Seizure overview

# Overview
A seizure is a transient event that is due to excessive or synchronous neuronal activity in the brain. The term 'seizure' is derived from a Greek word that means 'to take hold'. In 2017, the International League Against Epilepsy (ILAE) classified seizure by its onsets as focal (aware/impaired awareness, motor, nonmotor, focal to tonic-clonic seizures), generalized (motor, nonmotor), and unknown (motor, nonmotor, and unclassified). Seizures may be provoked (by hypoglycemia or alcohol withdrawal, etc) or spontaneous (by underlying epilepsy). It is estimated that 11% of the population experience a seizure in their life compared to the estimation of 3% for epilepsy. Risk factors that can precipitate or provoke seizure include, excessive sleep deprivation, alcohol use, illicit drug use, some medications that reduce the seizure threshold, toxins, homeostasis abnormality due to organ failure, metabolic abnormalities, and medical and surgical histories that may be important in assessing the patients risk for future seizures. Some of the causes of seizure include, brain injury, brain hemorrhage, encephalitis, high fever, chronic alcohol use, chronic sleep deprivation, medications, metabolic abnormalities, withdrawal from alcohol or drugs. Signs and symptoms of seizures depend on the area of the brain that it originates from. Seizure can be associated with loss of consciousness, confusion, visual or other sensory symptoms, body shaking, limb jerking, or a brief loss of awareness. Diagnosis of seizure is done by taking the patient's history, physical examination, laboratory investigation,  EEG, and brain imaging. In the acute setting, seizures are initially treated with benzodiazepines (lorazepam or midazolam), followed by phenytoin or phenobarbital. Treatment with antiepileptic drugs (AEDs) may be required in some patients.
Prevention is based on controlling the risk factors that may provoke a seizure.

# Historical Perspective
The term 'seizure' is derived from a Greek word that means 'to take hold'. Epilepsy was first described by Hippocrates in Ancient Greece (460377 B.C.). Until the 18th century, epilepsy was considered an idiopathic disease originating in the brain. The foundation of the modern knowledge of epilepsy was through the work of William Cullen and Samuel A. In the 20th century, rapid development in medical imaging occurred with development in brain CT, brain MRI, and PET scan.

# Classification
In 2017, the International League Against Epilepsy (ILAE) classified seizure by its onsets as focal (aware/impaired awareness, motor, nonmotor, focal to tonic-clonic seizures), generalized (motor, nonmotor), and unknown (motor, nonmotor, and unclassified). In 1981, the International League Against Epilepsy (ILAE) classified epileptic seizures as partial seizures (simple partial seizures, complex partial seizures, and partial seizures evolving to secondarily generalized seizures), generalized seizures (absence seizures, myoclonic seizures, clonic seizures, tonic seizures, tonic-clonic seizures (grand mal), and atonic seizures), and unclassified epileptic seizures.

# Pathophysiology
Normally, seizures do not occur because the membrane stability of neurons is maintained, and the discharges that lead to seizures are prevented from transferring. In a normal brain,  some circumstances can provoke seizures, such as: hyponatremia, drug withdrawal, and hypoglycemia. Abnormalities in different parts of the nervous system may cause seizure, such as: brain regions, cells, ions, networks, and receptors. The imbalance of excessive excitation and reduced inhibition can cause seizures and is also responsible for prolonging it if the imbalance persists. Glutamate is the most common excitatory neurotransmitter and acts on the N-methyl-D-aspartate (NMDA) receptor. However, NMDA antagonist drugs have not been clinically successful. Gamma-aminobutyric acid (GABA) is the most common inhibition neurotransmitter. GABA inhibits excess excitation of the neurons by activating the GABAA receptor. Increasing the inhibition of GABA (even if the inhibition is not damaged) may be helpful in a seizure, since it may overwhelm the excess excitation of the seizure. Examples of GABA-enhancing drugs are benzodiazepines, barbiturates, propofol, and some anesthetics. However, these drugs are not suitable for long term therapy since patients usually become tolerant to their effect.

# Causes
Some of the causes of seizure include, brain injury, brain hemorrhage, encephalitis, high fever, chronic alcohol use, chronic sleep deprivation, medications, metabolic abnormalities, withdrawal from alcohol or drugs.

# Differentiating Seizure from Other Diseases
Differential diagnosis of epileptic seizures may include, concussion, drug intoxication or withdrawal, migraine, psychogenic non-epileptic events, panic attacks, sleep disorders, syncope, transient global amnesia, transient ischemic attack (TIA).

# Epidemiology and Demographics
It is estimated that 11% of the population experience a seizure in their life compared to the estimation of 3% for epilepsy. In the US, seizure is estimated to account for 1 million or 1% of emergency department (ED) visits annually. The incidence of acute symptomatic seizures is estimated to be 39 cases per 100,000 individuals in the US. Seizures are more common among males and people of African descent.

# Risk Factors
Risk factors that can precipitate or provoke seizure include, excessive sleep deprivation, alcohol use, illicit drug use, some medications that reduce the seizure threshold, toxins, homeostasis abnormality due to organ failure, metabolic abnormalities, and medical and surgical histories that may be important in assessing the patients risk for future seizures.

# Screening
The EEG monitoring has been recommended in neonates with known or suspected acute brain injury combined with encephalopathy, diseases associated with abnormal paroxysmal events, and in high-risk population.

# Natural History, Complications, and Prognosis
The recurrence rate of seizure within two years is 35% to 40% in patients with a first-time unprovoked seizure. Status epilepticus occurs in about 6%-7% of the patients with seizure in the emergency department (ED). The overall mortality rate of status epilepticus is approximately 22% (3% in pediatric patients to 26% in adults). Simple febrile seizures are considered normal in childhood and the prognosis is generally excellent. The recurrence rate is about 12% in children that have their first febrile seizure in infancy and about 50% in those who have their first febrile seizure later.

# Diagnosis

## Diagnostic Study of Choice
The basis of seizure investigation and diagnosis depends upon, a detailed history of any event before and after a seizure episode, investigation of co-existing conditions, a focused physical examination, laboratory evaluation, and brain imaging.

## History and Symptoms
The main part of the seizure history should be about the patients awareness, experience, and remembrance of the seizure. Symptoms of seizure include, aura, staring spells, myoclonic jerks, impaired awareness, paresthesias, lost of consciousness, Deja vu experiences and confusion.

## Physical Examination
The physical examination of patients with seizure may reveal: lateral tongue bites, nuchal rigidity or asterixis, bruises or scrapes on the body after falls, signs of a neurocutaneous syndrome associated with epilepsy on the skin, back pain, transient or persistent focal weakness or asymmetry, and urinary incontinence.

## Laboratory Findings
The laboratory tests for patients with seizure may include, hypoglycemia, hyponatremia, uremia, drug intoxication, ammonia levels, creatine kinase (CK) levels, lactate levels, prolactin levels. Elevated prolactin level may be helpful in differentiating generalized tonic-clonic or complex partial seizure from psychogenic non-epileptic seizures, only if the patients prolactin level is measured 10 to 20 minutes after a suspected seizure event. Analysis of the serum prolactin level is not effective in distinguishing a seizure from syncope. No conclusion could be established regarding serum prolactin changes following status epilepticus, repetitive seizures, and neonatal seizures.

## Electrocardiogram
An ECG in patients presenting with seizure is very crucial to prevent sudden unexpected death in epilepsy (SUDEP). Important signs to look for are, ST depression, T wave inversion, heart block, prolonged QT interval, Brugada Syndrome.

## X-ray
There are no x-ray findings associated with a seizure. CT scan and MRI are superior to x-ray for imaging findings associated with seizures.

## Echocardiography and Ultrasound
There are no echocardiography/ultrasound findings associated with seizures. However, an echocardiogram may be helpful in preventing sudden unexpected death in epilepsy (SUDEP) by looking for any functional or structural abnormality of the heart.

## CT
Computed tomography scan (CT scan) in the emergency department is helpful in ruling out hemorrhage or other lesions.

## MRI
MRI scan (preferably 3 teslas) should be performed in order to detect epileptogenic lesions. MRI is more sensitive in detecting some findings related to seizures such as hippocampal sclerosis and cortical dysplasia.

## Other Imaging Findings
3-T MRI may be helpful in patients with epilepsy and negative 1.5-T MRI.

## Other Diagnostic Studies
EEG with sleep deprivation is helpful when standard EEG does not detect any epileptiform changes. Lumbar puncture (LP) should be considered in those patients suspected of meningitis, encephalitis, subarachnoid hemorrhage.

# Treatment

## Medical Therapy
In the acute setting, seizures are initially treated with benzodiazepines (lorazepam or midazolam), followed by phenytoin or phenobarbitalAntiepileptic drugs (AEDs) are commonly used in treating focal and generalized epilepsies.

## Surgery
Surgery may be helpful in patients with focal epilepsy if there is no seizure control after two or more antiepileptic drugs (AEDs).
Laser interstitial thermal ablation and neurostimulation may be helpful as alternative therapies to surgery in some patients.

## Primary Prevention
Some of the preventable etiologies for epilepsy that should be considered in primary prevention include central nervous system (CNS) infection, CNS parasitosis, prenatal and perinatal brain insults, stroke, and traumatic brain injury (TBI). Factors that can precipitate or provoke seizure may include chronic sleep deprivation, alcohol use, illicit drug use, some medications that reduce the seizure threshold, toxins, homeostasis abnormalities due to organ failure, metabolic abnormalities, and medical and surgical histories that may be important in assessing the patients risk for future seizures.

## Secondary Prevention
Patients that have had a first seizure should be counseled for their seizure episode and the possible etiology, lifestyle modifications (safety measures and avoidance of the factors that can lower the seizure threshold and predispose to recurrences, such as sleep deprivation, use of alcohol, and illicit drugs), driving, antiepileptic drugs (AED) and their side effects, and follow-up. Patients, family members, friends, and co-workers should be counseled for seizure first aid during a seizure event such as removal of harmful objects, repositioning the patient in order to support breathing, timing the seizure, calling for help, not restraining or holding the patient down, and not putting anything in the patient's mouth.

## Cost-Effectiveness of Therapy
The national economical impact of epilepsy is estimated at $9.6 billion per year in the United States.

## Future or Investigational Therapies
Further studies are required for producing new drugs with novel mechanisms of action and finding new treatments by increasing the knowledge of the mechanisms of dietary therapy in epilepsy and the role that neurosteroid hormones have in exacerbating epilepsy.