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Epileptic Disorders : International... Aug 2023Pathogenic PRRT2 variants cause self-limited (familial) infantile epilepsy (SeLIE), which is responsive to sodium channel blocking antiseizure medications. The...
OBJECTIVE
Pathogenic PRRT2 variants cause self-limited (familial) infantile epilepsy (SeLIE), which is responsive to sodium channel blocking antiseizure medications. The interictal EEG is typically normal. We describe a cohort of infants with PRRT2-related SeLIE with striking peri-ictal EEG abnormalities.
METHODS
We included all infants diagnosed with PRRT2-related SeLIE during July 2020 to November 2021 at the Royal Children's Hospital, Melbourne. Clinical features and results of aetiologic investigations were collected from electronic medical records. All EEGs were reviewed independently by two epileptologists.
RESULTS
Ten infants presented with focal seizures at a median age of 5 months (range: 3-6 months). Eight had a family history of epilepsy, paroxysmal kinesigenic dyskinesia (PKD) or hemiplegic migraine. Seven of the eight infants with an EEG performed within 24 h of the most recent seizure had epileptiform discharges. Their EEGs showed focal sharp waves, spikes, polyspikes or fast activity independently over the left and right temporo-occipital regions. Conversely, the two infants with last known seizure greater than 24 h prior to their EEG had no epileptiform discharges. Oxcarbazepine was commenced in two infants and was effective. Eight infants were initially treated with levetiracetam, and all were subsequently switched to oxcarbazepine due to ongoing seizures or side effects.
SIGNIFICANCE
Posterior polymorphic focal epileptiform discharges on a peri-ictal EEG recording are a feature of PRRT2-related SeLIE. This finding, particularly in the presence of a family history of infantile epilepsy, PKD or hemiplegic migraine, suggests a diagnosis of PRRT2-related SeLIE and has important treatment implications.
Topics: Child; Humans; Infant; Epilepsy, Benign Neonatal; Oxcarbazepine; Hemiplegia; Mutation; Membrane Proteins; Nerve Tissue Proteins; Pedigree; Epilepsy; Seizures; Electroencephalography; Migraine Disorders
PubMed: 37170076
DOI: 10.1002/epd2.20072 -
International Journal of Biological... Jun 2024A stable Madhuca indica oil-in-water nanoemulsion (99-210 nm, zeta potential: > - 30 mV) was produced employing Tween 20 (surfactant) and Transcutol P...
A stable Madhuca indica oil-in-water nanoemulsion (99-210 nm, zeta potential: > - 30 mV) was produced employing Tween 20 (surfactant) and Transcutol P (co-surfactant) (3:1). The nanoemulsion (oil: S = 3:7, 5:5, and 7:3) were subsequently incorporated into oxcarbazepine-loaded carboxymethylxanthan gum (DS = 1.23) dispersion. The hydrogel microspheres were formed using the ionic gelation process. Higher oil concentration had a considerable impact on particle size, drug entrapment efficiency, and buoyancy. The maximum 92 % drug entrapment efficiency was achieved with the microspheres having oil: S ratio 5:5. FESEM study revealed that the microspheres were spherical in shape and had an orange peel-like surface roughness. FTIR analysis revealed a hydrogen bonding interaction between drug and polymer. Thermal and x-ray examinations revealed the transformation of crystalline oxcarbazepine into an amorphous form. The microspheres had a buoyancy period of 7.5 h with corresponding release of around 83 % drug in 8 h in simulated stomach fluid, governed by supercase-II transport mechanism. In vivo neurobehavioral studies on PTZ-induced rats demonstrated that the microspheres outperformed drug suspension in terms of rotarod retention, number of crossings, and rearing activity in open field. Thus, Madhuca indica oil-in-water nanoemulsion-entrapped carboxymethyl xanthan gum microspheres appeared to be useful for monitoring oxcarbazepine release and managing epileptic seizures.
Topics: Microspheres; Animals; Rats; Mannans; Hydrogels; Particle Size; Epilepsy; Male; Drug Carriers; Emulsions; Seizures; Drug Liberation; Plant Oils; Anticonvulsants; Galactose
PubMed: 38825290
DOI: 10.1016/j.ijbiomac.2024.132739 -
Toxins Aug 2023We sought to assess the efficacy of combining onabotulinumtoxinA (BoNTA) as add-on therapy to carbamazepine or oxcarbazepine in treatment-refractory patients with...
We sought to assess the efficacy of combining onabotulinumtoxinA (BoNTA) as add-on therapy to carbamazepine or oxcarbazepine in treatment-refractory patients with trigeminal neuralgia (TGN) who failed to respond (less than 30% response rate) to adequate monotherapy. We conducted a retrospective study on 15 patients with a definite diagnosis of TGN, according to the established criteria, and underwent BoNTA as part of their treatment plan. A single BoNTA session was administered subcutaneously, according to patients' perceived zone of pain, at different dosages ranging from 30 to 200 units (mean ± standard deviation: 87.3 ± 39.2). All patients (15/15; 100%) reported large reductions in the severity of their TGN-related neuropathic pain. The mean pain score on the VAS scale significantly decreased from 9.3 ± 1.1 to 3.7 ± 1.2 at 2 weeks after injecting BoNTA ( < 0.001) and remained stable at 4 and 24 weeks post-injection. Regarding the impact of BoNTA on patients' health-related quality of life, there were significant improvements in both the physical and mental health domains ( < 0.05) of SF-36 tool. BoNTA may be a safe and effective treatment option for patients with refractory TGN when added on to carbamazepine or oxcarbazepine. The use of a single BoNTA session for TGN treatment may be an alternative to surgical interventions and as add-on treatment to oral medications, providing patients with a minimally invasive, effective, safe and well-tolerated option.
Topics: Humans; Oxcarbazepine; Trigeminal Neuralgia; Botulinum Toxins, Type A; Follow-Up Studies; Quality of Life; Retrospective Studies; Carbamazepine; Pain
PubMed: 37755965
DOI: 10.3390/toxins15090539 -
Current Drug Safety 2024Spasticity is a common sequelae of stroke, and often these patients receive anti-spastic drugs such as baclofen or tizanidine. Stroke patients have multiple... (Review)
Review
INTRODUCTION
Spasticity is a common sequelae of stroke, and often these patients receive anti-spastic drugs such as baclofen or tizanidine. Stroke patients have multiple co-morbidities such as hypertension, diabetes, and seizure. Tizanidine is an α2 and imidazole receptor agonist at a spinal and supraspinal level resulting in reduced central sympathetic outflow and causing hypotension rarely, especially in those receiving beta-blockers or angiotensin-converting enzyme inhibitors.
CASE PRESENTATION
We report a 56-year-old hypertensive male presenting with altered sensorium who had recurrent intracerebral hemorrhage with left spastic hemiplegia and focal seizures. He was on amlodipine, atenolol, telmisartan and oxcarbazepine. After 3 doses of tizanidine 2mg, his blood pressure dropped from 140/90 to 80/40 mmHg and pulse from 82 bpm to 44 bpm. His blood counts, serum chemistry, procalcitonin, and Trop I were normal. ECG revealed sinus bradycardia. After 8 hours of withdrawing tizanidine, his blood pressure became 110/70 mmHg, and on the next day, it became 140/82 mmHg. His attendants were taught physiotherapy to minimize spasticity.
CONCLUSION
This patient highlights the need for close monitoring of patients receiving tizanidine co-medication with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These drugs have a synergistic effect on reducing the renin-angiotensin-aldosterone system, thereby hypotension and bradycardia.
Topics: Humans; Male; Middle Aged; Bradycardia; Hypotension, Controlled; Hypertension; Angiotensin-Converting Enzyme Inhibitors; Hypotension; Stroke; Seizures
PubMed: 37489780
DOI: 10.2174/1574886318666230725113855 -
Neurological Sciences : Official... Oct 2023Valproic acid (VPA) is a prevalent antiseizure medication (ASM) used to treat epilepsy. Valproate-related hyperammonemic encephalopathy (VHE) is a type of encephalopathy...
BACKGROUND
Valproic acid (VPA) is a prevalent antiseizure medication (ASM) used to treat epilepsy. Valproate-related hyperammonemic encephalopathy (VHE) is a type of encephalopathy that can occur during neurocritical situations. In VHE, the electroencephalogram (EEG) displays diffuse slow waves or periodic waves, and there is no generalized suppression pattern.
CASE PRESENTATION
We present a case of a 29-year-old female with a history of epilepsy who was admitted for convulsive status epilepticus (CSE), which was controlled by intravenous VPA, as well as oral VPA and phenytoin. The patient did not experience further convulsions but instead developed impaired consciousness. Continuous EEG monitoring revealed a generalized suppression pattern, and the patient was unresponsive. The patient's blood ammonia level was significantly elevated at 386.8 μmol/L, indicating VHE. Additionally, the patient's serum VPA level was 58.37 μg/ml (normal range: 50-100 μg/ml). After stopping VPA and phenytoin and transitioning to oxcarbazepine for anti-seizure and symptomatic treatment, the patient's EEG gradually returned to normal, and her consciousness was fully restored.
DISCUSSION
VHE can cause the EEG to display a generalized suppression pattern. It is crucial to recognize this specific situation and not to infer a poor prognosis based on this EEG pattern.
Topics: Humans; Female; Adult; Valproic Acid; Anticonvulsants; Phenytoin; Epilepsy; Brain Diseases; Electroencephalography; Neurotoxicity Syndromes; Hyperammonemia
PubMed: 37243793
DOI: 10.1007/s10072-023-06865-y -
Expert Opinion on Drug Metabolism &... Mar 2024We aimed to characterize newer antiseizure medications (ASMs)-induced hepatotoxicity in children and identify signals of disproportionate reporting of... (Review)
Review
BACKGROUND
We aimed to characterize newer antiseizure medications (ASMs)-induced hepatotoxicity in children and identify signals of disproportionate reporting of hepatotoxicity-related adverse drug events (ADEs).
RESEARCH DESIGN AND METHODS
Case reports reported to VigiBase were accessed using Empirica™ Signal software. To summarize characteristics of the retrieved cases, descriptive statistics were used. A disproportionality analysis was conducted using the Multi-item Gamma Poisson Shrinker algorithm, which calculates Empirical Bayesian Geometric Mean value and its lower and upper 95% confidence limits (EB05 and EB95, respectively). EB05 > 2, > 0 was considered a signal.
RESULTS
Based on 870 analyzed cases, a higher proportion of cases was reported in girls than in boys and in patients aged 2-11 years than in other age groups. Most cases were serious. In 25 cases, hepatotoxicity resulted in death. A high proportion of patients ( = 275, 31.61%) experienced hypersensitivity reactions, mostly due to lamotrigine. The disproportionality analysis yielded 17 signals concerning felbamate, lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and topiramate. Four signals were for severe liver injury and concerned felbamate, lamotrigine, levetiracetam, and topiramate. Gender-biased reporting frequency was detected for four ASM-ADE combinations.
CONCLUSION
Our results should serve to raise clinicians' awareness about the potential association between several newer ASMs and drug-induced liver injury in children.
Topics: Child; Female; Humans; Male; Adverse Drug Reaction Reporting Systems; Anticonvulsants; Bayes Theorem; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Felbamate; Lamotrigine; Levetiracetam; Topiramate; Child, Preschool
PubMed: 38380611
DOI: 10.1080/17425255.2024.2322114 -
Epileptic Disorders : International... Feb 2024HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies.
OBJECTIVE
HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies.
METHODS
Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay.
RESULTS
In this study, eight de novo variants of HCN1 genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic-clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay.
SIGNIFICANCE
Our research reported eight variants in HCN1 gene causing epilepsy; among these variants, five variants were never reported before. HCN1-related epilepsy usually starts infantile period, and focal secondary generalized tonic-clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for HCN1-related epilepsy.
Topics: Humans; Child; Oxcarbazepine; Levetiracetam; Retrospective Studies; Anticonvulsants; Epilepsy; Seizures; Valproic Acid; China
PubMed: 38009841
DOI: 10.1002/epd2.20182 -
Methods in Molecular Biology (Clifton,... 2024Oxcarbazepine (Trileptal) has been found effective in the treatment of tonic-clonic seizures and partial seizures with or without secondary generalization, with fewer...
Oxcarbazepine (Trileptal) has been found effective in the treatment of tonic-clonic seizures and partial seizures with or without secondary generalization, with fewer side effects than traditional therapy. Oxcarbazepine is a keto analogue of carbamazepine. It is rapidly reduced to 10-monohydroxy carbamazepine (MHD), its active metabolite. This assay measures concentrations for oxcarbazepine metabolite (MHD), internal standard (MHD 13C) solution is added to all the patient specimens resulting in precipitation of proteins. The analytes are separated using a Phenomenex Kinetex C18 column and are detected with a mass spectrophotometer utilizing multiple reaction monitoring (MRM). The analytes are qualitatively identified and quantitated from a calibration curve generated from calibrators included in the run.
Topics: Humans; Oxcarbazepine; Chromatography, Liquid; Tandem Mass Spectrometry; Carbamazepine; Seizures; Anticonvulsants; Chromatography, High Pressure Liquid; Reproducibility of Results
PubMed: 38036839
DOI: 10.1007/978-1-0716-3541-4_35 -
European Journal of Pharmacology Jan 2024Clinical studies documented that cenobamate (CNB) has a marked efficacy compared to other antiseizure medications (ASMs) in reducing focal seizures. To date, different...
Clinical studies documented that cenobamate (CNB) has a marked efficacy compared to other antiseizure medications (ASMs) in reducing focal seizures. To date, different aspects of CNB need to be clarified, including its efficacy against generalized seizures. Similarly, the pattern of drug-drug interactions between CNB and other ASMs also compels further investigation. This study aimed to detect the role of CNB on generalized seizures using the DBA/2 mouse model. We have also studied the effects of an adjunctive CNB treatment on the antiseizure properties of some ASMs against reflex seizures. The effects of this adjunctive treatment on motor performance, body temperature, and brain levels of ASMs were also evaluated. was able to antagonize seizures in DBA/2 mice. CNB, at 5 mg/kg, enhanced the antiseizure activity of ASMs, such as diazepam, clobazam, levetiracetam, perampanel, phenobarbital, topiramate, and valproate. No synergistic effects were observed when CNB was co-administered with some Na channel blockers. The increase in antiseizure activity was associated with a comparable intensification in motor impairment; however, the therapeutic index of combined treatment of ASMs with CNB was more favorable than the combination with vehicle except for carbamazepine, phenytoin, and oxcarbazepine. Since CNB did not significantly influence the brain levels of the ASMs studied, we suggest that pharmacokinetic interactions seem not probable. Overall, this study shows the ability of CNB to counteract generalized reflex seizures in mice. Moreover, our data documented an evident synergistic antiseizure effect for the combination of CNB with ASMs including phenobarbital, benzodiazepines, valproate, perampanel, topiramate, and levetiracetam.
Topics: Mice; Animals; Anticonvulsants; Epilepsy, Reflex; Valproic Acid; Topiramate; Levetiracetam; Drug Synergism; Mice, Inbred DBA; Seizures; Phenobarbital
PubMed: 38029871
DOI: 10.1016/j.ejphar.2023.176222 -
Epilepsy & Behavior : E&B May 2024This study aimed to compare and characterize the safety profiles of new antiseizure medications (ASMs) using a nationwide pharmacovigilance database from a long-term... (Comparative Study)
Comparative Study
OBJECTIVE
This study aimed to compare and characterize the safety profiles of new antiseizure medications (ASMs) using a nationwide pharmacovigilance database from a long-term perspective in Korea.
METHODS
We reviewed adverse event reports from the Korea Adverse Event Reporting System database between January 2013 and December 2022 for descriptive analysis of six new ASMs (lacosamide, levetiracetam, lamotrigine, oxcarbazepine, topiramate, and zonisamide). We investigated the frequency and characteristics of adverse drug reactions (ADRs) based on the MedDRA terminology, system organ classes, and modified WHO classification.
RESULTS
We identified 5,733 reported cases of ADRs. The commonly reported ADRs associated with total ASMs were rash/urticaria (1,822, 31.8 %), dizziness (409, 7.1 %), somnolence/drowsiness (311, 5.4 %), and hepatotoxic effects (273, 4.8 %). Type B (idiosyncratic) effects (2,932; 51.1 %) were more commonly reported than Type A (related to known drug mechanisms) effects (2,613; 45.6 %). Skin and subcutaneous tissue disorders and type B effects were most commonly reported for lamotrigine and oxcarbazepine, whereas nervous system disorders and type A effects were most commonly reported for lacosamide, topiramate, and zonisamide. The pediatric group (<18 years) exhibited skin and subcutaneous tissue disorders and type B effects relatively more frequently than the adult and older adult groups.
CONCLUSION
Hypersensitivity skin reactions and type B effects remained significant ADRs in the new ASMs; however, type A effects were more commonly reported in some ASMs. The pediatric group showed a higher rate of type B effects. Overall, new ASMs should also be used with caution.
Topics: Humans; Anticonvulsants; Republic of Korea; Adverse Drug Reaction Reporting Systems; Male; Female; Adult; Child; Middle Aged; Adolescent; Child, Preschool; Young Adult; Aged; Infant; Drug-Related Side Effects and Adverse Reactions; Pharmacovigilance; Topiramate; Oxcarbazepine; Databases, Factual; Lamotrigine; Lacosamide; Zonisamide; Infant, Newborn; Levetiracetam; Aged, 80 and over; Epilepsy
PubMed: 38636107
DOI: 10.1016/j.yebeh.2024.109784