Does the use of levetiracetam (Keppra) in a 6-year-old child with suspected seizure activity, normal MRI, and specific EEG findings change the differential diagnosis between syncope and seizure?

Does Levetiracetam Use Change the Differential Between Syncope and Seizure in This Case?

No, the initiation of levetiracetam does not change the differential diagnosis—in fact, the clinical presentation strongly suggests vasovagal syncope rather than seizure, and continuing antiepileptic therapy may be inappropriate. The presence of levetiracetam treatment should not bias you toward a seizure diagnosis when the clinical features point elsewhere.

Critical Clinical Features Favoring Syncope Over Seizure

Timing and Context of Events

• Clear vasovagal triggers are present: The episode occurred in the context of overheating (hot day, outdoor activity), which creates classic conditions for reflex syncope 1, 2
• Postural component: The event happened while sitting or standing, which is typical for vasovagal syncope 2
• Bradycardia documented: The presence of bradycardia strongly suggests a cardioinhibitory component of reflex syncope 2

Physical Findings During the Event

• Pallor is pathognomonic for syncope: This results from peripheral vasoconstriction and reduced cardiac output, and is distinctly uncommon in seizures 1, 2
• Brief tonic movements can occur in syncope: These develop after loss of consciousness due to cerebral hypoperfusion, not before as in epilepsy 1, 2
• Convulsive syncope is common: Syncope-induced movements occur in 12-90% of syncopal episodes and are brief, starting after consciousness is lost 2, 3

Recovery Pattern

• Immediate hunger upon regaining consciousness: This is characteristic of syncope recovery, not the post-ictal state of seizures 2
• Near-recurrence when sitting up: This is pathognomonic for vasovagal syncope and would not occur after a seizure 2
• Absence of post-ictal confusion: This is the single most powerful discriminating factor between syncope and epileptic seizures 3

The Diagnostic Pitfall: Tonic Posturing

The presence of tonic movements is misleading and does not indicate seizure. The European Society of Cardiology explicitly warns that syncope-induced convulsive movements are common and brief, occurring after loss of consciousness rather than coinciding with it as in epilepsy 1. These movements result from cerebral hypoperfusion, not epileptic activity 2, 3.

EEG and MRI Interpretation in Context

Normal MRI

• Normal MRI does not rule out epilepsy but reduces structural causes: However, in the absence of other epileptic features, a normal MRI combined with clinical syncope features argues against seizure 1

EEG Findings

• EEG is not recommended when syncope is the likely diagnosis: Guidelines state that EEG should only be obtained when epilepsy is suspected or clinical data are equivocal 1
• Interictal EEGs are normal in syncope: A normal interictal EEG cannot rule out epilepsy but must be interpreted in clinical context 1
• When uncertain, postpone epilepsy diagnosis rather than falsely diagnose it: This has significant treatment and psychosocial implications 1, 4

Levetiracetam: Indication and Appropriateness

FDA-Approved Indications

• Levetiracetam is indicated as adjunctive therapy for partial onset seizures in children ≥4 years, myoclonic seizures in adolescents ≥12 years, and primary generalized tonic-clonic seizures in children ≥6 years 5
• The 6-year-old patient falls within the age range for partial onset seizures if that diagnosis were correct 5

Risk of Inappropriate Treatment

• Escalating antiepileptic medication for apparent syncope exposes the patient to unnecessary side effects: Levetiracetam can cause behavioral adverse effects, including irritability and drowsiness, particularly in patients with neurobehavioral problems 6, 7
• The benefit-risk ratio must be carefully considered: Levetiracetam use should be based on confirmed epilepsy diagnosis, not ambiguous presentations 6

Recommended Management Approach

Cardiovascular Evaluation Takes Priority

• Given the bradycardia, pallor, and clear vasovagal trigger, cardiac assessment is more appropriate than escalating antiepileptic therapy 2
• Consider tilt table testing if recurrent episodes occur: Though not urgently needed for a single event, this can confirm vasovagal syncope 1, 2
• Tilt table testing has sensitivity of 20-90% and specificity of 83-100% in pediatric patients 1

Patient and Family Education

• Educate on vasovagal triggers: Avoid overheating, ensure adequate hydration, and recognize prodromal symptoms 2
• Teach counterpressure maneuvers: Physical maneuvers can abort vasovagal episodes 2
• Immediate supine positioning: At the first sign of symptoms, lie down with legs elevated to prevent full syncope 2

Medication Considerations

• Do not increase levetiracetam based on this presentation: The clinical picture does not support escalating antiepileptic therapy 2
• Consider discontinuing levetiracetam if diagnosis is revised to syncope: This should be done in consultation with neurology and with appropriate tapering
• If lifestyle measures fail and syncope recurs, consider midodrine: This has shown efficacy in pediatric vasovagal syncope, reducing recurrence from 80% to 22% in one trial 1
• Increased salt and fluid intake may be reasonable: Oral rehydration salts resulted in no further syncope in 56% versus 39% with placebo 1

Common Pitfalls to Avoid

• Do not let the presence of antiepileptic medication bias your diagnosis: The medication may have been started based on incomplete information 2
• Do not over-interpret brief tonic movements as seizure: These are common in syncope and occur after loss of consciousness 1, 2, 3
• Do not ignore the cardiovascular features: Bradycardia and pallor are strong indicators of syncope 2
• Do not assume incontinence or injury indicate seizure: Both are common in syncope and seizures 3