AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Partial epilepsies are epileptic disorders in which seizure semiology or findings at investigation disclose localized origin of seizures.

Pathophysiology

Most partial epilepsies are the result of a localized brain abnormality, even though in most patients it cannot be seen with imaging techniques.

Only a few partial epilepsies are genetic; most are lesional. Unfortunately, in the current classification, they are referred to as "idiopathic." The term "idiopathic" is often misunderstood in this setting. While generally idiopathic means "of unknown cause," idiopathic epilepsies are not truly of unknown cause. This terminology most likely will be corrected in the upcoming classification system of the International League Against Epilepsy (ILAE). Idiopathic epilepsies are determined genetically and have no apparent structural cause, with seizures as the only manifestation of the condition.

Frequency

United States

The prevalence of epilepsy is approximately 1% of the population. Most adult-onset epilepsies are partial epilepsies.

International

The international prevalence of epilepsy is similar to that in the United States.

Mortality/Morbidity

In the United States, the mortality rate from epilepsy was 0.8 deaths per 100,000 persons in 1979. The rate in 1986 was 0.7 deaths per 100,000 persons overall; it was 0.6 deaths per 100,000 persons for white males and females but 1.7 deaths per 100,000 persons for black males and 1 death per 100,000 persons for black females. No specific data are available for partial epilepsy.

Sex

Males and females are equally affected.

Age

The age-related incidence follows a U-shaped curve, with a peak in the first year of life and an increase during the sixth and seventh decades (see Image 1).

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Obtain a description of the seizures from the patient and witnesses, as it is critical.

• Partial seizures are divided into simple, complex, and those that evolve into secondary generalized seizures.
• Simple and complex seizures are distinguished solely on the basis of the state of consciousness. Consciousness usually is assessed by the ability of the patient to respond to external stimuli (ie, responsiveness). This is intact in simple partial seizures (SPS) and impaired in complex partial seizures (CPS).
• SPSs are subdivided further into 4 categories according to the symptoms present (motor, sensory, autonomic, psychic).
• • Motor symptoms can vary and include motor signs with or without march, versive movements, posturing, and phonatory symptoms.
  • Sensory symptoms include all 5 senses and a vertiginous sensation. With the exception of vertigo, these usually are characterized by elementary hallucinations.
  • Autonomic symptoms include the common rising epigastric sensation (typically observed in mesial temporal lobe epilepsy) and less frequent symptoms (eg, vasomotor phenomena, mydriasis).
  • Psychic symptoms are characterized by various experiences involving memory (déjà-vu, jamais-vu), affect (fear, pleasure), or other complex psychic phenomena such as illusions.
• CPS includes some complex symptomatology and, by definition, an impairment of consciousness. Automatism is a better term for "complex symptomatology." These consist of involuntary but coordinated motor activity, which tends to be purposeless and repetitive.
• • Common automatisms include lip smacking, chewing, fidgeting, and walking.
  • CPS can begin as SPS and seizures with impaired consciousness at onset.
  • CPSs are not subdivided according to coexisting symptoms, no matter how prominent.
• The third kind of partial seizure evolves into a generalized seizure.
• • This is divided further according to what precedes generalization (SPS only, CPS only, SPS evolving into CPS).
  • For clinical purposes, however, the partial phase of the seizure often is missed and many patients simply present with a convulsion (secondarily generalized tonic-clonic seizure).

Physical

In most focal epilepsies, examination is unrevealing. Direct neurologic examination should be done to elicit any cortical abnormality or dysfunction, which would depend on etiology and lesion site.

Causes

• Three genetic partial epilepsies are recognized.
• • Childhood epilepsy of occipital paroxysms
    • Age of onset is 15 months to 17 years.
    • One third of patients have a family history of epilepsy, especially rolandic epilepsy.
    • Symptoms include visual hallucination, blindness, hemianopia, visual illusions (eg, micropsia, macropsia, metamorphopsia), loss of consciousness, and unilateral clonic seizure, followed by migrainelike headache.
    • These attacks can occur while awake or while sleeping, more commonly during the transition period between wakefulness and sleep.
    • Sharp waves have a maximum occipital negativity, often occur in long bursts of spike-wave complexes, and are markedly activated by eye closure.
  • Benign childhood epilepsy with centrotemporal spikes
    • Age of onset is 2-12 years, with a strong peak at 8-9 years.
    • Characteristic ictal symptoms include guttural vocalizations, hypersalivation, drooling, sensations or movements of the mouth, dysphasia, and speech arrest.
    • Though these focal seizures are the most characteristic seizure types, they can be quite subtle and are missed easily; the most common mode of presentation is a nocturnal (secondary) generalized tonic-clonic seizure during sleep.
    • Neurologic examination is normal.
    • EEG findings are centrotemporal sharp waves with a characteristic morphology. They occur in repetitive bursts and often are bilateral. These sharp waves are activated markedly by nonrapid eye movement (non-REM) sleep.
    • The natural history is benign. This syndrome has an excellent prognosis regardless of treatment, with spontaneous remission by 14-16 years. If treatment is required, options may include carbamazepine, gabapentin, or valproate. Antiepileptic drugs (AEDs) always should be weaned by 14-16 years.
  • Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
    • This is a recently described syndrome that appears to be a genetic localization-related epilepsy.
    • It is caused by an identified single gene mutation. Several mutations of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) gene have been identified as the cause.
    • Onset is early in life.
    • Seizures are nocturnal and occur in clusters, mimicking parasomnias. They mostly are brief tonic seizures and rare tonic-clonic convulsions, often preceded by a nonspecific aura.
    • Interictal EEG may show epileptiform discharges with a frontal predominance, often observed only in sleep.
    • Despite its established genetic basis, the genetic findings are variable (locus heterogeneity); thus, definite diagnosis is difficult and largely one of exclusion.
    • Seizures often subside with age and may even disappear at adulthood. They usually are controlled with carbamazepine.
• Most partial epilepsies are caused by a localized brain abnormality, regardless of whether it is visible on imaging. This is the most common type of adult-onset epilepsy. These cases are characterized by seizures arising from a localized region of the brain. If the cause is found, they are said to be symptomatic. If imaging studies are normal, the cause remains elusive and they are said to be cryptogenic. The boundary between the two largely depends on diagnostic and imaging techniques, and etiologies such as low-grade tumors, hippocampal sclerosis, and subtle cortical dysplasias are identified more often because of advances in neuroimaging.

  Clinically, seizures may be simple partial or complex partial, with or without secondary generalization. Interictal EEG shows focal spikes or sharp waves, and ictal EEG shows a focal or regional discharge at onset. Because of dramatic differences in electroclinical semiology and management, localization-related epilepsies usually are divided into mesiotemporal and neocortical. The most common localization-related epilepsy in adults is mesiotemporal lobe epilepsy, but, in neonates and young children, this is less common than neocortical epilepsy.

• • Mesial temporal lobe epilepsy
    • The most common cause of temporal lobe epilepsy in candidates for epilepsy surgery in adults is hippocampal sclerosis, while in children, etiologies are dominated by cortical dysplasias and low-grade neoplasms.
    • Seizures typically are complex partial with automatisms, often preceded by a simple partial phase with sensory symptoms (ie, aura).
    • Auras commonly observed in temporal lobe epilepsy are epigastric (abdominal) and psychic auras, including déjà-vu or jamais-vu and fear.
    • CPSs of temporal lobe origin are semiologically "automator" with fine distal automatisms involving hands and/or fingers and orobuccal movements.
    • Interictal EEG typically shows temporal sharp waves maximal at anterior temporal or sphenoidal electrodes. Ictal EEG often shows well-defined rhythmic theta seizure patterns.
    • Diagnosis of mesial temporal lobe epilepsy often is confirmed by high-resolution MRI using dedicated epilepsy protocols. MRI is a strong predictor of a favorable surgical outcome, especially when concordant with ictal EEG, so much so that performing successful temporal lobectomies without ictal recordings may be possible. The availability and great sensitivity of MRI in this setting has greatly reduced the need for invasive EEG.
  • Neocortical seizures
    • Neocortical seizures may be simple partial or complex partial, with symptoms depending on the area of cortex affected.
    • Interictal EEG typically shows sharp waves or spikes outside of the anterior temporal region. Ictal EEG often shows regional or widespread discharges.
    • In general, localization of the epileptogenic zone by surface EEG (interictal and ictal) is less reliable for neocortical than for mesiotemporal epilepsy.
    • Epileptiform discharges can be absent on surface EEG when the focus is deep, as in supplementary sensorimotor area epilepsy.
    • Frontal discharges can spread rapidly and mimic "primary" generalized spike-wave complexes. This is referred to as "secondary bilateral synchrony" (with interictal epileptiform discharges that appear to be generalized but are in reality "secondarily generalized" focal discharges).
    • Strict criteria are required to attribute generalized discharges to secondary bilateral synchrony, focal or lateralized epileptiform discharges, or a structural lesion.
    • Neocortical extratemporal epilepsies may be difficult to localize precisely. Precise localization is important only when considering surgical treatment.
    • Certain syndromes are well characterized, including frontal, supplementary sensorimotor, parietal, and occipital lobe epilepsies.
    • Most adult-onset localization-related epilepsies do not have an identifiable etiology (ie, MRI is most often normal); this is well known. When a cause is found, it can include various structural lesions (eg, traumatic scars, neoplasms, vascular malformations, strokes, neuronal heterotopias).

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Benign epilepsy syndromes, as follows:

Neonates
While sleeping - Head banging and benign neonatal myoclonus
While awake - Jitteriness, head banging, masturbation, benign myoclonus of epilepsy, spasmodic torticollis, spasms nutans, opsoclonus, rumination, startle disease or hyperexplexia, shuddering attacks, alternating hemiplegia, infantile apnea, cyanotic breath-holding spells, pallid syncope

Children
While sleeping - Hypnagogic paroxysmal dystonia, nightmares, night terrors, sleep walking
While awake - Chorea, tics, paroxysmal choreoathetosis, stereotypic movements, head nodding, headache, recurrent abdominal pain, confusional migraine, benign paroxysmal vertigo, stool-withholding activity, rage attacks, Münchhausen syndrome by proxy

Late childhood
While awake - Syncope, narcolepsy and/or cataplexy, basilar migraine, tremor, panic disorder

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• At seizure onset, perform various tests to look for a clear cause. Because the type of seizure (partial vs generalized) often is not clear early on, investigate various causes of seizures, including structural abnormalities and toxic and metabolic disturbances.
• • Metabolic panel
  • Cerebrospinal fluid examination, if CNS infection is suspected (eg, fever, neck rigidity, mental status changes)
  • Level of anticonvulsant medication

Imaging Studies

• CT scan of brain without contrast is easily and rapidly available and appropriate in an emergency setting.
• MRI of the brain, with and without contrast, delineates structural detail and pathology; obtain a special temporal lobe cut for mesial temporal sclerosis.

Other Tests

• EEG is extremely useful to confirm the diagnosis of epilepsy and to confirm a partial onset. The sensitivity of routine EEG is low but increases somewhat with repeated recordings.
• When seizures are frequent (>1/wk), EEG-video monitoring allows a definitive diagnosis of epilepsy, including its type.

TREATMENT

Section 6 of 11  

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• Introduction
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• Medication
• Follow-up
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• Multimedia
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Medical Care

Many AEDs are available. In general, drugs have similar rates of efficacy. Important factors in choosing among various drugs include potential adverse effects, dosing schedules, drug interactions, available formulations, and cost.

Conventionally, phenytoin, carbamazepine, valproic acid, primidone, and phenobarbital have been used for generalized seizure or epilepsies. The US Food and Drug Administration (FDA) has approved the following medications during the last 10 years: gabapentin, lamotrigine, tiagabine, topiramate, zonisamide, levetiracetam, and oxcarbazepine. Most of these drugs are approved as adjuncts for partial epilepsy. Note that most epileptologists believe that all AEDs that have been approved by the FDA for adjunctive therapy may be effective as monotherapy, and their prescribing practices reflect this.

Surgical Care

Patients with medically refractory seizures may be candidates for nonpharmacologic treatments, which include epilepsy surgery and vagus nerve stimulation. Resective surgery is an underutilized therapeutic option. In the United States, an estimated 20,000-70,000 people each year are candidates for a potentially curative surgical procedure. However, only 5,000 surgeries are performed per year in the 150 epilepsy centers in the United States.

Consultations

If seizures are refractory to the first 2-3 trials of medication, refer patients to a comprehensive epilepsy center to evaluate other treatment options. Nonpharmacologic treatments include surgery, vagus nerve stimulation, and (rarely in adults) the ketogenic diet.

Diet

Consider the ketogenic diet as alternative therapy for children with difficult-to-control seizures. It is effective but very strict; compliance is extremely cumbersome.

MEDICATION

Section 7 of 11  

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• Introduction
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• Differentials
• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medications are the first-line treatment for epilepsy. All are effective, but all have potential adverse effects. Classic (old) agents include phenobarbital, primidone, phenytoin, carbamazepine, and valproate. After a 15-year hiatus in drug approvals, many new drugs have become available to treat epilepsy in the last 6 years. The new drugs approved in the United States are felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), topiramate (Topamax), tiagabine (Gabitril), levetiracetam (Keppra), zonisamide (Zonegran), and oxcarbazepine (Trileptal).

Drug Category: Antiepileptic agents

These agents prevent early posttraumatic seizure, which can increase the intracranial pressure (ICP) and neurotransmitter release as well as alter blood pressure and oxygen delivery.

Drug Name	Carbamazepine (Tegretol)
Description	May block posttetanic potentiation by reducing summation of temporal stimulation.
Adult Dose	200-400 mg PO bid/qid; not to exceed 1600 mg/d; following therapeutic response, may reduce dose to minimum effective level or discontinue treatment at least q3mo
Pediatric Dose	<6 years: 5 mg/kg/d PO divided tid/qid initial; not to exceed 35 mg/kg/d 6-12 years: 10 mg/kg/d PO divided bid/qid initial; not to exceed 1000 mg/d (susp 100 mg/5 mL)
Contraindications	Documented hypersensitivity; bone marrow depression; MAOIs within last 14 d
Interactions	Cimetidine, danazol, diltiazem, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, loratadine, terfenadine, isoniazid, niacinamide, nicotinamide, propoxyphene, ketoconazole, and valproate may increase plasma levels; cisplatin, doxorubicin HCl, felbamate, rifampin, phenobarbital, phenytoin, primidone, theophylline, itraconazole, and verapamil decrease plasma levels
Pregnancy	D - Unsafe in pregnancy
Precautions	Discontinue MAOIs for minimum of 14 d before starting this drug (or longer, if clinical situation permits) Caution in patients with a mixed-seizure disorder that includes atypical absence seizures, since carbamazepine associated with increased frequency of generalized convulsions in these patients; as dizziness and drowsiness may occur, caution patients on hazards of operating machinery or automobiles or engaging in other potentially dangerous activities; make patients aware of early toxic signs and symptoms of potential hematologic problem, dermatologic hypersensitivity, or hepatic reactions; since susp dose produces higher peak levels than same dose administered as tab, start patients given susp on lower doses and increase slowly to avoid unwanted adverse effects

Drug Name	Valproic acid (Depakote)
Description	Chemically unrelated to other drugs that treat seizure disorders. Although mechanism of action not established, activity may be related to increased brain levels of GABA or enhanced GABA action. Also may potentiate postsynaptic GABA responses, affect potassium channels, or have direct membrane-stabilizing effect. For conversion to monotherapy, concomitant AED dosage ordinarily can be reduced by approximately 25% every 2 wk. This reduction may start at initiation of therapy or be delayed by 1-2 wk if concern that seizures may occur with reduction. Monitor patients closely during this period for increased seizure frequency. As adjunctive therapy, divalproex sodium may be added to patient's regimen at 10-15 mg/kg/d. May increase by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response achieved at daily doses <60 mg/kg/d.
Adult Dose	10-15 mg/kg/d PO/IV divided bid/qid; titrate; not to exceed 60 mg/kg/d
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; hepatic dysfunction
Interactions	May potentiate CNS depressants (eg, alcohol, benzodiazepines); highly binding drugs (eg, aspirin, carbamazepine, dicumarol, phenytoin) may result in alteration of serum concentrations; increases phenobarbital level by reducing metabolism; concomitant clonazepam may produce absence status in patients with history of absence type seizures; concomitant lamotrigine increases half-life of lamotrigine and increases risk of skin rash; may potentiate effect of oral anticoagulants; may reduce clearance of zidovudine
Pregnancy	D - Unsafe in pregnancy
Precautions	Hyperammonemia with or without lethargy or coma is reported and may be present in absence of abnormal liver function tests; thrombocytopenia, inhibition of secondary phase of platelet aggregation, and abnormal coagulation parameters (eg, low fibrinogen) may occur—checking platelet counts and coagulation tests is recommended before initiating therapy and at periodic intervals; periodic plasma concentrations of concomitant AEDs are recommended during early course of therapy; partial elimination in urine as ketometabolite may lead to false interpretation of urine ketone test; weight gain, hair loss, and tremor may occur

Drug Name	Gabapentin (Neurontin)
Description	Structurally related to GABA, but does not interact with GABA receptors; not converted metabolically into GABA or GABA agonist; not inhibitor of GABA uptake or degradation. Does not exhibit affinity for other common receptor sites. Titration to effect can take place over several days (300 mg on day 1, 300 mg bid on day 2, 300 mg tid on day 3).
Adult Dose	300 mg PO qhs initial dose; increase over few days to 300-600 mg PO tid; not to exceed 3600 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Antacids may significantly reduce bioavailability (administer at least 2 h following antacids); may increase norethindrone levels significantly
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Do not discontinue suddenly; caution in older patients and patients with renal impairment—adjust dose in renal failure; somnolence, ataxia, fatigue, nausea and/or vomiting, and dizziness common adverse effects

Drug Name	Topiramate (Topamax)
Description	Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel-blocking action, potentiates inhibitory activity of neurotransmitter GABA. May block glutamate activity. Not necessary to monitor plasma concentrations to optimize therapy. On occasions, addition of topiramate to phenytoin may require adjustment of dose of phenytoin to achieve optimal clinical outcome.
Adult Dose	50 mg PO qhs initial; increase by 50 mg/wk; not to exceed 200 mg PO bid (IV preparation not available)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Other AEDs affect efficacy; phenytoin and carbamazepine decrease effects; affects other AEDs activity; may affect phenytoin and valproic acid levels; efficacy of OCDs may be compromised
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Common adverse effects include fatigue, nervousness, difficulty with concentration or attention, confusion, depression, anorexia, language problems, anxiety, mood problems, cognitive problems not otherwise specified, weight decrease, and tremor

Drug Name	Lamotrigine (Lamictal)
Description	Triazine derivative used in neuralgia. Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane.
Adult Dose	50 mg PO qd for 14 d, then 50 mg PO bid for 14 d; not to exceed 250 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Decreases valproic acid level; other AEDs, carbamazepine, and phenytoin reduce levels; conversely, valproic acid increases levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Most common adverse effects include dizziness, headache, blurred or double vision, lack of coordination, sleepiness, nausea, vomiting, and rash (life-threatening rash including Stevens-Johnson syndrome in 1 per 1000 adults and 1 per 50 children)

Drug Name	Felbamate (Felbatol)
Description	Oral AED with weak inhibitory effects on GABA-receptor binding and benzodiazepine-receptor binding. Has little activity at MK-801 receptor-binding site of NMDA receptor-ionophore complex. However, felbamate is antagonist at strychnine-insensitive glycine recognition site of NMDA receptor-ionophore complex. Not indicated as first-line antiepileptic treatment.
Adult Dose	400 mg PO tid initial dose; not to exceed 3600 mg/d
Pediatric Dose	15 mg/kg/d PO initial; not to exceed 45 mg/kg/d
Contraindications	Documented hypersensitivity
Interactions	Slightly decreases valproic acid levels; carbamazepine, phenytoin, and phenobarbital decrease levels; valproate increases level because it displaces drugs from protein binding
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Most commonly observed adverse events are dizziness and/or lightheadedness, asthenia and/or lack of energy, somnolence, nausea, nervousness and/or irritability, tremor, abdominal pain, and thinking abnormalities and/or difficulty with concentration or attention

Drug Name	Oxcarbazepine (Trileptal)
Description	Pharmacologic activity primarily through 10-monohydroxy metabolite (MHD) of oxcarbazepine. May block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Drug's anticonvulsant effect may also occur by affecting potassium conductance and high-voltage activated calcium channels. Drug pharmacokinetics are similar in older children (>8 y) and adults. Young children ( <8 y) have 30-40% greater clearance than older children and adults. Children <2 y have not been studied in controlled clinical trials.
Adult Dose	300 mg PO bid initial dose; not to exceed 2400 mg
Pediatric Dose	8-10 mg/kg PO; not to exceed 30 mg/kg/d bid
Contraindications	Documented hypersensitivity
Interactions	Low doses can reduce serum concentrations of carbamazepine, phenobarbital, phenytoin, and valproic acid; when administered in doses >1200 mg/d, phenytoin serum concentration may increase by up to 40% and phenobarbital concentration by up to 15%
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Commonly observed adverse effects include dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, and abnormal gait

Drug Name	Primidone (Mysoline)
Description	Decreases neuron excitability and increases seizure threshold.
Adult Dose	Days 1-3: 100-125 mg PO at bedtime Days 4-6: 100-125 mg PO bid Days 7-9: 100-125 mg PO tid Day 10 to Maintenance: 250 mg PO tid
Pediatric Dose	Days 1-3: 50 mg PO at bedtime Days 4-6: 50 mg PO bid Days 7-9: 100 mg PO bid Day 10 to Maintenance: 125 mg PO tid to 250 mg tid
Contraindications	Documented hypersensitivity; porphyria
Interactions	May decrease serum concentrations of ethosuximide, griseofulvin, valproic acid; phenytoin may decrease primidone serum levels; may decrease warfarin, oral contraceptive, cyclosporine efficacy; other CNS depressants increase CNS depression
Pregnancy	D - Unsafe in pregnancy
Precautions	Total daily dosage should not exceed 2 g; CBC count and chemistry panel should be checked every 6 mo; megaloblastic anemia may occur as a rare idiosyncratic response to primidone

Drug Name	Phenobarbital (Barbita, Luminal, Solfoton)
Description	Elevates seizure threshold, limits the spread of seizure activity, sedative.
Adult Dose	Seizure: 60 mg PO bid/tid; 300-800 mg or 15 mg/kg IV initial dose Status: 10-20 mg/kg IV single dose; may repeat prn Sedation: 10-40 mg PO/IV/IM tid
Pediatric Dose	Seizure <2 months: 3-5 mg/d PO/IV qd or divided bid 2 months-2 years: 5-8 mg/kg/d PO/IV qd or divided bid > 2 years: 3-5 mg/kg/d PO/IV qd or divided bid Status: 10-20 mg/kg IV single dose; may repeat 5-10 mg/kg; not to exceed 40 mg/kg
Contraindications	Documented hypersensitivity; manifest or latent porphyria; marked impairment of liver function or premonitory signs of hepatic coma; severe respiratory disease; intraarterial administration (consequences vary from transient pain to gangrene)
Interactions	Lowers plasma levels of warfarin; enhances metabolism of corticosteroids; appears to interfere with absorption of PO griseofulvin; variable effects on metabolism of phenytoin; sodium valproate decreases metabolism; may reduce effectiveness of oral contraceptives—patients treated with phenobarbital have been reported to became pregnant while taking oral contraceptives
Pregnancy	D - Unsafe in pregnancy
Precautions	Subcutaneous (ie, extravascular) administration produces tissue irritation ranging from tenderness and redness to necrosis, and is not recommended May be habit-forming; elderly or debilitated patients may react with marked excitement, depression, and confusion; should not be administered to patients showing premonitory signs of hepatic coma

Drug Name	Tiagabine (Gabitril)
Description	Mechanism of action against seizures unknown. Believed related to ability to enhance activity (GABA, major inhibitory neurotransmitter in CNS. May block GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on surfaces of postsynaptic cells; also may prevent propagation of neural impulses that contribute to seizures by GABAergic action. Modification of concomitant antiepilepsy drugs not necessary unless clinically indicated.
Adult Dose	4 mg PO qd initial dose; increase up to 56 mg/d divided bid/qid as adjunct treatment; take with food
Pediatric Dose	<12 years: Not recommended >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; EEG spike and wave pattern; impaired liver function
Interactions	Cleared more rapidly in patients treated with carbamazepine, phenytoin, primidone, and phenobarbital than in patients who have not received these drugs
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Has not been investigated in adequate and well-controlled clinical trials in patients <12 years; moderately severe to incapacitating generalized weakness in 1% of patients may occur

Drug Name	Zonisamide (Zonegran)
Description	Indicated for adjunct treatment of partial seizures with or without secondary generalization. Evidence that is effective in myoclonic and other generalized seizure types as well.
Adult Dose	100-600 mg/d PO effective dose 100 mg/d PO for 2 wk initial dose; increase 100 mg every 2 wk; >400 mg/d not shown to be of benefit
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May increase serum carbamazepine levels; carbamazepine may increase levels; phenobarbital may decrease levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Somnolence commonly reported; adjust dose in renal or hepatic failure; kidney stones may occur (4% of patients); skin rash can be serious reaction

Drug Name	Levetiracetam (Keppra)
Description	Used as add-on therapy for partial seizures. Mechanism of action unknown. Has favorable adverse effect profile, with no life-threatening toxicity reported.
Adult Dose	500 mg PO bid initial dose; increase by 1000 mg every 2 wk; typical dose 1000-3000 mg
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Clearance decreased in patients with renal impairment (correlated with CrCl); major side effects include somnolence, asthenia, incoordination, mild leukopenia (3%) and behavioral changes such as anxiety, hostility, emotional lability, depression and psychosis (1-2%), and depersonalization

Drug Name	Pregabalin (Lyrica)
Description	Structural derivative of GABA. Mechanism of action unknown. Binds with high affinity to alpha2-delta site (a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
Adult Dose	75 mg PO bid or 50 mg PO tid initially; if needed, may increase dose to maximum of 600 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May cause additive effects on cognitive and gross motor functioning when coadministered with drugs that cause dizziness or somnolence
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Discontinue gradually (over a minimum of 1 wk) to minimize increased seizure frequency in patients with seizure disorders; may cause insomnia, nausea, headache, or diarrhea with abrupt withdrawal; common adverse effects include dizziness, somnolence, blurred vision, weight gain, and peripheral edema; may elevate creatinine kinase level, decrease platelet count, and increase PR interval; doses >300 mg/d associated with higher rate of adverse effects and treatment discontinuation; decrease dose with renal impairment (ie, CrCl <60 mL/min)

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Patient Education

• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Epilepsy.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• In the United States, each state has its own laws and regulations about driving with epilepsy. Strict enforcement is nonexistent and depends on reporting by patients. In a few states, reporting the condition is mandatory for medical doctors. A loophole exists for interstate drivers, in that state governments have no regulations and regulations are poorly enforced federally. Required seizure-free periods for US drivers range from 3 months (many states) to 2 years (Vermont).

Special Concerns

• Understanding the conceptual difference between seizure and epileptic syndrome is important. An epileptic seizure is defined as a transient neurologic dysfunction resulting from an excessive abnormal electrical discharge of cerebral neurons. The clinical manifestations are numerous, including disturbances of consciousness, changes in emotions, changes in sensation, abnormal movements, and changes in visceral functions or behavior. Epilepsy is a group of disorders characterized by chronic, recurrent, paroxysmal changes in neurologic function caused by abnormalities in electrical activity of the brain. Differentiation is important for the following reasons: (1) permits determination of prognosis, (2) is essential to choosing appropriate drug therapy, and (3) is essential for surgical treatment.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  This graph illustrates the 2 peaks of incidence of epilepsy: early and late in life.
	View Full Size Image
Media type:  Graph

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Benbadis SR, Wolgamuth BR, Goren H, et al. Value of tongue biting in the diagnosis of seizures. Arch Intern Med. Nov 27 1995;155(21):2346-9. [Medline].
• Benbadis SR. Evaluation for surgical treatment of partial epilepsy: an overview. Wis Med J. 1995;94(9):500-4. [Medline].
• Benbadis SR, Luders HO. Epileptic syndromes: an underutilized concept. Epilepsia. Nov 1996;37(11):1029-34. [Medline].
• Benbadis SR, Tatum WO, Vale FL. When drugs don''t work: an algorithmic approach to medically intractable epilepsy. Neurology. Dec 26 2000;55(12):1780-4. [Medline].
• Benbadis SR, Tatum WO. Advances in the treatment of epilepsy. Am Fam Physician. Jul 1 2001;64(1):91-8. [Medline].
• Benbadis SR. Epileptic seizures and syndromes. Neurol Clin. May 2001;19(2):251-70. [Medline].
• Benbadis SR, Tatum WO. Overintepretation of EEGs and misdiagnosis of epilepsy. J Clin Neurophysiol. Feb 2003;20(1):42-4. [Medline].
• Dichter MA, Brodie MJ. New antiepileptic drugs. N Engl J Med. Jun 13 1996;334(24):1583-90. [Medline].
• Engel J. Classifications of the International League Against Epilepsy: time for reappraisal. Epilepsia. Sep 1998;39(9):1014-7. [Medline].
• Luders H, Acharya J, Baumgartner C, et al. Semiological seizure classification. Epilepsia. Sep 1998;39(9):1006-13. [Medline].
• Tatum WO, Galvez R, Benbadis S, Carrazana E. New antiepileptic drugs: into the new millennium. Arch Fam Med. Nov-Dec 2000;9(10):1135-41. [Medline].
• Wyllie E. Treatment of Epilepsy: Principles and Practice. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1996.

Article Last Updated: Oct 11, 2006