Randomized, controlled trials (RCT) to assess the efficacy and safety of epilepsy surgery were missing till 2001. In the first such study [4], 80 patients with temporal lobe epilepsy (TLE) were randomly assigned to surgery (n = 40) or treatment with ASMs for one year (n = 40). The primary outcome was seizure freedom and secondary outcome included seizure frequency and severity, quality of life (QOL), disability, and death.

At 1 year, the cumulative proportion of patients who were seizure free was 58% in the surgical group versus 8% in the medical group (P < 0.001). Patients in the surgical group had fewer complex-partial seizures (CPS) and significantly better quality of life (P < 0.001 for both comparisons) than the patients in the medical group. Four patients (10%) had adverse effects of surgery (mainly the expected mild language and memory-related problems such as word finding and short-term memory difficulties) while one patient in the medical group died. This study confirmed that in TLE, surgery is superior to prolonged medical therapy. This RCT also showed that randomized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects.

It has been well established that years of active epilepsy predict cognitive impairment in children and adolescents [5, 6]. Therefore, in order to investigate the effects of early surgery, i.e., whether it would be superior to continued medical management, Engel et al., conducted a multicenter, parallel-group RCT soon after the failure of 2 ASM trials in patients with temporal lobe epilepsy [7]. Thirty-eight patients (18 M/20 F; age ≥ 12 years) with MTS and refractory MTLE who were within 2 consecutive years of adequate trials of 2 ASMs were randomized to (1) continued ASM (n = 23), or (2) anterior mesial temporal lobectomy (AMTR) plus ASM treatment (n = 15) and were followed for two years. The primary outcome was seizure freedom during the second year of follow-up, and the secondary outcome was health-related quality of life (QOL), cognitive function, and social adaptation.

Seizure freedom during the second year of follow-up was reported in 11 of 15 patients in the surgical group versus none of the 23 in the medical group (P < 0.001). Also, improvement of QOL was higher in the surgical group (P = 0.01). Memory decline occurred in 4 patients (36%) after surgery. Adverse events included one stroke in a surgical case versus 3 cases of status epilepticus in the medical group. It was concluded that resective surgery plus ASM in patients with new refractory MTLE results in lower probability of seizures during second year of follow-up than continued ASM treatment alone.

There are different surgical methods depending on the patient and seizure type and other characteristics including:

A 43-year-old man developed seizures two years after surviving a left temporal aneurysm rupture. Following the surgery and aneurysm resection, he did well until the seizures started. Multiple ASMs were tried but he continued having partial seizures with secondary generalization about twice a month. His brain MRI findings were consistent with his history of prior surgery and an encephalomalacia involving the posterior temporal lobe. His video-EEG monitoring localized his seizure onset focus to the left temporal area including the posterior regions. His Wada test lateralized language to the left side and showed a significantly better memory function on the right. He was admitted for subdural grid placement in order to accurately localize the epileptogenic zone and perform language mapping prior to a prospective left temporal resective surgery (Figs. 25.4, 25.5, and 25.6).

Cortical mapping defined the language cortex next to the seizure focus. The patient underwent a left temporal lobectomy including the seizure foci while preserving the language and sensory cortex as depicted above. He had no language deficits after the resection. He has been completely seizure free since the surgery while continuing only one of his ASMs at minimal dose (he had one breakthrough seizure 5 years later after stopping his ASM but has remained seizure since resuming the ASM (follow-up since surgery >6 years)).

A 35-year-old woman presented with seizures since age 5 years. She described her seizures as “day dreaming, head turning, lip smacking, right-hand posturing and at times convulsions.” In the past, she had been on phenobarbital since childhood, as well as several other ASMs. Her current seizure frequency is about 3 times per week. She lives with her family, has never worked, and does not drive. Her mother reports behavioral problems (outbursts). After the first visit, while starting her presurgical evaluation, her ASM was changed to levetiracetam that resulted in some improvement in seizure frequency, but later she responded better to the combination therapy of levetiracetam and lamotrigine (i.e., her seizures decreased to 1–2 per month). Her high-resolution brain MRI was normal. A routine EEG showed left temporal spikes and video-EEG monitoring revealed left temporal ictal onset, but there were a few seizures with indeterminate localization. An invasive monitoring using subdural strip electrodes was performed to confirm the localization (Fig. 25.7). Resective surgery was curative.

Surgical outcome following surgery in MRI-negative (nonlesional) patients with refractory partial epilepsy can result in favorable outcome. A review of 399 patients has shown positive long-term outcome after 0.5–15.7 year (mean 6.2) follow-up period [25]. The seizure types included focal dyscognitive seizures (complex-partial): 237 (59%), GTCS: 119 (30%), focal without alteration of awareness (simple-partial seizures): 26 (6%), and mixed: 17 (4%). Of these 372 (93%) had temporal lobe, and 27 (7%) extra-temporal lobe resections. The pathology showed MTS in 113 patients (28%), gliosis in 237 (59%), and normal tissue in 49 (12%). The overall Engel Class I outcome is given as follows:

Almost all seizures occurred during the first year after surgery. The positive predictive factor was seizure control during the first follow-up year. A Class I outcome at first year indicated 92% probability of seizure remission at 10 years. Negative risk factors included (1) extra-temporal seizure focus (p < 0.001), (2) previous surgery (p < 0.001), (3) male gender (p = 0.035), and (4) normal tissue in pathology (p = 0.038).

A normal MRI is not against surgery in patients with TLE. Sixty-four adult patients with refractory TLE but normal MRI who had underwent TLE surgery (1996–2009) were followed for 1–14.5 years (mean 4.1). Standard anterior temporal lobectomy was done in 84% and an unremarkable pathology was reported in 45% of the patients. Complete seizure freedom rates are given as follows:

The negative predictors (risk factors) were (1) higher baseline seizure frequency and (2) preoperative generalized tonic–clonic seizures. Memory decline was reported with dominant hippocampus resections [26].

For the past 20 years, a 45-year-old man would wake up soon after falling asleep screaming and flailing his arms and legs for 30 s before full recovery. He is otherwise healthy. Currently he is on 4 ASMs. He has been on most of the available ASMs, clonazepam, and SSRIs, for seizures, sleep disorders, and “pseudoseizures,” respectively. In the past, he had experienced a few similar episodes during the day as well. His EEGs and polysomnogram have all been normal in the past. His current event frequency is 3–7 events per night. He is unemployed, does not drive, and his wife sleeps in a separate room (Figs. 25.8, 25.9, 25.10, 25.11, 25.12, and 25.13).