Abstracts

Rationale:
In patients with epilepsy, failure to control seizures with two medications adequately chosen and with appropriate dosing indicates drug resistance. In those patients who are not candidates for surgery, or who have already undergone surgery, or who already had a Vagus Nerve Stimulator (VNS) placed, if seizures persist, chances of pharmacological control are low. The availability of new anti-seizure drugs in clinical practice over the last decades has not improved the number of patients who become seizure free. In addition, seizure frequency and severity may even increase, resulting in cognitive and psychiatric dysfunction, injuries, status epilepticus and SUDEP. The clinical care of refractory epilepsy might be optimized by considering, in a systematic way, factors facilitating or limiting breakthrough seizures. For example, seizures’ control could be enhanced by inexpensive measures such as: i) improving compliance (for example, through frequent follow-up visits, engaging with patients and their families, treating depression), ii) diagnosing and treating any coexistent sleep disorders, iii) combining anti-seizure drugs with different mechanisms of action (rational polypharmacy), iv) limiting the trough fall of serum levels into the sub-therapeutic range by higher drug dosage (short of causing unacceptable side effects) and/or with more frequent daily schedules and/or long acting drug formulations. Each of these measures, taken alone, may exert only a limited therapeutic effect. However, a systematic and simultaneous implementation of all of them is more likely to yield a sizable, clinically significant, improvement. To the best knowledge of this writer, such an approach is not typically or routinely adopted in the care of patients with epilepsy.
Method:
I performed a retrospective chart review of 160 adult epilepsy patients followed at The University of Utah and at the Salt Lake City VA Medical center in whom the approach described above, with multiple measures, was implemented. These were followed for a time interval ranging between 1 and 6 years.
Results:
I identified 72 consecutive adult patients with drug-resistant epilepsy. In 14 patients (19%), the remission from seizures was longer than 12 months and longer than three-fold the duration of the longest inter-seizure interval. In 5 patients (7%), the remission was shorter than 12 months and/or shorter than three-fold the duration of the longest inter0seizure interval. In 17 patients (24%), there was a clinical improvement with a decrease in seizures’ frequency of 22+5% of previous activity. In 36 patients (50%), there was no definite clinical improvement. In this group, the median of seizures’ frequency remained at 2.5 attacks per month, but there was no progression such as higher seizure frequency, status epilepticus or SUDEP. Of interest, in at least 10 patients, the times of breakthrough seizures, coincided with trough levels. In these, seizures improved through a drug schedule/formulation attenuating trough level falls.
Conclusion:
The optimization of medical care through multiple measures attempted in this project is simple and effective: half of the patients exhibit better seizures’ control. In cases of refractory epilepsy, clinical management options are limited. Thus, even a partial improvement can improve the quality of life of a large number of people with epilepsy.
Funding:
:N/A