AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

Frontal lobe epilepsy is characterized by recurrent seizures arising from the frontal lobes. Frequently, seizure types are simple partial or complex partial, often with secondary generalization. Clinical manifestations tend to reflect the specific area of seizure onset and range from behavioral to motor or tonic/postural changes. Status epilepticus may be associated more commonly with frontal lobe seizures than with seizures arising from other areas.

Pathophysiology

Seizures may arise from any of the frontal lobe areas, including orbitofrontal, frontopolar, dorsolateral, opercular, supplementary motor area, motor cortex, or cingulate gyrus.

Disease conditions commonly associated with frontal lobe epilepsy are frequently symptomatic, including congenital causes such as cortical dysgenesis, gliosis, or vascular malformations; neoplasms; head trauma; infections; and anoxia.

With recent advances in genetic analysis, an expanded number of genetically inherited frontal lobe epilepsy syndromes have been described. Many of these syndromes are characterized by autosomal dominant inheritance.

Frequency

United States

The exact incidence of frontal lobe epilepsy is not known. In most centers frontal lobe epilepsy accounts for 20-30% of operative procedures involving intractable epilepsy.

Sex

No significant gender-based frequency difference has been reported for frontal lobe epilepsy.

Age

• Symptomatic frontal lobe epilepsy may affect patients of all ages.
• In a large series of cases, mean subject age was 28.5 years with age of epilepsy onset 9.3 years for left frontal epilepsy and 11.1 years for right frontal epilepsy.

CLINICAL

Section 3 of 10  

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

History

• Patients with frontal lobe seizures may present with a clear epileptic syndrome or with unusual behavioral or motor manifestations that are not immediately recognizable as seizures. A careful history should focus on specific characteristics of the episodes, including a detailed description by eyewitnesses, time and pattern of occurrence, precipitating factors, and response to medication.
• Features that help to distinguish frontal lobe seizures from nonepileptic events include stereotyped semiology, occurrence during sleep, brief duration (often <30 seconds), rapid secondary generalization, prominent motor manifestations, and complex automatisms. Despite this, the distinction remains very difficult to make on the basis of history alone, and patients with frontal lobe epilepsy often are directed first to psychiatrists rather than to neurologists. Details obtained about the seizure semiology may help to identify the specific frontal region of onset.
• • Prominent speech disturbances - May indicate dominant hemisphere involvement
  • Supplementary motor area (SMA) - Typically involve unilateral or asymmetric bilateral tonic posturing; may be associated with facial grimacing, vocalization, or speech arrest; seizures frequently preceded by a somatosensory aura; complex automatisms such as kicking, laughing, or pelvic thrusting may be present; responsiveness often preserved
  • Primary motor cortex - Usually simple partial motor seizures with clonic or myoclonic movements and preserved consciousness; jacksonian spread to adjacent cortical areas may occur, and secondary generalization is frequent; speech arrest and contralateral adversive or dystonic posturing may be present
  • Medial frontal, cingulate gyrus, orbitofrontal, or frontopolar regions - Complex behavioral events characterized by motor agitation and gestural automatisms; viscerosensory symptoms and strong emotional feelings often described; motor activity repetitive and may involve pelvic thrusting, pedaling, or thrashing, often accompanied by vocalizations or laughter/crying; seizures often bizarre and may be diagnosed incorrectly as psychogenic
  • Dorsolateral cortex - Tonic posturing or clonic movements often associated with either contralateral head and eye deviation, or less commonly, ipsilateral head turn
  • Operculum - Swallowing, salivation, mastication, epigastric aura, fear, and speech arrest often associated with clonic facial movements; gustatory hallucinations also may occur
  • Nonlocalizable frontal seizures - Rare, manifesting as brief staring spells accompanied by generalized spike/wave on EEG, which may be difficult to distinguish from primarily generalized absence seizures; may present as generalized tonic-clonic seizures without obvious focal onset
  • Nocturnal frontal lobe epilepsy - Autosomal dominant inheritance; seizures occur mainly during sleep; characterized by marked motor manifestations, including dystonic posturing, jerking, bending, and rocking; difficult to distinguish from parasomnias

Physical

A general physical and thorough neurologic examination should be performed in all patients with epilepsy.

• General examination
• • Signs suggestive of syndromes that may be associated with epilepsy, such as facial dysmorphisms
  • Skin abnormalities such as cafe-au-lait spots, hypomelanotic macules, or neurofibromas suggesting neurocutaneous syndromes
• Neurologic examination
• • As structural lesions are common, high incidence of neurologic abnormalities in patients with frontal lobe epilepsy
  • Particular emphasis on the motor examination

Causes

The majority of frontal lobe seizures are thought to be symptomatic, although many patients with frontal lobe seizures have no obvious lesions on MRI.

Significant advances in molecular genetic approaches have identified the genetic defects related to a family of frontal lobe epilepsies known as autosomal dominant nocturnal frontal lobe epilepsies (ADNFLE).

• Tumors
• • Recent reviews indicate that the epileptogenic lesion in approximately one third of patients with refractory frontal lobe seizures is a tumor.
  • Common pathologies include gangliogliomas, low-grade gliomas, and epidermoid tumors. High-grade tumors more often present with headache or focal deficits, but many are associated with seizures at some time in their course.
• Head trauma
• • Head trauma is a very frequent cause of damage to the frontal lobes. Risk of later epilepsy depends largely on the severity of trauma. The first seizure usually occurs within months, but may not occur for many years.
  • Pathologic examination of the frontal lobe frequently reveals meningocerebral cicatrix.
• Vascular malformations
• • Three main types are recognized—arteriovenous malformations, cavernous angiomas, and venous angiomas.
  • Arteriovenous malformations and cavernous angiomas are more likely to cause seizures than venous angiomas.
• Developmental lesions
• • With improvements in neuroimaging, cortical dysplasias increasingly are being recognized as epileptogenic lesions.
  • Other common developmental causes of frontal lobe seizures include hamartomas and nodular heterotopias.
• Gliosis
• • Gliosis is identified in many pathologic specimens following surgical resection for frontal lobe epilepsy.
  • It may follow head trauma, neonatal anoxia, or previous resection; often no cause is identified.
• Encephalitis: While encephalitis commonly produces temporal lobe epilepsy, frontal lobe seizures may occur.
• Inherited frontal lobe epilepsy
• • Three types of ADNFLE have been described. They are clinically characterized by brief nocturnal motor seizures that often occur in clusters, mainly during non-REM sleep. Seizures may also occur during daytime naps. A brief aura is typically followed by hyperkinetic or tonic activity, and typically shows a good response to carbamazepine. Differentiation from parasomnias remains a challenge.
  • ADNFLE was the first partial epilepsy identified as a single gene disorder. Mutations in 2 nicotinic acetylcholine receptor genes (nAChR alpha4 and beta2 subunits) have been associated with ADNFLE, with a third potential locus identified. Nicotine use is reported to be associated with decreased seizure frequency in patients with these mutations. Positron emission tomography studies in ADNFLE demonstrate decreased nAChR density in the right dorsolateral prefrontal region, but increased density in mesencephalon.
  • Other familial frontal lobe epilepsies have been identified, including a familial partial epilepsy with variable foci linked to chromosome 22.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Nocturnal paroxysmal dystonia (unclear if this represents an independent entity)

WORKUP

Section 5 of 10  

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

Lab Studies

• Blood tests should be performed to rule out a metabolic cause of new-onset seizures, eg, hypoglycemia or hypomagnesemia. Once the diagnosis of epilepsy is established, blood testing remains important in the management of patients who are taking anticonvulsants. Blood monitoring should be guided by the likely complications of a given anticonvulsant and, more importantly, by patient risk factors and symptoms.
• • Complete blood cell count: Monitor for neutropenia and thrombocytopenia.
  • Liver function tests
  • Anticonvulsant levels: Most anticonvulsants have a typical therapeutic window, although these levels should be used only as a guide; levels are less frequently monitored for the newer anticonvulsant agents.

Imaging Studies

• MRI
• • The imaging modality of choice in patients with frontal lobe seizures is MRI. Recent advances in MRI have improved the identification of underlying lesions, which are reported to be present in up to 50% of patients with frontal lobe epilepsy.
  • Optimally, MRI with gadolinium should be obtained with high resolution, 1 mm thick slices, and multiple sequences. If EEG or other testing indicates a potential epileptogenic zone, thin slices through the area of interest should be requested. Three-dimensional MRI may further increase the yield of testing.
• Position emission tomography
• • Position emission tomography is being used increasingly in the presurgical evaluation of patients with extratemporal epilepsy.
  • Interictal hypometabolism, reflective of focal dysfunction, may be seen in areas that were normal on MRI, although this finding is better established for temporal than for frontal lobe epilepsy. The role of tracer-imaging functions other than glucose metabolism, such as benzodiazepine receptors, still is being defined.
  • Decreased thalamic metabolism ipsilateral to the seizure focus may be seen in nonlesional frontal lobe epilepsy, particularly in association with a long duration of intractability.
• Single-photon emission computed tomography
• • Ictal single-photon emission computed tomography (SPECT) scan may be obtained during prolonged video-EEG monitoring.
  • Hyperperfusion seen on ictal SPECT scan is suggestive of an area of seizure onset. Sensitivity of ictal SPECT hyperperfusion is reported to be higher in frontal lobe epilepsy than in temporal lobe epilepsy.
  • As seizures in patients with frontal lobe epilepsy are often brief and may generalize rapidly, obtaining an ictal SPECT scan is difficult.
• Magnetic resonance spectroscopy
• • Magnetic resonance spectroscopy (MRS), while still mainly an experimental testing modality, is being increasingly used in the presurgical evaluation of intractable epilepsy.
  • MRS may demonstrate decreased NA/Cr ratios in the frontal epileptogenic zone, consistent with abnormalities of energy metabolism.

Other Tests

• Scalp EEG and prolonged video-EEG monitoring: All patients with frontal lobe epilepsy should undergo EEG evaluation. Patients with intractable epilepsy, or in whom the diagnosis is doubtful, should undergo prolonged video-EEG monitoring. If the events are primarily or exclusively nocturnal, polysomnography should be considered, with extended EEG montages if available.
• • Interictal EEG
    • Findings may be normal.
    • Spikes or sharp waves may be absent; may appear maximal unilaterally, bilaterally, or in the midline; or may appear generalized due to secondary bilateral synchrony.
    • Background rhythm abnormalities with or without focal slowing may be present.
  • Ictal EEG
    • Closely spaced frontal electrodes can enhance localization.
    • Ictal onset often is seen poorly from the scalp and is highly variable in appearance.
    • Muscle artifact may obscure EEG.
    • Lack of ictal discharge in the temporal lobes suggests a frontal onset.
    • Video analysis of seizure semiology may suggest frontal epilepsy.
    • Postictal slowing also can be confirmatory, and at times, localizing or lateralizing.
• Intracranial EEG: Patients with suspected frontal lobe epilepsy frequently require invasive EEG monitoring. Intracranial EEG is used for localizing the epileptogenic region and for functional mapping prior to resection. Electrode coverage of both frontal and temporal (and/or parietal) lobes may be needed.
• • Stereotactically placed depth electrodes have the greatest accuracy if the area of interest is well defined, but records from a small anatomic area.
  • Subdural strips and grids have less hemorrhagic risk, sample more broadly, and can be used to perform cortical mapping, but have higher infection risk and less anatomic specificity. Epidural pegs and screws are used less often than either depth or subdural electrodes.
  • Ictal onset most often appears as a low-voltage, high-frequency discharge (ie, buzz), although rhythmic activity at alpha, theta, or delta frequencies may be seen. Because of rapid bilateral synchrony, discharge on scalp recording may appear bilateral.

Histologic Findings

Tissue from surgical resections for intractable frontal lobe epilepsy may demonstrate evidence of a developmental lesion, tumor, gliosis, or vascular malformation.

TREATMENT

Section 6 of 10  

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

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 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, and oxcarbazepine.

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. 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. 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.
  • 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 - 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
  • The role for the Atkins and other low-carbohydrate diets in the treatment of intractable epilepsy has not yet been defined but is under investigation.

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

Section 7 of 10  

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

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.

Drug Category: Anticonvulsants

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Drug Name	Phenytoin (Dilantin Kapseals, Dilantin Infatabs)
Description	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 Dose	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 Dose	<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
Contraindications	Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome
Interactions	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
Pregnancy	D - Unsafe in pregnancy
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

Drug Name	Valproic acid, divalproex sodium (Depakote, Depakene, Depacon)
Description	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 Dose	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 Dose	<2 years: Not established; risk of hepatic failure >2 years: Administer as in adults
Contraindications	Documented hypersensitivity; hepatic disease/dysfunction
Interactions	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
Pregnancy	D - Unsafe in pregnancy
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

Drug Name	Gabapentin (Neurontin)
Description	Indicated for use in partial seizures with and without secondary generalization; has relatively few drug interactions and adverse effects.
Adult Dose	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 Dose	<12 years: Not established >12 years: Administer as in adults
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	Caution in severe renal disease

Drug Name	Lamotrigine (Lamictal)
Description	Newer agent, effective for partial seizures with or without secondary generalization. Main side effect of concern is rash, which may be severe.
Adult Dose	Dosing depends on coadministration of other anticonvulsants, specifically valproate; see dosing instructions for specific guidelines; slow titration recommended to prevent rash
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Acetaminophen increases renal clearance, decreasing effects; similarly, phenobarbital and phenytoin increase lamotrigine metabolism, causing decrease in lamotrigine levels; valproic acid increases half-life
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Serious or life-threatening rash, more likely children and patients on valproate; while many other adverse effects reported, all are infrequent or rare

Drug Name	Levetiracetam (Keppra)
Description	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 Dose	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 Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Somnolence, coordination abnormalities, and behavioral abnormalities may occur; requires adjustment for impaired renal function

Drug Name	Oxcarbazepine (Trileptal)
Description	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 Dose	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 Dose	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
Contraindications	Documented hypersensitivity
Interactions	Increases phenytoin level; may interact with oral contraceptives, calcium channel blockers
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hyponatremia may be clinically significant with sodium <125; serum sodium measurement recommended; somnolence, concentration difficulty, ataxia

Drug Name	Topiramate (Topamax)
Description	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 Dose	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 Dose	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
Contraindications	Documented hypersensitivity
Interactions	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
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Name	Zonisamide (Zonegran)
Description	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 Dose	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 Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May increase serum carbamazepine levels; carbamazepine may increase concentrations; phenobarbital may decrease levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause drowsiness, weight loss, ataxia, nausea, and slowing of mental activity

Drug Name	Tiagabine (Gabitril)
Description	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 Dose	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 Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Cleared more rapidly in patients treated with carbamazepine, phenytoin, primidone, or phenobarbital than in patients who have not received these drugs
Pregnancy	C - Safety for use during pregnancy has not been established.
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

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 10  

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

Further Outpatient Care

• Patients require frequent office visits during the titration and adjustment phase of anticonvulsants.
• • Examination should include evaluation for excessive nystagmus, tremor, and ataxia.
  • Baseline and follow-up blood testing may be needed.
• When seizure free on maintenance dose of medication, patients may be asked to come for follow-up 1-3 times a year.
• Patients who are seizure free for 2-5 years may be considered for a trial of medication withdrawal, depending on the individual case.

In/Out Patient Meds

• Folate should be added to the anticonvulsant regimen of female patients of childbearing age.

Deterrence/Prevention

• Frontal lobe epilepsy may be an early or late aftermath of head trauma. Measures should be taken to prevent head injury, including mandatory use of seat belts and bicycle helmets.
• Use of prophylactic anticonvulsants following head trauma has not demonstrated a decrease in the development of epilepsy.

Complications

• Status epilepticus - This is reported in up to 25% of patients with frontal lobe epilepsy. The episodes may be convulsive, nonconvulsive, or simple partial.
• Comorbid psychiatric or behavioral disturbance

Prognosis

• Approximately 65-75% of patients with frontal lobe seizures respond to appropriate anticonvulsants and become seizure free.
• The proportion of patients with medically refractory frontal lobe epilepsy who become seizure free from additional medications or surgical options is lower than in patients with temporal lobe epilepsy.
• An important feature in prognosis is the early recognition of frontal lobe seizures as an epileptic syndrome rather than a parasomnia or psychiatric condition.

Patient Education

• Patient education is important for all patients with epilepsy. Many patients benefit from joining one of the national or regional epilepsy support groups.
• Quality of life issues
• • "Stigma" of epilepsy
  • Living with restrictions
  • Living with long-term medical therapy

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Failure to diagnose the episodes as epilepsy, misdiagnosis as a psychiatric or parasomniac condition
• Driving restrictions
• • Certain states have mandatory reporting of seizures by physicians to the motor vehicle authorities (eg, Department of Motor Vehicles [DMV]).
  • Even in states that do not have mandatory reporting, physicians must document that the patient is aware of driving restrictions.
• Patients must be aware of the potential risks of pregnancy and epilepsy/anticonvulsants. Women of childbearing age who are taking anticonvulsants should be given folate supplementation.

REFERENCES

Section 10 of 10

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

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• Picard F, Bruel D, Servent D, et al. Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study. Brain. Aug 2006;129(Pt 8):2047-60. [Medline].
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Article Last Updated: Jan 9, 2007