RESUMEN
Seizure following cerebrospinal fluid (CSF) rhinorrhoea surgery or surgery of the skull base almost always implies postoperative meningoencephalitis, unless proven otherwise. Here, we present the case of a middle-aged female in her 40's who underwent surgical CSF fistula closure and developed seizure on the eighth postoperative day. She was diagnosed to have posterior reversible encephalopathy syndrome (PRES). Early diagnosis and prompt initiation of treatment ensured that she had a complete recovery. Although not reported in the literature, PRES should always be a differential diagnosis in such situations, as delay in diagnosis may result in significant morbidity and rarely mortality.
Asunto(s)
Rinorrea de Líquido Cefalorraquídeo , Complicaciones Posoperatorias , Convulsiones , Humanos , Femenino , Rinorrea de Líquido Cefalorraquídeo/cirugía , Rinorrea de Líquido Cefalorraquídeo/etiología , Rinorrea de Líquido Cefalorraquídeo/diagnóstico , Convulsiones/etiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Adulto , Síndrome de Leucoencefalopatía Posterior/diagnóstico , Síndrome de Leucoencefalopatía Posterior/etiología , Diagnóstico Diferencial , Imagen por Resonancia MagnéticaRESUMEN
Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial neoplasm of the central nervous system accounting for less than 1% of all astrocytomas. Similar to other gliomas, it can rarely arise from glial nests in the meninges, manifesting as an extra-axial mass mimicking a meningioma. Extra axial PXA is an extremely rare entity. Therefore, there are no standardized guidelines. In this article, we report the fourth case, so far, of a solitary primary extra-axial PXA mimicking a meningioma in a 23-year-old woman who presented with temporal seizures and features of raised intracranial pressure. Through this case, we tried to discuss all treatment options.
Asunto(s)
Astrocitoma , Neoplasias Meníngeas , Meningioma , Convulsiones , Humanos , Femenino , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/diagnóstico , Astrocitoma/patología , Astrocitoma/diagnóstico , Adulto Joven , Convulsiones/etiología , Meningioma/patología , Meningioma/diagnóstico , Diagnóstico Diferencial , Hipertensión Intracraneal/etiología , Hipertensión Intracraneal/diagnósticoRESUMEN
Automatic seizure detection has significant value in epilepsy diagnosis and treatment. Although a variety of deep learning models have been proposed to automatically learn electroencephalography (EEG) features for seizure detection, the generalization performance and computational burden of such deep models remain the bottleneck of practical application. In this study, a novel lightweight model based on random convolutional kernel transform (ROCKET) is developed for EEG feature learning for seizure detection. Specifically, random convolutional kernels are embedded into the structure of a wavelet scattering network instead of original wavelet transform convolutions. Then the significant EEG features are selected from the scattering coefficients and convolutional outputs by analysis of variance (ANOVA) and minimum redundancy-maximum relevance (MRMR) methods. This model not only preserves the merits of the fast-training process from ROCKET, but also provides insight into seizure detection by retaining only the helpful channels. The extreme gradient boosting (XGboost) classifier was combined with this EEG feature learning model to build a comprehensive seizure detection system that achieved promising epoch-based results, with over 90% of both sensitivity and specificity on the scalp and intracranial EEG databases. The experimental comparisons showed that the proposed method outperformed other state-of-the-art methods for cross-patient and patient-specific seizure detection.
Asunto(s)
Aprendizaje Profundo , Electroencefalografía , Convulsiones , Análisis de Ondículas , Humanos , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Electroencefalografía/métodos , Redes Neurales de la Computación , Procesamiento de Señales Asistido por Computador , Sensibilidad y Especificidad , Aprendizaje AutomáticoRESUMEN
Arachnoid cysts are sacs within the arachnoid membrane, filled with cerebrospinal fluid, and overwhelmingly asymptomatic; however, they can also lead to neurological symptoms such as epilepsy. The dependence of AC on epilepsy has been a subject of controversy because of studies with mixed results on whether AC contributes to seizure activity. This is a narrative review for the synthesis of available present research on the pathophysiological mechanisms of epilepsy, clinical presentation, and treatment options in patients with epilepsy and ACs. Some find no impactful association between ACs and seizures, while others point out the probable role of ACs in Epileptogenesis. Endoscopic fenestration and similar surgical interventions were found quite effective at reducing the frequency of seizures for selected patients, although not all of them achieve complete seizure control. Such a decision needs to be tailored on the basis of considerations such as localization and size of cysts and general health conditions. Future research should investigate the genetic and molecular basis of ACs and, based on large prospective long-term studies, define the AC-epilepsy relationship and refine treatment strategies in affected individuals.
Asunto(s)
Quistes Aracnoideos , Epilepsia , Convulsiones , Quistes Aracnoideos/cirugía , Quistes Aracnoideos/complicaciones , Humanos , Epilepsia/cirugíaRESUMEN
For patients with epilepsy, one of the biggest problems is the unpredictability of the time when the next seizure will occur. Interestingly, some epileptic patients experience a sensory sensation preceding seizures, called aura, which helps them move to safety before a seizure. Here, we describe the development of the first animal model of auras, which could allow for a more detailed study of this phenomenon. Specifically, in mice, we presented sensory stimuli (sound and light cues) a few seconds before kindling an animal to induce seizures. Animals were kindled by electrical stimulation in the basolateral amygdalar nucleus. Over the course of stimulation sessions, animals started showing progressively stronger freezing behavior to sensory cues preceding kindling. Interestingly, seizures are known to cause retrograde amnesia, thus it was surprising that the association between seizures and preceding sensory cues developed in all experimental animals. In summary, our experiments show that similarly to auras, a sensory sensation can be associated with incoming generalized seizures and is not erased by retrograde amnesia.
Asunto(s)
Señales (Psicología) , Modelos Animales de Enfermedad , Excitación Neurológica , Convulsiones , Animales , Ratones , Convulsiones/fisiopatología , Excitación Neurológica/fisiología , Masculino , Estimulación Eléctrica , Ratones Endogámicos C57BL , Estimulación AcústicaRESUMEN
Sulfuryl fluoride is a kind of pesticide with strong permeability, convenient use at low temperature, non-corrosive and other characteristics, which can kill food pests and has strong lethality to termites. In acute sulfuryl fluoride poisoning, patients can see recurrent convulsions, epileptic electroencephalogram abnormalities such as matrix spikes or high amplitude spikes. In this paper, a patient with sulfuryl fluoride poisoning with convulsion-based mental system symptoms was reported, and after clinical treatment with dexamethasone and phenobarbital sodium, the patient was cured and discharged.
Asunto(s)
Convulsiones , Humanos , Convulsiones/inducido químicamente , Masculino , Intoxicación por Gas , Adulto , Ácidos Sulfínicos/envenenamiento , Recurrencia , Plaguicidas/envenenamientoRESUMEN
BACKGROUND: Activation procedures (APs) are adopted during routine electroencephalography (rEEG) to provoke interictal epileptiform abnormalities (EAs). This study aimed to observe interictal and ictal (EAs) of different EEG patterns, provoked by various APs. METHODOLOGY: This cross-sectional study was performed in the neurology department of King Fahd hospital of university, Saudi Arabia. The EEGs and medical records of patients who presented for EEG recordings were screened initially, then 146 EEGs provoked EAs due to utilization of APs, were included for analysis. RESULTS: Among all EEGs with provoked EAs, Non-rapid eye movement sleep (NREM) provoked EAs in 93 (63.7%) patients with following patterns, focal spike wave discharges (FSWDs) 45 (P= 0.01), focal spike wave discharges with bilateral synchrony (FSWDBS) 27 (P=0.03) and generalized spike wave discharges (GSWDs) 46 (P=0.01). Intermittent photic stimulation (IPS) most significantly provoked FSWDs in 07 patient (P =0.01) and GSWDs in 30 patients (P=<0.001) 7 patients (P = 0.01) and GSWDs in 30 patients (P < 0.001). Hyperventilation (HV) was associated with a higher occurrence of GSWDs in 37 patients (P =0.01). Female sex 7 (P = 0.02), provoked GSWDs 3 (P = 0.03), NREM sleep 8 (P = 0.04), prolonged EEG record 3 (P = 0.02), clinical events during recording 5 (P ≤ 0.01), diagnosis of genetic 05 (P = 0.03), and immune-mediated epilepsies 2 (P = 0.001) were associated with the provocation of ictal EAs; however, in multiple logistic regression analysis, no statistically significant association of these variables (P ≥ 0.05 each) was noted. CONCLUSION: The provocation of EAs in rEEG with different APs varies according to circumstances, including seizure types, epilepsy etiology, and the type of AP applied. These clinical and procedural parameters affect the diagnostic yield of rEEG and need careful consideration during rEEG recordings. APs adopted during rEEG recording can induce FSWDs, FSWDBS, and GSWDs in the form of either interictal or ictal EAs in various etiologies of epilepsy. Ictal EAs may appear in the form of GSWDs, during NREM sleep, in prolonged EEG records; however, their independent association needs to be evaluated in larger sample studies. Further, prospective cohort studies with adequate sample sizes are warranted.
Résumé Contexte:Des procédures d'activation (AP) sont adoptées lors d'une électroencéphalographie de routine (rEEG) pour provoquer des anomalies épileptiformes (EA) intercritiques. Cette étude visait à observer les inter-critiques et critiques (EA) de différents modèles EEG, provoqués par divers PA.Méthodes:Cette étude transversale a été réalisée dans le département de neurologie de l'hôpital universitaire King Fahd de Khobar, en Arabie Saoudite. Les EEG et les dossiers médicaux des patients qui se sont présentés pour des enregistrements EEG ont été initialement examinés, puis 146 EEG avec des EA provoqués lors de l'utilisation des AP ont été inclus pour analyse.Résultats:Parmi tous les EEG avec des AE provoqués, le sommeil à mouvements oculaires non rapides (NREM) a provoqué des EA chez 93 (63,7 %) patients avec les schémas suivants : décharges d'ondes de pointe focales (FSWD) 45 (P = 0,01), onde de pointe focale avec bilatéral synchronisation (FSWBS) 27 (P = 0,03) et décharges d'ondes de pointe généralisées (GSWD) 46 (P = 0,01). La stimulation photique intermittente (IPS) a provoqué de manière plus significative des FSWD chez 07 patients (P = 0,01) et des GSWD chez 30 patients (P = < 0,001) 7 patients (P = 0,01) et des GSWD chez 30 patients (P < 0,001). L'hyperventilation (HV) était associée à une fréquence plus élevée de GSWD chez 37 patients (P = 0,01). Sexe féminin 07 (P = 0,02), GSWD provoqués 03 (P = 0,03), sommeil NREM 08 (P = 0,04), enregistrement EEG prolongé 03 (P = 0,02), événements cliniques lors de l'enregistrement 05 (P = < 0,01), diagnostic des épilepsies génétiques 05 (P = 0,03) et des épilepsies à médiation immunitaire 02 (P = 0,001) étaient associées à la provocation d'EA critiques, cependant, dans l'analyse de régression logistique multiple, aucune association statistiquement significative de ces variables (P = > 0,05 chacune) était noté.Conclusion:La provocation d'EA dans l'EEGr avec différents AP varie en fonction des circonstances, notamment des types de crises, de l'étiologie de l'épilepsie et du type d'AP appliqué. Ces paramètres cliniques et procéduraux affectent le rendement diagnostique du rEEG et doivent être soigneusement pris en compte lors des enregistrements rEEG. Les AP adoptés lors de l'enregistrement rEEG peuvent induire des FSWD, des FSWBS et des GSWD sous la forme d'EA inter-critiques ou critiques dans diverses étiologies de l'épilepsie. Les EA critiques peuvent apparaître sous forme de GSWD, pendant le sommeil NREM, dans les enregistrements EEG prolongés; cependant, leur association indépendante doit être évaluée dans des études sur un échantillon plus large. De plus, des études de cohortes prospectives avec des échantillons de taille adéquate sont justifiées.
Asunto(s)
Electroencefalografía , Epilepsia , Convulsiones , Humanos , Electroencefalografía/métodos , Femenino , Masculino , Estudios Transversales , Adulto , Epilepsia/fisiopatología , Epilepsia/diagnóstico , Arabia Saudita , Persona de Mediana Edad , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Adolescente , Adulto JovenRESUMEN
Drug-resistant epilepsy presents significant challenges in treating epileptic patients, leading to recurrent seizures and necessitating the use of polypharmacy with anti-epileptic drugs. Both of these conditions contribute to increased oxidative stress, which is detrimental to the brain. The aim of this study was to determine the role of vitamins C and E in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients. This was a double-blinded, randomized clinical trial with a placebo, parallel design, and block randomization. The subjects were drug-resistant epileptic patients aged 1-18 years who received routine treatment. Randomization was performed on 100 patients who were divided into the treatment or placebo groups. The patients received a combination of vitamin C (100 mg/day) and vitamin E (200 IU/day for those <5 years or 400 IU/day for those ≥5 years) or a placebo for eight weeks. Malondialdehyde (MDA) levels and seizure frequency were measured prior to and after the intervention. A total of 42 and 46 patients were followed till the end of the study in the intervention and placebo groups, respectively. Our data indicated that the MDA levels prior to treatment were not significantly different between the treatment and placebo groups (0.901 vs 0.890 mmol/mL, p=0.920) and were significantly reduced after the treatment in both the treatment group (p<0.001) and placebo group (p=0.028). The changes in MDA levels (between post- and pre-treatment) were also not significantly different between the two groups (p=0.181). Our per-protocol analysis indicated that the reduction in seizure frequency was significantly higher in the treatment group compared to the placebo group (95% vs 35%, p<0.001), with 92% and 60% relative and absolute risk reduction, respectively. The intention-to-treat analysis also indicated that the reduction in seizure frequency was significantly higher in the intervention group than in the control group (80% vs 32%, p<0.001), with relative and absolute risk reduction of 70% and 48%, respectively. There was no significant relationship between changes in MDA levels and seizure frequency in either group. In conclusion, vitamins C and E could reduce seizure frequency and, therefore, could be considered as adjuvant therapy in drug-resistant epileptic patients.
Asunto(s)
Antioxidantes , Ácido Ascórbico , Epilepsia Refractaria , Estrés Oxidativo , Vitamina E , Humanos , Estrés Oxidativo/efectos de los fármacos , Masculino , Femenino , Método Doble Ciego , Ácido Ascórbico/uso terapéutico , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacología , Epilepsia Refractaria/tratamiento farmacológico , Antioxidantes/uso terapéutico , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Adolescente , Vitamina E/administración & dosificación , Vitamina E/farmacología , Vitamina E/uso terapéutico , Niño , Preescolar , Malondialdehído , Lactante , Convulsiones/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/farmacología , Anticonvulsivantes/administración & dosificaciónRESUMEN
After seizures, the hyperactivation of extracellular signal-regulated kinases (ERK1/2) causes mitochondrial dysfunction. Through the guidance of dynamin-related protein 1 (DRP1), ERK1/2 plays a role in the pathogenesis of several illnesses. Herein, we speculate that ERK1/2 affects mitochondrial division and participates in the pathogenesis of epilepsy by regulating the activity of DRP1. LiCl-Pilocarpine was injected intraperitoneally to establish a rat model of status epilepticus (SE) for this study. Before SE induction, PD98059 and Mdivi-1 were injected intraperitoneally. The number of seizures and the latency period before the onset of the first seizure were then monitored. The analysis of Western blot was also used to measure the phosphorylated and total ERK1/2 and DRP1 protein expression levels in the rat hippocampus. In addition, immunohistochemistry revealed the distribution of ERK1/2 and DRP1 in neurons of hippocampal CA1 and CA3. Both PD98059 and Mdivi-1 reduced the susceptibility of rats to epileptic seizures, according to behavioral findings. By inhibiting ERK1/2 phosphorylation, the Western blot revealed that PD98059 indirectly reduced the phosphorylation of DRP1 at Ser616 (p-DRP1-Ser616). Eventually, the ERK1/2 and DRP1 were distributed in the cytoplasm of neurons by immunohistochemistry. Inhibition of ERK1/2 signaling pathways downregulates p-DRP1-Ser616 expression, which could inhibit DRP1-mediated excessive mitochondrial fission and then regulate the pathogenesis of epilepsy.
Asunto(s)
Dinaminas , Flavonoides , Dinámicas Mitocondriales , Pilocarpina , Quinazolinonas , Ratas Sprague-Dawley , Estado Epiléptico , Animales , Dinaminas/metabolismo , Dinaminas/genética , Dinámicas Mitocondriales/fisiología , Dinámicas Mitocondriales/efectos de los fármacos , Masculino , Pilocarpina/toxicidad , Estado Epiléptico/metabolismo , Estado Epiléptico/inducido químicamente , Flavonoides/farmacología , Quinazolinonas/farmacología , Sistema de Señalización de MAP Quinasas/fisiología , Ratas , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Convulsiones/metabolismo , Cloruro de Litio/farmacología , Modelos Animales de Enfermedad , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , FosforilaciónRESUMEN
An intravenous (IV) administration of midazolam may result in seizure-like activity or movement. This report describes 5 neonates who developed seizure-like movements after IV midazolam injection. The patients presented between 2019 and 2022 and were admitted to a neonatal intensive care unit located within an academic centre in Muscat, Oman. The abnormal movements occurred shortly after IV bolus administration of midazolam. None of the patients experienced seizure-like movements after receiving midazolam infusions. The seizure-like movements were aborted either spontaneously or by antiseizure medications. In addition, seizure recurrence was not observed in any of the infants during the later stages of their treatment. Since this adverse effect might be related to the speed of the bolus administration, IV midazolam must be given as a slow bolus over 2-3 minutes followed by a slow flush of normal saline. To prevent midazolam's potential adverse effect on newborns, neonatal caregivers must be aware of it.
Asunto(s)
Midazolam , Convulsiones , Humanos , Midazolam/efectos adversos , Midazolam/farmacología , Midazolam/administración & dosificación , Midazolam/uso terapéutico , Recién Nacido , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Masculino , Femenino , Omán , Hipnóticos y Sedantes/efectos adversos , Unidades de Cuidado Intensivo Neonatal , Anticonvulsivantes/efectos adversosRESUMEN
Kruppel-like factor 4 (Klf4) is a transcription factor that is involved in neuronal regeneration and the development of glutamatergic systems. However, it is unknown whether Klf4 is involved in acute seizure. To investigate the potential role of Klf4 in pentylenetetrazol (PTZ)-induced seizure, western blotting, immunofluorescence, behaviour test and electrophysiology were conducted in this study. We found that Klf4 protein and mRNA expression were increased in both the hippocampus (HP) and prefrontal cortex (PFC) after PTZ-induced seizure in mice. HP-specific knockout (KO) of Klf4 in mice decreased protein expression of Klf4 and the down-stream Klf4 target tumour protein 53 (TP53/P53). These molecular changes are accompanied by increased seizure latency, reduced immobility time in the forced swimming test and tail suspension test. Reduced hippocampal protein levels for synaptic proteins, including glutamate receptor 1 (GRIA1/GLUA1) and postsynaptic density protein 95 (DLG4/PSD95), were also observed after Klf4-KO, while increased mRNA levels of complement proteins were observed for complement component 1q subcomponent A (C1qa), complement component 1q subcomponent B (C1qb), complement component 1q subcomponent C (C1qc), complement component 3 (C3), complement component 4A (C4a) and complement component 4B (C4b). Moreover, c-Fos expression induced by PTZ was reduced by hippocampal conditional KO of Klf4. Electrophysiology showed that PTZ-induced action potential frequency was decreased by overexpression of Klf4. In conclusion, these findings suggest that Klf4 plays an important role in regulating PTZ-induced seizures and therefore constitutes a new molecular target that should be explored for the development of antiepileptic drugs.
Asunto(s)
Hipocampo , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel , Ratones Noqueados , Pentilenotetrazol , Convulsiones , Animales , Factor 4 Similar a Kruppel/metabolismo , Convulsiones/metabolismo , Convulsiones/inducido químicamente , Convulsiones/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Ratones , Hipocampo/metabolismo , Masculino , Corteza Prefrontal/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
The neuropeptide neurotensin can reduce status epilepticus and its associated consequences through induction of therapeutic hypothermia when bound to a molecule that can penetrate the blood-brain barrier.
Asunto(s)
Convulsiones , Humanos , Convulsiones/tratamiento farmacológico , Neurotensina/metabolismo , Barrera Hematoencefálica/metabolismo , Estado Epiléptico/tratamiento farmacológico , Animales , Hipotermia InducidaRESUMEN
BACKGROUND AND OBJECTIVES: Despite the success of presurgical network connectivity studies in predicting short-term (1-year) seizure outcomes, later seizure recurrence occurs in some patients with temporal lobe epilepsy (TLE). To uncover contributors to this recurrence, we investigated the relationship between functional connectivity and seizure outcomes at different time points after surgery in these patients. METHODS: Patients included were clinically diagnosed with unilateral mesial TLE after a standard clinical evaluation and underwent selective amygdalohippocampectomy. Healthy controls had no history of seizures or head injury. Using resting-state fMRI, we assessed the postsurgical functional connectivity node strength, computed as the node's total strength to all other nodes, between seizure-free (Engel Ia-Ib) and nonseizure-free (Engel Ic-IV) acquisitions. The change over time after surgery in different outcome groups in these nodes was also characterized. RESULTS: Patients with TLE (n = 32, mean age: 43.1 ± 11.9 years; 46.8% female) and 85 healthy controls (mean age: 37.7 ± 13.5 years; 48.2% female) were included. Resting fMRI was acquired before surgery and at least once after surgery in each patient (range 1-4 scans, 5-60 months). Differences between patients with (n = 30) and without (n = 18) seizure freedom were detected in the posterior insula ipsilateral to the resection (I-PIns: 95% CI -154.8 to -50.1, p = 2.8 × 10-4) and the bilateral central operculum (I-CO: 95% CI -163.2 to -65.1, p = 2.6 × 10-5, C-CO: 95% CI -172.7 to -55.8, p = 2.8 × 10-4). In these nodes, only those who were seizure-free had increased node strength after surgery that increased linearly over time (I-CO: 95% CI 1.0-5.2, p = 4.2 × 10-3, C-CO: 95% CI 1.0-5.2, p = 5.5 × 10-3, I-PIns: 95% CI 1.6-5.5, p = 0.9 × 10-3). Different outcome groups were not distinguished by node strength before surgery. DISCUSSION: The findings suggest that network evolution in the first 5 years after selective amygdalohippocampectomy surgery is related to seizure outcomes in TLE. This highlights the need to identify presurgical and surgical conditions that lead to disparate postsurgical trajectories between seizure-free and nonseizure-free patients to identify potential contributors to long-term seizure outcomes. However, the lack of including other surgical approaches may affect the generalizability of the results.
Asunto(s)
Epilepsia del Lóbulo Temporal , Imagen por Resonancia Magnética , Convulsiones , Humanos , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Convulsiones/cirugía , Convulsiones/fisiopatología , Convulsiones/diagnóstico por imagen , Hipocampo/cirugía , Hipocampo/diagnóstico por imagen , Hipocampo/fisiopatología , Amígdala del Cerebelo/cirugía , Amígdala del Cerebelo/fisiopatología , Amígdala del Cerebelo/diagnóstico por imagenRESUMEN
Mutations in voltage-gated sodium (Nav) channels, which are essential for generating and propagating action potentials, can lead to serious neurological disorders, such as epilepsy. However, disease-causing Nav channel mutations do not always result in severe symptoms, suggesting that the disease conditions are significantly affected by other genetic factors and various environmental exposures, collectively known as the "exposome". Notably, recent research emphasizes the pivotal role of commensal bacteria in neural development and function. Although these bacteria typically benefit the nervous system under normal conditions, their impact during pathological states remains largely unknown. Here, we investigated the influence of commensal microbes on seizure-like phenotypes exhibited by paraShu-a gain-of-function mutant of the Drosophila Nav channel gene, paralytic. Remarkably, the elimination of endogenous bacteria considerably ameliorated neurological impairments in paraShu. Consistently, reintroducing bacteria, specifically from the Lactobacillus or Acetobacter genera, heightened the phenotypic severity in the bacteria-deprived mutants. These findings posit that particular native bacteria contribute to the severity of seizure-like phenotypes in paraShu. We further uncovered that treating paraShu with antibiotics boosted Nrf2 signaling in the gut, and that global Nrf2 activation mirrored the effects of removing bacteria from paraShu. This raises the possibility that the removal of commensal bacteria suppresses the seizure-like manifestations through augmented antioxidant responses. Since bacterial removal during development was critical for suppression of adult paraShu phenotypes, our research sets the stage for subsequent studies, aiming to elucidate the interplay between commensal bacteria and the developing nervous system in conditions predisposed to the hyperexcitable nervous system.
Asunto(s)
Convulsiones , Canales de Sodio Activados por Voltaje , Animales , Convulsiones/genética , Canales de Sodio Activados por Voltaje/genética , Canales de Sodio Activados por Voltaje/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/microbiología , Fenotipo , Mutación , Acetobacter/genética , Acetobacter/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Simbiosis/genética , Microbioma GastrointestinalRESUMEN
Recently a novel genetically modified mouse strain with serum carboxylesterase knocked-out and the human acetylcholinesterase gene knocked-in (KIKO) was created to simulate human responses to nerve agent (NA) exposure and its standard medical treatment. A1 adenosine receptor (A1AR) agonist N-bicyclo-(2.2.1)-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone is a potent anticonvulsant and neuroprotectant (A/N) in both rat and KIKO mouse soman (GD) seizure models. In this study we utilized the KIKO mouse to evaluate further the basic pharmacologic A/N effects of ENBA as an adjunct to standard NA medical treatments (i.e., atropine sulfate, pralidoxime chloride [2-PAM], and midazolam). Male mice, implanted with cortical electroencephalographic (EEG) electrodes, were pretreated with asoxime (HI-6) and exposed to an epileptogenic dose of GD (33 µg/kg, s.c.) or saline (sham exposure) and then treated 15 min after seizure onset with ENBA at 15 mg/kg, i.p. (a minimum efficacy dose in suppressing NA-induced seizure) alone or as an adjunct to standard medical treatments. We collected EEG activity, seizure suppression outcomes, daily body temperature and weight, heart rate, toxic signs, neuropathology, and lethality data for up to 14 days. Without ENBA, death from NA exposure was 45%, while with ENBA, either alone or in combination with midazolam, the survival improved to 80% and 90%, respectively. Additionally, seizure was suppressed quickly and permanently, toxic signs, hypothermia, and bradycardia recovered by 48 h, and no neuropathology was evident. Our findings confirmed that ENBA is a potent A/N adjunct for delayed medical treatments of NA exposure.
Asunto(s)
Acetilcolinesterasa , Agonistas del Receptor de Adenosina A1 , Modelos Animales de Enfermedad , Convulsiones , Soman , Animales , Soman/toxicidad , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Masculino , Agonistas del Receptor de Adenosina A1/farmacología , Humanos , Ratones , Acetilcolinesterasa/metabolismo , Electroencefalografía , Adenosina/análogos & derivados , Adenosina/farmacología , Ratones Noqueados , Anticonvulsivantes/farmacología , Anticonvulsivantes/toxicidadRESUMEN
INTRODUCTION: It is unclear how tranexamic acid (TXA) affects blood loss and seizures in meningioma resections. We performed a systematic review and meta-analysis and tried to evaluate the effectiveness and safety of TXA use for patients undergoing meningioma resections. METHODS: Regards to this systematic review and meta-analysis (registered with CRD42023416693), we searched PubMed, Embase (Ovid), EBSCO, and Cochrane central library up to and including Oct 2023. Patients undergoing meningioma resections treated with TXA and placebo or no treatment were eligible for this study. This would allow delineation of the impact of TXA on blood loss, postoperative seizure, and other complication incidences. RESULTS: Four prospective cohort studies with 781 patients (390 patients in the TXA group and 391 patients in the control group) were conducted via a systematic review and meta-analysis. The results suggested that the application of TXA for patients undergoing meningioma resections reduced mean blood loss of 252 mL with 95% confidence interval (CI) -469.26 to -34.67 (P = 0.02) and I2 of 94% but did not increase postoperative seizure (risk ratio: 1.08; 95%CI: 0.54 to 2.15; P = 0.84) and other complication rates. CONCLUSIONS: This systematic review and meta-analysis suggests that the administration of TXA could reduce blood loss in patients undergoing intracerebral meningioma resection. REGISTRY INFORMATION: The systematic review protocol has been registered at PROSPERO (Registration No. CRD42023416693) on April 23, 2023.
Asunto(s)
Pérdida de Sangre Quirúrgica , Meningioma , Convulsiones , Ácido Tranexámico , Humanos , Meningioma/cirugía , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/efectos adversos , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & control , Pérdida de Sangre Quirúrgica/prevención & control , Antifibrinolíticos/uso terapéutico , Antifibrinolíticos/efectos adversos , Neoplasias Meníngeas/cirugía , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
Epilepsy is a chronic neurological disorder characterized by recurrent seizures that affects over 70 million people worldwide. Although many antiepileptic drugs that block seizures are available, they have little effect on preventing and curing epilepsy, and their side effects sometimes lead to serious morbidity. Therefore, prophylactic agents with anticonvulsant properties and no adverse effects need to be identified. Recent studies on probiotic administration have reported a variety of beneficial effects on the central nervous system via the microbiota-gut-brain axis. In this study, we investigated the effects of the oral administration of Bifidobacterium breve strain A1 [MCC1274] (B. breve A1) on tonic-clonic seizure in a pentylenetetrazole (PTZ)-induced kindling mouse (KD mouse) model. We found that the oral administration of B. breve A1 every other day for 15 days significantly reduced the seizure score, which gradually increased with repetitive injections of PTZ in KD mice. The administration of B. breve A1, but not saline, to KD mice significantly increased the level of Akt Ser473 phosphorylation (p-Akt) in the hippocampus; this increase was maintained for a minimum of 24 h after PTZ administration. Treatment of B. breve A1-administered KD mice with the selective inhibitor of integrin-linked kinase (ILK) Cpd22 significantly increased the seizure score and blocked the antiepileptic effect of B. breve A1. Moreover, Cpd22 blocked the B. breve A1-induced increase in hippocampal p-Akt levels. These results suggest that the ILK-induced phosphorylation of Akt Ser473 in the hippocampus might be involved in the antiepileptic effect of B. breve A1.
Asunto(s)
Bifidobacterium breve , Modelos Animales de Enfermedad , Excitación Neurológica , Pentilenotetrazol , Probióticos , Proteínas Serina-Treonina Quinasas , Convulsiones , Transducción de Señal , Animales , Probióticos/administración & dosificación , Probióticos/farmacología , Ratones , Convulsiones/metabolismo , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Bifidobacterium breve/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Administración Oral , Excitación Neurológica/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , FosforilaciónRESUMEN
Recently, we have described the first supermolecular nanoentities of vitamin B12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptamethyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstrate the first example of the formation of nanoparticles of this nucleotide-free analogue of vitamin B12 in protein nanocarriers and neuroprotective activity in vivo of the own nanoform of the drug. The preparation and characterization of nanocarriers based on bovine serum albumin (BSA) loaded with vitamin B12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B12 is tightly retained by the protein structure and exists in an incorporated state in the form of nanoparticles. The effect of encapsulated drugs on the character and severity of primary generalized seizures in rats induced by the pharmacotoxicant thiosemicarbazide was studied. Cyanocobalamin and ACCby exhibited a neuroprotective effect. The best influence of the encapsulation on the effectiveness of the drugs was achieved in the case of AСCby, whose bioavailability as a neuroprotector did not change upon introduction in BSA particles, i.e., 33â¯% of surviving animals were observed upon ACCby administration in free form and in encapsulated state. No surviving rats were observed without the administration of drugs. Thus, BSA nanocarriers loaded by nanoparticles of nucleotide-free analogues of vitamin B12, including hydrophobic ones, can be recommended for neuroprotection and targeted delivery.
Asunto(s)
Portadores de Fármacos , Nanopartículas , Fármacos Neuroprotectores , Albúmina Sérica Bovina , Vitamina B 12 , Animales , Vitamina B 12/análogos & derivados , Vitamina B 12/química , Vitamina B 12/farmacología , Albúmina Sérica Bovina/química , Nanopartículas/química , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Portadores de Fármacos/química , Ratas , Masculino , Ratas Wistar , Bovinos , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & controlRESUMEN
PURPOSE: The 2HELPS2B score is an invaluable tool for assessing seizure risk in critically ill patients with unconsciousness. However, this can be challenging for non-epileptologists to use owing to its reliance on electroencephalogram (EEG) analysis. Thus, identifying clinical manifestations associated with high 2HELPS2B scores is crucial. METHODS: We examined patients who underwent EEG for acute impaired consciousness in the emergency department between 2020 and 2022. We evaluated the clinical manifestations immediately prior to the EEG tests and identified those associated with a 2HELPS2B score ≥ 2. Additionally, we investigated clinical outcomes in accordance with these manifestations and the 2HELPS2B score. RESULTS: A total of 78 patients were included in this study. While the median 2HELPS2B score was 1 (range: 0-6), 13 patients (16.6%) showed electrographic/electroclinical seizures or status epilepticus and 16 patients (20.5%) showed ictal-interictal continuum in their EEGs. Abnormal muscle tonus (p = 0.034) and eye deviation (p = 0.021) were Significantly associated with a 2HELPS2B score ≥ 2. The presence of these manifestations (p < 0.001) and a 2HELPS2B score ≥ 2 (p < 0.001) were both significantly associated with a favorable response to anti-seizure medication. Conversely, patients with a 2HELPS2B score ≥ 2 who exhibited these clinical manifestations were more likely to be non-dischargeable (p = 0.053), have prolonged intensive care unit stays (p = 0.002), or require extended ventilator use (p = 0.082). CONCLUSION: Abnormal muscle tonus and eye deviation were significant manifestations compatible with a 2HELPS2B score ≥ 2 and may indicate an increased risk of seizures or the severity of the epileptic condition.
Asunto(s)
Trastornos de la Conciencia , Electroencefalografía , Convulsiones , Humanos , Masculino , Femenino , Persona de Mediana Edad , Electroencefalografía/métodos , Anciano , Trastornos de la Conciencia/diagnóstico , Trastornos de la Conciencia/fisiopatología , Trastornos de la Conciencia/etiología , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Adulto , Anciano de 80 o más Años , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Enfermedad Crítica , Inconsciencia/diagnósticoRESUMEN
BACKGROUND: Neurological emergencies are one of the major diagnosis groups in the Emergency Medical Services (EMS) with the highest rate of misdiagnosis. Despite the knowledge of time sensitivity and the importance of prehospital factors, prehospital delay is common. Although several stroke triage scales have been developed, a gold standard in the prehospital setting is lacking. OBJECTIVES: Our aim was to evaluate the perception of neurological emergencies by EMS personnel and to identify current problems, difficulties and opportunities for improvement in the prehospital management of stroke, seizure, non-specific neurological symptoms, and paediatric neurological emergencies. METHODS: The study was conducted as an online survey through SoSci Survey and was made available from March 1st to June 30th 2023 to all personnel working in emergency medical services. The access link was distributed through snowballing, social media, and through a QR code on a promotional poster. The survey was completed anonymously. The final survey consisted of 30 questions in German on the topics of neurological emergencies, general neurological assessment, specific neurological examination including paediatric assessment, stroke, and seizures, and finally suggestions for improvement. RESULTS: The largest group of participants were paramedics, who estimated to encounter neurological emergencies at a general rate of 20-60%. When unease was felt, the main reasons were ambiguity of symptoms and insufficient admission capacity of hospitals. The biggest challenges were highly varied. Almost 80% of participants assumed that the neurological assessment would be omitted in difficult patient groups such as demented, intoxicated or children. 75% felt uncomfortable making a paediatric assessment, 50% were unfamiliar with the Paediatric Glasgow Coma Scale. CONCLUSIONS: Support through more standardized practical training and defined, uniform guidelines is needed. There was also a clear need for peer collaboration, feedback and case sharing. Digitalization, the usage of telemedicine and updated versions of the documentation protocols including paediatric adaptations to current guidelines could further improve current neurological assessment in the prehospital setting.