Evaluation of Efficacy of Epilepsy Surgery for Dominant Mesial Temporal Lobe Epilepsy without Hippocampal Sclerosis

Original Research | Journal of Clinical Neuroscience 111 (2023) 16-21

Introduction

Approximately 0.5%-1% of the global population suffers from epilepsy (Fiest et al. 2017), with about 30% of these patients being refractory to medication (Schiller & Najjar 2008), termed medically refractory epilepsy. For these patients, surgical treatments such as lesion resection or palliative therapies (including vagus nerve stimulation and corpus callosotomy) may be considered. To date, the most mature and successful epilepsy surgery is anterior temporal lobectomy (ATL) targeting mesial temporal lobe epilepsy (MTLE) (Spencer 1991).

While ATL is more effective than medication for medically refractory MTLE (Wiebe et al. 2001), and many studies have confirmed its favorable outcomes (McIntosh et al. 2001; Özkaara et al. 2008), there remain unresolved issues in the treatment of MTLE with ATL. Especially in patients with MTLE without hippocampal sclerosis (HS) on the dominant side, ATL may impair memory function (Martin et al. 2002), and postoperative psychological decline can reduce quality of life (QOL) (Glosser et al. 2000).

To protect memory function in these patients, multiple hippocampal transection (MHT) was developed as an alternative surgical method, achieving some successful cases (Shimizu et al. 2006; Usami et al. 2016; Patil & Andrews 2013). However, MHT has not yet been established as a standard surgical approach, with limited reports supporting its efficacy and a lack of detailed studies on patients’ postoperative status beyond memory function.

In this study, we investigated the detailed surgical outcomes of MHT in dominant-side MTLE patients without HS. In addition to seizure control and memory function, we reviewed postoperative psychological decline and drug withdrawal states, factors known to affect patients’ QOL (Mikati et al. 2006; Pirio Richardson et al. 2004).

Background and Source

This study was conducted by Abe Daisu, Inaji Motoki, Hashimoto Satoka, Maehara Taketoshi of the Neurosurgery Department and Takagi Shunsuke of the Graduate School of Psychiatry and Behavioral Sciences at Tokyo Medical and Dental University. The research was published on March 13, 2023, in the Journal of Clinical Neuroscience.

Methods

Study Subjects

A retrospective analysis was conducted on clinical records of 30 patients with dominant-side MTLE without HS treated at Tokyo Medical and Dental University from 2007 to 2020. All patients underwent preoperative examinations, including MRI, FDG-PET, and long-term video EEG monitoring and had memory and language-dominant hemispheres determined by functional MRI or Wada test. All patients were followed for more than two years postoperatively.

Surgical Indications

At our institution, MHT is indicated for patients whose seizure type and all preoperative examinations (including video EEG, FDG-PET, MEG, and ECOG) consistently showed a seizure focus in the dominant mesial temporal lobe, with no hippocampal sclerosis on MRI and normal memory function on cognitive testing.

Surgical Procedure

All patients underwent conventional anterior temporal lobectomy. In cases with HS, the standard ATL method was used to resect the amygdala, hippocampus, and parahippocampus. In cases without HS, the anterior part of the middle temporal gyrus was transected, and the lateral ventricle was opened using navigation guidance. Incisions were made at 5mm intervals in the hippocampus without resecting the amygdala, hippocampus, or parahippocampus. In one patient from the ATL group and all patients from the MHT group, subdural electrodes were implanted and ECOG recordings were performed to assess resection efficacy.

Seizure Control Evaluation

Seizure control was evaluated using the Engel classification (Engel et al. 1993). Additionally, we tracked the number of antiseizure medications (ASMs) required postoperatively to assess the impact of surgery on medication withdrawal status. If no seizures occurred for over a year, medication withdrawal was considered with patient consent (Maehara & Ohno 2011).

Cognitive Function Assessment

Memory and cognitive function were assessed using the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) and the Wechsler Memory Scale-Revised (WMS-R). Each patient underwent neurocognitive assessments preoperatively and one year postoperatively.

Postoperative Psychological Complications

All patients were interviewed by a psychiatrist specializing in epilepsy to evaluate psychological status and conducted Global Assessment of Functioning (GAF) scores pre- and post-operatively. Postoperative psychological or psychiatric issues were managed by psychiatric care, prescribing antipsychotic drugs as needed. Patients who were newly prescribed antipsychotic drugs postoperatively were deemed to have psychological deterioration, including existing and new psychiatric symptoms.

Statistical Analysis

Two-way repeated measures analysis of variance (ANOVA) and paired t-tests were used to assess changes in WAIS-III and WMS-R scores over time. Changes in ASMs were analyzed using the Wilcoxon rank-sum test, and differences in Engel classification and psychological complications were analyzed using Fisher’s exact test. Changes in GAF scores were investigated using the Wilcoxon signed-rank test. Statistical significance was set at 5%.

Results

Patient Characteristics

This study included 30 patients with an average age of 29. Of these, 23 were diagnosed with MTLE with HS and underwent ATL, and the remaining 7 underwent MHT due to normal MRI findings preoperatively.

Seizure Control Outcomes

In the ATL group, 70% of patients (16 cases) achieved Engel Class I seizure control, whereas in the MHT group, it was 71% (5 cases). The ASM reduced from an average of 2.4 to 1.9 postoperatively (p=0.01) in the ATL group, while the MHT group showed no significant change (from 2.1 to 2.0, p=0.77). Although there was no significant difference in seizure control between the two groups (p=0.73), 48% of patients in the ATL group (11 cases) experienced psychological issues postoperatively, while no psychological complications were observed in the MHT group.

Cognitive Function Changes

Postoperative cognitive testing showed no decline in cognitive function in both ATL and MHT groups. Particularly in the MHT group, short-term and visual memory declines were transient and recovered within a year postoperatively. The ATL group exhibited cognitive function improvements in performance IQ, general memory, and attention concentration one year postoperatively (p=0.0004, 0.01, 0.04, and 0.001 respectively).

Postoperative Psychological Deterioration

In the ATL group, 48% of patients experienced psychological deterioration and required psychiatric medication postoperatively, whereas no such cases were observed in the MHT group. The GAF score of the ATL group dropped from 92 preoperatively to 73 postoperatively (p<0.01), whereas no decrease was observed in the MHT group, indicating that MHT is less likely to cause postoperative psychological issues compared to ATL.

Conclusions

MHT can achieve equivalent seizure control postoperatively, protect cognitive function, and reduce postoperative psychological complications. Thus, for dominant MTLE patients without HS, MHT can be considered a treatment option. Future multicenter, large-sample prospective studies are needed to further validate the efficacy and safety of MHT.

Significance and Value of the Study

By comparing the effects of MHT and ATL in treating dominant mesial temporal lobe epilepsy, especially in patients without hippocampal sclerosis, this study provides important references for clinical practice. These findings have significant implications for improving epilepsy surgical methods and optimizing patients’ postoperative quality of life.

Highlights

1. Seizure Control Efficacy: MHT matches ATL in terms of seizure control efficacy.
2. Cognitive Protection: MHT preserves or improves patients’ memory and cognitive functions.
3. Psychological Complications: MHT significantly reduces postoperative psychological complications.

With these research results, clinicians can consider MHT as a first-choice surgical option for dominant-side mesial temporal lobe epilepsy without hippocampal sclerosis, thus better protecting patients’ cognitive function and overall quality of life.