Epilepsy

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.

Contents
1 Diagnosis
2 Causes
2.1 "Normal" provocants
3 Types of seizure
4 Seizure syndromes
5 Treatment
5.1 Responding to a seizure 
 
Diagnosis
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)[1]
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.

Causes
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[2]. 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.

"Normal" provocants
Some people with epilepsy have certain triggers or provocants that will reliably produce a seizure. If the provocant can reasonably 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 lights.

For example, some people (especially young children) have seizures when exposed to certain patterns of flashing/flickering lights. This is a special type of reflex epilepsy called photosensitive epilepsy. Such seizures are often informally called "Pokémon seizures," after an article was published describing an outbreak of photosensitive seizures due to broadcast of an episode of the popular children's television show Pokémon. While some of the children involved doubtless had photosensitive epilepsy, some investigators believe that the majority of the 12,000 affected in this outbreak actually were having psychogenic non-epileptic seizures[3].

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
It is important to note that seizures are symptoms of specific illnesses, one example being epilepsy. Other diseases that can cause seizures include brain tumors, infection (e.g., encephalitis), traumatic injury to the brain, and metabolic or electrolyte abnormalities. Seizures arising from these conditions are not considered epilepsy because, once the inciting event is removed or alleviated, the seizures stop. 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.
Frontal lobe epilepsy
Lennox-Gastaut syndrome

Treatment
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.