| Epilepsy | |
|---|---|
| Other names: Seizure disorder | |
 | |
| Generalized 3 Hzspike-and-wave discharges on anelectroencephalogram | |
 | |
| Specialty | Neurology |
| Symptoms | Periods of vigorous shaking, nearly undetectable spells[1] |
| Duration | Long term[2] |
| Causes | Unknown,brain injury,stroke,brain tumors, infections of the brain,birth defects[2][3][4] |
| Diagnostic method | Electroencephalogram, ruling out other possible causes[5] |
| Differential diagnosis | Fainting,alcohol withdrawal,electrolyte problems[5] |
| Treatment | Medication,surgery,neurostimulation, dietary changes[6][7] |
| Prognosis | Controllable in 70%[8] |
| Frequency | 50 million (2022)[1] |
| Deaths | 125,000 (2015)[9] |
Epilepsy is a group ofneurological disorders characterized by recurrentepileptic seizures.[10] Epileptic seizures are episodes that can vary from brief and nearly undetectable periods to long periods of vigorous shaking.[1] These episodes can result in physical injuries, including occasionallybroken bones.[2] In epilepsy, seizures have a tendency to recur and, as a rule, have no immediate underlying cause.[11] Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy.[12] People with epilepsy may be treated differently in various areas of the world and experience varying degrees ofsocial stigma due to their condition.[2]
The underlying mechanism of epileptic seizures is excessive and abnormalneuronal activity in thecortex of the brain.[12] The reason this occurs in most cases of epilepsy is unknown.[2] Some cases occur as the result ofbrain injury,stroke,brain tumors, infections of the brain, orbirth defects through a process known asepileptogenesis.[2][3][4] Knowngenetic mutations are directly linked to a small proportion of cases.[5][13] The diagnosis involves ruling out other conditions that might cause similar symptoms, such asfainting, and determining if another cause of seizures is present, such asalcohol withdrawal orelectrolyte problems.[5] This may be partly done byimaging the brain and performingblood tests.[5] Epilepsy can often be confirmed with anelectroencephalogram (EEG), but a normal test does not rule out the condition.[5]
Epilepsy that occurs as a result of other issues may be preventable.[2] Seizures are controllable with medication in about 70% of cases;[8] inexpensive anti-seizure medications are often available.[2] In those whose seizures do not respond to medication,surgery,neurostimulation or dietary changes may then be considered.[6][7] Not all cases of epilepsy are lifelong, and many people improve to the point that treatment is no longer needed.[2]
As of 2022[update], about 50 million people have epilepsy (0.5-1% of the population).[14][1] Around 70% of cases occur in thedeveloping 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 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] and the chance of experiencing a second seizure is 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 wordepilepsy is fromAncient Greek ἐπιλαμβάνειν, 'to seize, possess, or afflict'.[23]
Epilepsy is characterized by a long-term risk of recurrentseizures.[24] These seizures may present in several ways depending on the part of the brain involved and the person's age.[24][25]
The most common type (60%) of seizures areconvulsive.[25] Of these, one-third begin asgeneralized seizures from the start, affecting both hemispheres of the brain.[25] Two-thirds begin asfocal seizures (which affect one hemisphere of the brain) which may then progress togeneralized seizures.[25] The remaining 40% of seizures are non-convulsive. An example of this type is theabsence seizure, which presents as a decreased level of consciousness and usually lasts about 10 seconds.[3][26]
Focal seizures are often preceded by certain experiences, known asauras.[27] They include sensory (visual, hearing, or smell), psychic, autonomic, and motor phenomena.[3] Jerking activity may start in a specific muscle group and spread to surrounding muscle groups in which case it is known as aJacksonian march.[28]Automatisms may occur, which are non-consciously-generated activities and mostly simple repetitive movements like smacking of 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 andatonic seizures.[29] They all involve loss ofconsciousness and typically happen without warning.
Tonic-clonic seizures occur with a contraction of the limbs followed by their extension along with 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] The tongue may be bitten at either the tip or on the sides during a seizure.[31] Intonic-clonic seizure, bites to the sides are more common.[31] Tongue bites are also relatively common inpsychogenic non-epileptic seizures.[31]
Myoclonic seizures involve spasms of muscles in either a few areas or all over.[32] Absence seizures can be subtle with only a slight turn of the head or eye blinking.[3] The person does not fall over and returns to normal right after it ends.[3] Atonic seizures involve the loss of muscle activity for greater than one second.[28] This typically occurs on both sides of the body.[28]
About 6% of those with epilepsy have seizures that are often triggered by specific events and are known asreflex seizures.[33] Those withreflex epilepsy have seizures that are only triggered by specific stimuli.[34] Common triggers include flashing lights and sudden noises.[33] In certain types of epilepsy, seizures happen more often duringsleep,[35] and in other types they occur almost only when sleeping.[36]
After the active portion of a seizure (theictal state) there is typically a period of recovery during which there is confusion, referred to as thepostictal period before a normallevel of consciousness returns.[27] It usually lasts 3 to 15 minutes[37] but may last for hours.[38] Other common symptoms include feeling tired,headache, difficulty speaking, and abnormal behavior.[38]Psychosis after a seizure is relatively common, occurring in 6–10% of people.[39] Often people do not remember what happened during this time.[38] Localized weakness, known asTodd's paralysis, may also occur after a focal seizure. When it occurs it typically lasts for seconds to minutes but may rarely last for a day or two.[40]
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 amongchildren 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 includedepression,anxiety,obsessive–compulsive disorder (OCD),[41] andmigraine.[42]Attention deficit hyperactivity disorder affects three to five times more children with epilepsy than children without the condition.[43] ADHD and epilepsy have significant consequences on a child's behavioral, learning, and social development.[44] Epilepsy is also more common in children withautism.[45]
Epilepsy can have both genetic and acquired causes, with interaction of these factors in many cases.[46] Established acquired causes include serious brain trauma, stroke, tumours and problems in the brain as a result of a previousinfection.[46] In about 60% of cases the cause is unknown.[25][30] Epilepsies caused bygenetic,congenital, ordevelopmental conditions are more common among younger people, whilebrain tumors andstrokes 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 asacute symptomatic seizures and are in the broader classification ofseizure-related disorders rather than epilepsy itself.[47][48]
Genetics is believed to be involved in the majority of cases, either directly or indirectly.[13] Some epilepsies are due to a single gene defect (1–2%); most are due to the interaction of multiple genes and environmental factors.[13] Each of the single gene defects is rare, with more than 200 in all described.[49] Most genes involved affection channels, either directly or indirectly.[46] These include genes forion channels themselves,enzymes,GABA, andG protein-coupled receptors.[32]
Inidentical twins, if one is affected there is a 50–60% chance that the other will also be affected.[13] In non-identical twins the risk is 15%.[13] These risks are greater in those with generalized rather than focal seizures.[13] If both twins are affected, most of the time they have the same epileptic syndrome (70–90%).[13] Other close relatives of a person with epilepsy have a risk five times that of the general population.[50] Between 1 and 10% of those withDown syndrome and 90% of those withAngelman syndrome have epilepsy.[50]
Epilepsy may occur as a result of a number of other conditions including tumors,strokes, head trauma, previousinfections of the central nervous system, genetic abnormalities, and as a result of brain damage around the time of birth.[29][30] Of those with brain tumors, almost 30% have epilepsy, making them the cause of about 4% of cases.[50] The risk is greatest for tumors in thetemporal lobe and those that grow slowly.[50] Other mass lesions such ascerebral cavernous malformations andarteriovenous malformations have risks as high as 40–60%.[50] Of those who have had a stroke, 2–4% develop epilepsy.[50] In the United Kingdom strokes account for 15% of cases and it is believed to be the cause in 30% of the elderly.[25][50] Between 6 and 20% of epilepsy is believed to be due to head trauma.[50]Mild brain injury increases the risk about two-fold whilesevere brain injury increases the risk seven-fold.[50] In those who have experienced a high-powered gunshot wound to the head, the risk is about 50%.[50]
Some evidence links epilepsy andceliac disease andnon-celiac gluten sensitivity, while other evidence does not. There appears to be a specific syndrome which includes coeliac disease, epilepsy and calcifications in the brain.[51][52] 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.[52]
The risk of epilepsy followingmeningitis is less than 10%; that disease more commonly causes seizures during the infection itself.[50] Inherpes simplex encephalitis the risk of a seizure is around 50%[50] with a high risk of epilepsy following (up to 25%).[53][54] A form of an infection with thepork tapeworm (cysticercosis), in the brain, is known asneurocysticercosis, and is the cause of up to half of epilepsy cases in areas of the world where the parasite is common.[50] Epilepsy may also occur after other brain infections such ascerebral malaria,toxoplasmosis, andtoxocariasis.[50] Chronic alcohol use increases the risk of epilepsy: those who drink sixunits of alcohol per day have a 2.5-fold increase in risk.[50] Other risks includeAlzheimer's disease,multiple sclerosis,tuberous sclerosis, andautoimmune encephalitis.[50] Getting vaccinated does not increase the risk of epilepsy.[50]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 withcerebral palsy have an increased risk of epilepsy, with half of people withspastic quadriplegia andspastic hemiplegia having the disease.[55]
Normally brain electrical activity is non-synchronous, as neurons do not normally fire in sync with each other, but rather fire in order as signals travel throughout the brain.[3] Its activity is regulated by various factors both within theneuron and the cellular environment. Factors within the neuron include the type, number and distribution ofion channels, changes toreceptors and changes ofgene expression.[56] Factors around the neuron includeion concentrations,synaptic plasticity and regulation oftransmitter breakdown byglial cells.[56][57] Chronicinflammation also appears to play a role.[58]
The exact mechanism of epilepsy is unknown,[59] 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 excessivesynchronization.[60][61]
In epilepsy, the resistance of excitatory neurons to fire during this period is decreased.[3] This may occur due to changes inion channels or inhibitory neurons not functioning properly.[3] This then results in a specific area from which seizures may develop, known as a "seizure focus".[3] Another mechanism of epilepsy may be the up-regulation of excitatory circuits or down-regulation of inhibitory circuits following an injury to the brain.[3][4] These secondary epilepsies occur through processes known asepileptogenesis.[3][4] Failure of theblood–brain barrier may also be a causal mechanism as it would allow substances in the blood to enter the brain.[62]
There is evidence thatepileptic seizures are usually not a random event. Seizures are often brought on by factors such as stress, alcohol abuse, flickering light, or a lack of sleep, among others. The termseizure threshold is used to indicate the amount ofstimulus necessary to bring about a seizure. Seizure threshold is lowered in epilepsy.[60]
In epileptic seizures a group of neurons begin firing in an abnormal, excessive,[25] and synchronized manner.[3] This results in a wave of depolarization known as aparoxysmal depolarizing shift.[63] Normally, after anexcitatory neuron fires it becomes more resistant to firing for a period of time.[3] This is due in part to the effect of inhibitory neurons, electrical changes within the excitatory neuron, and the negative effects ofadenosine.[3]
Focal seizures begin in onehemisphere 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.[64]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.[64]
The diagnosis of epilepsy is typically made based on observation of the seizure onset and the underlying cause.[25] Anelectroencephalogram (EEG) to look for abnormal patterns of brain waves andneuroimaging (CT scan orMRI) to look at the structure of the brain are also usually part of the workup.[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.[65]
Epilepsy is a disorder of the brain defined by any of the following conditions:[66]
|
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.[66]
This 2014 definition of theInternational League Against Epilepsy[66] 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."[12][67]
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.[66]
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.[66]
In contrast to theclassification 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 thediagnostic workup results preferably in the seizure itself being classified (e.g. tonic-clonic) and in the underlying disease being identified (e.g.hippocampal sclerosis).[65] The name of the diagnosis finally made depends on the available diagnostic results and the applied definitions and classifications (of seizures and epilepsies) and its respective terminology.
TheInternational League Against Epilepsy (ILAE) provided a classification of the epilepsies andepileptic syndromes in 1989 as follows:[68]
|
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.[69] In 2010 the ILAE Commission for Classification of the Epilepsies addressed this issue and divided epilepsies into three categories (genetic, structural/metabolic, unknown cause)[70] that were refined in their 2011 recommendation into four categories and a number of subcategories reflecting recent technologic and scientific advances.[71]
|
Cases of epilepsy may be organized intoepilepsy 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 whatanti-seizure medication should be tried.[29][72]
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.[48] Less serious examples arebenign rolandic epilepsy (2.8 per 100,000),childhood absence epilepsy (0.8 per 100,000) andjuvenile myoclonic epilepsy (0.7 per 100,000).[48] Severe syndromes with diffuse brain dysfunction caused, at least partly, by some aspect of epilepsy, are also referred to as epileptic encephalopathies. These are associated with frequentseizures that are resistant to treatment and severe cognitive dysfunction, for instanceLennox–Gastaut syndrome andWest syndrome.[73] Genetics is believed to play an important role in epilepsies by a number of mechanisms. Simple and complex modes ofinheritance have been identified for some of them. However, extensive screening have failed to identify many singlegene variants of large effect.[74] 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, includingCHD2 andSYNGAP1[75][76][77] andDNM1,GABBR2,FASN andRYR3.[78]
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.[71] Theidiopathic (unknown cause) category of the 2011 classification includes syndromes in which the general clinical features and/or age specificity strongly point to a presumed genetic cause.[71] Some childhood epilepsy syndromes are included in the unknown cause category in which the cause is presumed genetic, for instancebenign rolandic epilepsy. Others are included insymptomatic despite a presumed genetic cause (in at least in some cases), for instanceLennox-Gastaut syndrome.[71] Clinical syndromes in which epilepsy is not the main feature (e.g.Angelman syndrome) were categorizedsymptomatic but it was argued to include these within the categoryidiopathic.[71] Classification of epilepsies and particularly of epilepsy syndromes will change with advances in research.
Anelectroencephalogram (EEG) can assist in showing brain activity suggestive of an increased risk of seizures. It is only recommended for those who are likely to have had an epileptic seizure on the basis of symptoms. In the diagnosis of epilepsy, electroencephalography may help distinguish the type of seizure or syndrome present. In children it is typically only needed after a second seizure. It cannot be used to rule out the diagnosis and may be falsely positive in those without the disease. In certain situations it may be useful to perform the EEG while the affected individual is sleeping or sleep deprived.[65]
Diagnostic imaging byCT scan andMRI is recommended after a first non-febrile seizure to detect structural problems in and around the brain.[65] 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.[65][79]
For adults, the testing of electrolyte,blood glucose and calcium levels is important to rule out problems with these as causes.[65] Anelectrocardiogram can rule out problems with the rhythm of the heart.[65] A lumbar puncture may be useful to diagnose acentral nervous system infection but is not routinely needed.[20] In children additional tests may be required such as urine biochemistry and blood testing looking formetabolic disorders.[65][80]
A high bloodprolactin level within the first 20 minutes following a seizure may be useful to help confirm an epileptic seizure as opposed topsychogenic non-epileptic seizure.[81][82] Serum prolactin level is less useful for detecting focal seizures.[83] If it is normal an epileptic seizure is still possible[82] and a serum prolactin does not separate epileptic seizures from syncope.[84] It is not recommended as a routine part of the diagnosis of epilepsy.[65]
Diagnosis of epilepsy can be difficult. A number of other conditions may present very similar signs and symptoms to seizures, includingsyncope,hyperventilation,migraines,narcolepsy,panic attacks andpsychogenic non-epileptic seizures (PNES).[85][86] In particular asyncope can be accompanied by a short episode of convulsions.[87]Nocturnal frontal lobe epilepsy, often misdiagnosed as nightmares, was considered to be aparasomnia but later identified to be an epilepsy syndrome.[88] Attacks of the movement disorderparoxysmal dyskinesia may be taken for epileptic seizures.[89] The cause of adrop attack can be, among many others, anatonic seizure.[86]
Children may have behaviors that are easily mistaken for epileptic seizures but are not. These includebreath-holding spells,bed wetting,night terrors,tics andshudder attacks.[86]Gastroesophageal reflux may cause arching of the back andtwisting of the head to the side in infants, which may be mistaken for tonic-clonic seizures.[86]
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.[87][90] Approximately 20% of the people seen at epilepsy clinics have PNES[20] and of those who have PNES about 10% also have epilepsy;[91] separating the two based on the seizure episode alone without further testing is often difficult.[91]
While many cases are not preventable, efforts to reduce head injuries, provide good care around the time of birth, and reduce environmental parasites such as thepork 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]
Epilepsy is usually treated with dailymedication once a second seizure has occurred,[25][65] while medication may be started after the first seizure in those at high risk for subsequent seizures.[65] Supporting people'sself management of their condition may be useful.[92] In drug-resistant cases differentmanagement options may be looked at including a special diet, the implantation of aneurostimulator, orneurosurgery.
Rolling a person with an active tonic-clonic seizure onto their side and into therecovery position helps prevent fluids from getting into the lungs.[93] Putting fingers, a bite block or tongue depressor in the mouth is not recommended as it might make the personvomit or result in the rescuer being bitten.[27][93] Efforts should be taken to prevent further self-injury.[27]Spinal precautions are generally not needed.[93]
If a seizure lasts longer than 5 minutes or if there are more than two seizures in an hour without a return to a normal level of consciousness between them, it is considered amedical emergency known asstatus epilepticus.[65][94] This may requiremedical help to keep the airway open and protected;[65] anasopharyngeal airway may be useful for this.[93] At home the recommended initial medication for seizure of a long duration ismidazolam placed in the mouth.[95]Diazepam may also be usedrectally.[95] In hospital, intravenouslorazepam is preferred.[65] If two doses ofbenzodiazepines are not effective, other medications such asphenytoin are recommended.[65] Convulsive status epilepticus that does not respond to initial treatment typically requires admission to theintensive care unit and treatment with stronger agents such asthiopentone orpropofol.[65]
The mainstay treatment of epilepsy isanticonvulsant medications, possibly for the person's entire life.[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.[95] A single medication is recommended initially;[96] if this is not effective, switching to a single other medication is recommended.[65] Two medications at once is recommended only if a single medication does not work.[65] 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%.[97] About 30% of people continue to have seizures despite anticonvulsant treatment.[8]
There are a number of medications available includingphenytoin,carbamazepine andvalproate. Evidence suggests that phenytoin, carbamazepine, and valproate may be equally effective in both focal and generalized seizures.[98][99]Controlled release carbamazepine appears to work as well as immediate release carbamazepine, and may have fewerside effects.[100] In the United Kingdom, carbamazepine orlamotrigine are recommended as first-line treatment for focal seizures, withlevetiracetam and valproate as second-line due to issues of cost and side effects.[65] Valproate is recommended first-line for generalized seizures with lamotrigine being second-line.[65] In those with absence seizures,ethosuximide or valproate are recommended; valproate is particularly effective in myoclonic seizures and tonic or atonic seizures.[65] If seizures are well-controlled on a particular treatment, it is not usually necessary to routinely check the medication levels in the blood.[65]
The least expensive anticonvulsant isphenobarbital at around US$5 a year.[19] TheWorld Health Organization gives it a first-line recommendation in the developing world and it is commonly used there.[101][102] Access however may be difficult as some countries label it as acontrolled drug.[19]
Adverse effects from medications are reported in 10 to 90% of people, depending on how and from whom the data is collected.[103] Most adverse effects are dose-related and mild.[103] Some examples include mood changes, sleepiness, or an unsteadiness in gait.[103] Certain medications have side effects that are not related to dose such as rashes, liver toxicity, orsuppression of the bone marrow.[103] Up to a quarter of people stop treatment due to adverse effects.[103] Some medications are associated withbirth defects when used in pregnancy.[65] Many of the common used medications, such as valproate, phenytoin, carbamazepine, phenobarbitol, and gabapentin have been reported to cause increased risk of birth defects,[104] especially when used during thefirst trimester.[105] 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.[105] Among the antiepileptic medications, levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects.[104]
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.[65][106] 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.[79]
Epilepsy surgery may be an option for people with focal seizures that remain a problem despite other treatments.[107][108] These other treatments include at least a trial of two or three medications.[109] The goal of surgery is total control of seizures[110] and this may be achieved in 60–70% of cases.[109] Common procedures include cutting out thehippocampus via an anterior temporal lobe resection, removal of tumors, and removing parts of theneocortex.[109] Some procedures such as acorpus callosotomy are attempted in an effort to decrease the number of seizures rather than cure the condition.[109] Following surgery, medications may be slowly withdrawn in many cases.[109][107]
Neurostimulation may be another option in those who are not candidates for surgery.[65] Three types have been used in those who do not respond to medications:vagus nerve stimulation,anterior thalamic stimulation, andclosed-loop responsive stimulation.[6][111][112]
There is promising evidence that aketogenic diet (high-fat,low-carbohydrate, adequate-protein) decreases the number of seizures and eliminate seizures in some; however, further research is necessary.[7] It is a reasonable option in those who have epilepsy that is not improved with medications and for whom surgery is not an option.[7] About 10% stay on the diet for a few years due to issues of effectiveness and tolerability.[7] Side effects include stomach and intestinal problems in 30%, and there are long-term concerns about heart disease.[7] Less radical diets are easier to tolerate and may be effective.[7] It is unclear why this diet works.[113] In people with coeliac disease or non-celiac gluten sensitivity and occipital calcifications, agluten-free diet may decrease the frequency of seizures.[52]
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.[114]Operant-based biofeedback based on the EEG waves has some support in those who do not respond to medications.[115] Psychological methods should not, however, be used to replace medications.[65]
Exercise has been proposed as possibly useful for preventing seizures,[116] with some data to support this claim.[117] Some dogs, commonly referred to asseizure dogs, may help during or after a seizure.[118][119] It is not clear if dogs have the ability to predict seizures before they occur.[120]
There is moderate-quality evidence supporting the use of psychological interventions along with other treatments in epilepsy.[121] This can improve quality of life, enhance emotional wellbeing, and reduce fatigue in adults and adolescents.[121] Psychological interventions may also improve seizure control for some individuals by promoting self-management and adherence.[121]
As an add-on therapy in those who are not well controlled with other medications,cannabidiol appears to be useful in some children.[122] In 2018 the FDA approved this product forLennox–Gastaut syndrome andDravet syndrome.[123]
Alternative medicine, includingacupuncture,[124] routinevitamins,[125] andyoga,[126] have no reliableevidence to support their use in epilepsy.Melatonin, as of 2016[update], is insufficiently supported by evidence.[127] The trials were of poor methodological quality and it was not possible to draw any definitive conclusions.[127]
Epilepsy cannot usually be cured, but medication can control seizures effectively in about 70% of cases.[8] 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.[6] 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.[128] 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]
People with epilepsy are at an increased risk of death.[129] This increase is between 1.6 and 4.1 fold greater than that of the general population.[130] The greatest increase in mortality from epilepsy is among the elderly.[130] Those with epilepsy due to an unknown cause have little increased risk.[130]
Mortality is often related to: the underlying cause of the seizures,status epilepticus,suicide,trauma, andsudden unexpected death in epilepsy (SUDEP).[129] Death from status epilepticus is primarily due to an underlying problem rather than missing doses of medications.[129] The risk of suicide is between 2 and 6 times higher in those with epilepsy;[131][132] the cause of this is unclear.[131] SUDEP appears to be partly related to the frequency of generalized tonic-clonic seizures[133] and accounts for about 15% of epilepsy-related deaths;[128] it is unclear how to decrease its risk.[133]
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]
Epilepsy is one of the most common serious neurological disorders[134] affecting about 50 million people as of 2022[update].[1] 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][48] Most of those with the disorder (80%) are in low income populations[135] or thedeveloping 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.[48][136] 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.[136] This has been attributed partly to better survival following strokes in the elderly.[48]
The oldest medical records show that epilepsy has been affecting people at least since the beginning of recorded history.[137] Throughoutancient history, the disease was thought to be a spiritual condition.[137] The world's oldest description of an epileptic seizure comes from a text inAkkadian (a language used in ancientMesopotamia) and was written around 2000 BC.[23] The person described in the text was diagnosed as being under the influence of a moon god, and underwent anexorcism.[23] Epileptic seizures are listed in theCode of Hammurabi (c. 1790 BC) as reason for which a purchased slave may be returned for a refund,[23] and theEdwin Smith Papyrus (c. 1700 BC) describes cases of individuals with epileptic convulsions.[23]
The oldest known detailed record of the disease itself is in theSakikku, aBabyloniancuneiform medical text from 1067–1046 BC.[137] This text gives signs and symptoms, details treatment and likely outcomes,[23] and describes many features of the different seizure types.[137] 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.[137] Around 900 BC,Punarvasu Atreya described epilepsy as loss of consciousness;[138] this definition was carried forward into theAyurvedic text ofCharaka Samhita (about 400 BC).[139]
Theancient 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 thesacred disease (ἠ ἱερὰ νόσος).[23][140] Epilepsy appears within Greek mythology: it is associated with the Moon goddessesSelene andArtemis, who afflicted those who upset them. The Greeks thought that important figures such asJulius Caesar andHercules had the disease.[23] The notable exception to this divine and spiritual view was that of the school ofHippocrates. In the fifth century BC, Hippocrates rejected the idea that the disease was caused by spirits. In his landmark workOn the Sacred Disease, he proposed that epilepsy was not divine in origin and instead was a medically treatable problem originating in the brain.[23][137] He accused those of attributing a sacred cause to the disease of spreading ignorance through a belief in superstitious magic.[23] Hippocrates proposed thatheredity 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 thesacred disease, he used the termgreat disease, giving rise to the modern termgrand 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.[137] Evil spirits continued to be blamed until at least the 17th century.[137]
InAncient Rome people did not eat or drink with the same pottery as that used by someone who was affected.[141] People of the time would spit on their chest believing that this would keep the problem from affecting them.[141] According toApuleius and other ancient physicians, in order to detect epilepsy, it was common to light a piece ofgagates, whose smoke would trigger the seizure.[142] Occasionally a spinningpotter's wheel was used, perhaps a reference tophotosensitive epilepsy.[143]
In most cultures, persons with epilepsy have been stigmatized, shunned, or even imprisoned. As late as in the second half of the 20th century, inTanzania and other parts of Africa epilepsy was associated with possession by evil spirits, witchcraft, or poisoning and was believed by many to be contagious.[144] In theSalpêtrière, the birthplace of modern neurology,Jean-Martin Charcot found people with epilepsy side by side with the mentally ill, those with chronicsyphilis, and the criminally insane.[citation needed] Inancient Rome, epilepsy was known as themorbus comitialis ('disease of the assembly hall') and was seen as a curse from the gods. In northern Italy, epilepsy was once traditionally known as Saint Valentine's malady.[145]
In the mid-1800s, the first effective anti-seizure medication,bromide, was introduced.[103] The first modern treatment,phenobarbital, was developed in 1912, with phenytoin coming into use in 1938.[146]
Stigma is commonly experienced, around the world, by those with epilepsy.[147] It can affect people economically, socially and culturally.[147] In India and China, epilepsy may be used as justification to deny marriage.[30] People in some areas still believe those with epilepsy to becursed.[19] In parts of Africa, such asTanzania andUganda, epilepsy is incorrectly claimed to be associated with possession by evil spirits, witchcraft, or poisoning and is believed by many to becontagious.[144][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.[48]
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.[148]
Those with epilepsy are at about twice the risk of being involved in amotor 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] In some places physicians are required by law to report if a person has had a seizure to the licensing body while in others the requirement is only that they encourage the person in question to report it themselves.[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 the physician 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.[149] The amount of time a person must be free from seizures before they can drive varies by country.[149] Many countries require one to three years without seizures.[149] In the United States the time needed without a seizure is determined by each state and is between three months and one year.[149]
Those with epilepsy or seizures are typically denied a pilot license.[150] 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.[151] Those with febrile seizures and drug related seizures may also be considered.[151] In the United States, theFederal Aviation Administration does not allow those with epilepsy to get a commercial pilot license.[152] 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.[153] In the United Kingdom, a fullnational private pilot license requires the same standards as a professional driver's license.[154] This requires a period of ten years without seizures while off medications.[155] Those who do not meet this requirement may acquire a restricted license if free from seizures for five years.[154]
There are organizations that provide support for people and families affected by epilepsy. TheOut of the Shadows campaign, a joint effort by the World Health Organization, theInternational League Against Epilepsy and theInternational Bureau for Epilepsy, provides help internationally.[30] In the United States, theEpilepsy 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.[156] The Epilepsy Foundation, some hospitals, and some individuals also run support groups in the United States.[157]
International Epilepsy Day (World Epilepsy Day) began in 2015 and occurs on the second Monday in February.[158][159]
Seizure prediction refers to attempts to forecast epileptic seizures based on the EEG before they occur.[160] As of 2011[update], no effective mechanism to predict seizures has been developed.[160]Kindling, where repeated exposures to events that could cause seizures eventually causes seizures more easily, has been used to createanimal models of epilepsy.[161]
Gene therapy is being studied in some types of epilepsy.[162] Medications that alter immune function, such asintravenous immunoglobulins, are poorly supported by evidence.[163] Noninvasivestereotactic radiosurgery is, as of 2012[update], being compared to standard surgery for certain types of epilepsy.[164]
Epilepsy occurs in a number of other animals including dogs and cats and is the most common brain disorder in dogs.[165] It is typically treated with anticonvulsants such as phenobarbital orbromide in dogs and phenobarbital in cats.[165]Imepitoin is also used in dogs.[166] While generalized seizures in horses are fairly easy to diagnose, it may be more difficult in non-generalized seizures and EEGs may be useful.[167]
{{cite journal}}:Unknown parameter|displayauthors= ignored (help){{cite journal}}:|author1= has generic name (help)CS1 maint: numeric names: authors list (link){{cite journal}}: CS1 maint: unflagged free DOI (link){{cite journal}}: CS1 maint: unflagged free DOI (link){{cite journal}}:Unknown parameter|authors= ignored (help)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.
{{cite book}}: CS1 maint: multiple names: authors list (link)| Classification | |
|---|---|
| External resources |