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Epilepsy

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, purposeless and synchronized electrical discharge in the brain cells called neurons.[1] The occurrence of two or more unprovoked seizures defines epilepsy.[12] 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 immediate underlying cause.[12] Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy.[13] 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.[12]

Epilepsy
Other namesSeizure disorder
Generalized 3 Hz spike-and-wave discharges on an electroencephalogram
SpecialtyNeurology
SymptomsPeriods of vigorous shaking, nearly undetectable spells[1]
DurationLong term[1]
CausesUnknown, brain injury, stroke, brain tumors, infections of the brain, birth defects[1][2][3]
Diagnostic methodElectroencephalogram, ruling out other possible causes[4]
Differential diagnosisFainting, alcohol withdrawal, electrolyte problems[4]
TreatmentMedication, surgery, neurostimulation, dietary changes[5][6]
PrognosisControllable in 69%[7]
Frequency39 million / 0.5% (2015)[8]
Deaths125,000 (2015)[9]

The underlying mechanism of an epileptic seizure is excessive and abnormal neuronal activity in the cortex of the brain[13] which can be observed in the electroencephalogram (EEG) of an individual. The reason this occurs in most cases of epilepsy is unknown (cryptogenic);[1] some cases occur as the result of brain injury, stroke, brain tumors, infections of the brain, or birth defects through a process known as epileptogenesis.[1][2][3] Known genetic mutations are directly linked to a small proportion of cases.[4][14] The diagnosis involves ruling out other conditions that might cause similar symptoms, such as fainting, and determining if another cause of seizures is present, such as alcohol withdrawal or electrolyte problems.[4] This may be partly done by imaging the brain and performing 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.[11] Nearly 80% of cases occur in the developing world.[1] In 2015, it resulted in 125,000 deaths, an increase from 112,000 in 1990.[9][15] Epilepsy is more common in older people.[16][17] In the developed world, onset of new cases occurs most frequently in babies and the elderly.[18] 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.[19] About 5–10% of people will have an unprovoked seizure by the age of 80,[20] with the chance of experiencing a second seizure rising to between 40% and 50%.[21] 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.[22] The word epilepsy is from Ancient Greek ἐπιλαμβάνειν, "to seize, possess, or afflict".[23]

Signs and symptoms

 
A still image of a generalized seizure
 
A bite to the tip of the tongue due to a seizure

Epilepsy is characterized by a long-term risk of recurrent epileptic seizures.[24] These seizures may present in several ways depending on the parts of the brain involved and the person's age.[24][25]

Seizures

The most common type (60%) of seizures are convulsive which involve involuntary muscle contractions.[25] Of these, one-third begin as generalized seizures from the start, affecting both hemispheres of the brain and impairing consciousness.[25] Two-thirds begin as focal seizures (which affect one hemisphere of the brain) which may progress to generalized seizures.[25] 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][26]

Certain experiences, known as auras often precede focal seizures.[27] The seizures can include sensory (visual, hearing, or smell), psychic, autonomic, and motor phenomena depending on which part of the brain is involved.[2] 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.[28] 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.[28]

There are six main types of generalized seizures: tonic-clonic, tonic, clonic, myoclonic, absence, and atonic seizures.[29] 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 chest muscles, followed by a shaking of the limbs in unison (clonic phase). Tonic seizures produce constant contractions of the muscles. A person often turns blue as breathing is stopped. In clonic seizures there is shaking of the limbs in unison. After the shaking has stopped it may take 10–30 minutes for the person to return to normal; this period is called the "postictal state" or "postictal phase." Loss of bowel or bladder control may occur during a seizure.[30] People experiencing a seizure may bite their tongue, either the tip or on the sides;[31] in tonic-clonic seizure, bites to the sides are more common.[31] Tongue bites are also relatively common in psychogenic non-epileptic seizures.[31] Psychogenic non-epileptic seizures are seizure like behavior without an associated synchronised electrical discharge on EEG and are considered a dissociative disorder.[31]

Myoclonic seizures involve very brief muscle spasms in either a few areas or all over.[32][33] These sometimes cause the person to fall, which can cause injury.[32] 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,[28] typically occurring on both sides of the body.[28] Rarer seizure types can cause involuntary unnatural laughter (gelastic), crying (dyscrastic), or more complex experiences such as déjà vu.[33]

About 6% of those with epilepsy have seizures that are often triggered by specific events and are known as reflex seizures.[34] Those with reflex epilepsy have seizures that are only triggered by specific stimuli.[35] Common triggers include flashing lights and sudden noises.[34] In certain types of epilepsy, seizures happen more often during sleep,[36] and in other types they occur almost only when sleeping.[37] Recently the International League against epilepsy has published new uniform guidelines for the classification of seizures as well as epilepsies along with their cause and comorbidities.[38]

Seizure clusters

Patients with epilepsy may experience seizure clusters which may be broadly defined as an acute deterioration in seizure control.[39] The prevalence of seizure clusters is uncertain given that studies have used different definitions to define them.[40] However, estimates suggest that the prevalence may range from 5% to 50% of epilepsy patients.[41] Refractory epilepsy patients who have a high seizure frequency are at the greatest risk for having seizure clusters.[42][43][44] Seizure clusters are associated with increased healthcare use, worse quality of life, impaired psychosocial functioning, and possibly increased mortality.[40][45] Benzodiazepines are used as an acute treatment for seizure clusters.[46]

Post-ictal

After the active portion of a seizure (the ictal state) there is typically a period of recovery during which there is confusion, referred to as the postictal period, before a normal level of consciousness returns.[27] It usually lasts 3 to 15 minutes[47] but may last for hours.[48] Other common symptoms include feeling tired, headache, difficulty speaking, and abnormal behavior.[48] Psychosis after a seizure is relatively common, occurring in 6–10% of people.[49] Often people do not remember what happened during this time.[48] Localized weakness, known as Todd's paralysis, may also occur after a focal seizure. It would typically last for seconds to minutes but may rarely last for a day or two.[50]

Psychosocial

Epilepsy can have adverse effects on social and psychological well-being.[25] These effects may include social isolation, stigmatization, or disability.[25] They may result in lower educational achievement and worse employment outcomes.[25] Learning disabilities are common in those with the condition, and especially among children with epilepsy.[25] The stigma of epilepsy can also affect the families of those with the disorder.[30]

Certain disorders occur more often in people with epilepsy, depending partly on the epilepsy syndrome present. These include depression, anxiety, obsessive–compulsive disorder (OCD),[51] and migraine.[52] Attention deficit hyperactivity disorder (ADHD) affects three to five times more children with epilepsy than children without the condition.[53] ADHD and epilepsy have significant consequences on a child's behavioral, learning, and social development.[54] Epilepsy is also more common in children with autism.[55]

Approximately, one-in-three people with epilepsy have a lifetime history of a psychiatric disorder.[56] 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).[57] 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.[58]

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).[59][60][61][62] Anxiety disorders and depression may explain more variability in quality of life than seizure type or frequency.[63] There is evidence that both depression and anxiety disorders are underdiagnosed and undertreated in patients with epilepsy.[64]

Causes

Epilepsy can have both genetic and acquired causes, with the interaction of these factors in many cases.[65][66] Established acquired causes include serious brain trauma, stroke, tumours, and brain problems resulting from a previous infection.[65] In about 60% of cases, the cause is unknown.[25][30] Epilepsies caused by genetic, congenital, or developmental conditions are more common among younger people, while brain tumors and strokes are more likely in older people.[25]

Seizures may also occur as a consequence of other health problems;[29] if they occur right around a specific cause, such as a stroke, head injury, toxic ingestion, or metabolic problem, they are known as acute symptomatic seizures and are in the broader classification of seizure-related disorders rather than epilepsy itself.[67][68]

Genetics

Genetics is believed to be involved in the majority of cases, either directly or indirectly.[14] Some epilepsies are due to a single gene defect (1–2%); most are due to the interaction of multiple genes and environmental factors.[14] Each of the single gene defects is rare, with more than 200 in all described.[69] Most genes involved affect ion channels, either directly or indirectly.[65] These include genes for ion channels themselves, enzymes, GABA, and G protein-coupled receptors.[32]

In identical twins, if one is affected, there is a 50–60% chance that the other will also be affected.[14] In non-identical twins, the risk is 15%.[14] These risks are greater in those with generalized rather than focal seizures.[14] If both twins are affected, most of the time they have the same epileptic syndrome (70–90%).[14] Other close relatives of a person with epilepsy have a risk five times that of the general population.[70] Between 1 and 10% of those with Down syndrome and 90% of those with Angelman syndrome have epilepsy.[70]

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.[71]

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.[72][73] 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.[73] In addition, abnormal mTOR activity is believed to alter neural excitability.[74] The prevalence of epilepsy is estimated to be 80-90%.[71][74] The majority of cases of epilepsy present within the first 3 years of life and are medically refractory.[75] 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.[76] 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.[77] The prevalence of epilepsy is 75-100% and is higher in those with bilateral involvement.[77] Seizures typically occur within the first two years of life and are refractory in nearly half of cases.[78] However, high rates of seizure freedom with surgery have been reported in as many as 83%.[79]

Neurofibromatosis type 1 is the most common phakomatoses and occurs in approximately 1 in 3,000 live births.[80] 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%.[81] 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.[82]

Acquired

 
Traumatic brain injury victim who temporarily developed epilepsy; note removed area of frontal and parietal bone.

Epilepsy may occur as a result of several other conditions, including tumors, strokes, head trauma, previous infections of the central nervous system, genetic abnormalities, and as a result of brain damage around the time of birth.[29][30] Of those with brain tumors, almost 30% have epilepsy, making them the cause of about 4% of cases.[70] The risk is greatest for tumors in the temporal lobe and those that grow slowly.[70] Other mass lesions such as cerebral cavernous malformations and arteriovenous malformations have risks as high as 40–60%.[70] Of those who have had a stroke, 6–10% develop epilepsy.[83][84] Risk factors for post-stroke epilepsy include stroke severity, cortical involvement, hemorrhage and early seizures.[85][86] Between 6 and 20% of epilepsy is believed to be due to head trauma.[70] Mild brain injury increases the risk about two-fold while severe brain injury increases the risk seven-fold.[70] In those who have experienced a high-powered gunshot wound to the head, the risk is about 50%.[70]

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.[87][88] 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.[88]

The risk of epilepsy following meningitis is less than 10%; it more commonly causes seizures during the infection itself.[70] In herpes simplex encephalitis the risk of a seizure is around 50%[70] with a high risk of epilepsy following (up to 25%).[89][90] A form of an infection with the pork tapeworm (cysticercosis), in the brain, is known as neurocysticercosis, and is the cause of up to half of epilepsy cases in areas of the world where the parasite is common.[70] Epilepsy may also occur after other brain infections such as cerebral malaria, toxoplasmosis, and toxocariasis.[70] Chronic alcohol use increases the risk of epilepsy: those who drink six units of alcohol per day have a 2.5-fold increase in risk.[70] Other risks include Alzheimer's disease, multiple sclerosis, and autoimmune encephalitis.[70] Getting vaccinated does not increase the risk of epilepsy.[70] 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.[19] People with cerebral palsy have an increased risk of epilepsy, with half of people with spastic quadriplegia and spastic hemiplegia having the disease.[91]

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.[2] Neuron activity is regulated by various factors both within the cell and the cellular environment. Factors within the neuron include the type, number and distribution of ion channels, changes to receptors and changes of gene expression.[92] Factors around the neuron include ion concentrations, synaptic plasticity and regulation of transmitter breakdown by glial cells.[92][93]

Epilepsy

The exact mechanism for epilepsy is unknown,[94] 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.[95][96] Changes in MicroRNAs (miRNAs) levels seems to play a leading role. MicroRNAs (miRNAs) 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[97]

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.[98]

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.[95]

In epileptic seizures a group of neurons begin firing in an abnormal, excessive,[25] and synchronized manner.[2] This results in a wave of depolarization known as a paroxysmal depolarizing shift.[99] Normally, after an 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.[29] Some types of seizures may change brain structure, while others appear to have little effect.[100] 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.[100]

The seizures can be described on different scales, from the cellular level[101][better source needed] to the whole brain.[102] 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.[25] An electroencephalogram (EEG) to look for abnormal patterns of brain waves and neuroimaging (CT scan or MRI) to look at the structure of the brain are also usually part of the initial investigations.[25] While figuring out a specific epileptic syndrome is often attempted, it is not always possible.[25] Video and EEG monitoring may be useful in difficult cases.[103]

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."[104][105]

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.[12]

Classification

 
Revised operational scheme of seizure classification, ILAE, 2017

In contrast to the classification of seizures which focuses on what happens during a seizure, the classification of epilepsies focuses on the underlying causes. When a person is admitted to hospital after an epileptic seizure the diagnostic workup results preferably in the seizure itself being classified (e.g. tonic-clonic) and in the underlying disease being identified (e.g. hippocampal sclerosis).[103] 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:[106]

  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.[107] In 2010 the ILAE Commission for Classification of the Epilepsies addressed this issue and divided epilepsies into three categories (genetic, structural/metabolic, unknown cause)[108] that were refined in their 2011 recommendation into four categories and a number of subcategories reflecting recent technologic and scientific advances.[109]

  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)[109]
A revised, operational classification of seizure types has been introduced by the ILAE.[110] 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.[111] 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.[111] 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".[111] New seizure types now believed to be generalized are eyelid myoclonia, myoclonic atonic, myoclonic absence, and myoclonic tonic-clonic.[111] Sometimes it is possible to classify seizures as focal or generalized based on presenting features even though onset in not known.[111] 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.[111]

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.[29][112]

The International League against Epilepsy has recently taken the massive and commendable task of clarifying various epilepsy syndromes across ages with mandatory.[113] 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.[68] Less serious examples are benign rolandic epilepsy (2.8 per 100,000), childhood absence epilepsy (0.8 per 100,000) and juvenile myoclonic epilepsy (0.7 per 100,000).[68] Severe syndromes with diffuse brain dysfunction caused, at least partly, by some aspect of epilepsy, are also referred to as developmental and epileptic encephalopathies. These are associated with frequent seizures that are resistant to treatment and cognitive dysfunction, for instance Lennox–Gastaut syndrome (1–2% of all persons with epilepsy),[114] Dravet syndrome(1: 15000-40000 worldwide[115]), and West syndrome(1–9: 100000[116]).[117] 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.[118] 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[119][120][121] and DNM1, GABBR2, FASN and RYR3.[122]

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.[109] 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.[109] Some childhood epilepsy syndromes are included in the unknown cause category in which the cause is presumed genetic, for instance benign rolandic epilepsy.[109] 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.[109] Classification of epilepsies and particularly of epilepsy syndromes will change with advances in research.[109]

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.[123] 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.[123] In certain situations it may be useful to perform the EEG while the affected individual is sleeping or sleep deprived.[103]

Diagnostic imaging by CT scan and MRI is recommended after a first non-febrile seizure to detect structural problems in and around the brain.[103] MRI is generally a better imaging test except when bleeding is suspected, for which CT is more sensitive and more easily available.[20] If someone attends the emergency room with a seizure but returns to normal quickly, imaging tests may be done at a later point.[20] 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.[103][124]

For adults, the testing of electrolyte, blood glucose and calcium levels is important to rule out problems with these as causes.[103] An electrocardiogram can rule out problems with the rhythm of the heart.[103] A lumbar puncture may be useful to diagnose a central nervous system infection but is not routinely needed.[20] In children additional tests may be required such as urine biochemistry and blood testing looking for metabolic disorders.[103][125] 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.[126] For those with negative genetic testing, in some it might be important to repeat or re-analyze previous genetic studies after 2–3 years.[127]

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.[128][129] Serum prolactin level is less useful for detecting focal seizures.[130] If it is normal an epileptic seizure is still possible[129] and a serum prolactin does not separate epileptic seizures from syncope.[131] It is not recommended as a routine part of the diagnosis of epilepsy.[103]

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).[132][133] In particular, syncope can be accompanied by a short episode of convulsions.[134] Nocturnal frontal lobe epilepsy, often misdiagnosed as nightmares, was considered to be a parasomnia but later identified to be an epilepsy syndrome.[135] Attacks of the movement disorder paroxysmal dyskinesia may be taken for epileptic seizures.[136] The cause of a drop attack can be, among many others, an atonic seizure.[133]

Children may have behaviors that are easily mistaken for epileptic seizures but are not. These include breath-holding spells, bedwetting, night terrors, tics and shudder attacks.[133] 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.[133]

Misdiagnosis is frequent (occurring in about 5 to 30% of cases).[25] Different studies showed that in many cases seizure-like attacks in apparent treatment-resistant epilepsy have a cardiovascular cause.[134][137] Approximately 20% of the people seen at epilepsy clinics have PNES[20] and of those who have PNES about 10% also have epilepsy;[138] separating the two based on the seizure episode alone without further testing is often difficult.[138]

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.[30] Efforts in one part of Central America to decrease rates of pork tapeworm resulted in a 50% decrease in new cases of epilepsy.[19]

Complication

Epilepsy can be dangerous when seizure occurs at certain times. The possibility of drowning and having car accident is higher. It is also dangerous when seizure occurs during pregnancy. Certain anti-epileptic medications increase the risk of birth defects. It is also found that people with epilepsy are more likely to have psychological problems.[139] Other complications include aspiration pneumonia and difficulty learning.[140]

Management

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

Epilepsy is usually treated with daily medication once a second seizure has occurred,[25][103] while medication may be started after the first seizure in those at high risk for subsequent seizures.[103] Supporting people's self management of their condition may be useful.[141] In drug-resistant cases different management options may be looked at including a special diet, the implantation of a 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.[142] 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.[27][142] Efforts should be taken to prevent further self-injury.[27] Spinal precautions are generally not needed.[142]

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.[103][143] This may require medical help to keep the airway open and protected;[103] a nasopharyngeal airway may be useful for this.[142] At home the recommended initial medication for seizure of a long duration is midazolam placed in the nose or mouth.[144] Diazepam may also be used rectally.[144] In hospital, intravenous lorazepam is preferred.[103]

If two doses of benzodiazepines are not effective, other medications such as phenytoin are recommended.[103] ] 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.[103] Most institutions have a preferred pathway or protocol to be used in a seizure emergency like status epilepticus.[103] These protocols have been found to be effective in reducing time to delivery of treatment.[103]

Medications

 
Anticonvulsants

The mainstay treatment of epilepsy is anticonvulsant medications, possibly for the person's entire life.[11][25] The choice of anticonvulsant is based on seizure type, epilepsy syndrome, other medications used, other health problems, and the person's age and lifestyle.[144] A single medication is recommended initially;[145] if this is not effective, switching to a single other medication is recommended.[103] Two medications at once is recommended only if a single medication does not work.[103] 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%.[146] About 30% of people continue to have seizures despite anticonvulsant treatment.[7]

There are a number of medications available including phenytoin, carbamazepine and valproate. Evidence suggests that phenytoin, carbamazepine, and valproate may be equally effective in both focal and generalized seizures.[147][148] Controlled release carbamazepine appears to work as well as immediate release carbamazepine, and may have fewer side effects.[149] Recently, Nux vomica[150] and Cicuta virosa[151] have been shown to produce significant anti-epileptic effects and no side effects. This could prove to be very helpful for a large segment of population. 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.[103][152] Valproate is recommended first-line for generalized seizures with lamotrigine being second-line.[103] In those with absence seizures, ethosuximide or valproate are recommended; valproate is particularly effective in myoclonic seizures and tonic or atonic seizures.[103] If seizures are well-controlled on a particular treatment, it is not usually necessary to routinely check the medication levels in the blood.[103]

The least expensive anticonvulsant is phenobarbital at around US$5 a year.[19] The World Health Organization gives it a first-line recommendation in the developing world and it is commonly used there.[153][154] Access however may be difficult as some countries label it as a controlled drug.[19]

Adverse effects from medications are reported in 10 to 90% of people, depending on how and from whom the data is collected.[155] Most adverse effects are dose-related and mild.[155] Some examples include mood changes, sleepiness, or an unsteadiness in gait.[155] Certain medications have side effects that are not related to dose such as rashes, liver toxicity, or suppression of the bone marrow.[155] Up to a quarter of people stop treatment due to adverse effects.[155] Some medications are associated with birth defects when used in pregnancy.[103] Many of the common used medications, such as valproate, phenytoin, carbamazepine, phenobarbital, and gabapentin have been reported to cause increased risk of birth defects,[156] especially when used during the first trimester.[157] 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.[157] Among the antiepileptic medications, levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects.[156]

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.[103][158] Stopping is possible in about 70% of children and 60% of adults.[30] Measuring medication levels is not generally needed in those whose seizures are well controlled.[124]

Surgery

Epilepsy surgery should be considered for any person with epilepsy who is medically refractory.[159] Patients are evaluated on a 'Case by case' epilepsy in centres that are familiar and have expertise in epilepsy surgery.[159] 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

Neurostimulation via neuro-cybernetic prosthesis implantation, may be another option in those who are not candidates for surgery, providing chronic, pulsatile electrical stimulation of specific nerve or brain regions, alongside standard care.[103] Three types have been used in those who do not respond to medications: vagus nerve stimulation (VNS), anterior thalamic stimulation, and 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, when compared with low-level VNS (l-VNS).[165] In a 2022 Cochrane review of 4 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 3 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 ketogenic diet (high-fat, low-carbohydrate, adequate-protein) decreases the number of seizures and eliminates seizures in some; however, further research is necessary.[6] It is a reasonable option in those who have epilepsy that is not improved with medications and for whom surgery is not an option.[6] About 10% stay on the diet for a few years due to issues of effectiveness and tolerability.[6] Side effects include stomach and intestinal problems in 30%, and there are long-term concerns about heart disease.[6] Less radical diets are easier to tolerate and may be effective.[6] It is unclear why this diet works.[166] In people with coeliac disease or non-celiac gluten sensitivity and occipital calcifications, a gluten-free diet may decrease the frequency of seizures.[88]

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.[167] Operant-based biofeedback based on the EEG waves has some support in those who do not respond to medications.[168] Psychological methods should not, however, be used to replace medications.[103]

Exercise has been proposed as possibly useful for preventing seizures,[169] with some data to support this claim.[170] Some dogs, commonly referred to as seizure dogs, may help during or after a seizure.[171][172] It is not clear if dogs have the ability to predict seizures before they occur.[173]

There is moderate-quality evidence supporting the use of psychological interventions along with other treatments in epilepsy.[174] This can improve quality of life, enhance emotional wellbeing, and reduce fatigue in adults and adolescents.[174] Psychological interventions may also improve seizure control for some individuals by promoting self-management and adherence.[174]

As an add-on therapy in those who are not well controlled with other medications, cannabidiol appears to be useful in some children.[175][176] In 2018 the FDA approved this product for Lennox–Gastaut syndrome and Dravet syndrome.[177]

There are a few studies on the use of dexamethasone for the successful treatment of drug-resistant seizures in both adults and children.[178]

In pregnancy

In women of childbearing age, use of antiepileptic drugs is a major concern balancing possible side effects on the fetus against risk from uncontrolled seizures.[179] Use of AEDs entail teratogenic effects including intrauterine growth retardation, major congenital malformations, and developmental (neurocognitive) and behavioral issues, that need to be discussed with the patient at the time of starting the AEDs and before they plan pregnancy.[179] Most women with epilepsy receive safe and effective treatment and have normal children, however, risks exist.[179] The International League Against Epilepsy created a task force on women and epilepsy which published consensus recommendations to guide therapy decisions until more definitive evidence is available in the future.[179]

Alternative medicine

Alternative medicine, including acupuncture,[180] routine 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]

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.[25] 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.[186] In the developing world, 75% of people are either untreated or not appropriately treated.[30] In Africa, 90% do not get treatment.[30] This is partly related to appropriate medications not being available or being too expensive.[30]

Mortality

People with epilepsy are at an increased risk of death.[187] This increase is between 1.6 and 4.1 fold greater than that of the general population.[188] The greatest increase in mortality from epilepsy is among the elderly.[188] Those with epilepsy due to an unknown cause have little increased risk.[188]

Mortality is often related to: the underlying cause of the seizures, status epilepticus, suicide, trauma, and sudden unexpected death in epilepsy (SUDEP).[187] Death from status epilepticus is primarily due to an underlying problem rather than missing doses of medications.[187] The risk of suicide is between 2 and 6 times higher in those with epilepsy;[189][190] the cause of this is unclear.[189] SUDEP appears to be partly related to the frequency of generalized tonic-clonic seizures[191] and accounts for about 15% of epilepsy-related deaths;[186] it is unclear how to decrease its risk.[191] Risk factors for SUDEP include nocturnal generalized tonic-clonic seizures, seizures, Sleeping along and medically intractable epilepsy.[192]

In the United Kingdom, it is estimated that 40–60% of deaths are possibly preventable.[25] In the developing world, many deaths are due to untreated epilepsy leading to falls or status epilepticus.[19]

Epidemiology

Epilepsy is one of the most common serious neurological disorders[193] affecting about 39 million people as of 2015.[8] It affects 1% of the population by age 20 and 3% of the population by age 75.[17] It is more common in males than females with the overall difference being small.[19][68] Most of those with the disorder (80%) are in low income populations[194] or the developing world.[30]

The estimated prevalence of active epilepsy (as of 2012) 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.[68][195] Epilepsy begins each year in 40–70 per 100,000 in developed countries and 80–140 per 100,000 in developing countries.[30] Poverty is a risk and includes both being from a poor country and being poor relative to others within one's country.[19] In the developed world epilepsy most commonly starts either in the young or in the old.[19] 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.[19] In developed countries the number of cases a year has decreased in children and increased among the elderly between the 1970s and 2003.[195] This has been attributed partly to better survival following strokes in the elderly.[68]

History

 
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.[196] Throughout ancient history, the disease was thought to be a spiritual condition.[196] 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.[23] The person described in the text was diagnosed as being under the influence of a moon god, and underwent an exorcism.[23] 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,[23] and the Edwin Smith Papyrus (c. 1700 BC) describes cases of individuals with epileptic convulsions.[23]

The oldest known detailed record of the disease itself is in the Sakikku, a Babylonian cuneiform medical text from 1067–1046 BC.[196] This text gives signs and symptoms, details treatment and likely outcomes,[23] and describes many features of the different seizure types.[196] 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.[196] Around 900 BC, Punarvasu Atreya described epilepsy as loss of consciousness;[197] this definition was carried forward into the Ayurvedic text of Charaka Samhita (c. 400 BC).[198]

The ancient Greeks had contradictory views of the disease. They thought of epilepsy as a form of spiritual possession, but also associated the condition with genius and the divine. One of the names they gave to it was the sacred disease (Greek: ἠ ἱερὰ νόσος).[23][199] 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.[23] 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.[23][196] He accused those of attributing a sacred cause to the disease of spreading ignorance through a belief in superstitious magic.[23] 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.[23] 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.[23] Despite his work detailing the physical origins of the disease, his view was not accepted at the time.[196] Evil spirits continued to be blamed until at least the 17th century.[196]

In Ancient Rome people did not eat or drink with the same pottery as that used by someone who was affected.[200] People of the time would spit on their chest believing that this would keep the problem from affecting them.[200] 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.[201] Occasionally a spinning potter's wheel was used, perhaps a reference to photosensitive epilepsy.[202]

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.[203] 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.[204] In Ancient Rome, epilepsy was known as the Latin: morbus comitialis, lit.'disease of the assembly hall' and was seen as a curse from the gods. In northern Italy, epilepsy was once traditionally known as Saint Valentine's malady.[205] 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.[206] Around the same time period, epilepsy was known in France as the French: haut-mal, lit.'high evil', French: mal-de terre, lit.'earthen sickness', French: mal de Saint Jean, lit.'Saint John's sickness', French: mal des enfans, lit.'child sickness', and French: mal-caduc, lit.'falling sickness'.[206] Patients of epilepsy in France were also known as French: tombeurs, lit.'people who fall', due to the seizures and loss of consciousness in an epileptic episode.[206]

In the mid-19th century, the first effective anti-seizure medication, bromide, was introduced.[155] The first modern treatment, phenobarbital, was developed in 1912, with phenytoin coming into use in 1938.[207]

Society and culture

Stigma

Social stigma is commonly experienced, around the world, by those with epilepsy.[12][208] It can affect people economically, socially and culturally.[208] In India and China, epilepsy may be used as justification to deny marriage.[30] People in some areas still believe those with epilepsy to be cursed.[19] 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.[203][19] Before 1971 in the United Kingdom, epilepsy was considered grounds for the annulment of marriage.[30] The stigma may result in some people with epilepsy denying that they have ever had seizures.[68]

Economics

Seizures result in direct economic costs of about one billion dollars in the United States.[20] Epilepsy resulted in economic costs in Europe of around 15.5 billion euros in 2004.[25] In India epilepsy is estimated to result in costs of US$1.7 billion or 0.5% of the GDP.[30] It is the cause of about 1% of emergency department visits (2% for emergency departments for children) in the United States.[209]

Vehicles

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.[22] 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 nonmotor seizures as opposed to those with motor seizures at epilepsy onset.[210] 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.[22] Countries that require physician reporting include Sweden, Austria, Denmark and Spain.[22] 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.[22] In Canada, the United States and Australia the requirements around reporting vary by province or state.[22] If seizures are well controlled most feel allowing driving is reasonable.[211] The amount of time a person must be free from seizures before he can drive varies by country.[211] Many countries require one to three years without seizures.[211] In the United States the time needed without a seizure is determined by each state and is between three months and one year.[211]

Those with epilepsy or seizures are typically denied a pilot license.[212] 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.[213] Those with febrile seizures and drug related seizures may also be considered.[213] In the United States, the Federal Aviation Administration does not allow those with epilepsy to get a commercial pilot license.[214] 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.[215] In the United Kingdom, a full national private pilot license requires the same standards as a professional driver's license.[216] This requires a period of ten years without seizures while off medications.[217] Those who do not meet this requirement may acquire a restricted license if free from seizures for five years.[216]

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.[30] 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.[218] The Epilepsy Foundation, some hospitals, and some individuals also run support groups in the United States.[219] 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.[220][221]

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.[222]

Research

Seizure prediction and modeling

Seizure prediction refers to attempts to forecast epileptic seizures based on the EEG before they occur.[223] As of 2011, no effective mechanism to predict seizures has been developed.[223] 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.

Kindling, where repeated exposures to events that could cause seizures eventually causes seizures more easily, has been used to create animal models of epilepsy.[224] 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.[225] 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.[226] Among these models, the strain of GAERS (Genetic Absence Epilepsy Rats from Strasbourg) was characterized in the 80' and has helped to understand the mechanisms underlying Childhood Absence Epilepsy.[227]

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.[228]

Potential future therapies

Gene therapy is being studied in some types of epilepsy.[229] Medications that alter immune function, such as intravenous immunoglobulins, are poorly supported by evidence.[230] Noninvasive stereotactic radiosurgery is, as of 2012, being compared to standard surgery for certain types of epilepsy.[231]

Other animals

Epilepsy occurs in a number of other animals including dogs and cats; it is in fact the most common brain disorder in dogs.[232] It is typically treated with anticonvulsants such as phenobarbital or bromide in dogs and phenobarbital in cats.[232] Imepitoin is also used in dogs.[233] While generalized seizures in horses are fairly easy to diagnose, it may be more difficult in non-generalized seizures and EEGs may be useful.[234]

References

  1. ^ a b c d e f g h i j k l "Epilepsy Fact sheet". WHO. February 2016. from the original on 11 March 2016. Retrieved 4 March 2016.
  2. ^ a b c d e f g h i j k l m n o Hammer GD, McPhee SJ, eds. (2010). "7". Pathophysiology of disease: an introduction to clinical medicine (6th ed.). New York: McGraw-Hill Medical. ISBN 978-0-07-162167-0.
  3. ^ a b c d Goldberg EM, Coulter DA (May 2013). "Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction". Nature Reviews. Neuroscience. 14 (5): 337–49. doi:10.1038/nrn3482. PMC 3982383. PMID 23595016.
  4. ^ a b c d e f Longo DL (2012). "369 Seizures and Epilepsy". Harrison's principles of internal medicine (18th ed.). McGraw-Hill. p. 3258. ISBN 978-0-07-174887-2.
  5. ^ a b c d Bergey GK (June 2013). "Neurostimulation in the treatment of epilepsy". Experimental Neurology. 244: 87–95. doi:10.1016/j.expneurol.2013.04.004. PMID 23583414. S2CID 45244964.
  6. ^ a b c d e f g Martin-McGill, Kirsty J.; Jackson, Cerian F.; Bresnahan, Rebecca; Levy, Robert G.; Cooper, Paul N. (7 November 2018). "Ketogenic diets for drug-resistant epilepsy". The Cochrane Database of Systematic Reviews. 11 (11): CD001903. doi:10.1002/14651858.CD001903.pub4. ISSN 1469-493X. PMC 6517043. PMID 30403286.
  7. ^ a b c d e Eadie MJ (December 2012). "Shortcomings in the current treatment of epilepsy". Expert Review of Neurotherapeutics. 12 (12): 1419–27. doi:10.1586/ern.12.129. PMID 23237349. S2CID 207221378.
  8. ^ a b Vos, Theo; Allen, Christine; Arora, Megha; Barber, Ryan M.; Bhutta, Zulfiqar A.; Brown, Alexandria; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Z.; Coggeshall, Megan; Cornaby, Leslie; Dandona, Lalit; Dicker, Daniel J.; Dilegge, Tina; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Fleming, Tom; Forouzanfar, Mohammad H.; Fullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Johnson, Catherine O.; Kassebaum, Nicholas J.; Kawashima, Toana; et al. (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
  9. ^ a b Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, Ryan M.; Bhutta, Zulfiqar A.; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Zian; Coates, Matthew M.; Coggeshall, Megan; Dandona, Lalit; Dicker, Daniel J.; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Foreman, Kyle; Forouzanfar, Mohammad H.; Fraser, Maya S.; Fullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Huynh, Chantal; Johnson, Catherine O.; Kassebaum, Nicholas J.; Kinfu, Yohannes; et al. (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC 5388903. PMID 27733281.
  10. ^ a b c d e f g h 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 (April 2014). "ILAE official report: a practical clinical definition of epilepsy". Epilepsia. 55 (4): 475–82. doi:10.1111/epi.12550. PMID 24730690. S2CID 35958237.
  11. ^ a b c d e f Ghosh, Shampa; Sinha, Jitendra Kumar; Khan, Tarab; Devaraju, Kuramkote Shivanna; Singh, Prabhakar; Vaibhav, Kumar; Gaur, Pankaj (May 2021). "Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy". Biomedicines. 9 (5): 470. doi:10.3390/biomedicines9050470. PMC 8146518. PMID 33923061.
  12. ^ a b c d e "Epilepsy". www.who.int. Retrieved 1 April 2023.
  13. ^ a b Fisher, RS; van Emde Boas, W; Blume, W; Elger, C; Genton, P; Lee, P; Engel J, Jr (April 2005). "Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)". Epilepsia. 46 (4): 470–2. doi:10.1111/j.0013-9580.2005.66104.x. PMID 15816939. S2CID 21130724.
  14. ^ a b c d e f g Pandolfo, M. (November 2011). "Genetics of epilepsy". Seminars in Neurology. 31 (5): 506–18. doi:10.1055/s-0031-1299789. PMID 22266888.
  15. ^ N, Mohsen; et al. (GBD 2013 Mortality Causes of Death Collaborators) (January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". The Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. hdl:11655/15525. PMC 4340604. PMID 25530442.
  16. ^ Brodie MJ, Elder AT, Kwan P (November 2009). "Epilepsy in later life". The Lancet. Neurology. 8 (11): 1019–30. doi:10.1016/S1474-4422(09)70240-6. PMID 19800848. S2CID 14318073.
  17. ^ a b Holmes TR, Browne GL (2008). Handbook of epilepsy (4th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 7. ISBN 978-0-7817-7397-3.
  18. ^ Wyllie's treatment of epilepsy: principles and practice (5th ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 2010. ISBN 978-1-58255-937-7. from the original on 24 June 2016.
  19. ^ a b c d e f g h i j k l Newton CR, Garcia HH (September 2012). "Epilepsy in poor regions of the world". Lancet. 380 (9848): 1193–201. doi:10.1016/S0140-6736(12)61381-6. PMID 23021288. S2CID 13933909.
  20. ^ a b c d e f Wilden JA, Cohen-Gadol AA (August 2012). "Evaluation of first nonfebrile seizures". American Family Physician. 86 (4): 334–40. PMID 22963022.
  21. ^ Berg AT (2008). "Risk of recurrence after a first unprovoked seizure". Epilepsia. 49 Suppl 1: 13–8. doi:10.1111/j.1528-1167.2008.01444.x. PMID 18184149. S2CID 28114460.
  22. ^ a b c d e f L Devlin A, Odell M, L Charlton J, Koppel S (December 2012). "Epilepsy and driving: current status of research". Epilepsy Research. 102 (3): 135–52. doi:10.1016/j.eplepsyres.2012.08.003. PMID 22981339. S2CID 30673360.
  23. ^ a b c d e f g h i j k l Magiorkinis E, Sidiropoulou K, Diamantis A (January 2010). "Hallmarks in the history of epilepsy: epilepsy in antiquity". Epilepsy & Behavior. 17 (1): 103–8. doi:10.1016/j.yebeh.2009.10.023. PMID 19963440. S2CID 26340115.
  24. ^ a b Duncan JS, Sander JW, Sisodiya SM, Walker MC (April 2006). (PDF). Lancet. 367 (9516): 1087–1100. doi:10.1016/S0140-6736(06)68477-8. PMID 16581409. S2CID 7361318. Archived from the original (PDF) on 24 March 2013. Retrieved 10 January 2012.
  25. ^ 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. (PDF) from the original on 16 December 2013.
  26. ^ Hughes, JR (August 2009). "Absence seizures: a review of recent reports with new concepts". Epilepsy & Behavior. 15 (4): 404–12. doi:10.1016/j.yebeh.2009.06.007. PMID 19632158. S2CID 22023692.
  27. ^ a b c d Shearer P. "Seizures and Status Epilepticus: Diagnosis and Management in the Emergency Department". Emergency Medicine Practice. from the original on 30 December 2010.
  28. ^ a b c d Bradley WG (2012). "67". Bradley's neurology in clinical practice (6th ed.). Philadelphia, PA: Elsevier/Saunders. ISBN 978-1-4377-0434-1.
  29. ^ 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. (PDF) from the original on 16 December 2013.
  30. ^ 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.
  31. ^ a b c d Engel J (2008). Epilepsy: a comprehensive textbook (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 2797. ISBN 978-0-7817-5777-5. from the original on 20 May 2016.
  32. ^ a b c Simon DA, Greenberg MJ, Aminoff RP (2012). "12". Clinical neurology (8th ed.). New York: McGraw-Hill Medical. ISBN 978-0-07-175905-2.
  33. ^ a b Stephenson, John B. P. (1990). Fits and faints. London: Mac Keith Press. ISBN 0-632-02811-4. OCLC 25711319.
  34. ^ a b Steven C. Schachter, ed. (2008). Behavioral aspects of epilepsy: principles and practice ([Online-Ausg.]. ed.). New York: Demos. p. 125. ISBN 978-1-933864-04-4.
  35. ^ Xue LY, Ritaccio AL (March 2006). "Reflex seizures and reflex epilepsy". American Journal of Electroneurodiagnostic Technology. 46 (1): 39–48. doi:10.1080/1086508X.2006.11079556. PMID 16605171. S2CID 10098600.
  36. ^ Malow BA (November 2005). "Sleep and epilepsy". Neurologic Clinics. 23 (4): 1127–47. doi:10.1016/j.ncl.2005.07.002. PMID 16243619.
  37. ^ Tinuper P, Provini F, Bisulli F, Vignatelli L, Plazzi G, Vetrugno R, Montagna P, Lugaresi E (August 2007). "Movement disorders in sleep: guidelines for differentiating epileptic from non-epileptic motor phenomena arising from sleep". Sleep Medicine Reviews. 11 (4): 255–67. doi:10.1016/j.smrv.2007.01.001. PMID 17379548.
  38. ^ 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 (April 2017). "ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology". Epilepsia. 58 (4): 512–521. doi:10.1111/epi.13709. PMC 5386840. PMID 28276062.
  39. ^ Mitchell, W. G. (1996). "Status epilepticus and acute repetitive seizures in children, adolescents, and young adults: etiology, outcome, and treatment". Epilepsia. 37 Suppl 1: S74–80. doi:10.1111/j.1528-1157.1996.tb06025.x. ISSN 0013-9580. PMID 8647055. S2CID 14510863.
  40. ^ a b Jafarpour, Saba; Hirsch, Lawrence J.; Gaínza-Lein, Marina; Kellinghaus, Christoph; Detyniecki, Kamil (1 May 2019). "Seizure cluster: Definition, prevalence, consequences, and management". Seizure. 68: 9–15. doi:10.1016/j.seizure.2018.05.013. ISSN 1532-2688. PMID 29871784. S2CID 46942965.
  41. ^ Faught, Edward (23 August 2022). "Economic aspects of treating seizure clusters". Epilepsia. 63 Suppl 1: S45–S54. doi:10.1111/epi.17340. ISSN 1528-1167. PMID 35999172. S2CID 251744416.
  42. ^ Haut, Sheryl R.; Shinnar, Shlomo; Moshé, Solomon L. (11 January 2005). "Seizure clustering: risks and outcomes". Epilepsia. 46 (1): 146–149. doi:10.1111/j.0013-9580.2005.29004.x. ISSN 0013-9580. PMID 15660781. S2CID 37102974.
  43. ^ Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J.; Katz, Austen; Legge, Alexander; Wong, Rebecca A.; Jiang, Alfred; Kato, Kenneth; Buchsbaum, Richard; Detyniecki, Kamil (1 July 2017). "Prevalence and risk factors of seizure clusters in adult patients with epilepsy". Epilepsy Research. 133: 98–102. doi:10.1016/j.eplepsyres.2017.04.016. ISSN 0920-1211. PMID 28475999. S2CID 4735843.
  44. ^ Komaragiri, Arpitha; Detyniecki, Kamil; Hirsch, Lawrence J. (1 June 2016). "Seizure clusters: A common, understudied and undertreated phenomenon in refractory epilepsy". Epilepsy & Behavior. 59: 83–86. doi:10.1016/j.yebeh.2016.02.030. ISSN 1525-5069. PMID 27116535. S2CID 3880221.
  45. ^ Chung, Steve; Szaflarski, Jerzy P.; Choi, Eun Jung; Wilson, Jessica Claire; Kharawala, Saifuddin; Kaur, Gavneet; Hirsch, Lawrence J. (1 November 2021). "A systematic review of seizure clusters: Prevalence, risk factors, burden of disease and treatment patterns". Epilepsy Research. 177: 106748. doi:10.1016/j.eplepsyres.2021.106748. ISSN 1872-6844. PMID 34521043. S2CID 237380380.
  46. ^ Gidal, Barry; Detyniecki, Kamil (23 August 2022). "Rescue therapies for seizure clusters: Pharmacology and target of treatments". Epilepsia. 63 Suppl 1 (Suppl 1): S34–S44. doi:10.1111/epi.17341. ISSN 1528-1167. PMC 9543841. PMID 35999174. S2CID 251744444.
  47. ^ Holmes TR (2008). Handbook of epilepsy (4th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 34. ISBN 978-0-7817-7397-3.
  48. ^ a b c Panayiotopoulos CP (2010). A clinical guide to epileptic syndromes and their treatment based on the ILAE classifications and practice parameter guidelines (Rev. 2nd ed.). London: Springer. p. 445. ISBN 978-1-84628-644-5.
  49. ^ Wheless JW, ed. (2009). Advanced therapy in epilepsy. Shelton, Conn.: People's Medical Pub. House. p. 443. ISBN 978-1-60795-004-2.
  50. ^ Larner AJ (2010). A dictionary of neurological signs (3rd ed.). New York: Springer. p. 348. ISBN 978-1-4419-7095-4.
  51. ^ Kaplan PW (November 2011). "Obsessive-compulsive disorder in chronic epilepsy". Epilepsy & Behavior. 22 (3): 428–32. doi:10.1016/j.yebeh.2011.07.029. PMID 21889913. S2CID 42945523.
  52. ^ Stefan H (2012). Epilepsy Part I: Basic Principles and Diagnosis E-Book: Handbook of Clinical Neurology (Volume 107 of Handbook of Clinical Neurology ed.). Newnes. p. 471. ISBN 978-0-444-53505-4.
  53. ^ Plioplys S, Dunn DW, Caplan R (November 2007). "10-year research update review: psychiatric problems in children with epilepsy". Journal of the American Academy of Child and Adolescent Psychiatry. 46 (11): 1389–402. doi:10.1097/chi.0b013e31815597fc. PMID 18049289.
  54. ^ Reilly CJ (May–June 2011). "Attention deficit hyperactivity disorder (ADHD) in childhood epilepsy". Research in Developmental Disabilities. 32 (3): 883–93. doi:10.1016/j.ridd.2011.01.019. PMID 21310586.
  55. ^ Levisohn PM (2007). "The autism-epilepsy connection". Epilepsia. 48 Suppl 9 (Suppl 9): 33–5. doi:10.1111/j.1528-1167.2007.01399.x. PMID 18047599.
  56. ^ Lin, Jack J; Mula, Marco; Hermann, Bruce P (29 September 2012). "Uncovering the neurobehavioural comorbidities of epilepsy over the lifespan". The Lancet. 380 (9848): 1180–1192. doi:10.1016/s0140-6736(12)61455-x. ISSN 0140-6736. PMC 3838617. PMID 23021287.
  57. ^ Kanner, Andres M.; Schachter, Steven C.; Barry, John J.; Hersdorffer, Dale C.; Mula, Marco; Trimble, Michael; Hermann, Bruce; Ettinger, Alan E.; Dunn, David; Caplan, Rochelle; Ryvlin, Philippe; Gilliam, Frank (1 June 2012). "Depression and epilepsy: Epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence". Epilepsy & Behavior. 24 (2): 156–168. doi:10.1016/j.yebeh.2012.01.007. ISSN 1525-5050. PMID 22632406. S2CID 24369127.
  58. ^ Adelow, C.; Andersson, T.; Ahlbom, A.; Tomson, T. (25 January 2012). "Hospitalization for psychiatric disorders before and after onset of unprovoked seizures/epilepsy". Neurology. 78 (6): 396–401. doi:10.1212/wnl.0b013e318245f461. ISSN 0028-3878. PMID 22282649. S2CID 207120740.
  59. ^ Taylor, Rod S.; Sander, Josemir W.; Taylor, Rebecca J.; Baker, Gus A. (29 August 2011). "Predictors of health-related quality of life and costs in adults with epilepsy: A systematic review". Epilepsia. 52 (12): 2168–2180. doi:10.1111/j.1528-1167.2011.03213.x. ISSN 0013-9580. PMID 21883177. S2CID 30039598.
  60. ^ Lacey, Cameron J.; Salzberg, Michael R.; Roberts, Helene; Trauer, Tom; D’Souza, Wendyl J. (29 July 2009). "Psychiatric comorbidity and impact on health service utilization in a community sample of patients with epilepsy". Epilepsia. 50 (8): 1991–1994. doi:10.1111/j.1528-1167.2009.02165.x. ISSN 0013-9580. PMID 19490049. S2CID 27842830.
  61. ^ Nogueira, Mateus H.; Yasuda, Clarissa L.; Coan, Ana C.; Kanner, Andres M.; Cendes, Fernando (26 May 2017). "Concurrent mood and anxiety disorders are associated with pharmacoresistant seizures in patients with MTLE". Epilepsia. 58 (7): 1268–1276. doi:10.1111/epi.13781. ISSN 0013-9580. PMID 28555776. S2CID 2519902.
  62. ^ Kanner, A. M.; Byrne, R.; Chicharro, A.; Wuu, J.; Frey, M. (2 March 2009). "A lifetime psychiatric history predicts a worse seizure outcome following temporal lobectomy". Neurology. 72 (9): 793–799. doi:10.1212/01.wnl.0000343850.85763.9c. ISSN 0028-3878. PMID 19255406. S2CID 10497821.
  63. ^ Boylan, L. S.; Flint, L. A.; Labovitz, D. L.; Jackson, S. C.; Starner, K.; Devinsky, O. (26 January 2004). "Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy". Neurology. 62 (2): 258–261. doi:10.1212/01.wnl.0000103282.62353.85. ISSN 0028-3878. PMID 14745064. S2CID 24173332.
  64. ^ Munger Clary, Heidi M.; Croxton, Rachel D.; Allan, Jonathan; Lovato, James; Brenes, Gretchen; Snively, Beverly M.; Wan, Mingyu; Kimball, James; Wong, Matthew H.; O'Donovan, Cormac A.; Conner, Kelly; Jones, Victor; Duncan, Pamela (1 March 2020). "Who is willing to participate in research? A screening model for an anxiety and depression trial in the epilepsy clinic". Epilepsy & Behavior. 104 (Pt A): 106907. doi:10.1016/j.yebeh.2020.106907. ISSN 1525-5050. PMC 7282472. PMID 32000099.
  65. ^ a b c Berkovic SF, Mulley JC, Scheffer IE, Petrou S (2006). "Human epilepsies: interaction of genetic and acquired factors". Trends in Neurosciences. 29 (7): 391–7. doi:10.1016/j.tins.2006.05.009. PMID 16769131. S2CID 205403084.
  66. ^ Balestrini, Simona; Arzimanoglou, Alexis; Blümcke, Ingmar; Scheffer, Ingrid E.; Wiebe, Samuel; Zelano, Johan; Walker, Matthew C. (February 2021). "The aetiologies of epilepsy". Epileptic Disorders. 23 (1): 1–16. doi:10.1684/epd.2021.1255. PMID 33720020. S2CID 232231196.
  67. ^ 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, ILAE Commission on Epidemiology (September 2011). "Standards for epidemiologic studies and surveillance of epilepsy". Epilepsia. 52 Suppl 7: 2–26. doi:10.1111/j.1528-1167.2011.03121.x. PMID 21899536. S2CID 8505004.
  68. ^ a b c d e f g Neligan A, Hauser WA, Sander JW (2012). "The epidemiology of the epilepsies". Epilepsy. Handbook of Clinical Neurology. Vol. 107. pp. 113–33. doi:10.1016/B978-0-444-52898-8.00006-9. ISBN 978-0-444-52898-8. PMID 22938966.
  69. ^ Dhavendra Kumar, ed. (2008). Genomics and clinical medicine. Oxford: Oxford University Press. p. 279. ISBN 978-0-19-972005-7. from the original on 21 May 2016.
  70. ^ a b c d e f g h i j k l m n o Bhalla D, Godet B, Druet-Cabanac M, Preux PM (June 2011). "Etiologies of epilepsy: a comprehensive review". Expert Review of Neurotherapeutics. 11 (6): 861–76. doi:10.1586/ern.11.51. PMID 21651333. S2CID 21190601.
  71. ^ a b Stafstrom, Carl E.; Staedtke, Verena; Comi, Anne M. (2017). "Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge-Weber Syndrome". Frontiers in Neurology. 8: 87. doi:10.3389/fneur.2017.00087. ISSN 1664-2295. PMC 5355446. PMID 28367137.
  72. ^ O'Callaghan, F. J.; Shiell, A. W.; Osborne, J. P.; Martyn, C. N. (16 May 1998). "Prevalence of tuberous sclerosis estimated by capture-recapture analysis". Lancet. 351 (9114): 1490. doi:10.1016/S0140-6736(05)78872-3. ISSN 0140-6736. PMID 9605811. S2CID 9262685.
  73. ^ a b Northrup, Hope; Aronow, Mary E.; Bebin, E. Martina; Bissler, John; Darling, Thomas N.; de Vries, Petrus J.; Frost, Michael D.; Fuchs, Zoë; Gosnell, Elizabeth S.; Gupta, Nishant; Jansen, Anna C. (October 2021). "Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations". Pediatric Neurology. 123: 50–66. doi:10.1016/j.pediatrneurol.2021.07.011. ISSN 1873-5150. PMID 34399110.
  74. ^ a b Curatolo, Paolo (March 2015). "Mechanistic target of rapamycin (mTOR) in tuberous sclerosis complex-associated epilepsy". Pediatric Neurology. 52 (3): 281–289. doi:10.1016/j.pediatrneurol.2014.10.028. ISSN 1873-5150. PMID 25591831.
  75. ^ Moavero, Romina; Cerminara, Caterina; Curatolo, Paolo (November 2010). "Epilepsy secondary to tuberous sclerosis: lessons learned and current challenges". Child's Nervous System. 26 (11): 1495–1504. doi:10.1007/s00381-010-1128-8. ISSN 1433-0350. PMID 20358377. S2CID 35481466.
  76. ^ Shirley, Matthew D.; Tang, Hao; Gallione, Carol J.; Baugher, Joseph D.; Frelin, Laurence P.; Cohen, Bernard; North, Paula E.; Marchuk, Douglas A.; Comi, Anne M.; Pevsner, Jonathan (23 May 2013). "Sturge–Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in GNAQ". The New England Journal of Medicine. 368 (21): 1971–1979. doi:10.1056/NEJMoa1213507. ISSN 0028-4793. PMC 3749068. PMID 23656586.
  77. ^ a b Sudarsanam, Annapurna; Ardern-Holmes, Simone L. (May 2014). "Sturge-Weber syndrome: from the past to the present". European Journal of Paediatric Neurology. 18 (3): 257–266. doi:10.1016/j.ejpn.2013.10.003. ISSN 1532-2130. PMID 24275166.
  78. ^ Sugano, Hidenori; Iimura, Yasushi; Igarashi, Ayuko; Nakazawa, Mika; Suzuki, Hiroharu; Mitsuhashi, Takumi; Nakajima, Madoka; Higo, Takuma; Ueda, Tetsuya; Nakanishi, Hajime; Niijima, Shinichi (1 April 2021). "Extent of Leptomeningeal Capillary Malformation is Associated With Severity of Epilepsy in Sturge-Weber Syndrome". Pediatric Neurology. 117: 64–71. doi:10.1016/j.pediatrneurol.2020.12.012. ISSN 0887-8994. PMID 33677229. S2CID 232140769.
  79. ^ Wang, Shu; Pan, Junhong; Zhao, Meng; Wang, Xiongfei; Zhang, Chunsheng; Li, Tianfu; Wang, Mengyang; Wang, Jing; Zhou, Jian; Liu, Changqing; Sun, Yongxing (21 December 2021). "Characteristics, surgical outcomes, and influential factors of epilepsy in Sturge-Weber syndrome". Brain: A Journal of Neurology. 145 (10): 3431–3443. doi:10.1093/brain/awab470. ISSN 1460-2156. PMID 34932802.
  80. ^ Lammert, Marga; Friedman, Jan M.; Kluwe, Lan; Mautner, Victor F. (January 2005). "Prevalence of neurofibromatosis 1 in German children at elementary school enrollment". Archives of Dermatology. 141 (1): 71–74. doi:10.1001/archderm.141.1.71. ISSN 0003-987X. PMID 15655144.
  81. ^ Ostendorf, Adam P.; Gutmann, David H.; Weisenberg, Judith L. Z. (October 2013). "Epilepsy in individuals with neurofibromatosis type 1". Epilepsia. 54 (10): 1810–1814. doi:10.1111/epi.12348. ISSN 1528-1167. PMID 24032542. S2CID 1603461.
  82. ^ Barba, Carmen; Jacques, Thomas; Kahane, Philippe; Polster, Tilman; Isnard, Jean; Leijten, Frans S. S.; Ozkara, Cigdem; Tassi, Laura; Giordano, Flavio; Castagna, Maura; John, Alison (August 2013). "Epilepsy surgery in Neurofibromatosis Type 1". Epilepsy Research. 105 (3): 384–395. doi:10.1016/j.eplepsyres.2013.02.021. ISSN 1872-6844. PMID 23597854. S2CID 25785144.
  83. ^ Galovic, Marian; Döhler, Nico; Erdélyi-Canavese, Barbara; Felbecker, Ansgar; Siebel, Philip; Conrad, Julian; Evers, Stefan; Winklehner, Michael; von Oertzen, Tim J.; Haring, Hans-Peter; Serafini, Anna; Gregoraci, Giorgia; Valente, Mariarosaria; Janes, Francesco; Gigli, Gian Luigi (1 February 2018). "Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study". The Lancet. Neurology. 17 (2): 143–152. doi:10.1016/S1474-4422(17)30404-0. ISSN 1474-4465. PMID 29413315. S2CID 21665713.
  84. ^ Ren, Zhong; Wen, Quan; Yan, Xue; Wang, Ying; Zhang, Yidan (1 September 2022). "Post-stroke epilepsy and risk of all-cause mortality: A systematic review and meta-analysis of cohort studies". Clinical Neurology and Neurosurgery. 220: 107362. doi:10.1016/j.clineuro.2022.107362. ISSN 0303-8467. PMID 35839716. S2CID 250317784.
  85. ^ Zelano, Johan; Holtkamp, Martin; Agarwal, Nivedita; Lattanzi, Simona; Trinka, Eugen; Brigo, Francesco (1 June 2020). "How to diagnose and treat post-stroke seizures and epilepsy". Epileptic Disorders: International Epilepsy Journal with Videotape. 22 (3): 252–263. doi:10.1684/epd.2020.1159. ISSN 1950-6945. PMID 32597766. S2CID 220254988.
  86. ^ Zöllner, Johann Philipp; Schmitt, Friedhelm C.; Rosenow, Felix; Kohlhase, Konstantin; Seiler, Alexander; Strzelczyk, Adam; Stefan, Hermann (6 December 2021). "Seizures and epilepsy in patients with ischaemic stroke". Neurological Research and Practice. 3 (1): 63. doi:10.1186/s42466-021-00161-w. ISSN 2524-3489. PMC 8647498. PMID 34865660.
  87. ^ Grossman G (April 2008). "Neurological complications of coeliac disease: what is the evidence?". Practical Neurology. 8 (2): 77–89. doi:10.1136/jnnp.2007.139717. PMID 18344378. S2CID 28327166.
  88. ^ a b c Jackson JR, Eaton WW, Cascella NG, Fasano A, Kelly DL (March 2012). "Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity". The Psychiatric Quarterly. 83 (1): 91–102. doi:10.1007/s11126-011-9186-y. PMC 3641836. PMID 21877216.
  89. ^ Shorvon SD (2011). The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children. Cambridge University Press. p. 467. ISBN 978-1-139-49578-3.
  90. ^ Sellner J, Trinka E (October 2012). "Seizures and epilepsy in herpes simplex virus encephalitis: current concepts and future directions of pathogenesis and management". Journal of Neurology. 259 (10): 2019–30. doi:10.1007/s00415-012-6494-6. PMID 22527234. S2CID 24701310.
  91. ^ Hadjipanayis A, Hadjichristodoulou C, Youroukos S (October 1997). "Epilepsy in patients with cerebral palsy". Developmental Medicine and Child Neurology. 39 (10): 659–63. doi:10.1111/j.1469-8749.1997.tb07359.x. PMID 9352726.
  92. ^ a b Bromfield EB (2006). An Introduction to Epilepsy. American Epilepsy Society.
  93. ^ Blumenfeld H (2005). "Cellular and network mechanisms of spike-wave seizures". Epilepsia. 46 Suppl 9 (Suppl.9): 21–33. doi:10.1111/j.1528-1167.2005.00311.x. PMID 16302873.
  94. ^ Noebels JL, Avoli M (29 June 2012). Jasper's Basic Mechanisms of the Epilepsies. Oxford University Press. pp. 466, 470. ISBN 9780199746545. Retrieved 16 October 2014.
  95. ^ a b Le Van Quyen M, Navarro V, Martinerie J, Baulac M, Varela FJ (2003). "Toward a neurodynamical understanding of ictogenesis". Epilepsia. 44 Suppl 12 (Suppl.12): 30–43. doi:10.1111/j.0013-9580.2003.12007.x. PMID 14641559.
  96. ^ Lopes da Silva F, Blanes W, Kalitzin SN, Parra J, Suffczynski P, Velis DN (2003). "Epilepsies as dynamical diseases of brain systems: basic models of the transition between normal and epileptic activity". Epilepsia. 44 Suppl 12 (Suppl.12): 72–83. doi:10.1111/j.0013-9580.2003.12005.x. PMID 14641563. S2CID 10071296.
  97. ^ D. C. Henshall, H. M. Hamer, R. J. Pasterkamp, D. B. Goldstein, J. Kjems, J. H. M Prehn, S. Schorge, K. Lamottke and F. Rosenow. MicroRNAs in Epilepsy: Pathophysiology and Clinical Utility. The Lancet Neurology, Volume 15, Issue 13, 2016, 1368–1376.https://doi.org/10.1016/S1474-4422(16)30246-0
  98. ^ Oby E, Janigro D (November 2006). "The blood-brain barrier and epilepsy". Epilepsia. 47 (11): 1761–74. doi:10.1111/j.1528-1167.2006.00817.x. PMID 17116015. S2CID 15074513.
  99. ^ Somjen GG (2004). Ions in the Brain Normal Function, Seizures, and Stroke. New York: Oxford University Press. p. 167. ISBN 978-0-19-803459-9.
  100. ^ a b Engel J, Pedley TA, eds. (2008). Epilepsy: a comprehensive textbook (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 483. ISBN 978-0-7817-5777-5.
  101. ^ Depannemaecker, Damien; Ivanov, Anton; Lillo, Davide; Spek, Len; Bernard, Christophe; Jirsa, Viktor (17 February 2021). "A unified physiological framework of transitions between seizures, sustained ictal activity and depolarization block at the single neuron level". bioRxiv: 2020.10.23.352021. doi:10.1101/2020.10.23.352021. S2CID 225962412. {{cite journal}}: Cite journal requires |journal= (help)
  102. ^ Depannemaecker, Damien; Destexhe, Alain; Jirsa, Viktor; Bernard, Christophe (August 2021). "Modeling seizures: From single neurons to networks". Seizure. 90: 4–8. doi:10.1016/j.seizure.2021.06.015. ISSN 1059-1311. PMID 34219016. S2CID 235468072.
  103. ^ 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. (PDF) from the original on 16 December 2013.
  104. ^ Fisher R, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J (2005). "Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)". Epilepsia. 46 (4): 470–2. doi:10.1111/j.0013-9580.2005.66104.x. PMID 15816939.
  105. ^ Panayiotopoulos, CP (December 2011). "The new ILAE report on terminology and concepts for organization of epileptic seizures: a clinician's critical view and contribution". Epilepsia. 52 (12): 2155–60. doi:10.1111/j.1528-1167.2011.03288.x. PMID 22004554.
  106. ^ "Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy". Epilepsia. 30 (4): 389–99. 1989. doi:10.1111/j.1528-1157.1989.tb05316.x. PMID 2502382. S2CID 3483250.
  107. ^ Engel J (August 2006). "ILAE classification of epilepsy syndromes". Epilepsy Research. 70 Suppl 1 (Suppl 1): S5–10. doi:10.1016/j.eplepsyres.2005.11.014. PMID 16822650. S2CID 10663593.
  108. ^ 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 (April 2010). "Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009". Epilepsia. 51 (4): 676–85. doi:10.1111/j.1528-1167.2010.02522.x. PMID 20196795.
  109. ^ a b c d e f g Shorvon SD (June 2011). "The etiologic classification of epilepsy". Epilepsia. 52 (6): 1052–7. doi:10.1111/j.1528-1167.2011.03041.x. PMID 21449936.
  110. ^ "Operational Classification of Seizure Types (2017)".{{cite web}}: CS1 maint: url-status (link)
  111. ^ a b c d e f Fisher, RS; Cross, JH; French, JA; Higurashi, N; Hirsch, E; Jansen, FE; Lagae, L; Moshé, SL; Peltola, J; Roulet Perez, E; Scheffer, IE; Zuberi, SM (April 2017). "Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology". Epilepsia. 58 (4): 522–530. doi:10.1111/epi.13670. hdl:11343/292620. PMID 28276060. S2CID 21037500.
  112. ^ "Epilepsy syndromes". International league against epilepsy. from the original on 6 October 2014. Retrieved 6 October 2014.
  113. ^ Wirrell, E; Tinuper, P; Perucca, E; Moshé, SL (June 2022). "Introduction to the epilepsy syndrome papers". Epilepsia. 63 (6): 1330–1332. doi:10.1111/epi.17262. PMID 35503711. S2CID 248503717.
  114. ^ Asadi-Pooya, Ali.A (2018). "Lennox-Gastaut syndrome: a comprehensive review". Neurological Sciences. 39 (3): 403–414. doi:10.1007/s10072-017-3188-y. PMID 29124439. S2CID 4243468.{{cite journal}}: CS1 maint: url-status (link)
  115. ^ Chemaly, Nicole; Nabbout, Rima. "Dravet Syndrome".{{cite web}}: CS1 maint: url-status (link)
  116. ^ Chipaux, Mathilde. "West syndrome".{{cite web}}: CS1 maint: url-status (link)
  117. ^ Nordli DR (October 2012). "Epileptic encephalopathies in infants and children". Journal of Clinical Neurophysiology. 29 (5): 420–4. doi:10.1097/WNP.0b013e31826bd961. PMID 23027099. S2CID 41884825.
  118. ^ Heinzen EL, Depondt C, Cavalleri GL, Ruzzo EK, Walley NM, Need AC, et al. (August 2012). "Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy". American Journal of Human Genetics. 91 (2): 293–302. doi:10.1016/j.ajhg.2012.06.016. PMC 3415540. PMID 22863189.
  119. ^ Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, et al. (July 2013). "Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1". Nature Genetics. 45 (7): 825–30. doi:10.1038/ng.2646. PMC 3704157. PMID 23708187.
  120. ^ Chénier S, Yoon G, Argiropoulos B, Lauzon J, Laframboise R, Ahn JW, et al. (2014). "CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems". Journal of Neurodevelopmental Disorders. 6 (1): 9. doi:10.1186/1866-1955-6-9. PMC 4022362. PMID 24834135.
  121. ^ Suls A, Jaehn JA, Kecskés A, Weber Y, Weckhuysen S, Craiu DC, et al. (November 2013). "De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome". American Journal of Human Genetics. 93 (5): 967–75. doi:10.1016/j.ajhg.2013.09.017. PMC 3824114. PMID 24207121.
  122. ^ EuroEPINOMICS-RES Consortium (October 2014). "De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies". American Journal of Human Genetics. 95 (4): 360–70. doi:10.1016/j.ajhg.2014.08.013. PMC 4185114. PMID 25262651.
  123. ^ a b "1 Guidance | Epilepsies: Diagnosis and management | Guidance | NICE".{{cite web}}: CS1 maint: url-status (link)
  124. ^ a b "American Epilepsy Society Choosing Wisely". www.choosingwisely.org. 14 August 2018. Retrieved 30 August 2018.
  125. ^ Wallace SJ, Farrell K, eds. (2004). Epilepsy in children (2nd ed.). London: Arnold. p. 354. ISBN 978-0-340-80814-6.
  126. ^ Chen, Wei-Liang; Mefford, Heather C. (July 2021). "Diagnostic Considerations in the Epilepsies-Testing Strategies, Test Type Advantages, and Limitations". Neurotherapeutics. 18 (3): 1468–1477. doi:10.1007/s13311-021-01121-7. ISSN 1878-7479. PMC 8608977. PMID 34532824.
  127. ^ Aledo-Serrano, Angel; Sánchez-Alcudia, Rocío; Toledano, Rafael; García-Morales, Irene; Beltrán-Corbellini, Álvaro; del Pino, Isabel; Gil-Nagel, Antonio (2021). "Developmental and epileptic encephalopathies after negative or inconclusive genetic testing: what is next?". Journal of Translational Genetics and Genomics. 5 (4): 443–455. doi:10.20517/jtgg.2021.40. S2CID 244944239.
  128. ^ Luef, G (October 2010). "Hormonal alterations following seizures". Epilepsy & Behavior. 19 (2): 131–3. doi:10.1016/j.yebeh.2010.06.026. PMID 20696621. S2CID 945952.
  129. ^ a b Ahmad S, Beckett MW (2004). "Value of serum prolactin in the management of syncope". Emergency Medicine Journal. 21 (2): 3e–3. doi:10.1136/emj.2003.008870. PMC 1726305. PMID 14988379.
  130. ^ Shukla G, Bhatia M, Vivekanandhan S, et al. (2004). "Serum prolactin levels for differentiation of nonepileptic versus true seizures: limited utility". Epilepsy & Behavior. 5 (4): 517–21. doi:10.1016/j.yebeh.2004.03.004. PMID 15256189. S2CID 2381873.
  131. ^ Chen DK, So YT, Fisher RS (2005). "Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology". Neurology. 65 (5): 668–75. doi:10.1212/01.wnl.0000178391.96957.d0. PMID 16157897.
  132. ^ Brodtkorb E (2013). "Common imitators of epilepsy". Acta Neurologica Scandinavica. Supplementum. 127 (196): 5–10. doi:10.1111/ane.12043. PMID 23190285. S2CID 1373740.
  133. ^ a b c d Marx JA, ed. (2010). Rosen's emergency medicine: concepts and clinical practice (7th ed.). Philadelphia: Mosby/Elsevier. p. 2228. ISBN 978-0-323-05472-0.
  134. ^ a b Zaidi A, Clough P, Cooper P, Scheepers B, Fitzpatrick AP (July 2000). "Misdiagnosis of epilepsy: many seizure-like attacks have a cardiovascular cause". Journal of the American College of Cardiology. 36 (1): 181–4. doi:10.1016/S0735-1097(00)00700-2. PMID 10898432.
  135. ^ Bisulli F, Vignatelli L, Provini F, Leta C, Lugaresi E, Tinuper P (December 2011). "Parasomnias and nocturnal frontal lobe epilepsy (NFLE): lights and shadows—controversial points in the differential diagnosis". Sleep Medicine. 12 Suppl 2 (Suppl2): S27–32. doi:10.1016/j.sleep.2011.10.008. PMID 22136895.
  136. ^ Zhou JQ, Zhou LM, Fang ZY, Wang Q, Chen ZY, Yang LB, Chen SD, Cai XD (January 2011). "Analyzing clinical and electrophysiological characteristics of Paroxysmal Dyskinesia". Journal of Research in Medical Sciences. 16 (1): 110–4. PMC 3063430. PMID 21448393.
  137. ^ Akhtar MJ (March 2002). "All seizures are not epilepsy: many have a cardiovascular cause". The Journal of the Pakistan Medical Association. 52 (3): 116–20. PMID 12071066.
  138. ^ a b Jerome E (2013). Seizures and epilepsy (2nd ed.). New York: Oxford University Press. p. 462. ISBN 9780195328547.
  139. ^ "Epilepsy – Symptoms and causes". Mayo Clinic. Retrieved 1 April 2022.
  140. ^ "Epilepsy: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 1 April 2022.
  141. ^ 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 (March 2017). "Self-management in epilepsy: Why and how you should incorporate self-management in your practice". Epilepsy & Behavior. 68: 220–224. doi:10.1016/j.yebeh.2016.11.015. PMC 5381244. PMID 28202408.
  142. ^ a b c d Michael GE, O'Connor RE (February 2011). "The diagnosis and management of seizures and status epilepticus in the prehospital setting". Emergency Medicine Clinics of North America. 29 (1): 29–39. doi:10.1016/j.emc.2010.08.003. PMID 21109100.
  143. ^ Wheless JW, Willmore J, Brumback RA (2009). Advanced therapy in epilepsy. Shelton, Conn.: People's Medical Pub. House. p. 144. ISBN 9781607950042.
  144. ^ 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. (PDF) from the original on 16 December 2013.
  145. ^ Wyllie E (2012). Wyllie's Treatment of Epilepsy: Principles and Practice. Lippincott Williams & Wilkins. p. 187. ISBN 978-1-4511-5348-4.
  146. ^ Flanagan SR, Zaretsky H, Moroz A, eds. (2010). Medical aspects of disability; a handbook for the rehabilitation professional (4th ed.). New York: Springer. p. 182. ISBN 978-0-8261-2784-6.
  147. ^ Nevitt, SJ; Marson, AG; Tudur Smith, C (18 July 2019). "Carbamazepine versus phenytoin monotherapy for epilepsy: an individual participant data review". The Cochrane Database of Systematic Reviews. 2019 (7): CD001911. doi:10.1002/14651858.CD001911.pub4. PMC 6637502. PMID 31318037.
  148. ^ Nevitt, SJ; Marson, AG; Weston, J; Tudur Smith, C (9 August 2018). "Sodium valproate versus phenytoin monotherapy for epilepsy: an individual participant data review". The Cochrane Database of Systematic Reviews. 2018 (8): CD001769. doi:10.1002/14651858.CD001769.pub4. PMC 6513104. PMID 30091458.
  149. ^ Powell G, Saunders M, Rigby A, Marson AG (December 2016). "Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy". The Cochrane Database of Systematic Reviews. 12 (4): CD007124. doi:10.1002/14651858.CD007124.pub5. PMC 6463840. PMID 27933615.
  150. ^ Mishra, Priya; Mittal, Amit Kumar; Rajput, Satyendra Kumar; Sinha, Jitendra Kumar (1 March 2021). "Cognition and memory impairment attenuation via reduction of oxidative stress in acute and chronic mice models of epilepsy using antiepileptogenic Nux vomica". Journal of Ethnopharmacology. 267: 113509. doi:10.1016/j.jep.2020.113509. ISSN 1872-7573. PMID 33141053. S2CID 226241066.
  151. ^ Mishra, Priya; Sinha, Jitendra Kumar; Rajput, Satyendra Kumar (February 2021). "Efficacy of Cicuta virosa medicinal preparations against pentylenetetrazole-induced seizures". Epilepsy & Behavior. 115: 107653. doi:10.1016/j.yebeh.2020.107653. ISSN 1525-5069. PMID 33358679. S2CID 229372930.
  152. ^ Nevitt, Sarah J.; Sudell, Maria; Cividini, Sofia; Marson, Anthony G.; Tudur Smith, Catrin (1 April 2022). "Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data". The Cochrane Database of Systematic Reviews. 2022 (4): CD011412. doi:10.1002/14651858.CD011412.pub4. ISSN 1469-493X. PMC 8974892. PMID 35363878.
  153. ^ Ilangaratne NB, Mannakkara NN, Bell GS, Sander JW (December 2012). "Phenobarbital: missing in action". Bulletin of the World Health Organization. 90 (12): 871–871A. doi:10.2471/BLT.12.113183. PMC 3524964. PMID 23284189.
  154. ^ Shorvon S, Perucca E, Engel J Jr, eds. (2009). The treatment of epilepsy (3rd ed.). Chichester, UK: Wiley-Blackwell. p. 587. ISBN 9781444316674. from the original on 21 May 2016.
  155. ^ a b c d e f Perucca P, Gilliam FG (September 2012). "Adverse effects of antiepileptic drugs". The Lancet. Neurology. 11 (9): 792–802. doi:10.1016/S1474-4422(12)70153-9. PMID 22832500. S2CID 25540685.
  156. ^ a b Weston J, Bromley R, Jackson CF, Adab N, Clayton-Smith J, Greenhalgh J, Hounsome J, McKay AJ, Tudur Smith C, Marson AG (November 2016). "Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child". The Cochrane Database of Systematic Reviews. 11 (11): CD010224. doi:10.1002/14651858.CD010224.pub2. PMC 6465055. PMID 27819746.
  157. ^ a b Kamyar M, Varner M (June 2013). "Epilepsy in pregnancy". Clinical Obstetrics and Gynecology. 56 (2): 330–41. doi:10.1097/GRF.0b013e31828f2436. PMID 23563876. S2CID 20150531.
  158. ^ Lawrence S. Neinstein, ed. (2008). Adolescent health care: a practical guide (5th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 335. ISBN 978-0-7817-9256-1.
  159. ^ a b Brodie, MJ; Elder, AT; Kwan, P (November 2009). "Epilepsy in later life". The Lancet. Neurology. 8 (11): 1019–30. doi:10.1016/S1474-4422(09)70240-6. PMID 19800848. S2CID 14318073.
  160. ^ a b Krucoff, MO; Chan, AY; Harward, SC; Rahimpour, S; Rolston, JD; Muh, C; Englot, DJ (December 2017). "Rates and predictors of success and failure in repeat epilepsy surgery: A meta-analysis and systematic review". Epilepsia. 58 (12): 2133–2142. doi:10.1111/epi.13920. PMC 5716856. PMID 28994113.
  161. ^ Benoit, PW; Yagiela, A; Fort, NF (February 1980). "Pharmacologic correlation between local anesthetic-induced myotoxicity and disturbances of intracellular calcium distribution". Toxicology and Applied Pharmacology. 52 (2): 187–98. doi:10.1016/0041-008x(80)90105-2. PMID 7361318.
  162. ^ a b c d e Duncan, JS (April 2007). "Epilepsy surgery". Clinical Medicine. 7 (2): 137–42. doi:10.7861/clinmedicine.7-2-137. PMC 4951827. PMID 17491501.
  163. ^ Birbeck, GL; Hays, RD; Cui, X; Vickrey, BG (May 2002). "Seizure reduction and quality of life improvements in people with epilepsy". Epilepsia. 43 (5): 535–8. doi:10.1046/j.1528-1157.2002.32201.x. PMID 12027916. S2CID 23577753.
  164. ^ Edwards CA, Kouzani A, Lee KH, Ross EK (September 2017). "Neurostimulation Devices for the Treatment of Neurologic Disorders". Mayo Clinic Proceedings. 92 (9): 1427–1444. doi:10.1016/j.mayocp.2017.05.005. PMID 28870357.
  165. ^ a b c d e f Panebianco M, Rigby A, Marson AG (14 July 2022). "Vagus nerve stimulation for focal seizures". The Cochrane Database of Systematic Reviews. 2022 (7): CD002896. doi:10.1002/14651858.CD002896.pub3. PMC 9281624. PMID 35833911.
  166. ^ Maria BL, ed. (2009). Current management in child neurology (4th ed.). Hamilton, Ont.: BC Decker. p. 180. ISBN 978-1-60795-000-4. from the original on 24 June 2016.
  167. ^ Verrotti A, Tocco AM, Salladini C, Latini G, Chiarelli F (November 2005). "Human photosensitivity: from pathophysiology to treatment". European Journal of Neurology. 12 (11): 828–41. doi:10.1111/j.1468-1331.2005.01085.x. PMID 16241971. S2CID 23001888.
  168. ^ Tan G, Thornby J, Hammond DC, Strehl U, Canady B, Arnemann K, Kaiser DA (July 2009). "Meta-analysis of EEG biofeedback in treating epilepsy". Clinical EEG and Neuroscience. 40 (3): 173–9. doi:10.1177/155005940904000310. PMID 19715180. S2CID 16682327.
  169. ^ Arida RM, Scorza FA, Scorza CA, Cavalheiro EA (March 2009). "Is physical activity beneficial for recovery in temporal lobe epilepsy? Evidences from animal studies". Neuroscience and Biobehavioral Reviews. 33 (3): 422–31. doi:10.1016/j.neubiorev.2008.11.002. PMID 19059282. S2CID 30918370.
  170. ^ Arida RM, Cavalheiro EA, da Silva AC, Scorza FA (2008). "Physical activity and epilepsy: proven and predicted benefits". Sports Medicine. 38 (7): 607–15. doi:10.2165/00007256-200838070-00006. PMID 18557661. S2CID 24048241.
  171. ^ Di Vito L, Naldi I, Mostacci B, Licchetta L, Bisulli F, Tinuper P (June 2010). "A seizure response dog: video recording of reacting behaviour during repetitive prolonged seizures". Epileptic Disorders. 12 (2): 142–5. doi:10.1684/epd.2010.0313. PMID 20472528. S2CID 3337471. from the original on 6 October 2014.
  172. ^ Kirton A, Winter A, Wirrell E, Snead OC (October 2008). "Seizure response dogs: evaluation of a formal training program". Epilepsy & Behavior. 13 (3): 499–504. doi:10.1016/j.yebeh.2008.05.011. PMID 18595778. S2CID 27549519.
  173. ^ Doherty MJ, Haltiner AM (January 2007). "Wag the dog: skepticism on seizure alert canines". Neurology. 68 (4): 309. CiteSeerX 10.1.1.1003.1543. doi:10.1212/01.wnl.0000252369.82956.a3. PMID 17242343. S2CID 33328776.
  174. ^ a b c Michaelis R, Tang V, Wagner JL, Modi AC, LaFrance Jr WC, Goldstein LH, Lundgren T, Reuber M (October 2017). "Psychological treatments for people with epilepsy". Cochrane Database of Systematic Reviews. 10 (10): CD012081. doi:10.1002/14651858.CD012081.pub2. PMC 6485515. PMID 29078005.{{cite journal}}: CS1 maint: uses authors parameter (link)
  175. ^ Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, Herkes GK, Farrell M, Degenhardt L (July 2018). "Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence". Journal of Neurology, Neurosurgery, and Psychiatry. 89 (7): 741–753. doi:10.1136/jnnp-2017-317168. PMID 29511052.
  176. ^ "Cannabis derivative may reduce seizures in some severe drug-resistant epilepsies, but adverse events increase". NIHR Evidence (Plain English summary). 26 June 2018. doi:10.3310/signal-000606. S2CID 242083755.
  177. ^ "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.
  178. ^ "Archive of "Journal of Investigative Medicine High Impact Case Reports". – PMC". www.ncbi.nlm.nih.gov.
  179. ^ a b c d Tomson, T; Battino, D; Bromley, R; Kochen, S; Meador, K; Pennell, P; Thomas, SV (1 December 2019). "Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy". Epileptic Disorders. 21 (6): 497–517. doi:10.1684/epd.2019.1105 (inactive 1 March 2023). PMID 31782407.{{cite journal}}: CS1 maint: DOI inactive as of March 2023 (link)
  180. ^ Cheuk DK, Wong V (May 2014). "Acupuncture for epilepsy". The Cochrane Database of Systematic Reviews. 2014 (5): CD005062. doi:10.1002/14651858.CD005062.pub4. PMC 10105317. PMID 24801225.
  181. ^ Ranganathan LN, Ramaratnam S (April 2005). "Vitamins for epilepsy". The Cochrane Database of Systematic Reviews (2): CD004304. doi:10.1002/14651858.CD004304.pub2. PMID 15846704.
  182. ^ Panebianco M, Sridharan K, Ramaratnam S (October 2017). "Yoga for epilepsy". The Cochrane Database of Systematic Reviews. 10 (10): CD001524. doi:10.1002/14651858.CD001524.pub3. PMC 6485327. PMID 28982217.
  183. ^ a b Brigo F, Igwe SC, Del Felice A (August 2016). "Melatonin as add-on treatment for epilepsy". The Cochrane Database of Systematic Reviews. 2016 (8): CD006967. doi:10.1002/14651858.CD006967.pub4. PMC 7386917. PMID 27513702.
  184. ^ He, Li-Ying; Hu, Mei-Bian; Li, Ruo-Lan; Zhao, Rong; Fan, Lin-Hong; He, Lin; Lu, Feng; Ye, Xun; Huang, Yong-Liang; Wu, Chun-Jie (2021). "Natural Medicines for the Treatment of Epilepsy: Bioactive Components, Pharmacology and Mechanism". Frontiers in Pharmacology. 12: 604040. doi:10.3389/fphar.2021.604040. PMC 7969896. PMID 33746751.
  185. ^ Aguiar, C. C.; Almeida, A. B.; Araújo, P. V.; De Abreu, R. N.; Chaves, E. M.; Do Vale, O. C.; MacÊdo, D. S.; Woods, D. J.; Fonteles, M. M.; Vasconcelos, S. M. (2012). "Oxidative Stress and Epilepsy: Literature Review". Oxidative Medicine and Cellular Longevity. 2012: 795259. doi:10.1155/2012/795259. PMC 3403512. PMID 22848783.
  186. ^ a b Kwan P (2012). Fast facts: epilepsy (5th ed.). Abingdon, Oxford, UK: Health Press. p. 10. ISBN 978-1-908541-12-3.
  187. ^ a b c Hitiris N, Mohanraj R, Norrie J, Brodie MJ (May 2007). "Mortality in epilepsy". Epilepsy & Behavior. 10 (3): 363–76. doi:10.1016/j.yebeh.2007.01.005. PMID 17337248. S2CID 39107474.
  188. ^ a b c Shorvon S, Perucca E, Engel J, eds. (2009). The treatment of epilepsy (3rd ed.). Chichester, UK: Wiley-Blackwell. p. 28. ISBN 978-1-4443-1667-4. from the original on 10 June 2016.
  189. ^ a b Bagary M (April 2011). "Epilepsy, antiepileptic drugs and suicidality". Current Opinion in Neurology. 24 (2): 177–82. doi:10.1097/WCO.0b013e328344533e. PMID 21293270.
  190. ^ Mula M, Sander JW (August 2013). "Suicide risk in people with epilepsy taking antiepileptic drugs". Bipolar Disorders. 15 (5): 622–7. doi:10.1111/bdi.12091. PMID 23755740. S2CID 40681400.
  191. ^ a b Ryvlin P, Nashef L, Tomson T (May 2013). "Prevention of sudden unexpected death in epilepsy: a realistic goal?". Epilepsia. 54 Suppl 2: 23–8. doi:10.1111/epi.12180. PMID 23646967.
  192. ^ Kløvgaard, M; Sabers, A; Ryvlin, P (November 2022). "Update on Sudden Unexpected Death in Epilepsy". Neurologic Clinics. 40 (4): 741–754. doi:10.1016/j.ncl.2022.06.001. PMID 36270688. S2CID 252617763.
  193. ^ Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R (January 2007). "How common are the "common" neurologic disorders?". Neurology. 68 (5): 326–37. doi:10.1212/01.wnl.0000252807.38124.a3. PMID 17261678. S2CID 208246679.
  194. ^ Espinosa-Jovel, Camilo; Toledano, Rafael; Aledo-Serrano, Ángel; García-Morales, Irene; Gil-Nagel, Antonio (1 March 2018). "Epidemiological profile of epilepsy in low income populations". Seizure: European Journal of Epilepsy. 56: 67–72. doi:10.1016/j.seizure.2018.02.002. ISSN 1059-1311. PMID 29453113.
  195. ^ a b Sander JW (April 2003). "The epidemiology of epilepsy revisited". Current Opinion in Neurology. 16 (2): 165–70. doi:10.1097/00019052-200304000-00008. PMID 12644744.
  196. ^ a b c d e f g h Saraceno B, Avanzini G, Lee P, eds. (2005). Atlas: Epilepsy Care in the World (PDF). World Health Organization. ISBN 978-92-4-156303-1. Retrieved 20 December 2013.
  197. ^ Eadie MJ, Bladin PF (2001). A Disease Once Sacred: A History of the Medical Understanding of Epilepsy. John Libbey Eurotext. ISBN 978-0-86196-607-3.
  198. ^ . World Health Organization. February 2001. Archived from the original on 30 October 2013. Retrieved 27 December 2013.
  199. ^ "Epilepsy: historical overview". World Health Organization. from the original on 20 January 2011. Retrieved 20 March 2011.
  200. ^ a b Temkin O (1 March 1994). The Falling Sickness: A History of Epilepsy from the Greeks to the Beginnings of Modern Neurology. JHU Press. p. Section 1. ISBN 9781421400532.
  201. ^ Stol M (1993). Epilepsy in Babylonia. BRILL. p. 143. ISBN 978-9072371638.
  202. ^ Harding GF, Jeavons PM (1994). Photosensitive Epilepsy. Cambridge University Press. p. 2. ISBN 9781898683025.
  203. ^ a b Jilek-Aall L (March 1999). "Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures". Epilepsia. 40 (3): 382–6. doi:10.1111/j.1528-1157.1999.tb00723.x. PMID 10080524.
  204. ^ "Epilepsy and its Management: A Review". ResearchGate. January 2012. Retrieved 22 February 2022.
  205. ^ Illes J (2011). Encyclopedia of Mystics, Saints & Sages. HarperCollins. p. 1238. ISBN 978-0-06-209854-2. 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.
  206. ^ a b c Lewis, Ellis (17 February 2012). Report of The Trial and Conviction of John Haggerty, for The Murder of Melchoir Fordney, Late of The City of Lancaster, Pennsylvania. Gale, Making of Modern Law. p. 62. ISBN 9781275311367.
  207. ^ Caravati EM (2004). Medical toxicology (3rd ed.). Philadelphia [u.a.]: Lippincott Williams & Wilkins. p. 789. ISBN 978-0-7817-2845-4.
  208. ^ a b de Boer HM (December 2010). "Epilepsy stigma: moving from a global problem to global solutions". Seizure. 19 (10): 630–6. doi:10.1016/j.seizure.2010.10.017. PMID 21075013. S2CID 17282975.
  209. ^ Martindale JL, Goldstein JN, Pallin DJ (February 2011). "Emergency department seizure epidemiology". Emergency Medicine Clinics of North America. 29 (1): 15–27. doi:10.1016/j.emc.2010.08.002. PMID 21109099.
epilepsy, epilepsia, epileptic, redirect, here, journal, epilepsia, journal, comics, epileptic, comics, group, communicable, neurological, disorders, characterized, recurrent, epileptic, seizures, epileptic, seizure, clinical, manifestation, abnormal, excessiv. Epilepsia and Epileptic redirect here For the journal see Epilepsia journal For the comics see Epileptic comics 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 purposeless and synchronized electrical discharge in the brain cells called neurons 1 The occurrence of two or more unprovoked seizures defines epilepsy 12 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 immediate underlying cause 12 Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy 13 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 12 EpilepsyOther namesSeizure disorderGeneralized 3 Hz spike and wave discharges on an electroencephalogramSpecialtyNeurologySymptomsPeriods of vigorous shaking nearly undetectable spells 1 DurationLong term 1 CausesUnknown brain injury stroke brain tumors infections of the brain birth defects 1 2 3 Diagnostic methodElectroencephalogram ruling out other possible causes 4 Differential diagnosisFainting alcohol withdrawal electrolyte problems 4 TreatmentMedication surgery neurostimulation dietary changes 5 6 PrognosisControllable in 69 7 Frequency39 million 0 5 2015 8 Deaths125 000 2015 9 The underlying mechanism of an epileptic seizure is excessive and abnormal neuronal activity in the cortex of the brain 13 which can be observed in the electroencephalogram EEG of an individual The reason this occurs in most cases of epilepsy is unknown cryptogenic 1 some cases occur as the result of brain injury stroke brain tumors infections of the brain or birth defects through a process known as epileptogenesis 1 2 3 Known genetic mutations are directly linked to a small proportion of cases 4 14 The diagnosis involves ruling out other conditions that might cause similar symptoms such as fainting and determining if another cause of seizures is present such as alcohol withdrawal or electrolyte problems 4 This may be partly done by imaging the brain and performing 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 update about 50 million people have epilepsy 11 Nearly 80 of cases occur in the developing world 1 In 2015 it resulted in 125 000 deaths an increase from 112 000 in 1990 9 15 Epilepsy is more common in older people 16 17 In the developed world onset of new cases occurs most frequently in babies and the elderly 18 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 19 About 5 10 of people will have an unprovoked seizure by the age of 80 20 with the chance of experiencing a second seizure rising to between 40 and 50 21 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 22 The word epilepsy is from Ancient Greek ἐpilambanein to seize possess or afflict 23 Contents 1 Signs and symptoms 1 1 Seizures 1 1 1 Seizure clusters 1 2 Post ictal 1 3 Psychosocial 2 Causes 2 1 Genetics 2 1 1 Phakomatoses 2 2 Acquired 3 Mechanism 3 1 Epilepsy 3 2 Seizures 4 Diagnosis 4 1 Definition 4 2 Classification 4 3 Syndromes 4 4 Tests 4 5 Differential diagnosis 5 Prevention 6 Complication 7 Management 7 1 First aid 7 2 Medications 7 3 Surgery 7 4 Neurostimulation 7 4 1 Vagus nerve stimulation 7 5 Diet 7 6 Other 7 7 In pregnancy 7 8 Alternative medicine 8 Prognosis 8 1 Mortality 9 Epidemiology 10 History 11 Society and culture 11 1 Stigma 11 2 Economics 11 3 Vehicles 11 4 Support organizations 12 Research 12 1 Seizure prediction and modeling 12 2 Potential future therapies 13 Other animals 14 References 15 Further reading 16 External linksSigns and symptoms Edit A still image of a generalized seizure A bite to the tip of the tongue due to a seizure Epilepsy is characterized by a long term risk of recurrent epileptic seizures 24 These seizures may present in several ways depending on the parts of the brain involved and the person s age 24 25 Seizures Edit Main article Epileptic seizure The most common type 60 of seizures are convulsive which involve involuntary muscle contractions 25 Of these one third begin as generalized seizures from the start affecting both hemispheres of the brain and impairing consciousness 25 Two thirds begin as focal seizures which affect one hemisphere of the brain which may progress to generalized seizures 25 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 26 Certain experiences known as auras often precede focal seizures 27 The seizures can include sensory visual hearing or smell psychic autonomic and motor phenomena depending on which part of the brain is involved 2 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 28 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 28 There are six main types of generalized seizures tonic clonic tonic clonic myoclonic absence and atonic seizures 29 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 chest muscles followed by a shaking of the limbs in unison clonic phase Tonic seizures produce constant contractions of the muscles A person often turns blue as breathing is stopped In clonic seizures there is shaking of the limbs in unison After the shaking has stopped it may take 10 30 minutes for the person to return to normal this period is called the postictal state or postictal phase Loss of bowel or bladder control may occur during a seizure 30 People experiencing a seizure may bite their tongue either the tip or on the sides 31 in tonic clonic seizure bites to the sides are more common 31 Tongue bites are also relatively common in psychogenic non epileptic seizures 31 Psychogenic non epileptic seizures are seizure like behavior without an associated synchronised electrical discharge on EEG and are considered a dissociative disorder 31 Myoclonic seizures involve very brief muscle spasms in either a few areas or all over 32 33 These sometimes cause the person to fall which can cause injury 32 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 28 typically occurring on both sides of the body 28 Rarer seizure types can cause involuntary unnatural laughter gelastic crying dyscrastic or more complex experiences such as deja vu 33 About 6 of those with epilepsy have seizures that are often triggered by specific events and are known as reflex seizures 34 Those with reflex epilepsy have seizures that are only triggered by specific stimuli 35 Common triggers include flashing lights and sudden noises 34 In certain types of epilepsy seizures happen more often during sleep 36 and in other types they occur almost only when sleeping 37 Recently the International League against epilepsy has published new uniform guidelines for the classification of seizures as well as epilepsies along with their cause and comorbidities 38 Seizure clusters Edit Patients with epilepsy may experience seizure clusters which may be broadly defined as an acute deterioration in seizure control 39 The prevalence of seizure clusters is uncertain given that studies have used different definitions to define them 40 However estimates suggest that the prevalence may range from 5 to 50 of epilepsy patients 41 Refractory epilepsy patients who have a high seizure frequency are at the greatest risk for having seizure clusters 42 43 44 Seizure clusters are associated with increased healthcare use worse quality of life impaired psychosocial functioning and possibly increased mortality 40 45 Benzodiazepines are used as an acute treatment for seizure clusters 46 Post ictal Edit After the active portion of a seizure the ictal state there is typically a period of recovery during which there is confusion referred to as the postictal period before a normal level of consciousness returns 27 It usually lasts 3 to 15 minutes 47 but may last for hours 48 Other common symptoms include feeling tired headache difficulty speaking and abnormal behavior 48 Psychosis after a seizure is relatively common occurring in 6 10 of people 49 Often people do not remember what happened during this time 48 Localized weakness known as Todd s paralysis may also occur after a focal seizure It would typically last for seconds to minutes but may rarely last for a day or two 50 Psychosocial Edit Epilepsy can have adverse effects on social and psychological well being 25 These effects may include social isolation stigmatization or disability 25 They may result in lower educational achievement and worse employment outcomes 25 Learning disabilities are common in those with the condition and especially among children with epilepsy 25 The stigma of epilepsy can also affect the families of those with the disorder 30 Certain disorders occur more often in people with epilepsy depending partly on the epilepsy syndrome present These include depression anxiety obsessive compulsive disorder OCD 51 and migraine 52 Attention deficit hyperactivity disorder ADHD affects three to five times more children with epilepsy than children without the condition 53 ADHD and epilepsy have significant consequences on a child s behavioral learning and social development 54 Epilepsy is also more common in children with autism 55 Approximately one in three people with epilepsy have a lifetime history of a psychiatric disorder 56 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 57 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 58 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 59 60 61 62 Anxiety disorders and depression may explain more variability in quality of life than seizure type or frequency 63 There is evidence that both depression and anxiety disorders are underdiagnosed and undertreated in patients with epilepsy 64 Causes EditSee also Causes of seizures Epilepsy can have both genetic and acquired causes with the interaction of these factors in many cases 65 66 Established acquired causes include serious brain trauma stroke tumours and brain problems resulting from a previous infection 65 In about 60 of cases the cause is unknown 25 30 Epilepsies caused by genetic congenital or developmental conditions are more common among younger people while brain tumors and strokes are more likely in older people 25 Seizures may also occur as a consequence of other health problems 29 if they occur right around a specific cause such as a stroke head injury toxic ingestion or metabolic problem they are known as acute symptomatic seizures and are in the broader classification of seizure related disorders rather than epilepsy itself 67 68 Genetics Edit Genetics is believed to be involved in the majority of cases either directly or indirectly 14 Some epilepsies are due to a single gene defect 1 2 most are due to the interaction of multiple genes and environmental factors 14 Each of the single gene defects is rare with more than 200 in all described 69 Most genes involved affect ion channels either directly or indirectly 65 These include genes for ion channels themselves enzymes GABA and G protein coupled receptors 32 In identical twins if one is affected there is a 50 60 chance that the other will also be affected 14 In non identical twins the risk is 15 14 These risks are greater in those with generalized rather than focal seizures 14 If both twins are affected most of the time they have the same epileptic syndrome 70 90 14 Other close relatives of a person with epilepsy have a risk five times that of the general population 70 Between 1 and 10 of those with Down syndrome and 90 of those with Angelman syndrome have epilepsy 70 Phakomatoses Edit 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 71 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 72 73 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 73 In addition abnormal mTOR activity is believed to alter neural excitability 74 The prevalence of epilepsy is estimated to be 80 90 71 74 The majority of cases of epilepsy present within the first 3 years of life and are medically refractory 75 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 76 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 77 The prevalence of epilepsy is 75 100 and is higher in those with bilateral involvement 77 Seizures typically occur within the first two years of life and are refractory in nearly half of cases 78 However high rates of seizure freedom with surgery have been reported in as many as 83 79 Neurofibromatosis type 1 is the most common phakomatoses and occurs in approximately 1 in 3 000 live births 80 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 81 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 82 Acquired Edit Traumatic brain injury victim who temporarily developed epilepsy note removed area of frontal and parietal bone Epilepsy may occur as a result of several other conditions including tumors strokes head trauma previous infections of the central nervous system genetic abnormalities and as a result of brain damage around the time of birth 29 30 Of those with brain tumors almost 30 have epilepsy making them the cause of about 4 of cases 70 The risk is greatest for tumors in the temporal lobe and those that grow slowly 70 Other mass lesions such as cerebral cavernous malformations and arteriovenous malformations have risks as high as 40 60 70 Of those who have had a stroke 6 10 develop epilepsy 83 84 Risk factors for post stroke epilepsy include stroke severity cortical involvement hemorrhage and early seizures 85 86 Between 6 and 20 of epilepsy is believed to be due to head trauma 70 Mild brain injury increases the risk about two fold while severe brain injury increases the risk seven fold 70 In those who have experienced a high powered gunshot wound to the head the risk is about 50 70 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 87 88 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 88 The risk of epilepsy following meningitis is less than 10 it more commonly causes seizures during the infection itself 70 In herpes simplex encephalitis the risk of a seizure is around 50 70 with a high risk of epilepsy following up to 25 89 90 A form of an infection with the pork tapeworm cysticercosis in the brain is known as neurocysticercosis and is the cause of up to half of epilepsy cases in areas of the world where the parasite is common 70 Epilepsy may also occur after other brain infections such as cerebral malaria toxoplasmosis and toxocariasis 70 Chronic alcohol use increases the risk of epilepsy those who drink six units of alcohol per day have a 2 5 fold increase in risk 70 Other risks include Alzheimer s disease multiple sclerosis and autoimmune encephalitis 70 Getting vaccinated does not increase the risk of epilepsy 70 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 19 People with cerebral palsy have an increased risk of epilepsy with half of people with spastic quadriplegia and spastic hemiplegia having the disease 91 Mechanism EditNormally 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 2 Neuron activity is regulated by various factors both within the cell and the cellular environment Factors within the neuron include the type number and distribution of ion channels changes to receptors and changes of gene expression 92 Factors around the neuron include ion concentrations synaptic plasticity and regulation of transmitter breakdown by glial cells 92 93 Epilepsy Edit The exact mechanism for epilepsy is unknown 94 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 95 96 Changes in MicroRNAs miRNAs levels seems to play a leading role MicroRNAs miRNAs 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 97 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 98 Seizures Edit 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 95 In epileptic seizures a group of neurons begin firing in an abnormal excessive 25 and synchronized manner 2 This results in a wave of depolarization known as a paroxysmal depolarizing shift 99 Normally after an 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 29 Some types of seizures may change brain structure while others appear to have little effect 100 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 100 The seizures can be described on different scales from the cellular level 101 better source needed to the whole brain 102 These are several concomitant factor which on different scale can drive the brain to pathological states and trigger a seizure Diagnosis Edit 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 25 An electroencephalogram EEG to look for abnormal patterns of brain waves and neuroimaging CT scan or MRI to look at the structure of the brain are also usually part of the initial investigations 25 While figuring out a specific epileptic syndrome is often attempted it is not always possible 25 Video and EEG monitoring may be useful in difficult cases 103 Definition Edit Epilepsy is a disorder of the brain defined by any of the following conditions 10 At least two unprovoked or reflex seizures occurring more than 24 hours apart 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 Diagnosis of an epilepsy syndromeFurthermore 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 104 105 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 12 Classification Edit Revised operational scheme of seizure classification ILAE 2017 In contrast to the classification of seizures which focuses on what happens during a seizure the classification of epilepsies focuses on the underlying causes When a person is admitted to hospital after an epileptic seizure the diagnostic workup results preferably in the seizure itself being classified e g tonic clonic and in the underlying disease being identified e g hippocampal sclerosis 103 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 106 Localization related epilepsies and syndromes Unknown cause e g benign childhood epilepsy with centrotemporal spikes Symptomatic cryptogenic e g temporal lobe epilepsy Generalized Unknown cause e g childhood absence epilepsy Cryptogenic or symptomatic e g Lennox Gastaut syndrome Symptomatic e g early infantile epileptic encephalopathy with burst suppression Epilepsies and syndromes undetermined whether focal or generalized With both generalized and focal seizures e g epilepsy with continuous spike waves during slow wave sleep 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 107 In 2010 the ILAE Commission for Classification of the Epilepsies addressed this issue and divided epilepsies into three categories genetic structural metabolic unknown cause 108 that were refined in their 2011 recommendation into four categories and a number of subcategories reflecting recent technologic and scientific advances 109 Unknown cause mostly genetic or presumed genetic origin Pure epilepsies due to single gene disorders Pure epilepsies with complex inheritance Symptomatic associated with gross anatomic or pathologic abnormalities Mostly genetic or developmental causation Childhood epilepsy syndromes Progressive myoclonic epilepsies Neurocutaneous syndromes Other neurologic single gene disorders Disorders of chromosome function Developmental anomalies of cerebral structure Mostly acquired causes Hippocampal sclerosis Perinatal and infantile causes Cerebral trauma tumor or infection Cerebrovascular disorders Cerebral immunologic disorders Degenerative and other neurologic conditions Provoked a specific systemic or environmental factor is the predominant cause of the seizures Provoking factors Reflex epilepsies Cryptogenic presumed symptomatic nature in which the cause has not been identified 109 A revised operational classification of seizure types has been introduced by the ILAE 110 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 111 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 111 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 111 New seizure types now believed to be generalized are eyelid myoclonia myoclonic atonic myoclonic absence and myoclonic tonic clonic 111 Sometimes it is possible to classify seizures as focal or generalized based on presenting features even though onset in not known 111 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 111 Syndromes Edit 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 29 112 The International League against Epilepsy has recently taken the massive and commendable task of clarifying various epilepsy syndromes across ages with mandatory 113 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 68 Less serious examples are benign rolandic epilepsy 2 8 per 100 000 childhood absence epilepsy 0 8 per 100 000 and juvenile myoclonic epilepsy 0 7 per 100 000 68 Severe syndromes with diffuse brain dysfunction caused at least partly by some aspect of epilepsy are also referred to as developmental and epileptic encephalopathies These are associated with frequent seizures that are resistant to treatment and cognitive dysfunction for instance Lennox Gastaut syndrome 1 2 of all persons with epilepsy 114 Dravet syndrome 1 15000 40000 worldwide 115 and West syndrome 1 9 100000 116 117 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 118 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 119 120 121 and DNM1 GABBR2 FASN and RYR3 122 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 109 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 109 Some childhood epilepsy syndromes are included in the unknown cause category in which the cause is presumed genetic for instance benign rolandic epilepsy 109 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 109 Classification of epilepsies and particularly of epilepsy syndromes will change with advances in research 109 Tests Edit 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 123 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 123 In certain situations it may be useful to perform the EEG while the affected individual is sleeping or sleep deprived 103 Diagnostic imaging by CT scan and MRI is recommended after a first non febrile seizure to detect structural problems in and around the brain 103 MRI is generally a better imaging test except when bleeding is suspected for which CT is more sensitive and more easily available 20 If someone attends the emergency room with a seizure but returns to normal quickly imaging tests may be done at a later point 20 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 103 124 For adults the testing of electrolyte blood glucose and calcium levels is important to rule out problems with these as causes 103 An electrocardiogram can rule out problems with the rhythm of the heart 103 A lumbar puncture may be useful to diagnose a central nervous system infection but is not routinely needed 20 In children additional tests may be required such as urine biochemistry and blood testing looking for metabolic disorders 103 125 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 126 For those with negative genetic testing in some it might be important to repeat or re analyze previous genetic studies after 2 3 years 127 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 128 129 Serum prolactin level is less useful for detecting focal seizures 130 If it is normal an epileptic seizure is still possible 129 and a serum prolactin does not separate epileptic seizures from syncope 131 It is not recommended as a routine part of the diagnosis of epilepsy 103 Differential diagnosis Edit 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 132 133 In particular syncope can be accompanied by a short episode of convulsions 134 Nocturnal frontal lobe epilepsy often misdiagnosed as nightmares was considered to be a parasomnia but later identified to be an epilepsy syndrome 135 Attacks of the movement disorder paroxysmal dyskinesia may be taken for epileptic seizures 136 The cause of a drop attack can be among many others an atonic seizure 133 Children may have behaviors that are easily mistaken for epileptic seizures but are not These include breath holding spells bedwetting night terrors tics and shudder attacks 133 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 133 Misdiagnosis is frequent occurring in about 5 to 30 of cases 25 Different studies showed that in many cases seizure like attacks in apparent treatment resistant epilepsy have a cardiovascular cause 134 137 Approximately 20 of the people seen at epilepsy clinics have PNES 20 and of those who have PNES about 10 also have epilepsy 138 separating the two based on the seizure episode alone without further testing is often difficult 138 Prevention EditWhile 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 30 Efforts in one part of Central America to decrease rates of pork tapeworm resulted in a 50 decrease in new cases of epilepsy 19 Complication EditEpilepsy can be dangerous when seizure occurs at certain times The possibility of drowning and having car accident is higher It is also dangerous when seizure occurs during pregnancy Certain anti epileptic medications increase the risk of birth defects It is also found that people with epilepsy are more likely to have psychological problems 139 Other complications include aspiration pneumonia and difficulty learning 140 Management Edit Wristbands or bracelets denoting their condition are occasionally worn by epileptics should they need medical assistance Epilepsy is usually treated with daily medication once a second seizure has occurred 25 103 while medication may be started after the first seizure in those at high risk for subsequent seizures 103 Supporting people s self management of their condition may be useful 141 In drug resistant cases different management options may be looked at including a special diet the implantation of a neurostimulator or neurosurgery First aid Edit Rolling people with an active tonic clonic seizure onto their side and into the recovery position helps prevent fluids from getting into the lungs 142 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 27 142 Efforts should be taken to prevent further self injury 27 Spinal precautions are generally not needed 142 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 103 143 This may require medical help to keep the airway open and protected 103 a nasopharyngeal airway may be useful for this 142 At home the recommended initial medication for seizure of a long duration is midazolam placed in the nose or mouth 144 Diazepam may also be used rectally 144 In hospital intravenous lorazepam is preferred 103 If two doses of benzodiazepines are not effective other medications such as phenytoin are recommended 103 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 103 Most institutions have a preferred pathway or protocol to be used in a seizure emergency like status epilepticus 103 These protocols have been found to be effective in reducing time to delivery of treatment 103 Medications Edit Anticonvulsants The mainstay treatment of epilepsy is anticonvulsant medications possibly for the person s entire life 11 25 The choice of anticonvulsant is based on seizure type epilepsy syndrome other medications used other health problems and the person s age and lifestyle 144 A single medication is recommended initially 145 if this is not effective switching to a single other medication is recommended 103 Two medications at once is recommended only if a single medication does not work 103 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 4 146 About 30 of people continue to have seizures despite anticonvulsant treatment 7 There are a number of medications available including phenytoin carbamazepine and valproate Evidence suggests that phenytoin carbamazepine and valproate may be equally effective in both focal and generalized seizures 147 148 Controlled release carbamazepine appears to work as well as immediate release carbamazepine and may have fewer side effects 149 Recently Nux vomica 150 and Cicuta virosa 151 have been shown to produce significant anti epileptic effects and no side effects This could prove to be very helpful for a large segment of population 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 103 152 Valproate is recommended first line for generalized seizures with lamotrigine being second line 103 In those with absence seizures ethosuximide or valproate are recommended valproate is particularly effective in myoclonic seizures and tonic or atonic seizures 103 If seizures are well controlled on a particular treatment it is not usually necessary to routinely check the medication levels in the blood 103 The least expensive anticonvulsant is phenobarbital at around US 5 a year 19 The World Health Organization gives it a first line recommendation in the developing world and it is commonly used there 153 154 Access however may be difficult as some countries label it as a controlled drug 19 Adverse effects from medications are reported in 10 to 90 of people depending on how and from whom the data is collected 155 Most adverse effects are dose related and mild 155 Some examples include mood changes sleepiness or an unsteadiness in gait 155 Certain medications have side effects that are not related to dose such as rashes liver toxicity or suppression of the bone marrow 155 Up to a quarter of people stop treatment due to adverse effects 155 Some medications are associated with birth defects when used in pregnancy 103 Many of the common used medications such as valproate phenytoin carbamazepine phenobarbital and gabapentin have been reported to cause increased risk of birth defects 156 especially when used during the first trimester 157 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 157 Among the antiepileptic medications levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects 156 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 103 158 Stopping is possible in about 70 of children and 60 of adults 30 Measuring medication levels is not generally needed in those whose seizures are well controlled 124 Surgery Edit Epilepsy surgery should be considered for any person with epilepsy who is medically refractory 159 Patients are evaluated on a Case by case epilepsy in centres that are familiar and have expertise in epilepsy surgery 159 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 Edit Neurostimulation via neuro cybernetic prosthesis implantation may be another option in those who are not candidates for surgery providing chronic pulsatile electrical stimulation of specific nerve or brain regions alongside standard care 103 Three types have been used in those who do not respond to medications vagus nerve stimulation VNS anterior thalamic stimulation and closed loop responsive stimulation RNS 5 164 165 Vagus nerve stimulation Edit Non pharmacological modulation of neurotransmitters via high level VNS h VNS may reduce seizure frequency in children and adults who do not respond to medical and or surgical therapy when compared with low level VNS l VNS 165 In a 2022 Cochrane review of 4 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 3 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 Edit There is promising evidence that a ketogenic diet high fat low carbohydrate adequate protein decreases the number of seizures and eliminates seizures in some however further research is necessary 6 It is a reasonable option in those who have epilepsy that is not improved with medications and for whom surgery is not an option 6 About 10 stay on the diet for a few years due to issues of effectiveness and tolerability 6 Side effects include stomach and intestinal problems in 30 and there are long term concerns about heart disease 6 Less radical diets are easier to tolerate and may be effective 6 It is unclear why this diet works 166 In people with coeliac disease or non celiac gluten sensitivity and occipital calcifications a gluten free diet may decrease the frequency of seizures 88 Other Edit 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 167 Operant based biofeedback based on the EEG waves has some support in those who do not respond to medications 168 Psychological methods should not however be used to replace medications 103 Exercise has been proposed as possibly useful for preventing seizures 169 with some data to support this claim 170 Some dogs commonly referred to as seizure dogs may help during or after a seizure 171 172 It is not clear if dogs have the ability to predict seizures before they occur 173 There is moderate quality evidence supporting the use of psychological interventions along with other treatments in epilepsy 174 This can improve quality of life enhance emotional wellbeing and reduce fatigue in adults and adolescents 174 Psychological interventions may also improve seizure control for some individuals by promoting self management and adherence 174 As an add on therapy in those who are not well controlled with other medications cannabidiol appears to be useful in some children 175 176 In 2018 the FDA approved this product for Lennox Gastaut syndrome and Dravet syndrome 177 There are a few studies on the use of dexamethasone for the successful treatment of drug resistant seizures in both adults and children 178 In pregnancy Edit In women of childbearing age use of antiepileptic drugs is a major concern balancing possible side effects on the fetus against risk from uncontrolled seizures 179 Use of AEDs entail teratogenic effects including intrauterine growth retardation major congenital malformations and developmental neurocognitive and behavioral issues that need to be discussed with the patient at the time of starting the AEDs and before they plan pregnancy 179 Most women with epilepsy receive safe and effective treatment and have normal children however risks exist 179 The International League Against Epilepsy created a task force on women and epilepsy which published consensus recommendations to guide therapy decisions until more definitive evidence is available in the future 179 Alternative medicine Edit Alternative medicine including acupuncture 180 routine vitamins 181 and yoga 182 have no reliable evidence to support their use in epilepsy Melatonin as of 2016 update 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 Prognosis Edit 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 25 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 186 In the developing world 75 of people are either untreated or not appropriately treated 30 In Africa 90 do not get treatment 30 This is partly related to appropriate medications not being available or being too expensive 30 Mortality Edit People with epilepsy are at an increased risk of death 187 This increase is between 1 6 and 4 1 fold greater than that of the general population 188 The greatest increase in mortality from epilepsy is among the elderly 188 Those with epilepsy due to an unknown cause have little increased risk 188 Mortality is often related to the underlying cause of the seizures status epilepticus suicide trauma and sudden unexpected death in epilepsy SUDEP 187 Death from status epilepticus is primarily due to an underlying problem rather than missing doses of medications 187 The risk of suicide is between 2 and 6 times higher in those with epilepsy 189 190 the cause of this is unclear 189 SUDEP appears to be partly related to the frequency of generalized tonic clonic seizures 191 and accounts for about 15 of epilepsy related deaths 186 it is unclear how to decrease its risk 191 Risk factors for SUDEP include nocturnal generalized tonic clonic seizures seizures Sleeping along and medically intractable epilepsy 192 In the United Kingdom it is estimated that 40 60 of deaths are possibly preventable 25 In the developing world many deaths are due to untreated epilepsy leading to falls or status epilepticus 19 Epidemiology EditEpilepsy is one of the most common serious neurological disorders 193 affecting about 39 million people as of 2015 update 8 It affects 1 of the population by age 20 and 3 of the population by age 75 17 It is more common in males than females with the overall difference being small 19 68 Most of those with the disorder 80 are in low income populations 194 or the developing world 30 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 68 195 Epilepsy begins each year in 40 70 per 100 000 in developed countries and 80 140 per 100 000 in developing countries 30 Poverty is a risk and includes both being from a poor country and being poor relative to others within one s country 19 In the developed world epilepsy most commonly starts either in the young or in the old 19 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 19 In developed countries the number of cases a year has decreased in children and increased among the elderly between the 1970s and 2003 195 This has been attributed partly to better survival following strokes in the elderly 68 History EditSee 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 196 Throughout ancient history the disease was thought to be a spiritual condition 196 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 23 The person described in the text was diagnosed as being under the influence of a moon god and underwent an exorcism 23 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 23 and the Edwin Smith Papyrus c 1700 BC describes cases of individuals with epileptic convulsions 23 The oldest known detailed record of the disease itself is in the Sakikku a Babylonian cuneiform medical text from 1067 1046 BC 196 This text gives signs and symptoms details treatment and likely outcomes 23 and describes many features of the different seizure types 196 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 196 Around 900 BC Punarvasu Atreya described epilepsy as loss of consciousness 197 this definition was carried forward into the Ayurvedic text of Charaka Samhita c 400 BC 198 The ancient Greeks had contradictory views of the disease They thought of epilepsy as a form of spiritual possession but also associated the condition with genius and the divine One of the names they gave to it was the sacred disease Greek ἠ ἱerὰ nosos 23 199 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 23 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 23 196 He accused those of attributing a sacred cause to the disease of spreading ignorance through a belief in superstitious magic 23 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 23 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 23 Despite his work detailing the physical origins of the disease his view was not accepted at the time 196 Evil spirits continued to be blamed until at least the 17th century 196 In Ancient Rome people did not eat or drink with the same pottery as that used by someone who was affected 200 People of the time would spit on their chest believing that this would keep the problem from affecting them 200 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 201 Occasionally a spinning potter s wheel was used perhaps a reference to photosensitive epilepsy 202 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 203 In the Salpetriere 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 204 In Ancient Rome epilepsy was known as the Latin morbus comitialis lit disease of the assembly hall and was seen as a curse from the gods In northern Italy epilepsy was once traditionally known as Saint Valentine s malady 205 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 206 Around the same time period epilepsy was known in France as the French haut mal lit high evil French mal de terre lit earthen sickness French mal de Saint Jean lit Saint John s sickness French mal des enfans lit child sickness and French mal caduc lit falling sickness 206 Patients of epilepsy in France were also known as French tombeurs lit people who fall due to the seizures and loss of consciousness in an epileptic episode 206 In the mid 19th century the first effective anti seizure medication bromide was introduced 155 The first modern treatment phenobarbital was developed in 1912 with phenytoin coming into use in 1938 207 Society and culture EditSee also List of people with epilepsy Stigma Edit Social stigma is commonly experienced around the world by those with epilepsy 12 208 It can affect people economically socially and culturally 208 In India and China epilepsy may be used as justification to deny marriage 30 People in some areas still believe those with epilepsy to be cursed 19 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 203 19 Before 1971 in the United Kingdom epilepsy was considered grounds for the annulment of marriage 30 The stigma may result in some people with epilepsy denying that they have ever had seizures 68 Economics Edit Seizures result in direct economic costs of about one billion dollars in the United States 20 Epilepsy resulted in economic costs in Europe of around 15 5 billion euros in 2004 25 In India epilepsy is estimated to result in costs of US 1 7 billion or 0 5 of the GDP 30 It is the cause of about 1 of emergency department visits 2 for emergency departments for children in the United States 209 Vehicles Edit 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 22 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 nonmotor seizures as opposed to those with motor seizures at epilepsy onset 210 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 22 Countries that require physician reporting include Sweden Austria Denmark and Spain 22 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 22 In Canada the United States and Australia the requirements around reporting vary by province or state 22 If seizures are well controlled most feel allowing driving is reasonable 211 The amount of time a person must be free from seizures before he can drive varies by country 211 Many countries require one to three years without seizures 211 In the United States the time needed without a seizure is determined by each state and is between three months and one year 211 Those with epilepsy or seizures are typically denied a pilot license 212 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 213 Those with febrile seizures and drug related seizures may also be considered 213 In the United States the Federal Aviation Administration does not allow those with epilepsy to get a commercial pilot license 214 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 215 In the United Kingdom a full national private pilot license requires the same standards as a professional driver s license 216 This requires a period of ten years without seizures while off medications 217 Those who do not meet this requirement may acquire a restricted license if free from seizures for five years 216 Support organizations Edit 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 30 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 218 The Epilepsy Foundation some hospitals and some individuals also run support groups in the United States 219 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 220 221 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 222 Research EditSee also Computational models in epilepsy Seizure prediction and modeling Edit Seizure prediction refers to attempts to forecast epileptic seizures based on the EEG before they occur 223 As of 2011 update no effective mechanism to predict seizures has been developed 223 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 Kindling where repeated exposures to events that could cause seizures eventually causes seizures more easily has been used to create animal models of epilepsy 224 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 225 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 226 Among these models the strain of GAERS Genetic Absence Epilepsy Rats from Strasbourg was characterized in the 80 and has helped to understand the mechanisms underlying Childhood Absence Epilepsy 227 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 228 Potential future therapies Edit Gene therapy is being studied in some types of epilepsy 229 Medications that alter immune function such as intravenous immunoglobulins are poorly supported by evidence 230 Noninvasive stereotactic radiosurgery is as of 2012 update being compared to standard surgery for certain types of epilepsy 231 Other animals EditMain 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 232 It is typically treated with anticonvulsants such as phenobarbital or bromide in dogs and phenobarbital in cats 232 Imepitoin is also used in dogs 233 While generalized seizures in horses are fairly easy to diagnose it may be more difficult in non generalized seizures and EEGs may be useful 234 References Edit 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 a b c d e f g h i j k l m n o Hammer GD McPhee SJ eds 2010 7 Pathophysiology of disease an introduction to clinical medicine 6th ed New York McGraw Hill Medical ISBN 978 0 07 162167 0 a b c d Goldberg EM Coulter DA May 2013 Mechanisms of epileptogenesis a convergence on neural circuit dysfunction Nature Reviews Neuroscience 14 5 337 49 doi 10 1038 nrn3482 PMC 3982383 PMID 23595016 a b c d e f Longo DL 2012 369 Seizures and Epilepsy Harrison s principles of internal medicine 18th ed McGraw Hill p 3258 ISBN 978 0 07 174887 2 a b c d Bergey GK June 2013 Neurostimulation in the treatment of epilepsy Experimental Neurology 244 87 95 doi 10 1016 j expneurol 2013 04 004 PMID 23583414 S2CID 45244964 a b c d e f g Martin McGill Kirsty J Jackson Cerian F Bresnahan Rebecca Levy Robert G Cooper Paul N 7 November 2018 Ketogenic diets for drug resistant epilepsy The Cochrane Database of Systematic Reviews 11 11 CD001903 doi 10 1002 14651858 CD001903 pub4 ISSN 1469 493X PMC 6517043 PMID 30403286 a b c d e Eadie MJ December 2012 Shortcomings in the current treatment of epilepsy Expert Review of Neurotherapeutics 12 12 1419 27 doi 10 1586 ern 12 129 PMID 23237349 S2CID 207221378 a b Vos Theo Allen Christine Arora Megha Barber Ryan M Bhutta Zulfiqar A Brown Alexandria Carter Austin Casey Daniel C Charlson Fiona J Chen Alan Z Coggeshall Megan Cornaby Leslie Dandona Lalit Dicker Daniel J Dilegge Tina Erskine Holly E Ferrari Alize J Fitzmaurice Christina Fleming Tom Forouzanfar Mohammad H Fullman Nancy Gething Peter W Goldberg Ellen M Graetz Nicholas Haagsma Juanita A Hay Simon I Johnson Catherine O Kassebaum Nicholas J Kawashima Toana et al October 2016 Global regional and national incidence prevalence and years lived with disability for 310 diseases and injuries 1990 2015 a systematic analysis for the Global Burden of Disease Study 2015 Lancet 388 10053 1545 1602 doi 10 1016 S0140 6736 16 31678 6 PMC 5055577 PMID 27733282 a b Wang Haidong Naghavi Mohsen Allen Christine Barber Ryan M Bhutta Zulfiqar A Carter Austin Casey Daniel C Charlson Fiona J Chen Alan Zian Coates Matthew M Coggeshall Megan Dandona Lalit Dicker Daniel J Erskine Holly E Ferrari Alize J Fitzmaurice Christina Foreman Kyle Forouzanfar Mohammad H Fraser Maya S Fullman Nancy Gething Peter W Goldberg Ellen M Graetz Nicholas Haagsma Juanita A Hay Simon I Huynh Chantal Johnson Catherine O Kassebaum Nicholas J Kinfu Yohannes et al October 2016 Global regional and national life expectancy all cause mortality and cause specific mortality for 249 causes of death 1980 2015 a systematic analysis for the Global Burden of Disease Study 2015 Lancet 388 10053 1459 1544 doi 10 1016 s0140 6736 16 31012 1 PMC 5388903 PMID 27733281 a b c d e f g h 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 Moshe SL Perucca E Scheffer IE Tomson T Watanabe M Wiebe S April 2014 ILAE official report a practical clinical definition of epilepsy Epilepsia 55 4 475 82 doi 10 1111 epi 12550 PMID 24730690 S2CID 35958237 a b c d e f Ghosh Shampa Sinha Jitendra Kumar Khan Tarab Devaraju Kuramkote Shivanna Singh Prabhakar Vaibhav Kumar Gaur Pankaj May 2021 Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy Biomedicines 9 5 470 doi 10 3390 biomedicines9050470 PMC 8146518 PMID 33923061 a b c d e Epilepsy www who int Retrieved 1 April 2023 a b Fisher RS van Emde Boas W Blume W Elger C Genton P Lee P Engel J Jr April 2005 Epileptic seizures and epilepsy definitions proposed by the International League Against Epilepsy ILAE and the International Bureau for Epilepsy IBE Epilepsia 46 4 470 2 doi 10 1111 j 0013 9580 2005 66104 x PMID 15816939 S2CID 21130724 a b c d e f g Pandolfo M November 2011 Genetics of epilepsy Seminars in Neurology 31 5 506 18 doi 10 1055 s 0031 1299789 PMID 22266888 N Mohsen et al GBD 2013 Mortality Causes of Death Collaborators January 2015 Global regional and national age sex specific all cause and cause specific mortality for 240 causes of death 1990 2013 a systematic analysis for the Global Burden of Disease Study 2013 The Lancet 385 9963 117 71 doi 10 1016 S0140 6736 14 61682 2 hdl 11655 15525 PMC 4340604 PMID 25530442 Brodie MJ Elder AT Kwan P November 2009 Epilepsy in later life The Lancet Neurology 8 11 1019 30 doi 10 1016 S1474 4422 09 70240 6 PMID 19800848 S2CID 14318073 a b Holmes TR Browne GL 2008 Handbook of epilepsy 4th ed Philadelphia Lippincott Williams amp Wilkins p 7 ISBN 978 0 7817 7397 3 Wyllie s treatment of epilepsy principles and practice 5th ed Philadelphia Wolters Kluwer Lippincott Williams amp Wilkins 2010 ISBN 978 1 58255 937 7 Archived from the original on 24 June 2016 a b c d e f g h i j k l Newton CR Garcia HH September 2012 Epilepsy in poor regions of the world Lancet 380 9848 1193 201 doi 10 1016 S0140 6736 12 61381 6 PMID 23021288 S2CID 13933909 a b c d e f Wilden JA Cohen Gadol AA August 2012 Evaluation of first nonfebrile seizures American Family Physician 86 4 334 40 PMID 22963022 Berg AT 2008 Risk of recurrence after a first unprovoked seizure Epilepsia 49 Suppl 1 13 8 doi 10 1111 j 1528 1167 2008 01444 x PMID 18184149 S2CID 28114460 a b c d e f L Devlin A Odell M L Charlton J Koppel S December 2012 Epilepsy and driving current status of research Epilepsy Research 102 3 135 52 doi 10 1016 j eplepsyres 2012 08 003 PMID 22981339 S2CID 30673360 a b c d e f g h i j k l Magiorkinis E Sidiropoulou K Diamantis A January 2010 Hallmarks in the history of epilepsy epilepsy in antiquity Epilepsy amp Behavior 17 1 103 8 doi 10 1016 j yebeh 2009 10 023 PMID 19963440 S2CID 26340115 a b Duncan JS Sander JW Sisodiya SM Walker MC April 2006 Adult epilepsy PDF Lancet 367 9516 1087 1100 doi 10 1016 S0140 6736 06 68477 8 PMID 16581409 S2CID 7361318 Archived from the original PDF on 24 March 2013 Retrieved 10 January 2012 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 Hughes JR August 2009 Absence seizures a review of recent reports with new concepts Epilepsy amp Behavior 15 4 404 12 doi 10 1016 j yebeh 2009 06 007 PMID 19632158 S2CID 22023692 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 a b c d Bradley WG 2012 67 Bradley s neurology in clinical practice 6th ed Philadelphia PA Elsevier Saunders ISBN 978 1 4377 0434 1 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 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 a b c d Engel J 2008 Epilepsy a comprehensive textbook 2nd ed Philadelphia Wolters Kluwer Health Lippincott Williams amp Wilkins p 2797 ISBN 978 0 7817 5777 5 Archived from the original on 20 May 2016 a b c Simon DA Greenberg MJ Aminoff RP 2012 12 Clinical neurology 8th ed New York McGraw Hill Medical ISBN 978 0 07 175905 2 a b Stephenson John B P 1990 Fits and faints London Mac Keith Press ISBN 0 632 02811 4 OCLC 25711319 a b Steven C Schachter ed 2008 Behavioral aspects of epilepsy principles and practice Online Ausg ed New York Demos p 125 ISBN 978 1 933864 04 4 Xue LY Ritaccio AL March 2006 Reflex seizures and reflex epilepsy American Journal of Electroneurodiagnostic Technology 46 1 39 48 doi 10 1080 1086508X 2006 11079556 PMID 16605171 S2CID 10098600 Malow BA November 2005 Sleep and epilepsy Neurologic Clinics 23 4 1127 47 doi 10 1016 j ncl 2005 07 002 PMID 16243619 Tinuper P Provini F Bisulli F Vignatelli L Plazzi G Vetrugno R Montagna P Lugaresi E August 2007 Movement disorders in sleep guidelines for differentiating epileptic from non epileptic motor phenomena arising from sleep Sleep Medicine Reviews 11 4 255 67 doi 10 1016 j smrv 2007 01 001 PMID 17379548 Scheffer IE Berkovic S Capovilla G Connolly MB French J Guilhoto L Hirsch E Jain S Mathern GW Moshe SL Nordli DR Perucca E Tomson T Wiebe S Zhang YH Zuberi SM April 2017 ILAE classification of the epilepsies Position paper of the ILAE Commission for Classification and Terminology Epilepsia 58 4 512 521 doi 10 1111 epi 13709 PMC 5386840 PMID 28276062 Mitchell W G 1996 Status epilepticus and acute repetitive seizures in children adolescents and young adults etiology outcome and treatment Epilepsia 37 Suppl 1 S74 80 doi 10 1111 j 1528 1157 1996 tb06025 x ISSN 0013 9580 PMID 8647055 S2CID 14510863 a b Jafarpour Saba Hirsch Lawrence J Gainza Lein Marina Kellinghaus Christoph Detyniecki Kamil 1 May 2019 Seizure cluster Definition prevalence consequences and management Seizure 68 9 15 doi 10 1016 j seizure 2018 05 013 ISSN 1532 2688 PMID 29871784 S2CID 46942965 Faught Edward 23 August 2022 Economic aspects of treating seizure clusters Epilepsia 63 Suppl 1 S45 S54 doi 10 1111 epi 17340 ISSN 1528 1167 PMID 35999172 S2CID 251744416 Haut Sheryl R Shinnar Shlomo Moshe Solomon L 11 January 2005 Seizure clustering risks and outcomes Epilepsia 46 1 146 149 doi 10 1111 j 0013 9580 2005 29004 x ISSN 0013 9580 PMID 15660781 S2CID 37102974 Chen Baibing Choi Hyunmi Hirsch Lawrence J Katz Austen Legge Alexander Wong Rebecca A Jiang Alfred Kato Kenneth Buchsbaum Richard Detyniecki Kamil 1 July 2017 Prevalence and risk factors of seizure clusters in adult patients with epilepsy Epilepsy Research 133 98 102 doi 10 1016 j eplepsyres 2017 04 016 ISSN 0920 1211 PMID 28475999 S2CID 4735843 Komaragiri Arpitha Detyniecki Kamil Hirsch Lawrence J 1 June 2016 Seizure clusters A common understudied and undertreated phenomenon in refractory epilepsy Epilepsy amp Behavior 59 83 86 doi 10 1016 j yebeh 2016 02 030 ISSN 1525 5069 PMID 27116535 S2CID 3880221 Chung Steve Szaflarski Jerzy P Choi Eun Jung Wilson Jessica Claire Kharawala Saifuddin Kaur Gavneet Hirsch Lawrence J 1 November 2021 A systematic review of seizure clusters Prevalence risk factors burden of disease and treatment patterns Epilepsy Research 177 106748 doi 10 1016 j eplepsyres 2021 106748 ISSN 1872 6844 PMID 34521043 S2CID 237380380 Gidal Barry Detyniecki Kamil 23 August 2022 Rescue therapies for seizure clusters Pharmacology and target of treatments Epilepsia 63 Suppl 1 Suppl 1 S34 S44 doi 10 1111 epi 17341 ISSN 1528 1167 PMC 9543841 PMID 35999174 S2CID 251744444 Holmes TR 2008 Handbook of epilepsy 4th ed Philadelphia Lippincott Williams amp Wilkins p 34 ISBN 978 0 7817 7397 3 a b c Panayiotopoulos CP 2010 A clinical guide to epileptic syndromes and their treatment based on the ILAE classifications and practice parameter guidelines Rev 2nd ed London Springer p 445 ISBN 978 1 84628 644 5 Wheless JW ed 2009 Advanced therapy in epilepsy Shelton Conn People s Medical Pub House p 443 ISBN 978 1 60795 004 2 Larner AJ 2010 A dictionary of neurological signs 3rd ed New York Springer p 348 ISBN 978 1 4419 7095 4 Kaplan PW November 2011 Obsessive compulsive disorder in chronic epilepsy Epilepsy amp Behavior 22 3 428 32 doi 10 1016 j yebeh 2011 07 029 PMID 21889913 S2CID 42945523 Stefan H 2012 Epilepsy Part I Basic Principles and Diagnosis E Book Handbook of Clinical Neurology Volume 107 of Handbook of Clinical Neurology ed Newnes p 471 ISBN 978 0 444 53505 4 Plioplys S Dunn DW Caplan R November 2007 10 year research update review psychiatric problems in children with epilepsy Journal of the American Academy of Child and Adolescent Psychiatry 46 11 1389 402 doi 10 1097 chi 0b013e31815597fc PMID 18049289 Reilly CJ May June 2011 Attention deficit hyperactivity disorder ADHD in childhood epilepsy Research in Developmental Disabilities 32 3 883 93 doi 10 1016 j ridd 2011 01 019 PMID 21310586 Levisohn PM 2007 The autism epilepsy connection Epilepsia 48 Suppl 9 Suppl 9 33 5 doi 10 1111 j 1528 1167 2007 01399 x PMID 18047599 Lin Jack J Mula Marco Hermann Bruce P 29 September 2012 Uncovering the neurobehavioural comorbidities of epilepsy over the lifespan The Lancet 380 9848 1180 1192 doi 10 1016 s0140 6736 12 61455 x ISSN 0140 6736 PMC 3838617 PMID 23021287 Kanner Andres M Schachter Steven C Barry John J Hersdorffer Dale C Mula Marco Trimble Michael Hermann Bruce Ettinger Alan E Dunn David Caplan Rochelle Ryvlin Philippe Gilliam Frank 1 June 2012 Depression and epilepsy Epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence Epilepsy amp Behavior 24 2 156 168 doi 10 1016 j yebeh 2012 01 007 ISSN 1525 5050 PMID 22632406 S2CID 24369127 Adelow C Andersson T Ahlbom A Tomson T 25 January 2012 Hospitalization for psychiatric disorders before and after onset of unprovoked seizures epilepsy Neurology 78 6 396 401 doi 10 1212 wnl 0b013e318245f461 ISSN 0028 3878 PMID 22282649 S2CID 207120740 Taylor Rod S Sander Josemir W Taylor Rebecca J Baker Gus A 29 August 2011 Predictors of health related quality of life and costs in adults with epilepsy A systematic review Epilepsia 52 12 2168 2180 doi 10 1111 j 1528 1167 2011 03213 x ISSN 0013 9580 PMID 21883177 S2CID 30039598 Lacey Cameron J Salzberg Michael R Roberts Helene Trauer Tom D Souza Wendyl J 29 July 2009 Psychiatric comorbidity and impact on health service utilization in a community sample of patients with epilepsy Epilepsia 50 8 1991 1994 doi 10 1111 j 1528 1167 2009 02165 x ISSN 0013 9580 PMID 19490049 S2CID 27842830 Nogueira Mateus H Yasuda Clarissa L Coan Ana C Kanner Andres M Cendes Fernando 26 May 2017 Concurrent mood and anxiety disorders are associated with pharmacoresistant seizures in patients with MTLE Epilepsia 58 7 1268 1276 doi 10 1111 epi 13781 ISSN 0013 9580 PMID 28555776 S2CID 2519902 Kanner A M Byrne R Chicharro A Wuu J Frey M 2 March 2009 A lifetime psychiatric history predicts a worse seizure outcome following temporal lobectomy Neurology 72 9 793 799 doi 10 1212 01 wnl 0000343850 85763 9c ISSN 0028 3878 PMID 19255406 S2CID 10497821 Boylan L S Flint L A Labovitz D L Jackson S C Starner K Devinsky O 26 January 2004 Depression but not seizure frequency predicts quality of life in treatment resistant epilepsy Neurology 62 2 258 261 doi 10 1212 01 wnl 0000103282 62353 85 ISSN 0028 3878 PMID 14745064 S2CID 24173332 Munger Clary Heidi M Croxton Rachel D Allan Jonathan Lovato James Brenes Gretchen Snively Beverly M Wan Mingyu Kimball James Wong Matthew H O Donovan Cormac A Conner Kelly Jones Victor Duncan Pamela 1 March 2020 Who is willing to participate in research A screening model for an anxiety and depression trial in the epilepsy clinic Epilepsy amp Behavior 104 Pt A 106907 doi 10 1016 j yebeh 2020 106907 ISSN 1525 5050 PMC 7282472 PMID 32000099 a b c Berkovic SF Mulley JC Scheffer IE Petrou S 2006 Human epilepsies interaction of genetic and acquired factors Trends in Neurosciences 29 7 391 7 doi 10 1016 j tins 2006 05 009 PMID 16769131 S2CID 205403084 Balestrini Simona Arzimanoglou Alexis Blumcke Ingmar Scheffer Ingrid E Wiebe Samuel Zelano Johan Walker Matthew C February 2021 The aetiologies of epilepsy Epileptic Disorders 23 1 1 16 doi 10 1684 epd 2021 1255 PMID 33720020 S2CID 232231196 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 ILAE Commission on Epidemiology September 2011 Standards for epidemiologic studies and surveillance of epilepsy Epilepsia 52 Suppl 7 2 26 doi 10 1111 j 1528 1167 2011 03121 x PMID 21899536 S2CID 8505004 a b c d e f g Neligan A Hauser WA Sander JW 2012 The epidemiology of the epilepsies Epilepsy Handbook of Clinical Neurology Vol 107 pp 113 33 doi 10 1016 B978 0 444 52898 8 00006 9 ISBN 978 0 444 52898 8 PMID 22938966 Dhavendra Kumar ed 2008 Genomics and clinical medicine Oxford Oxford University Press p 279 ISBN 978 0 19 972005 7 Archived from the original on 21 May 2016 a b c d e f g h i j k l m n o Bhalla D Godet B Druet Cabanac M Preux PM June 2011 Etiologies of epilepsy a comprehensive review Expert Review of Neurotherapeutics 11 6 861 76 doi 10 1586 ern 11 51 PMID 21651333 S2CID 21190601 a b Stafstrom Carl E Staedtke Verena Comi Anne M 2017 Epilepsy Mechanisms in Neurocutaneous Disorders Tuberous Sclerosis Complex Neurofibromatosis Type 1 and Sturge Weber Syndrome Frontiers in Neurology 8 87 doi 10 3389 fneur 2017 00087 ISSN 1664 2295 PMC 5355446 PMID 28367137 O Callaghan F J Shiell A W Osborne J P Martyn C N 16 May 1998 Prevalence of tuberous sclerosis estimated by capture recapture analysis Lancet 351 9114 1490 doi 10 1016 S0140 6736 05 78872 3 ISSN 0140 6736 PMID 9605811 S2CID 9262685 a b Northrup Hope Aronow Mary E Bebin E Martina Bissler John Darling Thomas N de Vries Petrus J Frost Michael D Fuchs Zoe Gosnell Elizabeth S Gupta Nishant Jansen Anna C October 2021 Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations Pediatric Neurology 123 50 66 doi 10 1016 j pediatrneurol 2021 07 011 ISSN 1873 5150 PMID 34399110 a b Curatolo Paolo March 2015 Mechanistic target of rapamycin mTOR in tuberous sclerosis complex associated epilepsy Pediatric Neurology 52 3 281 289 doi 10 1016 j pediatrneurol 2014 10 028 ISSN 1873 5150 PMID 25591831 Moavero Romina Cerminara Caterina Curatolo Paolo November 2010 Epilepsy secondary to tuberous sclerosis lessons learned and current challenges Child s Nervous System 26 11 1495 1504 doi 10 1007 s00381 010 1128 8 ISSN 1433 0350 PMID 20358377 S2CID 35481466 Shirley Matthew D Tang Hao Gallione Carol J Baugher Joseph D Frelin Laurence P Cohen Bernard North Paula E Marchuk Douglas A Comi Anne M Pevsner Jonathan 23 May 2013 Sturge Weber Syndrome and Port Wine Stains Caused by Somatic Mutation in GNAQ The New England Journal of Medicine 368 21 1971 1979 doi 10 1056 NEJMoa1213507 ISSN 0028 4793 PMC 3749068 PMID 23656586 a b Sudarsanam Annapurna Ardern Holmes Simone L May 2014 Sturge Weber syndrome from the past to the present European Journal of Paediatric Neurology 18 3 257 266 doi 10 1016 j ejpn 2013 10 003 ISSN 1532 2130 PMID 24275166 Sugano Hidenori Iimura Yasushi Igarashi Ayuko Nakazawa Mika Suzuki Hiroharu Mitsuhashi Takumi Nakajima Madoka Higo Takuma Ueda Tetsuya Nakanishi Hajime Niijima Shinichi 1 April 2021 Extent of Leptomeningeal Capillary Malformation is Associated With Severity of Epilepsy in Sturge Weber Syndrome Pediatric Neurology 117 64 71 doi 10 1016 j pediatrneurol 2020 12 012 ISSN 0887 8994 PMID 33677229 S2CID 232140769 Wang Shu Pan Junhong Zhao Meng Wang Xiongfei Zhang Chunsheng Li Tianfu Wang Mengyang Wang Jing Zhou Jian Liu Changqing Sun Yongxing 21 December 2021 Characteristics surgical outcomes and influential factors of epilepsy in Sturge Weber syndrome Brain A Journal of Neurology 145 10 3431 3443 doi 10 1093 brain awab470 ISSN 1460 2156 PMID 34932802 Lammert Marga Friedman Jan M Kluwe Lan Mautner Victor F January 2005 Prevalence of neurofibromatosis 1 in German children at elementary school enrollment Archives of Dermatology 141 1 71 74 doi 10 1001 archderm 141 1 71 ISSN 0003 987X PMID 15655144 Ostendorf Adam P Gutmann David H Weisenberg Judith L Z October 2013 Epilepsy in individuals with neurofibromatosis type 1 Epilepsia 54 10 1810 1814 doi 10 1111 epi 12348 ISSN 1528 1167 PMID 24032542 S2CID 1603461 Barba Carmen Jacques Thomas Kahane Philippe Polster Tilman Isnard Jean Leijten Frans S S Ozkara Cigdem Tassi Laura Giordano Flavio Castagna Maura John Alison August 2013 Epilepsy surgery in Neurofibromatosis Type 1 Epilepsy Research 105 3 384 395 doi 10 1016 j eplepsyres 2013 02 021 ISSN 1872 6844 PMID 23597854 S2CID 25785144 Galovic Marian Dohler Nico Erdelyi Canavese Barbara Felbecker Ansgar Siebel Philip Conrad Julian Evers Stefan Winklehner Michael von Oertzen Tim J Haring Hans Peter Serafini Anna Gregoraci Giorgia Valente Mariarosaria Janes Francesco Gigli Gian Luigi 1 February 2018 Prediction of late seizures after ischaemic stroke with a novel prognostic model the SeLECT score a multivariable prediction model development and validation study The Lancet Neurology 17 2 143 152 doi 10 1016 S1474 4422 17 30404 0 ISSN 1474 4465 PMID 29413315 S2CID 21665713 Ren Zhong Wen Quan Yan Xue Wang Ying Zhang Yidan 1 September 2022 Post stroke epilepsy and risk of all cause mortality A systematic review and meta analysis of cohort studies Clinical Neurology and Neurosurgery 220 107362 doi 10 1016 j clineuro 2022 107362 ISSN 0303 8467 PMID 35839716 S2CID 250317784 Zelano Johan Holtkamp Martin Agarwal Nivedita Lattanzi Simona Trinka Eugen Brigo Francesco 1 June 2020 How to diagnose and treat post stroke seizures and epilepsy Epileptic Disorders International Epilepsy Journal with Videotape 22 3 252 263 doi 10 1684 epd 2020 1159 ISSN 1950 6945 PMID 32597766 S2CID 220254988 Zollner Johann Philipp Schmitt Friedhelm C Rosenow Felix Kohlhase Konstantin Seiler Alexander Strzelczyk Adam Stefan Hermann 6 December 2021 Seizures and epilepsy in patients with ischaemic stroke Neurological Research and Practice 3 1 63 doi 10 1186 s42466 021 00161 w ISSN 2524 3489 PMC 8647498 PMID 34865660 Grossman G April 2008 Neurological complications of coeliac disease what is the evidence Practical Neurology 8 2 77 89 doi 10 1136 jnnp 2007 139717 PMID 18344378 S2CID 28327166 a b c Jackson JR Eaton WW Cascella NG Fasano A Kelly DL March 2012 Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity The Psychiatric Quarterly 83 1 91 102 doi 10 1007 s11126 011 9186 y PMC 3641836 PMID 21877216 Shorvon SD 2011 The Causes of Epilepsy Common and Uncommon Causes in Adults and Children Cambridge University Press p 467 ISBN 978 1 139 49578 3 Sellner J Trinka E October 2012 Seizures and epilepsy in herpes simplex virus encephalitis current concepts and future directions of pathogenesis and management Journal of Neurology 259 10 2019 30 doi 10 1007 s00415 012 6494 6 PMID 22527234 S2CID 24701310 Hadjipanayis A Hadjichristodoulou C Youroukos S October 1997 Epilepsy in patients with cerebral palsy Developmental Medicine and Child Neurology 39 10 659 63 doi 10 1111 j 1469 8749 1997 tb07359 x PMID 9352726 a b Bromfield EB 2006 An Introduction to Epilepsy American Epilepsy Society Blumenfeld H 2005 Cellular and network mechanisms of spike wave seizures Epilepsia 46 Suppl 9 Suppl 9 21 33 doi 10 1111 j 1528 1167 2005 00311 x PMID 16302873 Noebels JL Avoli M 29 June 2012 Jasper s Basic Mechanisms of the Epilepsies Oxford University Press pp 466 470 ISBN 9780199746545 Retrieved 16 October 2014 a b Le Van Quyen M Navarro V Martinerie J Baulac M Varela FJ 2003 Toward a neurodynamical understanding of ictogenesis Epilepsia 44 Suppl 12 Suppl 12 30 43 doi 10 1111 j 0013 9580 2003 12007 x PMID 14641559 Lopes da Silva F Blanes W Kalitzin SN Parra J Suffczynski P Velis DN 2003 Epilepsies as dynamical diseases of brain systems basic models of the transition between normal and epileptic activity Epilepsia 44 Suppl 12 Suppl 12 72 83 doi 10 1111 j 0013 9580 2003 12005 x PMID 14641563 S2CID 10071296 D C Henshall H M Hamer R J Pasterkamp D B Goldstein J Kjems J H M Prehn S Schorge K Lamottke and F Rosenow MicroRNAs in Epilepsy Pathophysiology and Clinical Utility The Lancet Neurology Volume 15 Issue 13 2016 1368 1376 https doi org 10 1016 S1474 4422 16 30246 0 Oby E Janigro D November 2006 The blood brain barrier and epilepsy Epilepsia 47 11 1761 74 doi 10 1111 j 1528 1167 2006 00817 x PMID 17116015 S2CID 15074513 Somjen GG 2004 Ions in the Brain Normal Function Seizures and Stroke New York Oxford University Press p 167 ISBN 978 0 19 803459 9 a b Engel J Pedley TA eds 2008 Epilepsy a comprehensive textbook 2nd ed Philadelphia Wolters Kluwer Health Lippincott Williams amp Wilkins p 483 ISBN 978 0 7817 5777 5 Depannemaecker Damien Ivanov Anton Lillo Davide Spek Len Bernard Christophe Jirsa Viktor 17 February 2021 A unified physiological framework of transitions between seizures sustained ictal activity and depolarization block at the single neuron level bioRxiv 2020 10 23 352021 doi 10 1101 2020 10 23 352021 S2CID 225962412 a href Template Cite journal html title Template Cite journal cite journal a Cite journal requires journal help Depannemaecker Damien Destexhe Alain Jirsa Viktor Bernard Christophe August 2021 Modeling seizures From single neurons to networks Seizure 90 4 8 doi 10 1016 j seizure 2021 06 015 ISSN 1059 1311 PMID 34219016 S2CID 235468072 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 Fisher R van Emde Boas W Blume W Elger C Genton P Lee P Engel J 2005 Epileptic seizures and epilepsy definitions proposed by the International League Against Epilepsy ILAE and the International Bureau for Epilepsy IBE Epilepsia 46 4 470 2 doi 10 1111 j 0013 9580 2005 66104 x PMID 15816939 Panayiotopoulos CP December 2011 The new ILAE report on terminology and concepts for organization of epileptic seizures a clinician s critical view and contribution Epilepsia 52 12 2155 60 doi 10 1111 j 1528 1167 2011 03288 x PMID 22004554 Proposal for revised classification of epilepsies and epileptic syndromes Commission on Classification and Terminology of the International League Against Epilepsy Epilepsia 30 4 389 99 1989 doi 10 1111 j 1528 1157 1989 tb05316 x PMID 2502382 S2CID 3483250 Engel J August 2006 ILAE classification of epilepsy syndromes Epilepsy Research 70 Suppl 1 Suppl 1 S5 10 doi 10 1016 j eplepsyres 2005 11 014 PMID 16822650 S2CID 10663593 Berg AT Berkovic SF Brodie MJ Buchhalter J Cross JH van Emde Boas W Engel J French J Glauser TA Mathern GW Moshe SL Nordli D Plouin P Scheffer IE April 2010 Revised terminology and concepts for organization of seizures and epilepsies report of the ILAE Commission on Classification and Terminology 2005 2009 Epilepsia 51 4 676 85 doi 10 1111 j 1528 1167 2010 02522 x PMID 20196795 a b c d e f g Shorvon SD June 2011 The etiologic classification of epilepsy Epilepsia 52 6 1052 7 doi 10 1111 j 1528 1167 2011 03041 x PMID 21449936 Operational Classification of Seizure Types 2017 a href Template Cite web html title Template Cite web cite web a CS1 maint url status link a b c d e f Fisher RS Cross JH French JA Higurashi N Hirsch E Jansen FE Lagae L Moshe SL Peltola J Roulet Perez E Scheffer IE Zuberi SM April 2017 Operational classification of seizure types by the International League Against Epilepsy Position Paper of the ILAE Commission for Classification and Terminology Epilepsia 58 4 522 530 doi 10 1111 epi 13670 hdl 11343 292620 PMID 28276060 S2CID 21037500 Epilepsy syndromes International league against epilepsy Archived from the original on 6 October 2014 Retrieved 6 October 2014 Wirrell E Tinuper P Perucca E Moshe SL June 2022 Introduction to the epilepsy syndrome papers Epilepsia 63 6 1330 1332 doi 10 1111 epi 17262 PMID 35503711 S2CID 248503717 Asadi Pooya Ali A 2018 Lennox Gastaut syndrome a comprehensive review Neurological Sciences 39 3 403 414 doi 10 1007 s10072 017 3188 y PMID 29124439 S2CID 4243468 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint url status link Chemaly Nicole Nabbout Rima Dravet Syndrome a href Template Cite web html title Template Cite web cite web a CS1 maint url status link Chipaux Mathilde West syndrome a href Template Cite web html title Template Cite web cite web a CS1 maint url status link Nordli DR October 2012 Epileptic encephalopathies in infants and children Journal of Clinical Neurophysiology 29 5 420 4 doi 10 1097 WNP 0b013e31826bd961 PMID 23027099 S2CID 41884825 Heinzen EL Depondt C Cavalleri GL Ruzzo EK Walley NM Need AC et al August 2012 Exome sequencing followed by large scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy American Journal of Human Genetics 91 2 293 302 doi 10 1016 j ajhg 2012 06 016 PMC 3415540 PMID 22863189 Carvill GL Heavin SB Yendle SC McMahon JM O Roak BJ Cook J et al July 2013 Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 Nature Genetics 45 7 825 30 doi 10 1038 ng 2646 PMC 3704157 PMID 23708187 Chenier S Yoon G Argiropoulos B Lauzon J Laframboise R Ahn JW et al 2014 CHD2 haploinsufficiency is associated with developmental delay intellectual disability epilepsy and neurobehavioural problems Journal of Neurodevelopmental Disorders 6 1 9 doi 10 1186 1866 1955 6 9 PMC 4022362 PMID 24834135 Suls A Jaehn JA Kecskes A Weber Y Weckhuysen S Craiu DC et al November 2013 De novo loss of function mutations in CHD2 cause a fever sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome American Journal of Human Genetics 93 5 967 75 doi 10 1016 j ajhg 2013 09 017 PMC 3824114 PMID 24207121 EuroEPINOMICS RES Consortium October 2014 De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies American Journal of Human Genetics 95 4 360 70 doi 10 1016 j ajhg 2014 08 013 PMC 4185114 PMID 25262651 a b 1 Guidance Epilepsies Diagnosis and management Guidance NICE a href Template Cite web html title Template Cite web cite web a CS1 maint url status link a b American Epilepsy Society Choosing Wisely www choosingwisely org 14 August 2018 Retrieved 30 August 2018 Wallace SJ Farrell K eds 2004 Epilepsy in children 2nd ed London Arnold p 354 ISBN 978 0 340 80814 6 Chen Wei Liang Mefford Heather C July 2021 Diagnostic Considerations in the Epilepsies Testing Strategies Test Type Advantages and Limitations Neurotherapeutics 18 3 1468 1477 doi 10 1007 s13311 021 01121 7 ISSN 1878 7479 PMC 8608977 PMID 34532824 Aledo Serrano Angel Sanchez Alcudia Rocio Toledano Rafael Garcia Morales Irene Beltran Corbellini Alvaro del Pino Isabel Gil Nagel Antonio 2021 Developmental and epileptic encephalopathies after negative or inconclusive genetic testing what is next Journal of Translational Genetics and Genomics 5 4 443 455 doi 10 20517 jtgg 2021 40 S2CID 244944239 Luef G October 2010 Hormonal alterations following seizures Epilepsy amp Behavior 19 2 131 3 doi 10 1016 j yebeh 2010 06 026 PMID 20696621 S2CID 945952 a b Ahmad S Beckett MW 2004 Value of serum prolactin in the management of syncope Emergency Medicine Journal 21 2 3e 3 doi 10 1136 emj 2003 008870 PMC 1726305 PMID 14988379 Shukla G Bhatia M Vivekanandhan S et al 2004 Serum prolactin levels for differentiation of nonepileptic versus true seizures limited utility Epilepsy amp Behavior 5 4 517 21 doi 10 1016 j yebeh 2004 03 004 PMID 15256189 S2CID 2381873 Chen DK So YT Fisher RS 2005 Use of serum prolactin in diagnosing epileptic seizures report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 65 5 668 75 doi 10 1212 01 wnl 0000178391 96957 d0 PMID 16157897 Brodtkorb E 2013 Common imitators of epilepsy Acta Neurologica Scandinavica Supplementum 127 196 5 10 doi 10 1111 ane 12043 PMID 23190285 S2CID 1373740 a b c d Marx JA ed 2010 Rosen s emergency medicine concepts and clinical practice 7th ed Philadelphia Mosby Elsevier p 2228 ISBN 978 0 323 05472 0 a b Zaidi A Clough P Cooper P Scheepers B Fitzpatrick AP July 2000 Misdiagnosis of epilepsy many seizure like attacks have a cardiovascular cause Journal of the American College of Cardiology 36 1 181 4 doi 10 1016 S0735 1097 00 00700 2 PMID 10898432 Bisulli F Vignatelli L Provini F Leta C Lugaresi E Tinuper P December 2011 Parasomnias and nocturnal frontal lobe epilepsy NFLE lights and shadows controversial points in the differential diagnosis Sleep Medicine 12 Suppl 2 Suppl2 S27 32 doi 10 1016 j sleep 2011 10 008 PMID 22136895 Zhou JQ Zhou LM Fang ZY Wang Q Chen ZY Yang LB Chen SD Cai XD January 2011 Analyzing clinical and electrophysiological characteristics of Paroxysmal Dyskinesia Journal of Research in Medical Sciences 16 1 110 4 PMC 3063430 PMID 21448393 Akhtar MJ March 2002 All seizures are not epilepsy many have a cardiovascular cause The Journal of the Pakistan Medical Association 52 3 116 20 PMID 12071066 a b Jerome E 2013 Seizures and epilepsy 2nd ed New York Oxford University Press p 462 ISBN 9780195328547 Epilepsy Symptoms and causes Mayo Clinic Retrieved 1 April 2022 Epilepsy MedlinePlus Medical Encyclopedia medlineplus gov Retrieved 1 April 2022 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 March 2017 Self management in epilepsy Why and how you should incorporate self management in your practice Epilepsy amp Behavior 68 220 224 doi 10 1016 j yebeh 2016 11 015 PMC 5381244 PMID 28202408 a b c d Michael GE O Connor RE February 2011 The diagnosis and management of seizures and status epilepticus in the prehospital setting Emergency Medicine Clinics of North America 29 1 29 39 doi 10 1016 j emc 2010 08 003 PMID 21109100 Wheless JW Willmore J Brumback RA 2009 Advanced therapy in epilepsy Shelton Conn People s Medical Pub House p 144 ISBN 9781607950042 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 Wyllie E 2012 Wyllie s Treatment of Epilepsy Principles and Practice Lippincott Williams amp Wilkins p 187 ISBN 978 1 4511 5348 4 Flanagan SR Zaretsky H Moroz A eds 2010 Medical aspects of disability a handbook for the rehabilitation professional 4th ed New York Springer p 182 ISBN 978 0 8261 2784 6 Nevitt SJ Marson AG Tudur Smith C 18 July 2019 Carbamazepine versus phenytoin monotherapy for epilepsy an individual participant data review The Cochrane Database of Systematic Reviews 2019 7 CD001911 doi 10 1002 14651858 CD001911 pub4 PMC 6637502 PMID 31318037 Nevitt SJ Marson AG Weston J Tudur Smith C 9 August 2018 Sodium valproate versus phenytoin monotherapy for epilepsy an individual participant data review The Cochrane Database of Systematic Reviews 2018 8 CD001769 doi 10 1002 14651858 CD001769 pub4 PMC 6513104 PMID 30091458 Powell G Saunders M Rigby A Marson AG December 2016 Immediate release versus controlled release carbamazepine in the treatment of epilepsy The Cochrane Database of Systematic Reviews 12 4 CD007124 doi 10 1002 14651858 CD007124 pub5 PMC 6463840 PMID 27933615 Mishra Priya Mittal Amit Kumar Rajput Satyendra Kumar Sinha Jitendra Kumar 1 March 2021 Cognition and memory impairment attenuation via reduction of oxidative stress in acute and chronic mice models of epilepsy using antiepileptogenic Nux vomica Journal of Ethnopharmacology 267 113509 doi 10 1016 j jep 2020 113509 ISSN 1872 7573 PMID 33141053 S2CID 226241066 Mishra Priya Sinha Jitendra Kumar Rajput Satyendra Kumar February 2021 Efficacy of Cicuta virosa medicinal preparations against pentylenetetrazole induced seizures Epilepsy amp Behavior 115 107653 doi 10 1016 j yebeh 2020 107653 ISSN 1525 5069 PMID 33358679 S2CID 229372930 Nevitt Sarah J Sudell Maria Cividini Sofia Marson Anthony G Tudur Smith Catrin 1 April 2022 Antiepileptic drug monotherapy for epilepsy a network meta analysis of individual participant data The Cochrane Database of Systematic Reviews 2022 4 CD011412 doi 10 1002 14651858 CD011412 pub4 ISSN 1469 493X PMC 8974892 PMID 35363878 Ilangaratne NB Mannakkara NN Bell GS Sander JW December 2012 Phenobarbital missing in action Bulletin of the World Health Organization 90 12 871 871A doi 10 2471 BLT 12 113183 PMC 3524964 PMID 23284189 Shorvon S Perucca E Engel J Jr eds 2009 The treatment of epilepsy 3rd ed Chichester UK Wiley Blackwell p 587 ISBN 9781444316674 Archived from the original on 21 May 2016 a b c d e f Perucca P Gilliam FG September 2012 Adverse effects of antiepileptic drugs The Lancet Neurology 11 9 792 802 doi 10 1016 S1474 4422 12 70153 9 PMID 22832500 S2CID 25540685 a b Weston J Bromley R Jackson CF Adab N Clayton Smith J Greenhalgh J Hounsome J McKay AJ Tudur Smith C Marson AG November 2016 Monotherapy treatment of epilepsy in pregnancy congenital malformation outcomes in the child The Cochrane Database of Systematic Reviews 11 11 CD010224 doi 10 1002 14651858 CD010224 pub2 PMC 6465055 PMID 27819746 a b Kamyar M Varner M June 2013 Epilepsy in pregnancy Clinical Obstetrics and Gynecology 56 2 330 41 doi 10 1097 GRF 0b013e31828f2436 PMID 23563876 S2CID 20150531 Lawrence S Neinstein ed 2008 Adolescent health care a practical guide 5th ed Philadelphia Lippincott Williams amp Wilkins p 335 ISBN 978 0 7817 9256 1 a b Brodie MJ Elder AT Kwan P November 2009 Epilepsy in later life The Lancet Neurology 8 11 1019 30 doi 10 1016 S1474 4422 09 70240 6 PMID 19800848 S2CID 14318073 a b Krucoff MO Chan AY Harward SC Rahimpour S Rolston JD Muh C Englot DJ December 2017 Rates and predictors of success and failure in repeat epilepsy surgery A meta analysis and systematic review Epilepsia 58 12 2133 2142 doi 10 1111 epi 13920 PMC 5716856 PMID 28994113 Benoit PW Yagiela A Fort NF February 1980 Pharmacologic correlation between local anesthetic induced myotoxicity and disturbances of intracellular calcium distribution Toxicology and Applied Pharmacology 52 2 187 98 doi 10 1016 0041 008x 80 90105 2 PMID 7361318 a b c d e Duncan JS April 2007 Epilepsy surgery Clinical Medicine 7 2 137 42 doi 10 7861 clinmedicine 7 2 137 PMC 4951827 PMID 17491501 Birbeck GL Hays RD Cui X Vickrey BG May 2002 Seizure reduction and quality of life improvements in people with epilepsy Epilepsia 43 5 535 8 doi 10 1046 j 1528 1157 2002 32201 x PMID 12027916 S2CID 23577753 Edwards CA Kouzani A Lee KH Ross EK September 2017 Neurostimulation Devices for the Treatment of Neurologic Disorders Mayo Clinic Proceedings 92 9 1427 1444 doi 10 1016 j mayocp 2017 05 005 PMID 28870357 a b c d e f Panebianco M Rigby A Marson AG 14 July 2022 Vagus nerve stimulation for focal seizures The Cochrane Database of Systematic Reviews 2022 7 CD002896 doi 10 1002 14651858 CD002896 pub3 PMC 9281624 PMID 35833911 Maria BL ed 2009 Current management in child neurology 4th ed Hamilton Ont BC Decker p 180 ISBN 978 1 60795 000 4 Archived from the original on 24 June 2016 Verrotti A Tocco AM Salladini C Latini G Chiarelli F November 2005 Human photosensitivity from pathophysiology to treatment European Journal of Neurology 12 11 828 41 doi 10 1111 j 1468 1331 2005 01085 x PMID 16241971 S2CID 23001888 Tan G Thornby J Hammond DC Strehl U Canady B Arnemann K Kaiser DA July 2009 Meta analysis of EEG biofeedback in treating epilepsy Clinical EEG and Neuroscience 40 3 173 9 doi 10 1177 155005940904000310 PMID 19715180 S2CID 16682327 Arida RM Scorza FA Scorza CA Cavalheiro EA March 2009 Is physical activity beneficial for recovery in temporal lobe epilepsy Evidences from animal studies Neuroscience and Biobehavioral Reviews 33 3 422 31 doi 10 1016 j neubiorev 2008 11 002 PMID 19059282 S2CID 30918370 Arida RM Cavalheiro EA da Silva AC Scorza FA 2008 Physical activity and epilepsy proven and predicted benefits Sports Medicine 38 7 607 15 doi 10 2165 00007256 200838070 00006 PMID 18557661 S2CID 24048241 Di Vito L Naldi I Mostacci B Licchetta L Bisulli F Tinuper P June 2010 A seizure response dog video recording of reacting behaviour during repetitive prolonged seizures Epileptic Disorders 12 2 142 5 doi 10 1684 epd 2010 0313 PMID 20472528 S2CID 3337471 Archived from the original on 6 October 2014 Kirton A Winter A Wirrell E Snead OC October 2008 Seizure response dogs evaluation of a formal training program Epilepsy amp Behavior 13 3 499 504 doi 10 1016 j yebeh 2008 05 011 PMID 18595778 S2CID 27549519 Doherty MJ Haltiner AM January 2007 Wag the dog skepticism on seizure alert canines Neurology 68 4 309 CiteSeerX 10 1 1 1003 1543 doi 10 1212 01 wnl 0000252369 82956 a3 PMID 17242343 S2CID 33328776 a b c Michaelis R Tang V Wagner JL Modi AC LaFrance Jr WC Goldstein LH Lundgren T Reuber M October 2017 Psychological treatments for people with epilepsy Cochrane Database of Systematic Reviews 10 10 CD012081 doi 10 1002 14651858 CD012081 pub2 PMC 6485515 PMID 29078005 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint uses authors parameter link Stockings E Zagic D Campbell G Weier M Hall WD Nielsen S Herkes GK Farrell M Degenhardt L July 2018 Evidence for cannabis and cannabinoids for epilepsy a systematic review of controlled and observational evidence Journal of Neurology Neurosurgery and Psychiatry 89 7 741 753 doi 10 1136 jnnp 2017 317168 PMID 29511052 Cannabis derivative may reduce seizures in some severe drug resistant epilepsies but adverse events increase NIHR Evidence Plain English summary 26 June 2018 doi 10 3310 signal 000606 S2CID 242083755 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 Archive of Journal of Investigative Medicine High Impact Case Reports PMC www ncbi nlm nih gov a b c d Tomson T Battino D Bromley R Kochen S Meador K Pennell P Thomas SV 1 December 2019 Management of epilepsy in pregnancy a report from the International League Against Epilepsy Task Force on Women and Pregnancy Epileptic Disorders 21 6 497 517 doi 10 1684 epd 2019 1105 inactive 1 March 2023 PMID 31782407 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint DOI inactive as of March 2023 link Cheuk DK Wong V May 2014 Acupuncture for epilepsy The Cochrane Database of Systematic Reviews 2014 5 CD005062 doi 10 1002 14651858 CD005062 pub4 PMC 10105317 PMID 24801225 Ranganathan LN Ramaratnam S April 2005 Vitamins for epilepsy The Cochrane Database of Systematic Reviews 2 CD004304 doi 10 1002 14651858 CD004304 pub2 PMID 15846704 Panebianco M Sridharan K Ramaratnam S October 2017 Yoga for epilepsy The Cochrane Database of Systematic Reviews 10 10 CD001524 doi 10 1002 14651858 CD001524 pub3 PMC 6485327 PMID 28982217 a b Brigo F Igwe SC Del Felice A August 2016 Melatonin as add on treatment for epilepsy The Cochrane Database of Systematic Reviews 2016 8 CD006967 doi 10 1002 14651858 CD006967 pub4 PMC 7386917 PMID 27513702 He Li Ying Hu Mei Bian Li Ruo Lan Zhao Rong Fan Lin Hong He Lin Lu Feng Ye Xun Huang Yong Liang Wu Chun Jie 2021 Natural Medicines for the Treatment of Epilepsy Bioactive Components Pharmacology and Mechanism Frontiers in Pharmacology 12 604040 doi 10 3389 fphar 2021 604040 PMC 7969896 PMID 33746751 Aguiar C C Almeida A B Araujo P V De Abreu R N Chaves E M Do Vale O C MacEdo D S Woods D J Fonteles M M Vasconcelos S M 2012 Oxidative Stress and Epilepsy Literature Review Oxidative Medicine and Cellular Longevity 2012 795259 doi 10 1155 2012 795259 PMC 3403512 PMID 22848783 a b Kwan P 2012 Fast facts epilepsy 5th ed Abingdon Oxford UK Health Press p 10 ISBN 978 1 908541 12 3 a b c Hitiris N Mohanraj R Norrie J Brodie MJ May 2007 Mortality in epilepsy Epilepsy amp Behavior 10 3 363 76 doi 10 1016 j yebeh 2007 01 005 PMID 17337248 S2CID 39107474 a b c Shorvon S Perucca E Engel J eds 2009 The treatment of epilepsy 3rd ed Chichester UK Wiley Blackwell p 28 ISBN 978 1 4443 1667 4 Archived from the original on 10 June 2016 a b Bagary M April 2011 Epilepsy antiepileptic drugs and suicidality Current Opinion in Neurology 24 2 177 82 doi 10 1097 WCO 0b013e328344533e PMID 21293270 Mula M Sander JW August 2013 Suicide risk in people with epilepsy taking antiepileptic drugs Bipolar Disorders 15 5 622 7 doi 10 1111 bdi 12091 PMID 23755740 S2CID 40681400 a b Ryvlin P Nashef L Tomson T May 2013 Prevention of sudden unexpected death in epilepsy a realistic goal Epilepsia 54 Suppl 2 23 8 doi 10 1111 epi 12180 PMID 23646967 Klovgaard M Sabers A Ryvlin P November 2022 Update on Sudden Unexpected Death in Epilepsy Neurologic Clinics 40 4 741 754 doi 10 1016 j ncl 2022 06 001 PMID 36270688 S2CID 252617763 Hirtz D Thurman DJ Gwinn Hardy K Mohamed M Chaudhuri AR Zalutsky R January 2007 How common are the common neurologic disorders Neurology 68 5 326 37 doi 10 1212 01 wnl 0000252807 38124 a3 PMID 17261678 S2CID 208246679 Espinosa Jovel Camilo Toledano Rafael Aledo Serrano Angel Garcia Morales Irene Gil Nagel Antonio 1 March 2018 Epidemiological profile of epilepsy in low income populations Seizure European Journal of Epilepsy 56 67 72 doi 10 1016 j seizure 2018 02 002 ISSN 1059 1311 PMID 29453113 a b Sander JW April 2003 The epidemiology of epilepsy revisited Current Opinion in Neurology 16 2 165 70 doi 10 1097 00019052 200304000 00008 PMID 12644744 a b c d e f g h Saraceno B Avanzini G Lee P eds 2005 Atlas Epilepsy Care in the World PDF World Health Organization ISBN 978 92 4 156303 1 Retrieved 20 December 2013 Eadie MJ Bladin PF 2001 A Disease Once Sacred A History of the Medical Understanding of Epilepsy John Libbey Eurotext ISBN 978 0 86196 607 3 Epilepsy An historical overview World Health Organization February 2001 Archived from the original on 30 October 2013 Retrieved 27 December 2013 Epilepsy historical overview World Health Organization Archived from the original on 20 January 2011 Retrieved 20 March 2011 a b Temkin O 1 March 1994 The Falling Sickness A History of Epilepsy from the Greeks to the Beginnings of Modern Neurology JHU Press p Section 1 ISBN 9781421400532 Stol M 1993 Epilepsy in Babylonia BRILL p 143 ISBN 978 9072371638 Harding GF Jeavons PM 1994 Photosensitive Epilepsy Cambridge University Press p 2 ISBN 9781898683025 a b Jilek Aall L March 1999 Morbus sacer in Africa some religious aspects of epilepsy in traditional cultures Epilepsia 40 3 382 6 doi 10 1111 j 1528 1157 1999 tb00723 x PMID 10080524 Epilepsy and its Management A Review ResearchGate January 2012 Retrieved 22 February 2022 Illes J 2011 Encyclopedia of Mystics Saints amp Sages HarperCollins p 1238 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 a b c Lewis Ellis 17 February 2012 Report of The Trial and Conviction of John Haggerty for The Murder of Melchoir Fordney Late of The City of Lancaster Pennsylvania Gale Making of Modern Law p 62 ISBN 9781275311367 Caravati EM 2004 Medical toxicology 3rd ed Philadelphia u a Lippincott Williams amp Wilkins p 789 ISBN 978 0 7817 2845 4 a b de Boer HM December 2010 Epilepsy stigma moving from a global problem to global solutions Seizure 19 10 630 6 doi 10 1016 j seizure 2010 10 017 PMID 21075013 S2CID 17282975 Martindale JL Goldstein JN Pallin DJ February 2011 Emergency department seizure epidemiology Emergency Medicine Clinics of North America 29 1 15 27 doi 10 1016 j emc 2010 08 002 PMID 21109099 span, wikipedia, wiki, book, books, library,

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