Ortiz-Guerrero, Gloria

Abstract Objective Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an effective therapy for frontotemporal and limbic drug‐resistant focal epilepsies. The pulvinar nucleus (PUL) is an emerging neuromodulation target for seizure networks involving the posterior quadrant and temporal lobe. This study evaluates the safety and effectiveness of combined bilateral ANT plus PUL DBS for posterior quadrant and temporal lobe epilepsies. Methods We conducted a single‐center retrospective cohort study of patients receiving combined ANT/PUL DBS between 2021 and 2025. Outcomes included median seizure rate reduction (MSR), responder rate (RR; >50% seizure frequency reduction), and stimulation‐related side effects, assessed across ANT, PUL, and concurrent ANT/PUL stimulation settings. Acute surgical complications were evaluated. Statistical significance was assessed using two‐sided Wilcoxon signed‐rank tests with Holm–Bonferroni correction. Results Nine patients with combined ANT/PUL DBS were identified, and eight patients had sufficient follow‐up for inclusion (median follow‐up = 20 months). Posterior predominant structural abnormalities were present in eight of nine patients. There were no acute surgical complications. Three instances of transient stimulation‐related side effects resolved with parameter adjustments, whereas one patient required rescue antiseizure medication in addition to programming changes. Eight patients received periods of ANT stimulation, six PUL stimulation, and seven combined ANT/PUL stimulation. Regarding overall outcome, at last follow‐up, there was a significant 80.8% MSR ( p = .0078) and 87.5% RR, with two patients receiving ANT and six ANT/PUL stimulation. Regarding target‐specific MSR, concurrent ANT/PUL DBS (68.8% MSR) showed a trend toward superior performance relative to ANT (43.3%) and PUL DBS (17.5%) alone, although subgroup analysis of target‐specific performance did not reach statistical significance. Significance Combined four‐lead ANT/PUL DBS appears safe and effective for patients with drug‐resistant posterior quadrant and temporal lobe epilepsies. Dual‐network neuromodulation may provide greater flexibility to individually optimize neuromodulation for complex seizure networks.

Abstract High‐titer glutamic acid decarboxylase 65 (GAD65) antibodies (>20 nmol/L) are linked to chronic focal epilepsy, usually of temporal regional onset. Identification of these antibodies has treatment and prognostic implications. We compared patients with drug‐resistant epilepsy and high‐titer GAD65 antibodies to an age‐ and sex‐matched control group with drug‐resistant GAD65 antibody–negative temporal lobe epilepsy. From 1432 patients presented at a single‐center surgical epilepsy conference (2007–2024), we identified 15 patients (1% from surgical epilepsy conference: 13 female, 86.7%) with high‐titer serum GAD65 antibodies (median serum titer = 960 nmol/L; range 34–4678). The median age at epilepsy onset was 25 years (range 4–44). All had temporal regional‐onset epilepsy; 53% had bitemporal seizures. Three patients had limbic encephalitis, and three developed mesial temporal sclerosis. Those with GAD65 antibody–associated epilepsy were more likely to have depression and/or anxiety and less likely to undergo resection after evaluation than those in the control group. Although seizure types, electroencephalography (EEG), imaging, and autoimmune history were not statistically significantly different from the control group, we found that musicogenic seizures, limbic encephalitis, and type 1 diabetes occurred only in GAD65‐positive patients. These features, when present, may suggest an autoimmune etiology and warrant antibody testing. Identifying patients with GAD65 antibody–associated epilepsy is important due to its drug resistance, lower rate of satisfactory surgical outcomes, and potential responsiveness to immunotherapy. Further research is needed to define the optimal treatment and distinguish this subgroup from other causes of drug‐resistant epilepsy.

While hormonal changes have been recognised to influence seizure control and have been studied in association with menstrual cycles and pregnancy, there is a paucity of data on the menopause transition in epilepsy. Given the known effects of sex steroid hormones on neuronal excitability, their endogenous fluctuations during perimenopause, as well as menopause hormone treatments, may alter seizure control. Epilepsy may also be associated with premature ovarian insufficiency and early menopause. This is especially important for epilepsy-related comorbidities, for which menopause can constitute a second hit, such as osteoporosis. Additional considerations for females with epilepsy across the menopause continuum include changes in antiseizure medication clearance and potential interactions with menopausal hormone therapy or other concomitant medications. This comprehensive review summarises the currently available literature on epilepsy and menopause, highlights gaps in knowledge, and underscores the need for research efforts, particularly longitudinal studies investigating the menopause transition.

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Summary: The lack of reliable seizure detection remains a significant challenge for epilepsy care. A clinical deep brain stimulation (DBS) system provides constrained ambulatory brain recordings; however, limited data exist on the use of DBS recordings for seizure detection and lateralization. We present the case of an 18-year-old patient with drug-resistant focal epilepsy, who had seizure detection and lateralization by DBS recordings. Prior stereotactic-EEG, including a thalamus lead, identified independent left orbitofrontal and mesial temporal onset seizures. Notably, low-frequency thalamic ictal power was significantly elevated relative to baseline awake and sleep states. The patient was subsequently implanted with an anterior nucleus of the thalamus DBS system. Postimplantation, low-frequency power-in-band (5.3–10.3 Hz) recordings were initiated. Nursing staff identified four typical clinical seizures during the inpatient DBS recording period. Thalamic DBS trends contained relative peaks that were coincident with each nurse-reported seizure. Peri-ictal power was uniformly maximal ipsilateral to the seizure network. This case demonstrates the feasibility of seizure detection and lateralization by a thalamic DBS system for some individuals, and suggests DBS sensing parameter selection may be guided by thalamic stereotactic EEG. Further research is necessary to assess the generalizability of DBS seizure detection across individuals and diverse seizure networks.

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