Treatment Of Seizure Disorders Research Articles

ANTICONVULSANTS

In addition to their use in the treatment of seizure disorders and various otherwise treatment-refractory psychiatric cases (e.g. mania), anticonvulsants have pined recognition for their beneficial effect in the treatment of aggressive behavior. In particular, carbamazepine has been consistently shown to be effective in lowering aggression regardless of psychiatric or neurological condition. Empirical studies of the effectiveness of anticonvulsants in decreasing aggression are reviewed and evaluated. Cost benefit factors related to the use of anticonvulsants in the treatment of violent individuals are evaluated. Finally, a protocol for the implementation and monitoring of anticonvulsant treatment is presented.

Treatment of seizure disorders with very frequent refractory centrotemporal spikes: Efficacy of clonazepam, acetazolamide, and clorazepate

Treatment of seizure disorders with very frequent refractory centrotemporal spikes: Efficacy of clonazepam, acetazolamide, and clorazepate

Epilepsy: principles of surgical management.

In his keynote address, the author reviews early work in the surgical management of the epilepsies and presents a state-of-the-art review of current basic science and clinical indications for and results from corpus callosotomy for the treatment of seizure disorders.

Critical Issues in the Treatment of Epilepsy

Classification of seizure types and evaluation and treatment of seizure disorders are discussed. Once the diagnosis of a seizure is made, the seizure type must be identified; this will help in determining the treatment. In partial seizures, the electrical discharge occurs focally, while generalized seizures involve both cerebral hemispheres simultaneously. Magnetic resonance imaging is the preferred test in the evaluation of patients with seizures, although computed tomography and electroencephalography can also be helpful. Selection of an antiepileptic drug (AED) is based on efficacy, toxicity, and, to a lesser degree, cost. Adverse reactions occur in up to 50% of patients. First-line AEDs include carbamazepine, ethosuximide, phenobarbital, primidone, phenytoin, and valproic acid. Serum AED concentrations can be helpful in managing patients with epilepsy. The serum concentrations required to control seizures or resulting in toxicity may vary among patients. Most seizures are manageable with oral AEDs. Medications of choice in status epilepticus include diazepam, lorazepam, phenytoin, and phenobarbital. The key to treating epilepsy is correct diagnosis of the seizure type and, when possible, the type of epilepsy. Most patients with epilepsy respond to one of the first-line AEDs; second-line agents may be useful in patients who do not respond to one or a combination of the first-line agents.

New method for the determination of four antiepileptic drugs in human plasma by high performance liquid chromatography

The concurrent administration of several antiepileptic drugs for the treatment of seizure disorders has become common practice. Lamotrigine is a new antiepileptic given in combination with other antiepileptic drugs, but which is not routinely measured in clinical laboratories. An isocratic high-performance liquid chromatographic method is described for the simultaneous measuring lamotrigine, carbamazepine, phenobarbital and phenytoin within 10 minutes. The chromatographic system used an Hichrom Spherisorb CN column (20 cm×4 mm, i.d., 5 μm particle size), a μBondapak CN precolumn, and a mobile phase consisting of methanol : acetonitrile : 5 mM sodium acetate (5:20:75: by volume, pH adjusted to 6.3 with acetic acid). BWA 725C was used as internal standard. The drugs were extracted from 200 μl of plasma with ethyl acetate, acetonitrile and 5 mM sodium acetate. After evaporation of the organic layer and reconstitution in mobile phase, 25 μl of extract was eluted with mobile phase at a flow rate of 1.2 ml/min. The eluted drugs were detected by their absorption at 205 nm and quantified from their peak heights. The method was found to be rapid, relatively simple to perform and sufficiently sensitive to determine each drug over its entire therapeutic range. Lower limits of detection varied from 50–100 ng/ml, absolute recoveries from 93–98%, and mean intra- and inter-assay CVs were <3.0%.

Clinical Pharmacology of Antiepileptic Drugs: Selected Topics

This article illustrates basic principles of clinical pharmacology presented in article 1 with specific examples from the treatment of seizure disorders. The discussion includes protein binding, the role of a major carbamazepine metabolite, alterations in pharmacology of AEDs in the elderly, and AED withdrawal. The last topic, in particular, is a good example of the interaction of pharmacokinetic and pharmacodynamic considerations in explaining the clinical effects of a drug.

Use of intravenous immune globulin in the treatment of seizure disorders

Recurrent seizures are a significant cause of childhood morbidity. Often the underlying pathogenesis is unknown. Studies from several laboratories have suggested a relationship between perturbations of humoral immunity and clinical epilepsy. Brain-specific antigens have been observed in the systemic circulation after brain injury. This can be followed by the appearance of antibodies to neuronal tissues in both serum and cerebrospinal fluid. Moreover, there appears to be disproportionate representation of persons with coexisting humoral immune deficiencies among patients with chronic epilepsy. Interestingly, a potent immunosuppressant, adrenocorticotropic hormone, has long been the principal treatment for infantile spasms. Given this body of information associating humoral immunity with recurrent seizures, several investigators have recently attempted to treat intractable childhood epilepsy with high-dose intravenous immune globulin. Although the number of patients treated is small and it is not possible to make comparisons between individual studies, nevertheless the results have been encouraging. Five patients with intractable seizures who failed to respond to conventional therapy were treated with an outpatient regimen of intravenous immune globulin (1 gm/kg/day) for 2 days. Two patients showed significant clinical improvement while a third had an equivocal response. Immunologic analysis of these patients before therapy revealed a surprisingly high incidence of immune abnormalities. We conclude that intravenous immune globulin may be useful in the treatment of selected patients with chronic epilepsy unresponsive to anticonvulsants.

The functional states of the thalamus and the associated neuronal interplay.

The functional states of the thalamus and the associated neuronal interplay.

Comparison of monotherapy with valproate and other antiepileptic drugs in the treatment of seizure disorders

Comparative data strongly suggest that valproate is the drug of choice for patients with primary and secondarily generalized epilepsies and that it is as effective as other antiepileptic drugs in the treatment of less clearly defined or partial epilepsies beginning in adult life. In simple absence epilepsy, several studies found no significant difference in efficacy between valproate and ethosuximide. In all primary generalized epilepsies, valproate has in many studies produced an excellent response, with one comparative study showing that valproate was as effective as phenytoin. Infantile spasms responded as well to valproate as to adrenocorticotropic hormone in several studies, while valproate produced fewer side effects. More long-term studies designed to compare the efficacy of monotherapy with valproate with that of other antiepileptic drugs are needed, and several are underway in both Europe and the United States.

Treatment of seizure disorders and pharmaceutical compositions useful therein: Nikolaus Seiler, Shakir Sarhan, Strasbourg, France assigned to Merrell Dow Pharmaceuticals Inc

Treatment of seizure disorders and pharmaceutical compositions useful therein: Nikolaus Seiler, Shakir Sarhan, Strasbourg, France assigned to Merrell Dow Pharmaceuticals Inc

Treatment of seizure disorders and myoclonus

Treatment of seizure disorders and myoclonus

Psychiatric Indications for Carbamazepine

Carbamazepine, a drug initially used for the treatment of seizure disorders, is currently being investigated for its usefulness with psychiatric patients. Affectively disturbed patients in particular have received attention. This article presents three clinical vignettes of patients helped by carbamazepine and suggests future research directions.

Recent advances in the diagnosis and treatment of seizure disorders

Epilepsy is a symptom of central nervous system dysfunction, not a specific disease. Epileptic seizures may occur as a complication of hereditary or acquired disease of the nervous system, such as Tay-Sachs disease, head injury, or infectious meningitis; of systemic disease such as metastatic cancer, or lupus erythematosus; or metabolic derangements such as hypo-calcemia or hyponatremia (which may also play a role in seizures accompanying renal or hepatic disease). Drug toxicity may also be a cause of seizures. Patients who recover from an acute illness such as CNS infection may suffer from persistent epilepsy. In the case of most of the approximately 2 million people with epilepsy in the USA (10% have more than 1 seizure per month), however, no definite cause for their illness can be found.

Cellular Mechanisms of Benzodiazepine Action

BENZODIAZEPINES are in common clinical use because they possess a fortunate combination of important therapeutic properties. They are effective in the treatment of two common clinical conditions—anxiety and insomnia—and they are useful in the treatment of seizure disorders and certain kinds of spasticity as well. In addition to these therapeutic actions, these drugs lack significant side effects outside of the CNS and have low toxicity, factors that have contributed to their widespread clinical use. Since the introduction of chlordiazepoxide hydrochloride (Librium) in 1960, research into the cellular mechanisms of benzodiazepine action has increased in parallel with the use of these agents. In this review, some recent advances in elucidating the mechanisms of action of benzodiazepines in the CNS are described. The principal lines of basic research on benzodiazepines fall into two general categories: biochemical and electrophysiological. Although they will be discussed separately, they represent complementary strategies for achieving a comprehensive

School involvement in the treatment of seizure disorders.

In has long been recognized that school personnel can play an important role in the treatment of seizure disorders. In order to better understand their involvement in the treatment process, two state-wide studies of special education programs were conducted. Teachers completed questionnaires for 315 pupils in their classrooms who were receiving drug therapy for a seizure disorder, and the mothers of 130 of these children were interviewed by telephone. The two investigations yielded similar results. Teachers were often not informed about the overt features of the seizures, side effects of the medication, or seizure management, even in the case of students who experienced seizures and/or side effects in school. In 70% of the cases, teachers were involved in either evaluating the response to treatment, administering medication, or managing (coping with) seizures in the classroom. They usually interacted with parents or other school personnel; direct communication with the physician was virtually nonexistent. Over one-third of the students were rated as more drowsy or sleepy than their peers, and, according to teachers, drug-induced impairments in adaptive behavior were a common problem. Collectively, these data suggest that in many cases, no one has assumed responsibility for coordinating the delivery of services for psychosocial treatment needs.

Seizure Disorders Among Prisoners

To the Editor.— Drs King and Young relied on the rates that anticonvulsant medications were actually prescribed by the physicians who provide medical care in various correctional institutions and concluded that the incidence of seizure disorders is increased among prisoners. Unfortunately, the authors have failed to consider several of the following possible sources of bias: (1) As a generalization, prisoners are skilled at manipulating others to get what they want. (2) One might anticipate a certain willingness by prisoners to go to some lengths to obtain a sedative, and phenobarbital, commonly used in the treatment of seizure disorders, is a coveted downer. (3) A false-negative error in the treatment of a seizure disorder would be highly visible to many members of a prison community and possibly highly embarrassing for a prison physician, while a false-positive error would not be noticed in an environment wherein the watchword must be don't rock

Seizure Disorders Among Prisoners-Reply

We generally agree with the caveats of Dr Bader and Dr French regarding the use of anticonvulsant prescription rates in estimating the prevalence of seizure disorders among prisoners. In some institutions there is a tendency for prisoners to be overmedicated. At one maximum-security institution cited and discussed in our article, 6% of the population were using prescribed anticonvulsants. At three other institutions of similar size, there was close agreement between the rates (1.7%, 1.8%, and 1.9%) of anticonvulsants prescribed. These latter rates are in close agreement with the 1.8% rate of epilepsy by physician diagnoses in studies of the North Carolina prisons and New York City jails. 1,2 We agree that prison physicians are careful to avoid a false-negative error in the treatment of seizure disorders. Unfortunately, in many prisons and jails adequate specialized diagnostic and consultative resources are not readily accessible. Thus, it is possible that false-positive

1119 DYSTONIA ASSOCIATED WITH CARBAMAZEPINE USE

Carbamazepine (Tegretolr) is used effectively in the treatment of seizure disorders and trigeminal neuralgia. Reported side effects are primarily neurological, occur infrequently and rarely require discontinuation of the drug. We have cared for 3 children in whom 4 episodes of dystonia and opisthotonus occurred in association with carbamazepine use. The patients, a 2 yr. old with microcephaly, a 3 yr. old with cerebral dysgenesis and a 5 yr. old with spastic quadraplegia; all had seizures requiring multiple anticonvulsants. In all 3 patients carbamazepine was introduced and gradually increased to a maximum of 25 mg/kg/d. Symptoms began 2-3 weeks after introduction of therapy and subsided within 3 weeks after discontinuation. In one case a 2nd course of carbamazepine resulted in a return of the dystonia. No hematologic or hepatic abnormalities were noted. Blood levels of concurrently administered anticonvulsants, including phenytoin, were within therapeutic range. A single carbamazepine blood level obtained during one of the episodes was also therapeutic (5.1 mcg/ml). Early reports of carbamazepine's beneficial effect in some dystonic syndromes have not been supported by further clinical trials. It has also been reported to enhance the release of ADH. Our observation of incapacitating but reversible dystonia raises further question about the effects of carbamazepine on the central nervous system. The need exists for an awareness of this complication in physicians caring for neurologically handicapped children.

Drugs 5 years later: carbamazepine.

Carbamazepine was approved 5 years ago by the FDA for treatment of pain associated with trigeminal neuralgia and glossopharyngeal neuralgia. It is now the principal drug for treatment of these conditions. Studies have shown that it is also effective in the treatment of the lightning pains associated with tabes dorsalis; however, it was not approved by the FDA for this condition. Carbamazepine is used most of the world outside the United States as an anticonvulsant. Currently, controlled studies in the United States are under way to determine its efficacy in treating seizure disorders. Because carbamazepine has many side reactions, completely listed in the package insert, patients receiving this drug must be followed closely.

CURRENT CONCEPTS IN THERAPY: TREATMENT OF SEIZURE DISORDERS (EPILEPSY). (CONCLUDED FROM DECEMBER 12).

CURRENT CONCEPTS IN THERAPY: TREATMENT OF SEIZURE DISORDERS (EPILEPSY). (CONCLUDED FROM DECEMBER 12).