Motor Seizures Research Articles

Selective striatal fast-spiking interneuron inhibition induces cortical seizure.

Whether striatal fast-spiking interneurons are involved in cortical synchronization remains elusive. We performed acute microinjections of a selective FSI-AMPA receptor antagonist into the sensorimotor striatum of non-human primates to verify whether selective FSI inhibition within the sensorimotor striatum could potentially modify cortical excitability, thereby triggering focal seizures. Experiments were performed on three fascicularis monkeys. During each experimental session, low volumes of IEM-1460 (4-8 μL) were injected slowly at 1 μL/min. Spontaneous behavioral changes were classified according to the Racine scale modified for primates. These induced motor behaviors were correlated with electroencephalographic (EEG and EMG) measures. Power spectrum and time-frequency analysis were performed and compared between each period of interest. Pharmacological selective inhibition of striatal fast-spiking INs induced focal motor seizures. Back averaging confirmed that myoclonic activity was closely linked to cortical spikes-and-waves epileptic activity, with a significant increase in cortical EEG power in all studied frequency bands (p < .0001). Thus, striatal FSIs likely play a role in controlling cortical excitability through the cortico-striato-thalamo-cortical pathway. They may contribute to the pathophysiology of focal motor epilepsies by modulating the threshold at which focal motor seizures are triggered.

Ketamine as an Alternative Anesthetic for Augmenting Seizure Durations During Electroconvulsive Therapy: A Retrospective Observational Study.

Electroconvulsive therapy (ECT) is highly effective for severe psychiatric disorders; however, short seizure durations may lead to ineffective therapy. This retrospective study aimed to examine the risks and benefits of switching to ketamine anesthesia to augment seizure durations during an acute course of ECT. We included 33 patients who underwent ketamine anesthesia due to suboptimal seizures during an acute course of ECT. We assessed seizure duration, stimulus dose, hemodynamic variability, and postseizure complications before and after switching to ketamine. Age was significantly associated with suboptimal seizures during ECT ( P = 0.040). After switching to ketamine, 32 patients (97%) experienced prolonged seizure duration. Ketamine significantly prolonged both electroencephalogram and motor seizure durations with a mean difference of 34.6 seconds (95% confidence interval [CI], 26.4-42.7 seconds; P < 0.001) and 26.6 seconds (95% CI, 19.6-33.6 seconds; P < 0.001), respectively. It also significantly reduced stimulus dose (mean difference, -209.5 mC [95% CI, -244.9 to -174.1 mC]; P < 0.001). In addition, maximum changes in systolic blood pressure and heart rate during ECT sessions significantly increased with ketamine (mean difference, 27.2 mm Hg [95% CI, 12.0-42.4 mm Hg; P = 0.001]; 25.7 beats per minute [95% CI, 14.5-36.8 beats per minute; P < 0.001], respectively). Patients reported more headaches with ketamine ( P = 0.041). Our results provide evidence that ketamine as an alternative anesthetic can augment seizure durations in specific patients experiencing suboptimal seizures during an acute course of ECT. However, its use requires greater attention to circulatory management and postseizure complications.

Comorbidity of cerebral palsy and epilepsy with autism in children

Background. Cerebral palsy is often combined with epilepsy (up to about 50 % of children). The treatment of epilepsy limits the rehabilitation of cerebral palsy, and the rehabilitation of cerebral palsy often provokes epileptic seizures. Epilepsy in children with cerebral palsy is often manifested in a form of developmental and epileptic encephalopathy with spike-and-wave activation in sleep, which is characterized by epileptiform activity according to the type of benign epileptiform patterns of childhood with a high index on the electroencephalogram (up to 100 %), severe epileptic seizures of a status course, and mental disorders by type autism-like behavior (the so-called atypical autism) and disorders of speech communication. The problem of comorbidity of cerebral palsy, epilepsy and autism remains relevant and needs further study.Aim. To study the features of autism spectrum disorder in a group of children with a combination of cerebral palsy and epilepsy.Materials and methods. We examined 100 patients aged 3–10 years with various forms of cerebral palsy, combined with epilepsy, to identify the clinical features of autism spectrum disorder. Criteria for inclusion in the study: age 3–10 years; verified diagnosis of epilepsy in combination with cerebral palsy and autism spectrum disorder; informed consent of the patient’s parents to participate in the study. Criteria for exclusion from the study: severe somatic diseases and disorders of the sense organs (in particular, kyphoscoliosis, gastrostomy and others, as well as deafness, blindness); age less than 3 or more than 10 years.Results. The average age of visiting a psychiatrist was 5.4 ± 0.5 years. The reasons for visit were: violation of the communication (76 %), decreased eye contact (75 %), lack of compassion for surrounding or adjacent animals (100 %), dysphoric disorders (77.1 %), aggression (55 %), autoaggression (40 %), phobias (90 %), impaired speech development (18 %). Perinatal brain damage was diagnosed in 100 % of cases. Epilepsy was manifested by focal motor seizures. Patients with complex treatment (drugs and pedagogical correction) have more pronounced positive dynamics compared with patients who received only drug therapy or only rehabilitation (p &lt;0.05).Conclusion. In children with a combination of cerebral palsy and epilepsy, the cause of autism is perinatal lesions of the central nervous system, as well as the severity of motor pathology and the presence of continued epileptiform activity on the electroencephalogram. Autism in this group of children requires timely recognition and medical and pedagogical correction.

Bioequivalence Study of Two Tablet Formulations of Clonazepam 2mg: A Randomized, Open-Label, Crossover Study in Healthy Mexican Volunteers Under Fasting Conditions.

The prevalence of neurological disorders is high among the Mexican population. Clonazepam is primarily indicated to treat panic disorders, certain kinds of epilepsy such as status epilepticus, childhood motor seizures (petit mal absence, Lennox-Gastaut syndrome, and infantile spasms), anxiety, and muscle spasm. This study was performed to compare bioequivalence between two oral tablet formulations of clonazepam 2mg in healthy Mexican volunteers under fasting conditions. This phaseI, randomized, open-label, two-treatment, crossover study included 30healthy volunteers. Subjects were randomly assigned to either test or reference formulation of clonazepam 2mg. Each study period was separated by 21-day washout period. Blood samples were collected at pre-dose and up to 72h after drug administration. Clonazepam concentrations were determined using a validated ultra-flow liquid chromatography-tandem mass spectrometric method. Pharmacokinetic parameters were determined using a non-compartmental method. Two formulations were considered bioequivalent if geometric mean ratios (test/reference) were between 80% and 125%. Safety was evaluated by recording adverse events. Pharmacokinetic parameters were comparable between test and reference formulations. The mean maximum plasma concentration (Cmax) was ≈ 13ng/mL, area under the plasma concentration-time curve from time0 to last measurable concentration (AUC0-t) was ≈ 360ngh/mL, time to reach maximum plasma concentration (Tmax) was ≈ 3h, and elimination half-life (t1/2) was ≈ 43h. Geometric mean ratios (90% confidence interval) of Cmax (99.2-115.3%), AUC0-t (100.6-110.6%), and AUC0-∞ (98.5-111.6%) were within the bioequivalence range. Seven non-serious adverse events (mostly asymptomatic hypotension) were recorded. The test and reference formulations of clonazepam 2mg were bioequivalent and well tolerated in healthy Mexican volunteers under fasting conditions. 213301410B0051 (Approved on April 13, 2021).

Long-term treatment with ganaxolone for seizures associated with cyclin-dependent kinase-like 5 deficiency disorder: Two-year open-label extension follow-up.

In the placebo-controlled, double-blind phase of the Marigold study (NCT03572933), ganaxolone significantly reduced major motor seizure frequency (MMSF) in patients with cyclin-dependent kinase-like 5 deficiency disorder (CDD). We report 2-year safety and clinical outcomes data from the open-label extension (OLE) phase of Marigold. Patients with CDD who completed the double-blind phase were eligible to continue in the OLE. Efficacy assessments included MMSF reduction from prerandomization baseline, responder rates, and Clinical Global Impression-Improvement scores, including assessment of seizure intensity and duration (CGI-CSID). Safety assessments included treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Of 101 patients who enrolled in Marigold, 88 (87.1%) entered the OLE (median age = 5 years, 79.5% female). Median 28-day MMSF at baseline was 50.6. At 2 years in the OLE (months 22-24), MMSF was reduced by a median of 48.2% (n = 50); when missing data were imputed, median reduction in MMSF was 43.8% using a mixed effects model and 27.4% using a last observation carried forward model. During months 22-24, 23 of 50 (46.0%) patients experienced reductions in MMSF of ≥50%; 12 of 50 (24.0%) patients experienced MMSF reductions of ≥75%. During months 22-24, 40 of 49 (81.6%) patients were rated by caregivers as having improvement in seizure-related outcomes based on CGI-CSID scores. Thirty-seven patients discontinued ganaxolone due to lack of efficacy (n = 13), withdrawal by caregiver (n = 12), adverse event (n = 10), physician decision (n = 1), or death (n = 1; unrelated to study drug). The most common treatment-related TEAEs were somnolence (17.0%), seizure (11.4%), and decreased appetite (5.7%). Patients reported serious TEAEs (n = 28, 31.8%); those reported in ≥3% of patients were seizure (n = 6), pneumonia (n = 5), acute respiratory failure (n = 3), aspiration pneumonia (n = 3), and dehydration (n = 3). Sustained reductions in MMSF at 2 years in the OLE support the efficacy of ganaxolone in seizures associated with CDD. Safety findings in the OLE were consistent with the double-blind phase.

Automatic classification of hyperkinetic, tonic, and tonic-clonic seizures using unsupervised clustering of video signals.

This study evaluated the accuracy of motion signals extracted from video monitoring data to differentiate epileptic motor seizures in patients with drug-resistant epilepsy. 3D near-infrared video was recorded by the Nelli® seizure monitoring system (Tampere, Finland). 10 patients with 130 seizures were included in the training dataset, and 17 different patients with 98 seizures formed the testing dataset. Only seizures with unequivocal hyperkinetic, tonic, and tonic-clonic semiology were included. Motion features from the catch22 feature collection extracted from video were explored to transform the patients' videos into numerical time series for clustering and visualization. Changes in feature generation provided incremental discrimination power to differentiate between hyperkinetic, tonic, and tonic-clonic seizures. Temporal motion features showed the best results in the unsupervised clustering analysis. Using these features, the system differentiated hyperkinetic, tonic and tonic-clonic seizures with 91, 88, and 45% accuracy after 100 cross-validation runs, respectively. F1-scores were 93, 90, and 37%, respectively. Overall accuracy and f1-score were 74%. The selected features of motion distinguished semiological differences within epileptic seizure types, enabling seizure classification to distinct motor seizure types. Further studies are needed with a larger dataset and additional seizure types. These results indicate the potential of video-based hybrid seizure monitoring systems to facilitate seizure classification improving the algorithmic processing and thus streamlining the clinical workflow for human annotators in hybrid (algorithmic-human) seizure monitoring systems.

FRI627 Lost In The Striato-sphere: Diabetic Striatopathy In An Elderly Patient Who Was Lost To Follow-up

Abstract Disclosure: C.L. Loughner: None. E. Mahmood: None. A. Sheharyar: None. Introduction: Diabetic striatopathy (DS) represents a spectrum of central nervous system derangements associated with uncontrolled hyperglycemia.1 The most common site of brain involvement is the putamen but can involve any region of the striatal nuclei. The exact mechanism behind DS remains unclear, but current theories postulate hyperosmolarity-related ischemic events that lead to breakdown in the blood-brain barrier and mineral deposition2. We present a case of DS demonstrating a rare neurologic complication resulting from uncontrolled diabetes mellitus. Clinical Case: An 82-year-old female was admitted for workup following new-onset left-sided involuntary jerking movements. On exam, there were choreiform movements in the left upper and lower extremities. Initially, Levetiracetam was started for possible focal motor seizures but with no improvement. MRI brain showed T1 hyperintensity of the right lentiform nucleus, consistent with DS. She had moved recently from out of state and had inconsistent follow-up for type 2 diabetes mellitus for years. Her HbA1c was 13.8%. She was non-compliant with glucose monitoring and insulin therapy. With a comprehensive treatment plan including Haloperidol, physical therapy, improved CGM compliance, and four-times-daily insulin regimen, her chorea improved and resolved completely over a few weeks. Clinical Lesson: DS can present with a variety of neurologic manifestations, including chorea. While choreiform movements can severely impact a patient’s life, they are rarely permanent if treated with either glycemic control or anti-chorea medications. This case highlights the importance to recognize rarer complications of diabetes and the impact of good glycemic control for successful treatment of diabetic striatopathy.

Adaptability of Pediatric Residents for the International League Against Epilepsy-2017 Seizure Classification with a Modular Education Program.

The aim of this study was to evaluate the adaptability of pediatric residents to the current seizure classification of the International League Against Epilepsy-2017 (ILAE-2017) using a modular education program (MEP). The MEP design consisted of 8 modules, including 5 modules for the current version of the ILAE-2017 seizure classification and 3 modules for the older ILAE-1981 version. The MEP was implemented with a group of pediatric residents, and it comprised 50 illustrative pediatric seizure videos along with an instruction manual kit that included a seizure determinator. Following a 3-month follow-up period, a posttest was conducted using 58 new videos in the MEP. The overall success rates of the participants were similar both ILAE-2017 (41%) and ILAE-1981 (38.5%) seizure classifications in the post-MEP test. Regarding the ILAE-2017 mod- ules, the participants demonstrated a higher proficiency in classifying focal nonmotor seizures (56.3%) compared to focal motor seizures (34.9%). However, when it came to generalized seizures, the participants had significantly lower accuracy rates for generalized nonmotor seizures (26%) compared to generalized motor seizures (46%) with the ILAE-2017 classifica- tion. The seizure types that were most commonly misclassified, with an error rate exceeding 50%, were automatisms and myoclonic seizures within the focal seizure modules and atypical absences in generalized seizure modules of ILAE-2017. The single-day MEP yielded modest results, with a success rate of 41% in terms of the initial adaptability of pediatric residents to the ILAE-2017 seizure classification. However, to ensure successful implementation of the ILAE-2017 classification in clinical practice, additional booster applications of the MEP are required.

The recurrent WASF1 nonsense variant identified in two unaffected Chinese families with neurodevelopmental disorder: case report and review of the literatures

BackgroundNeurodevelopmental disorder with absent language and variable seizures (NEDALVS, # 618707) are characterized by delayed speech and motor development, ocular abnormalities, and seizures. NEDAVLS is an autosomal dominant disorder caused by de novo mutations in the wasp protein family member 1 (WASF1) gene.Case presentationWe identified a de novo nonsense variant c.1516 C > T (p.Arg506*) of WASF1 gene (NM_003931.3) in two pediatric female patients with delayed motor and language development.ConclusionThis case demonstrates the effective role of WES in the diagnosis of NEDALVS. To the best of our knowledge, this variant has not been reported in the Chinese population. This contributes to our further understanding of the disease and to research related to the genetic and clinical heterogeneity, the treatment and prognosis of the disease.

Update in the Understanding, Diagnosis, and Management of Sturge Weber Syndrome: Case Report

Sturge-Weber Syndrome (SWS) is a congenital, vascular, neurocutaneous, uncommon disease associated with facial angiomas port wine birthmark (PWB) or “nevus flammeus”, cerebral vascularity alterations (leptomeningeal vascular malformation), and ocular disorders. It is the third most common neurocutaneous syndrome after neurofibromatosis and tuberous sclerosis. GNAQ R183Q is the most frequent related mutation, caused by a postzygotic, somatic, gain-of-function. 75% of patients present seizures during the first year of life, mainly focal motor seizures, with or without consciousness impairment. We present the case of a 33-year-old female with a diagnosis of SWS, with refractory seizures that started at 4 months of age. In this admission, she presented upper and lower respiratory tract infections that culminated in a convulsive status epilepticus (CSE), the reason for which she required sedation and advanced airway management with adjustment of the anti-seizure medication (ASM). An electroencephalogram (EEG) was performed that reported epileptic activity, as well as an imaging study with data suggestive of calcification in the frontal and right parietal region, compatible with vascular malformation.

Treatment of Refractory Epilepsy With MEK Inhibitor in Patients With RASopathy

BackgroundSeveral specific syndromes within the RASopathies spectrum lead to an increased risk of seizures up to developing refractory epileptic encephalopathy. Management remains symptomatic. MethodsHere we report two patients treated with trametinib, a MEK1-2 inhibitor, as a precision strategy for drug-resistant epilepsy. Patient 1 is a six-year-old girl with cardiofaciocutaneous syndrome (BRAF p.F595L, germline mutation), and Patient 2 is a 14-month-old boy with Schimmelpenning syndrome (KRAS p.G12D, postzygotic somatic mutation). Trametinib was initiated at a dosage of 0.025 mg/kg/day. ResultsPatient 1 had multiple seizures per day, multifocal motor to bilateral tonic-clonic. Electroencephalography (EEG) showed a dramatic reduction in EEG discharges three months after trametinib onset, while a marked clinical improvement occurred after about five months, at the same dosage, and the girl is currently seizure-free for more than six months.Patient 2 had left cerebral hemiatrophy leading to right focal motor seizures, multiple per week to multiple per day, since the age of three months. On trametinib, he experienced an early benefit, remaining seizure-free for more than three months. However, after six months we observed recurrence of seizures. After 22 months of treatment, trametinib was discontinued because of a suspected drug-induced inflammatory colitis. After discontinuation, we observed a significant clinical and EEG “rebound effect.” ConclusionsWe provide proof of concept that MEK inhibition is a promising approach for the treatment of patients with refractory epilepsy with selected germline and mosaic RASopathies. Future trials are encouraged to better investigate their potentials and limitations.

ROLE OF MRI IN EVALUATION OF SEIZURE DISORDER

Objectives: The present study was conducted to identify structural abnormalities on the brain imaging that may be associated with the cause of seizures and to study the spectrum of MRI findings in patients with seizures. Methods: This time-bound descriptive study was conducted on 100 seizure patients in the department of radiodiagnosis of GMC, Patiala. Informed consent was obtained and then MR imaging of brain was done. The results were analyzed. Results: Mean age was 39.59±15.96 years (range: 18–85 years) with 70% male and 30% female patients. The majority of the patients (80%) had generalized tonic–clonic seizures, followed by myoclonic seizures (8%), simple partial seizures (5%), complex partial seizures (2%), absence seizures (2%), motor seizures (1%), febrile seizures (1%), and tonic seizures (1%). The mean seizure duration was 2.15±1.48 months. On magnetic resource imaging (MRI), 44% patients had normal MRI. In remaining patients, MRI findings were infarct with gliosis (20%), ring enhancing lesions (18%), atrophy (6%), neoplasm (4%), thrombosis (3%), venous malformation (2%), and developmental malformations (3%). Conclusion: The most common type of seizures is GTCS. MRI can be normal in the majority of the patients of seizures. Common MRI abnormalities were infarct with gliosis and ring-enhancing lesions. Hence, MRI plays a significant role in the initial evaluation of seizures patients to rule out any organic or developmental lesions.

SDPS-08 OSSEOUS METASTASES IN H3G34-MUTANT DIFFUSE HEMISPHERIC GLIOMAS

Abstract Subset of patients with H3G34 gliomas may present with extra-CNS metastasis further complicating both diagnosis and treatment. We describe a case of a 19-year-old female presenting initially with focal motor seizure in right leg along with leg pain. MRI of the leg showed an ill-defined right distal femur expansile osteolytic lesion with central fluid signal, thick rim enhancement, endosteal scalloping, cortical invasion, and smooth enhancing periosteal reaction/soft tissue extension associated with surrounding enhancing marrow signal abnormality worrisome for lesion extension. Contrast brain MRI exhibited multiple frontal and partial lobe T2 FLAIR hyperintense lesions. The largest lesion demonstrated contrast enhancement, internal foci of restricted diffusion, and a focus of intratumoral hemorrhage. A whole-body PET/CT showed intensely FDG-avid lytic lesion in the right distal femur, with FDG activity along the biopsy tract. Hypermetabolic lytic metastases to the right femoral head and mid-sacral body were also observed. A craniotomy with brain lesion biopsy two months later indicated preliminary histopathology of malignant small round blue cell neoplasm. A biopsy from the distal right femur was non-diagnostic of malignancy but a sacral bone biopsy reported malignant small blue cell neoplasm, consistent with involvement by the patient's known cranial neoplasm. Final pathological diagnosis including molecular diagnostics was consistent with WHO grade 4 IDH-wildtype H3G34 mutant diffuse hemispheric glioma with osseous metastases. Patient was treated with chemoradiotherapy with temozolomide (TMZ). Following the sixth cycle of TMZ, MRI brain imaging was stable. Apart from holocephalic headaches, the patient had no significant medication side effects and was seizure-free. A second whole-body PET scan showed improvement and interval decrease in FDG uptake of the sacrum and right femoral head. Given the stress that patients with H3G34 can experience and the poor prognosis, it is imperative to expand our knowledge and ascertain accurate screening and diagnostic methodologies.

Peri-ictal heart rate changes in patients with epilepsy.

Heart rate (HR) changes associated with seizures are promising biomarkers in epilepsy. The aim of our study is to reveal possible HR changes in the peri-ictal period. Long-term video-EEG monitorization records of generalized and focal epilepsy patients were reviewed. HRs were calculated in the pre-ictal (2 min before the first seizure activity in EEG), ictal (the time from the first seizure activity on the EEG to the end of the seizure), and in the interictal period (at least 2 h before or 12 h after the seizure). Interictal, pre-ictal, and ictal HRs were compared with each other. In addition, it was investigated whether peri-ictal HR changes differ between generalized and focal seizure patients. Focal motor seizures were observed in 21, and generalized tonic-clonic seizures were observed in 18 of 39 (22 female and 17 male) patients studied. HRs in the pre-ictal and ictal periods were significantly higher than in the interictal period. This significant increase in HR was validated separately in both focal and generalized seizure groups and was not different between the two groups. Our study supports previous studies showing the presence of increased peri-ictal HR and also provides new insights by comparing focal and generalized motor seizures. We think that our findings may contribute to the development of early warning signs in epilepsy patients.

Interoception in functional motor symptoms and functional seizures: Preliminary evidence of intact accuracy alongside reduced insight and altered sensibility

Altered interoception may be a pathophysiological mechanism in functional neurological disorder (FND). However, findings have been inconsistent across interoceptive dimensions in FND including functional motor symptoms (FMS) and seizures (FS). Here, individuals with FMS/FS (n = 17) and healthy controls (HC, n = 17) completed measures of interoceptive accuracy and insight (adapted heartbeat tracking task [HTT] with confidence ratings), a time estimation control task (TET) and the Multidimensional Assessment of Interoceptive Awareness–2 (MAIA-2) to assess interoceptive sensibility. The groups did not differ in interoceptive accuracy (p = 1.00, g = 0.00) or confidence (p = .99, g = 0.004), although the FMS/FS group displayed lower scores on the “Not-Distracting” (p < .001, g = 1.42) and “Trusting” (p = .005, g = 1.17) MAIA-2 subscales, relative to HCs. The groups did not differ in TET performance (p = .82, g = 0.08). There was a positive relationship between HTT accuracy and confidence (insight) in HCs (r = .61, p = .016) but not in FMS/FS (r = 0.11, p = .69). HTT confidence was positively correlated with MAIA-2 “Self-Regulation” (r = 0.77, p = .002) and negatively correlated with FND symptom severity (r = −0.84, p < .001) and impact (r = −0.86, p < .001) in FMS/FS. Impaired interoceptive accuracy may not be a core feature in FMS/FS, but reduced insight and altered sensibility may be relevant. Reduced certainty in self-evaluations of bodily experiences may contribute to the pathogenesis of FND symptoms.

The cerebellum contributes to generalized seizures by altering activity in the ventral posteromedial nucleus

Thalamo-cortical networks are central to seizures, yet it is unclear how these circuits initiate seizures. We test whether a facial region of the thalamus, the ventral posteromedial nucleus (VPM), is a source of generalized, convulsive motor seizures and if convergent VPM input drives the behavior. To address this question, we devise an in vivo optogenetic mouse model to elicit convulsive motor seizures by driving these inputs and perform single-unit recordings during awake, convulsive seizures to define the local activity of thalamic neurons before, during, and after seizure onset. We find dynamic activity with biphasic properties, raising the possibility that heterogenous activity promotes seizures. Virus tracing identifies cerebellar and cerebral cortical afferents as robust contributors to the seizures. Of these inputs, only microinfusion of lidocaine into the cerebellar nuclei blocks seizure initiation. Our data reveal the VPM as a source of generalized convulsive seizures, with cerebellar input providing critical signals.

Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy.

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory, resistant to antiepileptic drugs, and has a high recurrence rate. The pathogenesis of temporal lobe epilepsy is complex and is not fully understood. Intracellular calcium dynamics have been implicated in temporal lobe epilepsy. However, the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown, and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice. In this study, we used a multi-channel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process. We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes. In particular, cortical spreading depression, which has recently been frequently used to represent the continuously and substantially increased calcium signals, was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from grade II to grade V. However, vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures. Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to grade I episodes. In addition, the latency of cortical spreading depression was prolonged, and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced. Intriguingly, it was possible to rescue the altered intracellular calcium dynamics. Via simultaneous analysis of calcium signals and epileptic behaviors, we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced, and that the end-point behaviors of temporal lobe epilepsy were improved. Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades. Furthermore, the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy, thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Mitochondrial Proteome Changes in Rett Syndrome.

Rett syndrome (RTT) is a genetic neurodevelopmental disorder with mutations in the X-chromosomal MECP2 (methyl-CpG-binding protein 2) gene. Most patients are young girls. For 7-18 months after birth, they hardly present any symptoms; later they develop mental problems, a lack of communication, irregular sleep and breathing, motor dysfunction, hand stereotypies, and seizures. The complex pathology involves mitochondrial structure and function. Mecp2-/y hippocampal astrocytes show increased mitochondrial contents. Neurons and glia suffer from oxidative stress, a lack of ATP, and increased hypoxia vulnerability. This spectrum of changes demands comprehensive molecular studies of mitochondria to further define their pathogenic role in RTT. Therefore, we applied a comparative proteomic approach for the first time to study the entity of mitochondrial proteins in a mouse model of RTT. In the neocortex and hippocampus of symptomatic male mice, two-dimensional gel electrophoresis and subsequent mass-spectrometry identified various differentially expressed mitochondrial proteins, including components of respiratory chain complexes I and III and the ATP-synthase FoF1 complex. The NADH-ubiquinone oxidoreductase 75 kDa subunit, NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, NADH dehydrogenase [ubiquinone] flavoprotein 2, cytochrome b-c1 complex subunit 1, and ATP synthase subunit d are upregulated either in the hippocampus alone or both the hippocampus and neocortex of Mecp2-/y mice. Furthermore, the regulatory mitochondrial proteins mitofusin-1, HSP60, and 14-3-3 protein theta are decreased in the Mecp2-/y neocortex. The expressional changes identified provide further details of the altered mitochondrial function and morphology in RTT. They emphasize brain-region-specific alterations of the mitochondrial proteome and support the notion of a metabolic component of this devastating disorder.

Etomidate versus Propofol for Electroconvulsive Therapy in Patients with Major Depressive Disorders in Terms of Clinical Responses to Treatment: A Retrospective Analysis.

General anesthetic agents may be associated with the clinical efficacy of electroconvulsive therapy (ECT), as they may influence seizure quality and duration. Hence, a retrospective study was conducted to compare the clinical effects and seizure variables of etomidate and propofol during ECT. Patients treated with ECT under anesthesia with etomidate (n = 43) or propofol (n = 12) were retrospectively analyzed. Seizure variables (seizure duration, intensity, and threshold) and hemodynamic changes during ECT were assessed and recorded. Clinical responses to treatment were evaluated using the Clinical Global Impression scale and mood at discharge after the course of ECT. Adverse effects were also recorded. The demographic characteristics were similar between the two groups. There were no significant differences in the Clinical Global Impression scale scores, mood at discharge, and adverse effects between the two groups (p > 0.05); however, etomidate was associated with a significantly longer motor (42.0 vs. 23.65 s, p < 0.001) and electroencephalogram (51.8 vs. 33.5 s, p < 0.001) seizure duration than propofol. In conclusion, etomidate showed more favorable seizure profiles than propofol during ECT; however, both agents (etomidate and propofol) were associated with similar clinical efficacy profiles at discharge.

Adult hemiconvulsive hemiatrophy syndrome: a novel clinicoradiologic disorder in adults.

The association of focal motor seizures with cerebral hemiatrophy is a recognised rare paediatric syndrome known as 'hemiconvulsion, hemiatrophy and epilepsy' (HHE). To date, HHE has not been reported in adults. We present four adult patients with striking similarities to HHE, following alcohol withdrawal in chronic alcoholics. We document the imaging findings in the acute and subacute phases, discuss the underlying mechanisms and present a hypothesis regarding the pathophysiology.