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Epilepsy is a group of neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures are episodes that can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly such as broken bones or through causing accidents. In epilepsy, seizures have a tendency to recur and have no immediate underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to their condition.
A seizure, formally known as an epileptic seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with loss of consciousness, to shaking movements involving only part of the body with variable levels of consciousness, to a subtle momentary loss of awareness. Most of the time these episodes last less than two minutes and it takes some time to return to normal. Loss of bladder control may occur.
Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.
Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for generalized or focal seizures. It is taken by mouth.
Lamotrigine, sold as the brand name Lamictal among others, is an anticonvulsant medication used to treat epilepsy and to delay or prevent the recurrence of depressive episodes in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome. In bipolar disorder, lamotrigine has not been shown to reliably treat acute depression; but for patients with bipolar disorder who are not currently symptomatic, it appears to be effective in reducing the risk of future episodes of depression.
Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat epilepsy and bipolar disorder. For epilepsy it is used for both focal seizures and generalized seizures. It has been used both alone and as add-on therapy in people with bipolar who have had no success with other treatments. It is taken by mouth.
Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formulation or by injection into a vein.
Primidone, sold under various brand names, is a barbiturate medication that is used to treat partial and generalized seizures, as well as essential tremors. It is taken by mouth.
Sudden Unexpected Death in Epilepsy (SUDEP) is a fatal complication of epilepsy. It is defined as the sudden and unexpected, non-traumatic and non-drowning death of a person with epilepsy, without a toxicological or anatomical cause of death detected during the post-mortem examination.
Rufinamide is an anticonvulsant medication. It is used in combination with other medication and therapy to treat Lennox–Gastaut syndrome and various other seizure disorders. Rufinamide, a triazole derivative, was developed in 2004 by Novartis Pharma, AG, and is manufactured by Eisai.
Racine stages are a categorization of epileptic seizures proposed by Ronald J. Racine in 1972. Prior to Racine's research in epilepsy, a quantifiable means to describe seizure intensities and their causes was not readily available. Racine's work allowed for epilepsy to be understood on a level previously thought impossible.
Seletracetam is a pyrrolidone-derived drug of the racetam family that is structurally related to levetiracetam. It was under development by UCB Pharmaceuticals as a more potent and effective anticonvulsant drug to replace levetiracetam but its development has been halted.
Lacosamide, sold under the brand name Vimpat among others, is a medication used in the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain. It is used by mouth or intravenously.
Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by physical trauma to the brain. A person with PTE suffers repeated post-traumatic seizures more than a week after the initial injury. PTE is estimated to constitute 5% of all cases of epilepsy and over 20% of cases of acquired epilepsy.
Spike-and-wave is a pattern of the electroencephalogram (EEG) typically observed during epileptic seizures. A spike-and-wave discharge is a regular, symmetrical, generalized EEG pattern seen particularly during absence epilepsy, also known as ‘petit mal’ epilepsy. The basic mechanisms underlying these patterns are complex and involve part of the cerebral cortex, the thalamocortical network, and intrinsic neuronal mechanisms. The first spike-and-wave pattern was recorded in the early twentieth century by Hans Berger. Many aspects of the pattern are still being researched and discovered, and still many aspects are uncertain. The spike-and-wave pattern is most commonly researched in absence epilepsy, but is common in several epilepsies such as Lennox-Gastaut syndrome (LGS) and Ohtahara syndrome. Antiepileptic drugs (AEDs) are commonly prescribed to treat epileptic seizures, and new ones are being discovered with fewer adverse effects. Today, most of the research is focused on the origin of the generalized bilateral spike-and-wave discharge. One proposal suggests that a thalamocortical (TC) loop is involved in the initiation spike-and-wave oscillations. Although there are several theories, the use of animal models has provided new insight on spike-and-wave discharge in humans.
Kindling is a commonly used model for the development of seizures and epilepsy in which the duration and behavioral involvement of induced seizures increases after seizures are induced repeatedly. The kindling model was first proposed in the late 1960s by Graham V. Goddard and colleagues. Although kindling is a widely used model, its applicability to human epilepsy is controversial.
A convulsant is a drug which induces convulsions and/or epileptic seizures, the opposite of an anticonvulsant. These drugs generally act as stimulants at low doses, but are not used for this purpose due to the risk of convulsions and consequent excitotoxicity. Most convulsants are antagonists at either the GABAA or glycine receptors, or ionotropic glutamate receptor agonists. Many other drugs may cause convulsions as a side effect at high doses but only drugs whose primary action is to cause convulsions are known as convulsants. Nerve agents such as sarin, which were developed as chemical weapons, produce convulsions as a major part of their toxidrome, but also produce a number of other effects in the body and are usually classified separately.
Perampanel, sold under the brand name Fycompa, is an anti-epileptic medication developed by Eisai Co. that is used in addition to other drugs to treat partial seizures and generalized tonic-clonic seizures for people older than twelve years. It was first approved in 2012, and as of 2016, its optimal role in the treatment of epilepsy relative to other drugs was not clear. It was the first antiepileptic drug in the class of selective non-competitive antagonist of AMPA receptors.
There are many causes of seizures. The factors that lead to a seizure are often complex and it may not be possible to determine what causes a particular seizure, what causes it to happen at a particular time, or how often seizures occur.
Gene therapy is being studied for some forms of epilepsy. It relies on viral or non-viral vectors to deliver DNA or RNA to target brain areas where seizures arise, in order to prevent the development of epilepsy or to reduce the frequency and/or severity of seizures. Gene therapy has delivered promising results in early stage clinical trials for other neurological disorders such as Parkinson's disease, raising the hope that it will become a treatment for intractable epilepsy.
References
- ↑ Sarkisian, Matthew R. (31 May 2001). "Overview of the Current Animal Models for Human Seizure and Epileptic Disorders". Epilepsy & Behavior. 2 (3): 201–216. doi:10.1006/ebeh.2001.0193. PMID 12609365.
- ↑ Chang, Bernard S.; Lowenstein, Daniel H. (25 September 2003). "Epilepsy". New England Journal of Medicine. 349 (13): 1257–1266. doi:10.1056/NEJMra022308. PMID 14507951.
- ↑ Löscher, Wolfgang (31 May 2011). "Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs". Seizure. 20 (5): 359–368. doi: 10.1016/j.seizure.2011.01.003 . PMID 21292505 . Retrieved 1 August 2012.
- ↑ Cela, Elvis; McFarlan, Amanda R.; Chung, Andrew J.; Wang, Taiji; Chierzi, Sabrina; Murai, Keith K.; Sjöström, P. Jesper (March 27, 2019). "An Optogenetic Kindling Model of Neocortical Epilepsy". Scientific Reports. 9 (1): 5236. doi:10.1038/s41598-019-41533-2. ISSN 2045-2322. PMC 6437216 . PMID 30918286.