Clinical Approach to Seizures

Pediatric Comprehensive Framework

1
Symptom Overview
Overview
2
Pathophysiology
Mechanism
3
History Taking
History
4
Physical Examination
Examination
5
Differential Diagnosis
Differential
6
Investigations
Workup
7
Clinical Decision-Making
Algorithm
8
Pearls and Pitfalls
Summary

1. Symptom Overview

Understanding the clinical significance and classification of seizures in children

Seizures are among the most common neurological emergencies in pediatric practice, affecting approximately 4-10% of children by age 16. Febrile seizures alone occur in 2-5% of children between 6 months and 5 years of age, making them the most common type of childhood seizure. Epilepsy, defined as recurrent unprovoked seizures, affects approximately 0.5-1% of children worldwide, with the highest incidence occurring in the first year of life. Seizures account for approximately 1-2% of all pediatric emergency department visits and represent a significant source of parental anxiety and healthcare utilization.

Definition

A seizure is a transient occurrence of signs and/or symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain. It represents a sudden, uncontrolled electrical disturbance that can cause changes in behavior, movements, feelings, and levels of consciousness. In children, the clinical manifestation varies significantly based on age, brain maturation, and the location and extent of abnormal neuronal discharge.

Key Epidemiology

Incidence: 25-60 per 100,000 children per year
Febrile seizures: 2-5% of children aged 6 months to 5 years
Epilepsy prevalence: 0.5-1% of children

Peak incidence: First year of life
Status epilepticus: 10-40 per 100,000 children per year
First unprovoked seizure: 30% risk of recurrence within 2 years

Classification by Seizure Type (ILAE 2017)

The International League Against Epilepsy (ILAE) 2017 classification provides a standardized framework for categorizing seizures based on onset, awareness, and motor versus non-motor manifestations.

Onset Type	Subcategory	Key Features	Common Pediatric Examples
Focal Onset	Aware (simple partial)	Consciousness preserved; motor, sensory, autonomic, or psychic symptoms	Benign rolandic epilepsy, focal motor seizures
	Impaired awareness (complex partial)	Altered consciousness; automatisms common	Temporal lobe epilepsy, mesial temporal sclerosis
	Focal to bilateral tonic-clonic	Begins focally, then generalizes	Structural lesions, focal cortical dysplasia
	Motor vs Non-motor	Clonic, tonic, myoclonic, or sensory, cognitive, emotional	Various focal epilepsy syndromes
Generalized Onset	Tonic-clonic (grand mal)	Bilateral stiffening then rhythmic jerking; postictal confusion	Juvenile myoclonic epilepsy, genetic generalized epilepsies
	Absence (petit mal)	Brief staring spells; abrupt onset and offset; minimal postictal state	Childhood absence epilepsy (4-8 years peak)
	Myoclonic	Brief, shock-like jerks; may be single or repetitive	Juvenile myoclonic epilepsy, Dravet syndrome
	Atonic (drop attacks)	Sudden loss of muscle tone; falls	Lennox-Gastaut syndrome, myoclonic-atonic epilepsy
Unknown Onset	Unclassified	Insufficient information to classify	Unwitnessed seizures, incomplete history

Classification by Duration

Category	Duration	Clinical Significance	Management Implications
Self-limited seizure	Less than 5 minutes	Most seizures terminate spontaneously; low risk of neuronal injury	Supportive care; rescue medication typically not required
Prolonged seizure	5-30 minutes	Increased risk of progression to status epilepticus; may require intervention	Administer rescue benzodiazepine after 5 minutes of continuous seizure activity
Status epilepticus	Greater than 5 minutes (operational) or greater than 30 minutes (traditional)	Medical emergency; risk of permanent neuronal injury increases with duration	Emergency treatment protocol; IV access; escalating antiseizure therapy
Refractory status epilepticus	Persists despite two appropriate antiseizure medications	High morbidity and mortality; may require ICU admission	Continuous infusion of anesthetic agents; EEG monitoring

Updated Definition of Status Epilepticus

The operational definition of status epilepticus has been revised to 5 minutes of continuous seizure activity or recurrent seizures without return to baseline. This earlier threshold reflects evidence that seizures lasting beyond 5 minutes are unlikely to self-terminate and that earlier treatment improves outcomes. In children, the 5-minute rule should prompt administration of first-line benzodiazepine therapy.

Classification by Etiology

Provoked (Acute Symptomatic) Seizures

Seizures occurring in close temporal relationship to an acute central nervous system insult or systemic disturbance:

Febrile seizures — most common provoked seizure in children
Metabolic disturbances — hypoglycemia, hyponatremia, hypocalcemia
Central nervous system infections — meningitis, encephalitis
Traumatic brain injury — within 7 days of injury
Toxic exposures — medications, drugs, environmental toxins
Acute stroke or intracranial hemorrhage

Unprovoked Seizures

Seizures occurring without an identifiable acute precipitant:

Genetic/Idiopathic epilepsy — childhood absence, juvenile myoclonic epilepsy
Structural — cortical malformations, tumors, mesial temporal sclerosis
Metabolic — inborn errors of metabolism (chronic)
Immune — autoimmune encephalitis
Infectious — post-infectious epilepsy
Unknown — no identifiable cause despite workup

Age-Specific Seizure Patterns

The clinical manifestation of seizures varies dramatically with age due to differences in brain maturation, myelination, and neuronal connectivity.

Age Group	Common Seizure Types	Typical Presentations	Important Considerations
Neonates (0-28 days)	Subtle, tonic, clonic, myoclonic	Lip smacking, eye deviation, bicycling movements, apnea, desaturation	Often subtle and difficult to recognize; high index of suspicion needed; EEG confirmation often required
Infants (1-12 months)	Infantile spasms, focal seizures, febrile seizures (after 6 months)	Clusters of brief flexor or extensor spasms; subtle behavioral arrest	Infantile spasms are a medical emergency requiring urgent EEG; West syndrome triad
Toddlers (1-3 years)	Febrile seizures, generalized tonic-clonic, focal seizures	Generalized stiffening and shaking with fever; focal motor activity	Peak age for febrile seizures; distinguish simple from complex febrile seizures
Preschool (3-5 years)	Febrile seizures, absence seizures emerging, focal epilepsies	Staring spells; brief unresponsiveness; generalized convulsions	Absence seizures may be mistaken for inattention; upper age limit for febrile seizures
School age (6-12 years)	Childhood absence epilepsy, benign rolandic epilepsy, focal seizures	Frequent brief staring spells; nocturnal focal motor seizures with drooling	Childhood absence epilepsy peaks at 4-8 years; benign rolandic epilepsy peaks at 7-10 years
Adolescents (12-18 years)	Juvenile myoclonic epilepsy, juvenile absence epilepsy, focal epilepsies	Morning myoclonic jerks; generalized tonic-clonic seizures on awakening	Sleep deprivation and alcohol are common triggers; lifelong treatment often needed for juvenile myoclonic epilepsy

Febrile Seizures: Special Considerations

Febrile seizures deserve special attention given their high prevalence and the anxiety they cause families.

Feature	Simple Febrile Seizure	Complex Febrile Seizure
Duration	Less than 15 minutes	Greater than 15 minutes
Seizure type	Generalized	Focal features present
Recurrence in 24 hours	Does not recur	May recur within 24 hours
Postictal state	Brief (less than 1 hour)	Prolonged or focal deficits (Todd paralysis)
Age	6 months to 5 years	Any age with fever, but features suggest underlying pathology
Recurrence risk	Approximately 30% overall	Higher recurrence risk; increased epilepsy risk
Epilepsy risk	Approximately 1-2% (slightly above general population)	4-15% depending on features

Key Concept: The “3 Cs” of Pediatric Seizure Evaluation

Characterize — Define the seizure type (focal vs generalized, motor vs non-motor, awareness)
Cause — Identify provoked versus unprovoked; determine underlying etiology
Consequences — Assess risk of recurrence, impact on development, and need for treatment

2. Pathophysiology and Mechanisms

Understanding the underlying mechanisms of seizures in the developing brain

Seizures result from an imbalance between excitatory and inhibitory neurotransmission in the brain, leading to abnormal hypersynchronous neuronal firing. In the developing pediatric brain, unique maturational factors create increased seizure susceptibility compared to adults. Understanding these mechanisms is essential for rational diagnostic and therapeutic approaches.

The Seizure Threshold Concept

Every brain has an inherent “seizure threshold” — the point at which the balance between excitation and inhibition tips toward uncontrolled neuronal firing. Seizures occur when factors lower this threshold (proconvulsant) or when excitatory inputs exceed the threshold capacity.

Factors That Lower Seizure Threshold

Fever (most significant in children)
Sleep deprivation
Metabolic disturbances (hypoglycemia, hyponatremia)
Certain medications (tramadol, bupropion, fluoroquinolones)
Alcohol or benzodiazepine withdrawal
Photic stimulation (in susceptible individuals)
Hyperventilation
Stress and emotional factors

Factors That Raise Seizure Threshold

Antiseizure medications
Adequate sleep
Metabolic homeostasis
Ketogenic diet (increases GABA, decreases glutamate)
Vagus nerve stimulation
Normal body temperature
Avoidance of known triggers

Neuronal Excitation and Inhibition

Component	Mechanism	Clinical Relevance
Glutamate (Excitatory)	Primary excitatory neurotransmitter; acts on NMDA, AMPA, and kainate receptors; causes neuronal depolarization via sodium and calcium influx	Excessive glutamatergic activity leads to seizures; excitotoxicity causes neuronal injury in prolonged seizures; NMDA receptor antagonists (ketamine) can terminate refractory status epilepticus
GABA (Inhibitory)	Primary inhibitory neurotransmitter; GABA-A receptors cause chloride influx and hyperpolarization; GABA-B receptors cause potassium efflux	Benzodiazepines and barbiturates enhance GABA-A function; first-line treatment for status epilepticus; GABA-A receptor internalization occurs with prolonged seizures, reducing benzodiazepine efficacy
Voltage-gated sodium channels	Responsible for action potential generation and propagation; mutations cause channelopathies	Target of many antiseizure medications (phenytoin, carbamazepine, lamotrigine); SCN1A mutations cause Dravet syndrome
Voltage-gated calcium channels	T-type calcium channels involved in thalamocortical oscillations generating absence seizures	Ethosuximide blocks T-type calcium channels; first-line for childhood absence epilepsy
Potassium channels	Responsible for repolarization; mutations cause neonatal epilepsies	KCNQ2/KCNQ3 mutations cause benign familial neonatal seizures; ezogabine opens potassium channels

The Immature Brain: Why Children Are More Susceptible

The pediatric brain has several developmental features that increase seizure susceptibility compared to the mature adult brain.

Developmental Factor	Mechanism	Clinical Implication
Excitatory GABA in early life	GABA is depolarizing (excitatory) in neonates due to high intracellular chloride; switches to inhibitory by 2-3 months	Benzodiazepines may be less effective in neonates; phenobarbital (enhances chloride conductance regardless of gradient) may be preferred
Increased NMDA receptor expression	Higher density of NMDA receptors in developing brain for synaptic plasticity and learning	Greater excitability; increased susceptibility to excitotoxic injury during prolonged seizures
Incomplete myelination	Myelination continues until early adulthood; incomplete insulation of axons	Altered seizure propagation patterns; different semiology by age; “subtle” seizures more common in neonates
Immature blood-brain barrier	More permeable blood-brain barrier in young infants	Increased vulnerability to systemic metabolic disturbances; some medications penetrate better
Temperature sensitivity	Immature thermoregulation; rapid temperature changes affect neuronal excitability	Febrile seizures are unique to childhood; fever dramatically lowers seizure threshold in young children
Ongoing synaptogenesis	Rapid synaptic formation and pruning during critical periods	Seizures during development may disrupt normal brain wiring; potential for cognitive impact

Clinical Pearl: GABA Paradox in Neonates

In neonates, GABA acts as an excitatory neurotransmitter because the chloride gradient is reversed (high intracellular chloride due to immature potassium-chloride co-transporter KCC2). This explains why benzodiazepines may paradoxically worsen neonatal seizures in some cases and why phenobarbital is often preferred as first-line treatment in this age group. The switch from excitatory to inhibitory GABA signaling occurs around 2-3 months of age.

Mechanisms by Condition

Condition	Pathophysiological Mechanism	Treatment Implication
Febrile seizures	Fever increases neuronal excitability through temperature-sensitive ion channels and inflammatory cytokines (interleukin-1β); immature thermoregulation and myelination contribute	Antipyretics do not prevent febrile seizures (temperature change rate matters more than peak); benzodiazepines for prolonged febrile seizures
Infantile spasms (West syndrome)	Dysfunction of the hypothalamic-pituitary-adrenal axis; excess corticotropin-releasing hormone (CRH) in immature brain causes spasms; multiple etiologies converge on this pathway	ACTH or vigabatrin are first-line treatments (ACTH suppresses CRH); vigabatrin especially effective for tuberous sclerosis
Childhood absence epilepsy	Abnormal thalamocortical circuit oscillations; T-type calcium channels in thalamic relay neurons generate 3 Hz spike-and-wave discharges	Ethosuximide blocks T-type calcium channels; valproate also effective; carbamazepine and phenytoin may worsen absences
Benign rolandic epilepsy	Focal hyperexcitability in centrotemporal (rolandic) cortex; age-dependent expression related to cortical maturation; genetic predisposition	Often does not require treatment; resolves by adolescence; if treated, levetiracetam or carbamazepine are options
Dravet syndrome	SCN1A mutation causes loss of function in sodium channels of inhibitory interneurons, leading to disinhibition and hyperexcitability; fever-sensitive	Sodium channel blockers (carbamazepine, phenytoin, lamotrigine) are contraindicated; valproate, clobazam, stiripentol, cannabidiol, fenfluramine are used
Hypoglycemic seizures	Glucose is the brain’s primary energy substrate; hypoglycemia causes neuronal energy failure and membrane depolarization; also impairs GABA synthesis	Immediate glucose administration (2 mL/kg of D10W in infants); investigate underlying cause; seizures resolve with normoglycemia
Hyponatremic seizures	Rapid decrease in serum sodium causes water shift into neurons (cerebral edema); neuronal swelling and membrane instability trigger seizures	Hypertonic saline (3%) to raise sodium 4-6 mEq/L acutely; avoid overcorrection (osmotic demyelination syndrome)
Hypocalcemic seizures	Calcium stabilizes neuronal membranes; hypocalcemia increases membrane excitability and lowers seizure threshold	IV calcium gluconate 10% (1-2 mL/kg); monitor for cardiac effects; investigate underlying cause (hypoparathyroidism, vitamin D deficiency)
Pyridoxine-dependent epilepsy	ALDH7A1 mutation causes accumulation of toxic metabolites that inactivate pyridoxal phosphate (active vitamin B6), which is essential for GABA synthesis	Pyridoxine trial (100 mg IV) for any treatment-resistant neonatal seizures; lifelong pyridoxine supplementation required

Phases of a Seizure

Phase	Description	Clinical Features
Prodrome	Hours to days before seizure; may reflect building excitability	Mood changes, irritability, headache, sleep disturbance (not all patients experience this)
Aura	Focal seizure onset with preserved awareness; represents localized cortical activation	Epigastric rising sensation, déjà vu, fear, visual or auditory phenomena (valuable for localization)
Ictal phase	Active seizure; hypersynchronous neuronal discharge	Motor activity (tonic, clonic, myoclonic), altered awareness, autonomic changes, behavioral arrest
Postictal phase	Recovery period; neuronal exhaustion and active inhibition	Confusion, sleepiness, headache, focal weakness (Todd paralysis), amnesia; duration varies (minutes to hours)

Consequences of Prolonged Seizures

Understanding why prolonged seizures cause harm guides the urgency of treatment.

0-5 Minutes

Compensated phase:

Increased cerebral blood flow
Increased glucose delivery
Metabolic demands met
Most seizures self-terminate

5-30 Minutes

Transitional phase:

GABA-A receptor internalization begins
Decreasing benzodiazepine efficacy
Increasing NMDA receptor expression
Emerging metabolic acidosis

Beyond 30 Minutes

Decompensated phase:

Cerebral metabolic failure
Excitotoxic neuronal injury
Systemic complications (hyperthermia, rhabdomyolysis)
Pharmacoresistance established

Time-Dependent Pharmacoresistance

As seizure duration increases, benzodiazepine efficacy decreases dramatically due to GABA-A receptor internalization. Studies show that benzodiazepines terminate approximately 80% of seizures when given within the first 5 minutes, but only 40% when given after 30 minutes. This underscores the critical importance of early treatment — “time is brain” applies to status epilepticus just as it does to stroke.

Seizure Propagation Patterns

Focal to Bilateral Spread

Seizure begins in one hemisphere

Spreads via corpus callosum

Results in bilateral tonic-clonic activity

May have lateralizing features early

Generalized from Onset

Bilateral hemispheric involvement from start

Thalamocortical circuits often involved

Absence and myoclonic seizures

No focal features or aura

Focal Remaining Focal

Seizure activity confined to one region

May have preserved awareness

Motor, sensory, or autonomic symptoms

Localizing value for etiology

Multifocal

Multiple independent seizure foci

Often seen in severe epileptic encephalopathies

Lennox-Gastaut syndrome

Poor prognosis; treatment-resistant

Clinical Pearl: Fever and Seizure Threshold

The rate of temperature rise, rather than the peak temperature, appears to be more important in triggering febrile seizures. This explains why antipyretics do not prevent febrile seizures — by the time fever is detected, the rapid temperature rise has already occurred. Inflammatory cytokines, particularly interleukin-1β, directly enhance neuronal excitability through effects on glutamate receptors and ion channels, independent of temperature itself.

3. History Taking

A comprehensive approach to eliciting the seizure history in children

Red Flags — Require Urgent Evaluation

Prolonged seizure (greater than 5 minutes) — status epilepticus; immediate treatment needed
Focal neurological deficits persisting beyond 1 hour — structural lesion, stroke
Signs of increased intracranial pressure — headache, vomiting, papilledema, altered consciousness
Meningeal signs — fever with neck stiffness, photophobia; CNS infection
Seizure in neonate — always warrants full septic and metabolic workup
First seizure with fever in infant less than 6 months — meningitis must be excluded

Developmental regression — neurodegenerative disorder, epileptic encephalopathy
Infantile spasms pattern — clusters of flexor/extensor spasms; West syndrome emergency
Signs of non-accidental injury — bruising, retinal hemorrhages, inconsistent history
Seizure following head trauma — intracranial hemorrhage, diffuse axonal injury
Known cardiac disease with syncope/seizure — arrhythmogenic cause
Toxic ingestion suspected — immediate toxicology evaluation needed

The history is the cornerstone of seizure diagnosis — in most cases, the diagnosis is made based on a detailed eyewitness account rather than investigations. Since the child often has no memory of the event, obtaining a thorough history from caregivers and any witnesses is essential. Video recordings of events, if available, are invaluable.

Systematic History: The “SEIZURES” Approach

Use the mnemonic “SEIZURES” to ensure comprehensive history taking:

S — Start and Setting: What was the child doing? Where were they? Were they awake or asleep? Any warning signs or aura?
E — Event Description: What exactly happened? Eye deviation? Limb movements (tonic, clonic, asymmetric)? Color change? Automatisms? Incontinence?
I — Ictal Duration: How long did it last? Was it timed? Did it stop on its own or require medication?
Z — Zone of Onset: Did it start in one part of the body? Which side? Did it spread? (Lateralization helps localize)
U — Unresponsiveness: Was the child aware during the event? Could they respond to voice or commands? Any memory of the event?
R — Recovery (Postictal): How long until back to normal? Confusion? Sleepiness? Weakness on one side (Todd paralysis)? Headache?
E — Episodes Before: Is this the first event? Previous similar episodes? Staring spells? Myoclonic jerks? Sleep-related events?
S — Surrounding Factors: Fever? Sleep deprivation? Illness? Medications? Possible ingestion? Recent head injury? Triggers?

Detailed Event Description

The most critical aspect of seizure history is obtaining a precise, moment-by-moment description of the event from an eyewitness.

Aspect	Key Questions	Why It Matters
Prodrome/Warning	“Did your child say they felt strange beforehand? Any behavior change in the hours/minutes before?”	Aura suggests focal onset; prodrome may help with seizure anticipation and safety planning
Initial manifestation	“What was the very first thing you noticed? Which part of the body moved first?”	Focal onset localizes seizure origin; helps distinguish seizure types
Eye position	“Were the eyes open or closed? Were they looking in any particular direction? Did the eyes roll up?”	Eyes typically deviate toward seizure focus; eyes closed suggests psychogenic event
Motor activity	“Was there stiffening (tonic)? Rhythmic jerking (clonic)? Whole body or one side? Did it change over time?”	Characterizes seizure type; asymmetry suggests focal onset; progression pattern is diagnostic
Breathing and color	“Did they stop breathing? Did they turn blue (cyanosis) or pale? Where did the color change occur?”	Central cyanosis common in generalized tonic-clonic seizures; pallor suggests syncope
Automatisms	“Were there any repetitive movements like lip smacking, chewing, hand fumbling, or picking at clothes?”	Automatisms suggest focal seizure with impaired awareness (temporal lobe common)
Responsiveness	“Did they respond when you called their name? Could they follow commands during the event?”	Preserved awareness suggests focal aware seizure; impaired awareness has different implications
Duration	“Exactly how long did the shaking/staring last? Did you time it? It often feels longer than it is.”	Duration greater than 5 minutes requires intervention; parental estimates often inaccurate
Termination	“How did it stop? Gradually or suddenly? Did it stop on its own or was medication given?”	Abrupt offset typical for absence seizures; gradual for generalized tonic-clonic seizures
Postictal state	“After it stopped, was your child confused? Sleepy? How long until completely back to normal? Any weakness?”	Prolonged postictal state suggests generalized tonic-clonic seizure; Todd paralysis localizes focus

Clinical Pearl: Ask for Video

Always ask: “Did anyone take a video on their phone?” Home video recordings have revolutionized seizure diagnosis. A video can provide more diagnostic information than the most detailed verbal description and can distinguish seizures from seizure mimics. Encourage families to safely record future events if possible (ensuring the child is in a safe position first).

Targeted Questions by Suspected Cause

Suspected Cause	Key Features	Ask This Question
Febrile seizure	Age 6 months to 5 years; fever; generalized; brief	“Did your child have a fever? How high? Was this the first sign of illness or had they been sick for a while?”
Absence epilepsy	Brief staring; multiple daily episodes; school-age child	“Does your child have frequent brief ‘blank spells’ where they stare and don’t respond? How many per day? Can you interrupt them?”
Juvenile myoclonic epilepsy	Morning myoclonic jerks; adolescent; sleep deprivation trigger	“Does your teenager have sudden jerking movements, especially in the morning? Do they drop things at breakfast? Any seizures after a late night?”
Infantile spasms	Clusters of brief spasms; developmental regression; infant	“Does your baby have clusters of sudden movements where they flex forward or extend? How many in a cluster? Have you noticed any change in development?”
Benign rolandic epilepsy	Nocturnal focal motor seizures; drooling; speech arrest; school age	“Do the seizures happen during sleep? Does one side of the face twitch? Is there drooling or difficulty speaking during the event?”
Temporal lobe epilepsy	Aura (rising sensation, déjà vu); automatisms; impaired awareness	“Does your child describe any warning before the seizure — like a funny feeling in the stomach or a sense that something strange is happening?”
Hypoglycemia	Pallor, sweating, shakiness before event; diabetic or fasting child	“Was your child pale or sweaty before the seizure? When did they last eat? Do they have diabetes? Were they sick and not eating well?”
Meningitis/Encephalitis	Fever, headache, altered consciousness, neck stiffness	“Has your child complained of severe headache? Are they more sleepy or confused than usual? Is there neck stiffness or sensitivity to light?”
Toxic ingestion	Access to medications or substances; altered mental status	“Could your child have gotten into any medications, cleaning products, or other substances? Are there any medications missing from the house?”
Syncope (seizure mimic)	Upright position; prodrome (lightheadedness, vision changes); rapid recovery	“Was your child standing when this happened? Did they say they felt lightheaded or that their vision went dark? How quickly did they recover?”
Breath-holding spell (infant/toddler)	Triggered by crying/upset; color change precedes stiffening; rapid recovery	“Did this happen after your child was upset and crying? Did they stop breathing and turn blue or pale before the stiffening?”

Past Medical History

Birth and Perinatal History

Gestational age: Prematurity increases seizure risk
Birth weight: Small for gestational age associated with increased risk
Delivery complications: Hypoxic-ischemic encephalopathy, birth trauma
NICU admission: Duration, intubation, seizures in neonatal period
Neonatal infections: Meningitis, sepsis, TORCH infections
Congenital anomalies: Associated with certain epilepsy syndromes
Maternal factors: Infections, medications, substance use during pregnancy

Developmental History

Gross motor milestones: Head control, sitting, walking — delays may indicate underlying pathology
Fine motor milestones: Reaching, grasping, pincer grasp
Language milestones: Babbling, first words, sentences — regression is a red flag
Social milestones: Smiling, eye contact, interactive play
Current developmental level: School performance, learning difficulties
Any regression: Loss of previously acquired skills is highly concerning
Behavioral concerns: Autism spectrum features, attention difficulties

Family History

Key Family History Questions:

Epilepsy in first-degree relatives: Increases risk 2-4 fold; specific syndromes have strong heritability
Febrile seizures in family: Strong genetic component; 10-20% of children with febrile seizures have affected family members
Sudden unexplained deaths: May indicate inherited cardiac arrhythmia (long QT syndrome) or epilepsy (SUDEP)
Neurodevelopmental disorders: Intellectual disability, autism spectrum disorder in family
Neurodegenerative diseases: Progressive conditions with seizures as a feature
Consanguinity: Increases risk of autosomal recessive metabolic and genetic conditions
Specific epilepsy syndromes: Some have clear inheritance patterns (benign familial neonatal seizures, genetic generalized epilepsies)

Medication and Social History

Medications That Can Cause Seizures

Antihistamines (diphenhydramine overdose) — anticholinergic toxicity
Tramadol — lowers seizure threshold significantly
Bupropion — dose-dependent seizure risk
Isoniazid — pyridoxine depletion; treat with IV pyridoxine
Fluoroquinolones — GABA antagonism
Beta-lactam antibiotics (high doses) — especially with renal impairment
Theophylline/Caffeine toxicity — adenosine antagonism
Stimulant medications (overdose) — amphetamines, methylphenidate
Tricyclic antidepressants — sodium channel blockade in overdose
Withdrawal: Benzodiazepines, barbiturates, alcohol (adolescents)

Social and Environmental History

Household medications: Potential for accidental ingestion
Substance use (adolescents): Alcohol, recreational drugs, energy drinks
Sleep habits: Sleep deprivation is a major seizure trigger
Screen time: Photosensitive epilepsy; video game induced seizures
School performance: Cognitive effects of seizures or medications
Childcare/School setting: Witnessed events; seizure action plan needed
Home safety: Supervision, water safety, heights
Psychosocial stressors: May trigger psychogenic non-epileptic events
Travel history: Neurocysticercosis in endemic areas

Immunization Status

Vaccine	Seizure Association	Clinical Notes
DTaP (Pertussis component)	Febrile seizures may occur 0-3 days post-vaccination	Risk is approximately 1 in 14,000 doses; simple febrile seizures; no long-term consequences; vaccination should continue
MMR	Febrile seizures may occur 7-14 days post-vaccination	Corresponds to vaccine-induced immune response; risk approximately 1 in 3,000; benefits far outweigh risks
Influenza	Small increased risk of febrile seizures when co-administered with pneumococcal vaccine	Absolute risk remains very low; vaccination recommended especially for children with epilepsy

Important Note on Vaccines and Seizures

While vaccines can rarely trigger febrile seizures in susceptible children, they do not cause epilepsy. Children with epilepsy should receive all routine vaccinations. The risks of vaccine-preventable diseases (including encephalitis and seizures from infections like measles) far outweigh the small risk of vaccine-associated febrile seizures.

Review of Systems — Seizure-Relevant

System	Symptoms to Ask About	Relevance
Neurological	Headaches, vision changes, weakness, numbness, gait problems	Structural lesion, increased intracranial pressure, progressive condition
Cardiovascular	Palpitations, syncope, exercise intolerance, chest pain	Arrhythmia-induced syncope can mimic seizures; long QT syndrome
Infectious	Fever, neck stiffness, photophobia, rash, recent illness	CNS infection (meningitis, encephalitis)
Gastrointestinal	Vomiting (especially morning), poor feeding, abdominal pain	Increased intracranial pressure; metabolic disturbance
Endocrine/Metabolic	Excessive thirst/urination, weight changes, sweating, shakiness	Diabetes (hypoglycemia); electrolyte disturbances; inborn errors of metabolism
Dermatological	Skin lesions, birthmarks, café-au-lait spots, hypopigmented macules	Neurocutaneous syndromes (tuberous sclerosis, neurofibromatosis, Sturge-Weber)

4. Physical Examination

A systematic approach to examining the child with seizures

Systematic Framework: Use a comprehensive “Head to Toe” approach for every child presenting with seizures. The examination serves to: (1) identify signs of ongoing seizure activity, (2) detect underlying etiology, (3) recognize complications, and (4) establish baseline neurological status.

Initial Rapid Assessment (If Actively Seizing)

Immediate Assessment During Active Seizure

Airway: Position child safely; suction if needed; do NOT put anything in mouth
Breathing: Observe respiratory effort; provide oxygen if cyanotic; prepare for bag-mask ventilation
Circulation: Assess heart rate and perfusion; obtain IV/IO access
Disability: Note seizure type, duration, and evolution; check glucose immediately
Exposure: Look for trauma, rash, needle marks, medical alert jewelry

Time the seizure! Start treatment if seizure duration exceeds 5 minutes.

Vital Signs

Vital signs must be interpreted using age-appropriate normal values. Abnormalities may indicate underlying cause or seizure complications.

Age	Heart Rate (bpm)	Respiratory Rate (/min)	Systolic BP (mmHg)	Temperature
Neonate (0-28 days)	100-160	30-60	60-90	Normal: 36.5-37.5°C Fever: ≥38°C Post-ictal hyperthermia may occur
Infant (1-12 months)	100-150	25-40	80-100
Toddler (1-3 years)	90-140	20-30	90-105
Preschool (3-5 years)	80-120	20-25	95-110
School age (6-12 years)	70-110	18-22	100-120
Adolescent (13-18 years)	60-100	12-20	110-130

Vital Sign Abnormality	Clinical Significance	Consider
Fever	Most common seizure trigger in children; may indicate infection	Febrile seizure (if age 6 months-5 years); CNS infection; systemic infection triggering seizure
Tachycardia	Common immediately post-ictal; may persist with fever, dehydration, or ongoing seizure	Autonomic response; dehydration; sepsis; arrhythmia as cause
Bradycardia	May occur ictally; concerning if persistent post-ictally	Ictal bradycardia; increased intracranial pressure; medication effect
Hypertension	Common post-ictal finding; may indicate increased intracranial pressure if persistent	Autonomic response; increased intracranial pressure; hypertensive encephalopathy
Hypotension	Unusual; suggests severe systemic illness	Sepsis; toxic ingestion; prolonged status epilepticus with systemic compromise
Oxygen desaturation	Common during and immediately after generalized tonic-clonic seizure	Ictal apnea; aspiration; airway obstruction; prolonged postictal depression

Growth Parameters

Parameter	What to Assess	Abnormalities and Significance
Weight	Plot on age-appropriate growth chart; compare to previous measurements	Failure to thrive may indicate chronic illness, metabolic disorder, or neglect
Height/Length	Plot on growth chart; assess proportionality	Short stature may be associated with certain genetic/metabolic syndromes
Head circumference	Essential in children under 2 years; plot on growth chart	Macrocephaly: hydrocephalus, megalencephaly, storage disorders; Microcephaly: congenital infection, genetic syndromes, perinatal injury

General Inspection

Level of consciousness: Alert, drowsy, obtunded, comatose; use pediatric Glasgow Coma Scale; postictal drowsiness is expected but should improve
General appearance: Well versus ill-appearing; toxic appearance suggests serious infection
Respiratory effort: Work of breathing; stridor; grunting (may indicate aspiration or infection)
Color: Pallor, cyanosis (central versus peripheral), flushing
Posture: Decorticate or decerebrate posturing indicates severe brain injury; asymmetric posture suggests focal pathology
Movement: Spontaneous movements; asymmetry; abnormal movements (ongoing subtle seizure activity)
Dysmorphic features: May suggest genetic syndrome associated with epilepsy
Nutritional status: Wasting may indicate chronic illness or neglect

Skin Examination

The skin examination is crucial in pediatric seizures as it may reveal neurocutaneous syndromes or signs of underlying conditions.

Finding	Description	Associated Condition
Hypopigmented macules (ash leaf spots)	Oval or leaf-shaped white patches; best seen with Wood lamp	Tuberous sclerosis complex — infantile spasms, focal seizures, intellectual disability
Facial angiofibromas (adenoma sebaceum)	Red papules on face, especially nasolabial folds; appear after age 3-4	Tuberous sclerosis complex
Shagreen patch	Thickened, orange-peel textured plaque, usually on lower back	Tuberous sclerosis complex
Café-au-lait spots	Flat, uniformly hyperpigmented macules; ≥6 spots >5mm (prepubertal) is diagnostic	Neurofibromatosis type 1 — seizures in 4-7% of patients
Axillary/inguinal freckling	Multiple freckles in skinfolds	Neurofibromatosis type 1
Port-wine stain (facial)	Unilateral facial capillary malformation in V1 distribution	Sturge-Weber syndrome — focal seizures, hemiparesis, glaucoma
Petechiae/Purpura	Non-blanching red/purple spots	Meningococcal sepsis; other causes of DIC; trauma (non-accidental injury)
Bruising in unusual locations	Bruises on ears, neck, trunk, buttocks in non-mobile child	Non-accidental injury — consider abusive head trauma
Linear hypopigmentation (lines of Blaschko)	Whorled or linear hypopigmented streaks following developmental lines	Hypomelanosis of Ito — seizures, developmental delay

Clinical Pearl: Wood Lamp Examination

In children with infantile spasms or unexplained seizures, always perform a Wood lamp examination of the skin in a darkened room. Ash leaf spots of tuberous sclerosis may be subtle and only visible under ultraviolet light, especially in fair-skinned children. Finding even one ash leaf spot in an infant with spasms should prompt urgent evaluation for tuberous sclerosis complex and consideration of vigabatrin as first-line treatment.

Head and Fontanelle Examination

Finding	Assessment	Clinical Significance
Anterior fontanelle (infants)	Assess with child calm and upright; should be soft and flat	Bulging: increased intracranial pressure, meningitis, hydrocephalus; Sunken: dehydration
Head circumference	Measure occipitofrontal circumference; plot on growth chart	Macrocephaly or microcephaly as discussed above
Skull shape	Assess for asymmetry, ridging along sutures	Craniosynostosis; positional plagiocephaly; may be associated with increased intracranial pressure
Scalp	Inspect for bruising, swelling, lacerations	Traumatic injury; subgaleal hematoma; non-accidental injury
Cranial bruits	Auscultate over anterior fontanelle, temples, orbits	Arteriovenous malformation; increased intracranial blood flow

Eye Examination

Component	Assessment	Abnormal Findings and Significance
Pupils	Size, symmetry, reactivity to light	Asymmetric pupils: structural lesion, herniation; Fixed dilated: severe brain injury, anticholinergic toxicity; Pinpoint: opioid toxicity, pontine lesion
Eye movements	Conjugate gaze; nystagmus; eye deviation	Tonic eye deviation during/after seizure (eyes deviate toward seizure focus in early ictal phase); Nystagmus may indicate ongoing subtle seizure or medication toxicity
Fundoscopy	Optic disc, retina, vessels	Papilledema: increased intracranial pressure (may take hours-days to develop); Retinal hemorrhages: abusive head trauma (highly specific), severe hypertension
Visual fields	Confrontation testing if cooperative	Homonymous hemianopia suggests occipital or optic tract lesion
Iris	Look for Lisch nodules (iris hamartomas)	Neurofibromatosis type 1 (seen in >90% of adults with NF1, less common in young children)

Neurological Examination

A thorough neurological examination is essential but should be adapted to the child’s age and level of cooperation.

Mental Status

Level of alertness: Use pediatric Glasgow Coma Scale for objective assessment
Orientation: To person, place, time (age-appropriate)
Attention: Ability to focus and follow commands
Language: Comprehension and expression; dysphasia suggests focal lesion
Interaction: Eye contact, social responsiveness (especially in young children)

Component	Assessment (Age-Adapted)	Abnormal Findings
Cranial Nerves	Facial symmetry, eye movements, pupillary responses, gag reflex, tongue movement	Facial weakness (CN VII), eye movement abnormalities (CN III, IV, VI), absent gag (CN IX, X), tongue deviation (CN XII)
Motor — Tone	Passive movement of limbs; compare sides; assess for spasticity, rigidity, hypotonia	Hypotonia: post-ictal, metabolic, neuromuscular; Increased tone: upper motor neuron lesion, cerebral palsy
Motor — Strength	Observe spontaneous movement; formal strength testing if cooperative (graded 0-5)	Hemiparesis: focal lesion contralateral to weakness; may be Todd paralysis (resolves within 48 hours)
Deep tendon reflexes	Biceps, triceps, brachioradialis, patellar, Achilles; compare sides	Asymmetry suggests focal pathology; hyperreflexia suggests upper motor neuron lesion; hyporeflexia may be post-ictal
Plantar response	Stroke lateral sole from heel to toe	Extensor (Babinski) is normal up to 12-18 months; in older children, suggests upper motor neuron lesion
Coordination	Finger-to-nose, rapid alternating movements, gait observation	Ataxia: cerebellar lesion, medication toxicity (phenytoin), post-ictal
Gait	Observe walking, running, heel-to-toe walking (if developmentally appropriate)	Hemiplegic gait, ataxic gait, or refusal to walk may indicate focal pathology
Sensory	Light touch, pinprick, proprioception (limited in young children)	Hemisensory loss suggests thalamic or cortical lesion

Meningeal Signs

Sign	How to Assess	Interpretation
Neck stiffness	Passive flexion of neck with patient supine; resistance or pain indicates stiffness	Positive in meningitis, subarachnoid hemorrhage; may be absent in infants and immunocompromised
Kernig sign	Flex hip to 90°, then attempt to extend knee; positive if painful or resisted	Meningeal irritation
Brudzinski sign	Passive neck flexion causes involuntary hip and knee flexion	Meningeal irritation

Important: Meningeal Signs in Infants

Classic meningeal signs (neck stiffness, Kernig, Brudzinski) are often absent in infants with meningitis. In young infants, signs of meningitis may be subtle and non-specific: irritability, poor feeding, bulging fontanelle, altered consciousness, or fever without source. Maintain a low threshold for lumbar puncture in febrile infants with seizures, especially those under 6-12 months of age.

Cardiovascular Examination

Heart rate and rhythm: Arrhythmia may cause syncope mimicking seizure
Murmurs: May indicate structural heart disease; endocarditis can cause embolic stroke with seizures
Peripheral pulses: Assess for coarctation (femoral pulse delay); emboli
Perfusion: Capillary refill, skin color, temperature

Abdominal Examination

Hepatomegaly: Metabolic storage disorders, inborn errors of metabolism
Splenomegaly: Metabolic disorders, infection
Organomegaly: Consider glycogen storage diseases, lysosomal disorders

Summary: Expected Findings by Etiology

Condition	General	Neurological	Other Key Findings
Simple febrile seizure	Febrile, may appear unwell from underlying infection	Normal post-ictal examination; no focal deficits	Source of fever (otitis, pharyngitis, viral illness); normal fontanelle
Meningitis	Ill-appearing, febrile, may be irritable or lethargic	Meningeal signs (may be absent in infants); altered consciousness	Bulging fontanelle; petechial rash (meningococcal); photophobia
Encephalitis	Febrile, altered mental status	Focal deficits; altered consciousness; may have movement disorders	Behavioral changes; memory impairment; may progress rapidly
Intracranial mass/tumor	May have signs of increased intracranial pressure	Focal deficits; papilledema; sixth nerve palsy	Morning headache and vomiting; personality changes; gait disturbance
Abusive head trauma	Variable; may appear well or critically ill	Variable; may have focal deficits; bulging fontanelle	Retinal hemorrhages; bruising in unusual locations; inconsistent history
Tuberous sclerosis	May be normal	May be normal or have developmental delay	Hypopigmented macules; facial angiofibromas; cardiac rhabdomyomas
Childhood absence epilepsy	Normal	Completely normal between seizures	May be able to induce absence with hyperventilation (3 minutes)
Benign rolandic epilepsy	Normal	Normal examination	Normal; diagnosis based on history and characteristic EEG
Hypoglycemia	May be pale, sweaty, tremulous	Altered consciousness; seizure resolves with glucose	Confirm with bedside glucose; look for signs of underlying cause
Toxic ingestion	Variable depending on toxin	May have altered pupils, tone abnormalities, movement disorders	Toxidrome pattern; medication bottles; characteristic findings

Important Teaching Point: Normal Examination is Common

Many children with epilepsy, including those with common syndromes like childhood absence epilepsy, benign rolandic epilepsy, and juvenile myoclonic epilepsy, have completely normal physical examinations between seizures. A normal examination does not exclude epilepsy. The diagnosis is primarily clinical, based on the history and characteristic semiology of events, supported by EEG findings.

Developmental Assessment

Formal developmental assessment is important in children with seizures, as developmental delay may indicate underlying etiology or be a consequence of seizures/epileptic encephalopathy.

Age	Gross Motor	Fine Motor	Language	Social
2 months	Lifts head prone	Hands unfisted	Coos	Social smile
4 months	Head control, rolls front to back	Reaches for objects	Laughs, squeals	Enjoys social interaction
6 months	Sits with support	Transfers objects hand to hand	Babbles	Stranger anxiety emerging
9 months	Sits independently, crawls	Pincer grasp developing	Says “mama/dada” non-specifically	Waves bye-bye
12 months	Pulls to stand, cruises	Pincer grasp	1-2 words with meaning	Separation anxiety; points
18 months	Walks independently	Stacks 2-3 blocks; scribbles	10-20 words; follows simple commands	Parallel play
2 years	Runs, kicks ball	Stacks 6 blocks; turns pages	2-word phrases; 50+ words	Imaginative play

5. Differential Diagnosis

Systematic approach organized by probability, age, and clinical features

The differential diagnosis of seizures in children requires consideration of both true seizures (epileptic events) and seizure mimics (non-epileptic paroxysmal events). The approach varies significantly by age, as certain conditions are age-specific. Always consider whether the event is a provoked seizure (acute symptomatic), an unprovoked seizure (suggesting epilepsy), or a non-epileptic event.

Diagnostic Framework for Pediatric Seizures:

Step 1: Is this a seizure or a seizure mimic? (History and video are key)
Step 2: If seizure, is it provoked (acute symptomatic) or unprovoked?
Step 3: What is the seizure type? (Focal vs generalized; specific semiology)
Step 4: What is the underlying etiology? (Genetic, structural, metabolic, immune, infectious, unknown)
Step 5: Does this fit a recognized epilepsy syndrome?

First Seizure in Children: Differential by Probability

Probability	Condition	Key Features	Red Flags
COMMON (approximately 70%)	Febrile seizure	Age 6 months-5 years; fever; generalized tonic-clonic; brief duration; rapid recovery	Complex features (focal, prolonged >15 min, recurrent in 24 hours); age <6 months or >5 years
	Viral illness-associated	Concurrent viral infection (gastroenteritis, respiratory); may or may not have fever	Persistent altered consciousness; focal features; clustering
	First unprovoked seizure	No identifiable acute cause; may be first presentation of epilepsy	Focal features suggesting structural lesion; developmental regression
	Seizure mimic (not a seizure)	Breath-holding spell, syncope, sleep phenomena, behavioral event	Features atypical for mimics suggest true seizure
LESS COMMON (approximately 20%)	Central nervous system infection	Fever, altered consciousness, meningeal signs; may have focal seizures	Rapid deterioration; petechial rash; bulging fontanelle
	Metabolic disturbance	Hypoglycemia, hyponatremia, hypocalcemia; often in context of illness	Persistent seizures until corrected; signs of underlying disease
	Traumatic brain injury	History of head trauma; may have external signs of injury	Altered consciousness; focal deficits; signs of skull fracture
	Toxic ingestion	Access to medications/toxins; toxidrome features; altered consciousness	Cardiovascular instability; specific toxidrome; coma
UNCOMMON BUT SERIOUS (approximately 10%)	Intracranial mass/tumor	Progressive headache, vomiting; focal seizures; papilledema	Rapid neurological deterioration; signs of herniation
	Stroke (arterial ischemic or hemorrhagic)	Acute focal deficits; may present with seizure as first sign	Persistent focal deficits; altered consciousness
	Abusive head trauma	Infant with altered consciousness; retinal hemorrhages; inconsistent history	Any features of non-accidental injury; multiple injuries
	Autoimmune encephalitis	Behavioral changes, movement disorders, seizures; subacute onset	Rapid progression; psychiatric features; refractory seizures

Age-Based Differential Diagnosis

The differential diagnosis varies significantly by age due to developmental factors and age-specific conditions.

Neonates (0-28 days)

Category	Conditions	Key Features
Hypoxic-ischemic encephalopathy	Most common cause of neonatal seizures	History of perinatal distress; onset within first 24-72 hours; multifocal seizures
Intracranial hemorrhage	Intraventricular, subdural, subarachnoid hemorrhage	Prematurity (IVH); birth trauma; may have bulging fontanelle
Central nervous system infection	Bacterial meningitis, viral encephalitis (HSV), congenital infections (TORCH)	Fever or hypothermia; poor feeding; lethargy; may have rash or hepatosplenomegaly
Metabolic disturbances	Hypoglycemia, hypocalcemia, hypomagnesemia, hypo/hypernatremia	Jitteriness; poor feeding; may have underlying endocrine or metabolic cause
Inborn errors of metabolism	Pyridoxine-dependent epilepsy, maple syrup urine disease, urea cycle defects, non-ketotic hyperglycinemia	Treatment-resistant seizures; metabolic acidosis; unusual odor; encephalopathy
Brain malformations	Lissencephaly, polymicrogyria, cortical dysplasia, holoprosencephaly	May have dysmorphic features; microcephaly; developmental concerns
Neonatal epilepsy syndromes	Benign familial neonatal epilepsy, early myoclonic encephalopathy, Ohtahara syndrome	Family history (benign); burst-suppression on EEG (severe syndromes)
Drug withdrawal	Maternal opioid, benzodiazepine, SSRI use	Maternal history; onset 24-72 hours after birth; irritability, tremor

Neonatal Seizure Emergency

All neonatal seizures are considered serious until proven otherwise. Key urgent considerations:

Herpes simplex encephalitis: Start acyclovir empirically if any suspicion (fever, CSF pleocytosis, temporal lobe involvement)
Bacterial meningitis: Empiric antibiotics after blood culture and LP
Hypoglycemia: Check glucose immediately and treat if low
Pyridoxine-dependent seizures: Give pyridoxine trial (100mg IV) for refractory seizures

Infants (1-12 months)

Probability	Condition	Key Features
COMMON	Febrile seizures (after 6 months)	Fever with viral illness; generalized; brief; rapid recovery
COMMON	Viral illness-associated seizures	Gastroenteritis (rotavirus), respiratory infections; may cluster
LESS COMMON	Infantile spasms (West syndrome)	Clusters of flexor/extensor spasms; developmental regression; onset 4-8 months peak
LESS COMMON	CNS infection	Meningitis, encephalitis; fever, irritability, bulging fontanelle
UNCOMMON	Dravet syndrome	Prolonged febrile seizures starting around 6 months; fever-sensitive; later myoclonic and absence seizures
UNCOMMON	Structural brain abnormalities	Cortical malformations, tuberous sclerosis, tumors

Infantile Spasms: A Medical Emergency

Infantile spasms require urgent recognition and treatment to optimize neurodevelopmental outcomes. Key features:

Clusters of brief spasms (flexor, extensor, or mixed), often upon awakening
Developmental regression or stagnation
EEG shows hypsarrhythmia (chaotic high-amplitude pattern)
Treatment delay worsens prognosis — aim to start treatment within 1-2 weeks of diagnosis
First-line: ACTH or vigabatrin (vigabatrin preferred if tuberous sclerosis)

Toddlers and Preschool (1-5 years)

Probability	Condition	Key Features
COMMON	Febrile seizures	Peak incidence 12-18 months; most common cause of seizures in this age group
	Viral illness-associated	Especially gastroenteritis; may occur without significant fever
	Breath-holding spells (mimic)	Triggered by upset/crying; cyanotic or pallid; brief stiffening; rapid recovery
LESS COMMON	Genetic epilepsy syndromes emerging	Dravet syndrome progression; myoclonic-atonic epilepsy (Doose syndrome)
LESS COMMON	CNS infection	Meningitis, encephalitis; distinguish from febrile seizure
UNCOMMON	Toxic ingestion	Peak age for accidental ingestion; access to medications
UNCOMMON	Brain tumors	Posterior fossa tumors common in this age; headache, vomiting, ataxia

School Age (6-12 years)

Probability	Condition	Key Features
COMMON	Childhood absence epilepsy	Peak 4-8 years; brief staring spells; multiple daily; 3 Hz spike-wave on EEG
	Benign epilepsy with centrotemporal spikes (rolandic)	Peak 7-10 years; nocturnal focal motor seizures; drooling; speech arrest
	First unprovoked generalized tonic-clonic seizure	May be first presentation of genetic generalized epilepsy
LESS COMMON	Focal epilepsies	Temporal lobe epilepsy; may have aura, automatisms, impaired awareness
LESS COMMON	Syncope (mimic)	Vasovagal; prodrome of lightheadedness; upright position; rapid recovery
UNCOMMON	Autoimmune encephalitis	Behavioral changes, psychiatric symptoms, movement disorders, seizures
UNCOMMON	Brain tumors	Supratentorial tumors more common; focal seizures; headache

Adolescents (12-18 years)

Probability	Condition	Key Features
COMMON	Juvenile myoclonic epilepsy	Morning myoclonic jerks; generalized tonic-clonic on awakening; sleep deprivation trigger
	Juvenile absence epilepsy	Less frequent absences than childhood form; more likely to have generalized tonic-clonic seizures
	Syncope (mimic)	Vasovagal common; orthostatic; situational (hair brushing, prolonged standing)
LESS COMMON	Focal epilepsies	Temporal, frontal lobe epilepsy; may have psychiatric comorbidity
LESS COMMON	Psychogenic non-epileptic seizures	Atypical features; variable semiology; eyes closed; psychological stressors
UNCOMMON	Substance-related	Alcohol withdrawal, illicit drugs (stimulants, synthetic cannabinoids), energy drinks
UNCOMMON	Cardiac arrhythmia (mimic)	Long QT syndrome; may present as “seizure” with syncope and convulsive movements

Seizure Mimics: Non-Epileptic Paroxysmal Events

Approximately 20-30% of children referred for “seizures” have non-epileptic events. Accurate diagnosis prevents unnecessary antiseizure medication and directs appropriate treatment.

Mimic	Age Group	Key Features	Distinguishing from Seizure
Breath-holding spells	6 months – 6 years (peak 1-2 years)	Triggered by upset, pain, or startle; cyanotic or pallid; brief stiffening/limpness; rapid recovery	Always triggered by emotional upset or minor injury; color change PRECEDES stiffening; no postictal confusion
Syncope (vasovagal)	Any age (more common in adolescents)	Prodrome (lightheadedness, vision changes, nausea); upright position; pallor; brief convulsive movements possible	Upright position; prodrome present; pallor before event; rapid recovery (<1-2 minutes); brief tonic or myoclonic movements may occur but are not sustained clonic activity
Reflex anoxic seizures	Infants and toddlers	Triggered by pain, surprise; pallor; asystole; brief tonic posturing	Clear trigger (minor bump, cold food); pallid rather than cyanotic; may have brief asystole on ECG during event
Sleep phenomena	Any age	Night terrors, confusional arousals, hypnic jerks, sleep myoclonus	Occur only during sleep-wake transitions; stereotyped pattern; no postictal state; normal EEG
Benign neonatal sleep myoclonus	Neonates	Rhythmic jerking during sleep ONLY; stops when awakened	Exclusively during sleep; stops immediately with arousal; normal EEG
Infantile gratification disorder (masturbation)	Infants and toddlers	Rhythmic movements, flushing, sweating; may appear “zoned out”; easily distractible	Can be interrupted by distraction; no postictal state; video is diagnostic; normal EEG
Shuddering attacks	Infants	Brief shuddering/trembling episodes; associated with excitement or frustration	Very brief (seconds); no loss of awareness; associated with emotional state; normal EEG
Sandifer syndrome	Infants	Dystonic posturing of head/neck; associated with gastroesophageal reflux	Associated with feeds; relieved by treating reflux; no alteration of consciousness
Tics	School age and adolescents	Stereotyped movements; suppressible; preceded by urge; wax and wane	Can be suppressed (temporarily); preceded by premonitory urge; no loss of awareness
Stereotypies	Any age (common in autism)	Repetitive, patterned movements (hand flapping, rocking); interruptible	Occur when excited or focused; can be interrupted; awareness preserved; often associated with developmental disorders
Daydreaming/Inattention	School age	Staring, inattention; responsive to stimulation	Can be interrupted by calling name or touch; no automatisms; no postictal state; unlike absence seizures
Psychogenic non-epileptic seizures	Older children and adolescents	Variable semiology; often prolonged; eyes typically closed; suggestible	Eyes closed (seizures usually eyes open); out-of-phase limb movements; pelvic thrusting; responsiveness during “seizure”; normal ictal EEG
Cardiac arrhythmia (long QT syndrome)	Any age	Syncope with exercise, swimming, or startle; may have convulsive movements	Triggered by exercise, swimming, loud noise; family history of sudden death; prolonged QTc on ECG

Anatomical/Etiological Approach

Genetic/Idiopathic

Childhood absence epilepsy

Juvenile myoclonic epilepsy

Benign rolandic epilepsy

Genetic generalized epilepsies

Benign familial neonatal seizures

Dravet syndrome (SCN1A)

Structural

Cortical dysplasia

Tuberous sclerosis

Brain tumors

Stroke (arterial or venous)

Traumatic brain injury

Hippocampal sclerosis

Metabolic/Toxic

Hypoglycemia

Electrolyte disturbances

Inborn errors of metabolism

Pyridoxine-dependent epilepsy

Toxic ingestions

Drug withdrawal

Infectious/Immune

Bacterial meningitis

Viral encephalitis (HSV, enterovirus)

Autoimmune encephalitis (anti-NMDA receptor)

Rasmussen encephalitis

Febrile infection-related epilepsy syndrome (FIRES)

Drug-Induced Seizures in Children

Drug/Substance	Mechanism	Key Features	Management Notes
Antihistamines (diphenhydramine)	Anticholinergic toxicity; lowers seizure threshold	Tachycardia, mydriasis, flushing, urinary retention, delirium	Supportive care; benzodiazepines for seizures; physostigmine in severe cases
Tricyclic antidepressants	Sodium channel blockade; anticholinergic effects	Wide QRS, arrhythmias, seizures, altered consciousness	Sodium bicarbonate for cardiac toxicity; benzodiazepines; avoid class IA/IC antiarrhythmics
Isoniazid	Depletes pyridoxine (vitamin B6), reducing GABA synthesis	Refractory seizures, metabolic acidosis, coma	Pyridoxine 1g IV for each gram of isoniazid ingested (or 5g empirically)
Tramadol	Lowers seizure threshold; serotonergic effects	Seizures even at therapeutic doses; serotonin syndrome features	Benzodiazepines; avoid in patients with epilepsy
Bupropion	Lowers seizure threshold; dose-dependent	Seizures, tachycardia, agitation	Supportive care; benzodiazepines
Camphor	Direct CNS stimulant	Found in topical preparations (Vicks VapoRub); seizures with ingestion	Supportive care; benzodiazepines; decontamination if early
Theophylline/Caffeine	Adenosine antagonism; CNS stimulation	Tachycardia, vomiting, seizures; caffeine toxicity from energy drinks	Benzodiazepines; hemodialysis in severe cases
Sympathomimetics (amphetamines, cocaine)	CNS stimulation; hyperthermia	Hypertension, tachycardia, hyperthermia, agitation, seizures	Benzodiazepines; cooling; avoid beta-blockers
Synthetic cannabinoids	Variable; often unpredictable	Agitation, psychosis, seizures; may be severe	Supportive care; benzodiazepines
Withdrawal (benzodiazepines, alcohol)	Loss of GABA-ergic inhibition	Onset 24-72 hours after cessation; tremor, autonomic instability	Benzodiazepine replacement; gradual taper

Quick Reference: “If You See This, Think This”

Clinical Clue	Think This First	Key Next Step
Infant with clusters of brief spasms + regression	Infantile spasms (West syndrome)	Urgent EEG; start treatment within days if confirmed
6-month-old with prolonged febrile seizures recurring	Dravet syndrome	Genetic testing (SCN1A); avoid sodium channel blockers
School-age child with multiple daily staring spells	Childhood absence epilepsy	EEG with hyperventilation; consider ethosuximide
Adolescent with morning myoclonic jerks + generalized tonic-clonic seizure	Juvenile myoclonic epilepsy	EEG; valproate or levetiracetam; lifelong treatment usually needed
Nocturnal focal seizures with drooling in school-age child	Benign rolandic epilepsy	EEG (centrotemporal spikes); may not need treatment; resolves by adolescence
Neonate with refractory seizures + metabolic acidosis	Inborn error of metabolism	Metabolic workup; pyridoxine trial; urgent genetics/metabolics consultation
Toddler with seizure triggered by crying and turning blue	Breath-holding spell (not a seizure)	Reassurance; check iron studies; no antiseizure medication needed
Adolescent with “seizure” during exercise + family history of sudden death	Long QT syndrome (cardiac syncope)	ECG; avoid QT-prolonging drugs; cardiology referral
Child with seizure + port-wine stain on face	Sturge-Weber syndrome	MRI brain with contrast; ophthalmology referral (glaucoma)
Infant with spasms + hypopigmented skin lesions	Tuberous sclerosis complex	MRI, echocardiogram, renal ultrasound; vigabatrin is first-line for spasms

6. Diagnostic Investigations

A stepwise, evidence-based approach guided by clinical context

The investigation of pediatric seizures should be guided by the clinical presentation, age of the child, seizure type, and presence or absence of red flags. Not every child with a seizure requires extensive testing. The goals of investigation are to: (1) identify treatable causes, (2) classify the seizure/epilepsy type, (3) determine prognosis, and (4) guide treatment decisions.

Guiding Principles for Investigation:

Clinical context determines the extent of workup — a simple febrile seizure requires minimal investigation
Neonatal seizures always warrant comprehensive evaluation
First unprovoked seizure in an otherwise well child may require EEG and MRI but not emergency labs
Status epilepticus or seizures with red flags require urgent, comprehensive workup
Consider radiation exposure when ordering CT scans in children

Immediate Bedside Testing

Test	When to Perform	What to Look For	Clinical Notes
Point-of-care glucose	ALL patients with seizure or altered consciousness	Hypoglycemia (<60 mg/dL or <3.3 mmol/L); target varies by age (neonates: <45 mg/dL)	Most critical immediate test; treat before waiting for lab confirmation if clinically hypoglycemic
Temperature	All patients	Fever suggests febrile seizure or infection; hypothermia in neonates may indicate sepsis	Fever does not exclude CNS infection — maintain appropriate suspicion
Oxygen saturation	All patients	Desaturation during/after seizure; persistent hypoxia suggests ongoing seizure or aspiration	May be transiently low post-ictally; persistent hypoxia requires intervention
Heart rate and ECG rhythm	All patients; ECG if cardiac cause suspected	Arrhythmias; prolonged QTc (>460ms pediatric); bradycardia	Long QT syndrome can present as “seizure”; obtain formal 12-lead ECG if syncope features

Laboratory Investigations

Baseline Laboratory Tests

Test	Indications	What to Look For	Clinical Notes
Serum glucose (laboratory)	All patients with seizure (if not already confirmed normal)	Hypoglycemia; consider underlying cause if recurrent	Bedside glucose sufficient in most cases; lab confirmation if abnormal
Electrolytes (Na, K, Ca, Mg)	Neonates; ill-appearing children; prolonged/recurrent seizures; children on diuretics or with GI losses	Hyponatremia (<135 mmol/L); hypocalcemia; hypomagnesemia	Routine electrolytes NOT required for simple febrile seizure in well-appearing child
Complete blood count	Fever with seizure; suspected infection; ill-appearing	Leukocytosis (infection); anemia; thrombocytopenia	Guides infection workup; not routine for unprovoked seizure in well child
Blood gas (venous or arterial)	Prolonged seizure; status epilepticus; respiratory compromise; suspected metabolic disorder	Metabolic acidosis (lactic acidosis post-seizure; inborn error of metabolism); respiratory status	Transient lactic acidosis expected post-ictally; persistent acidosis concerning for metabolic disorder
Liver and renal function	Ill-appearing; suspected metabolic disease; before starting certain antiseizure medications	Elevated ammonia (urea cycle defects); hepatic dysfunction; renal impairment	Baseline before valproate; monitor with chronic antiseizure medication use
Ammonia	Neonatal seizures; encephalopathy; suspected urea cycle defect; recurrent unexplained vomiting	Elevated ammonia (>100 μmol/L concerning; >200 μmol/L urgent)	Must be collected and processed correctly (on ice, immediate analysis); false elevations common
Lactate	Suspected mitochondrial disease; recurrent metabolic decompensation; post-status epilepticus	Elevated lactate (>2.5 mmol/L); lactate:pyruvate ratio if mitochondrial disease suspected	Transient elevation expected after seizure; persistent elevation suggests metabolic etiology

Toxicology Screening

Test	Indications	Detects	Limitations
Urine drug screen	Altered mental status with seizure; adolescent; suspected ingestion; inconsistent history	Amphetamines, benzodiazepines, opioids, cannabinoids, cocaine, PCP	Does not detect synthetic cannabinoids, many prescription drugs; false positives/negatives occur
Serum drug levels	Suspected specific ingestion; therapeutic drug monitoring	Specific drug levels (acetaminophen, salicylates, antiseizure medications, digoxin, lithium)	Acetaminophen and salicylate levels should be checked in any intentional ingestion
Blood alcohol level	Adolescents; altered mental status; suspected alcohol involvement	Ethanol level	Consider ethylene glycol, methanol if osmolar gap present

Lumbar Puncture

When is Lumbar Puncture Indicated?

Lumbar puncture should be performed when CNS infection is suspected. Specific indications include:

Mandatory: Infants <6 months with first febrile seizure (meningeal signs unreliable)
Strongly consider: Infants 6-12 months with febrile seizure (especially if unimmunized or on antibiotics)
Consider: Any child with meningeal signs, prolonged postictal state, or persistent altered consciousness
Consider: Complex febrile seizure, especially if child appears ill
Required: Suspected encephalitis or meningitis regardless of age

Contraindications: Signs of increased intracranial pressure, hemodynamic instability, coagulopathy, skin infection at LP site. If LP contraindicated but infection suspected, start empiric antibiotics and image before LP.

CSF Parameter	Normal Values	Bacterial Meningitis	Viral Meningitis/Encephalitis
Opening pressure	<20 cm H₂O	Often elevated	Normal or mildly elevated
Appearance	Clear, colorless	Cloudy/turbid	Usually clear
WBC count	<5 cells/μL (neonates <20)	>1000 cells/μL (neutrophil predominant)	10-500 cells/μL (lymphocyte predominant)
Protein	<45 mg/dL (neonates <150)	Markedly elevated (>100 mg/dL)	Normal or mildly elevated
Glucose	>50% of serum glucose	Low (<40 mg/dL or <50% serum)	Usually normal
Gram stain	No organisms	May show bacteria (60-80% sensitive)	Negative

Electroencephalography (EEG)

EEG is the most important investigation for characterizing seizures and diagnosing epilepsy. It records electrical activity of the brain and can identify epileptiform abnormalities.

EEG Type	Indications	Advantages	Limitations
Routine EEG (20-40 minutes)	First unprovoked seizure; suspected epilepsy; classification of seizure type	Widely available; relatively quick; includes hyperventilation and photic stimulation	Brief recording; may miss interictal abnormalities (normal in 50% after first seizure)
Sleep-deprived EEG	Normal routine EEG with high suspicion for epilepsy; suspected sleep-related epilepsy	Increased yield for detecting epileptiform activity; captures sleep	Requires patient cooperation for sleep deprivation; may be difficult in young children
Prolonged EEG (1-24 hours)	Frequent events; need to capture typical event; suspected subclinical seizures	Greater chance of capturing events and interictal discharges	More resource-intensive; may require admission
Continuous EEG monitoring	Status epilepticus; ICU patients; coma; suspected non-convulsive seizures	Detects subclinical seizures; monitors treatment response	Resource-intensive; requires specialized interpretation
Video-EEG monitoring	Characterizing seizure semiology; presurgical evaluation; distinguishing epileptic from non-epileptic events	Correlates clinical events with EEG; gold standard for diagnosis	Requires admission; may need multiple days to capture events

Key EEG Patterns in Pediatric Epilepsy

EEG Pattern	Description	Associated Condition
3 Hz generalized spike-and-wave	Regular, bilateral, synchronous spike-and-wave at 3 Hz; induced by hyperventilation	Childhood absence epilepsy (highly characteristic)
4-6 Hz generalized polyspike-and-wave	Fast spike-and-wave; polyspikes; often on awakening	Juvenile myoclonic epilepsy
Centrotemporal spikes	High-amplitude spikes in central/temporal regions; activated by sleep	Benign epilepsy with centrotemporal spikes (rolandic epilepsy)
Hypsarrhythmia	Chaotic, high-amplitude, disorganized background with multifocal spikes	Infantile spasms (West syndrome)
Slow spike-and-wave (<2.5 Hz)	Slow, generalized spike-and-wave; often with background slowing	Lennox-Gastaut syndrome
Burst-suppression	Alternating bursts of activity with periods of suppression	Severe epileptic encephalopathy (Ohtahara syndrome); anoxic brain injury
Focal spikes or sharp waves	Localized epileptiform discharges in one region	Focal epilepsy; may indicate structural lesion
Generalized slowing	Diffuse slow-wave activity; loss of normal background rhythms	Encephalopathy (metabolic, infectious, post-ictal); may be non-specific

Important: Normal EEG Does Not Exclude Epilepsy

A single routine EEG is normal in approximately 50% of children after a first unprovoked seizure. Interictal epileptiform discharges are not always present, and a normal EEG does not rule out epilepsy. If clinical suspicion is high and routine EEG is normal, consider sleep-deprived EEG, prolonged EEG, or repeat testing. Conversely, some epileptiform patterns (especially centrotemporal spikes) can be seen in children who never have clinical seizures.

Neuroimaging

When to Image

Scenario	Imaging Urgency	Modality	Rationale
Simple febrile seizure	NOT indicated	None	Extremely low yield; no benefit; unnecessary radiation/sedation
Complex febrile seizure	Not routine; consider if focal or prolonged	MRI preferred (non-urgent)	Low yield but may identify structural abnormality in some
First unprovoked seizure (well child, back to baseline)	Non-urgent (can be outpatient)	MRI brain	Identifies structural etiology in 10-20%; helps classify epilepsy
Focal seizure	Indicated	MRI brain with epilepsy protocol	Higher yield for structural abnormality; guides management
Infantile spasms	Urgent	MRI brain	Identifies tuberous sclerosis, cortical malformations, other structural causes
Neonatal seizures	Urgent	Cranial ultrasound (bedside) followed by MRI	High yield for structural, ischemic, hemorrhagic lesions
Status epilepticus	Urgent (after stabilization)	CT initially if unstable; MRI when stable	Rule out mass lesion, hemorrhage; CT if herniation suspected
Focal neurological deficits	Urgent	CT emergently; MRI for definitive evaluation	Rule out mass lesion, stroke, hemorrhage
Signs of increased intracranial pressure	Emergent	CT head (non-contrast)	Rapid evaluation before LP; identify mass effect, hydrocephalus
Suspected non-accidental injury	Urgent	CT initially; MRI for detailed evaluation	Identify subdural hematoma, parenchymal injury; medicolegal implications

CT versus MRI

CT Head

Advantages: Rapid; widely available; no sedation usually needed; good for acute hemorrhage, fractures
Disadvantages: Radiation exposure (significant concern in children); limited soft tissue detail; misses many epileptogenic lesions
Use for: Emergent evaluation when hemorrhage, mass effect, or herniation suspected

MRI Brain

Advantages: No radiation; superior soft tissue detail; detects cortical dysplasia, mesial temporal sclerosis, small tumors
Disadvantages: Longer scan time; often requires sedation in young children; less available emergently
Use for: Definitive imaging for all epilepsy evaluations; epilepsy protocol sequences recommended

Clinical Pearl: Epilepsy Protocol MRI

When ordering MRI for epilepsy evaluation, specifically request an “epilepsy protocol” which includes thin coronal and axial T2/FLAIR sequences through the temporal lobes to detect hippocampal sclerosis, and high-resolution 3D T1-weighted imaging for cortical malformations. A standard brain MRI may miss subtle epileptogenic lesions. Communication with neuroradiology about the clinical question improves yield.

Metabolic and Genetic Testing

When to Pursue Metabolic Workup

Indication	Tests to Consider	Conditions Detected
Neonatal seizures (all)	Glucose, electrolytes, ammonia, lactate, amino acids, acylcarnitine profile, urine organic acids	Hypoglycemia, electrolyte disturbances, urea cycle defects, organic acidurias, fatty acid oxidation defects
Refractory neonatal seizures	Pyridoxine trial (100mg IV); pyridoxal phosphate trial; CSF neurotransmitters; genetic testing	Pyridoxine-dependent epilepsy, pyridoxal phosphate-responsive epilepsy, folinic acid-responsive seizures
Developmental regression with seizures	Lysosomal enzymes, urine glycosaminoglycans, very long chain fatty acids, CSF lactate	Lysosomal storage disorders, peroxisomal disorders, mitochondrial disease
Myoclonic epilepsy with developmental delay	Urine organic acids, plasma amino acids, biotinidase, genetic testing	Neuronal ceroid lipofuscinosis, biotinidase deficiency, genetic epileptic encephalopathies
Encephalopathy with seizures	Ammonia, lactate, glucose, amino acids, organic acids	Urea cycle defects, organic acidurias, mitochondrial disorders

Genetic Testing

Test	Indications	Examples of Conditions Detected
Epilepsy gene panel	Epileptic encephalopathy; early-onset epilepsy; specific syndrome suspected	Dravet syndrome (SCN1A), KCNQ2 epilepsy, CDKL5 deficiency, many others
Chromosomal microarray	Epilepsy with developmental delay, dysmorphic features, multiple congenital anomalies	Copy number variants; microdeletion/duplication syndromes (15q11-13, 1p36, etc.)
Whole exome/genome sequencing	Unexplained epileptic encephalopathy; negative targeted testing; research/diagnosis	Novel variants; atypical presentations of known disorders
Single gene testing	High suspicion for specific disorder based on phenotype	SCN1A (Dravet); TSC1/TSC2 (tuberous sclerosis); MECP2 (Rett syndrome)

Investigation Pathways by Clinical Scenario

Simple Febrile Seizure

Minimal Investigation Needed:

Identify and treat source of fever
No routine blood work, EEG, or imaging required
Consider LP only if: age <6 months, meningeal signs, prolonged postictal state, or child appears ill
Educate family about febrile seizures and recurrence risk

First Unprovoked Seizure (Well Child, Back to Baseline)

Not Routinely Needed

Blood work (unless specific indication)
Lumbar puncture (unless infection suspected)
Emergency CT (unless focal deficits or not back to baseline)

Neonatal Seizure Workup

Comprehensive Neonatal Seizure Evaluation

All neonatal seizures require thorough investigation:

Immediate: Glucose, electrolytes (Ca, Mg, Na), blood gas
Infection workup: CBC, blood culture, LP (if stable), consider HSV PCR
Metabolic: Ammonia, lactate, amino acids, acylcarnitine, urine organic acids
EEG: Continuous EEG monitoring preferred; confirms seizures and guides treatment
Imaging: Cranial ultrasound (bedside); MRI brain
Consider: Pyridoxine trial for refractory seizures; genetic testing if cause unclear

Status Epilepticus Workup

Phase	Investigations	Purpose
Immediate (while treating)	Point-of-care glucose; monitor vitals and oxygen saturation	Identify and treat reversible causes immediately
Early (once IV access)	Glucose, electrolytes, calcium, magnesium, CBC, blood gas, antiseizure medication levels (if applicable)	Identify metabolic causes; guide ongoing treatment
As indicated	Toxicology screen; ammonia; lactate; liver/renal function	Evaluate for toxic, metabolic, or organ dysfunction
After stabilization	CT head (if not returning to baseline or focal signs); LP (if infection suspected)	Rule out structural lesion; evaluate for CNS infection
Ongoing	Continuous EEG monitoring; MRI brain (when stable)	Detect ongoing subclinical seizures; identify underlying etiology

Antiseizure Medication Levels

Medication	Therapeutic Range	When to Check	Notes
Phenobarbital	15-40 μg/mL	Trough level; after loading; suspected toxicity; breakthrough seizures	Long half-life; sedation common at higher levels
Phenytoin	10-20 μg/mL (total); 1-2 μg/mL (free)	After loading; suspected toxicity; breakthrough seizures; altered albumin	Nonlinear kinetics; check free level if low albumin or renal failure
Valproic acid	50-100 μg/mL	Trough level; suspected toxicity; breakthrough seizures	Free level if low albumin; monitor liver function and ammonia
Carbamazepine	4-12 μg/mL	Trough level; suspected toxicity; breakthrough seizures	Auto-induction; levels may change over first weeks
Levetiracetam	12-46 μg/mL (less established)	Generally not required; may check for compliance or toxicity	Levels correlate less well with efficacy; clinical response more important

7. Clinical Decision-Making

Practical algorithms and decision pathways for pediatric seizures

Step 1: Is This Urgent?

The first priority is to identify patients requiring immediate intervention. Use this triage framework to guide urgency of response.

Clinical Scenario	Urgency Level	Immediate Action
Active seizure (ongoing or >5 minutes)	EMERGENT	ABCs; position safely; check glucose; administer benzodiazepine; call for help; start timer
Post-ictal with respiratory compromise	EMERGENT	Airway management; suction; oxygen; recovery position; prepare for possible recurrence
Signs of increased intracranial pressure	EMERGENT	Elevate head of bed; urgent CT; neurosurgery consultation; treat seizure if present
Suspected meningitis/encephalitis	EMERGENT	IV access; blood cultures; empiric antibiotics and acyclovir; LP when safe
Suspected abusive head trauma	EMERGENT	Stabilize; CT head; full trauma evaluation; child protection team; do not discharge
Infantile spasms (clusters of spasms)	URGENT	Urgent EEG (within 24-48 hours); pediatric neurology referral same day; early treatment critical
Neonatal seizure (any)	URGENT	Full septic and metabolic workup; continuous EEG monitoring; treat underlying cause
First febrile seizure with complex features	URGENT	Evaluate for CNS infection; consider LP especially if <12 months; observation
Focal neurological deficits persisting >1 hour	URGENT	Urgent neuroimaging (CT then MRI); stroke protocol if appropriate; neurology consultation
Simple febrile seizure (well child, back to baseline)	ROUTINE	Identify fever source; parental education; discharge with safety netting
First unprovoked seizure (well child, normal exam)	ROUTINE	EEG and MRI (can be outpatient); neurology referral; seizure safety education
Known epilepsy with typical breakthrough seizure	ROUTINE	Review adherence and triggers; check medication levels if indicated; adjust therapy if needed

Step 2: Classify the Event

Provoked Seizure

Acute symptomatic seizure with identifiable trigger:

Febrile seizure
Metabolic (hypoglycemia, electrolyte)
CNS infection
Toxic ingestion
Acute head trauma

Action: Treat underlying cause; antiseizure medication usually not needed long-term

Unprovoked Seizure

No identifiable acute precipitant:

First unprovoked seizure
Epilepsy (recurrent unprovoked)
Remote symptomatic (prior brain injury)

Action: EEG and MRI; consider antiseizure medication; neurology referral

Non-Epileptic Event

Paroxysmal event that is not a seizure:

Breath-holding spell
Syncope
Sleep phenomena
Movement disorder
Psychogenic event

Action: Correct diagnosis; reassurance; treat underlying condition; no antiseizure medication

Step 3: Age-Based Decision Algorithms

Algorithm A: Neonatal Seizures (0-28 days)

Step	Action	Key Considerations
1. Stabilize	ABCs; IV access; check glucose immediately	Treat hypoglycemia (D10W 2 mL/kg) before anything else
2. Confirm seizure	Continuous EEG monitoring if available; clinical observation	Neonatal seizures can be subtle; EEG confirmation ideal
3. Laboratory workup	Glucose, electrolytes (Ca, Mg, Na), blood gas, ammonia, lactate, infection workup	Correct electrolyte abnormalities; start antibiotics if infection possible
4. Treat seizure	Phenobarbital 20 mg/kg IV first-line	May repeat 10 mg/kg x2; max 40 mg/kg loading dose
5. Consider treatable causes	Pyridoxine trial 100 mg IV if refractory; acyclovir if HSV possible	Do not miss pyridoxine-dependent epilepsy or herpes encephalitis
6. Neuroimaging	Cranial ultrasound (bedside); MRI when stable	Identifies HIE, hemorrhage, malformations
7. Metabolic/genetic workup	Amino acids, acylcarnitine, urine organic acids; consider genetic testing	Early diagnosis of inborn errors can guide specific treatment

Algorithm B: Febrile Seizures (6 months – 5 years)

Question	If Yes	If No
Is the child still seizing or was seizure >5 minutes?	Treat as status epilepticus; benzodiazepine; full workup	Proceed to next question
Are there signs of meningitis or CNS infection?	LP mandatory; empiric antibiotics; consider acyclovir	Proceed to next question
Is the child <6 months old?	This is NOT a simple febrile seizure; full workup including LP	Proceed to next question
Is the child 6-12 months AND unimmunized or on antibiotics?	Strongly consider LP (meningeal signs unreliable at this age)	Proceed to next question
Were there complex features? (focal, >15 min, recurrent in 24 hours, prolonged postictal)	Complex febrile seizure; period of observation; consider workup based on features	Simple febrile seizure
Simple febrile seizure confirmed?	Identify fever source; educate family; discharge with safety netting; no EEG/imaging/labs needed	Re-evaluate classification

Key Points for Febrile Seizure Management

No routine blood tests, EEG, or neuroimaging for simple febrile seizures
Antipyretics do not prevent febrile seizures (but can be used for comfort)
Recurrence risk: ~30% overall; higher if first seizure at younger age or lower fever threshold
Epilepsy risk: ~1-2% for simple febrile seizures (only slightly above baseline)
Parent education is the most important intervention — provide written information

Algorithm C: First Unprovoked Seizure (Any Age)

Step	Action	Rationale
1. Ensure back to baseline	Complete neurological examination; confirm return to normal function	Persistent deficits require urgent imaging and evaluation
2. Detailed history	Event description; prodrome; postictal state; possible triggers; family history	Determines seizure type and guides further workup
3. Obtain EEG	Routine EEG (ideally within 24-48 hours; captures sleep if possible)	Epileptiform abnormalities predict higher recurrence risk; helps classify epilepsy type
4. Obtain MRI	MRI brain with epilepsy protocol (can be scheduled outpatient)	Identifies structural etiology in 10-20%; guides prognosis and treatment
5. Decision: Treat or observe?	Discuss with family; consider recurrence risk and individual factors	After single seizure, recurrence risk ~30% over 2 years; treatment decision is individualized
6. Seizure safety counseling	Water safety, heights, driving restrictions (adolescents), first aid	Essential for all patients regardless of treatment decision
7. Neurology referral	Arrange follow-up with pediatric neurology	For ongoing management, EEG interpretation, treatment decisions

Algorithm D: Status Epilepticus Protocol

Time-Based Status Epilepticus Protocol

Start the clock when seizure begins (or when you arrive if already seizing)

Time	Stage	Actions
0-5 minutes	Stabilization	ABCs: Position safely, suction, oxygen Check glucose (treat if low) Obtain IV/IO access (do not delay treatment) Monitor vitals
5 minutes	First-line therapy	IV/IO: Lorazepam 0.1 mg/kg (max 4 mg) OR Midazolam 0.2 mg/kg (max 10 mg) No IV access: IM Midazolam 0.2 mg/kg (max 10 mg) OR Rectal diazepam 0.5 mg/kg (max 20 mg) OR Intranasal midazolam 0.2 mg/kg May repeat benzodiazepine once after 5 minutes if still seizing
15-20 minutes	Second-line therapy	Options (choose one): Levetiracetam 60 mg/kg IV (max 4500 mg) over 15 minutes Fosphenytoin 20 mg PE/kg IV (max 1500 mg PE) over 10-20 minutes Valproate 40 mg/kg IV (max 3000 mg) over 10 minutes (avoid if metabolic disease suspected) Phenobarbital 20 mg/kg IV over 10-20 minutes (especially in neonates)
30-40 minutes	Refractory status epilepticus	Call for ICU/anesthesia support May give second dose of second-line agent OR different second-line agent Prepare for intubation and continuous infusion
>40-60 minutes	Super-refractory status	RSI and intubation Continuous infusion: Midazolam 0.2 mg/kg bolus then 0.1-0.4 mg/kg/hr OR Pentobarbital OR Propofol (caution in children) Continuous EEG monitoring ICU admission

“What Do I Do If…” Decision Reference

Clinical Situation	Immediate Action	Next Steps
Parent reports “staring spells” multiple times daily	Detailed history; attempt hyperventilation for 3 minutes in office to provoke event	EEG (looking for 3 Hz spike-wave); if absence epilepsy confirmed, ethosuximide or valproate
Infant with clusters of brief spasms, especially on waking	Urgent EEG (same day or next day); video if possible	If infantile spasms confirmed (hypsarrhythmia), start treatment within days; do not wait for MRI
6-month-old with recurrent prolonged febrile seizures	Consider Dravet syndrome; avoid sodium channel blockers	Genetic testing for SCN1A; prescribe rescue benzodiazepine; neurology referral
Adolescent with morning jerks who drops things at breakfast	High suspicion for juvenile myoclonic epilepsy; history of sleep deprivation as trigger	EEG; counsel on sleep hygiene and avoiding alcohol; valproate or levetiracetam
Child has “seizure” with exercise; family history of sudden death	This may be cardiac syncope, not seizure; obtain ECG immediately	If prolonged QTc (>460 ms), cardiology referral urgently; genetic testing for long QT syndrome
Child has seizure and port-wine stain on face	Suspect Sturge-Weber syndrome	MRI with contrast (leptomeningeal angioma); ophthalmology referral (glaucoma risk); antiseizure medication
Neonate with seizures refractory to phenobarbital	Give pyridoxine 100 mg IV while monitoring EEG	If seizures stop, continue pyridoxine and test for pyridoxine-dependent epilepsy; comprehensive metabolic workup
Child with known epilepsy having more frequent seizures	Check medication adherence; recent illness; sleep deprivation; medication levels	Optimize current medication before adding second agent; review diagnosis if atypical
School reports child is “daydreaming” but child is interruptible	Likely not absence seizures (absences cannot be interrupted); consider ADHD or normal daydreaming	EEG if doubt remains; ADHD evaluation if appropriate
Toddler has event with crying, turning blue, then brief stiffening	Classic cyanotic breath-holding spell (NOT a seizure)	Reassurance; check iron studies (iron deficiency may increase spells); no antiseizure medication needed

When to Start Antiseizure Medication

Generally START Treatment

Two or more unprovoked seizures (meets criteria for epilepsy)
Single seizure with high recurrence risk:
- Epileptiform EEG abnormalities
- Structural brain abnormality on MRI
- Significant neurological deficit
- Status epilepticus as first presentation
Epilepsy syndrome diagnosed (e.g., juvenile myoclonic epilepsy)
Infantile spasms (urgent treatment)
High-risk occupation/activity (adolescent drivers)

May DEFER Treatment

Single unprovoked seizure with:
- Normal EEG
- Normal MRI
- Normal neurological examination
Benign rolandic epilepsy (may not require treatment)
Childhood absence epilepsy with very infrequent seizures
Patient/family preference after informed discussion
Provoked seizures (treat underlying cause instead)

When to Refer to Pediatric Neurology

Urgency	Indications
EMERGENT (same day)	Suspected infantile spasms; neonatal seizures; status epilepticus; new focal deficits; suspected epileptic encephalopathy
URGENT (within 1-2 weeks)	First unprovoked seizure; frequent seizures; suspected epilepsy syndrome; abnormal EEG requiring interpretation
ROUTINE (within 1-2 months)	Stable epilepsy for ongoing management; complex febrile seizures for counseling; medication adjustment

Troubleshooting: Seizures Not Controlled

Ask These Questions When Seizures Persist Despite Treatment

Is the diagnosis correct? Could these be non-epileptic events (psychogenic, cardiac, other)?
Is the epilepsy syndrome correctly identified? Some medications worsen certain epilepsy types (e.g., carbamazepine worsening absence seizures)
Is medication adherence adequate? Check levels; discuss barriers to adherence
Is the dose optimized? Has the medication been titrated to adequate levels before adding another?
Are there ongoing triggers? Sleep deprivation, illness, alcohol (adolescents), stress
Is there a structural lesion amenable to surgery? Consider epilepsy surgery workup for drug-resistant focal epilepsy
Has genetic testing been done? May identify precision therapy options
Have dietary therapies been considered? Ketogenic diet effective for many refractory epilepsies

8. Clinical Pearls and Pitfalls

Practical wisdom — learn from experience and avoid common mistakes

Must-Know Clinical Pearls

History is king: The diagnosis of seizure and seizure type is made primarily from the history. A detailed eyewitness account is more valuable than any investigation. Always ask if there is a video of the event.

Time the seizure: Seizures feel longer than they are. Actual timing is crucial because treatment decisions depend on duration. Encourage parents to look at a clock or phone when a seizure starts.

5 minutes = action: The operational definition of status epilepticus is 5 minutes of continuous seizure activity. Do not wait for 30 minutes — give a benzodiazepine after 5 minutes of continuous seizure.

Febrile seizures are common and benign: Simple febrile seizures affect 2-5% of children, do not cause brain damage, have an excellent prognosis, and require only parental education — no EEG, no imaging, no routine labs.

Antipyretics do not prevent febrile seizures: While antipyretics can improve comfort, they do not prevent febrile seizures because it is the rate of temperature rise (not the peak) that triggers seizures, and this occurs before fever is detected.

Infantile spasms are an emergency: Delays in treatment of infantile spasms worsen neurodevelopmental outcomes. If you suspect spasms, get an urgent EEG and involve pediatric neurology immediately — do not wait weeks for an outpatient appointment.

Wood lamp for tuberous sclerosis: In any infant with spasms or unexplained seizures, perform a Wood lamp examination in a dark room. Ash leaf spots may be the only clue to tuberous sclerosis and change management (vigabatrin becomes first-line).

Absence seizures are interruptible — daydreaming is too: If a child can be interrupted by calling their name or touching them, it is likely not an absence seizure. True absence seizures cannot be interrupted, have an abrupt onset and offset, and last only 5-15 seconds.

Eye closure suggests non-epileptic event: During epileptic seizures, eyes are typically open. Eyes closed during a “seizure” suggests a psychogenic non-epileptic event or syncope — look for other atypical features.

Pyridoxine trial for refractory neonatal seizures: For any neonate with seizures not responding to standard treatment, give pyridoxine 100 mg IV while monitoring EEG. Pyridoxine-dependent epilepsy is treatable but fatal if missed.

Normal EEG does not exclude epilepsy: A single routine EEG is normal in ~50% of patients after a first seizure. If clinical suspicion is high and EEG is normal, repeat with sleep deprivation or prolonged monitoring.

Think cardiac in exercise-induced “seizures”: A child who collapses with a “seizure” during exercise, swimming, or with sudden startle (loud noise) may have long QT syndrome. Get an ECG. Family history of sudden death is a major red flag.

Critical Pitfalls to Avoid

Waiting too long to treat status epilepticus: Benzodiazepine efficacy decreases dramatically with time due to GABA receptor internalization. Do not wait — treat at 5 minutes. Every minute of delay worsens outcomes.

Missing meningitis in infants with febrile seizures: Classic meningeal signs (neck stiffness, Kernig, Brudzinski) are often absent in infants. Have a low threshold for LP in febrile infants <12 months with seizures, especially if they appear ill or are not back to baseline.

Dismissing infantile spasms as “startle” or “colic”: Infantile spasms are subtle and may be mistaken for normal infant movements or Moro reflex. A cluster of brief spasms with developmental regression is infantile spasms until proven otherwise — this is a medical emergency.

Using sodium channel blockers in Dravet syndrome: Carbamazepine, oxcarbazepine, phenytoin, and lamotrigine can worsen seizures and trigger status epilepticus in Dravet syndrome. Always consider Dravet in an infant with prolonged or recurrent febrile seizures starting around 6 months.

Ordering unnecessary tests for simple febrile seizures: Simple febrile seizures do not require blood tests, EEG, or neuroimaging. Excessive testing increases cost, anxiety, and radiation exposure without clinical benefit.

Forgetting to check glucose: Hypoglycemia is a reversible cause of seizures and encephalopathy. Every child with a seizure should have a point-of-care glucose checked immediately. Treat first, confirm later.

Using carbamazepine or phenytoin for absence or myoclonic seizures: These medications can worsen absence and myoclonic seizures. If a child with “epilepsy” worsens on carbamazepine, reconsider the diagnosis — they may have genetic generalized epilepsy.

Diagnosing epilepsy after a single provoked seizure: A seizure caused by fever, hypoglycemia, or another acute precipitant is not epilepsy. Epilepsy is defined as two or more unprovoked seizures or one unprovoked seizure with high recurrence risk.

Missing non-accidental injury: An infant with seizures, altered consciousness, and no clear history should raise suspicion for abusive head trauma. Look for retinal hemorrhages, unexplained bruising, and inconsistent history. This diagnosis saves lives.

Assuming recurrent events are all the same: Children can have both epileptic seizures and non-epileptic events. If events are changing character or not responding to treatment, reconsider whether all events are seizures.

Neglecting seizure safety counseling: Every family needs education on seizure first aid, when to call emergency services, water safety, and (for adolescents) driving restrictions. This is as important as prescribing medication.

Key Takeaways

Seizures are common in children — febrile seizures alone affect 2-5% of children, and most have an excellent prognosis.
The diagnosis is clinical — a detailed history from an eyewitness is the most valuable diagnostic tool. Always ask for video.
Status epilepticus is a time-sensitive emergency — give a benzodiazepine after 5 minutes of continuous seizure activity; do not wait.
Age matters — the differential diagnosis, clinical presentation, and management vary significantly by age group.
Not all paroxysmal events are seizures — breath-holding spells, syncope, and psychogenic events are common mimics.
Simple febrile seizures require minimal workup — education and reassurance are the main interventions.
Infantile spasms are a medical emergency — early treatment (within days) improves neurodevelopmental outcomes.
Some medications can worsen certain epilepsy types — know which drugs are contraindicated in which syndromes.
Normal examination and normal EEG do not exclude epilepsy — the diagnosis is primarily clinical.
Seizure safety counseling is essential for every patient and family — this includes first aid, water safety, and activity restrictions.

Quick Reference Algorithm

Systematic Approach to Pediatric Seizures:

Stabilize: If actively seizing, ensure ABCs, check glucose, give benzodiazepine if >5 minutes, time the seizure.
Characterize: Was this truly a seizure? If so, what type? Obtain detailed eyewitness history and video if available.
Classify: Is this a provoked seizure, unprovoked seizure, or non-epileptic event? Age and context are key.
Investigate: Tailor workup to clinical scenario — simple febrile seizure needs little; neonatal seizure needs comprehensive evaluation.
Identify: Look for underlying etiology (genetic, structural, metabolic, infectious, immune) and specific epilepsy syndrome.
Treat: Address underlying cause if present; decide on antiseizure medication based on recurrence risk and syndrome.
Educate: Provide seizure first aid training, safety counseling, and written information to all families.
Refer: Involve pediatric neurology for unprovoked seizures, epilepsy diagnosis, or any diagnostic uncertainty.
Follow up: Ensure appropriate monitoring, medication adjustment, and ongoing support for children with epilepsy.