Tag: Epilepsy

Pediatric Seizures (2025)

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by Neema Francis, Faiz Ahmad, Thiagarajan Jaiganesh

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You Have A New Patient!

A 5-year-old female was brought into the ED as her parents noticed that she was not very responsive. She was diagnosed with otitis media 3 days ago and has been taking oral amoxicillin for it. This morning, she became irritable and was less active than usual. On arrival at the ED triage, the patient was tachypneic (40 bpm), tachycardic (145 bpm), and had a temperature of 39.4°C.

The image was produced by using ideogram 2.0.

The child did not respond to vocal stimuli but was opening her eyes spontaneously. She had a sluggish pupillary response to light, and she seemed unaware of her surroundings. Suddenly, the patient began seizing, with her eyes up-rolled and her hands clenched and stretched downwards.

What Do You Need To Know?

Importance

Pediatric seizures are a significant health concern due to their high incidence, diagnostic complexity, diverse causes, and potential for severe consequences. Seizures are among the most common neurological disorders in children, with approximately 4–10% experiencing at least one seizure by age 16 [1,2]. The incidence is highest in the first year of life and remains substantial throughout childhood, particularly in children under three years old [3]. Seizures can result from various causes, including fever, infections, genetic disorders, head injuries, metabolic disturbances, and structural CNS abnormalities, which often complicates diagnosis and treatment [3,4]. Prolonged seizures, such as status epilepticus lasting five minutes or more, can lead to lactic acidosis, neuronal injury, network alterations, or even neuronal death, particularly when lasting beyond 30 minutes [3]. These severe outcomes impact development, quality of life, and increase the risk of comorbidities such as intellectual disability, depression, and anxiety. Children with epilepsy face a 5–10 times higher mortality risk compared to their peers and are prone to medical complications and long-term educational and social challenges [3,5]. The condition places a significant burden on healthcare systems and induces considerable psychological stress on children and their families [6,7]. 

Epidemiology

Seizures affect up to 10% of children, with incidence rates ranging from 33.3 to 82 cases per 100,000 annually, peaking in the first year of life and declining during adolescence [6,8]. Most (94%) of children presenting to the emergency department (ED) with a first seizure are under 6 years of age [4]. Febrile seizures, the most common type in young children, affect 3–4% of all children, primarily those under five years old [5,6]. Neonatal seizures, with distinct characteristics due to brain immaturity, are a common neurological condition in newborns [9]. Key risk factors include a family history of seizures, fever, CNS infections (e.g., meningitis, viral infections), head injuries, pre-existing neurological conditions, and maternal factors such as alcohol use, smoking, and prenatal exposures [3,7].

Seizures can be symptomatic or idiopathic. Acute symptomatic seizures arise from recent events, while remote symptomatic seizures result from chronic conditions. Generalized tonic-clonic seizures are the most frequent type [4], while status epilepticus (SE), a critical condition, is often triggered by fever or CNS infections in children [3]. Genetic factors, metabolic disorders, electrolyte imbalances, and structural brain abnormalities are recognized as key causes [6]. Mortality in pediatric epilepsy is 2–4 times higher than the general population and significantly elevated in children with neurological comorbidities, with sudden unexpected death in epilepsy (SUDEP) as a leading cause [3]. Febrile seizures are often benign, but complex febrile seizures may increase the risk of future epilepsy [2,6]. 

Pathophysiology

The pathophysiology of pediatric seizures involves complex interactions of neuronal excitation and inhibition in the brain, influenced by age, developmental stage, and underlying conditions [9]. Seizures arise from abnormal, excessive, and synchronous neuronal activity, leading to transient signs and symptoms such as involuntary muscle activity [3,9]. This activity stems from an imbalance between excitatory and inhibitory neurotransmission.

Basic Mechanisms of Seizures

The primary mechanism behind seizures involves either a deficit in neuronal inhibition or an excess of excitatory stimuli. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) plays a crucial role. In mature brains, GABA inhibits neuronal firing, maintaining balance in the central nervous system [3]. However, in neonatal brains, the immature GABA system can paradoxically cause excitation, making neonates more susceptible to seizures [9]. Additionally, alterations in GABA function, such as receptor dysfunction, can lead to prolonged and high-intensity neuronal stimulation, further increasing excitability. Voltage-gated ion channels and excitatory neurotransmitters like glutamate also contribute to seizure generation. Glutamate receptors, such as NMDA and AMPA, are primary excitatory receptors in the CNS and are involved in seizure propagation.

Age-Related Factors and Neuronal Imbalance

The immature state of the neonatal brain predisposes it to seizures due to developmental differences. In early life, the formation of excitatory synapses occurs before the development of inhibitory synapses, contributing to an imbalance in neuronal activity [7,9]. Additionally, the GABA receptor in neonates can cause depolarization rather than hyperpolarization, further enhancing neuronal excitability. Ion channel imbalances, especially the premature maturation of channels involved in depolarization, exacerbate this vulnerability [7].

Specific Factors Contributing to Seizures

Several specific factors influence seizure pathophysiology:

  1. Genetic Factors: Mutations in genes regulating synapse development, ion transport, protein phosphorylation, and gene transcription can disrupt neuronal activity [7].
  2. Metabolic Disturbances: Conditions like hypoglycemia, hypocalcemia, hyponatremia, and other metabolic imbalances impair neuronal function, triggering seizures [2,3].
  3. Hypoxic Conditions: Perinatal asphyxia and hypoxic-ischemic encephalopathy damage brain cells, increasing seizure risk [2,6,7].
  4. Infections: CNS infections such as meningitis and encephalitis disrupt normal brain function, leading to seizures [2,4,10].
  5. Structural Abnormalities: Malformations of cortical development and acquired lesions alter neuronal networks, predisposing to seizures [2,9].
  6. Fever: Although the exact mechanism is unclear, fever lowers the seizure threshold in some children, particularly those prone to febrile seizures [2]. In febrile seizures, inflammatory mediators such as IL-1 have been shown to increase neuronal stimulation. Animal models and preliminary studies suggest that these mediators play a role in seizure pathophysiology, although the clinical significance remains under investigation.

Medical History

A detailed history is crucial for accurately diagnosing and managing seizures in children. The history should focus on the events immediately preceding the seizure, the seizure itself, and the period following the seizure. It is important to obtain information from the child (when possible) and any witnesses [2]. When taking a medical history for pediatric seizures in the emergency department, it is important to gather information about the following key features [2,3,7-9,11,12]:

1. History of Present Illness:

  • Onset and duration of seizures: This information helps determine the type and underlying cause of the seizure. Note how the event began, including any preceding aura. An aura is a subjective sensation or experience that may precede a seizure [2,9].
  • Precipitating factors: Certain triggers, such as sleep deprivation, fever, trauma, or stress, can increase the likelihood of seizures in some children [2,4,7].
  • Description of the seizure: A detailed description of the seizure (e.g., focal or generalized) is crucial, including the child’s behavior, movements, and any changes in consciousness. Any evidence of partial (focal) onset, such as twitching or jerking on one side of the body, should also be noted [2]. It is also important to note if the child experienced incontinence during the seizure. It’s important to gather information about the postictal period including the length of the period, and any focal neurologic deficits, such as weakness or confusion, that may be present after the seizure. Also important is whether the child was able to easily fall back asleep after the seizure.
  • Current symptoms and vital signs: Assess the child’s current symptoms, vital signs, and whether they have recovered from the seizure or not.

2. Past Medical History:

  • Developmental and medical history: Information about the child’s developmental milestones and any previous medical conditions or treatments is important in identifying potential causes of seizures [6].
  • Immunization status: Some seizures are related to diseases that are preventable by vaccination, so it’s important to inquire about the child’s immunization history.
  • Previous seizures: This may indicate an underlying neurological condition or epilepsy. 
  • Previous treatment for seizures: Determine whether the child has received prior treatment for seizures, including medications, and if these treatments were effective [2].

3. Medication History:

  • Assess whether the child is taking any medications that can lower the seizure threshold or exacerbate seizures.

4. Family History:

  • A family history of seizures or other neurological disorders may suggest a genetic predisposition.

It is important to note that seizures may sometimes occur without a clear cause. The emergency department’s priority is stabilizing the patient and preventing further seizures or complications.

Several risk factors for pediatric seizures should be considered during medical history-taking. There may be a higher likelihood of seizures occurring in children who have a familial history of seizures or epilepsy. Children born prematurely or with a low birth weight may be at an increased risk of seizures because they are more likely to have brain injuries or developmental problems. Children with neurological disorders, such as cerebral palsy, or brain injuries, such as traumatic brain injury, may also be at an increased risk of seizures because these conditions can cause abnormal electrical activity in the brain. Metabolic disorders, such as hypoglycemia or hyponatremia, are also known risk factors. Certain infections, such as meningitis or encephalitis, can cause inflammation in the brain and are thus predisposing factors for pediatric seizures. Developmental disorders, such as autism or intellectual disability, have also been identified as risk factors for pediatric seizures. Having one or more of these risk factors does not necessarily mean that a child will develop seizures, but it is essential to be aware of them to detect seizures early and initiate appropriate treatment.

As with all medical emergencies, it is important to look out for red flags. Concerns should be raised if the seizure was delayed or related to a head injury. Developmental delay or regression should be ruled out. Bleeding disorders or anticoagulation therapy are important considerations during history-taking in cases of pediatric seizures. It is also critical to rule out CNS infections as a possible cause of the seizure. Red flags in the history may include fever, headache, photophobia, vomiting, bulging fontanelles, neck stiffness, decreased consciousness, and focal neurologic symptoms.

Physical Examination

A thorough physical examination is essential when evaluating a child with a suspected seizure. It aids in identifying underlying causes, associated conditions, and guiding further diagnostic and treatment decisions. The examination should be performed in conjunction with a detailed history and adapted to the child’s clinical condition and developmental stage [7,12]. Children with seizures may have developmental delays or regression, which can indicate an underlying problem.

Initial Assessment

  1. Stabilization: If the child is actively seizing, focus on stabilizing the airway, breathing, and circulation (ABC) and stopping the seizure [2,10,12].
  2. Vital Signs [2,5,7]:
    • Temperature: Identify fever (above 38°C/100.4°F), the most common cause of seizures in children.
    • Heart Rate and Blood Pressure: Monitor for abnormalities that may indicate underlying conditions or complications.
    • Oxygen Saturation: Ensure adequate oxygenation.

General Appearance

  1. Level of Consciousness: Assess alertness and orientation. Note any altered mental status, which may suggest ongoing issues like status epilepticus or other underlying conditions [4,10].
  2. Activity Level and Responsiveness: Observe for irritability, excessive sleepiness, or signs of distress. Are they irritable? Are they playful? Are they well-kept? Look for signs of neglect or child abuse.
  3. Dysmorphic Features: Look for unusual physical features that may suggest a genetic or developmental syndrome [2].

Head and Neck Examination

  1. Head Circumference: Measure head size, especially in infants, as microcephaly can indicate an underlying condition [2,6].
  2. Signs of Trauma: Check for bruising or swelling that may suggest head injury.
  3. Fontanelles: In infants, examine the anterior fontanelle for bulging, which may indicate increased intracranial pressure.
  4. VP Shunt: Assess for ventriculoperitoneal (VP) shunt placement and any signs of malfunction or infection [2].
  5. Meningeal Signs: Look for nuchal rigidity or other signs of meningeal irritation, suggesting CNS infection [12].
  6. Eye and ear examination: Changes in pupils, papilledema, and retinal hemorrhages, or abnormal movements of the eyes that can indicate brain injury. Bulging tympanic membranes can indicate otitis media.

Skin Examination

  1. Bruising: Identify unexplained bruising, which may point to bleeding disorders or child abuse.
  2. Skin Rashes: Look for signs such as café au lait spots (indicative of neurofibromatosis), adenoma sebaceum or ash leaf spots (associated with tuberous sclerosis) [6], and port wine stains (typical of Sturge-Weber syndrome).
  3. Neurocutaneous Markers: Use a Woods lamp to detect signs of neurocutaneous syndromes.

Cardiovascular and Abdominal Examination

  1. Heart Sounds: Listen for abnormalities that may indicate a cardiac issue. Heart murmurs or arrhythmias that may be related to seizures.
  2. Abdomen: Palpate for masses or organomegaly, which may suggest a metabolic disorder. Children with metabolic disorders, such as liver or kidney disease, may have an enlarged liver or spleen, which can contribute to seizures.

Neurological Examination [2,4,12]

  1. Mental Status: Evaluate consciousness, orientation, and behavior.
  2. Cranial Nerves: Check pupillary responses, eye movements, and facial symmetry.
  3. Motor Function: Assess muscle strength, tone, symmetry, and any abnormal movements. Look for Todd’s paresis or focal weakness post-seizure.
  4. Reflexes: Evaluate deep tendon reflexes, noting asymmetry.
  5. Meningeal signs: Brudzinski’s or Kernig’s sign. Neck stiffness should also be assessed.
  6. Sensory Function: Test sensory responses, noting any deficits.
  7. Gait and Coordination: Observe gait, coordination, and balance in age-appropriate children.

Postictal Examination [6]

  1. Neurological Status: Note persistent confusion, weakness, or other deficits during the postictal phase, which may help localize the seizure origin.
  2. Symmetry: Pay close attention to symmetrical muscle tone, reflexes, and movements to identify potential focal brain issues.

Important Considerations

  1. Age-Appropriate Assessment: Adjust the neurological exam based on the child’s developmental stage, as young children may not fully cooperate [6].
  2. Clinical Context: Always interpret findings within the context of the child’s history and other clinical information [12].

Alternative Diagnoses

It is important to distinguish between true seizures and seizure mimics in the pediatric population, as the causes, treatment options, and outcomes can be quite different [14,15]. Examples of seizure mimics include vasovagal syncope, breath-holding spells, reflex anoxic seizures, arrhythmias, and non-epileptic paroxysmal events. It is helpful to look for clues in the history to rule out such mimics. A vagal reflex can be precipitated by a sudden fright or minor trauma. Temper tantrums should prompt consideration of breath-holding spells, which can lead to hypoxia and, in turn, a short tonic-clonic event with a quick recovery time. Visual and auditory changes paired with lightheadedness are suggestive of a vasovagal attack. A history of palpitations or strenuous exercise just before the event could indicate arrhythmias.

Certain symptoms can indicate a genuine seizure [14,15], including but not limited to:

  • Biting of the tongue on one side (high specificity).
  • Swift blinking of the eyes.
  • Fixed gaze with dilated pupils.
  • Repetitive lip movements.
  • Elevated heart rate and blood pressure during the episode.
  • A post-seizure phase.

Fevers are the most common cause of seizures in children [16]. Febrile convulsions can be further categorized into simple or complex febrile seizures:

  • Simple febrile seizures are generalized, last less than 15 minutes, and occur only once within a 24-hour timeframe. They are typically not associated with neurological deficits or other significant findings.
  • Complex febrile seizures last longer than 15 minutes, are focal (involving only one part of the body), or occur multiple times within a 24-hour period. While both types of febrile seizures are generally benign, complex febrile seizures require further investigation to rule out organic causes and carry a slightly higher risk of developing into epilepsy or other neurological disorders later in life.

In an afebrile child presenting with seizures, the differential diagnoses are extensive. Possible causes include:

  • Structural abnormalities in the brain, such as tumors, cysts, or malformations [16].
  • Metabolic disturbances, such as hypoglycemia, electrolyte imbalances, or trauma.

Status epilepticus is a medical emergency, defined as a seizure lasting longer than 5 minutes or recurrent seizures without regaining consciousness in between [16]. It can occur in both children and neonates and is associated with significant morbidity and mortality. Non-convulsive status epilepticus should be considered in any child with an altered mental status; it is ill-defined and remains a diagnosis of exclusion.

Neonatal seizures can be caused by a variety of factors, including hypoxic-ischemic encephalopathy, metabolic disturbances, infections, and intracranial hemorrhage [16]. Neonatal seizures can have serious consequences if left untreated, including brain damage and developmental delays.

Acing Diagnostic Testing

A bedside blood glucose level should be obtained as soon as possible to rule out hypoglycemia [4,15,17]. Venous blood gas, magnesium, and phosphorus levels are also valuable investigations to assess other electrolyte imbalances [12]. When there is concern for metabolic or respiratory disturbance, an arterial blood gas test may be considered [10]. Basic laboratory tests, including CBC, CRP, urine and blood cultures, are indicated when there is suspicion of underlying infections [2,4]. Beta HCG levels may be measured in pediatric seizures because a rare cause of seizures in children is a brain tumor called a germinoma, which secretes beta HCG. Beta HCG can be detected in blood or cerebrospinal fluid (CSF) to help confirm the diagnosis. Ammonia, Lactate, Pyruvate, if an inborn error of metabolism is suspected, these tests may be performed [2]. Antiepileptic drug  levels should be measured in children with known seizure disorders to ensure they are receiving an appropriate dose. Under-dosing can result in continued seizures, while overdosing can lead to side effects such as drowsiness, nausea, or confusion. A toxicology screen may be ordered if there is a concern for drug or alcohol use [12].

Imaging studies such as CT or MRI should be considered for children with focal seizures, persistent seizures despite acute management, or seizures in children under six months of age [4,6]. Signs of elevated intracranial pressure (ICP) also warrant imaging, especially in the context of a history of bleeding disorders or anticoagulant use. Although MRI provides superior anatomic detail, it often requires sedation, which can interfere with the patient’s assessment, making CT the preferred initial imaging study.

Lumbar puncture is recommended for infants aged 6 to 12 months who have not received adequate vaccination against H. influenzae or Streptococcus pneumoniae, or whose vaccination status is unknown, as these bacteria are common causes of bacterial meningitis in this age group [6]. Additionally, lumbar puncture should be considered in infants receiving active antibiotic therapy, as antibiotics can mask meningeal signs. Infants with focal or prolonged seizures, abnormal neurological examinations, or toxic appearance are high-risk groups in which lumbar puncture is strongly advised.

 

An electroencephalogram (EEG) is a non-invasive test that measures electrical activity in the brain and is crucial for identifying seizure activity and epileptiform discharges [5,6,18]. It aids in classifying seizure disorders, such as generalized or partial seizures, and can detect specific patterns associated with particular epilepsy syndromes [18]. Ideally, an EEG should be performed within 24 hours of the seizure to maximize its diagnostic utility [6].

Risk Stratification

The range of potential causes for non-febrile seizures in pediatric patients is broad, including metabolic imbalances, mass lesions, and non-accidental trauma. One specific diagnosis that is relatively common in children under 6 months of age and easily detectable to prevent extensive invasive testing is hyponatremia caused by formula over-dilution. In the emergency department, 3 ml/kg of 3% hypertonic saline is the mainstay of therapy.

A first febrile seizure is concerning and requires prompt evaluation and management [16]. It may be a sign of an underlying medical condition. Some factors increase the risk of bacterial infection, such as age less than 6 months or more than 60 months with the first febrile seizure, or age less than 12 months with incomplete or unknown immunization history. In addition, a first febrile seizure in a clinically unwell child with symptoms of infection, meningeal signs, or dehydration may indicate a more serious underlying condition and requires urgent medical attention.

Febrile status epilepticus, which is a prolonged seizure lasting more than 30 minutes or a series of seizures without full recovery between them, is another potential complication that can occur in the context of a febrile illness. It is important to recognize the signs and symptoms of febrile status epilepticus, such as a fever, stiff neck, or convulsions, and seek immediate medical attention to prevent serious neurological damage.

Management

The management of pediatric seizures in the emergency department primarily focuses on stabilizing the patient, treating the underlying cause, and preventing further seizures or complications [16,19]. The initial management of an actively seizing child includes ensuring that the child’s airway is protected and providing adequate oxygen and circulatory support. Oxygen can be supplied via a nasal cannula or simple face mask, and preparations for endotracheal intubation should be made if airway management requires escalation. The next step is to assess vital signs and check blood glucose levels to rule out hypoglycemia. Intravenous (IV) or intraosseous (IO) access should be established promptly, and the patient should be connected to a monitor by this stage. In febrile seizures, antipyretic therapy is the mainstay of treatment to relieve symptoms and is usually sufficient. Seizures lasting 15 minutes or longer should be managed in accordance with status epilepticus protocols, with the goal of rapidly stopping the seizure using antiepileptic medications to prevent permanent neuronal injury.

A seizure lasting 5 minutes is highly likely to be prolonged; thus, most protocols use a 5-minute definition. Initial management includes maintaining airway, breathing, and circulation (ABCs), administering oxygen, and preparing for intubation if required [16,19]. Hypoglycemia, defined as a capillary blood glucose (CBG) level of less than 60 mg%, should be corrected with a bolus of IV 10% dextrose at 5 mL/kg; this can be repeated to normalize serum glucose levels. IV or IO access should be secured, and blood samples should be sent for investigations. Benzodiazepines are the first-line antiepileptic agents. Options include intramuscular (IM) Midazolam (10 mg for patients >40 kg; 5 mg for patients 13–40 kg), IV Lorazepam (0.1 mg/kg/dose, maximum 4 mg/dose; can be repeated once), or IV Diazepam (0.15–0.2 mg/kg/dose, maximum 10 mg/dose; can be repeated once). If these are not feasible, IV Phenobarbital (15 mg/kg/dose as a single dose), rectal Diazepam (0.2–0.5 mg/kg, maximum 10 mg/dose; can be repeated once), or intranasal/buccal Midazolam may be used.

If first-line therapy is unsuccessful, second-line agents should be administered. Options include IV Fosphenytoin (20 mg PE/kg, maximum 1,500 mg PE/dose as a single dose), IV Valproic Acid (40 mg/kg, maximum 3,000 mg/dose as a single dose), or IV Levetiracetam (60 mg/kg, maximum 4,500 mg/dose as a single dose). IV Phenobarbital (15 mg/kg as a single dose) is another option if other agents are not appropriate. If first- and second-line therapies fail, anesthetic doses of Thiopental, Midazolam, Phenobarbital, or Propofol can be administered. This requires continuous EEG monitoring.

If the patient responds to any of these agents and returns to baseline, symptomatic medical therapy should be initiated. Management of non-convulsive status epilepticus follows a similar approach to that of convulsive status epilepticus. (Figure 1) [20]

Figure 1 - Interventions and management of SE in the ED and inpatient setting [2]. (SEHA pediatric seizure algorithm. Permission granted by Dr. Thiagarajan Jaiganesh)

In neonates, the same stabilization principles apply, including maintaining ABCs, collecting blood samples, and checking and correcting electrolytes [16]. IV Phenobarbitone (20 mg/kg) is administered as the first-line antiepileptic; this can be repeated in 5 mg/kg boluses every 15 minutes (maximum dose of 40 mg/kg) until the seizure is aborted. If the seizure persists, IV Phenytoin (15–20 mg/kg), diluted in equal parts with normal saline, should be administered at a maximum rate of 1 mg/kg/min over 35–40 minutes.

If the seizure remains unresolved, IV Lorazepam (0.05–0.1 mg/kg) or Diazepam (0.25 mg/kg bolus or 0.5 mg/kg rectal) may be used. Alternatively, IV Midazolam can be administered as a continuous infusion; this involves an initial IV bolus of 0.15 mg/kg followed by a continuous infusion starting at 1 μg/kg/min, increasing by 0.5–1 μg/kg/min every 2 minutes (maximum 18 μg/kg/min). Lastly, if all else fails, 100 mg IV or oral Pyridoxine may be administered. This is particularly useful for treating Pyridoxine-dependent neonatal seizures or seizures caused by Isoniazid (INH) toxicity. (Figure 2) [21].

Figure 2 - Neonatal seizure algorithm [21] - Open access https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857130/figure/Fig2/

When To Admit This Patient

In most cases, hospitalization is not necessary after a first unprovoked seizure, provided that a neurological examination is normal and prompt follow-up evaluation can be arranged [13]. Consultation with a neurologist and electroencephalography (EEG) can typically be performed on an outpatient basis. However, children who have experienced a prolonged seizure or who do not return to their baseline state within a few hours should be admitted to the hospital.

Hospitalization should also be considered in cases of extreme parental anxiety or if adequate follow-up evaluation cannot be arranged. It is essential to counsel parents about the increased likelihood of recurrence, which is approximately 33% overall. The risk of recurrence is higher in children under 18 months of age, when the temperature during the first convulsion is below 40°C, when the first seizure occurs within an hour of the onset of fever, or if there is a family history of febrile seizures.

Revisiting Your Patient

The image was produced by using ideogram 2.0.

Our patient was immediately moved to the resuscitation unit, placed on a simple face mask, and connected to monitors. She was administered rectal Diazepam; however, the seizure did not resolve. By this time, intraosseous (IO) access was established, and 0.1 mg/kg of Lorazepam (same as the IV dose) was given. This successfully aborted the seizure.

At this point, her vitals were as follows: temperature (T) 40°C, heart rate (HR) 93, respiratory rate (RR) 29, and blood pressure (BP) 118/90. She was lethargic and responsive only to painful stimuli. Other notable findings on examination included a full and tense anterior fontanelle, questionable neck rigidity, red and bulging tympanic membranes, reactive but unfocused pupils, a normal heart, lungs, and abdomen, good color and perfusion, and no petechiae or rashes. The patient displayed weak movement in all limbs and hyperactive deep tendon reflexes.

Pediatrics was consulted, and a presumptive diagnosis of meningitis was made. A complete blood count (CBC), C-reactive protein (CRP), blood culture, and chemistry panel were drawn. IV access was established at this point. Since increased intracranial pressure (ICP) was suspected, a lumbar puncture (LP) was initially deferred, and she was immediately given 500 mg of IV Ceftriaxone. A stat CT scan of the brain was normal, so an LP was performed, revealing visibly turbid cerebrospinal fluid (CSF).

The CSF analysis showed a white blood cell (WBC) count greater than 1000 cells/μL, with 95% neutrophils and 5% monocytes, a total protein level of 75 mg/dL, and a glucose level of 25 mg/dL. A Gram stain of the CSF revealed numerous WBCs and a few gram-positive cocci. She was admitted to the pediatric intensive care unit (PICU) for further management.

Authors

Picture of Neema Francis

Neema Francis

Dr. Neema Francis was born and raised in Dubai, UAE. She is currently a fourth-year emergency medicine resident at Tawam Hospital. She graduated with an MBBS from Gulf Medical University in 2020 and completed her internship at Sheikh Shakbout Medical City in 2021. Dr. Francis has a passion for volunteering and has been involved in various healthcare initiatives. She is also a competent researcher with publications to her name and a keen interest in emergency medicine and pediatric emergency medicine.

Picture of Faiz Ahmad

Faiz Ahmad

Picture of Thiagarajan Jaiganesh

Thiagarajan Jaiganesh

Dr. Jaiganesh is a Chairman and Consultant in Adult and Pediatric Emergency Medicine and serves as an Adjunct Assistant Professor at UAE University. As the former Director of the Emergency Medicine Residency Program at Tawam Hospital in Al Ain, UAE, Dr. Jaiganesh is dedicated to training the next generation of emergency medicine professionals. With a strong academic and professional background, Dr. Jaiganesh has published numerous peer-reviewed articles on emergency medicine and contributes as a Section Editor and Chapter Author for notable medical texts, including the Oxford Handbook for Medical School. A sought-after speaker, Dr. Jaiganesh has been invited to present at numerous national and international conferences and serves as an instructor in various life support courses. Additionally, Dr. Jaiganesh is an expert in medico-legal and clinical negligence matters, providing valuable insights into complex legal and ethical cases in healthcare.

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  18. Tharp BR. An overview of pediatric seizure disorders and epileptic syndromes. Epilepsia. 1987;28(Suppl 1):S36-S45. doi:10.1111/j.1528-1157.1987.tb05755.x.
  19. Friedman J. Emergency management of the pediatric patient with generalized convulsive status epilepticus. Paediatr Child Health. 2011;16(2):91-104. doi:10.1093/pch/16.2.91.
  20. Al-Hashaykeh NO, et al. Pediatric Status Epilepticus Clinical Practice Guideline. SEHA Pediatric Critical Care Council; 2023.
  21. Vegda H, Krishnan V, Variane G, Bagayi V, Ivain P, Pressler RM. Neonatal seizures—perspective in low-and middle-income countries. Indian J Pediatr. 2022;89(3):245-253. doi:10.1007/s12098-021-04039-2.

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Epilepsy and Status Epilepticus (2024)

~ iEM Education Project Team ~ Leave a comment

by Rand Redwan Al Sari & Imad Khojah

Authors
Listen

You have a new patient!

A 22-year-old woman is brought to the ER because of violent, jerky movements of her limbs that started 30 minutes ago. Her husband reports that the patient has a history of epilepsy. She is unresponsive. Her examination reveals tonic-clonic episodes and blood in her mouth. How would you manage this case? What are the initial steps you would take? What actions are needed to stop the seizure?

a-photo-of-a-22-year-old-female-patient-with-seizure (the image was produced by using ideogram 2.0)

What do you need to know?

Epidemiology and Importance

Epilepsy is one of the most common neurological diseases that can present to the emergency department [1]. It affects about 50 million people around the world, with an incidence of approximately 50.4 to 81.7 per 100,000 per year [1]. Epilepsy refers to having a lower seizure threshold than normal due to genetic, pathological, or unknown causes [2]. It is characterized by recurrent unprovoked seizures that present with motor, sensory, autonomic, or cognitive function alterations [2]. Previously diagnosed patients can present to the ED with breakthrough seizures due to factors like changes in the anti-seizure regimen or noncompliance with medication [2]. Other factors like sleep deprivation, stress, and flashing lights can also precipitate breakthrough seizures [2].

Prolonged or repetitive uncontrollable seizures are termed status epilepticus [2,3]. This emergency requires prompt treatment to prevent neuronal injury, severe disability, coma, or death [3]. The overall case fatality rates can reach up to 15% [2].

Pathophysiology

Neurons are normally stabilized by a balance between excitatory and inhibitory neurotransmitters [2]. A disruption of this balance leads to abnormal electrical discharge [2]. This discharge can propagate to nearby areas in the brain, which is evident clinically by the stepwise spread of the seizure (known as Jacksonian March) [2, 4]. Loss of consciousness in some cases is explained by the widespread involvement of large areas of the brain [2]. Many drugs used to restore this balance work by enhancing inhibitory activity through targeting GABAA subtype receptors [2]. Prolongation of the seizure leads to sequestration of GABAA receptors and upregulation of excitatory receptors; therefore, patients become unresponsive to medication [2, 5]. This explains the importance of timely treatment through early seizure control to prevent morbidity and mortality in patients with status epilepticus [2,3].

Medical History

A common scenario presenting to the ER is a patient complaining of a seizure-like episode with a sudden loss of consciousness and motor activity involvement [6]. However, various other presentations of seizures and other differential diagnoses with similar complaints should not be neglected. If the patient presents with status epilepticus, timely management, depending on the seizure type, is urgently needed (see management) [2].

Through history and examination, distinguishing a seizure from other acute medical conditions is important. An accurate diagnosis has crucial, direct consequences for activity restriction and therapy planning. Paying attention to features, especially at the onset, can help in identifying the seizure type for therapeutic implications and facilitate communication between physicians. Semiology at onset is important to classify seizures as focal, focal with impaired awareness (complex seizures), generalized, or unknown [7]. Further classification divides motor and non-motor seizures based on the descriptive assessment of the first symptom, which can vary widely according to the area of the brain affected [2].

The main aim of history-taking is to identify seizures from other similar conditions, classify them, identify triggers of new seizures, and detect a cause for a decreased seizure threshold in a patient previously diagnosed with epilepsy [8].

It is important for any patient with seizures to consider critical causes such as eclampsia, toxic ingestion, hypoglycemia, electrolyte imbalance, and increased intracranial pressure [9]. Emergent diagnoses, such as infection, acute brain injury, and serious mimics of seizure activity, must be identified and treated as soon as possible [2].

Initial history approach to a patient with suspected seizure [2] is a systematic evaluation, starting with the assessment of whether the event is likely to be a seizure, followed by differentiation of first-time versus recurrent seizures, and identifying factors that may trigger or reduce seizure thresholds [10].

Algorithmic Approach in Seizure History [2]

Determining Likelihood of a Seizure

The process begins by evaluating whether the event could be a seizure. Key indicators include:

  • Aura: A subjective sensation preceding the seizure.
  • Abrupt onset: Sudden occurrence of the event.
  • Non-suppressible limb shaking: Movements that are not voluntary or suppressible.
  • Postictal state: A transient neurological state after the event, characterized by confusion or fatigue.
  • History of epilepsy: Previous diagnosis or known history can strongly support the likelihood.

If these features are absent, the clinician is prompted to consider alternative diagnoses, such as:

  • Syncope (fainting),
  • Stroke,
  • Complex migraine, or
  • Non-epileptic spells, which may mimic seizures but lack neurological underpinnings.

Differentiating First-Time Seizures

If the event is determined to likely be a seizure, the next step is assessing whether it is the patient’s first seizure. For first-time events, the focus shifts to identifying potential triggers, including:

  • Medications: Use of or withdrawal from drugs that may lower the seizure threshold.
  • Exposures: Environmental or toxicological factors.
  • Immunosuppression: Conditions that may predispose to infections affecting the brain.
  • History of head trauma: A common precipitant for seizures.
  • Pregnancy: Associated risks like eclampsia.

Characterization of the Seizure

If it is not a first-time seizure, further characterization of the event is essential. Key aspects include:

  • Onset: Understanding preceding events to identify immediate triggers and auras.
  • Duration: Length of the seizure episode.
  • Awareness: Assessing the patient’s level of consciousness during the seizure.
  • Automatisms: Involuntary, purposeless movements that occur during the seizure and can be observed by others.
  • Postictal state: The presence of transient neurological deficits following the seizure (absent in some types, such as absence seizures).

The clinician also verifies whether the current event is consistent with the patient’s previous seizure patterns.

Exploring Factors Reducing the Seizure Threshold

For patients with recurrent seizures, it is crucial to evaluate factors that might decrease the seizure threshold, including:

  • Non-compliance or changes to anti-seizure drug (ASD) regimens.
  • Illness or trauma: Physical or psychological stressors.
  • Drug or alcohol use: Acute intoxication or withdrawal.
  • Catamenial exacerbations: Hormonal influences in menstruating individuals.
  • Pregnancy: Increased risk of seizures due to physiological changes or complications.
  • Sleep deprivation: A well-documented precipitant of seizures.

This step ensures that modifiable triggers or exacerbating factors are identified and addressed.

Physical Examination

Physical examination is crucial for identifying etiologies and directing the management plan. During an active seizure, pay close attention to posture, motor activity, eye deviation, and nystagmus, observing asymmetries and focal findings [11]. Check if the clonic activity is suppressible by applying gentle pressure. Unlike insuppressible seizures, suppression suggests a different diagnosis, such as nonepileptic spells or movement disorders. Check for mydriasis in the eyes, which is commonly found during seizures, but its persistence afterward can indicate toxic exposure [2].

Vital signs should be measured after seizure activity has ceased. They are of high importance and may direct the physician to possible causes (e.g., fever suggests meningoencephalitis, tachycardia and hypertension suggest toxic sympathomimetic exposure, while hypertension and bradycardia can indicate herniation syndromes) [2].

Moreover, a general examination should aim to search for both findings and sequelae of the seizures. Physical findings such as nuchal rigidity, stigmata of substance abuse, and lymphadenopathy may be present. Potential sequelae of seizures should also be assessed [12]. Evaluation of soft tissue and skeletal trauma is important, as injuries are common. Check for head trauma, tongue injury, shoulder dislocation, bone fractures, or aspiration [2].

Finally, a complete neurological examination should be performed. Immediately following the seizure, hyperreflexia, focal motor deficit (Todd’s paralysis), and extensor plantar response (positive Babinski) can occur and are expected to generally resolve within an hour [13]. If Todd’s paralysis does not resolve quickly, it raises the suspicion of a focal structural deficit that caused the seizure (e.g., stroke). The persistence of altered consciousness or signs of ongoing subtle seizures, such as automatisms, abnormal eye movements, and facial myoclonus, suggests the persistence of the seizure and must not be missed (nonconvulsive seizures and status epilepticus) [2].

Alternative Diagnoses

Although no single clinical finding or diagnostic modality is 100% confirmatory of the diagnosis of seizures [14, 15], understanding the circumstances of the event and the factors surrounding it can help rule out or confirm diagnoses with similar presentations [2].

Findings that make the diagnosis of seizures more probable include postictal disorientation and amnesia, cyanosis during the event, lateral tongue biting, non-suppressible limb shaking, and dystonic posturing [2, 15].

If the patient experienced diaphoresis, palpitations, nausea, and vomiting before the seizure, it may suggest transient cerebral ischemia due to arrhythmias [2].

The presence of motor activity, commonly including a tonic extension of the trunk or myoclonic jerks of the extremities associated with bradycardia, raises the suspicion of convulsive syncope [16]. Once cerebral perfusion is restored, convulsions stop without any postictal period [2].

The diagnosis of migraine can sometimes be misleading due to the presence of a preceding aura that might be confused with nonconvulsive seizures (e.g., the positive visual phenomenon in occipital seizures) [17]. Unlike occipital seizures, migraines have a peak preceded by gradual evolution and followed by gradual resolution. Moreover, patients typically have a positive history of migraines with a similar presentation [2].

Nonepileptic spells or psychogenic seizures mimic status epilepticus in their presentation [18]. Due to the prolonged duration of the spells (five minutes or more, and sometimes exceeding 20 minutes), patients commonly receive high doses of benzodiazepines and need to be monitored for any respiratory compromise. Findings consistent with this diagnosis include a stop-and-go pattern of the convulsions, horizontal head shaking, forward pelvic thrusting, asynchronous bilateral convulsions with eyes closed, a short postictal period despite the long duration of spells, avoidance of noxious stimuli, and preserved recollection of events. Furthermore, laboratory testing lacks reactive leukocytosis and lactic acidosis, which are present in nearly all cases of prolonged generalized convulsive seizures or status epilepticus [2, 19].

Acing Diagnostic Testing

Due to the challenges of diagnosing a seizure, seeking diagnostic testing is of high value. Laboratory studies, radiology, and other special procedures frequently provide important elements in patient assessment [20]. Although some cases require extensive metabolic testing, it is not indicated for cases with an unremarkable history and normal examination findings. Serum glucose levels should be measured in all cases, as hypoglycemia is a common cause of provoked seizures [21]. It is also important to note that hypoglycemia could result from prolonged seizures. If correcting the glucose level does not stop a seizure, an alternate diagnosis should be evaluated. Lactic acid and creatinine kinase should also be measured in cases of prolonged seizures to assess for acute metabolic acidosis and rhabdomyolysis, respectively [22]. A low level of lactic acid during a prolonged convulsive episode makes a seizure less likely (nonepileptic convulsions) [2].

On the other hand, the presence of advanced age, comorbidities, abnormal examination findings, or an ill appearance demands comprehensive metabolic testing. Such testing includes serum glucose, creatinine kinase, lactic acid, electrolytes, complete blood count, urea nitrogen, creatinine, AST, ALT, anti-seizure drug levels, pregnancy tests, and drug-of-abuse screening. Checking for electrolyte derangements is important, as these can trigger seizures (e.g., hyponatremia, hypocalcemia, and hypomagnesemia) [23]. Patients with a low bicarbonate level should undergo blood gas analysis. An anion gap metabolic acidosis resulting from lactic acidosis is expected to decline within the first hour after the convulsive seizure stops unless another cause is present. Liver enzymes are tested to check for liver-mediated metabolic abnormalities that can impact therapeutic decisions [2].

Furthermore, patients on antiseizure medication should have their levels checked to confirm compliance. Some drugs are known to be epileptogenic, and it may be necessary to test their levels as well. Drug-of-abuse screening can also be considered in patients presenting with first-time seizures, despite the fact that such testing cannot prove causation or change outcomes [2, 24].

Urgent neuroimaging is indicated for most cases of a first-time seizure, whereas patients with epilepsy who have returned to baseline do not require one. Prompt neuroimaging and CT consideration in the ER is indicated for patients with coma, focal neurological deficits, immunocompromised states, advanced age, anticoagulation use, malignancy, previous intracranial hemorrhage, severe thunderclap headache, status epilepticus, neurocutaneous syndromes, or suspected trauma [25]. Computed tomography (CT) is widely available, but MRI and CT perfusion can provide additional information. If an infection is suspected, lumbar puncture is indicated [2].

Electroencephalography (EEG) is useful for diagnosing nonconvulsive seizures, epilepsy, nonepileptic spells, and status epilepticus [26]. EEG can guide therapy and monitor the treatment of refractory cases. Although it is not cost-effective, it is a high-yield modality for cases with an unclear diagnosis [2].

Lastly, ECG monitoring might benefit patients with preceding or ongoing cardiac symptoms. It can provide early clues in cases of drug toxicity and help understand the etiology of the seizure [2, 27].

Risk Stratification

The presentation and findings of a seizure case can provide clues as to whether this case has any red flags that demand urgent care. History and examination findings such as immunocompromisation, the presence of a thunderclap headache, sudden neurological deficit, status epilepticus presentation, head trauma, persistent altered consciousness, and concurrent infection can indicate a worse outcome [10]. Such patients require extensive investigations and prompt treatment to minimize morbidity and mortality due to the cause of the seizure or as a consequence of the seizures themselves [28]. Critical care for these patient groups is essential to reduce complications such as infection-related issues, irreversible intracranial structural disease, refractory status epilepticus, hemodynamic compromise, and death [2].

The risks of experiencing a secondary seizure following the current presentation may change the management plan to include secondary seizure prophylaxis. Risk stratification, weighing the chances of recurrence (higher in patients with previous brain insult, abnormal EEG, brain imaging abnormalities, and the presence of nocturnal seizures) against the risks of adverse effects from antiseizure medication, should be conducted in collaboration with a consulting neurologist [2].

Management

The initial priorities in managing unstable patients are to recognize and treat hypoxia, hypotension, and hypoglycemia, and to initiate pharmacologic treatment when needed [2, 28, 29].

Initial stabilization of patients with active seizures presenting to the ER includes the following [2, 28, 29]:

  • Assess airway, breathing, and circulation: Do not use nasopharyngeal airway devices during the seizure, as they can cause injury and increase the risk of aspiration.
  • Pulse oximetry.
  • Electrocardiogram (ECG).
  • Finger stick: If the glucose level is less than 60 mg/dL, administer IV dextrose.
  • Aspiration precaution: Place the patient in the lateral decubitus position.
  • Abortive treatment: Administer if the seizure lasts more than 5 minutes or in the case of hemodynamic compromise.

First-line therapy [2, 28, 29]

The first-line pharmacological therapies for managing epilepsy, include three benzodiazepine agents: diazepam, lorazepam, and midazolam. These agents are commonly used for their rapid onset and efficacy in controlling seizures, especially status epilepticus. The table includes critical details on dosing, frequency, maximum permissible dose, pregnancy category, and specific cautions.

  1. Diazepam
  • Dose per kilogram: 0.15-0.2 mg/kg intravenously (IV).
  • Frequency: Administered every 5 minutes as needed.
  • Maximum Dose: Limited to 10 mg per individual dose and a cumulative total of 30 mg across all doses.
  • Pregnancy Category: D (indicating a potential risk to the fetus, but benefits may outweigh risks in life-threatening situations).
  • Cautions/Comments:
    • Continuous monitoring of respiration is essential due to the risk of respiratory depression, a common side effect of benzodiazepines.
  1. Lorazepam
  • Dose per kilogram: 0.1 mg/kg intravenously (IV).
  • Frequency: Administered every 5 minutes as necessary.
  • Maximum Dose: 4 mg per dose, with a cumulative maximum of 12 mg across all doses.
  • Pregnancy Category: D.
  • Cautions/Comments:
    • Similar to diazepam, respiratory monitoring is mandatory.
    • Intramuscular (IM) administration is contraindicated for lorazepam, likely due to inconsistent absorption or slower onset compared to IV administration.
  1. Midazolam
  • Dose per kilogram: 0.2 mg/kg, administered via multiple routes including IV, intramuscular (IM), or intranasal (IN).
  • Frequency: Doses can be repeated every 5 minutes as needed.
  • Maximum Dose: 10 mg per individual dose.
  • Pregnancy Category: D.
  • Cautions/Comments:
    • Respiratory monitoring is critical due to the sedative effects of midazolam.
    • The half-life of midazolam is approximately 7 hours, making it a relatively short-acting agent compared to others, which can influence its clinical use depending on seizure recurrence risk.

All three agents are effective for rapid seizure control but share common risks, including respiratory depression, necessitating vigilant monitoring, particularly in critical care or emergency settings. Their classification in pregnancy category D highlights the need for careful consideration of maternal and fetal risks versus benefits. Midazolam offers more flexibility in administration routes, making it a practical choice in situations where IV access is not readily available.

If the seizure stops, coordinate a disposition plan and consider non-convulsive status epilepticus in patients who do not return to baseline. However, if the seizure does not stop, ensure adequate dosing of first-line therapy, then proceed to second-line therapy, and finally to third-line therapy, one step at a time [2, 28, 29].

Second-line therapy [2, 28, 29]

The second-line treatment options for epilepsy, include on a variety of antiepileptic drugs. These agents are typically used when first-line benzodiazepines are insufficient to control seizures. The table details dosing, frequency, maximum permissible doses, pregnancy categories, and relevant cautions for clinical use.

  1. Levetiracetam
  • Dose per kilogram: 40-60 mg/kg administered intravenously (IV).
  • Frequency: Administered once over a 10-minute period.
  • Maximum Dose: 4500 mg.
  • Pregnancy Category: C (indicating that risks cannot be ruled out, but the drug may be used if benefits outweigh potential risks).
  • Cautions/Comments:
    • Requires renal clearance, so dose adjustments may be necessary in patients with renal impairment.
  1. Fosphenytoin
  • Dose per kilogram: 10-20 mg PE/kg (phenytoin equivalents) given IV or intramuscularly (IM).
  • Frequency: Additional 5 mg PE/kg can be administered after 10 minutes if needed.
  • Maximum Dose: 150 mg PE/kg.
  • Pregnancy Category: D (associated with risk but can be used in life-threatening situations).
  • Cautions/Comments:
    • Can cause hypotension and dysrhythmias, requiring cardiac monitoring during administration.
  1. Lacosamide
  • Dose per kilogram: 200-400 mg IV.
  • Frequency: An additional 5 mg/kg can be administered if necessary.
  • Maximum Dose: 250 mg.
  • Pregnancy Category: C.
  • Cautions/Comments:
    • Can cause arrhythmias.
    • Renal clearance is required, so adjustments are needed for patients with renal insufficiency.
  1. Phenobarbital
  • Dose per kilogram: 15-20 mg/kg IV.
  • Frequency: Additional 5-10 mg/kg can be given as needed.
  • Maximum Dose: Not explicitly mentioned but calculated based on repeated doses.
  • Pregnancy Category: D.
  • Cautions/Comments:
    • Monitor respiration closely due to the sedative and respiratory depressant effects.
    • A strong P450 enzyme inducer, which can affect the metabolism of other drugs.
  1. Phenytoin
  • Dose per kilogram: 15-20 mg/kg IV.
  • Frequency: Additional 5-10 mg/kg can be administered if necessary.
  • Maximum Dose: 30 mg/kg.
  • Pregnancy Category: D.
  • Cautions/Comments:
    • Risk of hypotension and dysrhythmias during administration, necessitating monitoring.
    • A strong P450 enzyme inducer, which impacts the metabolism of other medications.
  1. Valproic Acid
  • Dose per kilogram: 20-40 mg/kg IV.
  • Frequency: Additional doses of 20 mg/kg can be administered if necessary.
  • Maximum Dose: 3000 mg.
  • Pregnancy Category: D.
  • Cautions/Comments:
    • Strong P450 enzyme inducer.
    • May cause hepatotoxicity and platelet dysfunction, warranting caution in patients with liver disease or coagulopathy.

The second-line agents are reserved for scenarios where first-line therapy fails to achieve seizure control. Each agent has specific risks and monitoring requirements. For example:

  • Levetiracetam and lacosamide are generally well-tolerated but require dose adjustments in renal impairment.
  • Phenobarbital, phenytoin, and valproic acid necessitate respiratory and hepatic monitoring due to their systemic side effects.
  • Fosphenytoin and phenytoin require cardiac monitoring due to their potential to induce arrhythmias.

The choice of agent depends on the patient’s clinical status, underlying conditions, and the safety profile of the drug.

Third-line therapy [2, 28, 29]

The third-line therapy agents for managing refractory epilepsy, particularly in patients requiring intubation, mechanical ventilation, and hemodynamic support are administered in critical care settings to control seizures when first- and second-line therapies fail. Each drug is described with its dosing regimen, frequency, maximum dose, pregnancy category, and significant precautions.

  1. Ketamine
  • Dose per kilogram:
    • Loading dose: 1.5 mg/kg intravenously (IV).
    • Maintenance dose: 0.5 mg/kg every 3-5 minutes as needed.
  • Maximum Dose: Not explicitly stated, but administered as required to control seizures.
  • Pregnancy Category: N (Not classified).
  • Cautions/Comments:
    • Ketamine acts as an NMDA antagonist, a unique mechanism among anticonvulsants.
    • Hypotension is a potential side effect, necessitating blood pressure monitoring.
  1. Midazolam
  • Dose per kilogram:
    • Loading dose: 0.2 mg/kg IV.
    • Maintenance dose: 0.2-0.4 mg/kg every 3-5 minutes.
  • Maximum Dose: 2 mg/kg for the loading dose.
  • Pregnancy Category: D (Risk to the fetus exists, but use may be justified in emergencies).
  • Cautions/Comments:
    • Midazolam may cause hypotension and requires continuous hemodynamic monitoring.
  1. Pentobarbital
  • Dose per kilogram:
    • Loading dose: 5-15 mg/kg IV.
    • Additional doses of 5-10 mg/kg may be given if required.
  • Maximum Dose: 25 mg/kg for the loading dose.
  • Pregnancy Category: D.
  • Cautions/Comments:
    • Pentobarbital has a long half-life (22 hours), which makes it effective for sustained seizure control but may prolong sedation.
    • It carries significant risks, including hypotension, ileus, myocardial suppression, immunosuppression, and thrombocytopenia, requiring vigilant monitoring in an intensive care setting.
  1. Propofol Infusion
  • Dose per kilogram:
    • Loading dose: 1-2 mg/kg IV.
    • Maintenance dose: 0.5-2 mg/kg every 3-5 minutes as needed.
  • Maximum Dose: 10 mg/kg for the loading dose.
  • Pregnancy Category: B (Lower risk, but use must be cautious).
  • Cautions/Comments:
    • Propofol has a short half-life (0.6 hours), allowing for rapid onset and recovery.
    • Side effects include hypotension, respiratory depression, hypertriglyceridemia, pancreatitis, and the rare but potentially fatal propofol infusion syndrome. Close monitoring of triglycerides and cardiac function is necessary.

Third-line therapies are used in severe, refractory cases of epilepsy where intubation, ventilation, and hemodynamic support are required. These drugs induce deep sedation or anesthesia to suppress seizure activity effectively. Key considerations for their use include:

  • Ketamine: Offers a unique mechanism (NMDA antagonism), useful in resistant cases.
  • Midazolam and pentobarbital: Provide effective sedation but require careful respiratory and cardiovascular monitoring due to risks of hypotension and prolonged sedation.
  • Propofol: Its short duration of action allows for precise titration, but metabolic side effects and infusion syndrome necessitate caution.

The choice of agent depends on the clinical scenario, patient stability, and institutional protocols. These medications are used alongside comprehensive critical care support to manage complications and optimize outcomes.

Special Patient Groups

Certain notes are important to remember regarding special patient groups. In cases of seizures during pregnancy, considering the diagnosis of eclampsia is a high priority. Magnesium is the drug of choice for acute eclamptic seizures [30]. If a pregnant patient was previously diagnosed with epilepsy, a lower seizure threshold may result due to noncompliance, adjusted regimens, sleep deprivation, nausea and vomiting, or increased drug clearance. When managing status epilepticus, the risks to the fetus from the seizure are higher than the risks from the medication; therefore, manage the patient as you would a nonpregnant individual [31]. In the case of a new, non-eclamptic seizure, a workup is indicated as previously mentioned [2].

When To Admit This Patient

The decision to admit or discharge should be individualized based on the underlying illness, recurrence risk, and need for maintenance pharmacotherapy [32]. Admission for observation alongside neurological consultation should be considered for patients with an uncertain diagnosis, a history of neurological disease or other comorbidities, or in situations where follow-up is unlikely. In contrast, patients can be discharged home with early referral to a neurologist if they have normal examination findings, no significant comorbidities, no known structural brain disease, did not require more than a single dose of benzodiazepines, and are expected to comply with follow-up instructions [2].

Discharge instructions should include guidance on car driving, potentially dangerous activities (e.g., swimming, cycling, climbing ladders), and information regarding any needed follow-up [2, 33].

Revisiting Your Patient

A 22-year-old woman with a previous history of epilepsy was brought to the ER due to generalized tonic-clonic insuppressible movements of her limbs that started 15 minutes ago.

You immediately assessed the airway, breathing, and circulation and placed the patient in the lateral decubitus position to prevent aspiration, as she had a tongue injury. Blood sugar was measured using a finger stick, ruling out hypoglycemia. Lorazepam was then administered as abortive treatment.

You began taking a history from her husband. They were having lunch together when his wife suddenly started seizing, and he was unable to stop it. She had not regained consciousness since then. He mentioned that she had been inconsistent with her antiepileptic medication because she wanted to get pregnant and had read online about potential harms of the medications on a growing baby.

Her lactic acid level was high, her pregnancy test was negative, and the rest of her laboratory findings were within normal limits.

The patient was diagnosed with status epilepticus, a medical emergency requiring urgent management. The ABC approach was performed to ensure the patient’s safety, followed by the administration of benzodiazepines. If first-line therapy fails, second- and third-line therapies should be administered sequentially. Inconsistency with antiepileptic medication highlights the need for patient education and further discussion regarding her concerns and available treatment options.

Authors

Picture of Rand Redwan Al Sari

Rand Redwan Al Sari

Dr Rand Al Sari is a dedicated General Physician practicing in Saudi Arabia. With a strong commitment to patient care, she is also actively engaged in medical research, staying at the forefront of healthcare advancements and integrating this knowledge into her clinical practice. Passionate about medical writing and journaling, Dr Al Sari reflects on her experiences to contribute meaningfully to the medical community, with a focus on evidence-based healthcare and improving patient outcomes.

Picture of Imad Khojah

Imad Khojah

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Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

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