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Frontiers in Neurology 2024Poststroke seizure is a potential complication of stroke, which is the most frequent acute symptomatic seizure in adults. Patients with stroke may present with an... (Review)
Review
Poststroke seizure is a potential complication of stroke, which is the most frequent acute symptomatic seizure in adults. Patients with stroke may present with an abnormal or aggressive behavior accompanied by altered mental status and symptoms, such as hemiparesis, dysarthria, and sensory deficits. Although stroke manifestations that mimic seizures are rare, diagnosing poststroke seizures can be challenging when accompanied with negative postictal symptoms. Differential diagnoses of poststroke seizures include movement disorders, syncope, and functional (nonepileptic) seizures, which may present with symptoms similar to seizures. Furthermore, it is important to determine whether poststroke seizures occur early or late. Seizures occurring within and after 7 d of stroke onset were classified as early and late seizures, respectively. Early seizures have the same clinical course as acute symptomatic seizures; they rarely recur or require long-term antiseizure medication. Conversely, late seizures are associated with a risk of recurrence similar to that of unprovoked seizures in a patient with a focal lesion, thereby requiring long-term administration of antiseizure medication. After diagnosis, concerns regarding treatment strategies, treatment duration, and administration of primary and secondary prophylaxis often arise. Antiseizure medication decisions for the initiation of short-term primary and long-term secondary seizure prophylaxis should be considered for patients with stroke. Antiseizure drugs such as lamotrigine, carbamazepine, lacosamide, levetiracetam, phenytoin, and valproate may be administered. Poststroke seizures should be diagnosed systematically through history with differential diagnosis; in addition, classifying them as early or late seizures can help to determine treatment strategies.
PubMed: 38660095
DOI: 10.3389/fneur.2024.1337960 -
Epilepsy Research Nov 2023This retrospective chart review examined dose reductions and discontinuations of concomitant antiseizure medications (ASMs) following cenobamate initiation and...
This retrospective chart review examined dose reductions and discontinuations of concomitant antiseizure medications (ASMs) following cenobamate initiation and maintenance in patients with epilepsy treated at MetroHealth (Cleveland, OH) between 9/1/2020-9/26/2022. Concomitant ASM dose adjustments and treatment-emergent adverse events (TEAEs) were assessed. Efficacy (100 % seizure reduction) was examined among patients who received cenobamate for ≥ 3 months at data cutoff (including titration). As of 9/26/2022, 95 patients received cenobamate (mean age, 45.9 years; 48.4 % female, median exposure 7.5 months). Five patients (5.3 %) discontinued (n = 1 withdrawal by patient; n = 1 noncompliance; n = 3 adverse event). Among the 90 patients taking cenobamate at data cutoff, 50 % (45/90) discontinued ≥ 1 concomitant ASM, most commonly clobazam (n = 18), levetiracetam (n = 10), and phenytoin (n = 7); 21 patients (23.3 %) had additional concomitant ASM dose reductions, most commonly phenytoin (n = 6) and clobazam (n = 4). Sixteen patients received cenobamate monotherapy. Among 79 patients who received cenobamate for ≥ 3 months at data cutoff, 51.9 % (41/79) were seizure-free for ≥ 3 months. Of the 41 seizure-free patients, 58.5 % (24/41) were taking 100 mg/day of cenobamate. Sixteen of the 95 cenobamate-treated patients (16.8 %) reported 22 TEAEs. The most common TEAE was fatigue (n = 7). These data suggest that cenobamate therapy may allow reduction or elimination of polytherapy in some patients.
Topics: Humans; Female; Middle Aged; Male; Drug Tapering; Retrospective Studies; Clobazam; Phenytoin; Anticonvulsants; Treatment Outcome
PubMed: 37871541
DOI: 10.1016/j.eplepsyres.2023.107242 -
Small (Weinheim An Der Bergstrasse,... Jul 2023Phenytoin (PHT) is a first-line antiepileptic drug in clinics, which could decrease neuronal bioelectric activity by blocking the voltage-operated sodium channels....
Phenytoin (PHT) is a first-line antiepileptic drug in clinics, which could decrease neuronal bioelectric activity by blocking the voltage-operated sodium channels. However, the intrinsically low blood-brain-barrier (BBB)-crossing capability of PHT and upregulated expression level of the efflux transporter p-glycoprotein (P-gp) coded by the gene Abcb1 in epileptic neurons limit its efficacy in vivo. Herein, a nanointegrated strategy to overcome PHT resistance mechanisms for enhanced antiepileptic efficacy is reported. Specifically, PHT is first incorporated into calcium phosphate (CaP) nanoparticles through biomineralization, followed by the surface modification of the PEGylated BBB-penetrating TAT peptide. The CaP@PHT-PEG-TAT nanoformulation could effectively cross the BBB to be taken in by epileptic neurons. Afterward, the acidic lysosomal environment would trigger their complete degradation to release Ca and PHT into the cytosol. Ca ions would inhibit mitochondrial oxidative phosphorylation to reverse cellular hypoxia to block hypoxia-inducible factor-1α (Hif1α)-Abcb1-axis, as well as disrupt adenosine triphosphate generation, leading to simultaneous suppression of the expression and drug efflux capacity of P-gp to enhance PHT retention. This study offers an approach for effective therapeutic intervention against drug-resistant epilepsy.
Topics: Humans; Phenytoin; ATP Binding Cassette Transporter, Subfamily B, Member 1; Epilepsy; Seizures; Anticonvulsants; Neurons; Calcium Phosphates
PubMed: 37029709
DOI: 10.1002/smll.202300395 -
Biomedicines Oct 2023Four 5,5'-diphenylhydantoin Schiff bases possessing different aromatic species (-) were recently synthesized and characterized using spectroscopic and electrochemical...
Four 5,5'-diphenylhydantoin Schiff bases possessing different aromatic species (-) were recently synthesized and characterized using spectroscopic and electrochemical tools. The present study aimed to ascertain the anticonvulsant activity of the novel phenytoin derivatives , , , and , containing different electron-donor and electron-acceptor groups, and their possible mechanism of action. The exhibited the highest potency to suppress the seizure spread with ED = 8.29 mg/kg, comparable to phenytoin (ED = 5.96 mg/kg). While did not produce neurotoxicity and sedation, it decreased locomotion and stereotypy compared to control. When administered in combination, the four Schiff bases decreased the phenytoin ED by more than 2× and raised the protective index by more than 7× (phenytoin+). The strongest correlation between in-vivo and docking study results was found for ligands' interaction energies with kappa and delta receptors. These data, combined with the worst interaction energies of our ligands with the mu receptor, suggest that the primary mechanism of their action involves the kappa and delta receptors, where the selectivity to the kappa receptor leads to higher biological effects. Our findings suggest that the four Schiff bases might be promising candidates with potential applications as a safe and effective adjuvant in epilepsy.
PubMed: 38001914
DOI: 10.3390/biomedicines11112912 -
Frontiers in Pharmacology 2023Captisol-enabled-fosphenytoin sodium (CE-fosphenytoin sodium) injection is a modified formulation of fosphenytoin sodium. We aim to compare the intravenous and...
Comparison of pharmacokinetics and safety between CE-fosphenytoin sodium, fosphenytoin sodium, and phenytoin sodium after intravenous and intramuscular administration in healthy volunteers.
Captisol-enabled-fosphenytoin sodium (CE-fosphenytoin sodium) injection is a modified formulation of fosphenytoin sodium. We aim to compare the intravenous and intramuscular bioavailability and safety between CE-fosphenytoin sodium, fosphenytoin sodium (Cerebyx), and phenytoin sodium (intravenous injection only). In pivotal study 1, 54 subjects were divided into three sequence groups that receive intravenous injection of 250 mg of phenytoin sodium equivalent (PE), CE-fosphenytoin sodium (T), or fosphenytoin sodium (R1) and 250 mg of phenytoin sodium (R2) in period 1. After a 14-day washout period, 36 subjects were randomized to two treatment sequence groups (T-R1 or R1-T, = 18 per group) in period 2, in which the subjects who received R2 in period 1 were removed, those who received T in period 1 used R1 (T-R1), while those who previously received R1 used T (R1-T). In pivotal study 2, a single intramuscular dose of T (400 mg PE) or R1 (400 mg PE) was administered according to the individual sequential treatment assignment in each period. There was a washout (14 days) period before receiving the next period study drug. T and R1 have similar pharmacokinetic characteristics regarding total and free phenytoin, showing bioequivalence of both drugs in the intravenous and intramuscular administration. The geometric mean ratio was close to 1 (0.98-1.06). The AUC of total and free phenytoin in subjects who intravenously received T and R1 was very similar to those who received R2, although their C was lower than that of the subjects who received R2. Overall, treatment with T and R1 was safe and well-tolerated, without serious adverse events (SAEs) or grade III adverse events (AEs). With intravenous (i.v.) or intramuscular (i.m.) treatment, the incidence of drug-related AEs using T was similar to that using R1. Treatment with T and R1 had clearly superior tolerability than that with R2. CE-fosphenytoin sodium is a promising substitute for fosphenytoin sodium. http://www.chinadrugtrials.org.cn/, CTR20202154 (11 November 2020).
PubMed: 38044946
DOI: 10.3389/fphar.2023.1204075 -
BioRxiv : the Preprint Server For... Oct 2023The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric...
OBJECTIVE
The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group.
METHODS
A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness.
RESULTS
Across all epilepsies, reduced total cerebellar volume was observed (=0.42). Maximum volume loss was observed in the corpus medullare (=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (= 0.47), Crus I/II (= 0.39), VIIIA (=0.45) and VIIIB (=0.40). Earlier age at seizure onset (=0.05) and longer epilepsy duration (=0.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls.
SIGNIFICANCE
We provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy.
PubMed: 37961570
DOI: 10.1101/2023.10.21.562994 -
Journal of Pharmacy Practice Jun 2024Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic...
Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 μg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.
PubMed: 38871356
DOI: 10.1177/08971900241262379 -
Cureus Jul 2023Stevens-Johnson syndrome (SJS) is a dreaded hypersensitivity reaction and a rare immune disorder. We present a Stevens-Johnson syndrome induced by herbal kadha, which...
Stevens-Johnson syndrome (SJS) is a dreaded hypersensitivity reaction and a rare immune disorder. We present a Stevens-Johnson syndrome induced by herbal kadha, which may be the first case. A ten-year-old boy presented with massive sloughing, redness, oedematous skin, an oral ulcer, and an inability to feed or drink for two days. The present symptoms started after 12 hours of consuming herbal Kadha, given by a private practitioner in clinics where he was treated for fever. After not responding to earlier treatment, the patient was referred to the present Institute. The patient had a history of seizure disorder and had been on tablet phenytoin for seven months with no history of adverse reactions to it. He was treated in the intensive care unit. Fortunately, he responded to treatment and recovered fully. He received treatment in the form of immunoglobulin and steroids. Phenytoin and herbal kadha were withdrawn, and Clobazam was continued. Natural herbal medicines can develop severe adverse effects. Physicians should remain aware that drug interactions can likely be seen with drugs with a narrow therapeutic index combined with herbal preparations. Clinicians should do more research on the interaction between herbal and prescription medications.
PubMed: 37637620
DOI: 10.7759/cureus.42407 -
Medicinal Research Reviews Jul 2024Diabetic foot ulcer (DFU) is one of the most costly and serious complications of diabetes. Treatment of DFU is usually challenging and new approaches are required to... (Review)
Review
Diabetic foot ulcer (DFU) is one of the most costly and serious complications of diabetes. Treatment of DFU is usually challenging and new approaches are required to improve the therapeutic efficiencies. This review aims to update new and upcoming adjunctive therapies with noninvasive characterization for DFU, focusing on bioactive dressings, bioengineered tissues, mesenchymal stem cell (MSC) based therapy, platelet and cytokine-based therapy, topical oxygen therapy, and some repurposed drugs such as hypoglycemic agents, blood pressure medications, phenytoin, vitamins, and magnesium. Although the mentioned therapies may contribute to the improvement of DFU to a certain extent, most of the evidence come from clinical trials with small sample size and inconsistent selections of DFU patients. Further studies with high design quality and adequate sample sizes are necessitated. In addition, no single approach would completely correct the complex pathogenesis of DFU. Reasonable selection and combination of these techniques should be considered.
Topics: Humans; Diabetic Foot; Bandages; Animals
PubMed: 38279968
DOI: 10.1002/med.22020 -
CNS Drugs Nov 2023Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The...
Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012-2021) from a University Hospital in Germany.
BACKGROUND AND OBJECTIVES
Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials.
METHODS
The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly.
RESULTS
This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021.
CONCLUSION
Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.
Topics: Humans; Child; Adult; Female; Middle Aged; Aged; Aged, 80 and over; Male; Anticonvulsants; Phenytoin; Midazolam; Levetiracetam; Valproic Acid; Propofol; Lacosamide; Hospitals, University; Status Epilepticus; Phenobarbital; Benzodiazepines; Medical Records
PubMed: 37979095
DOI: 10.1007/s40263-023-01049-w