Epilepsy 10511 226061435 2008-07-16T17:32:58Z Dwayne Reed 7262504 added image of mri for patient with macrocephaly {{Otheruses4|the [[neurological disorder]] as it affects humans|[[Veterinary medicine|veterinary]] information|Epilepsy in animals}} {{redirect|Epileptic|the graphic novel|Epileptic (graphic novel)}} {{DiseaseDisorder infobox | Name = Epilepsy | Image = [[Image:Structural.gif]]| Caption = Para-sagittal MRI of the head in a patient with benign familial macrocephaly. | ICD10 = {{ICD10|G|40||g|40}}-{{ICD10|G|41||g|40}} | ICD9 = {{ICD9|345}} | MedlinePlus = 000694 | eMedicineSubj = neuro | eMedicineTopic = 415 | DiseasesDB = 4366 | MeshID = D004827 | }} '''Epilepsy''' is a common [[chronic (medicine)|chronic]] [[neurological disorder]] that is characterized by recurrent unprovoked [[seizure (medicine)|seizures]].<ref name="PMID8330566">{{cite journal | author = Commission on Epidemiology and Prognosis, International League Against Epilepsy | title = Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. | journal = Epilepsia | volume = 34 | issue = 4 | pages = 592–6 | year = 1993 | pmid = 8330566 | url = http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1528-1157.1993.tb00433.x | doi = 10.1111/j.1528-1157.1993.tb00433.x <!--Retrieved from URL by DOI bot--> }}</ref><ref name="PMID11580774">{{cite journal | author = Blume W, Lüders H, Mizrahi E, Tassinari C, van Emde Boas W, Engel J | title = Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. | journal = Epilepsia | volume = 42 | issue = 9 | pages = 1212–8 | year = 2001 | pmid = 11580774 | url = http://www.blackwell-synergy.com/doi/full/10.1046/j.1528-1157.2001.22001.x | doi = 10.1046/j.1528-1157.2001.22001.x <!--Retrieved from URL by DOI bot--> }}</ref> These seizures are transient signs and/or symptoms due to abnormal, excessive or synchronous neuronal activity in the brain.<ref name="Fisher2005">{{cite journal | author = Fisher R, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J | title = Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). | journal = Epilepsia | volume = 46 | issue = 4 | pages = 470–2 | year = 2005 | pmid = 15816939 | url = http://www.blackwell-synergy.com/doi/full/10.1111/j.0013-9580.2005.66104.x | doi = 10.1111/j.0013-9580.2005.66104.x }}</ref> About 50 million people worldwide have epilepsy at any one time.<ref name="World Health Organization">{{cite web | url=http://www.who.int/mediacentre/factsheets/fs165/en/ | title = Epilepsy: aetiogy <nowiki>[</nowiki>''sic''<nowiki>]</nowiki>, epidemiology and prognosis | month = February | year = 2001 | accessdate = 2007-06-14 | publisher = [[World Health Organization]]}}</ref> Epilepsy is usually controlled, but not cured, with medication, although [[surgery]] may be considered in difficult cases. However, it is important to note that over 30% of people with epilepsy do not have seizure control even with the best available medications. Not all epilepsy syndromes are lifelong – some forms are confined to particular stages of childhood. Epilepsy should not be understood as a single disorder, but rather as a group of syndromes with vastly divergent symptoms but all involving episodic abnormal electrical activity in the brain. ==Classification== Epilepsies are classified in five ways: # By their first cause (or [[etiology]]). # By the observable manifestations of the seizures, known as semiology. # By the location in the brain where the seizures originate. # As a part of discrete, identifiable medical [[syndrome]]s. # By the event that triggers the seizures, as in [[primary reading epilepsy]]. In 1981, the [http://www.ilae.org/ International League Against Epilepsy] (ILAE) proposed a classification scheme for individual seizures that remains in common use.<ref name="ILEA1981">{{cite journal | author = | title = Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. | journal = Epilepsia | volume = 22 | issue = 4 | pages = 489–501 | year = 1981 | pmid = 6790275}}</ref> This classification is based on observation (clinical and EEG) rather than the underlying pathophysiology or anatomy and is outlined later on in this article. In 1989, the ILAE proposed a classification scheme for epilepsies and epileptic syndromes.<ref name="ILEA1989">{{cite journal | author = | title = Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. | journal = Epilepsia | volume = 30 | issue = 4 | pages = 389–99 | year =1989 | pmid = 2502382}}</ref> This can be broadly described as a two-axis scheme having the cause on one axis and the extent of localisation within the brain on the other. Since 1997, the ILAE have been working on a new scheme that has five axes: ictal phenomenon, seizure type, syndrome, etiology and impairment.<ref name="ILAE">{{cite web | url = http://www.ilae-epilepsy.org/Visitors/Centre/ctf/overview.cfm | title = A Proposed Diagnostic Scheme For People With Epileptic Seizures And With Epilepsy: Report Of The Ilae Task Force On Classification And Terminology | accessdate = 2006-07-18 | author = Jerome Engel | publisher = ILAE }}</ref> ==Diagnosis== The diagnosis of epilepsy requires the presence of recurrent, unprovoked seizures; accordingly, it is usually made based on the [[medical history]]. [[Electroencephalography|EEG]], brain [[MRI]], [[SPECT]], [[Positron emission tomography|PET]], and [[magnetoencephalography]] may be useful to discover an [[etiology]] for the epilepsy, discover the affected brain region, or classify the epileptic syndrome, but these studies are not useful in making the initial diagnosis. [[Long-term video-EEG monitoring]] for epilepsy is the gold standard for diagnosis, but it is not routinely employed owing to its high cost, low availability and inconvenience. Convulsive or other seizure-like activity, non-epileptic in origin, can be observed in many other medical conditions. These [[non-epileptic seizures]] can be hard to differentiate and may lead to misdiagnosis. Epilepsy covers conditions with different aetiologies, natural histories and prognoses, each requiring different management strategies. A full medical diagnosis requires a definite categorisation of seizure and syndrome types.<ref>{{cite web | author=C P Panayiotopoulos and M Koutroumanidis | title=The significance of the syndromic diagnosis of the epilepsies | month=September | year=2005 | url=http://www.e-epilepsy.org.uk/pages/articles/show_article.cfm?id=33 | publisher=[[National Society for Epilepsy]]}}</ref> ==Triggers== The diagnosis of epilepsy requires that the seizures be unprovoked, with the implication that the provocant is assumed to be something obviously harmful. Seizures due to alcohol or drug withdrawal, or immediately after a head injury, for example, do not imply a diagnosis of epilepsy. Most forms of epilepsy result in seizures that happen apparently spontaneously and at random. However, in some epilepsy syndromes, the provocant can reasonably be considered to be part of normal daily life. Examples of these ''normal provocants'' include reading, hot water on the head, [[hyperventilation]], and flashing or flickering lights. This last provocant is a special type of [[reflex epilepsy]] called [[photosensitive epilepsy]]. Although it is mistakenly assumed that photosensitivity is a common element to all forms of epilepsy, among both patients and the public, only between 2-14% of people with epilepsy are affected by flickering lights{{Fact|date=April 2008}}. Photosensitivity amongst the general population is in the range of 0.3-3%. Though, most people who are sensitive to light will never have a seizure during their life. Certain environmental factors can lead to an increased likelihood of seizures in someone with epilepsy or in certain syndromes, for example: *Being asleep *The transition between sleep and wakefulness ([[hypnagogia]]) *Tiredness and sleep deprivation *[[Illness]] *[[Constipation]] *[[Menstruation]] *Stress or anxiety *Alcohol consumption *Pictures with excessive flashing ==Epidemiology== Epilepsy is one of the most common of the serious neurological disorders.<ref>{{cite journal|author=Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R|title=How common are the 'common' neurologic disorders?|journal=Neurology|volume=68|issue=5|pages=326–37|date=[[2007-01-30]]|pmid=17261678|doi=10.1212/01.wnl.0000252807.38124.a3}}</ref> [[Genetic disorder|Genetic]], [[congenital]], and [[Developmental disorder|developmental]] conditions are mostly associated with it among younger patients; [[tumor]]s are more likely over age 40; [[head trauma]] and [[central nervous system infection]]s may occur at any age. The [[prevalence]] of active epilepsy is roughly in the range 5–10 per 1000 people. Up to 50 per 1000 people experience non[[febrile seizure]]s at some point in life; epilepsy's [[lifetime prevalence]] is relatively high because most patients either stop having seizures or (less commonly) die of it. Epilepsy's approximate annual [[incidence rate]] is 40–70 per 100,000 in industrialized countries and 100–190 per 100,000 in resource-poor countries; socioeconomically deprived people are at higher risk. In industrialized countries the incidence rate decreased in children but increased among the elderly during the three decades prior to 2003, for reasons not fully understood.<ref>{{cite journal|author=Sander JW|title=The epidemiology of epilepsy revisited|journal=Curr Opin Neurol|volume=16|issue=2|pages=165–70|date=2003|pmid=12644744 | doi = 10.1097/00019052-200304000-00008 <!--Retrieved from Yahoo! by DOI bot-->}}</ref> Children with epilepsy are three to nine times more likely to have mental health problems than healthy children. Although the search for risk factors has often produced inconsistent results, there is evidence that the development of mental health problems in children with epilepsy is moderated and mediated by family risk factors. [[Attention-deficit/hyperactivity disorder]] (ADHD) affects three to five times more children with epilepsy than children in the general population, and children with epilepsy also have significantly higher rates of depression and anxiety. <ref>{{cite journal |journal=J Am Acad Child Adolesc Psychiatry |date=2007 |volume=46 |issue=11 |pages=1389–402 |title= 10-year research update review: psychiatric problems in children with epilepsy |author= Plioplys S, Dunn DW, Caplan R |doi=10.1097/chi.0b013e31815597fc |pmid=18049289}}</ref> There is a strikingly higher prevalence of epilepsy in children with [[autism]], and evidence suggests that epilepsy is a risk factor for autism, independent of other central nervous system problems.<ref>{{cite journal |journal=Epilepsia |date=2007 |volume=48 |issue= Suppl 9 |pages=33–5 |title= The autism-epilepsy connection |author= Levisohn PM |pmid=18047599}}</ref> ==Seizure types== {{Main|Seizure types}} Seizure types are organized firstly according to whether the source of the seizure within the brain is localized ([[Focal seizures|''partial'' or ''focal'']] onset seizures) or distributed (''generalized'' seizures). Partial seizures are further divided on the extent to which consciousness is affected. If it is unaffected, then it is a ''[[Simple partial seizure|simple partial]]'' seizure; otherwise it is a ''[[Complex partial seizure|complex partial]]'' (psychomotor) seizure. A partial seizure may spread within the brain - a process known as ''secondary generalization''. Generalized seizures are divided according to the effect on the body but all involve loss of consciousness. These include [[Absence seizure|absence]] (petit mal), [[Myoclonus|myoclonic]], [[Clonus|clonic]], tonic, [[Tonic-clonic seizure|tonic-clonic]] (grand mal) and [[Atonic seizure|atonic]] seizures. ==Seizure syndromes== There are many different epilepsy syndromes, each presenting with its own unique combination of seizure type, typical age of onset, EEG findings, treatment, and prognosis. Below are some common seizure syndromes: * ''[[Infantile spasms]] ([[West syndrome]])'' is associated with brain development abnormalities, [[tuberous sclerosis]], and perinatal insults to the brain. It affects infants (as implied by its name), which by definition is between 30 days to 1 year of life. It carries a poor prognosis such that only 5-10% of children with infantile spasms will develop normal to near-normal function, while more than two-thirds will have severe deficits. The typical seizures are characterized by sudden flexor and extensor spasms of head, trunk, and extremities. The key EEG finding in these patients is a [[hypsarrhythmia]], or a high-voltage slow wave with multifocal spikes. The first line treatment for these patients is [[adrenocorticotropic hormone]] ([[ACTH]] or [[corticotropin]]) since traditional antiepileptic drugs generally cannot adequately control seizure activity. [[Vigabatrin]] is also used in many countries, and is particularly effective when tuberous sclerosis is the cause of seizures. [[Image:Spike-waves.png|right|thumb|Generalized 3 Hz spike and wave discharges in EEG]] * ''[[Childhood absence epilepsy]]'' affects children between the ages of 4 and 12 years of age. These patients have recurrent absence seizures that can occur hundreds of times a day. On EEG, one finds the stereotyped generalized 3 Hz spike and wave discharges. A subset of these patients will also develop generalized tonic-clonic seizures. This condition carries a fairly good prognosis in that these children do not usually show cognitive decline or neurological deficits. First line treatment for pure absence seizures is [[ethosuximide]]. If patients do not respond or have mixed seizures along with their absence seizures, then [[valproic acid]] can be used. * ''[[Dravet's syndrome]]'' Severe myoclonic epilepsy of infancy (SMEI). This very rare syndrome is delimitated from benign myoclonic epilepsy by its severity and must be differentiated from the Lennox-Gastaut syndrome and Doose’s myoclonic-astatic epilepsy. Onset is in the first year of life and symptoms peak at about 5 months of age with febrile hemiclonic or generalized status epilepticus. Boys are twice as often affected as girls. Prognosis is poor. In 2005, there were at least around 450 cases reported in the worldwide literature but now it is impossible to count the known cases because many probably have been published twice because of the genetic research. Most cases are sporadic. Family history of epilepsy and febrile convulsions is present in around 25 percent of the cases, but familial cases are exceptional.<ref>{{cite web|url=http://www.dravet.com|title=Dravet Syndrome|accessdate=2007-12-16}}</ref> * ''[[Benign focal epilepsies of childhood]]'' The most common syndromes comprising the benign focal epilepsies of childhood include Benign Childhood Epilepsy with Centro-Temporal Spikes (or benign rolandic epilepsy), and Benign Childhood Epilepsy with Occipital Paroxysms. Benign rolandic epilepsy begins in children between the ages of 3 and 16 years. Apart from their seizure disorder, these patients are otherwise normal. Seizures typically occur at night, and are brief, focal motor events affecting facial and pharyngeal muscles, though may be generalized convulsions as well. Focal seizures may be less frequently reported than more obvious generalized seizures. Between seizures, patients have a stereotyped EEG pattern that includes di- or triphasic sharp waves over the central-midtemporal (Rolandic) regions. Prognosis is quite good overall with seizures disappearing by adolescence. There is no consensus on the first line treatment, however most cases respond well to most [[anticonvulsant]]s. * ''[[Juvenile myoclonic epilepsy]]'' (JME) begins in patients aged 8 to 20 years. These patients have normal IQ and are otherwise neurologically intact. JME is thought to be genetic, though that is not to say that JME will show in immediate family members. The seizures are morning myoclonic jerks often with generalized tonic-clonic seizures that occur just after waking. 'Petit mal' or absence seizures are less common in cases of JME, but are known to occur more often in young girls. EEG readings reveal generalized spikes with 4-6 Hz spike wave discharges and multiple spike discharges. Interestingly, these patients are often first diagnosed when they have their first generalized tonic-clonic seizure later in life when they experience sleep deprivation (e.g., freshman year in college after staying up late to study for exams). Alcohol is a major contributing factor and those with severe JME should monitor their intake of units. [[Valproic acid]] is the first line treatment, whereas carbamazepine can actually worsen symptoms. This condition is lifelong, thus patients must be taught appropriate sleep hygiene to prevent generalized tonic-clonic seizures. The severity of JME varies from person to person - some will experience full blown tonic-clonic seizures regularly, others will suffer only under sufficient stress from lack of sleep and intoxication. * ''[[Temporal lobe epilepsy]]'' is the most common epilepsy of adults. In most cases, the epileptogenic region is found in the mesial temporal structures (e.g., the hippocampus, amygdala, and parahippocampal gyrus). Seizures begin in late childhood and adolescence. There is an association with febrile seizures in childhood, and some studies have shown herpes simplex virus (HSV) DNA in these regions, suggesting that perhaps this epilepsy has an infectious etiology. Most of these patients have complex partial seizures sometimes preceded by an [[Aura (symptom)|aura]], and some TLE patients also suffer from secondary generalised [[tonic-clonic seizures]]. If the patient does not respond sufficiently to medical treatment, surgery may be considered. * ''[[Fetal alcohol syndrome]]'' (FAS) is caused by prenatal [[alcohol]] exposure and results in [[central nervous system]] (CNS) damage. Seizure disorders due to prenatal alcohol exposure are one of several possible criteria for diagnosing FASD; however, any seizure disorder due to postnatal insult does not qualify as a diagnostic criterion for FASD.<ref>Astley, S.J. (2004). ''Diagnostic Guide for Fetal Alcohol Spectrum Disorders: The 4-Digit Diagnostic Code''. Seattle: University of Washington. Can be downloaded at http://depts.washington.edu/fasdpn.</ref> * ''[[Autosomal dominant nocturnal frontal lobe epilepsy]]'' (ADNFLE) is a rare epileptic disorder that causes frequent violent seizures during sleep. These seizures often involve complex motor movements, such as hand clenching, arm raising/lowering, and knee bending. Vocalizations such as shouting, moaning, or crying are also common. ADNFLE is often misdiagnosed as nightmares. Attacks often occur in clusters and typically first manifest in childhood. ADNFLE has a genetic basis with four known loci, three with known causative genes. These genes encode various [[nicotinic acetylcholine receptor]] α and β subunits CHRNA4, CHRNB2, and CHRNA2. * ''[[Frontal lobe epilepsy]]'' * ''[[Lennox-Gastaut syndrome]]'' * ''[[Occipital lobe epilepsy]]'' ==Treatment== Epilepsy is usually treated with [[medication]] prescribed by a [[physician]]; [[primary care]]givers, [[neurologist]]s, and [[neurosurgeon]]s all frequently care for people with epilepsy. In some cases the implantation of a stimulator of the [[vagus nerve]], or a special diet can be helpful. Neurosurgical operations for epilepsy can be [[palliative]], reducing the frequency or severity of seizures; or, in some patients, an operation can be curative. ===Responding to a seizure=== In most cases, the proper emergency response to a generalized [[tonic-clonic seizure|tonic-clonic epileptic seizure]] is simply to prevent the patient from self-injury by moving him or her away from sharp edges, placing something soft beneath the [[head (anatomy)|head]], and carefully rolling the person into the [[recovery position]] to avoid [[asphyxiation]]. In some cases the person may seem to start [[snoring]] loudly following a seizure, before coming to. This merely indicates that the person is beginning to breathe properly and does not mean he or she is suffocating. Should the person regurgitate, the material should be allowed to drip out the side of the person's mouth by itself. If a seizure lasts longer than 5 minutes, or if the seizures begin coming in 'waves' one after the other - then [[Emergency Medical Services]] should be contacted immediately. Prolonged seizures may develop into ''[[status epilepticus]]'', a dangerous condition requiring hospitalization and emergency treatment. Objects should '''never''' be placed in a person's [[mouth]] by anybody - including paramedics - during a seizure as this could result in serious injury to either party. Despite common [[folklore]], it is not possible for a person to swallow their own [[tongue]] during a seizure. However, it is possible that the person will bite their own tongue, especially if an object is placed in the mouth. With other types of seizures such as simple partial seizures and [[complex partial seizures]] where the person is not convulsing but may be hallucinating, disoriented, distressed, or unconscious, the person should be reassured, gently guided away from danger, and sometimes it may be necessary to protect the person from self-injury, but physical force should be used only as a last resort as this could distress the person even more. In complex partial seizures where the person is unconscious, attempts to rouse the person should not be made as the seizure must take its full course. After a seizure, the person may pass into a deep sleep or otherwise they will be disoriented and often unaware that they have just had a seizure, as amnesia is common with complex partial seizures. The person should remain observed until they have completely recovered, as with a tonic-clonic seizure. After a seizure, it is typical for a person to be exhausted and confused. Often the person is not immediately aware that they have just had a seizure. During this time one should stay with the person - reassuring and comforting them - until they appear to act as they normally would. Seldom during seizures do people lose bladder or bowel control. In some instances the person may [[vomit]] after coming to. People should not eat or drink until they have returned to their normal level of awareness, and they should not be allowed to wander about unsupervised. Many patients will sleep deeply for a few hours after a seizure - this is common for those having just experienced a more violent type of seizure such as a tonic-clonic. In about 50% of people with epilepsy, headaches may occur after a seizure. These headaches share many features with migraines, and respond to the same medications. It is helpful if those present at the time of a seizure make note of how long and how severe the seizure was. It is also helpful to note any mannerisms displayed during the seizure. For example, the individual may twist the body to the right or left, may blink, might mumble nonsense words, or might pull at clothing. Any observed behaviors, when relayed to a neurologist, may be of help in diagnosing the type of seizure which occurred. ===Pharmacologic treatment=== {{main|Anticonvulsant}} '''Mechanisms of Drug Action''':- 1- Sodium channel blockers (voltage dependent) 2- Calcium channel blockers (T-type) 3- Potentiate the effect of GABA (inhibitory) 4- Decrease the excitatory transmission (glutaminic) Some medications can be taken daily in order to prevent seizures altogether or reduce the frequency of their occurrence. These are termed "anticonvulsant" or "antiepileptic" drugs (sometimes AEDs). All such drugs have side effects that are idiosyncratic and others that are dosage-dependent. It is not possible to predict who will suffer from side effects or at what dose the side effects will appear. Some people with epilepsy will experience a complete remission when treated with an anticonvulsant medication. If this does not occur, the dose of medication may be increased, or another medication may be added to the first. The general strategy is to increase the medication dose until either the seizures are controlled, or until dose-limiting side effects appear; at which point the medication dose is reduced to the highest amount that does not produce undesirable side effects. A study found that in 83% of patients on a two drug regime to control their epilepsy could be slowly transferred completely off of one of the drugs and be controlled with a single drug regime without any increase in seizure frequency. Surprisingly it was found that 36% of patients showed greater seizure control on a single drug regime for epilepsy control than on a two drug regime. Side effects were also decreased in those taking a single drug regime. It was concluded that overall a reduction in polypharmacy may be benefitial for most patients who have intractable epilepsy.<ref>{{cite journal |author=Schmidt D |year=1983 |month=Jun |title=Reduction of two-drug therapy in intractable epilepsy |journal=Epilepsia |volume=24 |issue=3 |pages=368–76 |pmid=6406214 |doi=10.1111/j.1528-1157.1983.tb04900.x}}</ref> Serum levels of AEDs can be checked to determine [[Compliance (medicine)|medication compliance]] and to assess the effects of drug-drug interactions; some physicians do not use serum levels to fine tune medication, but other physicians believe that serum levels provide excellent data for tailoring medications to suit an individual's specific and relatively variable body chemistry. For example, therapeutic doses (the dose at which seizures are controlled and side effects are minimal and tolerable) may vary widely from among patients. The therapeutic ranges provided by pharmaceutical companies are only ranges and by using blood serum levels and seizures diaries, better seizure control can sometimes be reached. In some cases (such as a seizure flurry) serum levels can be useful to know if the level is very high or very low. If a person's epilepsy cannot be brought under control after adequate trials of two or three (experts vary here) different drugs, that person's epilepsy is generally said to be 'medically refractory.' Various drugs may prevent seizures or reduce seizure frequency: these include [[carbamazepine]] (common brand name Tegretol), [[clobazam]] (Frisium), [[clonazepam]] (Klonopin), [[ethosuximide]] (Zarontin), [[felbamate]] (Felbatol), [[fosphenytoin]] (Cerebyx), [[gabapentin]] (Neurontin), [[lamotrigine]] (Lamictal), [[levetiracetam]] (Keppra), [[oxcarbazepine]] (Trileptal), [[phenobarbital]] (Luminal), [[phenytoin]] (Dilantin), [[pregabalin]] (Lyrica), [[primidone]] (Mysoline), [[sodium valproate]] (Epilim), [[tiagabine]] (Gabitril), [[topiramate]] (Topamax), [[valproate semisodium]] (Depakote, Epival), [[valproic acid]] (Depakene, Convulex), [[vigabatrin]] (Sabril), and [[zonisamide]] (Zonegran). Other drugs are commonly used to abort an active seizure or interrupt a seizure flurry; these include [[diazepam]] (Valium) and [[lorazepam]] (Ativan). Drugs used only in the treatment of refractory [[status epilepticus]] include [[paraldehyde]] (Paral), [[midazolam]] (Versed), and [[pentobarbital]] (Nembutal). [[Potassium bromide|Bromides]] were the first of the effective anticonvulsant pure compounds, but are no longer used in humans<ref name="BromideDogs">{{cite web | last = Clemmons DVM, PhD | first = R.M. | year = 1997 | url = http://neuro.vetmed.ufl.edu/neuro/seizures/seizures.htm | title = Seizure Disorders in Dogs and Cats | work = The Neurology Service at the VMTH | publisher = University of Florida’s Veterinary Medical Teaching Hospital | accessdate = 2006-03-29 }}</ref> due to their [[toxicity]] and low [[efficacy]]. It has been found that taking [[valproic acid|valproates]] while pregnant can have high chances of reduced IQ towards children.<ref>{{cite web | url = http://www.medscape.com/viewarticle/549073 | title = NEAD: In Utero Exposure To Valproate Linked to Poor Cognitive Outcomes in Kids | last = Cassels | first = Caroline | date = [[December 8]] [[2006]] | publisher = Medscape | accessdate = 2007-05-23}}</ref><ref>{{cite journal |author=Meador KJ, Baker GA, Finnell RH, ''et al'' |title=In utero antiepileptic drug exposure: fetal death and malformations |journal=Neurology |volume=67 |issue=3 |pages=407–12 |year=2006 |pmid=16894099 |doi=10.1212/01.wnl.0000227919.81208.b2}}</ref> Many epileptics have found that [[medical marijuana|marijuana]] is an effective medical treatment of epilepsy, and a telephone survey conducted in 2003 revealed that more than twice as many epileptics use marijuana than the general population.<ref>[http://www.epilepsy.com/node/481932 Epilepsy and marijuana | epilepsy.com<!-- Bot generated title -->]</ref><ref>http://www.medscape.com/viewarticle/465891</ref> ===Surgical treatment=== Surgical treatment can be an option for epilepsy when an underlying brain abnormality, such as a benign [[tumor]] or an area of scar tissue (e.g. [[hippocampal sclerosis]]) can be identified. The abnormality must be removable by a neurosurgeon. Surgery is usually only offered to patients when their epilepsy has not been controlled by adequate attempts with multiple medications. Before surgery is offered, the medical team conducts many tests to assess whether removal of brain tissue will result in unacceptable problems with [[memory]], [[visual perception|vision]], [[language]] or [[Locomotion|movement]], which are controlled by different parts of the [[brain]]. These tests usually include a [[neuropsychology|neuropsychological evaluation]], which sometimes includes an [[intracarotid sodium amobarbital test]] ([[Wada test]]) - although this invasive procedure is being replaced by non-invasive functional MRI in many centres. Resective surgery, as opposed to palliative, successfully eliminates or significantly reduces seizures in about 50-90% of the patients who undergo it (the exact percentage depends on the particulars of the case and surgeon in question.) Many patients decide not to undergo surgery owing to fear or the uncertainty of having a brain operation. The most common form of resective surgical treatment for epilepsy is to remove the front part of either the right or left [[temporal lobe]]. A study of 48 patients who underwent this operation, [[anterior temporal lobectomy]], between 1965 and 1974 determined the long-term success of the procedure. Of the 48 patients, 21 had had no seizures that caused loss of consciousness since the operation. Three others had been free of seizures for at least 19 years. The rest had either never been completely free of seizures or had died between the time of the surgery and commencement of the study.<ref name="Neurology2005-Kelley">{{cite journal | author=Kelley K, Theodore WH | title=Prognosis 30 years after temporal lobectomy | journal=Neurology | year=2005 | pages=1974–6 | volume=64 | issue=11 | pmid=15955959 | doi=10.1212/01.WNL.0000163998.01543.CF}}</ref> [[Palliative]] surgery for epilepsy is intended to reduce the frequency or severity of seizures. Examples are [[callosotomy]] or [[commissurotomy]] to prevent seizures from generalizing (spreading to involve the entire brain), which results in a loss of consciousness. This procedure can therefore prevent injury due to the person falling to the ground after losing consciousness. It is performed only when the seizures cannot be controlled by other means. Resective surgery can be considered palliative if it is undertaken with the expectation that it will reduce but not eliminate seizures. [[Hemispherectomy]] is a drastic operation in which most or all of one half of the cerebral cortex is removed. It is reserved for people suffering from the most catastrophic epilepsies, such as those due to [[Rasmussen syndrome]]. If the surgery is performed on very young patients (2-5 years old), the remaining hemisphere may acquire some rudimentary motor control of the ipsilateral body; in older patients, paralysis results on the side of the body opposite to the part of the brain that was removed. Because of these and other side effects it is usually reserved for patients who have exhausted other treatment options. ===Other treatment=== The [[ketogenic diet]] can be effective and is mainly used in children whose epilepsy has not been controlled with medication. As with anticonvulsant drugs, the mechanism behind the effect is not fully understood. The ketogenic diet is very high in [[fat]] and very low in [[carbohydrate]]s. This treatment was developed in the 1920s at the [[Mayo clinic]], but was largely forgotten with the discovery of modern anti-epileptic drugs. Since the 1990s, it has returned to the anti-epileptic treatment arsenal and is available from most paediatric epilepsy centres. A [http://www.hopkinsmedicine.org/press/1998/DECEMBER/981207.HTM study conducted by Johns Hopkins] reported that 50% of those patients starting the Ketogenic diet reported a decrease in seizures of 50% or more, with 29% of patients reporting a 90% reduction in symptoms; these patients had previously tried an average of six anticonvulsant drugs. [[Vagus nerve stimulation]] (VNS) is a recently developed form of seizure control which uses an implanted electrical device, similar in size, shape and implant location to a [[heart pacemaker]], which connects to the [[vagus nerve]] in the [[neck]]. Once in place the device can be set to emit electronic pulses, stimulating the vagus nerve at pre-set intervals and milliamp levels. Treatment studies have shown that approximately 50% of those treated in this fashion will show significant seizure frequency reduction. The Responsive Neurostimulator System (RNS) is currently undergoing clinical study prior to FDA approval. This system relies upon a device implanted just under the scalp. The leads attached to the device are implanted either on the brain surface or in the brain area itself and are located close to the area where the seizures are believed to start. When a seizure begins, small amounts of electrical stimulation are delivered to suppress it. This system is different from the VNS system in that the RNS relies on direct brain stimulation and the RNS is a responsive system. The VNS pulses at predetermined intervals previously set by medical personnel. The RNS system is designed to respond to detected signs that a seizure is about to begin and can record events and allow customized response patterns which may provide a greater degree of seizure control.<ref> {{cite web | url = http://www.seizurestudy.com/BrainSeizureFAQ.html | title = Patient FAQ | accessdate = 2007-11-02 | work = RNS System | publisher = NeuroPace }}</ref> A [[seizure response dog]] is a form of [[service dog]] that is trained to summon help or ensure personal safety when a seizure occurs. These are not suitable for everybody and not all dogs can be so trained. Rarely, a dog may develop the ability to sense a seizure before it occurs.<ref>{{cite news | first = Marianne | last = Barriaux | title = Dogs trained to warn of an imminent epileptic fit | url = http://business.guardian.co.uk/story/0,,1923146,00.html | publisher = The Guardian | date = [[2006-10-16]] | accessdate = 2006-11-24 }}</ref> A number of [[systematic review]]s by the [[Cochrane Collaboration]] into treatments for epilepsy looked at [[acupuncture]],<ref name="Cheuk2006">{{cite journal | author=Cheuk D, Wong V | title=Acupuncture for epilepsy | journal=Cochrane Database Syst Rev | year=2006 | pages=CD005062 | issue=2 | pmid=16625622 | doi=10.1002/14651858.CD005062.pub2}} </ref> [[psychological]] interventions,<ref name="Ramaratnam2005">{{cite journal | author=Ramaratnam S, Baker GA, Goldstein LH | title=Psychological treatments for epilepsy | journal=Cochrane Database Syst Rev | year=2005 | pages=CD002029 | issue=4 | pmid=16235293 | doi=10.1002/14651858.CD002029.pub2}} </ref> [[vitamins]]<ref name="Ranganathan2005">{{cite journal | author=Ranganathan LN, Ramaratnam S | title=Vitamins for epilepsy | journal=Cochrane Database Syst Rev | year=2005 | pages=CD004304 | issue=2 | pmid=15846704 | doi=10.1002/14651858.CD004304.pub2}} </ref> and [[yoga]]<ref name="Ramaratnam2000">{{cite journal | author=Ramaratnam S, Sridharan K | title=Yoga for epilepsy | journal=Cochrane Database Syst Rev | year=2000 | pages=CD001524 | issue=3 | pmid=10908505 | doi=10.1002/14651858.CD001524}} </ref> and found there is no reliable [[Evidence-based medicine|evidence]] to support the use of these as treatments for epilepsy. Further studies are needed on the subject. ==Pathophysiology== [[Mutation]]s in several [[gene]]s have been linked to some types of epilepsy. Several genes that code for [[protein]] subunits of [[voltage-gated ion channel|voltage-gated]] and [[ligand-gated ion channel|ligand-gated]] [[ion channel]]s have been associated with forms of generalized epilepsy and infantile seizure syndromes.<ref name="JClinInvestigation2005-Miriam>{{cite journal | author=Miriam H. Meisler and Jennifer A. Kearney | title=Sodium channel mutations in epilepsy and other neurological disorders | journal=Journal of Clinical Investigation | volume=115 | issue=8 | year=2005 | pages=2010–2017 | pmid=16075041 {{Doi|10.1172/JCI25466}} | doi=10.1172/JCI25466}}</ref> Several ligand-gated ion channels have been linked to some types of frontal and generalized epilepsies. Epilepsy-related mutations in some non-ion channel genes have also been identified. One interesting finding in animals is that repeated low-level electrical stimulation to some brain sites can lead to permanent increases in seizure susceptibility: in other words, a permanent decrease in seizure "threshold." This phenomenon, known as [[kindling]] (by analogy with the use of burning twigs to start a larger fire) was discovered by Dr. [[Graham Goddard]] in 1967. Chemical stimulation can also induce seizures; repeated exposures to some pesticides have been shown to induce seizures in both humans and animals. One mechanism proposed for this is called [[excitotoxicity]]. The roles of kindling and excitotoxicity, if any, in human epilepsy are currently hotly debated. Other causes of epilepsy are brain lesions, where there is scar tissue or another abnormal mass of tissue in an area of the brain. ==History and stigma== The word '''epilepsy''' is derived from the Greek ''epilepsia'', which in turn can be broken into ''epi-'' (upon) and ''lepsis'' (to take hold of, or seizure)<ref name="etymology">{{cite web | last =Harper | first =Douglas | year = 2001 | url =http://www.etymonline.com/index.php?term=epilepsy | title =epilepsy | work =Online Etymological Dictionary | accessdate =2005-06-05 }}</ref> In the past, epilepsy was associated with [[religion|religious]] experiences and even [[demon]]ic [[Spiritual possession|possession]]. In ancient times, epilepsy was known as the "Sacred Disease" because people thought that epileptic seizures were a form of attack by [[demon]]s, or that the [[Vision (religion)|visions]] experienced by persons with epilepsy were sent by the [[deity|gods]]. Among [[animist]] [[Hmong people|Hmong]] families, for example, epilepsy was understood as an attack by an evil spirit, but the affected person could become revered as a [[shaman]] through these otherworldly experiences.<ref>http://www.epilepsy.com/articles/ar_1063680870.html</ref> However, in most cultures, persons with epilepsy have been stigmatized, shunned, or even imprisoned; in the [[Salpêtrière]], the birthplace of modern neurology, [[Jean-Martin Charcot]] found people with epilepsy side-by-side with the mentally retarded, those with chronic [[syphilis]], and the criminally insane. In [[Tanzania]] to this day, as with other parts of Africa, epilepsy is associated with possession by evil spirits, witchcraft, or poisoning and is believed by many to be contagious.<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10080524&dopt=Abstract Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures.] Jilek-Aall L. PMID: 10080524 Retrieved [[8 October]] 2006. </ref> In ancient Rome, epilepsy was known as the ''Morbus Comitialis'' ('disease of the assembly hall') and was seen as a curse from the gods. Stigma continues to this day, in both the public and private spheres, but polls suggest it is generally decreasing with time, at least in the developed world; [[Hippocrates]] remarked that epilepsy would cease to be considered divine the day it was understood.<ref name="Hippocrates">Hippocrates [http://quote.wikipedia.org/wiki/Hippocrates quotes]</ref> ==Controversy== There has been some relatively mild controversy surrounding the standards for diagnosis for partial-complex seizures and how these standards are applied in practice, both among some [[surrealism|surrealists]][http://www.geocities.com/more_xtian/bx4p18.html] and in particular as regards [[Mary Baker Eddy]], founder of [[Christian Science]]. In [[April 2003]], the [[BBC]] TV science programme ''Horizon'' featured discussion of research by American neurologist [[Gregory Holmes]] indicating that [[Ellen G. White]], spiritual founder of the [[Seventh-day Adventist Church]], may have suffered from '''temporal lobe epilepsy''' as a result of brain damage due to an accident suffered at age nine &ndash; the epilepsy supposedly being responsible for her powerful religious experiences. ==Notable people with epilepsy== {{Main|List of people with epilepsy}} Many notable people, past and present, have carried the diagnosis of epilepsy. In many cases, their epilepsy is a footnote to their accomplishments; for some, it played an integral role in their fame. Historical diagnoses of epilepsy are not always certain; there is controversy about what is considered an acceptable amount of evidence in support of such a diagnosis. ==Legal implications== {{main|Epilepsy and driving}} Most people diagnosed with epilepsy are forbidden by their local laws from operating vehicles. However, there are usually exceptions for those who can prove that they have stabilized their condition. Those few whose seizures do not cause impairment of consciousness, or whose seizures only arise from sleep, may be exempt from such restrictions, depending on local laws. There is an ongoing debate in [[bioethics]] over ''who'' should bear the burden of ensuring that an epilepsy patient does not drive a car or fly an airplane. In the [[United States of America|U.S.]], people with epilepsy can drive if their seizures are controlled with treatment and they meet the licensing requirements in their state. How long they have to be free of seizures varies in different states, but it is most likely to be between three months and a year.<ref name="EpilepsyFndtn-Driving">Epilepsy Foundation [http://www.epilepsyfoundation.org/answerplace/Social/driving/drivingu.cfm Driving and You - Can you drive an automobile if you have epilepsy?].</ref><ref name="EpilepsyFndtn-StateLaws">Epilepsy Foundation [http://www.epilepsyfoundation.org/living/wellness/transportation/drivinglaws.cfm Driver Information by State]</ref> The majority of the 50 states place the burden on patients to report their condition to appropriate licensing authorities so that their privileges can be revoked where appropriate. A minority of states place the burden of reporting on the patient's physician. After reporting is carried out, it is usually the driver's licensing agency that decides to revoke or restrict a driver's license. In the [[United Kingdom|UK]], it is the responsibility of the patients to inform the [[Driver and Vehicle Licensing Agency]] (DVLA) if they have epilepsy.<ref name ="UKEpilepsy-Driving">UK [[Epilepsy Action]]: Driving and Epilepsy, [http://www.epilepsy.org.uk/info/driving/seizure.html I've had a seizure. What should I do?]</ref> The DVLA rules are quite complex,<ref name="DVLA-Driving">UK Driver and Vehicle Licensing Agency [http://www.dvla.gov.uk/at_a_glance/content.htm Guide to the Current Medical Standards Of Fitness to Drive]. Full details for doctors regarding epilepsy are given in the [http://www.dvla.gov.uk/at_a_glance/ch1_neurological.htm#appendix Appendix]. Information for drivers can be found in [http://www.dvla.gov.uk/drivers/dmed1_files/group1.htm#nc Medical Rules - Group 1 Licence Holders]</ref> but in summary,<ref name="UKEpilepsyActionBooklet">UK Epilepsy Action: booklet with further details about driving [http://www.epilepsy.org.uk/downloads/pdf/epilepsyaction_driving.pdf PDF]</ref> those continuing to have seizures or who are within 6 months of medication change may have their licence revoked. A doctor who becomes aware that a patient with uncontrolled epilepsy is continuing to drive has, after reminding the patient of their responsibility, a duty to break [[confidentiality]] and inform the DVLA. The doctor should advise the patient of the disclosure and the reasons why their failure to notify the agency obliged the doctor to act. The Epilepsy Foundation's Jeanne A. Carpenter
 Epilepsy Legal Defense Fund is dedicated to advancing the rights of people with epilepsy by changing discriminatory practices, policies and laws and to ending epilepsy-related discrimination and injustice through education and increased access to legal services for individuals with epilepsy through a system of managed referrals and legal support to a nationwide network of attorneys committed to this cause. Additionally, the Epilepsy Foundation is a vigorous advocate for people with epilepsy. In the United States, the Foundation has been active in Congress, the executive branch, and the courts, focusing attention on the needs of those with epilepsy. Priorities for the Foundation include: the availability of affordable quality health care, the search for the cure, and the protection of civil rights for people with epilepsy. ==Epilepsy in popular culture== *[[The Lost Prince]] - A 2003 British television drama about Prince John, who had epilepsy *[[Black Eyed Peas]] song [[Let's Get Retarded]] contains the lyrics 'Bop your head like epilepsy'. *[[Degrassi]] - The character [[Caitlyn Ryan]] has epilepsy. ==Important investigators of epilepsy== *[[Jean-Martin Charcot]] *[[John Hughlings Jackson]] *[[Hans Berger]] *[[Herbert Jasper]] *[[Wilder Penfield]] *[[H. Houston Merritt]] *[[William G. Lennox]] ==See also== *[[Citizens United for Research in Epilepsy (CURE)]] *[[Non-epileptic seizures]] *[[Epilepsy in animals]] *[[Seizure response dog]] *[[Jacksonian seizure]] *[[Photosensitive epilepsy]] *[[Post-traumatic epilepsy]] *[[Temporal lobe epilepsy]] *[[Abdominal epilepsy]] *[[Generalised epilepsy]] *[[ISAS (Ictal-Interictal SPECT Analysis by SPM)]] *[[Medical research related to low-carbohydrate diets]] ==References== {{reflist|2}} ==External links== *{{DMOZ|Health/Conditions_and_Diseases/Neurological_Disorders/Epilepsy}} {{Diseases of the nervous system}} [[Category:Medical terms]] [[Category:Neurological disorders]] [[Category:Neurology]] [[Category:Epilepsy|*]] [[Category:Greek loanwords]] {{Link FA|de}} [[ar:صرع]] [[ay:T'uku usu]] [[bn:মৃগী]] [[bs:Epilepsija]] [[br:Drougsant]] [[bg:Епилепсия]] [[ca:Epilèpsia]] [[cs:Epilepsie]] [[da:Epilepsi]] [[de:Epilepsie]] [[et:Epilepsia]] [[el:Επιληψία]] [[es:Epilepsia]] [[eo:Epilepsio]] [[eu:Epilepsia]] [[fr:Épilepsie]] [[gl:Epilepsia]] [[hr:Epilepsija]] [[io:Epilepsio]] [[id:Epilepsi]] [[is:Flogaveiki]] [[it:Epilessia]] [[he:מחלת הנפילה]] [[ku:Epîlepsî]] [[lt:Epilepsija]] [[hu:Epilepszia]] [[ml:അപസ്‌മാരം]] [[nl:Epilepsie]] [[ja:てんかん]] [[no:Epilepsi]] [[nrm:Haut ma]] [[pl:Padaczka]] [[pt:Epilepsia]] [[ru:Эпилепсия]] [[sq:Epilepsia]] [[simple:Epilepsy]] [[sk:Epilepsia]] [[sl:Epilepsija]] [[sr:Епилепсија]] [[fi:Epilepsia]] [[sv:Epilepsi]] [[tr:Epilepsi]] [[zh:癫痫]]