Array ( [0] => {{Short description|Group of neurological disorders causing seizures}} [1] => {{cs1 config|name-list-style=vanc|display-authors=6}} [2] => {{Redirect2|Epilepsia|Epileptic|the journal|Epilepsia (journal)|the comics|Epileptic (comics)}} [3] => {{Use dmy dates|date=February 2023}} [4] => {{Infobox medical condition (new) [5] => | name = Epilepsy [6] => | synonyms = Seizure disorder [7] => | image = Spike-waves.png [8] => | alt = The electroencephalogram recording of a person with childhood absence epilepsy showing a seizure. The waves are black on a white background. [9] => | caption = Generalized 3 [[Hz]] [[spike-and-wave]] discharges on an [[electroencephalogram]] [10] => | field = [[Neurology]] [11] => | symptoms = Periods of loss of consciousness, abnormal shaking, staring, change in vision, mood changes and/or other cognitive disturbances [12] => | complications = [13] => | onset = [14] => | duration = Long term [15] => | causes = Unknown, [[Brain damage|brain injury]], stroke, [[brain tumor]]s, infections of the brain, [[birth defects]] [16] => | risks = [17] => | diagnosis = Electroencephalogram, ruling out other possible causes [18] => | differential = [[Syncope (medicine)|Fainting]], [[alcohol withdrawal]], [[electrolyte problems]] [19] => | prevention = [20] => | treatment = Medication, [[Epilepsy_surgery|surgery]], [[neurostimulation]], dietary changes [21] => | medication = [22] => | prognosis = Controllable in 69% [23] => | frequency = 39 million / 0.5% (2015) [24] => | deaths = 125,000 (2015) [25] => }} [26] => [27] => '''Epilepsy''' is a group of [[Non-communicable disease|non-communicable]] [[neurological disorder]]s characterized by recurrent [[Seizure|epileptic seizure]]s.{{cite journal | vauthors = Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshé SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S | title = ILAE official report: a practical clinical definition of epilepsy | journal = Epilepsia | volume = 55 | issue = 4 | pages = 475–482 | date = April 2014 | pmid = 24730690 | doi = 10.1111/epi.12550 | s2cid = 35958237 | doi-access = free }} An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the [[neuron]]s. The occurrence of two or more unprovoked seizures defines epilepsy.{{cite web |title=Epilepsy |url=https://www.who.int/en/news-room/fact-sheets/detail/epilepsy |website=www.who.int |access-date=1 April 2023 |language=en}} The occurrence of just one seizure may warrant the definition (set out by the [[International League Against Epilepsy]]) in a more clinical usage where recurrence may be able to be prejudged. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly such as broken bones or through causing accidents. In epilepsy, seizures tend to recur and may have no detectable underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy.{{cite journal | vauthors = Fisher RS, 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 = 470–472 | date = April 2005 | pmid = 15816939 | doi = 10.1111/j.0013-9580.2005.66104.x | s2cid = 21130724 | doi-access = free }} People with epilepsy may be treated differently in various areas of the world and experience varying degrees of [[social stigma]] due to the alarming nature of their symptoms. [28] => [29] => The underlying mechanism of an epileptic seizure is excessive and abnormal [[neuronal]] activity in the [[cerebral cortex|cortex of the brain]] which can be observed in the [[electroencephalogram]] (EEG) of an individual. The reason this occurs in most cases of epilepsy is unknown ([[Cryptogenic disease|cryptogenic]]); some cases occur as the result of [[Brain damage|brain injury]], stroke, [[brain tumor]]s, infections of the brain, or [[birth defects]] through a process known as [[epileptogenesis]]. Known [[genetic mutations]] are directly linked to a small proportion of cases.{{cite journal | vauthors = Pandolfo M | title = Genetics of epilepsy | journal = Seminars in Neurology | volume = 31 | issue = 5 | pages = 506–518 | date = November 2011 | pmid = 22266888 | doi = 10.1055/s-0031-1299789 | s2cid = 260320566 }} The diagnosis involves ruling out other conditions that might cause similar [[symptom]]s, such as [[Syncope (medicine)|fainting]], and determining if another cause of seizures is present, such as [[alcohol withdrawal]] or [[electrolyte]] problems. This may be partly done by [[neuroimaging|imaging the brain]] and performing [[blood tests]]. Epilepsy can often be confirmed with an EEG, but a normal test does not rule out the condition.{{cite book | vauthors = Longo DL |title=Harrison's principles of internal medicine |year=2012 |publisher=McGraw-Hill |isbn=978-0-07-174887-2 |page=3258 |edition=18th|chapter=369 Seizures and Epilepsy}} [30] => [31] => Epilepsy that occurs as a result of other issues may be preventable. Seizures are controllable with medication in about 69% of cases;{{cite journal | vauthors = Eadie MJ | title = Shortcomings in the current treatment of epilepsy | journal = Expert Review of Neurotherapeutics | volume = 12 | issue = 12 | pages = 1419–1427 | date = December 2012 | pmid = 23237349 | doi = 10.1586/ern.12.129 | s2cid = 207221378 }} inexpensive anti-seizure medications are often available. In those whose seizures do not respond to medication; [[Epilepsy_surgery|surgery]], [[neurostimulation]] or [[Ketogenic diet|dietary changes]] may then be considered.{{cite journal | vauthors = Bergey GK | title = Neurostimulation in the treatment of epilepsy | journal = Experimental Neurology | volume = 244 | pages = 87–95 | date = June 2013 | pmid = 23583414 | doi = 10.1016/j.expneurol.2013.04.004 | s2cid = 45244964 }}{{cite journal |vauthors=Martin-McGill KJ, Bresnahan R, Levy RG, Cooper PN |date=June 2020 |title=Ketogenic diets for drug-resistant epilepsy |journal=The Cochrane Database of Systematic Reviews |volume= 2020|issue= 6|pages= CD001903|doi=10.1002/14651858.CD001903.pub5 |pmc= 7387249|pmid=32588435}} Not all cases of epilepsy are lifelong, and many people improve to the point that treatment is no longer needed. [32] => [33] => {{as of|2020}}, about 50 million people have epilepsy. Nearly 80% of cases occur in the [[developing world]].{{cite web|title=Epilepsy Fact sheet|url=https://www.who.int/mediacentre/factsheets/fs999/en/|website=WHO|access-date=4 March 2016|date=February 2016|url-status=live|archive-url=https://web.archive.org/web/20160311001129/http://www.who.int/mediacentre/factsheets/fs999/en/|archive-date=11 March 2016}} In 2015, it resulted in 125,000 deaths, an increase from 112,000 in 1990.{{cite journal | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 | vauthors = Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, Casey DC, Charlson FJ, Chen AZ, Coates MM, Coggeshall M, Dandona L, Dicker DJ, Erskine HE, Ferrari AJ, Fitzmaurice C, Foreman K, Forouzanfar MH, Fraser MS, Fullman N, Gething PW, Goldberg EM, Graetz N, Haagsma JA, Hay SI, Huynh C, Johnson CO, Kassebaum NJ, Kinfu Y, Kulikoff XR }}{{cite journal | title = 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 | journal = Lancet | volume = 385 | issue = 9963 | pages = 117–171 | date = January 2015 | pmid = 25530442 | pmc = 4340604 | doi = 10.1016/S0140-6736(14)61682-2 | hdl = 11655/15525 | vauthors = Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou M, etal | collaboration = GBD 2013 Mortality and Causes of Death Collaborators }} Epilepsy is more common in older people.{{cite book| vauthors = Holmes TR, Browne GL |title=Handbook of epilepsy|year=2008 |publisher=Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-7397-3 |edition=4th |page=7 |url=https://books.google.com/books?id=gLOv8XZ5u48C&pg=PA7 }} In the [[developed world]], onset of new cases occurs most frequently in babies and the elderly.{{cite book|title=Wyllie's treatment of epilepsy: principles and practice.|year=2010|publisher=Wolters Kluwer/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-1-58255-937-7|edition=5th|url=https://books.google.com/books?id=mxE2FYWoY0wC&pg=PA291|url-status=live|archive-url=https://web.archive.org/web/20160624113503/https://books.google.com/books?id=mxE2FYWoY0wC&pg=PA291|archive-date=24 June 2016}} In the developing world, onset is more common at the extremes of age – in younger children and in older children and young adults due to differences in the frequency of the underlying causes.{{cite journal | vauthors = Newton CR, Garcia HH | title = Epilepsy in poor regions of the world | journal = Lancet | volume = 380 | issue = 9848 | pages = 1193–1201 | date = September 2012 | pmid = 23021288 | doi = 10.1016/S0140-6736(12)61381-6 | s2cid = 13933909 | url = http://elartu.tntu.edu.ua/handle/lib/29589 }} About 5–10% of people will have an unprovoked seizure by the age of 80.{{cite journal | vauthors = Wilden JA, Cohen-Gadol AA | title = Evaluation of first nonfebrile seizures | journal = American Family Physician | volume = 86 | issue = 4 | pages = 334–340 | date = August 2012 | pmid = 22963022 }} The chance of experiencing a second seizure within two years after the first is around 40%.{{cite journal | vauthors = Neligan A, Adan G, Nevitt SJ, Pullen A, Sander JW, Bonnett L, Marson AG | title = Prognosis of adults and children following a first unprovoked seizure | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD013847 | date = January 2023 | pmid = 36688481 | pmc = 9869434 | doi = 10.1002/14651858.CD013847.pub2 | collaboration = Cochrane Epilepsy Group }}{{Cite journal |date=16 August 2023 |title=Epilepsy: what are the chances of having a second seizure? |url=https://evidence.nihr.ac.uk/alert/epilepsy-what-are-the-chances-of-having-a-second-seizure/ |journal=NIHR Evidence |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_59456 |s2cid=260965684}} In many areas of the world, those with epilepsy either have restrictions placed on their ability to drive or are not permitted to drive until they are free of seizures for a specific length of time.{{cite journal | vauthors = L Devlin A, Odell M, L Charlton J, Koppel S | title = Epilepsy and driving: current status of research | journal = Epilepsy Research | volume = 102 | issue = 3 | pages = 135–152 | date = December 2012 | pmid = 22981339 | doi = 10.1016/j.eplepsyres.2012.08.003 | s2cid = 30673360 }} The word ''epilepsy'' is from [[Ancient Greek]] {{Lang|grc|ἐπιλαμβάνειν}}, 'to seize, possess, or afflict'.{{cite journal | vauthors = Magiorkinis E, Sidiropoulou K, Diamantis A | title = Hallmarks in the history of epilepsy: epilepsy in antiquity | journal = Epilepsy & Behavior | volume = 17 | issue = 1 | pages = 103–108 | date = January 2010 | pmid = 19963440 | doi = 10.1016/j.yebeh.2009.10.023 | s2cid = 26340115 }} [34] => {{TOC limit}} [35] => [36] => ==Signs and symptoms== [37] => [[File:Attaque; Periode Epileptoide. Planche XVII. Wellcome L0074938.jpg|thumb|upright=1.4|A still image of a generalized seizure]] [38] => Epilepsy is characterized by a long-term risk of recurrent [[epileptic seizures]].{{cite journal | vauthors = Duncan JS, Sander JW, Sisodiya SM, Walker MC | title = Adult epilepsy | journal = Lancet | volume = 367 | issue = 9516 | pages = 1087–1100 | date = April 2006 | pmid = 16581409 | doi = 10.1016/S0140-6736(06)68477-8 | url = http://www.acutemed.co.uk/docs/Epilepsy,%20Lancet%204-06.pdf | url-status = dead | access-date = 10 January 2012 | s2cid = 7361318 | archive-url = https://web.archive.org/web/20130324031646/http://www.acutemed.co.uk/docs/Epilepsy%2C%20Lancet%204-06.pdf | archive-date = 24 March 2013 }} These seizures may present in several ways depending on the parts of the brain involved and the person's age.{{cite book |title=The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care |author=National Clinical Guideline Centre |publisher=National Institute for Health and Clinical Excellence |url=http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |date=January 2012 |pages=21–28 |url-status=live |archive-url=https://web.archive.org/web/20131216151008/http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |archive-date=16 December 2013}} [39] => [40] => ===Seizures=== [41] => {{Main|Epileptic seizure}} [42] => The most common type (60%) of seizures are [[convulsive]] which involve involuntary muscle contractions. Of these, one-third begin as [[generalized seizure]]s from the start, affecting both hemispheres of the brain and impairing [[consciousness]]. Two-thirds begin as [[focal seizure]]s (which affect one hemisphere of the brain) which may progress to generalized seizures. The remaining 40% of seizures are non-convulsive. An example of this type is the [[absence seizure]], which presents as a decreased level of consciousness and usually lasts about 10 seconds.{{cite book | veditors = Hammer GD, McPhee SJ |title=Pathophysiology of disease: an introduction to clinical medicine|year=2010|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-162167-0|edition=6th|chapter=7}}{{cite journal | vauthors = Hughes JR | title = Absence seizures: a review of recent reports with new concepts | journal = Epilepsy & Behavior | volume = 15 | issue = 4 | pages = 404–412 | date = August 2009 | pmid = 19632158 | doi = 10.1016/j.yebeh.2009.06.007 | s2cid = 22023692 }} [43] => [44] => [45] => Certain experiences, known as [[Aura (symptom)|auras]] often precede focal seizures. The seizures can include sensory (visual, hearing, or smell), psychic, autonomic, and motor phenomena depending on which part of the brain is involved. Muscle jerks may start in a specific muscle group and spread to surrounding muscle groups in which case it is known as a [[Jacksonian march]].{{cite book| vauthors = Bradley WG |title=Bradley's neurology in clinical practice.|year=2012|publisher=Elsevier/Saunders|location=Philadelphia, PA|isbn=978-1-4377-0434-1|edition=6th|chapter=67}} [[Automatism (medicine)|Automatisms]] may occur, which are non-consciously generated activities and mostly simple repetitive movements like smacking the lips or more complex activities such as attempts to pick up something. [46] => [47] => [48] => There are six main types of generalized seizures: [49] => * [[Tonic–clonic seizure|tonic-clonic]], [50] => * [[Tonic seizure|tonic]], [51] => * [[clonic seizure|clonic]], [52] => * [[Myoclonus|myoclonic]], [53] => * [[Absence seizure|absence]], and [54] => * [[atonic seizure]]s.{{cite book |title=The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care |author=National Clinical Guideline Centre |publisher=National Institute for Health and Clinical Excellence |url=http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |date=January 2012 |pages=119–129 |url-status=live |archive-url=https://web.archive.org/web/20131216151008/http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |archive-date=16 December 2013}} [55] => [56] => They all involve loss of consciousness and typically happen without warning. [57] => [58] => Tonic-clonic seizures occur with a contraction of the limbs followed by their extension and arching of the back which lasts 10–30 seconds (the tonic phase). A cry may be heard due to contraction of the [[Pectoral muscles|chest muscles]], 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 10–30 minutes 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.{{cite web | url=https://www.who.int/mediacentre/factsheets/fs999/en/ | title = Epilepsy | series = Fact Sheets |date =October 2012 | access-date = 24 January 2013 | publisher = [[World Health Organization]]}} People experiencing a seizure may bite their tongue, either the tip or on the sides; in [[tonic-clonic seizure]], bites to the sides are more common.{{cite book| vauthors = Engel J |title=Epilepsy: a comprehensive textbook|year=2008|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-5777-5|page=2797|url=https://books.google.com/books?id=6Kq4Zt2KOpcC&pg=PA2797|edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20160520033255/https://books.google.com/books?id=6Kq4Zt2KOpcC&pg=PA2797|archive-date=20 May 2016}} Tongue bites are also relatively common in [[psychogenic non-epileptic seizures]]. Psychogenic non-epileptic seizures are seizure like behavior without an associated synchronised electrical discharge on EEG and are considered a dissociative disorder. [59] => [60] => Myoclonic seizures involve very brief muscle spasms in either a few areas or all over. These sometimes cause the person to fall, which can cause injury. Absence seizures can be subtle with only a slight turn of the head or eye blinking with impaired consciousness; typically, the person does not fall over and returns to normal right after it ends. Atonic seizures involve losing muscle activity for greater than one second, typically occurring on both sides of the body. Rarer seizure types can cause involuntary unnatural laughter (gelastic), crying (dyscrastic), or more complex experiences such as ''[[déjà vu]]''.{{Cite book | vauthors = Stephenson JB |url=https://www.worldcat.org/oclc/25711319 |title=Fits and faints |date=1990 |publisher=Mac Keith Press |isbn=0-632-02811-4 |location=London |oclc=25711319}} [61] => [62] => [63] => About 6% of those with epilepsy have seizures that are often triggered by specific events and are known as [[reflex seizure]]s.{{cite book|title=Behavioral aspects of epilepsy: principles and practice|year=2008|publisher=Demos|location=New York|isbn=978-1-933864-04-4|page=125|url=https://books.google.com/books?id=a6Ygv5_RKKsC&pg=PA125|edition=[Online-Ausg.].|editor=Steven C. Schachter }} Those with [[reflex epilepsy]] have seizures that are only triggered by specific stimuli.{{cite journal | vauthors = Xue LY, Ritaccio AL | title = Reflex seizures and reflex epilepsy | journal = American Journal of Electroneurodiagnostic Technology | volume = 46 | issue = 1 | pages = 39–48 | date = March 2006 | pmid = 16605171 | doi = 10.1080/1086508X.2006.11079556 | s2cid = 10098600 }} Common triggers include flashing lights and sudden noises. In certain types of epilepsy, seizures happen more often during [[sleep]],{{cite journal | vauthors = Malow BA | title = Sleep and epilepsy | journal = Neurologic Clinics | volume = 23 | issue = 4 | pages = 1127–1147 | date = November 2005 | pmid = 16243619 | doi = 10.1016/j.ncl.2005.07.002 }} and in other types they occur almost only when sleeping.{{cite journal | vauthors = Tinuper P, Provini F, Bisulli F, Vignatelli L, Plazzi G, Vetrugno R, Montagna P, Lugaresi E | title = Movement disorders in sleep: guidelines for differentiating epileptic from non-epileptic motor phenomena arising from sleep | journal = Sleep Medicine Reviews | volume = 11 | issue = 4 | pages = 255–267 | date = August 2007 | pmid = 17379548 | doi = 10.1016/j.smrv.2007.01.001 }} In 2017, the [[International League Against Epilepsy]] published new uniform guidelines for the classification of seizures as well as epilepsies along with their cause and comorbidities.{{cite journal | vauthors = Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM | title = ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology | journal = Epilepsia | volume = 58 | issue = 4 | pages = 512–521 | date = April 2017 | pmid = 28276062 | pmc = 5386840 | doi = 10.1111/epi.13709 }} [64] => [65] => ==== Seizure clusters ==== [66] => Patients with epilepsy may experience seizure clusters which may be broadly defined as an acute deterioration in seizure control.{{cite journal | vauthors = Mitchell WG | title = Status epilepticus and acute repetitive seizures in children, adolescents, and young adults: etiology, outcome, and treatment | journal = Epilepsia | volume = 37 | issue = s1 | pages = S74–S80 | date = 1996 | pmid = 8647055 | doi = 10.1111/j.1528-1157.1996.tb06025.x | s2cid = 14510863 }} The prevalence of seizure clusters is uncertain given that studies have used different definitions to define them.{{cite journal | vauthors = Jafarpour S, Hirsch LJ, Gaínza-Lein M, Kellinghaus C, Detyniecki K | title = Seizure cluster: Definition, prevalence, consequences, and management | journal = Seizure | volume = 68 | pages = 9–15 | date = May 2019 | pmid = 29871784 | doi = 10.1016/j.seizure.2018.05.013 | s2cid = 46942965 | doi-access = free }} However, estimates suggest that the prevalence may range from 5% to 50% of epilepsy patients.{{cite journal | vauthors = Faught E | title = Economic aspects of treating seizure clusters | journal = Epilepsia | volume = 63 | issue = Suppl 1 | pages = S45–S54 | date = September 2022 | pmid = 35999172 | doi = 10.1111/epi.17340 | s2cid = 251744416 }} Refractory epilepsy patients who have a high seizure frequency are at the greatest risk for having seizure clusters.{{cite journal | vauthors = Haut SR, Shinnar S, Moshé SL | title = Seizure clustering: risks and outcomes | journal = Epilepsia | volume = 46 | issue = 1 | pages = 146–149 | date = January 2005 | pmid = 15660781 | doi = 10.1111/j.0013-9580.2005.29004.x | s2cid = 37102974 | doi-access = free }}{{cite journal | vauthors = Chen B, Choi H, Hirsch LJ, Katz A, Legge A, Wong RA, Jiang A, Kato K, Buchsbaum R, Detyniecki K | title = Prevalence and risk factors of seizure clusters in adult patients with epilepsy | journal = Epilepsy Research | volume = 133 | pages = 98–102 | date = July 2017 | pmid = 28475999 | doi = 10.1016/j.eplepsyres.2017.04.016 | s2cid = 4735843 }}{{cite journal | vauthors = Komaragiri A, Detyniecki K, Hirsch LJ | title = Seizure clusters: A common, understudied and undertreated phenomenon in refractory epilepsy | journal = Epilepsy & Behavior | volume = 59 | pages = 83–86 | date = June 2016 | pmid = 27116535 | doi = 10.1016/j.yebeh.2016.02.030 | s2cid = 3880221 }} Seizure clusters are associated with increased healthcare use, worse quality of life, impaired psychosocial functioning, and possibly increased mortality.{{cite journal | vauthors = Chung S, Szaflarski JP, Choi EJ, Wilson JC, Kharawala S, Kaur G, Hirsch LJ | title = A systematic review of seizure clusters: Prevalence, risk factors, burden of disease and treatment patterns | journal = Epilepsy Research | volume = 177 | pages = 106748 | date = November 2021 | pmid = 34521043 | doi = 10.1016/j.eplepsyres.2021.106748 | s2cid = 237380380 }} Benzodiazepines are used as an acute treatment for seizure clusters.{{cite journal | vauthors = Gidal B, Detyniecki K | title = Rescue therapies for seizure clusters: Pharmacology and target of treatments | journal = Epilepsia | volume = 63 | issue = Suppl 1 | pages = S34–S44 | date = September 2022 | pmid = 35999174 | pmc = 9543841 | doi = 10.1111/epi.17341 | s2cid = 251744444 }} [67] => [68] => ===Post-ictal=== [69] => After the active portion of a seizure (the [[ictal]] state) there is typically a period of recovery during which there is confusion, referred to as the [[postictal]] period, before a normal [[level of consciousness]] returns. It usually lasts 3 to 15 minutes{{cite book| vauthors = Holmes TR |title=Handbook of epilepsy|year=2008|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-7397-3|page=34|url=https://books.google.com/books?id=gLOv8XZ5u48C&pg=PA34 |edition=4th }} but may last for hours. Other common symptoms include feeling tired, [[ictal headache|headache]], difficulty speaking, and abnormal behavior.{{cite book| vauthors = Panayiotopoulos CP |title=A clinical guide to epileptic syndromes and their treatment based on the ILAE classifications and practice parameter guidelines |year=2010 |publisher=Springer |location=London |isbn=978-1-84628-644-5 |page=445 |url=https://books.google.com/books?id=yJQQzPTcbYIC&pg=PA445 |edition=Rev. 2nd }} [[Psychosis]] after a seizure is relatively common, occurring in 6–10% of people.{{cite book|title=Advanced therapy in epilepsy|year=2009|publisher=People's Medical Pub. House|location=Shelton, Conn.|isbn=978-1-60795-004-2|page=443|url=https://books.google.com/books?id=4W7UI-FPZmoC&pg=PA443| veditors = Wheless JW }} Often people do not remember what happened during this time. Localized weakness, known as [[Todd's paralysis]], may also occur after a focal seizure. It would typically last for seconds to minutes but may rarely last for a day or two.{{cite book| vauthors = Larner AJ |title=A dictionary of neurological signs|publisher=Springer|location=New York|isbn=978-1-4419-7095-4|page=348|url=https://books.google.com/books?id=mY-6eweiQm8C&pg=PA348|edition=3rd|year=2010 }} [70] => [71] => ===Psychosocial=== [72] => Epilepsy can have adverse effects on social and psychological well-being. These effects may include social isolation, stigmatization, or disability. They may result in lower educational achievement and worse employment outcomes. Learning disabilities are common in those with the condition, and especially among [[epilepsy in children|children with epilepsy]]. The stigma of epilepsy can also affect the families of those with the disorder. [73] => [74] => [75] => Certain disorders occur more often in people with epilepsy, depending partly on the epilepsy syndrome present. These include [[major depressive disorder|depression]], [[anxiety disorder|anxiety]], [[obsessive–compulsive disorder]] (OCD),{{cite journal | vauthors = Kaplan PW | title = Obsessive-compulsive disorder in chronic epilepsy | journal = Epilepsy & Behavior | volume = 22 | issue = 3 | pages = 428–432 | date = November 2011 | pmid = 21889913 | doi = 10.1016/j.yebeh.2011.07.029 | s2cid = 42945523 | url = https://zenodo.org/record/896942 }} and [[migraine]].{{cite book| vauthors = Stefan H |title=Epilepsy Part I: Basic Principles and Diagnosis E-Book: Handbook of Clinical Neurology|year=2012|publisher=Newnes|isbn=978-0-444-53505-4|page=471|url=https://books.google.com/books?id=K-1UqhH2BtoC&pg=PA471|edition=Volume 107 of Handbook of Clinical Neurology}} [[Attention deficit hyperactivity disorder]] (ADHD) affects three to five times more children with epilepsy than children without the condition.{{cite journal | vauthors = Plioplys S, Dunn DW, Caplan R | title = 10-year research update review: psychiatric problems in children with epilepsy | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 46 | issue = 11 | pages = 1389–1402 | date = November 2007 | pmid = 18049289 | doi = 10.1097/chi.0b013e31815597fc }} ADHD and epilepsy have significant consequences on a child's behavioral, learning, and social development.{{cite journal | vauthors = Reilly CJ | title = Attention deficit hyperactivity disorder (ADHD) in childhood epilepsy | journal = Research in Developmental Disabilities | volume = 32 | issue = 3 | pages = 883–893 | date = May–June 2011 | pmid = 21310586 | doi = 10.1016/j.ridd.2011.01.019 }} Epilepsy is also more common in children with [[autism spectrum|autism]].{{cite journal | vauthors = Levisohn PM | title = The autism-epilepsy connection | journal = Epilepsia | volume = 48 | issue = Suppl 9 | pages = 33–35 | year = 2007 | pmid = 18047599 | doi = 10.1111/j.1528-1167.2007.01399.x | doi-access = free }} [76] => [77] => Approximately, one-in-three people with epilepsy have a lifetime history of a psychiatric disorder.{{cite journal | vauthors = Lin JJ, Mula M, Hermann BP | title = Uncovering the neurobehavioural comorbidities of epilepsy over the lifespan | journal = Lancet | volume = 380 | issue = 9848 | pages = 1180–1192 | date = September 2012 | pmid = 23021287 | pmc = 3838617 | doi = 10.1016/s0140-6736(12)61455-x }} There are believed to be multiple causes for this including pathophysiological changes related to the epilepsy itself as well as adverse experiences related to living with epilepsy (e.g., stigma, discrimination).{{cite journal | vauthors = Kanner AM, Schachter SC, Barry JJ, Hesdorffer DC, Mula M, Trimble M, Hermann B, Ettinger AE, Dunn D, Caplan R, Ryvlin P, Gilliam F, LaFrance WC | title = Depression and epilepsy: epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence | journal = Epilepsy & Behavior | volume = 24 | issue = 2 | pages = 156–168 | date = June 2012 | pmid = 22632406 | doi = 10.1016/j.yebeh.2012.01.007 | s2cid = 24369127 }} In addition, it is thought that the relationship between epilepsy and psychiatric disorders is not unilateral but rather bidirectional. For example, patients with depression have an increased risk for developing new-onset epilepsy.{{cite journal | vauthors = Adelöw C, Andersson T, Ahlbom A, Tomson T | title = Hospitalization for psychiatric disorders before and after onset of unprovoked seizures/epilepsy | journal = Neurology | volume = 78 | issue = 6 | pages = 396–401 | date = February 2012 | pmid = 22282649 | doi = 10.1212/wnl.0b013e318245f461 | s2cid = 207120740 }} [78] => [79] => The presence of comorbid depression or anxiety in patients with epilepsy is associated with a poorer quality of life, increased mortality, increased healthcare use and a worse response to treatment (including surgical).{{cite journal | vauthors = Taylor RS, Sander JW, Taylor RJ, Baker GA | title = Predictors of health-related quality of life and costs in adults with epilepsy: a systematic review | journal = Epilepsia | volume = 52 | issue = 12 | pages = 2168–2180 | date = December 2011 | pmid = 21883177 | doi = 10.1111/j.1528-1167.2011.03213.x | s2cid = 30039598 | doi-access = free }}{{cite journal | vauthors = Lacey CJ, Salzberg MR, Roberts H, Trauer T, D'Souza WJ | title = Psychiatric comorbidity and impact on health service utilization in a community sample of patients with epilepsy | journal = Epilepsia | volume = 50 | issue = 8 | pages = 1991–1994 | date = August 2009 | pmid = 19490049 | doi = 10.1111/j.1528-1167.2009.02165.x | s2cid = 27842830 | doi-access = free }}{{cite journal | vauthors = Nogueira MH, Yasuda CL, Coan AC, Kanner AM, Cendes F | title = Concurrent mood and anxiety disorders are associated with pharmacoresistant seizures in patients with MTLE | journal = Epilepsia | volume = 58 | issue = 7 | pages = 1268–1276 | date = July 2017 | pmid = 28555776 | doi = 10.1111/epi.13781 | s2cid = 2519902 | doi-access = free }}{{cite journal | vauthors = Kanner AM, Byrne R, Chicharro A, Wuu J, Frey M | title = A lifetime psychiatric history predicts a worse seizure outcome following temporal lobectomy | journal = Neurology | volume = 72 | issue = 9 | pages = 793–799 | date = March 2009 | pmid = 19255406 | doi = 10.1212/01.wnl.0000343850.85763.9c | s2cid = 10497821 }} Anxiety disorders and depression may explain more variability in quality of life than seizure type or frequency.{{cite journal | vauthors = Boylan LS, Flint LA, Labovitz DL, Jackson SC, Starner K, Devinsky O | title = Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy | journal = Neurology | volume = 62 | issue = 2 | pages = 258–261 | date = January 2004 | pmid = 14745064 | doi = 10.1212/01.wnl.0000103282.62353.85 | s2cid = 24173332 }} There is evidence that both depression and anxiety disorders are underdiagnosed and undertreated in patients with epilepsy.{{cite journal | vauthors = Munger Clary HM, Croxton RD, Allan J, Lovato J, Brenes G, Snively BM, Wan M, Kimball J, Wong MH, O'Donovan CA, Conner K, Jones V, Duncan P | title = Who is willing to participate in research? A screening model for an anxiety and depression trial in the epilepsy clinic | journal = Epilepsy & Behavior | volume = 104 | issue = Pt A | pages = 106907 | date = March 2020 | pmid = 32000099 | pmc = 7282472 | doi = 10.1016/j.yebeh.2020.106907 }} [80] => [81] => == Causes == [82] => {{See also|Causes of seizures}} [83] => Epilepsy can have both genetic and acquired causes, with the interaction of these factors in many cases.{{cite journal | vauthors = Balestrini S, Arzimanoglou A, Blümcke I, Scheffer IE, Wiebe S, Zelano J, Walker MC | title = The aetiologies of epilepsy | journal = Epileptic Disorders | volume = 23 | issue = 1 | pages = 1–16 | date = February 2021 | pmid = 33720020 | doi = 10.1684/epd.2021.1255 | s2cid = 232231196 | doi-access = free }} Established acquired causes include serious brain trauma, stroke, tumours, and brain problems resulting from a previous infection.{{cite journal | vauthors = Berkovic SF, Mulley JC, Scheffer IE, Petrou S | title = Human epilepsies: interaction of genetic and acquired factors | journal = Trends in Neurosciences | volume = 29 | issue = 7 | pages = 391–397 | date = July 2006 | pmid = 16769131 | doi = 10.1016/j.tins.2006.05.009 | s2cid = 205403084 }} In about 60% of cases, the cause is unknown. Epilepsies caused by [[genetic disorder|genetic]], [[congenital]], or [[Developmental disorder|developmental]] conditions are more common among younger people, while [[brain tumor]]s and [[strokes]] are more likely in older people. [84] => [85] => Seizures may also occur as a consequence of other health problems; if they occur right around a specific cause, such as a stroke, head injury, toxic ingestion, or metabolic problem, they are known as [[acute symptomatic seizure]]s and are in the broader classification of [[seizure-related disorders]] rather than epilepsy itself.{{cite journal | vauthors = Thurman 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 | title = Standards for epidemiologic studies and surveillance of epilepsy | journal = Epilepsia | volume = 52 | issue = Suppl 7 | pages = 2–26 | date = September 2011 | pmid = 21899536 | doi = 10.1111/j.1528-1167.2011.03121.x | s2cid = 8505004 | doi-access = free }} [86] => [87] => ===Genetics=== [88] => Genetics is believed to be involved in the majority of cases, either directly or indirectly.{{cite journal | vauthors = Steinlein OK | title = Genetics and epilepsy | journal = Dialogues in Clinical Neuroscience | volume = 10 | issue = 1 | pages = 29–38 | date = 2008-03-31 | pmid = 18472482 | pmc = 3181863 | doi = 10.31887/DCNS.2008.10.1/oksteinlein }} Some epilepsies are due to a [[single-gene disorder|single gene defect]] (1–2%); most are due to the interaction of multiple genes and environmental factors. Each of the single gene defects is rare, with more than 200 in all described.{{cite book|title=Genomics and clinical medicine|year=2008|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-972005-7|page=279|url=https://books.google.com/books?id=BbeWA-gbiiwC&pg=PA279|editor=Dhavendra Kumar|url-status=live|archive-url=https://web.archive.org/web/20160521201336/https://books.google.com/books?id=BbeWA-gbiiwC&pg=PA279|archive-date=21 May 2016}} Most genes involved affect [[ion channel]]s, either directly or indirectly. These include genes for ion channels, [[enzyme]]s, [[GABA receptor|GABA]], and [[G protein-coupled receptor]]s.{{cite book| vauthors = Simon DA, Greenberg MJ, Aminoff RP |title=Clinical neurology|year=2012|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-175905-2|edition=8th|chapter=12}} [89] => [90] => In [[twin|identical twins]], if one is affected, there is a 50–60% chance that the other will also be affected. In non-identical twins, the risk is 15%. These risks are greater in those with generalized rather than focal seizures. If both twins are affected, most of the time they have the same epileptic syndrome (70–90%). Other close relatives of a person with epilepsy have a risk five times that of the general population.{{cite journal | vauthors = Bhalla D, Godet B, Druet-Cabanac M, Preux PM | title = Etiologies of epilepsy: a comprehensive review | journal = Expert Review of Neurotherapeutics | volume = 11 | issue = 6 | pages = 861–876 | date = June 2011 | pmid = 21651333 | doi = 10.1586/ern.11.51 | s2cid = 21190601 }} Between 1 and 10% of those with [[Down syndrome]] and 90% of those with [[Angelman syndrome]] have epilepsy. [91] => [92] => ==== Phakomatoses ==== [93] => [[Phakomatosis|Phakomatoses]], also known as neurocutaneous disorders, are a group of multisystemic diseases that most prominently affect the skin and central nervous system. They are caused by defective development of the embryonic ectodermal tissue that is most often due to a single genetic mutation. The brain, as well as other neural tissue and the skin, are all derived from the ectoderm and thus defective development may result in epilepsy as well as other manifestations such as autism and intellectual disability. Some types of phakomatoses such as tuberous sclerosis complex and Sturge-Weber syndrome have a higher prevalence of epilepsy relative to others such as [[Neurofibromatosis type I|neurofibromatosis type 1]].{{cite journal | vauthors = Stafstrom CE, Staedtke V, Comi AM | title = Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge-Weber Syndrome | journal = Frontiers in Neurology | volume = 8 | pages = 87 | date = 2017 | pmid = 28367137 | pmc = 5355446 | doi = 10.3389/fneur.2017.00087 | doi-access = free }} [94] => [95] => [[Tuberous sclerosis|Tuberous sclerosis complex]] is an autosomal dominant disorder that is caused by mutations in either the [[TSC1]] or [[TSC2]] gene and it affects approximately 1 in 6,000–10,000 live births.{{cite journal | vauthors = O'Callaghan FJ, Shiell AW, Osborne JP, Martyn CN | title = Prevalence of tuberous sclerosis estimated by capture-recapture analysis | journal = Lancet | volume = 351 | issue = 9114 | pages = 1490 | date = May 1998 | pmid = 9605811 | doi = 10.1016/S0140-6736(05)78872-3 | s2cid = 9262685 }}{{cite journal | vauthors = Northrup H, Aronow ME, Bebin EM, Bissler J, Darling TN, de Vries PJ, Frost MD, Fuchs Z, Gosnell ES, Gupta N, Jansen AC, Jóźwiak S, Kingswood JC, Knilans TK, McCormack FX, Pounders A, Roberds SL, Rodriguez-Buritica DF, Roth J, Sampson JR, Sparagana S, Thiele EA, Weiner HL, Wheless JW, Towbin AJ, Krueger DA | title = Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations | journal = Pediatric Neurology | volume = 123 | pages = 50–66 | date = October 2021 | pmid = 34399110 | doi = 10.1016/j.pediatrneurol.2021.07.011 | doi-access = free }} These mutations result in the upregulation of the [[MTOR|mechanistic target of rapamycin (mTOR)]] pathway which leads to the growth of tumors in many organs including the brain, skin, heart, eyes and kidneys. In addition, abnormal mTOR activity is believed to alter neural excitability.{{cite journal | vauthors = Curatolo P | title = Mechanistic target of rapamycin (mTOR) in tuberous sclerosis complex-associated epilepsy | journal = Pediatric Neurology | volume = 52 | issue = 3 | pages = 281–289 | date = March 2015 | pmid = 25591831 | doi = 10.1016/j.pediatrneurol.2014.10.028 }} The prevalence of epilepsy is estimated to be 80-90%. The majority of cases of epilepsy present within the first 3 years of life and are medically refractory.{{cite journal | vauthors = Moavero R, Cerminara C, Curatolo P | title = Epilepsy secondary to tuberous sclerosis: lessons learned and current challenges | journal = Child's Nervous System | volume = 26 | issue = 11 | pages = 1495–1504 | date = November 2010 | pmid = 20358377 | doi = 10.1007/s00381-010-1128-8 | s2cid = 35481466 }} Relatively recent developments for the treatment of epilepsy in TSC patients include [[mTOR inhibitors]], cannabidiol and vigabatrin. Epilepsy surgery is often pursued. [96] => [97] => [[Sturge–Weber syndrome|Sturge-Weber syndrome]] is caused by an activating somatic mutation in the [[GNAQ]] gene and it affects approximately 1 in 20,000–50,000 live births.{{cite journal | vauthors = Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J | title = Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ | journal = The New England Journal of Medicine | volume = 368 | issue = 21 | pages = 1971–1979 | date = May 2013 | pmid = 23656586 | pmc = 3749068 | doi = 10.1056/NEJMoa1213507 }} The mutation results in vascular malformations affecting the brain, skin and eyes. The typical presentation includes a facial port-wine birthmark, ocular angiomas and cerebral vascular malformations which are most often unilateral but are bilateral in 15% of cases.{{cite journal | vauthors = Sudarsanam A, Ardern-Holmes SL | title = Sturge-Weber syndrome: from the past to the present | journal = European Journal of Paediatric Neurology | volume = 18 | issue = 3 | pages = 257–266 | date = May 2014 | pmid = 24275166 | doi = 10.1016/j.ejpn.2013.10.003 }} The prevalence of epilepsy is 75-100% and is higher in those with bilateral involvement. Seizures typically occur within the first two years of life and are refractory in nearly half of cases.{{cite journal | vauthors = Sugano H, Iimura Y, Igarashi A, Nakazawa M, Suzuki H, Mitsuhashi T, Nakajima M, Higo T, Ueda T, Nakanishi H, Niijima S, Karagiozov K, Arai H | title = Extent of Leptomeningeal Capillary Malformation is Associated With Severity of Epilepsy in Sturge-Weber Syndrome | journal = Pediatric Neurology | volume = 117 | pages = 64–71 | date = April 2021 | pmid = 33677229 | doi = 10.1016/j.pediatrneurol.2020.12.012 | s2cid = 232140769 | doi-access = free }} However, high rates of seizure freedom with surgery have been reported in as many as 83%.{{cite journal | vauthors = Wang S, Pan J, Zhao M, Wang X, Zhang C, Li T, Wang M, Wang J, Zhou J, Liu C, Sun Y, Zhu M, Qi X, Luan G, Guan Y | title = Characteristics, surgical outcomes, and influential factors of epilepsy in Sturge-Weber syndrome | journal = Brain | volume = 145 | issue = 10 | pages = 3431–3443 | date = October 2022 | pmid = 34932802 | doi = 10.1093/brain/awab470 | doi-access = free }} [98] => [99] => [[Neurofibromatosis type I|Neurofibromatosis type 1]] is the most common phakomatoses and occurs in approximately 1 in 3,000 live births.{{cite journal | vauthors = Lammert M, Friedman JM, Kluwe L, Mautner VF | title = Prevalence of neurofibromatosis 1 in German children at elementary school enrollment | journal = Archives of Dermatology | volume = 141 | issue = 1 | pages = 71–74 | date = January 2005 | pmid = 15655144 | doi = 10.1001/archderm.141.1.71 | doi-access = free }} It is caused by autosomal dominant mutations in the [[Neurofibromin 1]] gene. Clinical manifestations are variable but may include hyperpigmented skin marks, hamartomas of the iris called [[Lisch nodule]]s, [[neurofibroma]]s, optic pathway gliomas and cognitive impairment. The prevalence of epilepsy is estimated to be 4–7%.{{cite journal | vauthors = Ostendorf AP, Gutmann DH, Weisenberg JL | title = Epilepsy in individuals with neurofibromatosis type 1 | journal = Epilepsia | volume = 54 | issue = 10 | pages = 1810–1814 | date = October 2013 | pmid = 24032542 | doi = 10.1111/epi.12348 | s2cid = 1603461 }} Seizures are typically easier to control with anti-seizure medications relative to other phakomatoses but in some refractory cases surgery may need to be pursued.{{cite journal | vauthors = Barba C, Jacques T, Kahane P, Polster T, Isnard J, Leijten FS, Ozkara C, Tassi L, Giordano F, Castagna M, John A, Oz B, Salon C, Streichenberger N, Cross JH, Guerrini R | title = Epilepsy surgery in Neurofibromatosis Type 1 | journal = Epilepsy Research | volume = 105 | issue = 3 | pages = 384–395 | date = August 2013 | pmid = 23597854 | doi = 10.1016/j.eplepsyres.2013.02.021 | s2cid = 25785144 }} [100] => [101] => ===Acquired=== [102] => Epilepsy may occur as a result of several other conditions, including tumors, strokes, head trauma, previous [[infections of the central nervous system]], genetic abnormalities, and as a result of brain damage around the time of birth. Of those with brain tumors, almost 30% have epilepsy, making them the cause of about 4% of cases. The risk is greatest for tumors in the [[temporal lobe]] and those that grow slowly. Other mass lesions such as [[Central nervous system cavernous hemangioma|cerebral cavernous malformations]] and [[Cerebral arteriovenous malformation|arteriovenous malformations]] have risks as high as 40{{endash}}60%. Of those who have had a stroke, 6–10% develop epilepsy.{{cite journal | vauthors = Galovic M, Döhler N, Erdélyi-Canavese B, Felbecker A, Siebel P, Conrad J, Evers S, Winklehner M, von Oertzen TJ, Haring HP, Serafini A, Gregoraci G, Valente M, Janes F, Gigli GL, Keezer MR, Duncan JS, Sander JW, Koepp MJ, Tettenborn B | title = Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study | journal = The Lancet. Neurology | volume = 17 | issue = 2 | pages = 143–152 | date = February 2018 | pmid = 29413315 | doi = 10.1016/S1474-4422(17)30404-0 | s2cid = 21665713 | url = https://discovery.ucl.ac.uk/id/eprint/10043594/ }}{{cite journal | vauthors = Ren Z, Wen Q, Yan X, Wang Y, Zhang Y | title = Post-stroke epilepsy and risk of all-cause mortality: A systematic review and meta-analysis of cohort studies | journal = Clinical Neurology and Neurosurgery | volume = 220 | pages = 107362 | date = September 2022 | pmid = 35839716 | doi = 10.1016/j.clineuro.2022.107362 | s2cid = 250317784 }} Risk factors for post-stroke epilepsy include stroke severity, cortical involvement, hemorrhage and early seizures.{{cite journal | vauthors = Zelano J, Holtkamp M, Agarwal N, Lattanzi S, Trinka E, Brigo F | title = How to diagnose and treat post-stroke seizures and epilepsy | journal = Epileptic Disorders | volume = 22 | issue = 3 | pages = 252–263 | date = June 2020 | pmid = 32597766 | doi = 10.1684/epd.2020.1159 | s2cid = 220254988 | doi-access = free }}{{cite journal | vauthors = Zöllner JP, Schmitt FC, Rosenow F, Kohlhase K, Seiler A, Strzelczyk A, Stefan H | title = Seizures and epilepsy in patients with ischaemic stroke | journal = Neurological Research and Practice | volume = 3 | issue = 1 | pages = 63 | date = December 2021 | pmid = 34865660 | pmc = 8647498 | doi = 10.1186/s42466-021-00161-w | doi-access = free }} Between 6 and 20% of epilepsy is believed to be due to head trauma. [[Mild brain injury]] increases the risk about two-fold while [[severe brain injury]] increases the risk seven-fold. In those who have experienced a high-powered gunshot wound to the head, the risk is about 50%. [103] => [104] => Some evidence links epilepsy and [[celiac disease]] and [[non-celiac gluten sensitivity]], while other evidence does not. There appears to be a specific syndrome that includes coeliac disease, epilepsy, and calcifications in the brain.{{cite journal | vauthors = Grossman G | title = Neurological complications of coeliac disease: what is the evidence? | journal = Practical Neurology | volume = 8 | issue = 2 | pages = 77–89 | date = April 2008 | pmid = 18344378 | doi = 10.1136/jnnp.2007.139717 | s2cid = 28327166 }} A 2012 review estimates that between 1% and 6% of people with epilepsy have coeliac disease while 1% of the general population has the condition.{{cite journal | vauthors = Jackson JR, Eaton WW, Cascella NG, Fasano A, Kelly DL | title = Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity | journal = The Psychiatric Quarterly | volume = 83 | issue = 1 | pages = 91–102 | date = March 2012 | pmid = 21877216 | pmc = 3641836 | doi = 10.1007/s11126-011-9186-y }} [105] => [106] => The risk of epilepsy following [[meningitis]] is less than 10%; it more commonly causes seizures during the infection itself. In [[herpes simplex encephalitis]] the risk of a seizure is around 50% with a high risk of epilepsy following (up to 25%).{{cite book|title=The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children|year=2011|publisher=Cambridge University Press|isbn=978-1-139-49578-3 |page=467 |url=https://books.google.com/books?id=BUs-AYMBbC0C&pg=PA467| vauthors = Shorvon SD }}{{cite journal | vauthors = Sellner J, Trinka E | title = Seizures and epilepsy in herpes simplex virus encephalitis: current concepts and future directions of pathogenesis and management | journal = Journal of Neurology | volume = 259 | issue = 10 | pages = 2019–2030 | date = October 2012 | pmid = 22527234 | doi = 10.1007/s00415-012-6494-6 | s2cid = 24701310 }} A form of an infection with the [[Taenia solium|pork tapeworm]] ([[cysticercosis]]), in the brain, is known as [[neurocysticercosis]], and is the cause of up to half of epilepsy cases in areas of the world where the parasite is common. Epilepsy may also occur after other brain infections such as [[malaria|cerebral malaria]], [[toxoplasmosis]], and [[toxocariasis]]. Chronic alcohol use increases the risk of epilepsy: those who drink six [[units of alcohol]] per day have a 2.5-fold increase in risk. Other risks include [[Alzheimer's disease]], [[multiple sclerosis]], and [[autoimmune encephalitis]]. Getting vaccinated does not increase the risk of epilepsy. [[Malnutrition]] is a risk factor seen mostly in the developing world, although it is unclear however if it is a direct cause or an association. People with [[cerebral palsy]] have an increased risk of epilepsy, with half of people with [[spastic quadriplegia]] and [[spastic hemiplegia]] having the disease.{{cite journal | vauthors = Hadjipanayis A, Hadjichristodoulou C, Youroukos S | title = Epilepsy in patients with cerebral palsy | journal = Developmental Medicine and Child Neurology | volume = 39 | issue = 10 | pages = 659–663 | date = October 1997 | pmid = 9352726 | doi = 10.1111/j.1469-8749.1997.tb07359.x | doi-access = free }} [107] => [108] => == Mechanism == [109] => Normally brain electrical activity is non-synchronous, as large numbers of neurons do not normally fire at the same time, but rather fire in order as signals travel throughout the brain. [[Neuron]] activity is regulated by various factors both within the cell and the cellular environment. Factors within the neuron include the type, number and distribution of ion channels, changes to [[Receptor (biochemistry)|receptors]] and changes of [[gene expression]]. Factors around the neuron include [[ion]] concentrations, [[synaptic plasticity]] and regulation of [[neurotransmitter|transmitter]] breakdown by [[Neuroglia|glial cells]].{{cite book | title = An Introduction to Epilepsy | publisher = American Epilepsy Society | year = 2006 | vauthors = Bromfield EB | chapter = Basic Mechanisms Underlying Seizures and Epilepsy | url = https://www.ncbi.nlm.nih.gov/books/NBK2510/ }}{{cite journal | vauthors = Blumenfeld H | title = Cellular and network mechanisms of spike-wave seizures | journal = Epilepsia | volume = 46 | issue = Suppl.9 | pages = 21–33 | year = 2005 | pmid = 16302873 | doi = 10.1111/j.1528-1167.2005.00311.x | doi-access = free }} [110] => [111] => ===Epilepsy=== [112] => The exact mechanism of epilepsy is unknown,{{cite book| vauthors = Noebels JL, Avoli M |title = Jasper's Basic Mechanisms of the Epilepsies|url = https://books.google.com/books?id=T2_LVTB7ftgC&pg=466|publisher = Oxford University Press|date = 29 June 2012|isbn = 978-0-19-974654-5|pages = 466, 470|access-date = 16 October 2014}} but a little is known about its cellular and network mechanisms. However, it is unknown under which circumstances the brain shifts into the activity of a seizure with its excessive [[neural oscillation|synchronization]].{{cite journal | vauthors = Le Van Quyen M, Navarro V, Martinerie J, Baulac M, Varela FJ | title = Toward a neurodynamical understanding of ictogenesis | journal = Epilepsia | volume = 44 | issue = Suppl.12 | pages = 30–43 | year = 2003 | pmid = 14641559 | doi = 10.1111/j.0013-9580.2003.12007.x | doi-access = free }}{{cite journal | vauthors = Lopes da Silva F, Blanes W, Kalitzin SN, Parra J, Suffczynski P, Velis DN | title = Epilepsies as dynamical diseases of brain systems: basic models of the transition between normal and epileptic activity | journal = Epilepsia | volume = 44 | issue = Suppl.12 | pages = 72–83 | year = 2003 | pmid = 14641563 | doi = 10.1111/j.0013-9580.2003.12005.x | s2cid = 10071296 }} Changes in [[microRNA]]s (miRNAs) levels seems to play a leading role. MicroRNAs are a family of small [[non-coding RNA]]s that control the expression levels of multiple proteins by decreasing [[Messenger RNA|mRNA]] stability and translation, and could therefore be key regulatory mechanisms and therapeutic targets in epilepsy.{{cite journal | vauthors = Henshall DC, Hamer HM, Pasterkamp RJ, Goldstein DB, Kjems J, Prehn JH, Schorge S, Lamottke K, Rosenow F | title = MicroRNAs in epilepsy: pathophysiology and clinical utility | journal = The Lancet. Neurology | volume = 15 | issue = 13 | pages = 1368–1376 | date = December 2016 | pmid = 27839653 | doi = 10.1016/S1474-4422(16)30246-0 | s2cid = 39170104 | url = https://discovery.ucl.ac.uk/id/eprint/1530917/ }}{{cite journal | vauthors = Henshall DC | title = MicroRNA and epilepsy: profiling, functions and potential clinical applications | journal = Current Opinion in Neurology | volume = 27 | issue = 2 | pages = 199–205 | date = April 2014 | pmid = 24553459 | pmc = 4127484 | doi = 10.1097/WCO.0000000000000079 }} [113] => [114] => In epilepsy, the resistance of excitatory neurons to fire during this period is decreased. This may occur due to changes in ion channels or inhibitory neurons not functioning properly. This then results in a specific area from which seizures may develop, known as a "seizure focus". Another mechanism of epilepsy may be the up-regulation of excitatory circuits or down-regulation of inhibitory circuits following an injury to the brain. These secondary epilepsies occur through processes known as [[epileptogenesis]].{{cite journal | vauthors = Goldberg EM, Coulter DA | title = Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction | journal = Nature Reviews. Neuroscience | volume = 14 | issue = 5 | pages = 337–349 | date = May 2013 | pmid = 23595016 | pmc = 3982383 | doi = 10.1038/nrn3482 }} Failure of the [[blood–brain barrier]] may also be a causal mechanism as it would allow substances in the blood to enter the brain.{{cite journal | vauthors = Oby E, Janigro D | title = The blood-brain barrier and epilepsy | journal = Epilepsia | volume = 47 | issue = 11 | pages = 1761–1774 | date = November 2006 | pmid = 17116015 | doi = 10.1111/j.1528-1167.2006.00817.x | s2cid = 15074513 | doi-access = free }} [115] => [116] => ===Seizures=== [117] => There is evidence that epileptic seizures are usually not a random event. Seizures are often brought on by factors (also known as triggers) such as stress, [[Alcohol use disorder|excessive alcohol use]], flickering light, or a lack of sleep, among others. The term [[seizure threshold]] is used to indicate the amount of [[Stimulus (physiology)|stimulus]] necessary to bring about a seizure; this threshold is lowered in epilepsy. [118] => [119] => In epileptic seizures a group of neurons begin firing in an abnormal, excessive, and synchronized manner. This results in a wave of depolarization known as a [[paroxysmal depolarizing shift]].{{cite book| vauthors = Somjen GG |title=Ions in the Brain Normal Function, Seizures, and Stroke.|year=2004|publisher=Oxford University Press|location=New York|isbn=978-0-19-803459-9|page=167|url=https://books.google.com/books?id=WjSoQVt-taYC&pg=PA167 }} Normally, after an [[excitatory neuron]] fires it becomes more resistant to firing for a period of time. This is due in part to the effect of inhibitory neurons, electrical changes within the excitatory neuron, and the negative effects of [[adenosine]]. [120] => [121] => Focal seizures begin in one area of the brain while generalized seizures begin in both [[cerebral hemisphere|hemispheres]]. Some types of seizures may change brain structure, while others appear to have little effect.{{cite book|title=Epilepsy: a comprehensive textbook|year=2008|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-5777-5|page=483|url=https://books.google.com/books?id=TwlXrOBkAS8C&pg=PA483|edition=2nd| veditors = Engel J, Pedley TA }} [[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. [122] => [123] => The seizures can be described on different scales, from the cellular level{{cite journal | vauthors = Depannemaecker D, Ivanov A, Lillo D, Spek L, Bernard C, Jirsa V | title = A unified physiological framework of transitions between seizures, sustained ictal activity and depolarization block at the single neuron level | journal = Journal of Computational Neuroscience | volume = 50 | issue = 1 | pages = 33–49 | date = February 2022 | pmid = 35031915 | pmc = 8818009 | doi = 10.1007/s10827-022-00811-1 }} to the whole brain.{{cite journal | vauthors = Depannemaecker D, Destexhe A, Jirsa V, Bernard C | title = Modeling seizures: From single neurons to networks | journal = Seizure | volume = 90 | pages = 4–8 | date = August 2021 | pmid = 34219016 | doi = 10.1016/j.seizure.2021.06.015 | s2cid = 235468072 | doi-access = free }} These are several concomitant factor, which on different scale can "drive" the brain to pathological states and trigger a seizure. [124] => [125] => ==Diagnosis== [126] => [[File:EEG Recording Cap.jpg|thumb|upright=1.4|An [[electroencephalography|EEG]] can aid in locating the focus of the epileptic seizure.]] [127] => [128] => The diagnosis of epilepsy is typically made based on observation of the seizure onset and the underlying cause. An [[electroencephalogram]] (EEG) to look for abnormal patterns of brain waves and [[neuroimaging]] ([[CT scan]] or [[MRI]]) to look at the structure of the brain are also usually part of the initial investigations. While figuring out a specific epileptic syndrome is often attempted, it is not always possible. [[Long-term video-EEG monitoring|Video and EEG monitoring]] may be useful in difficult cases.{{cite book |title=The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care |author=National Clinical Guideline Centre |publisher=National Institute for Health and Clinical Excellence |url=http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |date=January 2012 |pages=57–83 |url-status=live |archive-url=https://web.archive.org/web/20131216151008/http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |archive-date=16 December 2013}} [129] => [130] => ===Definition=== [131] => Epilepsy is a disorder of the brain defined by any of the following conditions: [132] => :{| cellpadding=5 style="border:1px solid #ccc" [133] => |- bgcolor="#fafafa" [134] => | [135] => # At least two unprovoked (or reflex) seizures occurring more than 24 hours apart [136] => # 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 years [137] => # Diagnosis of an epilepsy syndrome [138] => |} [139] => [140] => Furthermore, epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy syndrome but are now past that age or those who have remained seizure-free for the last 10 years, with no seizure medicines for the last 5 years. [141] => [142] => This 2014 definition of the [[International League Against Epilepsy]] (ILAE) is a clarification of the ILAE 2005 conceptual definition, according to which epilepsy is "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."{{cite journal | vauthors = Fisher RS, 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 = 470–472 | date = April 2005 | pmid = 15816939 | doi = 10.1111/j.0013-9580.2005.66104.x | doi-access = free }}{{cite journal | vauthors = Panayiotopoulos CP | title = The new ILAE report on terminology and concepts for organization of epileptic seizures: a clinician's critical view and contribution | journal = Epilepsia | volume = 52 | issue = 12 | pages = 2155–2160 | date = December 2011 | pmid = 22004554 | doi = 10.1111/j.1528-1167.2011.03288.x | doi-access = free }} [143] => [144] => It is, therefore, possible to outgrow epilepsy or to undergo treatment that causes epilepsy to be resolved, but with no 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. [145] => [146] => The definition is practical in nature and is designed for clinical use. In particular, it aims to clarify when an "enduring predisposition" according to the 2005 conceptual definition is present. 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. [147] => [148] => The ILAE definition for one seizure needs an understanding of projecting an ''enduring predisposition'' to the generation of epileptic seizures. WHO, for instance, chooses to just use the traditional definition of two unprovoked seizures. [149] => [150] => ===Classification=== [151] => [[File:ILAE classification of seizure types 2017.png|thumb|Revised operational scheme of seizure classification, ILAE, 2017]] [152] => In contrast to the [[seizure types|classification of seizures]] which 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]]). 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. [153] => [154] => The International League Against Epilepsy (ILAE) provided a classification of the epilepsies and [[List of epilepsy syndromes|epileptic syndromes]] in 1989 as follows:{{cite journal | vauthors = | 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 = 389–399 | year = 1989 | pmid = 2502382 | doi = 10.1111/j.1528-1157.1989.tb05316.x | s2cid = 3483250 }} [155] => [156] => :{| cellpadding=5 style="border:1px solid #ccc" [157] => |- bgcolor="#fafafa" [158] => | [159] => # Localization-related epilepsies and syndromes [160] => ## Unknown cause (e.g. benign childhood epilepsy with centrotemporal spikes) [161] => ## Symptomatic/[[cryptogenic disease|cryptogenic]] (e.g. [[temporal lobe epilepsy]]) [162] => # Generalized [163] => ## Unknown cause (e.g. childhood absence epilepsy) [164] => ## Cryptogenic or symptomatic (e.g. Lennox-Gastaut syndrome) [165] => ## Symptomatic (e.g. early infantile epileptic encephalopathy with burst suppression) [166] => # Epilepsies and syndromes undetermined whether focal or generalized [167] => ## With both generalized and focal seizures (e.g. epilepsy with continuous spike-waves during slow wave sleep) [168] => # Special syndromes (with situation-related seizures) [169] => |} [170] => [171] => 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.{{cite journal | vauthors = Engel J | title = ILAE classification of epilepsy syndromes | journal = Epilepsy Research | volume = 70 | issue = Suppl 1 | pages = S5-10 | date = August 2006 | pmid = 16822650 | doi = 10.1016/j.eplepsyres.2005.11.014 | s2cid = 10663593 }} In 2010 the ILAE Commission for Classification of the Epilepsies addressed this issue and divided epilepsies into three categories (genetic, structural/metabolic, unknown cause){{cite journal | vauthors = Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, Engel J, French J, Glauser TA, Mathern GW, Moshé SL, Nordli D, Plouin P, Scheffer IE | title = Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009 | journal = Epilepsia | volume = 51 | issue = 4 | pages = 676–685 | date = April 2010 | pmid = 20196795 | doi = 10.1111/j.1528-1167.2010.02522.x | doi-access = free }} which were refined in their 2011 recommendation into four categories and a number of subcategories reflecting recent technological and scientific advances.{{cite journal | vauthors = Shorvon SD | title = The etiologic classification of epilepsy | journal = Epilepsia | volume = 52 | issue = 6 | pages = 1052–1057 | date = June 2011 | pmid = 21449936 | doi = 10.1111/j.1528-1167.2011.03041.x | doi-access = free }} [172] => [173] => :{| cellpadding=5 style="border:1px solid #ccc" [174] => |- bgcolor="#fafafa" [175] => | [176] => # Unknown cause (mostly genetic or presumed genetic origin) [177] => ## Pure epilepsies due to single gene disorders [178] => ## Pure epilepsies with complex inheritance [179] => # Symptomatic (associated with gross anatomic or pathologic abnormalities) [180] => ## Mostly genetic or developmental causation [181] => ### Childhood epilepsy syndromes [182] => ### Progressive myoclonic epilepsies [183] => ### Neurocutaneous syndromes [184] => ### Other neurologic single gene disorders [185] => ### Disorders of chromosome function [186] => ### Developmental anomalies of cerebral structure [187] => ## Mostly acquired causes [188] => ### Hippocampal sclerosis [189] => ### Perinatal and infantile causes [190] => ### Cerebral trauma, tumor or infection [191] => ### Cerebrovascular disorders [192] => ### Cerebral immunologic disorders [193] => ### Degenerative and other neurologic conditions [194] => # Provoked (a specific systemic or environmental factor is the predominant cause of the seizures) [195] => ## Provoking factors [196] => ## Reflex epilepsies [197] => # Cryptogenic (presumed symptomatic nature in which the cause has not been identified) [198] => |} A revised, operational classification of seizure types has been introduced by the ILAE.{{Cite web|title=Operational Classification of Seizure Types (2017)|url=https://www.ilae.org/guidelines/definition-and-classification/operational-classification-2017|url-status=live|archive-url=https://web.archive.org/web/20230409152557/https://www.ilae.org/guidelines/definition-and-classification/operational-classification-2017|archive-date=Apr 9, 2023}} It allows more clearly understood terms and clearly defines focal and generalized onset dichotomy, when possible, even without observing the seizures based on description by patient or observers.{{cite journal | vauthors = Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, Lagae L, Moshé SL, Peltola J, Roulet Perez E, Scheffer IE, Zuberi SM | title = Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology | journal = Epilepsia | volume = 58 | issue = 4 | pages = 522–530 | date = April 2017 | pmid = 28276060 | doi = 10.1111/epi.13670 | s2cid = 21037500 | hdl = 11343/292620 | hdl-access = free }} The essential changes in terminology are that "partial" is called "focal" with awareness used as a classifier for focal seizures -based on description focal seizures are now defined as behavioral arrest, automatisms, cognitive, autonomic, emotional or hyperkinetic variants while atonic, myoclonic, clonic, infantile spasms, and tonic seizures may be either focal or generalized based on their onset. Several terms that were not clear or consistent in the description were removed such as dyscognitive, psychic, simple, and complex partial, while "secondarily generalized" is replaced by a clearer term "focal to bilateral tonic-clonic seizure". New seizure types now believed to be generalized are eyelid myoclonia, myoclonic atonic, myoclonic absence, and myoclonic tonic-clonic. Sometimes it is possible to classify seizures as focal or generalized based on presenting features even though onset in not known. This system is based on the 1981 seizure classification modified in 2010 and principally is the same with an effort to improve the flexibility and clarity of use to understand seizure types better in keeping with current knowledge. [199] => [200] => ===Syndromes=== [201] => {{Main|Epilepsy syndromes}} [202] => Cases of epilepsy may be organized into [[epilepsy syndromes]] by the specific features that are present. These features include the age that seizure begin, the seizure types, [[electroencephalography|EEG]] findings, among others. Identifying an epilepsy syndrome is useful as it helps determine the underlying causes as well as what [[anticonvulsant|anti-seizure medication]] should be tried.{{ cite web | title = Epilepsy syndromes | url = https://www.epilepsydiagnosis.org/syndrome/epilepsy-syndrome-groupoverview.html | publisher = International league against epilepsy | access-date = 6 October 2014 | url-status = live | archive-url = https://web.archive.org/web/20141006173716/https://www.epilepsydiagnosis.org/syndrome/epilepsy-syndrome-groupoverview.html | archive-date = 6 October 2014}} [203] => [204] => 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. Less serious examples are [[benign rolandic epilepsy]] (2.8 per 100,000), [[childhood absence epilepsy]] (0.8 per 100,000) and [[juvenile myoclonic epilepsy]] (0.7 per 100,000). Severe syndromes with diffuse brain dysfunction caused, at least partly, by some aspect of epilepsy, are also referred to as developmental and epileptic encephalopathies. These are associated with frequent [[seizures]] that are resistant to treatment and cognitive dysfunction, for instance [[Lennox–Gastaut syndrome]] (1–2% of all persons with epilepsy),{{cite journal | vauthors = Asadi-Pooya AA | title = Lennox-Gastaut syndrome: a comprehensive review | journal = Neurological Sciences | volume = 39 | issue = 3 | pages = 403–414 | date = March 2018 | pmid = 29124439 | doi = 10.1007/s10072-017-3188-y | s2cid = 4243468 }} [[Dravet syndrome]](1: 15000-40000 worldwide{{Cite web| vauthors = Chemaly N, Nabbout R |title=Dravet Syndrome|url=https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=33069&lng=EN}}), and [[West syndrome|West syndrome(1–9: 100000]]{{Cite web| vauthors = Chipaux M |title=West syndrome|url=https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=33069&lng=EN}}).{{cite journal | vauthors = Nordli DR | title = Epileptic encephalopathies in infants and children | journal = Journal of Clinical Neurophysiology | volume = 29 | issue = 5 | pages = 420–424 | date = October 2012 | pmid = 23027099 | doi = 10.1097/WNP.0b013e31826bd961 | s2cid = 41884825 }} Genetics is believed to play an important role in epilepsies by a number of mechanisms. Simple and complex modes of [[inheritance]] have been identified for some of them. However, extensive screening have failed to identify many single [[gene]] variants of large effect.{{cite journal | vauthors = 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 | title = Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy | journal = American Journal of Human Genetics | volume = 91 | issue = 2 | pages = 293–302 | date = August 2012 | pmid = 22863189 | pmc = 3415540 | doi = 10.1016/j.ajhg.2012.06.016 }} 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, including [[CHD2]] and [[SYNGAP1]]{{cite journal | vauthors = Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC | title = Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 | journal = Nature Genetics | volume = 45 | issue = 7 | pages = 825–830 | date = July 2013 | pmid = 23708187 | pmc = 3704157 | doi = 10.1038/ng.2646 }}{{cite journal | vauthors = Chénier 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 | title = CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems | journal = Journal of Neurodevelopmental Disorders | volume = 6 | issue = 1 | pages = 9 | year = 2014 | pmid = 24834135 | pmc = 4022362 | doi = 10.1186/1866-1955-6-9 | doi-access = free }}{{cite journal | vauthors = Suls A, Jaehn JA, Kecskés A, Weber Y, Weckhuysen S, Craiu DC, Siekierska A, Djémié 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, Møller RS, Linnankivi T, Dimova P, Striano P, Zara F, Marini C, Guerrini R, Depienne C, Baulac S, Kuhlenbäumer G, Crawford AD, Lehesjoki AE, de Witte PA, Palotie A, Lerche H, Esguerra CV, De Jonghe P, Helbig I | title = De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome | journal = American Journal of Human Genetics | volume = 93 | issue = 5 | pages = 967–975 | date = November 2013 | pmid = 24207121 | pmc = 3824114 | doi = 10.1016/j.ajhg.2013.09.017 }} and [[DNM1]], [[GABBR2]], [[Fatty acid synthase|FASN]] and [[RYR3]].{{cite journal | vauthors = ((EuroEPINOMICS-RES Consortium)) | title = De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies | journal = American Journal of Human Genetics | volume = 95 | issue = 4 | pages = 360–370 | date = October 2014 | pmid = 25262651 | pmc = 4185114 | doi = 10.1016/j.ajhg.2014.08.013 }} [205] => [206] => 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. The ''idiopathic'' (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. Some childhood epilepsy syndromes are included in the unknown cause category in which the cause is presumed genetic, for instance benign rolandic epilepsy. Clinical syndromes in which epilepsy is not the main feature (e.g. Angelman syndrome) were categorized ''symptomatic'' but it was argued to include these within the category ''idiopathic''. Classification of epilepsies and particularly of epilepsy syndromes will change with advances in research. [207] => [208] => ===Tests=== [209] => [210] => An electroencephalogram (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.{{Cite web|title=1 Guidance | Epilepsies: Diagnosis and management | Guidance | NICE|date=11 January 2012 |url=https://www.nice.org.uk/guidance/cg137/chapter/1-Guidance#following-a-first-seizure}} In children it is typically only needed after a second seizure unless specified by a specialist. 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. [211] => [212] => [213] => Diagnostic imaging by [[X-ray computed tomography|CT scan]] and [[Magnetic resonance imaging|MRI]] is recommended after a first non-febrile seizure to detect structural problems in and around the brain. MRI is generally a better imaging test except when bleeding is suspected, for which CT is more sensitive and more easily available. If someone attends the emergency room with a seizure but returns to normal quickly, imaging tests may be done at a later point. 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. [214] => [215] => [216] => For adults, the testing of electrolyte, [[blood glucose]] and calcium levels is important to rule out problems with these as causes. An [[electrocardiogram]] can rule out problems with the rhythm of the heart. A lumbar puncture may be useful to diagnose a [[central nervous system]] infection but is not routinely needed. In children additional tests may be required such as urine biochemistry and blood testing looking for [[metabolic disorder]]s.{{cite book | veditors = Wallace SJ, Farrell K |title=Epilepsy in children|year=2004|publisher=Arnold|location=London|isbn=978-0-340-80814-6|page=354|url=https://books.google.com/books?id=kKtiW-wTPh4C&pg=PA354|edition=2nd }} Together with EEG and neuroimaging, [[genetic testing]] is becoming one of the most important diagnostic technique for epilepsy, as a diagnosis might be achieved in a relevant proportion of cases with severe epilepsies, both in children and adults.{{cite journal | vauthors = Chen WL, Mefford HC | title = Diagnostic Considerations in the Epilepsies-Testing Strategies, Test Type Advantages, and Limitations | journal = Neurotherapeutics | volume = 18 | issue = 3 | pages = 1468–1477 | date = July 2021 | pmid = 34532824 | pmc = 8608977 | doi = 10.1007/s13311-021-01121-7 }} For those with negative genetic testing, in some it might be important to repeat or re-analyze previous genetic studies after 2–3 years.{{Cite journal| vauthors = Aledo-Serrano A, Sánchez-Alcudia R, Toledano R, García-Morales I, Beltrán-Corbellini Á, del Pino I, Gil-Nagel A |date=2021|title=Developmental and epileptic encephalopathies after negative or inconclusive genetic testing: what is next?|url=https://jtggjournal.com/article/view/4433|journal=Journal of Translational Genetics and Genomics|volume=5 |issue=4 |pages=443–455 |doi=10.20517/jtgg.2021.40|s2cid=244944239|doi-access=free}} [217] => [218] => A high blood [[prolactin]] level within the first 20 minutes following a seizure may be useful to help confirm an epileptic seizure as opposed to [[psychogenic non-epileptic seizure]].{{cite journal | vauthors = Luef G | title = Hormonal alterations following seizures | journal = Epilepsy & Behavior | volume = 19 | issue = 2 | pages = 131–133 | date = October 2010 | pmid = 20696621 | doi = 10.1016/j.yebeh.2010.06.026 | s2cid = 945952 }}{{cite journal | vauthors = Ahmad S, Beckett MW | title = Value of serum prolactin in the management of syncope | journal = Emergency Medicine Journal | volume = 21 | issue = 2 | pages = 3e–3 | date = March 2004 | pmid = 14988379 | pmc = 1726305 | doi = 10.1136/emj.2003.008870 }} Serum prolactin level is less useful for detecting focal seizures.{{cite journal | vauthors = Shukla G, Bhatia M, Vivekanandhan S, Gupta N, Tripathi M, Srivastava A, Pandey RM, Jain S | title = Serum prolactin levels for differentiation of nonepileptic versus true seizures: limited utility | journal = Epilepsy & Behavior | volume = 5 | issue = 4 | pages = 517–521 | date = August 2004 | pmid = 15256189 | doi = 10.1016/j.yebeh.2004.03.004 | s2cid = 2381873 }} If it is normal an epileptic seizure is still possible and a serum prolactin does not separate epileptic seizures from syncope.{{cite journal | vauthors = Chen DK, So YT, Fisher RS | title = Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 65 | issue = 5 | pages = 668–675 | date = September 2005 | pmid = 16157897 | doi = 10.1212/01.wnl.0000178391.96957.d0 | doi-access = free }} It is not recommended as a routine part of the diagnosis of epilepsy. [219] => [220] => ===Differential diagnosis=== [221] => Diagnosis of epilepsy can be difficult. A number of other conditions may present very similar signs and symptoms to seizures, including [[syncope (medicine)|syncope]], [[Hyperventilation syndrome|hyperventilation]], migraines, [[narcolepsy]], [[panic attack]]s and psychogenic non-epileptic seizures (PNES).{{cite journal | vauthors = Brodtkorb E | title = Common imitators of epilepsy | journal = Acta Neurologica Scandinavica. Supplementum | volume = 127 | issue = 196 | pages = 5–10 | year = 2013 | pmid = 23190285 | doi = 10.1111/ane.12043 | s2cid = 1373740 | doi-access = free }} In particular, syncope can be accompanied by a short episode of convulsions.{{cite journal | vauthors = Zaidi A, Clough P, Cooper P, Scheepers B, Fitzpatrick AP | title = Misdiagnosis of epilepsy: many seizure-like attacks have a cardiovascular cause | journal = Journal of the American College of Cardiology | volume = 36 | issue = 1 | pages = 181–184 | date = July 2000 | pmid = 10898432 | doi = 10.1016/S0735-1097(00)00700-2 }} [[Autosomal dominant nocturnal frontal lobe epilepsy|Nocturnal frontal lobe epilepsy]], often misdiagnosed as nightmares, was considered to be a [[parasomnia]] but later identified to be an epilepsy syndrome.{{cite journal | vauthors = Bisulli F, Vignatelli L, Provini F, Leta C, Lugaresi E, Tinuper P | title = Parasomnias and nocturnal frontal lobe epilepsy (NFLE): lights and shadows--controversial points in the differential diagnosis | journal = Sleep Medicine | volume = 12 | issue = Suppl 2 | pages = S27–S32 | date = December 2011 | pmid = 22136895 | doi = 10.1016/j.sleep.2011.10.008 }} Attacks of the movement disorder [[paroxysmal dyskinesia]] may be taken for epileptic seizures.{{cite journal | vauthors = Zhou JQ, Zhou LM, Fang ZY, Wang Q, Chen ZY, Yang LB, Chen SD, Cai XD | title = Analyzing clinical and electrophysiological characteristics of Paroxysmal Dyskinesia | journal = Journal of Research in Medical Sciences | volume = 16 | issue = 1 | pages = 110–114 | date = January 2011 | pmid = 21448393 | pmc = 3063430 }} The cause of a [[drop attack]] can be, among many others, an atonic seizure. [222] => [223] => Children may have behaviors that are easily mistaken for epileptic seizures but are not. These include [[breath-holding spell]]s, [[nocturnal enuresis|bedwetting]], [[night terror]]s, [[tic]]s and [[shudder attacks]]. [[Gastroesophageal reflux]] may cause arching of the back and [[torticollis|twisting of the head to the side]] in infants, which may be mistaken for tonic-clonic seizures.{{cite book |title=Rosen's emergency medicine: concepts and clinical practice |year=2010 |publisher=Mosby/Elsevier |location=Philadelphia |isbn=978-0-323-05472-0 |page=2228 |url= https://books.google.com/books?id=u7TNcpCeqx8C&pg=PA2228 |edition=7th | veditors = Marx JA }} [224] => [225] => Misdiagnosis is frequent (occurring in about 5 to 30% of cases). Different studies showed that in many cases seizure-like attacks in apparent treatment-resistant epilepsy have a cardiovascular cause.{{cite journal | vauthors = Akhtar MJ | title = All seizures are not epilepsy: many have a cardiovascular cause | journal = JPMA. The Journal of the Pakistan Medical Association | volume = 52 | issue = 3 | pages = 116–120 | date = March 2002 | pmid = 12071066 }} Approximately 20% of the people seen at epilepsy clinics have PNES and of those who have PNES about 10% also have epilepsy;{{cite book| vauthors = Jerome E |title=Seizures and epilepsy|publisher=Oxford University Press|location=New York|isbn=978-0-19-532854-7|page=462|year=2013|url=https://books.google.com/books?id=5PgjmjugIX8C&pg=PA462|edition=2nd }} separating the two based on the seizure episode alone without further testing is often difficult. [226] => [227] => ==Prevention== [228] => 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 the pork tapeworm may be effective. Efforts in one part of Central America to decrease rates of pork tapeworm resulted in a 50% decrease in new cases of epilepsy. [229] => [230] => == Complications == [231] => Epilepsy can be dangerous when seizure occurs at certain times. The risk of drowning or being involved in a motor vehicle collision is higher. It is also found that people with epilepsy are more likely to have psychological problems.{{Cite web |title=Epilepsy – Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/epilepsy/symptoms-causes/syc-20350093 |access-date=1 April 2022 |website=Mayo Clinic |language=en}} Other complications include aspiration pneumonia and difficulty learning.{{Cite web |title=Epilepsy: MedlinePlus Medical Encyclopedia |url=https://medlineplus.gov/ency/article/000694.htm |access-date=1 April 2022 |website=medlineplus.gov |language=en}} [232] => [233] => ==Management== [234] => [[File:Epilepsy Medical Alert Wrist Bracelets 2018.jpg|thumb|upright=1.4|Wristbands or bracelets denoting their condition are occasionally worn by people with epilepsy should they need medical assistance.]] [235] => [236] => Epilepsy is usually treated with daily medication once a second seizure has occurred, while medication may be started after the first seizure in those at high risk for subsequent seizures. Supporting people's [[self care|self-management]] of their condition may be useful.{{cite journal | vauthors = Helmers SL, Kobau R, Sajatovic M, Jobst BC, Privitera M, Devinsky O, Labiner D, Escoffery C, Begley CE, Shegog R, Pandey D, Fraser RT, Johnson EK, Thompson NJ, Horvath KJ | title = Self-management in epilepsy: Why and how you should incorporate self-management in your practice | journal = Epilepsy & Behavior | volume = 68 | pages = 220–224 | date = March 2017 | pmid = 28202408 | pmc = 5381244 | doi = 10.1016/j.yebeh.2016.11.015 }} In drug-resistant cases different [[management of drug-resistant epilepsy|management options]] may be considered, including special diets, the implantation of a [[neurostimulator]], or [[neurosurgery]]. [237] => [238] => ===First aid=== [239] => Rolling people with an active tonic-clonic seizure onto their side and into the [[recovery position]] helps prevent fluids from getting into the lungs.{{cite journal | vauthors = Michael GE, O'Connor RE | title = The diagnosis and management of seizures and status epilepticus in the prehospital setting | journal = Emergency Medicine Clinics of North America | volume = 29 | issue = 1 | pages = 29–39 | date = February 2011 | pmid = 21109100 | doi = 10.1016/j.emc.2010.08.003 }} Putting fingers, a bite block or tongue depressor in the mouth is not recommended as it might make the person vomit or result in the rescuer being bitten. Efforts should be taken to prevent further self-injury.{{cite web| vauthors = Shearer P |title=Seizures and Status Epilepticus: Diagnosis and Management in the Emergency Department|url=http://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=77|work=Emergency Medicine Practice|url-status=live|archive-url=https://web.archive.org/web/20101230141114/https://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=77|archive-date=30 December 2010}} [[Spinal precautions]] are generally not needed. [240] => [241] => If a seizure lasts longer than 5 minutes or if there are more than two seizures in 5 minutes without a return to a normal level of consciousness between them, it is considered a [[medical emergency]] known as [[status epilepticus]].{{cite book|title=Advanced therapy in epilepsy|year=2009|publisher=People's Medical Pub. House|location=Shelton, Conn.|isbn=978-1-60795-004-2|page=144|url=https://books.google.com/books?id=4W7UI-FPZmoC&pg=PA144| vauthors = Wheless JW, Willmore J, Brumback RA }} This may require [[airway management|medical help to keep the airway open and protected]]; a [[nasopharyngeal airway]] may be useful for this. At home the recommended initial medication for seizure of a long duration is [[midazolam]] placed in the nose or mouth.{{cite book |title=The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care |author=National Clinical Guideline Centre |publisher=National Institute for Health and Clinical Excellence |url=http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |date=January 2012 |url-status=live |archive-url=https://web.archive.org/web/20131216151008/http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |archive-date=16 December 2013}} [[Diazepam]] may also be used [[suppository|rectally]]. In hospital, intravenous [[lorazepam]] is preferred. [242] => [243] => If two doses of [[benzodiazepines]] are not effective, other medications such as [[phenytoin]] are recommended. Convulsive status epilepticus that does not respond to initial treatment typically requires admission to the [[intensive care unit]] and treatment with stronger agents such as midazolam infusion, ketamine, thiopentone or propofol. Most institutions have a preferred pathway or protocol to be used in a seizure emergency like status epilepticus. These protocols have been found to be effective in reducing time to delivery of treatment. [244] => [245] => ===Medications=== [246] => [[File:Anticonvulsants.jpg|thumb|upright=1.4|Anticonvulsants]] [247] => The mainstay treatment of epilepsy is anticonvulsant medications, possibly for the person's entire life. The choice of anticonvulsant is based on seizure type, epilepsy syndrome, other medications used, other health problems, and the person's age and lifestyle. A single medication is recommended initially;{{cite book|title=Wyllie's Treatment of Epilepsy: Principles and Practice |year=2012 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-5348-4 |page=187 |url=https://books.google.com/books?id=j9t6Qg0kkuUC&pg=RA1-PA187| vauthors = Wyllie E }} if this is not effective, switching to a single other medication is recommended. Two medications at once is recommended only if a single medication does not work. 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%.{{cite book |title=Medical aspects of disability; a handbook for the rehabilitation professional |year=2010 |publisher=Springer |location=New York |isbn=978-0-8261-2784-6 |page=182 |url=https://books.google.com/books?id=azCbzY2q0_kC&pg=PA182 |edition=4th | veditors = Flanagan SR, Zaretsky H, Moroz A}} About 30% of people continue to have seizures despite anticonvulsant treatment. [248] => [249] => [250] => There are a number of medications available including phenytoin, [[carbamazepine]] and [[valproate]]. Evidence suggests that phenytoin, carbamazepine, and valproate may be equally effective in both focal and generalized seizures.{{cite journal | vauthors = Nevitt SJ, Marson AG, Tudur Smith C | title = Carbamazepine versus phenytoin monotherapy for epilepsy: an individual participant data review | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 7 | pages = CD001911 | date = July 2019 | pmid = 31318037 | pmc = 6637502 | doi = 10.1002/14651858.CD001911.pub4 }}{{cite journal | vauthors = Nevitt SJ, Marson AG, Weston J, Tudur Smith C | title = Sodium valproate versus phenytoin monotherapy for epilepsy: an individual participant data review | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 8 | pages = CD001769 | date = August 2018 | pmid = 30091458 | pmc = 6513104 | doi = 10.1002/14651858.CD001769.pub4 }} [[Controlled release]] carbamazepine appears to work as well as immediate release carbamazepine, and may have fewer [[side effect]]s.{{cite journal | vauthors = Powell G, Saunders M, Rigby A, Marson AG | title = Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy | journal = The Cochrane Database of Systematic Reviews | volume = 12 | issue = 12 | pages = CD007124 | date = December 2016 | pmid = 27933615 | pmc = 6463840 | doi = 10.1002/14651858.CD007124.pub5 }} In the United Kingdom, carbamazepine or [[lamotrigine]] are recommended as first-line treatment for focal seizures, with [[levetiracetam]] and valproate as second-line due to issues of cost and side effects.{{cite journal | vauthors = Nevitt SJ, Sudell M, Cividini S, Marson AG, Tudur Smith C | title = Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 4 | pages = CD011412 | date = April 2022 | pmid = 35363878 | pmc = 8974892 | doi = 10.1002/14651858.CD011412.pub4 }} Valproate is recommended first-line for generalized seizures with lamotrigine being second-line. In those with absence seizures, [[ethosuximide]] or valproate are recommended; valproate is particularly effective in myoclonic seizures and tonic or atonic seizures. If seizures are well-controlled on a particular treatment, it is not usually necessary to routinely check the medication levels in the blood. [251] => [252] => [253] => The least expensive anticonvulsant is [[phenobarbital]] at around US$5 a year. The [[World Health Organization]] gives it a first-line recommendation in the developing world and it is commonly used there.{{cite journal | vauthors = Ilangaratne NB, Mannakkara NN, Bell GS, Sander JW | title = Phenobarbital: missing in action | journal = Bulletin of the World Health Organization | volume = 90 | issue = 12 | pages = 871–871A | date = December 2012 | pmid = 23284189 | pmc = 3524964 | doi = 10.2471/BLT.12.113183 }}{{cite book | veditors = Shorvon S, Perucca E, Engel Jr J |title=The treatment of epilepsy|year=2009|publisher=Wiley-Blackwell|location=Chichester, UK|isbn=978-1-4443-1667-4|page=587|url=https://books.google.com/books?id=rFFzFzZJtasC&pg=PA587|edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20160521102931/https://books.google.com/books?id=rFFzFzZJtasC&pg=PA587|archive-date=21 May 2016}} Access, however, may be difficult as some countries label it as a [[controlled drug]]. [254] => [255] => [256] => Adverse effects from medications are reported in 10% to 90% of people, depending on how and from whom the data is collected. Most adverse effects are dose-related and mild. Some examples include mood changes, sleepiness, or an unsteadiness in gait. Certain medications have side effects that are not related to dose such as rashes, liver toxicity, or [[aplastic anemia|suppression of the bone marrow]]. Up to a quarter of people stop treatment due to adverse effects. Some medications are associated with [[birth defect]]s when used in pregnancy. Many of the common used medications, such as valproate, phenytoin, carbamazepine, phenobarbital, and gabapentin have been reported to cause increased risk of birth defects,{{cite journal | vauthors = Bromley R, Adab N, Bluett-Duncan M, Clayton-Smith J, Christensen J, Edwards K, Greenhalgh J, Hill RA, Jackson CF, Khanom S, McGinty RN, Tudur Smith C, Pulman J, Marson AG | title = Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 8 | pages = CD010224 | date = August 2023 | pmid = 37647086 | pmc = 10463554 | doi = 10.1002/14651858.CD010224.pub3 }} especially when used during the [[first trimester]]. 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.{{cite journal | vauthors = Kamyar M, Varner M | title = Epilepsy in pregnancy | journal = Clinical Obstetrics and Gynecology | volume = 56 | issue = 2 | pages = 330–341 | date = June 2013 | pmid = 23563876 | doi = 10.1097/GRF.0b013e31828f2436 | s2cid = 20150531 }} Among the antiepileptic medications, levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects. [257] => [258] => [259] => 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.{{cite book|title=Adolescent health care: a practical guide|year=2008|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-9256-1|page=335|url=https://books.google.com/books?id=er8dQPxgcz0C&pg=PA335|edition=5th|editor=Lawrence S. Neinstein}} Stopping is possible in about 70% of children and 60% of adults. Measuring medication levels is not generally needed in those whose seizures are well controlled.{{cite web |title=American Epilepsy Society Choosing Wisely |url=http://www.choosingwisely.org/societies/american-epilepsy-society/ |website=www.choosingwisely.org |date=14 August 2018 |access-date=30 August 2018}} [260] => [261] => ===Surgery=== [262] => [[Epilepsy surgery]] should be considered for any person with epilepsy who is medically refractory.{{cite journal |vauthors=Brodie MJ, Elder AT, Kwan P |date=November 2009 |title=Epilepsy in later life |url=https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(09)70240-6/fulltext |journal=The Lancet. Neurology |volume=8 |issue=11 |pages=1019–1030 |doi=10.1016/S1474-4422(09)70240-6 |pmid=19800848 |s2cid=14318073}} Patients are evaluated on a case-by-case basis in centres that are familiar with and have expertise in epilepsy surgery. Epilepsy surgery may be an option for people with focal seizures that remain a problem despite other treatments.{{cite journal | vauthors = Krucoff MO, Chan AY, Harward SC, Rahimpour S, Rolston JD, Muh C, Englot DJ | title = Rates and predictors of success and failure in repeat epilepsy surgery: A meta-analysis and systematic review | journal = Epilepsia | volume = 58 | issue = 12 | pages = 2133–2142 | date = December 2017 | pmid = 28994113 | pmc = 5716856 | doi = 10.1111/epi.13920 }}{{cite journal | vauthors = Benoit PW, Yagiela A, Fort NF | title = Pharmacologic correlation between local anesthetic-induced myotoxicity and disturbances of intracellular calcium distribution | journal = Toxicology and Applied Pharmacology | volume = 52 | issue = 2 | pages = 187–198 | date = February 1980 | pmid = 7361318 | doi = 10.1016/0041-008x(80)90105-2 }} These other treatments include at least a trial of two or three medications.{{cite journal | vauthors = Duncan JS | title = Epilepsy surgery | journal = Clinical Medicine | volume = 7 | issue = 2 | pages = 137–142 | date = April 2007 | pmid = 17491501 | pmc = 4951827 | doi = 10.7861/clinmedicine.7-2-137 }} The goal of surgery has been total control of seizures.{{cite journal | vauthors = Birbeck GL, Hays RD, Cui X, Vickrey BG | title = Seizure reduction and quality of life improvements in people with epilepsy | journal = Epilepsia | volume = 43 | issue = 5 | pages = 535–538 | date = May 2002 | pmid = 12027916 | doi = 10.1046/j.1528-1157.2002.32201.x | s2cid = 23577753 | doi-access = free }} However, most physicians believe that even palliative surgery where the burden of seizures is reduced significantly can help in achieving developmental progress or reversal of developmental stagnation in children with drug-resistant epilepsy and this may be achieved in 60–70% of cases. Common procedures include cutting out the hippocampus via an anterior temporal lobe resection, removal of tumors, and removing parts of the [[neocortex]]. Some procedures such as a [[corpus callosotomy]] are attempted in an effort to decrease the number of seizures rather than cure the condition. Following surgery, medications may be slowly withdrawn in many cases. [263] => [264] => === Neurostimulation === [265] => [[Neurostimulation]] via [[Brain–computer interface|neuro-cybernetic prosthesis]] implantation may be another option in those who are not candidates for surgery, providing chronic, pulsatile electrical stimulation of specific nerve or brain regions, alongside standard care. Three types have been used in those who do not respond to medications: [[vagus nerve stimulation|vagus nerve stimulation (VNS)]], [[anterior thalamic stimulation]], and [[closed-loop responsive stimulation]] (RNS).{{cite journal | vauthors = Edwards CA, Kouzani A, Lee KH, Ross EK | title = Neurostimulation Devices for the Treatment of Neurologic Disorders | journal = Mayo Clinic Proceedings | volume = 92 | issue = 9 | pages = 1427–1444 | date = September 2017 | pmid = 28870357 | doi = 10.1016/j.mayocp.2017.05.005 | doi-access = free }}{{cite journal | vauthors = Panebianco M, Rigby A, Marson AG | title = Vagus nerve stimulation for focal seizures | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 7 | pages = CD002896 | date = July 2022 | pmid = 35833911 | pmc = 9281624 | doi = 10.1002/14651858.CD002896.pub3 | doi-access = free }} [266] => [267] => ==== Vagus nerve stimulation ==== [268] => Non-pharmacological modulation of neurotransmitters via high-level VNS (h-VNS) may reduce seizure frequency in children and adults who do not respond to medical and/or surgical therapy, when compared with low-level VNS (l-VNS). In a 2022 [[Cochrane (organisation)|Cochrane]] review of four [[randomized controlled trial]]s, with moderate certainty of evidence, people receiving h-VNS treatment were 73% more likely (13% more likely to 164% more likely) to experience a reduction in seizure frequency by at least 50% (the minimum threshold defined for individual clinical response). Potentially 249 (163 to 380) per 1000 people with drug-resistant epilepsy may achieve a 50% reduction in seizures following h-VNS, benefiting an additional 105 per 1000 people compared with l-VNS. [269] => [270] => This outcome was limited by the number of studies available, and the quality of one trial in particular, wherein three people received l-VNS in error. A [[sensitivity analysis]] suggested that the best case scenario was that the likelihood of clinical response to h-VNS may be 91% (27% to 189%) higher than those receiving l-VNS. In the worst-case scenario, the likelihood of clinical response to h-VNS was still 61% higher (7% higher to 143% higher) than l-VNS. [271] => [272] => Despite the potential benefit for h-VNS treatment, the Cochrane review also found that the risk of several adverse-effects was greater than those receiving l-VNS. There was moderate certainty of evidence that voice alteration or hoarseness risk may be 2.17(1.49 to 3.17) fold higher than people receiving l-VNS. [[Dyspnoea]] risk was also 2.45 (1.07 to 5.60) times that of l-VNS recipients, although the low number of events and studies meant that the certainty of evidence was low. The risk of rebound-withdrawal symptoms, coughing, pain and paraesthesia was unclear. [273] => [274] => ===Diet=== [275] => There is promising evidence that a [[ketogenic diet]] (high-fat, [[low-carbohydrate diet|low-carbohydrate]], adequate-[[protein (nutrient)|protein]]) decreases the number of seizures and eliminates seizures in some; however, further research is necessary. A 2022 systematic review of the literature has found some evidence to support that a ketogenic diet or [[modified Atkins diet]] can be helpful in the treatment of epilepsy in some infants.{{cite report | vauthors = Treadwell JR, Wu M, Tsou AY | title = Management of Infantile Epilepsies: A Systematic Review | date = 2022 | pmid = 36383706 | doi = 10.23970/AHRQEPCCER252 | s2cid = 254357105 }} These types of diets may be beneficial for children with drug-resistant epilepsy; the use for adults remains uncertain. The most commonly reported adverse effects were vomiting, constipation and diarrhoea. It is unclear why this diet works.{{cite book | veditors = Maria BL |title=Current management in child neurology|year=2009|publisher=BC Decker|location=Hamilton, Ont.|isbn=978-1-60795-000-4|page=180|url=https://books.google.com/books?id=lxhs51fE85wC&pg=PA180|edition=4th|url-status=live|archive-url=https://web.archive.org/web/20160624092756/https://books.google.com/books?id=lxhs51fE85wC&pg=PA180|archive-date=24 June 2016}} In people with coeliac disease or non-celiac gluten sensitivity and occipital calcifications, a [[gluten-free diet]] may decrease the frequency of seizures. [276] => [277] => ===Other=== [278] => Avoidance therapy consists of minimizing or eliminating triggers. For example, those who are sensitive to light may have success with using a small television, avoiding video games, or wearing dark glasses.{{cite journal | vauthors = Verrotti A, Tocco AM, Salladini C, Latini G, Chiarelli F | title = Human photosensitivity: from pathophysiology to treatment | journal = European Journal of Neurology | volume = 12 | issue = 11 | pages = 828–841 | date = November 2005 | pmid = 16241971 | doi = 10.1111/j.1468-1331.2005.01085.x | s2cid = 23001888 }} [[Operant-based biofeedback]] based on the EEG waves has some support in those who do not respond to medications.{{cite journal | vauthors = Tan G, Thornby J, Hammond DC, Strehl U, Canady B, Arnemann K, Kaiser DA | title = Meta-analysis of EEG biofeedback in treating epilepsy | journal = Clinical EEG and Neuroscience | volume = 40 | issue = 3 | pages = 173–179 | date = July 2009 | pmid = 19715180 | doi = 10.1177/155005940904000310 | s2cid = 16682327 }} Psychological methods should not, however, be used to replace medications. [279] => [280] => Exercise has been proposed as possibly useful for preventing seizures,{{cite journal | vauthors = Arida RM, Scorza FA, Scorza CA, Cavalheiro EA | title = Is physical activity beneficial for recovery in temporal lobe epilepsy? Evidences from animal studies | journal = Neuroscience and Biobehavioral Reviews | volume = 33 | issue = 3 | pages = 422–431 | date = March 2009 | pmid = 19059282 | doi = 10.1016/j.neubiorev.2008.11.002 | s2cid = 30918370 }} with some data to support this claim.{{cite journal | vauthors = Arida RM, Cavalheiro EA, da Silva AC, Scorza FA | title = Physical activity and epilepsy: proven and predicted benefits | journal = Sports Medicine | volume = 38 | issue = 7 | pages = 607–615 | year = 2008 | pmid = 18557661 | doi = 10.2165/00007256-200838070-00006 | s2cid = 24048241 }} Some dogs, commonly referred to as [[seizure dog]]s, may help during or after a seizure.{{cite journal | vauthors = Di Vito L, Naldi I, Mostacci B, Licchetta L, Bisulli F, Tinuper P | title = A seizure response dog: video recording of reacting behaviour during repetitive prolonged seizures | journal = Epileptic Disorders | volume = 12 | issue = 2 | pages = 142–145 | date = June 2010 | pmid = 20472528 | doi = 10.1684/epd.2010.0313 | url = http://www.jle.com/en/revues/epd/e-docs/a_seizure_response_dog_video_recording_of_reacting_behaviour_during_repetitive_prolonged_seizures_284959/article.phtml | url-status = live | s2cid = 3337471 | archive-url = https://web.archive.org/web/20141006083557/http://www.jle.com/en/revues/epd/e-docs/a_seizure_response_dog_video_recording_of_reacting_behaviour_during_repetitive_prolonged_seizures_284959/article.phtml | archive-date = 6 October 2014 }}{{cite journal | vauthors = Kirton A, Winter A, Wirrell E, Snead OC | title = Seizure response dogs: evaluation of a formal training program | journal = Epilepsy & Behavior | volume = 13 | issue = 3 | pages = 499–504 | date = October 2008 | pmid = 18595778 | doi = 10.1016/j.yebeh.2008.05.011 | s2cid = 27549519 }} It is not clear if dogs have the ability to predict seizures before they occur.{{cite journal | vauthors = Doherty MJ, Haltiner AM | title = Wag the dog: skepticism on seizure alert canines | journal = Neurology | volume = 68 | issue = 4 | pages = 309 | date = January 2007 | pmid = 17242343 | doi = 10.1212/01.wnl.0000252369.82956.a3 | s2cid = 33328776 | citeseerx = 10.1.1.1003.1543 }} [281] => [282] => There is moderate-quality evidence supporting the use of psychological interventions along with other treatments in epilepsy. This can improve quality of life, enhance emotional wellbeing, and reduce fatigue in adults and adolescents.{{cite journal | vauthors = Michaelis R, Tang V, Wagner JL, Modi AC, LaFrance WC, Goldstein LH, Lundgren T, Reuber M | title = Psychological treatments for people with epilepsy | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 10 | pages = CD012081 | date = October 2017 | pmid = 29078005 | pmc = 6485515 | doi = 10.1002/14651858.CD012081.pub2 }} Psychological interventions may also improve seizure control for some individuals by promoting self-management and adherence. [283] => [284] => As an add-on therapy in those who are not well controlled with other medications, [[cannabidiol]] appears to be useful in some children.{{cite journal | vauthors = Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, Herkes GK, Farrell M, Degenhardt L | title = Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 89 | issue = 7 | pages = 741–753 | date = July 2018 | pmid = 29511052 | doi = 10.1136/jnnp-2017-317168 | doi-access = free | hdl = 1959.4/unsworks_50076 | hdl-access = free }}{{Cite journal |date=26 June 2018 |title=Cannabis derivative may reduce seizures in some severe drug-resistant epilepsies, but adverse events increase |url=https://evidence.nihr.ac.uk/alert/cannabis-derivative-may-reduce-seizures-in-some-severe-drug-resistant-epilepsies-but-adverse-events-increase |journal=NIHR Evidence |type=Plain English summary |doi=10.3310/signal-000606|s2cid=242083755 }} In 2018 the FDA approved this product for Lennox–Gastaut syndrome and Dravet syndrome.{{cite web |title=Press Announcements - FDA approves first drug {{sic|comprised |hide=y|of}} an active ingredient derived from marijuana to treat rare, severe forms of epilepsy |url=https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm |website=www.fda.gov |access-date=4 October 2018 |language=en |date=25 June 2018}} [285] => [286] => There are a few studies on the use of [[dexamethasone]] for the successful treatment of drug-resistant seizures in both adults and children.{{cite web |title=Archive of "Journal of Investigative Medicine High Impact Case Reports". – PMC |url=https://www.ncbi.nlm.nih.gov/pmc/journals/2607/ |website=www.ncbi.nlm.nih.gov}} [287] => [288] => ===Alternative medicine=== [289] => Alternative medicine, including [[acupuncture]],{{cite journal | vauthors = Cheuk DK, Wong V | title = Acupuncture for epilepsy | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 5 | pages = CD005062 | date = May 2014 | pmid = 24801225 | pmc = 10105317 | doi = 10.1002/14651858.CD005062.pub4 }} routine [[vitamins]],{{cite journal | vauthors = Ranganathan LN, Ramaratnam S | title = Vitamins for epilepsy | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD004304 | date = April 2005 | pmid = 15846704 | doi = 10.1002/14651858.CD004304.pub2 }} and [[yoga]],{{cite journal | vauthors = Panebianco M, Sridharan K, Ramaratnam S | title = Yoga for epilepsy | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 10 | pages = CD001524 | date = October 2017 | pmid = 28982217 | pmc = 6485327 | doi = 10.1002/14651858.CD001524.pub3 }} have no reliable [[Evidence-based medicine|evidence]] to support their use in epilepsy. [[Melatonin]], {{as of|2016|lc=y}}, is insufficiently supported by evidence.{{cite journal | vauthors = Brigo F, Igwe SC, Del Felice A | title = Melatonin as add-on treatment for epilepsy | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 8 | pages = CD006967 | date = August 2016 | pmid = 27513702 | pmc = 7386917 | doi = 10.1002/14651858.CD006967.pub4 }} The trials were of poor methodological quality and it was not possible to draw any definitive conclusions. [290] => [291] => Several supplements (with varied reliabilities of evidence) have been reported to be helpful for drug-resistant epilepsy. These include high-dose Omega-3, berberine, Manuka honey, reishi and lion's mane mushrooms, curcumin,{{cite journal | vauthors = He LY, Hu MB, Li RL, Zhao R, Fan LH, He L, Lu F, Ye X, Huang YL, Wu CJ | title = Natural Medicines for the Treatment of Epilepsy: Bioactive Components, Pharmacology and Mechanism | journal = Frontiers in Pharmacology | volume = 12 | pages = 604040 | year = 2021 | pmid = 33746751 | pmc = 7969896 | doi = 10.3389/fphar.2021.604040 | doi-access = free }} vitamin E, coenzyme Q-10, and resveratrol. The reason these can work (in theory) is that they reduce inflammation or oxidative stress, two of the major mechanism contributing to epilepsy.{{cite journal | vauthors = Aguiar CC, Almeida AB, Araújo PV, de Abreu RN, Chaves EM, do Vale OC, Macêdo DS, Woods DJ, Fonteles MM, Vasconcelos SM | title = Oxidative stress and epilepsy: literature review | journal = Oxidative Medicine and Cellular Longevity | volume = 2012 | pages = 795259 | year = 2012 | pmid = 22848783 | pmc = 3403512 | doi = 10.1155/2012/795259 | doi-access = free }} [292] => [293] => == Contraception and pregnancy == [294] => {{See also|Epilepsy and pregnancy}} [295] => Women of child-bearing age, including those with epilepsy, are at risk of [[unintended pregnancies]] if they are not using an effective form of [[contraception]].{{cite journal | vauthors = King A, Gerard EE | title = Contraception, fecundity, and pregnancy in women with epilepsy: an update on recent literature | journal = Current Opinion in Neurology | volume = 35 | issue = 2 | pages = 161–168 | date = April 2022 | pmid = 35191408 | pmc = 9230745 | doi = 10.1097/WCO.0000000000001039 }} Women with epilepsy may experience a temporary increase in seizure frequency when they begin [[hormonal contraception]]. [296] => [297] => Some anti-seizure medications interact with enzymes in the liver and cause the drugs in hormonal contraception to be broken down more quickly. These [[enzyme inducer|enzyme inducing]] drugs make hormonal contraception less effective, and this is particularly hazardous if the anti-seizure medication is associated with birth defects.{{cite journal | vauthors = Reimers A, Brodtkorb E, Sabers A | title = Interactions between hormonal contraception and antiepileptic drugs: Clinical and mechanistic considerations | journal = Seizure | volume = 28 | pages = 66–70 | date = May 2015 | pmid = 25843765 | doi = 10.1016/j.seizure.2015.03.006 | s2cid = 18210697 | doi-access = free }} Potent enzyme-inducing anti-seizure medications include [[carbamazepine]], [[eslicarbazepine acetate]], [[oxcarbazepine]], [[phenobarbital]], [[phenytoin]], [[primidone]], and [[rufinamide]]. The drugs [[perampanel]] and [[topiramate]] can be enzyme-inducing at higher doses.{{cite web |title=Enzyme-inducing antiepileptic drugs |url=https://cks.nice.org.uk/topics/epilepsy/prescribing-information/enzyme-inducing-antiepileptic-drugs/ |website=NICE |access-date=2 November 2023 |date=May 2023}} Conversely, hormonal contraception can lower the amount of the anti-seizure medication [[lamotrigine]] circulating in the body, making it less effective. The failure rate of oral contraceptives, when used correctly, is 1%, but this increases to between 3–6% in women with epilepsy. Overall, [[intrauterine devices]] (IUDs) are preferred for women with epilepsy who are not intending to become pregnant. [298] => [299] => Women with epilepsy, especially if they have other medical conditions, may have a slightly lower, but still high, chance of becoming pregnant. Women with [[infertility]] have about the same chance of success with [[in vitro fertilisation]] or other forms of [[assisted reproductive technology]] as women without epilepsy. There may be a higher risk of [[pregnancy loss]]. [300] => [301] => Once pregnant, there are two main concerns related to [[pregnancy]]. The first concern is about the risk of seizures during pregnancy, and the second concern is that the anti-seizure medications may result in [[birth defects]]. Most women with epilepsy must continue treatment with anti-seizure drugs, and the treatment goal is to balance the need to prevent seizures with the need to prevent drug-induced birth defects.{{cite journal |vauthors=Tomson T, Battino D, Bromley R, Kochen S, Meador K, Pennell P, Thomas SV |date=December 2019 |title=Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy |journal=Epileptic Disorders |volume=21 |issue=6 |pages=497–517 |doi=10.1684/epd.2019.1105 |pmid=31782407|hdl=11336/119061 |hdl-access=free }} [302] => [303] => Pregnancy does not seem to change seizure frequency very much. When seizures happen, however, they can cause some pregnancy complications, such as [[Preterm birth|pre-term births]] or the babies being [[Small for gestational age|smaller than usual]] when they are born. [304] => [305] => All pregnancies have a risk of birth defects, e.g., due to [[smoking during pregnancy]]. In addition to this typical level of risk, some anti-seizure drugs significantly increase the risk of birth defects and [[intrauterine growth restriction]], as well as [[Developmental disorder|developmental]], [[Neurocognitive disorder|neurocognitive]], and [[Emotional and behavioral disorders|behavioral disorders]]. Most women with epilepsy receive safe and effective treatment and have typical, healthy children. The highest risks are associated with specific anti-seizure drugs, such as valproic acid and carbamazepine, and with higher doses. [[Folic acid supplementation]], such as through [[Prenatal vitamin|prenatal vitamins]], reduced the risk. Planning pregnancies in advance gives women with epilepsy an opportunity to switch to a lower-risk treatment program and reduced drug doses. [306] => [307] => Although anti-seizure drugs can be found in [[breast milk]], women with epilepsy [[Breastfeeding and medications|can breastfeed]] their babies, and the benefits usually outweigh the risks. [308] => [309] => ==Prognosis== [310] => [[File:Epilepsy world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.4|Deaths due to epilepsy per million persons in 2012 {{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0–7}}{{legend|#ffe820|8–10}}{{legend|#ffd820|11–13}}{{legend|#ffc020|14–17}}{{legend|#ffa020|18–21}}{{legend|#ff9a20|22–28}}{{legend|#f08015|29–37}}{{legend|#e06815|38–67}}{{legend|#d85010|68–100}}{{legend|#d02010|101–232}}{{div col end}}]] [311] => [312] => Epilepsy cannot usually be cured, but medication can control seizures effectively in about 70% of cases. Of those with generalized seizures, more than 80% can be well controlled with medications while this is true in only 50% of people with focal seizures. One predictor of long-term outcome is the number of seizures that occur in the first six months. 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.{{cite book| vauthors = Kwan P |title=Fast facts: epilepsy|year=2012|publisher=Health Press|location=Abingdon, Oxford, UK|isbn=978-1-908541-12-3|page=10|edition=5th}} In the developing world, 75% of people are either untreated or not appropriately treated. In Africa, 90% do not get treatment. This is partly related to appropriate medications not being available or being too expensive. [313] => [314] => ===Mortality=== [315] => People with epilepsy are at an increased risk of death. This increase is between 1.6 and 4.1-fold greater than that of the general population.{{cite book | veditors = Shorvon S, Perucca E, Engel J |title=The treatment of epilepsy|year=2009|publisher=Wiley-Blackwell|location=Chichester, UK|isbn=978-1-4443-1667-4|page=28|url=https://books.google.com/books?id=rFFzFzZJtasC&pg=PA28|edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20160610155113/https://books.google.com/books?id=rFFzFzZJtasC&pg=PA28|archive-date=10 June 2016}} The greatest increase in mortality from epilepsy is among the elderly. Those with epilepsy due to an unknown cause have little increased risk. [316] => [317] => Mortality is often related to the underlying cause of the seizures, status epilepticus, suicide, [[major trauma|trauma]], and [[sudden unexpected death in epilepsy]] (SUDEP).{{cite journal | vauthors = Hitiris N, Mohanraj R, Norrie J, Brodie MJ | title = Mortality in epilepsy | journal = Epilepsy & Behavior | volume = 10 | issue = 3 | pages = 363–376 | date = May 2007 | pmid = 17337248 | doi = 10.1016/j.yebeh.2007.01.005 | s2cid = 39107474 }} Death from status epilepticus is primarily due to an underlying problem rather than missing doses of medications. The risk of suicide is between two and six times higher in those with epilepsy;{{cite journal | vauthors = Bagary M | title = Epilepsy, antiepileptic drugs and suicidality | journal = Current Opinion in Neurology | volume = 24 | issue = 2 | pages = 177–182 | date = April 2011 | pmid = 21293270 | doi = 10.1097/WCO.0b013e328344533e }}{{cite journal | vauthors = Mula M, Sander JW | title = Suicide risk in people with epilepsy taking antiepileptic drugs | journal = Bipolar Disorders | volume = 15 | issue = 5 | pages = 622–627 | date = August 2013 | pmid = 23755740 | doi = 10.1111/bdi.12091 | s2cid = 40681400 }} the cause of this is unclear. SUDEP appears to be partly related to the frequency of generalized tonic-clonic seizures{{cite journal | vauthors = Ryvlin P, Nashef L, Tomson T | title = Prevention of sudden unexpected death in epilepsy: a realistic goal? | journal = Epilepsia | volume = 54 | issue = Suppl 2 | pages = 23–28 | date = May 2013 | pmid = 23646967 | doi = 10.1111/epi.12180 | doi-access = free }} and accounts for about 15% of epilepsy-related deaths; it is unclear how to decrease its risk. [318] => Risk factors for SUDEP include nocturnal generalized tonic-clonic seizures, seizures, sleeping alone and medically intractable epilepsy.{{cite journal | vauthors = Kløvgaard M, Sabers A, Ryvlin P | title = Update on Sudden Unexpected Death in Epilepsy | journal = Neurologic Clinics | volume = 40 | issue = 4 | pages = 741–754 | date = November 2022 | pmid = 36270688 | doi = 10.1016/j.ncl.2022.06.001 | s2cid = 252617763 }} [319] => [320] => In the United Kingdom, it is estimated that 40–60% of deaths are possibly preventable. In the developing world, many deaths are due to untreated epilepsy leading to falls or status epilepticus. [321] => [322] => ==Epidemiology== [323] => Epilepsy is one of the most common serious neurological disorders{{cite journal | vauthors = 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 = 326–337 | date = January 2007 | pmid = 17261678 | doi = 10.1212/01.wnl.0000252807.38124.a3 | s2cid = 208246679 }} affecting about 39 million people {{as of|2015|lc=y}}.{{cite journal | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 | vauthors = Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, Casey DC, Charlson FJ, Chen AZ, Coggeshall M, Cornaby L, Dandona L, Dicker DJ, Dilegge T, Erskine HE, Ferrari AJ, Fitzmaurice C, Fleming T, Forouzanfar MH, Fullman N, Gething PW, Goldberg EM, Graetz N, Haagsma JA, Hay SI, Johnson CO, Kassebaum NJ, Kawashima T, Kemmer L }} It affects 1% of the population by age 20 and 3% of the population by age 75. It is more common in males than females with the overall difference being small. Most of those with the disorder (80%) are in low income populations{{cite journal | vauthors = Espinosa-Jovel C, Toledano R, Aledo-Serrano Á, García-Morales I, Gil-Nagel A | title = Epidemiological profile of epilepsy in low income populations | journal = Seizure | volume = 56 | pages = 67–72 | date = March 2018 | pmid = 29453113 | doi = 10.1016/j.seizure.2018.02.002 | doi-access = free }} or the [[developing world]]. [324] => [325] => The estimated prevalence of active epilepsy ({{as of|2012|lc=y}}) is in the range 3–10 per 1,000, with active epilepsy defined as someone with epilepsy who has had a least one unprovoked seizure in the last five years. Epilepsy begins each year in 40–70 per 100,000 in developed countries and 80–140 per 100,000 in developing countries. Poverty is a risk and includes both being from a poor country and being poor relative to others within one's country. In the developed world epilepsy most commonly starts either in the young or in the old. 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. In developed countries the number of cases a year has decreased in children and increased among the elderly between the 1970s and 2003.{{cite journal | vauthors = Sander JW | title = The epidemiology of epilepsy revisited | journal = Current Opinion in Neurology | volume = 16 | issue = 2 | pages = 165–170 | date = April 2003 | pmid = 12644744 | doi = 10.1097/00019052-200304000-00008 }} This has been attributed partly to better survival following strokes in the elderly. [326] => [327] => ==History== [328] => {{See also|On the Sacred Disease}} [329] => [[File:Hippocrates rubens.jpg|thumb|upright=1.4|Hippocrates, 17th century engraving by [[Peter Paul Rubens]] of an antique bust]] [330] => The oldest medical records show that epilepsy has been affecting people at least since the beginning of recorded history.{{cite book | veditors = Saraceno B, Avanzini G, Lee P | title=Atlas: Epilepsy Care in the World | publisher=World Health Organization | year=2005 | url=https://www.who.int/publications/i/item/9241563036 | isbn=978-92-4-156303-1 | access-date=21 October 2023 }} Throughout [[ancient history]], the disease was thought to be a spiritual condition. The world's oldest description of an epileptic seizure comes from a text in [[Akkadian language|Akkadian]] (a language used in ancient [[Mesopotamia]]) and was written around 2000 BC. The person described in the text was diagnosed as being under the influence of a moon god, and underwent an [[exorcism]]. Epileptic seizures are listed in the [[Code of Hammurabi]] ({{circa|1790 BC}}) as reason for which a purchased slave may be returned for a refund, and the [[Edwin Smith Papyrus]] ({{circa|1700 BC}}) describes cases of individuals with epileptic convulsions. [331] => [332] => The oldest known detailed record of the disease itself is in the ''[[Sakikku]]'', a [[Babylonia]]n [[cuneiform]] medical text from 1067{{endash}}1046 BC. This text gives signs and symptoms, details treatment and likely outcomes, and describes many features of the different seizure types. 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. Around 900 BC, [[Punarvasu Atreya]] described epilepsy as loss of consciousness;{{cite book| vauthors = Eadie MJ, Bladin PF |title=A Disease Once Sacred: A History of the Medical Understanding of Epilepsy|url=https://books.google.com/books?id=ZhNW0AJPAzgC|year=2001|publisher=John Libbey Eurotext|isbn=978-0-86196-607-3 }} this definition was carried forward into the [[Ayurveda|Ayurvedic]] text of [[Charaka Samhita]] ({{circa|400 BC}}).{{cite web|title=Epilepsy: An historical overview |url=https://www.who.int/inf-fs/en/fact168.html |work=World Health Organization |access-date=27 December 2013 |date=Feb 2001 |url-status=dead |archive-url=https://web.archive.org/web/20131030115816/http://www.who.int/inf-fs/en/fact168.html |archive-date=30 October 2013 }} [333] => [334] => The [[Ancient Greece|ancient Greeks]] had 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 the ''sacred disease'' ({{Lang-grc|ἠ ἱερὰ νόσος}}).{{cite web |url=http://allcountries.org/health/epilepsy_historical_overview.html |title=Epilepsy: historical overview |work=World Health Organization |access-date=20 March 2011 |url-status=live |archive-url=https://web.archive.org/web/20110120101205/http://www.allcountries.org/health/epilepsy_historical_overview.html |archive-date=20 January 2011}} Epilepsy appears within Greek mythology: it is associated with the Moon goddesses [[Selene]] and [[Artemis]], who afflicted those who upset them. The Greeks thought that important figures such as [[Julius Caesar]] and [[Hercules]] had the disease. The notable exception to this divine and spiritual view was that of the school of [[Hippocrates]]. In the fifth century BC, Hippocrates rejected the idea that the disease was caused by spirits. In his landmark work ''[[On the Sacred Disease]]'', he proposed that epilepsy was not divine in origin and instead was a medically treatable problem originating in the brain. He accused those of attributing a sacred cause to the disease of spreading ignorance through a belief in superstitious magic. Hippocrates proposed that [[heredity]] was 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. Instead of referring to it as the ''sacred disease'', he used the term ''great disease'', giving rise to the modern term ''grand mal'', used for tonic–clonic seizures. Despite his work detailing the physical origins of the disease, his view was not accepted at the time. Evil spirits continued to be blamed until at least the 17th century. [335] => [336] => In [[Ancient Rome]] people did not eat or drink with the same pottery as that used by someone who was affected.{{cite book| vauthors = Temkin O |title=The Falling Sickness: A History of Epilepsy from the Greeks to the Beginnings of Modern Neurology|publisher=JHU Press|isbn=978-1-4214-0053-2|page=Section 1|url=https://books.google.com/books?id=w33hgy52XKkC&pg=PT22|language=en|date=1 March 1994}} People of the time would spit on their chest believing that this would keep the problem from affecting them. According to [[Apuleius]] and other ancient physicians, to detect epilepsy, it was common to light a piece of [[Jet (lignite)|''gagates'']], whose smoke would trigger the seizure.{{cite book| vauthors = Stol M |title=Epilepsy in Babylonia|date=1993|publisher=BRILL|isbn=978-90-72371-63-8|page=143|url=https://books.google.com/books?id=Tu-MYstDdvoC&pg=PA143|language=en}} Occasionally a spinning [[potter's wheel]] was used, perhaps a reference to [[photosensitive epilepsy]].{{cite book| vauthors = Harding GF, Jeavons PM |title=Photosensitive Epilepsy|date=1994|publisher=Cambridge University Press|isbn=978-1-898683-02-5|page=2|url=https://books.google.com/books?id=oBmE6J0S7r4C&pg=PA2|language=en}} [337] => [338] => In most cultures, persons with epilepsy have been stigmatized, shunned, or even imprisoned. As late as in the second half of the 20th century, in [[Tanzania]] and other parts of Africa epilepsy was associated with possession by evil spirits, witchcraft, or poisoning and was believed by many to be contagious.{{cite journal | vauthors = Jilek-Aall L | title = Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures | journal = Epilepsia | volume = 40 | issue = 3 | pages = 382–386 | date = March 1999 | pmid = 10080524 | doi = 10.1111/j.1528-1157.1999.tb00723.x | doi-access = free }} In the [[Salpêtrière]], the birthplace of modern neurology, [[Jean-Martin Charcot]] found people with epilepsy side by side with the mentally ill, those with chronic [[syphilis]], and the criminally insane.{{Cite web|date=January 2012|title=Epilepsy and its Management: A Review|url=https://www.researchgate.net/publication/286200646|access-date=22 February 2022|website=[[ResearchGate]]}} In Ancient Rome, epilepsy was known as the {{Lang|la|morbus comitialis}} or 'disease of the assembly hall' and was seen as a curse from the gods. In northern Italy, epilepsy was traditionally known as Saint Valentine's malady.{{cite book| vauthors = Illes J |title=Encyclopedia of Mystics, Saints & Sages|url=https://books.google.com/books?id=QLuQZUo8bQMC&pg=PT1238|year=2011|publisher=HarperCollins|isbn=978-0-06-209854-2|page=1238|quote=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.|url-status=live|archive-url=https://web.archive.org/web/20140111113232/http://books.google.com/books?id=QLuQZUo8bQMC&pg=PT1238|archive-date=11 January 2014}} In at least the 1840s in the United States of America, epilepsy was known as the ''falling sickness'' or ''the falling fits'', and was considered a form of medical [[insanity]].{{cite book | vauthors = Lewis E |isbn = 978-1-275-31136-7 |date = 17 February 2012 |publisher = Gale, Making of Modern Law|title = Report of The Trial and Conviction of John Haggerty, for The Murder of Melchoir Fordney, Late of The City of Lancaster, Pennsylvania |page = 62}} Around the same time period, epilepsy was known in France as the {{Lang|fr|haut-mal}} {{Lit|high evil}}, {{Lang|fr|mal-de terre}} {{Lit|earthen sickness}}, {{lang|fr|mal de Saint Jean}} {{lit|[[John the Baptist|Saint John]]'s sickness}}, {{lang|fr|mal des enfans}} {{lit|child sickness}}, and {{lang|fr|mal-caduc}} {{lit|falling sickness}}. Patients of epilepsy in France were also known as {{lang|fr|tombeurs}} {{lit|people who fall}}, due to the seizures and loss of consciousness in an epileptic episode. [339] => [340] => In the mid-19th century, the first effective anti-seizure medication, [[bromide]], was introduced.{{cite journal | vauthors = Perucca P, Gilliam FG | title = Adverse effects of antiepileptic drugs | journal = The Lancet. Neurology | volume = 11 | issue = 9 | pages = 792–802 | date = September 2012 | pmid = 22832500 | doi = 10.1016/S1474-4422(12)70153-9 | s2cid = 25540685 }} The first modern treatment, phenobarbital, was developed in 1912, with phenytoin coming into use in 1938.{{cite book|title=Medical toxicology|year=2004|publisher=Lippincott Williams & Wilkins|location=Philadelphia [u.a.]|isbn=978-0-7817-2845-4|page=789|url=https://books.google.com/books?id=BfdighlyGiwC&pg=PA789| vauthors = Caravati EM |edition=3rd }} [341] => [342] => ==Society and culture== [343] => {{See also|List of people with epilepsy}} [344] => [345] => ===Stigma=== [346] => [[Social stigma]] is commonly experienced, around the world, by those with epilepsy.{{cite journal | vauthors = de Boer HM | title = Epilepsy stigma: moving from a global problem to global solutions | journal = Seizure | volume = 19 | issue = 10 | pages = 630–636 | date = December 2010 | pmid = 21075013 | doi = 10.1016/j.seizure.2010.10.017 | s2cid = 17282975 | doi-access = free }} It can affect people economically, socially and culturally. In India and China, epilepsy may be used as justification to deny marriage. People in some areas still believe those with epilepsy to be [[curse]]d. In parts of Africa, such as Tanzania and [[Uganda]], epilepsy is claimed to be associated with possession by evil spirits, witchcraft, or poisoning and is incorrectly believed by many to be [[contagious disease|contagious]]. Before 1971 in the United Kingdom, epilepsy was considered grounds for the annulment of marriage. The stigma may result in some people with epilepsy denying that they have ever had seizures.{{cite book | vauthors = Neligan A, Hauser WA, Sander JW | chapter = The epidemiology of the epilepsies | volume = 107 | pages = 113–33 | year = 2012 | pmid = 22938966 | doi = 10.1016/B978-0-444-52898-8.00006-9 | isbn = 978-0-444-52898-8 | series = Handbook of Clinical Neurology | title = Epilepsy }} [347] => [348] => ===Economics=== [349] => [350] => Seizures result in direct economic costs of about one billion dollars in the United States. Epilepsy resulted in economic costs in Europe of around 15.5 billion euros in 2004. In India epilepsy is estimated to result in costs of US$1.7 billion or 0.5% of the GDP. It is the cause of about 1% of emergency department visits (2% for emergency departments for children) in the United States.{{cite journal | vauthors = Martindale JL, Goldstein JN, Pallin DJ | title = Emergency department seizure epidemiology | journal = Emergency Medicine Clinics of North America | volume = 29 | issue = 1 | pages = 15–27 | date = February 2011 | pmid = 21109099 | doi = 10.1016/j.emc.2010.08.002 }} [351] => [352] => ===Vehicles=== [353] => {{See also|Epilepsy and driving}} [354] => Those with epilepsy are at about twice the risk of being involved in a [[motor vehicular collision]] and thus in many areas of the world are not allowed to drive or only able to drive if certain conditions are met. Diagnostic delay has been suggested to be a cause of some potentially avoidable motor vehicle collisions since at least one study showed that most motor vehicle accidents occurred in those with undiagnosed non-motor seizures as opposed to those with motor seizures at epilepsy onset.{{cite journal | vauthors = Pellinen J, Tafuro E, Yang A, Price D, Friedman D, Holmes M, Barnard S, Detyniecki K, Hegde M, Hixson J, Haut S, Kälviäinen R, French J | title = Focal nonmotor versus motor seizures: The impact on diagnostic delay in focal epilepsy | journal = Epilepsia | volume = 61 | issue = 12 | pages = 2643–2652 | date = December 2020 | pmid = 33078409 | doi = 10.1111/epi.16707 | s2cid = 224811014 }} 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 himself. Countries that require physician reporting include Sweden, Austria, Denmark and Spain. Countries that require the individual to report include the UK and New Zealand, and physicians may report if they believe the individual has not already. In Canada, the United States and Australia the requirements around reporting vary by province or state. If seizures are well controlled most feel allowing driving is reasonable. The amount of time a person must be free from seizures before he can drive varies by country. Many countries require one to three years without seizures. In the United States the time needed without a seizure is determined by each state and is between three months and one year.{{cite book|title=Epilepsy: a comprehensive textbook|year=2008|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-5777-5|page=2279|url=https://books.google.com/books?id=6Kq4Zt2KOpcC&pg=PA2279|edition=2nd| veditors = Engel J, Pedley TA }} [355] => [356] => Those with epilepsy or seizures are typically denied a pilot license.{{cite book| vauthors = Bor R |title=Aviation Mental Health: Psychological Implications for Air Transportation|year=2012|publisher=Ashgate Publishing|isbn=978-1-4094-8491-2|page=148|url=https://books.google.com/books?id=bS98mtcqRdUC&pg=PA148 }} [357] => * 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.{{cite web|title=Seizure Disorders|url=http://www.tc.gc.ca/eng/civilaviation/publications/tp13312-2-neurology-seizure-2179.htm|work=Transport Canada|publisher=Government of Canada|access-date=29 December 2013|url-status=dead|archive-url=https://web.archive.org/web/20131230232523/http://www.tc.gc.ca/eng/civilaviation/publications/tp13312-2-neurology-seizure-2179.htm|archive-date=30 December 2013}} Those with febrile seizures and drug related seizures may also be considered. [358] => * In the United States, the [[Federal Aviation Administration]] does not allow those with epilepsy to get a commercial pilot license.{{cite book| vauthors = Wilner AN |title=Epilepsy 199 answers: a doctor responds to his patients' questions|year=2008|publisher=Demos Health|location=New York|isbn=978-1-934559-96-3|page=52|url=https://books.google.com/books?id=_yVGV1_FP4wC&pg=RA1-PT52|edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20160517061331/https://books.google.com/books?id=_yVGV1_FP4wC&pg=RA1-PT52|archive-date=17 May 2016}} 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.{{cite web|title=Guide for Aviation Medical Examiners|url=http://www.faa.gov/about/office_org/headquarters_offices/avs/offices/aam/ame/guide/app_process/exam_tech/item46/amd/nc/|work=Federal Aviation Administration|access-date=29 December 2013|url-status=live|archive-url=https://web.archive.org/web/20131017045628/http://www.faa.gov/about/office_org/headquarters_offices/avs/offices/aam/ame/guide/app_process/exam_tech/item46/amd/nc/|archive-date=17 October 2013}} [359] => * In the United Kingdom, a full [[national private pilot license]] requires the same standards as a professional driver's license.{{cite web|title=National PPL (NPPL) Medical Requirements|url=http://www.caa.co.uk/default.aspx?catid=49&pagetype=90&pageid=12133|work=Civil Aviation Authority|access-date=29 December 2013|url-status=live|archive-url=https://web.archive.org/web/20131016233956/http://www.caa.co.uk/default.aspx?catid=49&pagetype=90&pageid=12133|archive-date=16 October 2013}} This requires a period of ten years without seizures while off medications.{{cite web|title=For Medical Practitioners: At a glance Guide to the current Medical Standards of Fitness to Drive|url=https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/258991/aagv1.pdf|access-date=29 December 2013|author=Drivers Medical Group|pages=8|year=2013|url-status=live|archive-url=https://web.archive.org/web/20131230235214/https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/258991/aagv1.pdf|archive-date=30 December 2013}} Those who do not meet this requirement may acquire a restricted license if free from seizures for five years. [360] => [361] => ===Support organizations=== [362] => There are organizations that provide support for people and families affected by epilepsy. The ''Out of the Shadows'' campaign, a joint effort by the World Health Organization, the ILAE and the [[International Bureau for Epilepsy]], provides help internationally. In the United States, the [[Epilepsy Foundation]] is a national organization that works to increase the acceptance of those with the disorder, their ability to function in society and to promote research for a cure.{{cite web|title=Epilepsy Foundation of America – EFA|url=http://healthfinder.gov/FindServices/Organizations/Organization.aspx?code=HR0238|website=Healthfinder.gov|publisher=[[US Department of Health and Human Services]]|access-date=28 July 2014|date=28 April 2011|url-status=live|archive-url=https://web.archive.org/web/20140716080153/http://healthfinder.gov/FindServices/Organizations/Organization.aspx?code=HR0238|archive-date=16 July 2014}} The Epilepsy Foundation, some hospitals, and some individuals also run support groups in the United States.{{cite book | veditors = Engel J, Pedley TA |title=Epilepsy: a comprehensive textbook|date=2008|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-5777-5 |page=2245 |edition=2nd |url=https://books.google.com/books?id=6Kq4Zt2KOpcC&pg=PA2245}} In Australia, the [[Epilepsy Foundation of Victoria|Epilepsy Foundation]] provides support, delivers education and training and funds research for people living with epilepsy. [363] => [364] => International Epilepsy Day (World Epilepsy Day) began in 2015 and occurs on the second Monday in February.{{cite journal | vauthors = Aleem MA | title = World epilepsy day | journal = Epilepsia | volume = 56 | issue = 2 | pages = 168 | date = February 2015 | pmid = 25404065 | doi = 10.1111/epi.12814 | s2cid = 11256074 }}{{cite journal | vauthors = Perucca E | title = Commentary: why an international epilepsy day? | journal = Epilepsia | volume = 56 | issue = 2 | pages = 170–171 | date = February 2015 | pmid = 25403985 | doi = 10.1111/epi.12813 | doi-access = free }} [365] => [366] => [[Purple Day]], a different world-wide epilepsy awareness day for epilepsy, was initiated by a nine-year-old Canadian named Cassidy Megan in 2008, and is every year on 26 March.{{cite web|url=http://time.com/5215273/purple-day-epilepsy-awareness-day/|title=People Are Wearing Purple Today for Epilepsy Awareness Day. Here's What That Is|website=Time.com|date=26 March 2018| vauthors = Carr F |access-date=18 April 2018}} [367] => [368] => ==Research== [369] => {{See also|Computational models in epilepsy}} [370] => [371] => ===Seizure prediction and modeling=== [372] => Seizure prediction refers to attempts to forecast epileptic seizures based on the [[Electroencephalography|EEG]] before they occur. {{as of|2011}}, no effective mechanism to predict seizures has been developed.{{cite journal | vauthors = Carney PR, Myers S, Geyer JD | title = Seizure prediction: methods | journal = Epilepsy & Behavior | volume = 22 | issue = Suppl 1 | pages = S94-101 | date = December 2011 | pmid = 22078526 | pmc = 3233702 | doi = 10.1016/j.yebeh.2011.09.001 }} Although no effective device that can predict seizures is available, the science behind seizure prediction and ability to deliver such a tool has made progress. [373] => [374] => [[kindling model|Kindling]], where repeated exposures to events that could cause seizures eventually causes seizures more easily, has been used to create [[animal model]]s of epilepsy.{{cite book |title= Epilepsy: a comprehensive textbook |year=2008 |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-5777-5 |page=426 |url=https://books.google.com/books?id=TwlXrOBkAS8C&pg=PA426 |edition=2nd | veditors =Engel J }} [375] => Different [[animal model]]s of epilepsy have been characterized in rodents that recapitulate the EEG and behavioral concomitants of different forms of epilepsy, in particular the occurrence of recurrent spontaneous seizures.Guillemain, I., Kahane, P. & Depaulis, A. Animal models to study aetiopathology of epilepsy: what are the features to model? Epileptic Disord 14, 217–225 (2012). Because epileptic seizures of different kinds are observed naturally in some of these animals, strains of mice and rats have been selected to be used as genetic models of epilepsy. In particular, several lines of mice and rats display spike-and-wave discharges when EEG recorded and have been studied to understand absence epilepsy.Jarre, G., Guillemain, I., and, C. D. M. of S. & 2017. Genetic Models of Absence Epilepsy in Rats and Mice. Elsevier 455–471 (2017) Among these models, the strain of [[GAERS]] (Genetic Absence Epilepsy Rats from Strasbourg) was characterized in the 1980s and has helped to understand the mechanisms underlying childhood absence epilepsy.Depaulis, A. & Charpier, S. Pathophysiology of absence epilepsy: Insights from genetic models. Neurosci Lett 667, 53–65 (2018) [376] => [377] => Rat brain slices serve as a valuable model for assessing the potential of compounds in reducing epileptiform activity. By evaluating the frequency of epileptiform bursting in hippocampal networks, researchers can identify promising candidates for novel anti-seizure drugs.{{cite journal | vauthors = Morris G, Heiland M, Lamottke K, Guan H, Hill T, Zhou Y, Zhu Q, Schorge S, Henshall DC | title = BICS01 Mediates Reversible Anti-seizure Effects in Brain Slice Models of Epilepsy | journal = Frontiers in Neurology | volume = 12 | page = 791608 | date = January 2022 | pmid = 35069421 | pmc = 8770400 | doi = 10.3389/fneur.2021.791608 | doi-access = free }} [378] => [379] => One of the hypotheses present in the literature is based on inflammatory pathways. Studies supporting this mechanism revealed that inflammatory, glycolipid, and oxidative factors are higher in epilepsy patients, especially those with generalized epilepsy.{{cite journal | vauthors = Kegler A, Pascotini ET, Caprara AL, Arend J, Gabbi P, Duarte MM, Royes LF, Fighera MR | title = Relationship between seizure type, metabolic profile, and inflammatory markers in blood samples of patients with epilepsy | journal = Epileptic Disorders | volume = 23 | issue = 1 | pages = 74–84 | date = February 2021 | pmid = 33602662 | doi = 10.1684/epd.2021.1236 | s2cid = 231962819 }} [380] => [381] => ===Potential future therapies=== [382] => [[Gene therapy for epilepsy|Gene therapy]] is being studied in some types of epilepsy.{{cite journal | vauthors = Walker MC, Schorge S, Kullmann DM, Wykes RC, Heeroma JH, Mantoan L | title = Gene therapy in status epilepticus | journal = Epilepsia | volume = 54 | issue = Suppl 6 | pages = 43–45 | date = September 2013 | pmid = 24001071 | doi = 10.1111/epi.12275 | s2cid = 13942394 | doi-access = free }} Medications that alter immune function, such as [[intravenous immunoglobulin]]s, may reduce the frequency of seizures when including in normal care as an add-on therapy; however, further research is required to determine whether these medications are very well tolerated in children and in adults with epilepsy.{{cite journal | vauthors = Panebianco M, Walker L, Marson AG | title = Immunomodulatory interventions for focal epilepsy | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 10 | pages = CD009945 | date = October 2023 | pmid = 37842826 | doi = 10.1002/14651858.CD009945.pub3 | pmc = 10577807 | collaboration = Cochrane Epilepsy Group | pmc-embargo-date = October 16, 2024 }} Noninvasive [[stereotactic radiosurgery]] is, {{as of|2012|lc=y}}, being compared to standard surgery for certain types of epilepsy.{{cite journal | vauthors = Quigg M, Rolston J, Barbaro NM | title = Radiosurgery for epilepsy: clinical experience and potential antiepileptic mechanisms | journal = Epilepsia | volume = 53 | issue = 1 | pages = 7–15 | date = January 2012 | pmid = 22191545 | pmc = 3519388 | doi = 10.1111/j.1528-1167.2011.03339.x }} [383] => [384] => ==Other animals== [385] => {{Main|Epilepsy in animals}} [386] => Epilepsy occurs in a number of other animals including dogs and cats; it is in fact the most common brain disorder in dogs.{{cite journal | vauthors = Thomas WB | title = Idiopathic epilepsy in dogs and cats | journal = The Veterinary Clinics of North America. Small Animal Practice | volume = 40 | issue = 1 | pages = 161–179 | date = January 2010 | pmid = 19942062 | doi = 10.1016/j.cvsm.2009.09.004 }} It is typically treated with anticonvulsants such as phenobarbital or bromide in dogs and phenobarbital in cats. [[Imepitoin]] is also used in dogs.{{cite journal | vauthors = Rundfeldt C, Löscher W | title = The pharmacology of imepitoin: the first partial benzodiazepine receptor agonist developed for the treatment of epilepsy | journal = CNS Drugs | volume = 28 | issue = 1 | pages = 29–43 | date = January 2014 | pmid = 24357084 | doi = 10.1007/s40263-013-0129-z | s2cid = 31627280 }} While generalized seizures in horses are fairly easy to diagnose, it may be more difficult in non-generalized seizures and [[EEG]]s may be useful.{{cite journal | vauthors = van der Ree M, Wijnberg I | title = A review on epilepsy in the horse and the potential of Ambulatory EEG as a diagnostic tool | journal = The Veterinary Quarterly | volume = 32 | issue = 3–4 | pages = 159–167 | date = 2012 | pmid = 23163553 | doi = 10.1080/01652176.2012.744496 | s2cid = 24726314 | doi-access = free }} [387] => [388] => == References == [389] => {{Reflist}} [390] => [391] => == Further reading == [392] => {{Refbegin}} [393] => * {{cite journal | vauthors = Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM | title = ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology | journal = Epilepsia | volume = 58 | issue = 4 | pages = 512–521 | date = April 2017 | pmid = 28276062 | pmc = 5386840 | doi = 10.1111/epi.13709 }} [394] => * {{cite book|title=Atlas, epilepsy care in the world, 2005|year=2005|publisher=Department of Mental Health and Substance Abuse, World Health Organization|location=Geneva|isbn=978-92-4-156303-1|url=https://www.who.int/publications/i/item/9241563036 |author=Programme for Neurological Diseases and Neuroscience |others=Global Campaign against Epilepsy; International League against Epilepsy}} [395] => {{Refend}} [396] => [397] => == External links == [398] => {{Commons category|Epilepsy}} [399] => {{Wikiquote}} [400] => * {{cite web|title=Epilepsy Basics: An Overview for Behavioral Health Providers|date=30 May 2019|publisher=Epilepsy Foundation|website=YouTube|url=https://www.youtube.com/watch?v=Aplka9d7N8A| archive-url=https://ghostarchive.org/varchive/youtube/20211211/Aplka9d7N8A| archive-date=11 December 2021 | url-status=live}}{{cbignore}} [401] => * {{cite web|title=What To Do If Someone Has A Seizure – First Aid Training – St John Ambulance|date=1 February 2017|publisher=St John Ambulance|website=YouTube|url=https://www.youtube.com/watch?v=Ovsw7tdneqE| archive-url=https://ghostarchive.org/varchive/youtube/20211211/Ovsw7tdneqE| archive-date=11 December 2021 | url-status=live}}{{cbignore}} [402] => * {{curlie|Health/Conditions_and_Diseases/Neurological_Disorders/Epilepsy/}} [403] => * [https://www.who.int/mediacentre/factsheets/fs999/en/ World Health Organization fact sheet] [404] => {{Medical resources [405] => | ICD11 = {{ICD11|8A60}}, {{ICD11|8A61}}, {{ICD11|8A62}}, {{ICD11|8A66}}, {{ICD11|8A6Y}}, {{ICD11|8A6Z}} [406] => | ICD10 = {{ICD10|G40}}, {{ICD10|G41}} [407] => | ICD9 = {{ICD9|345}} [408] => | MedlinePlus = 000694 [409] => | eMedicineSubj = neuro [410] => | eMedicineTopic = 415 [411] => | DiseasesDB = 4366 [412] => | MeshID = D004827 [413] => }} [414] => [415] => {{Diseases of the nervous system}} [416] => {{Seizures and epilepsy}} [417] => {{Authority control}} [418] => [419] => {{Good article}} [420] => [421] => [[Category:Epilepsy| ]] [422] => [[Category:Articles containing video clips]] [423] => [[Category:Disorders causing seizures]] [424] => [[Category:Neurological disorders in children]] [425] => [[Category:Wikipedia medicine articles ready to translate (full)]] [426] => [[Category:Wikipedia neurology articles ready to translate]] [] => )
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Epilepsy

Epilepsy is a neurological disorder characterized by recurrent and unpredictable seizures. It affects approximately 50 million people worldwide, making it one of the most common neurological conditions.

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It affects approximately 50 million people worldwide, making it one of the most common neurological conditions. The condition can start at any age and has various causes, including genetics, brain injury, tumors, and infections. Seizures in epilepsy can manifest in different ways, such as convulsions, loss of consciousness, altered senses, or repetitive movements. The duration and severity of seizures vary and can have a significant impact on the individual's daily life. Additionally, people with epilepsy may experience other health problems, including mood disorders, learning difficulties, and memory impairment. Diagnosis of epilepsy involves a thorough medical history, physical examination, and various tests to determine the underlying cause and type of seizures. Treatment options include medication, surgery, and dietary modifications. Anti-epileptic drugs are typically the first-line treatment and are effective in controlling seizures in the majority of cases. Living with epilepsy often requires lifestyle adjustments and precautions to minimize seizure triggers and ensure safety during episodes. Supportive care, education, and awareness about epilepsy are essential to help individuals with the condition lead fulfilling lives and reduce stigma and discrimination associated with the disorder. Research on epilepsy focuses on better understanding its causes, developing new treatments, and improving seizure prediction and prevention. The Epilepsy Foundation, a prominent organization, aims to advance research and support individuals with epilepsy through advocacy and education. Epilepsy has been studied throughout history, with early mentions dating back to ancient texts. Despite progress in understanding and managing the condition, epilepsy remains a significant health concern, and efforts are ongoing to improve its diagnosis, treatment, and overall impact on affected individuals.

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