deprived patients shows epileptiform abnormalities in half of
patients whose first EEG was normal. Rarely, repeated EEGs are normal, and epilepsy may have
to be diagnosed on clinical grounds.
Prognosis
Drug therapy completely eliminates seizures in 1/3 of patients and greatly reduces the frequency
of seizures in another 1/3. About 2/3 of patients with well-controlled seizures can eventually
discontinue drugs without relapse.
Most patients with epilepsy become neurologically normal between seizures, although overuse of
anticonvulsants can dull alertness. Progressive mental deterioration is usually related to the
neurologic disease that caused the seizures. Left temporal lobe epilepsy is associated with verbal
memory abnormalities; right temporal lobe epilepsy sometimes causes visual spatial memory
abnormalities. The outlook is best when no brain lesion is demonstrable.
Treatment
General principles: Treatment aims primarily to control seizures. A causative disorder may need
to be treated as well.
A normal life should be encouraged. Exercise is recommended; even such sports as swimming
and horseback riding can be permitted with proper safeguards. Most state licensing agencies
permit automobile driving after seizures have stopped for 1 yr. Social activities should be
encouraged. Alcohol intake should be minimized. Cocaine and several other illicit drugs can
trigger seizures.
Family members must be taught a commonsense attitude toward the patient. Overprotection
should be replaced with sympathetic support that lessens feelings of inferiority and selfconsciousness and other emotional handicaps; prevention of invalidism should be emphasized.
Institutional care is rarely advisable and should be reserved for severely retarded patients and for
patients with seizures so frequent and violent despite drug therapy that they cannot be cared for
elsewhere.
During a seizure, injury should be prevented. Protecting the tongue should not be attempted
because teeth may be damaged. Inserting a finger to straighten the tongue is dangerous and
unnecessary. Clothing around the neck should be loosened, and a pillow placed under the head.
The patient should be rolled onto his side to prevent aspiration. A responsible fellow worker may
be trained to give emergency aid if the patient agrees.
Causative or precipitating factors should be eliminated. Progressive structural lesions of the brain
(eg, tumors, abscesses) should be sought and promptly treated. After definitive treatment of
structural lesions, continued medical treatment (eg, anticonvulsants) is usually necessary. Other
physical disorders (eg, systemic infections, endocrine abnormalities) should be corrected.
Head injuries with skull fractures, intracranial hemorrhages, focal neurologic deficits, or amnesia
cause posttraumatic epilepsy in 25 to 75% of cases. Prophylactic treatment with anticonvulsant
drugs after the head injury reduces the probability of early posttraumatic seizures during the first
few weeks after the injury but does not prevent the development of permanent posttraumatic
epilepsy months or years later.
Drug therapy: No single drug controls all types of seizures, and different drugs are required for
different patients. Patients rarely require several drugs. The drug of choice for the particular type
of epilepsy is started at relatively low dose and increased over about 1 wk to the standard
therapeutic dose. After about 1 wk at this dose, blood levels are measured to determine whether
the effective therapeutic level has been reached. If seizures continue, the daily dose is increased
by small increments. If toxic blood levels or toxic symptoms develop before seizures are
controlled, a second anticonvulsant is added, again guarding against toxicity. Interaction between
drugs can interfere with their rate of metabolic degradation. The initial, failed anticonvulsant is
then withdrawn gradually. Once seizures are controlled, the drug should be continued without
interruption until at least 1 yr is seizure-free. At that time, discontinuing the drug should be
considered, because about 2/3 of such patients remain seizure-free without drugs. Static
encephalopathy and structural brain lesions increase the risk of relapse off medication. Patients
whose attacks were initially difficult to control, those who failed a drug-free trial, and those with
important social reasons for avoiding seizures should be treated indefinitely.
The most effective anticonvulsants for long-term use and their doses for children and adults are
given in Table 172-3. Once the drug response is known, blood levels are less useful to follow
than the clinical course. Some patients have toxic symptoms at low levels; others tolerate high
levels without symptoms.
For generalized tonic-clonic seizures, phenytoin, carbamazepine, or valproate is the drug of
choice. For adults, phenytoin can be given in divided doses or at bedtime. If seizures continue,
the dose can be increased cautiously to 500 mg/day with blood level monitoring. At a higher
dose, dividing the daily dose may reduce toxic symptoms.
For partial seizures, treatment begins with carbamazepine, phenytoin, or valproate. If seizures
persist despite high doses of these drugs, gabapentin, lamotrigine, or topiramate may be added.
For absence seizures, ethosuximide orally is preferred. Valproate and clonazepam orally are
effective, but tolerance to clonazepam often develops. Acetazolamide is reserved for refractory
cases.
Atonic seizures, myoclonic seizures, and infantile spasms are difficult to treat. Valproate is
preferred, followed, if unsuccessful, by clonazepam. Ethosuximide is sometimes effective, as is
acetazolamide (in dosages as for absence seizures). Phenytoin has limited effectiveness. For
infantile spasms, corticosteroids for 8 to 10 wk are often effective. The optimal corticosteroid
regimen is controversial. ACTH 20 to 60 U/day IM may be used. A ketogenic diet may help but is
difficult to maintain. Carbamazepine may make patients with primary generalized epilepsy and
multiple seizure types worse.
Status epilepticus can be terminated by giving diazepam 10 to 20 mg (for adults) IV or up to 2
doses (if necessary) of lorazepam 4 mg IV. For children, IV diazepam up to 0.3 mg/kg or
lorazepam up to 0.1 mg/kg is given. For adults, phenytoin 1.5 g IV may be given to prevent
recurrence. Fosphenytoin, a water-soluble product, is an alternative that in equivalent doses
reduces the incidence of hypotension and phlebitis. Anesthetic IV doses of phenobarbital,
lorazepam, or pentobarbital may be necessary in refractory cases; in such instances, intubation
and O2 therapy are required to prevent hypoxemia.
In acute generalized tonic-clonic seizures due to febrile illnesses, ingestion of alcohol or other
toxins, or acute metabolic disturbance, the causative condition must be treated as well as the
seizures. Status epilepticus should be treated at once. If only one seizure has occurred,
phenytoin should be given in full dosage (see Table 172-3) for 7 to 10 days; afterward, a decision
concerning long-term therapy must be made. After a first seizure, 1/3 of patients have recurrent
attacks, followed by chronic epilepsy. Anticonvulsants are of little value in preventing alcohol
withdrawal seizures.
Benign febrile convulsions do not require treatment because of the favorable prognosis
compared with the potential toxic effects of anticonvulsants in a young child. For patients with
complicated febrile seizures or other risk factors for recurrence (listed above), recurrence rates
for febrile seizures can be reduced by continuous prophylactic treatment with phenobarbital 5 to
10 mg/kg/day. However, no evidence suggests that such treatment of complicated febrile
seizures prevents the development of recurrent nonfebrile seizures (epilepsy). Furthermore,
phenobarbital given chronically to children measurably reduces their learning capacity.
Adverse effects: Possible toxic effects of anticonvulsants are listed in Table 172-3. All
anticonvulsants may cause an allergic scarlatiniform or morbilliform rash.
Patients receiving carbamazepine should have a CBC once a month for the first year of therapy.
If the WBC or RBC count decreases significantly, the drug should be discontinued immediately.
Patients receiving valproate should have liver function tests every 3 mo for 1 yr; if serum
transaminases or ammonia levels increase significantly (to > 2 times the upper limit of normal),
the drug should be discontinued. An increase in ammonia up to 1.5 times the upper limit of
normal can be tolerated safely.
When an overdose reaction occurs, the amount of drug is reduced until the reaction subsides.
When more serious acute poisoning occurs, the patient is given ipecac syrup or, if obtunded, is
lavaged. After emesis or lavage, activated charcoal is administered, followed by a saline cathartic
(eg, magnesium citrate). The suspect drug should be discontinued, and a new anticonvulsant
started simultaneously.
Fetal antiepileptic drug syndrome (cleft lip, cleft palate, cardiac defects, microcephaly, growth
retardation, developmental delay, abnormal facies, digital hypoplasia) occurs in 4% of the
children of epileptic women who take anticonvulsants during pregnancy. Among commonly used
drugs, carbamazepine appears to be the least teratogenic, but only slightly so; valproate may be
the most teratogenic. Yet, because uncontrolled generalized seizures during pregnancy lead to
fetal injury and death, continued treatment with anticonvulsants is generally advisable (see Ch.
249).
Surgical therapy: About 10 to 20% of patients have seizures that are refractory to medical
treatment. Most patients whose seizures originate from a local area of abnormal brain function
improve markedly when the epileptic focus is resected. Some are completely cured. Because
extensive monitoring and skilled medical-surgical teamwork are required, these patients are best
managed in specialized centers.
Vagus nerve stimulation: Intermittent electrical stimulation of the left vagus nerve with an
implanted pacemaker-like device reduces the number of partial seizures by one third. After the
device is programmed, patients can activate it with a magnet when they sense a seizure is
imminent. Vagus nerve stimulation is used as an adjunct to an anticonvulsant. Adverse effects
include a deepening of the voice during stimulation, cough, and hoarseness. Complications are
minimal. Duration of effectiveness is not well established.
Table 172-1 causes of seizures
Table 172-2 partial seizures
Table 172-3 drugs used in epilepsy