Efficacy of the Ketogenic Diet for Intractable Seizure Disorders Review of 58 Cases
Am Fam Doctor. 1998 Apr 1;57(vii):1589-1600.
Meet related patient information handout on managing epilepsy, written by the authors of this commodity.
Article Sections
- Abstruse
- Management of Patients with New Seizures
- Medical Management of Epilepsy: General Principles
- Medical Direction: The New Agents
- The Medically Refractory Patient
- Final Comment
- References
While the evaluation and treatment of patients with seizures or epilepsy is often challenging, modernistic therapy provides many patients with complete seizure control. After a start seizure, evaluation should focus on excluding an underlying neurologic or medical condition, assessing the relative risk of seizure recurrence and determining whether treatment is indicated. Successful management of patients with recurrent seizures begins with the institution of an accurate diagnosis of epilepsy syndrome followed by handling using an appropriate medication in a manner that optimizes efficacy. The goal of therapy is to completely control seizures without producing unacceptable medication side effects. Patients who do not reach complete seizure control should be referred to an epilepsy specialist, since new medications and surgical treatments offer patients unprecedented options in seizure command.
Epileptic seizures are a common and important medical problem, with about ane in 11 persons experiencing at least ane seizure at some point.ane Epilepsy—the tendency to take recurrent, unprovoked seizures—occurs with a prevalence of about 0.five percent and a cumulative lifetime incidence of 3 per centum.2 The direction of patients with epilepsy is oftentimes challenging, every bit evidenced by a recent report that over one one-half of all patients with epilepsy proceed to feel at least occasional seizures despite handling with antiepileptic medications.three New clinical advances offering considerable hope to these patients. This article reviews the practical clinical implications of contempo studies on the epidemiology, diagnosis and management of epilepsy.
Management of Patients with New Seizures
- Abstruse
- Management of Patients with New Seizures
- Medical Management of Epilepsy: General Principles
- Medical Direction: The New Agents
- The Medically Refractory Patient
- Final Comment
- References
Despite numerous technologic advances in the evaluation of neurologic disorders, diagnosis of the get-go seizure is still based predominantly on the patient's medical history. Many paroxysmal events may exist dislocated with epileptic seizures, including syncope, movement disorders, parasomnias and psychogenic seizures.
Probably the almost common entity that is dislocated with epileptic seizures is syncope. Studies in which volunteers were videotaped during induced syncopal events illustrate the common occurrence of repetitive clonic, myoclonic or dystonic movements on fainting.4 These movements, however, rarely persist beyond five to 10 seconds and practise not exhibit the organized progression from tonic to clonic phase seen in a convulsive seizure. Thus, a detailed history of the motor activeness, together with the usual questions regarding premonitory symptoms, postictal country, natural language-biting, incontinence and provoking factors, can often aid distinguish between these two common entities.
Diagnostic Evaluation
Diagnostic studies must be tailored to individual patients. Basic laboratory evaluation focuses on detecting systemic disturbances potentially associated with seizures and includes a complete blood count and measurements of electrolytes, calcium, magnesium, phosphorus, blood urea nitrogen, creatinine and glucose. Consideration likewise should be given to obtaining a toxicology screen and evaluating hepatic office with synthetic and enzyme studies. Lumbar puncture is essential in patients in whom meningitis or encephalitis is suspected, besides every bit in immunocompromised patients, since occult meningitis is a common finding in this group.5
Most government recommend that all patients who experience an unprovoked seizure undergo a brain imaging study in an effort to find underlying cerebral lesions (e.g., tumor, abscess, vascular malformation, stroke, traumatic injury). In nonurgent cases, the imaging modality of pick is magnetic resonance imaging (MRI), since it is more sensitive than computed tomography (CT) in identifying these lesions. In patients presenting with a seizure in whom the history or test suggests new focal deficits, persistent altered mental status, fever, recent trauma, persistent headache, cancer, treatment with anticoagulation or immunocompromised country, emergent neuroimaging is recommended.half-dozen This is usually accomplished with a CT scan, given its widespread availability and speed and its superior ability in the detection of astute hemorrhage, compared with MRI.
Electroencephalography (EEG) is often helpful in the evaluation of patients presenting with a seizure. The utility of EEG includes detection of epileptiform activity, strengthening the putative diagnosis; identification of focal electrocerebral abnormalities suggesting a focal structural brain lesion; and documentation of specific epileptiform patterns associated with particular epilepsy syndromes (for example, generalized spike-and-moving ridge discharges associated with a generalized epilepsy, or focal discharges associated with a localization-related epilepsy).
Multiple recordings increase the diagnostic yield of the EEG; while approximately 30 to 50 per centum of patients with epilepsy demonstrate epileptiform abnormalities on the first EEG, the yield increases to threescore to 90 percent with repeated recordings.seven Various maneuvers increase the likelihood of recording epileptiform discharges, including sleep deprivation before the study, recording a portion of the EEG every bit the patient sleeps, recording the EEG as the patient hyperventilates for several minutes, and subjecting the patient to stroboscopic photic stimulation during the study. The EEG is also helpful in assessing the risk of seizure recurrence. A contempo prospective written report of EEGs performed in patients with untreated idiopathic first seizures plant that the presence of epileptiform abnormalities on EEG was associated with a recurrence run a risk of 83 percent, compared with 41 percent in patients with nonspecific abnormalities and 12 per centum in patients in whom routine and partially sleep-deprived EEGs were normal.8
While nearly physicians adopt not to prescribe ongoing antiepileptic therapy for patients with a unmarried seizure, the decision to treat initial seizures with medication remains controversial. Several factors should exist considered when making a decision, including the likelihood of recurrent seizures, the take a chance of the treatment itself, the ability of the handling to decrease the risk of recurrent seizures and the consequence of farther seizures to the patient. Since these factors vary from patient to patient, information technology seems unlikely that a single approach tin can be recommended. Contempo studies have better defined some of these factors so that treatment decisions tin can exist individualized.
Early nonrandomized studies of antiepileptic drug treatment in patients presenting with a first seizure did not demonstrate a reduced likelihood of seizure recurrence. These information were used to support the concept of non treating a patient with a beginning seizure, although the inherent bias associated with nonrandomization was probably responsible for the results. In 3 contempo randomized trials, antiepileptic drug treatment was associated with a pregnant reduction in recurrence risk, although the benefit persisted only for the time that the patient was taking medication.9–11 Thus, taking an antiepileptic drug for a discrete period of time did not decrease the long-term risk of somewhen developing a chronic seizure disorder.12 The finding that antiepileptic drugs are effective in preventing recurrent seizures is important in that patients with a very high risk of seizure recurrence may cull to take medication to lessen that take chances.
In a meta-analysis13 of 16 studies with median follow-upward ranging from one to five years, the run a risk of seizure recurrence post-obit an unprovoked seizure was 51 percent. The 2 most important prognostic factors influencing risk of recurrence included etiology of the seizures and EEG findings. Patients whose seizures were likely symptomatic of remote cerebral injury were more likely to experience recurrence than those whose seizures were judged to exist idiopathic, with two-year recurrence risks of 57 percentage versus 32 percent.13 As previously mentioned, patients with epileptiform disturbances (spikes or sharp waves) on the interictal EEG are more than likely to feel recurrence than those with not-epileptiform abnormalities or those with a normal EEG.8 This information helps to individualize treatment and counseling after a patient's starting time seizure.
In addition to because the probability of recurrence, one must also consider the potential psychologic, social and vocational consequences of further seizures. Since children are not as likely to have astringent social or vocational repercussions from a single recurrence, they are rarely treated for a first seizure. Some adults, nevertheless, feel that the consequences of fifty-fifty a unmarried recurrent seizure would dramatically bear on their lives, and they may choose to take medication to subtract the chance of a recurrence.
Medical Management of Epilepsy: General Principles
- Abstract
- Management of Patients with New Seizures
- Medical Direction of Epilepsy: Full general Principles
- Medical Management: The New Agents
- The Medically Refractory Patient
- Final Annotate
- References
The goal of treating patients with epilepsy is to control seizures completely without causing unacceptable side effects. In the past several years, a number of new antiepileptic drugs accept become available, and more volition soon be released.
To achieve optimal handling results, several strategies should be used (Table ane). The nearly of import step is to select an antiepileptic drug that is appropriate for the patient'due south particular type of epilepsy. A specific epilepsy syndrome diagnosis is based on the history of the patient'south seizure types, neurologic status and EEG findings (Table 2).
TABLE one
Medication Treatment Strategies for Patients with Epilepsy
| Establish an epilepsy syndrome diagnosis for each patient (Table 2) |
| Select medications appropriate for that epilepsy syndrome (Table 2) |
| From the appropriate medications, choose the agent best suited for the patient based on patient and medication characteristics (Tabular array three) |
| Initiate and titrate the medication at advisable dosages, increments and rates to enhance tolerability (Table iii) |
| Increase the medication, regardless of serum levels, until complete seizure control is achieved or until persistent, unacceptable side furnishings occur |
| If satisfactory seizure command is not accomplished, modify to another agent advisable for the epilepsy syndrome being treated; the goal should be antiepileptic drug monotherapy in each patient, when possible |
| If trials with i or two agents fail to achieve acceptable results, refer the patient to an epilepsy specialist for consultation |
TABLE two
Epilepsy Syndromes
| Generalized* | Localization-related (fractional or focal)† | |||
|---|---|---|---|---|
| Idiopathic‡ | Seizure types: absenteeism, myoclonic, tonic-clonic | Seizure types: simple fractional (awareness unimpaired), circuitous partial (sensation impaired), secondarily generalized tonic-clonic | ||
| Neurologic examination: normal | Neurologic test: normal | |||
| Neuroimaging: normal | Neuroimaging: normal | |||
| EEG: Normal background with fast (three to 6 Hz) generalized fasten-and-wave discharges | EEG: Normal background with focal epileptiform discharges | |||
| Common examples: | Mutual examples: | |||
| Childhood absence epilepsy Juvenile myoclonic epilepsy Epilepsy with generalized tonic-clonic seizures on awakening | Benign babyhood epilepsy with centro-temporal spikes (Rolandic epilepsy) Benign epilepsy with occipital paroxysms | |||
| Handling: valproate (Depakote), ethosuximide (Zarontin [constructive for absenteeism seizures merely]), lamotrigine (Lamictal), topiramate (Topamax), felbamate (Felbatol) | Handling: carbamazepine (Tegretol), phenytoin (Dilantin) | |||
| | ||||
| Symptomatic¶ | Seizure types: atypical absence, myoclonic, tonic, atonic, tonic-clonic | Seizure types: simple partial (awareness unimpaired), circuitous partial (sensation dumb), secondarily generalized tonic-clonic | ||
| Neurologic examination: diffuse or multifocal abnormalities | Neurologic examination: focal abnormalities or normal | |||
| Neuroimaging: diffuse or multifocal abnormalities common | Neuroimaging: focal abnormalities common | |||
| EEG: Abnormal background with slow (<iii Hz) generalized and/or multifocal epileptiform discharges | EEG: Normal or abnormal background with focal or multifocal epileptiform discharges | |||
| Common examples: | Common examples: | |||
| Lennox-Gastaut syndrome | Temporal lobe epilepsy | |||
| Progressive myoclonus epilepsies | Frontal lobe epilepsy | |||
| Handling: valproate, lamotrigine, topiramate, felbamate, ketogenic diet, corpus callosotomy | Treatment: carbamazepine, phenytoin, valproate, new agents (gabapentin [Neurontin], lamotrigine, tiagabine [Gabitril] topiramate, felbamate), vagus nerve stimulator, resective surgery | |||
The four wide categories of epilepsy syndromes are idiopathic generalized, symptomatic generalized, idiopathic localization-related and symptomatic localization-related. The importance of making a syndromic diagnosis is illustrated by juvenile myoclonic epilepsy, a common idiopathic generalized epilepsy syndrome in which patients may feel absence, myoclonic and convulsive (clonic-tonic-clonic or tonic-clonic) seizures. If phenytoin (Dilantin) or carbamazepine (Tegretol) is used for treatment, the nonconvulsive seizures are often worsened. In contrast, valproate (Depakote) provides consummate seizure control in nigh patients.
While patients with generalized-onset epilepsies (such as juvenile myoclonic epilepsy) respond best to valproate, whatever of the major medications (except ethosuximide [Zarontin]) may be effective in patients with localization-related (partial-onset) epilepsy. In patients with partial epilepsy, big studies have consistently demonstrated similar efficacy for phenytoin, carbamazepine, valproate, primidone (Mysoline) and phenobarbital, although the barbiturates are oftentimes poorly tolerated as a outcome of their sedating backdrop.14–16
Thus, in patients with localization-related epilepsies, drug selection is heavily influenced by the side effect profile, price and dosing frequency of each agent (Table 3). The long-term corrective consequences (which include coarsening of the facial features, gingival hyperplasia, hirsutism and enlargement of the lips) for many patients taking chronic phenytoin therapy, for instance, make this a poor first choice for children and immature adults. Nevertheless, the once-daily dosing scheme and low price make it an attractive amanuensis for other patients. Carbamazepine, especially the new extended-release preparations, is an excellent choice for many children and adults with localization-related epilepsies. Valproate, in addition to existence the drug of choice for well-nigh of the generalized epilepsies, is also efficacious in the treatment of the localization-related syndromes. Appropriately, information technology is a good offset selection in patients in whom the epilepsy syndrome is not clearly defined.
In one case the preferred medication has been chosen, therapy should be initiated at an advisable dosing schedule and increased at an appropriate dosing increment and rate (Table 3). For any of the antiepileptic drugs, we recommend that dosage increases continue—regardless of serum drug levels—until complete seizure control is achieved or until persistent, unacceptable side effects occur.
TABLE iii
Oral Antiepileptic Medications
| Generic proper name | Trade name | Strengths available* (mg) | Typical adult starting dosage† | Typical increment and rate of ascent‡ | Nigh mutual dose-related adverse effects | Non–dose-related and idiosyncratic reactions | Cost per calendar month¶ |
|---|---|---|---|---|---|---|---|
| Carbamazepine | Tegretol | 100, 200 | 200 mg twice a day | 200 mg per calendar week (taken three or four times a day) | Dizziness, somnolence, clutter, nausea, vomiting, diplopia, blurred vision | Hyponatremia, rash, Stevens-Johnson syndrome, leukopenia, aplastic anemia, agranulocytosis, transaminitis, hepatic failure | $ 68.00 (1,200 mg per twenty-four hour period) |
| Tegretol-XR | 100, 200, 400 | 200 mg twice a day | 200 mg per week (taken twice a day) | 68.00 | |||
| Carbatrol | 200, 300 | 200 mg twice a day | 200 mg per week (taken twice a day) | North/A | |||
| Ethosuximide | Zarontin | 250 | 250 mg every day to 250 mg twice a twenty-four hours | 250 mg per week | Anorexia, nausea, vomiting, drowsiness, headache, dizziness | Rash, Stevens-Johnson syndrome, hemopoietic complications | 71.00 (750 mg per day) |
| Felbamate | Felbatol | 400, 600 | 400 mg three times daily | 400 to 600 mg per week | Anorexia, airsickness, insomnia, nausea, headache, dizziness | Aplastic anemia, hepatic failure | 174.00 (iii,600 mg Per day) |
| Gabapentin | Neurontin | 100, 300, 400 | 300 mg daily to three times a day | 300 mg per week (taken iii or four times a mean solar day) | Somnolence, dizziness, clutter, fatigue | Rash, weight gain, beliefs changes, peripheral edema | 240.00 (2,700 mg Per day) |
| Lamotrigine | Lamictal | 25, 100, 150, 200 | 25 mg every other day (with valproate [Depakote]), to 25 mg twice a day (with carbamazepine, phenobarbital or phenytoin [Dilantin]) | 25 mg per 2 weeks (taken twice a day) | Dizziness, ataxia, somnolence, headache, diplopia, blurred vision, nausea, airsickness, rash | Rash, Stevens- Johnson syndrome, transaminitis | 174.00 (600 mg per day |
| Phenobarbital | 15, 30, lx, 100 | 100 mg every solar day | fifteen to 30 mg per week | Somnolence, cognitive and beliefs effects | Rash, Stevens-Johnson syndrome, hemopoietic complications, transaminitis, hepatic failure | 4.00 (200 mg per 24-hour interval) | |
| Phenytoin | Dilantin | 30, 50, 100 | 300 mg every twenty-four hours | 25 to xxx mg per week | Ataxia, diplopia, slurred oral communication, defoliation | Rash, Stevens-Johnson syndrome, hemopoietic complications, gingival hyperplasia, coarsening of facial features, transaminitis, hepatic failure | $ 32.00 (400 mg per day) |
| Tiagabine | Gabitril | 4, 12, 16, 20 | 4 mg every twenty-four hours | four mg per week (taken 2 to four times a twenty-four hour period) | Dizziness, nervousness, asthenia, confusion, tremor | Not established | 149.00 (56 mg per 24-hour interval) |
| Topiramate | Topamax | 25, 100, 200 | 25 mg twice a day | 50 mg per week | Somnolence, dizziness, ataxia, slurred speech, psychomotor slowing, cognitive issues | Anemia, acne, alopecia, weight loss, transaminitis, nephrolithiasis | 173.00 (400 mg per day) |
| Valproate | Depakote | 125, 250, 500 | 250 mg 3 times a solar day | 250 mg per calendar week | Nausea, vomiting, tremor, thrombo-cytopenia | Weight gain, hair changes/loss, transaminitis, hepatic failure, rash, Stevens-Johnson syndrome | 106.00 (one,500 mg per day) |
For patients with relatively exceptional seizures (in whom it is difficult to estimate the response to treatment without waiting many months or years for the next seizure to occur), we believe a logical arroyo is to promptly increment the medication to the maximum tolerated dosage and maintain it at this level. This can be achieved by increasing the agent until the patient begins to experience expected dose-related side effects, so reducing the dosage to the immediately previous dosage that did not produce the adverse furnishings. Once a steady state with the refined dosage has been achieved, information technology is useful to check the trough drug serum level as a reference point for the maximum tolerated dosage.
If the patient somewhen experiences a seizure when the serum level is at the reference point, the trial of medication can be considered a failure. This procedure enables assessment of efficacy in a manner significantly more efficient than just outset at an average dosage and waiting for the adjacent seizure before the next increase is implemented. If acceptable seizure control—which should be defined as complete seizure control for most patients—is non achieved at the maximum tolerated dosage of the outset medication, consideration should exist given to referring the patient for neurologic consultation, if this has not yet been undertaken. Usually, a second amanuensis will need to be added.
Every bit the dosage of the new medication is titrated up, the original medication is gradually tapered until monotherapy with the new agent is achieved. The particulars of the transition are dictated by the specific pharmacokinetic and pharmacodynamic interactions of the medications being used and the clinical condition of the patient. The new medication is then increased to the maximum tolerated dosage. We recommend that patients who fail to respond to two medications be promptly referred to an epileptologist for further evaluation.
A common error in the use of antiepileptic drugs is to base dosing on serum levels. Serum levels provide just a rough indication of the likelihood of response or dose-related side effects. In society to achieve complete seizure control, many patients require serum levels above the upper "therapeutic" limit ("toxic" levels) but tolerate these levels without ill furnishings. Furthermore, toxic levels reflect the serum concentration at which patients may experience dose-related side furnishings, symptoms that may be bothersome only are generally not life-threatening and are fully reversible with reduction of the dosage. Thus, toxic antiepileptic drug levels are dissimilar toxic levels for other drugs (e.one thousand., digoxin, lithium, theophylline), in which elevated levels are often associated with serious medical complications and are, therefore, to be avoided. In the treatment of patients with epilepsy, the clinical condition of the patient—seizure command and occurrence of adverse effects—should guide dosing of antiepileptic drugs, rather than serum drug levels.
Serum drug levels are useful for documenting the level corresponding to the maximum tolerated dosage of antiepileptic medication, assessing medication status and patient compliance when a quantum seizure has occurred, sorting out the likely crusade of nonspecific medication side effects when patients are taking multiple medications, ensuring an advisable medication level in patients who are unable to written report adverse effects (for example, young children and cognitively impaired individuals), and titrating medication dosages throughout pregnancy. In the absenteeism of one of these clinical indications, repeated "routine" determination of antiepileptic drug levels are of lilliputian value.
In general, obtaining other laboratory studies on an ongoing, "routine" ground is also of piffling value.17 We recommend obtaining hematologic and serum chemistry studies (complete blood cell count with differential and platelet count, electrolytes and liver enzymes) before instituting whatever antiepileptic medication to establish a baseline and to identify whatever preexisting abnormalities. We notice that repeat studies during the early on phases of handling (for example, at one and iii months) are sometimes useful in identifying abnormalities that may exist reflected in laboratory studies merely are not withal apparent clinically (for example, pregnant thrombocytopenia or hyponatremia). Laboratory studies should also be obtained if a patient presents with signs or symptoms compatible with a possible drug-induced status and on a routine (perhaps annual) basis in patients less able to communicate untoward effects (such every bit multiply handicapped institutionalized patients). Patients existence treated with felbamate (Felbatol) require more frequent laboratory monitoring. Specific recommendations are provided in the package insert for the drug.
Medical Direction: The New Agents
- Abstruse
- Management of Patients with New Seizures
- Medical Management of Epilepsy: General Principles
- Medical Management: The New Agents
- The Medically Refractory Patient
- Last Comment
- References
Before the release of felbamate in 1993, no new antiepileptic drug had been licensed in the Us for xv years. Over the past four years, five new drugs have been introduced, and five new formulations of previously available drugs accept been released. These new agents offer physicians expanded treatment options for patients, although the verbal roles for these medications are withal being determined.18
Felbamate was canonical by the U.S. Food and Drug Administration (FDA) in 1993 for use as adjunctive (i.e., add-on) treatment or monotherapy in adults with localization-related epilepsy and as adjunctive therapy in children with Lennox-Gastaut syndrome (symptomatic generalized epilepsy consisting of multiple types of generalized seizures). Unfortunately, felbamate has been associated with ii types of often fatal idiosyncratic reactions, aplastic anemia and fulminant hepatic failure, and therefore should only be used in patients in whom the benefits clearly outweigh the risks. Ideally, patients should exist evaluated and managed by an epileptologist if the use of felbamate is nether consideration.
Gabapentin (Neurontin), licensed in the United states in tardily 1993, is canonical for utilize as adjunctive therapy in patients 12 years of age or older with localization-related epilepsy. Gabapentin offers a number of unique pharmacokinetic and pharmacodynamic properties, making it well suited for use in patients in whom drug-drug interactions must be avoided (such as those with multiple medical problems, those taking other medications and the elderly). A disadvantage of the agent is the requirement for three or four times daily dosing.
Lamotrigine (Lamictal) was approved in 1994 equally adjunctive handling for localization-related epilepsy in adults. It appears to exhibit a broad spectrum of antiepileptic activity. The agent is used as an culling in patients with localization-related or generalized epilepsies. Evidence from controlled studies19 and clinical use suggests that lamotrigine is particularly helpful in patients with symptomatic generalized epilepsies. Information technology is typically taken twice daily. In April 1997, a new boxed alarm was added to the labeling of lamotrigine concerning reports of severe, potentially life-threatening rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Rates for potentially serious rashes, estimated from clinical studies, are approximately one in one,000 for adults and one in l to 100 in children. Equally utilize of this amanuensis increases, a more than accurate determination of the frequency of life-threatening rash should be possible. In the United States, lamotrigine is non licensed for use in children and, at the present time, we recommend its use only in children with epilepsy refractory to other medications in whom the potential benefits of the drug outweigh the risks and preferably under the supervision of an epilepsy specialist.
Topiramate (Topamax), released in early on 1997, is indicated for employ as adjunctive therapy in adults with localization-related epilepsy. Preliminary studies also propose efficacy in some generalized epilepsies. Cognitive effects plant the main dose-limiting toxicity for topiramate, and patients taking this drug have an increased incidence of nephrolithiasis.
Tiagabine (Gabitril) received FDA blessing in October 1997 as adjunctive therapy for patients 12 years of age or older with localization-related epilepsy. This novel antiepileptic drug selectively inhibits uptake of gamma-aminobutyric acrid (GABA) and prolongs the elapsing of inhibitory activity at postsynaptic receptors. Initial studies propose that dose-limiting side furnishings are mainly neurocognitive in nature, such as dizziness and nervousness.
Fosphenytoin (Cerebyx), a parenteral phenytoin prodrug, provides several significant advantages over standard parenteral phenytoin. It is easier to administer, is better tolerated and can be administered intravenously or intramuscularly. Uses for the amanuensis include intravenous assistants for the treatment of status epilepticus and handling of patients who are unable to take oral medication or in whom a more rapid attainment of a therapeutic drug level is desired. The only disadvantage of the agent is its increased expense compared with standard parenteral phenytoin.
Extended-release carbamazepine (Tegretol-XR and Carbatrol) allows twice-daily dosing. These formulations provide increased convenience to patients, improve patient compliance and provide more consequent serum levels of carbamazepine (potentially reducing height-level toxicity and trough-level seizures). Tegretol-XR consists of an extended-release tablet with a unique delivery organisation that must non be divided or chewed. The tablet is not digested, although its contents are slowly released during gastrointestinal transit. Carbatrol is formulated every bit a multi-component sheathing consisting of firsthand-, extended-and enteric-release beads. The capsule may be swallowed intact or opened and sprinkled on food for use in young children.
A parenteral training of valproate (Depacon) is now available and is indicated as an intravenous culling in patients for whom oral assistants of valproate is temporarily non feasible. At present, the agent is non indicated for the treatment of status epilepticus.
Diazepam rectal gel (Diastat) recently became available in the United States and is helpful in controlling acute repetitive seizures in patients with refractory epilepsy. It is indicated for intermittent use in the management of selected, refractory patients with epilepsy on stable antiepileptic drug regimens who are prone to bouts of increased seizure activity. The main benefit of the formulation is the ease of rectal administration.
The Medically Refractory Patient
- Abstract
- Management of Patients with New Seizures
- Medical Management of Epilepsy: General Principles
- Medical Management: The New Agents
- The Medically Refractory Patient
- Concluding Comment
- References
Participants in a 1990 National Institutes of Health consensus briefing estimated that approximately 20 per centum of patients with epilepsy, or 400,000 Americans, have intractable seizures.20 The arrival of newly licensed antiepileptic drugs is unlikely to dramatically alter the number of patients with refractory epilepsy. One review of experimental trials suggests that less than 2 percent of patients in whom conventional medications have failed will become seizure-free during a trial with a new medication.21 Since the possibility of obtaining seizure control diminishes with successive drug trials, we recommend that patients exist referred to a comprehensive epilepsy center if two or three first-line medications neglect to control seizures.
The trouble of refractory seizures is of import since patients with ongoing seizures are discipline to considerable physical risk. Studies consistently suggest that people with epilepsy, peculiarly those who feel convulsions, are at hazard of dying equally a consequence of their seizures. Indeed, the lifetime gamble of dying a seizure-related death (from status epilepticus, accidents or sudden unexplained death) is approximately 25 per centum in patients with poorly controlled epilepsy.22 When seizures can be controlled for an extended period, however, rates of mortality approach those of the full general population.23
The psychosocial consequences of poorly controlled seizures are also of major concern. Patients with epilepsy are by and large undereducated and underemployed for their level of function. Recently, investigators accept found that employment status improves in patients following seizure surgery, especially if seizures are abolished.24 Fifty-fifty rare rest seizures adversely affect the chance for employment. These observations propose that complete seizure control may be necessary to optimize a patient's quality of life. In improver, the psychosocial and concrete consequences of imperfectly controlled epilepsy underscore the importance of prompt referral to a eye specializing in the diagnosis and care of patients with epilepsy when patients neglect to completely respond to handling.
Several options exist for patients whose seizures prove refractory to the licensed antiepileptic drugs, including handling with experimental medications as office of an investigational protocol, the ketogenic diet, implantation of a vagus nerve stimulator and seizure surgery.
Vagus Nerve Stimulator
The vagus nerve stimulator is a novel, not-pharmacologic treatment for epileptic patients whose seizures are uncontrolled by medication. The device was approved by the FDA in mid-1997 for implantation in patients over 12 years of age with medically refractory localization-related epilepsy. Nether general anesthesia, a bipolar lead is wrapped around the left vagus nerve and tunneled to the infraclavicular region, where it is connected to a signal generator. This point generator delivers a precise pattern of stimulation to the vagus nerve; the parameters for stimulation are not-invasively programmed past the doc using a computerized programming wand. Typically, the device stimulates for 30 seconds every 5 minutes. In addition, by using a hand-held magnet the patient or a caregiver tin manually activate the stimulator at the onset of a seizure with the goal of terminating the seizure before it escalates. Randomized, controlled and blinded studies accept demonstrated the vagus nerve stimulator to exist efficacious in reducing the frequency of seizures in some patients, with approximately xxx pct of patients experiencing at least a l percent reduction in seizure frequency.25,26 Ongoing trials are evaluating the effectiveness of the device in reducing seizures associated with the generalized epilepsies.
Seizure Surgery
Seizure surgery should exist considered for patients in whom antiepileptic drugs fail to completely control seizures. In determining whether a patient with intractable epilepsy is a surgical candidate, information technology is important to confirm an anatomic and syndromic diagnosis appropriate for surgical treatment (Table 2). Patients with progressive metabolic or neurodegenerative conditions are generally considered poor candidates for surgery. Otherwise, most patients with intractable epilepsy should exist considered potential candidates for seizure surgery.
Anterior temporal lobe resection is the most common procedure performed for the treatment of epilepsy. Since surgery often results in complete seizure control, studies of epilepsy surgery differ from medication trials in that they typically recognize complete command of seizures as a primary outcome mensurate. Since seizure command is the most of import goal of surgery, the performance is considered a success if the patient becomes seizure-free, even if medication is still required.
Over fourth dimension, the trend has gradually turned toward improve surgical outcome in patients undergoing anterior temporal resections.27 Improved outcomes probably reflect the enhanced power to localize epileptogenic tissue with modern imaging and EEG techniques (Figure i). Currently, 80 percent of all patients undergoing temporal lobe resections at our center become seizure-free. Furthermore, patients with evidence of mesial temporal sclerosis on MRI take a prospect for a seizure-costless outcome that is greater than ninety percent.28
FIGURE 1.
High-resolution coronal magnetic resonance prototype in a patient with longstanding medically refractory temporal lobe epilepsy. Atrophy of the left hippocampus is credible (light arrows). The right hippocampus is of normal size and appearance (dark arrows). Patients with the finding of unilateral hippocampal atrophy and ictal electroencephalographic recordings that demonstrate concordant seizure localization have a very high likelihood (greater than 90 percent) of becoming seizure-costless with surgical treatment.
Occupational upshot improves afterward surgery in patients of all ages, although patients who undergo surgery earlier typically accomplish a improve occupational upshot score equally a result of better preoperative function.29 Since patients with chronic epilepsy often have been chronically disabled from their vocation, it is non surprising that they practise non become employed immediately after successful surgery.24
Almost patients undergoing seizure surgery are young and otherwise healthy, which probably explains the depression rates of surgical morbidity. Permanent, astringent deficits related to the surgery are rare. However, subtle changes in verbal skills, particularly naming, are sometimes present postoperatively in a minority of patients undergoing language-dominant temporal lobe resections.30
Concluding Comment
- Abstract
- Management of Patients with New Seizures
- Medical Management of Epilepsy: General Principles
- Medical Management: The New Agents
- The Medically Refractory Patient
- Final Comment
- References
Patients with epilepsy now take available to them more therapeutic options than ever before. In guild for patients to benefit from these advances, physicians must be attuned to making an accurate diagnosis of epilepsy syndrome, selecting and using medications properly, and promptly referring patients who practice not completely reply to treatment to a comprehensive epilepsy center.
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