Management of Well-Controlled Seizures with New Focal Symptoms
For your patient with well-controlled seizures who now reports intermittent left-sided facial tingling (likely a focal aware seizure or aura) and occasional short-term memory loss, optimize the current antiepileptic drug (AED) dosage before adding a second medication, verify medication adherence, and systematically search for reversible precipitating factors.
Immediate Assessment Priorities
Check medication compliance first – non-adherence is the most common cause of breakthrough seizures even when drug levels appear adequate. 1 Obtain serum drug levels of the current AED to confirm therapeutic concentrations and assess whether the patient is actually taking the medication as prescribed. 2
Search for precipitating factors systematically:
- Sleep deprivation 1
- Alcohol consumption 1
- Intercurrent illness 1
- New medications that may lower seizure threshold or interact with current AED 1
- Metabolic disturbances (hypoglycemia, hyponatremia) 1
Diagnostic Work-Up for New Focal Symptoms
Obtain outpatient EEG to detect subclinical seizure activity and characterize the focal nature of these events. Abnormal EEG findings predict higher seizure recurrence risk and should guide treatment adjustments. 3 If the patient has persistent altered mental status or fails to return to baseline between episodes, consider urgent EEG to rule out non-convulsive status epilepticus. 1, 2
Arrange outpatient MRI with epilepsy protocol (if not done recently) because MRI detects structural abnormalities in approximately 55% of patients with focal seizures, whereas CT identifies only 18% of such lesions. 3 MRI is particularly important for detecting temporal lobe pathology, cortical dysplasia, tumors, or other epileptogenic substrates that may explain new focal symptoms. 3
Medication Optimization Strategy
Step 1: Optimize Current Monotherapy
Increase the current AED dose gradually to the maximum tolerated dose – this achieves additional seizure control in approximately 20% of patients with breakthrough seizures. 4 The goal is complete seizure freedom without adverse effects. 5
Titrate slowly to avoid unnecessary side effects from rapid escalation. 6 If the patient develops intolerable adverse effects during dose escalation without achieving better seizure control, reduce the dose back to the previous tolerable level. 4
Balance adverse effects against seizure control – if dosing to the limit of tolerability does not provide additional benefit (which occurs in many patients), reduce the dose rather than continuing an ineffective high dose. 4
Step 2: Consider Switching vs. Adding
If maximum tolerated monotherapy fails, switch to a different first-line AED rather than immediately adding a second drug. 5 Approximately 47% of patients respond to a second monotherapy agent after failing the first. 1
Reserve combination therapy only for patients who have failed two or more sequential monotherapies. 2, 5 Polypharmacy increases the risk of adverse effects, drug interactions, and non-compliance. 6
Step 3: If Combination Therapy Becomes Necessary
Select the second AED based on mechanism of action and interaction profile:
Levetiracetam offers the most favorable profile with minimal drug interactions, no enzyme induction, and good tolerability. 2 Standard dosing is 500–1500 mg twice daily, with gradual titration. 1
Valproate is highly effective (79% success rate as second-line agent) with minimal cardiorespiratory effects, but is absolutely contraindicated in women of childbearing potential due to teratogenicity. 2, 1
Lamotrigine may be used for focal seizures but requires slow titration over several weeks to minimize Stevens-Johnson syndrome risk. 1
Avoid carbamazepine as add-on therapy if the patient is already on another enzyme-inducing AED, as the combination increases pharmacodynamic neurotoxicity. 6 Carbamazepine also has nonlinear pharmacokinetics requiring therapeutic drug monitoring. 7
When adding a second drug, slowly reduce the first AED dose if the patient experiences adverse effects, ideally before fully loading the second agent. 4 If the patient does not benefit unequivocally from two-drug therapy within 3 months (and approximately 75% will not), slowly transition back to monotherapy with the second drug and consider a third agent. 4
Monitoring and Follow-Up
Question the patient about seizure occurrences at each follow-up visit to assess treatment efficacy and detect subtle breakthrough events. 2
Obtain therapeutic drug monitoring when using drugs with nonlinear pharmacokinetics (phenytoin, carbamazepine), when drug interactions are expected, or when toxicity is suspected. 7 However, avoid targeting concentrations within the "therapeutic range" in patients who are well controlled at lower concentrations – this is a common cause of overtreatment. 6
Re-evaluate the overall drug load regularly to prevent overtreatment. Great benefits without loss of seizure control are often gained by slowly reducing excessive medication burden in chronic epilepsy. 4
Critical Pitfalls to Avoid
Do not add a second AED without first optimizing the dose of the first drug. Many patients are switched prematurely without exploring the full dosage range of the initial agent. 7
Do not assume the new symptoms represent treatment failure – verify compliance, check drug levels, and rule out precipitating factors before escalating therapy. 1, 2
Do not use unnecessarily high maintenance dosages based on misinterpretation of "therapeutic ranges" rather than clinical response. 6 The goal is the lowest effective dose that provides seizure control. 7
Do not continue ineffective polypharmacy – if two-drug therapy does not provide clear benefit within 3 months, simplify the regimen rather than adding a third agent. 4
Refer to an epilepsy specialist if seizures remain incompletely controlled after two sequential monotherapy attempts or if combination therapy is being considered. 7