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The results of surgical treatment of epileptic seizures have gradually improved in the past decade, approaching 60% to 90% seizure-free outcome in temporal lobe epilepsy and 45% to 66% in extratemporal lobe epilepsy. Unfortunately some patients continue with seizures after epilepsy surgery and the studies have shown that approximately the 3% to 15% of patients with a previous failed surgical procedure are reoperated. Selected patients may be candidates for further surgery, potentially leading to a significant decrease in the frequency and severity of seizures. In patients with intractable partial epilepsy there are many possible factors, alone or in combination, that could be related to the failure of resection. Some of the factors could be genetic or acquired predisposition to epileptogenicity. In this article we report a case with intractable epilepsy that required three interventions to render seizure free. We analyzed our specific case in the light of previous reports on reoperation and enumerate the potential reasons for reoperation that could apply to all patients with failure of an initial procedure.
The results of surgical treatment of epileptic seizures have improved in the past two decades, approaching 60% to 90% seizure-free outcome in patients with temporal lobe epilepsy and 40% to 60% in extratemporal lobe epilepsy.1 However, there are few alternative treatment options to patients who fail epilepsy surgery such as reoperation, use of electrical stimulation and new medications. Reoperation for recurrent temporal epilepsy was first reported in 1954 by Penfield. Selected patients may be candidates for reoperation, potentially leading to a significant decrease in seizure burden. The frequency of reoperation reported in the literature is variable, ranging from 3% to 14%.2–4
The success after a second surgical procedure is variable and different studies have reported different seizure-free rates. Awad et al reported that 47% of patients were seizure free after a second procedure,2 Germano et al 63%,5 Gonzalez-Martinez 38%,6 and Salanova 57%.7
With recent advances in neuroimaging and more frequent use of noninvasive video-electroencephalography (VEEG) monitoring, a more comprehensive and accurate evaluation of the epileptogenic zone should be accomplished before the first epilepsy surgery. In patients with intractable partial epilepsy there are many possible factors, alone or in combination, that could be related to the failure of resection. Some of the factors could be related to acquired and genetic predisposition to continuous seizures.
We present a 27-year-old, right-handed male with no previous history of febrile seizures, head trauma, central nervous system infections or family history of seizures.
Since the age of 5, the patient had complex partial seizures with and without secondary generalization plus occasional grand mal seizures. The seizures were not preceded by an aura and the patient had oral and bimanual automatisms, bipedal automatisms and loss of awareness during the seizures with no postictal confusion. This patient had a high frequency of seizures (10–15 seizures per day) since his epilepsy began. Over the years he failed to the following medications: topiramate, carbamazepine, levetiracetam and valproic acid.
This patient had the first investigation for epilepsy surgery when he was 17 years old. Before surgery he was taking the combination of valproic acid and carbamazepine with adequate doses, and adequate therapeutic levels with no response. In pre-operative investigation, scalp EEG showed his seizures originated over the right frontal area. The patient had intracranial recording with electrodes covering the orbito-frontal area, the frontal convexity and the fronto-polar area, which supported the previous localization.
The patient had a small resection of the fronto-polar area (Figure 1). He was rendered seizure free for 6 months and the medications were stopped. Pathology was consistent with cortical dysplasia.
At the end of the first year after surgery the patient’s seizures restarted with the same frequency as before the intervention. The patient was retreated with the same medications used before surgery with no response and in the following years he failed to levetiracetam and topiramate. Also the patient was implanted with a vagal nerve stimulator when he was 20 years old, with no response.
The patient had a second investigation when he was 22 years old. The scalp EEG pointed to the seizure onset being over the right frontal area. Two ictal single photon emission computed tomography (SPECT) scans were taken showing an onset over the right orbito-frontal area. A decision was made to perform a right orbito-frontal resection without the necessity of intracranial recording (Figure 2). The pathology was consistent with cortical dysplasia. The resection was performed and the patient rendered seizure free for 6 months and then the medications were stopped.
At the end of the first year after surgery, patient’s seizures restarted with the same frequency as prior to surgery. Before the second procedure patient was on the combination of topiramate and levetiracetam. These medications were restarted after the surgery with no success. Over the years more medications were added due to the high frequency of seizures and before being assessed in our center he was on a combination of 4 medications, clobazam 10 mg twice daily, lamotrigine 250 mg twice daily, phenytoin 400 mg per day, and oxcarbazepine 600 mg twice daily. A telemetry investigation was done recording 40 seizures with a potential onset over the right frontal vs temporal area (see Figure 3A), with very rapid secondary generalization.
Interictally, the EEG also showed independent right frontal and temporal spikes (Figure 3B) and during sleep the EEG showed a generalized polyspike wave (Figure 3C). An intracranial investigation was performed in this patient covering the remaining areas of the right frontal lobe and the temporal area (Figure 3D). The seizures have a simultaneous onset over the right frontal convexity and the neocortical aspect of the temporal area (Figure 3C).
A right frontal resection was performed sparing the motor strip and a standard temporal lobectomy was also performed. The patient had some postoperative seizures in the first 2 days characterized by jerks in the face and arm. These disappeared after 1 week and were attributed to inflammation related with the intracranial procedure. These seizures were treated with valproic acid IV, a daily dose of 20 mg per kg for 7 days. The patient did not have any modification in the anti-epileptic drugs and was rendered seizure free after 1 week.
The patient remained seizure free for 2 years with no modifications in the medications. No cognitive testing was done before surgery because of the high frequency of seizures and no significant cognitive decline was seen after surgery. The patient was able to get a driver licence after 1 year and started working as a clerk.
This patient had 3 surgical interventions before he became seizure free. This is a very illustrative case of refractory epilepsy and shows many aspects common to all patients requiring reoperation after epilepsy surgery.
Potential reasons for surgery failure are as follows:
Resective epilepsy surgery is the most effective treatment for patients with pharmacoresistant, localization-related epilepsy, and surgery is the intervention that is most likely to render patients free from seizures.
The frequency of reoperation reported in the literature is variable, ranging from 3% to 14%.
When surgery fails, the correct understanding of why seizures occur, identifying patients who are at risk, and how to manage adverse outcomes when they do occur, is one of the most important endeavors facing epileptologists today.
Multiple factors are related to reoperations. Some of these are acquired characteristics of the patients, others are related to pitfalls in the investigation of patients, genetic predisposition, imaging or pathologic findings, and development of new epileptogenic foci.
Reoperation may be an appropriate alternative form of treatment for selected patients with intractable partial epilepsy who fail to respond to initial surgery.
Dr Téllez-Zenteno receives grants from the Royal University Hospital Foundation in Saskatoon and the University of Saskatchewan.