Resective surgery is the first choice for treating focal DRE when a single seizure focus can be well localized and surgery can be performed safely without causing intolerable neurologic deficits [46]. The optimal outcome of surgical intervention is a complete cessation of seizures without any postsurgical deficits [17, 59]. The accurate demarcation of both seizure foci and eloquent cortices is essential for this purpose [23, 60]. During the surgical procedure, the epileptogenic tissue (epileptogenic zone [61]), and not only the lesion needs to be removed in order to achieve seizure freedom. Importantly, the epileptogenic zone is a theoretical construct defined by the minimum amount of tissue that has to be removed to gain seizure freedom [33], but the exact zone cannot be characterized reliably by presurgical investigations [59, 61]. Therefore, a compromise between the extent of surgically removed tissue and the reduction of potential impairment is required [59]. Interestingly, health-related quality of life worsens after surgery if persistent seizures are accompanied by memory decline, but the latter alone doesn’t result in a negative assessment [62]. For MTLE-HS patients, a standard ATL is not only a well-established surgical routine, but also a well-established compromise between seizure control and none or at most minimal neuropsychological and neurological impairments. An alternative surgical procedure is selective amygdalohippocampectomy [63]. Eventually, the neurosurgeon should use the method which is the standard of care in this center and which he feels most comfortable with. In the end, a highly localized epileptic focus predicts the best surgical outcome and not the surgical procedure applied [64].

Complications are commonly transient or minor, major complications are rare, and the surgical seizure outcome in LMIC is comparable to that of HIC [9]. The development of a primary standard routine, taken from the well-established mentoring center and adapted to the local conditions, is a valuable tool to implement and improve local surgical care of patients. But the local circumstances and equipment can be quite distinct from what is normally used by the mentoring experts, which may require creative solutions [65]. Working together can also be hampered by language barriers, local customs, unexpected routines, or unfamiliar interactions. Successful mentoring thus also depends on a motivated surgical team in order to overcome such obstacles and focus primarily on the surgical implementation. To make epilepsy surgery an established practice, it is further recommended that surgical procedures should be performed on a regular base rather than conducted as single events [9, 20, 58].

It is the responsibility of the neurosurgeon, within the context of the multidisciplinary team, to decide whether surgery is feasible and advisable [66]. Therefore, the surgeon must adequately understand and interpret the diagnostic data to identify as accurately as possible the epileptogenic zone where surgery has to be carried out. Consequently, the role of the neurosurgeon is not limited to the surgical procedure itself. He is also an integral part of the multidisciplinary team to decide on surgical interventions, especially when it comes to predicting the likelihood of success or failure of a particular procedure for a given candidate [46, 59, 66]. Thus, the participation of the neurosurgeon in multidisciplinary case conferences is mandatory. To fulfill this role, the surgeon should not only be trained in epilepsy-related surgical techniques, but also be tought knowledge of seizure semiology and the corresponding radiological findings [46].

A surgeon is also essential if invasive diagnostics like intracranial EEG are required to clarify the seizure onset zone [6, 58], but the surgical requirements in terms of equipment and competency must be met for any chosen procedure [15, 23]. Stereotactic EEG recording through intracranial electrodes is an increasingly common procedure in HIC [67], but this invasive technique requires robotic or stereotactic system assistance and an appropriate epilepsy monitoring unit. Consequently, it is quite demanding in terms of equipment, expertise, and diagnostic resources, which might be a major barrier to adoption in resource-limited settings. Such expensive state-of-the-art equipment may not be feasible for local surgical epilepsy centers in LMIC, so cost-effective methods are crucial [15] and low-cost options should be used first. For example, further diagnostics to clarify a suspected bilateral epileptic focus can be carried out with subdural or depth EEG recordings, but also with foramen ovale electrode recordings [26]. This technique is less demanding, minimally invasive, and less expensive compared with subdural or depth EEG recordings, but also provides an effective way to assess lateralization of the seizure focus in MTLE patients [68].

Patients hope to gain seizure remission by surgical intervention. However, for some patients, surgery might not be effective or even worsen the situation (Engel class III or IV [58, 69]). Reasons could be a wrong localization or an incomplete resection of the epileptogenic zone. In both cases, reoperation may be beneficial for the patient [70]. In rare cases, patients might possess an occult epileptogenic area with a higher threshold for seizure activity that is activated after the resection of the primary epileptogenic region [69]. Hidden bitemporal onset zones do not exhibit particular clinical semiology or preoperative discordant information and are therefore not seen on initial diagnostic studies. Those patients are not eligible for a second surgical resection, but neurostimulation might be an option [70]. In the event of surgical failure, patients should be reexamined to determine the cause of failure and to clarify further options [71]. While multiple seizures within the first postsurgical year are in general associated with a poor long-term prognosis [72], it should be noted that some patients with persistent seizures after surgery may achieve long-term remission without changes in ASM or further surgical intervention (so called running-down phenomenon [29, 73]).

In a prospective longitudinal cohort follow-up study over a period of up to 18 years, the risk of recurrences for surgical MTLE-HS patients was 22% in the first 24 months, followed by a further 1.4% annually [74]. This finding depicts a dualistic dynamic of acquired epilepsy and demonstrates that MTLE-HS patients, in addition to surgical failures, remain at significant risk for seizure recurrence after surgical intervention, even if they have been seizure-free for more than 5 years [29, 75]. Hence, the overall outcome evaluation is also a factor of time [57, 74, 75, 76]. In the aforementioned study, 62% of MTLE-HS patients remained completely seizure-free 18 years after surgery [74], and in another 26-year follow-up study, 57% of patients with temporal resection remained seizure-free during the observation period [76]. Importantly, epilepsy and in particular acquired MTLE is a network disease, where the process of epileptogenesis turns the neural network into a pathological condition. Those alterations go beyond the epileptic focus [77, 78], and the brain remains prone to pathological synchronization. Accordingly, late recurrences often behave like new-onset epilepsy [72]. However, a second focus is not common in humans and late recurrences usually do not presage the return of frequent uncontrolled seizures, but are rather rare events in most patients. Half of the patients with recurrences who are seizure-free initially (for at least one year after surgery) have one or fewer seizures per year [79] and half of the patients with late recurrences (being seizure-free for at least five years after surgery) subsequently enter remission [75]. Importantly, a change in ASM might result in seizure occurrence [80, 81, 82, 83, 84] and tapering or omission of ASM could cause postsurgical seizures [29]. MTLE-HS is special in the sense that surgery might turn a DRE in a drug-controlled one [85]. Hence, precaution should be taken in the reduction or a switch of ASM and drug discontinuation should not be done directly after surgery. On the other hand, continous use of ASM does not prevent seizure recurrences [77, 80, 86] and vice versa discontinuation of medication after one [87] or two years [88] is not associated with an increased relapse rate. Furthermore, most patients who experience seizures after drug-discontinuation become seizure-free with continued medication [83]. Taking together, ASM should be continued after surgery, but there is no favorable time to eventually start tapering or finally withdraw ASM [89]. The decision to stay with, reduce or discontinue ASM depends, at least in part, on patient preference [75], but patients should be fully informed of the steps taken and well monitored and counseled [90]. Notably, seizure freedom is the main factor for a positive assessment of the quality of life (QoL) [91, 92, 93, 94, 95] and by far the most important predictor for improvement in QoL after surgery [96], whereas continued medication is unrelated to this dimension [97].

In developing countries, epilepsy surgery offers the opportunity to reduce stigma and improve QoL [92, 97, 98, 99, 100, 101, 102], also with a positive impact on patients with low resources and precarious social circumstances [103]. Sustained and meaningful improvements in QoL, as patients hope for from surgical interventions, are mainly achieved within the first two years after surgery [91, 97]. Unfortunately, half of the relapses also occur during this period. Therefore, in addition to direct postoperative care, patients should receive appropriate counseling during this two years after surgery, if possible (pillar III, Fig. 1).

Although there is generally a marked improvement in QoL after epilepsy surgery, this is of course not a guaranteed effect. To achieve meaningful improvement in QoL from a patient’s perspective, the patient must acknowledge a change as important for his or her life. In this way, QoL is a useful method to assess patient’s satisfaction with the treatment [97], but the assessment of QoL is highly dependent on the focused dimension [96]. Seizure freedom is just one dimension, another are comorbidities that can exacerbate the burden of epilepsy and may need to be treated in parallel. In developing countries, parasitic and infectious diseases are the most common comorbidities [104]. Neurocysticercosis for example is the major cause of acquired epilepsy in tropical low-income countries [105]. However, psychiatric comorbidities are also a common phenomenon in refractory focal epilepsy (e.g., 40% of patients [106]), especially depression and anxiety disorders [107]. For example, in an epidemiological survey in Canadian communities [108], these two disorders were found in 30% of epilepsy patients, and comparable or higher rates are assumed in LMIC [104]. It is thus beneficial if possible to include a psychiatrist in the assessment team [109], and psychiatric disorders as well as other comorbidities should be evaluated as part of the presurgical diagnostic process whenever possible [110]. Patients hope to gain remission of disease burden through surgical epilepsy intervention, but patients who undergo surgical resection are prone to psychiatric disorders in the postsurgical period, either as an exacerbation of a known psychiatric diagnosis or the development of a new disorder. These postsurgical psychiatric disorders can significantly affect the QoL and overshadow a positive outcome of surgical seizure treatment [92, 111]. Surgical intervention may also have a positive impact on existing depression and anxiety in some cases [112], but unrealistic expectations have a negative impact on patient’s QoL rating [96]. It should be recognized that surgical intervention is intended to relieve or reduce seizures and not to treat possible comorbidities, which may persist afterwards and should be treated separately. Patients should develop realistic expectations in order to adequately assess the benefits of surgery, and thus it is particularly important to appropriately explain outcome perspectives to patients and their families. Although seizure freedom is the patient’s primary concern and an important predictor of improvement in QoL, a reduction in seizure frequency could already be judged positively. It is worth to mention that although patient selection is a decisive factor for the final success in terms of seizure-free rates, a medical project does not aim to achieve optimal statistic performance, but to help patients in the best possible way by balancing outcome perspectives with risk factors and patient expectations. In the end, surgery is beneficial for the vast majority of drug-resistant MTLE patients [91] and it is generally associated with an improvement in QoL that then lasts for decades [76, 96].

Presurgical evaluation and epilepsy surgery requires training and experience that is unlikely to be present in developing countries [15, 45]. For a sustainable approach, well-trained people are essential to train future specialists on site [19]. Thus, if a surgical epilepsy program should have a lasting impact, in addition to building on locally available technology, training of local professionals is critical, and the project has to create appropriate educational opportunities [23]. This could include visits by established experts to local facilities, accompanied by local training units [26], to provide knowledge transfer, advice and consultation. It is a valuable tool to initiate direct partnerships between individual professionals and to carry out profession-specific training and knowledge transfer. On the other hand, local workshops, joined internships and training sessions in larger groups are fruitful to disseminate knowledge and initiate team building. Both parts can be integrated into focused events, depending on the availability of resources and opportunities. In the end, the surgical decision-making involves a multidisciplinary team, making team building an important element [20, 58]. When it comes to the surgical intervention itself, a tandem approach has proven effective, with the experienced surgeon initially acting as primary surgeon to advise the local surgical team and care for the establishment of appropriate routines, followed by the newly introduced neurosurgeon who then performs surgery under the supervision of the experienced colleague [15, 21, 26, 58, 113].

In general, time abroad can be spent in a single block (e.g., Boling W, et al.[15]) or in multiple units (e.g., Dugladze, et al. [26]), but time is a valuable resource, in particular for clinicians beneficially participating in a mentoring program. Hence, the essential time for a stay abroad should be carefully considered. Notably, many activities can be planned and implemented through volunteerism, but financial support, e.g., from governmental programs or developmental aid, is needed at least to cover travel expenses. It is also helpful that information technology can link the center in a LMIC with the partner organization’s experts, e.g., for data analysis, treatment recommendations, and patient selection [15, 114]. This is well in line with the increasing global trend, fostered by pandemic situation such as a Covid-19 crisis, to take advantage of videoconferencing, electronic communications, and virtual case conferencing. Data transmission is ubiquitous nowadays, it can be exploited for mentoring or even be established as an independent building block [114]. Electronic communication allows experienced colleagues to participate remotely in joined case conferences, discuss diagnostic findings, or advise on the management of ASM [15, 26, 114, 115]. Initial personal contact is highly valued in the introductory phase and in initiating tandem partnerships, but workflows in presurgical diagnostics and postsurgical care (pillar I and III in Fig. 1) could also be organized via electronic communication channels. However, from our own experience, internships, joined local case conferences and workshops are generally appreciated [26]. Regardless of the choice of building blocks, the appropriate workflow must be organized in interdisciplinary cooperation.

The integration of various building blocks is one side, the stepwise approach from a basic routine to more challenging scenarios the other (Fig. 1). Proper selection of appropriate diagnostics and their accurate interpretation at each stage is required to ensure the balance between outcome perspective and risk factors [110]. This path must be followed according to local constraints in terms of available technology, increasing expertise, patient needs, and economic constraints. The evolution of a center from a stepwise perspective does not imply continuous improvement in surgical outcomes, as basic surgical epilepsy centers achieve comparable outcomes to well-established ones [9, 21, 22, 24, 45, 48, 116, 117]. Rather, the evolution implies the types of patients that can be treated and the different procedures that have been performed over the years [19]. Experienced and well-established centers can usually offer a broad range of diagnostic and interventional tools, whereas newly established centers should initially defer more difficult-to-treat patients to a later date as experiences develops, or refer them to a better equipped and/or more qualified surgical epilepsy center [20]. Such an evolution is nicely illustrated in a recent report from the neurosurgical center in Semarang, Indonesia [58]. The surgical program started with MTLE patients with seizure-related lesion, under the direction of mentoring universities from Japan, but invasive recordings and surgery in patients without MRI confirmed lesions were initially unfeasible. Subsequently, the spectrum was expanded with the introduction of subdural electrode recordings, long-term EEG and PET examination for difficult cases. Selective amygdalohippocampectomy and the treatment of extratemporal lobe epilepsy were introduced [58] and the center was enabled to perform surgery for radiologically normal appearing temporal lobe epilepsy patients [118]. The evolution of a center in this sense means that more and more complex investigative and surgical procedures are added [19, 116], while a major challenge for such a development often lies in the paucity or resources [32, 118].

A single epilepsy center may already have a large impact in small countries such as Georgia [26], but for large countries such as India or China, a multi-tiered system of epilepsy centers with different levels of expertise is advisable [16, 19, 32, 116]. At the most basic level, specially trained physicians would treat and care for patients with epilepsy according to standard protocols, simple centers could perform temporal lobectomy according to standardized protocols for diagnosis, assessment, and surgery, while comprehensive epilepsy surgery centers are needed for further diagnostics and more complex surgical scenarios. Partnerships with regional epilepsy centers are an appropriate means to improve local access to surgical care through specialized centers [119], and appropriate training of rural physicians or medical personnel is essential to identify referral candidates. For this reason, integration of all levels of epilepsy care is needed to close the surgical treatment gap in the long term [120]. It is noteworthy that even if epilepsy surgery already exists in an LMIC, surgical centers are most likely located in the major cities [9] and are not sufficient to cover all the needs [10, 116, 121, 122]. Thus, on the one hand, capacity building is an important issue, and on the other hand, there is a parallel need to raise awareness of surgical options in order to extend the impact to rural areas.

Teamwork is essential for the road to success [123] and it is crucial that all stakeholders, including patients and their families, are appropriately integrated [66]. At best, patients should receive comprehensive advice [124], and surgical epilepsy interventions should be introduced as a treatment option in the case of DRE right from the beginning of a newly diagnosed epilepsy [27, 39]. Patients who have achieved seizure freedom and/or experienced a meaningful improvement in their QoL through epilepsy surgery are the best advocates for a surgical program to publicize the effort. However, as pointed out by Sylaja & Radhakrishnan [20], one patient satisfied with the outcome of epilepsy surgery may inform five other epilepsy patients, but one dissatisfied patient will spread its adversity to 50 others. Realistic concepts are valuable tools for avoiding exaggerated or false expectations. Misconceptions and concerns are also found in HIC for both, physicians [28, 125, 126, 127, 128] and patients [28, 124, 129, 130], adding to the surgical treatment gap [44, 131] and making epilepsy surgery to one of the most underutilized interventions of all proven effective therapies [2, 27]. Cultural beliefs and local attitudes must also be taken into account [132]. People with epilepsy may suffer serious disadvantages due to misunderstanding or stigmatization, e.g., association of epilepsy with mental disease, insanity or as divine punishment [133, 134, 135, 136, 137, 138]. Stigma in the form of prevailing local beliefs associated with negative stereotypes may be quite resilient and might have a greater negative impact than the disease itself [139]. In addition, patients may have significant decision-making conflicts or fear of brain surgery [140], and rather than a promising therapeutic approach, it may still be viewed a last resort by professionals [40]. Therefore, to achieve a lasting impact, it is also important to work with the local public and professionals, educating and informing them about epilepsy and, in particular, about the possibilities and potential of surgical interventions [20]. Public relations can thus be a valuable tool for raising awareness and promoting acceptance of epilepsy surgery [26, 141], including one’s own project work, which can be developed to a separate building block.