Patient Overview

• Age/Sex: 7-year-old girl
• Presenting complaint: Frequent "staring spells" during class, noticed by her teacher over 4 months

Salient Features of the Case

1. Seizure Characteristics (Classic Absence Seizures)

2. Impact on Daily Life

• Academic decline: dropped from top third to near bottom of class
• Teacher misidentified episodes as ADHD/daydreaming
• Psychosocial concern: family is low-income, worried about cost of tests and medications

3. Family History

• Maternal aunt had "seizures as a child" that resolved in her teens - suggests genetic generalized epilepsy (autosomal dominant tendency)

4. Background / Negative History (Important Negatives)

• Normal birth, development, and immunizations
• No febrile seizures, head trauma, CNS infection, or hypoxic-ischemic injury
• No prior hospitalizations or current medications

5. Physical Examination

• Completely normal neurological exam between episodes
• No neurocutaneous stigmata (rules out tuberous sclerosis, Sturge-Weber, NF1)
• No papilledema, no focal deficits
• Normal attention and cognition between episodes

6. Investigations

Summary Diagnosis

1. Typical semiology (brief, frequent, abrupt-onset/offset absence seizures with automatisms)
2. Age of onset (peak 4-10 years)
3. Family history of childhood-onset seizures
4. Normal interictal neurology
5. Bedside hyperventilation provocation positive
6. EEG showing classic 3-Hz generalized spike-and-wave discharges

Key Teaching Points Embedded in the Case

• Differential diagnosis: ADHD, daydreaming, focal impaired awareness seizures (temporal lobe), breath-holding spells
• Why sodium channel blockers are contraindicated in generalized epilepsy (e.g., carbamazepine, oxcarbazepine can worsen absence seizures)
• First-line treatment: Ethosuximide or valproic acid for CAE
• Status epilepticus protocol: Time-based algorithm if seizures become prolonged
• Prognosis: CAE generally has a favorable prognosis; many children achieve seizure freedom in adolescence (consistent with the maternal aunt's history)

Learning Objective 1

Apply the ILAE Operational Definition of Epilepsy and the 2017 ILAE Seizure Classification

ILAE Definition of Epilepsy

1. At least two unprovoked seizures occurring more than 24 hours apart
2. One unprovoked seizure with a probability of further seizures similar to the general recurrence risk after two unprovoked seizures (i.e., ≥60% over the next 10 years)
3. Diagnosis of an epilepsy syndrome (e.g., childhood absence epilepsy, juvenile myoclonic epilepsy)

In Camille's case: She has had hundreds of episodes over 4 months - this clearly satisfies the definition. Additionally, her clinical picture, EEG, and age of onset fit a recognized syndrome - Childhood Absence Epilepsy (CAE).

2017 ILAE Seizure Classification

• Motor: Tonic-clonic (grand mal), tonic, clonic, myoclonic, atonic (drop attacks), epileptic spasms
• Non-motor (Absence): Typical absence, atypical absence, myoclonic absence, eyelid myoclonia

• Sudden cessation of activity and awareness
• Brief duration (5-10 seconds)
• Eyelid flutter + automatisms (lip-smacking, picking)
• No postictal period
• Resumes activity exactly where she left off

Epilepsy Type Classification

Learning Objective 2

Differentiate Absence Seizures from Their Clinical Mimics

Key Clinical Pearl: Hyperventilation Provocation

In Camille: 3 minutes of supervised hyperventilation reproduced her exact episode - she stopped counting, stared for 8 seconds, then resumed counting from where she stopped, completely unaware of the interruption. This is pathognomonic for absence seizures.

Learning Objective 3

Evaluate Investigations in Childhood Epilepsy: EEG, Lab Studies, and Neuroimaging

Electroencephalography (EEG) - Central Investigation

• Confirms epileptiform activity
• Characterizes seizure type (focal vs. generalized)
• Helps diagnose the epilepsy syndrome
• Guides medication choice

• Normal interictal background (between seizures)
• 3-Hz generalized spike-and-wave discharges (bilaterally synchronous, symmetric)
  • Provoked or spontaneous during hyperventilation
  • Lasting 4-20 seconds, correlating exactly with clinical absence
  • No focal slowing, no photoparoxysmal response (in typical CAE)

Camille's EEG: Normal background + hyperventilation-provoked bilateral 3-Hz spike-and-wave lasting 6-10 seconds, with clinical arrest during bursts. This is diagnostic.

• First simple febrile seizure in a child 6 months-5 years with no focal features
• Clear-cut provoked seizure (e.g., hypoglycemia)

Laboratory Studies

In Camille: All labs normal - they serve to confirm this is not a metabolic cause and to establish pre-treatment baselines.

• In a child with a clearly established epilepsy syndrome and normal development (e.g., not every follow-up visit)
• Routine daily monitoring is not needed for well-controlled patients

Neuroimaging (MRI Brain)

1. Seizures are consistent with a recognized generalized epilepsy syndrome
2. EEG shows characteristic generalized 3-Hz spike-and-wave
3. Neurological examination is normal
4. No focal EEG features

• Focal seizures present
• Abnormal neurological exam
• Developmental regression
• Refractory seizures despite appropriate treatment
• Age of onset <2 years (high chance of structural cause)

Learning Objective 4

Formulate an Evidence-Based Antiseizure Medication (ASM) Plan for CAE and Explain Why Sodium Channel Blockers Are Harmful

First-Line Medications for CAE

For Camille (7-year-old girl, pure absence): Ethosuximide is the drug of choice.

Why Sodium Channel Blockers Worsen Generalized Absence Seizures

• Carbamazepine (CBZ)
• Oxcarbazepine
• Phenytoin
• Lacosamide

1. Absence seizures arise from thalamocortical circuit oscillations - the rhythm is driven by T-type calcium (Ca2+) channels in thalamic relay neurons, not primarily by sodium channels
2. Carbamazepine and phenytoin have no effect on T-type Ca2+ channels
3. These drugs can paradoxically worsen absence and myoclonic seizures - possibly by altering thalamocortical synchrony or having proconvulsant effects on generalized circuits
4. Clinical consequence: A child with CAE given carbamazepine (incorrectly prescribed for "seizures") will have an increase in absence frequency - a common clinical trap

Learning Objective 5

Apply a Time-Based Algorithm for Acute Management of Prolonged Convulsive Seizure and Convulsive Status Epilepticus (CSE)

Definitions

• Prolonged seizure: Lasting >5 minutes (for convulsive seizures) - treat as impending SE
• Convulsive Status Epilepticus (CSE): Continuous convulsive seizure activity lasting >5 minutes, OR two or more seizures without recovery of consciousness between them
  • Old definition was 30 minutes; current operational threshold for treatment initiation is 5 minutes

Time-Based Management Algorithm

T = 0 min: Seizure begins
         ↓
T = 5 min: PHASE 1 — Benzodiazepine (First-line)
  - IV access present: IV Lorazepam 0.1 mg/kg (max 4 mg/dose)
  - IV access absent (prehospital/community):
      • IM Midazolam 0.2 mg/kg (preferred - RAMPART trial)
      • IN Midazolam 0.2 mg/kg
      • Rectal Diazepam 0.5 mg/kg
      • Buccal Midazolam
  - Can repeat benzodiazepine once after 5 minutes if no response
         ↓
T = 20 min: PHASE 2 — Second-line (Benzodiazepine-Refractory SE)
  Choose ONE:
  • IV Levetiracetam 60 mg/kg (max 4500 mg) — safest profile
  • IV Valproate 40 mg/kg (avoid if liver disease, metabolic disorder)
  • IV Fosphenytoin 20 mg PE/kg (avoid in known generalized epilepsy)
  These three are equally effective after BZD failure (~50% cessation rate)
         ↓
T = 40 min: PHASE 3 — Refractory SE (second agent fails)
  • Repeat second-line agent OR
  • Anesthetic doses:
      - IV Midazolam infusion 0.05-0.4 mg/kg/hr
      - IV Propofol infusion
      - IV Thiopental/Pentobarbital infusion
  • ICU admission, continuous EEG monitoring, intubation
         ↓
Super-Refractory SE: Seizures persist >24 hours despite anesthesia
  • Consider: Ketamine, Immunotherapy (steroids, IVIG), Ketogenic diet, 
    Hypothermia, Vagal nerve stimulation

Why This Matters for Camille

• No IV access needed
• Faster administration
• RAMPART trial showed IM midazolam superior to IV lorazepam in prehospital SE in children

Learning Objective 6

Long-Term Care of a Child with Epilepsy

1. Medication Adherence

• Missed doses are the most common cause of breakthrough seizures
• For Camille's family (low-income, market vendor mother): simplify regimen - once or twice daily dosing preferred
• Ethosuximide is available as syrup (easier for children) and capsules
• Educate family: never abruptly stop ASMs (risk of withdrawal seizures)
• Pill diary, phone reminders, blister packs can help

2. Safety and Lifestyle Counseling

• Sleep deprivation (especially important in generalized epilepsies)
• Excessive stress
• Missed medications

3. School and Psychosocial Impact

• Camille has already experienced academic decline and social stigma ("labeled as inattentive/ADHD")
• Teacher education is critical: explain absence seizures, provide a written seizure action plan
• Valproate and ethosuximide can both affect attention - Kaplan & Sadock notes: "36% of 393 children with new-onset childhood absence epilepsy receiving valproate had attentional difficulties" - monitor carefully
• Screen for comorbid learning disabilities, anxiety, depression (common in children with epilepsy)
• Neuropsychological testing if academic performance does not improve after seizure control

4. Comorbidities to Screen For

5. Medication Withdrawal

• For CAE: attempt withdrawal after 2 years of seizure freedom
• EEG normalization supports decision to wean (though not mandatory)
• Taper slowly over 3-6 months (never abrupt withdrawal)
• Risk factors for relapse: EEG still showing spike-wave, abnormal neurological exam, onset in adolescence
• CAE has an excellent prognosis - 70-80% of children achieve complete remission by adolescence

Camille's maternal aunt: "had seizures as a child that stopped in her teens" - this likely represents the natural history of CAE.

6. Prognosis

Summary Table