Surgical Management of Epilepsy in Older Adults: Focus on Neurostimulation and Neuromodulation

Surgical management of drug-resistant epilepsy (ie, seizures that are not controlled by adequate trials of 2 antiseizure medications either in sequence or in combination) presents unique considerations and challenges in older compared with younger adults.¹ These are especially relevant to clinical practice given the global demographic trends toward an aging population.² Older adults are more likely to have chronic medical and psychiatric comorbidities, susceptibility to adverse effects from polypharmacy, medical frailty or functional disability, and cognitive dysfunction, which may affect operative and neuropsychological risks with resective surgery.^3-5 Recent advances in epilepsy surgery have favored the development of neurostimulation devices and minimally invasive, stereotactic, intraoperative imaging–guided, or robot-assisted techniques, which may pose a more favorable risk–benefit profile to conventional approaches both in general and for the older population in particular. Furthermore, the surgical risk profile for older adults has improved over the years, and older individuals are healthier than in the past and are expected to live longer.⁶ Although recent studies have proposed that older age should not be considered an outright contraindication to epilepsy surgery, general neurologists are less likely than epileptologists to refer older adults for surgical evaluation.^7,8

Within the population of older adults with epilepsy who present to an epilepsy center, it is important to distinguish between those with late-onset epilepsy presenting earlier in their disease course and those with epilepsy onset between childhood and young adulthood presenting later in their disease course, because the etiologic spectrum may differ widely. However, both groups may be amenable to surgical or neuromodulatory treatments.¹ Late-onset epilepsies are more often attributable to (or associated with) cerebrovascular disease, remote traumatic brain injury, brain tumors, autoimmune or antibody-mediated disease, or neurodegenerative conditions. On the other hand, long-standing epilepsy with delayed presentation is more likely to be caused by genetic mutations or malformations of cortical development. Whereas generalized epilepsies predominantly present at younger ages and the majority of adult-onset epilepsies are focal in localization, several cases of late-onset generalized epilepsy have been reported, and some individuals with generalized or multifocal epilepsies may only be referred for presurgical evaluation in adulthood.⁹

The goal of this review is to provide an overview of surgical management in older adults with drug-resistant epilepsy with a focus on neurostimulation and neuromodulatory approaches, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and brain-responsive neurostimulation (RNS). Recent advances in resective and ablative surgery, intracranial EEG monitoring, transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), and focused ultrasound (FUS) are discussed briefly. The use of neurostimulation devices and ablative procedures has increased considerably over the past decade, whereas traditional epilepsy surgery volumes have plateaued or declined, which highlights the importance of understanding the landscape of neuromodulation, as well as the benefits and limitations of individual approaches.¹⁰ For the purpose of this discussion, older adults are usually defined as age ≥65 years, but many studies on surgical epilepsy treatment used various age thresholds (eg, age ≥50 years or ≥60 years).^1,7,9

Resective and Ablative Epilepsy Surgery

Individuals with drug-resistant epilepsy in any age group must be referred to a comprehensive epilepsy center for consideration of a presurgical diagnostic evaluation to determine candidacy for resective or ablative epilepsy surgery.¹¹ Traditionally, epilepsy surgery has been prioritized for individuals age <30 years and pursued with reasonable caution for older individuals, in part due to the assumed likelihood of poor seizure outcome or unacceptable risk of complication. There are also concerns regarding secondary epileptogenesis or kindling among individuals with longer epilepsy duration, which could expand the epileptogenic zone beyond the initial focal region and confer a worse prognosis for epilepsy surgery.^12,13 However, several cohort studies have demonstrated comparable seizure and neuropsychological outcomes between older and younger adults, albeit with greater effects on individual cognitive domains in older adults, particularly after temporal resections in the language-dominant hemisphere.^14-24 As such, both the general neurologist and the epileptologist should consider more than an individual’s age when determining their candidacy for surgical epilepsy evaluation and treatments. It is important to consider both conventional resective approaches and minimally invasive ablative alternatives for older adults with a favorable preoperative risk profile given the potential for a successful outcome.

Resective Surgery

In a recent systematic review and meta-analysis, Vary O’Neal et al⁷ aggregated 11 case series and 14 cohort studies reporting the seizure outcomes following epilepsy surgery in older adults, including some studies that compared the outcomes between older and younger adults. This analysis found similar rates of seizure freedom among older (70.1% [95% CI, 65.3% to 74.7%]) and younger (70.4% [95% CI, 66.3% to 74.4%]) adults after resective surgery. However, older adults were more likely to experience complications (26.2% [95% CI, 21.3% to 31.7%] vs 9.1% [95% CI, 4.9% to 16.2%]), especially minor complications. This suggests that there is a comparable likelihood of meaningful benefit with resective surgery for older and younger adults if resection is reasonable for the individual’s epilepsy localization, but selecting the appropriate individuals based on other comorbidities is important to reduce the chance of complications. Limited resection procedures, such as selective amygdalohippocampectomy, can also be considered to reduce the likelihood of cognitive deficits.

Intracranial EEG Monitoring

When noninvasive diagnostics are either insufficient or conflicting in their localization of the epileptogenic zone, invasive EEG monitoring may be indicated to delineate the seizure onset zone more precisely and guide surgical management. There are 2 primary methods of intracranial monitoring: stereoencephalography (SEEG; depth electrodes inserted via burr holes) and subdural electrodes (SDE; grids and strips inserted via craniotomy). A hybrid of the 2 approaches is sometimes used, when appropriate. There is a trend toward increased use of SEEG relative to SDE with several potential contributors including increased adoption of robotic assistant platforms for stereotactic electrode implantation, fewer complications associated with SEEG, and an increased appreciation for the 3-dimensional epileptogenic network mapping afforded by SEEG.^25-27 In addition, SEEG provides the opportunity for targeted radiofrequency ablation (ie, radiofrequency thermocoagulation) of tissue surrounding SEEG contacts strongly implicated in the epileptogenic network.^28,29 Although this has a low likelihood of resulting in seizure freedom, transient reductions in seizure frequency may indicate a partial perturbation of the epileptogenic network that can be completed by a definitive resection.³⁰

Only one study has specifically addressed the safety of intracranial EEG monitoring in the older adult population.⁶ In a series of 21 individuals age ≥60 years from the Cleveland Clinic, 16 underwent SEEG and 5 underwent SDE. Two individuals experienced complications (1 individual receiving SDE developed aphasia and decreased responsiveness requiring emergent electrode explant, and 1 individual receiving SEEG died of intracranial hemorrhage). Because intracranial EEG evaluation is sometimes required to identify an optimal surgical plan, it should be considered in lower-risk older adults who are more likely to undergo epilepsy surgery to balance the procedural risks and benefits.

Ablative Surgery

Laser Interstitial Thermal Therapy and Stereotactic Radiosurgery. Ablative epilepsy surgeries are minimally invasive procedures performed either via a craniotomy or noninvasively by converging waves to create a focal, well-defined lesion using stereotaxis with or without intraoperative MRI guidance for navigation and lesion monitoring. Two procedures, laser interstitial thermal therapy (LITT) and stereotactic radiosurgery (SRS), are used in clinical practice and are discussed here, whereas emerging ablative FUS techniques are discussed separately along with neuromodulatory FUS techniques later in this review.

LITT is performed by inserting a laser guide via a craniotomy under intraoperative MRI guidance, followed by laser thermal ablation of tissue under MRI thermometry to monitor lesion size. This technique has been used most often to perform selective amygdalohippocampectomies for treatment of mesial temporal lobe epilepsy; however, it has also been used to treat nonlesional focal epilepsies, focal cortical dysplasias, tuberous sclerosis, and deeper lesions, such as hypothalamic hamartomas and periventricular nodular heterotopias, in addition to performing partial corpus callosotomies.³¹ In general, seizure freedom rates associated with LITT for mesial temporal lobe epilepsy are ~50%, making it a moderately effective treatment.^32,33 There is one small published case series comparing LITT (n=7) with selective anteromesial temporal resection (n=7) in individuals age >50 years with mesial temporal lobe epilepsy.³⁴ Seizure outcome data were available at 1 year of follow-up for 5 out of 7 individuals receiving LITT (4 of whom were seizure-free; the other experienced seizure reduction) and all 7 individuals receiving selective resection (all of whom were seizure-free); the difference was not statistically significant, but the study was likely underpowered for this analysis. This study was also able to find significant differences in operative time (shorter for LITT by ~1 hour on average), operating room and hospitalization charges (higher for LITT by $25,768 and $21,347, respectively), hospital length of stay (shorter for LITT by 1 day), and pain control requirements (lower for LITT by 16.7 mg of IV morphine equivalent per day). However, no significant changes in neuropsychological performance were seen in either group.

SRS is performed under stereotactic guidance by converging multiple beams of ionized radiation upon a target to attain sufficient energy intensity to ablate the tissue. It is a noninvasive technique that can nevertheless generate sufficient lesion size to yield similar seizure freedom rates (on average, 40% to 50%) to LITT for mesial temporal lobe epilepsy.^32,33 However, SRS involves exposure to radiation. Although there have been no specific studies published on the use of SRS in older adults, findings from the Radiosurgery Versus Open Surgery for Mesial Temporal Lobe Epilepsy (ROSE) trial (NCT00860145), which directly compared SRS with anterior temporal resection for treatment of mesial temporal lobe epilepsy, are noteworthy because the trial failed to establish the noninferiority of SRS (52% seizure freedom) vs resection (78% seizure freedom).³⁵

Minimally invasive ablative approaches are gaining interest in practice. Although these procedures produce smaller lesions and are generally associated with lower rates of seizure freedom compared with resective surgery, they may still be beneficial for reducing seizures and do not preclude subsequent resection in the case of treatment failure.³³ One limitation of these techniques compared with resection is the inability to obtain surgical pathology to confirm epilepsy etiology, which can be particularly important for suspected tumors or radiographically ambiguous lesions. Specific studies in older adults are needed.

Neurostimulation Devices

Individuals who are ineligible or reticent to undergo resective or ablative surgeries may still be considered for neurostimulation devices, which are the only neuromodulatory approaches approved by major regulatory agencies on the basis of randomized controlled clinical trials.³⁶ VNS, DBS, and RNS are approved for treatment of focal epilepsy in the United States, and VNS is also approved by the European Union for the treatment of generalized epilepsy; RNS is not approved outside the United States at this time, unlike VNS and DBS. Whereas the benchmark for success for epilepsy surgery is seizure freedom, the primary goal of neuromodulatory devices is to lessen the frequency or severity of seizures, with responders defined as having ≥50% reduction in seizure frequency. The lower expected likelihood of achieving seizure freedom with neuromodulation has led to these devices being described as palliative treatments, but additional benefits of these devices include shorter postoperative recovery time, mitigation of neuropsychological injury associated with resection or ablation, increase in expected response rate over time, favorable tolerability compared with antiseizure medications, and potential risk reduction for sudden unexpected death in epilepsy.^36-38 In addition, seizure frequency and severity correspond to opportunity and likelihood for injuries that could be sustained during seizures, which include head trauma, joint dislocations, and bone fractures, and their ensuing complications, which have the potential to significantly affect morbidity in older adults.³⁹

Neurostimulation devices can be classified according to several factors (Table 1), including implant location (intracranial vs extracranial), stimulation triggers (open-loop [cycling] vs closed-loop [responsive] vs manual [user-triggered]), and recording of relevant physiologic data (heart rate vs local field potentials vs electrocorticography). Each device has relative advantages and limitations for the older adult population, as summarized in Table 2.⁴⁰ Whereas comprehensive descriptions of each device can be found in recent reviews, this section describes the evidence base regarding the use and outcomes of these devices in the older adult population.^7,36,37

Vagus Nerve Stimulation

VNS targets the left vagus nerve to deliver cycling stimulation to the nucleus tractus solitarius to modulate noradrenergic activity in the locus coeruleus and other brainstem, limbic, and neocortical regions, and thereby reduce epileptiform activity and the propensity for seizures. Initially developed by Cyberonics (Houston, TX) and now manufactured by LivaNova (London, United Kingdom), VNS was designed to stimulate in an open-loop fashion, with current delivered at programmed intervals that can be interrupted or reset with a manual trigger by swiping a magnet over the generator in response to a seizure. Subsequently, a closed-loop stimulation paradigm was added on AspireSR (LivaNova, London, United Kingdom) and SenTiva (LivaNova, London, United Kingdom) to provide additional current in response to ictal tachycardia sensed by the device, and physicians can now program sequential setting changes to occur at set intervals to allow individuals to reach optimal settings sooner between clinic visits. Although largely used for focal epilepsy, VNS is also used off-label outside of the European Union for treatment of generalized or multifocal epilepsies in adults as well as children.

As the first neurostimulator approved for treatment of drug-resistant epilepsy, VNS has the largest body of literature reporting on outcomes in older adults compared with other neurostimulators. Sirven et al⁴¹ reported on the subgroup of older adults (defined as age ≥50 years) from the pivotal clinical trials⁴² that did not include individuals age >70 years. This cohort consisted of 45 individuals (37 who were age 50 to 59 years; 7 who were age 60 to 69 years; and 1 who was age ≥70 years) with at least 3 months of follow-up and 31 individuals with at least 1 year of follow-up implanted at 16 sites in the United States. Responder rates increased from 27% at 3 months to 67% at 1 year, but there were no seizure-free individuals among the cohort. There were no procedural complications, and reported adverse effects (the most frequent being vocal hoarseness in 58%, coughing in 36%, dysesthesias in 27%, paresthesias in 16%, and dyspnea in 9%) did not lead to discontinuing VNS. A second study by Chrastina et al⁴³ compared seizure outcomes between 11 individuals age ≥50 years (including 5 individuals age ≥60 years) and 92 individuals age <50 years, all implanted at a single epilepsy center in the Czech Republic. There were no statistically significant differences between responder rates among older adults (64%) and younger adults (52%) at 1 year of follow-up or at final follow-up (60% for older adults vs 66% for younger adults). This study also found that longer epilepsy duration was, somewhat paradoxically, associated with 7% increased odds of responding to VNS (odds ratio [OR], 1.07), which reached statistical significance after 1 year of follow-up, but this association did not remain statistically significant at final follow-up. A third study by Riestenberg et al⁴⁴ reported a cohort of individuals age ≤59 years (the authors did not report how many were age >50 years) and found that age at epilepsy onset ≥15 years, epilepsy duration ≥8 years, and left-hand dominance were significant predictors of VNS response, whereas age at implant ≥35 years was significant in univariate but not multivariate analysis.

Noninvasive applications of vagal neuromodulation, namely transcutaneous VNS targeting either the auricular branch or the cervical bundle of the vagus nerve, have also been proposed and studied for the treatment of drug-resistant epilepsy.^45,46 While transcutaneous VNS has not been specifically studied for treatment of epilepsy in older adults, it has garnered interest for treatment of memory, mood, and sleep dysfunction in neurodegenerative diseases in older adults due to its safety.⁴⁷ Similarly, trigeminal nerve stimulation has been evaluated for the treatment of epilepsy given its favorable tolerability, but its use in older adults has not been specifically studied.^48-50

Deep Brain Stimulation

DBS targets the anterior nucleus of the thalamus (ANT), which is connected to the hippocampus within the Papez circuit, for delivery of open-loop stimulation bilaterally to affect epileptogenic activity within the limbic network. This network is particularly relevant for epilepsies with onset from temporal and frontal regions, which were applicable to most individuals included in the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) trial (NCT00101933) and are of particular interest in older adults given the contribution of regional injury from neurodegenerative diseases, traumatic brain injury, and stroke to seizure risk. Although the Activa PC, Percept PC, and Percept RC devices manufactured by Medtronic (Minneapolis, MN) are approved specifically for targeting the ANT for treatment of drug-resistant epilepsy, DBS has been studied in other implant sites (eg, centromedian thalamic nucleus, hippocampus, nucleus accumbens, cerebellum), and other devices including Vercise (Boston Scientific, Marlborough, MA), Infinity (Abbott, Chicago, IL), and Liberta RC (Abbott, Chicago, IL) for other indications (movement disorders and psychiatric conditions) have been used off-label for the treatment of epilepsy.⁵¹ The newer Medtronic Percept device with SenSight directional leads has the capability to tailor the orientation of the stimulation field, similar to the functionality of DBS for movement disorders, as well as record thalamic local field potentials, and recent data suggest that these may serve as biomarkers of therapeutic response.^36,52

Although the SANTE trial included individuals from age 18 to 65 years and the European Medtronic Registry for Epilepsy (MORE; NCT01521754) included adults age ≥18 years, the maximum age included in both studies was not reported.^53,54 There have not been dedicated case reports or series of ANT-DBS in older adults; therefore, the safety and efficacy in this cohort have not been specifically demonstrated. However, there are specifics of DBS therapy that warrant discussion for the older adult population. Subjective worsening of mood disorders and memory difficulties were the most common adverse effects in the SANTE study, being reported in 15% and 13% of individuals in the active treatment group, respectively. However, objective measurements of mood and memory were found to be largely unaffected, except for some improvements in visuospatial recall, design fluency, executive function, and visual attention.⁵⁵ Medtronic DBS also provides the capability for individuals to switch between physician-set treatment settings, including switching their device to MRI mode, which may provide older adults with barriers to attending frequent clinic visits a degree of flexibility in managing their device.

Responsive Neurostimulation

Developed by NeuroPace, the RNS System (NeuroPace, Mountain View, CA) is designed to target 1 or 2 epileptogenic foci with 2 leads (may be a combination of subdural strip or intraparenchymal depth electrodes) that have the capability to monitor electrocorticography signals continuously, detect epileptic activity tailored to the individual’s ictal signature, deliver closed-loop stimulation in response to abnormal detections, and chronically record electrocorticography waveforms of interest for physician review. Patients and caregivers can also swipe a magnet over the device, analogous to the VNS system, in response to seizures or clinical episodes to save epochs of electrocorticography that may assist in tailoring detection settings but without manually triggering stimulation. These detections can clarify whether epileptic discharges in the implanted region are correlated with new episodic behaviors or symptoms, lateralize bilateral mesial temporal epilepsy, predict clinical response to antiseizure medications, and even potentially forecast the risk for impending seizures.³⁶ Whereas this approach was traditionally applied to mesial temporal or neocortical locations that were otherwise surgically unamenable, recent studies, including 2 clinical trials for idiopathic generalized epilepsy (RNS System NAUTILUS Study; NCT05147571) and Lennox-Gastaut syndrome (RNS System LGS Feasibility Study; NCT05339126), have begun to explore thalamic implantation and responsive stimulation.⁵⁶

The pivotal trial recruited individuals age 18 to 70 years, with the oldest participant age 66 years.⁵⁷ Although a secondary analysis was not performed to elucidate the safety and efficacy among the older adult population included within the clinical trials, a single-center retrospective cohort of older (≥50 years; n=11) and younger (<50 years; n=44) adults was reported by Zawar et al⁵⁸ and found statistically insignificant differences in responder (64% for older adults vs 52% for younger adults) and seizure freedom (27% for older adults vs 11.4% for younger adults) rates. Notably, despite comparable mean preimplant antiseizure medication numbers between the 2 groups, the mean number of antiseizure medications postimplant was lower in the older adult group. Adverse effects included implant site pain in 1 individual and dizziness in 1 individual, neither of which resulted in discontinuation of therapy.

Focused Ultrasound

Magnetic resonance–guided FUS is an emerging noninvasive technique that uses acoustic waves converged on a focus to either ablate brain tissue or modulate brain activity depending on the frequency and intensity of the waves.⁵⁹ High-intensity FUS (HIFU) uses thermal energy to create lesions, whereas low-intensity FUS (LIFU) uses nonthermal energy to modulate or transiently affect tissue activity. In addition, FUS has been investigated for modulating the blood–brain barrier to facilitate delivery of immunotherapy and chemotherapeutic treatments, particularly for the treatment of brain tumors.⁶⁰ The use of intraoperative imaging allows for both precise targeting of deep lesions and, in addition to other recent advances in FUS platforms, mitigating the need for a craniotomy.^59,60

Although preclinical animal studies dating back to the 1960s have shown antiseizure effects of ultrasound therapy, the clinical implementation of FUS remains in its infancy in the field of epilepsy despite successes in treating other neuropsychiatric conditions and tumors.⁵⁹ This is due in part to a concern regarding the balance between HIFU lesion size and thermal injury to surrounding tissue, with larger lesions (or longer duration of sonication) being potentially more effective for ablating the epileptogenic zone and controlling seizures (akin to standard temporal lobectomy) but also more likely to cause unwanted heating to nearby normal tissue.⁶¹ This has been circumvented in some ways by applying HIFU to small, well-defined targets more likely to lead to a good seizure outcome. Partly inspired by the use of HIFU as an alternative to DBS in the treatment of Parkinson disease and essential tremor, a phase 1 open-label trial of unilateral anterior thalamotomy for focal epilepsy was performed (A Pilot Study: Focused Ultrasound Thalamotomy for the Prevention of Secondary Generalization in Focal Onset Epilepsy; NCT03417297), which included 2 individuals, 1 of whom was age 57 with temporal lobe epilepsy related to a cavernous malformation who remained seizure-free for 1 year after the procedure.⁶² Two case reports from Japan described younger adults who also remained seizure-free during the 1-year follow-up period after multiple sonication sessions to ablate either the hippocampus to treat mesial temporal lobe epilepsy or a hypothalamic hamartoma to treat gelastic epilepsy.^63,64 Thus far, there have been no reports of HIFU for targeting small developmental malformations (cortical dysplasias or heterotopias) or SEEG-confirmed seizure onset zones, which may be future directions for clinical investigation.

With regard to LIFU, several studies have demonstrated the safety of lower-intensity sonication of the mesial temporal and neocortical structures.⁶⁵ Stern et al⁶⁶ performed serial low-intensity sonications of the mesial temporal region followed by poststimulation MRI and neuropsychological testing in 8 adults (including 1 individual age 65 years) with drug-resistant mesial temporal lobe epilepsy just before scheduled anteromesial temporal resection, which allowed for confirmation of safety using MRI, cognitive performance, and histology. In another pilot study of 6 younger adults, LIFU was performed during SEEG monitoring, which demonstrated lack of cortical edema on poststimulation MRI, changes in interictal discharge frequency in all individuals (decreased in 4, increased in 2), changes in seizure frequency in 3 individuals (decreased in 2, increased in 1 due to subclinical seizures), and absence of tissue damage on histologic sections in 1 individual who underwent focal corticectomy.⁶⁷ Thus far, no clinical studies have evaluated the effectiveness of repeated LIFU sessions for modulating the epileptogenic network and affecting seizure frequency beyond the acute phase.

FUS has potential to be a safer, less invasive alternative to conventional surgery (even LITT) or implanted devices for older adults due to the lack of craniotomy and the possibility to repeat sonication to expand ablation volume or replicate neuromodulatory effects. One interesting conceivable workflow for FUS in epilepsy is to perform LIFU to confirm the target, probe the epileptogenic network, and assess therapeutic response before performing HIFU, somewhat analogous to the use of radiofrequency ablation during SEEG monitoring to assess for a modification of seizure frequency before proceeding with a larger definitive resection. However, this prospect for both HIFU and LIFU is investigational, and more clinical studies are needed.

Transcranial Electrical and Magnetic Stimulation

TES, including transcranial direct current stimulation (tDCS), and repetitive TMS (rTMS) have been used for many years in basic and cognitive neuroscience research to modulate regional neuronal activity by inducing transient hyper- or hypoexcitability depending on the stimulation parameters.⁶⁸ tDCS consists of a battery that generates weak electrical currents between 2 electrodes, an anode and a cathode applied to the scalp, inducing subjacent changes in neuronal membranes and altering firing potential. rTMS is performed using a magnetic coil that delivers repeated magnetic pulses over a brain region to modulate regional electrical activity. Both techniques have been found to induce changes beyond the duration of therapy with a favorable safety profile demonstrated in both healthy controls and participants with epilepsy, raising the potential for noninvasive neuromodulation.^69,70

tDCS and rTMS have been posited as potential treatments for epilepsy but have not yet entered the standard clinical armamentarium. Recent systematic reviews of tDCS and TMS interventions suggested improvements in seizure frequency (3.2 fewer seizures per month with tDCS, 30% reduction in seizure frequency with rTMS), but there was considerable heterogeneity in stimulation parameters and outcome reporting that limits confidence in these findings.^71,72 These interventions included some older adults (age 50 to 75 years), but no specific study has been performed to assess the utility of TES or TMS in the management of older adults with drug-resistant epilepsy. In addition, TES and TMS are unable to induce effective changes in deeper regions, so these approaches may be best suited for targeting superficial cortical epileptogenic regions.⁷³

Conclusions

The mainstays of epilepsy management for both younger and older adults are as follows:

• Prioritizing accurate, prompt diagnosis using video EEG monitoring if needed to detect interictal epileptiform discharges or characterize events as epileptic or nonepileptic
• Identifying the etiology, most often with history, neurologic examination, and neuroimaging; lumbar puncture may be indicated to evaluate for infectious, inflammatory, or autoimmune causes
• Personalizing antiseizure medication treatment with regard to comorbidities and potential drug–drug interactions, following the general guidance to “start low and go slow” in terms of dose titration
• Recognizing when referral to a comprehensive epilepsy center is necessary for multidisciplinary evaluation and management of drug-resistant epilepsy and its psychosocial consequences
• Engaging in collaborative decision-making with individuals with drug-resistant epilepsy (or proxies if decision-making capacity is impaired) to review all reasonable surgical, ablative, and neuromodulatory options and enable an informed decision

Emerging trends in epilepsy surgery favor minimally invasive and neuromodulatory treatments, which pose certain advantages for older adults with epilepsy. However, recent studies on the safety and effectiveness of epilepsy surgery and intracranial EEG monitoring in this population suggest that age should not be the sole deterrent to planning and offering resection. Across all interventions, more prospective and controlled studies are needed to better establish the ideal surgical candidate among the population of older adults with drug-resistant epilepsy and develop predictive tools to estimate likelihood of a favorable surgical outcome.