Long-term efficacy of subthalamic nucleus deep brain stimulation in focal motor seizures and implications for candidate selection.

To compare seizure parameters and treatment burden between methohexital and propofol during routine electroconvulsive therapy (ECT), focusing on seizure duration, treatment efficiency, and missed seizures. This retrospective chart review examined differences in seizure outcomes between 2 commonly used agents, methohexital and propofol, at the Parkwood Institute from October 2017 to October 2019. A total of 132 adult patients were included: 47 received methohexital (mean age 60.9±15.4; 44.7% male) and 85 received propofol (mean age 55.1±17.1; 35.3% male). No significant demographic differences were observed. Methohexital was associated with longer motor (35.6±19.7 vs. 23.4±11.7s; P<0.001) and EEG (50.8±28 vs. 36.8±19.2s; P=0.003) seizure durations. It was also directly associated with a higher number of total ECT treatments (13±6.5 vs. 11±5.3; β=0.29, P<0.001), though the raw difference was only marginally significant (P=0.08). Missed seizures were slightly fewer with methohexital (1.9±2.9 vs. 2.4±2.1; P=0.251). Multilevel structural equation modelling revealed a statistically significant indirect pathway through which methohexital influenced treatment continuity (Estimate = -0.743, P=0.044, standardized β=-0.061), mediated through motor seizure slope and missed seizures. While methohexital may initially enhance seizure quality, its decline in efficacy over time may compromise treatment efficiency. These findings suggest methohexital's initial seizure advantages may be offset by declining seizure duration across treatments and its downstream association with missed seizures. These findings may inform more efficient ECT anesthetic choices.

Wearable photoplethysmography (PPG) is increasingly used for seizure detection due to its ability to unobtrusively estimate heart rate (HR). However, the vulnerability of PPG to body movements often leads to unreliable HR estimates, compromising accurate seizure detection. Although this limitation is well recognized, methods for rejecting artifactual HR measures-and their impact on seizure detection performance-have not yet been studied. We sourced data from the PROMISE trial, a home-based study in children with refractory epilepsy that evaluated the performance of the NightWatch (NW) in detecting nocturnal motor seizures. We applied a novel pulse-based quality assessment (PQA) method that evaluates the quality of each individual PPG pulse and excludes compromised ones prior to HR estimation. We compared the performance of PQA with two alternatives: HR-based quality assessment (HRQA), rejecting extreme outliers in consecutive inter-beat intervals, and no quality assessment (noQA). We assessed the impact of PQA, HRQA, and noQA on seizure detection performance by applying HR increase thresholds from 30% to 80% relative to the baseline. A permutation test with bootstrapping was applied for all statistical comparisons. We analyzed 741 NW alarms, comprising 135 true seizures and 606 non-seizure events in 28 children (46% female; age: 9.1 ± 3.3 years). Averaged across all evaluated detection thresholds, both PQA and HRQA significantly improved seizure detection performance compared to noQA (p < 0.005). PQA led to mean increases of 0.248 in sensitivity, 0.025 in positive predictive value (PPV), and 0.082 in F1-score. HRQA showed mean increases of 0.081 in sensitivity, 0.040 in PPV, and 0.056 in F1-score. At clinically relevant sensitivity levels (0.8, 0.85, and 0.9), PQA showed a relative improvement over HRQA, with F1-scores increasing by 4%-15% and PPV by 5%-19%. Implementing PPG quality assessment-particularly pulse-based-improves the performance of wearable HR-based seizure detection. This study aimed to improve seizure detection in wearable devices by introducing a new method for assessing the quality of the heart rate (HR) data derived from a light sensor called photoplethysmography (PPG). By applying our method to data from children with epilepsy, we showed that discarding low-quality PPG data before HR estimation leads to better seizure detection, allowing more seizures to be correctly identified. This improvement is important because it enhances seizure detection performance through a software-only upgrade.

To describe the perinatal and neurological outcomes of fetuses with occipital encephalocele treated with intrauterine repair by open microneurosurgery. Between 2021 and 2025, a consecutive cohort of fetuses with occipital encephalocele referred to two fetal surgery centers in Nicaragua and Mexico were selected for intrauterine correction by open fetal microneurosurgery. Inclusion criteria were fetuses at less than 28 weeks with isolated occipital encephalocele, Chiari III malformation (obliteration of the cisterna magna with protrusion of cerebral tissue), and microcephaly. We report the procedure-related characteristics, perinatal and neurological outcomes (hydrocephalus, meningitis, seizures, cognitive delay, motor dysfunction, and visual impairment) within the first 12 months of age. Twelve cases were evaluated during the study period but only 6 cases were selected for fetal intervention. Open fetal microneurosurgery was successfully performed in all cases at a median gestational age (GA) of 25+2 weeks+days, with a median surgical time of 93 minutes. Regression of Chiari and reversal of microcephaly was observed in 4/6 and 6/6 cases, respectively. The median GA at birth was 36+5 weeks+days. Preterm rupture of the membranes and preterm delivery was reported in 3/6 cases. No cases of perinatal death were reported. Within the first 12 months of age, none of the children developed meningitis, cognitive delay, or hydrocephalus requiring ventriculoperitoneal shunting. Motor dysfunction, seizures and visual disorders were reported in 1/6, 1/6 and 3/6 cases, respectively. In fetuses with occipital encephalocele, open fetal microneurosurgery is feasible and is associated with good perinatal and neurological outcomes.

We describe a 65-year-old man with rheumatoid arthritis presenting with focal motor seizures and progressive right frontoparietal leptomeningeal enhancement. Biopsy was consistent with an inflammatory process. He improved with corticosteroids and rituximab. Our case highlights consideration of CNS involvement of rheumatoid arthritis in patients presenting with new neurologic symptoms.

Prevalence and predictive factors of epilepsy in multiple sclerosis: A cross-sectional study from Saudi Arabia.

Background: Rasmussen encephalitis, a rare and progressive inflammatory condition of the brain, is distinguished by its unilateral hemispheric manifestation, the presence of medically intractable focal seizures, and a progressive deterioration of neurological function. Prompt identification is crucial to enable the initiation of immunotherapy and the evaluation of surgical options. Case Presentation A 14-year-old boy, who had been healthy before, came to the hospital with a history of focal motor seizures that had been happening for eight months. These seizures, which started in the right arm, became more frequent and then developed into focal impaired-awareness seizures, sometimes followed by generalized tonic clonic seizures. Despite trying different anti convulsants including levetiracetam, valproate, and clobazam, the seizures weren't wellcontrolled. Over time, the patient showed increasing weakness on the right side, along with problems with fine motor skills and a decline in scholastic performance. An electroencephalogram (EEG) showed ongoing epileptiform activity and focal slowing in the left cerebral hemisphere. An MRI scan showed atrophy of the left hemisphere and marked ventricular dilatation and marked loss of cortical volume favouring the findings of rasmussen’s encephalitis Management: The patient received high-dose corticosteroids, followed by intravenous immunoglobulin therapy. This treatment led to a temporary and partial reduction in the frequency of seizures. Because of the ongoing seizures and the worsening neurological problems, an evaluation for functional hemispherotomy was started. Conclusion: This case highlights the importance of recognizing Rasmussen encephalitis in adolescents who have progressive focal epilepsy and neurological dysfunction with long lasting unilateral inflammation of cerebral cortex leading to seizures and which is refractory to treatment and it progresses as prodormal phase, acute phase where there is neurological decline and late residual phase. Early diagnosis, along with a quick surgical evaluation, is essential for improving long-term neurological outcomes.

Genetic analysis of self-limiting familial infantile epilepsy caused by PRRT2 variants in Indian patients.

BackgroundZBTB18 encodes a C2H2‐type zinc finger protein that acts as a transcriptional repressor and is essential for neurodevelopment. Variants in ZBTB18 are associated with intellectual developmental disorder, autosomal dominant 22 (MRD22). Patients with MRD22 present with intellectual disability (ID), corpus callosum anomalies, hypotonia, microcephaly, growth problems, epilepsy, and variable facial dysmorphism.MethodsWhole exome sequencing (WES) was performed to identify the molecular etiology. Sanger sequencing was used to validate the variant. Clinical assessments were conducted using brain magnetic resonance imaging (MRI) and electroencephalogram (EEG).ResultsOur patient presented with sleep‐associated focal motor seizures, characterized by right‐sided clonic movements with impaired consciousness, accompanied by atypical absence seizures. She also exhibited global developmental delay, unexplained ankle hypertonia, and unique juvenile facies (characterized by a lack of complex emotional expression, a fixed gaze, and an overall immature facial gestalt). Video EEG demonstrated hypsarrhythmia, whereas brain MRI revealed no structural abnormalities at the age of 2.5 years. The patient received antiepileptic therapy, and seizure control was successfully achieved following perampanel treatment. A de novo ZBTB18 variant (NM_205768.3: c.1474delA (p.Arg492Aspfs∗11)) was identified in our patient.ConclusionTo conclude, we report a de novo ZBTB18 frameshift variant (NM_205768.3: c.1474delA (p.Arg492Aspfs∗11)) in a female patient presenting with global developmental delay, epilepsy, ankle hypertonia, and unique juvenile facies. Notably, seizures were ultimately controlled with perampanel, which may provide a therapeutic insight for drug‐resistant epilepsy in MRD22. Our study expands the phenotypic and genetic spectrum of ZBTB18 and provides novel insights into the clinical management of MRD22.

A 53-year-old man who had defaulted on treatment for clinically diagnosed leprosy presented with four-month history of low-grade fever and progressive cognitive impairment. He started having left focal motor seizures with progressive left hemiparesis, followed by right focal seizures and right hemiparesis prior to hospital admission. Examination revealed axillary lymphadenopathy along with asymmetric (Left > Right) quadriparesis. Cerebrospinal fluid (CSF) evaluation did not reveal pleocytosis or hypoglycorrhachia with negative infective and inflammatory workup. Magnetic Resonance Imaging (MRI) was suggestive of abnormal signals in the cerebral cortices with swelling and a paraspinal abscess (Figure). Paraspinal tap was Culture negative with Cartridge based nucleic Acid Amplification test (CBNAAT) Positive for Mycobacterium Tuberculosis. Axillary lymph node biopsy was suggestive of caseous necrosis. He was started on Anti-Tubercular Therapy (ATT) with Multi Drug Therapy (MDT) for Leprosy and steroids along with anti-seizure medications (ASM) with significant clinical and radiological improvement in follow up. During his follow up he was ambulatory and independent in the intermediate term. Unfortunately, he contracted pneumonia in follow up and succumbed to sepsis related complications. Parenchymal involvement in the form of cortical encephalitis/cerebritis is an extremely rare presentation of CNS tuberculosis, characterised by T2/FLAIR hyperintense lesions with patchy or gyriform enhancement.

Deoxyhypusine synthase (DHPS) syndrome is a rare, autosomal recessive neurodevelopmental disorder caused by biallelic pathogenic variants in theDHPSgene, which encodes deoxyhypusine synthase. This enzyme is essential for the post-translational hypusination of eukaryotic translation initiation factor 5A (eIF5A), a modification crucial for cell viability, protein synthesis, and neuronal development. Patients with DHPS deficiency typically present with global developmental delays, intellectual disabilities, speech and motor impairments, seizures, and various dysmorphic features. Molecular studies show thatDHPSmutations disrupt eIF5A hypusination, impairing translation elongation and cellular homeostasis. Animal and cellular models have confirmed the neurotoxic effects of impaired hypusination. Although no targeted therapy is available, advances in understanding the molecular basis of the disorder have enabled translational research, including modulation of polyamine metabolism. Here, we describe the development of a gene therapy strategy to deliverDHPScDNA to mutant human brain cells in cortical organoids derived from patient stem cells, successfully restoring hypusination. This approach also improved survival in a mouse model of DHPS deficiency, highlighting the potential of rescuing DHPS expression as a treatment.

Epileptic seizures significantly impact individuals' safety, independence, and quality of life. Traditional monitoring systems are effective in clinical settings but lack portability for daily use. This project addresses these limitations by developing a wearable device for real-time epileptic seizure detection, enhancing patient safety and bridging the gap between clinical monitoring and everyday management. The low-cost, daily-use prototype improves detection accuracy and minimizes false alarms by strategically placing the device on the back for enhanced stability and sensor performance. The system uses an Arduino Mega microcontroller for control, a gyroscope for motion detection, GPS for location tracking, and GSM for emergency alerts. Each component was individually tested before integration. The device was evaluated for detecting tonic-clonic seizures, verifying audio and SMS alerts, and monitoring performance via a custom mobile app. Field testing over three weeks confirmed its effectiveness, with the buzzer alerting nearby individuals and SMS notifications enabling faster emergency response. The system demonstrated reliable detection of motor seizures with high accuracy and minimal false positives. Future enhancements include miniaturizing the device with a PCB, improving battery life, and integrating EEG monitoring for comprehensive seizure detection.

Dystrophinopathies, including Duchenne and Becker muscular dystrophy, are multisystem disorders characterized by progressive motor decline, epilepsy, cognitive impairments, and psychosocial challenges. However, data from Turkey, particularly from caregivers, remain limited. This study evaluated caregiver-reported outcomes of motor function, cognitive abilities, language, attention, fine motor skills, social functioning, and seizure history in dystrophinopathies. A cross-sectional survey was conducted with 267 primary caregivers using a structured questionnaire via Google Forms. The survey addressed motor function, seizure history, educational participation, cognitive and language abilities, attention, fine motor skills, and social functioning. Motor assessment showed that 35.2% of participants required a wheelchair. Febrile seizures occurred in 5% and epilepsy in 2.3%, with only half of affected individuals receiving antiseizure medication. Educational participation varied: 56.8% attended mainstream schooling independently, while 5.7% could not access education due to combined motor and cognitive impairments. Language difficulties included expressive (34.9%) and receptive delays (23.9%), as well as problems with word retrieval (18.8%) and comprehension of complex sentences (26.1%). Learning difficulties were common, especially in memory retention (32.1%) and arithmetic (26.3%). Attention problems were reported in 39.8% of cases. Fine motor difficulties involved pencil use (35.2%) and writing alignment (30.9%). Social challenges included impaired peer communication (32.2%) and low self-confidence (35.3%). Dystrophinopathies impose a major extramuscular burden beyond motor decline, including epilepsy, cognitive deficits, and psychosocial difficulties. Importantly, the caregiver perspective highlights underrecognized cognitive and behavioral challenges, as well as barriers to education, providing actionable insights to guide multidisciplinary follow-up. These findings emphasize the importance of early recognition and comprehensive care that integrates neurological, educational, and psychosocial support to improve outcomes for individuals with dystrophinopathies.

BackgroundTranscranial electrical stimulation (TES) has limited spatial focus and depth penetration, constraining its therapeutic efficacy. Intersectional Short-Pulse (ISP) stimulation was developed to overcome these limitations by delivering rapidly switching pulses that can be temporally integrated by neuronal membranes. Here, we aimed to establish the biophysical basis of ISP-induced temporal summation and to test whether this mechanism enables effective brain modulation in vivo.MethodsWe combined finite-element modeling, cadaver measurements (n = 2 human cadavers), and biophysically realistic NEURON simulations to characterize the spatial and temporal properties of ISP-induced electric fields. In vivo whole-cell patch-clamp recordings were performed in the rat somatosensory cortex (female Wistar rat) to test the membrane-level integration of sequential electric field pulses. Functional efficacy was evaluated using closed-loop ISP stimulation in a hippocampal kindling model of temporal lobe epilepsy in male Long–Evans rats (n = 11 animals, >500 induced seizures analyzed across conditions).ResultsHere we show that neurons integrate sequential ISP pulses in a non-vectorial, temporally accumulative manner, consistent with membrane-level charge integration rather than extracellular field superposition. ISP and conventional TES simulations produced similar instantaneous field magnitudes, but ISP stimulation resulted in more uniform neuronal excitability across brain depths. Closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 45% and 35% compared to SHAM stimulation and conventional TES, and significantly reduced motor seizure severity.ConclusionsISP stimulation provides a non-invasive neuromodulation approach that enhances deep brain engagement through rapid, temporally structured pulse sequences. These findings demonstrate effective seizure suppression in a rodent model and support the translational potential of ISP for disorders involving pathological neural dynamics.

ObjectiveCurrently available wearable devices for detecting focal seizures primarily target major motor seizures or involve semi‐invasive subscalp implants. There is a pressing need for accurate, non‐invasive methods to detect diverse focal seizures for long‐term, out‐of‐hospital monitoring.MethodsIn this multicenter study (SeizeIT2), people with refractory focal epilepsy undergoing long‐term video‐electroencephalography (EEG) monitoring were simultaneously recorded with the Sensor Dot, a multimodal wearable device using EEG and electrocardiography (ECG). Wearable recordings were first processed with an offline detection algorithm, after which the algorithm‐labeled segments underwent blinded review by a human expert, and results were compared with ground truth video‐EEG. Post‐hoc analyses were performed to evaluate how specific seizure characteristics, defined by the gold‐standard recordings, influenced detection sensitivity.ResultsWe recruited 192 adult participants, documenting a total of 616 focal seizures. The mean duration of Sensor Dot monitoring was 5 days. The seizure detection algorithm achieved an overall sensitivity of 0.73, precision of 0.004 and F1 score of 0.01. Following human review, a precision of 0.83 was achieved, albeit with a sensitivity of 0.31, resulting in an F1 score of 0.45. Seizure detection was influenced by the seizure type (focal impaired awareness seizure (FIAS) or focal‐to‐bilateral tonic–clonic seizures (FBTCS)) and the presence of a distinct ictal pattern on behind‐the‐ear EEG, constituting mostly temporal lobe seizures. In a post‐hoc subgroup analysis of seizures with a clear ictal EEG pattern and ictal tachycardia (as determined by the ground truth), a sensitivity of 0.74 was observed, whereas a sensitivity of 0.60 was achieved when there was visible electrographic seizure activity without tachycardia.SignificanceThe overall performance of the Sensor Dot in focal seizure detection was limited in an unselected group of focal seizure types. Our findings suggest that the proposed approach, combining algorithm‐based detection with human review, provides detection performance comparable with diary self‐reporting, in terms of sensitivity, but with higher precision (0.83 vs. 0.60). Our findings suggest that this multimodal approach may be particularly beneficial for the subset of patients whose seizures are characterized by distinct ictal EEG patterns and tachycardia—features frequently seen in temporal lobe epilepsy. However, the prospective utility of these markers for patient selection requires further validation.Plain Language SummaryWearable devices may help improve seizure detection in people with epilepsy, but few non‐invasive options exist for detecting focal seizures. We studied a behind‐the‐ear wearable device (Sensor Dot) using automated analysis combined with expert review. Overall, this approach resulted in detection of seizures with low sensitivity but high precision. Post‐hoc subgroup analysis suggested that for seizures characterized by a distinct ictal EEG pattern and tachycardia—features often seen in temporal lobe epilepsy—this multimodal approach achieved a sensitivity of 0.74. Further prospective validation is required to confirm if this performance can be replicated through pre‐monitoring patient selection.

Distinct neuronal mechanisms for motor impairment and seizures in a novel mouse model of SCN8A epileptic encephalopathy.

Anti-LGI-1 autoimmune encephalitis: Insights from literature and a very late-onset case report.

Introduction: Therapeutic drug monitoring is a means of monitoring anti-epileptic treatment. The objective of this study was to conduct therapeutic drug monitoring of the three most commonly prescribed anti-epileptic drugs in Mali. Methods: This was a cross-sectional, prospective study conducted over an eight-month period. It focused on the pharmacological therapeutic follow-up of carbamazepine (CBZ), phenobarbital (PB), and valproic acid (VPA) in 80 epilepsy patients monitored at the Neurology Department of Point G University Hospital. Results: The majority of participants were aged between 18 and 70 (65%). Generalised motor seizures were more common (76.20%). Carbamazepine was the most commonly prescribed drug (60.32%), followed by phenobarbital (20.63%) and valproic acid (19.05%). The combination of CBZ/PB was the most commonly observed, at 47.06%. Among patients taking carbamazepine, 2% were underdosed and 23% were overdosed. 75% of patients taking phenobarbital were underdosed. Half of patients taking valproic acid were underdosed and 5% were overdosed. Conclusion: Pharmacological therapeutic monitoring is an indispensable tool in the management of epilepsy. However, efforts must be made to introduce this practice into routine healthcare in Mali. Keywords: Therapeutic monitoring, Carbamazepine, Phenobarbital, Valproic acid, Mali

Enzyme replacement therapy for CLN1 batten disease that crosses the blood-brain-barrier.

Management of Movement Disorders in Chronic Neurological Conditions and Palliative Care: A Retrospective Cohort Study.