What is the best course of action for a middle-aged male with a history of tonic-clonic seizures, hypertension, vitamin D deficiency, and prediabetes, who presents with word-finding difficulty, cognitive delay, sluggish eye response, unsteady gait, intermittent dizziness, and a constant occipital headache, after having two recent seizures and not adhering to his levetiracetam (Keppra) medication regimen?

Immediate Emergency Department Evaluation is Mandatory

This patient requires immediate emergency department evaluation and should not have been allowed to leave the clinic, even with signed AMA documentation. The constellation of word-finding difficulty, cognitive delay, sluggish pupillary response, unsteady gait, and persistent severe occipital headache following two recent seizures represents concerning neurologic findings that demand urgent neuroimaging and comprehensive evaluation to rule out life-threatening complications 1.

Critical Red Flags Requiring Emergent Evaluation

Post-Seizure Complications

• Intracranial hemorrhage must be excluded given the persistent 8/10 occipital headache, cognitive changes, and focal neurologic findings following two tonic-clonic seizures 2.

• Generalized tonic-clonic seizures can cause serious complications including intracranial hemorrhage, myocardial infarction, and acute renal failure, though these occur in <1% of cases 2.

• The combination of persistent headache, cognitive impairment, and focal neurologic signs (sluggish pupillary response, word-finding difficulty) raises concern for structural lesions including subdural hematoma, cortical vein thrombosis, or post-ictal cerebral edema 3.

Specific Neurologic Concerns

• Cortical vein thrombosis can present with severe headache, seizures, and focal neurologic deficits, and may show ipsilateral dural enhancement on imaging 3.

• Word-finding difficulties in epilepsy patients can correlate with left temporo-occipital hypometabolism and suggest ongoing cerebral dysfunction beyond simple post-ictal state 3.

• Cognitive impairment and word-finding difficulty persisting beyond the immediate post-ictal period warrant urgent neuroimaging to exclude structural causes 3.

Immediate Management Upon ED Arrival

Diagnostic Workup

• Emergent non-contrast CT head to exclude intracranial hemorrhage, mass lesion, or acute stroke 1.

• Laboratory evaluation including:

  • Complete blood count (levetiracetam can cause minor decreases in WBC and neutrophils) 4
  • Comprehensive metabolic panel including calcium and magnesium (hypocalcemia can precipitate seizures and worsen control) 3, 5
  • Creatine kinase (elevated in 59.4% post-GTCS, with rhabdomyolysis occurring in 1.9%) 2
  • Troponin I (elevated in 12% of post-GTCS patients, especially older individuals) 2
  • Levetiracetam serum level to assess compliance 1

• Consider MRI with venography if CT is non-diagnostic but clinical suspicion remains high for cortical vein thrombosis or other vascular complications 3.

• EEG monitoring if altered mental status persists, as non-convulsive status epilepticus occurs in >50% of cases with prolonged altered consciousness 1.

Cardiovascular Monitoring

• Continuous cardiac monitoring and blood pressure assessment given that sinus tachycardia occurs in 41.2% and hypertensive urgencies affect 7.8% of post-GTCS patients 2.

• Troponin elevation is particularly important to assess in this patient given his hypertension and the 12% incidence of elevated troponin post-GTCS 2.

Seizure Management and Medication Adherence

Immediate Antiepileptic Therapy

• Resume levetiracetam immediately at previously prescribed dose (typically 500-1500 mg twice daily for chronic management) 1, 4.

• The patient's admission of non-compliance ("did not feel he needed the medication") directly caused breakthrough seizures and must be addressed 1.

• Non-compliance is a common cause of breakthrough seizures and must be verified through serum drug levels 1.

Addressing Medication Non-Adherence

• Patient education is critical: Patients must understand that levetiracetam should be taken only as prescribed, and that AEDs may increase risk of suicidal thoughts and behavioral changes 4.

• Counsel on behavioral side effects: Levetiracetam may cause aggression, agitation, anger, anxiety, apathy, depression, hostility, and irritability 4.

• Emphasize seizure risks: The patient and family must understand that uncontrolled seizures carry significant morbidity and mortality risks, including sudden unexpected death in epilepsy (SUDEP), traumatic injuries (affecting 45.7% of post-GTCS patients), and serious complications 2.

Long-Term Management Considerations

Neurology Referral is Essential

• Neurology referral should be strongly reconsidered despite prior cost concerns, given:

  • Breakthrough seizures due to non-compliance
  • Concerning post-ictal neurologic findings
  • Need for comprehensive epilepsy management and monitoring 3

• Patients with uncontrolled tonic-clonic seizures require specialist evaluation to optimize therapy and assess for underlying structural causes 6, 7.

Medication Optimization

• Levetiracetam remains appropriate first-line therapy for generalized tonic-clonic seizures with 68-73% efficacy and minimal drug interactions 1, 6, 7.

• Advantages of levetiracetam include:

  • No significant cytochrome P450 interactions (important given multiple comorbidities) 8, 4
  • Minimal cardiovascular effects 1
  • Rapid absorption and linear pharmacokinetics 4

• If seizures remain uncontrolled on adequate levetiracetam monotherapy, consider adding valproate (though avoid in women of childbearing potential) or switching to alternative agents 1, 6, 7.

Metabolic Screening

• Screen for calcium and vitamin D deficiency, as these can precipitate breakthrough seizures, particularly in patients on enzyme-inducing AEDs (though levetiracetam is not enzyme-inducing) 5.

• Address vitamin D deficiency (documented in PMH) as this may contribute to seizure susceptibility 5.

Critical Safety Measures

Seizure Precautions

• Strict seizure precautions including no driving until seizure-free for state-mandated period (typically 3-12 months) 4.

• Avoid heights, swimming alone, operating machinery, or other hazardous activities until seizure control is established 4.

• Family education on seizure first aid: Do not restrain during seizures, do not put anything in mouth, position on side, time seizure duration, and call 911 if seizure lasts >5 minutes 1.

Return Precautions

• Immediate ED return if:
  • Any further seizures occur
  • Worsening headache or neurologic symptoms
  • Altered mental status
  • Focal weakness or sensory changes
  • Visual disturbances
  • Chest pain or shortness of breath 3

Common Pitfalls to Avoid

• Never allow patients with acute neurologic findings post-seizure to defer emergency evaluation, even with AMA documentation—the risk of missing life-threatening complications is too high 3, 2.

• Do not attribute all post-ictal symptoms to "normal" post-seizure state—persistent cognitive changes, focal findings, or severe headache warrant imaging 1.

• Do not underestimate the importance of medication compliance counseling—non-adherence is a leading cause of breakthrough seizures and must be addressed directly 1.

• Do not delay neuroimaging for laboratory results in patients with active concerning neurologic findings 1.