:Epilepsy
{{Short description|Group of neurological disorders causing seizures}}
{{Redirect2|Epilepsia|Epileptic|the journal|Epilepsia (journal)|the comics|Epileptic (comics)}}
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{{Use dmy dates|date=February 2023}}
{{Infobox medical condition (new)
| name = Epilepsy
| synonyms = Seizure disorder
Neurological disability
| image = Spike-waves.png
| alt = The electroencephalogram recording of a person with childhood absence epilepsy showing a seizure. The waves are black on a white background.
| caption = Generalized 3 Hz spike-and-wave discharges on an electroencephalogram
| field = Neurology
| symptoms = Periods of loss of consciousness, abnormal shaking, staring, change in vision, mood changes and/or other cognitive disturbances
| complications =
| onset =
| causes = Unknown, brain injury, stroke, brain tumors, infections of the brain, birth defects
| risks =
| diagnosis = Electroencephalogram, ruling out other possible causes
| differential = Fainting, alcohol withdrawal, electrolyte problems
| prevention =
| treatment = Medication, surgery, neurostimulation, dietary changes
| medication =
| prognosis = Controllable in 69%
| frequency = 51.7 million/0.68% (2021)
}}
Epilepsy is a group of non-communicable neurological disorders characterized by a tendency for recurrent, unprovoked seizures.{{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 | doi-access = free }} A seizure is a sudden burst of abnormal electrical activity in the brain that can cause a variety of symptoms, ranging from brief lapses of awareness or muscle jerks to prolonged convulsions.{{cite web |date=February 2016 |title=Epilepsy Fact sheet |url=https://www.who.int/mediacentre/factsheets/fs999/en/ |url-status=live |archive-url=https://web.archive.org/web/20160311001129/http://www.who.int/mediacentre/factsheets/fs999/en/ |archive-date=11 March 2016 |access-date=4 March 2016 |website=WHO}} These episodes can result in physical injuries, either directly, such as broken bones, or through causing accidents. The diagnosis of epilepsy typically requires at least two unprovoked seizures occurring more than 24 hours apart.{{cite web |title=Epilepsy |url=https://www.who.int/en/news-room/fact-sheets/detail/epilepsy |access-date=1 April 2023 |website=World Health Organization |language=en}} In some cases, however, it may be diagnosed after a single unprovoked seizure if clinical evidence suggests a high risk of recurrence. Isolated seizures that occur without recurrence risk or are provoked by identifiable causes are not considered indicative of epilepsy.{{cite journal |vauthors=Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J |date=April 2005 |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 |doi=10.1111/j.0013-9580.2005.66104.x |pmid=15816939 |doi-access=free}}
The underlying cause is often unknown, but epilepsy can result from brain injury, stroke, infections, tumors, genetic conditions, or developmental abnormalities.{{cite journal |vauthors=Pandolfo M |date=November 2011 |title=Genetics of epilepsy |journal=Seminars in Neurology |volume=31 |issue=5 |pages=506–518 |doi=10.1055/s-0031-1299789 |pmid=22266888}}{{cite book |title=Pathophysiology of disease: an introduction to clinical medicine |publisher=McGraw-Hill Medical |year=2010 |isbn=978-0-07-162167-0 |veditors=Hammer GD, McPhee SJ |edition=6th |location=New York |chapter=7}}{{cite journal |vauthors=Goldberg EM, Coulter DA |date=May 2013 |title=Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction |journal=Nature Reviews. Neuroscience |volume=14 |issue=5 |pages=337–349 |doi=10.1038/nrn3482 |pmc=3982383 |pmid=23595016}} Epilepsy that occurs as a result of other issues may be preventable. Diagnosis involves ruling out other conditions that can resemble seizures, and may include neuroimaging, blood tests, and electroencephalography (EEG).{{cite book |title=Harrison's principles of internal medicine |vauthors=Longo DL |publisher=McGraw-Hill |year=2012 |isbn=978-0-07-174887-2 |edition=18th |page=3258 |chapter=369 Seizures and Epilepsy}}
Most cases of epilepsy — approximately 69% — can be effectively controlled with anti-seizure medications,{{cite journal |vauthors=Eadie MJ |date=December 2012 |title=Shortcomings in the current treatment of epilepsy |journal=Expert Review of Neurotherapeutics |volume=12 |issue=12 |pages=1419–1427 |doi=10.1586/ern.12.129 |pmid=23237349}} and inexpensive treatment options are widely available. For those whose seizures do not respond to drugs, other approaches such as surgery, neurostimulation or dietary changes may be considered.{{cite journal |vauthors=Bergey GK |date=June 2013 |title=Neurostimulation in the treatment of epilepsy |journal=Experimental Neurology |volume=244 |pages=87–95 |doi=10.1016/j.expneurol.2013.04.004 |pmid=23583414}}{{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.
{{as of|2021}}, approximately 51 million people worldwide have epilepsy, with nearly 80% of cases occurring in low- and middle-income countries. The burden of epilepsy in low-income countries is more than twice that in high-income countries, likely due to higher exposure to risk factors such as perinatal injury, infections, and traumatic brain injury, combined with limited access to healthcare.{{cite journal |vauthors=Newton CR, Garcia HH |date=September 2012 |title=Epilepsy in poor regions of the world |url=http://elartu.tntu.edu.ua/handle/lib/29589 |journal=Lancet |volume=380 |issue=9848 |pages=1193–1201 |doi=10.1016/S0140-6736(12)61381-6 |pmid=23021288}} In 2021, epilepsy was responsible for an estimated 140,000 deaths, an increase from 125,000 in 1990.{{cite journal | vauthors=Sinmetz JD, Seeher KM, Schiess N, Nichols E, Cao B, Servili C, et al | journal=The Lancet Neurology | title=Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 | volume=23 | issue=4 | pages=344–381 | publisher=Elsevier | date=1 April 2024 | doi=10.1016/S1474-4422(24)00038-3| pmid=38493795 | pmc=10949203 | hdl=1959.4/102176 | hdl-access=free }}
Epilepsy is more common in both children and older adults.{{cite journal |vauthors=Brodie MJ, Elder AT, Kwan P |date=November 2009 |title=Epilepsy in later life |journal=The Lancet. Neurology |volume=8 |issue=11 |pages=1019–1030 |doi=10.1016/S1474-4422(09)70240-6 |pmid=19800848}}{{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 }} 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 report |title=Epilepsy: what are the chances of having a second seizure? |date=16 August 2023 |doi=10.3310/nihrevidence_59456 }}
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.{{cite web |date=October 2012 |title=Epilepsy |url=https://www.who.int/mediacentre/factsheets/fs999/en/ |access-date=24 January 2013 |series=Fact Sheets |publisher=World Health Organization}} In many countries, people with epilepsy face driving restrictions and must be seizure-free for a set period before regaining eligibility to drive.{{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 }} 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 }}
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Signs and symptoms
File:Attaque; Periode Epileptoide. Planche XVII. Wellcome L0074938.jpg
Epilepsy is characterized by a long-term tendency to experience recurrent, unprovoked seizures.{{cite journal |vauthors=Duncan JS, Sander JW, Sisodiya SM, Walker MC |date=April 2006 |title=Adult epilepsy |journal=Lancet |volume=367 |issue=9516 |pages=1087–1100 |doi=10.1016/S0140-6736(06)68477-8 |pmid=16581409}} They may vary widely in their presentation depending on the affected brain regions, age of onset, and type of epilepsy.{{cite book |author=National Clinical Guideline Centre |url=http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |title=The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care |date=January 2012 |publisher=National Institute for Health and Clinical Excellence |pages=21–28 |archive-url=https://web.archive.org/web/20131216151008/http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |archive-date=16 December 2013 |url-status=live}}
=Seizures=
{{Main|Epileptic seizure}}
According to the 2025 classification by the International League Against Epilepsy (ILAE), seizures are grouped into four main classes: focal, generalized, unknown (whether focal or generalized), and unclassified.{{Cite journal |last1=Beniczky |first1=Sándor |last2=Trinka |first2=Eugen |last3=Wirrell |first3=Elaine |last4=Abdulla |first4=Fatema |last5=Al Baradie |first5=Raidah |last6=Alonso Vanegas |first6=Mario |last7=Auvin |first7=Stéphane |last8=Singh |first8=Mamta Bhushan |last9=Blumenfeld |first9=Hal |last10=Bogacz Fressola |first10=Alicia |last11=Caraballo |first11=Roberto |last12=Carreno |first12=Mar |last13=Cendes |first13=Fernando |last14=Charway |first14=Augustina |last15=Cook |first15=Mark |date=2025-04-23 |title=Updated classification of epileptic seizures: Position paper of the International League Against Epilepsy |url=https://onlinelibrary.wiley.com/doi/10.1111/epi.18338 |journal=Epilepsia |language=en |doi=10.1111/epi.18338 |pmid=40264351 |issn=0013-9580|doi-access=free }}
== Focal seizures ==
Focal seizures originate in one hemisphere of the brain and may involve localized or distributed networks.{{Cite journal |last1=Berg |first1=Anne T. |last2=Berkovic |first2=Samuel F. |last3=Brodie |first3=Martin J. |last4=Buchhalter |first4=Jeffrey |last5=Cross |first5=J. Helen |last6=Van Emde Boas |first6=Walter |last7=Engel |first7=Jerome |last8=French |first8=Jacqueline |last9=Glauser |first9=Tracy A. |last10=Mathern |first10=Gary W. |last11=Moshé |first11=Solomon L. |last12=Nordli |first12=Douglas |last13=Plouin |first13=Perrine |last14=Scheffer |first14=Ingrid E. |date=2010 |title=Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009 |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2010.02522.x |journal=Epilepsia |language=en |volume=51 |issue=4 |pages=676–685 |doi=10.1111/j.1528-1167.2010.02522.x |pmid=20196795 |issn=1528-1167}} For a given seizure type, the site of onset tends to be consistent across episodes. Once initiated, the seizure may remain localized or spread to adjacent areas, and in some cases, may propagate to the opposite hemisphere (contralateral spread).
They are further classified based on the state of consciousness during the episode:
- Focal preserved consciousness seizure: the person remains aware and responsive.
- Focal impaired consciousness seizure: awareness and/or responsiveness are affected.
Certain experiences, known as auras often precede focal seizures.{{cite web |title=Seizures and Status Epilepticus: Diagnosis and Management in the Emergency Department |url=http://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=77 |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 |work=Emergency Medicine Practice |vauthors=Shearer P}} 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 |title=Bradley's neurology in clinical practice. |vauthors=Bradley WG |publisher=Elsevier/Saunders |year=2012 |isbn=978-1-4377-0434-1 |edition=6th |location=Philadelphia, PA |chapter=67}}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. Some focal seizures can evolve into focal-to-bilateral tonic-clonic seizures, where abnormal brain activity spreads to both hemispheres.
== Generalized seizures ==
Generalized seizures originate at a single point within the brain and quickly spread to involve networks across both hemispheres. Although the spread is rapid, the onset may appear asymmetric in some cases. These seizures typically impair consciousness from the outset and can take several forms, including:
- Generalized tonic–clonic seizures, often with an initial tonic phase followed by clonic jerking;
- Absence seizures, which may present with eye blinking or automatisms;
- Other generalized seizures, a category that includes tonic, clonic, myoclonic, atonic seizures and epileptic spasms.{{cite book |author=National Clinical Guideline Centre |url=http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |title=The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care |date=January 2012 |publisher=National Institute for Health and Clinical Excellence |pages=119–129 |archive-url=https://web.archive.org/web/20131216151008/http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |archive-date=16 December 2013 |url-status=live}}
Tonic–clonic seizures are among the most recognizable seizure types, typically involving sudden loss of consciousness, stiffening (tonic phase), and rhythmic jerking (clonic phase) of the limbs.{{cite book |url=https://books.google.com/books?id=6Kq4Zt2KOpcC&pg=PA2797 |title=Epilepsy: a comprehensive textbook |vauthors=Engel J |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |year=2008 |isbn=978-0-7817-5777-5 |edition=2nd |location=Philadelphia |page=2797 |archive-url=https://web.archive.org/web/20160520033255/https://books.google.com/books?id=6Kq4Zt2KOpcC&pg=PA2797 |archive-date=20 May 2016 |url-status=live}} This form of seizure — whether focal to bilateral, generalized, or of unknown onset — is given particular emphasis due to their clinical severity; they are associated with the highest risk of injury, medical complications, and sudden unexpected death in epilepsy (SUDEP).
Myoclonic seizures involve sudden, brief muscle jerks, which may affect specific muscle groups or the whole body.{{cite book |title=Clinical neurology |vauthors=Simon DA, Greenberg MJ, Aminoff RP |publisher=McGraw-Hill Medical |year=2012 |isbn=978-0-07-175905-2 |edition=8th |location=New York |chapter=12}}{{Cite book |url=https://www.worldcat.org/oclc/25711319 |title=Fits and faints |vauthors=Stephenson JB |date=1990 |publisher=Mac Keith Press |isbn=0-632-02811-4 |location=London |oclc=25711319}} They can cause falls and injury. Absence seizures are characterized by brief lapses in awareness, sometimes accompanied by subtle movements such as blinking or slight head turning. The person typically recovers immediately afterward without confusion. Atonic seizures involve a sudden loss of muscle tone, often resulting in falls.
== Triggers and reflex seizures ==
Certain external or internal factors may increase the likelihood of a seizure in individuals with epilepsy. These triggers do not cause epilepsy but can lower the seizure threshold in people who are already susceptible. Common triggers include sleep deprivation, stress, fever, illness, menstruation, alcohol, and certain medications. These do not cause seizures by themselves, but lower the threshold in people who are already susceptible.
A small subset of individuals have reflex epilepsy, in which seizures are reliably provoked by specific stimuli. These reflex seizures account for about 6% of epilepsy cases.{{cite journal |vauthors=Xue LY, Ritaccio AL |date=March 2006 |title=Reflex seizures and reflex epilepsy |journal=American Journal of Electroneurodiagnostic Technology |volume=46 |issue=1 |pages=39–48 |doi=10.1080/1086508X.2006.11079556 |pmid=16605171}}{{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 }} Common triggers include flashing lights (photosensitive epilepsy), sudden sounds, or specific cognitive tasks such as reading or performing calculations. In some epilepsy syndromes, seizures occur more frequently during sleep or upon awakening.{{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 }}{{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 }}
== Seizure clusters ==
Seizure clusters refer to multiple seizures occurring over a short period of time, with incomplete recovery between events. They are distinct from status epilepticus, though the two may overlap. Definitions vary across studies, but seizure clusters are typically described as two or more seizures within 24 hours or a noticeable increase in seizure frequency over a person’s usual baseline. Estimates of their prevalence range widely — from 5% to 50% of people with epilepsy — largely due to differing definitions and populations studied.{{cite journal |vauthors=Jafarpour S, Hirsch LJ, Gaínza-Lein M, Kellinghaus C, Detyniecki K |date=May 2019 |title=Seizure cluster: Definition, prevalence, consequences, and management |journal=Seizure |volume=68 |pages=9–15 |doi=10.1016/j.seizure.2018.05.013 |pmid=29871784 |doi-access=free}}{{cite journal |vauthors=Faught E |date=September 2022 |title=Economic aspects of treating seizure clusters |journal=Epilepsia |volume=63 |issue=Suppl 1 |pages=S45–S54 |doi=10.1111/epi.17340 |pmid=35999172}} Seizure clusters are more common in individuals with drug-resistant epilepsy, high baseline seizure frequency, or certain epilepsy syndromes.{{cite journal |vauthors=Haut SR, Shinnar S, Moshé SL |date=January 2005 |title=Seizure clustering: risks and outcomes |journal=Epilepsia |volume=46 |issue=1 |pages=146–149 |doi=10.1111/j.0013-9580.2005.29004.x |pmid=15660781 |doi-access=free}} They are associated with increased emergency care utilization, worse quality of life, impaired psychosocial functioning, and possibly elevated risk of mortality.{{cite journal |vauthors=Chung S, Szaflarski JP, Choi EJ, Wilson JC, Kharawala S, Kaur G, Hirsch LJ |date=November 2021 |title=A systematic review of seizure clusters: Prevalence, risk factors, burden of disease and treatment patterns |journal=Epilepsy Research |volume=177 |pages=106748 |doi=10.1016/j.eplepsyres.2021.106748 |pmid=34521043}}
=Postictal state=
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 state, before a normal level of consciousness returns, lasting minutes to days.{{Cite journal |last1=Pottkämper |first1=Julia C. M. |last2=Hofmeijer |first2=Jeannette |last3=van Waarde |first3=Jeroen A. |last4=van Putten |first4=Michel J. A. M. |year=2020 |title=The postictal state-What do we know? |journal=Epilepsia |volume=61 |issue=6 |pages=1045–1061 |doi=10.1111/epi.16519 |issn=1528-1167 |pmc=7317965 |pmid=32396219}}{{cite book |url=https://books.google.com/books?id=yJQQzPTcbYIC&pg=PA445 |title=A clinical guide to epileptic syndromes and their treatment based on the ILAE classifications and practice parameter guidelines |vauthors=Panayiotopoulos CP |publisher=Springer |year=2010 |isbn=978-1-84628-644-5 |edition=Rev. 2nd |location=London |page=445}} This period is marked by confusion, headache, fatigue, or speech and motor disturbances. Some may experience Todd's paralysis, a transient focal weakness.{{cite book |url=https://books.google.com/books?id=mY-6eweiQm8C&pg=PA348 |title=A dictionary of neurological signs |vauthors=Larner AJ |publisher=Springer |year=2010 |isbn=978-1-4419-7095-4 |edition=3rd |location=New York |page=348}} Postictal psychosis occurs in approximately 2% of individuals with epilepsy, particularly after clusters of generalized tonic–clonic seizures.{{Cite journal |last1=Clancy |first1=Maurice J. |last2=Clarke |first2=Mary C. |last3=Connor |first3=Dearbhla J. |last4=Cannon |first4=Mary |last5=Cotter |first5=David R. |date=2014-03-13 |title=The prevalence of psychosis in epilepsy; a systematic review and meta-analysis |journal=BMC Psychiatry |language=en |volume=14 |issue=1 |pages=75 |doi=10.1186/1471-244X-14-75 |doi-access=free |issn=1471-244X |pmc=3995617 |pmid=24625201}}{{cite book |url=https://books.google.com/books?id=yJQQzPTcbYIC&pg=PA445 |title=A clinical guide to epileptic syndromes and their treatment based on the ILAE classifications and practice parameter guidelines |vauthors=Panayiotopoulos CP |publisher=Springer |year=2010 |isbn=978-1-84628-644-5 |edition=Rev. 2nd |location=London |page=445}}
=Psychosocial=
Epilepsy can have substantial effects on psychological and social well-being. People with the condition may experience social isolation, stigma, or functional disability, which can contribute to lower educational attainment and reduced employment opportunities. These challenges often extend to family members, who may also encounter stigma and increased caregiving burden.
Several psychiatric and neurodevelopmental disorders are more common in individuals with epilepsy. These include depression, anxiety, obsessive–compulsive disorder (OCD),{{cite journal |vauthors=Kaplan PW |date=November 2011 |title=Obsessive-compulsive disorder in chronic epilepsy |journal=Epilepsy & Behavior |volume=22 |issue=3 |pages=428–432 |doi=10.1016/j.yebeh.2011.07.029 |pmid=21889913}} and migraine.{{cite book |url=https://books.google.com/books?id=K-1UqhH2BtoC&pg=PA471 |title=Epilepsy Part I: Basic Principles and Diagnosis E-Book: Handbook of Clinical Neurology |vauthors=Stefan H |publisher=Newnes |year=2012 |isbn=978-0-444-53505-4 |edition=Volume 107 of Handbook of Clinical Neurology |page=471}} Attention deficit hyperactivity disorder (ADHD) is particularly prevalent among children with epilepsy, occurring three to five times more often than in the general population. ADHD and epilepsy together can markedly affect behavior, learning, and social development.{{cite journal |vauthors=Reilly CJ |date=May–June 2011 |title=Attention deficit hyperactivity disorder (ADHD) in childhood epilepsy |journal=Research in Developmental Disabilities |volume=32 |issue=3 |pages=883–893 |doi=10.1016/j.ridd.2011.01.019 |pmid=21310586}} Epilepsy is also more common in children with autism spectrum disorder.{{cite journal |vauthors=Levisohn PM |year=2007 |title=The autism-epilepsy connection |journal=Epilepsia |volume=48 |issue=Suppl 9 |pages=33–35 |doi=10.1111/j.1528-1167.2007.01399.x |pmid=18047599 |doi-access=free}}
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 }} This association is thought to reflect a combination of shared neurobiological mechanisms and the psychosocial impact of living with a chronic neurological condition.{{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 }} Some research also suggests that psychiatric conditions such as depression may precede the onset of epilepsy in certain individuals, particularly those with focal epilepsy. However, the nature of this association remains under investigation and may involve shared pathways, diagnostic overlap, or other confounding factors.{{cite journal |vauthors=Adelöw C, Andersson T, Ahlbom A, Tomson T |date=February 2012 |title=Hospitalization for psychiatric disorders before and after onset of unprovoked seizures/epilepsy |journal=Neurology |volume=78 |issue=6 |pages=396–401 |doi=10.1212/wnl.0b013e318245f461 |pmid=22282649}}
Comorbid depression and anxiety are associated with poorer quality of life,{{cite journal |vauthors=Taylor RS, Sander JW, Taylor RJ, Baker GA |date=December 2011 |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 |doi=10.1111/j.1528-1167.2011.03213.x |pmid=21883177 |doi-access=free}} increased healthcare utilization, reduced treatment response (including to surgery), and higher mortality.{{cite journal |vauthors=Lacey CJ, Salzberg MR, Roberts H, Trauer T, D'Souza WJ |date=August 2009 |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 |doi=10.1111/j.1528-1167.2009.02165.x |pmid=19490049 |doi-access=free}} Some studies suggest that these psychiatric conditions may influence quality of life more than seizure type or frequency.{{cite journal |vauthors=Boylan LS, Flint LA, Labovitz DL, Jackson SC, Starner K, Devinsky O |date=January 2004 |title=Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy |journal=Neurology |volume=62 |issue=2 |pages=258–261 |doi=10.1212/01.wnl.0000103282.62353.85 |pmid=14745064}} Despite their clinical importance, depression and anxiety often go underdiagnosed and undertreated in people 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 |date=March 2020 |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 |doi=10.1016/j.yebeh.2020.106907 |pmc=7282472 |pmid=32000099}}
Causes
{{See also|Causes of seizures}}
Epilepsy can result from a wide range of genetic and acquired factors, and in many cases, both play a role.{{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 | doi-access = free | hdl = 2158/1262349 | hdl-access = free }} Acquired causes include serious traumatic brain injury, stroke, brain tumors, and central nervous system infections.{{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 }} Despite advances in diagnostic tools, no clear cause is identified in approximately 60% of cases. The distribution of causes often varies with age. Epilepsies associated with genetic, congenital, or developmental conditions are more common in children, while epilepsy related to stroke or tumors is more frequently seen in older adults.
Seizures may also occur as a direct response to acute health conditions such as stroke, head trauma, metabolic disturbances, or toxic exposures.{{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 |date=September 2011 |title=Standards for epidemiologic studies and surveillance of epilepsy |journal=Epilepsia |volume=52 |issue=Suppl 7 |pages=2–26 |doi=10.1111/j.1528-1167.2011.03121.x |pmid=21899536 |doi-access=free}} These are known as acute symptomatic seizures and are distinct from epilepsy, which involves a recurrent tendency to have unprovoked seizures over time.{{cite book |title=Epilepsy |vauthors=Neligan A, Hauser WA, Sander JW |year=2012 |isbn=978-0-444-52898-8 |series=Handbook of Clinical Neurology |volume=107 |pages=113–33 |chapter=The epidemiology of the epilepsies |doi=10.1016/B978-0-444-52898-8.00006-9 |pmid=22938966}}{{cite book |author=National Clinical Guideline Centre |url=http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |title=The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care |date=January 2012 |publisher=National Institute for Health and Clinical Excellence |pages=119–129 |archive-url=https://web.archive.org/web/20131216151008/http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |archive-date=16 December 2013 |url-status=live}}
The International League Against Epilepsy (ILAE) classifies the causes of epilepsy into six broad categories: structural, genetic, infectious, metabolic, immune, and unknown. These categories are not mutually exclusive, and more than one may apply in an individual case.{{Cite journal |last1=Scheffer |first1=Ingrid E. |last2=Berkovic |first2=Samuel |last3=Capovilla |first3=Giuseppe |last4=Connolly |first4=Mary B. |last5=French |first5=Jacqueline |last6=Guilhoto |first6=Laura |last7=Hirsch |first7=Edouard |last8=Jain |first8=Satish |last9=Mathern |first9=Gary W. |last10=Moshé |first10=Solomon L. |last11=Nordli |first11=Douglas R. |last12=Perucca |first12=Emilio |last13=Tomson |first13=Torbjörn |last14=Wiebe |first14=Samuel |last15=Zhang |first15=Yue-Hua |date=2017 |title=ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology |journal=Epilepsia |language=en |volume=58 |issue=4 |pages=512–521 |doi=10.1111/epi.13709 |issn=0013-9580 |pmc=5386840 |pmid=28276062}}
= Structural =
Structural causes of epilepsy refer to abnormalities in the anatomy of the brain that increase the risk of seizures. These may be acquired — such as from a stroke, traumatic brain injury, brain tumor, or central nervous system infection — or developmental and genetic in origin, as seen in conditions like focal cortical dysplasia or certain congenital brain malformations. A major example is mesial temporal sclerosis (MTS), a common cause of temporal lobe epilepsy.{{Cite journal |last=Thom |first=Maria |date=2014 |title=Review: Hippocampal sclerosis in epilepsy: a neuropathology review |journal=Neuropathology and Applied Neurobiology |language=en |volume=40 |issue=5 |pages=520–543 |doi=10.1111/nan.12150 |issn=1365-2990 |pmc=4265206 |pmid=24762203}}
Traumatic brain injury is estimated to cause between 6% and 20% of epilepsy cases, depending on severity, mechanism, and study population. 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%.{{cite journal |vauthors=Bhalla D, Godet B, Druet-Cabanac M, Preux PM |date=June 2011 |title=Etiologies of epilepsy: a comprehensive review |journal=Expert Review of Neurotherapeutics |volume=11 |issue=6 |pages=861–876 |doi=10.1586/ern.11.51 |pmid=21651333}} Stroke is a major cause of epilepsy, particularly in older adults.{{cite journal |vauthors=Zelano J, Holtkamp M, Agarwal N, Lattanzi S, Trinka E, Brigo F |date=June 2020 |title=How to diagnose and treat post-stroke seizures and epilepsy |journal=Epileptic Disorders |volume=22 |issue=3 |pages=252–263 |doi=10.1684/epd.2020.1159 |pmid=32597766 |doi-access=free}} Approximately 6% to 10% of individuals who experience a stroke develop epilepsy, most often within the first few years after the event. The risk is highest following severe strokes that involve cortical regions, especially in cases of intracerebral hemorrhage.{{cite journal |vauthors=Zöllner JP, Schmitt FC, Rosenow F, Kohlhase K, Seiler A, Strzelczyk A, Stefan H |date=December 2021 |title=Seizures and epilepsy in patients with ischaemic stroke |journal=Neurological Research and Practice |volume=3 |issue=1 |pages=63 |doi=10.1186/s42466-021-00161-w |pmc=8647498 |pmid=34865660 |doi-access=free}} Brain tumors are implicated in approximately 4% of epilepsy cases, with seizures occurring in nearly 30% of individuals with intracranial neoplasms.
In clinical practice, a structural cause is typically identified through neuroimaging (such as MRI), which reveals an abnormality that plausibly accounts for the individual's seizure semiology and EEG findings. The lesion must be epileptogenic, meaning that it is capable of generating seizures. Infections like encephalitis or brain abscess may lead to permanent structural damage, increasing the risk of epilepsy even after the infection resolves.
Structural damage can also result from perinatal brain injury, such as hypoxic-ischemic encephalopathy, especially in low- and middle-income countries where access to prenatal and neonatal care may be limited. When seizures are linked to a clearly defined structural lesion, epilepsy surgery may be considered — particularly in individuals whose seizures do not respond to medication.
=Genetics=
Genetic causes of epilepsy are those in which a person’s genes directly contribute to the development of seizures. This includes cases where a specific mutation has been identified, as well as situations where the family history and clinical features strongly suggest a genetic basis, even if no known mutation is found. In the updated classification by the ILAE, the term genetic replaces the older term idiopathic, to highlight that these epilepsies arise from inherited or spontaneous changes in a person’s biology — not from injury or infection.
Genetic factors are believed to contribute to many cases of epilepsy, either directly or by increasing vulnerability to other causes.{{cite journal |vauthors=Steinlein OK |date=2008-03-31 |title=Genetics and epilepsy |journal=Dialogues in Clinical Neuroscience |volume=10 |issue=1 |pages=29–38 |doi=10.31887/DCNS.2008.10.1/oksteinlein |pmc=3181863 |pmid=18472482}} Some forms are caused by a single gene defect, which account for around 1–2% of cases. However, most are due to a combination of multiple genes and environmental influences. Many of the genes known to play a role in epilepsy affect how brain cells send electrical signals, especially those involved in ion channels, receptors, or signaling proteins.
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 |date=August 2012 |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 |doi=10.1016/j.ajhg.2012.06.016 |pmc=3415540 |pmid=22863189}} 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 |date=July 2013 |title=Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 |journal=Nature Genetics |volume=45 |issue=7 |pages=825–830 |doi=10.1038/ng.2646 |pmc=3704157 |pmid=23708187}}{{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 |year=2014 |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 |doi=10.1186/1866-1955-6-9 |pmc=4022362 |pmid=24834135 |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 |date=November 2013 |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 |doi=10.1016/j.ajhg.2013.09.017 |pmc=3824114 |pmid=24207121}} and DNM1, GABBR2, FASN and RYR3.{{cite journal |vauthors=((EuroEPINOMICS-RES Consortium)) |date=October 2014 |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 |doi=10.1016/j.ajhg.2014.08.013 |pmc=4185114 |pmid=25262651}}
Some genetic disorders, including phakomatoses such as tuberous sclerosis complex and Sturge–Weber syndrome, are strongly associated with epilepsy.{{cite journal |vauthors=Stafstrom CE, Staedtke V, Comi AM |date=2017 |title=Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge-Weber Syndrome |journal=Frontiers in Neurology |volume=8 |pages=87 |doi=10.3389/fneur.2017.00087 |pmc=5355446 |pmid=28367137 |doi-access=free}} These conditions are often discussed separately due to their multisystem involvement and high epilepsy burden.
= Infectious =
Infectious causes include infections of the central nervous system that directly affect brain tissue and lead to long-term seizure susceptibility. Examples include herpes simplex encephalitis, which carries a high risk of developing epilepsy, and neurocysticercosis, a major preventable cause of epilepsy in endemic regions. Other infections such as cerebral malaria, toxoplasmosis, and toxocariasis. Some infections cause seizures during the acute illness, but only a subset result in chronic epilepsy.
=Immune=
Immune causes include conditions like autoimmune encephalitis, in which the immune system attacks brain tissue, often presenting with seizures. Certain autoimmune epilepsies are associated with specific autoantibodies, including those against the NMDA receptor, LGI1, and CASPR2. These cases often present with rapid-onset, difficult-to-treat seizures.
Celiac disease has also been associated with epilepsy in rare syndromic forms, such as the triad of epilepsy, cerebral calcifications, and celiac disease.{{cite journal |vauthors=Jackson JR, Eaton WW, Cascella NG, Fasano A, Kelly DL |date=March 2012 |title=Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity |journal=The Psychiatric Quarterly |volume=83 |issue=1 |pages=91–102 |doi=10.1007/s11126-011-9186-y |pmc=3641836 |pmid=21877216}}{{cite journal |vauthors=Grossman G |date=April 2008 |title=Neurological complications of coeliac disease: what is the evidence? |journal=Practical Neurology |volume=8 |issue=2 |pages=77–89 |doi=10.1136/jnnp.2007.139717 |pmid=18344378}}
= Metabolic =
Metabolic causes of epilepsy include metabolic disorders that disrupt the brain’s normal function. In rare cases, epilepsy may result from inborn errors of metabolism, such as mitochondrial diseases, urea cycle disorders, or glucose transporter type 1 (GLUT1) deficiency. These often present early in life and may be associated with developmental delays, movement disorders, or other neurological symptoms.
Seizures can also occur in the context of acquired metabolic disturbances, such as hypoglycemia, hyponatremia, or hypocalcemia. These seizures are often considered acute symptomatic seizures, and are not epilepsy.
Some forms of malnutrition, particularly in low- and middle-income countries, have been associated with a higher risk of epilepsy, although it remains unclear whether the relationship is causal or due to other contributing factors.
= Unknown =
Unknown causes of epilepsy refer to cases where no clear structural, genetic, infectious, immune, or metabolic origin can be identified despite thorough evaluation. This category acknowledges the limits of current diagnostic techniques and scientific understanding. A substantial proportion of epilepsy cases still fall into this group, particularly in regions with limited access to advanced testing.
Mechanism
Understanding the mechanism of epilepsy involves two related but distinct questions: how the brain develops a long-term tendency to generate seizures (epileptogenesis), and how individual seizures begin and spread (ictogenesis). While these processes are not yet fully understood, research has identified a number of cellular, molecular, and network-level changes that contribute to each.{{Cite journal |last=Pitkänen |first=Asla |last2=Engel |first2=Jerome |date=2014 |title=Past and present definitions of epileptogenesis and its biomarkers |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC3996117/ |journal=Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics |volume=11 |issue=2 |pages=231–241 |doi=10.1007/s13311-014-0257-2 |issn=1878-7479 |pmc=3996117 |pmid=24492975}}
= Seizures =
In a healthy brain, neurons communicate through electrical signals that are generally desynchronized. This activity is tightly regulated by a balance between excitatory and inhibitory influences. Intracellular factors that influence neuronal excitability include the type, number, and distribution of ion channels, as well as alterations in receptor function and gene expression. Extracellular factors include ionic concentrations in the surrounding environment, synaptic plasticity, and the regulation of neurotransmitter breakdown by glial cells.{{cite journal |vauthors=Blumenfeld H |year=2005 |title=Cellular and network mechanisms of spike-wave seizures |journal=Epilepsia |volume=46 |issue=Suppl.9 |pages=21–33 |doi=10.1111/j.1528-1167.2005.00311.x |pmid=16302873 |doi-access=free}}{{cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK2510/ |title=An Introduction to Epilepsy |vauthors=Bromfield EB |publisher=American Epilepsy Society |year=2006 |chapter=Basic Mechanisms Underlying Seizures and Epilepsy}}
During a seizure, this balance breaks down, leading to a sudden and excessive synchronization of neuronal firing. A localized group of neurons may begin firing together in an abnormal and repetitive pattern, overwhelming normal inhibitory controls. This abnormal activity can remain confined to a specific region of the brain or propagate to other areas. The process by which this transition occurs is known as ictogenesis. It involves a shift in network dynamics, typically beginning with excessive excitatory activity in a susceptible area of cortex — known as a seizure focus — and failure of inhibitory mechanisms to contain it. At the cellular level, ictogenesis is often marked by a paroxysmal depolarizing shift, a characteristic pattern of sustained neuronal depolarization followed by rapid repetitive firing.{{cite book |url=https://books.google.com/books?id=WjSoQVt-taYC&pg=PA167 |title=Ions in the Brain Normal Function, Seizures, and Stroke. |vauthors=Somjen GG |publisher=Oxford University Press |year=2004 |isbn=978-0-19-803459-9 |location=New York |page=167}} As excitatory feedback loops engage and inhibition further declines, the seizure may become self-sustaining and spread to other regions of the brain.{{cite book |url=https://books.google.com/books?id=TwlXrOBkAS8C&pg=PA483 |title=Epilepsy: a comprehensive textbook |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |year=2008 |isbn=978-0-7817-5777-5 |veditors=Engel J, Pedley TA |edition=2nd |location=Philadelphia |page=483}}
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, excessive alcohol use, flickering light, or a lack of sleep, among others. The term seizure threshold is used to indicate the amount of stimulus necessary to bring about a seizure; this threshold is lowered in epilepsy.{{cite journal |vauthors=Le Van Quyen M, Navarro V, Martinerie J, Baulac M, Varela FJ |year=2003 |title=Toward a neurodynamical understanding of ictogenesis |journal=Epilepsia |volume=44 |issue=Suppl.12 |pages=30–43 |doi=10.1111/j.0013-9580.2003.12007.x |pmid=14641559 |doi-access=free}} 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 |date=February 2022 |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 |doi=10.1007/s10827-022-00811-1 |pmc=8818009 |pmid=35031915}} to the whole brain.{{cite journal |vauthors=Depannemaecker D, Destexhe A, Jirsa V, Bernard C |date=August 2021 |title=Modeling seizures: From single neurons to networks |journal=Seizure |volume=90 |pages=4–8 |doi=10.1016/j.seizure.2021.06.015 |pmid=34219016 |doi-access=free}}
= Epilepsy =
While ictogenesis explains how individual seizures arise, it does not account for why the brain develops a persistent tendency to generate them. This longer-term process is known as epileptogenesis — the sequence of biological events that transforms a previously non-epileptic brain into one capable of producing spontaneous seizures. It can occur after a wide range of brain insults, including traumatic brain injury, stroke, central nervous system infections, brain tumors, or prolonged seizures (such as status epilepticus). In most cases, no clear cause is identified. Although not fully understood, it involves a range of biological changes, including neuronal loss, synaptic reorganization, gliosis, neuroinflammation, and disruption of the blood–brain barrier.{{cite book |url=https://books.google.com/books?id=T2_LVTB7ftgC&pg=466 |title=Jasper's Basic Mechanisms of the Epilepsies |vauthors=Noebels JL, Avoli M |date=29 June 2012 |publisher=Oxford University Press |isbn=978-0-19-974654-5 |pages=466, 470 |access-date=16 October 2014}}
Together, these changes contribute to the formation of hyperexcitable neural networks, often anchored around a seizure focus. Once established, this pathological network increases the brain's susceptibility to seizures, even in the absence of ongoing injury. Although many of the processes underlying ictogenesis and epileptogenesis have been identified, the exact mechanisms by which the brain transitions into a seizure or becomes epileptic remain unknown. Research continues to explore how genetic, molecular, and network-level factors interact to produce the diverse manifestations of epilepsy.
Diagnosis
The diagnosis of epilepsy is primarily clinical, based on a thorough evaluation of the person’s history, seizure features, and risk of recurrence. While diagnostic tests such as electroencephalograms and neuroimaging can support the diagnosis, there is no single test that can confirm or exclude epilepsy.
Clinicians must also distinguish epileptic seizures from other conditions that can mimic them and determine whether the event was provoked by an acute, reversible cause or if it suggests a long-term tendency for unprovoked seizures.
=Definition=
According to the International League Against Epilepsy (ILAE), a diagnosis of epilepsy can be made when any one of the following criteria is met:
:
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The ILAE also introduced the concept of resolved epilepsy, which applies to individuals who are past the typical age range for an age-dependent syndrome, or who have remained seizure-free for at least 10 years, including the last 5 years without medication.
TThis 2014 practical definition built upon the broader 2005 conceptual framework, which defined epilepsy as a disorder involving an enduring predisposition to generate epileptic seizures. The updated criteria incorporated recurrence risk and reflected the realities of clinical decision-making. While widely adopted in clinical settings, other definitions—such as the traditional “two unprovoked seizures” rule still used by the World Health Organization — remain appropriate in epidemiology and public health contexts, provided they are clearly stated. The 2014 revision also shifted terminology, referring to epilepsy as a disease rather than a disorder, to reflect its medical seriousness and public health impact.{{cite journal |vauthors=Panayiotopoulos CP |date=December 2011 |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 |doi=10.1111/j.1528-1167.2011.03288.x |pmid=22004554 |doi-access=free}}
=Classification=
File:ILAE classification of seizure types 2017.png
Once epilepsy is diagnosed, the ILAE recommends a three-level framework to guide further classification and management:
- Identify the seizure type, based on clinical features and EEG (e.g., focal aware seizure, generalized absence)
- Determine the epilepsy type, such as focal, generalized, combined, or unknown
- Identify an epilepsy syndrome, if applicable
Not all levels can always be determined; in some cases, only the seizure type is identifiable. The etiology — whether structural, genetic, infectious, metabolic, immune, or unknown — should be considered at each stage of classification, as it often influences treatment and prognosis.{{cite journal |vauthors=Shorvon SD |date=June 2011 |title=The etiologic classification of epilepsy |journal=Epilepsia |volume=52 |issue=6 |pages=1052–1057 |doi=10.1111/j.1528-1167.2011.03041.x |pmid=21449936 |doi-access=free}}
The classification of epilepsies has evolved significantly over time.{{cite journal |vauthors= |year=1989 |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 |doi=10.1111/j.1528-1157.1989.tb05316.x |pmid=2502382}} Earlier systems emphasized seizure location and used terms such as “partial” or “cryptogenic,” which have been replaced in the modern framework.{{cite journal |vauthors=Engel J |date=August 2006 |title=ILAE classification of epilepsy syndromes |journal=Epilepsy Research |volume=70 |issue=Suppl 1 |pages=S5-10 |doi=10.1016/j.eplepsyres.2005.11.014 |pmid=16822650}}{{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 |date=April 2010 |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 |doi=10.1111/j.1528-1167.2010.02522.x |pmid=20196795 |doi-access=free}} The current system, introduced in 2017, reflects advances in neuroimaging, genetics, and clinical understanding, and allows for a more individualized and dynamic diagnostic approach.
=Syndromes=
{{Main|Epilepsy syndromes}}
An epilepsy syndrome is a specific diagnosis based on a combination of features, including seizure types, age of onset, EEG patterns, imaging findings, and associated symptoms or comorbidities. In many cases, a known genetic or structural cause may also support the diagnosis. Recognizing a syndrome can guide treatment decisions, inform prognosis, and provide clarity for individuals and families navigating an epilepsy diagnosis.{{cite web |title=Epilepsy syndromes |url=https://www.epilepsydiagnosis.org/syndrome/epilepsy-syndrome-groupoverview.html |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 |access-date=6 October 2014 |publisher=International league against epilepsy}}{{Cite journal |last1=Wirrell |first1=Elaine C. |last2=Nabbout |first2=Rima |last3=Scheffer |first3=Ingrid E. |last4=Alsaadi |first4=Taoufik |last5=Bogacz |first5=Alicia |last6=French |first6=Jacqueline A. |last7=Hirsch |first7=Edouard |last8=Jain |first8=Satish |last9=Kaneko |first9=Sunao |last10=Riney |first10=Kate |last11=Samia |first11=Pauline |last12=Snead |first12=O. Carter |last13=Somerville |first13=Ernest |last14=Specchio |first14=Nicola |last15=Trinka |first15=Eugen |date=2022 |title=Methodology for classification and definition of epilepsy syndromes with list of syndromes: Report of the ILAE Task Force on Nosology and Definitions |url=https://onlinelibrary.wiley.com/doi/10.1111/epi.17237 |journal=Epilepsia |language=en |volume=63 |issue=6 |pages=1333–1348 |doi=10.1111/epi.17237 |issn=1528-1167}}
Some syndromes are self-limited and age-dependent, such as childhood absence epilepsy, juvenile myoclonic epilepsy, and self-limited epilepsy with centrotemporal spikes. These typically respond well to treatment or remit with age. In contrast, more severe syndromes fall under the category of developmental and epileptic encephalopathies (DEEs).{{Cite journal |last1=Raga |first1=Sharika |last2=Specchio |first2=Nicola |last3=Rheims |first3=Sylvain |last4=Wilmshurst |first4=Jo M. |date=2021-02-01 |title=Developmental and epileptic encephalopathies: recognition and approaches to care |url=https://pubmed.ncbi.nlm.nih.gov/33632673 |journal=Epileptic Disorders: International Epilepsy Journal with Videotape |volume=23 |issue=1 |pages=40–52 |doi=10.1684/epd.2021.1244 |issn=1950-6945 |pmid=33632673|doi-access=free }} These include Lennox–Gastaut syndrome, West syndrome, and Dravet syndrome, which are associated with early onset, drug-resistant seizures, and significant neurodevelopmental impairments.{{cite journal |vauthors=Nordli DR |date=October 2012 |title=Epileptic encephalopathies in infants and children |journal=Journal of Clinical Neurophysiology |volume=29 |issue=5 |pages=420–424 |doi=10.1097/WNP.0b013e31826bd961 |pmid=23027099}}
Some epilepsy syndromes do not yet fit neatly within current etiological categories, particularly when no definitive cause has been identified. In many cases, a genetic cause is presumed based on age of onset, family history, and electroclinical features, even if no mutation has been found. As genetic and neuroimaging technologies continue to evolve, the classification of epilepsy syndromes is expected to become more precise.
=Tests=
File:EEG Recording Cap.jpg can aid in locating the focus of the epileptic seizure.l]]The diagnostic evaluation of epilepsy begins with confirming whether the reported event was in fact a seizure. A detailed clinical history remains essential, supported by eyewitness accounts and, when possible, video recordings. The initial assessment aims to distinguish epileptic seizures from common mimics such as syncope, psychogenic non-epileptic seizures, or transient ischemic attacks.
Following clinical evaluation, selected tests may be used to rule out acute causes and seizure mimics. A 12-lead electrocardiogram (ECG) is recommended for all individuals presenting with a first seizure, to screen for cardiac arrhythmias and other cardiovascular conditions that may resemble epilepsy. Blood tests may be performed to identify metabolic disturbances such as hypoglycemia, electrolyte imbalances, or renal and hepatic dysfunction, particularly in acute settings.{{Cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK581165/ |title=Epilepsies in children, young people and adults |date=2022 |publisher=National Institute for Health and Care Excellence (NICE) |isbn=978-1-4731-4513-9 |series=National Institute for Health and Care Excellence: Guidelines |location=London |pmid=35700280}}
Once epilepsy is suspected, electroencephalography (EEG) is used to support the diagnosis, classify seizure types, and help identify specific epilepsy syndromes. A routine EEG may include activation techniques such as hyperventilation or photic stimulation. However, a normal EEG does not rule out epilepsy. When initial EEG findings are inconclusive, further studies such as sleep-deprived EEG, ambulatory EEG, or long-term video EEG monitoring may be considered.
Neuroimaging, usually with magnetic resonance imaging (MRI), is recommended to detect structural causes of epilepsy. If MRI is contraindicated or unavailable, computed tomography (CT) may be considered. Imaging should be interpreted by radiologists with expertise in epilepsy.
Additional tests may be guided by clinical context. Genetic testing may be considered in individuals with early-onset epilepsy, developmental delay, or features of a known genetic epilepsy syndrome. Testing for neuronal antibodies may be appropriate in suspected cases of autoimmune encephalitis, particularly when seizures are new-onset, rapidly progressive, or resistant to standard treatment. Metabolic testing may be pursued in infants or children with unexplained epilepsy, especially when developmental regression or multisystem involvement is present.
Serum prolactin may occasionally be measured after a suspected seizure, particularly to help distinguish epileptic seizures from non-epileptic events. While it can be elevated following certain seizure types, the test lacks sufficient sensitivity and specificity and is not recommended for routine use.
=Differential diagnosis=
A number of conditions can resemble epileptic seizures, leading to potential misdiagnosis. Accurate diagnosis is essential, as inappropriate treatment may delay effective care or cause harm. Common mimics include fainting (syncope), psychogenic non-epileptic seizures (PNES), transient ischemic attacks, migraine, narcolepsy, and various sleep or movement disorders.{{cite journal |vauthors=Brodtkorb E |year=2013 |title=Common imitators of epilepsy |journal=Acta Neurologica Scandinavica. Supplementum |volume=127 |issue=196 |pages=5–10 |doi=10.1111/ane.12043 |pmid=23190285 |doi-access=free}}{{cite book |url=https://books.google.com/books?id=u7TNcpCeqx8C&pg=PA2228 |title=Rosen's emergency medicine: concepts and clinical practice |publisher=Mosby/Elsevier |year=2010 |isbn=978-0-323-05472-0 |veditors=Marx JA |edition=7th |location=Philadelphia |page=2228}} In children, reflux, breath-holding spells, and parasomnias such as night terrors may also resemble seizures.
Psychogenic non-epileptic seizures (PNES) are a particularly important consideration, especially in individuals with refractory epilepsy. PNES are involuntary episodes that resemble epileptic seizures but are not associated with abnormal electrical discharges. They are classified as functional neurological disorders and are typically associated with psychological distress or trauma. Studies suggest that approximately 20% of individuals referred to epilepsy centers are diagnosed with PNES, and up to 10% of these individuals also have coexisting epilepsy.{{cite book |url=https://books.google.com/books?id=5PgjmjugIX8C&pg=PA462 |title=Seizures and epilepsy |vauthors=Jerome E |publisher=Oxford University Press |year=2013 |isbn=978-0-19-532854-7 |edition=2nd |location=New York |page=462}} Differentiating between the two can be difficult and often requires prolonged video EEG monitoring.
Misdiagnosis remains a significant concern in epilepsy. Reported rates vary widely — from 2% to 71% — depending on factors such as clinical setting, patient population, diagnostic criteria, and physician expertise.{{Cite journal |last=Oto |first=Maria (Meritxell) |date=2017-01-01 |title=The misdiagnosis of epilepsy: Appraising risks and managing uncertainty |url=https://www.sciencedirect.com/science/article/pii/S1059131116302977 |journal=Seizure |series=25th Anniversary Issue |volume=44 |pages=143–146 |doi=10.1016/j.seizure.2016.11.029 |issn=1059-1311}}{{Cite journal |last=Xu |first=Ying |last2=Nguyen |first2=Dennis |last3=Mohamed |first3=Armin |last4=Carcel |first4=Cheryl |last5=Li |first5=Qiang |last6=Kutlubaev |first6=Mansur A. |last7=Anderson |first7=Craig S. |last8=Hackett |first8=Maree L. |date=2016-10-01 |title=Frequency of a false positive diagnosis of epilepsy: A systematic review of observational studies |url=https://www.seizure-journal.com/article/S1059-1311(16)30133-9/fulltext |journal=Seizure - European Journal of Epilepsy |language=English |volume=41 |pages=167–174 |doi=10.1016/j.seizure.2016.08.005 |issn=1059-1311 |pmid=27592470}} While epilepsy can be mistakenly diagnosed in individuals with other conditions, the opposite can also occur: certain forms of epilepsy, particularly those with subtle or nocturnal symptoms,{{Cite journal |last=Miano |first=Silvia |last2=Peraita-Adrados |first2=Rosa |date=2013-03-01 |title=[Nocturnal frontal lobe epilepsy is often misdiagnosed as sleep disorders in children: a case series] |url=https://pubmed.ncbi.nlm.nih.gov/23440753 |journal=Revista De Neurologia |volume=56 |issue=5 |pages=257–267 |issn=1576-6578 |pmid=23440753}} may be mistaken for behavioral or psychological disorders. Delays in diagnosis can lead to prolonged morbidity and inappropriate treatment, highlighting the importance of careful clinical assessment and appropriate use of EEG and video documentation.
Prevention
Although many causes of epilepsy are not preventable, several known risk factors are modifiable. Perinatal care, including prevention of birth trauma, hypoxia, and maternal infections, can lower the risk of epilepsy in infants. Vaccination programs, especially against neurotropic infections such as measles and meningitis, play a key role in preventing epilepsy caused by central nervous system infections. In low- and middle-income countries, neurocysticercosis remains a major preventable cause of epilepsy, which can be reduced through improved sanitation and food safety. In older adults, reducing the risk of stroke, traumatic brain injury, and cardiovascular disease may also help prevent epilepsy.
Complications
Epilepsy can lead to a range of medical, psychological, and social complications, particularly when seizures are frequent or uncontrolled. One of the most serious risks is injury during a seizure, including falls, burns, or accidents while driving, swimming, or operating machinery. The risk of drowning is significantly increased in people with epilepsy, especially those with poor seizure control. Aspiration pneumonia may also occur during or after seizures, particularly generalized tonic–clonic seizures.
People with epilepsy are at greater risk for mental health conditions, including depression, anxiety, and social isolation. These challenges are often compounded by stigma, employment difficulties, and driving restrictions. In children, epilepsy — especially when drug-resistant — can interfere with cognitive development and academic performance.
A rare but serious complication is sudden unexpected death in epilepsy (SUDEP), which is most often associated with uncontrolled generalized tonic–clonic seizures, particularly during sleep.
Medication side effects, including fatigue, mood changes, and cognitive slowing, may also contribute to complications in some individuals. Comprehensive management aims to reduce these risks by achieving seizure control, minimizing adverse effects, and addressing comorbid conditions.
Management
File:Epilepsy Medical Alert Wrist Bracelets 2018.jpg
The primary goals of epilepsy management are to control seizures, minimize treatment side effects, and optimize quality of life. Management strategies are individualized based on the type of seizures or epilepsy syndrome, the underlying cause when known, the person’s age and comorbidities, and their preferences and life circumstances.
Supporting people's 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 options may be considered, including special diets, the implantation of a neurostimulator, or neurosurgery.
=First aid and acute management of seizures=
During a generalized tonic–clonic seizure, the primary goals are to ensure safety and prevent injury. The following steps should be taken:{{cite journal |vauthors=Michael GE, O'Connor RE |date=February 2011 |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 |doi=10.1016/j.emc.2010.08.003 |pmid=21109100}}
- Stay calm and remove any potential hazards from the area. Clear the space of sharp objects, furniture, or anything that might cause injury.
- If the person is standing, gently guide them to the ground to avoid a fall.
- Position the person on their side and into the recovery position, which helps keep the airway clear and reduces the risk of choking. If possible, place something soft (e.g., a jacket or cushion) under their head to prevent injury.
- Do not restrain their movements or attempt to hold them down. Do not put anything in their mouth, as this may cause harm.
If the seizure lasts longer than 5 minutes or if multiple seizures occur without full recovery in between, it is important to call for emergency medical assistance immediately, as it is considered a medical emergency known as status epilepticus.{{cite book |url=https://books.google.com/books?id=4W7UI-FPZmoC&pg=PA144 |title=Advanced therapy in epilepsy |vauthors=Wheless JW, Willmore J, Brumback RA |publisher=People's Medical Pub. House |year=2009 |isbn=978-1-60795-004-2 |location=Shelton, Conn. |page=144}}
Convulsive status epilepticus requires immediate medical attention to prevent serious complications. In a community setting (such as at home or in the ambulance), first-line treatment includes the administration of benzodiazepines. If the person has an individualized emergency management plan — which may have been developed with healthcare providers and outlines personalized treatment steps (such as the use of buccal midazolam or rectal diazepam) — this plan should be followed immediately. In hospital, intravenous lorazepam is preferred.
If seizures continue after the first dose of benzodiazepine, emergency medical services should be contacted, and further doses can be given. For ongoing seizures, levetiracetam, phenytoin, or sodium valproate may be used as second-line treatments, with levetiracetam preferred for its quicker action and fewer side effects.
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.
=Medications=
The primary treatment for epilepsy involves the use of antiseizure medications (ASMs), which aim to control seizures while minimizing side effects. Treatment plans should be individualized, taking into account the seizure type, epilepsy syndrome, patient age, sex, comorbidities, lifestyle factors, and the potential for drug interactions.
First-line treatment for most individuals with epilepsy is monotherapy with a single ASM. For many people with epilepsy, seizure control is achieved with a single medication, but some may require combination therapy if seizures are not well-controlled with monotherapy.
There are a number of medications available including phenytoin, carbamazepine and valproate. Evidence suggests that these drugs are similarly effective for both focal and generalized seizures, although their side-effect profiles vary.{{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 effects.{{cite journal |last1=Powell |first1=Graham |last2=Saunders |first2=Matthew |last3=Rigby |first3=Alexandra |last4=Marson |first4=Anthony G |title=Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy |journal=Cochrane Database of Systematic Reviews |date=9 December 2016 |volume=2017 |issue=4 |pages=CD007124 |doi=10.1002/14651858.CD007124.pub5 |pmid=27933615 |pmc=6463840 }} In the UK, carbamazepine or lamotrigine are recommended as first-line treatments for focal seizures, with levetiracetam and valproate used as second-line treatments due to concerns about cost and side effects. Valproate is the first-line choice for generalized seizures, while lamotrigine is used as second-line. For absence seizures, ethosuximide or valproate are recommended, with valproate also being effective for myoclonic and tonic–clonic seizures.{{cite journal |vauthors=Nevitt SJ, Sudell M, Cividini S, Marson AG, Tudur Smith C |date=April 2022 |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 |doi=10.1002/14651858.CD011412.pub4 |pmc=8974892 |pmid=35363878}}
Controlled-release formulations of carbamazepine may be preferred in some cases, as they appear to be equally effective as immediate-release carbamazepine but may have fewer side effects. Once a person’s seizures are well-controlled on a specific treatment, it is generally not necessary to routinely check medication blood levels, unless there are concerns about side effects or toxicity.
In low- and middle-income countries (LMICs), the management of epilepsy is often hindered by limited access to medications, diagnostic tools, and specialized care. While phenytoin and carbamazepine are commonly used as first-line treatments due to their availability and low cost, newer drugs like levetiracetam and lamotrigine may not be accessible. Additionally, surgical options and advanced therapies, such as vagus nerve stimulation or resective surgery, are typically inaccessible due to high costs and lack of infrastructure.
The least expensive anticonvulsant is phenobarbital at around US$5 a year. The World Health Organization gives it a first-line recommendation in LMICs and it is commonly used in these countries.{{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.
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 suppression of the bone marrow. Up to a quarter of people stop treatment due to adverse effects. Some medications are associated with birth defects when used in pregnancy.{{cite book |author=National Clinical Guideline Centre |url=http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |title=The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care |date=January 2012 |publisher=National Institute for Health and Clinical Excellence |pages=57–83 |archive-url=https://web.archive.org/web/20131216151008/http://www.nice.org.uk/nicemedia/live/13635/57784/57784.pdf |archive-date=16 December 2013 |url-status=live}} 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 }} Among the antiepileptic medications, levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects.
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}}
=Surgery=
Epilepsy surgery is an important treatment option for individuals with drug-resistant epilepsy,{{Cite journal |last=Engel |first=Jerome |date=2018 |title=The current place of epilepsy surgery |url=https://pubmed.ncbi.nlm.nih.gov/29278548 |journal=Current Opinion in Neurology |volume=31 |issue=2 |pages=192–197 |doi=10.1097/WCO.0000000000000528 |issn=1473-6551 |pmc=6009838 |pmid=29278548}} typically defined as the failure of at least two appropriately chosen and tolerated antiseizure medications.{{Cite journal |last=Kwan |first=P. |last2=Brodie |first2=M. J. |date=2000-02-03 |title=Early identification of refractory epilepsy |url=https://pubmed.ncbi.nlm.nih.gov/10660394 |journal=The New England Journal of Medicine |volume=342 |issue=5 |pages=314–319 |doi=10.1056/NEJM200002033420503 |issn=0028-4793 |pmid=10660394}} Surgery is most effective in cases of focal epilepsy, where seizures originate from a specific area of the brain that can be safely removed.{{cite journal |vauthors=Benoit PW, Yagiela A, Fort NF |date=February 1980 |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 |bibcode=1980ToxAP..52..187B |doi=10.1016/0041-008x(80)90105-2 |pmid=7361318}}{{cite journal |vauthors=Krucoff MO, Chan AY, Harward SC, Rahimpour S, Rolston JD, Muh C, Englot DJ |date=December 2017 |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 |doi=10.1111/epi.13920 |pmc=5716856 |pmid=28994113}}
Although epilepsy surgery has demonstrated strong evidence of efficacy — especially in drug-resistant focal epilepsy — it remains underutilized worldwide and is often reserved for individuals whose condition has reached an advanced or chronic stage. Early consideration and referral for surgical evaluation can improve long-term outcomes and quality of life. This evaluation, conducted in specialized epilepsy centers, includes seizure classification, long-term video EEG monitoring, high-resolution MRI with epilepsy-specific protocols, neuropsychological assessment, and sometimes functional imaging or invasive monitoring. Early referral improves the likelihood of successful outcomes and avoids prolonged periods of unnecessary disability.{{Cite journal |last=Rosenow |first=Felix |last2=Bast |first2=Thomas |last3=Czech |first3=Thomas |last4=Feucht |first4=Martha |last5=Hans |first5=Volkmar H. |last6=Helmstaedter |first6=Christoph |last7=Huppertz |first7=Hans-Jürgen |last8=Noachtar |first8=Soheyl |last9=Oltmanns |first9=Frank |last10=Polster |first10=Tilman |last11=Seeck |first11=Margitta |last12=Trinka |first12=Eugen |last13=Wagner |first13=Kathrin |last14=Strzelczyk |first14=Adam |date=2016 |title=Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by the Austrian, German, and Swiss working group on presurgical epilepsy diagnosis and operative epilepsy treatment |url=https://onlinelibrary.wiley.com/doi/full/10.1111/epi.13449 |journal=Epilepsia |language=en |volume=57 |issue=8 |pages=1215–1220 |doi=10.1111/epi.13449 |issn=1528-1167}}
The primary goal of epilepsy surgery is to achieve seizure freedom,{{cite journal |vauthors=Birbeck GL, Hays RD, Cui X, Vickrey BG |date=May 2002 |title=Seizure reduction and quality of life improvements in people with epilepsy |journal=Epilepsia |volume=43 |issue=5 |pages=535–538 |doi=10.1046/j.1528-1157.2002.32201.x |pmid=12027916 |doi-access=free}} but even when that is not possible, palliative procedures that significantly reduce seizure frequency can lead to meaningful improvements in quality of life and development — particularly in children. Studies suggest that 60-70% of individuals with drug-resistant focal epilepsy experience a substantial reduction in seizures following surgery.{{cite journal |vauthors=Duncan JS |date=April 2007 |title=Epilepsy surgery |journal=Clinical Medicine |volume=7 |issue=2 |pages=137–142 |doi=10.7861/clinmedicine.7-2-137 |pmc=4951827 |pmid=17491501}}
Common procedures include anterior temporal lobe resection, which often involves removal of the hippocampus in cases of mesial temporal lobe epilepsy, as well as lesionectomy for tumors or cortical dysplasia, and lobectomy for larger seizure foci. In cases where resection is not possible, procedures such as corpus callosotomy may help reduce the severity and spread of seizures. In addition to traditional resective techniques, minimally invasive approaches such as MRI-guided laser interstitial thermal therapy (LITT) have gained traction as safer alternatives in select cases, particularly where reducing cognitive impact and recovery time is a priority.{{Cite journal |last=Sharma |first=Mayur |last2=Ball |first2=Tyler |last3=Alhourani |first3=Ahmad |last4=Ugiliweneza |first4=Beatrice |last5=Wang |first5=Dengzhi |last6=Boakye |first6=Maxwell |last7=Neimat |first7=Joseph S. |date=2020-04-01 |title=Inverse national trends of laser interstitial thermal therapy and open surgical procedures for refractory epilepsy: a Nationwide Inpatient Sample–based propensity score matching analysis |url=https://thejns.org/focus/view/journals/neurosurg-focus/48/4/article-pE11.xml |journal=Neurosurgical Focus |language=en-US |volume=48 |issue=4 |pages=E11 |doi=10.3171/2020.1.FOCUS19935 |issn=1092-0684|doi-access=free }} In many cases, antiseizure medications can be tapered following successful surgery, though long-term monitoring remains essential. Surgical treatment is not limited to adults. A 2023 systematic review found that early surgery in children under 3 years with drug-resistant epilepsy can result in meaningful seizure reduction or freedom when other treatments have failed.{{Cite journal |last1=Tsou |first1=Amy Y. |last2=Kessler |first2=Sudha Kilaru |last3=Wu |first3=Mingche |last4=Abend |first4=Nicholas S. |last5=Massey |first5=Shavonne L. |last6=Treadwell |first6=Jonathan R. |date=2023-01-03 |title=Surgical Treatments for Epilepsies in Children Aged 1–36 Months: A Systematic Review |journal=Neurology |volume=100 |issue=1 |pages=e1–e15 |doi=10.1212/WNL.0000000000201012 |pmc=9827129 |pmid=36270898}}
Although epilepsy surgery has demonstrated efficacy, it is still rarely used around the world, and is typically reserved for cases where the condition has reached an advanced stage.
== Neuromodulation ==
Neuromodulation therapies, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS), are treatment options for individuals with drug-resistant epilepsy who are not candidates for resective surgery, or for whom previous surgery has not resulted in seizure freedom.{{cite journal |vauthors=Panebianco M, Rigby A, Marson AG |date=July 2022 |title=Vagus nerve stimulation for focal seizures |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=7 |pages=CD002896 |doi=10.1002/14651858.CD002896.pub3 |pmc=9281624 |pmid=35833911 |doi-access=free}}{{cite journal |vauthors=Edwards CA, Kouzani A, Lee KH, Ross EK |date=September 2017 |title=Neurostimulation Devices for the Treatment of Neurologic Disorders |journal=Mayo Clinic Proceedings |volume=92 |issue=9 |pages=1427–1444 |doi=10.1016/j.mayocp.2017.05.005 |pmid=28870357 |doi-access=free}}{{Cite journal |last=Englot |first=Dario J |last2=Chang |first2=Edward F. |last3=Auguste |first3=Kurtis I |date=2011 |title=Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response |url=https://pubmed.ncbi.nlm.nih.gov/21838505 |journal=Journal of Neurosurgery |volume=115 |issue=6 |pages=1248–1255 |doi=10.3171/2011.7.JNS11977 |issn=1933-0693 |pmid=21838505}} These therapies aim to reduce seizure frequency and severity by delivering controlled electrical stimulation to targeted neural circuits.
=Diet=
Dietary therapy, particularly the ketogenic diet (high-fat, low-carbohydrate, adequate-protein), is a non-pharmacological treatment option used primarily in children with drug-resistant epilepsy. Evidence suggests that children on a classical ketogenic diet may be up to three times more likely to achieve seizure freedom and up to six times more likely to experience a ≥50% reduction in seizure frequency compared to those receiving standard care. Modified versions of the diet, such as the modified Atkins diet, are better tolerated but may be less effective.{{cite report |title=Management of Infantile Epilepsies: A Systematic Review |date=2022 |doi=10.23970/AHRQEPCCER252 |pmid=36383706 |vauthors=Treadwell JR, Wu M, Tsou AY}} In adults, the ketogenic diet has shown limited evidence of achieving seizure freedom, though it may increase the likelihood of seizure reduction. However, further research is necessary.
It is typically supervised by a multidisciplinary team, including neurologists and dietitians, due to its restrictive nature and potential side effects, such as vomiting, constipation and diarrhoea. Regular monitoring of nutritional status, blood parameters, and growth is recommended. It is unclear why this diet works.{{cite book |url=https://books.google.com/books?id=lxhs51fE85wC&pg=PA180 |title=Current management in child neurology |publisher=BC Decker |year=2009 |isbn=978-1-60795-000-4 |veditors=Maria BL |edition=4th |location=Hamilton, Ont. |page=180 |archive-url=https://web.archive.org/web/20160624092756/https://books.google.com/books?id=lxhs51fE85wC&pg=PA180 |archive-date=24 June 2016 |url-status=live}} A gluten-free diet has been proposed in rare cases of epilepsy associated with celiac disease and occipital calcifications, though evidence is limited and based on small case series.
= Adjunctive and complementary therapies =
There is moderate-quality evidence supporting the use of psychological interventions — such as cognitive behavioral therapy (CBT), relaxation techniques, and self-management training — alongside standard treatment.{{cite journal |vauthors=Michaelis R, Tang V, Wagner JL, Modi AC, LaFrance WC, Goldstein LH, Lundgren T, Reuber M |date=October 2017 |title=Psychological treatments for people with epilepsy |journal=The Cochrane Database of Systematic Reviews |volume=10 |issue=10 |pages=CD012081 |doi=10.1002/14651858.CD012081.pub2 |pmc=6485515 |pmid=29078005}} These approaches may improve quality of life, emotional wellbeing, and treatment adherence; however, evidences targeting seizure control are uncertain.{{Cite journal |last=Li |first=Dongxu |last2=Song |first2=Yuqi |last3=Zhang |first3=Shuyu |last4=Qiu |first4=Juan |last5=Zhang |first5=Rui |last6=Wu |first6=Jiayi |last7=Wu |first7=Ziyan |last8=Wei |first8=Junwen |last9=Xiang |first9=Xuefeng |last10=Zhang |first10=Yue |last11=Yu |first11=Liangdong |last12=Wang |first12=Honghan |last13=Niu |first13=Ping |last14=Fan |first14=Chuan |last15=Li |first15=Xiaoming |date=2023-01-01 |title=Cognitive behavior therapy for depression in people with epilepsy: A systematic review and meta-analysis |url=https://www.sciencedirect.com/science/article/abs/pii/S1525505022005054 |journal=Epilepsy & Behavior |volume=138 |pages=109056 |doi=10.1016/j.yebeh.2022.109056 |issn=1525-5050}} 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 |date=November 2005 |title=Human photosensitivity: from pathophysiology to treatment |journal=European Journal of Neurology |volume=12 |issue=11 |pages=828–841 |doi=10.1111/j.1468-1331.2005.01085.x |pmid=16241971}} Biofeedback, particularly EEG-based operant conditioning, has shown preliminary benefit in some people with drug-resistant epilepsy.{{cite journal |vauthors=Tan G, Thornby J, Hammond DC, Strehl U, Canady B, Arnemann K, Kaiser DA |date=July 2009 |title=Meta-analysis of EEG biofeedback in treating epilepsy |journal=Clinical EEG and Neuroscience |volume=40 |issue=3 |pages=173–179 |doi=10.1177/155005940904000310 |pmid=19715180}} However, these methods are considered adjunctive and are not recommended as standalone treatments.
Cannabidiol (CBD) has shown benefit as an add-on therapy in certain severe childhood epilepsies. A purified form of CBD was approved by the U.S. FDA in 2018 and by the European Medicines Agency (EMA) in 2020 for the treatment of Dravet syndrome, Lennox–Gastaut syndrome, and tuberous sclerosis complex.{{cite journal |vauthors=Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, Herkes GK, Farrell M, Degenhardt L |date=July 2018 |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 |doi=10.1136/jnnp-2017-317168 |pmid=29511052 |doi-access=free |hdl-access=free |hdl=1959.4/unsworks_50076}}{{cite report |title=Cannabis derivative may reduce seizures in some severe drug-resistant epilepsies, but adverse events increase |date=26 June 2018 |doi=10.3310/signal-000606}}{{cite web |date=25 June 2018 |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 |access-date=4 October 2018 |website=www.fda.gov |language=en}}
Regular physical activity is generally considered safe and may have beneficial effects on seizure frequency, mood, and overall wellbeing.{{cite journal |vauthors=Arida RM, Scorza FA, Scorza CA, Cavalheiro EA |date=March 2009 |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 |doi=10.1016/j.neubiorev.2008.11.002 |pmid=19059282}} While evidence remains limited, some studies suggest that moderate exercise can reduce seizure burden in certain individuals.{{cite journal |vauthors=Arida RM, Cavalheiro EA, da Silva AC, Scorza FA |year=2008 |title=Physical activity and epilepsy: proven and predicted benefits |journal=Sports Medicine |volume=38 |issue=7 |pages=607–615 |doi=10.2165/00007256-200838070-00006 |pmid=18557661}} Seizure response dogs have been trained to assist individuals during or after seizures by providing physical support or alerting others.{{cite journal |vauthors=Di Vito L, Naldi I, Mostacci B, Licchetta L, Bisulli F, Tinuper P |date=June 2010 |title=A seizure response dog: video recording of reacting behaviour during repetitive prolonged seizures |journal=Epileptic Disorders |volume=12 |issue=2 |pages=142–145 |doi=10.1684/epd.2010.0313 |pmid=20472528}}{{cite journal |vauthors=Kirton A, Winter A, Wirrell E, Snead OC |date=October 2008 |title=Seizure response dogs: evaluation of a formal training program |journal=Epilepsy & Behavior |volume=13 |issue=3 |pages=499–504 |doi=10.1016/j.yebeh.2008.05.011 |pmid=18595778}} Although anecdotal reports claim that some dogs can anticipate seizures, there is no conclusive scientific evidence supporting the consistent ability of dogs to predict seizures before they occur.{{cite journal |vauthors=Doherty MJ, Haltiner AM |date=January 2007 |title=Wag the dog: skepticism on seizure alert canines |journal=Neurology |volume=68 |issue=4 |pages=309 |doi=10.1212/01.wnl.0000252369.82956.a3 |pmid=17242343}}
Various forms of 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 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.
Contraception and pregnancy
{{See also|Epilepsy and pregnancy}}
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.
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 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 | 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.
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.
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 }}
Pregnancy does not seem to change seizure frequency very much. When seizures happen, however, they can cause some pregnancy complications, such as pre-term births or the babies being smaller than usual when they are born.
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, neurocognitive, and 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 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.
Although anti-seizure drugs can be found in breast milk, women with epilepsy can breastfeed their babies, and the benefits usually outweigh the risks.
Prognosis
File:Epilepsy world map-Deaths per million persons-WHO2012.svg
Epilepsy is generally considered a chronic neurological condition, but its long-term course can vary widely depending on factors such as seizure type, underlying cause, and response to treatment. Although epilepsy is not typically "cured," in many cases it may be considered resolved. According to the ILAE, epilepsy is considered to be resolved in individuals who have been seizure-free for at least 10 years, with no antiseizure medications for the last 5 of those years.
Approximately 60–70% of individuals with epilepsy achieve good seizure control with appropriate antiseizure medications, and many can maintain long-term remission. However, outcomes vary significantly by epilepsy type and etiology. Early treatment response is one of the strongest predictors of long-term outcome, with poor early control correlating with lower chances of remission. Several factors — such as structural brain abnormalities, comorbid developmental disorders, or a high frequency of seizures at onset — have been associated with worse outcomes, although findings are not always consistent.{{Cite journal |last=Mohanraj |first=Rajiv |last2=Brodie |first2=Martin J. |date=2013-06-01 |title=Early predictors of outcome in newly diagnosed epilepsy |url=https://www.sciencedirect.com/science/article/pii/S1059131113000368 |journal=Seizure |volume=22 |issue=5 |pages=333–344 |doi=10.1016/j.seizure.2013.02.002 |issn=1059-1311|doi-access=free }}
Epilepsy disproportionately affects low- and middle-income countries, where nearly 80% of the global epilepsy population resides.{{Cite journal |last=Vergonjeanne |first=Marion |last2=Auditeau |first2=Emilie |last3=Erazo |first3=Daniells |last4=Luna |first4=Jaime |last5=Gelle |first5=Thibaut |last6=Gbessemehlan |first6=Antoine |last7=Boumediene |first7=Farid |last8=Preux |first8=Pierre-Marie |last9=QUINET Collaboration |date=2021-09-21 |title=Epidemiology of Epilepsy in Low- and Middle-Income Countries: Experience of a Standardized Questionnaire over the Past Two Decades |url=https://karger.com/ned/article-abstract/55/5/369/825238/Epidemiology-of-Epilepsy-in-Low-and-Middle-Income?redirectedFrom=fulltext |journal=Neuroepidemiology |volume=55 |issue=5 |pages=369–380 |doi=10.1159/000517065 |issn=0251-5350}} In these countries, to 75% of individuals with epilepsy do not receive the treatment they need. Untreated epilepsy is associated with elevated risk of injury, psychiatric comorbidities, and early death, including sudden unexpected death in epilepsy (SUDEP).
=Mortality=
People with epilepsy may have a higher risk of premature death compared to those without the condition. This risk is estimated to be between 1.6 and 4.1 times 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 a relatively low increase in risk.
Mortality is often related to the underlying cause of the seizures, status epilepticus, suicide, 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 }} 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 }} 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;{{cite book |title=Fast facts: epilepsy |vauthors=Kwan P |publisher=Health Press |year=2012 |isbn=978-1-908541-12-3 |edition=5th |location=Abingdon, Oxford, UK |page=10}} it is unclear how to decrease its risk. 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 }}
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.
Epidemiology
Epilepsy is one of the most common serious neurological disorders, affecting approximately 50 million people globally as of 2021,{{cite web |date=2021 |title=GBD 2021 Cause and Risk Summary: EPILEPSY |url=https://www.healthdata.org/research-analysis/diseases-injuries-risks/factsheets/2021-epilepsy-level-1-impairment |url-status=live |archive-url=https://web.archive.org/web/20240719233622/https://www.healthdata.org/sites/default/files/disease_and_injury/gbd_2021/topic_pdf/cause/193.pdf |archive-date=19 July 2024 |access-date=19 July 2024 |website=Institute for Health Metrics and Evaluation (IHME) |publisher=University of Washington |publication-place=Seattle, USA}}{{Cite journal |last=Feigin |first=Valery L. |last2=Vos |first2=Theo |last3=Nair |first3=Balakrishnan Sukumaran |last4=Hay |first4=Simon I. |last5=Abate |first5=Yohannes Habtegiorgis |last6=Magied |first6=Abdallah H. A. Abd Al |last7=ElHafeez |first7=Samar Abd |last8=Abdelkader |first8=Atef |last9=Abdollahifar |first9=Mohammad-Amin |last10=Abdullahi |first10=Auwal |last11=Aboagye |first11=Richard Gyan |last12=Abreu |first12=Lucas Guimarães |last13=Rumeileh |first13=Samir Abu |last14=Abualruz |first14=Hasan |last15=Aburuz |first15=Salahdein |date=2025-03-01 |title=Global, regional, and national burden of epilepsy, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 |url=https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(24)00302-5/fulltext |journal=The Lancet Public Health |language=English |volume=10 |issue=3 |pages=e203–e227 |doi=10.1016/S2468-2667(24)00302-5 |issn=2468-2667 |pmid=40015291|hdl=10067/1585180151162165141 |hdl-access=free }} with the majority living in low- and middle-income countries.{{cite journal |vauthors=Espinosa-Jovel C, Toledano R, Aledo-Serrano Á, García-Morales I, Gil-Nagel A |date=March 2018 |title=Epidemiological profile of epilepsy in low income populations |journal=Seizure |volume=56 |pages=67–72 |doi=10.1016/j.seizure.2018.02.002 |pmid=29453113 |doi-access=free}} The point prevalence of active epilepsy is generally reported between 5 and 7 per 1,000 people, while lifetime prevalence is slightly higher, typically between 6 and 9 per 1,000.{{Cite journal |last=Fiest |first=Kirsten M. |last2=Sauro |first2=Khara M. |last3=Wiebe |first3=Samuel |last4=Patten |first4=Scott B. |last5=Kwon |first5=Churl-Su |last6=Dykeman |first6=Jonathan |last7=Pringsheim |first7=Tamara |last8=Lorenzetti |first8=Diane L. |last9=Jetté |first9=Nathalie |date=2017 |title=Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies |url=https://www.neurology.org/doi/10.1212/WNL.0000000000003509 |journal=Neurology |language=en |volume=88 |issue=3 |pages=296–303 |doi=10.1212/WNL.0000000000003509 |issn=0028-3878 |pmc=5272794 |pmid=27986877}} Both prevalence and incidence are higher in low-income regions. The annual incidence of epilepsy — the rate of new diagnoses each year — is estimated at 50 to 70 new cases per 100,000 people globally, based on population studies. Rates are significantly higher in low- and middle-income countries, and, within high-income countries, higher incidence has also been observed among lower socioeconomic groups and some ethnic minorities.
Epilepsy can develop at any age, but its incidence is highest in early infancy and in older adults, following a bimodal distribution. In high-income countries, the incidence peaks during the first year of life, declines during adulthood, and rises again in people over age 85. The increase in older adults is associated with age-related conditions such as stroke, brain tumors, and neurodegenerative diseases. In low- and middle-income countries, incidence more often peaks in older children and young adults, which may reflect the effects of trauma, infections, and underdiagnosis in the elderly. Epilepsy is slightly more common in males than females, a difference that may be influenced by risk factor exposure and underreporting in women in some regions due to sociocultural factors.{{Cite journal |last=Beghi |first=E |date=2019 |title=The Epidemiology of Epilepsy |url=https://pubmed.ncbi.nlm.nih.gov/31852003/ |journal=Neuroepidemiology |volume=54 |issue=2 |pages=185-191 |doi=10.1159/000503831}}
Beyond prevalence and incidence, epilepsy imposes a significant global burden in terms of disability, stigma, and premature mortality. The disorder is responsible for an estimated 13 million disability-adjusted life years (DALYs) worldwide each year, with the majority of this burden falling on individuals in low-resource settings where access to diagnosis and treatment remains limited.
History
{{See also|On the Sacred Disease}}
File:Hippocrates rubens.jpg of an antique bust]]
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 condition was thought to be of a spiritual cause. The world's oldest description of an epileptic seizure comes from a text in 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.
The oldest known detailed record of the condition itself is in the Sakikku, a Babylonian 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 epilepsy, 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 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 }}
The ancient Greeks had contradictory views of the condition. 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 ({{Langx|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 condition. 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 condition 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 condition of spreading ignorance through a belief in superstitious magic. Hippocrates proposed that heredity was important as a cause, described worse outcomes if the condition 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 condition, his view was not accepted at the time. Evil spirits continued to be blamed until at least the 17th century.
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 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}}
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|Saint John's sickness}}, {{lang|fr|mal des enfans}} {{lit|child sickness}}, and {{lang|fr|mal-caduc}} {{lit|falling sickness}}. People 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.
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 }} 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 }}
Society and culture
{{See also|List of people with epilepsy}}Epilepsy has significant social and cultural implications that vary across regions and contexts. People with epilepsy may experience social stigma, legal restrictions, economic disadvantage, and barriers to education and employment. Public perceptions of the condition are shaped by cultural beliefs, media portrayals, and the level of awareness in a given society. Efforts by advocacy groups and international organizations aim to improve public understanding, reduce stigma, and promote access to care. Social consequences such as educational exclusion, unemployment, and social isolation further compound the impact on quality of life. Despite the availability of effective antiseizure medications and cost-effective treatment strategies, a large treatment gap persists in many countries, underscoring the need for strengthened health systems and public health interventions.
=Stigma=
Social stigma is commonly experienced by people with epilepsy worldwide, and it can have economic, social, and cultural consequences.{{cite journal |vauthors=de Boer HM |date=December 2010 |title=Epilepsy stigma: moving from a global problem to global solutions |journal=Seizure |volume=19 |issue=10 |pages=630–636 |doi=10.1016/j.seizure.2010.10.017 |pmid=21075013 |doi-access=free}} Misconceptions about the condition — including beliefs that it is contagious, a form of madness, or caused by supernatural forces — persist in many communities. In parts of Africa, including Tanzania and Uganda, epilepsy is sometimes associated with spirit possession, witchcraft, or poisoning, and is incorrectly believed to be contagious. Similar stigmatizing beliefs have been reported in other regions, such as India and China, where epilepsy may be cited as grounds for denying marriage. In the United Kingdom, epilepsy was legally considered valid grounds for annulling a marriage until 1971.
Stigma can also affect how people respond to a diagnosis. Some individuals with epilepsy may deny having had seizures, fearing discrimination. A 2024 cross-sectional study found that 64.8% of relatives of people with epilepsy reported experiencing moderate levels of stigma, which was associated with more negative attitudes toward the condition. Greater stigma was observed among relatives of patients with more frequent seizures or poor medication adherence.{{cite journal |last1=Erkal |first1=Emre |last2=Kiyak |first2=Emine |last3=Uren |first3=Yavuz |last4=Milanlioglu |first4=Aysel |date=October 2024 |title=Determination of stigma and attitude in relatives of patients with epilepsy |journal=Seizure: European Journal of Epilepsy |volume=121 |pages=64–69 |doi=10.1016/j.seizure.2024.07.022 |pmid=39089140}}
Negative perceptions of epilepsy can also affect educational opportunities and academic outcomes.{{Cite journal |last=Jacoby |first=Ann |last2=Austin |first2=Joan K. |date=2007 |title=Social stigma for adults and children with epilepsy |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2007.01391.x |journal=Epilepsia |language=en |volume=48 |issue=s9 |pages=6–9 |doi=10.1111/j.1528-1167.2007.01391.x |issn=1528-1167}} Children with epilepsy are at increased risk of underachievement in school due to a combination of neurological factors, m edication side effects, and the effects of social exclusion.{{Cite journal |last=Camfield |first=Carol S. |last2=Camfield |first2=Peter R. |date=2007 |title=Long‐term social outcomes for children with epilepsy |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2007.01390.x |journal=Epilepsia |language=en |volume=48 |issue=s9 |pages=3–5 |doi=10.1111/j.1528-1167.2007.01390.x |issn=0013-9580}} These challenges can lead to long-term disadvantages in learning and social development. In some cases, students are placed in special education classes regardless of their actual cognitive abilities or excluded from school activities out of fear of seizures.
In adulthood, stigma can result in reduced employment opportunities and workplace discrimination. Adults with epilepsy are more likely to be unemployed or underemployed than the general population, a disparity often driven by employer concerns about safety, productivity, or liability. Disclosure of an epilepsy diagnosis in job applications or interviews may lead to discrimination, although nondisclosure can limit access to workplace accommodations.
= Economic impact =
Epilepsy is associated with a substantial economic burden at both the individual and societal levels. Direct costs include expenses related to diagnosis, treatment, and long-term management, such as antiseizure medications and hospitalizations. Indirect costs may arise from lost productivity, unemployment, and premature death. In many countries, especially those with limited health infrastructure, individuals with epilepsy and their families often bear the majority of healthcare expenses out of pocket. A 2021 modeling study estimated the total global cost of epilepsy at approximately $119.27 billion annually, based on per capita cost projections applied to an estimated 52.51 million people living with epilepsy worldwide, while accounting for the treatment gap.{{Cite journal |last=Begley |first=Charles |last2=Wagner |first2=Ryan G |last3=Abraham |first3=Annette |last4=Beghi |first4=Ettore |last5=Newton |first5=Charles |last6=Kwon |first6=Churl Su |last7=Labiner |first7=David |last8=Winkler |first8=Andrea S. |date=2022 |title=The global cost of epilepsy: A systematic review and extrapolation |url=https://onlinelibrary.wiley.com/doi/10.1111/epi.17165 |journal=Epilepsia |language=en |volume=63 |issue=4 |pages=892–903 |doi=10.1111/epi.17165 |issn=0013-9580}} The treatment gap — referring to the proportion of people with epilepsy who do not receive appropriate care — remains high in low- and middle-income countries, exacerbating the economic burden through avoidable seizures, injuries, and emergency care.
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 }}
= Driving and legal restrictions =
{{See also|Epilepsy and driving}}
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 }} In some places physicians are required by law to report if a person has had a seizure to the licensing body while in others the requirement is only that they encourage the person in question to report it themselves. 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 they 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 }}
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 }}
- 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.
- 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}}
- 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.
= Advocacy and support organizations =
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 provides support, delivers education and training and funds research for people living with epilepsy.
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 }}{{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 }}
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 magazine|url=https://time.com/5215273/purple-day-epilepsy-awareness-day/|title=People Are Wearing Purple Today for Epilepsy Awareness Day. Here's What That Is|magazine=Time|date=26 March 2018| vauthors = Carr F |access-date=18 April 2018}}
Research directions
Epilepsy research aims to uncover the causes of seizures, improve diagnosis, and develop more effective treatments. It spans genetics, neuroscience, pharmacology, and biomedical engineering, with the shared goal of reducing the burden of disease. Researchers also study how epilepsy develops (epileptogenesis), seeking ways to prevent it entirely.
= Animal models =
Animal models play a central role in epilepsy research, providing insight into seizure mechanisms, disease progression, and treatment effects. Rodents are most commonly used, with models based on chemical induction (e.g. kainic acid, pilocarpine), electrical stimulation (e.g. kindling), genetic mutations, and others.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). Other species, including zebrafish, dogs, and non-human primates, are also employed to capture features not easily replicated in rodents, such as complex behaviors or chronic seizure patterns. These models help researchers study epileptogenesis, test antiseizure drugs, and explore surgical or neuromodulatory interventions. While no model captures the full complexity of human epilepsy, they remain essential for translational research.{{Cite journal |last=Grone |first=Brian P |last2=Baraban |first2=Scott C |date=2015 |title=Animal models in epilepsy research: legacies and new directions |url=https://www.nature.com/articles/nn.3934 |journal=Nature Neuroscience |language=en |volume=18 |issue=3 |pages=339–343 |doi=10.1038/nn.3934 |issn=1097-6256}}
= Genetics and molecular research =
Advances in genetics have transformed the understanding of epilepsy, particularly in early-onset and treatment-resistant forms. Mutations in genes affecting ion channels, synaptic transmission, and mTOR signaling pathways have been linked to a growing number of epilepsy syndromes, including Dravet syndrome (SCN1A), PCDH19-related epilepsy, and familial focal epilepsies. High-throughput sequencing has enabled the discovery of de novo mutations in severe developmental and epileptic encephalopathies. In parallel, research into polygenic risk and epigenetic mechanisms is expanding the view of common epilepsies as complex traits. Molecular studies also support the development of targeted therapies, such as precision treatments for specific genetic subtypes.{{Cite journal |last=Perucca |first=Piero |last2=Perucca |first2=Emilio |date=2019-05-01 |title=Identifying mutations in epilepsy genes: Impact on treatment selection |url=https://www.sciencedirect.com/science/article/abs/pii/S0920121119300270 |journal=Epilepsy Research |volume=152 |pages=18–30 |doi=10.1016/j.eplepsyres.2019.03.001 |issn=0920-1211}}
= Epileptogenesis and biomarkers =
Understanding how epilepsy develops (epileptogenesis) is a major focus of current research. This includes identifying biomarkers that predict who is at risk of developing epilepsy. EEG patterns, neuroimaging features, and molecular signals in blood or cerebrospinal fluid are being investigated as early indicators. The goal is to detect epilepsy before chronic seizures begin and to develop interventions that prevent or halt this process. While no validated biomarker is yet in clinical use, this area holds promise for future disease-modifying therapies.{{Cite journal |last=Pitkänen |first=Asla |last2=Engel |first2=Jerome |date=2014-04-01 |title=Past and Present Definitions of Epileptogenesis and Its Biomarkers |url=https://www.sciencedirect.com/science/article/pii/S1878747923008930 |journal=Neurotherapeutics |volume=11 |issue=2 |pages=231–241 |doi=10.1007/s13311-014-0257-2 |issn=1878-7479|pmc=3996117 }}
= Antiseizure drug development =
The development of new antiseizure medications remains a priority, especially for people with drug-resistant epilepsy. Current research focuses on compounds with novel mechanisms of action, better safety profiles, and disease-modifying potential. High-throughput screening, including zebrafish and organoid models, accelerates early-stage discovery, while pharmacogenomic studies aim to personalize drug selection. Cannabinoids and neurosteroids are also under investigation for specific syndromes and seizure types.{{Cite journal |last=Löscher |first=Wolfgang |last2=Klein |first2=Pavel |date=2021 |title=The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8408078/ |journal=CNS drugs |volume=35 |issue=9 |pages=935–963 |doi=10.1007/s40263-021-00827-8 |issn=1179-1934 |pmc=8408078 |pmid=34145528}}{{Cite journal |last=Rho |first=Jong M |last2=White |first2=H Steve |date=2018 |title=Brief history of anti-seizure drug development |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6293064/ |journal=Epilepsia Open |volume=3 |issue=Suppl Suppl 2 |pages=114–119 |doi=10.1002/epi4.12268 |issn=2470-9239 |pmc=6293064 |pmid=30564769}}
=Seizure prediction=
The unpredictability of seizures is a major concern for many people with epilepsy, and seizure prediction has been a longstanding focus of research. Early efforts were limited by small datasets and inconsistent results; however, advances in computational modeling, long-term EEG recording, and machine learning have led to renewed interest in the field. Public EEG databases and algorithm competitions have helped standardize evaluation and fostered the development of more accurate methods. In one clinical trial, prospective seizure prediction using intracranial EEG was achieved in a small group of participants. Current approaches often integrate network models of brain activity, multimodal data sources, and closed-loop systems capable of both detecting and responding to pre-ictal changes. These developments have laid the groundwork for future large-scale clinical trials and the potential integration of seizure forecasting into clinical practice.{{Cite journal |last=Kuhlmann |first=Levin |last2=Lehnertz |first2=Klaus |last3=Richardson |first3=Mark P. |last4=Schelter |first4=Björn |last5=Zaveri |first5=Hitten P. |date=2018 |title=Seizure prediction — ready for a new era |url=https://www.nature.com/articles/s41582-018-0055-2 |journal=Nature Reviews Neurology |language=en |volume=14 |issue=10 |pages=618–630 |doi=10.1038/s41582-018-0055-2 |issn=1759-4766|hdl=2164/11941 |hdl-access=free }}
= Mechanistic modeling and alternative pathways =
Mathematical and computational models are increasingly used to simulate the neural dynamics underlying seizures. Reductionist models such as the Epileptor use ordinary differential equations to replicate interictal and ictal discharges observed in experimental data.{{Cite journal |last1=Jirsa |first1=Viktor K. |last2=Stacey |first2=William C. |last3=Quilichini |first3=Pascale P. |last4=Ivanov |first4=Anton I. |last5=Bernard |first5=Christophe |date=August 2014 |title=On the nature of seizure dynamics |journal=Brain |language=en |volume=137 |issue=8 |pages=2210–2230 |doi=10.1093/brain/awu133 |issn=1460-2156 |pmc=4107736 |pmid=24919973}} More detailed versions, including the Epileptor-2, incorporate physiological variables such as ion concentrations and synaptic resource availability.{{Cite journal |last1=Chizhov |first1=Anton V. |last2=Zefirov |first2=Artyom V. |last3=Amakhin |first3=Dmitry V. |last4=Smirnova |first4=Elena Yu |last5=Zaitsev |first5=Aleksey V. |date=2018-05-31 |title=Minimal model of interictal and ictal discharges "Epileptor-2" |journal=PLOS Computational Biology |language=en |volume=14 |issue=5 |pages=e1006186 |bibcode=2018PLSCB..14E6186C |doi=10.1371/journal.pcbi.1006186 |issn=1553-7358 |pmc=6005638 |pmid=29851959 |doi-access=free}} These models suggest that fluctuations in extracellular potassium and intracellular sodium levels may play a key role in the emergence and termination of seizures.{{Cite web |title=Epileptor-2 model |url=https://www.ioffe.ru/CompPhysLab/MyPrograms/Epileptor-2/Epileptor-2.html}}
=Potential future therapies=
Several novel therapeutic strategies are under investigation 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 | doi-access = free }} Medications that alter immune function, such as intravenous immunoglobulins, 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 }} 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 }}
Other animals
{{Main|Epilepsy in animals}}
Epilepsy has also been documented in several animal species, particularly dogs and cats.{{cite journal |vauthors=Thomas WB |date=January 2010 |title=Idiopathic epilepsy in dogs and cats |journal=The Veterinary Clinics of North America. Small Animal Practice |volume=40 |issue=1 |pages=161–179 |doi=10.1016/j.cvsm.2009.09.004 |pmid=19942062}} Veterinary treatments often use similar antiepileptic drugs, such as phenobarbital or levetiracetam. In horses, diagnosis can be challenging, especially in focal seizures,{{cite journal |vauthors=van der Ree M, Wijnberg I |date=2012 |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 |doi=10.1080/01652176.2012.744496 |pmid=23163553 |doi-access=free}} and conditions such as juvenile idiopathic epilepsy have been reported in foals.{{cite journal |last1=Ciosek |first1=Julia |last2=Kimes |first2=Abigail |last3=Vinardell |first3=Tatiana |last4=Miller |first4=Donald C |last5=Antczak |first5=Douglas F |last6=Brooks |first6=Samantha |date=23 August 2023 |title=Juvenile idiopathic epilepsy in Arabian horses is not a single-gene disorder |journal=Journal of Heredity |volume=114 |issue=5 |pages=488–491 |doi=10.1093/jhered/esad029 |pmid=37145017}}
See also
References
{{Reflist}}
Further reading
{{Refbegin}}
- {{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 }}
- {{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}}
{{Refend}}
- {{Cite journal| last1 = Wilson| first1 = J. V.| last2 = Reynolds| first2 = E. H. | title = Texts and documents. Translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy | journal = Medical History | volume = 34 | issue = 2 | pages = 185–198| doi = 10.1017/s0025727300050651 | date = April 1990 | pmid = 2187129 | pmc = 1036070}}
External links
{{Commons category|Epilepsy}}
{{Wikiquote}}
- {{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}}
- {{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}}
- [https://www.who.int/mediacentre/factsheets/fs999/en/ World Health Organization fact sheet]
{{Medical resources
| ICD11 = {{ICD11|8A60}}, {{ICD11|8A61}}, {{ICD11|8A62}}, {{ICD11|8A66}}, {{ICD11|8A6Y}}, {{ICD11|8A6Z}}
| ICD10 = {{ICD10|G40}}, {{ICD10|G41}}
| ICD9 = {{ICD9|345}}
| MedlinePlus = 000694
| eMedicineSubj = neuro
| eMedicineTopic = 415
| DiseasesDB = 4366
| MeshID = D004827
}}
{{Diseases of the nervous system}}
{{Seizures and epilepsy}}
{{Authority control}}
{{Good article}}
Category:Articles containing video clips
Category:Disorders causing seizures
Category:Neurological disorders in children
Category:Wikipedia medicine articles ready to translate (full)