Iron single-atom nanozyme-mediated laser interstitial thermal therapy and anti-inflammatory effect for epilepsy.

Purpose Positive behaviour support (PBS) is a specialised behavioural intervention framework which adopts a functional approach to self-injurious behaviour and focuses on skill-building. While there is a wealth of scientific literature supporting PBS, much of this research is focused on younger children and those who are vocal. This paper aims to apply PBS to teach communication skills to an adolescent with complex needs. Design/methodology/approach In this study, the authors report on an autistic adolescent with a seizure disorder and partial visual impairment who emitted high rates of self-injurious behaviour. Specifically, the authors tested the impact of teaching contextually appropriate signs across a variety of situations. Findings The teaching procedures were effective in that there were observed increases in communicative requests across contexts and a decrease in self-injurious behaviour. Originality/value The authors discuss the application of PBS to directly target the quality-of-life of individuals with complex needs through greater access to the community due to the reduction of self-injurious behaviour, more participation in outings with caregivers and increased autonomy by requesting for one’s needs and wants.

Spreading depression is a neurophysiological phenomenon that isobserved in the central nervous system of many species, from insects to humans. In essence, spreading depression is a slowly propagating wave of mass depolarization (that is, spreading depolarization), aptly termed a 'brain tsunami', which successively engulfs contiguous brain regions, causing transient neuronal hyperexcitability at its leading edge, followed by complete but reversible neuronal silence lasting minutes. This wave cannot be detected in routine scalp EEG recordings, which contributes to its under-recognized status as a disease biomarker. Here, we present an evidence-based view of spreading depression as a probable cause of characteristic neurological signs and symptoms in numerous neurological conditions. Although migraine aura is a widely recognized manifestation of spreading depression, the clinical signs and symptoms of spreading depressions arising from structural brain pathology have remained an orphan concept with no established name or place in clinical terminology. Therefore, clinicians have long used the term 'migraine aura' to describe the transient neurological manifestations of spreading depression that occur entirely outside of the context of a migraine attack. As migraine is a primary headache disorder not caused by known structural pathology, this terminology is not only erroneous but could also lead to serious misdiagnoses. Consequently, we advocate for the clinical adoption of the more specific mechanistic term spreading depression to describe these clinical episodes. We believe it is imperative to recognize spreading depression as a generic mechanism underlying certain inherited or acquired neurological deficits and to differentiate between structural and non-structural aetiologies, as is done in seizure disorders.

Seizure disorders are a significant public health concern, affecting millions of people worldwide. Despite their prevalence, seizure disorders remain shrouded in stigma and misinformation, leading to social and economic exclusion of affected individuals. This study aimed to investigate the awareness and attitude towards seizure disorders among university students in Nigeria. This study adopted a cross-sectional design. A quantitative research design was employed, with a questionnaire administered to 356 respondents. The results showed a significant lack of awareness about seizure disorders, with only 14.6% of respondents knowing someone with a seizure disorder. Most respondents (95.5%) were unsure what to do if someone experienced a seizure. However, the majority of respondents (83.2%) believed that education about seizure disorders can reduce stigma. The study also revealed a positive attitude towards seizure disorders, with 69.7% of respondents believing that people with seizure disorders should have the same opportunities as others. This study highlights the need for increased awareness and education about seizure disorders among university students and building on the positive attitude towards seizure disorders to promote inclusivity and equality. Education about seizure disorders should be incorporated into school curricula, raising awareness through campaigns, and promoting inclusivity and equality for individuals with seizure disorders.

It is well known that bipolar disorder (BD) and epilepsy (EP) are common neurological diseases. The objective of this study was to screen for potential biomarkers applicable to the diagnosis of EP and BD. The gene expression profiles from both the BD and EP datasets were sourced from the Gene Expression Omnibus database. To pinpoint the core shared genes, we conducted differential expression analysis as well as weighted gene co-expression network analysis. Additionally, we leveraged protein–protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment to uncover the pathogenic genes of BD and EP, as well as their underlying mechanisms. Using least absolute shrinkage and selection operator regression, support vector machine–recursive feature elimination, and random forest, hub genes were determined via rigorous examination. Subsequently, predictive nomograms and receiver operating characteristic curves were crafted to forecast BD and EP. A single-gene set enrichment analysis was executed meticulously on every diagnostic gene, aiming to identify shared signaling pathways. To round things off, the cell-type identification by estimating relative subsets of RNA transcripts algorithm analysis explored immune cell infiltration within BD and EP samples. After analyzing the intersection of weighted gene co-expression network analysis significant module genes and the differentially expressed genes, we pinpointed 113 genes of interest. Our protein–protein interaction analysis revealed 3 pivotal modules, each harboring 14 genes, which are considered pivotal for diagnosing BD and EP. The machine learning models consistently highlighted 2 genes – Regulators of G-protein signaling 4 and gamma-aminobutyric acid type A receptor subunit alpha1 – as universal diagnostic biomarkers. Furthermore, the immune infiltration analysis disclosed that activated M2 macrophages and mast cells are integral players in the onset of BD and EP.

Seizure disorders, including epilepsy and febrile seizures, affect around 5% of all children in Western countries. Although these conditions may be associated with psychosocial challenges, their impact on school well-being remains unclear. We examined the association of childhood epilepsy and febrile seizures with school well-being. We conducted a register-based cohort study including children born in Denmark (2000-2014) who participated in the Danish National Well-being Survey (2015-2022) [a survey mandated by law in all public mainstream schools in Denmark]. Children with epilepsy and febrile seizures were matched (1:10) by age and sex to unaffected children. Children with epilepsy and febrile seizures were identified from hospital contacts and antiseizure medication use. Poor school well-being was defined using systematic survey data. Adjusted odds ratios (aORs) with 95% CIs were estimated using logistic regression. Among 770,988 eligible children, 6,862 (0.9%) had epilepsy and 30,851 (4.0%) had febrile seizures, matched to 68,620 and 308,510 unaffected peers, respectively. Among children with epilepsy, 7% of assessments in grades 0-3 indicated poor overall well-being versus 6% in matched peers (aOR, 1.12; 95% CI, 0.99-1.28). In grades 4-9, 10% versus 8% indicated poor well-being (aOR, 1.18; 95% CI, 1.10-1.27), and the association was strongest for academic well-being (aOR, 1.35; 95% CI, 1.27-1.43). Children with febrile seizures had odds of poor well-being similar to their matched peers. Childhood epilepsy was associated with marginally poorer school well-being, although more pronounced in later grades and academic domains, underscoring the need for educational and psychosocial support. Febrile seizures were not associated with poor well-being, providing reassurance for affected children and their families.

Ketogenic diet causes bone loss in growing and adult mice and reduces the skeletal response to exercise.

The impact of long-travel distances is unknown in grade 2 glioma (G2G) patients. Here, the onco-functional outcomes following awake surgery for IDH-mutated G2G were compared between loco-regional versus international patients. G2G patients who underwent awake connectome-guided surgery and followed ≥ 1 year postoperatively were selected, with comparison across loco-regional patients (group 1) and foreigners (group 2). This consecutive cohort comprised 284 patients (mean age: 37.4 ± 9.6 years) with seizures in 225 cases (79.2%) and a mean KPS score of 95.1 ± 6.3. The preoperative mean tumor volume was 56.1 ± 46.8cc. The postoperative mean KPS score was 94.1 ± 6.5, with 0.3% of persistent deterioration, and 214 patients resuming employment (88.8%). The mean EOR was 92.2 ± 8.3%, with a mean residual tumor volume of 5.9 ± 8.7cc. There were 162 astrocytomas (57%) and 122 oligodendrogliomas. The mean follow-up was 7.3 ± 3.9 years with a median OS > 19 years. Foreigners (n = 151) had more preoperative intractable epilepsy (p = 0.05) with a higher rate of left gliomas (p = 0.019) in insular/paralimbic location (p = 0.031), while loco-regional patients (n = 133) had more right gliomas in frontal location (p = 0.028). The EOR was similar in both groups, whereas foreigners had less supratotal resections (p = 0.034). The KPS score was better in international patients at 3 months postoperatively (p = 0.008) although there was no difference in RTW proportion and median OS (> 19 years in both groups). This original series demonstrates that, although international patients undergoing awake surgery for G2G may recover more quickly with less supramarginal resections, RTW rate and OS were similar. Traveling large distances is not associated with long-term onco-functional outcomes.

Background: Febrile seizures are the most common seizure disorder in early childhood and a frequent cause of paediatric emergency department visits. Fever height is often perceived as a key determinant of seizure risk, although evidence supporting this association remains inconsistent. To evaluate whether the height of fever at presentation is associated with the incidence or recurrence of febrile seizures in young children presenting to a paediatric emergency department. Methods: This was a single-centre descriptive observational audit conducted in a paediatric emergency unit over a one-month period. Children aged 11–48 months presenting with febrile seizures were included. Demographic data, seizure characteristics, maximum recorded body temperature, recurrence during the same illness episode, and management outcomes were collected. Mean fever temperatures between children with recurrent and non-recurrent seizures were compared using an independent t-test. Associations between categorical variables were analyzed using the Chi-square test. Results: Thirty children were included, with a mean age of 22.1 months; 73.3% were male. Typical febrile seizures accounted for 86.7% of cases. Recurrent seizures occurred in 36.7% of children. The mean fever temperature at presentation was 101.35°F. There was no statistically significant difference in fever height between children with recurrent and non-recurrent seizures (t=1.78, p=0.092). No significant association was observed between seizure type and gender. Most children were managed conservatively, with low rates of anticonvulsant use (13.3%) and hospital admission (13.3%). Caregiver counselling was provided in all cases. Conclusion: Fever height at presentation was not associated with seizure incidence or recurrence in children with febrile seizures. These findings support guideline-recommended conservative management and reinforce that absolute fever temperature alone should not influence clinical decision-making in uncomplicated febrile seizures.

Background: Febrile seizures are the most common seizure disorder in children, occurring in 2-5% of those aged 6 months to 5 years. Although usually benign, they cause significant parental anxiety. This study aimed to evaluate the association of iron deficiency anemia with febrile seizures in pediatric patients. Methods: A hospital-based prospective case-control study was conducted in the department of pediatrics, American international institute of medical sciences, Udaipur, from March 2023 to August 2024. A total of 100 children aged 6 months-5 years were enrolled, including 50 with febrile seizures (cases) and 50 age-matched febrile children without seizures (controls). Hematological parameters (Hb, MCV, MCH, MCHC, RDW and ferritin) and serum electrolytes (Na⁺, K⁺ and Ca²⁺) were measured. Results: The mean hemoglobin level was significantly lower in cases (9.18±1.86 g/dL) compared to controls (10.65±1.12 g/dL; p=0.001). Other red cell indices and ferritin were lower in cases but not statistically significant. Electrolyte levels were comparable in both groups. Hospitalization was required more frequently among cases (60%) than controls (8%; p<0.001). Complex seizures (62%) were more common than simple seizures (38%), and nearly half (46%) had recurrent episodes. Conclusions: The study demonstrates a significant association between low hemoglobin and febrile seizures, reinforcing IDA as an important, modifiable risk factor. Routine screening and correction of anemia in early childhood may reduce the incidence and recurrence of febrile seizures.

Background: Seizure disorders represent a significant proportion of paediatric neurological presentations, with febrile convulsions being the most common cause in children under five years of age. Understanding the clinical characteristics and etiological factors is essential for appropriate management and parental counselling. Aim of this study is to evaluate the etiological spectrum and clinical characteristics of febrile convulsions and epilepsy among paediatric patients presenting to a tertiary care center. Methods: A prospective observational study was conducted at Government Medical College Krishnagiri in Department of Paediatrics over one year. Paediatric patients presenting with seizures were consecutively enrolled. Comprehensive clinical evaluation, laboratory investigations, and neurological assessments were performed. Data were analyzed using appropriate statistical methods. Results: Among 209 seizure cases, 83 (39.7%) were febrile seizures with an overall incidence of 2.57%, while 126 (60.3%) were epileptic seizures with an incidence of 3.9%. Male predominance was observed in both groups (febrile seizures 62.65%, epilepsy 58.73%). Simple febrile seizures constituted 67.47% of cases, with upper respiratory tract infections being the leading cause (63.85%). In epilepsy cases, generalized seizures were most common (67.46%), with acute symptomatic causes accounting for 47.62% of cases. Mortality was observed in 12.70% of epilepsy cases, predominantly in the acute symptomatic group (73.33% of deaths). Conclusions: While febrile seizures are generally benign, they cause significant parental anxiety and require accurate clinical assessment. Epilepsy in the pediatric population shows higher prevalence in developing countries, with infectious etiologies playing a major role. Comprehensive evaluation and appropriate management strategies are essential for optimal outcomes.

A bstract A seizure disorder is one of the most common comorbid neurologic conditions that may be present in children. Providing perioperative care for these children may be required during elective, urgent, or emergent procedures unrelated to their primary seizure disorder or during surgical procedures aimed at lessening their seizure burden when pharmacologic therapy is ineffective. Regardless of the surgical procedure, perioperative care requires a staged approach with specific considerations during the preoperative evaluation, intraoperative care, and the postoperative period related to the primary seizure disorder or other associated comorbid conditions. This educational review outlines the perioperative care of infants and children with an underlying seizure disorder with a focus on preoperative preparation including perioperative dosing of anti-epileptic drugs, intraoperative care including the impact of commonly administered anesthetic agents on the seizure foci, choice of intraoperative medications and neuromuscular blocking agents, as well as a review of issues that may be encountered during postoperative care including strategies for pain management.

Rare pathogenic variants in many genes contribute to neurodevelopmental disorders (NDDs), including intellectual disability and/or global developmental delay (ID), autism spectrum disorder (ASD), epilepsy (EP), and cerebral palsy (CP). These conditions frequently co-occur and share genetic etiologies, yet the broader phenotypic effects and the extent of shared versus distinct genetic influences remain unclear. Here, we adopt a cross-disorder framework to examine NDD genes across four diagnostic categories, characterize gene-associated phenotypic profiles, and identify convergent pathways that help refine how pathogenic variants in these genes shapes clinical outcomes. Using a discovery cohort of 8,973 probands with disease-causing variants in 263 NDD genes, we performed phenotype-based gene clustering and identified six distinct gene clusters. These clusters reveal structured patterns of genetic overlap, showing that subsets of NDD genes preferentially contribute to specific disorder combinations of ID, ASD, EP, and CP. The largest gene cluster was characterized by ID, whereas the other five included one enriched for ASD and ID, two for EP and ID and two for CP and ID, each with significantly differing frequencies. In an independent validation cohort of 19,704 probands, five of the six clusters were replicated. Gene Ontology enrichment analyses revealed distinct biological processes in each cluster, suggesting that coherent molecular mechanisms underlie the differing NDD diagnostic profiles. Together these findings demonstrate that NDD genes fall into coherent clusters that consistently map onto characteristic phenotype profiles, providing a framework to inform future therapeutic strategies and support early prognostication for individuals with pathogenic variants in NDD genes.

Introduction: Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and dose-dependent non-linear pharmacokinetics. Even minor changes in metabolism or protein binding may precipitate toxicity and neurological manifestations may mimic cerebellar or cerebrovascular disorders, creating diagnostic confusion. Case Presentation: A 26-year-old woman with a 15-year history of seizure disorder on phenytoin and levetiracetam presented with one week of progressive gait instability, bilateral lower limb weakness and impaired coordination. She had a history of posterior circulation stroke one month earlier. Neurological examination revealed reduced power in both lower limbs (3/5) and impaired finger–nose testing bilaterally. Laboratory investigations were largely unremarkable except for an elevated serum phenytoin level of 35 µg/mL (therapeutic range 10–20 µg/mL). Phenytoin was discontinued, and the patient was managed with levetiracetam, valproate, supportive care and monitoring, resulting in marked clinical improvement. Conclusion: Phenytoin toxicity should be suspected in patients on chronic therapy who develop new-onset cerebellar signs or neurological deterioration. Therapeutic drug monitoring and early drug withdrawal are crucial to prevent complications and avoid misdiagnosis.

Auditory areas on the superior temporal plane and lateral convexity are key initial stages of speech processing in the human cortex, representing acoustic and phonetic attributes in a temporally precise manner. More complex representations in auditory-related cortex along the ventral and dorsal processing streams and prefrontal cortex are associated with perception and action. In this study, we used intracranial electroencephalography (iEEG) to clarify where and how activity leading to perceptually driven behavioral events emerges. Participants were patients undergoing iEEG monitoring for medically intractable epilepsy. Stimuli were monosyllabic words, and participants pressed a button in response to a semantic target category. Significant high gamma activity after stimulus onset and immediately prior to motor response defined stimulus- and behavior-related activity patterns, respectively. The stimulus-related pattern was more common than behavior-related throughout the cortical auditory hierarchy as well as sensorimotor cortex. Behavior-related activity was sparsely represented, with the highest prevalence in the prefrontal cortex and a more limited representation in anterior temporal and parieto-occipital cortex. Hemispheric asymmetries included a higher prevalence of stimulus-related activity in the right sensorimotor cortex and a higher prevalence of the behavior-related pattern in the left prefrontal cortex. Faster behavioral responses were associated with greater stimulus-locked high gamma power in non-core auditory, prefrontal, and premotor cortex. Results reveal the cortical distribution of sensory stimulus-driven responses and activity time-locked to behavior and provide insights into neural substrates of speech perception.

SummaryBackgroundExisting Tuberculosis (TB) elimination strategies show limited impact, with suboptimal uptake of tuberculosis preventive treatment (TPT) and increasing TB incidence after the COVID-19 pandemic. Real-world evidence on reduction of tuberculosis in high-burden communities is needed to inform future TB elimination strategies.MethodsSince 2017, a comprehensive TB screening and TPT program known as Zero TB in Kids (ZTBK) was implemented in congregate settings of Tibetan communities in India. TB disease, TB infection (TBI), tuberculin skin test (TST) conversion, and TPT uptake were measured periodically.FindingsSchoolchildren and adults in 63 institutes (n = 20,068; 67,637 person-years) were screened. TPT was given to 3847 participants. TB incidence decreased 83% between 2017 [576 (95% CI: 455–718)/100,000] and 2024 [97 (47–179)/100,000]. TB infection (TBI) prevalence decreased 32% between 2017 [22% (95% CI: 21–23%)] and 2024 [15.5% (14–17%)]. TB incidence (640/100,000) and TBI prevalence (28%) were higher in the institutes that were never screened before under ZTBK. Among participants who did not receive TPT, TB disease prevalence decreased 84% between 2017 [910 (95% CI: 675–1204)/100,000] and 2024 [147 (48–343)/100,000], indicating a herd benefit. After one round of TB screening and TPT, between 2018 and 2019, TST conversion decreased 59% for children and 47% for adolescents. Risk of TBI was greater for males (aPR: 1.23; 95% CI: 1.16–1.30). TB risk was 82% lower for schoolchildren receiving TPT. Participants with seizure disorder [aPR: 0.31 (95% CI: 0.15–0.65)] and hepatitis B [0.71 (0.6–0.84)] were less likely to receive TPT.InterpretationSignificant reduction of TB transmission and burden can be achieved using the existing tools of TB control. Surveillance of TBI and TPT must be widely adopted for schools and congregate settings with high TB burden.Funding10.13039/100000002National Institutes of Health-10.13039/100000060National Institute of Allergy and Infectious Diseases (NIAID) (K01-AI148583), STOP TB Partnership (STBP/TBREACH/GSA/W7-7692), NIAID-Johns Hopkins Center for AIDS Research (90100777), Foundations, and Philanthropy.

Abstract Introduction Syncope is a common clinical problem[1] posing a diagnostic and therapeutic challenge, due to varied presentations and underlying pathologies[2]. Although an MDT approach is a recognised key component in patient care[3], there is no current guidance in the context of syncope. The Syncope Service in QEUH Glasgow is run by Geriatricians with a specialist interest in Syncope. A formalised monthly MDT, introduced in November 2017, involves Geriatricians, Cardiologists, a Neurologist and Cardiac Physiologists. Method A retrospective case note analysis undertaken for patients reviewed at the Syncope MDT (November 2017–March 2023), assessed the impact on diagnosis, further investigation and treatment initiation. Results 149 patients, with an average age of 65, were discussed at the MDT. The reasons for referral were cardiology specialist advice (62.4%), neurology specialist advice (19.5%) and multi-specialty case review (16.8%). Following discussion, cases of unexplained syncope decreased from 28.9% to 21%. The diagnosis of a cardiac rhythm abnormality increased from 11.4% to 19.5%, and a provisional diagnosis of a seizure disorder increased from 12.8% to a confirmed 14.8%, without the need for additional specialty clinic review. The MDT facilitated prompt access to investigations such as ILR (9.4%) and commencement of appropriate treatment such as anti-epileptic medication (6.6%) or PPM insertion (8.6%). Conclusion By leveraging the collective expertise of diverse healthcare professionals, the syncope MDT enhances diagnostic precision, facilitates comprehensive investigations and streamlines the patient journey.

Calcium (Ca2+) homeostasis is fundamental to neuronal physiology, including in the regulation of membrane excitability and synaptic transmission. Disruptions in the ion transporters regulating Ca2+ influx and efflux are clearly linked to seizure disorders and age-related neurodegenerative disease. Yet, the specific contributions of variants in genes encoding these transporters to neurological disease remain to be fully understood. Drosophila melanogaster has proven to be a powerful genetic model for uncovering such mechanisms, particularly through studies of mutants that display temperature-sensitive (TS) behavioral phenotypes.In a forward genetic screen, we identified a mutant line that exhibited TS convulsions along with progressive, age-dependent neurodegeneration. We mapped the mutation to Nckx30c, specifically within the transmembrane ion-binding region of this K+-dependent Na+/Ca2+ exchanger. Characterization of this mutant, together with a second Nckx30c allele, revealed TS convulsions, impaired locomotion, a markedly shortened lifespan, neurodegeneration with age, along with structural defects at larval and adult neuromuscular junctions (NMJs). Nckx30c mutants also displayed altered neural motor circuit performance. Gene expression analysis confirmed that Nckx30c levels were reduced in heads of Nckx30c loss-of-function mutants. Tissue-specific manipulation revealed that knockdown of Nckx30c in neurons recapitulated the TS convulsions, locomotor defects, and shortened lifespan phenotypes.Drosophila Nckx30c is highly conserved and shares homology with mammalian SLC24A2, a solute carrier family 24 member whose neurological role is not yet fully elucidated. Our work establishes Nckx30c as an essential regulator of neuronal health and provides an in vivo framework for investigating the contribution of SLC24A2 to neuronal Ca2+ homeostasis, seizures and age-related neurodegeneration.

Epilepsy surgery is an effective treatment option for patients with medically refractory epilepsy due to mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE). The success of surgery depends on the accurate localization of the epileptogenic zone, which can be challenging due to the subtle imaging features. The aim of this project was to provide an in-depth electro-clinical characterization of MOGHE in patients with medically intractable epilepsy, and to assess the role of stereo-electroencephalography (SEEG) in tailoring the resection and optimizing surgical outcome. This single-center retrospective study analyzes a cohort of patients with medically intractable focal epilepsy who underwent surgery and had confirmed MOGHE on pathology evaluation. Clinical data, including demographics, electroclinical features (scalp EEG and invasive monitoring when available), surgical interventions, and postoperative outcomes were extracted from electronic medical records. Of 23 patients identified, 10 (43%) underwent SEEG as part of their standard care. Seizure outcome data were available for 22 patients in this series. Median post-operative follow-up duration was 3.8 years. Fourteen patients (64%) were seizure-free (Engel 1). Seizure freedom in the SEEG group was 80% (n = 8/10), in comparison to the non-SEEG group (50%, n = 6/12). Success rate was related to complete resection of the regions sampled by SEEG electrodes involved in ictal onset, and a more extensive resection of the lesion (or near total lobectomy). Our results underscore the pivotal role of SEEG in enhancing surgical outcomes in patients with drug-resistant epilepsy due to MOGHE. SEEG proved particularly beneficial in defining resection margins, especially in cases where non-invasive data were discordant, scalp EEG patterns were generalized or poorly localized, and imaging findings were nonspecific, diffuse, or normal, making lesion identification challenging.

Evaluation of epilepsy in 8p-related disorders.