What is the cause and appropriate work-up for absence seizures in a pediatric patient with a history of seizures?

Absence Seizures: Cause and Work-Up

Etiology

Absence seizures have a genetic basis in the vast majority of cases, particularly in neurologically normal children, and are not typically caused by structural brain lesions. 1, 2

• Childhood absence epilepsy and other primary generalized epilepsies have genetic underpinnings rather than structural causes 1, 2
• Unlike focal seizures, absence seizures are not typically associated with tumors, infection, infarction, traumatic brain injury, vascular malformations, or developmental abnormalities 3
• The genetic nature of these seizures explains why neuroimaging yields are extremely low in neurologically normal patients with typical absence seizures 1

Clinical Diagnosis

The diagnosis of absence seizures requires documented loss of awareness during staring episodes, as staring alone should not be used to diagnose absence seizures. 4

Key Clinical Features to Identify:

• Seizure characteristics: Brief (seconds) generalized seizures with sudden onset and termination, impairment of consciousness, and no warning or aura 4, 5
• Motor manifestations: Myoclonia (particularly facial muscles), clonic, tonic, or atonic components may accompany the absence 5
• Automatisms: May be present during the seizure 5
• Absence of focal features: No aura, no focal neurological signs, and no post-ictal focal deficits—any focal feature would suggest focal seizures with impaired awareness rather than true absence seizures 4
• Age of onset: Typically starts in childhood (ages 4-10 years for childhood absence epilepsy) or adolescence 5

Critical Diagnostic Pitfall:

• Focal seizures with impaired awareness can mimic absence seizures but typically have focal features, may have auras, and show different EEG patterns 4

Essential Work-Up

Electroencephalography (EEG)

EEG with hyperventilation is the essential diagnostic test for absence seizures and should be performed in all suspected cases. 5

• Characteristic EEG pattern: Generalized 3-4 Hz spike-and-wave or polyspike-and-wave discharges 5
• Hyperventilation provocation: Precipitates absence seizures in approximately 90% of untreated patients, making this activation technique mandatory 5
• Ictal EEG features: Discharges may be brief (2-5 seconds) or long (15-30 seconds), continuous or fragmented 5
• EEG is required to distinguish absence seizures from focal seizures with impaired awareness and to confirm the diagnosis 4, 5

Neuroimaging

MRI is rarely indicated in neurologically normal children with typical absence seizures because the rate of positive intracranial findings is extremely low given their genetic basis. 1

When Imaging is NOT Indicated:

• Neurologically normal children with characteristic clinical features of absence seizures 1
• Patients with typical primary generalized epilepsy (childhood absence epilepsy) who have characteristic clinical and EEG features 1
• Patients with adequate response to antiepileptic drugs 1
• Only 2% of low-risk patients (no predisposing condition, no focal seizure features) had abnormal MRI findings 1, 3

When Imaging MAY Be Indicated:

• Abnormal neurological examination 1
• Presence of focal seizure features 1
• Atypical features suggesting secondary causes 1
• Refractory seizures not responding to appropriate antiepileptic therapy 1

Imaging Modality Selection (if indicated):

• MRI is superior to CT and should be the primary imaging modality for any neuroimaging evaluation 3
• CT has very limited role with only 6% positivity for generalized seizures versus 50% for focal epilepsy 1
• Advanced imaging (FDG-PET/CT, SPECT) has no role in the routine work-up of absence seizures 1

Additional Diagnostic Considerations

Glucose transporter type 1 (GLUT1) deficiency must be ruled out in specific clinical scenarios. 6

• Consider GLUT1 deficiency testing if absences started before age 4 years 6
• Consider GLUT1 deficiency if neurological signs are present 6
• This is particularly important in pharmaco-resistant cases 6

Algorithmic Approach to Work-Up

1. Obtain detailed clinical history focusing on:

   • Exact description of seizure events (duration, frequency, triggers)
   • Age of onset
   • Presence or absence of aura or focal features
   • Family history of seizures
   • Response to hyperventilation or other triggers 5, 7

2. Perform neurological examination to identify:

   • Any focal neurological deficits
   • Developmental abnormalities
   • Signs suggesting structural pathology 1

3. Obtain EEG with hyperventilation to:

   • Document characteristic 3-4 Hz generalized spike-and-wave discharges
   • Provoke absence seizures during recording
   • Exclude focal features 5, 7

4. Determine need for neuroimaging based on:

   • Skip imaging if: Neurologically normal, typical clinical features, characteristic EEG, no focal features 1
   • Obtain MRI if: Abnormal neurological exam, focal features, atypical presentation, or refractory to appropriate therapy 1

5. Consider GLUT1 deficiency testing if:

   • Onset before age 4 years
   • Neurological signs present
   • Pharmaco-resistant 6