Temporal lobe epilepsy (TLE) was defined in 1985 by the International League Against Epilepsy (ILAE) as a condition characterized by recurrent, unprovoked seizures originating from the medial or lateral temporal lobe. The seizures associated with this condition consist of simple partial seizures without loss of awareness, now categorized as focal aware seizures, and complex partial seizures (ie, with loss of awareness), now called focal impaired awareness seizures. Secondarily generalized seizures are now called focal to bilateral tonic-clonic seizures under the updated 2017 ILAE classication.[1] Temporal lobe epilepsy is a common type of epilepsy that is sometimes difficult to diagnose, but once diagnosed it can be effectively treated with medications. Medically intractable temporal lobe epilepsy is amenable to epilepsy surgery with a very high seizure-free rate.
Common features of temporal lobe epilepsy include the following:
Auras/focal aware may be classified by symptom type, as follows:
Features of temporal lobe complex partial seizure may include the following:
See Presentation for more detail.
A good history and physical is tantamount for diagnosis of TLE. Diagnostic modalities that may be considered include the following:
See Workup for more detail.
Older antiepileptic drugs (AEDs) used for seizure control in temporal lobe epilepsy have some long-term side effects and require lab monitoring:
Newer AEDs appear to be comparably effective but with fewer side effects and don't requre lab monitoring for the most part:
Nonpharmacologic treatments for temporal lobe epilepsy are as follows:
See Treatment and Medication for more detail.
The temporal lobe is the most epileptogenic region of the brain. In fact, 90% of patients with temporal interictal epileptiform abnormalities on their electroencephalograms (EEGs) have a history of seizures.
Temporal lobe epilepsy was defined in 1985 by the International League Against Epilepsy (ILAE) as a condition characterized by recurrent, unprovoked seizures originating from the medial or lateral temporal lobe. The ILAE released an updated classifcation in 2017.[1]
The seizures associated with temporal lobe epilepsy consist of simple partial seizures without loss of awareness (now termed focal aware) and complex partial seizures (ie, with loss of awareness; now termed focal impaired awareness). The individual loses awareness during a complex partial (focal aware) seizure because the seizure spreads to involve both temporal lobes, which causes impairment of memory. The partial seizures may secondarily generalize. As humans have 2 temporal lobes, one side is domininant for language function, and, if there is marked aphasia, seizure focus may be lateralized to the left temporal lobe for most right-handed people.
For more information, see Epilepsy and Seizures.
Approximately two thirds of patients with temporal lobe epilepsy treated surgically have hippocampal sclerosis as the pathologic substrate. Hippocampal sclerosis involves hippocampal cell loss in the CA1 and CA3 regions and the dentate hilus. The CA2 region is relatively spared.
Hippocampal sclerosis produces a clinical syndrome called mesial temporal lobe epilepsy (MTLE).
The clinical correlate of hippocampal sclerosis on neuroimaging on magnetic resonance imaging (MRI) is called mesial temporal lobe sclerosis (MTS), which is high-signal intensity on either T2-weighted or fluid-attenuated inversion recovery (FLAIR)–sequence MRIs and/or atrophy of the hippocampi.
The etiologies of temporal lobe epilepsy include the following:
The last of the above etiologies, idiopathic, is rare. Familial temporal lobe epilepsy was described by Berkovic and colleagues,[2] and partial epilepsy with auditory features was described by Scheffer and colleagues.
A subset of children with complex febrile convulsions appears to be at risk of developing temporal lobe epilepsy in later life. Complex febrile seizures are febrile seizures that last longer than 15 minutes, have focal features, or recur within 24 hours.
The association of simple febrile seizure with temporal lobe epilepsy has been controversial.
Go to Febrile Seizures for complete information on this topic.
Approximately 50% of patients with epilepsy have partial epilepsy. Partial epilepsy is often of temporal lobe origin. However, the true prevalence of temporal lobe epilepsy is not known, since not all cases of presumed temporal lobe epilepsy are confirmed by video-electroencephalography and most cases are classified by clinical history and interictal electroencephalogram (EEG) findings alone.
Temporal lobe epilepsy is not more common in one sex, but female patients may experience catamenial epilepsy, which is an increase in seizures during the menstrual period.
Epilepsy occurs in all age groups. Recently, a significant increase in new-onset seizures in elderly persons has been recognized.
In comparison with the general population, morbidity and mortality are increased in persons with temporal lobe epilepsy, due to increased accidents from the episodes of consciousness loss.
Mortality also results from sudden unexpected death in epilepsy (SUDEP). Patients with refractory temporal lobe epilepsy, especially those with secondarily generalized tonic clonic seizures, have a risk of sudden death that is 50 times greater than that in the general population.
Epilepsy surgery seems to modify the risk of SUDEP if the patient remains seizure free. In patients who have undergone surgery, the mortality rate becomes equivalent to that of the general age- and sex-matched population.
The presence of a seizure-free state 2 years after anterior temporal lobectomy is predictive of long-term seizure-free outcome for the patient.
About 47–60% of patients become seizure free with medical treatment. After 3 first-line antiepileptic drugs (AEDs) have failed, the chance for seizure freedom is 5–10%. The ILAE now has a formal definition of medically intractable/drug-resistant epilepsy, which defined as after a patient has had an adequate trial with 2 antiepileptic drugs and is still having seizures. Surgery in well-selected patients with refractory temporal lobe epilepsy yields a seizure-free outcome rate of 70–80%.
Physicians should carefully document on the chart that they have explained to their female patients with epilepsy about the increased risk of fetal anomalies associated with antiepileptic medications, a 2-fold increase (4–6%), and the increased risk of neural tube defects with valproate (1.5–2.0%) and carbamazepine (0.5%).
Patients should be told that most women with epilepsy have healthy children (90–95%). They also should be told that the chance of a normal pregnancy outcome is increased with planned pregnancies, improved seizure control, folate supplementation (0.4–4 mg each day prior to pregnancy), minimizing the number of AEDs used, and never abruptly discontinuing AEDs without consulting the physician.
For patient education information, see the Brain and Nervous System Center, as well as Epilepsy.
Patients with temporal lobe epilepsy typically have material-specific deficits in memory function as the hippocampi are important structures for memory function. Those patients with dominant temporal lobe epilepsy often have impaired language function as demonstrated by reduced naming ability on the Boston Naming Test. Some patients with non-dominant temporal lobe epilepsy may have an altered emotional component to their speech called prosody. The hippocampal memory function is tested with the intracarotid amytal test, also termed the Wada test for temporal lobectomy.
Aura, now called focal aware, seizures[1] occur in approximately 80% of temporal lobe seizures. They are a common feature of simple partial seizures (focal aware), and usually precede complex partial seizures (focal impaired awareness) of temporal lobe origin. Auras may be classified by symptom type, that is, by somatosensory, special sensory, autonomic, or psychic symptoms, described below. If a patient has one seizure focus, the seizure semiology tends to be stereotyped.
Olfactory and gustatory illusions and hallucinations may occur. Acharya et al found that olfactory auras are more commonly associated with temporal lobe tumors than with other causes of temporal lobe epilepsy.[3]
Auditory hallucinations consist of a buzzing sound, a voice or voices, or muffling of ambient sounds. This type of aura is more common with neocortical temporal lobe epilepsy than with other types of temporal lobe epilepsy.
Patients may report distortions of shape , size, and distance of objects. Things may appear shrunken (micropsia) or larger (macropsia) than usual. These visual illusions are unlike the visual hallucinations associated with occipital lobe seizure in that no formed elementary visual image is noted, such as the visual image of a face that may be seen with seizures arising from the fusiform or the inferior temporal gyrus.
Tilting of structures has been reported. Vertigo has been described with seizures in the posterior superior temporal gyrus.
Patients may have a feeling of déjà vu or jamais vu, a sense of familiarity or unfamiliarity, respectively.
Patients may experience depersonalization (ie, feeling of detachment from oneself) or derealization (ie, surroundings appear unreal).
Fear or anxiety usually is associated with seizures arising from the amygdala. Sometimes, the fear is strong, described as an "impending sense of doom."
Patients may describe a sense of dissociation or autoscopy, in which they report seeing their own body from outside.
Autonomic phenomena are characterized by changes in heart rate, piloerection, and sweating. Patients may experience an epigastric "rising" sensation or nausea.
Following the aura, a temporal lobe complex partial seizure begins with a motionless stare, blinking, and behavioral arrest. Oral alimentary automatisms such as lip smacking, chewing, and swallowing may be noted. Manual automatisms or unilateral dystonic posturing of a limb also may be observed.
Patients may continue their ongoing motor activity or react to their surroundings in a semipurposeful manner (ie, reactive automatisms). They can have repetitive, stereotyped, manual automatisms. Sometimes there is a nose wipe at the end of the seizure and the hand used can be lateralizing.
A complex partial seizure may evolve to a secondarily generalized tonic-clonic seizure. Often, the documentation of a seizure notes only the generalized tonic-clonic component of the seizure. A careful history from the patient or an observer is needed to elicit the partial features of either a simple seizure or a complex partial seizure before the secondarily generalized seizure is important.
Patients usually experience a postictal period of confusion, which distinguishes temporal lobe epilepsy from absence seizures, which are not associated with postictal confusion. In addition, absence seizures are not associated with auras or with complex automatisms. Postictal aphasia suggests onset in the language-dominant temporal lobe.
Most auras and automatisms last a very short period—seconds or 1-2 minutes. The postictal phase may last for a longer period (several minutes). By definition, amnesia occurs during a complex partial seizure because of bilateral hemispheric involvement.
Most of the time there are few findings in the temporal lobe epilepsy patient. The most useful test is to look for facial asymmetry with spontanous emotion, with flattening of the contralateral nasolabial fold.[4]
The risk of temporal lobe epilepsy is poorly controlled focal impaired awareness seizues, which leads to disability in home, work, and pulic safety such as driving restrictions. If the seizures often progress to bilateral tonic clonic then there is an increased risk of sudden unexpected death in epilepsy.
Electroencephalography (EEG) and neuroimaging are basic workup of seizures and epilepsy. MRI is the neuroimaging modality of choice for patients with temporal lobe epilepsy. Other imaging modalities that can be used in the diagnosis of temporal lobe epilepsy include computed tomography (CT) scanning, positron emission tomography (PET) scanning, single-photon emission CT (SPECT) scanning, MR spectroscopy, and magnetoencephalography (MEG).
CT scanning of the head is often obtained in the emergency department, as it is ubiquitous and is adequate for assessing blood and large lesions, but the resolution is not that of MRI.
As mentioned, MRI is the neuroimaging modality of choice for patients with temporal lobe epilepsy. Most brain MRI scans do not include coronal images, but for temporal lobe epilepsy this sequence is more informative than are the axial and sagittal cuts.
Thin, coronal, oblique slices of 1.5–2 mm with no gap, using spoiled gradient recall images (SPGR) are recommended.
All patients with newly diagnosed temporal lobe epilepsy should have a high-resolution MRI scan with at least a 1.5-Tesla MRI, although the availability of a stronger magnet like 3-Tesla is increasing resolution.
High-resolution MRI shows hippocampal atrophy in many patients with temporal lobe epilepsy by visual analysis alone, and, although volumetric studies can be performed, they are labor intensive. Hippocampal atrophy is bilateral in 10–15% of cases. An increase in the T2-weighted signal intensity in the hippocampus may be seen on fluid-attenuated inversion recovery (FLAIR) MRI; this finding is also consistent with hippocampal sclerosis.
PET with 18-fluorodeoxyglucose (PET-FDG) is a useful tool for interictal seizure localization in surgical candidates when the MRI result is normal.
PET-FDG scans usually are performed as an adjunctive measure to delineate the epileptogenic zone.
Interictal deficits include reduced glucose metabolism in the medial and lateral temporal lobe. PET scans can be fused with either CT or MRI and are useful in the presurgical evaluation.
Ictal PET scan recordings are rare, and EEG should be obtained during PET scan to determine if the the study is incterictal or ictal.
SPECT scanning is also an adjunctive imaging modality useful only for surgical candidates; the accuracy of seizure localization is about 80–90%.
Ictal SPECT scans done with hexamethylpropyleneamine oxime (HMPAO) show hyperperfusion in the region of seizure onset. The characteristic pattern is hyperperfusion of the medial and lateral temporal lobe. This requires ictal injection within 30 seconds of seizure onset. The ictal SPECT scan subtracted from the interictal scan (SISCOM) can be very useful in the presurgical evaluation.
Interictal SPECT testing is less sensitive than are PET-FDG and ictal SPECT scanning and is not used routinely for localization of the epileptogenic zone.
Magnetic resonance spectroscopy (MRS) may be clinically useful in selected patients with possbile neoplstic process. It has great research applications.
Electroencephalography should be performed in all patients with suspected temporal lobe epilepsy.
Epileptiform discharges: Interictal abnormalities, consisting of spike/sharp and slow complexes, usually are located in the anterior temporal region (F7/F8 and T3/T4 electrodes) or basal temporal electrodes (most commonly T1/T2 and in research settings, T9/T10 and F9/F10). During video-EEG monitoring, sphenoidal electrodes can be useful.
One third of patients with temporal lobe epilepsy have bilaterally independent, temporal interictal epileptiform abnormalities.
Ictal recordings from patients with typical temporal lobe epilepsy usually exhibit 5-7 Hz, rhythmic, sharp theta activity, maximal in the sphenoidal and the basal temporal electrodes on the side of seizure origin.
In documented temporal lobe seizures, lateralized postictal slowing, when present, is a reliable lateralizing finding.
A patient with temporal lobe epilepsy can have a normal EEG. The yield of the EEG can be increased on a repeat study with prolonged recordings, and, in certain patients, activation with sleep deprivation can be useful.
Video-EEG telemetry is used as part of the presurgical evaluation. It also is used if the diagnosis of temporal lobe epilepsy is suspected but still in question and in patients suspected of having psychogenic seizures.
Intracranial EEG with placement of intracranial subdural electrodes is done only if the patient is a surgical candidate and MRI and other non-invasive EEG data are not sufficiently localizing.
Another complementary method to assess cerebral physiologic activity similar to EEG is magnetoencephalography (MEG), which measures the magnetic fields generated by the epileptic spikes. The main use of MEG is the co-registration with the MRI to give magnetic source imaging (MSI) in 3-dimensional space. The spikes that are analyzed for MSI are interictal spikes and this is not as informative as ictal EEG recordings in surgical evaluations.
In the past, a prolactin level could be obtained after a prolonged temporal lobe seizure, or a seizure that spread to become bilateral tonic clonic, but there have been some issues of sensitivity and specifcity.
There are many AEDs used for seizure control in temporal lobe epilepsy.
Neurostimulation is a treatment option if the patient is refractory and is not a good surgical resective candidate. Vagus nerve stimulation (VNS) was approved by the US Food and Drug Administration (FDA) in 1997 for the treatment of intractable partial epilepsy in patients aged 4 years and older. Responsive neurostimulation (RNS) is another option when the seizure focus is known and it could treat multifocal epilepsy. Deep brain stimulation (DBS) is awaiting FDA approval but has been available in other countries.
Temporal lobectomy is the definitive treatment for medically intractable temporal lobe epilepsy, as it has a high seizure-free rate. For patients who had mesial temporal lobe epilepsy and disabling seizures for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs, Engel et al found that resective surgery plus AED treatment resulted in a lower probability of seizures for at least 2 years posttreatment, as well as improved health-related quality of life, than continued AED treatment alone.[5]
About 47–60% of new-onset partial seizures are controlled effectively by the first drug. Studies in 1985 and 1992 by the US Department of Veterans Affairs (VA) have shown that the 3 major AEDs, phenytoin, carbamazepine, and valproate, are equally effective in controlling partial seizures, but carbamazepine was better tolerated. One VA study in the elderly compared carbamazepine, gabapentin, and lamotrigine and in this group lamotrigine had the best profile in terms of tolerability, and carbamazepine had the least.
The newer AEDs, such as gabapentin, topiramate, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, lacoasmide, and zonisamide, have similar efficacy than the older AEDs, but they stand out predominantly in having far less side effects in day-to-day use, as well as in long-term side effects. The newer drugs are easier to use in terms of having far fewer drug-drug interactions than do the older AEDs.
Vigabatrin and felbamate are reserved for intractable epilepsy patients due to the potential of serious adverse events.
A major advance in epilepsy treatment is the extended-release formulations, which allow for some AEDs to be used once a day for better adherence. Some of the AEDs with extended-release formulations also have better tolerability, improving quality of life for patients with epilepsy.
About 40% of patients continue to have seizures in spite of trials with 3 AEDs. Semah and colleagues showed that seizures are more likely to be refractory to AEDs in patients with hippocampal sclerosis.[6]
Go to Antiepileptic Drugs for complete information on this topic.
Vagus nerve stimulation (VNS) was approved by the FDA in 1997 for the treatment of intractable partial epilepsy and is now approved for patients aged 4 years or older. In VNS, a battery-operated stimulator device is implanted in the chest and an electrode is attached to the left vagus nerve in the neck.
VNS has been found to result in a mean reduction in seizure frequency of 25–28% at 3 months but with improvement to about 40% by year 1. The exact mechanism through which VNS exerts its antiepileptic effect is not known. A newer model of VNS monitors heart rate and provides responsive stimulation to heart rate increases that may be associated with seizures. Patients and caregivers can also deliver extra stimulation with a magnet.
Adverse effects of VNS treatment include hoarseness of voice, cough, local pain, paresthesias, dysphagia, and dyspnea when the device is on and almost none when the device is off, but the settings can be titrated so that side effects are minimized. VNS does not have the adverse effects associated with AEDs and is used adjunctively with AEDs.
Go to Vagus Nerve Stimulation for complete information on this topic.
Responsive neurostimulation (RNS) is another stimulator device implanted into the skull with electrodes over or in the seizure focus. It monitors EEG activity and stimulates when seizures are detected. The RNS stimulation is not perceptible to the patient.
Deep brain stimulation (DBS) has been in use for Parkinson disease and has been studied for epilepsy and is awaiting FDA approval.
Temporal lobectomy is the definitive treatment for medically intractable temporal lobe epilepsy. When seizures are not controlled by 2 different AED trials, the patient should be considered for a presurgical evaluation. These patients are not likely to achieve seizure control with medications alone (5-10% chance of becoming seizure free).
The presence of unilateral hippocampal sclerosis or mesial temporal sclerosis (MTS) and concordant EEG findings predict seizure-free outcome in patients considered for surgery.
Foldvary and colleagues showed that a higher monthly preoperative seizure frequency is associated with a less favorable surgical outcome.[7]
An extensive presurgical assessment for the feasibility of surgery is essential. This includes MRI, interictal and ictal EEG, neuropsychological testing, and the intracarotid amobarbital test called the Wada test.
Seizure-free state at 2 years postoperatively is predictive of long-term seizure-free outcome. In well-selected cases, 70-80% of patients with refractory temporal lobe epilepsy become seizure free after surgery.
Go to Epilepsy Surgery for complete information on this topic.
Selective amygdalohippocampectomy (SAH) is a more targeted mesial temporal resection that spares the temporal neocortex. Bandt et al examined seizure response rates, complications, and neuropsychological outcomes of trans-middle temporal gyrus SAH for medically intractable mesial temporal lobe epilepsy in 76 adult patients, 19 of whom underwent preoperative and postoperative neuropsychological evaluations.[8]
In this study, favorable seizure response rates were achieved in 92% of the patients, and rates of surgical morbidity were low.[8] Whereas a decline in verbal memory was observed in the left SAH group, improvements in memory were seen in the right SAH group.
The most common medicolegal issue arises from the fact that different states in the United States have different rules regarding the physician's responsibility to report a patient with diagnosed epilepsy.
For example, California, along with four other states, mandates that the physician is responsible for reporting a patient with new-onset seizure or epilepsy that may impair safe dririvng to the Department of Motor Vehicles (DMV).
The dietary therapy that can be tried for intractable epilepsy is the ketogenic diet or the Modified Atkins diet.
For the longest time, 4 principal medications were used for partial seizures: phenytoin, carbamazepine, valproate, and phenobarbital. However, a number of newer medications have been approved by the FDA since 1995. Some of these newer AEDs are approved as monotherapy, but how they compare with the older AEDs is not known.
The initial choice of medication depends on many factors, including side-effect profile, dosage schedule, and comorbid conditions. The major VA trials did not show any significant difference in seizure control among the 4 older AEDs. Adverse effects were greater with phenobarbital and with primidone and least with carbamazepine.
Single-drug therapy is the goal, and the dosage of each medication prescribed should be increased until either seizures are controlled or adverse effects occur.
The new AEDs have a class-wide warning about suicidal ideation mandated by the FDA, which arose from 4 suicides amongst 40,000 patients exposed to AEDs. The patient should be evaluated for mood changes, which may need treatment.
Clinical Context: Carbamazepine affects sodium channels during sustained, rapid, repetitive firing. The extended release form is preferred (Tegretol XR or Carbatrol) because of twice-daily dosing, which improves compliance and leads to more stable blood levels. No intravenous (IV) formulation is available.
Clinical Context: Phenytoin is one of oldest drugs known for treatment of seizures. In young women, it can coarsen facial features and can cause hirsutism and gingival hyperplasia. In addition, frequent blood-level determinations are required in patients taking the drug, because of nonlinear pharmacokinetics. Long-term use has been associated with peripheral neuropathy and osteopenia.
Clinical Context: This anticonvulsant is effective for a broad spectrum of seizure types; it is believed to exert its anticonvulsant effect by increasing gamma-aminobutyric acid (GABA) levels in the brain. Valproate is approved for monotherapy or adjunctive therapy for partial seizures and generalized tonic-clonic seizures. Depakene is available as a capsule or syrup, and Depakote is available as a tablet or sprinkle.
Clinical Context: Lamotrigine is a newer AED; it was approved as an adjunctive therapy and a crossover monotherapy for partial seizures. It also blocks sodium channels during sustained, rapid, repetitive neuronal firing. The drug is FDA approved for children younger than age 16 years only for Lennox-Gastaut syndrome; it is not FDA approved for children with partial seizures, because of an increased incidence of rash.
Clinical Context: Gabapentin is approved by the FDA as an adjunctive therapy for partial seizures. It is structurally related to GABA but does not affect GABA directly, although it is thought to modulate the calcium channel.
Clinical Context: Topiramate is approved by the FDA as a monotherapy or an adjunctive therapy for partial seizures and symptomatic generalized seizures. It exerts action by 4 mechanisms: sodium-channel blockade, enhancement of GABA activity, antagonism of AMPA/kainate-type glutamate excitatory receptors, and weak inhibition of carbonic anhydrase.
Clinical Context: This drug enhances GABA activity by inhibiting uptake in neurons and astrocytes. Tiagabine can be used as an add-on therapy for partial seizures. It has been known to exacerbate seizures with spike-wave stupor. Some patients who were receiving off label and never had seizures had seizures induced with tiagabine when it was used with another medication, which lowers the seizure threshold.
Clinical Context: Zonisamide is approved in the United States for adjunctive use in the treatment of partial seizures. It has been studied extensively in Japanese and European trials for primary generalized seizures. The drug blocks T-type calcium currents and prolongs sodium-channel inactivation. It is also a weak carbonic anhydrase inhibitor. In monotherapy, it has a long half-life (70 h).
Clinical Context: Oxcarbazepine is approved by the FDA as a monotherapy and as an adjunctive therapy for partial epilepsy in adults and children aged 2-16 years. It blocks sodium-activated channels during sustained, rapid, repetitive firing. Oxcarbazepine has antiepileptic activity, but its monohydroxy (MHD) metabolite is the most active compound. Oxcarbazepine is different from carbamazepine, which generates a 10-11 epoxide metabolite.
Clinical Context: This drug was approved by the FDA in 1999 as an add-on therapy for partial seizures. It is also FDA approved as an add-on therapy for juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures. The drug's mechanism of action is thought to be related to the binding of levetiracetam to presynaptic vesicle protein. The medication has a favorable adverse effect profile overall, except for behavioral changes.
Clinical Context: Felbamate is approved for medically refractory partial seizures and Lennox-Gastaut syndrome. It has multiple mechanisms of action, including blockade of the glycine site of the N-methyl-D-aspartate (NMDA) receptor, potentiation of GABAergic activity, and inhibition of voltage-sensitive sodium channels. However, felbamate has a high rate of life-threatening side effects, so the benefits and risks of the drug need to be carefully addressed.
Clinical Context: Pregabalin was approved in 2005 for adjunctive use in partial seizures in adults. Its mechanism of action (calcium-channel modulation) is similar to that of gabapentin, but it is more potent and has linear pharmacokinetics.
Clinical Context: Rufinamide is structurally unrelated to other current antiepileptics. It modulates sodium-channel activity, particularly through prolongation of the channel's inactive state. The drug significantly slows sodium-channel recovery and limits sustained, repetitive firing of sodium-dependent action potentials. Rufinamide is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome.
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: Vigabatrin is a structural derivative of GABA. Its mechanism of action is unknown. Vigabatrin 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. It is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
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.
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.