INTRODUCTION
Mesial temporal lobe epilepsy is the most common form of focal epilepsy in adults and is frequently refractory to medical treatment [1]. Hippocampectomy, either as part of an anterior temporal lobectomy or as a selective amygdalohippocampectomy, has been shown to provide excellent seizure control, with long-term seizure-freedom rates of 70-80% in appropriately selected patients [2-7]. Recent advances in endoscopic surgery have enabled less-invasive routes to the hippocampus. Two techniques are of particular interest: the endoscopic trans-orbital approach (TOA), which uses the lateral orbital wall to spare the neocortex, and the endoscopic trans-middle temporal approach (TMTA), which accesses the temporal horn through a small corticectomy in the middle temporal gyrus. Both aim to minimize tissue disruption while maintaining seizure control, but differ in anatomical trajectory, technical demands, and complication profile.
This study reviews and compares the endoscopic TOA and TMTA for hippocampectomy, focusing on surgical feasibility, outcomes, and risks.
METHODS
Literature search strategy
An artificial intelligence (AI)-assisted literature search was performed to identify studies describing endoscopic approaches to hippocampectomy, with a specific focus on the endoscopic trans-orbital and endoscopic middle temporal gyrus corridors. The search combined conventional database queries with AI-based semantic search tools to maximize retrieval of relevant publications, including studies that may not be captured by keyword-only strategies.
Electronic databases (PubMed, Embase, and Scopus) were searched from inception to May 2025 using a combination of Medical Subject Headings (MeSH) and free-text terms: “hippocampectomy,” “amygdalohippocampectomy,” “endoscopic,” “transorbital,” “trans-orbital,” “middle temporal gyrus,” “temporal approach,” “temporal horn,” and “mesial temporal lobe epilepsy.” Boolean operators (“AND,” “OR”) were applied to refine results. The AI-assisted component provided semantic expansion of search terms, identification of related anatomical synonyms, and cross-linking of relevant references cited in retrieved articles. Reference lists of included studies and relevant review articles were manually screened to identify further eligible publications.
Studies were included if they described a purely endoscopic or endoscope-assisted hippocampectomy or selective amygdalohippocampectomy; clearly specified the surgical corridor as trans-orbital or middle temporal gyrus (transcortical or transsulcal); reported either cadaveric feasibility data or clinical outcomes; and provided extractable data on patient number, seizure control, visual field outcomes, and other complications. Exclusion criteria included the use of microscopic approach without endoscopic assistance, procedures that did not include hippocampal resection, and an inability to separate data specific to the surgical approach.
Data extraction and synthesis
Two reviewers independently screened all identified titles, abstracts, and full texts. Disagreements were resolved by consensus. For each included study, the following variables were extracted: first author, year, study type, surgical approach, patient number, seizure control rate, incidence of visual field defects, other complications, and endoscope use.
Data were organized and synthesized descriptively. Due to heterogeneity in study design and outcome measures, a formal meta-analysis was not performed. Instead, a narrative comparative analysis was conducted to highlight key anatomical, technical, and clinical differences between the TOA and TMTA. The study selection process is summarized in a PRISMA (https://www.prisma-statement.org/) flow diagram (Fig. 1).
Diffusion-tensor imaging-magnetic resonance imaging data acquisition and optic radiation fiber tracking
For illustrative purposes, diffusion-tensor imaging data from a neurologically normal individual were used to evaluate the anatomical relationships among the hippocampus, amygdala, and Meyer’s loop. The images were processed and reconstructed using commercially available software (Elements; Brainlab) following previously published protocols [8]. After correction for cranial distortion and co-registration with T1-weighted anatomical images, regions of interest were placed over the lateral geniculate body and the optic tract ipsilateral to the side of approach. Optic radiation tractography was then performed using a minimum fiber-length threshold of 35 mm and a fractional anisotropy cutoff of 0.15. Three-dimensional reconstructions were generated to demonstrate the expected surgical trajectories for the TOAs and TMTAs (Fig. 2).
RESULTS
Seven studies met the inclusion criteria following the literature search (Table 1) [9-15]. Of these, four studies used an anterior approach (three trans-orbital and one anterior transmaxillary) and three employed a lateral approach through the middle temporal gyrus. Three were cadaveric feasibility studies, and four were clinical series or case reports.
Among the clinical studies, the total number of patients was 14 (13 trans-orbital/anterior group; 1 middle temporal gyrus group). Although the sample sizes were small, all patients remained seizure-free during the reported follow-up periods. No cases of visual field defects were documented in the included clinical series. Reported complications were minimal, with no permanent morbidity described.
Cadaveric studies consistently demonstrated adequate exposure of the hippocampus and amygdala through both approaches, with anatomic preservation of critical structures when performed according to described techniques.
Surgical techniques
A review of the surgical techniques described in the included studies revealed consistent procedural patterns within each approach category.
For the TOA, most authors employed either an upper eyelid (transpalpebral) incision or an eyebrow/lateral canthal skin incision to minimize visible scarring. The lateral orbital rim and wall were partially drilled or removed to create a bony window toward the anterior temporal fossa. Dissection proceeded along the inferior orbital fissure toward the temporal pole, avoiding injury to orbital contents and anterior cranial nerves. The temporal horn was then opened, and the amygdala and hippocampus were exposed and resected using 0° and 30° endoscopes. Reconstruction of the orbital wall was performed in some cases with titanium mesh or plates to restore anatomical contour.
For the TMTA, a small keyhole craniotomy was created over the middle temporal gyrus, typically anterior to the vein of Labbé and above the zygomatic arch. A minimal corticectomy, which was placed in the inferior portion of the gyrus to reduce the risk to Meyer’s loop, was made to enter the subcortical white matter and reach the temporal horn. The hippocampus and amygdala were then identified and resected under pure endoscopic or endoscope-assisted visualization. The cortical entry was kept as small as possible to minimize disruption of eloquent white-matter tracts and reduce the risk of postoperative visual or language deficits.
DISCUSSION
Hippocampectomy remains a cornerstone of surgical management of mesial temporal lobe epilepsy, offering high rates of long-term seizure control in appropriately selected patients [16,17]. Traditionally performed through open approaches such as anterior temporal lobectomy with amygdalohippocampectomy, the procedure has well-established efficacy but carries risks of visual field deficits, cognitive decline, and other complications related to cortical and white-matter disruption [5,18,19].
The advent of high-definition endoscopy and refined skull base techniques has enabled the development of minimally invasive routes to the hippocampus. These approaches aim to preserve brain structures, minimize cosmetic impact, and potentially reduce morbidity while maintaining seizure control efficacy. In this review, a total of seven studies (three cadaveric and four clinical) were identified, encompassing 14 patients (13 trans-orbital/anterior and 1 middle temporal gyrus). All reported seizure freedom during follow-up, with no visual field deficits or permanent morbidity documented. Cadaveric studies confirmed that both approaches allow for reliable exposure of the hippocampus and amygdala when anatomical landmarks are respected.
COMPARATIVE ANALYSIS AND ANATOMICAL CONSIDERATIONS
TOA provides access through the lateral orbital wall, sparing the temporal neocortex and white matter. Cadaveric data indicate that up to 97% of hippocampal length can be exposed, while clinical reports show excellent cosmetic outcomes through transpalpebral or eyelid-crease incisions [9]. However, risks include injury to orbital contents, extraocular muscles, and cranial nerves traversing the cavernous sinus [20]. TMTA uses a small corticectomy through the middle temporal gyrus to reach the temporal horn. This provides a shorter, more direct route and wider exposure, but involves cortical and subcortical transgression, increasing the risk to Meyer’s loop, temporal vasculature, and language pathways (Fig. 2) [13,14].
Table 2 summarizes these differences. In brief, TOA minimizes cortical disruption and favors cosmesis but entails orbital risks, whereas TMTA offers broader access at the expense of potential neocortical and visual pathway injury. The choice of approach should be guided by lesion location, surgical goals, and patient-specific anatomical constraints.
FUTURE DIRECTIONS
Both approaches remain in early stages of clinical application. Larger, prospective, multicenter studies are required to establish their comparative efficacy, neurocognitive outcomes, and long-term complication profiles. Integration of advanced tools such as image-guided navigation, tractography-based planning, and augmented reality overlays may further improve safety, particularly in preserving Meyer’s loop and other eloquent structures. From a clinical standpoint, the TOA may be preferable in anterior mesial temporal pathologies prioritizing cosmesis and neocortical preservation, whereas the middle temporal approach may be appropriate for cases requiring broader access or when orbital expertise is limited. Ultimately, these minimally invasive techniques should be regarded as complementary surgical strategies for mesial temporal lobe epilepsy.
LIMITATIONS
The present review is limited by the small number of published studies, heterogeneous designs, and small patient volume, which precludes a meaningful statistical comparison of the approaches. Follow-up durations were short, and detailed neurocognitive and visual assessments were largely absent. In addition, most data were derived from cadaveric feasibility studies or isolated case reports, restricting generalizability to broader clinical practice.
CONCLUSION
Both the endoscopic TOA and TMTA appear to be safe, effective, and minimally invasive routes for hippocampectomy, but the current evidence is limited. Larger prospective studies are required to better define their comparative advantages, patient selection criteria, and long-term outcomes.
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