Focus On: Seizures - What Is the Mechanism Underlying Clinical Manifestations of Seizure Activity as Seen in the ED?

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ACEP News
October 2007

By Bohdan M. Minczak MS, MD, PhD

Learning Objectives

After reading this article, the physician should be able to:

  • Describe the basic pathophysiological mechanisms andetiologies of seizures.
  • Describe the appropriate treatment and disposition of patients presenting to the ED with seizures of various etiologies.
  • Define what a seizure actually is.


Seizure is a commonly encountered chief complaint in the emergency department. Although the meaning of the word "seizure" seems obvious to both the seasoned emergency physician and the neophyte practitioner, the chief complaint listed on the chart may not accurately represent the presenting condition of the patient.

Indeed, the patient, family, bystanders, and even emergency medical personnel (EMTs, paramedics, first responders, police officers, etc.) may describe the antecedent event leading to hospital presentation as having been a "seizure," when in fact a cardiovascular event (such as myocardial infarction, cardiac arrhythmia, stroke, hypoglycemic event, or other unspecified syncopal episode) may have taken place. Some lay personnel consider patient collapse as a manifestation of a seizure; however, the underlying cause of the event may not have been seizure related at all.

In this article, the author will review what seizures are and describe the mechanism(s) causing seizures. Based on their causative mechanisms, various seizures will be classified, a diagnostic and treatment approach described, and a disposition recommended for the patient.

The word "seizure," when used accurately, describes the excessive, chaotic discharge of cerebral neurons. The actual seizure is the aberrant neuronal activity taking place in the brain. The resultant observable events (such as tonic-clonic jerky movements of the musculoskeletal system; bowel and/or bladder incontinence; biting of the buccal mucosa and/or tongue; and accompanying "post-ictal" period of confusion) are somatic, neurological and musculoskeletal manifestations of the "neuronal seizure" activity.

Anatomy and Physiology

The brain, spinal cord, and musculature interact via nerve cells called neurons, the functional units of the central nervous system.

The neuron is made up of a soma or cell body; dendrites that receive information from other axons or various receptors; and axons that transmit information from the cell body to the terminal boutons at the distal end of the axons. Neurons interface with other nerve cells via small gaps called synapses. At the synapse, an axonal terminal bouton is in close proximity to a dendrite of another axon. At the synapse, a chemical neurotransmitter is released from the axonal terminal bouton as a result of an action potential, the electrophysiologic voltage change manifested in the axon due to a transient variation in the sodium and potassium permeability of the axon. This neurotransmitter diffuses across the synapse and binds to receptors on the dendrites of the next axon.

When the permeabilities of the membrane's ionic channels for sodium and potassium are varied sequentially, a fluctuation in the membrane voltage occurs, which is termed the action potential.

As the sodium attempts to enter the nerve cell, the potassium permeability increases as the potassium channels open, and the membrane begins to repolarize to the "resting" membrane potential. The nerve cell repolarizes and is ready for the next action potential to come along. These action potentials are also modified by the flux of chloride ions and the presence or absence of GABA activity in the membrane of the axon.

The pathways for information exchange between the brain and musculature can be divided into two general groups. One group of neurons provides afferent (sensory) input to the spinal cord and brain from the skeletal muscle and various receptors in the muscle and skeletal tissue, ligaments and tendons. Another group of neurons provide efferent (motor) output from the brain and spinal cord to the musculature or muscular motor unit.

A neuron or group of neurons in the brain can become hyperexcitable or irritable due to hypoxia, ischemia, hypoglycemia, or electrolyte abnormalities that affect the action potential and cause these nerve cells to discharge action potentials irregularly without adequate suppression and attenuation of the abnormal activity. If this occurs, the corresponding muscle fascicles may begin to contract inappropriately, thus producing seizure-like activity.

Depending on where the focus of this aberrant discharge is in a particular region of the brain, the corresponding motor or sensory area will be affected, leading to either motor symptoms such as tonic-clonic contractions or sensory manifestations of seizure-like activity, such as paresthesias, déjà vu, or hallucinations (auditory, visual, or olfactory).

These foci of aberrant electrical activity (the seizure) may be isolated, or the focus may spread and involve various areas of the brain, leading to chaotic, uninhibited discharge of electrical activity of various neurons in the brain. The resultant motor and/or sensory activity manifested by and experienced by the patient is clinically described as a seizure.

Control of the seizure can be accomplished by suppressing the action potential via manipulation of sodium and potassium ion permeabilities, rendering the axon refractory to the action potential, or blocking transmission of impulses at the synapse by blocking the neurotransmitter from binding to its receptor site, or preventing its release and/or synthesis.

Evidence of Seizure

Determining if a true seizure has taken place can often present a challenge to the emergency physician.

If, on presentation, the patient lost consciousness and manifested persistent, jerky, tonic-clonic muscular activity, followed by a period of confusion after the activity had ceased (the "post-ictal period"), then there is little reason to doubt that a true seizure has taken place.

However, if the seizure has stopped by the time the emergency physician and health care team initiate evaluation of the patient, then other signs of seizure, such as bowel/bladder incontinence or injury to the buccal mucosa or tongue secondary to biting during the seizure, must be identified.

Further evidence to support that a true seizure has taken place may be laboratory findings such as an increased white blood cell count, usually due to demargination of white blood cells from the extravascular space, or the presence of an anion gap. Other tests are available that can provide evidence of recent seizure activity, but these tests (serum prolactin levels and EEG) are seldom used in the emergency department.

Some seizures do not present with generalized muscle contractions but may manifest as a period of staring or focal shaking. Some seizures may have an atypical presentation and may even go unnoticed or undiagnosed. Other events perceived as seizures are actually pseudoseizures.

Classification and Recognition

Seizures can be grouped into three classifications: generalized, focal or partial, and focal/partial with secondary generalization. Generalized seizures can be further classified as tonic-clonic seizures (grand mal), absence seizures (petit mal) and atonic (drop attacks).

Generalized tonic-clonic grand mal seizures present with a loss of consciousness and the initiation of subsequent tonic contractions of muscles of the whole body. The muscle contractions then become "jerk like" or clonic. This activity may persist for several minutes. After the muscle twitching stops, the patient usually experiences a period of confusion, flat affect, and often mild lethargy. This is termed the post-ictal period.

An absence or petit mal seizure presents with sudden loss of awareness, interruption of activity, and loss of body position control and proprioception. This may last for a few moments to several minutes. After the event, there is a brief post-ictal period, usually much shorter than the post-ictal period that accompanies the grand mal type of seizure.

An atonic drop attack usually presents as a sudden fall to the ground, often with accompanying injury. This occurs because of the complete loss of postural control.

Focal/partial seizures are confined to a particular region of the brain and manifest as aberrant movement in one area of the body. Focal or partial seizures can be classified as simple partial or complex partial seizures.

Simple partial or focal seizures may have various presentations depending on which area of the brain has been affected. If a motor area of the brain has been affected, there will be aberrant movement of the specific area of the body corresponding to the affected area of the cerebral cortex. If a nonmotor area is affected, then there may be sensory manifestation of the seizure such as déjà vu, auditory or olfactory hallucinations, or paresthesias.

A complex partial seizure may present as interruption or cessation of ongoing motor activity with the development of aimless ambulation, lip smacking, or other automatisms.

Focal/partial seizures with secondary generalization start in one area of the brain and then proceed to spread and involve other areas of the brain. This produces an aberrant motor activity in one area of the body and then subsequently involves the entire body. This seizure progresses to loss of postural control and in some cases, eventual tonic-clonic activity of the entire body. A pseudoseizure is not really a seizure, with no manifestation of any seizure activity on an EEG.

Approach to the Patient

On initial evaluation of a patient who is actually manifesting seizure-like activity (such as tonic-clonic jerky body movements), the emergency physician must attempt to protect the seizing patient from physical trauma (such as falling and striking his or her head on a nearby object or the floor) via gentle restraint. Provide airway support and assistance with oxygenation as needed, because oxygen demands increase during the excessive muscle activity. If possible, take measures to prevent aspiration, such as turning the patient on his or her side.

If the seizure activity does not terminate within 5 minutes, the emergency physician must intervene with medication to terminate this activity. This is done to lower the potential for neuronal/brain injury secondary to neuronal electrical activity.

Then the emergency physician must ascertain that the patient has a functional airway, that the patient is breathing effectively, and that the heart and circulatory system are providing adequate blood flow to the vital organs.

As the evaluation proceeds, the emergency physician will assess the patient's blood pressure, capillary refill, pulse oximetry reading, and bedside glucose determination.

Subsequently, the emergency physician and health care team will attempt to conduct a history and physical examination of the patient. Special attention must be paid to the physical examination of the patient, particularly to ascertain if there is any evidence of trauma to the head or other areas of the body that may have either precipitated the trauma or that may have occurred as a result of the seizure (tongue laceration, buccal mucosa trauma, etc).

The skin should be evaluated for signs of a rash or lesion that could suggest meningococcemia. The heart should be auscultated to determine if a murmur is present that could suggest subacute bacterial endocarditis and embolization which may have caused a seizure. In addition, a thorough neurological examination should be performed to look for neurological deficits or fundoscopic changes indicative of elevated intracranial pressure.

Based on the data obtained, the key question then becomes: Has a seizure indeed occurred? If the conclusion is that the patient actually had a seizure, then the etiology of the seizure must be sought. This may entail utilizing appropriate diagnostic laboratory tests and/or diagnostic imaging in order to determine the appropriate treatment and disposition for the patient.

If the emergency physician and the health care team are presented with a patient who is unresponsive and brought for evaluation of a possible seizure that was witnessed by bystanders, several important questions must be asked to determine if a seizure has occurred and, if so, what type. The key questions are:

  • What type of seizure activity was observed to occur?
  • What was the patient doing at the time of the seizure, and when did the seizure start?
  • In what part of the body did the aberrant movement or activity start?
  • Did it progress?
  • How long did the activity last?

To remember these questions, think of the mnemonic COLD: Character, Onset, Location and Duration.

In addition to this information, it would be useful to obtain the patient's past medical history, history of prior seizures, trauma, neoplasm, current medications if any, and social history. Also, it would be helpful to determine if any recent alcohol or illicit drug use has been a factor that may have contributed to the current presentation of the patient's condition.

First-Line Benzodiazepines for Treatment of Seizure

Drug Dosage Comments
Lorazepam 2-4 mg IV push Total of 10-15 mg. Has increased efficacyand longer half-life/seizure control.
Diazepam 5-10 mg IV push Total of 30 mg in 8 hours.
Midazolam 0.05 mg/kg IM Can be used as needed to treat status, if IV not available.
Source: Dr. Minczak

Determining the Cause

Once the patient is stable and has been appropriately examined, the cause for the seizure can be pursued. To assist in the formation of the differential diagnosis and to facilitate decision-making regarding appropriate diagnostic testing, the emergency physician should consider the possible causes of seizures in various patients.

In the older adult, seizures often occur as a result of stroke, brain tumor, intracerebral hemorrhage, metabolic derangements such as hypoglycemia, low or high sodium, hypocalcemia, uremia or liver failure. In the young adult, seizure may be due to trauma, alcohol abuse or withdrawal, or brain tumor. In the adolescent, seizures can occur secondary to trauma, drug or alcohol abuse and withdrawal, arteriovenous malformations, or they may be idiopathic.

In the child, seizures are often categorized as "febrile seizures," or they may occur as a result of trauma or infection, or they may be idiopathic. Finally, in the infant, seizures can occur as a result of birth trauma, hypoxia, intracranial trauma, infection, electrolyte abnormalities, low magnesium, low sodium, hypocalcemia, congenital and genetic disorders, and pyridoxine deficiency.

In the pregnant female, eclampsia must be considered in the differential diagnosis.

Diagnostic Testing and Imaging

The choice of laboratory tests and diagnostic imaging of the seizure patient depends on the presentation of the patient and the circumstances of the seizure. For example, if the patient has a known seizure history, is on medications for seizure control and has had a single, unprovoked seizure, a simple determination of his/her serum anticonvulsant level may be sufficient to determine cause and guide treatment.

If this is a new-onset seizure, then more extensive testing may be warranted. Tests that may be useful include sodium, potassium, BUN, creatinine, glucose, calcium, and magnesium. A toxicology screen to test for cocaine, theophylline levels, stimulants, lidocaine, and antidepressants and other frequently abused substances may be helpful. If there is doubt regarding the likelihood of seizure, then calculation of an anion gap and checking for an elevated white blood cell count may be helpful in determining if a seizure has taken place and may point to the etiology of a seizure, such as sepsis/infection.

If the patient has had a new-onset seizure or experienced trauma, then a head CT is advisable to determine if there may be a subdural hematoma, subarachnoid bleed, hemorrhagic stroke, or epidural hematoma. In addition, if the patient is having a prolonged post-ictal period or the patient will be incapable of getting appropriate follow-up care, then the patient should be evaluated by head CT.

If the patient is a young infant or an elderly individual in whom the emergency physician suspects an infectious process in the CSF, then a lumbar puncture should be considered to detect white blood cells, bacteria, changes in protein, or the presence of blood in the CSF.

In a pregnant female, all of the above should be considered, as well as a check for proteinuria, liver enzymes and platelets, and elevated blood pressure to rule out the possibility of eclampsia as the cause of seizures.

Treatment of Seizures

Many seizures will stop without pharmacological intervention. However, if the seizure continues beyond 5 minutes, or if multiple seizures are occurring and "status epilepticus" is considered where the seizures are not spontaneously stopping, and the time of recurrent seizures is approaching 30 minutes, treatment with medication must begin. The first-line drugs are the benzodiazepines (see related table). If multiple doses of benzodiazepines are ineffective in terminating the seizure, then a loading dose of anti-epileptic drugs should be considered (see related table).

Patient Disposition

Patients with known seizure disorder and who have had a single, unprovoked seizure may only need to have their serum anticonvulsant drug levels checked and treated, and do not need to be admitted to the hospital.

Patients who present with a new-onset seizure should be admitted for a complete workup and further neurological and/or neurosurgical evaluation if the clinical circumstances warrant an admission, such as a subarachnoid bleed, etc. If there are no significant findings, but the patient will not be able to obtain appropriate follow-up care, then admission should be considered.

Regarding children and febrile seizures, usually if the history, physical exam, and family history support the diagnosis of a febrile seizure, then admission is not necessary, especially if appropriate follow-up care is available and the social situation is appropriate.

Any pregnant female with eclampsia needs delivery, magnesium sulfate, and admission.

Summary

Seizures are the result of chaotic neuronal discharge from cerebral neurons. This discharge alone (the electrical activity of the neurons) is toxic to the nerve cells, not the metabolic byproducts produced during the seizure activity. The seizure can be treated via suppression of the sodium channels in the neurons or by the potentiating of GABA receptors in the nerve cells.

Further interruption of the seizure-like activity can occur at the synapses, via the interruption of neuro-chemical synaptic transmission, via medications that block release of the neurotransmitter, or medications that block the binding of the neurotransmitter to the post-synaptic receptors. Also, blocking synthesis of the neurotransmitter has been pharmacologically attempted.

Seizures that do not spontaneously stop require pharmacologic intervention. The first-line medications are benzodiazepines, followed by anticonvulsant medication.

If the patient presents with a first-time seizure, strongly consider admission of the patient. If the etiology of the patient's seizure has been determined and treated appropriately and the patient has appropriate follow-up, the emergency physician may consider discharge with appropriate follow-up care.

Treatment Choices if Benzodiazepines Are Ineffective

Drug Dosage Comments
Phenytoin 18-20 mg/kg IV Total dose 30 mg/kg. Use cardiac monitor during infusion. Infuse at less than 50 mg/min, watch for QRS greater than 50%, hypotension.
Fosphenytoin 15-20 PE/kg IV/IM Phenytoin equivalent. Faster therapeutic level/prodrug of phenytoin.
Phenobarbital1 5 mg/kg IV Total dose 600 mg. Infuse at less than 100 mg/min. Watch for respiratory depression.
Pentobarbital 12 mg/kg IV Use if above agents have failed.
Lidocaine 1-1.5 mg/kg May stop status.
Propofo l2 mg/kg May use in status. Intubate patient prior to use if possible. Watch for hypotension.
Levetiracetam Loading dose. New literature is pending.(Keppra)
Magnesium sulfate 4-6 g, 10% solution IV In the United States, for eclampsia. Elsewhere (United Kingdom, Europe, and Australia), phenytoin and benzodiazepines are used. Watch for respiratory compromise, cardiac arrhythmia, loss of reflexes.
Source: Dr. Minczak

Contributors

Dr. Bohdan (Dan) M. Minczak is an assistant professor of emergency medicine and assistant medical director of EMS Services at the Thomas Jefferson University Hospital in Philadelphia, Pa. He is also an associate professor of physiology/biomedical sciences and lectures as a systems physiologist at the Philadelphia College of Osteopathic Medicine. Medical Editor Dr. Robert C. Solomon is an attending emergency physician at Trinity Health System in Steubenville, Ohio, and clinical assistant professor of emergency medicine at the West Virginia School of Osteopathic Medicine.

Disclosure

In accordance with the Accreditation Council for Continuing Medical Education (ACCME) Standards and American College of Emergency Physicians policy, contributors and editors must disclose to the program audience the existence of significant financial interests in or relationships with manufacturers of commercial products that might have a direct interest in the subject matter.

Dr. Minczak and Dr. Solomon have disclosed that they have no significant relationships with or financial interests in any commercial companies that pertain to this educational activity.

"Focus On: Seizures--What Is the Mechanism Underlying Various Clinical Manifestations of Seizure Activity as Seen in the Emergency Department?" has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME).

ACEP is accredited by the ACCME to provide continuing medical education for physicians. ACEP designates this educational activity for a maximum of one Category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he or she actually spent in the educational activity.

"Focus On: Seizures--What Is the Mechanism Underlying Clinical Manifestations of Seizure Activity as Seen in the Emergency Department?" is approved by ACEP for one ACEP Category 1 credit.

Disclaimer

ACEP makes every effort to ensure that contributors to College-sponsored programs are knowledgeable authorities in their fields. Participants are nevertheless advised that the statements and opinions expressed in this article are provided as guidelines and should not be construed as College policy. The material contained herein is not intended to establish policy, procedure, or a standard of care. The views expressed in this article are those of the contributors and not necessarily the opinion or recommendation of ACEP. The College disclaims any liability or responsibility for the consequences of any actions taken in reliance on those statements or opinions.

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