Does a delayed electroencephalogram (EEG) timing after a possible syncopal event impact the diagnosis of seizures and treatment with Keppra (levetiracetam) in a 6-year-old girl?

EEG Timing After Syncopal Events and Keppra Management

The timing of the EEG (one week post-event) significantly limits its diagnostic value for distinguishing true seizures from syncope, but this does not invalidate your concern about levetiracetam-induced behavioral side effects, which are well-documented and should prompt immediate medication reassessment.

Impact of Delayed EEG on Diagnostic Accuracy

A delayed EEG performed one week after a possible syncopal event has minimal utility for capturing ictal activity. 1

• Electrographic seizures require detection during or immediately after the event - guidelines recommend continuous EEG monitoring for at least 24-48 hours to capture seizure activity, with 28% of electrographic seizures detected only after 24 hours of monitoring and 94% detected within 48 hours. 1

• Post-ictal EEG changes typically resolve within hours to days, making a week-delayed study unlikely to show diagnostic abnormalities related to the acute event. 1

• The EEG may still show interictal epileptiform discharges if true epilepsy is present, but absence of such findings does not rule out seizures, nor does their presence confirm the syncopal events were actually seizures. 1

Critical Reassessment of the Seizure Diagnosis

Given the diagnostic uncertainty and emergence of behavioral symptoms, the original seizure diagnosis warrants reconsideration:

• Syncope and seizures can be clinically difficult to distinguish, particularly when the history is obtained retrospectively. 2

• The lack of immediate post-event EEG means you are treating based on clinical suspicion alone, without electrographic confirmation. 1

• Prophylactic antiepileptic drugs after uncertain events have no proven benefit and may cause harm, particularly cognitive and behavioral effects. 1

Levetiracetam Behavioral Side Effects: A Major Concern

Behavioral and psychiatric adverse effects are common with levetiracetam, particularly in children, and your concern is clinically justified:

Documented Behavioral Effects

• Behavioral symptoms occur in 37.6% of pediatric patients on levetiracetam compared to 18.6% on placebo, including agitation, anxiety, depression, emotional lability, hostility, and personality changes. 3

• Hostility occurs in 11.9% of levetiracetam-treated patients versus 6.2% on placebo. 3

• Irritability, aggression, and mood disorders are particularly prominent, with non-psychotic behavioral disorders occurring in 11.4% of patients. 3

• Levetiracetam can cause reversible autistic regression in vulnerable children, with stereotypies, severe deterioration in social and communicative skills, and mood lability that completely resolves upon discontinuation. 4

Dose-Related Considerations

• Your patient is on 2000 mg twice daily (4000 mg/day total), which appears to be an adult dose rather than weight-based pediatric dosing. 3

• The FDA-approved pediatric dosing is 60 mg/kg/day for most indications, and higher doses are associated with increased behavioral side effects. 3

Recommended Management Algorithm

Immediate Actions

1. Obtain urgent neurology consultation to reassess the original diagnosis given the delayed EEG timing and emergence of behavioral symptoms. 2, 5

2. Document specific behavioral changes systematically:

• Onset timing relative to levetiracetam initiation and dose escalation 3
• Nature of symptoms (aggression, mood lability, social withdrawal, irritability) 3, 4
• Impact on quality of life and daily functioning 3

3. Consider repeat EEG now (3 months post-event) to look for interictal epileptiform activity that would support true epilepsy diagnosis. 1, 5

Decision Framework for Medication Continuation

If behavioral side effects are confirmed and significantly impacting quality of life:

• Strongly consider discontinuing levetiracetam given the uncertain seizure diagnosis, delayed non-diagnostic EEG, and documented behavioral toxicity. 2, 5, 3

• Gradual taper over 2-4 weeks to minimize withdrawal seizure risk, even though the original diagnosis is uncertain. 3

• Do NOT continue prophylactic antiepileptic therapy indefinitely without documented recurrent seizures, particularly when causing behavioral harm. 5

If seizure diagnosis is confirmed on reassessment:

• Consider switching to an alternative antiepileptic drug with better behavioral tolerability rather than continuing levetiracetam at current dose. 1

• Alternative agents include ethosuximide or valproic acid depending on seizure type, though each has its own side effect profile. 1

Critical Pitfalls to Avoid

Do NOT assume the behavioral changes are unrelated to levetiracetam - the temporal relationship and documented frequency of these effects make medication causation highly likely. 3, 4

Do NOT continue escalating the levetiracetam dose - higher doses increase behavioral side effects without necessarily improving seizure control in this uncertain diagnostic scenario. 3, 6

Do NOT reflexively add psychiatric medications to treat levetiracetam-induced behavioral symptoms without first considering medication discontinuation. 3, 4

Do NOT use the delayed EEG as definitive evidence either for or against seizures - it has limited diagnostic value at one week post-event. 1

Quality of Life Prioritization

The emergence of emotional and behavioral side effects in a 6-year-old child represents a significant quality-of-life concern that may outweigh uncertain seizure prophylaxis benefits, particularly when:

• The original diagnosis lacks electrographic confirmation 1
• The events may have been syncope rather than seizures 2
• Behavioral effects can cause lasting social and developmental impact 4
• Complete resolution typically occurs upon medication discontinuation 4

Prioritize your patient's current behavioral and emotional well-being over prophylaxis for events that may not have been seizures in the first place. 2, 5, 3