eMedicine Specialties > Neurology > Seizures and Epilepsy
Frontal Lobe Epilepsy: Treatment & Medication
Updated: May 7, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- While a first seizure may not be treated, anticonvulsant therapy should be initiated once the diagnosis of epilepsy is established. Many nocturnal episodes with prominent motor manifestations respond extremely well to carbamazepine.
- An increasing number of anticonvulsants approved for use in partial epilepsies are available and may be used as monotherapy or in combination.
- Patients who do not respond to multiple medications may require evaluation for resective surgery. Other options include the ketogenic diet, modified Atkins diet, or vagal nerve stimulator.
- Anticonvulsant medications: While monotherapy is desirable, some patients require polytherapy for adequate seizure control. Choice of therapy may be influenced by factors such as tolerability of side effects and interactions with other medications.
- Older anticonvulsants include phenytoin, carbamazepine, valproic acid, and barbiturates.
- Newer anticonvulsants include gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, zonisamide, oxcarbazepine, and pregabalin.
Surgical Care
Patients with medically intractable epilepsy should be considered for resective epilepsy surgery. If resective surgery is not possible, other surgical options include corpus callosotomy, multiple subpial transections, or the vagal nerve stimulator.
- Resective surgery: Frontal cortical resection is the most commonly performed extratemporal cortical resection for intractable epilepsy.13 Although it is less successful than temporal lobe surgery, advances in presurgical evaluation continue to improve the outcome of frontal resections. Most studies indicate 20-50% of patients become seizure-free, with positive outcomes in up to 70% reported.
- Prognostic factors for good long-term outcome following surgery include no history of febrile seizures, neuroimaging detection of a potentially epileptogenic lesion, and focal beta (fast) ictal discharge on scalp EEG.13 Factors predictive of poor outcome include incomplete resection, tonic seizures, and interictal spikes in follow-up EEG.14 In general, the prognosis is best if a lesion is present and can be resected completely along with the adjacent cortex if it is a part of the epileptogenic zone. Usefulness of resecting areas of interictal spiking is controversial. Most recurrences occur early, typically within 6 months of resection.15
- Intraoperative electrocorticography has prognostic significance, especially if spikes are continuous or nearly so, as is often the case when cortical dysplasia is present. In these instances, absence of postresection epileptiform activity is a strong predictor of a favorable outcome. Although acute postoperative seizures are compatible with long-term seizure reduction following surgery, early postoperative seizure control is a significant prognostic factor for an excellent outcome.
- Besides the risk of cranial surgery, potential complications include motor weakness and behavioral changes.
- Corpus callosotomy
- This procedure is aimed at prevention of bilateral synchrony, thus preventing seizure generalization.
- Partial seizures that do not generalize often do not improve and may worsen.
- With the advent of improved surgical techniques, this procedure rarely is done for well-defined frontal lobe epilepsy.
- Multiple subpial transection
- In this procedure, multiple vertical transections are created, thus interrupting the pathways for horizontal ictal spread while preserving projection fibers important for function.
- It is performed in some centers, often in conjunction with resection, for epileptogenic zones that overlap with eloquent cortex.
- Vagal nerve stimulator
- A stimulator is implanted surgically, which provides stimulation of the left vagus nerve at a preset rate, typically 30 seconds every 5 minutes, and also may be activated by a hand-held magnet.
- This technique allows for patient self-activation of the device during an aura, which may, in some patients, terminate the seizure. The programmed stimulations may improve seizure control even in patients with no aura, allowing self-activation of the device.
Consultations
- Neurology/epileptology
- Patients with frontal lobe seizures should be evaluated by a neurologist.
- Patients with medically intractable frontal lobe epilepsy should be considered for referral to a comprehensive epilepsy center.
- Psychiatry
- Psychiatric or neuropsychiatric consultation may be useful for differentiating between frontal lobe epilepsy and nonepileptic conditions.
- Depression is often a comorbid condition with intractable epilepsy.
Diet
- Ketogenic diet: This high-fat diet, typically with a fat-carbohydrate ratio of 3-4:1, induces ketosis.
- Option for medically refractory epilepsy, most often used for children with symptomatic/cryptogenic generalized epilepsies
- May be difficult to maintain
- Limited experience in adults and in partial epilepsies
- More recently, the modified Atkins diet has been under investigation as an alternative to the ketogenic diet in patients with intractable epilepsy. Early reports are encouraging.16
Activity
- Patients with epilepsy who are not seizure free have the following restrictions:
- Driving: Duration of restriction varies by state.
- Operating heavy machinery
- Activities that involve unprotected heights
- Swimming alone
Medication
Anticonvulsants indicated for use in partial seizures are the medical treatment of choice. Patients generally require many years of treatment, so consideration of side effects is important. While most of the anticonvulsants are in pregnancy category C or D, the risk of medication to the fetus must be weighed against the risk of maternal seizures to the fetus. Because of the risk of level fluctuations, patients should not switch between brand and generic anticonvulsants, and if a generic is used, patients should receive the same generic formulation consistently.
Anticonvulsants
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.
Carbamazepine (Tegretol, Tegretol XR, Carbatrol)
First-line agent for partial seizures with or without secondary generalization; particularly effective in treatment of nocturnal motor/dystonic frontal lobe seizures; potential hematologic and other adverse effects; blood monitoring recommended.
Available as tablets, extended release tablets, extended release capsules, and suspension.
Patients who are not using extended release form often require tid dosing.
Adult
200 mg PO qd or bid initially; increase by 200 mg weekly as needed; maximal recommended dose 1200 mg/d in divided doses, although higher doses may be required in patients on other enzyme-inducing drugs
Pediatric
Small children frequently require suspension
<6 years: 10-20 mg/kg/d PO bid or tid for tab, qid for suspension; increase as needed up to 35 mg/kg/d in divided doses
6-12 years: 100 mg PO bid or half tsp qid; increase as needed by 100 mg/d, up to a maximum of 1000 mg/d in divided doses
>12 years: Administer as in adults
Danazol may increase serum levels significantly within 30 d (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 (their coadministration may increase carbamazepine levels)
Documented hypersensitivity; history of bone marrow depression; MAOIs within last 14 d
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBCs and serum iron at baseline prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness
Phenytoin (Dilantin Kapseals, Dilantin Infatabs)
Available as tab, cap, infatab, and susp. First-line agent for partial seizures; advantages include quickly achieving therapeutic level and possibility of once daily dosing (Dilantin Kapseals), which increases compliance.
Adult
Some patients require oral loading to attain therapeutic level quickly; phenytoin can be loaded as 1 g divided in 3 doses (400 mg-300 mg-300 mg) at 2-h intervals; maintenance dose of 300 mg/d should be started 24 h after loading; if patients are not to be loaded, initiate dosing at 300 mg/d, as tid, bid, or qd; further dosage increase should be based on response to treatment; because of zero order kinetics, increase by 30 mg or 50 mg
IV administration should be reserved for situations such as status epilepticus or for patients with IV access only; IV loading dose is 15-20 mg/kg; fosphenytoin is more expensive than IV phenytoin, but does not cause tissue necrosis or irritation when extravasated and may be given IM
Pediatric
<6 years: Initiate at 5 mg/kg/d PO in 2-3 divided doses; maintenance dose is 4-8 mg/kg
>6 years: May require adult dosing
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity
Barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid
Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Rapid IV infusion may result in death from cardiac arrest, marked by QRS widening
Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; caution in acute intermittent porphyria and diabetes (may elevate blood glucose level); discontinue use if hepatic dysfunction occurs
Valproic acid, divalproex sodium (Depakote, Depakene, Depacon)
Available as tablets, capsules, syrup, sprinkles, injection. Although considered first-line agent for treatment of primary generalized epilepsy, indicated for partial seizures as well, particularly for patients with secondary generalization. Must be used cautiously in women of childbearing age; has limited use in young children because of risk of hepatic failure, which may be fatal.
Adult
10-15 mg/kg/d PO in divided doses; increase by 5-10 mg/kg/d every wk; usual maximum dose 60 mg/kg/d
Alternatively, 20 mg/min IV 60-min infusion; faster rates have been used
Pediatric
<2 years: Not established; risk of hepatic failure
>2 years: Administer as in adults
Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may reduce levels significantly; in children, salicylates decrease protein binding and metabolism of valproate; 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); may increase zidovudine levels in HIV-seropositive patients
Documented hypersensitivity; hepatic disease/dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
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; determine platelet counts and bleeding time before initiating therapy, at periodic intervals, and prior to surgery; reduce dose or discontinue therapy if hemorrhage, bruising, or hemostasis/coagulation disorder occurs; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness
Gabapentin (Neurontin)
Indicated for use in partial seizures with and without secondary generalization; has relatively few drug interactions and adverse effects.
Adult
300 mg PO bid or tid; may be increased weekly up to 1800-2400 mg/d in divided doses; some patients require doses as high as 3600 mg/d or higher; renally excreted, dosage adjustment necessary for patients with renal dysfunction
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Antacids may significantly reduce bioavailability (administer at least 2 h following antacids); may increase norethindrone levels significantly
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 severe renal disease
Lamotrigine (Lamictal)
Newer agent, effective for partial seizures with or without secondary generalization. Main side effect of concern is rash, which may be severe.
Adult
Dosing depends on coadministration of other anticonvulsants, specifically valproate; see dosing instructions for specific guidelines; slow titration recommended to prevent rash
Pediatric
Not established
Acetaminophen increases renal clearance, decreasing effects; similarly, phenobarbital and phenytoin increase lamotrigine metabolism, causing decrease in lamotrigine 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
Serious or life-threatening rash, more likely children and patients on valproate; while many other adverse effects reported, all are infrequent or rare
Levetiracetam (Keppra)
Newer agent, effective for partial seizures with or without secondary generalization. Few adverse effects, no drug-drug interactions. Does not require blood monitoring, although slight decreases in RBC and WBC counts have been reported.
Adult
500 mg PO bid, increase additional 1000 mg/d in divided dosing every 2 wk to maximum recommended daily dosage of 3000 mg; slower titration may be better tolerated by some patients; no IV form available; requires adjustment for impaired renal function
Pediatric
Not established
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
Somnolence, coordination abnormalities, and behavioral abnormalities may occur; requires adjustment for impaired renal function
Oxcarbazepine (Trileptal)
Indicated as monotherapy or adjunctive therapy in treatment of partial seizures with or without secondary generalization. Mechanism of action similar to that of carbamazepine, without metabolism to epoxide. Active metabolite MHD (monohydroxy derivative).
If patient being converted from carbamazepine to oxcarbazepine, the inducing effect of carbamazepine on cytochrome P-450 enzymes will be reduced, and other AEDs may need adjustment. No IV form available. If added to phenytoin, may elevate phenytoin levels by as much as 20%.
Adult
Monotherapy: 150 mg or 300 mg PO bid initially; dose may be increased by 300 mg/d q3d; maximum recommended daily dose of 1200-2400 mg in divided dosing; elderly patients may require slower titrations
Pediatric
Approved for use as adjunctive therapy in children aged 4-16 years
Initiate at 8-10 mg/kg PO, generally not to exceed 600 mg/d in divided dosing; target dose based on weight
20-29 kg: 900 mg/d
29-39 kg: 1200 mg/d
>39 kg: 1800 mg/d
Increases phenytoin level; may interact with oral contraceptives, calcium channel blockers
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
Hyponatremia may be clinically significant with sodium <125; serum sodium measurement recommended; somnolence, concentration difficulty, ataxia
Topiramate (Topamax)
Indicated for adjunctive treatment of partial seizures with or without secondary generalization, and for tonic-clonic seizures. Approved for adults and for children aged 2-16. Has multiple mechanisms of action.
Adult
25-50 mg/d PO for 1 wk, then increase by 25-50 mg/d every wk in bid dosing to therapeutic dose of 200-400 mg/d
Pediatric
1-3 mg/kg/d PO for 1 wk, then increase by 1-3 mg/kg/d PO every 1-2 wk to target dose of 5-9 mg/kg/d taken bid
Phenytoin, carbamazepine, and valproic acid can decrease levels significantly; reduces digoxin and norethindrone levels; carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use with extreme caution concurrently with CNS depressants since may have an additive effect in CNS depression, as well as other cognitive or neuropsychiatric adverse events
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
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
Zonisamide (Zonegran)
Indicated for adjunctive treatment of partial seizures with or without secondary generalization. Evidence that is effective in myoclonic and other generalized seizure types as well.
Adult
100 mg/d PO for 2 wk, then increase by 100 mg/d every 2 wk to maximum of 400 mg/d; may be given qd or bid
Pediatric
Not established
May increase serum carbamazepine levels; carbamazepine may increase concentrations; phenobarbital may decrease 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
Tiagabine (Gabitril)
Indicated for adjunctive treatment of partial seizures with or without secondary generalization.
Mechanism of antiseizure action unknown. Believed to be related to ability to enhance activity of GABA, major inhibitory neurotransmitter in CNS.
Adult
Begin at 4 mg/d PO for 1 wk, increase by 4-8 mg/d per wk to maximum of 56 mg/d in 2-4 daily doses
Pediatric
Not established
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
Patients receiving valproate monotherapy may require lower doses or slower dose titration 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 of tiagabine; tiagabine should be withdrawn slowly to reduce potential for increased seizure frequency
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.
Adult
75 mg PO bid or 50 mg PO tid initially; 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)
More on Frontal Lobe Epilepsy |
| Overview: Frontal Lobe Epilepsy |
| Differential Diagnoses & Workup: Frontal Lobe Epilepsy |
 Treatment & Medication: Frontal Lobe Epilepsy |
| Follow-up: Frontal Lobe Epilepsy |
| References |
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Further Reading
Keywords
frontal lobe epilepsy, supplementary motor area seizures, primary motor cortex seizures, medial frontal seizures, cingulate gyrus seizures, orbitofrontal seizures, frontopolar seizures, dorsolateral cortex seizures, operculum seizures, seizure treatment, epilepsy treatment
