Epilepsy

This is a good article. Click here for more information.
Source: Wikipedia, the free encyclopedia.
(Redirected from
Epilepsia
)
"Epilepsia" and "Epileptic" redirect here. For the journal, see Epilepsia (journal). For the comics, see Epileptic (comics).

Epilepsy
Other namesSeizure disorder
electrolyte problems[4]
TreatmentMedication, surgery, neurostimulation, dietary changes[5][6]
PrognosisControllable in 69%[7]
Frequency39 million / 0.5% (2015)[8]
Deaths125,000 (2015)[9]

Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures.[10][11] An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the neurons.[1][12] The occurrence of two or more unprovoked seizures defines epilepsy.[13] The occurrence of just one seizure may warrant the definition (set out by the International League Against Epilepsy) in a more clinical usage where recurrence may be able to be prejudged.[10] Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain.[1] These episodes can result in physical injuries, either directly such as broken bones or through causing accidents.[1] In epilepsy, seizures tend to recur and may have no detectable underlying cause.[13] Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy.[14] 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.[13]

The underlying mechanism of an epileptic seizure is excessive and abnormal

blood tests.[4] Epilepsy can often be confirmed with an EEG, but a normal test does not rule out the condition.[4]

Epilepsy that occurs as a result of other issues may be preventable.[1] Seizures are controllable with medication in about 69% of cases;[7] inexpensive anti-seizure medications are often available.[1] In those whose seizures do not respond to medication; surgery, neurostimulation or dietary changes may then be considered.[11][5][6] Not all cases of epilepsy are lifelong, and many people improve to the point that treatment is no longer needed.[1]

As of 2020, about 50 million people have epilepsy.

developed world, onset of new cases occurs most frequently in babies and the elderly.[19] In the developing world, onset is more common at the extremes of age – in younger children and in older children and young adults due to differences in the frequency of the underlying causes.[20] About 5–10% of people will have an unprovoked seizure by the age of 80.[21] The chance of experiencing a second seizure within two years after the first is around 40%.[22][23] In many areas of the world, those with epilepsy either have restrictions placed on their ability to drive or are not permitted to drive until they are free of seizures for a specific length of time.[24] The word epilepsy is from Ancient Greek ἐπιλαμβάνειν, 'to seize, possess, or afflict'.[25]

Signs and symptoms

A still image of a generalized seizure

Epilepsy is characterized by a long-term risk of recurrent

epileptic seizures.[26] These seizures may present in several ways depending on the parts of the brain involved and the person's age.[26][27]

Seizures

Main article:
Epileptic seizure

The most common type (60%) of seizures are

generalized seizures from the start, affecting both hemispheres of the brain and impairing consciousness.[27] Two-thirds begin as focal seizures (which affect one hemisphere of the brain) which may progress to generalized seizures.[27] The remaining 40% of seizures are non-convulsive. An example of this type is the absence seizure, which presents as a decreased level of consciousness and usually lasts about 10 seconds.[2][28]

Certain experiences, known as

Jacksonian march.[30] 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.[30]

There are six main types of generalized seizures:

They all involve loss of consciousness and typically happen without warning.

Tonic-clonic seizures occur with a contraction of the limbs followed by their extension and arching of the back which lasts 10–30 seconds (the tonic phase). A cry may be heard due to contraction of the

psychogenic non-epileptic seizures.[33] Psychogenic non-epileptic seizures are seizure like behavior without an associated synchronised electrical discharge on EEG and are considered a dissociative disorder.[33]

Myoclonic seizures involve very brief muscle spasms in either a few areas or all over.[34][35] These sometimes cause the person to fall, which can cause injury.[34] Absence seizures can be subtle with only a slight turn of the head or eye blinking with impaired consciousness;[2] typically, the person does not fall over and returns to normal right after it ends.[2] Atonic seizures involve losing muscle activity for greater than one second,[30] typically occurring on both sides of the body.[30] Rarer seizure types can cause involuntary unnatural laughter (gelastic), crying (dyscrastic), or more complex experiences such as déjà vu.[35]

About 6% of those with epilepsy have seizures that are often triggered by specific events and are known as

reflex epilepsy have seizures that are only triggered by specific stimuli.[37] Common triggers include flashing lights and sudden noises.[36] In certain types of epilepsy, seizures happen more often during sleep,[38] and in other types they occur almost only when sleeping.[39] In 2017, the International League Against Epilepsy published new uniform guidelines for the classification of seizures as well as epilepsies along with their cause and comorbidities.[40]

Seizure clusters

Patients with epilepsy may experience seizure clusters which may be broadly defined as an acute deterioration in seizure control.[41] The prevalence of seizure clusters is uncertain given that studies have used different definitions to define them.[42] However, estimates suggest that the prevalence may range from 5% to 50% of epilepsy patients.[43] Refractory epilepsy patients who have a high seizure frequency are at the greatest risk for having seizure clusters.[44][45][46] Seizure clusters are associated with increased healthcare use, worse quality of life, impaired psychosocial functioning, and possibly increased mortality.[42][47] Benzodiazepines are used as an acute treatment for seizure clusters.[48]

Post-ictal

After the active portion of a seizure (the

Todd's paralysis, may also occur after a focal seizure. It would typically last for seconds to minutes but may rarely last for a day or two.[52]

Psychosocial

Epilepsy can have adverse effects on social and psychological well-being.[27] These effects may include social isolation, stigmatization, or disability.[27] They may result in lower educational achievement and worse employment outcomes.[27] Learning disabilities are common in those with the condition, and especially among children with epilepsy.[27] The stigma of epilepsy can also affect the families of those with the disorder.[32]

Certain disorders occur more often in people with epilepsy, depending partly on the epilepsy syndrome present. These include depression, anxiety, obsessive–compulsive disorder (OCD),[53] and migraine.[54] Attention deficit hyperactivity disorder (ADHD) affects three to five times more children with epilepsy than children without the condition.[55] ADHD and epilepsy have significant consequences on a child's behavioral, learning, and social development.[56] Epilepsy is also more common in children with autism.[57]

Approximately, one-in-three people with epilepsy have a lifetime history of a psychiatric disorder.[58] There are believed to be multiple causes for this including pathophysiological changes related to the epilepsy itself as well as adverse experiences related to living with epilepsy (e.g., stigma, discrimination).[59] In addition, it is thought that the relationship between epilepsy and psychiatric disorders is not unilateral but rather bidirectional. For example, patients with depression have an increased risk for developing new-onset epilepsy.[60]

The presence of comorbid depression or anxiety in patients with epilepsy is associated with a poorer quality of life, increased mortality, increased healthcare use and a worse response to treatment (including surgical).[61][62][63][64] Anxiety disorders and depression may explain more variability in quality of life than seizure type or frequency.[65] There is evidence that both depression and anxiety disorders are underdiagnosed and undertreated in patients with epilepsy.[66]

Causes

See also: Causes of seizures

Epilepsy can have both genetic and acquired causes, with the interaction of these factors in many cases.

strokes are more likely in older people.[27]

Seizures may also occur as a consequence of other health problems;

seizure-related disorders rather than epilepsy itself.[69][70]

Genetics

Genetics is believed to be involved in the majority of cases, either directly or indirectly.

single gene defect (1–2%); most are due to the interaction of multiple genes and environmental factors.[15] Each of the single gene defects is rare, with more than 200 in all described.[72] Most genes involved affect ion channels, either directly or indirectly.[67] These include genes for ion channels, enzymes, GABA, and G protein-coupled receptors.[34]

In identical twins, if one is affected, there is a 50–60% chance that the other will also be affected.[15] In non-identical twins, the risk is 15%.[15] These risks are greater in those with generalized rather than focal seizures.[15] If both twins are affected, most of the time they have the same epileptic syndrome (70–90%).[15] Other close relatives of a person with epilepsy have a risk five times that of the general population.[73] Between 1 and 10% of those with Down syndrome and 90% of those with Angelman syndrome have epilepsy.[73]

Phakomatoses

Phakomatoses, also known as neurocutaneous disorders, are a group of multisystemic diseases that most prominently affect the skin and central nervous system. They are caused by defective development of the embryonic ectodermal tissue that is most often due to a single genetic mutation. The brain, as well as other neural tissue and the skin, are all derived from the ectoderm and thus defective development may result in epilepsy as well as other manifestations such as autism and intellectual disability. Some types of phakomatoses such as tuberous sclerosis complex and Sturge-Weber syndrome have a higher prevalence of epilepsy relative to others such as neurofibromatosis type 1.[74]

Tuberous sclerosis complex is an autosomal dominant disorder that is caused by mutations in either the TSC1 or TSC2 gene and it affects approximately 1 in 6,000–10,000 live births.[75][76] These mutations result in the upregulation of the mechanistic target of rapamycin (mTOR) pathway which leads to the growth of tumors in many organs including the brain, skin, heart, eyes and kidneys.[76] In addition, abnormal mTOR activity is believed to alter neural excitability.[77] The prevalence of epilepsy is estimated to be 80-90%.[74][77] The majority of cases of epilepsy present within the first 3 years of life and are medically refractory.[78] Relatively recent developments for the treatment of epilepsy in TSC patients include mTOR inhibitors, cannabidiol and vigabatrin. Epilepsy surgery is often pursued.

Sturge-Weber syndrome is caused by an activating somatic mutation in the GNAQ gene and it affects approximately 1 in 20,000–50,000 live births.[79] The mutation results in vascular malformations affecting the brain, skin and eyes. The typical presentation includes a facial port-wine birthmark, ocular angiomas and cerebral vascular malformations which are most often unilateral but are bilateral in 15% of cases.[80] The prevalence of epilepsy is 75-100% and is higher in those with bilateral involvement.[80] Seizures typically occur within the first two years of life and are refractory in nearly half of cases.[81] However, high rates of seizure freedom with surgery have been reported in as many as 83%.[82]

Neurofibromatosis type 1 is the most common phakomatoses and occurs in approximately 1 in 3,000 live births.[83] It is caused by autosomal dominant mutations in the Neurofibromin 1 gene. Clinical manifestations are variable but may include hyperpigmented skin marks, hamartomas of the iris called Lisch nodules, neurofibromas, optic pathway gliomas and cognitive impairment. The prevalence of epilepsy is estimated to be 4–7%.[84] Seizures are typically easier to control with anti-seizure medications relative to other phakomatoses but in some refractory cases surgery may need to be pursued.[85]

Acquired

Epilepsy may occur as a result of several other conditions, including tumors, strokes, head trauma, previous

severe brain injury increases the risk seven-fold.[73] In those who have experienced a high-powered gunshot wound to the head, the risk is about 50%.[73]

Some evidence links epilepsy and

celiac disease and non-celiac gluten sensitivity, while other evidence does not. There appears to be a specific syndrome that includes coeliac disease, epilepsy, and calcifications in the brain.[90][91] A 2012 review estimates that between 1% and 6% of people with epilepsy have coeliac disease while 1% of the general population has the condition.[91]

The risk of epilepsy following

units of alcohol per day have a 2.5-fold increase in risk.[73] Other risks include Alzheimer's disease, multiple sclerosis, and autoimmune encephalitis.[73] Getting vaccinated does not increase the risk of epilepsy.[73] Malnutrition is a risk factor seen mostly in the developing world, although it is unclear however if it is a direct cause or an association.[20] People with cerebral palsy have an increased risk of epilepsy, with half of people with spastic quadriplegia and spastic hemiplegia having the disease.[94]

Mechanism

Normally brain electrical activity is non-synchronous, as large numbers of neurons do not normally fire at the same time, but rather fire in order as signals travel throughout the brain.

glial cells.[95][96]

Epilepsy

The exact mechanism of epilepsy is unknown,[97] but a little is known about its cellular and network mechanisms. However, it is unknown under which circumstances the brain shifts into the activity of a seizure with its excessive synchronization.[98][99] Changes in microRNAs (miRNAs) levels seems to play a leading role. MicroRNAs are a family of small non-coding RNAs that control the expression levels of multiple proteins by decreasing mRNA stability and translation, and could therefore be key regulatory mechanisms and therapeutic targets in epilepsy.[100][101]

In epilepsy, the resistance of excitatory neurons to fire during this period is decreased.[11][2] This may occur due to changes in ion channels or inhibitory neurons not functioning properly.[2] This then results in a specific area from which seizures may develop, known as a "seizure focus".[2] Another mechanism of epilepsy may be the up-regulation of excitatory circuits or down-regulation of inhibitory circuits following an injury to the brain.[2][3] These secondary epilepsies occur through processes known as epileptogenesis.[2][3] Failure of the blood–brain barrier may also be a causal mechanism as it would allow substances in the blood to enter the brain.[102]

Seizures

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.[98]

In epileptic seizures a group of neurons begin firing in an abnormal, excessive,

excitatory neuron fires it becomes more resistant to firing for a period of time.[2] This is due in part to the effect of inhibitory neurons, electrical changes within the excitatory neuron, and the negative effects of adenosine.[2]

Focal seizures begin in one area of the brain while generalized seizures begin in both hemispheres.[31] Some types of seizures may change brain structure, while others appear to have little effect.[104] Gliosis, neuronal loss, and atrophy of specific areas of the brain are linked to epilepsy but it is unclear if epilepsy causes these changes or if these changes result in epilepsy.[104]

The seizures can be described on different scales, from the cellular level[105] to the whole brain.[106] These are several concomitant factor, which on different scale can "drive" the brain to pathological states and trigger a seizure.

Diagnosis

An EEG can aid in locating the focus of the epileptic seizure.

The diagnosis of epilepsy is typically made based on observation of the seizure onset and the underlying cause.

MRI) to look at the structure of the brain are also usually part of the initial investigations.[27] While figuring out a specific epileptic syndrome is often attempted, it is not always possible.[27] Video and EEG monitoring may be useful in difficult cases.[107]

Definition

Epilepsy is a disorder of the brain defined by any of the following conditions:[10]

  1. At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
  2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years
  3. Diagnosis of an epilepsy syndrome

Furthermore, epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy syndrome but are now past that age or those who have remained seizure-free for the last 10 years, with no seizure medicines for the last 5 years.[10]

This 2014 definition of the International League Against Epilepsy[10] (ILAE) is a clarification of the ILAE 2005 conceptual definition, according to which epilepsy is "a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure."[108][109]

It is, therefore, possible to outgrow epilepsy or to undergo treatment that causes epilepsy to be resolved, but with no guarantee that it will not return. In the definition, epilepsy is now called a disease, rather than a disorder. This was a decision of the executive committee of the ILAE, taken because the word disorder, while perhaps having less stigma than does disease, also does not express the degree of seriousness that epilepsy deserves.[10]

The definition is practical in nature and is designed for clinical use. In particular, it aims to clarify when an "enduring predisposition" according to the 2005 conceptual definition is present. Researchers, statistically minded epidemiologists, and other specialized groups may choose to use the older definition or a definition of their own devising. The ILAE considers doing so is perfectly allowable, so long as it is clear what definition is being used.[10]

The ILAE definition for one seizure needs an understanding of projecting an enduring predisposition to the generation of epileptic seizures.[10] WHO, for instance, chooses to just use the traditional definition of two unprovoked seizures.[13]

Classification

Revised operational scheme of seizure classification, ILAE, 2017

In contrast to the

diagnostic workup results preferably in the seizure itself being classified (e.g. tonic-clonic) and in the underlying disease being identified (e.g. hippocampal sclerosis).[107]
The name of the diagnosis finally made depends on the available diagnostic results and the applied definitions and classifications (of seizures and epilepsies) and its respective terminology.

The International League Against Epilepsy (ILAE) provided a classification of the epilepsies and

epileptic syndromes in 1989 as follows:[110]

  1. Localization-related epilepsies and syndromes
    1. Unknown cause (e.g. benign childhood epilepsy with centrotemporal spikes)
    2. Symptomatic/
      cryptogenic (e.g. temporal lobe epilepsy
      )
  2. Generalized
    1. Unknown cause (e.g. childhood absence epilepsy)
    2. Cryptogenic or symptomatic (e.g. Lennox-Gastaut syndrome)
    3. Symptomatic (e.g. early infantile epileptic encephalopathy with burst suppression)
  3. Epilepsies and syndromes undetermined whether focal or generalized
    1. With both generalized and focal seizures (e.g. epilepsy with continuous spike-waves during slow wave sleep)
  4. Special syndromes (with situation-related seizures)

This classification was widely accepted but has also been criticized mainly because the underlying causes of epilepsy (which are a major determinant of clinical course and prognosis) were not covered in detail.[111] In 2010 the ILAE Commission for Classification of the Epilepsies addressed this issue and divided epilepsies into three categories (genetic, structural/metabolic, unknown cause)[112] which were refined in their 2011 recommendation into four categories and a number of subcategories reflecting recent technological and scientific advances.[113]

  1. Unknown cause (mostly genetic or presumed genetic origin)
    1. Pure epilepsies due to single gene disorders
    2. Pure epilepsies with complex inheritance
  2. Symptomatic (associated with gross anatomic or pathologic abnormalities)
    1. Mostly genetic or developmental causation
      1. Childhood epilepsy syndromes
      2. Progressive myoclonic epilepsies
      3. Neurocutaneous syndromes
      4. Other neurologic single gene disorders
      5. Disorders of chromosome function
      6. Developmental anomalies of cerebral structure
    2. Mostly acquired causes
      1. Hippocampal sclerosis
      2. Perinatal and infantile causes
      3. Cerebral trauma, tumor or infection
      4. Cerebrovascular disorders
      5. Cerebral immunologic disorders
      6. Degenerative and other neurologic conditions
  3. Provoked (a specific systemic or environmental factor is the predominant cause of the seizures)
    1. Provoking factors
    2. Reflex epilepsies
  4. Cryptogenic (presumed symptomatic nature in which the cause has not been identified)[113]
A revised, operational classification of seizure types has been introduced by the ILAE.[114] It allows more clearly understood terms and clearly defines focal and generalized onset dichotomy, when possible, even without observing the seizures based on description by patient or observers.[115] The essential changes in terminology are that "partial" is called "focal" with awareness used as a classifier for focal seizures -based on description focal seizures are now defined as behavioral arrest, automatisms, cognitive, autonomic, emotional or hyperkinetic variants while atonic, myoclonic, clonic, infantile spasms, and tonic seizures may be either focal or generalized based on their onset.[115] Several terms that were not clear or consistent in the description were removed such as dyscognitive, psychic, simple, and complex partial, while "secondarily generalized" is replaced by a clearer term "focal to bilateral tonic-clonic seizure".[115] New seizure types now believed to be generalized are eyelid myoclonia, myoclonic atonic, myoclonic absence, and myoclonic tonic-clonic.[115] Sometimes it is possible to classify seizures as focal or generalized based on presenting features even though onset in not known.[115] This system is based on the 1981 seizure classification modified in 2010 and principally is the same with an effort to improve the flexibility and clarity of use to understand seizure types better in keeping with current knowledge.[115]

Syndromes

Main article: Epilepsy syndromes

Cases of epilepsy may be organized into epilepsy syndromes by the specific features that are present. These features include the age that seizure begin, the seizure types, EEG findings, among others. Identifying an epilepsy syndrome is useful as it helps determine the underlying causes as well as what anti-seizure medication should be tried.[31][116]

The ability to categorize a case of epilepsy into a specific syndrome occurs more often with children since the onset of seizures is commonly early.

RYR3.[125]

Syndromes in which causes are not clearly identified are difficult to match with categories of the current classification of epilepsy. Categorization for these cases was made somewhat arbitrarily.[113] The idiopathic (unknown cause) category of the 2011 classification includes syndromes in which the general clinical features and/or age specificity strongly point to a presumed genetic cause.[113] Some childhood epilepsy syndromes are included in the unknown cause category in which the cause is presumed genetic, for instance benign rolandic epilepsy.[113] Clinical syndromes in which epilepsy is not the main feature (e.g. Angelman syndrome) were categorized symptomatic but it was argued to include these within the category idiopathic.[113] Classification of epilepsies and particularly of epilepsy syndromes will change with advances in research.[113]

Tests

An electroencephalogram (EEG) can assist in showing brain activity suggestive of an increased risk of seizures. It is only recommended for those who are likely to have had an epileptic seizure on the basis of symptoms. In the diagnosis of epilepsy, electroencephalography may help distinguish the type of seizure or syndrome present.[126] In children it is typically only needed after a second seizure unless specified by a specialist. It cannot be used to rule out the diagnosis and may be falsely positive in those without the disease.[126] In certain situations it may be useful to perform the EEG while the affected individual is sleeping or sleep deprived.[107]

Diagnostic imaging by

CT scan and MRI is recommended after a first non-febrile seizure to detect structural problems in and around the brain.[107] MRI is generally a better imaging test except when bleeding is suspected, for which CT is more sensitive and more easily available.[21] If someone attends the emergency room with a seizure but returns to normal quickly, imaging tests may be done at a later point.[21] If a person has a previous diagnosis of epilepsy with previous imaging, repeating the imaging is usually not needed even if there are subsequent seizures.[107][127]

For adults, the testing of electrolyte,

electrocardiogram can rule out problems with the rhythm of the heart.[107] A lumbar puncture may be useful to diagnose a central nervous system infection but is not routinely needed.[21] In children additional tests may be required such as urine biochemistry and blood testing looking for metabolic disorders.[107][128] Together with EEG and neuroimaging, genetic testing is becoming one of the most important diagnostic technique for epilepsy, as a diagnosis might be achieved in a relevant proportion of cases with severe epilepsies, both in children and adults.[129] For those with negative genetic testing, in some it might be important to repeat or re-analyze previous genetic studies after 2–3 years.[130]

A high blood prolactin level within the first 20 minutes following a seizure may be useful to help confirm an epileptic seizure as opposed to psychogenic non-epileptic seizure.[131][132] Serum prolactin level is less useful for detecting focal seizures.[133] If it is normal an epileptic seizure is still possible[132] and a serum prolactin does not separate epileptic seizures from syncope.[134] It is not recommended as a routine part of the diagnosis of epilepsy.[107]

Differential diagnosis

Diagnosis of epilepsy can be difficult. A number of other conditions may present very similar signs and symptoms to seizures, including syncope, hyperventilation, migraines, narcolepsy, panic attacks and psychogenic non-epileptic seizures (PNES).[135][136] In particular, syncope can be accompanied by a short episode of convulsions.[137] Nocturnal frontal lobe epilepsy, often misdiagnosed as nightmares, was considered to be a parasomnia but later identified to be an epilepsy syndrome.[138] Attacks of the movement disorder paroxysmal dyskinesia may be taken for epileptic seizures.[139] The cause of a drop attack can be, among many others, an atonic seizure.[136]

Children may have behaviors that are easily mistaken for epileptic seizures but are not. These include

Gastroesophageal reflux may cause arching of the back and twisting of the head to the side in infants, which may be mistaken for tonic-clonic seizures.[136]

Misdiagnosis is frequent (occurring in about 5 to 30% of cases).[27] Different studies showed that in many cases seizure-like attacks in apparent treatment-resistant epilepsy have a cardiovascular cause.[137][140] Approximately 20% of the people seen at epilepsy clinics have PNES[21] and of those who have PNES about 10% also have epilepsy;[141] separating the two based on the seizure episode alone without further testing is often difficult.[141]

Prevention

While many cases are not preventable, efforts to reduce head injuries,[7][11] provide good care around the time of birth, and reduce environmental parasites such as the pork tapeworm may be effective.[32] Efforts in one part of Central America to decrease rates of pork tapeworm resulted in a 50% decrease in new cases of epilepsy.[20]

Complications

Epilepsy can be dangerous when seizure occurs at certain times. The risk of drowning or being involved in a motor vehicle collision is higher. It is also found that people with epilepsy are more likely to have psychological problems.[142] Other complications include aspiration pneumonia and difficulty learning.[143]

Management

Wristbands or bracelets denoting their condition are occasionally worn by people with epilepsy should they need medical assistance.

Epilepsy is usually treated with daily medication once a second seizure has occurred,

neurostimulator, or neurosurgery
.

First aid

Rolling people with an active tonic-clonic seizure onto their side and into the recovery position helps prevent fluids from getting into the lungs.[145] Putting fingers, a bite block or tongue depressor in the mouth is not recommended as it might make the person vomit or result in the rescuer being bitten.[29][145] Efforts should be taken to prevent further self-injury.[29] Spinal precautions are generally not needed.[145]

If a seizure lasts longer than 5 minutes or if there are more than two seizures in 5 minutes without a return to a normal level of consciousness between them, it is considered a medical emergency known as status epilepticus.[107][146] This may require medical help to keep the airway open and protected;[107] a nasopharyngeal airway may be useful for this.[145] At home the recommended initial medication for seizure of a long duration is midazolam placed in the nose or mouth.[147] Diazepam may also be used rectally.[147] In hospital, intravenous lorazepam is preferred.[107]

If two doses of

benzodiazepines are not effective, other medications such as phenytoin are recommended.[107] Convulsive status epilepticus that does not respond to initial treatment typically requires admission to the intensive care unit and treatment with stronger agents such as midazolam infusion, ketamine, thiopentone or propofol.[107] Most institutions have a preferred pathway or protocol to be used in a seizure emergency like status epilepticus.[107] These protocols have been found to be effective in reducing time to delivery of treatment.[107]

Medications

Anticonvulsants

The mainstay treatment of epilepsy is anticonvulsant medications, possibly for the person's entire life.[11][27] The choice of anticonvulsant is based on seizure type, epilepsy syndrome, other medications used, other health problems, and the person's age and lifestyle.[147] A single medication is recommended initially;[148] if this is not effective, switching to a single other medication is recommended.[12][107] Two medications at once is recommended only if a single medication does not work.[107] In about half, the first agent is effective; a second single agent helps in about 13% and a third or two agents at the same time may help an additional 4%.[149] About 30% of people continue to have seizures despite anticonvulsant treatment.[7]

There are a number of medications available including phenytoin,

Controlled release carbamazepine appears to work as well as immediate release carbamazepine, and may have fewer side effects.[152] In the United Kingdom, carbamazepine or lamotrigine are recommended as first-line treatment for focal seizures, with levetiracetam and valproate as second-line due to issues of cost and side effects.[107][153] Valproate is recommended first-line for generalized seizures with lamotrigine being second-line.[107] In those with absence seizures, ethosuximide or valproate are recommended; valproate is particularly effective in myoclonic seizures and tonic or atonic seizures.[107] If seizures are well-controlled on a particular treatment, it is not usually necessary to routinely check the medication levels in the blood.[107]

The least expensive anticonvulsant is

controlled drug.[20]

Adverse effects from medications are reported in 10% to 90% of people, depending on how and from whom the data is collected.

first trimester.[158] 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.[158] Among the antiepileptic medications, levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects.[157]

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.[107][159] Stopping is possible in about 70% of children and 60% of adults.[32] Measuring medication levels is not generally needed in those whose seizures are well controlled.[127]

Surgery

Epilepsy surgery should be considered for any person with epilepsy who is medically refractory.[17] Patients are evaluated on a case-by-case basis in centres that are familiar with and have expertise in epilepsy surgery.[17] Epilepsy surgery may be an option for people with focal seizures that remain a problem despite other treatments.[160][161] These other treatments include at least a trial of two or three medications.[162] The goal of surgery has been total control of seizures.[163] However, most physicians believe that even palliative surgery where the burden of seizures is reduced significantly can help in achieving developmental progress or reversal of developmental stagnation in children with drug-resistant epilepsy and this may be achieved in 60–70% of cases.[162] Common procedures include cutting out the hippocampus via an anterior temporal lobe resection, removal of tumors, and removing parts of the neocortex.[162] Some procedures such as a corpus callosotomy are attempted in an effort to decrease the number of seizures rather than cure the condition.[162] Following surgery, medications may be slowly withdrawn in many cases.[162][160]

Neurostimulation

closed-loop responsive stimulation (RNS).[5][164][165]

Vagus nerve stimulation

Non-pharmacological modulation of neurotransmitters via high-level VNS (h-VNS) may reduce seizure frequency in children and adults who do not respond to medical and/or surgical therapy,[12] when compared with low-level VNS (l-VNS).[165] In a 2022 Cochrane review of four randomized controlled trials, with moderate certainty of evidence, people receiving h-VNS treatment were 73% more likely (13% more likely to 164% more likely) to experience a reduction in seizure frequency by at least 50% (the minimum threshold defined for individual clinical response).[165] Potentially 249 (163 to 380) per 1000 people with drug-resistant epilepsy may achieve a 50% reduction in seizures following h-VNS, benefiting an additional 105 per 1000 people compared with l-VNS.[165]

This outcome was limited by the number of studies available, and the quality of one trial in particular, wherein three people received l-VNS in error. A sensitivity analysis suggested that the best case scenario was that the likelihood of clinical response to h-VNS may be 91% (27% to 189%) higher than those receiving l-VNS. In the worst-case scenario, the likelihood of clinical response to h-VNS was still 61% higher (7% higher to 143% higher) than l-VNS.[165]

Despite the potential benefit for h-VNS treatment, the Cochrane review also found that the risk of several adverse-effects was greater than those receiving l-VNS. There was moderate certainty of evidence that voice alteration or hoarseness risk may be 2.17(1.49 to 3.17) fold higher than people receiving l-VNS.

Dyspnoea risk was also 2.45 (1.07 to 5.60) times that of l-VNS recipients, although the low number of events and studies meant that the certainty of evidence was low. The risk of rebound-withdrawal symptoms, coughing, pain and paraesthesia was unclear.[165]

Diet

There is promising evidence that a

modified Atkins diet can be helpful in the treatment of epilepsy in some infants.[166] These types of diets may be beneficial for children with drug-resistant epilepsy; the use for adults remains uncertain.[6] The most commonly reported adverse effects were vomiting, constipation and diarrhoea.[6] It is unclear why this diet works.[167] In people with coeliac disease or non-celiac gluten sensitivity and occipital calcifications, a gluten-free diet may decrease the frequency of seizures.[91]

Other

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.

Operant-based biofeedback based on the EEG waves has some support in those who do not respond to medications.[169] Psychological methods should not, however, be used to replace medications.[107]

Exercise has been proposed as possibly useful for preventing seizures,

seizure dogs, may help during or after a seizure.[172][173] It is not clear if dogs have the ability to predict seizures before they occur.[174]

There is moderate-quality evidence supporting the use of psychological interventions along with other treatments in epilepsy.[175] This can improve quality of life, enhance emotional wellbeing, and reduce fatigue in adults and adolescents.[175] Psychological interventions may also improve seizure control for some individuals by promoting self-management and adherence.[175]

As an add-on therapy in those who are not well controlled with other medications, cannabidiol appears to be useful in some children.[176][177] In 2018 the FDA approved this product for Lennox–Gastaut syndrome and Dravet syndrome.[178]

There are a few studies on the use of dexamethasone for the successful treatment of drug-resistant seizures in both adults and children.[179]

Alternative medicine

Alternative medicine, including

vitamins,[181] and yoga,[182] have no reliable evidence to support their use in epilepsy. Melatonin, as of 2016, is insufficiently supported by evidence.[183] The trials were of poor methodological quality and it was not possible to draw any definitive conclusions.[183]

Several supplements (with varied reliabilities of evidence) have been reported to be helpful for drug-resistant epilepsy. These include high-dose Omega-3, berberine, Manuka honey, reishi and lion's mane mushrooms, curcumin,[184] vitamin E, coenzyme Q-10, and resveratrol. The reason these can work (in theory) is that they reduce inflammation or oxidative stress, two of the major mechanism contributing to epilepsy.[185]

Contraception and pregnancy

See also: Epilepsy and pregnancy

Women of child-bearing age, including those with epilepsy, are at risk of

contraception.[186] Women with epilepsy may experience a temporary increase in seizure frequency when they begin hormonal contraception.[186]

Some anti-seizure medications interact with enzymes in the liver and cause the drugs in hormonal contraception to be broken down more quickly. These

intrauterine devices (IUDs) are preferred for women with epilepsy who are not intending to become pregnant.[186]

Women with epilepsy, especially if they have other medical conditions, may have a slightly lower, but still high, chance of becoming pregnant.[186] 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.[186] There may be a higher risk of pregnancy loss.[186]

Once pregnant, there are two main concerns related to

birth defects.[157] 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.[186][189]

Pregnancy does not seem to change seizure frequency very much.[186] 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.[186]

All pregnancies have a risk of birth defects, e.g., due to

Folic acid supplementation, such as through prenatal vitamins, reduced the risk.[186] Planning pregnancies in advance gives women with epilepsy an opportunity to switch to a lower-risk treatment program and reduced drug doses.[186]

Although anti-seizure drugs can be found in breast milk, women with epilepsy can breastfeed their babies, and the benefits usually outweigh the risks.[186]

Prognosis

Deaths due to epilepsy per million persons in 2012
  0–7
  8–10
  11–13
  14–17
  18–21
  22–28
  29–37
  38–67
  68–100
  101–232

Epilepsy cannot usually be cured, but medication can control seizures effectively in about 70% of cases.[7] Of those with generalized seizures, more than 80% can be well controlled with medications while this is true in only 50% of people with focal seizures.[5] One predictor of long-term outcome is the number of seizures that occur in the first six months.[27] Other factors increasing the risk of a poor outcome include little response to the initial treatment, generalized seizures, a family history of epilepsy, psychiatric problems, and waves on the EEG representing generalized epileptiform activity.[190] In the developing world, 75% of people are either untreated or not appropriately treated.[32] In Africa, 90% do not get treatment.[32] This is partly related to appropriate medications not being available or being too expensive.[32]

Mortality

People with epilepsy are at an increased risk of death.[191] This increase is between 1.6 and 4.1-fold greater than that of the general population.[192] The greatest increase in mortality from epilepsy is among the elderly.[192] Those with epilepsy due to an unknown cause have little increased risk.[192]

Mortality is often related to the underlying cause of the seizures, status epilepticus, suicide, trauma, and sudden unexpected death in epilepsy (SUDEP).[191] Death from status epilepticus is primarily due to an underlying problem rather than missing doses of medications.[191] The risk of suicide is between two and six times higher in those with epilepsy;[193][194] the cause of this is unclear.[193] SUDEP appears to be partly related to the frequency of generalized tonic-clonic seizures[195] and accounts for about 15% of epilepsy-related deaths;[190] it is unclear how to decrease its risk.[195] Risk factors for SUDEP include nocturnal generalized tonic-clonic seizures, seizures, sleeping alone and medically intractable epilepsy.[196]

In the United Kingdom, it is estimated that 40–60% of deaths are possibly preventable.[27] In the developing world, many deaths are due to untreated epilepsy leading to falls or status epilepticus.[20]

Epidemiology

Epilepsy is one of the most common serious neurological disorders

developing world.[32]

The estimated prevalence of active epilepsy (as of 2012[update]) is in the range 3–10 per 1,000, with active epilepsy defined as someone with epilepsy who has had a least one unprovoked seizure in the last five years.[70][199] Epilepsy begins each year in 40–70 per 100,000 in developed countries and 80–140 per 100,000 in developing countries.[32] Poverty is a risk and includes both being from a poor country and being poor relative to others within one's country.[20] In the developed world epilepsy most commonly starts either in the young or in the old.[20] In the developing world its onset is more common in older children and young adults due to the higher rates of trauma and infectious diseases.[20] In developed countries the number of cases a year has decreased in children and increased among the elderly between the 1970s and 2003.[199] This has been attributed partly to better survival following strokes in the elderly.[70]

History

See also: On the Sacred Disease
Hippocrates, 17th century engraving by Peter Paul Rubens of an antique bust

The oldest medical records show that epilepsy has been affecting people at least since the beginning of recorded history.[200] Throughout ancient history, the disease was thought to be a spiritual condition.[200] 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.[25] The person described in the text was diagnosed as being under the influence of a moon god, and underwent an exorcism.[25] Epileptic seizures are listed in the Code of Hammurabi (c. 1790 BC) as reason for which a purchased slave may be returned for a refund,[25] and the Edwin Smith Papyrus (c. 1700 BC) describes cases of individuals with epileptic convulsions.[25]

The oldest known detailed record of the disease itself is in the

Sakikku, a Babylonian cuneiform medical text from 1067–1046 BC.[200] This text gives signs and symptoms, details treatment and likely outcomes,[25] and describes many features of the different seizure types.[200] As the Babylonians had no biomedical understanding of the nature of disease, they attributed the seizures to possession by evil spirits and called for treating the condition through spiritual means.[200] Around 900 BC, Punarvasu Atreya described epilepsy as loss of consciousness;[201] this definition was carried forward into the Ayurvedic text of Charaka Samhita (c. 400 BC).[202]

The

Ancient Greek: ἠ ἱερὰ νόσος).[25][203] Epilepsy appears within Greek mythology: it is associated with the Moon goddesses Selene and Artemis, who afflicted those who upset them. The Greeks thought that important figures such as Julius Caesar and Hercules had the disease.[25] The notable exception to this divine and spiritual view was that of the school of Hippocrates. In the fifth century BC, Hippocrates rejected the idea that the disease was caused by spirits. In his landmark work On the Sacred Disease, he proposed that epilepsy was not divine in origin and instead was a medically treatable problem originating in the brain.[25][200] He accused those of attributing a sacred cause to the disease of spreading ignorance through a belief in superstitious magic.[25] Hippocrates proposed that heredity was important as a cause, described worse outcomes if the disease presents at an early age, and made note of the physical characteristics as well as the social shame associated with it.[25] 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.[25] Despite his work detailing the physical origins of the disease, his view was not accepted at the time.[200] Evil spirits continued to be blamed until at least the 17th century.[200]

In

gagates, whose smoke would trigger the seizure.[205] Occasionally a spinning potter's wheel was used, perhaps a reference to photosensitive epilepsy.[206]

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

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.[208] In Ancient Rome, epilepsy was known as the 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.[209] 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.[210] Around the same time period, epilepsy was known in France as the haut-mal lit. 'high evil', mal-de terre lit. 'earthen sickness', mal de Saint Jean lit. 'Saint John's sickness', mal des enfans lit. 'child sickness', and mal-caduc lit. 'falling sickness'.[210] Patients of epilepsy in France were also known as tombeurs lit. 'people who fall', due to the seizures and loss of consciousness in an epileptic episode.[210]

In the mid-19th century, the first effective anti-seizure medication, bromide, was introduced.[156] The first modern treatment, phenobarbital, was developed in 1912, with phenytoin coming into use in 1938.[211]

Society and culture

See also: List of people with epilepsy

Stigma

Social stigma is commonly experienced, around the world, by those with epilepsy.[13][212] It can affect people economically, socially and culturally.[212] In India and China, epilepsy may be used as justification to deny marriage.[32] People in some areas still believe those with epilepsy to be cursed.[20] In parts of Africa, such as Tanzania and Uganda, epilepsy is claimed to be associated with possession by evil spirits, witchcraft, or poisoning and is incorrectly believed by many to be contagious.[207][20] Before 1971 in the United Kingdom, epilepsy was considered grounds for the annulment of marriage.[32] The stigma may result in some people with epilepsy denying that they have ever had seizures.[70]

Economics

Seizures result in direct economic costs of about one billion dollars in the United States.[21] Epilepsy resulted in economic costs in Europe of around 15.5 billion euros in 2004.[27] In India epilepsy is estimated to result in costs of US$1.7 billion or 0.5% of the GDP.[32] It is the cause of about 1% of emergency department visits (2% for emergency departments for children) in the United States.[213]

Vehicles

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.[24] 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.[214] In some places physicians are required by law to report if a person has had a seizure to the licensing body while in others the requirement is only that they encourage the person in question to report it himself.[24] Countries that require physician reporting include Sweden, Austria, Denmark and Spain.[24] 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.[24] In Canada, the United States and Australia the requirements around reporting vary by province or state.[24] If seizures are well controlled most feel allowing driving is reasonable.[215] The amount of time a person must be free from seizures before he can drive varies by country.[215] Many countries require one to three years without seizures.[215] In the United States the time needed without a seizure is determined by each state and is between three months and one year.[215]

Those with epilepsy or seizures are typically denied a pilot license.[216]

  • 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.[217] Those with febrile seizures and drug related seizures may also be considered.[217]
  • In the United States, the Federal Aviation Administration does not allow those with epilepsy to get a commercial pilot license.[218] 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.[219]
  • In the United Kingdom, a full
    national private pilot license requires the same standards as a professional driver's license.[220] This requires a period of ten years without seizures while off medications.[221] Those who do not meet this requirement may acquire a restricted license if free from seizures for five years.[220]

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.[32] 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.[222] The Epilepsy Foundation, some hospitals, and some individuals also run support groups in the United States.[223] 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.[224][225]

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.[226]

Research

See also: Computational models in epilepsy

Seizure prediction and modeling

Seizure prediction refers to attempts to forecast epileptic seizures based on the EEG before they occur.[227] As of 2011, no effective mechanism to predict seizures has been developed.[227] Although no effective device that can predict seizures is available, the science behind seizure prediction and ability to deliver such a tool has made progress.

animal models of epilepsy.[228]
Different
animal models of epilepsy have been characterized in rodents that recapitulate the EEG and behavioral concomitants of different forms of epilepsy, in particular the occurrence of recurrent spontaneous seizures.[229] Because epileptic seizures of different kinds are observed naturally in some of these animals, strains of mice and rats have been selected to be used as genetic models of epilepsy. In particular, several lines of mice and rats display spike-and-wave discharges when EEG recorded and have been studied to understand absence epilepsy.[230] Among these models, the strain of GAERS (Genetic Absence Epilepsy Rats from Strasbourg) was characterized in the 1980s and has helped to understand the mechanisms underlying childhood absence epilepsy.[231]

Rat brain slices serve as a valuable model for assessing the potential of compounds in reducing epileptiform activity. By evaluating the frequency of epileptiform bursting in hippocampal networks, researchers can identify promising candidates for novel anti-seizure drugs.[232]

One of the hypotheses present in the literature is based on inflammatory pathways. Studies supporting this mechanism revealed that inflammatory, glycolipid, and oxidative factors are higher in epilepsy patients, especially those with generalized epilepsy.[233]

Potential future therapies

stereotactic radiosurgery is, as of 2012, being compared to standard surgery for certain types of epilepsy.[236]

Other animals

Main article: Epilepsy in animals

Epilepsy occurs in a number of other animals including dogs and cats; it is in fact the most common brain disorder in dogs.

EEGs may be useful.[239]

References

  1. ^ a b c d e f g h i j k l "Epilepsy Fact sheet". WHO. February 2016. Archived from the original on 11 March 2016. Retrieved 4 March 2016.
  2. ^
    ISBN 978-0-07-162167-0
    .
  3. ^
    PMID 23595016
    .
  4. ^
    ISBN 978-0-07-174887-2
    .
  5. ^
    S2CID 45244964
    .
  6. ^
    PMID 32588435
    .
  7. ^
    S2CID 207221378
    .
  8. ^
    PMID 27733282
    .
  9. ^
    PMID 27733281
    .
  10. ^
    S2CID 35958237
    .
  11. ^
    PMID 33923061
    .
  12. ^
    PMID 37759906
    .
  13. ^ a b c d e "Epilepsy". www.who.int. Retrieved 1 April 2023.
  14. ^
    S2CID 21130724
    .
  15. ^
    S2CID 260320566
    .
  16. PMID 25530442
    .
  17. ^
    S2CID 14318073
    .
  18. ^
    ISBN 978-0-7817-7397-3
    .
  19. ISBN 978-1-58255-937-7. Archived
    from the original on 24 June 2016.
  20. ^
    S2CID 13933909
    .
  21. ^
    PMID 22963022
    .
  22. PMID 36688481
    .
  23. S2CID 260965684
    .
  24. ^
    S2CID 30673360
    .
  25. ^
    S2CID 26340115
    .
  26. ^
    S2CID 7361318. Archived from the original
    (PDF) on 24 March 2013. Retrieved 10 January 2012.
  27. ^ a b c d e f g h i j k l m n o p q r s t National Clinical Guideline Centre (January 2012). The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care (PDF). National Institute for Health and Clinical Excellence. pp. 21–28. Archived (PDF) from the original on 16 December 2013.
  28. S2CID 22023692
    .
  29. ^ a b c d Shearer P. "Seizures and Status Epilepticus: Diagnosis and Management in the Emergency Department". Emergency Medicine Practice. Archived from the original on 30 December 2010.
  30. ^
    ISBN 978-1-4377-0434-1
    .
  31. ^ a b c d e National Clinical Guideline Centre (January 2012). The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care (PDF). National Institute for Health and Clinical Excellence. pp. 119–129. Archived (PDF) from the original on 16 December 2013.
  32. ^ a b c d e f g h i j k l m n o "Epilepsy". Fact Sheets. World Health Organization. October 2012. Retrieved 24 January 2013.
  33. ^
    ISBN 978-0-7817-5777-5. Archived
    from the original on 20 May 2016.
  34. ^
    ISBN 978-0-07-175905-2
    .
  35. ^
    OCLC 25711319
    .
  36. ^
    ISBN 978-1-933864-04-4
    .
  37. S2CID 10098600
    .
  38. PMID 16243619
    .
  39. PMID 17379548
    .
  40. PMID 28276062
    .
  41. S2CID 14510863
    .
  42. ^
    S2CID 46942965
    .
  43. S2CID 251744416
    .
  44. S2CID 37102974
    .
  45. S2CID 4735843
    .
  46. S2CID 3880221
    .
  47. S2CID 237380380
    .
  48. S2CID 251744444
    .
  49. ISBN 978-0-7817-7397-3
    .
  50. ^
    ISBN 978-1-84628-644-5
    .
  51. ISBN 978-1-60795-004-2
    .
  52. ISBN 978-1-4419-7095-4
    .
  53. S2CID 42945523
    .
  54. ISBN 978-0-444-53505-4
    .
  55. PMID 18049289
    .
  56. PMID 21310586
    .
  57. PMID 18047599
    .
  58. PMID 23021287
    .
  59. S2CID 24369127
    .
  60. S2CID 207120740
    .
  61. S2CID 30039598
    .
  62. S2CID 27842830
    .
  63. S2CID 2519902
    .
  64. S2CID 10497821
    .
  65. S2CID 24173332
    .
  66. PMID 32000099
    .
  67. ^
    S2CID 205403084
    .
  68. S2CID 232231196
    .
  69. S2CID 8505004
    .
  70. ^
    PMID 22938966
    .
  71. PMID 18472482
    .
  72. ISBN 978-0-19-972005-7. Archived
    from the original on 21 May 2016.
  73. ^
    S2CID 21190601
    .
  74. ^
    PMID 28367137
    .
  75. S2CID 9262685
    .
  76. ^
    PMID 34399110
    .
  77. ^
    PMID 25591831
    .
  78. S2CID 35481466
    .
  79. PMID 23656586
    .
  80. ^
    PMID 24275166
    .
  81. S2CID 232140769
    .
  82. PMID 34932802
    .
  83. PMID 15655144
    .
  84. S2CID 1603461
    .
  85. S2CID 25785144
    .
  86. S2CID 21665713
    .
  87. S2CID 250317784
    .
  88. S2CID 220254988
    .
  89. PMID 34865660
    .
  90. S2CID 28327166
    .
  91. ^
    PMID 21877216
    .
  92. ISBN 978-1-139-49578-3
    .
  93. S2CID 24701310
    .
  94. PMID 9352726
    .
  95. ^ a b Bromfield EB (2006). "Basic Mechanisms Underlying Seizures and Epilepsy". An Introduction to Epilepsy. American Epilepsy Society.
  96. PMID 16302873
    .
  97. ISBN 978-0-19-974654-5
    . Retrieved 16 October 2014.
  98. ^
    PMID 14641559
    .
  99. S2CID 10071296
    .
  100. S2CID 39170104
    .
  101. PMID 24553459
    .
  102. S2CID 15074513
    .
  103. ISBN 978-0-19-803459-9
    .
  104. ^
    ISBN 978-0-7817-5777-5
    .
  105. PMID 35031915
    .
  106. S2CID 235468072
    .
  107. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab National Clinical Guideline Centre (January 2012). The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care (PDF). National Institute for Health and Clinical Excellence. pp. 57–83. Archived (PDF) from the original on 16 December 2013.
  108. PMID 15816939
    .
  109. PMID 22004554
    .
  110. S2CID 3483250
    .
  111. S2CID 10663593
    .
  112. PMID 20196795
    .
  113. ^
    PMID 21449936
    .
  114. ^ "Operational Classification of Seizure Types (2017)". Archived from the original on 9 April 2023.
  115. ^
    S2CID 21037500
    .
  116. ^ "Epilepsy syndromes". International league against epilepsy. Archived from the original on 6 October 2014. Retrieved 6 October 2014.
  117. S2CID 4243468
    .
  118. ^ Chemaly N, Nabbout R. "Dravet Syndrome".
  119. ^ Chipaux M. "West syndrome".
  120. S2CID 41884825
    .
  121. PMID 22863189
    .
  122. PMID 23708187
    .
  123. PMID 24834135
    .
  124. PMID 24207121
    .
  125. PMID 25262651
    .
  126. ^ a b "1 Guidance | Epilepsies: Diagnosis and management | Guidance | NICE". 11 January 2012.
  127. ^ a b "American Epilepsy Society Choosing Wisely". www.choosingwisely.org. 14 August 2018. Retrieved 30 August 2018.
  128. ISBN 978-0-340-80814-6
    .
  129. PMID 34532824
    .
  130. S2CID 244944239
    .
  131. S2CID 945952
    .
  132. ^
    PMID 14988379
    .
  133. S2CID 2381873
    .
  134. PMID 16157897
    .
  135. S2CID 1373740
    .
  136. ^
    ISBN 978-0-323-05472-0
    .
  137. ^
    PMID 10898432
    .
  138. PMID 22136895
    .
  139. PMID 21448393
    .
  140. PMID 12071066
    .
  141. ^
    ISBN 978-0-19-532854-7
    .
  142. ^ "Epilepsy – Symptoms and causes". Mayo Clinic. Retrieved 1 April 2022.
  143. ^ "Epilepsy: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 1 April 2022.
  144. PMID 28202408
    .
  145. ^
    PMID 21109100
    .
  146. ISBN 978-1-60795-004-2
    .
  147. ^ a b c National Clinical Guideline Centre (January 2012). The Epilepsies: The diagnosis and management of the epilepsies in adults and children in primary and secondary care (PDF). National Institute for Health and Clinical Excellence. Archived (PDF) from the original on 16 December 2013.
  148. ISBN 978-1-4511-5348-4
    .
  149. ISBN 978-0-8261-2784-6
    .
  150. PMID 31318037
    .
  151. PMID 30091458
    .
  152. PMID 27933615
    .
  153. PMID 35363878
    .
  154. PMID 23284189
    .
  155. ISBN 978-1-4443-1667-4. Archived
    from the original on 21 May 2016.
  156. ^
    S2CID 25540685
    .
  157. ^
    PMID 37647086
    .
  158. ^
    S2CID 20150531
    .
  159. ISBN 978-0-7817-9256-1
    .
  160. ^
    PMID 28994113
    .
  161. PMID 7361318
    .
  162. ^
    PMID 17491501
    .
  163. S2CID 23577753
    .
  164. PMID 28870357
    .
  165. ^
    PMID 35833911
    .
  166. S2CID 254357105
    .
  167. ISBN 978-1-60795-000-4. Archived
    from the original on 24 June 2016.
  168. S2CID 23001888
    .
  169. S2CID 16682327
    .
  170. S2CID 30918370
    .
  171. S2CID 24048241
    .
  172. S2CID 3337471. Archived
    from the original on 6 October 2014.
  173. S2CID 27549519
    .
  174. S2CID 33328776
    .
  175. ^
    PMID 29078005
    .
  176. PMID 29511052
    .
  177. S2CID 242083755
    .
  178. ^ "Press Announcements - FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy". www.fda.gov. 25 June 2018. Retrieved 4 October 2018.
  179. ^ "Archive of "Journal of Investigative Medicine High Impact Case Reports". – PMC". www.ncbi.nlm.nih.gov.
  180. PMID 24801225
    .
  181. PMID 15846704
    .
  182. PMID 28982217
    .
  183. ^
    PMID 27513702
    .
  184. PMID 33746751
    .
  185. PMID 22848783
    .
  186. ^
    PMID 35191408
    .
  187. ^
    S2CID 18210697
    .
  188. ^ "Enzyme-inducing antiepileptic drugs". NICE. May 2023. Retrieved 2 November 2023.
  189. ^
    PMID 31782407
    .
  190. ^
    ISBN 978-1-908541-12-3
    .
  191. ^
    S2CID 39107474
    .
  192. ^
    ISBN 978-1-4443-1667-4. Archived
    from the original on 10 June 2016.
  193. ^
    PMID 21293270
    .
  194. S2CID 40681400
    .
  195. ^
    PMID 23646967
    .
  196. S2CID 252617763
    .
  197. S2CID 208246679
    .
  198. PMID 29453113
    .
  199. ^
    PMID 12644744
    .
  200. ^
    ISBN 978-92-4-156303-1
    . Retrieved 21 October 2023.
  201. ISBN 978-0-86196-607-3
    .
  202. ^ "Epilepsy: An historical overview". World Health Organization. February 2001. Archived from the original on 30 October 2013. Retrieved 27 December 2013.
  203. ^ "Epilepsy: historical overview". World Health Organization. Archived from the original on 20 January 2011. Retrieved 20 March 2011.
  204. ^
    ISBN 978-1-4214-0053-2
    .
  205. ISBN 978-90-72371-63-8
    .
  206. ISBN 978-1-898683-02-5
    .
  207. ^
    PMID 10080524
    .
  208. ^ "Epilepsy and its Management: A Review". ResearchGate. January 2012. Retrieved 22 February 2022.
  209. ISBN 978-0-06-209854-2. Archived
    from the original on 11 January 2014. 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.
  210. ^
    ISBN 978-1-275-31136-7
    .
  211. ISBN 978-0-7817-2845-4
    .
  212. ^
    S2CID 17282975
    .
  213. PMID 21109099
    .
  214. S2CID 224811014
    .
  215. ^
    ISBN 978-0-7817-5777-5
    .
  216. ISBN 978-1-4094-8491-2
    .
  217. ^ a b "Seizure Disorders". Transport Canada. Government of Canada. Archived from the original on 30 December 2013. Retrieved 29 December 2013.
  218. ISBN 978-1-934559-96-3. Archived
    from the original on 17 May 2016.
  219. ^ "Guide for Aviation Medical Examiners". Federal Aviation Administration. Archived from the original on 17 October 2013. Retrieved 29 December 2013.
  220. ^ a b "National PPL (NPPL) Medical Requirements". Civil Aviation Authority. Archived from the original on 16 October 2013. Retrieved 29 December 2013.
  221. ^ Drivers Medical Group (2013). "For Medical Practitioners: At a glance Guide to the current Medical Standards of Fitness to Drive" (PDF). p. 8. Archived (PDF) from the original on 30 December 2013. Retrieved 29 December 2013.
  222. US Department of Health and Human Services. 28 April 2011. Archived
    from the original on 16 July 2014. Retrieved 28 July 2014.
  223. ISBN 978-0-7817-5777-5
    .
  224. S2CID 11256074
    .
  225. PMID 25403985
    .
  226. ^ Carr F (26 March 2018). "People Are Wearing Purple Today for Epilepsy Awareness Day. Here's What That Is". Time.com. Retrieved 18 April 2018.
  227. ^
    PMID 22078526
    .
  228. ISBN 978-0-7817-5777-5
    .
  229. ^ 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).
  230. ^ Jarre, G., Guillemain, I., and, C. D. M. of S. & 2017. Genetic Models of Absence Epilepsy in Rats and Mice. Elsevier 455–471 (2017)
  231. ^ Depaulis, A. & Charpier, S. Pathophysiology of absence epilepsy: Insights from genetic models. Neurosci Lett 667, 53–65 (2018)
  232. PMID 35069421
    .
  233. S2CID 231962819
    .
  234. S2CID 13942394
    .
  235. PMID 37842826
    .
  236. PMID 22191545
    .
  237. ^
    PMID 19942062
    .
  238. S2CID 31627280
    .
  239. S2CID 24726314
    .

Further reading

External links

Wikimedia Commons has media related to Epilepsy.
Wikiquote has quotations related to Epilepsy.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Epilepsy&oldid=1218461392"