EpilepsyFrom Wikipedia, the free encyclopedia(Redirected fromEpilepsi)"Epilepsia" and "Epileptic" redirect here. For the journal, seeEpilepsia (journal). For the graphic novel, seeEpileptic (graphic novel).Epilepsy

Generalized 3Hz spike and wave discharges on an electroencephalogram

Classification and external resources

ICD-10G40-G41

ICD-9345

DiseasesDB4366

MedlinePlus000694

eMedicineneuro/415

MeSHD004827

Epilepsy(from theAncient Greekverb meaning "to seize, possess, or afflict")[1]is a group ofneurological disorderscharacterized byepileptic seizures.[2][3]Epileptic seizures are episodes that can vary from brief and nearly undetectable to long periods of vigorous shaking.[4]In epilepsy, seizures tend to recur, and have no immediate underlying cause[2]while seizures that occur due to a specific cause are not deemed to represent epilepsy.[5]The cause of most cases of epilepsy is unknown, although some people develop epilepsy as the result of brain injury,stroke, brain tumor, and drug and alcohol misuse. Genetic mutations are linked to a small proportion of the disease.[6]Epileptic seizures are the result of excessive and abnormalcorticalnerve cell activity in the brain.[5]The diagnosis typically involves ruling out other conditions that might cause similar symptoms such asfainting. Additionally, making the diagnosis involves determining if any other cause of seizures is present such asalcohol withdrawalorelectrolyteproblems.[6]This may be done byimaging the brainand performingblood tests.[6]Epilepsy can often be confirmed with anelectroencephalogram(EEG) but a normal test does not rule out the condition.[6]Seizures are controllable with medication in about 70% of cases.[7]In those whose seizures do not respond to medication,surgery,neurostimulationor dietary changes may be considered. Not all cases of epilepsy are lifelong, and many people improve to the point that medication is no longer needed.About 1% of people worldwide (65million) have epilepsy,[8]and nearly 80% of cases occur indeveloping countries.[4]In 2013 it resulted in 116,000 deaths up from 111,000 deaths in 1990.[9]Epilepsy becomes more common as people age.[10][11]In the developed world, onset of new cases occurs most frequently in infants and the elderly;[12]in the developing world this is in older children and young adults,[13]due to differences in the frequency of the underlying causes. About 510% of all people will have an unprovoked seizure by the age of 80,[14]and the chance of experiencing a second seizure is between 40 and 50%.[15]In many areas of the world those with epilepsy either have restrictions placed on their ability to drive or are not permitted to drive,[16]but most are able to return to driving after a period of time without seizures.Contents[hide] 1Signs and symptoms 1.1Seizures 1.2Postictal 1.3Psychosocial 2Causes 2.1Genetics 2.2Acquired 3Pathophysiology 3.1Epilepsy 3.2Seizures 4Diagnosis 4.1Definition 4.2Classification 4.3Syndromes 4.4Tests 4.5Differential diagnosis 5Prevention 6Management 6.1First aid 6.2Medications 6.3Surgery 6.4Other 6.5Alternative medicine 7Prognosis 7.1Mortality 8Epidemiology 9History 10Society and culture 10.1Stigma 10.2Economics 10.3Vehicles 10.4Support organizations 11Research 12Other animals 13References 14Further reading 15External linksSigns and symptoms[edit]

An instructional video about epileptic seizures

A bite to the tip of the tongue due to a seizureEpilepsy is characterized by a long-term risk of recurrentseizures.[17]These seizures may present in several ways depending on the part of the brain involved and the person's age.[17][18]Seizures[edit]The most common type (60%) of seizures areconvulsive.[18]Of these, one-third begin asgeneralized seizuresfrom the start, affecting both hemispheres of the brain.[18]Two-thirds begin aspartial seizures(which affect one hemisphere of the brain) which may then progress togeneralized seizures.[18]The remaining 40% of seizures are non-convulsive. An example of this type is theabsence seizure, which presents as a decreased level of consciousness and usually lasts about 10 seconds.[19][20]Partial seizuresare often preceded by certain experiences, known as anaura.[21]These may include sensory (visual, hearing or smell), psychic, autonomic, or motor phenomena.[19]Jerking activity may start in a specific muscle group and spread to surrounding muscle groups in which case it is known as aJacksonian march.[22]Automatismsmay occur; these are non-consciously generated activities and mostly simple repetitive movements like smacking of the lips or more complex activities such as attempts to pick something up.[22]There are six main types of generalized seizures:tonic-clonic, tonic,clonic,myoclonic, absence, andatonic seizures.[23]They all involve loss of consciousness and typically happen without warning.Tonic-clonic seizures present with a contraction of the limbs followed by their extension along with arching of the back which lasts 1030seconds (the tonic phase). A cry may be heard due to contraction of the chest muscles. This is then followed by a shaking of the limbs in unison (clonic phase). Tonic seizures produce constant contractions of the muscles. A person often turns blue as breathing is stopped. In clonic seizures there is shaking of the limbs in unison. After the shaking has stopped it may take 1030minutes for the person to return to normal; this period is called the "postictal state" or "postictal phase". Loss of bowel or bladder control may occur during a seizure.[4]The tongue may be bitten at either the tip or on the sides during a seizure.[24]Intonic-clonic seizure, bites to the sides are more common.[24]Tongue bites are also relatively common inpsychogenic non-epileptic seizures.[24]Myoclonic seizures involve spasms of muscles in either a few areas or all over.[25]Absence seizures can be subtle with only a slight turn of the head or eye blinking.[19]The person does not fall over and returns to normal right after it ends.[19]Atonic seizures involve the loss of muscle activity for greater than one second.[22]This typically occurs on both sides of the body.[22]About 6% of those with epilepsy have seizures that are often triggered by specific events and are known asreflex seizures.[26]Those withreflex epilepsyhave seizures that are only triggered by specific stimuli.[27]Common triggers include flashing lights and sudden noises.[26]In certain types of epilepsy, seizures happen more often duringsleep,[28]and in other types they occur almost only when sleeping.[29]Postictal[edit]After the active portion of a seizure, there is typically a period of confusion referred to as thepostictalperiod before a normallevel of consciousnessreturns.[21]This usually lasts 3 to 15 minutes[30]but may last for hours.[31]Other common symptoms include feeling tired,headache, difficulty speaking, and abnormal behavior.[31]Psychosisafter a seizure is relatively common, occurring in 610% of people.[32]Often people do not remember what happened during this time.[31]Localized weakness, known asTodd's paralysis, may also occur after a partial seizure. When it occurs it typically lasts for seconds to minutes but may rarely last for a day or two.[33]Psychosocial[edit]Epilepsy can have adverse effects on social and psychological well-being.[18]These effects may include social isolation, stigmatization, or disability.[18]They may result in lower educational achievement and worse employment outcomes.[18]Learning difficulties are common in those with the condition, and especially amongchildren with epilepsy.[18]The stigma of epilepsy can also affect the families of those with the disease.[4]Certain disorders occur more often in people with epilepsy, depending partly on the epilepsy syndrome present. These includedepression,anxiety disorders, andmigraines.[34]Attention deficit hyperactivity disorderaffects three to five times more children with epilepsy than children in the general population.[35]ADHD and epilepsy have significant consequences on a child's behavioral, learning, and social development.[36]Epilepsy is also more common inautisticpeople.[37]Causes[edit]See also:Causes of seizuresEpilepsy can have both genetic and acquired causes, with interaction of these factors in many cases.[38]Established acquired causes include serious brain trauma, stroke, tumours and problems in the brain as a result of a previous infective.[38]In about 60% of cases the cause is unknown.[4][18]Epilepsies caused bygenetic,congenital, ordevelopmentalconditions are more common among younger people, whilebrain tumorsandstrokesare more likely in older people.[18]Seizures may also occur as a consequence of other health problems;[23]if they occur right around a specific cause, such as a stroke, head injury, toxic ingestion or metabolic problem, they are known asacute symptomatic seizuresand are in the broader classification ofseizure-related disordersrather than epilepsy itself.[8][39]Genetics[edit]Genetics is believed to be involved in the majority of cases, either directly or indirectly.[40]Some epilepsies are due to a single gene defect (12%); most are due to the interaction of multiple genes and environmental factors.[40]Each of the single gene defects is rare, with more than 200 in all described.[41]Most genes involved affection channels, either directly or indirectly.[38]These include genes forion channelsthemselves,enzymes,GABA, andG protein-coupled receptors.[25]Inidentical twins, if one is affected there is a 5060% chance that the other will also be affected.[40]In non-identical twins the risk is 15%.[40]These risks are greater in those with generalized rather than partial seizures.[40]If both twins are affected, most of the time they have the same epileptic syndrome (7090%).[40]Other close relatives of a person with epilepsy have a risk five times that of the general population.[42]Between 1 and 10% of those withDown syndromeand 90% of those withAngelman syndromehave epilepsy.[42]Acquired[edit]Epilepsy may occur as a result of a number of other conditions including tumors,strokes, head trauma, previousinfections of the central nervous system, genetic abnormalities, and as a result of brain damage around the time of birth.[4][23]Of those with brain tumors, almost 30% have epilepsy, making them the cause of about 4% of cases.[42]The risk is greatest for tumors in the temporal lobe and those that grow slowly.[42]Other mass lesions such ascerebral cavernous malformationsandarteriovenous malformationshave risks as high as 4060%.[42]Of those who have had a stroke, 24% develop epilepsy.[42]In the United Kingdom strokes account for 15% of cases and it is believed to be the cause in 30% of the elderly.[18][42]Between 6 and 20% of epilepsy is believed to be due to head trauma.[42]Mild brain injuryincreases the risk about two-fold whilesevere brain injuryincreases the risk seven-fold.[42]In those who have experienced a high powered gunshot wound to the head, the risk is about 50%.[42]The risk of epilepsy followingmeningitisis less than 10%; that disease more commonly causes seizures during the infection itself.[42]Inherpes simplex encephalitisthe risk of a seizure is around 50%[42]with a high risk of epilepsy following (up to 25%).[43][44]Infection with thepork tapeworm, which can result inneurocysticercosis, is the cause of up to half of epilepsy cases in areas of the world where the parasite is common.[42]Epilepsy may also occur after other brain infections such ascerebral malaria,toxoplasmosis, andtoxocariasis.[42]Chronic alcohol use increases the risk of epilepsy: those who drink sixunits of alcoholper day have a two and a half fold increase in risk.[42]Other risks includeAlzheimer's disease,multiple sclerosis,tuberous sclerosis, andautoimmune encephalitis.[42]Getting vaccinated does not increase the risk of epilepsy.[42]Malnutritionis a risk factor seen mostly in the developing world, although it is unclear however if it is a direct cause or an association.[13]Pathophysiology[edit]Normally brain electrical activity is non-synchronous.[19]Its activity is regulated by various factors both within theneuronand the cellular environment. Factors within the neuron include the type, number and distribution ofion channels, changes toreceptorsand changes ofgene expression.[45]Factors around the neuron includeionconcentrations,synaptic plasticityand regulation oftransmitterbreakdown byglial cells.[45][46]Epilepsy[edit]The exact mechanism of epilepsy itself is unknown.[47]A little, however, is known about both the cellular and network mechanisms of epilepsy. However, it is unknown under which circumstances the brain shifts into the activity of a seizure with itsexcessive synchronization.[48][49]In epilepsy the resistance of excitatory neurons to fire during this period is decreased.[19]This may occur due to changes inion channelsor inhibitory neurons not functioning properly.[19]This then results in a specific area from which seizures may develop, known as a "seizure focus".[19]Another mechanism of epilepsy may be the up-regulation of excitatory circuits or down-regulation of inhibitory circuits following an injury to the brain.[19][50]These secondary epilepsies occur through processes known asepileptogenesis.[19][50]Failure of thebloodbrain barriermay also be a causal mechanism as it would allow substances in the blood to enter the brain.[51]Seizures[edit]There is evidence thatepileptic seizureare usually not a random event. Seizures are often brought on by factors such as lack of sleep, stress or flickering light among others. The termseizure thresholdis used to indicate the amount ofstimulusnecessary to bring about a seizure. Seizure threshold is lowered in epilepsy.[48]In epileptic seizures a group of neurons begin firing in an abnormal, excessive,[18]and synchronized manner.[19]This results in a wave of depolarization known as aparoxysmal depolarizing shift.[52]Normally, after anexcitatory neuronfires it becomes more resistant to firing for a period of time.[19]This is due in part to the effect of inhibitory neurons, electrical changes within the excitatory neuron, and the negative effects ofadenosine.[19]Partial seizures begin in onehemisphere of the brainwhile generalized seizures begin in both hemispheres.[23]Some types of seizures may change brain structure, while others appear to have little effect.[53]Gliosis, neuronal loss, and atrophy of specific areas of the brain are linked to epilepsy but it is unclear if epilepsy causes these changes or if these changes result in epilepsy.[53]Diagnosis[edit]

AnEEGcan aid in locating the focus of the epileptic seizure.The diagnosis of epilepsy is typically made based on the description of the seizure and the underlying cause.[18]Anelectroencephalogramandneuroimagingare also usually part of the workup.[18]While figuring out a specific epileptic syndrome is often attempted, it is not always possible.[18]Video and EEG monitoringmay be useful in difficult cases.[54]Definition[edit]Epilepsy is a disease of the brain defined by any of the following conditions:[3]1. At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years3. Diagnosis of an epilepsy syndrome

Furthermore epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy syndrome but are now past the that age or those who have remained seizure-free for the last 10 years, with no seizure medicines for the last 5 years.[3]This 2014 definition of theInternational League Against Epilepsy[3]is a refinement of their 2005 definition which was "a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure."[55][56]It is therefore possible to outgrow epilepsy or to undergo treatment that causes the epilepsy to be resolved. Resolution of epilepsy unfortunately does not guarantee that it will not return. In the definition, epilepsy is now called a disease, rather than a disorder. This was a decision of the executive committee of the ILAE, taken because the word "disorder," while perhaps having less stigma than does "disease," also does not express the degree of seriousness that epilepsy deserves.[3]The definition is practical in nature and is designed for clinical use. Researchers, statistically-minded epidemiologists and other specialized groups may choose to use the older definition or a definition of their own devising. The ILAE considers doing so is perfectly allowable, so long as it is clear what definition is being used.[3]Classification[edit]In contrast to theclassification of seizureswhich focuses on what happens during a seizure, the classification of epilepsies focuses on the underlying causes. When a person is admitted to hospital after an epileptic seizure the diagnostic workup results preferably in the seizure itself being classified (e.g. tonic-clonic) and in the underlying disease being identified (e.g. hippocampal sclerosis).[54]The name of the diagnosis finally made depends on the available diagnostic results and the applied definitions and classifications (of seizures and epilepsies) and its respective terminology.TheInternational League Against Epilepsy(ILAE) provided a classification of the epilepsies andepileptic syndromesin 1989 as follows:[57]1. Localization-related epilepsies and syndromes1. Unknown cause (e.g. benign childhood epilepsy with centrotemporal spikes)2. Symptomatic/cryptogenic(e.g. temporal lobe epilepsy)2. Generalized1. Unknown cause (e.g. childhood absence epilepsy)2. Cryptogenic or symptomatic (e.g. Lennox-Gastaut syndrome)3. Symptomatic (e.g. early infantile epileptic encephalopathy with suppression burst)3. Epilepsies and syndromes undetermined whether partial or generalized1. With both generalized and partial seizures (e.g. epilepsy with continuous spike-waves during slow wave sleep)4. Special syndromes (with situation-related seizures)[57]

This classification was widely accepted but has also been criticized mainly because the underlying causes of epilepsy (which are a major determinant of clinical course and prognosis) were not covered in detail.[58]In 2010 the ILAE Commission for Classification of the Epilepsies addressed this issue and divided epilepsies into three categories (genetic, structural/metabolic, unknown cause)[59]that were refined in their 2011 recommendation into four categories and a number of subcategories reflecting recent technologic and scientific advances.[60]1. Unknown cause (mostly genetic or presumed genetic origin)1. Pure epilepsies due to single gene disorders2. Pure epilepsies with complex inheritance2. Symptomatic (associated with gross anatomic or pathologic abnormalities)1. Mostly genetic or developmental causation1. Childhood epilepsy syndromes2. Progressive myoclonic epilepsies3. Neurocutaneous syndromes4. Other neurologic single gene disorders5. Disorders of chromosome function6. Developmental anomalies of cerebral structure2. Mostly acquired causes1. Hippocampal sclerosis2. Perinatal and infantile causes3. Cerebral trauma, tumor or infection4. Cerebrovascular disorders5. Cerebral immunologic disorders6. Degenerative and other neurologic conditions3. Provoked (a specific systemic or environmental factor is the predominant cause of the seizures)1. Provoking factors2. Reflex epilepsies4. Crytogenic (presumed symptomatic nature in which the cause has not been identified)[60]

Syndromes[edit]Main article:Epilepsy syndromesCases of epilepsy may be organized intoepilepsy syndromesby the specific features that are present. These features include the age that seizure begin, the seizure types,EEGfindings, among others. Identifying an epilepsy syndrome is useful as it helps determine the underlying causes as well as whatanti-seizure medicationshould be tried.[61][23]The ability to categorize a case of epilepsy into a specific syndrome occurs more often with children since the onset of seizures is commonly early.[39]Less serious examples arebenign rolandic epilepsy(2.8 per 100,000),childhood absence epilepsy(0.8 per 100,000) andjuvenile myoclonic epilepsy(0.7 per 100,000).[39]Severe syndromes with diffuse brain dysfunction caused, at least partly, by some aspect of epilepsy, are also referred to as epileptic encephalopathies. These are associated with frequentseizuresthat are resistant to treatment and severe cognitive dysfunction, for instanceLennox-Gastaut syndromeandWest syndrome.[62]Genetics is believed to play an important role in epilepsies by a number of mechanisms. Simple and complex modes ofinheritancehave been identified for some of them. However, extensive screening have failed to identify many singlegenevariants of large effect.[63]More recent exome and genome sequencing studies have begun to reveal a number of de novo gene mutations that are responsible for some epileptic encephalopathies, includingCHD2andSYNGAP1[64][65][66]andDMN1,GABBR2,FASNandRYR3,[67]Syndromes in which causes are not clearly identified are difficult to match with categories of the current classification of epilepsy. Categorization for these cases was made somewhat arbitrarily.[60]Theidiopathic(unknown cause) category of the 2011 classification includes syndromes in which the general clinical features and/or age specificity strongly point to a presumed genetic cause.[60]Some childhood epilepsy syndromes are included in the unknown cause category in which the cause is presumed genetic, for instancebenign rolandic epilepsy. Others are included insymptomaticdespite a presumed genetic cause (in at least in some cases), for instanceLennox-Gastaut syndrome.[60]Clinical syndromes in which epilepsy is not the main feature (e.g.Angelman syndrome) were categorizedsymptomaticbut it was argued to include these within the categoryidiopathic.[60]Classification of epilepsies and particularly of epilepsy syndromes will change with advances in research.Tests[edit]Anelectroencephalogram(EEG) can assist in showing brain activity suggestive of an increased risk of seizures. It is only recommended for those who are likely to have had an epileptic seizure on the basis of symptoms. In the diagnosis of epilepsy, electroencephalography may help distinguish the type of seizure or syndrome present. In children it is typically only needed after a second seizure. It cannot be used to rule out the diagnosis, and may be falsely positive in those without the disease. In certain situations it may be useful to perform the EEG while the affected individual is sleeping or sleep deprived.[54]Diagnostic imaging byCT scanandMRIis recommended after a first non-febrile seizure to detect structural problems in and around the brain.[54]MRI is generally a better imaging test except when bleeding is suspected, for which CT is more sensitive and more easily available.[14]If someone attends the emergency room with a seizure but returns to normal quickly, imaging tests may be done at a later point.[14]If a person has a previous diagnosis of epilepsy with previous imaging, repeating the imaging is usually not needed even if there are subsequent seizures.[54]For adults, the testing of electrolyte,blood glucoseand calcium levels is important to rule out problems with these as causes.[54]Anelectrocardiogramcan rule out problems with the rhythm of the heart.[54]A lumbar puncture may be useful to diagnose acentral nervous systeminfection but is not routinely needed.[14]In children additional tests may be required such as urine biochemistry and blood testing looking formetabolic disorders.[54][68]A high bloodprolactinlevel within the first 20 minutes following a seizure may be useful to confirm an epileptic seizure as opposed topsychogenic non-epileptic seizure.[69][70]Serum prolactin level is less useful for detecting partial seizures.[71]If it is normal an epileptic seizure is still possible[70]and a serum prolactin does not separate epileptic seizures from syncope.[72]It is not recommended as a routine part of the diagnosis of epilepsy.[54]Differential diagnosis[edit]Diagnosis of epilepsy can be difficult. A number of other conditions may present very similar signs and symptoms to seizures, includingsyncope,hyperventilation,migraines,narcolepsy,panic attacksandpsychogenic non-epileptic seizures(PNES).[73][74]In particular asyncopecan be accompanied by a short episode of convulsions.[75]Nocturnal frontal lobe epilepsy, often misdiagnosed as nightmares, was considered to be aparasomniabut later identified to be epileptic.[76]Attacks of the movement disorderparoxysmal dyskinesiamay be taken for epileptic seizures.[77]The cause of adrop attackcan be, among many others, anatonic seizure.[74]Children may have behaviors that are easily mistaken for epileptic seizures but are not. These includebreath-holding spells,bed wetting,night terrors,ticsandshudder attacks.[74]Gastroesophageal refluxmay cause arching of the back andtwisting of the head to the sidein infants, which may be mistaken for tonic-clonic seizures.[74]Misdiagnosis is frequent (occurring in about 5 to 30% of cases).[18]Different studies showed that in many cases seizure-like attacks in apparent treatment-resistant epilepsy have a cardiovascular cause.[75][78]Approximately 20% of the people seen at epilepsy clinics have PNES[14]and of those who have PNES about 10% also have epilepsy;[79]separating the two based on the seizure episode alone without further testing is often difficult.[79]Prevention[edit]While many cases are not preventable, efforts to reduce head injuries, provide good care around the time of birth, and reduce environmental parasites such as thepork tapewormmay be effective.[4]Efforts in one part of Central America to decrease rates of pork tapeworm resulted in a 50% decrease in new cases of epilepsy.[13]Management[edit]Epilepsy is usually treated with dailymedicationonce a second seizure has occurred,[18][54]but for those at high risk, medication may be started after the first seizure.[54]In some cases, a special diet, the implantation of aneurostimulator, or neurosurgery may be required.First aid[edit]Rolling a person with an active tonic-clonic seizure onto their side and into therecovery positionhelps prevent fluids from getting into the lungs.[80]Putting fingers, a bite block or tongue depressor in the mouth is not recommended as it might make the personvomitor result in the rescuer being bitten.[21][80]Efforts should be taken to prevent further self-injury.[21]Spinal precautionsare generally not needed.[80]If a seizure lasts longer than 5minutes or if there are more than two seizures in an hour without a return to a normal level of consciousness between them, it is considered amedical emergencyknown asstatus epilepticus.[54][81]This may requiremedical help to keep the airway open and protected;[54]anasopharyngeal airwaymay be useful for this.[80]At home the recommended initial medication for seizure of a long duration ismidazolamplaced in the mouth.[82]Diazepammay also be usedrectally.[82]In hospital, intravenouslorazepamis preferred.[54]If two doses ofbenzodiazepinesare not effective, other medications such asphenytoinare recommended.[54]Convulsive status epilepticus that does not respond to initial treatment typically requires admission to theintensive care unitand treatment with stronger agents such asthiopentoneorpropofol.[54]Medications[edit]

AnticonvulsantsThe mainstay treatment of epilepsy isanticonvulsantmedications, possibly for the person's entire life.[18]The choice of anticonvulsant is based on seizure type, epilepsy syndrome, other medications used, other health problems, and the person's age and lifestyle.[82]A single medication is recommended initially;[83]if this is not effective, switching to a single other medication is recommended.[54]Two medications at once is recommended only if a single medication does not work.[54]In about half, the first agent is effective; a second single agent helps in about 13% and a third or two agents at the same time may help an additional 4%.[84]About 30% of people continue to have seizures despite anticonvulsant treatment.[7]There are a number of medications available.Phenytoin,carbamazepineandvalproateappear to be equally effective in both partial and generalized seizures.[85][86]Controlled releasecarbamazepine appears to work as well as immediate release carbamazepine, and may have fewerside effects.[87]In the United Kingdom, carbamazepine orlamotrigineare recommended as first-line treatment for partial seizures, withlevetiracetamand valproate as second-line due to issues of cost and side effects.[54]Valproate is recommended first-line for generalized seizures with lamotrigine being second-line.[54]In those with absence seizures,ethosuximideor valproate are recommended; valproate is particularly effective in myoclonic seizures and tonic or atonic seizures.[54]If seizures are well-controlled on a particular treatment, it is not usually necessary to routinely check the medication levels in the blood.[54]The least expensive anticonvulsant isphenobarbitalat around $5USD a year.[13]TheWorld Health Organizationgives it a first-line recommendation in the developing world and it is commonly used there.[88][89]Access however may be difficult as some countries label it as acontrolled drug.[13]Adverse effects from medications are reported in 10 to 90% of people, depending on how and from whom the data is collected.[90]Most adverse effects are dose-related and mild.[90]Some examples include mood changes, sleepiness, or an unsteadiness in gait.[90]Certain medications have side effects that are not related to dose such as rashes, liver toxicity, orsuppression of the bone marrow.[90]Up to a quarter of people stop treatment due to adverse effects.[90]Some medications are associated withbirth defectswhen used in pregnancy.[54]Valproate is of particular concern, especially during thefirst trimester.[91]Despite this, treatment is often continued once effective, because the risk of untreated epilepsy is believed to be greater than the risk of the medications.[91]Slowly stopping medications may be reasonable in some people who do not have a seizure for two to four years; however, around a third of people have a recurrence, most often during the first six months.[54][92]Stopping is possible in about 70% of children and 60% of adults.[4]Surgery[edit]Epilepsy surgerymay be an option for people with partial seizures that remain a problem despite other treatments.[93]These other treatments include at least a trial of two or three medications.[94]The goal of surgery is total control of seizures[95]and this may be achieved in 6070% of cases.[94]Common procedures include cutting out thehippocampusvia an anteriortemporal loberesection, removal of tumors, and removing parts of theneocortex.[94]Some procedures such as acorpus callosotomyare attempted in an effort to decrease the number of seizures rather than cure the condition.[94]Following surgery, medications may be slowly withdrawn in many cases.[94]Neurostimulationmay be another option in those who are not candidates for surgery.[54]Three types have been shown to be effective in those who do not respond to medications:vagus nerve stimulation,anterior thalamic stimulation, andclosed-loop responsive stimulation.[96]Other[edit]Aketogenic diet(high-fat, low-carbohydrate, adequate-protein) appears to decrease the number of seizures by half in about 3040% of children.[97]It is a reasonable option in those who have epilepsy that is not improved with medications and for whom surgery is not an option.[97]About 10% stay on the diet for a few years due to issues of effectiveness and tolerability.[97]Side effects include stomach and intestinal problems in 30%, and there are long term concerns of heart disease.[97]Less radical diets are easier to tolerate and may be effective.[97]It is unclear why this diet works.[98]Exercise has been proposed as possibly useful for preventing seizures[99]with some data to support this claim.[100]Avoidance therapy consists of minimizing or eliminating triggers. For example, in those who are sensitive to light, using a small television, avoiding video-games or wearing dark glasses may be useful.[101]Operant-based biofeedbackbased on the EEG waves has some support in those who do not respond to medications.[102]Psychological methods should not, however, be used to replace medications.[54]Some dogs, also referred to asseizure dogs, may help during or after a seizure.[103][104]It is not clear if dogs have the ability to predict seizures before they occur.[105]Alternative medicine[edit]Alternative medicine, includingacupuncture,[106]psychologicalinterventions,[107]routinevitamins,[108]andyoga,[109]have no reliableevidenceto support their use in epilepsy. The use ofcannabisis not supported by the evidence.[110]Melatoninis insufficiently supported by evidence.[111]Prognosis[edit]

Disability-adjusted life yearfor epilepsy per 100,000inhabitants in 2004.no data275

Epilepsy cannot usually be cured, but medication can control seizures effectively in about 70% of cases.[7]Of those with generalized seizures, more than 80% can be well controlled with medications while this is true in only 50% of people with partial seizures.[96]One predictor of long-term outcome is the number of seizures that occur in the first six months.[18]Other factors increasing the risk of a poor outcome include little response to the initial treatment, generalized seizures, a family history of epilepsy, psychiatric problems, and waves on the EEG representing generalized epileptiform activity.[112]In the developing world 75% of people are either untreated or not appropriately treated.[4]In Africa 90% do not get treatment.[4]This is partly related to appropriate medications not being available or being too expensive.[4]Mortality[edit]People with epilepsy are at an increased risk of death.[113]This increase is between 1.6 and 4.1 fold greater than that of the general population[114]and is often related to: the underlying cause of the seizures,status epilepticus,suicide, trauma, andsudden unexpected death in epilepsy(SUDEP).[113]Death from status epilepticus is primarily due to an underlying problem rather than missing doses of medications.[113]The risk of suicide is increased between two and six times in those with epilepsy.[115][116]The cause of this is unclear.[115]SUDEP appears to be partly related to the frequency of generalized tonic-clonic seizures[117]and accounts for about 15% of epilepsy related deaths.[112]It is unclear how to decrease its risk.[117]The greatest increase in mortality from epilepsy is among the elderly.[114]Those with epilepsy due to an unknown cause have little increased risk.[114]In the United Kingdom it is estimated that 4060% of deaths are possibly preventable.[18]In the developing world many deaths are due to untreated epilepsy leading to falls or status epilepticus.[13]Epidemiology[edit]Epilepsy is one of the most common serious neurological disorders[118]affecting about 65million people globally.[8]It affects 1% of the population by age 20 and 3% of the population by age 75.[11]It is more common in males than females with the overall difference being small.[13][39]Most of those with the disease (80%) are in thedeveloping world.[4]The number of people who currently have active epilepsy is in the range 510 per 1,000, with active epilepsy defined as someone with epilepsy who has had a least one seizure in the last five years.[39][119]Epilepsy begins each year in 4070 per 100,000 in developed countries and 80140 per 100,000 in developing countries.[4]Poverty is a risk and includes both being from a poor country and being poor relative to others within one's country.[13]In the developed world epilepsy most commonly starts either in the young or in the old.[13]In the developing world its onset is more common in older children and young adults due to the higher rates of trauma and infectious diseases.[13]In developed countries the number of cases a year has decreased in children and increased among the elderly between the 1970s and 2003.[119]This has been attributed partly to better survival following strokes in the elderly.[39]History[edit]The oldest medical records show that epilepsy has been affecting people since the beginning of recorded history.[120]Throughoutancient history, the disorder was thought to be a spiritual condition.[120]The world's oldest description of an epileptic seizure comes from a text inAkkadian(a language used in ancientMesopotamia) and was written around 2000 BC.[1][1]The person described in the text was diagnosed as being under the influence of a Moon god, and underwent anexorcism.[1]Epileptic seizures are listed in theCode of Hammurabi(c. 1790 BC) as reason for which a purchased slave may be returned for a refund,[1]and theEdwin Smith Papyrus(c. 1700 BC) describes cases of individuals with epileptic convulsions.[1]The oldest known detailed record of the disorder itself is in theSakikku, aBabyloniancuneiformmedical text from 10671046 BC.[120]This text gives signs and symptoms, details treatment and likely outcomes,[1]and describes many features of the different seizure types.[120]As the Babylonians had no biomedical understanding of the nature of disease, they attributed the seizures to possession by evil spirits and called for treating the condition through spiritual means.[120]Around 900 BC,Punarvasu Atreyadescribed epilepsy as loss of consciousness;[121]this definition was carried forward into theAyurvedictext ofCharaka Samhita(about 400 BC).[122]

Hippocrates, 17th century engraving byPeter Paul Rubensof an antique bust.Theancient Greekshad contradictory views of the disease. They thought of epilepsy as a form of spiritual possession, but also associated the condition with genius and the divine. One of the names they gave to it was thesacred disease.[1][123]Epilepsy appears within Greek mythology: it is associated with the Moon goddessesSeleneandArtemis, who afflicted those who upset them. The Greeks thought that important figures such asJulius CaesarandHerculeshad the disease.[1]The notable exception to this divine and spiritual view was that of the school ofHippocrates. In the fifth century BC, Hippocrates rejected the idea that the disease was caused by spirits. In his landmark workOn the Sacred Disease, he proposed that epilepsy was not divine in origin and instead was a medically treatable problem originating in the brain.[1][120]He accused those of attributing a sacred cause to the disease of spreading ignorance through a belief in superstitious magic.[1]Hippocrates proposed thathereditywas important as a cause, described worse outcomes if the disease presents at an early age, and made note of the physical characteristics as well as the social shame associated with it.[1]Instead of referring to it as thesacred disease, he used the termgreat disease, giving rise to the modern termgrand mal, used for generalized seizures.[1]Despite his work detailing the physical origins of the disease, his view was not accepted at the time.[120]Evil spirits continued to be blamed until at least the 17th century.[120]In most cultures, persons with epilepsy have been stigmatized, shunned, or even imprisoned; in theSalptrire, the birthplace of modern neurology,Jean-Martin Charcotfound people with epilepsy side-by-side with the mentally ill, those with chronicsyphilis, and the criminally insane.[124]Inancient Rome, epilepsy was known as theMorbus Comitialis('disease of the assembly hall') and was seen as a curse from the gods. In northern Italy, epilepsy was once traditionally known as Saint Valentine's malady.[125]In the mid-1800s the first effective anti-seizure medication,bromide, was introduced.[90]The first modern treatment,phenobarbital, was developed in 1912, with phenytoin coming into use in 1938.[126]Society and culture[edit]See also:List of people with epilepsyStigma[edit]Stigmais commonly experienced, around the world, by those with epilepsy.[127]It can affect people economically, socially and culturally.[127]In India and China epilepsy may be used as justification to deny marriage.[4]People in some areas still believe those with epilepsy to becursed.[13]InTanzania, as in other parts of Africa, epilepsy is associated with possession by evil spirits, witchcraft, or poisoning and is believed by many to becontagious,[124]for which there is no evidence.[13]Before 1970 the United Kingdom had laws which prevented people with epilepsy from marrying.[4]The stigma may result in some people with epilepsy denying that they have ever had seizures.[39]Economics[edit]Seizures result in direct economic costs of about one billion dollars in the United States.[14]Epilepsy resulted in economic costs in Europe of around 15.5 billion Euros in 2004.[18]In India epilepsy is estimated to result in costs of 1.7billion USD or 0.5% of the GDP.[4]It is the cause of about 1% of emergency department visits (2% for emergency departments for children) in the United States.[128]Vehicles[edit]See also:Epilepsy and drivingThose with epilepsy are at about twice the risk of being involved in amotor vehicular collisionand thus in many areas of the world are not allowed to drive or only able to drive if certain conditions are met.[16]In some places physicians are required by law to report if a person has had a seizure to the licensing body while in others the requirement is only that they encourage the person in question to report it themselves.[16]Countries that require physician reporting include Sweden, Austria, Denmark and Spain.[16]Countries that require the individual to report include the UK, and New Zealand and the physician may report if they believe the individual has not already.[16]In Canada, the United States and Australia the requirements around reporting vary by province or state.[16]If seizures are well controlled most feel allowing driving is reasonable.[129]The amount of time a person must be free from seizures before they can drive varies by country.[129]Many countries require one to three years without seizures.[129]In the United States the time needed without a seizure is determined by each state and is between three months and one year.[129]Those with epilepsy or seizures are typically denied a pilot license.[130]In Canada if an individual has had no more than one seizure, they may be considered after five years for a limited license if all other testing is normal.[131]Those with febrile seizures and drug related seizures may also be considered.[131]In the United States, theFederal Aviation Administrationdoes not allow those with epilepsy to get a commercial pilot license.[132]Rarely, exceptions can be made for persons who have had an isolated seizure or febrile seizures and have remained free of seizures into adulthood without medication.[133]In the United Kingdom, a fullnational private pilot licenserequires the same standards as a professional driver's license.[134]This requires a period of ten years without seizures while off medications.[135]Those who do not meet this requirement may acquire a restricted license if free from seizures for five years.[134]Support organizations[edit]There are organizations that provide support for people and families affected by epilepsy. TheOut of the Shadowscampaign, a joint effort by the World Health Organization, the International League Against Epilepsy and theInternational Bureau for Epilepsy, provides help internationally.[4]The Joint Epilepsy Council serves the UK and Ireland.[54]In the United States, theEpilepsy Foundationis a national organization that works to increase the acceptance of those with the disease, their ability to function in society and to promote research for a cure.[136]The Epilepsy Foundation, some hospitals, and some individuals also run support groups in the United States.[137]Research[edit]Seizure prediction refers to attempts to forecastepileptic seizuresbased on the EEG before they occur.[138]As of 2011, no effective mechanism to predict seizures has been developed.[138]Kindling, where repeated exposures to events that could cause seizures eventually causes seizures more easily, has been used to createanimal modelsof epilepsy.[139]Gene therapyis being studied in some types of epilepsy.[140]Medications that alter immune function, such asintravenous immunoglobulins, are poorly supported by evidence.[141]Noninvasivestereotactic radiosurgeryis, as of 2012, being compared to standard surgery for certain types of epilepsy.[142]Other animals[edit]Main article:Epilepsy in animalsEpilepsy occurs in a number of other animals including dogs and cats and is the most common brain disorder in dogs.[143]It is typically treated with anticonvulsants such as phenobarbital orbromidein dogs and phenobarbital in cats.[144]Imepitoinis also being used in dogs.[145]While generalized seizures in horses are fairly easy to diagnose, it may be more difficult in non-generalized seizures and EEGs may be useful.[146]References[edit]1. ^Jump up to:abcdefghijklmMagiorkinis E, Kalliopi S, Diamantis A (January 2010). "Hallmarks in the history of epilepsy: epilepsy in antiquity".Epilepsy & behavior: E&B17(1): 103108.doi:10.1016/j.yebeh.2009.10.023.PMID19963440.2. ^Jump up to:abChang BS, Lowenstein DH (2003). "Epilepsy".N. Engl. J. Med.349(13): 125766.doi:10.1056/NEJMra022308.PMID14507951.3. ^Jump up to:abcdefFisher, Robert S; Acevedo, C; Arzimanoglou, A; Bogacz, A; Cross, JH; Elger, CE; Engel J, Jr; Forsgren, L; French, JA; Glynn, M; Hesdorffer, DC; Lee, BI; Mathern, GW; Mosh, SL; Perucca, E; Scheffer, IE; Tomson, T; Watanabe, M; Wiebe, S (April 2014)."ILAE Official Report: A practical clinical definition of epilepsy".Epilepsia55(4): 47582.doi:10.1111/epi.12550.PMID24730690.4. ^Jump up to:abcdefghijklmnopq"Epilepsy". Fact Sheets.World Health Organization. October 2012. RetrievedJanuary 24,2013.5. ^Jump up to:abFisher R, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J (2005)."Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)".Epilepsia46(4): 4702.doi:10.1111/j.0013-9580.2005.66104.x.PMID15816939.6. ^Jump up to:abcdLongo, Dan L (2012). "369 Seizures and Epilepsy".Harrison's principles of internal medicine(18th ed.). McGraw-Hill. p.3258.ISBN978-0-07-174887-2.7. ^Jump up to:abcEadie, MJ (December 2012). "Shortcomings in the current treatment of epilepsy.".Expert Review of Neurotherapeutics12(12): 141927.doi:10.1586/ern.12.129.PMID23237349.8. ^Jump up to:abcThurman, DJ; Beghi, E; Begley, CE; Berg, AT; Buchhalter, JR; Ding, D; Hesdorffer, DC; Hauser, WA; Kazis, L; Kobau, R; Kroner, B; Labiner, D; Liow, K; Logroscino, G; Medina, MT; Newton, CR; Parko, K; Paschal, A; Preux, PM; Sander, JW; Selassie, A; Theodore, W; Tomson, T; Wiebe, S; ILAE Commission on, Epidemiology (September 2011). "Standards for epidemiologic studies and surveillance of epilepsy.".Epilepsia. 52 Suppl 7: 226.doi:10.1111/j.1528-1167.2011.03121.x.PMID21899536.9. Jump up^GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.".Lancet385(9963): 11771.doi:10.1016/S0140-6736(14)61682-2.PMID25530442.10. Jump up^Brodie, MJ; Elder, AT; Kwan, P (November 2009). "Epilepsy in later life".Lancet neurology8(11): 101930.doi:10.1016/S1474-4422(09)70240-6.PMID19800848.11. ^Jump up to:abHolmes, Thomas R. Browne, Gregory L. (2008).Handbook of epilepsy(4th ed.). Philadelphia: Lippincott Williams & Wilkins. p.7.ISBN978-0-7817-7397-3.12. Jump up^Wyllie's treatment of epilepsy: principles and practice.(5th ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 2010.ISBN978-1-58255-937-7.13. ^Jump up to:abcdefghijklNewton, CR (29 September 2012). "Epilepsy in poor regions of the world.".Lancet380(9848): 1193201.doi:10.1016/S0140-6736(12)61381-6.PMID23021288.14. ^Jump up to:abcdefWilden, JA; Cohen-Gadol, AA (15 August 2012). "Evaluation of first nonfebrile seizures.".American family physician86(4): 33440.PMID22963022.15. Jump up^Berg, AT (2008). "Risk of recurrence after a first unprovoked seizure".Epilepsia. 49 Suppl 1: 138.doi:10.1111/j.1528-1167.2008.01444.x.PMID18184149.16. ^Jump up to:abcdefL Devlin, A; Odell, M; L Charlton, J; Koppel, S (December 2012). "Epilepsy and driving: current status of research.".Epilepsy research102(3): 13552.doi:10.1016/j.eplepsyres.2012.08.003.PMID22981339.17. ^Jump up to:abDuncan, JS; Sander, JW; Sisodiya, SM; Walker, MC (1 April 2006)."Adult epilepsy.".Lancet367(9516): 1087100.doi:10.1016/S0140-6736(06)68477-8.PMID16581409.18. ^Jump up to:abcdefghijklmnopqrstuNational Clinical Guideline Centre (2012), p.2128.19. ^Jump up to:abcdefghijklmHammer, edited by Stephen J. McPhee, Gary D. (2010). "7".Pathophysiology of disease: an introduction to clinical medicine(6th ed. ed.). New York: McGraw-Hill Medical.ISBN978-0-07-162167-0.20. Jump up^Hughes, JR (August 2009). "Absence seizures: a review of recent reports with new concepts.".Epilepsy & behavior: E&B15(4): 40412.doi:10.1016/j.yebeh.2009.06.007.PMID19632158.21. ^Jump up to:abcdShearer, Peter."Seizures and Status Epilepticus: Diagnosis and Management in the Emergency Department".Emergency Medicine Practice.22. ^Jump up to:abcdBradley, Walter G. (2012). "67".Bradley's neurology in clinical practice.(6th ed. ed.). Philadelphia, PA: Elsevier/Saunders.ISBN978-1-4377-0434-1.23. ^Jump up to:abcdeNational Clinical Guideline Centre (2012), p.119129.24. ^Jump up to:abcEngel, Jerome (2008).Epilepsy: a comprehensive textbook(2nd ed. ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p.2797.ISBN978-0-7817-5777-5.25. ^Jump up to:abSimon, David A. Greenberg, Michael J. Aminoff, Roger P. (2012). "12".Clinical neurology(8th ed. ed.). New York: McGraw-Hill Medical.ISBN978-0-07-175905-2.26. ^Jump up to:abSteven C. Schachter, ed. (2008).Behavioral aspects of epilepsy: principles and practice([Online-Ausg.]. ed.). New York: Demos. p.125.ISBN978-1-933864-04-4.27. Jump up^Xue, LY; Ritaccio, AL (March 2006). "Reflex seizures and reflex epilepsy.".American journal of electroneurodiagnostic technology46(1): 3948.PMID16605171.28. Jump up^Malow, BA (November 2005). "Sleep and epilepsy.".Neurologic Clinics23(4): 112747.doi:10.1016/j.ncl.2005.07.002.PMID16243619.29. Jump up^Tinuper, P; Provini, F; Bisulli, F; Vignatelli, L; Plazzi, G; Vetrugno, R; Montagna, P; Lugaresi, E (August 2007). "Movement disorders in sleep: guidelines for differentiating epileptic from non-epileptic motor phenomena arising from sleep.".Sleep medicine reviews11(4): 25567.doi:10.1016/j.smrv.2007.01.001.PMID17379548.30. Jump up^Holmes, Thomas R. (2008).Handbook of epilepsy(4th ed. ed.). Philadelphia: Lippincott Williams & Wilkins. p.34.ISBN978-0-7817-7397-3.31. ^Jump up to:abcPanayiotopoulos, CP (2010).A clinical guide to epileptic syndromes and their treatment based on the ILAE classifications and practice parameter guidelines(Rev. 2nd ed. ed.). London: Springer. p.445.ISBN978-1-84628-644-5.32. Jump up^James W. Wheless, ed. (2009).Advanced therapy in epilepsy. Shelton, Conn.: People's Medical Pub. House. p.443.ISBN978-1-60795-004-2.33. Jump up^Larner, Andrew J. (2010).A dictionary of neurological signs(3rd ed. ed.). New York: Springer. p.348.ISBN978-1-4419-7095-4.34. Jump up^Stefan, Hermann (2012).Epilepsy Part I: Basic Principles and Diagnosis E-Book: Handbook of Clinical Neurology(Volume 107 of Handbook of Clinical Neurology ed.). Newnes. p.471.ISBN978-0-444-53505-4.35. Jump up^Plioplys S, Dunn DW, Caplan R (2007). "10-year research update review: psychiatric problems in children with epilepsy".J Am Acad Child Adolesc Psychiatry46(11): 1389402.doi:10.1097/chi.0b013e31815597fc.PMID18049289.36. Jump up^Reilly CJ (MayJune 2011). "Attention Deficit Hyperactivity Disorder (ADHD) in Childhood Epilepsy".Research in Developmental Disabilities: A Multidisciplinary Journal32(3): 88393.doi:10.1016/j.ridd.2011.01.019.PMID21310586.37. Jump up^Levisohn PM (2007). "The autism-epilepsy connection".Epilepsia48(Suppl 9): 335.doi:10.1111/j.1528-1167.2007.01399.x.PMID18047599.38. ^Jump up to:abcBerkovic SF1, Mulley JC, Scheffer IE, Petrou S (2006). "Human epilepsies: interaction of genetic and acquired factors".Trends Neurosci29(7): 3917.doi:10.1016/j.tins.2006.05.009.PMID16769131.39. ^Jump up to:abcdefgNeligan, A; Hauser, WA; Sander, JW (2012). "The epidemiology of the epilepsies.".Handbook of clinical neurology107: 11333.doi:10.1016/B978-0-444-52898-8.00006-9.PMID22938966.40. ^Jump up to:abcdefPandolfo, M. (Nov 2011). "Genetics of epilepsy.".Semin Neurol31(5): 50618.doi:10.1055/s-0031-1299789.PMID22266888.41. Jump up^Dhavendra Kumar, ed. (2008).Genomics and clinical medicine. Oxford: Oxford University Press. p.279.ISBN978-0-19-972005-7.42. ^Jump up to:abcdefghijklmnopqBhalla, D.; Godet, B.; Druet-Cabanac, M.; Preux, PM. (Jun 2011). "Etiologies of epilepsy: a comprehensive review.".Expert Rev Neurother11(6): 86176.doi:10.1586/ern.11.51.PMID21651333.43. Jump up^Simon D. Shorvon (2011).The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children. Cambridge University Press. p.467.ISBN978-1-139-49578-3.44. Jump up^Sellner, J; Trinka, E (Oct 2012). "Seizures and epilepsy in herpes simplex virus encephalitis: current concepts and future directions of pathogenesis and management.".Journal of neurology259(10): 201930.doi:10.1007/s00415-012-6494-6.PMID22527234.45. ^Jump up to:abBromfield EB (2006).An Introduction to Epilepsy. American Epilepsy Society.46. Jump up^Blumenfeld, H (2005). "Cellular and Network Mechanisms of Spike-Wave Seizures".Epilepsia46(Suppl.9): 2133.doi:10.1111/j.1528-1167.2005.00311.x.PMID16302873.47. Jump up^Noebels, Jeffrey L.; Avoli, Massimo (2012-06-29).Jasper's Basic Mechanisms of the Epilepsies. Oxford University Press. pp.466, 470.ISBN9780199746545. Retrieved2014-10-16.48. ^Jump up to:abLe Van Quyen, M; Navarro, V; Martinerie, J; Baulac, M; Varela, FJ (2003). "Toward a Neurodynamical Understanding of Ictogenesis".Epilepsia44(Suppl.12): 3043.doi:10.1111/j.0013-9580.2003.12007.x.PMID14641559.49. Jump up^Lopes da Silva F1, Blanes W, Kalitzin SN, Parra J, Suffczynski P, Velis DN (2003). "Epilepsies as Dynamical Diseases of Brain Systems: Basic Models of the Transition Between Normal and Epileptic Activity".Epilepsia44(Suppl.12): 7283.doi:10.1111/j.0013-9580.2003.12005.x.PMID14641563.50. ^Jump up to:abGoldberg, EM; Coulter, DA (May 2013). "Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction.".Nature reviews. Neuroscience14(5): 33749.doi:10.1038/nrn3482.PMID23595016.51. Jump up^Oby, E; Janigro, D (November 2006). "The blood-brain barrier and epilepsy.".Epilepsia47(11): 176174.doi:10.1111/j.1528-1167.2006.00817.x.PMID17116015.52. Jump up^Somjen, George G. (2004).Ions in the Brain Normal Function, Seizures, and Stroke.New York: Oxford University Press. p.167.ISBN978-0-19-803459-9.53. ^Jump up to:abJerome Engel, Jr., Timothy A. Pedley, ed. (2008).Epilepsy: a comprehensive textbook(2nd ed. ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p.483.ISBN978-0-7817-5777-5.54. ^Jump up to:abcdefghijklmnopqrstuvwxyzaaNational Clinical Guideline Centre (2012), p.5783.55. Jump up^Robert S. Fisher, Walter van Emde Boas, Warren Blume, Christian Elger, Pierre Genton, Phillip Lee & Jerome Jr Engel (April 2005). "Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)".Epilepsia46(4): 470472.doi:10.1111/j.0013-9580.2005.66104.x.PMID15816939.56. Jump up^Panayiotopoulos, CP (December 2011). "The new ILAE report on terminology and concepts for organization of epileptic seizures: a clinician's critical view and contribution.".Epilepsia52(12): 215560.doi:10.1111/j.1528-1167.2011.03288.x.PMID22004554.57. ^Jump up to:ab"Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy".Epilepsia30(4): 38999. 1989.doi:10.1111/j.1528-1157.1989.tb05316.x.PMID2502382.58. Jump up^Engel J (2006). "ILAE classification of epilepsy syndromes".Epilepsy Res70(Suppl 1): 510.doi:10.1111/j.1528-1157.1981.tb06159.x.PMID16822650.59. Jump up^Berg A, Berkovic S, Brodie M, Buchhalter J, Cross J, van Emde, Boas W, Engel J, French J, Glauser T, Mathern G, Mosh S, Nordli D, Plouin P, Scheffer I. (2010). "Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology".Epilepsia51(6): 676685.doi:10.1111/j.1528-1167.2010.02522.x.PMID20196795.60. ^Jump up to:abcdefShorvon SD (2011). "The etiologic classification of epilepsy".Epilepsia52(6): 10521057.doi:10.1111/j.1528-1167.2011.03041.x.61. Jump up^"Epilepsy syndromes". International league against epilepsy. Retrieved2014-10-06.62. Jump up^Nordli DR jr (2012). "Epileptic encephalopathies in infants and children".J Clin Neurophysiol29(5): 4204.doi:10.1097/WNP.0b013e31826bd961.PMID23027099.63. Jump up^Heinzen EL, Depondt C, Cavalleri GL, Ruzzo EK, Walley NM, Need AC, Ge D, He M, Cirulli ET, Zhao Q, Cronin KD, Gumbs CE, Campbell CR, Hong LK, Maia JM, Shianna KV, McCormack M, Radtke RA, O'Conner GD, Mikati MA, Gallentine WB, Husain AM, Sinha SR, Chinthapalli K, Puranam RS, McNamara JO, Ottman R, Sisodiya SM, Delanty N, Goldstein DB (2012)."Exome sequencing followed by large-scale genotyping failed to identify single rare variants of large effect in "idiopathic" generalized epilepsy".Am J Hum Genet91(2): 293302.doi:10.1016/j.ajhg.2012.06.016.PMC3415540.PMID22863189.64. Jump up^Gemma L Carvill, Sinad B Heavin, Simone C Yendle, Jacinta M McMahon, Brian J O'Roak, Joseph Cook, Adiba Khan, Michael O Dorschner, Molly Weaver, Sophie Calvert, Stephen Malone, Geoffrey Wallace, Thorsten Stanley, Ann M E Bye, Andrew Bleasel, Katherine B Howell, Sara Kivity, Mark T Mackay, Victoria Rodriguez-Casero, Richard Webster, Amos Korczyn, Zaid Afawi, Nathanel Zelnick, Tally Lerman-Sagie, Dorit Lev, Rikke S Mller, Deepak Gill, Danielle M Andrade, Jeremy L Freeman, Lynette G Sadleir, Jay Shendure, Samuel F Berkovic, Ingrid E Scheffer & Heather C Mefford (2013)."Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2, SYNGAP1".Nature Genet45(3): 825830.doi:10.1148/radiology.159.3.3704157.PMC3704157.PMID23708187.65. Jump up^Chnier S, Yoon G, Argiropoulos B, Lauzon J, Laframboise R, Ahn JW, Ogilvie CM, Lionel AC, Marshall CR, Vaags AK, Hashemi B, Boisvert K, Mathonnet G, Tihy F, So J, Scherer SW, Lemyre E, Stavropoulos DJ (2014)."CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems".J Neurodev Disord6(1): 9.doi:10.1186/1866-1955-6-9.PMC4022362.PMID24834135.66. Jump up^Suls A, Jaehn JA, Kecsks A, Weber Y, Weckhuysen S, Craiu DC, Siekierska A, Djmi T, Afrikanova T, Gormley P, von Spiczak S, Kluger G, Iliescu CM, Talvik T, Talvik I, Meral C, Caglayan HS, Giraldez BG, Serratosa J, Lemke JR, Hoffman-Zacharska D, Szczepanik E, Barisic N, Komarek V, Hjalgrim H, Mller RS, Linnankivi T, Dimova P, Striano P, Zara F, Marini C, Guerrini R, Depienne C, Baulac S, Kuhlenbumer G, Crawford AD, Lehesjoki AE, de Witte PA, Palotie A, Lerche H, Esguerra CV, De Jonghe P, Helbig I; EuroEPINOMICS RES Consortium (2013)."De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome".Am J Hum Genet93(5): 967975.doi:10.1016/j.ajhg.2013.09.017.PMC3824114.PMID24207121.67. Jump up^EuroEPINOMICS-RES Consortium (2014)."De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies".Am J Hum Genet95(4): 360370.doi:10.1016/j.ajhg.2014.08.013.PMC4185114.PMID25262651.68. Jump up^Wallace, ed. by Sheila J.; Farrell, Kevin (2004).Epilepsy in children(2nd ed ed.). London: Arnold. p.354.ISBN978-0-340-80814-6.69. Jump up^Luef, G (October 2010). "Hormonal alterations following seizures.".Epilepsy & behavior: E&B19(2): 1313.doi:10.1016/j.yebeh.2010.06.026.PMID20696621.70. ^Jump up to:abAhmad S, Beckett MW (2004)."Value of serum prolactin in the management of syncope".Emergency medicine journal: EMJ21(2): e3.doi:10.1136/emj.2003.008870.PMC1726305.PMID14988379.71. Jump up^Shukla G, Bhatia M, Vivekanandhan S et al. (2004). "Serum prolactin levels for differentiation of nonepileptic versus true seizures: limited utility".Epilepsy & behavior: E&B5(4): 51721.doi:10.1016/j.yebeh.2004.03.004.PMID15256189.72. Jump up^Chen DK, So YT, Fisher RS (2005). "Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology".Neurology65(5): 66875.doi:10.1212/01.wnl.0000178391.96957.d0.PMID16157897.73. Jump up^Brodtkorb, E (2013). "Common imitators of epilepsy.".Acta neurologica Scandinavica. Supplementum127(196): 510.doi:10.1111/ane.12043.PMID23190285.74. ^Jump up to:abcdJohn A. Marx, ed. (2010).Rosen's emergency medicine: concepts and clinical practice(7th ed. ed.). Philadelphia: Mosby/Elsevier. p.2228.ISBN978-0-323-05472-0.75. ^Jump up to:abZaidi A, Clough P, Cooper P, Scheepers B, Fitzpatrick AP (2000)."Misdiagnosis of epilepsy: many seizure-like attacks have a cardiovascular cause".J Am Coll Cardiol36(1): 1814.doi:10.1016/S0735-1097(00)00700-2.PMID10898432.76. Jump up^Bisulli F1, Vignatelli L, Provini F, Leta C, Lugaresi E, Tinuper P (2011). "Parasomnias and nocturnal frontal lobe epilepsy (NFLE): lights and shadows - controversial points in the differential diagnosis".Sleep Med12(Suppl2): 2732.doi:10.1016/j.sleep.2011.10.008.PMID22136895.77. Jump up^Zhou, J. Q.; Zhou, L. M.; Fang, Z. Y.; Wang, Q.; Chen, Z. Y.; Yang, L. B.; Chen, S. D.; Cai, X. D. (2011)."Analyzing clinical and electrophysiological characteristics of Paroxysmal Dyskinesia".Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences16(1): 110114.PMC3063430.PMID21448393.78. Jump up^Akhtar MJ (2002). "All seizures are not epilepsy: many have a cardiovascular cause".J Pak Med Assoc52(3): 111620.PMID12071066.79. ^Jump up to:abJerome, Engel (2013).Seizures and epilepsy(2nd ed. ed.). New York: Oxford University Press. p.462.ISBN9780195328547.80. ^Jump up to:abcdMichael, GE.; O'Connor, RE. (Feb 2011). "The diagnosis and management of seizures and status epilepticus in the prehospital setting.".Emerg Med Clin North Am29(1): 2939.doi:10.1016/j.emc.2010.08.003.PMID21109100.81. Jump up^James W. Wheless, James Willmore, Roger A. Brumback (2009).Advanced therapy in epilepsy. Shelton, Conn.: People's Medical Pub. House. p.144.ISBN9781607950042.82. ^Jump up to:abcNational Clinical Guideline Centre (2012), pp.5556.83. Jump up^Elaine Wyllie (2012).Wyllie's Treatment of Epilepsy: Principles and Practice. Lippincott Williams & Wilkins. p.187.ISBN978-1-4511-5348-4.84. Jump up^Steven R. Flanagan, Herb Zaretsky, Alex Moroz,, ed. (2010).Medical aspects of disability; a handbook for the rehabilitation professional(4th ed. ed.). New York: Springer. p.182.ISBN978-0-8261-2784-6.85. Jump up^Nolan, SJ; Marson, AG; Pulman, J; Tudur Smith, C (23 August 2013). "Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures.".The Cochrane database of systematic reviews8: CD001769.doi:10.1002/14651858.CD001769.pub2.PMID23970302.86. Jump up^Tudur Smith, C; Marson, AG; Clough, HE; Williamson, PR (2002). "Carbamazepine versus phenytoin monotherapy for epilepsy.".The Cochrane database of systematic reviews(2): CD001911.doi:10.1002/14651858.CD001911.PMID12076427.87. Jump up^Powell, G; Saunders, M; Marson, AG (20 January 2010). "Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy.".The Cochrane database of systematic reviews(1): CD007124.doi:10.1002/14651858.CD007124.pub2.PMID20091617.88. Jump up^Ilangaratne, NB; Mannakkara, NN; Bell, GS; Sander, JW (Dec 1, 2012). "Phenobarbital: missing in action.".Bulletin of the World Health Organization90(12): 871871A.doi:10.2471/BLT.12.113183.PMID23284189.89. Jump up^Mosh, edited by Simon Shorvon, Emilio Perucca, Jerome Engel Jr.; foreword by Solomon (2009).The treatment of epilepsy(3rd ed. ed.). Chichester, UK: Wiley-Blackwell. p.587.ISBN9781444316674.90. ^Jump up to:abcdefPerucca, P; Gilliam, FG (September 2012). "Adverse effects of antiepileptic drugs.".Lancet neurology11(9): 792802.doi:10.1016/S1474-4422(12)70153-9.PMID22832500.91. ^Jump up to:abKamyar, M.; Varner, M. (Jun 2013). "Epilepsy in pregnancy.".Clin Obstet Gynecol56(2): 33041.doi:10.1097/GRF.0b013e31828f2436.PMID23563876.92. Jump up^Lawrence S. Neinstein, ed. (2008).Adolescent health care: a practical guide(5th ed. ed.). Philadelphia: Lippincott Williams & Wilkins. p.335.ISBN978-0-7817-9256-1.93. Jump up^Duncan, JS; Sander, JW; Sisodiya, SM; Walker, MC (1 April 2006). "Adult epilepsy".Lancet367(9516): 1087100.doi:10.1016/S0140-6736(06)68477-8.PMID16581409.94. ^Jump up to:abcdeDuncan, JS (April 2007). "Epilepsy surgery.".Clinical Medicine(London)7(2): 13742.doi:10.7861/clinmedicine.7-2-137.PMID17491501.95. Jump up^Birbeck GL, Hays RD, Cui X, Vickrey BG. (2002). "Seizure reduction and quality of life improvements in people with epilepsy".Epilepsia43(5): 535538.doi:10.1046/j.1528-1157.2002.32201.x.PMID12027916.96. ^Jump up to:abBergey, GK (June 2013). "Neurostimulation in the treatment of epilepsy.".Experimental neurology244: 8795.doi:10.1016/j.expneurol.2013.04.004.PMID23583414.97. ^Jump up to:abcdeLevy, RG; Cooper, PN; Giri, P (14 March 2012)."Ketogenic diet and other dietary treatments for epilepsy.".The Cochrane database of systematic reviews3: CD001903.doi:10.1002/14651858.CD001903.pub2.PMID22419282.98. Jump up^[editor], Bernard L. Maria (2009).Current management in child neurology(4th ed. ed.). Hamilton, Ont.: BC Decker. p.180.ISBN978-1-60795-000-4.99. Jump up^Arida, RM; Scorza, FA; Scorza, CA; Cavalheiro, EA (March 2009). "Is physical activity beneficial for recovery in temporal lobe epilepsy? Evidences from animal studies.".Neuroscience and biobehavioral reviews33(3): 42231.doi:10.1016/j.neubiorev.2008.11.002.PMID19059282.100. Jump up^Arida, RM; Cavalheiro, EA; da Silva, AC; Scorza, FA (2008). "Physical activity and epilepsy: proven and predicted benefits.".Sports medicine (Auckland, N.Z.)38(7): 60715.doi:10.2165/00007256-200838070-00006.PMID18557661.101. Jump up^Verrotti, A; Tocco, AM; Salladini, C; Latini, G; Chiarelli, F (November 2005). "Human photosensitivity: from pathophysiology to treatment.".European journal of neurology: the official journal of the European Federation of Neurological Societies12(11): 82841.doi:10.1111/j.1468-1331.2005.01085.x.PMID16241971.102. Jump up^Tan, G; Thornby, J; Hammond, DC; Strehl, U; Canady, B; Arnemann, K; Kaiser, DA (July 2009). "Meta-analysis of EEG biofeedback in treating epilepsy.".Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS)40(3): 1739.doi:10.1177/155005940904000310.PMID19715180.103. Jump up^Di Vito L1, Naldi I, Mostacci B, Licchetta L, Bisulli F, Tinuper P (2010)."A seizure response dog: video recording of reacting behaviour during repetitive prolonged seizures".Epileptic Disord12(2): 1425.doi:10.1684/epd.2010.0313.PMID20472528.104. Jump up^Kirton A1, Winter A, Wirrell E, Snead OC (2008). "Seizure response dogs: evaluation of a formal training program".Epilepsy Behav13(3): 499504.doi:10.1016/j.yebeh.2008.05.011.PMID18595778.105. Jump up^Doherty, MJ; Haltiner, AM (23 January 2007). "Wag the dog: skepticism on seizure alert canines.".Neurology68(4): 309.doi:10.1212/01.wnl.0000252369.82956.a3.PMID17242343.106. Jump up^Cheuk, DK; Wong, V (8 October 2008). "Acupuncture for epilepsy.".The Cochrane database of systematic reviews(4): CD005062.doi:10.1002/14651858.CD005062.pub3.PMID18843676.107. Jump up^Ramaratnam, S; Baker, GA; Goldstein, LH (16 July 2008). "Psychological treatments for epilepsy.".The Cochrane database of systematic reviews(3): CD002029.doi:10.1002/14651858.CD002029.pub3.PMID18646083.108. Jump up^Ranganathan, LN; Ramaratnam, S (18 April 2005). "Vitamins for epilepsy.".The Cochrane database of systematic reviews(2): CD004304.doi:10.1002/14651858.CD004304.pub2.PMID15846704.109. Jump up^Ramaratnam, S; Sridharan, K (2000). "Yoga for epilepsy.".The Cochrane database of systematic reviews(3): CD001524.doi:10.1002/14651858.CD001524.PMID10908505.110. Jump up^Gloss, D; Vickrey, B (13 June 2012). "Cannabinoids for epilepsy.".The Cochrane database of systematic reviews6: CD009270.doi:10.1002/14651858.CD009270.pub2.PMID22696383.111. Jump up^Brigo, F; Del Felice, A (13 June 2012). "Melatonin as add-on treatment for epilepsy.".The Cochrane database of systematic reviews6: CD006967.doi:10.1002/14651858.CD006967.pub2.PMID22696363.112. ^Jump up to:abKwan, Patrick (2012).Fast facts: epilepsy(5th ed. ed.). Abingdon, Oxford, UK: Health Press. p.10.ISBN1-908541-12-1.113. ^Jump up to:abcHitiris N, Mohanraj R, Norrie J, Brodie MJ (2007). "Mortality in epilepsy".Epilepsy Behavior10(3): 363376.doi:10.1016/j.yebeh.2007.01.005.PMID17337248.114. ^Jump up to:abcMosh, edited by Simon Shorvon, Emilio Perucca, Jerome Engel Jr.; foreword by Solomon (2009).The treatment of epilepsy(3rd ed. ed.). Chichester, UK: Wiley-Blackwell. p.28.ISBN978-1-4443-1667-4.115. ^Jump up to:abBagary, M (April 2011). "Epilepsy, antiepileptic drugs and suicidality.".Current opinion in neurology24(2): 17782.doi:10.1097/WCO.0b013e328344533e.PMID21293270.116. Jump up^Mula, M; Sander, JW (August 2013). "Suicide risk in people with epilepsy taking antiepileptic drugs.".Bipolar disorders15(5): 6227.doi:10.1111/bdi.12091.PMID23755740.117. ^Jump up to:abRyvlin, P; Nashef, L; Tomson, T (May 2013). "Prevention of sudden unexpected death in epilepsy: a realistic goal?".Epilepsia. 54 Suppl 2: 238.doi:10.1111/epi.12180.PMID23646967.118. Jump up^Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R (2007-01-30). "How common are the 'common' neurologic disorders?".Neurology68(5): 32637.doi:10.1212/01.wnl.0000252807.38124.a3.PMID17261678.119. ^Jump up to:abSander JW (2003). "The epidemiology of epilepsy revisited".Current Opinion in Neurology16(2): 16570.doi:10.1097/00019052-200304000-00008.PMID12644744.120. ^Jump up to:abcdefghSaraceno, B; Avanzini, G; Lee, P, eds. (2005).Atlas: Epilepsy Care in the World. World Health Organization.ISBN92-4-156303-6. Retrieved20 December2013.121. Jump up^Mervyn J. Eadie; Peter F. Bladin (2001).A Disease Once Sacred: A History of the Medical Understanding of Epilepsy. John Libbey Eurotext.ISBN978-0-86196-607-3.122. Jump up^"Epilepsy: An historical overview".World Health Organization. Feb 2001. Retrieved27 December2013.123. Jump up^"Epilepsy: historical overview".World Health Organization. Retrieved2011-03-20.124. ^Jump up to:abJilek-Aall, L (1999). "Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures".Epilepsia40(3): 3826.doi:10.1111/j.1528-1157.1999.tb00723.x.PMID10080524.125. Jump up^Illes, Judika (2011-10-11).Encyclopedia of Mystics, Saints & Sages. HarperCollins. p.1238.ISBN978-0-06-209854-2. Retrieved26 February2013.Saint Valentine is invoked for healing as well as love. He protects against fainting and is requested to heal epilepsy and other seizure disorders. In northern Italy, epilepsy was once traditionally known as Saint Valentine's Malady.126. Jump up^E. Martin Caravati (2004).Medical toxicology(3. ed. ed.). Philadelphia [u.a.]: Lippincott Williams & Wilkins. p.789.ISBN978-0-7817-2845-4.127. ^Jump up to:abde Boer, HM (Dec 2010). "Epilepsy stigma: moving from a global problem to global solutions.".Seizure: the journal of the British Epilepsy Association19(10): 6306.doi:10.1016/j.seizure.2010.10.017.PMID21075013.128. Jump up^Martindale, JL; Goldstein, JN; Pallin, DJ (February 2011). "Emergency department seizure epidemiology.".Emergency medicine clinics of North America29(1): 1527.doi:10.1016/j.emc.2010.08.002.PMID21109099.129. ^Jump up to:abcdJerome Engel, Jr.; Timothy A. Pedley, eds. (2008).Epilepsy: a comprehensive textbook(2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p.2279.ISBN978-0-7817-5777-5.130. Jump up^Bor, Robert (2012).Aviation Mental Health: Psychological Implications for Air Transportation. Ashgate Publishing. p.148.ISBN978-1-4094-8491-2.131. ^Jump up to:ab"Seizure Disorders".Transport Canada. Government of Canada. Retrieved29 December2013.132. Jump up^Wilner, Andrew N. (2008).Epilepsy 199 answers: a doctor responds to his patients' questions(3rd ed. ed.). New York: Demos Health. p.52.ISBN978-1-934559-96-3.133. Jump up^"Guide for Aviation Medical Examiners".Federal Aviation Administration. Retrieved29 December2013.134. ^Jump up to:ab"National PPL (NPPL) Medical Requirements".Civil Aviation Authority. Retrieved29 December2013.135. Jump up^Drivers Medical Group (2013)."For Medical Practitioners: At a glance Guide to the current Medical Standards of Fitness to Drive". p.8. Retrieved29 December2013.136. Jump up^"Epilepsy Foundation of America - EFA".Healthfinder.gov.US Department of Health and Human Services. April 28, 2011. RetrievedJuly 28,2014.137. Jump up^al., editors, Jerome Engel, Jr., Timothy A. Pedley; associate editors, Jean Aicardi ... et (2008).Epilepsy: a comprehensive textbook(2nd ed. ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p.2245.ISBN9780781757775.138. ^Jump up to:abCarney, PR.; Myers, S.; Geyer, JD. (Dec 2011). "Seizure prediction: methods.".Epilepsy Behav. 22 Suppl 1: S94101.doi:10.1016/j.yebeh.2011.09.001.PMID22078526.139. Jump up^Jerome Engel, ed. (2008).Epilepsy: a comprehensive textbook(2nd ed. ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p.426.ISBN9780781757775.140. Jump up^Walker, MC.; Schorge, S.; Kullmann, DM.; Wykes, RC.; Heeroma, JH.; Mantoan, L. (Sep 2013). "Gene therapy in status epilepticus.".Epilepsia. 54 Suppl 6: 435.doi:10.1111/epi.12275.PMID24001071.141. Jump up^Walker, L; Pirmohamed, M; Marson, AG (27 June 2013). "Immunomodulatory interventions for focal epilepsy syndromes.".The Cochrane database of systematic reviews6: CD009945.doi:10.1002/14651858.CD009945.pub2.PMID23803963.142. Jump up^Quigg, M; Rolston, J; Barbaro, NM (Jan 2012). "Radiosurgery for epilepsy: clinical experience and potential antiepileptic mechanisms.".Epilepsia53(1): 715.doi:10.1111/j.1528-1167.2011.03339.x.PMID22191545.143. Jump up^Thomas, WB (January 2010). "Idiopathic epilepsy in dogs and cats".Veterinary Clinics of North America, Small Animal Practice40(1): 16179.doi:10.1016/j.cvsm.2009.09.004.PMID19942062.144. Jump up^Thomas, WB (Jan 2010). "Idiopathic epilepsy in dogs and cats.".The Veterinary clinics of North America. Small animal practice40(1): 16179.doi:10.1016/j.cvsm.2009.09.004.PMID19942062.145. Jump up^Rundfeldt, C; Loescher, W (January 2014). "The pharmacology of imepitoin: The first partial benzodiazepine receptor agonist developed for the treatment of epilepsy".CNS Drugs28(1): 2943.doi:10.1007/s40263-013-0129-z.PMID24357084.146. Jump up^van der Ree, M; Wijnberg, I (2012). "A review on epilepsy in the horse and the potential of Ambulatory EEG as a diagnostic tool.".The Veterinary quarterly32(34): 15967.doi:10.1080/01652176.2012.744496.PMID23163553.