Temporal lobe epilepsy is of heterogeneous pathology. While many patients present with hippocampal sclerosis and ipsilateral mesiotemporal atrophy, a subgroup of patients without human-detectable sclerosis via structural MRI are characterized by ipsilateral amygdala enlargement and worse postsurgical outcomes. A bidirectional relationship between temporal lobe epilepsy and depression is well-established, with amygdala enlargement and neuroimmune alterations increasingly implicated as substrates for both. In this study, we interrogate the link between amygdala volume and psychiatric burden in temporal lobe epilepsy and evaluate gliosis as a possible substrate. We hypothesize that gliosis drives ipsilateral amygdala volume changes that underlie psychiatric burden in patients with no hippocampal sclerosis. To test these relationships, we analyzed two independent cross-sectional cohorts: (i) a Discovery cohort (43 patients, 80 controls) with structural MRI and robust psychiatric measures and (ii) a Mechanistic pilot cohort (10 patients, 9 controls) with both structural MRI and [18F]FEPPA PET/MR, an in vivo measure of gliosis, to conceptually replicate and extend findings from the Discovery cohort. Amygdala volumes were assessed with FreeSurfer. Psychiatric burden in the Discovery cohort was assessed with the Depressive Problems subscale from the Achenbach Adult Self-Report. Regional gliosis in the Mechanistic cohort was quantified using [18F]FEPPA PET, and an exploratory measure of psychiatric burden for this cohort was obtained via medical chart review. In the Discovery cohort, the group without hippocampal sclerosis showed significant ipsilateral enlargement of the whole amygdala, basolateral and central subnuclei compared to controls and the group with sclerosis and a group-dependent association between decreased amygdala volume and increased depressive symptoms. In the Mechanistic cohort, increased [18F]FEPPA binding was associated with reduced amygdala volume. Adjusting for this effect unmasked significant amygdala enlargement in the group without hippocampal sclerosis. Exploratory analysis revealed a possible central subnucleus-specific relationship between gliosis, volume and psychiatric burden in patients without sclerosis, such that amygdala volume was positively correlated with psychiatric burden specifically in patients with a greater degree of gliosis. These data associate amygdala volume alterations with psychiatric burden in patients without sclerosis and implicate gliosis as a potential mechanistic substrate. Findings support a conceptual shift towards understanding amygdala enlargement not as a static structural phenotype, but as a dynamic, glia-associated state that may confer risk for psychiatric illness. Consequently, patients without hippocampal sclerosis may derive a distinct dual benefit from therapeutic strategies targeted at underlying neuroimmune function.

Most antiseizure medicines act on a limited set of neuronal targets. Approximately a third of patients have treatment-resistant epilepsy, creating a need for mechanistically distinct drug targets. Human genetics can prioritise them, but epilepsy target-discovery has measured expression in plasma or bulk brain tissue and has yielded inconsistent candidate lists. Common-variant association for generalised epilepsy is enriched in neuronally expressed genes, so the cell type measured may determine which druggable targets are detectable. Genes at the genome-wide significant loci of the largest epilepsy meta-analysis were assessed by drug-target Mendelian randomisation (MR). A gene was retained only where the expression and disease signals colocalised on a single causal variant at a posterior probability above 0.8. Each gene was assessed across inhibitory neurons, excitatory neurons, four glial cell types, and bulk cortex, with fine-mapping and directional testing in FinnGen. Of the 23 prioritised genes screened, MR nominated ten and colocalisation retained 2. KCNIP2 colocalised with generalised epilepsy above the threshold in inhibitory neurons alone. Higher expression was associated with lower risk (posterior 0.95, odds ratio (OR) 0.64, and p = 2.5 × 10-11), with a weaker, directionally concordant sub-threshold signal in oligodendrocytes (posterior 0.53). The colocalising variant is shared with the neighbouring CUEDC2 (r 2 = 0.975), so the two genes cannot be separated on genetic evidence alone. In the bulk cortex, KCNIP2 carried a strong expression signal mapping to a different causal variant, with no colocalisation. AP3D1 colocalised across inhibitory neurons, excitatory neurons, and bulk cortex for generalised epilepsy and was associated with increased risk (OR 1.46). Both directions reproduced at the matched generalised-epilepsy endpoint in FinnGen, where KCNIP2 was protective and AP3D1 was risk-increasing. The colocalisation did not reproduce there, so FinnGen supports the direction of effect and not the shared-variant evidence. In epilepsy, the cellular compartment in which expression is measured can determine whether a drug-target signal is detected, so analyses restricted to plasma or bulk tissue may miss cell-type-restricted targets such as KCNIP2. The demonstration rests on this single locus. Cell-type-resolved colocalisation prioritises KCNIP2, which cannot be separated from CUEDC2, as a candidate for functional investigation, with AP3D1 being a genetically supported but pharmacologically intractable second locus.

Ischaemic stroke (IS) represents a leading cause of adult mortality and long-term disability globally, and post-stroke epilepsy (PSE) constitutes a severe complication that worsens neurological recovery and reduces quality of life, yet reliable early predictive biomarkers remain insufficient. The serum lactate-to-albumin ratio (LAR, mmol/g), an integrated indicator reflecting hypoxic-ischaemic stress, energy metabolic disturbance, and systemic inflammation, has emerged as a promising prognostic marker but has not been investigated for predicting PSE risk. This multicentre retrospective cohort study enrolled 21 459 acute IS patients from four centres to examine the association between admission LAR and 1-year PSE incidence. Multivariable logistic regression, restricted cubic spline (RCS) analysis, subgroup stratification, and sensitivity testing were applied for statistical evaluation. Overall, 936 patients (4.36%) developed PSE within one year. In the fully adjusted model, each 1-unit increment in LAR was associated with an odds ratio (OR) of 1.13 (95% CI: 1.04-1.22, P = 0.003) for PSE. Compared with the lowest LAR quartile (Q1), the highest quartile (Q4) conferred a markedly elevated risk (OR = 12.02, 95% CI: 7.91-18.90, P < 0.001), with a significant non-linear dose-response relationship and an inflection point at LAR = 0.06. The association was stronger in patients with atrial fibrillation or cortical stroke lesions, and sensitivity analyses confirmed result robustness. Taken together, these data indicate that serum LAR measured at admission behaves as an independent, non-linear correlate of PSE risk after acute IS. As a readily available biomarker derived from routine serum laboratory tests, LAR may serve as a promising candidate for early risk stratification in IS patients, although prospective studies are warranted to confirm its clinical utility.

In response to the recurring identification of medication-resistant idiopathic epilepsy (IE) in English Springer Spaniels (ESS), the objective of this retrospective questionnaire-based observational study was to delineate the phenotypic characteristics of IE in this breed in comparison to a cognate breed, the English Cocker Spaniel (ECS), employing a novel, validated, owner-completed multilingual online questionnaire. Owners of 49 ESS and ECS with seizures completed the questionnaire, of which 16 ESS and 14 ECS fulfilled the inclusion criteria and were subsequently included in the study cohort, while the remaining questionnaires were excluded due to incomplete or inconsistent information or because the criteria for IE were not fulfilled. At the time of the survey 43.3% of the dogs had died, including five that died in association with epilepsy. The median age at seizure onset was 2.5 years in ESS and ECS (range: 0,5-9 years; IQR 2.0-4.0 years). Notably a high proportion of dogs in both breeds had experienced ≥1 cluster seizure and ≥1 status epilepticus. In ECS a significantly higher rate of marked reduction in seizure severity following initiation of anti-seizure therapy compared to the ESS (p = 0.009) was observed. Both breeds exhibit a moderate to severe disease course, with ESS showing a comparatively poorer response to antiseizure drugs. Furthermore, 43.3% of dogs with suspected IE also had affected relatives. The owner-reported occurrence of IE in related dogs may suggest a potential hereditary component in both breeds.

This practice guideline from the American Epilepsy Society (AES) and the Congress of Neurological Surgeons (CNS) provides evidence-based recommendations for surgical treatment of epilepsy for adults and children. It is an update to previous practice parameters published by the Academy of Neurology in 2003. The multidisciplinary panel addressed resective procedures for mesial temporal epilepsy (MTLE), neocortical epilepsy, and resection/disconnection of hypothalamic hamartoma. It also examined evidence for callosotomy in developmental and epileptic encephalopathies. It did not intentionally address neurostimulation treatment. A comprehensive literature review was conducted using the Grading of Recommendations Assessment, Development and Education (GRADE) methodology, and GRADE was also used for decision-making. This guideline considers not only seizure outcomes but also other critical and important outcomes. Seizures, quality of life, mortality, adverse events, and verbal memory loss were considered critical outcomes, while other neuropsychological deficits besides verbal memory loss (ie, naming, fluency), neuropsychiatric, and social outcomes were considered important outcomes. Following the GRADE process, the following strong recommendation was made based on a moderate level of evidence: (1) anterior temporal lobectomy (ATL) is recommended for people with MTLE at low risk for cognitive decline. Due to very low to low certainty of evidence the panel suggested the following conditional recommendations: (1) ATL for people with MTLE at high risk for cognitive decline, (2) selective amygdalo-hippocampectomy (SAH) in MTLE, (3) laser interstitial thermal therapy (LITT) in MTLE, (4) neocortical resection in neocortical epilepsy, and (5) callosotomy in people with drop attacks, Lennox-Gastaut Syndrome (LGS) or developmental and epileptic encephalopathies. The panel recognized that conditional recommendations need to account for individual patient circumstances and mandate shared decision-making to ensure that decisions align with each person's values and preferences. For hypothalamic hamartoma, the panel strongly recommended LITT despite low levels of evidence due to a paradigmatic situation where open surgery has significant risks that outweigh the benefits. If LITT is not available, the panel suggested radiosurgery for hypothalamic hamartoma (conditional recommendation). The panel highlighted that every person with drug-resistant epilepsy should have access to a tertiary epilepsy care center that performs surgical procedures and advanced epilepsy diagnostics (good practice statement).

[This corrects the article DOI: 10.1016/j.ynirp.2025.100237.].

The International League Against Epilepsy (ILAE), working via a multidisciplinary task force, has issued a position paper with updated seizure classification guidelines (2025) replacing its previous guidance (2017), establishing a revised de-facto standard for clinical assessment and classification of epileptic seizures. The 2025 model simplifies the system, making it easier to adopt in different clinical settings while also clarifying the taxonomic rules, the definition of consciousness, and the application of phenomena-based descriptors. As a result, clinical practitioners, technologists, and medical software developers also face the challenge of adopting the new standard in their applications and workflows. To aid in the realization of this update in medical device software, this article presents a proposed numerical structure for ILAE 2025 edition of the seizure classification system as a definition of interacting bitfields, establishing an open reference implementation to support common storage and interoperability between software environments. Assigning each orthogonal concept to a single bit, we encode the core ontology and expanded descriptor set so that they fit into 32-bit and 128-bit unsigned integers, respectively. TypeScript, known for its expressiveness and practical applicability, is used as the implementation language for these definitions. Examples are provided to help implementers incorporate the proposed specification into their software, as well guidance for mapping from the ILAE 2017 type system to the updated ILAE 2025 type system. The reference specification, with test cases and examples, is maintained in a public code repository and available under a permissive license.

Brain-computer interfaces (BCIs) bypass peripheral nerves and muscles to establish direct information pathways between the brain and external devices, providing novel approaches for motor function reconstruction, communication assistance, and neurorehabilitation in patients with neurological disorders. However, conventional non-invasive BCIs relying on modalities such as electroencephalography (EEG), magnetoencephalography (MEG), or functional magnetic resonance imaging (fMRI) exhibit limitations in spatiotemporal resolution, portability, or real-time capability. Functional ultrasound (fUS), an emerging neuroimaging technology based on neurovascular coupling (NVC), detects cerebral blood volume changes at a spatial resolution of approximately 100 μm; its imaging frame interval is 200-500 ms, whereas its effective temporal resolution, limited by the hemodynamic response, is 1-2 s, offering a potential solution to overcome these constraints. This review comprehensively analyzed NVC-based fUS brain-computer interfaces from the dimensions of technical principles, clinical applications, future directions, and challenges. fUS has demonstrated significant clinical value in stroke assessment, epilepsy monitoring, and early identification of neurodegenerative diseases. Emerging technologies such as transcranial focused ultrasound neuromodulation, sonogenetics, and intravascular ultrasound are driving the evolution of fUS from single-signal "acquisition" toward bidirectional "acquisition-modulation" closed-loop systems, which remain at the proof-of-concept stage. However, the hemodynamic response latency relative to neural electrical activity (1-2 s), the yet-unclear biosafety of chronic ultrasound exposure, and insufficient decoding reliability under pathological conditions remain critical bottlenecks requiring urgent resolution. In conclusion, NVC-based fUS brain-computer interfaces provide a novel tool for precision diagnosis and treatment of neurological diseases. Future efforts should focus on conducting multicenter clinical trials and enhancing the robustness of decoding algorithms.