Seizure Disorders
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(See also Neurologic Disorders in Children: Febrile Seizures and see also Neurologic Disorders in Children: Neonatal Seizure Disorders.)

A seizure is an abnormal, unregulated electrical discharge that occurs within the brain’s cortical gray matter and transiently interrupts normal brain function. A seizure typically causes altered awareness, abnormal sensations, focal involuntary movements, or convulsions (widespread violent involuntary contraction of voluntary muscles).

About 2% of adults have a seizure at some time during their life. Two thirds of these people never have another one.

Definitions: Terminology can be confusing.

Epilepsy (also called epileptic seizure disorder) is a chronic brain disorder characterized by recurrent (≥ 2), unprovoked seizures (ie, not related to reversible stressors). Epilepsy is often idiopathic, but various brain disorders, such as malformations, strokes, and tumors, can cause symptomatic epilepsy.

Nonepileptic seizures are provoked by a temporary disorder or stressor (eg, metabolic disorders, CNS infections, cardiovascular disorders, drug toxicity or withdrawal). In children, fever can provoke a seizure (see Neurologic Disorders in Children: Febrile Seizures).

Symptomatic seizures are due to a known cause (eg, brain tumor, stroke). Symptomatic seizures are most common among neonates (see Neurologic Disorders in Children: Neonatal Seizure Disorders) and the elderly.

Psychogenic seizures (pseudoseizures) are symptoms that simulate seizures in patients with psychiatric disorders but that do not involve an abnormal electrical discharge in the brain.

Etiology

Common causes of seizures (see Table 1: Seizure Disorders: Causes of Seizures) vary by age of onset:

Before age 2: Developmental defects, birth injuries, and metabolic disorders

Ages 2 to 14: Idiopathic seizure disorders

Adults: Cerebral trauma, alcohol withdrawal, tumors, strokes, and unknown cause (in 50%)

The elderly: Tumors and strokes

In reflex epilepsy, a rare disorder, seizures are triggered predictably by an external stimulus, such as repetitive sounds, flashing lights, video games, or even touching certain parts of the body.

Table 1

Causes of Seizures

Condition
Examples

Autoimmune disorders
Cerebral vasculitis, multiple sclerosis (rarely)

Cerebral edema
Eclampsia, hypertensive encephalopathy

Cerebral ischemia or hypoxia
Cardiac arrhythmias, carbon monoxide toxicity, nonfatal drowning, near suffocation, stroke, vasculitis

Head trauma*
Birth injury, blunt or penetrating injuries

CNS infections
AIDS, brain abscess, falciparum malaria, meningitis, neurocysticercosis, neurosyphilis, rabies, tetanus, toxoplasmosis, viral encephalitis

Congenital or developmental abnormalities
Cortical malformations, genetic disorders (eg, fifth day fits†, lipid storage diseases such as Tay-Sachs disease), neuronal migration disorders (eg, heterotopias), phenylketonuria

Drugs and toxins‡
Cause seizures: Camphor, cocaine and other CNS stimulants, cyclosporine

, lead, pentylenetetrazol,
picrotoxin, strychnine, tacrolimus

Lower seizure threshold: Aminophylline

, antidepressants
(particularly tricyclics), sedating antihistamines, antimalarial drugs, some antipsychotics (eg, clozapine

), buspirone

,
fluoroquinolones, theophylline

Expanding intracranial lesions
Hemorrhage, hydrocephalus, tumors

Hyperpyrexia
Drug toxicity (eg, with amphetamines or cocaine), fever, heatstroke

Metabolic disturbances
Commonly, hypocalcemia, hypoglycemia, hyponatremia

Less commonly, aminoacidurias, hepatic or uremic encephalopathy, hyperglycemia, hypomagnesemia, hypernatremia

In neonates, vitamin B6 (pyridoxine) deficiency

Pressure-related
Decompression illness, hyperbaric O2 treatments

Withdrawal syndromes
Alcohol, anesthetics, barbiturates, benzodiazepines

*Posttraumatic seizures occur in 25 to 75% of patients who have brain contusion, skull fracture, intracranial hemorrhage, prolonged coma, or focal neurologic deficits.

†Fifth day fits (benign neonatal seizures) are tonic-clonic seizures occurring between 4 and 6 days of age in otherwise healthy infants; one form is inherited.

‡When given in toxic doses, various drugs can cause seizures.

Classification

Seizures are classified as generalized or partial.

Generalized: In generalized seizures, the aberrant electrical discharge diffusely involves the entire cortex of both hemispheres from the onset, and consciousness is usually lost. Generalized seizures result most often from metabolic disorders and sometimes from genetic disorders. Generalized seizures include the following:

Infantile spasms

Absence seizures

Tonic-clonic seizures

Atonic seizures

Myoclonic seizures

Partial seizures: In partial seizures, the excess neuronal discharge occurs in one cerebral cortex, and most often results from structural abnormalities. Partial seizures may be

Simple (no impairment of consciousness)

Complex (reduced but not complete loss of consciousness)

Partial seizures may be followed by a generalized seizure (called secondary generalization), which causes loss of consciousness. Secondary generalization occurs when a partial seizure spreads and activates the entire cerebrum bilaterally. Activation may occur so rapidly that the initial partial seizure is not clinically apparent or is very brief.

Symptoms and Signs

Seizures may be preceded by an aura. Auras may consist of sensory, autonomic, or psychic sensations (eg, paresthesias, a rising epigastric sensation, abnormal smells, a sensation of fear, a déjà vu sensation).

Most seizures end spontaneously in 1 to 2 min. Generalized seizures are often followed by a postictal state, characterized by deep sleep, headache, confusion, and muscle soreness; this state lasts from minutes to hours. Sometimes the postictal state includes Todd’s paralysis (a transient neurologic deficit, usually weakness, of the limb contralateral to the seizure focus).

Most patients appear neurologically normal between seizures, although high doses of the drugs used to treat seizure disorders, particularly anticonvulsants, can reduce alertness. Any progressive mental deterioration is usually related to the neurologic disorder that caused the seizures rather than to the seizures themselves. Rarely, seizures are unremitting.

Partial seizures: There are several types of partial seizures.

Simple partial seizures cause motor, sensory, or psychomotor symptoms without loss of consciousness. Specific symptoms reflect the affected area of the brain (see Table 2: Seizure Disorders: Manifestations of Partial Seizures by Site). In jacksonian seizures, focal motor symptoms begin in one hand, then march up the arm. Other focal seizures affect the face first, then spread to an arm and sometimes a leg. Some partial motor seizures begin with an arm raising and the head turning toward the moving arm.
Table 2

Manifestations of Partial Seizures by Site

Focal Manifestation
Site of Dysfunction

Bilateral tonic posture
Frontal lobe (supplementary motor cortex)

Simple movements (eg, limb twitching, jacksonian march)
Contralateral frontal lobe

Head and eye deviation with posturing
Supplementary motor cortex

Abnormal taste sensation (dysgeusia)
Insula

Visceral or autonomic abnormalities (eg, epigastric aura, salivation)
Insular-orbital-frontal cortex

Olfactory hallucinations
Anteromedial temporal lobe

Chewing movements, salivation, speech arrest
Amygdala, opercular region

Complex automatic behaviorisms
Temporal lobe

Visual hallucinations (formed images)
Posterior temporal lobe or amygdala-hippocampus

Localized sensory disturbances (eg, tingling or numbness of a limb or 1⁄2 the body)
Parietal lobe (sensory cortex)

Visual hallucinations (unformed images)
Occipital lobe

Epilepsia partialis continua, a rare disorder, causes focal motor seizures that usually involve the arm, hand, or one side of the face; seizures recur every few seconds or minutes for days to years at a time. In adults, the cause is usually a structural lesion (eg, stroke). In children, it is usually a focal cerebral cortical inflammatory process (eg, Rasmussen encephalitis), possibly caused by a chronic viral infection or autoimmune processes.

Complex partial seizures are often preceded by an aura. During the seizure, patients may stare. Consciousness is impaired, but patients have some awareness of the environment (eg, they purposefully withdraw from noxious stimuli). The following may also occur:

Oral automatisms (involuntary chewing or lip smacking)

Limb automatisms (eg, automatic purposeless movements of the hands)

Utterance of unintelligible sounds without understanding what they say

Resistance to assistance

Tonic or dystonic posturing of the extremity contralateral to the seizure focus

Head and eye deviation, usually in a direction contralateral to the seizure focus

Bicycling or pedaling movements of the legs if the seizure emanates from the medial frontal or orbitofrontal head regions

Motor symptoms subside after 1 to 2 min, but confusion and disorientation may continue for another 1 or 2 min. Postictal amnesia is common. Patients may lash out if restrained during the seizure or while recovering consciousness if the seizure generalizes. However, unprovoked aggressive behavior is unusual.

Left temporal lobe seizures may cause verbal memory abnormalities; right temporal lobe seizures may cause visual spatial memory abnormalities.

Generalized seizures: Consciousness is usually lost, and motor function is abnormal from the onset.

Infantile spasms (see Neurologic Disorders in Children: Infantile Spasms) are characterized by sudden flexion and adduction of the arms and forward flexion of the trunk. Seizures last a few seconds and recur many times a day. They occur only in the first 5 yr of life, then are replaced by other types of seizures. Developmental defects are usually present.

Typical absence seizures (formerly called petit mal seizures) consist of 10- to 30-sec loss of consciousness with eyelid fluttering; axial muscle tone may or may not be lost. Patients do not fall or convulse; they abruptly stop activity, then just as abruptly resume it, with no postictal symptoms or knowledge that a seizure 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 patients are sitting quietly, can be precipitated by hyperventilation, and rarely occur during exercise. Neurologic and cognitive examination results are usually normal.

Atypical absence seizures usually occur as part of the Lennox-Gastaut syndrome, a severe form of epilepsy that begins before age 4 yr. They differ from typical absence seizures as follows:

They last longer.

Jerking or automatic movements are more pronounced.

Loss of awareness is less complete.

Many patients have a history of damage to the nervous system, developmental delay, abnormal neurologic examination results, and other types of seizures. Atypical absence seizures usually continue into adulthood.

Atonic seizures occur most often in children, usually as part of Lennox-Gastaut syndrome. Atonic seizures are characterized by brief, complete loss of muscle tone and consciousness. Children fall or pitch to the ground, risking trauma, particularly head injury.

Tonic seizures occur most often during sleep, usually in children. The cause is usually the Lennox-Gastaut syndrome. Tonic (sustained) contraction of axial muscles may begin abruptly or gradually, then spread to the proximal muscles of the limbs. Tonic seizures usually last 10 to 15 sec. In longer tonic seizures, a few, rapid clonic jerks may occur as the tonic phase ends.

Tonic-clonic seizures may be primarily or secondarily generalized. Primarily generalized seizures typically begin with an outcry; they continue with loss of consciousness and falling, followed by tonic contraction, then clonic (rapidly alternating contraction and relaxation) motion of muscles of the extremities, trunk, and head. Urinary and fecal incontinence, tongue biting, and frothing at the mouth sometimes occur. Seizures usually last 1 to 2 min. There is no aura. Secondarily generalized tonic-clonic seizures begin with a simple partial or complex partial seizure.

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. The jerks may be bilateral or unilateral. Unlike other seizures with bilateral motor movements, consciousness is not lost unless the myoclonic seizure progresses into a generalized tonic-clonic seizure.

Juvenile myoclonic epilepsy is an epilepsy syndrome characterized by myoclonic, tonic-clonic, and absence seizures. It typically appears during adolescence. Seizures begin with a few bilateral, synchronous myoclonic jerks, followed in 90% by generalized tonic-clonic seizures. They often occur when patients awaken in the morning, especially after sleep deprivation or alcohol use. Absence seizures may occur in one third of patients.

Febrile seizures occur, by definition, with fever and in the absence of intracranial infection; they are considered a type of provoked seizure. They affect about 4% of children aged 3 mo to 5 yr (see Neurologic Disorders in Children: Febrile Seizures). Benign febrile seizures are brief, solitary, and generalized tonic-clonic in appearance. Complicated febrile seizures are focal, last > 15 min, or recur ≥ 2 times in 5 to 10 min

≥ 2 seizures between which patients do not fully regain consciousness

The previous definition of > 30-min duration was revised to encourage more prompt identification and treatment. Untreated generalized seizures lasting > 60 min may result in permanent brain damage; longer-lasting seizures may be fatal. Heart rate and temperature increase. Generalized convulsive status epilepticus has many causes, including rapid withdrawal of anticonvulsants and head trauma.

Complex partial status epilepticus and absence status epilepticus often manifest as prolonged episodes of mental status changes. EEG may be required for diagnosis.

Diagnosis

Clinical evaluation

For new-onset seizures, neuroimaging, laboratory testing, and usually EEG

For known seizure disorder, usually anticonvulsant levels

For new-onset or known seizure disorders, other testing as clinically indicated

Evaluation must determine whether the event was a seizure vs another cause of obtundation, a pseudoseizure, or syncope), then identify possible causes or precipitants. Patients with new-onset seizures are evaluated in an emergency department; they can sometimes be discharged after thorough evaluation. Those with a known seizure disorder may be evaluated in a physician’s office.

History: Patients should be asked about unusual sensations, suggesting an aura and thus a seizure, and about typical seizure manifestations. However, other conditions, such as suddenly decreased brain circulation (eg, due to ventricular arrhythmia) can have similar manifestations, including loss of consciousness and some myoclonic jerks.

History should include information about the first and any subsequent seizures (eg, duration, frequency, sequential evolution, longest and shortest interval between seizures, aura, postictal state, precipitating factors). All patients should be asked about risk factors for seizures:

Prior head trauma or CNS infection

Known neurologic disorders

Drug use or withdrawal, particularly of recreational drugs

Alcohol withdrawal

Nonadherence to anticonvulsants

Family history of seizures or neurologic disorders

Patients should also be asked about rare triggers (eg, repetitive sounds, flashing lights, video games, touching certain parts of the body) and about sleep deprivation, which can lower the seizure threshold.

Physical examination: A bitten tongue, incontinence (eg, urine or feces in clothing), or, in patients who have lost consciousness, prolonged confusion suggest seizure.

In pseudoseizures, generalized muscular activity and lack of response to verbal stimuli may at first glance suggest generalized tonic-clonic seizures. However, pseudoseizures can usually be distinguished from true seizures by clinical characteristics:

Pseudoseizures often last longer (several minutes or more).

Postictal confusion tends to be absent.

Typical tonic phase activity, followed by clonic phase, usually does not occur.

The progression of muscular activity does not correspond to true seizure patterns (eg, jerks moving from one side to the other and back [nonphysiologic progression]), exaggerated pelvic thrusting).

Intensity may wax and wane.

Vital signs, including temperature, usually remain normal.

Patients often actively resist passive eye opening.

Physical examination rarely indicates the cause when seizures are idiopathic but may provide clues when seizures are symptomatic (see Table 3: Seizure Disorders: Clinical Clues to the Causes of Symptomatic Seizures).
Table 3

Clinical Clues to the Causes of Symptomatic Seizures

Finding
Possible Cause

Fever and stiff neck
Meningitis

Subarachnoid hemorrhage

Meningoencephalitis

Papilledema
Increased intracranial pressure

Loss of spontaneous venous pulsations
Increased intracranial pressure (with less sensitivity*)

Focal neurologic defects (eg, asymmetry of reflexes or muscle strength)
Structural abnormality (eg, tumor, stroke)

Postictal paralysis

Generalized neuromuscular irritability (eg, tremulousness, hyperreflexia)
Drug toxicity (eg, sympathomimetics)

Withdrawal syndromes (eg, of alcohol or sedatives)

Certain metabolic disorders (eg, hypocalcemia, hypomagnesemia)

Skin lesions (eg, axillary freckling or café-au-lait spots, hypomelanotic skin macules, shagreen patches)
Neurocutaneous disorders (eg, neurofibromatosis, tuberous sclerosis)

*About 20% of people with normal intracranial pressure lose spontaneous venous pulsations.

Testing: Testing is done routinely, but normal results do not necessarily exclude a seizure disorder. Thus, the diagnosis may ultimately be clinical. Testing depends on the status of seizures and results of the neurologic examination.

If patients have a known seizure disorder and examination results are normal or unchanged, little testing is required except for blood anticonvulsant levels, unless patients have symptoms or signs of a treatable disorder such as trauma, infection, or a metabolic disorder. If seizures are new-onset or if examination results are abnormal for the first time, neuroimaging is required.

Head CT is usually done immediately to exclude a mass or hemorrhage. Some experts say that CT can be deferred and possibly avoided in children with typical febrile seizures whose neurologic status rapidly returns to normal.

Follow-up MRI is recommended when CT is negative. It provides better resolution of brain tumors and abscesses and can detect cortical dysplasias, cerebral venous thrombosis, and herpes encephalitis. An epilepsy-protocol MRI of the head uses high-resolution coronal T1 and T2 sequences, which can detect hippocampal atrophy or sclerosis. MRI can detect some common causes of seizures, such as malformations of cortical development in young children and mesial temporal sclerosis, traumatic gliosis, and small tumors in adults.

EEG is critical in the diagnosis of epileptic seizures, particularly of complex partial or absence status epilepticus, when EEG may be the most definitive indication of a seizure. EEG may detect epileptiform abnormalities (spikes, sharp waves, spike and slow-wave complexes, polyspike and slow-wave complexes). Epileptiform abnormalities may be bilateral and generalized in patients with generalized seizures and may be localized in patients with partial seizures. EEG findings may include the following:

Epileptiform abnormalities in temporal lobe foci between seizures (interictal) in complex partial seizures originating in the temporal lobe

Interictal symmetric bursts of 4- to 7-Hz epileptiform activity in primarily generalized tonic-clonic seizures

Focal epileptiform discharges in secondarily generalized seizures

Spikes and slow-wave discharges at a rate of 3/sec in typical absence seizures

Slow spike and wave discharges usually at a rate of 50% in another third. About 60% of patients whose seizures are well-controlled by drugs can eventually stop the drugs and remain seizure-free.

Sudden unexplained death in epilepsy (SUDEP) is a rare complication of unknown cause.

Treatment

Elimination of the cause if possible

Avoidance of or precautions during situations when loss of consciousness could be life threatening

Drugs to control seizures

Surgery if ≥ 2 drugs do not control seizures

Optimal treatment is to eliminate the causes whenever possible. If the cause cannot be corrected or identified, anticonvulsants are often required, particularly after a 2nd seizure; usefulness of anticonvulsants after a single seizure is controversial, and risks and benefits should be discussed with the patient. Because the risk of a subsequent seizure is low, drugs may be withheld until a 2nd seizure occurs, particularly in children. In children, certain anticonvulsants cause important behavior and learning problems.

During a generalized tonic-clonic seizure, injury should be prevented by loosening clothing around the neck and placing a pillow under the head. Attempting to protect the tongue is futile and likely to damage the patient’s teeth or the rescuer’s fingers. Patients should be rolled onto their left side to prevent aspiration. These measures should be taught to the patient’s family members and coworkers.

Because partial seizures can become generalized, patients are at risk of losing consciousness and thus should be advised to take certain precautions. Until seizures are controlled, patients should refrain from activities in which loss of consciousness could be life threatening (eg, driving, swimming, climbing, operating power tools, bathing in a bathtub). After seizures are completely controlled (typically for > 6 mo), many such activities can be resumed if appropriate safeguards (eg, lifeguards) are used, and patients should be encouraged to lead a normal life, including exercise and social activities. In a few states, physicians must report patients with seizures to the Department of Motor Vehicles. However, most states allow automobile driving after patients have been seizure-free for 6 mo to 1 yr.

Patients should be advised to avoid cocaine and some other illicit drugs (eg, phencyclidine

,
amphetamines), which can trigger seizures, and to avoid alcohol. Some drugs (eg, haloperidol

, phenothiazines) may lower seizure threshold and should be avoided if possible.

Family members must be taught a commonsense approach toward the patient. Overprotection should be replaced with sympathetic support that lessens negative feelings (eg, of inferiority or self-consciousness); invalidism should be prevented. Institutional care is rarely advisable and should be reserved for severely cognitively impaired patients and for patients with seizures so frequent and violent despite drug treatment that they cannot be cared for elsewhere.

Acute seizures and status epilepticus: Most seizures remit spontaneously in several minutes or less and do not require emergency drug treatment. Status epilepticus and most seizures lasting > 5 min require drugs to terminate the seizures, with monitoring of respiratory status. Endotracheal intubation is necessary if there is any indication of airway compromise. IV access should be quickly obtained, and lorazepam

0.05 to 0.1 mg/kg IV is given at a
rate of 2 mg/min. Larger doses are sometimes required. However, if seizures continue after about 8 mg is given, fosphenytoin

15 to 20 PE (phenytoin

equivalents)/kg IV is given at a
rate of 100 to 150 PE/min; phenytoin

15 to 20 mg/kg IV at a rate of 50 mg/min is a 2nd
choice. Additional seizures require an additional 5 to 10 PE/kg of fosphenytoin

or 5 to 10
mg/kg of phenytoin

. If IV access cannot be obtained, options include IM fosphenytoin

and
sublingual or rectal benzodiazepines.

Seizures that persist after use of lorazepam

and phenytoin

define refractory status
epilepticus. Recommendations for a 3rd anticonvulsant vary and include phenobarbital

,
propofol

, midazolam

, and valproate

. Phenobarbital

15 to 20 mg/kg IV at 100 mg/min
(3 mg/kg/min in children) is given; continued seizures require another 5 to 10 mg/kg. A loading dose of valproate

10 to 15 mg/kg IV is an alternative. At this point, if status epilepticus has
not abated, intubation and general anesthesia are necessary. The optimal anesthetic to use is controversial, but many physicians use propofol

15 to 20 mg/kg at 100 mg/min or
pentobarbital

5 to 8 mg/kg (loading dose) followed by infusion of 2 to 4 mg/kg/h until EEG
manifestations of seizure activity have been suppressed. Inhalational anesthetics are rarely used. After initial treatment, the cause of status epilepticus must be identified and treated.

Posttraumatic seizures: Drugs are given to prevent seizures if head injury causes significant structural injury (eg, large contusions or hematomas, brain laceration, depressed skull fracture) or a Glasgow Coma Scale (GCS) score of 1 wk after head injury, long-term treatment with drugs is required.
Clinical Calculator

Principles of long-term treatment: No single drug controls all types of seizures, and different patients require different drugs. Some patients require multiple drugs. (See also the practice guideline for the treatment of refractory epilepsy from the American Academy of Neurology and the American Epilepsy Society.) Some general principles apply:

A single drug, usually the 1st or 2nd one tried, controls epileptic seizures in about 60% of patients.

If seizures are difficult to control from the outset (in 30 to 40% of patients), ≥ 2 drugs may eventually be required.

If seizures are intractable (refractory to an adequate trial of ≥ 2 drugs), patients should be referred to an epilepsy center to determine whether they are candidates for surgery.

Some drugs (eg, phenytoin

, valproate

), given IV or orally, reach the targeted therapeutic
range very rapidly. Others (eg, lamotrigine

, topiramate

) must be started at a relatively low
dose and gradually increased over several weeks to the standard therapeutic dose, based on the patient’s lean body mass. Dose should be tailored to the patient’s tolerance of the drug. Some patients have symptoms of drug toxicity when blood drug levels are low; others tolerate high levels without symptoms. If seizures continue, the daily dose is increased by small increments. The appropriate dose of any drug is the lowest dose that stops all seizures and has the fewest adverse effects, regardless of blood drug level. Blood drug levels are only guidelines. Once drug response is known, following the clinical course is more useful than measuring blood levels.

If toxicity develops before seizures are controlled, the dose is reduced to the pretoxicity dose. Then, another drug is added at a low dose, which is gradually increased until seizures are controlled. Patients should be closely monitored because the 2 drugs can interact, interfering with either drug’s rate of metabolic degradation. The initial, ineffective drug is then slowly tapered and eventually withdrawn completely. Use of multiple drugs should be avoided if possible because incidence of adverse effects, poor adherence, and drug interactions increases significantly. Adding a 2nd drug helps about 10% of patients, but incidence of adverse effects more than doubles. The blood level of anticonvulsants is altered by many other drugs, and vice versa. Physicians should be aware of all potential drug-drug interactions before prescribing a new drug.

Once seizures are controlled, the drug should be continued without interruption until patients have been seizure-free for at least 2 yr. At that time, stopping the drug may be considered. Most of these drugs can be tapered by 10% every 2 wk. Relapse is more likely in patients who have had any of the following:

A seizure disorder since childhood

Need for > 1 drug to be seizure-free

Previous seizures while taking an anticonvulsant

Partial or myoclonic seizures

Underlying static encephalopathy

Abnormal EEG results within the last year

Of patients who relapse, about 60% do so within 1 yr, and 80% within 2 yr. Patients who have a relapse when they are not taking anticonvulsants should be treated indefinitely.

Drug choice for long-term treatment: The drugs preferred vary according to type of seizure (see Table 4: Seizure Disorders: Choice of Drugs for Seizures). For more detailed drug-specific information, see Table 5: Seizure Disorders: Drugs Used in Seizure Disordersa.

For partial seizures and generalized tonic-clonic seizures, the newer anticonvulsants (eg, clonazepam

, felbamate

, lamotrigine

, levetiracetam

, oxcarbazepine

, pregabalin,
tiagabine

, topiramate

, zosinamide) are no more effective than the established drugs.
However, the newer drugs tend to have fewer adverse effects and to be better tolerated.

Infantile spasms, atonic seizures, and myoclonic seizures are difficult to treat. Valproate

is
preferred, followed by clonazepam

. For infantile spasms, corticosteroids for 8 to 10 wk are
often effective. The optimal regimen is controversial. ACTH 20 to 60 units IM once/day may be used. A ketogenic diet (a very high fat diet that induces ketosis) may help but is difficult to maintain.

For juvenile myoclonic epilepsy, life-long treatment is usually recommended. Carbamazepine

, oxcarbazepine

, or gabapentin

can exacerbate the seizures.

For febrile seizures, drugs are not recommended unless children have a subsequent seizure in the absence of febrile illness. Previously, many physicians gave phenobarbital

or other
anticonvulsants to children with complicated febrile seizures to prevent nonfebrile seizures from developing, but this treatment does not appear effective, and long-term use of phenobarbital

reduces learning capacity.

For seizures due to alcohol withdrawal, drugs are not recommended. Instead, treating the withdrawal syndrome tends to prevent seizures. Treatment usually includes a benzodiazepine.

Table 4

Choice of Drugs for Seizures

Type
Drugs
Use

Primary generalized tonic-clonic seizures
Carbamazepine

Phenytoin

Valproate

Topiramate

First-line monotherapy

Lamotrigine

Levetiracetam

2nd-line monotherapy or adjunctive therapy

Zonisamide

Adjunctive therapy

Phenobarbital

Although effective, often considered 2nd-line monotherapy because it is sedating and can cause behavioral and learning problems in children

Partial seizures with or without secondary generalization
Carbamazepine

Lamotrigine

Oxcarbazepine

Phenytoin

Topiramate

Levetiracetam

First-line monotherapy

Gabapentin

Pregabalin

Valproate

Zonisamide

2nd-line monotherapy or adjunctive therapy

Felbamate

Tiagabine

Vigabatrin
3rd-line monotherapy or adjunctive therapy

Phenobarbital

Although effective, often considered less desirable because it is sedating and can cause behavioral problems in children

Typical absence seizures
Ethosuximide

Lamotrigine

Valproate

First-line monotherapy

Levetiracetam

Topiramate

Zonisamide

Also effective

Atypical absence seizures

Absence seizures associated with other seizure types
Valproate

Lamotrigine

Topiramate

Felbamate

First-line monotherapy

Clonazepam

Also effective, but often development of tolerance

Acetazolamide

Reserved for refractory cases

Infantile spasms

Atonic seizures

Myoclonic seizures
Valproate

Vigabatrin
First-line monotherapy; risk of irreversible visual field defects

Clonazepam

2nd-line

Tonic and atonic seizures in Lennox-Gastaut syndrome
Lamotrigine

Topiramate

First-line monotherapy

Felbamate

Sometimes alternative or adjunctive therapy for atonic seizures

Juvenile myoclonic epilepsy
Valproate

First-line monotherapy

Lamotrigine

Levetiracetam

Topiramate

Zonisamide

2nd-line monotherapy or adjunctive therapy

Unclassifiable seizures
Valproate

First-line monotherapy

Lamotrigine

2nd-line monotherapy

Levetiracetam

Topiramate

Zonisamide

3rd-line monotherapy or adjunctive therapy

Table 5

Drugs Used in Seizure Disordersa
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Adverse drug effects: All anticonvulsants may cause an allergic scarlatiniform or morbilliform rash, and none is completely safe during pregnancy (see Table: Pregnancy Complicated by Disease: Seizure Disorders in Pregnancy).

For patients taking carbamazepine

, CBC
should be monitored routinely for the first year of therapy. Decreases in WBC count and dose-dependent neutropenia (neutrophil count 2 times the upper limit of normal), the drug should be stopped. An increase in ammonia up to 1.5 times the upper limit of normal can be tolerated safely.

Carbamazepine

, phenytoin

, and valproate

are pregnancy category D drugs (ie,
teratogenicity occurs in animal and human pregnancies). Risk of neural tube defects is somewhat greater with valproate

than other commonly used anticonvulsants. The newer
drugs are category C (ie, teratogenicity occurs in animals, but human risk is unknown).

Fetal antiepileptic drug syndrome (cleft lip, cleft palate, cardiac defects, microcephaly, growth retardation, developmental delay, abnormal facies, limb or digit hypoplasia) occurs in 4% of children of women who take anticonvulsants during pregnancy. Yet, because uncontrolled generalized seizures during pregnancy can lead to fetal injury and death, continued treatment with drugs is generally advisable (see Pregnancy Complicated by Disease: Seizure Disorders in Pregnancy). The risk should be put in perspective: Alcohol is more toxic to the developing fetus than any anticonvulsant. Taking folate supplements before conception helps reduce risk of neural tube defects and should be recommended to all women who are of childbearing age and who take anticonvulsants.

Surgery: About 10 to 20% of patients have intractable seizures refractory to medical treatment and are potential surgical candidates. If seizures originate from a focal, resectable area in the brain, resection of the epileptic focus usually improves seizure control markedly. If the focus is in the anteromesial temporal lobe, resection eliminates seizures in about 60% of patients. After surgical resection, some patients remain seizure-free without taking anticonvulsants, but many still require the drugs, but in reduced doses and possibly as monotherapy. Because surgery requires extensive testing and monitoring, these patients are best treated in specialized epilepsy centers.

Vagus nerve stimulation: Intermittent electrical stimulation of the left vagus nerve with an implanted pacemaker-like device (vagus nerve stimulator) is used as an adjunct to drug therapy in patients who have intractable seizures and are not candidates for epilepsy surgery. This procedure reduces the number of partial seizures by ≥ 50% in about 40%. After the device is programmed, patients can activate it with a magnet to abort an imminent seizure. Adverse effects include deepening of the voice during stimulation, cough, and hoarseness. Complications are minimal. Duration of effectiveness is unclear.