|Classification and external resources|
Generalized 3 Hz spike and wave discharges in EEG
Epilepsy is a group of long term neurological disorders characterized by seizures. These seizures are short spell which vary from being nearly undetectable (electrographic seizures) to vigorous shaking. Epileptic seizures are recurrent and unprovoked, although some definitions require only a single seizure coinciding with evidence of changes in the brain predisposing to further episodes of seizures. Some definitions may include seizures caused by brain trauma, stroke, brain cancer, and drug and alcohol misuse among others; however, these are more properly classified as seizure-related disorders.
Epileptic seizures are the result of excessive cortical nerve cells activity in the brain. The diagnosis can sometimes be confirmed with an electroencephalogram. It also typically includes ruling out other conditions that might cause similar symptoms such as syncope.
Epilepsy is controllable, but not cured, with medication in about 70% of cases. In those who do not get control surgery, neurostimulation or dietary changes may be considered. Not all epilepsy syndromes are lifelong – some forms are confined to particular stages of childhood.
About 1% or 65 million people worldwide have epilepsy, and nearly 80% of cases occurs in developing countries. Epilepsy becomes more common as people age. Onset of new cases occurs most frequently in infants and the elderly. About 5–10% of all people will have an unprovoked seizure by the age of 80, and the chance of experiencing a second seizure is between 40% and 50%.
- 1 Signs and symptoms
- 2 Causes
- 3 Mechanism
- 4 Diagnosis
- 5 Management
- 6 Prognosis
- 7 Epidemiology
- 8 History
- 9 Society and culture
- 10 Research
- 11 Other animals
- 12 References
- 13 External links
Signs and symptoms
Epilepsy is characterized by a long term risk of recurrent seizures. These seizures may present in several ways depending on the part of the brain involved and the person's age. The most common type of seizures are convulsive (60%). Two-thirds of these begin as focal seizures and become generalized while one third begin as generalized seizures. The remaining 40% of seizures are non-convulsive. An example of this is an absence seizure, which presents as a decreased level of consciousness and usually lasts about 20 seconds.
Epilepsy can have adverse effects on social and psychological well being. In particular, the physical, emotional, and social functioning of youths can be affected by uncontrolled seizures. This can be from social isolation, stigmatization, or disability that can result from the disease. It may result in lower educational achievements and worse employment opportunities. Learning difficulties are common, especially among children with epilepsy.
Certain disorders occur more often in people with epilepsy, and depend partly which specific epilepsy is syndrome present. These disorders include depression and anxiety disorders, migraine and other headaches, infertility and low sex drive. Attention-deficit/hyperactivity disorder (ADHD) affects three to five times more children with epilepsy than children in the general population. ADHD and epilepsy have significant consequences on a child's behavioral, learning, and social development. Epilepsy is prevalent in autism.
Epilepsy is not a single disease but a symptom that can result from a number of different disorders. By definition the seizures occurs spontaneously and without an immediate cause. They may be genetic, due to structural or metabolic problems, or of unknown cause. In the United Kingdom the most common cause is "unknown" (60%). Other common causes include strokes (15%) and brain tumors (6%). Epileptic seizures that occur right around a specific cause are in the broader classification of seizure-related disorders rather than epilepsy itself.
Genetic, congenital, and developmental conditions are mostly common among younger people, while tumors and strokes are more likely in older people. Head trauma resulting in post-traumatic epilepsy and central nervous system infections may occur at any age.
Certain epilepsy syndromes, known as reflex epilepsy, may require specific triggers for seizures to occur. For example, those with primary reading epilepsy have seizures triggered by reading. Those with photosensitive epilepsy can have seizures triggered by flashing lights. Other precipitants can trigger an epileptic seizure in patients who otherwise would be susceptible to spontaneous seizures. For example, children with childhood absence epilepsy may be susceptible to hyperventilation. In fact, flashing lights and hyperventilation are activating procedures used in clinical EEG to help trigger seizures to aid diagnosis. Finally, other precipitants can facilitate, rather than obligately trigger, seizures in susceptible individuals. Emotional stress, sleep deprivation, sleep itself, heat stress, alcohol and febrile illness are examples of precipitants cited by patients with epilepsy. Notably, the influence of various precipitants varies with the epilepsy syndrome. Likewise, the menstrual cycle in women with epilepsy can influence patterns of seizure recurrence. Catamenial epilepsy is the term denoting seizures linked to the menstrual cycle.
Mutations in several genes have been linked to several types of epilepsy. Some genes that code for protein sub units of voltage-gated and ligand-gated ion channels have been associated with forms of generalized epilepsy and infantile seizure syndromes.
Just as there are many types of seizures, there are many types of epilepsy syndromes. Epilepsy classification includes more information about the person and the episodes than seizure type alone, such as clinical features (e.g., behavior during the seizure) and expected causes.
There are four main groups of epileptic syndrome which can be further divided into: benign Rolandic epilepsy, frontal lobe epilepsy, infantile spasms, juvenile myoclonic epilepsy,juvenile absence epilepsy, childhood absence epilepsy (pyknolepsy), hot water epilepsy, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, Dravet syndrome, progressive myoclonus epilepsies, reflex epilepsy, Rasmussen's syndrome, temporal lobe epilepsy, limbicepilepsy, status epilepticus, abdominal epilepsy, massive bilateral myoclonus, catamenial epilepsy, Jacksonian seizure disorder, Lafora disease, photosensitive epilepsy, etc.
Each type of epilepsy presents with its own unique combination of seizure type, typical age of onset, EEG findings, treatment, and prognosis. The most widespread classification of the epilepsies divides epilepsy syndromes by location or distribution of seizures (as revealed by the appearance of the seizures and by EEG) and by cause. Syndromes are divided into localization-related epilepsies, generalized epilepsies, or epilepsies of unknown localization.
Localization-related epilepsies, sometimes termed focal or partial epilepsies, arise from an epileptic focus, a small portion of the brain that serves as the irritant driving the epileptic response. Generalized epilepsies, in contrast, arise from many independent foci (multifocal epilepsies) or from epileptic circuits that involve the whole brain. Epilepsies of unknown localization remain unclear as to whether they arise from a portion of the brain or from more widespread circuits.
Some epileptic syndromes are difficult to fit within this classification scheme and fall in the unknown localization/cause category. People with seizures that occur only after specific event ("provoked seizures"), have "epilepsies" that fall into this category. Febrile convulsions are an example of seizures bound to a particular precipitant.
Epilepsy is a group of conditions caused by large numbers of neurons in the brain firing in an abnormal and excessive fashion. During seizures there are bunches of depolarizations that spread out in waves known as a paroxysmal depolarizing shift or depolarizing shift.
One speculated mechanism for some forms of inherited epilepsy is mutations of the genes that code for sodium channel proteins; these defective sodium channels stay open for too long, thus making the neuron hyper-excitable. Glutamate, an excitatory neurotransmitter, may therefore be released from these neurons in large amounts, which — by binding with nearby glutamatergic neurons — triggers excessive calcium (Ca2+) release in these post-synaptic cells. Such excessive calcium release can be neurotoxic to the affected cell. The hippocampus, which contains a large volume of just such glutamatergic neurons (and NMDA receptors, which are permeable to Ca2+ entry after binding of both glutamate and glycine), is especially vulnerable to epileptic seizure, subsequent spread of excitation, and possible neuronal death. Another possible mechanism involves mutations leading to ineffective GABA (the brain's most common inhibitory neurotransmitter) action. Epilepsy-related mutations in some non-ion channel genes have also been identified.
Much like the channelopathies in voltage-gated ion channels, several ligand-gated ion channels have been linked to some types of frontal and generalized epilepsies.
Acute brain insult such as stroke, infection, neurodegenerative disease, trauma, or a lesion on the brain can cause a normal brain to develop epilepsy over time; this process is called epileptogenesis. One interesting finding in animals is that repeated low-level electrical stimulation to some brain sites can lead to permanent increases in seizure susceptibility: in other words, a permanent decrease in seizure "threshold". This phenomenon, known as kindling (by analogy with the use of burning twigs to start a larger fire), was discovered by Dr. Graham Goddard in 1967. It is important to note that these "kindled" animals do not experience spontaneous seizures. Chemical stimulation can also induce seizures; repeated exposures to some pesticides have been shown to induce seizures in both humans and animals. One mechanism proposed for this is called excitotoxicity. The roles of kindling and excitotoxicity, if any, in human epilepsy are currently hotly debated.
Some other noted consequences of repeated seizures are neuronal loss, gliosis, parenchymal microhemorrhages, excess of starch bodies, leptomeningeal thickening, subpial gliosis, perivascular gliosis and perivascular atrophy.
Failure of blood–brain barrier may be involved in chronic or acute seizures. some studies implicate the interactions between a common blood protein—albumin and astrocytes. These findings suggest that acute seizures are a predictable consequence of disruption of the BBB by either artificial or inflammatory mechanisms. In addition, expression of drug resistance molecules and transporters at the BBB are a significant mechanism of resistance to commonly used anti-epileptic drugs.
The diagnosis of epilepsy is typically made based on the a description of the seizure and surrounding events. An electroencephalogram and neuroimaging are also usually part of the workup. While figuring out a specific epileptic syndrome is often attempted, it is not always possible. Video and EEG monitoring may be useful in difficult cases.
In practice epilepsy is defined as two or more epileptic seizures, separated by more than 24 hours, without a clear cause; where an epileptic seizure is defined as temporary signs and symptoms resulting from abnormal electrical activity within the brain. It can also be viewed as a disorder in which people have had at least one epileptic seizure with an ongoing risk of having more.
Officially the International League Against Epilepsy defines epilepsy as "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".
Epilepsies are classified in five ways:
- By their first cause
- By the characteristics of the seizures
- By the location in the brain where the seizures starts
- As a part of an identifiable medical syndromes
- By the event that triggers the seizures, such as reading or music
Those with seizures should be classified by seizure type, epilepsy syndrome, underlying cause, and events during and around the time of the seizures. Seizure types are organized firstly according to whether the source of the seizure within the brain is localized (focal seizures) or distributed (generalized seizures). Focal seizures were previously known as partial seizures. Partial seizures were further divided on the extent to which awareness is affected. If it is unaffected, then it was a simple partial seizure; otherwise it was a complex partial (psychomotor) seizure. A focal seizure may spread within the brain - a process known as secondary generalization. Generalized seizures are divided according to the effect on the body but all involve loss of consciousness. These include absence (petit mal), myoclonic, clonic, tonic, tonic-clonic (grand mal), and atonic seizures.
In adults testing electrolytes, blood glucose and calcium levels is important to rules these out as causes. As is an electrocardiogram. A lumbar puncture may be useful to diagnose a central nervous system infection but is not routinely needed. Routine antiseizure medical levels in the blood are not required in adults or children. In children additional tests may be required.
A high blood prolactin level within the first 20 minutes following a seizure may be useful to confirm an epileptic seizure as opposed to psychogenic non-epileptic seizure. Serum prolactin level is less useful for detecting partial seizures. If it is normal an epileptic seizure is still possible and a serum prolactin does not separate epileptic seizures from syncope. It is not recommended as a routine part of diagnosis epilepsy.
An electroencephalography is only recommended in those who likely had an epileptic seizure and may help determine 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. It certain situations it may be useful to prefer the EEG while sleeping or sleep deprived.
Diagnostic imaging by CT scan and MRI is recommended after a first non-febrile seizure to detect structural problems inside the brain. MRI is generally a better imaging test except when intracranial bleeding is suspected. Imaging may be done at a later point in time in those who return to there normal selves while in the emergency room. If a person has a previous diagnosis of epilepsy with previous imaging repeat imaging is not usually needed with subsequent seizures.
Diagnosis is difficult and misdiagnosis is frequent (occurring is about 5 to 30% of cases). A number of other conditions may present very similar to epilepsy including: syncopy, hyperventillation, and psychogenic non-epileptic seizures (PNES). Approximately one in five people seen at epilepsy clinics have PNES.
Children may exhibit behaviors that are easily mistaken for epileptic seizures but are not caused by epilepsy. These include: inattentive staring, benign shudders (among children younger than age 2, usually when they are tired or excited), self-gratification behaviors (nodding, rocking, head banging), and conversion disorder (flailing and jerking of the head). Conversion disorder can be distinguished from epilepsy as the episodes never occur during sleep and do not involve incontinence or self-injury.
Epilepsy is usually treated with daily medication once a second seizure has occurred. In those with high risk features they may be started after a first seizure. In some cases a special diet, the implantation of a neurostimulator, or neurosurgery can be helpful.
The proper initial response to a generalized tonic-clonic seizure is to roll the person on the side (recovery position) to prevent fluids from getting into the lungs. Should the person regurgitate, this should be allowed to drip out the side of the mouth. The person should be prevented from self-injury by moving them away from sharp edges, and placing something soft beneath the head.
The recommended initial medication for seizure of a long duration is midazolam placed in the check. Diazepam rectally may also be used. In hospital intravenous lorazepam is preferred. If two doses of benzodiazepines are not effective other medications such as phenytoin or pentobarbital are recommended.
The mainstay of treatment of epilepsy is anticonvulsant medications, typically for the person's entire life. The choice of anticonvulsant is based on seizure type, epilepsy syndrome, other medications and health problems, and the person's age and lifestyle. A single medication is recommended initially and if this is not effective a single other medication is than recommended. Two medications at once is only recommended if a single medication does not work. The first agent tried works in about half of people, while a second agent helps in about 13% and a third or two agents at the same time help an additional 4%. About 30% of people continue to have seizures despite anticonvulsant treatment.
There are a number of medications available. Phenytoin, carbamazepine and valproate appear to be equally effect in both focal and generalized seizures. Controlled release carbamazepine appears to work as well as immediate release carbamazepine however may have less side effects. In the United Kingdom carbamazepine or lamotrigine is recommended first line for focal seizure with levetiracetam and valproate being second line due to issues of cost and side effects. Valproate is recommended first line for generalized seizures with lamotrigine being second line. In those with absence seizures ethosuximide or valproate is recommended while in myoclonic seizures and tonic or atonic seizures valproate is recommended.
Side effects — 88% of people with epilepsy, in a European survey, reported at least one anticonvulsant related side-effect. Most side effects are mild and "dose-related". Some examples include mood changes, sleepiness, or unsteadiness in gait. Some medications have side effects that are not related to dose such as rashes, liver toxicity, or low red blood cells. Valproate may cause birth defects in the offspring of pregnant women.
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 occurring in the first six months.
Epilepsy surgery may be an option for people with focal seizures that remain a problem despite other treatments. These other treatments include at least a trial of two or three medications. The goal of surgery is total control of seizures, and this may be achieved in 60-70% of cases. Common procedures include: cutting out the hippocampus via an anterior temporal lobe resection, removal of tumors, and removing parts of the neocortex. Some procedures such as a corpus callosotomy are attempted in an effort to decrease the number of seizures rather than cure the condition. Following surgery medications may be slowly stopped in many.
Neurostimulation maybe another option in those who are not candidates for surgery. Three types shown to be effective in those who do not respond to medications: vagus nerve stimulation, anterior thalamic stimulation, and closed-loop responsive stimulation.
A ketogenic diet (high-fat, low-carbohydrate, adequate-protein) appears to decrease the number of seizures by half in about 30-40% of children. About 10% manage to stay on the diet for a few years, 30% had constipation, and other adverse effects were common. Less radical diets were easier to tolerate and may be effective. It is unclear why this diet works.
Avoidance therapy consists of minimizing or eliminating triggers. For example in those who are sensitive to light using a small television, avoiding video-games or wearing dark glasses may be useful. Some claim that seizure response dogs, a form of service dog, can predict seizures. Evidence for this, however, is poor. Operant-based biofeedback based on the EEG waves has some support in those who do not respond to medications. Psychological methods should not; however, be used to replace medications.
Alternative medicine, including acupuncture, psychological interventions, vitamins, and yoga, have no reliable evidence to support their use in epilepsy. Exercise has been proposed as possibly useful for preventing seizures with some data to support this claim. The use of cannabis is not supported by the evidence.
Of those with generalized seizure more than 80% can be well controlled with medications. This is true in only 50% of people with focal seizures. One predictors of long term outcomes is the number of seizures that occurs in the first six months. Other factors increasing the risk of a poor outcome include: little response to the initial treatment, generalized seizures, a family history of epilepsy, psychiatric problems, and waves on the EED representing generalized epileptiform activity.
People with epilepsy are at an increased risk of death. This increase is between 1.6 and 4.1 fold greater and is often related to: the underlying cause of the seizures, status epilepticus, suicide, trauma, and sudden unexpected death in epilepsy (SUDEP). Death from status epilepticus is primarily due to an underlying problem rather than missing doses of medications. The risk of suicide is increased between two and six times in those with epilepsy. The cause of this is unclear. SUDEP appears to be partly related to the frequency of generalized tonic-clonic seizures and accounts for about 15% of epilepsy related deaths. It is unclear how to decrease its risk. The greatest increase in mortality from epilepsy is among the elderly. While those with epilepsy due to an unknown cause have little risk. In the United Kingdom it is estimated that 40-60% of deaths are possibly preventable.
The number of people who currently have active epilepsy is in the range 5–10 per 1000. Up to 5% of people experience non febrile seizures at some point in life; epilepsy's lifetime prevalence is relatively high because most people either stop having seizures or (less commonly) die of it. Epilepsy's approximate annual incidence rate is 40–70 per 100,000 in developed countries and 100–190 per 100,000 in developing countries; socioeconomically deprived people are at higher risk. In developed countries the number of cases a year decreased in children and than increases among the elderly during the three decades prior to 2003, for reasons not fully understood.
The oldest known record of epilepsy comes from the Sakikkū, a Babylonian cuneiform medical text from about 1067 BCE. This text details many manifestations of the different seizure type recognizable today, and it emphasizes the supernatural nature of epilepsy, while the Ayurvedic text of Charaka Samhita (about 400 BC), describes epilepsy as "apasmara", i.e., "loss of consciousness".
The word epilepsy is derived from the Ancient Greek ἐπιληψία epilēpsía, which was from ἐπιλαμβάνειν ēpilambánein "to take hold of, to seize", which in turn was combined from ἐπί ēpí "upon" and λαμβάνειν lambánein "to take". Historically, the disease was often called in Germanic and Romance languages "falling sickness", "falling ill" or "falling evil".
In the past, epilepsy was associated with religious experiences and even demonic possession. In ancient times, epilepsy was known as the "Sacred Disease" (as described in a 5th-century BC treatise by Hippocrates, On the Sacred Disease) because people thought that epileptic seizures were a form of attack by demons, or that the visions experienced by persons with epilepsy were sent by the gods. Among animist Hmong families, for example, epilepsy was understood as an attack by an evil spirit, but the affected person could become revered as a shaman through these otherworldly experiences. The Greek physician Galen wrote that "the moon governs the periods of epileptic diseases" and hence the epilepsies were, by the Greeks and Latins, called lunatics. Hippocrates remarked that epilepsy would cease to be considered divine the day it was understood.
In most cultures, persons with epilepsy have been stigmatized, shunned, or even imprisoned; in the Salpêtrière, the birthplace of modern neurology, Jean-Martin Charcot found people with epilepsy side-by-side with the mentally handicapped, those with chronic syphilis, and the criminally insane. In Tanzania to this day, as with other parts of Africa, epilepsy is associated with possession by evil spirits, witchcraft, or poisoning and is believed by many to be contagious. In ancient Rome, epilepsy was known as the Morbus 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.
In the mid 1800s the first effective anti seizure medication, bromide, was introduced. The first modern treatment, phenobarbital, was developed in 1912, with phenytoin coming into use in 1938.
Society and culture
In the U.S., people with epilepsy can drive if their seizures are controlled with treatment and they meet the licensing requirements in their state. The amount of time someone needs to be free of seizures varies in different states, but is most likely to be between three months and a year. The majority of the 50 states place the burden on the people to report their condition to appropriate licensing authorities so that their privileges can be revoked where appropriate. A minority of states place the burden of reporting on the person's physician. After reporting is carried out, it is usually the driver's licensing agency that decides to revoke or restrict a driver's license.
In the UK, it is the responsibility of the patients to inform the Driver and Vehicle Licensing Agency (DVLA) if they have epilepsy. The DVLA rules are quite complex, but in summary, those who continue to have seizures or who are within 6 months of medication change may have their licence revoked. A person must be seizure free of an 'awake' seizure for 12 months (or had only 'sleep' seizures for 3 years or more) before they can apply for a license. A doctor who becomes aware that a patient with uncontrolled epilepsy is continuing to drive has, after reminding the patient of their responsibility, a duty to break confidentiality and inform the DVLA. The doctor should advise the patient of the disclosure and the reasons why their failure to notify the agency obliged the doctor to act.
In many countries, persons with any history of epilepsy are generally disqualified for the medical certifications required for all classes of pilot licenses. In the United States, FAA regulations disqualify applicants for medical certification with a history of epilepsy, although the final decision is made by FAA headquarters, and rare exceptions are sometimes made for persons who have had only an isolated seizure or two in childhood and have remained free of seizures in adulthood without medication.
In the United Kingdom, a sub-class of pilots license called the National Private Pilot's License has the same medical requirement standards as the DVLA motoring requirements, hence epileptics with one year absence free can, with certain exceptions, fly over UK airspace in certain types of aircraft.
Many notable people, past and present, have been diagnosised of epilepsy. In many cases, their epilepsy is a footnote to their accomplishments; for some, it played an integral role in their fame. Historical diagnoses of epilepsy are not always certain; there is controversy about what is considered an acceptable amount of evidence in support of such a diagnosis.
There are a number of non-profit organizations that provide support to people and families effected by epilepsy. In the UK this includes the Joint Epilepsy Council of the UK and Ireland. Purple day was established in 2008 to increase awareness around epilepsy and occurs on March 28.
Noninvasive surgery using the gamma knife or other devices used in radiosurgery is currently being investigated as an alternative to traditional open surgery in patients who would otherwise qualify for anterior temporal lobectomy. Gene therapy and its application in epilepsy, using viral vectors, is an area that has garnered increased interest due to its potential for use in the treatment of epilepsy among other neurological disorders. In pre-clinical settings, adeno-associated vectors have proved to be the most effective vector for use in the delivery of neuropeptides: adenosine, galanin, neuropeptide y, and somatostatin. To classify postoperative outcomes for epilepsy surgery, Jerome Engel proposed a grading scheme or Engel Class, which has become the de facto standard when reporting results in the medical literature.
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