Epilepsy Res. ;33() Bruno MK, Harden CL. Epilepsy in pregnant women. Curr Treat Options Neurol. ;4(1): New York: Elsevier, ;73– 2. Castro L, Bazil C, Walczak T. Nocturnal seizures disrupt sleep architecture and decrease sleep efficiency. On the Scientific and Empirical Investigation of the Epilepsies. Epileptic seizures due to thrombotic and embolic cerebrovascular disease in older patients .
and (Reference) Seizures Treats Epilepsy
Studies in which volunteers were videotaped during induced syncopal events illustrate the common occurrence of repetitive clonic, myoclonic or dystonic movements on fainting. Thus, a detailed history of the motor activity, together with the usual questions regarding premonitory symptoms, postictal state, tongue-biting, incontinence and provoking factors, can often help distinguish between these two common entities.
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 also should be given to obtaining a toxicology screen and evaluating hepatic function with synthetic and enzyme studies.
Lumbar puncture is essential in patients in whom meningitis or encephalitis is suspected, as well as in immunocompromised patients, since occult meningitis is a common finding in this group. Most authorities recommend that all patients who experience an unprovoked seizure undergo a brain imaging study in an effort to detect underlying cerebral lesions e. In nonurgent cases, the imaging modality of choice 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 examination suggests new focal deficits, persistent altered mental status, fever, recent trauma, persistent headache, cancer, treatment with anticoagulation or immunocompromised state, emergent neuroimaging is recommended.
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-wave 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 percent of patients with epilepsy demonstrate epileptiform abnormalities on the first EEG, the yield increases to 60 to 90 percent with repeated recordings. The EEG is also helpful in assessing the risk of seizure recurrence. A recent prospective study of EEGs performed in patients with untreated idiopathic first seizures found that the presence of epileptiform abnormalities on EEG was associated with a recurrence risk of 83 percent, compared with 41 percent in patients with nonspecific abnormalities and 12 percent in patients in whom routine and partially sleep-deprived EEGs were normal.
While most physicians prefer not to prescribe ongoing antiepileptic therapy for patients with a single seizure, the decision to treat initial seizures with medication remains controversial. Several factors should be considered when making a decision, including the likelihood of recurrent seizures, the risk of the treatment itself, the ability of the treatment to decrease the risk of recurrent seizures and the consequence of further seizures to the patient.
Since these factors vary from patient to patient, it seems unlikely that a single approach can be recommended. Recent studies have better defined some of these factors so that treatment decisions can be 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 data were used to support the concept of not treating a patient with a first seizure, although the inherent bias associated with nonrandomization was probably responsible for the results. In three recent randomized trials, antiepileptic drug treatment was associated with a significant reduction in recurrence risk, although the benefit persisted only for the time that the patient was taking medication.
In a meta-analysis 13 of 16 studies with median follow-up ranging from one to five years, the risk of seizure recurrence following an unprovoked seizure was 51 percent.
The two 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 be idiopathic, with two-year recurrence risks of 57 percent versus 32 percent.
In addition to considering 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 severe social or vocational repercussions from a single recurrence, they are rarely treated for a first seizure. Some adults, however, feel that the consequences of even a single recurrent seizure would dramatically affect their lives, and they may choose to take medication to decrease the chance of a recurrence.
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 have become available, and more will soon be released.
To achieve optimal treatment results, several strategies should be used Table 1. The most important step is to select an antiepileptic drug that is appropriate for the patient's particular type of epilepsy. A specific epilepsy syndrome diagnosis is based on the history of the patient's seizure types, neurologic status and EEG findings Table 2.
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 Table 3. Initiate and titrate the medication at appropriate dosages, increments and rates to enhance tolerability Table 3.
Increase the medication, regardless of serum levels, until complete seizure control is achieved or until persistent, unacceptable side effects occur. If satisfactory seizure control is not achieved, change to another agent appropriate for the epilepsy syndrome being treated; the goal should be antiepileptic drug monotherapy in each patient, when possible.
If trials with one or two agents fail to achieve acceptable results, refer the patient to an epilepsy specialist for consultation. Normal background with fast 3 to 6 Hz generalized spike-and-wave discharges. Childhood absence epilepsy Juvenile myoclonic epilepsy Epilepsy with generalized tonic-clonic seizures on awakening.
Benign childhood epilepsy with centro-temporal spikes Rolandic epilepsy Benign epilepsy with occipital paroxysms. Normal or abnormal background with focal or multifocal epileptiform discharges. The four broad 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 experience 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 complete seizure control in most patients.
While patients with generalized-onset epilepsies such as juvenile myoclonic epilepsy respond best to valproate, any of the major medications except ethosuximide [Zarontin] may be effective in patients with localization-related partial-onset epilepsy. In patients with partial epilepsy, large studies have consistently demonstrated similar efficacy for phenytoin, carbamazepine, valproate, primidone Mysoline and phenobarbital, although the barbiturates are often poorly tolerated as a result of their sedating properties.
Thus, in patients with localization-related epilepsies, drug selection is heavily influenced by the side effect profile, cost and dosing frequency of each agent Table 3. The long-term cosmetic consequences which include coarsening of the facial features, gingival hyperplasia, hirsutism and enlargement of the lips for many patients taking chronic phenytoin therapy, for example, make this a poor first choice for children and young adults. Yet, the once-daily dosing scheme and low cost make it an attractive agent 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 being the drug of choice for most of the generalized epilepsies, is also efficacious in the treatment of the localization-related syndromes.
Accordingly, it is a good first choice in patients in whom the epilepsy syndrome is not clearly defined. Once the preferred medication has been chosen, therapy should be initiated at an appropriate 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.
Hyponatremia, rash, Stevens-Johnson syndrome, leukopenia, aplastic anemia, agranulocytosis, transaminitis, hepatic failure. Dizziness, ataxia, somnolence, headache, diplopia, blurred vision, nausea, vomiting, rash. Rash, Stevens-Johnson syndrome, hemopoietic complications, transaminitis, hepatic failure. Rash, Stevens-Johnson syndrome, hemopoietic complications, gingival hyperplasia, coarsening of facial features, transaminitis, hepatic failure.
Somnolence, dizziness, ataxia, slurred speech, psychomotor slowing, cognitive problems. Dosages are for nonurgent initiation of medication; clinical circumstances may necessitate increased dosages and accelerated titration. See prescribing information for pediatric dosages, which are based on body weight and often must be administered more frequently than in adult dosages.
Note that phenytoin may be increased in mg increments by using a halved mg Dilantin Infatab tablet or by 30 mg using a mg Dilantin Kapseal capsule. Medical Economics Data, Cost to the patient will be higher, depending on prescription filling fee.
For patients with relatively infrequent seizures in whom it is difficult to gauge the response to treatment without waiting many months or years for the next seizure to occur , we believe a logical approach is to promptly increase the medication to the maximum tolerated dosage and maintain it at this level. This can be accomplished by increasing the agent until the patient begins to experience expected dose-related side effects, and then reducing the dosage to the immediately previous dosage that did not produce the adverse effects.
Once a steady state with the refined dosage has been achieved, it is useful to check the trough drug serum level as a reference point for the maximum tolerated dosage.
If the patient eventually 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 simply beginning at an average dosage and waiting for the next seizure before the next increase is implemented.
If adequate seizure control—which should be defined as complete seizure control for most patients—is not achieved at the maximum tolerated dosage of the first medication, consideration should be given to referring the patient for neurologic consultation, if this has not yet been undertaken. Usually, a second agent will need to be added. As 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 status 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 only a rough indication of the likelihood of response or dose-related side effects.
Furthermore, toxic levels reflect the serum concentration at which patients may experience dose-related side effects, symptoms that may be bothersome but are generally not life-threatening and are fully reversible with reduction of the dosage. Thus, toxic antiepileptic drug levels are unlike toxic levels for other drugs e. In the treatment of patients with epilepsy, the clinical status of the patient—seizure control 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 breakthrough seizure has occurred, sorting out the probable cause of nonspecific medication side effects when patients are taking multiple medications, ensuring an appropriate medication level in patients who are unable to report adverse effects for example, young children and cognitively impaired individuals , and titrating medication dosages throughout pregnancy.
We find that repeat studies during the early phases of treatment for example, at one and three months are sometimes useful in identifying abnormalities that may be reflected in laboratory studies but are not yet apparent clinically for example, significant thrombocytopenia or hyponatremia.
Laboratory studies should also be obtained if a patient presents with signs or symptoms compatible with a possible drug-induced condition and on a routine perhaps annual basis in patients less able to communicate untoward effects such as multiply handicapped institutionalized patients.
Patients being treated with felbamate Felbatol require more frequent laboratory monitoring. Specific recommendations are provided in the package insert for the drug.
Before the release of felbamate in , no new antiepileptic drug had been licensed in the United States for 15 years. Over the past four years, five new drugs have been introduced, and five new formulations of previously available drugs have been released. These new agents offer physicians expanded treatment options for patients, although the exact roles for these medications are still being determined.
Felbamate was approved by the U. Unfortunately, felbamate has been associated with two 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 be evaluated and managed by an epileptologist if the use of felbamate is under consideration. Gabapentin Neurontin , licensed in the United States in late , is approved for use 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 as adjunctive treatment for localization-related epilepsy in adults. It appears to exhibit a broad spectrum of antiepileptic activity. The agent is used as an alternative in patients with localization-related or generalized epilepsies.
Evidence from controlled studies 19 and clinical use suggests that lamotrigine is particularly helpful in patients with symptomatic generalized epilepsies. It is typically taken twice daily. In April , a new boxed warning 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 1, for adults and one in 50 to in children. As use of this agent increases, a more accurate determination of the frequency of life-threatening rash should be possible. In the United States, lamotrigine is not 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 , is indicated for use as adjunctive therapy in adults with localization-related epilepsy. Preliminary studies also suggest efficacy in some generalized epilepsies. Cognitive effects constitute the main dose-limiting toxicity for topiramate, and patients taking this drug have an increased incidence of nephrolithiasis. Tiagabine Gabitril received FDA approval in October 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 acid GABA and prolongs the duration of inhibitory activity at postsynaptic receptors.
Initial studies suggest that dose-limiting side effects 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 agent include intravenous administration for the treatment of status epilepticus and treatment 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 consistent serum levels of carbamazepine potentially reducing peak-level toxicity and trough-level seizures. Tegretol-XR consists of an extended-release tablet with a unique delivery system that must not be divided or chewed.
The tablet is not digested, although its contents are slowly released during gastrointestinal transit. Carbatrol is formulated as a multi-component capsule consisting of immediate-, extended-and enteric-release beads. The capsule may be swallowed intact or opened and sprinkled on food for use in young children. A parenteral preparation of valproate Depacon is now available and is indicated as an intravenous alternative in patients for whom oral administration of valproate is temporarily not feasible.
At present, the agent is not 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.
Epilepsy Unprovoked seizure epileptic seizure: Provocative factors for epilepsy Situational factors that can trigger epileptic seizures in epilepsy patients: Excessive physical exertion Sleep deprivation Strobe light flashing Loud music Provoked seizures Acute symptomatic seizures that are secondary to acute conditions: Metabolic and electrolyte disturbances: Common causes according to age group References: Ictal phase Sudden onset Rapid progression of symptoms Duration usually 1—3 minutes Postictal phase Varying degree of confusion , impaired alertness Residual neurologic symptoms e.
Focal seizures Origin Ictal phase Post-ictal phase Focal seizure with intact consciousness simple partial seizures Focal cerebral regions confined to one hemisphere Prodromal symptoms: Ictal phase Post-ictal phase Generalized motor seizure Tonic-clonic seizure Prodromal symptoms may occur hours before seizure onset e.
Brief loss of consciousness Interrupted motion or activity, blank stare , unresponsiveness Can occur several hundred times a day and usually ceases after 5—20 seconds Very subtle automatisms often go unnoticed! Confirm a seizure Patient history: If no epileptiform discharges are detected, diagnosis of pseudoseizures should be considered. In every patient with loss of consciousness during an ictal event , cardiogenic causes e.
West syndrome , benign epilepsy with centrotemporal spikes , juvenile absence epilepsy Constellation: Vasovagal syncope Stokes-Adams attack Carotid sinus syndrome Cardiac failure Orthostatic hypotension Stroke including transient ischemic attack Migraine Sleep disorders REM sleep behavior disorder Narcolepsy Breath-holding spell benign condition Occurs in children 6 months—6 years Strong association with iron deficiency anemia Clinical features Episodes of prolonged expiratory apnea Followed by loss of consciousness syncope Transient paroxysms of cyanosis or pallor Possibly generalized stiffness and jerky movements of the limbs anoxic seizure Triggers: Only if atypical presentation of BHS: CBC , serum ferritin rule out iron deficiency anemia Treatment: Acute management Cardiopulmonary resuscitation ABCs Avoid hazards Monitor vital signs especially oxygenation via pulse oximetry First seizure Long-term medical therapy is usually not required, unless there are abnormalities seen on EEG or MRI or the patient is in status epilepticus.
Remove cause or provoking factors e. Generalized convulsive status epilepticus GCSE: GCSE is a medical emergency and must be addressed as soon as possible! Coma , tonic-clonic movements, generalized convulsions After extended seizure activity, the clinical features may become less obvious but seizure activity may still be seen on EEG Nonconvulsive status epilepticus NCSE: Place patient in recovery position to prevent injury.
Quick neurological examination to determine type and cause of status epilepticus and general medical evaluation particularly airway , breathing, and circulation Establish secure IV access two, if possible , collection of blood for routine blood tests particularly electrolytes and glucose levels , toxicology screen, antiepileptic drug levels, and arterial blood gas ABG analysis Supportive therapy as necessary e.
IV lorazepam ; se cond line: Risk of seizure recurrence Overall risk of recurrence After the first unprovoked seizure within 2 years: State law may require that patients who have had a seizure not be permitted to drive or operate heavy machinery for a certain length of time.
Fever Idiopathic genetic association suspected Infections Traumatic brain injury Brain malformations Metabolic disorders. Traumatic brain injury Encephalitis Genetic disorders Illicit substance abuse. Alcohol withdrawal Traumatic brain injury Illicit substance abuse Brain tumors. Alcohol withdrawal Stroke or TIA Traumatic brain injury Brain tumors Metabolic disorders Vascular encephalopathies and vascular dementia in the elderly.
Focal cerebral regions confined to one hemisphere. Residual neurologic deficits depending on the affected cerebral region Todd's paralysis: Postictal weakness or paralysis of the affected limb or facial muscles for minutes or up to hours. Confusion Anterograde amnesia Aphasia Fatigue , possibly short phase of coma Muscular flaccidity and muscle pain Headache.
Management of Seizures and Epilepsy
REFERENCES Seizures and epilepsy: Hope through research. . Debate: Does genetic information in humans help us treat. Multiple references to epilepsy can be found in the ancient texts of all civilizations , of epilepsy and the topographic localization of epileptic seizures. .. Hospitalier Sainte Anne in Paris to treat patients with schizophrenia. Epilepsy is defined as a brain disorder characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic.