Frontal lobe epilepsy is characterized by recurrent seizures arising from the frontal lobes. Frequently, seizure types are focal onset with preserved or impaired awareness, often with progression to bilateral tonic-clonic activity. Status epilepticus may be associated more commonly with frontal lobe seizures than with seizures arising from other areas.
Time of day is an important characteristic for seizures originating in the frontal lobe, as the majority of these seizures occur between the hours of 2 am and noon.[1] A frontal lobe seizure is often the seizure type most difficult to diagnose as it can be easily mistaken for a parasomnia or nonepileptic event. The following features help to distinguish frontal lobe seizures from nonepileptic events:
Other history findings may vary according to the site of involvement, include the following:
Physical examination in focal lobe epilepsy is typically normal but may reveal signs suggestive of syndromes or structural lesions that may be associated with epilepsy, such as the following:
See Clinical Presentation for more detail.
For new-onset seizures, blood tests should be performed to rule out a metabolic cause (eg, hypoglycemia). For patients with an established diagnosis of epilepsy, blood testing for complications may include the following:
Brain imaging
Electroencephalography
See Workup for more detail.
Antiseizure therapy should be initiated once the diagnosis of epilepsy is established. Many nocturnal seizures with prominent motor manifestations respond extremely well to carbamazepine. Monotherapy is desirable, but some patients require polytherapy.
Patients with medically intractable epilepsy should be considered for resective epilepsy surgery. Other treatment options include the following:
See Treatment and Medication for more detail.
Frontal lobe epilepsy is characterized by recurrent seizures arising from the frontal lobes. Frequently, seizure types are focal onset with preserved or impaired awareness, often with progression to bilateral tonic-clonic activity. 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.
Frontal lobe epilepsy frequently overlaps with sleep-related hypermotor epilepsy (SHE; formerly known as nocturnal frontal lobe epilepsy), which is an epilepsy syndrome characterized by the occurrence of sleep-related hyperkinetic seizures with variable duration and complexity. However, SHE can occasionally arise from extrafrontal areas.[3]
Disease conditions commonly associated with frontal lobe epilepsy are frequently symptomatic, including congenital causes (such as cortical dysgenesis, gliosis, vascular malformations), neoplasms, head trauma, infections, and anoxia.
Owing to 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.
Quality-of-life issues for patients with epilepsy can include the following:
For more information, see Status Epilepticus.
Go to Epilepsy and Seizures for an overview of this topic.
With improvements in neuroimagine, cortical dysplasias are increasingly being identified as epileptogenic lesions. This is particularly true for patiens who were initially assumed to be nonlesional. Other common developmental causes of frontal lobe seizures include hamartomas and nodular heterotopias.
Reviews indicate that the epileptogenic lesion in approximately one third of patients with refractory frontal lobe seizures is a tumor.
Common tumors causing frontal lobe epilepsy 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 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.
Three main types are recognized: arteriovenous malformations, cavernous angiomas, and venous angiomas. Arteriovenous malformations and cavernous angiomas are more likely to cause seizures than are venous angiomas.
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.
Although encephalitis commonly produces temporal lobe epilepsy, frontal lobe seizures may occur.
The seizures of autosomal dominant sleep-related hypermotor epilepsy (SHE)(formerly known as ADNFLE for autosomal dominant nocturnal frontal lobe epilepsy), which are mostly originating in the frontal lobe, 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. Some patients may describe a brief aura, which is typically followed by hyperkinetic or tonic activity. Awareness is often preserved, and daytime seizures are rare. Seizure onset is typically in childhood, but can range from infancy to adulthood. Affected patients have normal neurologic exams and intellect. These seizures typically respond well to carbamazepine (often low doses) and are lifelong, though not progressive. Differentiation from parasomnias remains a challenge.
Autosomal dominant SHE was the first partial epilepsy identified as a single gene disorder. Mutations in 3 nicotinic acetylcholine receptor genes (nAChR alpha-2, alpha-4 and beta-2 subunits) have been associated with this epilepsy syndrome.[4] Additional causative mutations in the following genes were later identified: CRH, DEPDC5, KCNT1. Penetrance is 70%, and there can be significantly clinical heterogeneity among affected individuals in the same family. The KCNT1 pathogenic variant has been associated with a more severe phenotype.[5]
The exact incidence of frontal lobe epilepsy is not known. In most centers, however, frontal lobe epilepsy accounts for 20–30% of operative procedures involving intractable epilepsy.
No significant sex-based frequency difference has been reported for frontal lobe epilepsy in epidemiologic studies. However, a comparison of frontal lobe versus temporal lobe seizures captured during epilepsy monitoring has suggested a male predominance in frontal lobe seizures.[6]
Symptomatic frontal lobe epilepsy may affect patients of all ages.
In a large series of cases, the 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.
Complications of frontal lobe epilepsy may include status epilepticus or a comorbid psychiatric or behavioral disturbance.
Status epilepticus is reported in up to 25% of patients with frontal lobe epilepsy. The episodes may be convulsive, nonconvulsive, or focal without impaired awareness.
As with all epilepsy patients, particularly those with medically intractable seizures, patients with frontal lobe epilepsy should be counseled on the risk of SUDEP (sudden unexpected death in epilepsy patients). However, patients with frontal lobe epilepsy do not appear to have a higher incidence of SUDEP compared to other epilepsy populations.[7]
Approximately 65–75% of patients with frontal lobe seizures respond to appropriate anti-seizure medications and become seizure free. However, approximately 30% of patients will be intractable, many of whom will continue to have frequent nocturnal seizures.
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 as a parasomnia or a psychiatric condition.
Patient education is important for all patients with epilepsy. Many patients benefit from joining one of the national or regional epilepsy support groups.
Patients with epilepsy who are not seizure free have the following restrictions:
The majority of frontal lobe seizures are thought to be due to underlying structural lesions, although many patients with frontal lobe seizures have no obvious lesions on magnetic resonance imaging (MRI) scans.
A careful history should focus on specific characteristics of seizure episodes, including a detailed description by eyewitnesses, patterns of occurrence, precipitating factors, and response to medication. Time of day is an important characteristic for seizures originating in the frontal lobe, as the majority of these seizures occur between the hours of 2 am and noon.[1] Awareness may appear unimpaired when seizures are brief, and paitents may have absent or minimal post-ictal state.
Features that help to distinguish frontal lobe seizures from nonepileptic events include stereotyped semiology, occurrence during sleep, brief duration (often < 30 seconds), rapid bilateral evolution, prominent motor manifestations, and complex automatisms. Other features of frontal lobe seizures include significant voice alterations in ictal speech, with elevated pitch during verbal communication.[8]
Even when such characteristics are present, however, distinguishing frontal lobe seizures from nonepileptic events remains difficult based on history alone, and patients with frontal lobe epilepsy are often directed first to psychiatrists rather than to neurologists. Details obtained about the seizure semiology may help to identify the specific frontal region of onset.[9, 10]
Other history findings may include the following:
A general physical and thorough neurologic examination should be performed in all patients with epilepsy.
General examination may reveal 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, may also be found.
As structural lesions are common, neurologic abnormalities are common in patients with frontal lobe epilepsy. Pay particular attention to the motor examination.
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. Blood tests include the following:
With regard to the third item above, 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.
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 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. A field strength of 3 Tesla (3T) can further increase the identification of lesions.[2]
PET scanning is being increasingly used 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.
If the patient has very frequent seizures, and particularly if he/she does not recognize not all seizures, then consider performing an ambulatory EEG for the 48–72 hours leading up to the PET scan to establish whether the study was truly interictal.
Ictal single-photon emission computed tomography (SPECT) scans may be obtained during prolonged video-EEG monitoring.
Hyperperfusion seen on ictal SPECT scanning is suggestive of an area of seizure onset. The sensitivity of ictal SPECT scan 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 (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. However, there are no published studies examining this imaging modality specifically for frontal lobe epilepsy.
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. Electroencephalography is discussed further in the subsections below.
Magnetoencephalography (MEG) is a functional neuroimaging modality that uses the brain’s magnetic fields to map brain activity. One study found that source localization using MEG provided important localization information and impacted surgical outcome in patients with frontal lobe epilepsy.[13]
Tissue from surgical resections for intractable frontal lobe epilepsy may demonstrate evidence of a developmental lesion, tumor, gliosis, or vascular malformation. However, the histologic findings may be confounded by post-surgical changes.
There are no pathognomonic EEG findings for frontal lobe epilepsy. In fact, interictal EEGs may be normal. Spikes or sharp waves may be absent; may appear maximal unilaterally (frontal or frontopolar), bilaterally, or in the midline (vertex); or may appear generalized due to secondary bilateral synchrony.[14] Multifocal spikes may be associated with a higher tendency for a history of bilateral evolution to tonic-clonic seizures.[15]
Background rhythm abnormalities, with or without focal slowing, may be present and usually depend on the presence of a structural lesion.
Ictal onset often is seen poorly from the scalp and is highly variable in appearance. EEGs can also be affected by muscle artifact, which may obscure the findings. Closely spaced frontal electrodes can enhance localization in ictal EEGs.
Lack of ictal discharge in the temporal lobes may suggest a frontal onset.
Video analysis of seizure semiology is crucial and may suggest frontal lobe epilepsy when the EEG is unrevealing. Fencing posturing and lack of postictal confusion are highly suggestive of frontal lobe seizures.[4]
Clinical semiology can provide lateralization information, with many unilateral movements or postures predicting a contralateral seizure onset.[16]
Mesial frontal lobe seizures may be characterized by generalized epileptiform discharges at onset , which are maximal at vertex. Dorsolateral frontal lobe seizures are frequently characterized by focal rhythmic activity, and non-localizable seizures may manifest as diffuse attenuation of the background activity and non-localized rhythmic theta or delta at onset.[14]
Postictal slowing also can be confirmatory, and at times, localizing or lateralizing.
Go to EEG Video Monitoring for complete information on this topic.
High-density (HD) EEG and electrical source imaging (ESI) are additional neurophysiologic modalities that can aid in localization, particularly for patients undergoing surgical work-up. HD EEG refers to using 64 or more electrodes, which can improve the accuracy of localization compared to standard EEG arrays. ESI uses mathematical algorithms to plot the interictal epileptiform discharges or initial ictal discharge on MRI images. Using the patient’s MRI, as opposed to an MRI template, leads to more accurate localization. Of note, these modalities are only useful if the patient’s interictal and/or initial ictal discharges are well-visualized on scalp 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 when seizures arise close to eloquent cortex (eg, motor or language functional areas). Electrode coverage of 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 sample more broadly, and can be used to perform cortical mapping, but they have higher infection risk and less anatomic specificity.
Interictal high-frequency oscillations (HFO) have localizing value in frontal lobe epilepsy, with their pre-resection presence predicting a postoperative seizure-free outcome.[14, 17]
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.
While a first seizure may not be treated, anti-seizure medications should be initiated once the diagnosis of epilepsy is established. Many nocturnal episodes with prominent motor manifestations respond extremely well to carbamazepine.
Patients with medically intractable epilepsy should be considered for resective epilepsy surgery. If resective surgery is not possible, other surgical options include responsive neurostimulation, corpus callosotomy, multiple subpial transections, or vagus nerve stimulation.
While a first seizure may not be treated, anti-seizure medications 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 anti-seizure medications for use in focal epilepsies are available and may be used as monotherapy or in combination.
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 anti-seizure medications include phenytoin, carbamazepine, valproic acid, and barbiturates. Newer anti-seizure medications include gabapentin, lamotrigine, topiramate, levetiracetam, zonisamide, oxcarbazepine, pregabalin, lacosamide, clobazam, eslicarbazepine, and brivaracetam.
Approximately 30% of patients with frontal lobe epilepsy will be refractory to multiple medications, and they may require evaluation for resective surgery. Other options include dietary therapy (ketogenic diet or modified Atkins diet), vagal nerve stimulation, or responsive neurostimulation.
Go to Antiepileptic Drugs for complete information on this topic.
Folate should be added to the anti-seizure medication regimen of female patients of childbearing age to reduce the risk of neural tube defects.
Frontal cortical resection is the most commonly performed extratemporal cortical resection for intractable epilepsy.[18] 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.
In a case series of patients with post-traumatic epilepsy, 57% had temporal lobe epilepsy and 35% had frontal lobe epilepsy (FLE). The overall poorer epilepsy surgical outcomes for FLE when compared with temporal lobe epilepsy (similar in post-traumatic and non-traumatic cases) may be related to a larger epileptogenic zone in FLE, with difficult-to-define margins (especially in nonlesional cases), which results in inadequate resection.[19]
Go to Epilepsy Surgery for complete information on this topic.
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.[18]
Factors predictive of poor outcome include incomplete resection, tonic seizures, and interictal spikes on follow-up EEG.[20]
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.[21]
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.
This procedure is aimed at prevention of bilateral synchrony, thus preventing convulsions and/or falls. Focal seizures that do not generalize often do not improve and may worsen. With the advent of improved surgical techniques, this procedure is now rarely peformed for well-defined frontal lobe epilepsy.
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.
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.
Go to Vagus Nerve Stimulation for complete information on this topic.
Responsive neurostimulation (RNS) is a newer device that should be considered when seizure onset is in/near eloquent cortex or bilateral. The device has electrodes implanted in the suspected seizure-onset zones and can be programmed to detect seizures, and then stimulate to abort ictal activity. In one study, patients with frontal lobe epilepsy experienced a median percent seizure reduction of 70%.[22]
This high-fat diet, typically with a fat-carbohydrate ratio of 3-4:1, induces ketosis. Considerations include the following:
The modified Atkins diet has been under investigation as an alternative to the ketogenic diet in patients with intractable epilepsy. This diet is not as restrictive and does not require initial fasting, and thus may be better tolerated. Other alternatives to the ketogenic diet include the medium chain triglyceride diet and the low glycemic index treatment. Results have been encouraging, but data on its efficacy specifically for frontal lobe epilepsy are limited.[23, 24]
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 anti-seizure medications following head trauma has not been demonstrated to reduce the chance of epilepsy development.
Patients with epilepsy, particularly those with intractable epilepsy and frequent seizures, should be counseled regarding the risk of sudden unexplained death in epilepsy patients (SUDEP).
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.
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.
Patients require frequent office visits during the titration and adjustment phase of anti-seizure medications. Examination should include evaluation for excessive nystagmus, tremor, and ataxia. Baseline and follow-up blood testing may be needed.
When seizure free on a 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.
Anti-seizure medications indicated for use in focal seizures are the medical treatment of choice. Patients generally require many years of treatment, so consideration of side effects is important.
Although the effect of anti-seizure medications in pregnancy may be unfavorable, 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.
Clinical Context: This is a first-line agent for partial seizures with or without secondary generalization. Carbamazepine is particularly effective in the treatment of nocturnal motor/dystonic frontal lobe seizures. However, it carries a potential for hematologic and other adverse effects; blood monitoring is recommended. Carbamazepine is available in the form of tablets, extended release tablets, extended release capsules, and a suspension. Patients who are not using the extended release form often require dosing 3 times a day.
Clinical Context: Phenytoin is available as tablets, capsules, Infatabs, and suspension. It is a first-line agent for partial seizures. The advantages of phenytoin include an ability to quickly achieve a therapeutic level and the possibility of once-daily dosing (Dilantin Kapseals), which increases compliance.
Clinical Context: This is available in the form of tablets, capsules, solution, and sprinkles and is also available in injectable form. Although it is considered a first-line agent for the treatment of primary generalized epilepsy, the drug is indicated for partial seizures as well, particularly for patients with secondary generalization. It must be used cautiously in women of childbearing age. The drug has limited use in young children because of a risk of potentially fatal hepatic failure.
Clinical Context: Gabapentin is indicated for use in partial seizures with or without secondary generalization. It has relatively few drug interactions and adverse effects.
Clinical Context: Lamotrigine is a newer agent; it is effective for partial seizures with or without secondary generalization. The drug's main side effect of concern is rash, which may be severe.
Clinical Context: This is a newer agent; it is effective for partial seizures with or without secondary generalization. Levetiracetam has few adverse effects and no drug-drug interactions. It does not require blood monitoring, although slight decreases in red blood cell (RBC) and white blood cell (WBC) counts have been reported.
Clinical Context: Oxcarbazepine is indicated as monotherapy or adjunctive therapy in the treatment of partial seizures with or without secondary generalization. Its mechanism of action is similar to that of carbamazepine, without metabolism to epoxide. The active metabolite is MHD (monohydroxy derivative).
If a patient is being converted from carbamazepine to oxcarbazepine, the inducing effect of carbamazepine on cytochrome P-450 enzymes will be reduced, and other antiepilepsy drugs (AEDs) may need adjustment. There is no IV form available. If added to phenytoin, oxcarbazepine may elevate phenytoin levels by as much as 20%.
Clinical Context: Topiramate is indicated for the adjunctive treatment of partial seizures with or without secondary generalization, and for tonic-clonic seizures. It is approved for adults and for children aged 2-16 years. Topiramate has multiple mechanisms of action.
Clinical Context: This drug is indicated for adjunctive treatment of partial seizures with or without secondary generalization. Evidence exists that zonisamide is effective in myoclonic and other generalized seizure types as well.
Clinical Context: Tiagabine is indicated for adjunctive treatment of partial seizures with or without secondary generalization. The mechanism of antiseizure action unknown but is believed to be related to an ability to enhance the activity of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the central nervous system (CNS).
Clinical Context: Pregabalin is a structural derivative of GABA; its mechanism of action unknown. It binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, it reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium-channel function. The US Food and Drug Administration (FDA) approved pregabalin for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as an adjunctive therapy in partial-onset seizures.
Clinical Context: Ethotoin may act in the motor cortex where it may inhibit the spread of seizure activity. The activity of the brain stem centers responsible for the tonic phase of grand mal seizures may also be inhibited.
Clinical Context: Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. It is indicated for adjunctive therapy for partial-onset seizures.
Clinical Context: Vigabatrin is an irreversible inhibitor of GABA transaminase, thereby increasing the level of the inhibitory neurotransmitter GABA.
Clinical Context: Considered the drug of first choice for primary generalized epilepsy, valproate has a very wide spectrum and is effective in most seizure types, including myoclonic seizures. It has multiple mechanisms of anticonvulsant effects, including increasing gamma-aminobutyric acid (GABA) levels in brain as well as T-type calcium channel activity. The extended-release (ER) formulation allows for once-a-day administration.
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.