What is the differential diagnosis for a 5-year-old female child experiencing episodes of eye rolling followed by loss of consciousness, including a recent episode of generalized tonic-clonic seizure (GTCS)?

Differential Diagnosis for Recurrent Eye Rolling with Loss of Consciousness and Recent GTCS in a 5-Year-Old

The primary differential diagnosis includes epileptic seizures (specifically absence seizures progressing to generalized tonic-clonic seizures, self-limited epilepsy with autonomic seizures, or focal seizures with secondary generalization), with syncope and other non-epileptic causes being less likely given the clinical pattern. 1

Most Likely Diagnoses

1. Epileptic Seizures - Primary Consideration

Absence Seizures Evolving to GTCS:

• Eye rolling (upward gaze deviation) followed by loss of consciousness occurring 4-5 times over 3 months suggests recurrent seizure activity 1
• The recent progression to a witnessed GTCS strongly indicates an epileptic disorder rather than syncope 1
• Absence seizures in children involve altered consciousness where patients remain upright during typical attacks, but can progress to generalized tonic-clonic seizures 2
• The repetitive nature over 3 months with similar semiology points toward epilepsy rather than syncope 1

Self-Limited Epilepsy with Autonomic Seizures (SeLEAS):

• This syndrome affects 6% of children aged 1-15 years with afebrile seizures 3
• Presents with autonomic manifestations (which can include eye deviation and altered consciousness) that may be easily disregarded as non-seizure events 3
• Eye deviation with gaze fixation is a characteristic feature 3
• Can progress to secondary generalization as seen with the GTCS episode 3

Focal Seizures with Secondary Generalization:

• Eye rolling and head turning suggest possible focal onset from temporal or occipital regions 4
• Focal seizures can present with eye deviation, altered awareness, and progress to generalized tonic-clonic seizures 4
• Simple partial seizures may occur without complete loss of consciousness initially, then evolve 4

2. Syncope - Less Likely but Must Consider

Reflex Syncope:

• Movements can occur in syncope ("convulsive syncope"), but they are typically brief (<15 seconds), asynchronous, and occur after loss of consciousness and falling 1
• Syncope is usually triggered by specific situations (orthostatic stress, emotional stimuli, pain), which is not described here 1
• The recurrent nature without clear triggers and progression to GTCS makes syncope unlikely 1
• Pallor and sweating typically precede syncopal episodes, which are not mentioned 1

3. Other Considerations

Cardiac Arrhythmias:

• Can cause recurrent loss of consciousness but typically without eye rolling as a prominent feature 1
• Would not explain the progression to a witnessed GTCS 1

Metabolic Disorders:

• Hypoglycemia or electrolyte disturbances can cause altered consciousness but would typically have additional systemic symptoms 1

Critical Distinguishing Features

Features Favoring Epilepsy in This Case:

• Recurrent stereotyped episodes with similar semiology (eye rolling → loss of consciousness) 1
• Progression to witnessed GTCS - this is pathognomonic for epilepsy 1
• No clear triggers mentioned (syncope typically has identifiable triggers) 1
• Eye rolling/deviation as a prominent feature suggests focal seizure activity 3, 4
• Age-appropriate for childhood epilepsy syndromes 3, 5

Features Against Syncope:

• Syncope does not progress to generalized tonic-clonic seizures 1
• Movements in syncope are brief and occur after the fall, not as a prominent initial feature 1
• Multiple episodes over 3 months without clear precipitants argues against typical syncope 1
• Complete flaccidity during unconsciousness would favor syncope, but eye rolling suggests active seizure activity 1

Essential Diagnostic Workup

Immediate Investigations Required:

1. Electroencephalogram (EEG) - mandatory first-line test 1

   • Should be obtained within 24 hours of the GTCS for maximum diagnostic yield (51% sensitivity) 6
   • Interictal EEG is typically abnormal in epilepsy but normal in syncope 6, 7
   • Look for focal spikes/sharp waves (suggests partial seizures) or generalized spike-wave complexes (suggests generalized epilepsy) 4

2. MRI Brain - preferred neuroimaging modality 1, 7, 4

   • Indicated in essentially any child with partial seizures to identify structural lesions 4
   • Can identify malformations of cortical development, prior injury, or slow-growing tumors 1, 4

3. Detailed Witness Account 1

   • Exact description of eye movements (synchronous vs. asynchronous)
   • Timing of movements relative to loss of consciousness
   • Duration of unconsciousness and movements
   • Post-event state (immediate clearheadedness vs. prolonged confusion)
   • Presence of tongue biting (side vs. tip), incontinence, injury

4. Metabolic Screening 1

   • Glucose, electrolytes (calcium, magnesium, sodium)
   • Consider if systemic symptoms present

Critical Pitfalls to Avoid

• Do not dismiss eye rolling as a benign finding - it represents abnormal neuronal activity and suggests seizure activity 3, 4
• Do not attribute the GTCS to a separate event - the progression from recurrent episodes to GTCS indicates an evolving epileptic disorder 1
• Do not rely on normal routine EEG to exclude epilepsy - a normal EEG cannot rule out seizures in patients with clinically suspected partial seizures 4
• Do not misdiagnose autonomic seizures as non-epileptic events - SeLEAS can be easily missed as autonomic manifestations may be disregarded 3
• Do not delay neuroimaging - underlying structural lesions must be identified 1, 4

Summary of Most Likely Diagnoses (in order of probability):

1. Focal seizures with secondary generalization (eye deviation suggests focal onset) 3, 4
2. Self-limited epilepsy with autonomic seizures (SeLEAS) 3
3. Absence seizures evolving to GTCS (though typical absence doesn't usually present with prominent eye rolling) 2
4. Syncope with convulsive movements (much less likely given GTCS and recurrent pattern) 1