Epilepsy and Seizures Treatment & Management

The goal of treatment in patients with epileptic seizures is to achieve a seizure-free status without adverse effects. This goal is accomplished in more than 60% of patients who require treatment with anticonvulsants. Many patients experience adverse effects from these drugs, however, and some patients have seizures that are refractory to medical therapy. A 2017 study found that fewer than two thirds of patients with newly diagnosed epilepsy are seizure-free after 1 year. A smaller study published in 2000 found the seizure-free rate to be 64%, which is almost identical to the rate found in the newer study. ^[31]

Monotherapy is desirable because it decreases the likelihood of adverse effects and avoids drug interactions. In addition, monotherapy may be less expensive than polytherapy, as many of the older anticonvulsant agents have hepatic enzyme–inducing properties that decrease the serum level of the concomitant drug, thereby increasing the required dose of the concomitant drug.

People with seizures experience psychosocial adjustments after their diagnosis; therefore, social and/or vocational rehabilitation may be needed. Many physicians underestimate the consequences that an epilepsy diagnosis may have on patients. For example, patients with epilepsy may live in fear of experiencing the next seizure, and they may be unable to drive or work at heights.

Refer patients with intractable spells to a neurologist or an epileptologist for further workup, including video-electroencephalographic (EEG) monitoring, to characterize the etiology of their seizures. A neurosurgical consult is recommended when the possibility of surgical management is considered.

Recurrence risk

For patients who have had more than 1 unprovoked seizure, treatment with an anticonvulsant is recommended. However, the standard of care for a single unprovoked seizure is avoidance of typical precipitants (eg, alcohol, sleep deprivation); anticonvulsants are not recommended unless the patient has risk factors for recurrence.

The risk of recurrence in the 2 years after a first unprovoked seizure is 15-70%. Principal factors that increase the risk of recurrence are an abnormal brain magnetic resonance image (MRI) study, an abnormal electroencephalogram (EEG), and a partial-onset seizure.

On brain magnetic resonance imaging (MRI), a focal abnormality in the cortical or limbic regions that indicates a possible substrate for an epileptogenic zone is the finding that most often suggests increased risk for seizure recurrence. Diffuse abnormalities, such as hydrocephalus, may increase the risk by injuring the cerebral cortex.

Abnormalities on an EEG may include any of the following:

• Epileptiform discharges

• Focal slowing

• Diffuse background slowing

• Intermittent diffuse intermixed slowing

Epileptiform abnormalities and focal slowing are the EEG findings associated with the highest risk of seizure recurrence. Nevertheless, even a normal EEG does not eliminate recurrence risk.

The risk of recurrence in a person with 1 generalized tonic-clonic seizure, a normal EEG, a normal brain MRI, and no evidence of focal onset is about 15%; in this case, the patient is not treated. If a patient has all risk factors, the risk is approximately 80%, and the patient is treated.

The major unresolved question is how to treat patients with 1 abnormality, whose recurrence risk is 30-50%. One approach is to base the decision on a discussion with the patient that includes the risk of seizure recurrence, the risk of toxic effects from the anticonvulsant, and the benefits of avoiding another seizure. The clinician should also describe seizure precautions, including not driving for a specific time. Treatment with anticonvulsants does not alter the natural history of seizure recurrence; it only reduces the risk for the duration of treatment.

The First Seizure Trial Group randomly selected 397 patients with an unprovoked, generalized tonic-clonic first seizure to either receive prophylaxis with a conventional anticonvulsant (ie, carbamazepine, phenobarbital, phenytoin, valproic acid) or to receive no treatment and reported that about 18% of treated patients had seizure recurrence within 1 year, compared with 39% of untreated patients. ^[32] Therefore, patients must be told that anticonvulsants can reduce their risk of having another seizure but will not eliminate that risk.

The mainstay of seizure treatment is anticonvulsant medication. The drug of choice depends on an accurate diagnosis of the epileptic syndrome, as response to specific anticonvulsants varies among different syndromes. The difference in response probably reflects the different pathophysiologic mechanisms in the various types of seizure and the specific epileptic syndromes.

Some anticonvulsants (eg, lamotrigine, topiramate, valproic acid, zonisamide) have multiple mechanisms of action, and some (eg, phenytoin, carbamazepine, ethosuximide) have only 1 known mechanism of action. Anticonvulsants can be divided into large groups based on their mechanisms, as follows:

• Blockers of repetitive activation of the sodium channel: Phenytoin, carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, topiramate, cenobamate

• Enhancers of slow inactivation of the sodium channel: Lacosamide, rufinamide

• Gamma-aminobutyric acid (GABA)–A receptor enhancers: Phenobarbital, benzodiazepines, clobazam, ganaxolone 

• N -methyl-D-aspartic acid (NMDA) receptor blockers: Felbamate

• Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor blockers: Perampanel, topiramate

• T-calcium channel blockers: Ethosuximide, valproate

• N- and L-calcium channel blockers: Lamotrigine, topiramate, zonisamide, valproate

• H-current modulators: Gabapentin, lamotrigine

• Blockers of unique binding sites: Gabapentin, levetiracetam, perampanel

• Carbonic anhydrase inhibitors: Topiramate, zonisamide

• Neuronal potassium channel (KCNQ [Kv7]) opener: Ezogabine

• Other anticonvulsants: Cannabidiol, stiripentol, fenfluramine

For more information, see Antiepileptic Drugs.

This section discusses the use of anticonvulsant agents for absence, tonic or atonic, myoclonic, and tonic-clonic seizures. A discussion of treatment for focal-onset seizures, including refractory cases, also follows, with some findings from the Veterans Administration (VA) Cooperative Studies and Standard and New Antiepileptic Drugs (SANAD) trial.

Absence seizures

If only absence seizures are present, most neurologists treat them with ethosuximide. If absence seizures are present along with other seizure types (eg, generalized tonic-clonic seizures, myoclonic seizures), the choices are valproic acid, lamotrigine, or topiramate. Do not use carbamazepine, gabapentin or tiagabine, because these drugs may exacerbate absence seizures. It is uncertain whether pregabalin, a medication related to gabapentin, may also exacerbate this type of seizure.

Investigators of a single, double-blind, randomized, controlled trial that compared the efficacy, tolerability, and neuropsychologic effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy concluded that ethosuximide was the drug of choice for this clinical scenario. ^[33] Valproate was equally as effective as ethosuximide in newly diagnosed childhood absence epilepsy, but it was associated with more adverse effects.

Tonic or atonic, myoclonic, and tonic-clonic seizures

Tonic or atonic seizures are dramatic seizures. Patients with Lennox-Gastaut syndrome may have seizures, and this syndrome is best treated with broad-spectrum drugs (eg, valproic acid, lamotrigine, topiramate) or felbamate as a last resort. Other treatment modalities include the use of vagal nerve stimulation (VNS). The US Food and Drug Administration (FDA) has approved several agents—rufinamide, clobazam, ^[34]  extended-release topiramate, ^{[35, 36, 37, 38]} cannabidiol, ^{[39, 40, 41]}  and stiripentol ^[42]  —as adjunctive therapies for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex.

Myoclonic seizures have a bimodal distribution. Infants with myoclonic epilepsies usually have a poor prognosis; however, in late childhood and adolescence, the syndrome of juvenile myoclonic epilepsy (JME) is often the cause of myoclonic seizures. The seizures associated with JME are usually readily controlled with the appropriate broad-spectrum antiepileptic drug (AED), but JME has a high recurrence rate of approximately 80-90% after discontinuation of anticonvulsants.

The best medications for JME and myoclonic seizures are valproic acid, lamotrigine, and topiramate. Levetiracetam is approved by the FDA for adjunctive therapy of JME; this is the first medication approved for this syndrome. Anecdotal evidence suggests that zonisamide might be helpful in JME. Note that if partial seizure medications, such as phenytoin and carbamazepine, are used to treat JME, these agents may not only be ineffective, but in certain cases they may exacerbate the seizures.

Primary generalized tonic-clonic seizures respond to valproic acid, topiramate, or lamotrigine. Levetiracetam and perampanel are indicated as adjunctive therapy for these seizures.

Generalized and unclassified epilepsies

The SANAD trial investigators concluded that valproate should remain the drug of first choice for many patients with generalized and unclassified epilepsies, as it is better tolerated than topiramate and more efficacious than lamotrigine. ^[43] However, in women of childbearing age, the known potential adverse effects of valproate during pregnancy (ie, black box warnings of severe birth defects and impaired cognitive development) must be balanced against the benefits of seizure control. Levetiracetam and zonisamide were not included in SANAD, which tested only lamotrigine, topiramate, and valproate.

A 2014 study by Shallcross et al, however, indicated that whereas in utero exposure to the AED valproate is associated with language and motor development deficits in children, the same is not true for levetiracetam. In the study, valproate exposure resulted in children having lower scores on tests of comprehension, expressive language abilities, and motor skills compared with children exposed to levetiracetam. In fact, children exposed to levetiracetam did not differ from children unexposed to any AED on tests of thinking, movement, and language when tested at age 36-54 months. ^{[44, 45]}

Focal-onset seizures

In focal-onset seizures, there are many AED choices with monotherapy indications, including carbamazepine, cenobamate, lacosamide, lamotrigine, oxcarbazepine, and topiramate. (see Anticonvulsants in Specific Patient Populations, below). Adjunctive therapy with levetiracetam, tiagabine, gabapentin, pregabalin, lacosamide, cenobamate, or ezogabine may be considered if the first or second monotherapy trial with first-line treatments fails. Discussing the adverse-effect profiles of anticonvulsants with patients is important, because the efficacies of anticonvulsants appear to be similar. ^[46]

The VA Cooperative Study I clearly demonstrated similar efficacies for carbamazepine, phenytoin, primidone, and phenobarbital. ^[47] However, carbamazepine and phenytoin were tolerated better by men than women. The VA Cooperative Study II findings showed that carbamazepine and valproic acid had similar efficacies. ^[48] However, subset analysis for complex focal seizures suggested that carbamazepine may be a better choice than valproate. ^[48]

In elderly subjects (patients aged ≥60 years) in the VA Cooperative Study, lamotrigine and gabapentin were better tolerated than carbamazepine and were similarly effective. ^[49] However, gabapentin caused more adverse effects than lamotrigine. Those results led to the recommendation of lamotrigine as first-line monotherapy in elderly patients. ^[49]

The focal seizures arm of the SANAD trial demonstrated that although carbamazepine is the standard drug treatment, lamotrigine is clinically better with respect to time to treatment failure. ^[50] This study also determined that lamotrigine is a cost-effective alternative to carbamazepine for patients with focal-onset seizures. Carbamazepine, gabapentin, lamotrigine, oxcarbazepine, and topiramate were included for comparison. ^[50] However, the cost-effectiveness of medications has changed, as many new AEDs also have generic formulations.

All new medications have been tested as adjunctive therapy, and head-to-head comparisons of new drugs with carbamazepine have been conducted in Europe. In general, the new drugs have similar statistical efficacies but fewer adverse effects than carbamazepine; this puts the results of the SANAD trial somewhat in doubt, as the SANAD investigators did not find any important differences or trends for scores on the Adverse Events Profile among the drugs.

Of the new anticonvulsants, lamotrigine and topiramate appear to have broad spectrum of action in many seizure types. ^{[51, 52]} The American Academy of Neurology and the American Epilepsy Society assembled a task force that reviewed the literature and provided evidence-based recommendations for monotherapy, adjunctive therapy, treatment of primary generalized seizures, treatment in children, and treatment of subgroups of new-onset and refractory epilepsy. ^{[51, 52]}

If carbamazepine fails to control the seizures, lamotrigine, topiramate, tiagabine, gabapentin, levetiracetam, oxcarbazepine, pregabalin, and zonisamide are considered for second- or third-line therapy. Several new anticonvulsants, including lamotrigine, topiramate, and oxcarbazepine, are indicated as monotherapy. Although the new anticonvulsants are considered second- or third-line therapy, they can be used as first-line therapy in some patients, especially as these medications have become generic.

In October 2013, the FDA approved labeling changes for ezogabine, including a boxed warning, emphasizing increased risks for potentially permanent adverse effects, such as retinal abnormalities, vision loss, and skin discoloration. The agency recommended that the use of ezogabine be limited to patients who have had an inadequate response to several other therapies and in whom the treatment benefits outweigh the risks. The FDA also recommended eye examinations for patients before they start on ezogabine, as well as every 6 months over the course of treatment. ^{[53, 54, 55]}

Medically refractory epilepsy

Although the term medically refractory epilepsy has been used for cases that fail to respond to three antiepileptic drugs, the International League Against Epilepsy (ILAE) has proposed defining drug-resistant epilepsy as the failure to achieve sustained seizure freedom despite adequate trials of two antiepileptic drugs, either as monotherapy or in combination. ^{[56, 57]} The drugs must have been appropriately chosen and used, and failure must have occurred because of lack of efficacy and not because of adverse effects. 

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare developmental epileptic encephalopathy caused by mutations in the CDKL5 gene. 

Ganaxolone is a GABA_A receptor positive modulator. It binds specifically to GABA_A receptors to enhance their inhibitory effects. It is indicated for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2 years or older. CDD, a rare developmental epileptic encephalopathy, is largely a disease of pediatric and young adult patients. 

Approval was based on the phase 3 MARIGOLD trial. Patients treated with ganaxolone (n = 49) showed a median 30.7% reduction in 28-day major motor seizure frequency, compared with 6.9% reduction for those receiving placebo (n = 51) (p = 0.0036). In the open label extension study, patients treated with ganaxolone for at least 12 months (n = 48) experienced a median 49.6% reduction in major motor seizure frequency. ^[58]  

A study of the ILAE criteria in pediatric epilepsy patients found that the probability of achieving seizure freedom was 65%, 29%, 27% and 21%, respectively, with trials of successive therapeutic regimens. ^{[56, 57]} Patients with medically refractory epilepsy should be referred to an epileptologist.

Immunotherapy may be a viable treatment strategy in a subset of epileptic patients whose seizures are refractory to management with conventional AEDs and whose poor seizure control may result from the presence of neural-specific antibodies. ^{[59, 60]} Iorio et al found autoantibodies specific to neural antigen in 2 of 29 patients with epilepsy and other neurologic symptoms and/or autoimmune diseases (group 1) and in 9 of 30 patients with AED-resistant epilepsy (group 2).

Of the patients in group 2 who received (1) immunotherapy with intravenous (IV) steroids and IV immunoglobulin for 6 months, (2) IV methylprednisolone, IV immunoglobulin, and rituximab, or (3) IV steroids, 5 cycles of plasmapheresis, and oral steroids, 75% had a reduction in seizure frequency of 50% or greater. ^[60] The remaining patients in group 2 who received immunotherapy were evenly distributed between those who had a reduction in seizure frequency of 20-50% and those with a reduction of less than 20%. ^[60]  

Looking ahead

Future advances in AEDs will involve agents that alter the natural history of epilepsy and modify disease as opposed to providing primarily symptomatic treatment.

The use of anticonvulsants is slightly different in several populations of patients, including the following:

• Neonates

• Children

• Elderly patients

• Women on contraceptive agents

• Pregnant women ^[61]

• Patients with hepatic or renal insufficiency

• Human immunodeficiency virus (HIV) ̶ infected patients ^[62]

Neonates, children, and elderly patients

In general, neonates and children require similar loading doses per kilogram of body weight, but they tend to metabolize the drugs faster than adults. This younger population also has rapid increases in the total volume of distribution.

In contrast, elderly patients need lower initial and maintenance doses, owing to the following normal features of the aging process:

• Slowed hepatic metabolism

• Decreased renal clearance

• Decreased volumes of distribution

Women on contraceptive agents

Anticonvulsants that induce hepatic enzymes, such as carbamazepine, phenytoin, phenobarbital, primidone, felbamate, lamotrigine, topiramate, and oxcarbazepine, decrease the efficacy of oral contraceptive pills. Some anticonvulsants cause this drug interaction in a dose-dependent manner, with a negligible effect at low doses. Some obstetricians use a high-dose estrogen-progesterone contraceptive to counteract this effect. An alternative and possibly preferable approach is to use a second method of contraception.

Women of childbearing age and pregnant women

In 2009, the American Academy of Neurology and the American Epilepsy Society issued new guidelines for the management of antiepileptic drugs (AEDs) during pregnancy. ^{[61, 63, 64]} These guidelines cover obstetric complications and change in seizure frequency; teratogenesis and perinatal outcomes; and vitamin K, folic acid, blood levels, and breastfeeding.

Woman of childbearing age should take folic acid, at least 0.4 mg per day, to decrease the rate of neural-tube malformations in the fetus. In addition, evidence strongly suggests that, during pregnancy, women should take the medication that best controls their epilepsy. Switching medications during pregnancy is not recommended, because of the risk of losing seizure control and because it exposes the fetus to polypharmacy. Data from multiple studies show an exponential risk of birth defects as anticonvulsants are added in polytherapy.

Frequent drug serum levels should be obtained because of the many physiologic changes that take place during pregnancy, including changes in volume of distribution, protein binding, and hepatic metabolism and erratic absorption. In particular, decreased serum concentration of lamotrigine in the third trimester is well documented, and the dose needs to be adjusted after delivery.

Whether to perform amniocentesis is a personal decision between the woman and her obstetrician. The most important point is to have a clear idea about how the information obtained will be useful for clinical decision making.

Patients with hepatic and renal insufficiency

Gabapentin, pregabalin, levetiracetam, and lacosamide are excreted mostly by means of renal clearance, and their doses can be adjusted for renal insufficiency. These agents are useful in patients with hepatic failure, especially when a drug-induced etiology is suspected. Lamotrigine, which is metabolized by means of glucuronidation, a phase II reaction, is also used in some patients with hepatic insufficiency.

Considerable data are available on the use of phenytoin in the presence of hepatic and renal insufficiency. However, phenytoin is not a preferred medication because of its nonlinear kinetics, hepatic autoinduction, numerous drug interactions, and high degree of protein binding. Among all anticonvulsants, phenytoin, carbamazepine, valproic acid, and felbamate have been associated with acute hepatic injury.

After a person has been seizure free for typically 2-5 years, the physician may consider discontinuing that patient’s medication. Many patients outgrow many epileptic syndromes of childhood and do not need to take anticonvulsants. The relapse rate for seizures in adults is about 40-50%; for children, it is about 25%. This difference probably reflects the different epileptic syndromes that are prevalent in the 2 populations.

The recurrence rate during adulthood for patients with juvenile myoclonic epilepsy (JME) is about 80-90% in 2 years, even in patients who have spent many years being seizure free on low doses of appropriate anticonvulsants.

Risk of seizure recurrence

Many neurologists use the risk factors for new-onset seizures to assess patients for discontinuation of anticonvulsants. Normal findings on an electroencephalogram (EEG) and a brain magnetic resonance imaging (MRI) scan lower the risk of relapse after drug discontinuation, whereas epileptiform or focal abnormalities on an EEG and/or focal cortical or limbic abnormalities on a brain MRI scan significantly increase the relapse risk.

Additional factors associated with an increased risk of seizure recurrence after discontinuation include the following:

• Several seizure types (eg, worse if tonic or atonic seizures are present)

• High number and frequency of seizures

• Long duration of epilepsy before the seizures were controlled

• Short duration of seizure freedom

Seizure relapse

About 75% of seizure relapses after medication discontinuation occur in the first year, and at least 50% of patients who have another seizure do so in the first 3 months. Therefore, advise patients to observe strict seizure precautions (including not driving) during tapering and for at least 3 months after discontinuation, depending on state laws. The need to drive is an impediment for some patients, who may opt to continue therapy for that reason.

Some authors recommend that all anticonvulsants, except primidone, phenobarbital, and benzodiazepines, be gradually discontinued over 6-10 weeks if they were used for a long period. Discontinue primidone, phenobarbital, and benzodiazepines over 10-16 weeks.

A ketogenic or modified Atkins diet and vagal nerve stimulation (VNS) are nonpharmacologic methods for managing patients with seizures that are unresponsive to antiepileptic drugs. The ketogenic diet is typically used in children. The FDA has approved VNS stimulation for adolescents and adults with refractory partial epilepsy, but clinical experience also suggests efficacy and safety in children and in patients with generalized epilepsies.

Ketogenic diet and modified Atkins diet

The ketogenic diet, which relies heavily on the use of fat, such as hydrogenated vegetable oil shortening (eg, Crisco), has a role in the treatment of children with severe epilepsy. Support for the efficacy of these diets comes from large observational studies rather than from randomized, controlled trials. ^[65]

Although this diet is unquestionably effective in some refractory cases of seizure, a ketogenic diet is difficult to maintain; less than 10% of patients continue the diet after a year. Furthermore, any small carbohydrate intake (eg, lollypop, piece of candy) resets ketone metabolism for 2 weeks, thereby eliminating antiseizure efficacy. Consequently, some authors do not consider using this treatment in teenagers or adults unless all of the patient’s caloric intake is being delivered by means of a gastric tube.

Preliminary data have been published about improvement of seizure frequency following a modified Atkins (low-carbohydrate) diet that mimics the ketogenic diet but does not restrict protein, calories, and fluids. In small studies of children with intractable epilepsy, seizure reductions of more than 50% have been seen within 3 months in some children placed on this diet, particularly with carbohydrate limits of 10 g per day. ^{[66, 67]}

Preliminary studies of a modified Atkins diet have also been performed in adults. For example, Smith et al found that this diet demonstrates modest efficacy as adjunctive therapy for some adults with medically resistant epilepsy, and it may be also helpful for weight loss but can pose financial and logistical difficulties. ^[68]

Vagal nerve stimulation

VNS is a palliative technique that involves surgical implantation of a stimulating device (see Guidelines). VNS is FDA approved to treat medically refractory focal-onset epilepsy in patients older than 12 years. Some studies demonstrate its efficacy in focal-onset seizures and in a small number of patients with primary generalized epilepsy. Randomized studies showed modest efficacy at 3 months, but postmarketing experience showed delayed improvement in another group of patients.

According to the manufacturer's registry, efficacy of the stimulating device at 18 months is 40-50%, where efficacy is defined as a seizure reduction of 50% or more. Many patients report improvement in seizure intensity and general mood. However, seizure-free rates for pharmacologically intractable focal-onset epilepsy are less than 10%.

A meta-analysis of VNS clinical studies reported an average reduction in seizures of at least 50% in approximately 50% of patients at last follow-up. Although VNS was not initially FDA approved for children or patients with generalized epilepsy, the authors also found that these groups benefitted significantly from VNS.

Positive predictors of a favorable outcome with VNS therapy include posttraumatic epilepsy and tuberous sclerosis. Few patients achieve complete seizure freedom with VNS, and about a quarter of patients receive no benefit in their seizure frequency. ^[69] Some patients have clinical improvement in terms of milder and shorter seizures.

Implantable neurostimulator

The NeuroPace RNS System, a device that is implanted into the cranium, senses and records electrocorticographic patterns and delivers short trains of current pulses to interrupt ictal discharges in the brain. The Neurological Devices panel of the FDA concluded that this device was safe and effective in patients with partial-onset epilepsy in whom other antiepileptic treatment approaches have failed and that the benefits outweigh the risks. ^[70]

In November 2013, the FDA approved the NeuroPace RNS System for the reduction of seizures in patients with drug-resistant epilepsy. ^{[71, 72]} Approval was based on a clinical trial involving 191 subjects with drug-resistant epilepsy. The neurostimulator was implanted in all of these patients but activated in only half of them. After 3 months, the average number of seizures per month in patients with the activated device fell by a median of 34%, compared with an approximately 19% median reduction in patients with an unactivated device.

The 2 major kinds of brain surgery for epilepsy are palliative and potentially curative. In the past, the most common palliative surgery was anterior callosotomy, which was indicated for patients with intractable atonic seizures, who often sustain facial and neck injuries from falls. This surgery is still performed as the use of vagal nerve stimulation (VNS) in such patients has good efficacy.

Several curative surgeries are possible, including lobectomy and lesionectomy. In general, the epileptogenic zone must be mapped by using video-electroencephalographic (video-EEG) monitoring and, in some patients, with intracranial electrodes.

Lobectomy

Outcomes of temporal-lobe surgeries are better than those for surgeries in other areas. If a patient has unilateral temporal-lobe seizures (as observed on video-EEG) and unilateral hippocampal sclerosis (as observed on brain magnetic resonance imaging [MRI]), the likelihood of a class I outcome (no seizures or only auras) at 2 years is about 85%.

In a randomized, controlled trial of surgery in 80 patients with temporal lobe epilepsy, 58% of patients in the group randomized to anterior temporal lobe resective surgery were free from seizures impairing awareness at 1 year, as compared with 8% in the group that received anticonvulsant treatment. ^[73] Quality of life was also superior for patients in the surgical group.

According to research, MRI-guided selective laser amygdalohippocampectomy (SLAH) is at least as effective as standard resection. In a study of 7 patients who received SLAH and 10 patients who underwent standard resection (either open anterior temporal lobectomy or selective amygdalohippocampectomy), 9 of 10 patients in the latter group showed a significant decline on visual/verbal memory tasks (P< .002), compared with 1 of 7 patients in the former group. ^[44] Whereas 6 of 7 laser-ablation patients showed significant improvement on 1 or more memory measures, only 4 of 10 standard-resection patients did (P< .02). ^[44]

Lesionectomy

In a study presented at the 66th Annual Meeting of the American Epilepsy Society, investigators suggested that, in select pediatric patients, smaller lesionectomy resections in the surgical treatment of seizures may be as effective as larger resections, and they may spare children the functional and developmental deficits associated with the larger resections. ^{[74, 75]}

The researchers reported on the outcomes of 25 children with MRI-negative, intractable partial epilepsy who underwent focal corticectomies. Epileptogenic regions were identified by 3-dimensional EEG, single-photon emission computed tomography (SPECT) scanning, positron emission tomography (PET) scanning, and invasive EEG data. Seizure-free outcomes occurred in 3 of 7 patients with type I focal cortical dysplasia, 7 of 12 patients with type II focal cortical dysplasia, and 3 of 6 patients with mild malformations of cortical development. ^{[74, 75]}

Surgery for drug-resistant epilepsy

Although surgery for drug-resistant epilepsy is often considered a last resort, results of a multicenter trial suggested that early surgery may be helpful in some patients with newly intractable and disabling temporal lobe epilepsy. In this trial, patients who had had no more than 2 consecutive years of disabling seizures refractory to adequate trials of 2 anticonvulsant medications were randomized to anteromesial temporal lobe resection plus continued medication (n = 15) or continued medication alone (n = 23). ^[76]

At follow-up, 11 of the 15 surgery patients (73%) were seizure free during postoperative year 2; none of the patients in the medication-only group were seizure free over the same period. The researchers warned, however, that the results must be interpreted cautiously, as the trial was halted prematurely because of slow accrual. ^[66]

For more information on surgical management, see Identification of Potential Epilepsy Surgery Candidates and Outcome of Epilepsy Surgery.

The major problem for patients with seizures is the unpredictability of the next seizure. Clinicians should discuss the following types of seizure precautions with patients who have epileptic seizures or other spells of sudden-onset seizures:

• Driving

• Ascending heights

• Working with fire or cooking

• Using power tools or other dangerous equipment

• Taking unsupervised baths

• Swimming

These lifestyle precautions are clearly more applicable to some patients than to others. Document on the patient's chart that driving and occupational hazards for people with seizures were discussed.

Safety must be balanced with the risk for seizures. A patient with many poorly controlled diurnal seizures may exercise more caution than a patient who has only nocturnal seizures. Encourage the use of helmets to prevent head trauma while the patient is biking, skiing, or participating in other high-risk activities.

Driving motorized vehicles

Driving restrictions differ for each patient because of the individual features of their seizures, their degree of seizure control, and, in the United States, state laws. US physicians should be aware of the state regulations regarding driving, which vary considerably among states. If clinicians practice in a state that requires mandatory reporting of patients with epilepsy to the Department of Motor Vehicles, they must ensure they are compliant with state laws and have documentation. International variation regarding reporting is also considerable; some countries have more permissive or more restrictive laws regarding driving than does the United States.

Aside from state laws, recommendations regarding driving motorized vehicles also vary depending on whether the patient has seizures that occur exclusively during sleep. Consult current state and federal laws and regulations. For example, to resume commercial driving across state lines, a patient must have a 5-year seizure-free period. The recommendation for driving cars and trucks extends to the operation of other motorized vehicles, such as boats and motorcycles. Aircraft pilots are typically no longer permitted to fly.

Water precautions

Common sense dictates that patients with seizures should not swim alone, and they should be particularly aware of the importance of the presence of an adult lifeguard who can pull them out of the water if needed. Wearing a life jacket in a boat is important. Activities as simple as taking a bath may be risky, because a person can drown in as little as 1 inch of water during the flaccid postictal phase. In addition, a patient who has a seizure while waiting for bath water to warm up may suffer hot-water burns.

Heights, fire, and power tools

Patients with seizures may experience an episode in situations such as being up on a roof or engaging in some activity at considerable height from the floor. In addition, burns from injuries related to cooking are not uncommon, and injuries can occur with the use of power tools and other dangerous equipment. Caution—in particular, supervision—is advised when power tools are used, and the use of safety devices, such as an automatic shutoff switch, is recommended.

In 2018, the FDA cleared for marketing the first smart watch for seizure tracking and epilepsy management. The Embrace smart watch identifies convulsive seizures and sends an alert via text and phone message to caregivers. The watch also records sleep, rest, and physical activity data. The device was tested in a study of 135 epileptic patients and found the watch's algorithm detected 100% of patient seizures. ^[77]