Seizure Disorders and Epilepsy Nursing CE Course for APRNs

(i.e., retained or impaired awareness). Level of awareness is not used to classify generalized-onset seizures because this type impairs awareness. In addition, all seizures are then classified as motor or non-motor onset if applicable (Adamolekun, 2022b; Fisher et al., 2017; International League Against Epilepsy [ILAE], 2022h; Schachter, 2022a).

 

Focal-Onset Seizures

Focal-onset seizures originate within a hemisphere of the brain and may be localized or more widely distributed. For each seizure type, the beginning of the ictal phase (i.e., middle of the seizure) is consistent between seizures. They may exhibit specific patterns that involve the ipsilateral (i.e., same side) and/or contralateral (i.e., opposite side) hemisphere. Signs and symptoms during a seizure aid in identifying the specific area, lobe, or hemisphere involved in the seizure onset and further dissemination (Adamolekun, 2022b; ILAE, 2022e).

Focal seizures are first classified according to the level of awareness, which is critical to determine due to the impact on daily life functioning and safety. If a focal seizure does not impair awareness, it is classified as a focal aware seizure (formerly known as a simple partial seizure). If a seizure includes impaired awareness (patient loses awareness of their surroundings), it is classified as a focal impaired awareness seizure (formerly known as complex partial seizures). The initial sign/symptom is the most important as it identifies the region of the brain the seizure originates, even if the seizure has other features (Adamolekun, 2022b; ILAE, 2022e).

Focal seizures can be further classified by motor or non-motor onset:

• focal-onset motor seizures can include:
  • atonic (focal loss of muscle tone)
  • automatisms (coordinated, purposeless, repetitive motor activity)
  • clonic (focal rhythmic jerking)
  • epileptic spasms (focal extension or flexion of arms or flexion of trunk)
  • hyperkinetic (causing thrashing or pedaling)
  • myoclonic (brief, irregular focal jerking)
  • tonic (sustained focal stiffening of a limb or a side of the body)
• focal-onset non-motor seizures are further classified based on the first prominent feature:
  • sensory dysfunction (sensation present at onset such as tingling, flashing of lights, buzzing, odor, taste, dizziness, hot/cold feeling, or lightheadedness)
  • cognitive dysfunction (manifests as alterations of cognitive function or thoughts, including hallucination and illusions)
  • emotional dysfunction (manifests as alterations in mood or emotions, including fear, joy, and anxiety)
  • autonomic dysfunction (involves the autonomic nervous system and may begin with palpitations, epigastric sensations, pallor/flushing, erection, hypoventilation, urge to urinate or defecate, lacrimation, or pupillary dilation/constriction)
  • behavioral arrest (decrease in amplitude or arrest of ongoing motor activity during the seizure; Adamolekun, 2022b; ILAE, 2022e)

Focal seizures can affect a large area of the brain and engage bilateral networks that include both the cortical and subcortical structures, which results in a tonic-clonic seizure and loss of consciousness. These seizures occur when a focal-onset seizure spreads and activates the entire cerebrum. This seizure would be classified as a focal to bilateral tonic-clonic seizure, and the initial focal feature may be brief, making a diagnosis challenging (Adamolekun, 2022b; ILAE, 2022e).

Generalized-Onset Seizures

Generalized-onset seizures originate in both hemispheres; they usually impair awareness and result in a loss of consciousness. These seizures most often result from metabolic disorders and sometimes genetic disorders. Generalized-onset seizures are classified as motor or non-motor, although non-motor seizures may involve some motor activity. With generalized-onset motor seizures, the motor activity is usually bilateral. When the motor activity during a seizure is asymmetrical, differentiating between focal and generalized can be challenging (Adamolekun, 2022b; ILAE, 2022f). Generalized-onset seizures will have the following classifications:

• generalized-onset motor seizures:
  • tonic-clonic and variants (formerly known as grand mal)
  • tonic (generalized stiffening involving all limbs and without rhythmic jerking)
  • clonic (sustained rhythmic jerking)
  • atonic (loss of muscle tone)
  • myoclonic (rhythmic jerking not preceded by stiffening)
  • myoclonic-atonic (myoclonic jerking followed by atonia)
  • myoclonic-tonic-clonic (myoclonic jerking followed by tonic and clonic movements)
  • epileptic spasms (formerly known as infantile spasms)
• generalized-onset non-motor seizures are further classified based on the first prominent feature:
  • typical absence
  • atypical absence (less abrupt onset or termination or abnormal changes in tone)
  • myoclonic absence
  • eyelid myoclonia (Adamolekun, 2022b; ILAE, 2022f)

All absence seizures are classified as general-onset, but distinguishing them from focal impaired awareness seizures can be challenging. However, absence seizures tend to start and end more suddenly and occur more commonly in younger individuals; automatisms are usually less complex than focal impaired awareness seizures. A generalized seizure will have an originating point and rapidly engaging networks distributed bilaterally. They may include cortical and subcortical structures but not necessarily the entire cortex. Each seizure may appear localized, but the location and lateralization are inconsistent across seizures (Adamolekun, 2022b; ILAE, 2022f).

 

Unknown-Onset Seizures

The third classification, unknown-onset seizure, is used when the seizure has not been categorized as either focal or generalized. Often, this classification is used until more information is available. For example, if a patient enters the emergency department after a seizure, there may be inadequate information to categorize it properly. After a thorough workup, the classification may be updated from unknown onset to either focal or generalized. Seizures with an unknown onset can be motor or non-motor (Adamolekun, 2022b).

Over the years, seizure classification and terminology have evolved (Huff & Murr, 2022). Some seizure types appear in multiple categories within the new classification system. For example, Fisher and colleagues (2017) noted the following changes from 1981 to 2017:

• change in terminology from "partial" to "focal"
• change in seizure types to focal, generalized, or unknown onset
• seizures of unknown onset can have features that are classified
• awareness is a new term used as a classifier of focal seizures
• old terms (i.e., dyscognitive, simple partial, complex partial, psychic, and secondarily generalized) were eliminated from terminology related to seizure activity
• new terms for focal seizure types include automatisms, autonomic, behavior arrest, cognitive, emotional, hyperkinetic, sensory, and focal to bilateral tonic-clonic seizures; atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be either focal or generalized
• new generalized seizure types include absence with eyelid myoclonia, myoclonic absence, myoclonic-tonic-clonic, myoclonic-atonic, or epileptic spasms (Fisher et al., 2017)

Types of Epilepsy

Epilepsy classification involves three levels: the seizure type, the epilepsy type, and epilepsy syndrome. For clinicians to make the most appropriate diagnosis, a comprehensive history is obtained from a patient and their family. In addition, diagnostic testing is considered, such as imaging and electroencephalography (EEG). The etiology and the classification of epilepsy should be considered and may change as further information is acquired (Adamolekun, 2022b; ILAE, 2022c; Karceski, 2022).

Epilepsy can be classified as follows (ILAE, 2022c):

• Generalized seizures characterize generalized epilepsy and may be accompanied by typical interictal and/or ictal EEG findings. A family history of generalized seizures or epilepsy is supportive of this diagnosis. With genetic generalized epilepsy, generalized epileptiform EEG patterns (i.e., spike wave activity) are known to have a genetic etiology. This classification includes childhood absence epilepsy, juvenile myoclonic and absence epilepsy, or epilepsy with generalized tonic-clonic seizures.
• Focal epilepsy is characterized by focal seizures with typical interictal or ictal EEG findings (i.e., focal sharp waves or interictal slowing). Focal structural brain abnormalities can support this diagnosis. Focal epilepsies can be unifocal, multifocal, or hemispheric.
• Combined generalized and focal epilepsy is characterized by both generalized and focal seizures along with interictal or ictal EEG findings characteristic of each seizure type. Patients with Dravet syndrome or Lennox Gastaut syndrome (LGS) often have this type of epilepsy.
• Unknown epilepsy is used during the diagnostic process to denote epilepsy until a further determination is made between focal, generalized, or combined focal and generalized. This classification can be used when there is insufficient information (e.g. if the EEG is normal or uninformative).

 

Epilepsy Syndromes

In addition to identifying the etiology, epilepsy can be categorized into epilepsy syndromes based on clinical and electrical characteristics. These syndromes have a typical age of onset, seizure type, and EEG characteristics. Identifying an epilepsy syndrome is important when considering AEDs, as many syndromes can be aggravated by certain AEDs (ILAE, 2022d). Table 2 outlines epilepsy syndromes by age.

Table 2

Epilepsy Syndromes By Age

Age Category	Epilepsy Syndrome
Neonatal/Infantile	self-limited neonatal seizures and self-limited familial neonatal epilepsy: characterized by seizures that start in the neonatal period (4 to 7 days of life) and resolve by 4 to 6 months of age self-limited familial and non-familial infantile epilepsy: characterized by the onset of seizures in the infantile period (3 and 20 months of age) that spontaneously resolve early myoclonic encephalopathy: characterized by frequent, intractable myoclonic seizures and severe encephalopathy resulting in limited development and reduced life expectancy Ohtahara syndrome: characterized by frequent, intractable tonic seizures and severe early encephalopathy resulting in limited development and reduced life expectancy West syndrome: characterized by epileptic spasms in the first year of life Dravet syndrome: see below myoclonic epilepsy in infancy: uncommon and characterized by myoclonic seizures triggered by noise, touch, or photic stimulation epilepsy of infancy with migrating focal seizures: refractory focal seizures in the first year of life, with associated severe encephalopathy myoclonic encephalopathy in non-progressive disorders: repeated episodes of myoclonic status epilepticus that occur over prolonged periods febrile seizures plus genetic epilepsy with febrile seizures: febrile seizures that continue past the usual age of resolution and may be accompanied by afebrile generalized or focal seizures
Childhood	epilepsy with myoclonic-atonic seizures: characterized by the presence of myoclonic-atonic seizures in an otherwise healthy child epilepsy with eyelid myoclonias: characterized by daily eyelid myoclonias with or without the absences induced by eye closure and visual stimulation LGS: see below childhood absence epilepsy: genetic-idiopathic epilepsy characterized by daily absence seizures epilepsy with myoclonic absences: characterized by daily myoclonic absence seizures Panayiotopoulos syndrome: characterized by the early onset of focal autonomic seizures that are often prolonged childhood occipital epilepsy: self-limiting childhood epilepsy with onset between 15 months and 19 years of age; remission occurs within 2 to 4 years photosensitive occipital lobe epilepsy: characterized by visually induced focal occipital lobe seizures childhood epilepsy with centrotemporal spikes: self-limiting epilepsy seen between the ages of 3 and 14 with seizures that are brief and hemifacial but may evolve to focal or bilateral tonic-clonic if they occur nocturnally atypical childhood epilepsy with centrotemporal spikes: an atypical evolution of childhood epilepsy with centrotemporal spikes; self-limiting, frequent seizures of multiple types, including nocturnal focal motor and frontoparietal opercular seizures and daytime focal motor seizures with negative myoclonus and atypical absence seizures epileptic encephalopathy with continuous spike-and-wave patterns during sleep: characterized by continuous spike-and-wave patterns on EEG during sleep, seizures, and progressive cognitive, psychiatric, and behavioral decline Landau Kleffner syndrome: characterized by subacute onset of acquired aphasia in a previously developmentally normal child autosomal-dominant nocturnal frontal lobe epilepsy: familial epilepsy with focal seizures beginning in childhood
Adolescent/Adult	juvenile absence epilepsy: genetic/idiopathic epilepsy characterized by absence seizures that are not frequent; tonic-clonic seizures typically also occur juvenile myoclonic epilepsy: one of the most common genetic/idiopathic generalized epilepsies characterized by myoclonic and generalized tonic-clonic seizures epilepsy with generalized tonic-clonic seizures alone: common genetic/idiopathic generalized epilepsy with infrequent generalized tonic-clonic seizures, typically provoked by sleep deprivation autosomal dominant epilepsy with auditory features: genetic focal epilepsy with focal sensory/auditory seizures in family members other familial temporal lobe epilepsies: seizures with temporal lobe features and a family history of similar seizures
Any Age	familial focal epilepsy with variable foci: hereditary epilepsy with focal seizures arising from various regions in different family members reflex epilepsies: characterized by reflex seizures (i.e., in response to a stimulus or trigger) without spontaneous seizures progressive myoclonus epilepsies: characterized by myoclonic seizures with or without tonic-clonic seizures, progressive cognitive decline, and motor impairment

(Adamolekun, 2022b; ILAE, 2022d)

Lennox-Gastaut Syndrome

LGS is a severe form of childhood epilepsy characterized by multiple types of seizures, particularly tonic and atonic. LGS is considered an epileptic encephalopathy, meaning frequent seizure activity and abnormal EEG activity degrade cognitive function and cause behavioral difficulties, including hyperactivity, aggression, or agitation. Autism is common. Intellectual and behavioral challenges make daily life difficult for these individuals. The seizures usually begin in preschool but may not be diagnosed for years. LGS seizures are difficult to manage and continue throughout the patient's life. Children may not exhibit all the features of LGS and require close follow-up to ensure an accurate diagnosis. The onset of LGS is typically 1 to 7 years of age (peak at 3 to 5 years); an onset past 10 is rare. Emotional or developmental delays are usually recognized in a patient prior to LGS; boys are diagnosed more often than girls, but no racial differences are noted. Causes of LGS include brain malformations, perinatal asphyxia, central nervous system infection, tuberous sclerosis, severe head injury, and hereditary genetic and degenerative or metabolic disorders. One in 4 people suffering from LGS has no known cause (Adamolekun, 2022b; ILAE, 2022g). The following three features confirm the diagnosis:

• multiple seizure types, starting in childhood but emerging over time
• tonic
• atonic or drop attacks
• atypical absence
• myoclonic and
• generalized tonic-clonic
• focal seizures becoming more common in teens and adults
• characteristic EEG pattern with diffuse or widespread background slowing and slow spike-wave bursts in wakefulness with generalized paroxysmal fast activity found in sleep
• cognitive impairment, behavioral problems, or developmental delay may be present before the onset of seizures; they increase in severity over time with the onset of seizure activity (Adamolekun, 2022b; ILAE, 2022g)

Dravet Syndrome

Dravet syndrome is another rare and drug-resistant type of epilepsy beginning in an otherwise healthy infant's first year of life. The onset is typically a prolonged seizure on one side of the body occurring with a fever, with patients losing control of motor activity in the arm, face, foot, or other body parts. An affected infant is developmentally normal before the onset of seizures, with a decline afterward. By late childhood, they develop a crouched walk; these patients typically walk stooped due to non-physiologic tightening of particular ligaments and muscles. Most cases of Dravet syndrome are due to a severe sodium channel alpha-1 subunit (SCN1A) gene mutation and are associated with varying degrees of developmental disability. In most cases, the mutation is not present in the parents and is considered a new or random mutation in the child (Adamolekun, 2022b; ILAE, 2022a).

Seizures are typically tonic-clonic or clonic on one side of the body. The seizures last longer than 5 minutes and can result in status epilepticus. They recur every few weeks in infancy and early childhood. Seizure types vary among myoclonic, tonic-clonic, atypical, atonic, focal aware or impaired awareness, and tonic seizures. While the initial seizure is most often triggered by fever, subsequent seizures can be triggered by flashing lights, emotional stress, or excitement. An affected child develops appropriately up to age 2 but then misses developmental milestones and progresses slower as they age. A child with Dravet syndrome may have a low motor tone, an unsteady gait, crouched walking as they age, growth or nutritional deficits, and autonomic nervous system dysfunction, which may affect the heart, lungs, stomach, or intestines. This syndrome has mistakenly been linked to vaccines as children develop it near routine vaccinations, but numerous research studies have shown no linkage. Dietary therapy, vagus nerve stimulation, and combination medication therapies are used to control seizures (Adamolekun, 2022b; ILAE, 2022a).

Pathophysiology of Seizures

With advances in modern neuroimaging and genetic testing, the underlying etiologies of epilepsy are more commonly understood and more precisely described (ILAE, 2022b). Epilepsy etiology can include various factors:

• genetic: chromosomal or gene abnormalities
• structural: malformations of cortical development, vascular malformations, hippocampal sclerosis, traumatic brain injury, or tumors
• metabolic: creatinine disorders, folic acid-responsive seizures, glucose transporter 1 (GLUT1) deficiency, or cerebral folate deficiency
• immune: Rasmussen syndrome or antibody-mediated etiologies
• infectious: bacterial meningitis, cerebral malaria, cerebral toxoplasmosis, cytomegalovirus (CMV), HIV, or tuberculosis
• unknown: the underlying cause is not known (ILAE, 2022b)

The pathophysiology of seizures can be quite complex; however, a simplistic explanation is a distortion of the normal balance between excitation and inhibition in the brain. Everyone has some propensity to have a seizure, with a threshold varying along a continuum based on factors that increase susceptibility. The pathophysiology of focal seizures differs from generalized seizures, yet the overall cellular excitability from the imbalance of excitation and inhibition is increased with both forms. The imbalance can occur due to various alterations at many levels of brain function, from genetic or cellular signaling to broad neuronal circuits. The causes of the imbalances can be genetic or acquired. Genetic causes can occur at the circuit and receptor levels or abnormal ionic channel functioning, such as potassium channel mutations. Monogenic or polygenic mutations can result in epilepsy. Acquired cerebral injuries can also alter the circuit function, such as a prolonged fever or head trauma that causes alterations in hippocampal circuitry, leading to seizure activity. The developing brain in an infant or a child is especially prone to seizures with all the physiological changes taking place. However, seizures in children are less likely to cause structural damage than seizures in adults. Since the brain is involved in all bodily functions, multiple body areas can be affected during seizure activity (Huff & Murr, 2022; Ko, 2022).

Seizures start when susceptible cerebral neurons are excited, leading to synchronous discharges of larger groups of connected neurons. Glutamate is the most common excitatory neurotransmitter, while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter. Excessive excitation initiates abnormal electrical activity known as electrical paroxysmal depolarization shifts (PDS), which trigger epileptiform activity. The part of the brain affected will often determine the clinical features of the seizure. Generalized convulsive status epilepticus is accompanied by systemic changes that include increased catecholamine levels, hyperthermia, lactic acidosis, and respiratory compromise. In addition, the ongoing excessive electrical activity damages the brain (Huff & Murr, 2022). While the pathophysiology of seizure types may differ for focal onset versus generalized onset, the terms atonic, clonic, myoclonic, and tonic are used for both categories (Fisher et al., 2017).

 

Precipitating Factors

The triggers of seizures and epilepsy are numerous. They can vary based on the type of seizure (i.e., focal or generalized) and the seizure setting (i.e., acute symptomatic [occurs at the time of a systemic or brain insult] versus unprovoked). Acute symptomatic seizures are triggered by precipitating factors that are environmental, physical, clinical, or emotional. These triggers may vary from patient to patient. However, common themes are physical or emotional stress, alcohol or drug use, illness (particularly with increased temperatures or hypoglycemia or hyperglycemia), menstruation, or sleep deprivation. Missing doses of antiepileptic drugs (AED) or taking medications that interfere with the function of AEDs can also trigger a seizure. Further triggers in those with epilepsy include strobe lights or video games. Patients and caregivers/parents should be counseled to maintain a record or journal of seizure triggers, as these can help lessen the likelihood of a seizure being triggered in the future (Huff & Murr, 2022; Schachter, 2022a). Other common causes of seizures can include:

• acute toxic effects (e.g., sympathomimetics, antidepressants)
• electrolyte disturbances (e.g., hyponatremia, hypernatremia, hypocalcemia, hypomagnesia)
• withdrawal syndrome (e.g., benzodiazepines)
• sepsis
• CNS infection
• hypoxic brain injury
• ischemic or hemorrhagic stroke
• neoplasm
• traumatic brain injury
• inflammatory (e.g., receptor encephalitis, lupus cerebritis)
• hyperthyroidism
• uremia
• eclampsia (Huff & Murr, 2022; Schachter, 2022a)

 

Assessment and Diagnosis

Diagnosing seizures can be a challenge for healthcare providers (HCPs). Many disorders can cause behavioral changes, which can be confused with seizures or epilepsy. As the treatment of seizures requires an accurate diagnosis, determining the type of seizure or epilepsy is vital. HCPs must obtain clear descriptions of seizure activity, including the timing, potential triggers, symptoms, longevity, or any other descriptors that can aid in diagnosis. Patients with a new-onset seizure are typically evaluated within the emergency department and are often discharged after a thorough evaluation. Evaluation can often occur in the primary HCP office for patients with a known seizure disorder. Then, they may be referred to a neurologist or epilepsy specialist known as an epileptologist. An epileptologist is often used for high-risk cases such as pregnancy and childbirth or uncontrolled seizures. Identifying any underlying cause for the seizures and the location within the brain where the seizures are being generated is crucial. A detailed medical history, blood tests, EEG, and brain imaging—including a computer tomography (CT) scan, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans—are needed to diagnose the underlying etiology, specifically new-onset seizures. The diagnostic workup for a patient with a known seizure disorder may be limited to assessing AED levels (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a).

Epilepsy should only be diagnosed after ruling out epilepsy imitators, including the following:

• syncope and anoxic seizures (i.e., non-epileptic events caused by temporary impairment of blood flow to the brain)
• behavioral, psychological, or psychiatric disorders
• sleep-related conditions
• paroxysmal movement disorders
• migraine-associated disorders
• miscellaneous events, including:
  • shuddering attacks (i.e., non-epileptic stiffening, tonic posturing, or rapid shivering movements)
  • jitteriness
  • spasmus nutans (i.e., a rare, idiopathic disorder that involves nystagmus, head nodding, and torticollis)
  • increased intracranial pressure
  • spinal myoclonus
  • paroxysmal extreme pain disorder (ILAE, 2022e)

Medical History

A detailed history will be taken during the initial visit. This aims to characterize the seizure, rule out alternative diagnoses, and evaluate for underlying risk factors, including medical and family history and medications (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a). The history should include questions such as:

• Can you give me a description of what happened?
• Is there a family member or witness to the seizure or event who can give further descriptions, including information on loss of consciousness?
• What events led up to the event or seizure?
• Was there any drug or alcohol use prior to the event or seizure?
• Were you sleep-deprived leading up to the event or seizure?
• What was the setting of the event or seizure?
• Did you just stand up or change positions before the event or seizure?
• Was there a warning?
• How long did it last?
• Were there any after-effects following the event or seizure?
• Were you tired or confused after the event or seizure?
• Has there been more than one event or seizure?
• Have you ever seen an HCP for this condition before?
• If so, what tests have been run, and when?
• Have you been prescribed any medication for the condition? If so, what? What effect did it have? (Epilepsy Foundation, 2013)

An accurate description of the seizure is essential but can be challenging to obtain. Patients with focal seizures without impairment can usually describe the event, while those with focal seizures with impairment or generalized seizures cannot. Most seizures have a clear and abrupt clinical onset and rapid progression of symptoms over seconds. In addition, most seizures end spontaneously within 2 to 3 minutes. Ictal behaviors help determine the origin of a seizure and whether it is focal or generalized. See Table 3 for clinical manifestations of focal seizures by brain location. After the seizure, most patients will exhibit postictal confusion and decreased alertness. Some patients may also experience focal neurological deficits, including aphasia, weakness, or numbness. The postictal state can last seconds to several days, depending on the seizure type and underlying brain function. Most patients begin to recover alertness and responsiveness within 10 to 20 minutes of a generalized seizure, and prolonged symptoms warrant further evaluation (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a). HCPs should use the questions above to assess for precipitants or triggers for the seizure.

Table 3

Clinical Manifestations of Focal-Onset Seizures by Brain Location

Clinical Manifestation	Brain Location of Dysfunction
Simple movements (e.g., limb twitching)	Contralateral frontal lobe
Abnormal taste	Insula
Olfactory hallucinations	Anteromedial temportal lobe
Complex behavioral automatisms	Temporal lobe
Visual hallucinations	Occipital lobe
Bilateral tonic posture	Frontal lobe
Head and eye deviation with posturing	Supplementary motor cortex
Visceral or autonomic abnormalities (e.g., salivation or epigastric aura)	Insular-orbital-frontal cortex
Chewing movements, speech arrest, salivation	Amygdala, opercular region
Unusual behavior suggesting a sleep disorder or psychiatric cause	Frontal lobe
Localized sensory disturbances (e.g., numbness or tingling of limb or half the body)	Parietal lobe

(Adamolekun, 2022b)

Physical Examination

HCPs should conduct a physical examination for any patients who had a seizure. In addition to a general physical examination, a focused neurological examination is critical to assess for any deficits. For patients who have lost consciousness, HCPs should look for incontinence, a bitten tongue, or prolonged confusion to suggest a seizure. Posterior shoulder dislocation can occur during a seizure; therefore, any new shoulder pain or limited range of motion should warrant radiographic examination. HCPs should also look for signs of psychogenic non-epileptic seizures (PNES), previously known as pseudoseizures, which are paroxysmal changes in behavior that resemble epileptic seizures. However, PNES lacks an organic cause, and the expected EEG findings present with epileptic seizures (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a). PNES can resemble tonic-clonic generalized seizures but have distinguishing clinical characteristics:

• postictal confusion tends to be absent
• they last longer (several minutes or more)
• typical seizure activity usually does not occur (tonic phase, followed by clonic phase)
• muscular activity usually includes jerking from one side to the other and back and exaggerated pelvic thrusting
• vital signs remain normal
• patients often resist passive eye-opening
• intensity waxes and wanes (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a)

Diagnostic Testing

Since patients may have other diagnoses besides seizures, further testing may be needed. However, normal results do not necessarily exclude a seizure; therefore, the diagnosis may be clinically based. The gold standard for diagnosing a seizure is video EEG monitoring. Particularly for focal impaired awareness seizures or absence status epilepticus, EEG may provide the most definitive indication of a seizure. Additional tests may be ordered, including an MRI of the brain or a CT angiogram of the head and neck, carotid ultrasound, conventional angiography, PET scan, or cardiac Holter monitor. These tests should be used to rule out or confirm other diagnoses, such as transient ischemic attacks (TIAs), stroke, vasculitis, vascular malformations, or cardiac arrhythmias. An overnight sleep study (polysomnography) should be ordered to rule out parasomnias (abnormal movements during sleep) or obstructive sleep apnea. A movement disorder physiologic study may be needed to identify myoclonus or tremor (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a).

Blood tests should be performed to evaluate for infection, blood glucose abnormalities, electrolyte imbalances, blood urea nitrogen (BUN), creatinine, liver function, or genetic conditions. A lumbar puncture should be performed if an infection could be the source of the seizure. In addition, a neurological examination should be completed to assess behavior, mental, and motor functioning to identify any other deficits related to the nervous system (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a).

During an EEG, electrodes are attached to the patient's scalp using a paste-like substance. The electrodes record the electrical activity (impulses) of the brain. With epilepsy, patients often have changes in normal brain activity, as evidenced by alterations in the wave patterns on the EEG results, even when a seizure is not occurring. A video EEG is the preferred diagnostic method as it can provide insight into the patient's response during the seizure; it involves a simple camera recording of the patient during the EEG. Inpatient combined video-EEG monitoring can be done for 2 to 7 days, recording EEG activity and clinical behavior simultaneously. It is possible to perform ambulatory EEGs (without video) in which the patient wears the EEG at home; this provides recordings of the patient's brain activity over several days. A high-density EEG may be ordered to give a more precise determination of the areas of the brain affected by seizures. This EEG requires the electrodes to be much closer together than in a regular EEG, typically 0.5 cm apart. There is no specific patient preparation for an EEG unless sleep deprivation is utilized to help trigger a seizure (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a).

A normal EEG cannot exclude the diagnosis of epileptic seizures, especially when seizures are infrequent. The initial EEG may only detect abnormalities in 30% to 50% of patients with a known epileptic disorder. Serial EEGs can detect abnormalities in up to 80% to 90% of patients (Adamolekun, 2022b). EEG findings may include the following:

• epileptiform abnormalities in the temporal lobe foci between seizures for focal impaired-awareness seizures in the temporal lobe
• focal epileptiform discharges in focal-to-bilateral tonic-clonic seizures
• interictal bilateral symmetric bursts of 4- to 7-Hz epileptiform activity in generalized tonic-clonic seizures
• spikes and slow-wave discharges occurring bilaterally at a rate of 3/second and usually normal background EEG activity in typical absence seizures
• slow spike and wave discharges, usually at a rate of <2.5/second, with interictal disorganization of background activity and diffuse slow waves in typical absence seizures
• bilateral polyspike and wave abnormality at a rate of 4- to 6-Hz in juvenile myoclonic epilepsy (Adamolekun, 2022b)

A CT scan can be used to obtain cross-sectional images of the brain to evaluate for structural abnormalities that may be causing the seizures, such as tumors, cysts, or bleeding. A CT scan is a 3-dimensional (3D) computer-generated graphic based on x-ray images. Similarly, an MRI can detect lesions or abnormalities in the brain using powerful magnets and radio waves. A more in-depth MRI called a functional MRI (fMRI) can measure the changes in blood flow within the brain, as seen in Figure 1a. An fMRI may be used before surgery to locate critical functions precisely, such as movement or speech, so the surgeon can avoid injury to those areas during surgery. PET scans can detect brain function abnormalities. A small amount of radioactive tracer material is typically injected to help visualize chemical activity in certain tissues, as seen in Figure 1b. If the MRI, EEG, or other tests could not determine exactly where the seizures originated, a single-photon emission CT (SPECT) scan might be conducted. This test uses a radioactive tracer to provide a detailed, 3D map of the blood flow through the brain during seizures (Adamolekun, 2022b; Haider & Bullinger, 2022).

 

Figure 1

fMRI (a) and PET (b) Brain Scan Images

In addition to diagnostic testing, statistical parametric mapping (SPM), Curry analysis, or magnetoencephalography (MEG) can help determine exactly where the seizures originated. SPM is a method where tissue metabolism is assessed, as brain areas have an increased metabolic rate during seizures, to determine where the seizure originated. Curry analysis combines EEG data and an MRI of the brain to determine where the seizures are occurring. MEG measures the magnetic fields created through electrical brain activity to locate seizure onset areas (Haider & Bullinger, 2022).

Once an accurate diagnosis is established by identifying the seizure type and location of origin, proper treatment can be initiated. Some people may have a single seizure that is determined to be associated with an underlying condition; once this condition has been treated, the patient should not have any further seizures. However, ongoing seizures may be diagnosed as epilepsy (Haider & Bullinger, 2022).

Management of Epilepsy/Seizures

 

Acute Management

Since seizures have multiple etiologies not associated with epilepsy, the treatment modalities will also vary. Treatment for seizures not due to epilepsy will focus on finding the underlying condition and correcting it while also halting the seizure activity. Most seizures will resolve spontaneously within 2 minutes and do not require rapid administration of an AED. However, HCPs or prehospital personnel should secure intravenous (IV) access in case of subsequent seizures. If a subsequent seizure occurs or prolonged seizure activity is present, IV medications may be administered. In addition, if the cause of the seizure cannot be identified and corrected, medication should be considered. Medications are often unnecessary if the underlying cause is identified and treated since the risk of a subsequent seizure is low. Typical IV medications for seizures include benzodiazepines, such as lorazepam (Ativan) and diazepam (Valium). A patient diagnosed with epilepsy may be given IV benzodiazepines to stop a seizure, but repeated oral doses of a benzodiazepine are typically unnecessary. Oxygen therapy should be used as indicated. Patients having a seizure should never be restrained. In addition, nothing should be put in their mouth that could cause further injury, such as a bite guard (Adamolekun, 2022b; Huff & Murr, 2022; Schachter, 2022a).

AEDs are required to stop the seizure activity for patients with seizures lasting longer than 5 minutes or those in status epilepticus. The sooner these medications are initiated, the quicker the seizure activity can be controlled. These patients should be given lorazepam (Ativan) 0.05 to 0.1 mg/kg IV (typically 4 mg for adults) at a maximum of 2 mg/minute. Some patients may require a larger dose. If IV access is unavailable, midazolam (Versed) can be administered IM or diazepam (Valium) can be given intranasally or rectally. After lorazepam (Ativan) is given, a second, longer-acting AED should be given. No consensus exists on which longer-acting medication should be given (Adamolekun, 2022b; Drislane, 2022). The most common options include the following:

• fosphenytoin (Cerebyx) 15 to 20 phenytoin equivalents (Pes)/kg IV, given at a rate of 100 to 150 PE/minute (fosphenytoin [Cerebyx] is given in PEs, with fosphenytoin [Cerebyx] 1.5 mg being equivalent to phenytoin [Dilantin] 1 mg)
• levetiracetam (Keppra) loading dose of 60 mg/kg (max 4500 mg) infused over at least 15 minutes, followed by 1500 mg orally BID
• valproate sodium (Depacon) 20 to 40 mg/kg IV loading dose (maximum 3000 mg) at 10 mg/kg per minute, followed by 4 to 8 mg/kg orally TID
• phenytoin (Dilantin) 15 to 20 mg/g IV, at a rate of 50 mg/minute; this cannot be given through the same IV line as a benzodiazepine or any fluid with glucose/dextrose (Adamolekun, 2022b; Drislane, 2022)

If seizures persist after one of these options, an additional dose of fosphenytoin (Cerebyx) 5 to 10 PE/kg or phenytoin (Dilantin) 5 to 10 mg/kg should be given. If a third AED is warranted due to persistent seizure activity, phenobarbital (Luminal), propofol (Diprivan), midazolam (Versed), levetiracetam (Keppra), and valproate (Depacon) are recommended. Phenobarbital (Luminal) is given at a dose of 15 to 20 mg/kg IV at a rate of 100 mg/minute, with a second dose of 5 to 10 mg/kg if seizures persist. If status epilepticus is not resolved after a third AED, intubation and general anesthesia are necessary (Adamolekun, 2022b).

Similarly, rescue treatments may be needed during seizure activities outside a hospital or clinical setting. Many patients have emergency medications to be administered by others during an acute seizure (not routine medications that are taken daily), such as diazepam (Valium) or other benzodiazepines, to stop the seizure quickly. These drugs can be prescribed for emergency use with clear instructions on administration by family or friends outside a clinical setting. Emergency care may still be needed, depending on the situation. Rescue medications may be used for seizures that are unusual or last longer than typical events, cluster seizures (multiple short seizures), or breakthrough seizures that may occur during medication changes or with an acute illness. Diazepam (Valium) can be given rectally, or a dissolvable tablet can be placed under the tongue or between the cheek and gum for quick absorption. Benzodiazepines are not generally recommended for daily use due to their risk of abuse, dependence, or increased fall risk, particularly for adults over 65 (Adamolekun, 2022b).

The most important consideration is safety during seizures. Caregivers should be instructed to provide a safe environment during a seizure. Patients should be gently helped to the floor and placed on their side, and their airway must be kept clear. Clothing around the neck should be loosened, and something soft, such as a pillow, should be placed under the head. The caregiver should stay with the patient and observe any behaviors that can be reported to the HCP later to support the diagnosis and treatment plan. Caregivers should call 911 if the seizure lasts more than 5 minutes, the patient does not return to their typical mental and physical state, the patient is injured or pregnant, there are repeated seizures, the seizure is the first for the patient, the patient has difficulty breathing, or the seizure occurs in water (Adamolekun, 2022b).

 

Maintenance Treatment: Pharmacological

Epilepsy patients are typically placed on long-term AED therapy. However, no single drug can control all types of seizures, and many patients require different drugs. Roughly 60% of seizures are controlled by a single AED, while 30%-40% require a combination. The preferred AED varies based on seizure type, potential adverse effects of the drug, interactions with other medications, cost, patient age, childbearing plans, and comorbid conditions. HCPs should consider that some AEDs reach therapeutic ranges quickly while others increase gradually over weeks. In addition, patient tolerance for AEDs can vary significantly; therefore, dosing should start low and gradually increase while monitoring drug toxicity. The goal of AED therapy should be the lowest dose needed to stop all seizures with the fewest side effects. The use of multiple AEDs should be avoided if possible due to poor adherence and the risk of drug interactions, with the incidence of adverse effects doubling. Once seizures are controlled, the patient should continue therapy until seizure-free for at least 2 years. HCPs can then consider weaning the AED using a slow taper (i.e., 10% every 2 weeks). If the patient relapses, AEDs should be restarted and continued indefinitely. Table 4 reviews the choice of drugs based on the seizure type, and Table 5 reviews the most common AEDs and their associated nursing implications. AEDs are typically grouped by mode of action, although the precise mechanism of action is not known for many, and others have multiple actions (Adamolekun, 2022a, 2022b; Schachter, 2022b, 2023).

Table 4

Choice of Antileptic Drug Based on Seizure Type

Seizure Type	AEDs	Use
Generalized-onset tonic-clonic seizures	Divalproex (Depakote ER) Valproic acid (Depakene)	First-line monotherapy
	Lamotrigine (Lamictal) Levetiracetam (Keppra) Topiramate (Topamax)	Second-line monotherapy or adjunctive therapy
	Perampanel (Fycompa) Zonisamide (Zonegran)	Adjunctive therapy
	Phenobarbital (Luminal)	Second-line monotherapy due to sedating effects and possible behavioral problems in children
Various types of focal-onset and focal-to-bilateral tonic-clonic seizures	Carbamazepine (Tegretol) Fosphenytoin (Cerebyx) Lamotrigine (Lamictal) Levetiracetam (Keppra) Oxcarbazepine (Trileptal) Phenytoin (Dilantin) Topiramate (Topamax)	First-line monotherapy
	Cenobamate (Xcopri) Divalproex (Depakote ER) Eslicarbazepine (Aptiom) Gabapentin (Neurontin) Lacosamide (Vimpat) Perampanel (Fycompa) Pregabalin (Lyrica) Valproic acid (Depakene) Zonisamide (Zonegran)	Second-line monotherapy or adjunctive therapy
	Clobazam (Frisium) Felbamate (Felbatol) Tiagabine (Gabitril) Vigabatrin (Sabril)	Third-line monotherapy or adjunctive therapy
	Phenobarbital (Luminal)	Effective but less desirable due to sedating effects and can cause behavioral problems in children
Typical non-motor absence seizures	Divalproex (Depakote ER) Ethosuximide (Zarontin) Lamotrigine (Lamictal) Valproic acid (Depakene)	First-line monotherapy
	Clobazam (Frisium) Levetiracetam (Keppra) Topiramate (Topamax) Zonisamide (Zonegran)	Also effective
Atypical non-motor absence seizures Non-motor seizures associated with other seizure types	Divalproex (Depakote ER) Felbamate (Felbatol) Lamotrigine (Lamictal) Topiramate (Topamax) Valproic acid (Depakene)	First-line monotherapy
	Clonazepam (Klonopin)	Effective but often develops tolerance
	Acetazolamide (Diamox)	Reserved for refractory cases
Epileptic (infantile) spasms Atonic seizures Myoclonic seizures	Divalproex (Depakote ER) Valproic acid (Depakene)	First-line monotherapy
	Vigabatrin (Sabril)	Risk of irreversible visual field defects
	Clonazepam (Klonopin)	Second-line therapy
Dravet syndrome	Cannabidiol (Epidiolex) Clobazam (Frisium) Topiramate (Topamax) Valproic acid (Depakene)	Adjunctive therapy
Tonic and/or atonic seizures in LGS	Divalproex (Depakote ER) Lamotrigine (Lamictal) Topiramate (Topamax) Valproic acid (Depakene)	First-line monotherapy
	Cannabidiol (Epidiolex)	Adjunctive therapy
	Clobazam (Frisium) Felbamate (Felbatol) Zonisamide (Zonegran)	Alternative or adjunctive therapy for atonic seizures
Juvenile myoclonic epilepsy	Divalproex (Depakote ER) Valproic acid (Depakene)	First-line monotherapy
	Lamotrigine (Lamictal) Levetiracetam (Keppra) Topiramate (Topamax) Zonisamide (Zonegran)	Second-line monotherapy or adjunctive therapy
Unclassified seizures	Divalproex (Depakote ER) Valproic acid (Depakene)	First-line monotherapy
	Lamotrigine (Lamictal)	Second-line monotherapy
	Levetiracetam (Keppra) Topiramate (Topamax) Zonisamide (Zonegran)	Third-line monotherapy or adjunctive therapy

(Adamolekun, 2022a, 2022b)

Table 5

Common Antiepileptic Drugs

Medication: diazepam (Diastat, Intensol, Valium) Dosing: Diazepam (Diastat) can be given rectally as a gel from 2.5 mg/0.5 mL to 20 mg/5 mL Diazepam (Intensol) oral solution is available in 5 mg/mL or 5 mg/5 mL Diazepam (Valium) oral is available in 2/5/10 mg tabs. IV/IM diazepam (Valium) 5 mg/mL; typically dosed 5 to 10 mg IV/IM every 5 to 10 minutes, not to exceed 30 mg for status epilepticus Nursing Implications/Patient Education: Black Box Warning related to the concomitant use of opioids Contraindicated with any other respiratory depressants and in children younger than 6 months Avoid the use of diazepam (Diastat, Intensol, Valium) for >5 episodes per month or 1 episode every 5 days Women should be cautioned against getting pregnant or breastfeeding while on diazepam (Diastat, Intensol, Valium; previously pregnancy category D per the US Food and Drug Administration [FDA])

Medication: lorazepam (Ativan) Dosing: IV 4 mg given over 2 minutes for status epilepticus; can repeat the dose once after 10-15 minutes for continued seizure activity with no further dose advised Oral lorazepam (Ativan) is available in 0.5 mg, 1 mg, and 2 mg tablets, as well as oral solution 2 mg/mL Nursing Implications/Patient Education: Used for all types of seizures in emergencies May be used for co-existing anxiety Women should be cautioned against getting pregnant or breastfeeding while on lorazepam (previously pregnancy category D per the FDA)

Medication: phenytoin (Dilantin) Dosing: Capsules are taken orally in 100/200/300 mg extended-release (ER) or 100 mg immediate-release (IR) phenytoin sodium (Dilantin) Liquid suspension 125 mg/5 mL Nursing Implications/Patient Education: When changing from a trade name to a generic, the risk of seizure increases due to differences in absorption Used to treat temporal lobe epilepsy, refractory seizures, secondarily generalized seizures, focal aware, and tonic-clonic seizures Can take with food, but the administration should be consistent with timing and taking with or without food Patients should be warned not to stop taking abruptly, change the amount taken, or take more than is prescribed Capsules should be protected from light Monitor for suicidal tendencies Should not be used in patients with liver disease Interactions with herbals, grapefruit juice, and cigarettes are common Calcium-containing medications, including antacids, can decrease the absorption of phenytoin (Dilantin) Reduces the levels of other AEDs, including: carbamazepine (Tegretol, Carbatrol) felbamate (Felbatol) lamotrigine (Lamictal) tiagabine (Gabitril) topiramate (Topamax) valproic acid (Depakene) zonisamide (Zonegran) Can cause an overgrowth of the gums, particularly in children; patients should be counseled regarding good flossing daily and brushing twice daily Young people may develop increased growth and darkening of facial and body hair, called hirsutism, which can affect female self-esteem Women should be cautioned against getting pregnant or breastfeeding while on phenytoin (Dilantin; previously pregnancy category D per the FDA)

Medication: phenobarbital (Luminol) Dosing: 15 mg, 16.2 mg, 30 mg, 32.4 mg, 60 mg, 64.8 mg, 97.2 mg, and 100 mg tablets Liquid solution 20 mg/5 mL Starting dose for adults is 60 mg/day, with 30 mg increases every 2 to 4 weeks to a total of 90-120 mg/day Lower doses are typically needed for older adults Starting dose for children is 1 to 6 mg/kg/day Nursing Implications/Patient Education: Oldest AED on the market Take consistently with or without food Tablets can be crushed and put in foods Liquid solution can be given with milk, juice, or water Store at room temperature but protect from light Do not take more than prescribed If a dose is missed, the patient should take it immediately and then take the next dose when it is due; if the next dose is due within 4 hours, they should skip a dose and not take a double dose Patients should not operate heavy machinery or drive while taking this drug Patients should not mix with alcohol May cause behavioral problems in children Patients should supplement with vitamin D and calcium to prevent bone loss Bone density testing is recommended for patients taking this medication for more than 5 years Long-term use may cause changes to soft tissues in joints, heels, and knuckle pads; Dupuytren's contractures; fibrous tumors; or Peyronie's disease (hardening of a portion of the penis) Can be addictive Should taper rather than stop abruptly to decrease withdrawal symptoms Reduces the effectiveness of birth control pills Women should be cautioned against getting pregnant or breastfeeding while using phenobarbital (Luminol; previously pregnancy category D per the FDA); Patients should be monitored for suicidal tendencies

Medication: valproic acid (Depakene; oral), valproate sodium (Depacon; intravenous), divalproex sodium (Depakote DR/ER, sprinkles; oral) Dosing: 250 mg tablet Liquid solution 250 mg/5 mL Starting dose for adults is 5 to 12.5 mg/kg/day, increased by 5 to 10 mg/kg/day until seizures are controlled Most patients take 750 to 3000 mg/day in divided doses; over 4000 mg/day is not recommended Children need higher doses, and older adults often need less than adults Therapeutic level for valproic acid (Depakene) is generally 50-100 mcg/mL (less for older adults) Levels should be monitored upon initiation of therapy until desired therapeutic level is reached, with any modifications to the medication regime, and routinely every 3 months With any signs of toxicity, a level should be obtained Children achieve a therapeutic level in about 2 days; older adults may take about 5 days Nursing Implications/Patient Education: Capsules must be swallowed whole, taken on a full stomach, and with a full glass of water The liquid solution can be mixed with food or other liquid due to the taste If a dose is missed, the patient should take it immediately and then take the next dose when it is due; if the next dose is due within 4 hours, they should delay the next dose for a few hours but not take two doses together. Effective for most forms of epilepsy as well as absence seizures (preferred first line) Often used as the first choice for generalized tonic-clonic seizures Can be given in combination with another AED, such as phenytoin (Dilantin) or carbamazepine (Tegretol) Can cause photosensitivity, weight gain, hair loss, nausea/vomiting, dizziness, fatigue, behavioral changes (irritability in children, depression in adults), and rashes Rarely causes serious side effects, including liver damage, pancreatitis, or clotting problems Women should be cautioned against getting pregnant or breastfeeding while using valproic acid (Depakene; previously pregnancy category D per the FDA); pregnant women should take the standard 400 mcg of folic acid daily to decrease this risk, with daily supplementation of up to 4 mg/day for 1 to 2 months prior to pregnancy Do not mix with alcohol; can also interact with herbals and vitamins and cause increased levels of other AEDs Patients should be monitored for suicidal tendencies Young girls can have elevated testosterone, and polycystic ovarian syndrome is possible

Medication: topiramate (Topamax) Dosing: Tablets 25 mg, 50 mg, 100 mg, or 200 mg. Sprinkle capsules 15 mg, 25 mg ER capsules 25 mg, 50 mg, 100 mg, and 200 mg Children have the fewest side effects with a 15 to 25 mg or lower starting dose at a range of 1 to 3 mg/kg/day and given nightly for the first week; it can be increased slowly up to 5 to 9 mg/kg/day Adult dose 25 to 50 mg/day in 2 divided doses with a target dose of 200 to 400 mg/day; it may be added to an enzyme-inducing AED such as carbamazepine (Tegretol) as adjunctive therapy. Nursing Implications/Patient Education: Indicated for partial-onset or primary, generalized tonic-clonic seizures in patients aged 2 to 16 years; may be used as monotherapy for patients over 10 years old Tablets should be swallowed whole and not crushed The sprinkle capsule should be swallowed whole or opened and sprinkled on soft food but not chewed Should be taken consistently with or without food Pill bottles should be kept away from heat or light If a dose is missed, take the forgotten dose immediately, then take the next dose at the appropriate interval; avoid double-dosing. It can cause anorexia/weight loss, memory loss, nervousness, allergic dermatitis, or acute myopia Serious adverse effects include secondary angle-closure glaucoma, metabolic acidosis, kidney stones, osteoporosis, and psychiatric effects, including hallucinations, delusions, depression, aggressive or hostile behavior Avoid concurrent use of vitamin C or calcium due to kidney stone risk May decrease blood levels of other AEDs, including: carbamazepine (Tegretol, Tegretol XR, Carbatrol) phenytoin (Dilantin) phenobarbital (Luminol) primidone (Mysoline) Women should be cautioned against getting pregnant or breastfeeding while using topiramate (Topamax; previously pregnancy category D per the FDA). Women should take at least 400 mcg of folic acid if taken during pregnancy Patients should not mix with alcohol Patients should be monitored for suicidal tendencies Older adults excrete the drug more slowly than adults and are more likely to have side effects

Medication: carbamazepine (Tegretol) Dosing: 200 mg tablet 100 mg chewable tablet Liquid solution 100 mg/5 mL ER capsule available in 100/200/300 mg ER tablet available in 100/200/400 mg Initial dosing for children is 5 to 10 mg/kg/day in 2 divided doses; increase to no higher than 35 mg/kg/day in 2 divided doses Initial adult dose of 100 to 200 mg BID is titrated in increments of 100 to 200 mg per day per week up to a maintenance dose of 600 to 1200 mg per day; the maximum dose is 1600 mg daily The IR form is taken 3 to 4 times per day with ER dosing BID Therapeutic levels are 4 to 12 mg/L Nursing Implications/Patient Education: Used in all age groups for partial seizures, generalized tonic-clonic seizures, and mixed seizure patterns Patients should protect the liquid solution from sunlight/heat If a dose is missed, the patient should take the dose immediately and then take the next dose when it is due; if the next dose is due within 4 hours, skip the forgotten dose It can be taken on an empty stomach or with food but consistently Dose-related side effects include drowsiness, diplopia, headaches, N/V, and dizziness and are noticeable 3 to 4 hours after a dose Common adverse effects include hyponatremia, osteoporosis, rashes, photosensitivity, exfoliative dermatitis, or erythema multiforme Serious adverse effects include aplastic anemia, toxic hepatitis, pancreatitis, Stephens-Johnson syndrome, or toxic epidermal necrolysis Monitor for suicidal tendencies Should not be taken by patients with: allergy to tricyclic compounds liver disease history of hyponatremia serious blood disorder history of bone marrow suppression history of MOI inhibitor taken in the last 14 days or intend to take within the next 14 days heart arrhythmias such as AV block Interacts with the following medications, causing increased clearance: birth control pills valproic acid (Depakene) phenytoin (Dilantin) phenobarbital (Luminol) primidone (Mysoline) clonazepam (Klonopin) topiramate (Topamax) corticosteroids, such as prednisone (Orapred) warfarin (Coumadin) cyclosporine (Sandimmune) May cause possible congenital disabilities, including spina bifida and other neural tube defects; pregnant women should take the standard 400 mcg of folic acid daily to decrease this risk, with daily supplementation of up to 4 mg/day for 1 to 2 months prior to pregnancy During the last month of pregnancy, women should take 10 mg of vitamin K daily to prevent bleeding disorders affecting babies born to mothers on carbamazepine (Tegretol)

Medication: clonazepam (Klonopin) Dosing: 0.5 mg, 1 mg, 2 mg tablets 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, 2 mg wafers (orally disintegrating tablets) Initial dosing in children up to 10 years of age is 0.01 to 0.02 mg/kg/day for a total of 0.25 to 0.75 mg per day. Dosage should increase by no more than 0.01 to 0.02 mg/kg/day every 3 days up to 0.1 to 0.2 mg/kg/day as the final dosing Adult dosing starts at 0.5 to 1.5 mg/day in 2 to 3 divided doses; it can be increased by 0.5 to 1 mg every 3 to 7 days to a maximum dose of 10 mg daily Most adult patients take 2 to 4 mg/day Nursing Implications/Patient Education: Should be taken consistently with or without food Should not be mixed with alcohol If doses are not equally divided during the day, a larger dose should be taken at night Should be stored at room temperature If a dose is missed, take the forgotten dose immediately, then take the next dose at the appropriate interval; avoid double-dosing May be used in combination with valproic acid (Depakene) Used in myoclonic seizures and absence seizures Common side effects include drowsiness, dizziness, nausea, loss of appetite, depression, hyperactivity in children, and impaired attention or memory Can cause withdrawal symptoms if stopped abruptly Serious side effects include allergic reaction (anaphylaxis) sores in mouth or throat indicating a blood problem yellowing of skin or eyes (liver involvement) rash hallucinations or severe confusion Monitor for a suicidal tendency Contraindicated with sensitivity to benzodiazepines, liver dysfunction, and narrow-angle glaucoma patients Rarely given to patients over 65 years of age due to behavioral effects and fall risk Women should be cautioned against getting pregnant or breastfeeding while using clonazepam (Klonopin; previously pregnancy category D per the FDA)

(Adamolekun, 2022a, 2022b; Schachter, 2022b, 2023; Tucker, 2022)

HCPs should educate patients to take AEDs at the same time every day and maintain a routine, either with or without food, as appropriate. Consistency is vital to maintaining a therapeutic blood level and controlling seizure activity. Patients should be warned never to stop their medication(s) without the prescriber's knowledge and direction. Most medications must be tapered to avoid withdrawal symptoms or increased seizure activity (Schachter, 2022b).

Cannabis use in the treatment of epilepsy has also been studied. The medicinal properties of cannabis have been credited mainly to the two most biologically active phytocannabinoids, Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD; Mouhamed et al., 2018). CBD was isolated in 1940, and THC was isolated in 1964. In the 1990s, the human endocannabinoid system was discovered, and the cannabinoid receptors—CB1 and CB2—were cloned. In 2015, Rosenberg and colleagues evaluated four primary clinical trials to examine the efficacy and safety of medical cannabis (CBD) in seizures. Two studies showed a partial antiseizure effect with CBD, and two showed no statistically significant effect. However, these studies were small, with insufficient blinding or randomization and incomplete datasets (Rosenberg et al., 2015). Mouhamed and colleagues (2018) assessed treatment with THC as too broad for therapeutic purposes. Still, they found positive findings when they reviewed five trials published between 2013 and 2018 studying the use of CBD in treating drug-resistant epilepsy among children or young adults. These studies showed a more significant reduction in the frequency of atonic and partial seizures, followed by reductions in tonic/tonic-clonic seizures, with minimal reports of adverse effects. Of note, these studies did not utilize CBD as a replacement for the subjects' AED but as an adjunct. In 2018, the FDA approved cannabidiol (Epidiolex) for treating seizures associated with LGS and Dravet syndrome in patients 2 years and older. This is the first FDA-approved drug that contains a purified substance derived from marijuana. The efficacy of cannabidiol (Epidiolex) was evaluated through 3 randomized, double-blind, placebo-controlled clinical trials involving 516 patients with either LGS or Dravet syndrome. Within these studies, when cannabidiol (Epidiolex) was taken alongside other medications, it reduced the frequency of seizures better than placebo. The most common side effects include sedation, sleepiness, fatigue, weakness, malaise, and lethargy. Less common side effects include elevated liver enzymes, decreased appetite, diarrhea, skin rash, and insomnia. Cannabidiol (Epidiolex) is an oral solution of 100 mg/mL. For LGS and Dravet syndrome, the initial dose is 2.5 mg/kg orally BID that can be increased after 1 week to the suggested maintenance dose of 5 mg/kg BID. The maximum dose is 10 mg/kg BID (20 mg/kg daily). Seizures/epilepsy is one of the most common qualifying medical conditions in the US for legalized medical cannabis/marijuana (FDA, 2020; Schachter, 2023).

 

Nonpharmacological and Self-Management Strategies

Epilepsy can impact an individual in various ways. HCPs must tailor the treatment plan to the individual's unique needs. A new seizure diagnosis can accompany a loss of independence, employment, ability to drive, and self-esteem. Therefore, HCPs should address psychosocial issues when creating a plan of care (Adamolekun, 2022a; Epilepsy Foundation, 2019). Patients and their families should be given tools to manage this disorder, including:

• a medication list and schedule
• a healthcare contact list with phone numbers and other contact information for all HCPs and local EMS
• an online seizure diary or physical journal that maintains information about seizure activity and potential triggers
• a dietary diary (Adamolekun, 2022a; Epilepsy Foundation, 2019)

Empowering patients with tools to prepare them for adverse events, prevent future events, and ensure preparedness in all situations is important. The Epilepsy Foundation (2019b) offers an online diary and a mobile application to document details about an individual's seizure experience. The online resource is called My Seizure Diary. This self-management tool and medication list allows patients to track their health history, manage medication and other therapies, recognize triggers through tracking, and even communicate with their HCP. Seizure alert devices are also available; they help alert family members that a seizure is occurring. This can be particularly helpful for children to alert caregivers or family members of impending seizure activity. Service animals can also be trained to alert patients of impending seizure activity or alert caregivers when a seizure occurs, maintaining protection of the patient as well as activating an alert for help (Adamolekun, 2022a; Epilepsy Foundation, 2019).

Dietary therapy can be beneficial in the management of epilepsy. Diets like the classic ketogenic diet ( a high-fat, low-carbohydrate, moderate-protein diet) can help control seizures in many patients. These diets are used in conjunction with medications. The ketogenic diet focuses on the ratio of fat to carbohydrate and protein grams combined. Carbohydrates and proteins are restricted, and typically there is a 3:1 or 4:1 ratio of fat to carbohydrates/proteins. An HCP or a dietician can prescribe a specific number of calories, and the calories will be focused on foods high in fat, such as heavy whipping cream, butter, mayonnaise, and olive or canola oil. This diet is usually started in the hospital with extensive dietary teaching for the family and may begin with an 18- to 24-hour fast except for water to expedite ketosis. The patient and/or their family must track the carbohydrates in all foods and medications. Children who follow this diet may decrease their seizures by up to 50%, and another 10% to 15% become seizure-free on this diet. Most continue to take their medications; however, the diet may allow them to decrease the dose required. Side effects of this diet include kidney stones, high cholesterol, constipation, slowed growth, and bone fractures. Dietary supplements are typically needed, as this diet does not provide sufficient amounts of all essential micronutrients (e.g., calcium, vitamin D, and selenium). Other diets that have shown success are the low glycemic index diet, the medium-chain triglyceride (MCT) ketogenic diet, and the modified Atkins diet (Epilepsy Foundation, 2017).

Other treatment options that should be considered when medication and diet do not control seizures or cause intolerable side effects include surgery or implantable devices. If seizures are intractable, the patient should be referred to an epilepsy center to be evaluated for surgery. Surgeons may elect to remove the part of the brain that is causing seizures. Neuromodulation is electrical stimulation using a small implanted device that sends electrical currents to the affected area of the brain. Various devices are available, and each works differently; generally, the stimulation releases substances that change how the cells act and restores their normal state (Adamolekun, 2022a).

 

Pregnancy Considerations

Pregnancy can bring unique challenges to managing epilepsy. Women are affected by epilepsy differently than men, partially due to hormonal changes, menstrual cycles, and menopause. Estrogen increases the brain's electrical activity, and progesterone has the opposite effect. AEDs are often adjusted due to the different life phases of women, and pregnancy poses challenges to managing medications and protecting fetuses. AEDs are associated with an increased risk of teratogenicity, such as fetal antiepileptic drug syndrome (i.e., cleft lip, microcephaly, developmental delay, cardiac defects, growth restriction, and abnormal facies, limbs, or digits). Over 90% of women with a history of epilepsy have healthy babies, yet 10% may have congenital disabilities. The risk of seizure activity during pregnancy increases by 25%, and many require medication adjustments. In most cases, women with a history of epilepsy do not have difficulty becoming pregnant. However, valproate (Depakene, Depakote) can contribute to polycystic ovarian syndrome, making conception more difficult (Adamolekun, 2022a; Schachter, 2022b).

When considering pregnancy, women with epilepsy should plan ahead, as planned pregnancies have opportunities for the greatest outcomes. Seizures can cause falls, auto accidents, premature labor, miscarriage, or decreased oxygen delivery and heart rate in the baby. The healthcare team for any patient considering pregnancy should include a neurologist or an epilepsy specialist and an obstetrician to develop a treatment plan ahead of time that provides optimal opportunities for the mother and baby. Unfortunately, approximately 50% of all pregnancies in the US are unplanned. A pre-pregnancy plan should include a thorough review of AEDs. Baseline pre-pregnancy AED drug levels should be obtained, and ongoing pregnancy monitoring should occur as hormonal changes cause fluctuating medication levels. Many AEDs decrease B12 and folate levels; therefore, preconception supplements are needed to support nutritional deficiencies and decrease the risk of neural tube defects associated with some medications, particularly in the first trimester. The suggested daily dose of folic acid is a multivitamin with 400 mcg folate and daily supplementation of up to 4 mg/day for 1 to 2 months prior to pregnancy for women taking valproate (Depakene, Depakote) or carbamazepine (Tegretol). Patients hoping to become pregnant should pay close attention to seizure triggers and ensure healthy living with a healthy diet and exercise. There are no reported increases in seizures during delivery; however, if a seizure occurs, medications should be given to control it immediately. A Caesarean section should be considered if the mother is at risk of seizure or experiences a prolonged seizure during labor (Adamolekun, 2022a; Schachter, 2022b).

Medications to prevent seizures must be continued during pregnancy, as harm can come to the baby and mother with seizure activity. Risks increase when the mother takes multiple AEDs and at higher doses. Due to these risks to the fetus, valproate (Depakene, Depakote) should be avoided during pregnancy if possible. Phenobarbital (Luminal), pregabalin (Lyrica), and topiramate (Topamax) pose an intermediate risk; specifically, topiramate (Topamax) increases the risk of a cleft palate if used in early pregnancy. The lowest-risk AEDs are carbamazepine (Tegretol), lamotrigine (Lamictal), and levetiracetam (Keppra). At this time, there are many unknowns about AED use in pregnancy, but it is undeniable that the risk increases with higher dosages and multiple medications. Pregnant mothers should take the minimum effective dose of a single medication to control seizures whenever possible. Regarding breastfeeding, most studies monitoring children up to 6 years of age born to mothers taking AEDs found they had equal or higher IQs when compared to children who were bottle-fed. Therefore, mothers are advised to take their AED immediately after breastfeeding to decrease the amount of medication in the breast milk (Adamolekun, 2022a; Schachter, 2022b).

 

Older Adult Considerations

Seizure rates are highest in the first few years of life, taper through the 50s, and rise again later in life. Seizures increase with other age-related conditions like Parkinson's disease but also rise with renal failure, electrolyte or glucose disturbances, drug intoxication or withdrawal, trauma, degenerative illnesses like Alzheimer's disease, infectious diseases such as meningitis or encephalitis, and strokes. Treating adults over 65 can be challenging due to their sensitivity and reactions to AEDs. Gabapentin (Neurontin) and lamotrigine (Lamictal) have advantages for older adults due to few interactions with other drugs. Gabapentin (Neurontin) is approved as a single therapy for seizures with high efficacy. Generally, carbamazepine (Tegretol) or phenytoin (Dilantin) may decrease the effectiveness of other drugs that older adults are often taking, such as warfarin (Coumadin). If warfarin (Coumadin) is taken with any of these medications, the prothrombin time (PT) must be checked frequently, and the dose must be adjusted accordingly. These medications also lower folate and vitamin D levels, which are important in managing osteoporosis and decreasing fractures in older women. The four primary enzyme-inducing AEDs are carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital (Luminol), and primidone (Mysoline; Adamolekun, 2022a, 2022b; Schachter, 2022b, 2023). These medications stimulate metabolism and decrease the serum concentration of other AEDs, as well as:

• warfarin (Coumadin)
• acetaminophen (Tylenol)
• digoxin (Lanoxin)
• furosemide (Lasix)
• propranolol (Inderal)
• quinidine (Cardioquin)
• theophylline (Theo-Dur)
• tricyclic antidepressants such as amitriptyline (Elavil; Adamolekun, 2022a, 2022b; Schachter, 2022b, 2023)

These AEDs also inhibit the metabolism of the following medications, often requiring dosage adjustments to avoid toxicity:

• amiodarone (Pacerone)
• cimetidine (Tagamet)
• ranitidine (Zantac)
• erythromycin (Erythrocin)
• nifedipine (Procardia XL)
• isoniazid (Niazid)
• verapamil (Calan)
• trimethoprim (Primsol; Adamolekun, 2022a, 2022b; Schachter, 2022b, 2023)

Gabapentin (Neurontin) and lamotrigine (Lamictal) are not metabolized in the same way and do not cause these interactions. Other potential adverse effects of AEDs for older adults include:

• increased risk of falls due to ataxia from the medications
• risk of bradycardia or other arrhythmias from carbamazepine (Tegretol)
• risk of hyponatremia with carbamazepine (Tegretol) or oxycarbazepine (Trileptal)
• thrombocytopenia, parkinsonism, dementia, and hearing deficits with valproate (Depakene, Depakote; Adamolekun, 2022a, 2022b; Schachter, 2022b, 2023)

 

Beer's Criteria are guidelines used to direct appropriate medications for older adults. The criteria were published in 1991 and were intended to improve the selection of medications for those 65 and older. The criteria are updated periodically. The latest update lists benzodiazepines as potentially inappropriate medications (PIMs); they should be cautiously administered to older adults due to their increased sensitivity and slower ability to metabolize these medications. There is also a risk of impaired cognitive functioning, delirium, falls, fractures, and accidents in and out of the home with these drugs (Fick et al., 2019; Schachter, 2022b).

Febrile Seizures in Children

A febrile seizure is a common seizure disorder in pediatric patients associated with fever without other intracranial abnormalities or infections. Febrile seizures can be classified into simple, complex, and symptomatic. Children with a genetic predisposition can be more susceptible to febrile seizures. Viruses, bacteria, or vaccines can be causative agents of febrile seizures. Simple febrile seizures last under 15 minutes, are generalized, occur once within 24 hours, and have no focal component. A complex febrile seizure lasts longer than 15 minutes, has a focal component, or occurs more than once in 24 hours. A symptomatic febrile seizure is due to a fever in a child with a preexisting neurological abnormality. Acute management of a febrile seizure is to maintain a patent airway, ensure effective breathing, provide oxygen therapy as needed, protect the patient from injury, place them in a semi-prone position and preferably on the right side, loosen their clothing, and treat the fever with antipyretics such as acetaminophen (Tylenol) or ibuprofen (Motrin). According to the duration and severity, rectal diazepam can be given for any seizure over 5 minutes in length, or IV diazepam (Valium), lorazepam (Ativan), or phenobarbital (Luminal) can be given for seizures lasting longer than 15 minutes (Victorio, 2022).

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