The word epilepsy is derived from the Greek word epilambanein, meaning to attack or seize [3]. Conceptually, epilepsy is defined as "a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychologic, and social consequences of this condition" [5]. An isolated seizure does not indicate epilepsy. Approximately 7% to 8% of American adults will experience a seizure in their lifetime [2]. The majority of these seizures, however, are attributable to a specific cause, such as those mentioned above. Epilepsy, in contrast, is a recurrent illness [3]. It is a paroxysmal neurologic disorder consisting of recurrent episodes of alterations in level of consciousness, convulsive movements or other motor activity, sensory phenomena, behavioral abnormalities, and mental impairment. In clinical practice, epilepsy is considered to be present if any of the following conditions are present [6]:

The word epilepsy is derived from the Greek word epilambanein, meaning to attack or seize [3]. Conceptually, epilepsy is defined as "a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychologic, and social consequences of this condition" [5]. An isolated seizure does not indicate epilepsy. Approximately 7% to 8% of American adults will experience a seizure in their lifetime [2]. The majority of these seizures, however, are attributable to a specific cause, such as those mentioned above. Epilepsy, in contrast, is a recurrent illness [3]. It is a paroxysmal neurologic disorder consisting of recurrent episodes of alterations in level of consciousness, convulsive movements or other motor activity, sensory phenomena, behavioral abnormalities, and mental impairment. In clinical practice, epilepsy is considered to be present if any of the following conditions are present [6]:

Unfortunately, the word "epilepsy" is often inappropriately used as a generic term to describe disorders in which patients experience seizures. Compared to the 7% to 8% of Americans who will experience a seizure event in their lifetime, less than 2% of the adult population will be diagnosed with epilepsy [2,7].

One in 100 individuals will be diagnosed with epilepsy before 20 years of age [11]. By 75 years of age, roughly 2% of individuals will have active epilepsy and 7% to 10% will have experienced a seizure. New cases of the disorder are most common in individuals younger than 1 year of age and older than 55 years of age, largely because risk factors are highest in these age-groups [14]. In infants, birth injuries, high fevers, temporary metabolic abnormalities (e.g., abnormal blood sugar levels), brain disorders, and congenital defects are the primary causes of epilepsy. From 2 to 20 years of age, the cause is often unknown. After 25 years of age, brain tumors, other structural lesions, and alcohol withdrawal are the foremost contributing causes; however, in about half of this population, the cause is unknown [4]. Stroke is the cause of 50% of all seizures and 30% to 50% of epilepsy in elderly adults [17].

There are many possible etiologies that may lead to the development of seizures or the specific diagnosis of epilepsy. Epileptic seizures have three basic underlying causes: genetic, structural/metabolic, and unknown. For up to half of people with epilepsy, a cause is not known [3,8]. Some cases of epilepsy are of a genetic origin, but other forms of epilepsy are caused by structural or metabolic defects, which themselves may or may not have a genetic origin [8,23]. Other cases of epilepsy do not have any identifiable cause. Similar to structural/metabolic defects, the unidentified causes may have a heritable component.

Exposure to toxins is an additional etiology for the development of seizure events. Toxins, including lead, carbon monoxide, and pesticides (e.g., organophosphates, carbamates), have been implicated in the development of seizure activity. Prescription medications, including antibiotics, psychotropic agents, antiarrhythmic agents, anesthetics, barbiturates, and benzodiazepines, are known causes of seizures in susceptible individuals [34]. Radiographic contrast agents are another occasional causative factor. Drugs of abuse, such as alcohol, cocaine, amphetamines, barbiturates, and benzodiazepines, are known causative agents for the development of seizures, especially when associated with overdose and withdrawal [35].

The three generally recognized phases of a seizure are the prodrome (or preictal), ictal, and postictal stages [43]. Not all patients experience, nor do all seizures include, every phase. The prodromal phase can last several days preceding a seizure. The prodrome is generally characterized as malaise or emotional changes [43]. An aura occurs immediately prior to a seizure, usually lasting a few seconds. Patients often describe an aura as a warning. An aura may be autonomic or it may involve the auditory, olfactory, sensory, or visual senses. The description of an aura can vary and may include weakness, an epigastric sensation, a sense of fear, visual hallucinations, aphasia, headache, feelings of being hot or cold, or sensing unpleasant odors [43]. If a patient experiences auras (and not all do), the auras are usually fairly consistent in that individual. However, auras may vary in the same patient, and the use of antiepileptic drugs (AEDs) may alter or obscure the aura.

The ictal phase is the duration of the actual seizure activity [43]. The patient experiences a paroxysmal, uncontrolled, abnormal, and excessive discharge of electrical activity in the brain [43]. There are also corresponding EEG changes [41]. The clinical manifestations will coincide with the type of seizure activity that the patient is experiencing.

An atonic seizure or "drop attack" is evidenced by a seizure in which a patient suddenly collapses and/or falls, with the legs unable to support the body, or if seated, slumps and/or falls to the floor [3,44]. The patient is unconscious during the event but will regain consciousness after a short period of approximately 10 to 60 seconds [4,38,44]. The postictal period is short, and patients can generally continue with their activities. Less typically, individuals may experience a sudden loss of tone in the muscles of the jaw or neck. These seizures generally begin in childhood, between 2 and 5 years of age, or following widespread traumatic brain injuries in adults [46].

Focal seizures (previously referred to as "partial seizures") are the more common classification and originate in a circumscribed area or areas of the brain (i.e., a localized brain disturbance). This type of seizure occurs in 75% to 80% of patients with epilepsy [44]. Focal-onset seizures vary in terms of manifestations and severity and can result in changes in motor, sensory, and emotional functions, with or without impairment of consciousness. Focal seizures are further described according to symptoms and brain involvement [8]. Focal seizures should be classified by the earliest prominent feature (with the exception of a focal behavior arrest seizure) [10].

Focal seizures (previously referred to as "partial seizures") are the more common classification and originate in a circumscribed area or areas of the brain (i.e., a localized brain disturbance). This type of seizure occurs in 75% to 80% of patients with epilepsy [44]. Focal-onset seizures vary in terms of manifestations and severity and can result in changes in motor, sensory, and emotional functions, with or without impairment of consciousness. Focal seizures are further described according to symptoms and brain involvement [8]. Focal seizures should be classified by the earliest prominent feature (with the exception of a focal behavior arrest seizure) [10].

A focal motor seizure occurs from a focus in the region of the brain's motor cortex. Motor activity occurs in the corresponding part of the body innervated by the motor neurons that are affected. The hands and fingers have a large cortical representation; consequently, seizures are frequently noticed in these areas. The duration of these seizures is usually one to two minutes, although the patient may require additional time to completely recover after the event [4,7]. The patient will present with twitching/jerking movements in an extremity, the face, the eyes, or another area of the body. The patient remains fully conscious and aware of the seizure but has no control of the event [4]. These seizures usually remain localized, but the involuntary movement may spread centrally and involve an entire limb, one side of the body, or the entire body [4,10,44]. A Jacksonian march seizure involves the recruitment of additional muscles along the same side of the body in a progressive, step-wise fashion. The seizure may progress to involve other parts of the brain and affect other parts of the body [4].

The patient's history and the witnesses' detailed account of the seizure are critical elements in treating any patient with epilepsy [4]. These reports are often the primary mechanism to assess seizure intensity, duration, and frequency. An accurate and detailed seizure description is only achieved by asking open and pertinent questions. A seizure diary, kept by the patient and/or his or her family, can provide very useful information.

Psychogenic pseudoseizures can be difficult to diagnose accurately and often require simultaneous EEG and video monitoring. The patient often relates a history of sexual abuse, post-traumatic stress disorder, or other psychologic trauma [64]. The seizures may appear very similar to an epileptic seizure, but careful history and seizure descriptions are crucial to an accurate diagnosis. Frontal lobe epilepsy is often confused with pseudoepileptic seizures. Pseudoepileptic attacks have no physiologic CNS abnormalities. Injuries are uncommon with pseudoseizures. When eliciting the seizure description from the patient or witness, every detail can be important.

A 24-hour monitor recording may also be utilized, although it does not include video monitoring. Prolonged recording increases the likelihood of capturing a seizure event, especially those that occur infrequently or during sleep or are provoked by situations that are difficult to replicate [65]. The patient is also instructed to provide a diary of the events of the day and to document the time of any seizures that occur [58].

During an initial evaluation of a patient, a comprehensive laboratory profile should be completed. The laboratory results can assist in determining an etiology for the patient's seizures and aid in treatment decisions. If a causative factor is discovered, treatment will be essential to correct the underlying disorder. Otherwise, the laboratory results are useful in ascertaining which AED will be the most opportune for the patient. Initial laboratory evaluations should include electrolytes, a comprehensive metabolic panel, complete blood count (CBC), erythrocyte sedimentation rate, blood urea nitrogen, creatinine, and liver function tests [66]. If the history is suggestive, then toxic screens for drugs, alcohol, and toxin levels, such as lead, may be useful. A lumbar puncture may be performed to help rule out an infectious etiology of a seizure. In addition, measuring the pressure of cerebral spinal fluid is useful in the diagnosis of a possible mass lesion. Laboratory analysis of the cerebral spinal fluid may also be of benefit [71,72].

Febrile seizures are the most common seizure type in children, generally occurring between 6 months and 5 years of age. Febrile seizures are tonic-clonic seizures associated with a core temperature greater than 38 degrees Celsius with no other recognizable etiology [34,77]. Febrile seizures are classified as simple or complex [78]. Simple febrile seizures are generalized, short (last <15 minutes), do not recur within 24 hours, and have no associated focal neurologic findings [78]. In an infant younger than 6 months of age, a lumbar puncture is indicated to rule out meningitis, as typical signs may be absent [77]. Imaging and laboratory evaluations are completed if trauma or electrolyte disturbances are likely. Parents can minimize febrile convulsions with antipyretics and tepid sponge baths during febrile illnesses [78]. Usually, these children require no further intervention.

West syndrome is a severe epileptic disorder, usually beginning between 4 to 8 months of age [82]. The patient displays characteristic epileptic spasms, which are sudden jerky movements that often cluster. Although each child may experience spasms in a different manner, the event usually begins suddenly and occurs for a few seconds, usually upon awakening or after feeding, and attacks often occur in clusters of up to 100 spasms at a time. A typical spasm results in the patient extending his or her arms outward, with the head falling forward and the eyes gazing upward. These children have a distinctive EEG pattern called hypsarrhythmia. The EEG reveals bursts of electrical activity, including high voltage activity, with chaotic recordings [82].

Lennox-Gastaut syndrome is another severe epileptic disorder in children. Seizures usually begin before 4 years of age [83]. Seizure types, which vary among patients, include tonic, atonic, atypical absence, and myoclonic. There may be periods of frequent seizures mixed with brief, relatively seizure-free periods. Ordinarily, one of the seizure types causes the patient to fall. The EEG reveals characteristic slow spike-and-wave discharges. Most patients suffer from intellectual disabilities, especially if the onset occurs before 3 years of age. Many children will have a history of epileptic spasms and multiple disabilities, including cerebral palsy, blindness, and hearing impairment. In 30% to 35% of children, no cause can be found [83]. Treatment usually includes AEDs such as carbamazepine, topiramate, valproate, felbamate (adjunctive), or lamotrigine (adjunctive) [38,83]. In 2018, a drug comprised of purified cannabidiol (Epidiolex) was approved for the treatment of Lennox-Gastaut syndrome in patients 2 years of age and older [84]. Clobazam is indicated as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome [74,85]. There is usually no single AED that will control Lennox-Gastaut seizures. Children who improve initially may later show tolerance to a drug or have uncontrollable seizures [83].

Epilepsy affects approximately 300,000 elderly patients in the United States, which is the most rapidly growing population group with epilepsy [91]. Elderly patients with epilepsy may be difficult to manage. One of the primary concerns is that elderly patients are often prescribed multiple concomitant medications, which can predispose the patient to drug interactions and adverse effects. Another concern is that elderly individuals metabolize medications less effectively and often have an increased sensitivity to side effects. These side effects include fatigue, unsteadiness, and forgetfulness, which can lead to falls, broken bones, and a loss of independence [91]. Care should be taken to evaluate the patient and to provide therapies consistent with the patient's abilities and situation.

The mechanism of action of carbamazepine is generally recognized to be the inhibition of nerve impulses by repressing sodium ion influx across cell membranes in the motor cortex. This medication is used for first-line therapy in the treatment of generalized tonic-clonic and focal seizures. There is no indication for the use of carbamazepine in absence or myoclonic seizures [74,119].

Ethosuximide is effective in suppressing the paroxysmal spike-and-wave pattern that occurs in absence seizures. Furthermore, it has been found to depress nerve transmission in the motor cortex and increase the seizure threshold [74]. Ethosuximide is effective for the treatment of absence seizures; however, it is not efficacious for other forms of generalized seizures or focal seizures. Due to the documented hepatotoxicity of valproate in children, ethosuximide is often the preferred first choice. The medication is begun at a low dose, then increased to a maintenance dose. Administering ethosuximide in an incremental fashion (and with food or milk) decreases GI side effects [74]. Nausea, anorexia, drowsiness, and headache are the primary adverse reactions. These symptoms often decrease with continued dosing of the medication or by reducing the dose. Unusual reactions, such as aggression, delusional paranoid disorder, depression (with overt suicidal intentions), leukopenia, and rash, have been reported with this drug [74]. No harmful effects on intellectual functioning have been reported. There are also fewer drug interactions with this medication, especially with other AEDs.

In 2004, the FDA approved pregabalin as adjunctive therapy for adult patients with focal seizures. It has structural similarities to GABA but does not appear to mimic its functional properties. This medication binds to a subunit of calcium channels in the brain, preventing the neurotransmitter release associated with a seizure event [74]. Therefore, pregabalin tends to decrease the frequency of seizures when added to an AED regimen. Common side effects include dizziness, somnolence, ataxia, and blurred vision. Possible life-threatening reactions include anemia, heart failure, and Stevens-Johnson syndrome. Adverse effects may be dose-dependent or related to interactions with other medications [74]. However, studies have found no interactions with carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, or topiramate [130]. Pregabalin should not be immediately discontinued, but rather diminished gradually, due to a risk of increased seizure activity. The dosage should be tapered off over a period of at least one week [74].

A corpus callosotomy, or corpus callosum section, splices the innervations between the left and right brain by interrupting the corpus callosum. This type of surgery may be useful for generalized seizures to prohibit the spread of epileptic discharges. Corpus callosotomy is done primarily in children with severe seizures that start in one half of the brain and spread to the other side. Uncontrolled myoclonic, atonic, and tonic-clonic seizures may be reduced in severity or frequency after this procedure [3]. In some patients, generalized seizures may stop while other patients may have a worsening of focal seizures. A 60% to 70% decrease can be expected for more than 80% of patients. Approximately 10% to 15% of patients receive no worthwhile benefit [134]. Complications such as infection, cerebral edema, impaired muscular activity, visual defects, memory, and speech disorders may occur after this type of surgery. The rate of complications has been reported as high as 50%, including several deaths [134].

The theory behind the ketogenic diet is that it has the same effect on the body as fasting; that is, the body is forced to utilize fat as energy instead of glucose. This can increase ketosis, with a subsequent rise in serum ketones [3,150].

In the 1920s, this diet was studied as a treatment for patients with intractable epilepsy. As newer medications were discovered, the diet became perceived as a less favorable treatment option. Today, there are many respected centers located throughout the United States that prescribe and monitor the ketogenic diet as a complementary approach to standard AEDs [150,151]. If a patient's seizures are not controlled on usual medications or if the adverse effects of medications are numerous, the ketogenic diet may be considered. This diet should be prescribed and monitored by a physician in collaboration with a nutritionist [150].

Complications from seizures are varied and numerous. Patients can sustain injuries, both physical and neurologic. A patient with any type of seizure may sustain a physical injury, especially during impaired consciousness. Patients may experience abrasions, bruises, broken bones, burns, and oral lacerations, including tongue and cheek injuries. Other patients may experience a severe head injury or other trauma with sudden falls to the floor or falls from heights [3,38].

In 2016, the American Epilepsy Society (AES) issued new guidelines for the treatment of status epilepticus, which provide a time-dependent treatment algorithm consisting of four phases [164]. The first or "stabilization phase" occurs in the first five minutes of seizure activity and includes standard initial first aid interventions for seizures [164]. As with any emergency situation, the first priority is the maintenance of a clear airway. The patient sustains a rapid depletion of oxygen and other nutrients during status. Often, the individual is intubated to assist with oxygenation and the prevention of aspiration. The patient will usually require supplemental oxygen. Continuous assessment of all vital functions and neurologic status is necessary. Cardiac monitoring is required to identify dysrhythmias and to allow for appropriate intervention. The patient should be protected from injury and provided a safe environment with close supervision. Laboratory evaluations should be completed to assess AED levels and to check for any metabolic changes. The patient may require additional glucose, which is administered intravenously, to meet increased metabolic requirements. AEDs may be prescribed for intravenous injection and infusion [84,161,164].

Interventions for the initial therapy phase (minutes 5 to 20 of seizure activity) include a benzodiazepine (specifically IM midazolam, IV lorazepam, or IV diazepam). Although use of IM midazolam for status epilepticus is off-label, the AES guideline recommends it as the drug of choice when IM administration is necessary for emergent control [74,164]. Diazepam was once considered the drug of choice for the immediate treatment of status epilepticus; however, lorazepam has emerged as the preferred benzodiazepine for acute management of status epilepticus [84,164,165]. Lorazepam is less lipid-soluble than diazepam, with a distribution half-life of two to three hours versus 15 minutes for diazepam, providing a longer duration of clinical effect [165]. The anticonvulsant effects of lorazepam last 6 to 12 hours, and the typical dose ranges from 4–8 mg. This agent also has a broad spectrum of efficacy, terminating seizures in 75% to 80% of cases. Its primary adverse effect (respiratory depression) is identical to that of diazepam [84].

Epilepsy is a chronic disorder and often requires long-term management. The patient and family should be encouraged to obtain information about epilepsy through self-education. Local epilepsy organizations often provide written materials and information via other media. Frequently, the patient's family members or other significant persons require as much education as the patient because they will be observing the patient during the actual events. These significant persons should be educated to care for the patient during and after a seizure. They should be instructed to stay with the patient until he or she is conscious, time the seizure duration, and provide for the patient's safety. If consciousness returns without further incident and the seizure ends in less than five minutes, then the convulsion is considered to be uncomplicated and emergency attention is not necessary. In general, after a period of rest, the patient is able to resume caring for him or herself [158]. The spouse or other significant person is a crucial asset for the patient and can assist in differentiating between an emergency and an uncomplicated seizure, even though, to the general public, all seizures may appear to be emergencies. The assisting person is important in the prevention of injury and can also help the patient maintain an accurate seizure calendar and ensure medications are taken appropriately.

The prevention of childhood infection and toxic ingestions is crucial in averting the development of epilepsy. Meningitis, viral encephalitis, measles, mumps, and diphtheria can be minimized through appropriate immunization of children and adults. The prevention of toxic poisonings through screening and safety measures is essential. Lead poisoning continues to be problematic in many older homes [4,35].

Another area that may minimize the incidence of epilepsy is the reduction of motor vehicle accidents and the prevention of trauma. Traumatic injuries can occur through a variety of accidents and abuse. The utilization of safety belts and restraint devices in all motorized vehicles is essential for children and adults. Settings in which there is a potential for gunshot wounds should also be avoided to prevent the occurrence of head injuries and the subsequent development of epilepsy. Practicing safety during sporting activities is also essential. The prevention of abuse is vital in the reduction of head trauma-related epilepsy. Workplace injuries should be reviewed and reduced. Lastly, the prevention of substance abuse and the use of illicit drugs will assist in the reduction in the incidence of epilepsy [3,4,11,29,35].

For individuals with epilepsy, the safe operation of a motor vehicle is a complex issue. The caregiver must try to achieve a balance between providing the best care to the patient and providing the patient with the autonomy and freedom that often coincides with driving. Safety must be the highest priority for the patient and for other individuals. This issue is further complicated by a variety of state statutes and regulations.