Motor Seizures Research Articles

Emergent responsive neurostimulation in pediatric super-refractory epilepsia partialis continua.

Focal status epilepticus, particularly the motor variant of epilepsia partialis continua (EPC), is a rare condition characterized by near-continuous, chronic focal motor seizures, and associated with poor outcomes. Medications, including anesthetics, are often unsuccessful. Surgical resection can result in motor deficits. We report a medically complex pediatric case of super-refractory EPC that was successfully managed with combined focal resection and responsive neuromodulation. This case introduces neuromodulation as a treatment modality for this challenging condition.

SURG-45. OUTCOMES OF PATIENTS RECEIVING SURGICAL RESECTION AND STEREOTACTIC RADIOSURGERY VS. STEREOTACTIC RADIOSURGERY ALONE FOR MOTOR CORTEX METASTASES

Abstract BACKGROUND Local therapy for brain metastases typically involves stereotactic radiosurgery (SRS), with surgical resection considered for larger and/or symptomatic tumors. For lesions in eloquent areas, surgical management is controversial given the risks of neurologic deficits. This study compared clinical outcomes in patients with motor cortex metastases who received surgery + SRS or SRS alone. METHODS Patients treated for motor cortex metastases from 1/2018 – 12/2022 were identified. Demographic/preoperative variables included age, gender, race, tumor histology, adjuvant therapies, pre-treatment neurological exam, and Karnofsky Performance Scale. Treatment variables included the number of brain metastases, maximum tumor diameter, and radiation dose/number of fractions. Outcome measures included post-treatment neurological exam, seizures, and overall survival (OS). RESULTS 351 charts were identified – 80 surgery + SRS and 271 SRS alone. 50 consecutive patients in each group were included in this analysis. Surgery + SRS patients were younger (59.0 vs. 63.9; P=0.020) with larger tumors (2.8 vs. 0.83cm; P<0.001), while the SRS only group had more brain metastases per patient (2 vs. 6; P<0.001). No differences were seen in the remaining demographic/preoperative variables. Pre-treatment, surgery + SRS patients had significantly increased frequency (45/50, 90% vs. 25/50, 50%; P<0.001) and severity (4 vs. 5; P=0.001) of motor deficits, and a higher likelihood of seizures (25/50, 50% vs. 8/50, 16%; P<0.001). Despite the surgery + SRS group being more symptomatic pre-treatment, the frequency and severity of motor deficits and seizures was similar between cohort’s post-therapy. Surgery + SRS patients also demonstrated higher rates of pre- to post-treatment improvement in motor function (29/45, 64% vs. 3/25, 12%; P<0.001) and longer OS from the date of treatment (7.5 vs 4 months; P=0.021). CONCLUSION Given the equivalent neurological outcomes, higher rates of functional improvement, and improved oncologic outcomes, surgery should be a consideration for patients with brain metastases in eloquent areas, particularly those with symptomatic lesions.

Clinical characteristics and genetic analysis of mental retardation disorder with TRIO gene variant

Objective: To summarize the clinical and genetic characteristics of mental retardation disorder (MRD) with TRIO gene variant in children. Methods: Case series study. The data of 9 children with TRIO gene variants were collected retrospectively from August 2019 to March 2024 in Department of Neurology, Beijing Children's Hospital, Capital Medical University and Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University. The data included gender, age, intellectual and motor development, appearance, seizures, neuroimaging and genetic results. The clinical features and genotype-phenotype correlations were summarized. Results: Of the 9 children, 6 boys and 3 girls, 4 MRD63 children presented with moderate to severe developmental delays accompanied by macrocephaly; 5 MRD44 children had mild to moderate developmental delays with microcephaly. A total of 5 children had dysmorphic facial features (flat occiput, thick eyebrows, unibrow, large ears, short fingers, pale skin, yellow hair, and strabismus), 2 children experienced seizures (1 child with myoclonic seizure and 1 with absence seizure), 4 children had feeding difficulties, 1 child had congenital cataracts, 1 child had congenital heart disease, 1 child had recurrent infections, and 1 child had tiger-striped changes in the fundus examination. TRIO gene variants carried by the 9 children were all de novo, involving 8 variant sites, including 7 missense variants and 1 frameshift variant, c.3232C>T/p.R1078W (2 cases), c.3920A>G/p.Y1307C, c.4112A>T/p.H1371L, c.4283G>T/p.R1428L, c.4394A>G/p.N1465S, c.6041T>C/p.I2014T, c.6821G>A/p.R2274H, c.7027delC/p.Q2343Sfs*70. Among them, 2 sites are located in the Spectrin domain, 4 sites are in the GEFD1 domain, 2 sites are in the GEFD2 domain, and 1 site (frameshift variant) is in the PH2-SH3 domain. The individual with frameshift variant exhibit absence seizures, mild developmental delay, and the mildest phenotype. The child with myoclonic seizures was treated with valproic acid and levetiracetam for seizure control, while the child with absence epilepsy was treated with valproic acid and lamotrigine for seizure control. All 9 children underwent regular rehabilitation exercises, making slow progress. Conclusions: TRIO gene related MRD is characterized by varying degrees of developmental delay, and often accompanied by macrocephaly or microcephaly, dysmorphic facial features, and with or without seizures. The main variant types are missense variants, which are mostly concentrated in the Spectran domain and GEFD domain. p. R1078W may be a relative hotspot variant. The phenotype caused by the frameshift variant is relatively milder.

Effects of epileptic seizures on the quality of biosignals recorded from wearables.

Wearable nonelectroencephalographic biosignal recordings captured from the wrist offer enormous potential for seizure monitoring. However, signal quality remains a challenging factor affecting data reliability. Models trained for seizure detection depend on the quality of recordings in peri-ictal periods in performing a feature-based separation of ictal periods from interictal periods. Thus, this study aims to investigate the effect of epileptic seizures on signal quality, ensuring accurate and reliable monitoring. This study assesses the signal quality of wearable data during peri-ictal phases of generalized tonic-clonic and focal to bilateral tonic-clonic seizures (TCS), focal motor seizures (FMS), and focal nonmotor seizures (FNMS). We evaluated accelerometer (ACC) activity and the signal quality of electrodermal activity (EDA) and blood volume pulse (BVP) data. Additionally, we analyzed the influence of peri-ictal movements as assessed by ACC (ACC activity) on signal quality and examined intraictal subphases of focal to bilateral TCS. We analyzed 386 seizures from 111 individuals in three international epilepsy monitoring units. BVP signal quality and ACC activity levels differed between all seizure types. We found the largest decrease in BVP signal quality and increase in ACC activity when comparing the ictal phase to the pre- and postictal phases for TCS. Additionally, ACC activity was strongly negatively correlated with BVP signal quality for TCS and FMS, and weakly for FNMS. Intraictal analysis revealed that tonic and clonic subphases have the lowest BVP signal quality and the highest ACC activity. Motor elements of seizures significantly impair BVP signal quality, but do not have significant effect on EDA signal quality, as assessed by wrist-worn wearables. The results underscore the importance of signal quality assessment methods and careful selection of robust modalities to ensure reliable seizure detection. Future research is needed to explain whether seizure detection models' decisions are based on signal responses induced by physiological processes as opposed to artifacts.

Identification of a Novel Frameshift variant of the ATRX gene: a Case Report and Review of the genotype–phenotype relationship

BackgroundX-linked intellectual disability-hypotonic facies syndrome-1 (MRXHF1) and Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome are caused by pathogenic variant in the ATRX gene, a member of the switch/sucrose non-fermentable (SWI-SNF) protein family that exhibits chromatin remodeling activity. These syndromes show a wide spectrum of clinical manifestations, such as distinctive dysmorphic features, mild-to-profound intellectual disability, motor development delay, seizures, urogenital abnormalities, and gastrointestinal disorders.Case presentation and literature reviewA 3-year-old boy from a Chinese non-consanguineous family was diagnosed with MRXHF1 by whole-exome sequencing. Comprehensive family history information was obtained. The Medline database was searched until 1st Aug 2023 for articles related to ATRX pathogenic variant. Data on gene/protein mutations and clinical symptoms were extracted. The proband showed intellectual disability, motor development delay, typical facial abnormalities, urogenital defect, behavior problems, and optical nerve dysplasia. A novel frameshift mutation c.399_400dup, (p.Leu134Cysfs*2) in the ATRX gene was the primary cause, which occurs right before the ATRXDNMT3-DNMT3L (ADD) domain of ATRX protein. Missense mutation is the most common variation type. The ADD and helicase-like domains are the most frequently affected domains. Epilepsy, congenital heart disease, urogenital defect, acoustic defect, and optical defect are more prevalent in patients with frameshift mutations compared to those with missense mutations. There are more urogenital defects with C-terminal frameshift mutations than with N-terminal frameshift mutations.ConclusionWe described a novel frameshift mutation in the ATRX gene in a patient with MRXHF1 syndrome and summarized the genotype–phenotype relationship of ATRX pathogenic variant by variation type and affected protein domain. The regulatory mechanism underlying ATRX variant requires comprehensive analysis in future studies.

Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation.

Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by motor disfunction, seizures, intellectual disability, speech deficits, and autism-like behavior, showing high comorbidity with Autism Spectrum Disorders (ASD). It is known that stimulation of the serotonin receptor 7 (5-HT7R) can rescue some of the behavioral and neuroplasticity dysfunctions in animal models of Fragile X and Rett syndrome, two pathologies associated with ASD. In view of these observations, we hypothesised that alterations of 5-HT7R signalling might also be involved in AS. To test this hypothesis, we stimulated 5-HT7R with the selective agonist LP-211 to investigate its possible beneficial effects on synaptic dysfunctions and altered behavior in the AS mice model. In mutant mice, we observed impairment of the synaptic machinery of protein synthesis, which was reversed by 5-HT7R activation. Moreover, stimulation of 5-HT7R was able to: i) enhance dendritic spine density in hippocampal neurons, which was reduced in AS mice; ii) restore impaired long-term potentiation (LTP) in hippocampal slices of the AS mice; iii) improve cognitive performance of the mutant animals subjected to the fear conditioning paradigm. Altogether, our results, showing beneficial effects of 5-HT7R stimulation in restoring molecular and cognitive deficits associated with AS, suggest that targeting 5-HT7R could be a promising therapeutic approach for the pathology.

Deep brain stimulation of the subthalamic nucleus for a patient with drug resistant juvenile myoclonic epilepsy: 1year follow-up.

Drug-resistant juvenile myoclonic epilepsy (DR-JME) remains a significant challenge in neurology. Traditional management strategies often fail to achieve satisfactory control, necessitating innovative treatments. This case report aims to evaluate the efficacy and safety of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN-DBS) in a patient with DR-JME. We describe the treatment of a patient with DR-JME using STN-DBS. The patient underwent implantation and received high-frequency stimulation (HFS) at the STN. One year post-implantation, the patient demonstrated a substantial reduction in motor seizure frequency by 87.5%, with improvements in quality of life and seizure severity by 52.0% and 46.7%, respectively. No adverse events were reported during the follow-up period. This case represents the first report of favorable outcomes with STN-DBS in a patient with DR-JME, suggesting that long-term HFS of the STN may be a promising treatment option for patients suffering from this condition.

Characteristics of motion signal profiles of tonic-clonic, tonic, hyperkinetic, and motor seizures extracted from nocturnal video recordings.

In this study, characteristics of signal profiles formed by motion, oscillation, and sound signals were analyzed to evaluate generalizability and variability in a single patient setting (intra-patient variability) and between patients (inter-patient variability). As a secondary objective, the effect of brivaracetam intervention on signal profiles was explored. Patient data included 13 hyperkinetic seizures, 65 tonic seizures, 13 tonic-clonic seizures, and 138 motor seizures from 11 patients. All patients underwent an 8-week monitoring, and after a 3-week baseline, brivaracetam was initiated. Motion, oscillation, and sound features extracted from the video were used to form signal profiles. Variance of signals was calculated, and combined median and quartile visualizations were used to visualize the results. Similarly, the effect of intervention was visualized. Hyperkinetic motion signals showed a rapid increase in motion and sound signals without oscillations and achieved low intra-patient variance. Tonic component created a recognizable peak in motion signal typical for tonic and tonic-clonic seizures. For tonic seizures, inter-patient variance was low. Motor signal profiles were varying, and they did not form a generalizable signal profile. Visually recognizable changes were observed in the signal profiles of two patients. Video-based motion signal analysis enabled the extraction of motion features characteristic for different motor seizure types which might be useful in further development of this system. Tonic component formed a recognizable seizure signature in the motion signal. Hyperkinetic and motor seizures may have not only significantly different motion signal amplitude but also overlapping signal profile characteristics which might hamper their automatic differentiation. Motion signals might be useful in the assessment of movement intensity changes to evaluate the treatment effect. Further research is needed to test generalizability and to increase reliability of the results.

Fluctuations in resting motor threshold during electroconvulsive and magnetic seizure therapy

Objectives Magnetic seizure therapy (MST) is more benign than electroconvulsive therapy (ECT) in terms of cognitive impairment. However, whether these two ‘artificial seizures’ facilitate the central motor neural pathway and the motor cortical effects have not been investigated. The study aimed to compare the effects of ECT and MST on motor-evoked potential (MEP) in patients with mental disorders. Methods Forty-nine patients with mental disorders (major depressive disorder, bipolar disorder type II and schizophrenia [SCZ]) received 6 treatment sessions of vertex MST versus 6 bifrontal ECT treatments in a nonrandomized comparative clinical design. Data on the duration of motor seizures were collected for each treatment. MEP latency and the resting motor threshold (rMT) were measured at baseline and after every two treatments. Comparisons were performed between or within the groups. Results Seizure durations were significantly longer in the ECT group compared to the MST group across multiple sessions. Both MST and ECT demonstrated a significant reduction in rMT in the left and right hemispheres after the fourth (T3) and sixth treatments (T4) compared to baseline (T1). However, there were no significant changes in MEP latency within or between the groups throughout the treatment sessions. The only difference was that the rMT in the left cerebral hemisphere was significantly lower after T4 than after the second treatment (T2). There was no difference in rMT between the ECT and MST groups. Conclusions Both ECT and MST facilitate the central motor pathway, with a shared mechanism of increased motor cortex excitability.

Long-term Effect of Multichannel tDCS Protocol in Patients with Central Cortex Epilepsies Associated with Epilepsia Partialis Continua.

Epilepsia partialis continua (EPC) is a rare type of focal motor status epilepticus that causes continuous muscle jerking in a specific part of the body. Experiencing this type of seizure, along with other seizure types, such as focal motor seizures and focal to bilateral tonic-clonic seizures, can result in a disabling situation. Non-invasive brain stimulation methods like transcranial direct current stimulation (tDCS) show promise in reducing seizure frequency (SF) when medications are ineffective. However, research on tDCS for EPC and related seizures is limited. We evaluated personalized multichannel tDCS in drug-resistant EPC of diverse etiologies for long-term clinical efficacy We report three EPC patients undergoing a long-term protocol of multichannel tDCS. The patients received several cycles (11, 9, and 3) of five consecutive days of stimulation at 2mA for 2 × 20min, targeting the epileptogenic zone (EZ), including the central motor cortex with cathodal electrodes. The primary measurement was SF changes. In three cases, EPC was due to Rasmussen's Encephalitis (case 1), focal cortical dysplasia (case 2), or remained unknown (case 3). tDCS cycles were administered over 6 to 22 months. The outcomes comprised a reduction of at least 75% in seizure frequency for two patients, and in one case, a complete cessation of severe motor seizures. However, tDCS had no substantial impact on the continuous myoclonus characterizing EPC. No serious side effects were reported. Long-term application of tDCS cycles is well tolerated and can lead to a considerable reduction in disabling seizures in patients with various forms of epilepsy with EPC.

Glial expression of Drosophila UBE3A causes spontaneous seizures that can be modulated by 5-HT signaling

Misexpression of the E3 ubiquitin ligase gene UBE3A is thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, additional genomic copies of UBE3A give rise to the autism, muscle hypotonia and spontaneous seizures characteristics of the disorder. In a Drosophila model of Dup 15q syndrome, it was recently shown that glial-driven expression of the UBE3A ortholog dube3a led to a “bang-sensitive” phenotype, where mechanical shock triggers convulsions, suggesting glial dube3a expression contributes to hyperexcitability in flies. Here we directly compare the consequences of glial- and neuronal-driven dube3a expression on motor coordination and seizure susceptibility in Drosophila.To quantify seizure-related behavioral events, we developed and trained a hidden Markov model that identified these events based on automated video tracking of fly locomotion. Both glial and neuronal driven dube3a expression led to clear motor phenotypes. However, only glial-driven dube3a expression displayed spontaneous seizure-associated immobilization events, that were clearly observed at high-temperature (38 °C). Using a tethered fly preparation amenable to electrophysiological monitoring of seizure activity, we found glial-driven dube3a flies display aberrant spontaneous spike discharges which are bilaterally synchronized. Neither neuronal-dube3a overexpressing flies, nor control flies displayed these firing patterns. We previously performed a drug screen for FDA approved compounds that can suppress bang-sensitivity in glial-driven dube3a expressing flies and identified certain 5-HT modulators as strong seizure suppressors. Here we found glial-driven dube3a flies fed the serotonin reuptake inhibitor vortioxetine and the 5-HT2A antagonist ketanserin displayed reduced immobilization and spike bursting, consistent with the previous study. Together these findings highlight the potential for glial pathophysiology to drive Dup15q syndrome-related seizure activity.

Combined generalized and focal epilepsy with reflex features in Adaptor protein complex 4-associated hereditary spastic paraplegias: A cohort observational study

BackgroundPatients with genetic deficiency of the adaptor protein complex 4 (AP-4) exhibit earlyonset developmental delay, spastic diplegia, intellectual disability, speech impairment. The phenotype overlaps with other hereditary spastic paraplegias and cerebral palsies. Febrile seizures are common at onset. Epilepsy has been described in more than half of cases, arising in early infancy often with status epilepticus, but no typical seizure semiology or electroencephalographic features have been identified thus far. PurposeWe aimed to specifically investigate the epileptological characteristics of the syndrome to unveil possible biomarkers of seizure development and prognosis in AP-4 deficiency. MethodsObservational cohort study on patients with bi-allelic pathogenic variants in AP-4 subunits and epilepsy. We focused on the seizure semiology, electroencephalographic characteristics and response to antiseizure medications. ResultsPatients harboured pathogenic variants in AP4S1 (n = 5) or AP4M1 (n = 1). The phenotype included spastic paraparesis, intellectual disability, speech/language impairment, microcephaly, and MRI evidence of hypoplasia of the corpus callosum. In 66 % of the patients, febrile seizures preceded the onset of epilepsy, which spanned from infancy to adolescence (range=14 months-13 years). Absences (66 %) and focal motor seizures (50 %) were common. No patient met the criteria for drug-resistance. Peculiar electroencephalographic features arose after the epilepsy onset and persisted at long-term follow-up: bilateral and asynchronous focal discharges combined with independent diffuse spike-wave-discharges (100 %) and reflex abnormalities (66 %). ConclusionIn AP-4 complex disease, epilepsy could arise beyond early infancy, until adolescence, with variable combination of generalized and focal seizures. The prognosis was favourable. We observed a common electroencephalographic signature - combined focal/generalized and reflex abnormalities - which may constitute a biomarker of AP-4 deficiency with epilepsy, applicable to inform genetic testing and disentangle the differential diagnosis.

Dihydropyrimidinase enzyme deficiency and congenital isolated adrenocorticotrophin deficiency: dual genetic diagnosis in a Sri Lankan boy.

We report on a male patient who was investigated for frequent apneic episodes, feeding problems, hypotonia, and left-sided middle cerebral artery infarction in the magnetic resonance imaging at 2 weeks of age. Primary diagnosis of dihydropyrimidinase (DPYS) deficiency was suspected following the analysis of urine for organic acid; DPYS deficiency was strongly suggested by the presence of dihydrouracil, thymine, and uracil. Subsequent genetic evaluation by whole exome sequencing revealed 2 separate mutations, homozygous pathogenic variant c.1010T>C p.Leu337Pro of the DPYS gene, resulting in DPYS deficiency, and homozygous pathogenic variant c.535C>T p.Arg179* of TBX19 gene, which is associated with autosomal recessive congenital isolated adrenocorticotrophic hormone deficiency. Currently, the patient is 2 years old, and he has gross motor retardation and seizure disorder. We suggest that the clinical phenotype of the proband can be a result of mixed expression of both mutations.

Assessment of the potential protective effectsof culture filtrate ofTrichoderma harzianum to ameliorate the damagedhistoarchitecture of brain in epileptic rats.

The simultaneous hyperexcitability of the neural network is the most well-known manifestation of epilepsy that causes recurrent seizures. The current study was aimed to examine any potential safety benefits of the culture filtrate of Trichoderma harzianum (ThCF) to ameliorate damaged histoarchitecture of the brain in epileptic rats by assessing seizure intensity scale and behavioral impairments and follow up the spontaneous motor seizures during status epilepticus phases in rats. Twenty-four rats were divided into four groups; control (C), epileptic (EP) valproic acid-treated epileptic (EP-VPA), and epileptic treated with T. harzianum cultured filtrate (ThCF). In addition to a seizure intensity score and behavioral tests, routine H&E and Golgi-Copsch histopathology, were used to examine the cell somas, dendrites, axons, and neural spines. ThCF treatment increased activity and recorded movements during grooming, rearing, and ambulation frequency. Brain tissues of epileptic rats exhibited detached meninges, hypercellularity, mild edema in the cortex and markedly degenerated neurons, degenerated glial cells, and microcyst formation in the hippocampus. Moreover, brains of EP-ThCF were noticed with average blood vessels, and increased dendritogenesis. The current data revealed some of negative effects of epileptogenesis brought on by seizure intensity score and retarded histopathological alterations in the hippocampus. Therefore, the study is forecasting to identify novel active components from the metabolites of T. harzianum with a crucial therapeutic role in various disorders.

Clinical pattern, neuroimaging findings and outcome of Acute Disseminated Encephalomyelitis in children: A retrospective study.

To determine the clinical spectrum, neuroimaging findings, and outcome of Acute Disseminated Encephalomyelitis (ADEM) in children. We conducted a descriptive cross sectional study of all children aged 6 months to 18 years, diagnosed with ADEM at Aga Khan University Hospital, Karachi from January 2018 till December 2022. This retrospective study enrolled 30 cases of ADEM, with a mean age of 6.43 ± 4.079, including 13 males and 17 females. The average hospital stay was 7.29 ± 4.379 days. The most common clinical features were fever, headache, and altered consciousness, while motor deficit was observed in 15 (53.5%) patients. Abnormal cerebrospinal fluid was found in 14 (46.6%) patients. Brain MRI identified bilateral and multifocal lesions in 22 (78.6%) patients, with brainstem lesions detected in 7 (25%) patients. Treatment included IV methylprednisolone (22; 73%), IVIG (9; 30%), or both (6; 20%). Clinical improvement was observed in 25 (89.3%) patients, with residual weakness present in eight (26%) patients at discharge. There was one reported death. Long-term complications included motor deficits, seizures, poor scholastic performance, and behavioral issues. The clinical presentation of ADEM is variable, but the most common symptoms are fever, headache, and altered consciousness. Despite generally favorable outcome, long-term monitoring revealed that patients may experience motor deficits, seizures, cognitive impairment, and academic difficulties.

Evaluating the Efficacy of Vagus Nerve Stimulation across 'Minor' and 'Major' Seizure Types: A Retrospective Analysis of Clinical Outcomes in Pharmacoresistant Epilepsy.

Background: Evaluating the differential impact of vagus nerve stimulation (VNS) therapy across various seizure types, our study explores its efficacy specifically in patients with categorized minor and major seizures. Methods: We conducted a retrospective cohort study involving 76 patients with pharmacoresistant epilepsy treated at the University Emergency Hospital of Bucharest between 2021 and 2024. Seizures were classified as 'minor' (including focal-aware and non-motor/absence seizures) and 'major' (including focal to bilateral tonic-clonic and generalized motor seizures), based on modified International League Against Epilepsy (ILAE) criteria. This classification allowed us to assess the response to VNS therapy, defined by a 50% or greater reduction in seizure frequency at the 12-month follow-up. Results: Our findings reveal that major seizures respond more favorably to VNS therapy, significantly reducing both frequency and intensity. In contrast, minor seizures showed a less pronounced response in frequency reduction but noted improvements in neurocognitive functions, suggesting a nuanced benefit of VNS in these cases. Conclusion: The study underscores the importance of seizure type in determining the efficacy of VNS therapy, advocating for personalized treatment approaches based on seizure classification. This approach could potentially enhance clinical outcomes by tailoring VNS settings to specific seizure types, improving overall management strategies in pharmacoresistant epilepsy.

Phenotypic and mutational spectrum of 17 Chinese patients with Menkes Disease.

Menkes Disease (MD) is a fatal X-linked recessive disorder caused by mutations in the ATP7A gene. Severe cases typically die before the age of three. Mild MD and occipital horn syndrome are variants of MD characterized by a less severe phenotype and longer survival. This case series aims to validate previous findings, expand the clinical phenotype, identify novel ATP7A mutations of MD patients. Observational data with follow-up were collected from 17 genetically diagnosed Chinese MD patients. All 17 patients exhibited neurological symptoms, including delayed motor milestones (100%) and seizures (58.8%). Unspecific pregnancy or delivery complications occurred in 9 patients (52.9%). The most prevalent connective tissue problems were abnormal hair (76.5%), followed by skeletal and dental abnormalities (52.9%), skin problems (41.2%) and hernia (35.3%). Sensorineural hearing loss (17.6%) was previously unreported. Coronary artery aneurysm and patent foramen ovale (5.9%) were infrequent. One 16-year-old boy carries pathological exon 3-4 deletion, presents novel mild phenotype including short stature and cerebellar ataxia. Out of 13 patients with follow-up (median: 24 months), 7 patients (53.8%) died with median survival of 40 months (range: 21-48 months), 3 patients (23.1%) show severe motor development delay and 2 (15.4%) have refractory epilepsy, only the mild MD patient shows improved cerebellar ataxia. Sixteen ATP7A mutations were identified including 6 small indels (37.5%), 5 nonsense mutations (31.2%), 2 missense mutations (12.5%), 2 exon deletions (12.5%), and 1 splice site mutation (6.25%). Fourteen mutations were novel. Our study further broadens the phenotypic and genotypic spectrums of Menkes disease.

New-Onset Seizures and Seizure Worsening in the Course of COVID-19 Infection.

The aim of our study is to assess the clinical manifestations, investigation results, and outcomes in Bulgarian patients with seizures in the course of COVID-19 infection. We performed an open, prospective study during a 12-month period from January 2021 with the participation of 290inpatients and outpatients with seizures whoattended the Clinic of Neurology at the University Hospital in Plovdiv, Bulgaria. After a detailed anamnesis, they underwent neurological examination, EEG, neuroimaging, and lumbar puncture when needed. There was a prospective one-year follow-up regarding seizure frequency, EEG, and treatment. In 18 (5.9%) patients, seizures were related to COVID-19 infection. Nine (3.1%) patients had new-onset seizures, and in nine (3.1%) participants with epilepsy, there was a worsening of seizure frequency. New-onset seizures were more likely to occur inpeople above 65 years of age, within one to two months from the infection diagnosis. In one participant, seizures were related to fever. The most common seizure types were generalized tonic-clonic and focal motor seizures with/without loss of awareness. Antiseizure medications were started in seven participants. Viral encephalopathy was confirmed in two patients, one of them died. EEG showed focal epileptiform activity in four participants. The one-year prospective observation showed a favorable outcome in five patients who were without seizures, had normal EEG, and three were without treatment. Seizure frequency increase or seizure recurrence was typically observed for a short period of time in the epilepsy group. EEG was worsened in one patient and treatment changes were needed in five participants. In conclusion, our study results provide evidence about the progress and possible relationshipbetweennew-onset seizures and seizure worsening with COVID-19 infection.

Effects of ganaxolone on non-seizure outcomes in CDKL5 Deficiency Disorder: Double-blind placebo-controlled randomized trial

CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2–19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3–10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI –2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo.

The Effect of Remimazolam on Seizure Profile, Hemodynamics, and Recovery in Patients With Electroconvulsive Therapy Comparison With Propofol and Etomidate: A Retrospective Study.

To compare seizure-related, hemodynamic, and recovery outcomes when using remimazolam for ECT with those of other anesthetics, specifically propofol and etomidate. A total of 49 patients who underwent 405 ECT treatment sessions under general anesthesia were retrospectively analyzed. Remimazolam, propofol, and etomidate were used for 93, 138, and 174 ECT sessions, respectively. The primary outcome was durations of motor and electroencephalogram (EEG) seizure activity, whereas secondary outcomes included hemodynamics (ie, mean arterial pressure [MAP] and heart rate [HR] at various time points from induction to postanesthesia care unit [PACU] discharge), antihypertensive drugs administration after electrical stimulus, and recovery profiles (ie, length of PACU stay and incidence of postictal confusion). Durations of motor and EEG seizures were shorter for remimazolam than etomidate (motor, P < 0.001; EEG, P = 0.003) but similar compared with propofol (motor, P = 0.191; EEG, P = 0.850). During seizure, remimazolam showed a comparable MAP and HR to etomidate (MAP: P = 0.806; HR: P = 0.116). The antihypertensive drug use was lowest for remimazolam (6.8%), followed by propofol (35.6%) and etomidate (65.6%), and the mean length of PACU stay was comparable for remimazolam (19.7 min), propofol (22.8 min), and etomidate (24.5 min). The occurrence of postictal confusion did not differ among the 3 agents (P > 0.050). Remimazolam is a promising anesthetic option for ECT because of its comparable seizure profiles, stable hemodynamics, and comparable PACU stay when compared with propofol and etomidate without additional adverse events.