Seizure

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

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 patient’s 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.

The term ‘seizure’ is derived from a Greek word that means ‘to take hold’. Epilepsy was first described by Hippocrates in Ancient Greece (460–377 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.

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.

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.

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.

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).

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 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 patient’s risk for future seizures.

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.

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.

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.

The main part of the seizure history should be about the patient’s awareness, experience, and remembrance of the seizure. Symptoms of seizure include, aura, staring spells, myoclonic jerks, impaired awareness, paresthesias, lost of consciousness, Déjà vu experiences and confusion.

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.

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 patient’s 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.

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.

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.

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.

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

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.

3-T MRI may be helpful in patients with epilepsy and negative 1.5-T MRI.

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.

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 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.

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 patient’s risk for future seizures.

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.

The national economical impact of epilepsy is estimated at $9.6 billion per year in the United States.

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.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

The term ‘seizure’ is derived from a Greek word that means ‘to take hold’. Epilepsy was first described by Hippocrates in Ancient Greece (460–377 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.

• The term ‘seizure’ is derived from a Greek word that means ‘to take hold’.
• Different words have been used interchangeably in historical texts, such as epilepsy, epileptic seizure, attack, or convulsion.^[1]
• Epilepsy has been mentioned in many documents and texts throughout history including:^{[2][3][4][5][6]}
  • Babylonians (2000 years B.C)
  • Egyptians (1700 years B.C.)
  • Greeks (5–4th century B.C.)
  • Indian (Ayurveda)
  • Iranian (Avicenna)
  • Chinese
• Epilepsy was first described by Hippocrates in Ancient Greece (460–377 B.C.).^[6]
• 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. Tissot.^[6]
• In the 19th century, with the emphasis on classification, etiology, pathophysiology, and localization the understanding of epilepsy increased.
  • Electroencephalography (EEG) started to gain attention in the late 19th century.^[6]
• In the 20th century, rapid development in medical knowledge happened.^[6]
  • Brain computed tomography (CT) in the 1970’s^[7]
  • Brain magnetic resonance imaging (MRI) in the 1980’s
  • PET scan (positron emission tomography)

For more information about the historical perspective of epilepsy, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

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.

In 2017, the International League Against Epilepsy (ILAE) classified seizures by their onsets as:^[1][2]

• Focal (aware/impaired awareness)
  • Motor
    • Automatisms
    • Atonic
    • Clonic
    • Epileptic spasm
    • Hyperkinetic
    • Myoclonic
    • Tonic
  • Nonmotor
    • Autonomic
    • Behavior arrest
    • Cognitive
    • Emotional
    • Sensory
  • Focal to bilateral tonic-clonic seizures
• Generalized
  • Motor
    • Tonic-clonic
    • Clonic
    • Tonic
    • Myoclonic
    • Myoclonic-tonic-clonic
    • Myoclonic-atonic
    • Atonia
    • Epileptic spasm
  • Nonmotor (absence)
    • Typical
    • Atypical
    • Myoclonic
    • Eyelid myoclonia
• Unknown
  • Motor
    • Tonic-clonic
    • Epileptic Spasm
  • Nonmotor
    • Behavior arrest
  • Unclassified

In 1981, the International League Against Epilepsy (ILAE) classified epileptic seizures as:^[2][3]

• Partial seizures (focal, local)
  • Simple partial seizures – consciousness is not impaired
  • Complex partial seizures – consciousness is impaired (temporal lobe or psychomotor seizures)
  • Partial seizures evolving to secondarily generalized seizures
• Generalized seizures – initial involvement of both hemispheres, consciousness may be impaired
  • Absence seizures
  • Myoclonic seizures
  • Clonic seizures
  • Tonic seizures
  • Tonic-clonic seizures (Grand mal)
  • Atonic seizures
• Unclassified epileptic seizures

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

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.

Normally, seizures do not occur because the membrane stability of neurons is maintained, and the discharges that lead to seizures are prevented from transferring.^[1]

In a normal brain, some circumstances can provoke seizures, such as:^[1]

• Hyponatremia: Disrupion in electrochemical gradients across cell membranes causse instability.
• Drug withdrawal: Benzodiazepines, barbiturates, and alcohol may sensitize inhibitory GABAA receptors and stimulate a seizure.
• Hypoglycemia: Causes changes in the metabolism of cells.

Abnormalities in different parts of the nervous system may cause seizure, such as:^[1]

• Brain regions
• Cells
• Ions
• Networks
• Receptors

For example:

• Generalized tonic-clonic seizures is caused by abnormalities of the sodium channels or calcium channels.^[2]
• Autosomal dominant nocturnal frontal lobe epilepsy is caused by mutations in the acetylcholine receptor.^[3]
• The most common form of temporal lobe epilepsy is caused by abnormalities of cellular growth in that region.^[4]
• Local brain malformations cause abnormal networks of cells.^[5]

Pathophysiology of generalized tonic-clonic seizures

• Generalized tonic-clonic seizure initiates with an excessive excitation of neurons, leading to synchronous discharges of more neurons, and affects a part of the brain that causes the clinical signs and symptoms of the seizure.
• An imbalance in excessive excitation and reduced inhibition causes and maintains a seizure.^[6]

N-methyl-D-aspartate (NMDA) Receptor

• Glutamate is the most common neurotransmitter that causes excitation.^[7]
• Glutamate excitation effects are by the N-methyl-D-aspartate (NMDA) receptor.
• However, NMDA antagonist drugs have not been clinically successful, probably due to their effects on learning and memory.

Gamma aminobutyric acid (GABA) Receptor

• Gamma-aminobutyric acid (GABA) is the most common neurotransmitter that causes inhibition.^[6]
• In normal circumstances, 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, probably due to upregulation of GABA receptors or changes in receptor sensitivity.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Some medications produce an increased risk of seizures and electroconvulsive therapy (ECT) deliberately sets out to induce a seizure for the treatment of major depression. Many seizures have unknown causes. Seizures that are provoked are not associated with epilepsy, and people who experience such seizures are normally not diagnosed with epilepsy. However, the seizures described above resemble those of epilepsy both outwardly, and on EEG testing. Seizures can occur after a subject witnesses a traumatic event. This type of seizure is known as a psychogenic non-epileptic seizure and is related to post-traumatic stress disorder. A seizure trigger is a factor that can cause a seizure in a person who either has epilepsy or does not. There are many known causes of seizures, and in some patients, it is possible to determine what triggers seizures in general or has led to the onset of a particular seizure. But the factors that lead to a seizure are often so complex that it is not usually possible in all patients to determine what causes a particular seizure, what causes it to happen at a particular time, or how often seizures occur.^[1]

• Brain damage from prenatal or perinatal injuries
• Congenital abnormalities or genetic conditions with associated brain malformations
• A severe blow to the head
• A stroke that starves the brain of oxygen
• An infection of the brain such as meningitis, encephalitis, neurocysticercosis
• Certain genetic syndromes
• A brain tumor

• Hypoxia
• Metabolic abnormalities
• Infection
• Cerebrovascular etiologies
• Drug effects, withdrawal, intoxication
• Hypoxic-ischemic encephalopathy
• Febrile seizures in children
• Structural lesions
• Inborn errors of metabolism

• Disorders of sugar metabolism
• Organic acidemias
• Glycogen storage diseases
• Disorders of amino acid metabolism
• Urea cycle disorders
• Peroxisomal disorders
• Mitochondrial disorders
• Rasmussen’s encephalitis

Unprovoked seizures are often associated with epilepsy and related seizure disorders.

• Arteriovenous malformation (AVM) is a treatable medical condition that can cause seizures, headaches, and brain hemorrhages. An MRI can quickly confirm or reject this as a cause.
• Head injury
• Intoxication with drugs
• Drug toxicity, for example aminophylline or local anesthetics
• Normal doses of certain drugs that lower the seizure threshold, such as tricyclic antidepressants
• Infection, such as encephalitis or meningitis
• Fever leading to febrile convulsions (but see above)
• Metabolic disturbances, such as hypoglycaemia, hyponatremia or hypoxia
• Withdrawal from drugs (anticonvulsants and sedatives such as alcohol, barbiturates, and benzodiazepines)
• Space-occupying lesions in the brain (abscesses, tumors)
• Seizures during (or shortly after) pregnancy can be a sign of eclampsia.
• Binaural beat brainwave entrainment may trigger seizures in both epileptics and non-epileptics
• Stroke may cause seizures, with embolic strokes more likely to present with seizures; cerebral venous sinus thrombosis, a rare type of stroke, is more likely to be accompanied by seizures than other types of stroke
• Multiple sclerosis sufferers may rarely experience seizures

There are varying opinions on the likelihood of alcoholic beverages triggering a seizure. Consuming alcohol may temporarily reduce the likelihood of a seizure immediately following consumption. But after the blood alcohol content has dropped, chances may increase. This may occur, even in non-epileptics.^[2]

Heavy drinking in particular has been shown to possibly have some effect on seizures in epileptics. But studies have not found light drinking to increase the likelihood of having a seizure at all. EEGs taken of patients immediately following light alcohol consumption have not revealed any increase in seizure activity.^[3]

Consuming alcohol with food is less likely to trigger a seizure than consuming it without.^[4]

Consuming alcohol while using many anticonvulsants may reduce the likelihood of the medication working properly. In some cases, it may actually trigger a seizure. Depending on the medication, the effects vary.^[5]

Alcohol withdrawal is also responsible for seizures. This risk increases with each additional drink from which one has withdrawn.^[6]

Caffeine use can increase the occurrence of seizures, particularly if it interrupts normal sleep patterns.

Diet can play a role in a seizure occurring, and therefore, diet control in some cases can be used to prevent seizures.^[7] It is not known exactly what nutrients or lack thereof may contribute to or prevent a seizure. However, the ketogenic diet is practiced by some in order to control seizures.

Those with various medical conditions may suffer seizures as one of their symptoms. These include:

• Arteriovenous malformation
• Brain abscess
• Brain tumor
• Cavernoma
• Eclampsia
• Encephalitis
• Meningitis
• Multiple sclerosis
• Systemic lupus erythematosus

Some drugs may lower the seizure threshold when used doses intended for recreation. Drugs such as tramadol and methamphetamine have been noted to induce seizures in some, especially when used for long periods of time or in combination with other stimulants. Some drugs may reduce the risk of a seizure occurring. Withdrawals from drugs that act on the GABA receptors may lead to grand-mal seizures in people who have been heavily abusing drugs from the barbiturate or benzodiazepine families.

In children under the age of 5, fever of 102°F (39°C) or higher can lead to a seizure (usually tonic-clonic) known as a febrile seizure.

About 2-5% of all children will experience such a seizure during their childhood. Most of these children will also have some pre-existing neurological problem.^[8]

In most cases, a febrile seizure will not lead to epilepsy. But 30-40% of children who experience a febrile seizure will have more seizures in the future.^[9]

In adults and older children with epilepsy, illnesses with fever can be responsible for a seizure due to the stress that they cause. Additionally, in some patients, gastroenteritis, which causes vomiting and diarrhea, can lead to diminished absorption of anticonvulsants, thereby reducing protection against seizures.^[10]

^[11]

In some epileptics, flickering or flashing lights, such as strobe lights, can be responsible for the onset of a tonic clonic, absence, or myoclonic seizure.^[12] This condition is known as photosensitive epilepsy, and in some cases, the seizures can be triggered by activities that are harmless to others, such as watching television or playing video games, or by driving or riding during daylight along a road with spaced trees, thereby simulating the “flashing light” effect. Some people can suffer a seizure as a result of blinking one’s own eyes.^[13] Contrary to popular belief, this form of epilepsy is relatively uncommon, accounting for just 3% of all cases.^[14] In all other epileptics, such lights are no more capable of triggering a seizure than in a non-epileptic person.

A routine part of the EEG test involves exposing the patient to flickering lights in order to attempt to induce a seizure, to determine if such lights may be triggering a seizure in the patient, and to be able to read the wavelengths when such a seizure occurs.^[15]

A severe head injury, such as one suffered in a motor vehicle accident, fall, assault, or sports injury, can result in one or more seizures that can occur immediately after the fact or up to a significant amount of time later.^[16][17] This could be hours, days, or even years following the injury.

A brain injury can cause seizure(s) because of the unusual amount of energy that is discharged across of the brain when the injury occurs and thereafter. When there is damage to the temporal lobe of the brain, there is a disruption of the supply of oxygen.^[18]

The risk of seizure(s) from a closed head injury is about 15%.^[19] In some cases, a patient who has suffered a head injury is given anticonvulsants, even if no seizures have occurred, as a precaution to prevent them in the future.^[20]

See Catamenial epilepsy

Seizures may be a side effect of certain drugs, though with most, the effect is quite rare, and for most patients, they are safe. These include:^[21]

• Aminophylline
• Bupivicaine
• Bupropion
• Butyrophenones
• Chlorambucil
• Clozapine
• Enfluraneketamine
• Estrogen
• Fentanyl
• Insulin
• Lidocaine
• Meperidine
• Pentazocine
• Phenothiazines
• Prednisone
• Procaine
• Propoxyphene
• Theophylline
• Tramadol
• Tricyclic antidepressant
• The following antibiotics: Isoniazid, Lindane, Metronidazole, Nalidixic acid, and Penicillin, though Vitamin B6 taken along with them may prevent seizures
• Vitamin B1 deficiency (Thiamine deficiency) was reported to cause seizures, especially in alcoholics ^[22][23][24]
• Vitamin B12 depletion (Pyridoxine deficiency) was reported to be associated with pyridoxine-dependent seizures.^[25]
• Folic acid in large amounts was considered that might counteract the antiseizure effects of antiepileptic drugs and increase the seizure frequency in some children, although that concern is no longer held by epileptologists.^[26]

Sudden withdrawal from anticonvulsants may lead to seizures. It is for this reason that if a patient’s medication is changed, the patient will be weaned from the medication being discontinued following the start of a new medication.

Use of certain street drugs may also lead to seizures. These include amphetamines, cocaine, methylphenidate, and phenylpropanolamine (not all of the drugs pictured).^[27]

If treated with the wrong kind medication antiepileptic drugs (AED), seizures may increase, as most AEDs are developed to treat a particular type of seizure.

A missed dose or incorrectly timed dose of an anticonvulsant may be responsible for a breakthrough seizure, even if the patient has often missed doses in the past, and has not suffered a seizure as a result of the missed dose.^[28] Missed doses are one of the most common reasons for a breakthrough seizure. Even a single missed dose is capable of triggering a seizure in some patients.^[29] This is true, even when the patient has not suffered a seizure after previously missing much more of his/her medication. Doubling the next dose does not necessarily help.

Missed doses can occur as a result of the patient’s forgetfulness, unplanned lack of access to the medication, difficulty in affording the medication, or self-rationing of the medication when one’s supply is low, among other causes.

Sleep deprivation is the second most common trigger of seizures.^[30] In some cases, it has been responsible for the only seizure a person ever suffers.^[31] However, the reason for which sleep deprivation can trigger a seizure is unknown. One possible thought is that the amount of sleep one gets affects the amount of electrical activity in one’s brain.^[32]

Patients who are scheduled for an EEG test are asked to deprive themselves of some sleep the night before in order to be able to determine if sleep deprivation may be responsible for seizures.^[33]

In some cases, patients with epilepsy are advised to sleep 6-7 consecutive hours as opposed to broken-up sleep (e.g. 6 hours at night and a 2-hour nap) and to avoid caffeine and sleeping pills in order to prevent seizures.^[34]

In one study, emotional stress was reported by 30-60% prior to their seizures, thereby being the leading cause.^[35] This may include stress over hard work one is trying to accomplish, one’s obligations in life, worries, emotional problems, frustration, anger, anxiety, or many other problems.^[36]

Stress may trigger a seizure because it affects the hormone cortisol. Stress can also affect the part of the brain that regulates emotion.^[37][38] Although stress can alter levels of these hormones, it remains unclear whether or not stress can directly result in an increase in seizure frequency.

Cardiovascular	Arrhythmia, Arteriovenous malformation, Birth hypoxia, Heart failure, Congenital heart disease, Hypertensive encephalopathy, Hypotension, Hypovolemia, Hypoxia, Hypoxic encephalopathy, Hypoxic-ischemic encephalopathy, Malignant hypertension, Orthostatic hypotension, Perinatal hypoxia, Romano-Ward syndrome, Takayasu arteritis, Thrombophlebitis, Thrombosis, Valvular heart disease, Vein of Galen malformation, Vertebrobasilar dolichoectasia
Chemical/Poisoning	Alcohol withdrawal, Benzene hexachloride, Carbon monoxide toxicity, Carbon tetrachloride, Chemicals, Cyanides, Lead poisoning, Water hemlock poisoning
Dental	No underlying causes
Dermatologic	Aicardi Goutieres syndrome, Epidermal nevus syndrome, Incontinentia pigmenti achromians, Incontinentia pigmenti (Bloch Sulzberger syndrome), Linear sebaceous nevus, Neurocutaneous syndromes, Neurofibromatosis type 1, Oculocerebrocutaneous syndrome, Rhinophyma, Zunich neuroectodermal syndrome
Drug Side Effect	4-Aminopyridine, Acetaminophen and Oxycodone, Acyclovir, Almotriptan, Alprazolam, Amifampridine, Aminophylline, Amitriptyline, Amoxapine, Amoxicillin, Amphetamine, Amphotericin B, Ampicillin, Anticholinergics, Antihistamines, Antimalarials, Arabinoside, Aripiprazole, Articaine, Atenolol, Atomoxetine, Atorvastatin, Azathioprine, Aztreonam, Baclofen, Benztropine, Beractant, Bicuculline, bicisate dihydrochloride,Bromocriptine, Bupivacaine, Bupropion, Buspirone, Busulfan, Butyrophenones, Cabergoline, Caffeine, Captopril, Carbenicillin, Carmustine, Carisoprodol, Carvedilol, caspofungin acetate, Cefepime, Cefotetan disodium, Ceftazidime, Cefixime, Cefotetan, cefoxitin sodium, Ceftazidime, Cefuroxime, Cephalexin, Cephalosporins, Cefaclor, Ceritinib, Chlorambucil, Chloroquine, Chlorpromazine, Cidofovir, Cilastatin/imipenem, Cinacalcet, Ciprofloxacin, Cisplatin, Citalopram,Cyclopentolate, Clomiphene, Clomipramine, Clonazepam, Clorazepate, Clozapine, Cocaine, cortisone, Cyclobenzaprine, Cyclophosphamide, Cycloserine, Cyclosporin, Cyclosporine, Cysteamine , Cytosine, Cytarabine, Cytarabine liposome, cytomegalovirus immune globulin Dalfampridine, Dantrolene, Desipramine, Desmopressin, Dexamethasone, Dexmethylphenidate, Dextroamphetamine, Diazepam, Dicyclomine, Diphenhydramine, Disopyramide, Domperidone, Donepezil, Doripenem, Dothiepin, Doxepin, Doxorubicin Hydrochloride, Dronabinol, Duloxetine, Efavirenz, Enflurane, Entacapone, Enflurane, Enzalutamide, Ketamine, Ephedrine, Epoetin, Ergonovine, Erythropoietin, Escitalopram, Estazolam, Eszopiclone, Etoposide, Fentanyl, Flumazenil, Fluvoxamine, Fluoxetine, Fluphenazine, Flurazepam, Fluvastatin, Folinic acid, Foscarnet, Gabapentin, Gamma hydroxybutyrate, Ganciclovir, Gemifloxacin, Ginkgo biloba, Glatiramer, Glycerol phenylbutyrate,Goserelin, Haloperidol, Histrelin, Hydroxyzine, ibuprofen lysine, Iloperidone,Imipenem-Cilastatin, Indomethacin, Insulin, Interferon beta-1a, Interferon beta-1b, Interferon gamma, Iodixanol,Ioxilan, Isoniazid, Isotretinoin, Ivermectin, Ketamine, Ketorolac, levetiracetam, Levocarnitine, Levofloxacin, Lidocaine, Lindane, Linezolid, Lithium, Local anesthetics, Lomefloxacin, Lorazepam, Loxapine, Maprotiline, Mefenamic acid, Mefloquine, Megestrol, Memantine, Meperidine, Mephobarbital, Meropenem, Methocarbamol, Methohexital, Methotrexate, Methoxy polyethylene glycol-epoetin beta, Methylphenidate, Methylprednisolone, Methylxanthines, Metoclopramide, Metronidazole, Mexiletine, Mianserin, Minocycline hydrochloride, Mirtazapine, Mitoxantrone, miltefosine, Modafinil, Molindone, Montelukast, Moxifloxacin, Muromonab-CD3, Mycophenolate, Nabilone, Nalidixic acid, Nelarabine, Nikethamide, Nomifensine, Norfloxacin, Nortriptyline, Ofloxacin,Omacetaxine, Olanzapine, Ondansetron, Oxacillin, Oxaprozin, Oxcarbazepine, Oxybutynin, Oxycodone, Oxymorphone, Oxytocin, Paroxetine, Paregoric, Penicillins, Pentamidine Isethionate, Pentazocine, Pergolide, Perphenazine, Phencyclidine, Phenobarbital, *Peginterferon Beta-1a,permethrin,Phenothiazines, Phenylpropanolamine, Pimozide, Piperacillin, Pramipexole, Praziquantel, Prednisone, Primidone, Procainamide, Procaine, Promethazine, Propoxyphene, Propranolol, Protriptyline, Prochlorperazine, Pyrimethamine, Quetiapine, Ramelteon, Rasagiline, Reye’s Syndrome, Risperidone, Rivastigmine, Ropinirole, Selegiline, Serotonin reuptake inhibitors, Sertraline, Sibutramine, Sildenafil, Sodium oxydate, Sodium oxybate, Sodium sulfate, potassium sulfate and magnesium sulfate Strychnine, Sumatriptan, Sulfasalazine, Tacrine, Tacrolimus, Tadalafil, Terbutaline, Temazepam, Temozolomide, Terbutaline, Thalidomide, Thebaine, Theophylline, Thioridazine, Thiothixene, Tiagabine, Ticarcillin, Ticlopidine, Tinidazole, Tizanidine, Tolcapone, Tolterodine, Torsemide, Tramadol, Tranylcypromine, Triazolam, Tricyclic antidepressants, Trifluoperazine, Trihexyphenidyl, Valacyclovir, Valsartan, Vardenafil, Venlafaxine, Verapamil, Vincristine, Zaleplon, Zanamivir, Ziconotide, Zidovudine, Ziprasidone, Zolpidem
Ear Nose Throat	Rhinophyma
Endocrine	Barakat syndrome, Dysmorphism-hypogonadism-diabetes complex, Estrogen, Hyperglycemia, Hyperthyroidism, Hypoglycemia, Hypoparathyroidism, Hypothalamic-pituitary insufficiency, Hypothyroidism, KCNJ11-related permanent neonatal diabetes, Metabolic encephalopathy, Neonatal hypoglycemia, Neurocutaneous syndromes
Environmental	No underlying causes
Gastroenterologic	Alveolar Hydatid Disease, Hepatic failure
Genetic	17-beta-hydroxysteroid dehydrogenase X deficiency, 2-Hydroxyglutaricaciduria, 2-methylbutyryl-coenzyme A dehydrogenase deficiency, 22Q11 microdeletion, 6-Pyruvoyl tetrahydropterin synthase deficiency, Adenylosuccinate lyase deficiency, ADNFLE mutation, Aicardi Goutieres syndrome, Alexander disease, Alpha-L-iduronidase deficiency, Alpha-methylacyl-CoA racemase deficiency, Aminomethyltransferase deficiency, Angelman syndrome, Arginase deficiency, Arginine:glycine amidinotransferase deficiency, Arginosuccinate synthetase deficiency, ARX (Aristaless-related homeobox) mutations, Athabaskan brain stem dysgenesis, ATP6V0A2-related cutis laxa, Autosomal dominant lateral temporal epilepsy (ADLTE), Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), Barakat syndrome, Benign familial infantile convulsions, Benign familial infantile epilepsy, Benign familial neonatal convulsions, Benign familial neonatal seizure, Benign familial neonatal seizures, Benign infantile familial convulsions, Benign neonatal convulsions, Benign neonatal epilepsy, Benign partial epilepsy in infancy, Bifunctional peroxisomal enzyme deficiency, CADASIL syndrome, Carbamoylphosphate synthetase deficiency, Carbohydrate deficiency glycoprotein syndrome, Carnitine-acylcarnitine translocase deficiency, Cerebral dysgenesis associated with inborn errors of metabolism, Christianson syndrome, Chromosome 12p tetrasomy syndrome, Chromosome 14 ring syndrome, Chromosome 15q triplication syndrome, Chromosome 15q13.3 microdeletion syndrome, Chromosome 17q21.31 deletion syndrome, Chromosome 20 ring syndrome, Chromosome 4p trisomy, Chromosome 7q deletion syndrome, Chromosome 9q deletion syndrome, CK syndrome, Combined malonic and methylmalonic aciduria, Cystathionine beta-synthase deficiency, D-2-hydroxyglutarate dehydrogenase deficiency, D-glycerate kinase deficiency, DEND syndrome, Dihydropteridine reductase deficiency, Dihydropyrimidine dehydrogenase deficiency, Diomedi-Bernardi-Placidi syndrome, Down’s Syndrome, EBN1 mutation, EBN2 mutation, Familial Encephalopathy with neuroserpin inclusion bodies, Familial Febrile Convulsions, Familial infantile convulsions/paroxysmal choreoathetosis, Familial porencephaly, Fructose-1-phosphate aldolase deficiency, Fucosidosis, Fukuyama congenital muscular dystrophy, Fukuyama type muscular dystrophy, Fumarate hydratase deficiency, Galactosialidosis, Gamma-aminobutyrate transaminase deficiency, Gangliosidosis, Gaucher’s Disease, GEFS+ mutation, Generalized epilepsy with febrile seizures plus, Glutamate decarboxylase deficiency, Glutathione synthase deficiency, Glycerol kinase deficiency, Glycine decarboxylase deficiency, Glycogen storage diseases, Griscelli syndrome type 2, Guanidinoacetate methyltransferase deficiency, Hartnup disease, Huntington’s Chorea, Hydroxyacyl-coa dehydrogenase deficiency, Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome, Incontinentia pigmenti achromians, Infant epilepsy with migrant focal crisis, Infantile neuroaxonal dystrophy, Infantile-onset spinocerebellar ataxia, KCNJ11-related permanent neonatal diabetes, L-2-hydroxyglutarate dehydrogenase deficiency, LAMA2-related muscular dystrophy, Malonyl-CoA decarboxylase deficiency, Maple syrup urine disease, MELAS syndrome, MERRF syndrome, Methionine malabsorption, Methylenetetrahydrofolate reductase deficiency, Microcephaly-mental retardation-spasticity-epilepsy complex, Microcephaly-pontocerebellar hypoplasia-dyskinesia complex, Microphthalmia-dermal aplasia-sclerocornea syndrome, Migrating partial seizures of infancy, Mitochondrial aspartyl-tRNA synthetase deficiency, Mitochondrial complex III deficiency, Mitochondrial DNA depletion syndrome, Monosomy 1p36 syndrome, Mucolipidosis II alpha/beta, Neurocutaneous syndromes, Neuroectodermal melanolysosomal disease, Neurofibromatosis type 1, Nonketotic hyperglycemia, Oculocerebrocutaneous syndrome, OFD syndrome type IX, Ohtahara syndrome, Onychodystrophy, Ornithine carbamyltransferase deficiency, Organic acidemia, Pantothenate kinase associated neurodegeneration, Partington X-linked mental retardation, PEHO syndrome, Peroxisomal acyl-CoA oxidase deficiency, Peroxisomal disorders, Phenylketonuria, Phosphoethanolaminuria, Porphobilinogen synthase deficiency, Pyridoxine-5′-phosphate oxidase deficiency, Pyruvate carboxylase deficiency, Pyruvate dehydrogenase deficiency, Ramon syndrome, Recessive deafness-onychodystrophy-osteodystrophy-retardation syndrome, Rhizomelic chondrodysplasia punctata, Romano-Ward syndrome, Rubinstein-Taybi syndrome, Rud syndrome, Salla disease, Sandhoff disease, Sanjad-Sakati syndrome, Schaefer-Stein-Oshman syndrome, SeSAME syndrome, Short chain acyl-CoA dehydrogenase, Sialidosis type 1, Sickle cell crisis, Sjogren-Larsson syndrome, Sphingomyelinase deficiency, Spinocerebellar ataxia 13, Sturge-Weber syndrome, Succinic semialdehyde dehydrogenase deficiency, Succinyl-CoA synthetase deficiency, Tuberous sclerosis, Tyrosinaemia type 2, Unverricht-Lundborg syndrome, Urea cycle disorders, Von Hippel-Lindau Syndrome, X-linked Hamel type Neurodegenerative syndrome, X-linked Hypoparathyroidism, X-linked inherited conditions, X-linked Lissencephaly, X-linked mental retardation, X-linked Mental retardation syndromic due to JARID1C mutation, X-linked periventricular heterotopia, X-linked Wittwer type Mental retardation, Zellweger spectrum, Zunich neuroectodermal syndrome
Hematologic	Acute intermittent porphyria, Chester porphyria, Porphyria, Thrombotic thrombocytopenic purpura
Iatrogenic	Aqueous iodinated contrast agents, DTP vaccine, Extracorporeal membrane oxygenation, Hyperbaric oxygen, MMR vaccine
Infectious Disease	Acute disseminated encephalomyelitis, Alveolar Hydatid Disease, Ascariasis, Brain abscess, Central nervous system infection, Cysticercosis, Cytomegalovirus, Encephalitis, German measles, HIV, Intracranial abscess or granuloma, Malaria, Viral meningitis, Meningitis, Meningoencephalitis, Neurocysticercosis, Neurosyphilis, Paragonimiasis, Rabies, Ramsay Hunt syndrome, Schistosoma japonicum, Schistosomiasis, Syphilis, TORCH syndromes, Toxoplasmosis, Trypanosomiasis
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	Absence seizure, Acute disseminated encephalomyelitis, Acute neonatal encephalopathy, Aicardi Goutieres syndrome, Alexander disease, Alpers disease, Alveolar Hydatid Disease, Alzheimer’s Disease, Arterial ischemic stroke, Arteriovenous malformation, Astrocytoma, Athabaskan brain stem dysgenesis, Atonic seizure, Autonomic seizure, Autosomal dominant lateral temporal epilepsy (ADLTE), Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), Barakat syndrome, Battaglia Neri syndrome, Belgian type mental retardation, Belgian type Mental retardation syndrome, Benign childhood epilepsy with centrotemporal spikes, Benign childhood occipital seizures, Benign familial infantile convulsions, Benign familial infantile epilepsy, Benign familial neonatal convulsions, Benign familial neonatal seizure, Benign familial neonatal seizures, Benign infantile familial convulsions, Benign neonatal convulsions, Benign neonatal epilepsy, Benign partial epilepsy in infancy, Benign occipital epilepsy of childhood (Gastaut syndrome), Benign Rolandic epilepsy, Borjeson-Forssman-Lehmann syndrome, Brachydactyly-mental retardation syndrome, Brain abscess, Brain cancer, Brain hemorrhage, Brain injury, CADASIL syndrome, Carotid Sinus Syndrome, Catamenial epilepsy, Cavernoma, Cavernous haemangioma, Central nervous system infection, Cerebellar dyssynergia, Cerebral Aneurysm, Cerebral dysgenesis, Cerebral dysgenesis associated with inborn errors of metabolism, Cerebral infarction, Cerebral Palsy, Cerebral venous sinus thrombosis, Cerebrovascular disease, Ceroid lipofuscinosis, Christianson syndrome, Clonic seizures, Concussion, Congenital muscular dystrophy, Coproporphyria, Cornelia de Lange syndrome 2, Corpus callosum hypoplasia, Cortical dysplasia, Craniodiaphyseal dysplasia, Craniofacial dysmorphism-polysyndactyly syndrome, Creatine deficiency syndrome, Creutzfeldt-Jakob Disease, Crome syndrome, Dandy-Walker syndrome, Deafness-congenital onychodystrophy, Degenerative disease, Dementia, DEND syndrome, Dentatorubropallidoluysian degeneration, Double cortex syndrome, Down’s Syndrome, Dyke-Davidoff-Masson syndrome, Dysmorphism-hypogonadism-diabetes complex, Early infantile epileptic encephalopathy, Early myoclonic encephalopathy, East Syndrome, Eclampsia, Embolism, Encephalitis, Epidermal nevus syndrome, Epidural haemorrhage, Epilepsy-mental deterioration, Epilepsy-microcephaly-skeletal dysplasia, Epileptic encephalopathy, Episodic ataxia, Familial Encephalopathy with neuroserpin inclusion bodies, Familial Febrile Convulsions, Familial infantile convulsions/paroxysmal choreoathetosis, Familial porencephaly, Fat embolism, Fatty acid hydroxylase-associated neurodegeneration, Febrile convulsion, Febrile Seizures, Febrile seizures in children, Feigenbaum-Bergeron-Richardson syndrome, Flynn-Aird syndrome, Focal cortical dysplasia, Folate malabsorption, Fryns-Aftimos syndrome, Fukuyama congenital muscular dystrophy, Fukuyama type muscular dystrophy, Fumarate hydratase deficiency, Galactosialidosis, Gamma-aminobutyrate transaminase deficiency, Gangliosidosis, Gaucher’s Disease, Giant axonal neuropathy, Gurrieri-Sammito-Bellussi syndrome, Haw River syndrome, Head injury, Head trauma, Heat stroke, Hemimegalencephaly, Hippocampal sclerosis, Hirschsprung disease-microcephaly-mental retardation syndrome, Huntington’s Chorea, Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome, Incontinentia pigmenti achromians, Incontinentia pigmenti (Bloch Sulzberger syndrome), Infant epilepsy with migrant focal crisis, Infantile neuroaxonal dystrophy, Infantile-onset spinocerebellar ataxia, Intracranial abscess or granuloma, Intracranial hemorrhage, Intracranial space-occupying lesion, Intraventricular hemorrhage, Kernicterus, KCNJ11-related permanent neonatal diabetes, Kohlschutter syndrome, Kohlschutter-Tonz syndrome, Lafora body disease, Landau-Kleffner syndrome, Lennox-Gastaut syndrome, Linear sebaceous nevus, Lipoid proteinosis of Urbach and Wiethe, Lissencephaly, Lissencephaly with cerebellar hypoplasia, McDowall syndrome, McLeod neuroacanthocytosis syndrome, Meningioma, Meningitis, Meningoencephalitis, Metabolic encephalopathy, Microcephaly, Microcephaly-mental retardation-spasticity-epilepsy complex, Microcephaly-pontocerebellar hypoplasia-dyskinesia complex, Microphthalmia-dermal aplasia-sclerocornea syndrome, Migrating partial seizures of infancy, Migraine, Miller-Dieker syndrome, Movement disorders, Mowat-Wilson syndrome, Multiple sclerosis, Muscle-eye-brain disease, Myoclonic progressive familial epilepsy, Myoclonus progressive epilepsy of Unverricht and Lundborg, Nasu-Hakola disease, Navajo neurohepatopathy, Neurocutaneous syndromes, Neurocysticercosis, Neurodegenerative disorders, Neurodevelopmental lesions, Neuroectodermal melanolysosomal disease, Neurofibromatosis type 1, Neurosyphilis, Nicolaides-Baraitser syndrome, Nocturnal frontal lobe epilepsy, Oculocerebrocutaneous syndrome, Panayiotopoulos syndrome, Paraneoplastic limbic encephalitis, Paroxysmal dyskinesia, Parry-Romberg syndrome, Perisylvian syndrome, Photosensitive epilepsy, Pick’s Disease, Pitt-Hopkins syndrome, Pontocerebellar hypoplasia type 1, Pontocerebellar hypoplasia type 2a, Pontocerebellar hypoplasia with infantile spinal muscular atrophy, Porencephaly type 1, Posterior leucoencephalopathy syndrome, Presenile dementia, Rasmussen encephalitis, Renier-Gabreels-Jasper syndrome, Retinitis pigmentosa-polyneuropathy-epilepsy complex, Rett syndrome, Reversible posterior leukoencephalopathy syndrome, Schizencephaly, Seemanova-Lesny syndrome, Sinovenous thrombosis, Sotos syndrome, Space occupying lesion of the brain, Spastic tetraplegic, Stokes-Adams Syndrome, Stroke, Structural lesions, Subdural hemorrhage, Subependymal nodular heterotopia, Sudanophilic cerebral sclerosis, Temporal lobe epilepsy, Tonic seizure, Tonic-Clonic seizure, Transient Ischemic Attack, Tuberous sclerosis, Van der Knaap disease, Vasovagal syncope, Vein of Galen malformation, Vertebrobasilar dolichoectasia, Walker-Warburg syndrome, West syndrome, Wittwer sydnrome, Worster-Drought syndrome, Zellweger spectrum, Zunich neuroectodermal syndrome
Nutritional/Metabolic	No underlying causes
Obstetric/Gynecologic	Birth hypoxia, Childbirth trauma, Endometriosis
Oncologic	Astrocytoma, Brain cancer, Cavernoma, Cavernous haemangioma, Meningioma, Paraneoplastic limbic encephalitis, Rubinstein-Taybi syndrome
Ophthalmologic	No underlying causes
Overdose/Toxicity	Aluminium toxicity, Folic acid
Psychiatric	Autism, Panic attack
Pulmonary	Breath-holding spells, Hyperventilation, Respiratory failure
Renal/Electrolyte	Alkalosis, Barakat syndrome, Chronic Renal Failure, Dialysis disequilibrium syndrome, Hypernatremia, Hypocalcemia, Hypomagnesemia, Hyponatremia, Hypophosphatemia, Renal failure, Uremia
Rheumatology/Immunology/Allergy	Aicardi Goutieres syndrome, Lupus erythematosus, Paraneoplastic limbic encephalitis, Polyarteritis nodosa, Rasmussen encephalitis, Takayasu arteritis
Sexual	No underlying causes
Trauma	Childbirth trauma, Concussion, Perinatal trauma, Trauma
Urologic	No underlying causes
Miscellaneous	Asphyxiation, Besnier-Boeck-Schaumann disease, Binaural beat brainwave entrainment, Cholestanol storage disease, Fever, Flickering or flashing lights, Missed dose, Neonatal hypoglycemia, Night terrors, Pediatric apnea, Pellagra, Pyridoxine deficiency, Pyridoxine-dependent epilepsy, Sarcoidosis, Sleep deprivation, Sleep disorders, Stress, Syncope, Vitamin B1 deficiency (Thiamine deficiency), Vitamin B12 depletion (Pyridoxine deficiency), Withdrawal from drugs

• Breakthrough seizure

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Differential diagnosis of epileptic seizures may include: concussion, drug intoxication or withdrawal, migraine, psychogenic nonepileptic events, panic attacks, sleep disorders, syncope, transient global amnesia, and transient ischemic attack (TIA).

Differential diagnosis of epileptic seizures may include:^[1]

• Concussion
• Drug intoxication or withdrawal
• Migraine
• Psychogenic nonepileptic events
• Panic attacks
• Sleep disorders
• Syncope
• Transient global amnesia
• Transient ischemic attack (TIA)

A quick algorithm to differentiate seizure from other causes of altered mental status is demonstrated below:

Clinical presentation

Loss of conscoiusness

No

Yes

• Transient? • Rapid onset? • Short duration? • Spontaneous recovery?

Falls

Altered consciousnes

Yes

No

Coma

Aborted SCD

Others

T-LOC

Non-Traumatic

Traumatic

Syncope

Epileptic seizure

Psychogenic

Rare causes

• Reflex syncope • Orthostatic hypotension • Cardiac syncope

• Tonic • Clonic • Tonic-clonic • Atonic

• Pseudo-epileptic • Pseudo-syncopal

Abbreviations: SCD: Sudden cardiac death;T-LOC: Transient-Loss of consciousness.

The above algorithm adopted from ESC guideline [2]

It can be difficult to distinguish a seizure from other conditions causing a collapse, abnormal movements or other seizure manifestations. A 2007 evidence-based review from the American Academy of Neurology and the American Epilepsy Society recommends an electroencephalogram (EEG, brain wave activity) and brain imaging with CT scan or MRI scan in the work-up of adults presenting with a first apparently unprovoked seizure. Blood tests, lumbar puncture or toxicology screening can be helpful in specific circumstances suggestive of an underlying cause like meningitis or drug overdose, but there is insufficient evidence to support their routine use in the work-up of an adult with an apparently unprovoked first seizure.^[3]

Differentiating a seizure from other conditions such as syncope can be difficult. In addition, 5% of patients with a positive tilt table test may have seizure-like activity that seems to be due to cerebral hypoxia.^[4]

As seizures have a differential diagnosis, it is common for patients to be simultaneously investigated for cardiac and endocrine causes. Checking glucose levels, for example, is a mandatory action in the management of seizures as hypoglycemia may cause seizures, and failure to administer glucose would be harmful to the patient. Other causes typically considered are syncope and cardiac arrhythmias, and occasionally, panic attacks and cataplexy. For more information, see non-epileptic seizures.

Neurosyphilis can present with seizures and must be differentiated from other causes of seizures.^[5]

Diseases	Symptoms				Physical Examination					Past medical history	Diagnostic tests			Other Findings
	Headache	↓LOC	Motor weakness	Abnormal sensory	Motor Deficit	Sensory deficit	Speech difficulty	Gait abnormality	Cranial nerves		CT /MRI	CSF Findings	Gold standard test
Meningitis	+	–	–	–	–	+	+	–	–	History of fever and malaise	–	↑ Leukocytes, ↑ Protein ↓ Glucose	CSF analysis[6]	Fever, neck rigidity
Encephalitis	+	+	+/-	+/-	–	–	+	+/-	+	History of fever and malaise	+	↑ Leukocytes, ↓ Glucose	CSF PCR	Fever, seizures, focal neurologic abnormalities
Brain tumor[7]	+	–	–	–	+	+	+	–	+	Weight loss, fatigue	+	Cancer cells[8]	MRI	Cachexia, gradual progression of symptoms
Hemorrhagic stroke	+	+	+	+	+	+	+	+	–	Hypertension	+	–	CT scan without contrast[9][10]	Neck stiffness
Subdural hemorrhage	+	+	+	+	+	–	–	–	+	Trauma, fall	+	Xanthochromia[11]	CT scan without contrast[9][10]	Confusion, dizziness, nausea, vomiting
Neurosyphilis[12][5]	+	–	+	+	+	+	–	+	–	STIs	+	↑ Leukocytes and protein	CSF VDRL-specifc CSF FTA-Ab -sensitive[13]	Blindness, confusion, depression, Abnormal gait
Complex or atypical migraine	+	–	+	+	–	–	+	–	–	Family history of migraine	–	–	Clinical assesment	Presence of aura, nausea, vomiting
Hypertensive encephalopathy	+	+	–	–	–	–	+	+	–	Hypertension	+	–	Clinical assesment	Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy	–	+	–	–	–	+	+	+	+	History of alcohal abuse	–	–	Clinical assesment and lab findings	Ophthalmoplegia, confusion
CNS abscess	+	+	–	–	+	+	+	–	–	History of drug abuse, endocarditis, immunosupression	+	↑ leukocytes, ↓ glucose and ↑ protien	MRI is more sensitive and specific	High grade fever, fatigue,nausea, vomiting
Drug toxicity	–	+	–	+	+	+	–	+	–	–	–	–	Drug screen test	Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder	+	+	+	+	+	+	+	+		History of emotional stress	–	–	Diagnosis of exclusion	Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia)	–	+	+	+	+	+	–	–	+	–	–	Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia	Depends on the cause	Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation	–	–	+	+	–	+	+	+	+	History of relapses and remissions	+	↑ CSF IgG levels (monoclonal bands)	Clinical assesment and MRI [14]	Blurry vision, urinary incontinence, fatigue
Seizure	+	+	–	–	+	+	–	–	+	Previous history of seizures	–	Mass lesion	Clinical assesment and EEG [15]	Confusion, apathy, irritability,

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

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.

• In the United States, the incidence of acute symptomatic seizures is estimated to be 39 cases per 100,000 individuals.^[1]
• It is estimated that 11% of the population experience a seizure in their life compared to the estimation of 3% for epilepsy.^[2][3]

• In the US, the prevalence of seizure is estimated to be 1 million or 1% of emergency department (ED) visits annually.^[4]

• Status epilepticus occurs in about 6%-7% of the patients with seizure in the ED.^[5][6][7]
• In the United States, the incidence of status epilepticus was estimated between 126,000 to 195,000 patients per year with 22,200 to 42,000 deaths per year.^[8]
• The overall mortality rate of status epilepticus is approximately 22% (3% in pediatric patients to 26% in adults).^[8]

• Acute symptomatic seizures have the highest incidence among infants and small children, followed by those older than 75, and the lowest incidence among those between 25 to 34 years.^[4]
• Infants and children aged 1 to 5 years (mostly due to febrile seizure) followed by adults aged 41 to 50 years make up the most ED visits for seizure.^[4]

• Individuals of the African American race are more likely to have seizure-related ED visits compared to Whites.^[4]

• Males are more affected by seizures than females.^[4][1]
• The male to female ratio of a seizure-related ED visit is approximately 1.4 to 1.^[4]
• The male to female ratio of acute symptomatic seizures on a population level (not in the ED setting) is approximately 1.85 to 1 (lifetime risk of 5.0% in males and 2.7% in females).^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

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 patient’s risk for future seizures.

Risk factors that can precipitate or provoke seizure may include:^[1][2][3]

• Chronic sleep deprivation
• Alcohol use
• Illicit drug use
• Some medications that reduce the seizure threshold such as:
  • Bupropion
  • Cephalosporins
  • Clozapine
  • Fluoroquinolones
  • Tramadol
• Toxins
• Homeostasis abnormality due to organ failure
• Metabolic abnormalities
• Medical and surgical histories that may be important in assessing the patient’s risk for future seizures, such as:
  • Childhood development (such as delivery complications)
  • History of central nervous system (CNS) infections, diseases, or surgeries
  • History of head injuries (especially if there were loss of consciousness)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

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.

The EEG monitoring has been recommended in neonates with:^[1][2]

• Known or suspected acute brain injury combined with encephalopathy
• Differential diagnosis of abnormal paroxysmal events
• In high-risk population

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

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.

• The recurrence rate of seizure within 2 years is 35% to 40% in patients with a first-time unprovoked seizure.^[1]
• In a cohort study that followed patients for 10 years after an acute symptomatic seizure in an ED visit (excluding children with febrile seizure), the risk of recurrence was 13% in those patients who had an unprovoked seizure and 41% in those who had acute symptomatic status epilepticus.^[2]
• Status epilepticus occurs in about 6%-7% of the patients with seizure in the emergency department (ED).^[3][4][5]

Some complications that have been suggested in seizure include:^[6]

• Accidents and injuries
  • Mostly cranial soft tissue contusions or lacerations
• Lifestyle and psychosocial impact
  • Financial, social, and relationship problems such as driving, work-related activities, reduced productivity, stigma in society
• Comorbidities
  • Medical: stroke, ischaemic heart disease, cancer, migraine, vertigo, and sleep disorders
  • Psychiatric: depression and anxiety
  • Neurodegenerative diseases: dementia and Alzheimer disease (AD)
• Death

• 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.^[7][8]
  • The risk of epilepsy is the same as children without any history of febrile seizure.
• Complex febrile seizures increase the risk for epilepsy, and but do not increase the risk for a future simple febrile seizure.^[9]
• The overall mortality rate of status epilepticus is approximately 22% (3% in pediatric patients to 26% in adults).^[10]