Seizures in epilepsy

Carbamazepine is a tricyclic iminostilbene derivative and structurally related to the tricyclic antidepressants. It is used as a first-line agent for the management of generalized tonic-clonic epilepsy. It is also highly effective for partial seizures but has no efficacy in patients with absence seizures or atonic seizures. In epilepsy it supposedly has the same mechanism of action as phenytoin. An other well... 

In order to illustrate the kinds of arguments and considerations which are needed in relation to intention-to-treat, the discussion in this section will consider a set of applications where problems frequently arise. In Chapter 13 we will cover methods for the analysis of time-to-event or so-called survival data, but for the moment I would like to focus on endpoints within these areas that do not use the time-point at which randomisation occurs as the start point for the time-to-event measure. Examples include the time from rash healing to complete cessation of pain in Herpes Zoster, the time from six weeks after start of treatment to first seizure in epilepsy and time from eight weeks to relapse amongst responders at week 8 in severe depression. 

Nerve physiology (a) Switching mechanism in nerve cells from rest to achon potential (b) Epileptic brain, seizure in epilepsy... 

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

NTs it is now appropriate to consider what evidence there is for a malfunction of NT activity in epilepsy, particularly in those responsible for primary excitation and inhibition, i.e. the amino acids. Before doing so the epileptogenesis of absence seizures (petit mal) justifies separate consideration. 

A number of studies have shown that adenosine inhibits neuronal firing both in vitro and in vivo and is itself released during intense neuronal activity. It can protect against PTZ seizures in rodents while the antagonist theophylline is proconvulsant. No clear picture of its role in human epilepsy has emerged. 

Once it is concluded that the patient has seizures, the type of seizure and epilepsy syndrome, if any, must be determined. Proper identification and classification of the seizure type is most helpful in selecting appropriate pharmacotherapy. Without an accurate classification of the seizure type, it is possible to select a medication that is ineffective or even harmful to the patient. 

Additionally, the risk of a subsequent seizure must be determined. If there is an underlying treatable cause, such as hyponatremia or a CNS infection, the risks of another seizure and the development of epilepsy are very small. In these cases, the only pharmacotherapy that is necessary is to correct the underlying problem and possibly short-term use of an AED. Risk factors for repeated seizures in patients without an underlying disorder include ... 

Longo, B. M. and Mello, L. E. Supragranular mossy fiber sprouting is not necessary for spontaneous seizures in the intrahippocampal kainate model of epilepsy in the rat. Epilepsy Res. 32 172-182,1998. 

It is a first-line AED for patients with partial seizures. It is also approved for tonic-clonic seizures in primary generalized epilepsy. 

Epilepsy Adjunctive therapy in the treatment of partial seizures in adults with epilepsy. 

Epilepsy, adjunctive therapy Adjunctive therapy for partial seizures in adults with epilepsy and as adjunctive therapy in the generalized seizures of Lennox-Gastaut syndrome in pediatric (at least 2 years of age) and adult patients. 

Sudden unexplained death in epilepsy (SUDEP) During premarketing development, 20 sudden and unexplained deaths were recorded among 4700 patients with epilepsy (5747 patient-years of exposure). Some of these could represent seizure-related deaths in which the seizure was not observed (eg, at night). 

Epilepsy Adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients more than 12 years of age with epilepsy. Also indicated as adjunctive therapy for partial seizures in children 3 to 12 years of age. Postherpetic neuralgia For management of postherpetic neuralgia in adults. 

Seizures in patients without epilepsy Postmarketing reports have shown that tiagabine use has been associated with new onset seizures and status epilepticus in patients without epilepsy. 

Epilepsy For use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children 4 to 16 years of age with epilepsy. 

Vigabatrin is a new antiepileptic for use in epilepsy unresponsive to other therapy. It is an irreversible inhibitor of GABA-transaminase, the enzyme responsible for inactivation of the neurotransmitter GABA and it has shown efficacy against partial and secondarily generalized seizures. The principal unwanted effects are psychiatric disorders, including depression and psychosis, in a small number of patients. 

The first effective treatment of seizure disorders was the serendipitous finding in 1857 that potassium bromide could control seizures in some patients. Even though side effects were troublesome, the bromides were widely used for many years. Phenobarbital was introduced as a treatment for epilepsy in 1912 and was immediately shown to be markedly superior to bromides. While other barbiturates were synthesized and used, none were shown to be superior to phenobarbital, and the latter compound is still used. A chemically related... 

In epilepsy certain neurons and/or groups of neurons become hyperexcitable and begin firing bursts of action potentials that propagate in a synchronous manner to other brain structures (and in the case of generalized seizures, to practically all areas of the brain). These may be the result of abnormalities in neuronal membrane stability or in the connections among neurons. It is known that the epileptic bursts consist of sodium-dependent action potentials and a calcium-dependent depolarizing potential. 

Valproic acid has become a major AED against several seizure types. It is highly effective against absence seizures and myoclonic seizures. In addition, valproic acid can be used either alone or in combination with other drugs for the treatment of generalized tonic-clonic epilepsy and for partial seizures with complex symptoms. 

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