eMedicine Specialties > Neurology > Seizures and Epilepsy
Simple Partial Seizures: Treatment & Medication
Updated: Sep 3, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Numerous antiepilepsy drugs (AEDs) currently are approved worldwide with indications for SPS, and others are in development.
- No one drug of choice is recommended for SPS, since in clinical trials all the drugs have demonstrated similar levels of efficacy.
- Selection of the most appropriate medication is based on potential side effects, dosing schedules, available formulations, and individual factors.15,16,17,18,19
- Benign focal epilepsy of childhood is usually a self-limited condition; if no seizures with secondarily generalization occur, patient care need not include AEDs.
Surgical Care
- Patients with medically refractory seizures may be candidates for epilepsy surgery, especially if they have a well-localized seizure onset documented by video-EEG and a corresponding lesion on neuroimaging. Such cases should be carefully evaluated preoperatively with the resection properly planned by the epilepsy surgical team to minimize the risk of postoperative deficit.
- Focal cortical resection, amygdalo-hippocampectomy, lesionectomy, or gamma knife surgery may be the most appropriate procedure. The specific procedure should be tailored individually to the features of each case.
- Rasmussen encephalitis responds poorly to medical treatment and usually is treated by hemispherectomy to prevent involvement of the contralateral hemisphere.
- Patients whose seizures are medically refractory but are not good candidates for epilepsy surgery may be candidates for implantation of a vagal nerve stimulator (VNS).
Consultations
- Cardiac, gastrointestinal, psychiatric, or endocrine consultation, depending on individual cases, may be necessary in diagnostically difficult cases.
- Psychiatric consultation may be necessary for management of concurrent depression, anxiety, and/or non-epileptic events.
Diet
- Although a ketogenic diet has been used successfully in refractory seizures, it is not used commonly for patients exhibiting SPS exclusively (except children) who are not responding to medication.20
- The medium-chain triglyceride diet is more convenient and palatable, and does not result in hypercholesterolemia, although it appears to be less successful in the treatment of refractory seizures.21 The Atkins diet has also been reported to have some adjunctive benefit to some patients with refractory seizures.22
Activity
- As SPS do not impair consciousness, activity may not need to be restricted severely as with other types of seizures.
- Compliant patients with a consistent, exclusively SPS pattern, which does not interfere with the ability to manipulate the controls of a motor vehicle, are allowed legally to drive in states in which the motor vehicle authority approves exceptions to complete seizure control. Compliance with state guidelines may require self-reporting by patients or specific documentation of patient symptoms, compliance, and medications by the treating physician.
- The safety of swimming and other potentially hazardous recreational or employment activities should be evaluated on an individual basis.
- The ability to care for infants in an unsupervised setting should be evaluated on an individual basis.
Medication
Many anticonvulsants currently are approved by the US Food and Drug Administration (FDA) for partial seizures with and without secondary generalization. These drugs have approval for treatment of SPS as well. No single agent is the drug of choice for SPS.
Anticonvulsants
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.
Carbamazepine (Tegretol, Tegretol-XR, Carbatrol, Epitol)
Tricyclic compound extensively metabolized to active metabolite, CBZ-epoxide. Markedly induces its own metabolism and highly bound to plasma proteins. Available as 100 mg/mL susp; 100 mg chewable tab; 200 mg tab; 100, 200, and 400 mg delayed-release tab (Tegretol-XR); 200, 300 mg extended-release capsules (Carbatrol).
Adult
8-20 mg/kg/d PO bid/qid (all formulations—susp, chewable, or tab)
Pediatric
10-35 mg/kg/d PO bid/qid (all formulations—susp, chewable, or tab)
Decreases estrogen and progestin plasma concentrations with concurrent use of oral contraceptives; also decreases levels of cyclosporin, corticosteroids, protease inhibitors, theophylline, tricyclic antidepressants, antipsychotics, and warfarin
May increase danazol levels significantly within 30 days of coadministration (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels—either may increase carbamazepine level; propoxyphene, macrolides may increase carbamazepine levels
Documented hypersensitivity; concurrent MAOIs
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Common adverse effects include drowsiness, dizziness, diplopia, ataxia, blurry vision, osteopenia, peripheral neuropathy, hyponatremia, and alopecia
Idiosyncratic adverse effects include skin rash, hepatotoxicity, and rarely blood dyscrasias; caution with increased intraocular pressure; obtain CBCs and serum iron baseline prior to treatment, during first 2 months, and yearly or every other year thereafter; caution while driving or performing other tasks requiring alertness
Divalproex sodium (Depacon, Depakene, Depakote, Depakote-ER)
Branched chain fatty acid that undergoes oxidative metabolism and is highly protein bound. Amount of protein binding increases with dose. Available as 250 mg/5 mL syr; 250 mg capsules; 125 mg sprinkle capsules; 125, 250, 500 mg delayed-release tab; 250 and 500 mg extended-release tab, 100 mg/mL injectable solution.
Adult
Initial dose: 5-15 mg/kg/d PO
Maintenance dose: 15-60 mg/kg/d PO bid/qid
Pediatric
15-60 mg/kg/d PO bid/qid
Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce levels; in children, salicylates decrease protein binding and metabolism; may result in variable changes of carbamazepine concentrations with possible loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels while either may decrease valproate levels; may displace warfarin from protein-binding sites (monitor coagulation tests); salicylates displace valproate from plasma protein-binding sites; methylphenidate may increase toxicity; may increase zidovudine levels
Documented hypersensitivity; preexisting hepatotoxicity; age <2 y
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Common adverse effects include nausea, vomiting, drowsiness, tremor, dizziness, alopecia, weight gain, and thrombocytopenia at high serum concentrations
Idiosyncratic adverse effects include hepatotoxicity (especially children aged <2 y), pancreatitis, and blood dyscrasias
Thrombocytopenia and abnormal coagulation parameters have occurred—risk of thrombocytopenia increases significantly at total trough plasma concentrations >110 mcg/mL in females and 135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or hemostasis/coagulation disorder occur; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting
Gabapentin (Neurontin)
Saturable gastric absorption with virtually no protein binding and no metabolism, primarily renal excretion. Available as 100, 300, 400 mg capsules, and 600 mg and 800 mg tab, and 50 mg/mL solution.
Adult
300-1200 mg PO tid
Pediatric
30-60 mg/kg/d PO tid
Antacids may reduce bioavailability significantly (administer at least 2 h following antacids)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include fatigue, somnolence, dizziness, ataxia, ankle swelling, and mild weight gain; caution in severe renal disease
Lamotrigine (Lamictal)
Hepatically metabolized, moderate protein binding, with shorter half-life in presence of enzyme-inducing compounds. Available as 2, 5, and 25 mg dispersible tab; 25, 100, 150, and 200 mg tab.
Adult
With valproic acid: 200 mg PO qd
Without valproic acid: 300-500 mg/d PO bid
Pediatric
With valproic acid: 1-5 mg/kg/d PO qd or divided bid
Without valproic acid: 5-15 mg/kg/d PO qd or divided bid
Oral contraceptives may decrease lamotrigine levels; acetaminophen increases renal clearance, decreasing effects; similarly, phenobarbital and phenytoin increase metabolism, causing decrease in levels; valproic acid increases half-life
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include dizziness, ataxia, sedation, diplopia, and nausea
Idiosyncratic adverse effects include skin rash (risk of Stevens-Johnson especially increased in children, polytherapy with valproic acid, and with rapid dose titration), hepatotoxicity, and blood dyscrasias
Caution in impaired renal or hepatic function
Phenobarbital (Barbital, Luminal, Solfoton)
Highly metabolized, moderately protein bound with very long half-life and linear kinetics. Available as 16 mg capsule; 15, 20 mg/5 mL elixir; 15, 30, 60, 100 mg tab; 30 mg/mL, 60 mg/mL, 130 mg/mL injectable solution (all contain 69% propylene glycol).
Adult
Loading dose: 10-20 mg/kg PO qd
Maintenance dose: 1-3 mg/kg/d PO qd
Pediatric
Neonates: 3-4 mg/kg/d PO qd
<12 years: 3-7 mg/kg/d PO qd/bid
May decrease effects of chloramphenicol, digoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients whose coagulation tests are stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities may also occur)
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Adverse effects include sedation, dizziness, mood change, insomnia, hyperkinesias, cognitive dysfunction, osteomalacia, Dupuytren contracture, frozen shoulder, and decreased libido
Idiosyncratic adverse effects include skin rash, hepatotoxicity, and blood dyscrasias
In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia, since adverse reactions can occur; caution in myasthenia gravis and myxedema
Phenytoin (Dilantin, Phenytek)/ Fosphenytoin (Cerebyx)
Poorly soluble compound, highly protein bound, metabolized by cytochrome P-450 system, and has nonlinear pharmacokinetics.
Available as 125 mg/5 mL susp; 50 mg chewable tab; 30 mg capsules; 100 mg capsules; 50 mg/mL injectable phenytoin solution (contains propylene glycol).
Fosphenytoin is phosphorylated phenytoin, a prodrug that is highly soluble and converted rapidly to phenytoin; 50 mg phenytoin equivalent per mL solution (fosphenytoin).
Adult
Loading dose: 15-20 mg/kg PO; 10-20 mg/kg IV PE
Maintenance dose: 4-5 mg/kg/d PO qd/tid
Pediatric
4-7 mg/kg/d PO
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, ethanol (acute ingestion), omeprazole, phenacemide, phenylbutazone, succinimides, fluconazole, isoniazid, metronidazole, miconazole, sulfonamides, trimethoprim, and valproic acid may increase toxicity; phenytoin decreases efficacy of oral contraceptives
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Death from cardiac arrest has occurred after too-rapid IV administration of phenytoin, preceded sometimes by marked QRS widening (not reported with fosphenytoin)
Blood dyscrasias have occurred and thus blood counts and urinalysis should be done when therapy is begun and at monthly intervals for several months thereafter; discontinue use if skin rash appears—do not resume use if rash is exfoliative, bullous, or purpuric; administer cautiously to patients with acute intermittent porphyria; exercise caution when administering to patients with diabetes, may raise blood glucose levels; discontinue drug if hepatic dysfunction occurs
Primidone (Mysoline)
Metabolized to phenobarbital and phenylethylmalonamide (PEMA), which also possesses some weak anticonvulsant activity. Available as 250 mg/5 mL susp; 50, 250 mg tab.
Adult
250-2000 mg PO tid
Pediatric
10-25 mg/kg/d PO tid
Valproic acid increases toxicity; may decrease serum concentrations of ethosuximide, griseofulvin, valproic acid; phenytoin may decrease serum levels
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Common adverse effects include sedation, dizziness, mood change, insomnia, hyperkinesias, cognitive dysfunction, osteomalacia, Dupuytren contracture, frozen shoulder, and decreased libido
Idiosyncratic adverse effects include skin rash, hepatotoxicity, and blood dyscrasias
Tiagabine (Gabitril)
GABA reuptake inhibitor, with its metabolism enhanced by cytochrome P-450 inducers. Highly protein bound. Available as 2, 4, 12, and 16 mg tab.
Adult
32-56 mg/d PO bid/qid
Pediatric
4-32 mg/kg/d PO bid/qid
Cleared more rapidly in patients treated with carbamazepine, phenytoin, primidone, or phenobarbital than in patients who have not received these drugs
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include dizziness, asthenia, sedation, nervousness, irritability, and tremor, "knee-buckling"
Patients receiving valproate monotherapy may require lower doses or slower dose titration of tiagabine for clinical response; moderately severe to incapacitating generalized weakness has been reported following administration of tiagabine in as many as 1% of patients with epilepsy—weakness may resolve after reduction in dose or discontinuation; should be withdrawn slowly to reduce potential for increased seizure frequency; possible nonconvulsive status epilepticus in patients noted to have new altered mental status; can trigger seizures in nonepileptic patients
Topiramate (Topamax)
Undergoes moderate hepatic metabolism, and excreted largely by kidneys. Has low protein binding. Available as 15, 25 mg sprinkle capsules; 25, 100, and 200 mg tab.
Adult
200-600 mg/d PO bid
Pediatric
1-9 mg/kg/d PO bid
Phenytoin, carbamazepine, and valproic acid can decrease levels significantly; reduces digoxin and norethindrone levels; CNS depressants may have additive effect as well as other adverse cognitive or neuropsychiatric events, use with caution
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include sedation, fatigue, psychomotor slowing, difficulty in concentrating, confusion, paresthesias, weight loss
Risk of developing kidney stone increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; carbonic anhydrase inhibitor chemistry also increases risk of angle-closure glaucoma, mild metabolic acidosis, and oligohidrosis
Oxcarbazepine (Trileptal)
The pharmacological activity of oxcarbazepine is primarily performed by the 10-monohydroxy metabolite (MHD) of oxcarbazepine. May block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. 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 a 30-40% increased clearance compared with older children and adults. Available as 150-, 300-, and 600-mg tab and 300 mg/5 mL solution.
Adult
600-2400 mg/d PO bid
Pediatric
6-50 mg/kg/d PO bid
May decrease levels of dihydropyridine calcium antagonists and oral contraceptives; can reduce serum concentrations of carbamazepine, phenobarbital, phenytoin, and valproic acid; when oxcarbazepine is given in doses above 1200 mg/d, may increase phenytoin and phenobarbital serum concentrations significantly; oxcarbazepine may reduce serum concentrations of oral contraceptives; can increase clearance of felodipine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Can cause cognitive side effects; in persons with impaired renal function (creatinine clearance <30 mL/min), oxcarbazepine dose should begin at one-half usual starting dose; dose increments should be made more slowly; oxcarbazepine can cause hyponatremia (sodium <125 mmol/L); among persons with hypersensitivity to carbamazepine, 25-30% will have hypersensitivity to oxcarbazepine; rapid withdrawal of oxcarbazepine can cause exacerbation of seizures; observe for side effects and monitor plasma levels of concomitant anticonvulsants during dose titration; idiosyncratic reactions reported (serious skin rash and hypersensitivity syndrome)
Levetiracetam (Keppra)
Mechanism of action is unknown. Approved for adjunctive use in partial epilepsy. Available as 250-, 500-, 750-, and 1000-mg tab and 100 mg/mL solution.
Adult
1-3 g/d PO bid
Pediatric
10-30 mg/kg/d PO bid
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment; 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
Zonisamide (Zonegran)
Indicated for adjunctive treatment of partial seizures with or without secondary generalization. Available as 25-, 50-, and 100-mg sprinkle cap. There is evidence that it is effective in myoclonic and other generalized seizure types as well.
Adult
200-600 mg/d PO qd
Pediatric
2-12 mg/kg/d PO bid
May increase serum carbamazepine levels; carbamazepine may increase zonisamide concentrations; phenobarbital may decrease zonisamide levels
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause drowsiness, weight loss, ataxia, nausea, and slowing of mental activity
As carbonic anhydrase inhibitor can increase risk of renal stones and oligohidrosis
Pregabalin (Lyrica)
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.
Available as 25, 50, 75, 100, 150, 200, 225, 300 mg capsules
Adult
150-600 mg/d PO divided bid/tid; initially 50 mg PO tid or 75 mg PO bid, if needed, may increase dose to maximum of 600 mg/d
Pediatric
Not established
May cause additive effects on cognitive and gross motor functioning when coadministered with drugs that cause dizziness or somnolence
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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)
Lacosamide (Vimpat)
Selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. Indicated for adjunctive therapy for partial onset seizures.
Adult
50 mg PO bid initially; may increase at weekly intervals in 100-mg/d increments to a daily dose range of 200-400 mg/d
Switching from PO to IV: Initial total daily IV dose should be equivalent to total daily PO dose and infused IV over 30-60 min; also may divide total daily dose bid for up to 5 d
Switching from IV to PO: Switch to PO administration at equivalent daily dosage and frequency of IV administration
CrCl <30 mL/min: Not to exceed 300 mg/d
Mild-to-moderate hepatic impairment: Not to exceed 300 mg/d
Hemodialysis: Supplement with 50% of dose following 4-h hemodialysis
Pediatric
<17 years: Not established
>17 years: Administer as in adults
Data limited; CYP2C19 substrate; caution if coadministered with other drugs that affect heart conduction (eg, antiarrhythmic agents, drugs that increase PR interval)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with suicidal ideation and monitor for emergence or worsening of depression, suicidal thoughts or behavior, or unusual changes in mood or behavior; common adverse effects (>10%) include diplopia, headache, dizziness, and nausea; dose-dependent prolongation of PR interval may occur; patients with diabetic neuropathy may experience atrial fibrillation, atrial flutter, or syncope; warn patients that dizziness or ataxia may occur and to not abruptly discontinue drug; as with all antiepileptic drugs, withdraw gradually (over minimum of 1 wk) to decrease risk of increased seizure activity; 1 case of multiorgan hypersensitivity reaction observed (n=4011); shown in rats during neonatal and juvenile rats to interfere with CRMP-2 activity (protein involved in neuronal differentiation and axonal outgrowth) activity
More on Simple Partial Seizures |
| Overview: Simple Partial Seizures |
| Differential Diagnoses & Workup: Simple Partial Seizures |
 Treatment & Medication: Simple Partial Seizures |
| Follow-up: Simple Partial Seizures |
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References
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Further Reading
Keywords
focal seizures, simple localization-related epilepsy, SPS, epilepsy, simple partial status epilepticus, SPSE, epilepsia partialis continua, Kojewnikoff syndrome, periodic lateralized epileptiform discharges, PLEDs, Landau-Kleffner syndromes, epileptogenic zone, partial seizures, simple partial seizures
