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European Review For Medical and... Feb 2024This study aimed to investigate the association between serum galanin (GAL) and neuron-specific enolase (NSE) levels in children with convulsive status epilepticus (CSE)...
Correlation between serum galanin and neuron-specific enolase levels with EEG abnormalities in pediatric convulsive status epilepticus and the efficacy of triple drug therapy.
OBJECTIVE
This study aimed to investigate the association between serum galanin (GAL) and neuron-specific enolase (NSE) levels in children with convulsive status epilepticus (CSE) and their relationship with abnormal electroencephalogram (EEG) patterns. Additionally, the study assessed the effectiveness of a combination therapy involving midazolam, diazepam, and phenobarbital in treating CSE.
PATIENTS AND METHODS
The research involved 100 children diagnosed with CSE and included a control group of 50 healthy children. Serum GAL and NSE levels were measured, and EEGs were analyzed for abnormalities in the CSE group. Comparisons were made between the healthy control group and the CSE group, particularly within the first 24 hours after persistent seizures. The severity of EEG abnormalities was correlated with GAL and NSE levels. The treatment consisted of an observation group that received the triple therapy of midazolam, diazepam, and phenobarbital, while a control group received diazepam and phenobarbital. Clinical efficacy, symptom improvement, Status Epilepticus Severity Score (STESS), and adverse reactions were evaluated.
RESULTS
The results indicated elevated levels of GAL and NSE in the CSE group, with higher levels noted within 24 hours after persistent seizures. Furthermore, a positive correlation was observed between the severity of EEG abnormalities and GAL and NSE levels. The group receiving the triple therapy demonstrated superior efficacy, faster resolution of seizures and fever, reduced STESS scores, and fewer adverse reactions than the control group. In conclusion, this study highlights the positive correlation between serum GAL and NSE levels and the severity of EEG abnormalities in pediatric CSE. The triple therapy approach is effective in treating CSE, leading to improved clinical symptoms, reduced brain damage, and enhanced safety.
CONCLUSIONS
The study concludes that serum GAL and NSE levels in children with convulsive status epilepticus are positively correlated with the degree of EEG abnormalities. The combination therapy involving midazolam, diazepam, and phenobarbital is effective in treating children with convulsive status epilepticus, significantly improving clinical symptoms, reducing brain damage, and ensuring safety.
Topics: Child; Humans; Midazolam; Galanin; Status Epilepticus; Seizures; Diazepam; Phenobarbital; Electroencephalography; Brain Injuries; Phosphopyruvate Hydratase; Anticonvulsants
PubMed: 38375724
DOI: 10.26355/eurrev_202402_35358 -
Epilepsy & Behavior : E&B Nov 2023This study evaluated the impact of a newly established clinic for the diagnosis of pediatric epilepsy in a resource-limited center (Ifakara, Tanzania). (Observational Study)
Observational Study
PURPOSE
This study evaluated the impact of a newly established clinic for the diagnosis of pediatric epilepsy in a resource-limited center (Ifakara, Tanzania).
METHODS
Patients aged 0-18 years referred to the Pediatric Epilepsy Unit of Saint Francis Referral Hospital were recruited. Demographic and clinical data were collected through Kobo Toolbox and analyzed through a descriptive analysis..
RESULTS
143 patients were evaluated, and for 48 of them an EEG was recorded (abnormalities were detected in 80.85% of the cases). The diagnosis of epilepsy was confirmed in 87 patients. Focal epilepsy was diagnosed in 57 patients, generalized epilepsy in 24 patients, and forms of unknown onset in 6 patients. Epilepsy was excluded for 9 children. Etiologies included hypoxic-ischemic encephalopathy (39%), central nervous system infections (3.4%), and genetic diseases (3.4%). A specific epilepsy syndrome was diagnosed in 16 patients. 74 patients were under treatment; the most used antiseizure medication (ASM) was phenobarbital (43.36%), followed by carbamazepine (16.08%), sodium valproate (11.19%), phenytoin (2.8%), and lamotrigine (0.7%). Therapeutic changes were proposed to 95 patients, more frequently consisting of withdrawing phenobarbital (39.16%), switching to sodium valproate (27.97%), switching to or adjusting carbamazepine dosage (27.27%), and starting prednisone (2.8%). 76% of the patients with confirmed epilepsy achieved complete seizure freedom at the fourth follow-up consultation.
CONCLUSIONS
Our data depicted the epilepsy spectrum and highlighted the prognostic implications of improving the availability of ASMs such as sodium valproate and second- and third-generation ones in resource-limited countries.
Topics: Child; Humans; Valproic Acid; Tanzania; Epilepsy; Anticonvulsants; Carbamazepine; Phenobarbital; Benzodiazepines
PubMed: 37776594
DOI: 10.1016/j.yebeh.2023.109454 -
Veterinary World Feb 2024Dogs with idiopathic epilepsy (IE) experience a shortened lifespan, neurobehavioral changes, and an increased risk of comorbidities during the interictal period. There...
BACKGROUND AND AIM
Dogs with idiopathic epilepsy (IE) experience a shortened lifespan, neurobehavioral changes, and an increased risk of comorbidities during the interictal period. There have been several reports of sudden death in humans with epilepsy, suggesting changes in cardiac rhythm secondary to seizures. In veterinary medicine, there are still no such conclusive studies. The present study aimed to evaluate blood pressure values, electrocardiographic findings, and laboratory parameters in dogs with IE treated with phenobarbital and to correlate these findings with possible cardiac alterations.
MATERIALS AND METHODS
Twenty-one dogs were divided into 11 healthy dogs and 10 idiopathic epileptic dogs for blood analysis, computerized electrocardiogram, and oscillometer-based blood pressure measurement.
RESULTS
QRS complex and S-T interval values differed significantly between groups, but blood pressure values were not significantly different.
CONCLUSION
IE can occur with alterations in cardiac conduction and is a pathological condition.
PubMed: 38595650
DOI: 10.14202/vetworld.2024.356-360 -
Cureus Feb 2024This case report highlights the complexities of tizanidine withdrawal in a 68-year-old woman with chronic pain. Tizanidine, a widely used imidazole-derived muscle...
This case report highlights the complexities of tizanidine withdrawal in a 68-year-old woman with chronic pain. Tizanidine, a widely used imidazole-derived muscle relaxant, poses challenges due to the absence of standardized withdrawal protocols. The patient's presentation included hypertension and tachycardia following a gradual reduction in her outpatient tizanidine dose. During the de-escalation of tizanidine, the patient experienced withdrawal symptoms, including severe body aches, hypertension, and tachycardia. Management during withdrawal involved a unique approach using a one-time dose of phenobarbital, a measure that allowed the resolution of hemodynamic instability and pain with complete discontinuation of tizanidine. The ultimate decision to transition the patient to methocarbamol and stop taking tizanidine for pain control highlights the importance of individualized care. The patient has responded to this therapy upon follow-up.
PubMed: 38435197
DOI: 10.7759/cureus.53444 -
Cancer Management and Research 2024Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs,...
PURPOSE
Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs, generally bred for meat production, can be used to generate hepatocellular carcinoma (HCC) animal models. The goal of this study was to investigate how N-diethylnitrosamine (DENA) and phenobarbital (PB) together can generate HCC in ordinary farmed pigs.
MATERIALS AND METHODS
Conventional domestic swine () were used. DENA 15 mg/kg was intraperitoneally injected weekly for 12 weeks, while PB tablets (4 mg/kg) were also administered through food for 16 weeks. Blood testing and ultrasonography evaluation were performed to monitor the progress. Subsequently, computed tomography was conducted in cases with suspected nodules, followed by histopathological examination to confirm the diagnosis.
RESULTS
Ten swine (seven males, three females; age: 2 months; weight: 9-15 kg) were included in the study and followed up for 25 months; nine were experimental, and one was control for ethical considerations. The maximum weight of animals during this study reached 162-228 kg. The weight gain seen in the intervention swine was predominantly lower than that documented in the control. The laboratory analysis revealed no notable abnormalities in liver function markers but did demonstrate statistically significant changes in urea (p = 0.028) and creatinine (p = 0.003) levels. Ultrasonography and computed tomography showed multiple liver nodules with characteristics resembling HCC. Serial imaging screening and more extended observations revealed that all animals eventually developed tumors. Histopathological confirmation at 15-22 weeks post-induction revealed that all intervened swine developed multiple nodules of well-differentiated HCC and some with hepatic angiosarcoma.
CONCLUSION
This study successfully generated HCC in conventional domestic swine with a DENA and PB combination. This investigation required at least 15 months to develop tumors. This model will be beneficial for future investigations of HCC in large animals.
PubMed: 38560662
DOI: 10.2147/CMAR.S439787 -
PloS One 2024This retrospective cohort study described the obstetric and neonatal outcomes, antiseizure medication (ASM) use, and types of seizures in pregnant women with epilepsy...
This retrospective cohort study described the obstetric and neonatal outcomes, antiseizure medication (ASM) use, and types of seizures in pregnant women with epilepsy (PWWE). Data collected from the medical records of 224 PWWE aged < 40 years with controlled or refractory seizures and 492 pregnant women without epilepsy (PWNE) control group from high-risk maternity hospitals in Alagoas between 2008 and 2021 were included in this study. The obstetric and neonatal outcomes observed in PWWE were pregnancy-related hypertension (PrH) (18.4%), oligohydramnios (10.3%), stillbirth (6.4%), vaginal bleeding (6%), preeclampsia (4.7%), and polyhydramnios (3%). There was a greater likelihood of PrH in PWWE with generalized tonic-clonic seizures (GTCS) and that of maternal intensive care unit (ICU) admissions in those with GTCS and status epilepticus, and phenytoin and lamotrigine use. PWWE with GTCS had a higher risk of stillbirth and premature delivery. PWWE with status epilepticus were treated with lamotrigine. Phenobarbital (PB) with diazepam were commonly used in GTCS and status epilepticus. Total 14% patients did not use ASM, while 50.2% used monotherapy and 35.8% used polytherapy. Total 60.9% of patients used PB and 25.2% used carbamazepine. This study described the association between the adverse obstetric and neonatal outcomes and severe seizure types in PWWE.
Topics: Infant, Newborn; Female; Humans; Pregnancy; Lamotrigine; Pregnant Women; Retrospective Studies; Stillbirth; Brazil; Anticonvulsants; Seizures; Epilepsy; Phenobarbital; Status Epilepticus
PubMed: 38558080
DOI: 10.1371/journal.pone.0291190 -
Clinical Chemistry and Laboratory... Jun 2024Phenobarbital serves as an antiepileptic drug (AED) and finds application in the treatment of epilepsy either as monotherapy or adjunctive therapy. This drug exhibits...
An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of phenobarbital in human serum and plasma.
OBJECTIVES
Phenobarbital serves as an antiepileptic drug (AED) and finds application in the treatment of epilepsy either as monotherapy or adjunctive therapy. This drug exhibits various pharmacodynamic properties that account for its beneficial effects as well as potential side effects. Accurate measurement of its concentration is critical for optimizing AED therapy through appropriate dose adjustments. Therefore, our objective was to develop and validate a new reference measurement procedure (RMP) for the accurate quantification of phenobarbital levels in human serum and plasma.
METHODS
A sample preparation protocol based on protein precipitation followed by a high dilution step was established in combination with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using a C8 column to separate target analytes from known and unknown interferences. Assay validation and determination of measurement uncertainty were performed based on current guidelines. Selectivity and Specificity were assessed using spiked serum and plasma samples; to investigate possible matrix effects (MEs) a post-column infusion experiment and a comparison of standard line slopes was performed. Precision and accuracy were determined within a multiday precision experiment.
RESULTS
The RMP was shown to be highly selective and specific, with no evidence of matrix interferences. It can be used to quantify phenobarbital in the range of 1.92 to 72.0 μg/mL. Intermediate precision was less than 3.2 %, and repeatability coefficient of variation (CV) ranged from 1.3 to 2.0 % across all concentration levels. The relative mean bias ranged from -3.0 to -0.7 % for native serum levels, and from -2.8 to 0.8 % for Li-heparin plasma levels. The measurement uncertainties (k=1) for single measurements and target value assignment were 1.9 to 3.3 % and 0.9 to 1.6 %, respectively.
CONCLUSIONS
A novel LC-MS/MS-based candidate RMP for the quantification of phenobarbital in human serum and plasma is presented which can be used for the standardization of routine assays and the evaluation of clinically relevant samples.
Topics: Humans; Phenobarbital; Tandem Mass Spectrometry; Chromatography, Liquid; Anticonvulsants; Reference Standards; Blood Chemical Analysis; Indicator Dilution Techniques; Liquid Chromatography-Mass Spectrometry
PubMed: 38407268
DOI: 10.1515/cclm-2023-1104 -
Frontiers in Pharmacology 2023The WHO Model List of Essential Medicines for Children (EMLc) has not been systematically revised in the last few years. We conducted a survey addressed to healthcare...
Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project.
The WHO Model List of Essential Medicines for Children (EMLc) has not been systematically revised in the last few years. We conducted a survey addressed to healthcare professionals prescribing, preparing, or administering medicines to children and a narrative review to identify problematic paediatric formulations or missing medicines in all therapeutic fields to inform the review of the EMLc in 2023. A total of 285 physicians (63%), 28 nurses (6%) and 142 pharmacists (31%), mostly working in the hospital setting, reported at least one problematic medicine. 290 medicines were reported as missing (completely or the child-appropriate formulation). The top three most mentioned were ciprofloxacin together with phenobarbital and omeprazole. 387 medicines were reported as problematic (34% were oral liquid formulations, 34% tablets, 18% parenteral preparations. Mostly of the products were antibacterials (27%), cardiovascular medicines (11%) and antivirals (11%). The obtained responses show the perspective of healthcare workers working around the world, particularly in the European region (25%), in the African region (24%), and in the Region of the Americas (19%), with limited representation from Northern Africa and the Middle East. Our results need to be analysed with the outputs of other ongoing works before specific products can enter the WHO-hosted Global Accelerator for Paediatric formulations network prioritisation process. Efforts to develop appropriate formulations for children should be accelerated so that the uncertainties associated with off-label drug preparation and use are minimised, and therapeutic benefits are optimised.
PubMed: 37529704
DOI: 10.3389/fphar.2023.1200848 -
Frontiers in Pediatrics 2023It is generally recognized that genetic metabolic disorders can result in neurological symptoms such as seizures, developmental delay, and intellectual disability....
BACKGROUND
It is generally recognized that genetic metabolic disorders can result in neurological symptoms such as seizures, developmental delay, and intellectual disability. Heterogeneous clinical presentations make the diagnosis challenging.
CASE PRESENTATION
In this case report, we present a unique and complex genetic disorder observed in a female patient who exhibited three pathogenic gene variants in the , and genes. The convergence of these variants resulted in a multifaceted clinical presentation characterized by severe seizures of combined focal and generalized onset, metabolic dysfunction, and neurodevelopmental abnormalities. The identification and functional characterization of these gene variants shed light on the intricate interplay between these genes and the patient's phenotype. EEG revealed an epileptiform abnormality which presented in the inter-ictal period from the left frontal-central area and in the ictal period from the left mid-temporal area. The brain MRI revealed volume loss in the posterior periventricular area and parietal parenchyma, myelin destruction with no sign of hypoxic involvement, and left dominant enlargement of the lateral ventricles secondary to loss of central parenchyma. The patient was diagnosed through exome sequencing with Sifrim-Hitz-Weiss syndrome, development and epileptic encephalopathy-14, and medium-chain acyl-CoA dehydrogenase deficiency. An antiseizure medication regimen with valproic acid, levetiracetam, phenobarbital, and clonazepam was initiated. However, this led to only partial control of the seizures.
CONCLUSION
Clinical follow-up of the patient will further define the clinical spectrum of , and gene variants. It will also determine the long-term efficacy of the treatment of seizures and the development of precision medicine for epilepsy syndromes due to gain-of-function variants. Special emphasis should be put on the role and importance of large-scale genomic testing in understanding and diagnosing complex phenotypes and atypical epileptic syndromes.
PubMed: 37732012
DOI: 10.3389/fped.2023.1230056 -
Frontiers in Medicine 2024Crigler-Najjar syndrome (CNS) is caused by mutations in uridine 5'-diphosphate glucuronyltransferase (UGT1A1) resulting in enzyme deficiency and hyperbilirubinemia. Type...
BACKGROUND
Crigler-Najjar syndrome (CNS) is caused by mutations in uridine 5'-diphosphate glucuronyltransferase (UGT1A1) resulting in enzyme deficiency and hyperbilirubinemia. Type II CNS patients could respond to phenobarbital treatment and survive. This study presents a rare case of type II CNS.
CASE SUMMARY
The proband was a 29-year-old male patient admitted with severe jaundice. A hepatic biopsy showed bullous steatosis of the peri-central veins of the hepatic lobule, sediment of bile pigment, and mild periportal inflammation with normal liver plate structure. The type II CNS was diagnosed by routine genomic sequencing which found that the proband with the Gry71Arg/Tyr486Asp compound heterozygous mutations in the UGT1A1 gene. After treatment with phenobarbital (180 mg/day), his bilirubin levels fluctuated between 100 and 200 μmol/L for 6 months and without severe icterus.
CONCLUSION
Type II CNS could be diagnosed by routine gene sequencing and treated by phenobarbital.
PubMed: 38784231
DOI: 10.3389/fmed.2024.1354514