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Epilepsy (often referred to as a seizure disorder) is a chronic neurological condition characterized by recurrent unprovoked seizures. The condition is named from the Greek epilepsis ("to take a firm grip on"). It is commonly controlled with medication, although surgical methods are used as well.
The diagnosis of epilepsy requires the presence of recurrent, unprovoked seizures; accordingly, it is usually made based on the medical history. EEG, brain MRI, SPECT, PET, and magnetoencephalography may be useful to discover an etiology for the epilepsy, discover the affected brain region, or classify the epileptic syndrome, but these studies are not useful in making the initial diagnosis. Long-term video-EEG monitoring for epilepsy is the gold standard for diagnosis, but it is not routinely employed owing to its high cost and inconvenience. It is, however, sometimes used to distinguish
- psychogenic non-epileptic seizures from epilepsy. Convulsive or other seizure-like activity, non-epileptic in origin, can be observed in many other medical conditions, including: psychogenic non-epileptic seizures (often wrongly called "pseudoseizures") tics syncope (fainting) narcolepsy cataplexy parasomnias breath-holding spells of childhood non-epileptic myoclonus hypoglycemia and associated neuroglycopenia opsoclonus hyperekplexia paroxysmal kinesiogenic dyskinesia infantile gratification / masturbation (onanism) repetitive behaviors
Neurologists are often called upon to distinguish among the above diagnoses and epilepsy.
Epilepsies are classified five ways:
- By their first cause (or etiology).
- By the observable manifestations of the seizures, known as "semiology."
- By the location in the brain where the seizures originate.
- As a part of discrete, identifiable medical syndromes.
- By the event that triggers the seizures, as in primary reading epilepsy.
All the causes (or etiologies) of epilepsy are not known, but many predisposing factors have been identified, including brain damage resulting from malformations of brain development, head trauma, neurosurgical operations, other penetrating wounds of the brain, brain tumor, high fever, bacterial or viral encephalitis, stroke, intoxication, or acute or inborn disturbances of metabolism. Hereditary or genetic factors also play a role. Seizures may occur in any person under certain circumstances, including acute illness and drug overdoses, but these provoked seizures are not part of the definition of epilepsy. Epilepsy connotes that an individual has unprovoked seizures which recur over time. In about 50% of all cases, there is no cause for epilepsy that is currently detectable even with state of the art investigations. In about 50% of cases, evidence of a brain injury, scar or malformation is found, to which the epilepsy is attributed. In many, but not all cases, abnormal electrical activity can be detected in the brain with an electroencephalogram (EEG), either during or in between seizures. The most common ages of incidence are under the age of 18 and over the age of 65. It has been estimated that about 1% of the population meets the diagnostic criteria for epilepsy at any given time, but some theorize that the prevalence may be much higher in fact. A significant and measurable decline in cognitive function is known to be associated with epilepsy, although it has not been entirely clear to what extent this is due to the epilepsy itself or to the drugs used to treat it. Phenobarbital, in particular, has been shown to decrease IQ and classroom performance when used to treat epilepsy in children; the effects persist after the phenobarbital is stopped. Some newer anti-epileptic drugs are considered by some to have less severe cognitive effects than older drugs. On an individual level, a person's reaction to epileptic seizures and/or anti-epileptic drugs may be idiosyncratic, so it is difficult to predict how a particular person might be affected. Mutations in several genes have been linked to some types of epilepsy. Several genes that code for protein subunits of voltage-gated and ligand-gated ion channels have been associated with forms of generalized epilepsy and infantile seizure syndromes. Several ligand-gated ion channels have been linked to some types of frontal and generalized epilepsies. Epilepsy-related mutations in some non-ion channel genes have also been identified. 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. 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 people with epilepsy have certain triggers or provocants that will reliably produce a seizure. If the provocant can reasonably be considered to be part of normal daily life, and yet it causes a seizure, the seizures are considered 'unprovoked' for the purpose of diagnosing the person with epilepsy. Examples of these 'normal provocants' include reading, hot water on the head, hyperventilation and flashing or flickering lights. This last provocant is a special type of reflex epilepsy called photosensitive epilepsy.
Types of seizure
Epileptic seizures are classified both by their patterns of activity in the brain and their effects on behaviour. In terms of their pattern of activity, seizures may be described as either partial (focal) or generalised. Partial seizures only involve a localised part of the brain, whereas generalised seizures involve the entire cortex. The term 'secondary generalisation' may be used to describe a partial seizure that later spreads to the whole of the cortex and becomes generalised. Partial seizures may be further subdivided into both simple and complex seizures. This refers to the effect of such a seizure on consciousness; simple seizures cause no interruption to consciousness (although they may cause sensory distortions or other sensations), whereas complex seizures interrupt consciousness to varying degrees. This does not necessarily mean that the person experiencing this sort of seizure will fall unconscious (like fainting). For example, a complex partial seizure may involve the unconscious repetition of simple actions, gestures or verbal utterances, or simply a blank stare and apparent unawareness of the occurrence of the seizure, followed by no memory of the seizure. Other patients may report a feeling of tunnel vision or dissociation, which represents a diminishment of awareness without full loss of consciousness. Still other patients can perform complicated actions, such as travel or shopping, while in the midst of a complex partial seizure. The effects of partial seizures can be quite dependent on the area of the brain in which they are active. For example, a partial seizure in areas involved in perception may cause a particular sensory experience (for example, the perception of a scent, music or flashes of light) whereas, when centred in the motor cortex, a partial seizure might cause movement in particular groups of muscles. This type of seizure may also produce particular thoughts or internal visual images or even experiences which may be distinct but not easily described. Seizures centred on the temporal lobes are known to produce mystical or ecstatic experiences in some people. These may result in a misdiagnosis of psychosis or even schizophrenia, if other symptoms of seizure are disregarded and other tests are not performed. Unfortunately for those with epilepsy, anti-psychotic medications prescribed without anti-convulsants in this case can actually lower the seizure threshold further and worsen the symptoms. When the effects of a partial seizure appear as a 'warning sign' before a more serious seizure, they are known as an aura: it is frequently the case that a partial seizure will spread to other parts of the brain and eventually become generalized, resulting in a tonic-clonic convulsion. The subjective experience of an aura, like other partial seizures, will tend to reflect the function of the affected part of the brain. Generalised seizures can be sub-classified into a number of categories, depending on their behavioural effects: Absence seizures (sometimes referred to as petit mal seizures) involve an interruption to consciousness where the person experiencing the seizure seems to become vacant and unresponsive for a short period of time (usually up to 30 seconds). Slight muscle twitching may occur. Tonic-clonic seizures (sometimes referred to as grand mal seizures), involve an initial contraction of the muscles (tonic phase) which may involve tongue biting, urinary incontinence and the absence of breathing. This is followed by rhythmic muscle contractions (clonic phase). This type of seizure is usually what is referred to when the term 'epileptic fit' is used colloquially. Myoclonic seizures involve sporadic muscle contraction and can result in jerky movements of muscles or muscle groups. Atonic seizures involve the loss of muscle tone, causing the person to fall to the ground. These are sometimes called 'drop attacks' but should be distinguished from similar looking attacks that may occur in narcolepsy or cataplexy. Status epilepticus refers to continuous seizure activity with no recovery between successive tonic-clonic seizures. This is a life-threatening condition and emergency medical assistance should be called immediately if this is suspected. A tonic-clonic seizure lasting longer than 5 minutes (or two minutes longer than a given person's usual seizures) is usually considered grounds for calling the emergency services. Epilepsia partialis continua is a rare type of focal motor seizure (hands and face) which recurs every few seconds or minutes for extended periods (days or years). It is usually due to strokes in adults and focal cortical inflammatory processes in children (Rasmussen's encephalitis), possibly caused by chronic viral infections or autoimmune processes. Seizure syndromes There are many different epilepsy syndromes, each presenting with its own unique combination of seizure type, typical age of onset, EEG findings, treatment, and prognosis. Below are some common seizure syndromes: Infantile spasms (West syndrome) is associated with brain development abnormalities, tuberous sclerosis, and perinatal insults to the brain. It affects infants (as implied by its name), which by definition is between 30 days to 1 year of life. It carries a poor prognosis such that only 5-10% of children with infantile spasms will develop normal to near-normal function, while more than two-thirds will have severe deficits. The typical seizures are characterized by sudden flexor and extensor spasms of head, trunk, and extremities. The key EEG finding in these patients is a hypsarrythmia, or a high-voltage slow wave with multifocal spikes. The first line treatment for these patients is adrenocorticotropic hormone (ACTH or corticotropin) since traditional antiepileptic drugs generally cannot adequately control seizure activity. Vigabatrin is also used in many countries, and is particularly effective when tuberous sclerosis is the cause of seizures. Childhood absence epilepsy affects children between the ages of 4 and 12 years of age. These patients have recurrent absence seizures that can occur hundreds of times a day. On EEG, one finds the stereotyped generalized 3 Hz spike and wave discharges. A subset of these patients will also develop generalized tonic-clonic seizures. This condition carries a fairly good prognosis in that these children do not usually show cognitive decline or neurological deficits. First line treatment for pure absence seizures is ethosuximide. If patients do not respond or have mixed seizures along with their absence seizures, then valproic acid can be used. Benign focal epilepsy of childhood (Benign Rolandic epilepsy) begins in children between the ages of 4 and 13 years. Apart from their seizure disorder, these patients are otherwise normal. Seizures occur at night and sleep promotes secondary generalization. As such, parents only report generalized seizures because focal manifestations are often subtle and go unnoticed. Between seizures, patients have a stereotyped EEG pattern that includes di- or triphasic sharp waves over the central-midtemporal (Rolandic) regions. Prognosis is uniformly good with seizures disappearing by adolescence. Carbamazepine is the first line treatment, though phenytoin and phenobarbital have also been used with some efficacy. Juvenile myoclonic epilepsy (JME) begins in patients aged 8 to 20 years. These patients have normal IQ and are otherwise neurologically intact. There is usually a family history of similar seizures. The seizures are morning myoclonic jerks often with generalized tonic-clonic seizures that occur just after waking. EEG readings reveal generalized spikes with 4-6 Hz spike wave discharges and multiple spike discharges. Interestingly, thse patients are often first diagnosed when they have their first generalized tonic-clonic seizure later in life when they experience sleep deprivation (e.g., freshman year in college after staying up late to study for exams). Valproic acid is the first line treatment. This condition is lifelong, thus patients must be taught appropriate sleep hygiene to prevent generalized tonic-clonic seizures. Temporal lobe epilepsy is the most common epilepsy of adults. In most cases, the epileptogenic region is found in the mesial temporal structures (e.g., the hippocampus, amygdala, and parahippocampal gyrus). Seizures begin in late childhood and adolescence. There is an association with febrile seizures in childhood, and some studies have shown herpes simplex virus (HSV) DNA in these regions, suggesting that perhaps this epilepsy has an infectious etiology. Most of these patients have complex partial seizures often preceded by an aura.
Epilepsy is usually treated with medication prescribed by a physician; primary caregivers, neurologists, and neurosurgeons all frequently care for people with epilepsy. In some cases the implantation of a stimulator of the vagus nerve, or a special diet can be helpful. Neurosurgical operations for epilepsy can be palliative, reducing the frequency or severity of seizures; or, in some patients, an operation can be curative.
Responding to a seizure
In most cases, the proper emergency response to a generalized tonic-clonic epileptic seizure is simply to prevent the patient from self-injury by moving him or her away from sharp edges, placing something soft beneath the head, and carefully rolling the person onto his or her side to avoid asphyxiation. Should the person regurgitate, the material should be allowed to drip out the side of the patient's mouth by itself. If the seizure lasts longer than 5 minutes, Emergency Medical Services should be contacted. Prolonged seizures may develop into status epilepticus, a dangerous condition requiring hospitalization and emergency treatment. Objects should never be placed in a person's mouth during a seizure as this could result in injury to the person's mouth or obstruction of the airway. Despite common folklore, it is not possible for a person to swallow their own tongue during a seizure. After a seizure, it is typical for a person to be confused, disoriented, and possibly agitated or sleepy. It is important to stay with the person until this passes; people should not eat or drink until they have returned to their normal level of awareness, and they should not be allowed to wander about unsupervised. Many patients will sleep deeply for a few hours after a seizure; this is not dangerous. In about 50% of people with epilepsy, headaches may occur after a seizure. These headaches share many features with migraines, and respond to the same medications. Pharmacologic treatment Some medications can be taken daily in order to prevent seizures altogether or reduce the frequency of their occurrence. These are termed "anticonvulsant" or "antiepileptic" drugs (sometimes AEDs). All such drugs have side effects which are idiosyncratic and others which are dose-dependent; it is not possible to predict who will suffer from side effects or at what dose the side effects will appear. Some people with epilepsy will experience a complete remission when treated with an anticonvulsant medication. If this does not occur, the dose of medication may be increased, or another medication may be added to the first. The general strategy is to increase the medication dose until either the seizures are controlled, or until dose-limiting side effects appear; at which point the medication dose is reduced to the highest amount that did not produce undesirable side effects. Serum levels of AEDs can be checked to determine medication compliance and to assess the effects of drug-drug interactions; serum levels are generally not useful to predict anticonvulsant efficacy in an individual patient, though in some cases (such as a seizure flurry) it can be useful to know if the level is very high or very low. If a person's epilepsy cannot be brought under control after adequate trials of two different drugs, that person's epilepsy is generally said to be 'medically refractory.' Various drugs may prevent seizures or reduce seizure frequency: these include carbamazepine (common brand name Tegretol), clobazam (Frisium), clonazepam (Klonopin), ethosuximide (Zarontin), felbamate (Felbatol), fosphenytoin (Cerebyx), flurazepam (Dalmane), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), mephenytoin (Mesantoin), phenobarbital (Luminal), phenytoin (Dilantin), pregabalin (Lyrica), primidone (Mysoline), sodium valproate (Epilim), tiagabine (Gabitril), topiramate (Topamax), valproate semisodium (Depakote), valproic acid (Depakene, Convulex), and vigabatrin (Sabril). Other drugs are commonly used to abort an active seizure or interrupt a seizure flurry; these include diazepam (Valium) and lorazepam (Ativan). Drugs used only in the treatment of refractory status epilepticus include paraldehyde (Paral) and pentobarbital (Nembutal). Bromides were the first of the effective anticonvulsant pure compounds, but are no longer used due to their toxicities and low efficacy.
Surgical treatment can be an option for epilepsy when an underlying brain abnormality, such as a benign tumor or an area of scar tissue (e.g. hippocampal sclerosis) can be identified. The abnormality must be removable by a neurosurgeon. Surgery is usually only offered to patients when their epilepsy has not been controlled by adequate attempts with multiple medications. Before surgery is offered, the medical team performs many tests to assess whether removal of brain tissue will result in unacceptable problems with memory, vision, language or movement, which are controlled by different parts of the brain. Resective surgery, as opposed to palliative, successfully eliminates or significantly reduces seizures in about 80% of the patients who undergo it. Many patients decide not to undergo surgery owing to fear or the uncertainty of having a brain operation. The most common form of resective surgical treatment for epilepsy is to remove a portion of either the right or left temporal lobe, depending on where the seizures are occurring. A study of 48 patients who underwent this operation, anterior temporal lobectomy, between 1965 and 1974 determined the long-term success of the procedure. Of the 48 patients, 21 had had no seizures that caused loss of consciousness since the operation. Three others had been free of seizures for at least 19 years. The rest had either never been completely free of seizures or had died between the time of the surgery and commencement of the study. Palliative surgery for epilepsy is intended to reduce the frequency or severity of seizures. Examples are callosotomy or commissurotomy to prevent seizures from generalizing (spreading to involve the entire brain), which results in a loss of consciousness. This procedure can therefore prevent injury due to the person falling to the ground after losing consciousness. It is performed only when the seizures cannot be controlled by other means. Resective surgery can be considered palliative if it is undertaken with the expectation that it will reduce but not eliminate seizures. Hemispherectomy is a drastic operation in which most or all of one half of the cerebral cortex is removed. It is reserved for the most catastrophic epilepsies, such as those due to Rasmussen syndrome. If the surgery is performed on very young patients (2-5 years old), the remaining hemisphere may acquire some rudimentary motor control of the ipsilateral body; in older patients, paralysis results on the side of the body opposite to the part of the brain that was removed. Because of these and other side effects it is usually reserved for patients who have exhausted other treatment options.
Ketogenic diets may occasionally be effective in controlling some types of epilepsy; although the mechanism behind the effect is not fully understood, shifting of pH towards a metabolic acidosis and alteration of brain metabolism may be involved. Ketogenic diets are high in fat and extremely low in carbohydrates, with intake of fluids often limited. This treatment, originated as early as the 1920s at Johns Hopkins Medical Center, was largely abandoned with the discovery of modern anti-epileptic drugs, but recently has returned to the anti-epileptic treatment arsenal. Ketogenic diets are sometimes prescribed in severe cases where drugs have proven ineffective. There are several downsides to what initially seems a benign therapy, however. The ketogenic diet is not good for the heart or kidneys and medical problems resulting from the diet have been reported. In addition, the diet is extremely unpalatable and few patients are able to tolerate it for any length of time. Since a single potato chip is adequate to break the ketosis, staying on the diet requires either great willpower or perfect control of a person's dietary intake. People fed via gastrostomy or young children who receive all their food in the presence of a caregiver are better candidates. Vagus nerve stimulation is a recently developed form of seizure control which uses an implanted electrical device, similar in size, shape and implant location to a heart pacemaker, which connects to the vagus nerve in the neck. Once in place the device can be set to emit electronic pulses, stimulating the vagus nerve at pre-set intervals and milliamp levels. Treatment studies have shown that approximately 50% of people treated in this fashion will show significant seizure reduction. Some people with epilepsy receive a special dog which has the rare talent of sensing the onset of a seizure and is trained to alert the human so they can reach a safe location before their seizure puts them in danger. Other epilepsy care dogs do not sense seizures, but serve as companions and guardians during the loss of consciousness accompanying a seizure. The Institutes for The Achievement of Human Potential promulgate a home program consisting of a healthy diet, clean air, and respiratory training. This alternative approach is regarded as unscientific by most medical practicioners.
History and stigma
In the past, epilepsy was associated with religious experiences and even demonic possession. Apocryphally, epilepsy has been called 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. However, in many 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 retarded, chronic syphilitics, and the criminally insane. In Tanzania to this day, onlookers will not touch a person having an epileptic fit, owing to fear of demons, even if the seizure causes the person to fall into the cooking fire (the flickering light from fire may have provoked the seizure in the first place.) In ancient Rome, epilepsy was known as the Morbus Comitialis ('disease of the assembly hall') and was seen as a curse from the gods. Stigma continues to this day, in both the public and private spheres, but polls suggest it is generally decreasing with time, at least in the developed world; Hippocrates remarked that epilepsy would be considered divine only until it was understood.
Seizures have caused many fatal car accidents and plane crashes. Most people diagnosed with epilepsy are forbidden by their local laws from operating vehicles. However, there are usually exceptions for those who can prove that they have stabilized their condition. Those few whose seizures do not cause impairment of consciousness, or whose seizures only arise from sleep, may be exempt from such restrictions, depending on local laws. There is an ongoing debate in bioethics over who should bear the burden of ensuring that an epilepsy patient does not drive a car or fly an airplane. 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. How long (they) have to be free of seizures varies in different states, but it's most likely to be between three months and a year. The majority of the 50 states place the burden on patients to report their condition to appropriate licensing authorities so that their privileges can be revoked where appropriate. A minority of states (including California) place the burden of reporting on the patient'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. Empirical studies have demonstrated that these laws may deter epilepsy patients from seeking treatment from a physician for their condition because they fear the loss of their driving privileges. In the UK, it is the responsibility of the patient to inform the Driver and Vehicle Licensing Agency (DVLA) if they have epilepsy. The DVLA rules are quite complex, but in summary , those continuing to have seizures or who are within 6 months of medication change may have their license revoked. 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.
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