Clonic Research Articles

Acute anticonvulsant effects of dapsone on PTZ- and MES-induced seizures in mice: NLRP3 inflammasome inhibition and Nrf2/HO-1 pathway preservation.

Epilepsy, a neurological disorder characterized by recurrent seizures, presents considerable difficulties in treatment, particularly when dealing with drug-resistant cases. Dapsone, recognized for its anti-inflammatory properties, holds promise as a potential therapeutic option. However, its effectiveness in epilepsy requires further investigation. The aim of this study is to explore the effects of dapsone on seizure activity and neuroinflammation, particularly through the nuclear factor erythroid-2-related factor (Nrf2)/ Heme Oxygenase 1 (HO-1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathways, to better understand its therapeutic potential. To evaluate the effects of dapsone, two seizure models were utilized in mice: pentylenetetrazole (PTZ)-induced clonic seizures and maximal electroshock (MES)-induced generalized tonic-clonic seizures (GTCS) in mice. The impact of dapsone on neuroinflammatory markers and oxidative stress pathways, specifically Nrf2/HO-1 and NLRP3, as well as interleukin-1β (IL-1β), IL-8, and IL-18, was assessed using Western blotting and ELISA techniques. In this study, dapsone (2, 5, 10, and 20mg/kg, ip) showcased a significant increase in clonic seizure threshold following intravenous infusion of PTZ. Notably, doses of 5, 10, and 20mg/kg exhibited increased latency and decreased the number of seizures. Additionally, dapsone at 10 and 20mg/kg prevented the incidence of GTCS and subsequent mortality in the MES model. Furthermore, Dapsone demonstrated modulation of Nrf2/ HO-1 and NLRP3 IL-1 β/IL-18 pathways. This study highlights the therapeutic potential of dapsone in epilepsy, emphasizing the involvement of Nrf2/HO-1 and NLRP3 pathways. These findings provide a foundation for future clinical research aimed at developing dapsone-based therapies for drug-resistant epilepsy.

Abdominal Clonic Seizures Originating From the Postcentral Gyrus in an 8-Year-Old Boy.

Abdominal Clonic Seizures Originating From the Postcentral Gyrus in an 8-Year-Old Boy.

Ictal EEG of benign convulsion with mild gastroenteritis with in infants and children.

There are fewer reports on the ictal electroencephalogram(EEG) of convulsions in infants and children with mild gastroenteritis (BCWG). Our study retrospectively analyzed the ictal EEG characteristics of convulsive episodes of BCWG. The seizure-phase EEGs of children diagnosed with BCWG from September 2016 to January 2022 were searched and analyzed, and a total of thirteen seizure-phase EEGs of eight cases were analyzed retrospectively. The age of onset of the disease in the eight children ranged from one year to two years and seven months. No epileptiform discharges were found during the interictal EEG. A total of thirteen epileptic seizures were monitored, of which nine were focal with secondary generalisation. Scalp EEG showed three onset of EEG seizures were in the right occipital region, two were in the right parietal and occipital regions, one was in the right parietal, occipital and posterior temporal region, one was in the right posterior temporal region, one was in the right occipital and posterior temporal region and one was in the right central and central midline region. In addition, four non-convulsive epileptic seizures, which manifested themselves as a decrease in movement and consciousness, with local δ slow-wave activity in bilateral occipital regions evolved to diffuse δ slow wave activity in epileptic seizures. Focal secondary generalised tonic clonic seizures were the main type of seizures in BCWG, and the seizure onset may been mostly in posterior cephalic cortex. It was previously unreported that some children of BCWG may combine with non-convulsive epileptic seizures with the onset of slow wave activity in the occipital region bilaterally and evolving into diffuse δ slow wave activity, which was not easily detected by parents and clinicians.

Age-related impact of phenobarbital in suppressing prenatal alcohol exposure-related seizures in developing rats.

Prenatal alcohol exposure (PAE) during pregnancy can increase the prevalence of N-methyl-D-aspartate (NMDA)-induced generalized tonic-clonic seizures (GTCSs) in developing rats. However, it is unclear whether phenobarbital (PB) can suppress these PAE-related seizures. To explore this knowledge gap, we investigated the effects of acute PB treatment on NMDA-induced seizures in postpartum rats, prenatally exposed to alcohol on gestational day 18 (GD18), at two developmental stages: day 7 (P7), the equivalent of pre-term neonates, and day 15 (P15), the equivalent of full-term neonates. Timed-pregnant female Sprague-Dawley rats were given a single dose of alcohol or its vehicle on GD18 during the second-trimester equivalent. Male and female postpartum rats were tested for the effectiveness of single-dose treatment with either PB or its vehicle in suppressing NMDA-induced seizures. These seizures include wild running-like behavior (WRLB), flexion seizures (FSs), clonic seizures (CSs), generalized tonic-clonic seizures (GTCSs), and tonic seizures (TSs) in P7 and P15 rats. Analysis revealed that P7 rats were more likely to develop GTCSs after PB administration than P15 rats; this effect was associated with shorter latencies to develop NMDA-induced seizures. Moreover, PAE-related GTCSs are less responsive to PB treatment in P7 rats than in P15 rats. These findings suggest that the PAE-related GTCS model in P7 rats can be used to investigate the mechanisms underlying PB-resistant seizures in developing rats.

Prevalance of Non-Provoke Generalize Tonic-Clonic Seizure in Sporadic Alzheimer’s Disease

Background and Purpose: Alzheimer’s disease (AD) and epileptic seizure are among the most common health problems in the elderly population. This study aimed to estimate the prevalence rate and predictors of seizures in sporadic AD patients.Methods: The study was conducted by retrospectively for a period of 10 years examining the file records. Patients were selected among the patients diagnosed with probable sporadic late onset AD according to the National Institute of Neurological Communicative Disorders and Stroke AD and related disorders association criteria and the diagnostic and statistical manual of mental disorders (n=451). In our 213 sporadic AD patients who were followed up regularly and had a follow up examination in the last 6 months, the file records were examined, scanned and questioned for the presence of epileptic seizures.Results: The prevalence of non provoked generalized tonic clonic seizures in sporadic AD was found to be 6.57% (n=14). Neuroleptic use, presence of diabetes mellitus (DM) and/or treatment, presence of ischemic heart disease (IHD) and/or treatment were found to be 2.99 times, 1.91 times and 3.09 times higher in our patients who had seizures, respectively. When the factors that can affect seizures were examined, the use of neuroleptics and the presence of IHD and/or treatment were found to be statistically significant in terms of the risk of seizure in AD.Conclusions: The use of neuroleptics, the presence of IHD and DM and/or their medications could facilitate the development of unprovoked generalized tonic clonic seizures in sporadic AD. It is doubtful whether the seizures are primary or secondary generalized.

In-hospital new-onset seizures in patients admitted to the medical intensive care unit: An observational study and algorithmic approach.

Seizures are one of the most common neurological complications encountered in the intensive care unit (ICU). They can occur in the background of exacerbation of a known neurological disease or secondary to non-neurological conditions such as sepsis and metabolic disturbances. However, there is a paucity of literature on the incidence and pattern of new-onset seizures in ICUs. To study the incidence and patterns of new-onset seizures in patients admitted to the medical ICU. This was a prospective, multicenter, observational study performed in two tertiary care centers in Hyderabad, India over a period of 1 year. Patients upon ICU admission, who developed new-onset generalized tonic clonic seizures (GTCS), were enrolled. Those with a pre-existing seizure disorder, acute cerebrovascular accident, head injury, known structural brain lesions, or chronic liver disease were excluded as they have a higher likelihood of developing seizures. All enrolled patients were subjected to biochemical routines, radiological imaging of either computed tomography or magnetic resonance imaging, and other relevant laboratory tests as per clinical suspicion according to the protocol, and their data were recorded. Statistical analyses were conducted using descriptive statistics, χ 2 tests, and linear regression. A total of 61 of 2522 patients developed GTCS. Among all etiologies of seizures, metabolic causes were most frequent (35%) followed by infective causes (27%) and others (new-onset structural, drug withdrawal, drug-induced, toxicology-related, and miscellaneous factors). Logistic regression analysis showed that increased sodium and calcium levels were associated with a lower likelihood of developing seizures. This study identified the etiology of new-onset seizures developing in critically ill patients admitted to the ICU. These findings highlight the need for targeted monitoring of those at risk of developing seizures.

Exploring ketogenic diet resistance in glucose transporter type 1 deficiency syndrome: A comprehensive review and critical appraisal.

Glucose transporter type 1 deficiency syndrome (GLUT1DS) commonly presents with early-onset epilepsy that often resists conventional pharmacological treatment. Ketogenic diet therapy (KDT) is the preferred approach to address the underlying metabolic anomaly. However, a subset of GLUT1DS patients presents resistance to KDT, with the causes remaining elusive. This comprehensive literature review aims to explore the characteristics of KDT failure in GLUT1DS and identify risk factors within this population. Our goal is to improve counseling and prognostication for these patients. So, we conducted a comprehensive literature review on PubMed, focusing on studies documenting pediatric GLUT1DS patients with drug-resistant epilepsy unresponsive to KDT. We identified five cases of KDT failure in female GLUT1DS patients, aged 10 days to 13 years at diagnosis. Predominant seizure types were absence seizures, with a few cases of clonic, tonic, or myoclonic seizures. EEG consistently revealed 2-3.5 Hz generalized spike-and-wave discharges. Genetic investigations revealed point mutations and deletions in two cases each. Despite an in-depth search, no specific features were found to reliably distinguish KDT non-responders from responders, underscoring the need for further research. In cases of KDT ineffectiveness for seizure control in GLUT1DS patients, exploring alternative therapeutic strategies becomes imperative to managing symptoms while maintaining quality of life. Large-scale multicenter studies, facilitated through international collaborations like the European Network for Therapy in Rare Epilepsies (NETRE), hold promise in elucidating the complexities of this patient population and developing personalized therapeutic approaches. PLAIN LANGUAGE SUMMARY: Glucose transporter type 1 deficiency syndrome often causes difficult-to-treat epilepsy. The ketogenic diet works for many patients, but some do not respond. This review investigated cases of diet failure but could not identify common features among poor responders. Further research is needed to understand these cases and explore alternative treatments.

Age-related semiology changes over time

Understanding how seizure semiology changes with age is essential to determine the seizure onset zone. Epilepsy can be considered the prototypical neurologic disorder for demonstrating age-related changes over time. The maturational changes that occur in the brain over the lifespan demonstrate themselves most clearly through semiologic changes. Due to the immaturity of the neonatal brain, seizure recognition is challenging. Electroclinical seizures are classified as motor, non-motor, sequential, or unclassified and are typically focal in onset. During infancy, the most common seizure types are epileptic spasms, myoclonic, tonic, atonic, clonic, and hypomotor/behavioral arrest seizures. Correlation between seizure semiology and localization of seizure onset zone can be variable. The most observed seizure types in preschool-aged children are generalized myoclonic, generalized tonic, focal tonic, or clonic seizures. Many of the epileptic encephalopathies present at this age. Ictal behaviors continue to be limited, but lateralizing motor manifestations during focal seizures are better developed compared to infants. In school-aged children, the most common seizure types involve change in awareness. Seizure semiology at this age resembles that of adults, with increasing number and complexity of seizure components.

Sleep-related hypermotor seizures originating from the occipital lobe.

We present two unique cases of sleep-related hypermotor epilepsy (SHE) originating from the occipital lobe. Patients with sleep-related seizures and drug-resistant occipital lobe epilepsy were identified from the ANPHY lab stereo-electroencephalography (SEEG) research database at the Duke Comprehensive Epilepsy Center. We identified two young females with frequent sleep-related focal seizures and occasional focal to bilateral tonic clonic seizures characterized by hypermotor movements. During wakefulness, the semiology also involved an elementary visual aura. They meet the 2016 diagnostic criteria for SHE, and SEEG monitoring with cortical stimulation mapping identified an epileptogenic zone (EZ) within the occipital lobe, with most seizures occurring out of NREM 2 sleep. Responsive neurostimulation devices were implanted, which indicated a trend for event detections in nocturnal periods. Extrafrontal SHE has characteristically been described in the temporal, insular-opercular, and parietal lobes. Here, we demonstrate using SEEG-confirmed EZ identification, that SHE can also originate in the occipital lobe. In patients with sleep-related seizures and hypermotor behavior, occipital lobe seizures thus should not be excluded from the differential diagnosis. Key in identifying this rare localization is non-frontal aura semiology and delay to motor symptoms, which may be supported by a visual field deficit and structural MRI abnormality.

Chemogenetic silencing of the subiculum blocks acute chronic temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common form of medically-intractable epilepsy. Subicular hyperexcitability is frequently observed with TLE, presumably caused by impaired inhibition of local excitatory neurons. Here, we evaluated the effectiveness of silencing subicular pyramidal neurons to treat a rodent model of TLE. First, we generated a chronic TLE mouse model via initial intrahippocampal kainic acid (IHKA) injection. In the chronic state after first IHKA injection, behavioral seizures and histological abnormalities were reliably observed. We then injected an adeno-associated viral (AAV) vector carrying an inhibitory chemogenetic element, hM4Di, directly into the subiculum. Eight weeks after the first IHKA injection, acute seizures were induced by giving a second dose of kainic acid (KA), which mimicked generalized tonic–clonic seizures. Herein, precise control over generalized tonic–clonic seizure onset was achieved via this two-step process. We found that chemogenetic suppression of subicular pyramidal neurons had a robust anti-epileptogenesis effect in this acute-chronic model of TLE. These data confirm a crucial role of the subiculum in the propagation of hippocampal seizures and highlight the potential for using subicular chemogenetic manipulation to treat generalized tonic–clonic seizures.

ILAE neonatal seizure framework to aide in determining etiology.

To employ the neonatal seizure framework developed by the International League Against Epilepsy (ILAE) Neonatal Task force to assess its usefulness in determining the etiology of neonatal seizures. The members of the ILAE Neonatal Task Force evaluated 157 seizures from 146 neonates to determine internal validity and associations between semiology and a specific etiology. Provoked neonatal electrographic and electroclinical seizures were due to multiple etiologies. For electroclinical seizures, unilateral clonic seizures were typically seen with vascular etiologies, focal tonic seizures and sequential seizures with genetic etiologies, and myoclonic seizures with inborn errors of metabolism. Electrographic seizures were often seen in hypoxic-ischemic encephalopathy or vascular etiologies. These data suggest that the ILAE neonatal seizure classification may be used as a bedside tool to aid and guide workup to determine the etiology of seizures.

Anticonvulsant effects of pentoxifylline on seizures induced by pentylenetetrazole and maximal electroshock in male mice: The role of the nitrergic pathway

IntroductionEpilepsy remains a challenge, with one-third of patients experiencing refractory seizures despite current anti-seizure medications. The nitrergic system, which involves nitric oxide (NO) and NO synthase (NOS) enzymes, plays a complex role in seizure pathophysiology. Pentoxifylline (PTPh), an FDA-approved phosphodiesterase inhibitor, has anticonvulsant effects; however, its relationship with the pathway is unclear. This study focused at how the nitrergic system could be involved in PTPh’s anticonvulsant effects. MethodsSeizures were induced in male mice by intravenous pentylenetetrazole (PTZ) infusion (absence-like seizures), intraperitoneal PTZ injection, and maximal electroshock (generalized tonic-clonic seizures). PTPh was administered at various doses, alone or in combination with the NO precursor L-arginine, as well as non-selective (L-NAME) and selective NOS inhibitors (nNOS inhibitor 7-NI and iNOS inhibitor aminoguanidine). Seizure thresholds, latencies, incidence, and mortality were assessed. Moreover, in the next paradigm, using maximal electroshock model, we evaluate possible protective effects of PTPh against generalized tonic-clonic seizures and subsequent mortality. ResultsIn the intravenous PTZ model, PTPh (≥150 mg/kg) increased the seizure threshold, potentiated by L-arginine but reduced by L-NAME and 7-nitroindazole. In the intraperitoneal PTZ model, 150 mg/kg PTPh decreased tonic seizure frequency, which was mitigated by aminoguanidine. However, PTPh failed to prolong clonic seizure latency. In the maximal electroshock test, 100 mg/kg PTPh protected against tonic seizure incidence (reduced by aminoguanidine). Although PTPh could not reduce mortality, its combination with L-NAME or 7-nitroindazole increased mortality compared with the vehicle-treated group. ConclusionPTPh exerted anticonvulsant effects against absence-like and generalized tonic-clonic seizures, likely through modulation of the nitrergic system involving neuronal, endothelial, and inducible NOS isoform. These findings provide novel insights into the complex interplay between NO signaling and the anticonvulsant actions of PTPh, highlighting the potential therapeutic implications of targeting the NO pathway in epilepsy management.

Ivermectin as a promising therapeutic option for onchocerciasis-associated epilepsy.

Onchocerciasis, commonly known as river blindness, is a neglected tropical disease caused by the parasite Onchocerca volvulus. It can lead to blindness and visual impairment. Studies have also demonstrated a link between onchocerciasis and epilepsy, with there being a correlation between onchocerciasis endemicity and epilepsy prevalence. Onchocerciasis-associated epilepsy (OAE) emerges predominantly in individuals aged 3-18, with a notable prevalence in regions where onchocerciasis transmission persists. These areas exhibit elevated rates of epilepsy, underscoring the significant impact of ongoing onchocerciasis on the incidence of epilepsy, particularly within the specified age range. Both epilepsy prevalence and incidence have evolved over the past three decades in a Tanzanian area endemic for onchocerciasis. Researchers have studied the effects of the antiparasitic drug ivermectin on OAE. About one third of Ugandan patients saw reduced seizure frequency or intensity after one 150 μg/kg dose. Clinical research in the Congo among infected epileptics on anti-seizure medications (ASMs) suggested ivermectin may decrease seizure frequency following oral administration of ivermectin tablets (3 mg). Beyond its antiparasitic properties, ivermectin has demonstrated anticonvulsant effects against clonic and tonic-clonic seizures, likely through modulation of GABAA receptor and neuroinflammation. There is evidence of synergistic effects when combined with GABAergic ASMs like diazepam. As neuroinflammation plays a key role in OAE, ivermectin's anti-inflammatory properties by inhibiting cytokines like TNF-α and IL-1β are also relevant. While certain other antiparasitic drugs can interact with ASMs and have side effects like seizures, no such interactions or side effects have been reported for ivermectin. However, there is a need for more randomized controlled trials specifically evaluating ivermectin's impact on seizures in O. volvulus-infected epileptics on ASMs. Given its efficacy against parasites, limited side effects, and potential anticonvulsant mechanisms, ivermectin could be a favorable first-line treatment option, but further research is warranted to confirm benefits for OAE. PLAIN LANGUAGE SUMMARY: This article explores the potential benefits of ivermectin, a drug commonly used to treat parasitic infections, for reducing seizures in people with epilepsy linked to onchocerciasis, also known as river blindness. Research shows that ivermectin not only targets the parasitic cause of the disease but may also help reduce brain inflammation, which plays a key role in epilepsy. While early results are promising, more research is needed to confirm whether ivermectin can be a reliable treatment for epilepsy in people affected by this condition.

Genetic heterogeneity in familial forms of genetic generalized epilepsy: from mono- to oligogenism

Genetic generalized epilepsy (GGE) including childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy (JME), and GGE with tonic–clonic seizures (TCS) (GGE-TCS), is genetically influenced with a two- to four- fold increased risk in the first-degree relatives of patients. Since large families with GGE are very rare, international studies have focused on sporadic GGE patients using whole exome sequencing, suggesting that GGE are highly genetically heterogeneous and rather involve rare or ultra-rare variants. Moreover, a polygenic mode of inheritance is suspected in most cases. We performed SNP microarrays and whole exome sequencing in 20 families from Sudan, focusing on those with at least four affected members. Standard genetic filters and Endeavour algorithm for functional prioritization of genes selected likely susceptibility variants in FAT1, DCHS1 or ASTN2 genes. FAT1 and DCHS1 are adhesion transmembrane proteins interacting during brain development, while ASTN2 is involved in dendrite development. Our approach on familial forms of GGE is complementary to large-scale collaborative consortia studies of sporadic cases. Our study reinforces the hypothesis that GGE is genetically heterogeneous, even in a relatively limited geographic area, and mainly oligogenic, as supported by the low familial penetrance of GGE and by the Bayesian algorithm that we developed in a large pedigree with JME. Since populations with founder effect and endogamy are appropriate to study autosomal recessive pathologies, they would be also adapted to decipher genetic components of complex diseases, using the reported bayesian model.Graphical

Late-onset drug-resistant epilepsy in pyridoxamine 5′-phosphate oxidase deficiency: a case report

BackgroundPyridoxamine 5′-phosphate oxidase deficiency is a rare inborn error of vitamin B6 metabolism that presents with drug-resistant epileptic seizures. However, the condition is responsive to supplementation with the active vitamin B6 metabolite pyridoxal 5′-phosphate and, in some cases, pyridoxine. Case presentationIn this case report, a 10-year-old Iranian male of Fars ethnicity came to a regional hospital in Tehran, Iran with a chief complaint of tic-like movement. He had a history of unintentional, repetitive, and stereotypic movements of both arms since the age of 4 years. The physical examination depicted facial dimorphism. During admission, the patient experienced habitual hypermotor seizures and generalized tonic–clonic seizures. Ictal electroencephalography demonstrated a generalized background attenuation and bursts of generalized, predominantly left-sided, biphasic spike-wave complexes. Whole-genome sequencing revealed a pyridoxamine 5′-phosphate oxidase deficiency as the underlying cause of the drug-resistant seizures, resulting in a low serum level of pyridoxal 5′-phosphate. The patient underwent pyridoxine supplementation therapy, which ultimately resolved his seizures. At 6 months, he was seizure free.ConclusionPhysicians ought to be aware of manifestations of vitamin B6 deficiency such as mimicking tic and consider it in the differential for drug-resistant epilepsy.

ANTICONVULSANT EFFECT OF ISOLATED COMPOUNDS FROM THE LEAVES OF GLOBIMETULA BRAUNII ENGLER VAN TIEGH (LORANTHACEAE) IN MICE AND CHICKS

The anticonvulsant evaluation of globrauneine A (1), globrauneine C (2) globrauneine D (3), globrauneine F (4), lupeol (5), β-sitosterol (6), (1R,5S,7S)-7-[2-(4-hydroxyphenyl) ethyl]-2,6-dioxabi-cyclo [3. 3.1]-nonan-3-one (7), dodoneine (8), quercetin (9) and rutin (10) from Globimetula braunii leaves were analyzed with the aid of pentylenetetrazole-induced seizure test in mice (PTZ) and maximal electroshock seizure test in chicks (MEST), while the neurotoxicity was evaluated using the beam walking assay in mice. 50% of the tested mice were protected by Globrauneine A (1) and dodoneine (8) against PTZ-induced mortality. The mean onset of clonic spasm of the unprotected animals was increased by Quercetin (9) and also the mice were differentially protected against mortality. The tested compounds also produced significant (p<0.05) increase in the mean onset of seizure against pentylenetetrazole-induced seizure. The chicks were not protected by the tested compounds against MEST and the recovery time was not significantly reduced. In the beam assay, with the exception of dodoneine (8), the number of foot slips and the time taken to complete the task was not significantly changed by the tested isolated compounds, suggesting that the observed activities are not due to general CNS depression. The results suggest mild protective effects of these isolated compounds against seizure which might be useful in the control of petit mal epilepsy.

Clinical characteristics of patients with P4HTM variant-associated epilepsy and therapeutic exploration: a case report and literature review.

The P4HTM gene encodes a transmembrane prolyl 4-hydroxylase, which is responsible for the degradation of hypoxia-inducible transcription factors (HIF) under normoxia. Clinically, biallelic P4HTM variants have been identified in patients with hypotonia, hypoventilation, intellectual disabilities, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome). Seizure was one of the most prominent symptoms. However, the clinical features of patients with epilepsy associated with P4HTM variants remain unclear. In this report, we describe a one-month-old infant with HIDEA syndrome caused by compound heterozygous P4HTM variants (c.300dupG/p.Gly103Argfs*22 and c.488C > T/p.Ala163Val). The infant presented with clonic seizures of focal onset that responded well to valproate, but with profound intellectual disability and global developmental delay at the last follow-up at 3 years old. A review of the existing literature indicates that seizures in this population typically begin early in infancy, manifest in multiple types, and are relatively well controlled. Epilepsy seemed unrelated to developmental outcomes or disease progression. Valproate, which has HIF-1α inhibiting properties, may be a promising treatment avenue for this population.

Empagliflozin modulates seizure activity and oxidative stress in rats with epilepsy

Drug-resistant epilepsy, a commonly devastating condition, affects more than 50 million people globally. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of neurological disorders, and a potential association between epilepsy and subsequent T2DM has emerged. Inhibiting sodium-glucose linked transporters (SGLTs), which are differentially expressed in the brain, has been shown to reduce epileptic episode activity. This study aimed to evaluate the anticonvulsive effect of empagliflozin in rats with seizures induced by maximal electric shock (MES) and pentylenetetrazol (PTZ). Generalized tonic‒clonic seizures were induced in the rats using an electroconvulsive meter, and pentylenetetrazol was injected to induce absence seizures. The duration of all the stages of seizure and Racine stage scoring (RSS) were performed. Malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) levels in the brain tissues were determined. Histopathological analysis of the brain tissues was carried out. A significant (p <0.01) decrease in the duration of tonic hind limb extension (THLE), a significant decrease in the levels of pro-oxidants such as MDA and NO, and an increase in the levels of antioxidants such as GSH were observed in the low dose 10 mg/kg and high dose 20 mg/kg empagliflozin groups compared to the disease control group. Histopathological analysis revealed a greater number of healthy neurons with few dark-stained cells in the treatment groups, suggesting the neuroprotective effect of empagliflozin. The present study showed that empagliflozin modulates epileptic activity. Empagliflozin has a potential role in the management of epilepsy in diabetic patients.

A Clinical-Electrographic Profile of Neonatal Seizures and Their Etiologies in a Single Level III Neonatal Intensive Care Unit

Background: Seizures are the most frequent neurological emergency in neonatal period and can be associated with significant mortality and subsequent neuro-developmental disability if not recognized and managed early. Repaid identification of neonatal seizures and evaluation is critically required to identify and treat the underlying etiology. Clinicians face a major challenge in diagnosing and treating neonatal seizure because of inconspicuous clinical presentation, variable electro-clinical correlation. Assessing the combination of clinical presentation, etiological factors, different diagnostic tools, and treatments, can broaden the knowledge and understanding towards neonatal seizure providing better management and outcome. Objective: To study the characteristics of clinical and electrographic profile of neonatal seizure and the relations to their etiologies in neonatal intensive care unit. Methods: This is a descriptive cross sectional retrospective study of electronic health records with ICD- 10 diagnosis of neonatal seizure from birth to 28 days, who were admitted to neonatal intensive care unit at Sheikh Shakhbout Medical City between January 2020 to December 2021. Clinical data obtained including basic demographics: gender, gestational age, mode of delivery, birth weight, and Apgar score. Onset and type seizure, type of antiepileptic drugs administered, EEG findings, brain imaging, results of relevant laboratory tests and etiology of seizure were collected. Results: Total 31 neonates included in the study. Majority were male (71%), term (87%), and birth weight >2,5 kg (90%). Seizure within 24 hours was 58% and semiology was focal clonic in 32% of patient. No events in EEG in 81% and 6% had electrographic seizure (n=2). 94 % were treated with anti-convulsant, 86% of them before EEG. The majority (86%) received phenobarbitone as 1st line treatment and 83% received monotherapy. Leading causes of seizure were HIE (48%) followed by Vascular causes (16%). Seizure within 24 hours caused mainly by HIE (61%) and 60% of neonates with vascular and all infectious and genetic causes had seizure after 24 hours. In vascular causes, (60%) presented with focal clonic seizure. 60% of Multifocal epileptiform activity seen in HIE whereas focal presented more in vascular patient (36%). In HIE cases, 53% had normal brain MRI and 47% were abnormal. All cases with vascular causes had diagnostic abnormal MRI. The majority of HIE cases (87%) and all vascular cases received monotherapy. Conclusion: In this descriptive study of neonatal seizure, certain demographic data, clinical and electrographic characteristics had established links to their etiologies. Clinical events captured during EEG with no electrographic seizure are classified as non-epileptic clinical phenomenon. Diagnostic utility of EEG is required in diagnosis of involuntary movements and avoid unnecessary anti-seizure medications. Understanding the clinical-electrographic profile of neonatal seizure helps in the early recognition of specific etiologies, allowing an early diagnosis by organized diagnostic approach and management.

Retrospective evaluation of prescribing pattern and utilization of antiepileptic drugs in pediatric, neurosurgery, and psychiatry wards: A comparative study to the standard treatment guidelines.

Antiepileptic drugs (AED) are progressively utilized for off-label conditions other than epilepsy, like bipolar disorder and migraine. The objective of this study was to evaluate current prescribing patterns and utilization of AED in pediatric, neurosurgery, and psychiatry wards and to compare them to the standard treatment guidelines. A descriptive, cross-sectional study was conducted in Ayyub Teaching Hospital, Abbottabad from December 1st, 2018 to April 2019. Data on demographic and clinical characteristics, utilization patterns of AED, adherence to standard treatment guidelines, and frequency of potential drug-drug interactions were analyzed using descriptive statistics. Among 410 patients, 54.3% (n = 223) were male, 45.6%(n = 187) were female, and 63.7% (n = 261) were from the 1 to 18 years' age group. The majority 47.3% (n = 194) were from the pediatric ward followed by neurosurgery 28.7%(n = 118). Among the studied patients, 96.1% of them had comorbid conditions other than epilepsy alone. With regards to types of seizures unclassified seizures were the most common seizure type (59.8%; n = 245) followed by generalized tonic clonic seizures 23.4% (n = 96). In this study, the most frequently utilized AED was sodium valproate 59.0% (n = 242) followed by antiepileptic first-generation medicines were commonly used (76.3%). Although a total of 77.6% of the patients showed nonadherence to National Institute for Health and Care Excellence guidelines and 87.6% of them showed drug interactions. Findings from this study showed prescription patterns and utilization of AED in patients with epilepsy and non-epilepsy disorders which may help healthcare providers in making accurate clinical decisions.