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Cureus Feb 2023Background and objective Epilepsy is the commonest serious neurological condition and around 50 million people live with epilepsy (PWE). Primary and secondary...
Evaluation of Metabolic Parameters on Use of Newer Antiepileptics Versus Conventional Antiepileptics in Patients of Generalised Tonic-Clonic Seizure: An Observational Study.
Background and objective Epilepsy is the commonest serious neurological condition and around 50 million people live with epilepsy (PWE). Primary and secondary generalised tonic-clonic seizures (GTCS) together constitute up to 50% of adult and adolescent epilepsy. GTCS respond well to broad-spectrum AEDs like valproate, phenytoin, levetiracetam, lamotrigine, and topiramate. Carbamazepine and oxcarbazepine are considered alternatives. Metabolic derangements with the conventional AEDs (phenytoin causes loss of bone mass in women, phenytoin and carbamazepine produce increases in serum lipid and C-reactive protein, weight gain with valproate) are well documented. But, there is limited data regarding the effect of the newer AEDs on metabolic parameters. Thus, this study was undertaken to assess the effects of the newer AEDs on the metabolic profile of patients with epilepsy. Material and methods A prospective observational study was conducted in the Department of Pharmacology, in collaboration with the Department of Neurology at S.C.B. Medical College and Hospital, Cuttack. 100 diagnosed patients with GTCS receiving monotherapy of either conventional or newer anti-epileptics were included in the study. Their metabolic parameters like total cholesterol, serum sodium, serum TSH and fasting blood glucose were collected at baseline, three months, and six months. ADRs were collected during the entire study period and causality assessment was done using WHO-UMC Causality Assessment Scale. All the data were analysed using SPSS 20.0 after applying appropriate statistical tests. Results There was a significant increase in total cholesterol in all four groups (p=0.002) but a pathological increase in the phenytoin and oxcarbazepine groups. There was a significant rise in the serum TSH levels in all groups except levetiracetam, but a pathological increase was seen with phenytoin and valproate, i.e., the conventional ones. Statistically significant hyponatremia was seen with valproate and oxcarbazepine. A rise in the FBS was seen with both phenytoin and valproate (p=0.002) but a pathological rise was seen with phenytoin. Out of the total reported ADRs, 53.5% were seen with conventional AEDs, and the rest 46.5% were seen with newer ones. Conclusion The advent of newer anti-epileptic drugs has unfolded wider horizons to the treatment of epilepsy. Each of these drugs has a unique mechanism of action, making it less prone to resistance. Metabolic derangements are a key determinant in the compliance of these drugs as they can predispose to other co-morbidities. Periodic monitoring of the various metabolic parameters is useful and together with patient counselling can improve the effectiveness of the anti-epileptic drugs.
PubMed: 36960256
DOI: 10.7759/cureus.35181 -
SAGE Open Medical Case Reports 2023Posterior reversible encephalopathy syndrome is a clinical-neuroradiological syndrome with typical neuroimaging features of posterior cerebral white matter changes that...
Posterior reversible encephalopathy syndrome is a clinical-neuroradiological syndrome with typical neuroimaging features of posterior cerebral white matter changes that are usually reversible. However, there are only few reports of burns with posterior reversible encephalopathy syndrome in the literature. Hence, it is a clinical entity that many burn medicine physicians may be unfamiliar with. We report a case of severe burns complicated by posterior reversible encephalopathy syndrome in a 14-month-old male patient. On the eighth day of hospitalization, the child had persistent fever, occasional convulsions, eyes staring to the right, and high-pitched cry. Magnetic resonance imaging on day 10 showed the diagnosis is posterior reversible encephalopathy syndrome. We used hormone therapy to reduce cerebral oedema, oxcarbazepine to control convulsions, and multiple other drugs and physical measures to treat fever. The symptoms, signs, and imaging abnormalities of his posterior reversible encephalopathy syndrome were rapidly reversed in a short period of time. At the 1-year follow-up, the patient had recovered completely with no residual neurological signs and symptoms. To our knowledge, the patient may be the youngest recorded patient with both burns and posterior reversible encephalopathy syndrome. Careful observation, computed tomography, and magnetic resonance imaging can achieve early detection, early diagnosis, and early treatment of posterior reversible encephalopathy syndrome, which facilitates the achievement of desired therapeutic results. Further investigation is required to determine whether burns can serve as an independent posterior reversible encephalopathy syndrome causative factor and clarify the underlying pathogenesis mechanism.
PubMed: 36937809
DOI: 10.1177/2050313X231157988 -
Tremor and Other Hyperkinetic Movements... 2023There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin... (Review)
Review
BACKGROUND
There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review.
METHODS
We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in evidence-based reviews. We also have emphasized the pathogenetic implications for RLS of the successful use of these lesser known agents.
RESULTS
Alternative pharmacological agents include clonidine which reduces adrenergic transmission, adenosinergic agents such as dipyridamole, glutamate AMPA receptor blocking agents such as perampanel, glutamate NMDA receptor blocking agents such as amantadine and ketamine, various anticonvulsants (carbamazepine/oxcarbazepine, lamotrigine, topiramate, valproic acid, levetiracetam), anti-inflammatory agents such as steroids, as well as cannabis. Bupropion is also a good choice for the treatment of co-existent depression in RLS because of its pro-dopaminergic properties.
DISCUSSION
Clinicians should first follow evidence-based review recommendations for the treatment of RLS but when the clinical response is either incomplete or side effects are intolerable other options can be considered. We neither recommend nor discourage the use of these options, but leave it up to the clinician to make their own choices based upon the benefit and side effect profiles of each medication.
Topics: Humans; Anticonvulsants; Restless Legs Syndrome; Carbamazepine; Gabapentin; Glutamates
PubMed: 36873914
DOI: 10.5334/tohm.739 -
Progress in Neuro-psychopharmacology &... Jun 2023Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a...
OBJECTIVE
Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a series of matrices from combined samples of pregnant/breastfeeding women treated with anticonvulsants or lithium.
METHODS
We conducted a systematic literature search in PubMed/EMBASE for studies with concentrations of anticonvulsants/lithium from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal concentrations. When data from multiple studies were available, we calculated combined penetration ratios, weighting studies' mean by study size.
RESULTS
Ninety-one eligible studies for brivaracetam, carbamazepine, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, lithium, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproate, vigabatrin and zonisamide were identified. For amniotic fluid, the highest penetration ratios were estimated for levetiracetam (mean 3.56, range 1.27-5.85, n = 2) and lowest for valproate (mean 0.11, range 0.02-1.02, n = 57). For umbilical cord plasma, oxcarbazepine had the highest ratio (mean 1.59, range 0.11-4.33, n = 12) with clonazepam having the lowest (mean 0.55, range 0.52-0.59, n = 2). For breast milk, the highest ratios were observed for oxcarbazepine (mean 3.75, range 0.5-7.0, n = 2), whereas the lowest were observed for valproate (mean 0.04, range 0.01-0.22, n = 121).
DISCUSSION
We observed substantial variability between anticonvulsants and lithium regarding their ability to enter fetal/newborn circulation. Assessing concentrations of anticonvulsants and lithium in maternal samples can provide a surrogate of fetal/infant exposure, although patterns of concentration-dependent effects for maternal/neonatal safety are lacking.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Anticonvulsants; Fetal Blood; Lithium; Maternal-Fetal Exchange; Milk, Human
PubMed: 36805301
DOI: 10.1016/j.pnpbp.2023.110733 -
Pharmacological Research Mar 2023Despite recent advances in understanding the causes of epilepsy, especially the genetic, comprehending the biological mechanisms that lead to the epileptic phenotype...
Despite recent advances in understanding the causes of epilepsy, especially the genetic, comprehending the biological mechanisms that lead to the epileptic phenotype remains difficult. A paradigmatic case is constituted by the epilepsies caused by altered neuronal nicotinic acetylcholine receptors (nAChRs), which exert complex physiological functions in mature as well as developing brain. The ascending cholinergic projections exert potent control of forebrain excitability, and wide evidence implicates nAChR dysregulation as both cause and effect of epileptiform activity. First, tonic-clonic seizures are triggered by administration of high doses of nicotinic agonists, whereas non-convulsive doses have kindling effects. Second, sleep-related epilepsy can be caused by mutations on genes encoding nAChR subunits widely expressed in the forebrain (CHRNA4, CHRNB2, CHRNA2). Third, in animal models of acquired epilepsy, complex time-dependent alterations in cholinergic innervation are observed following repeated seizures. Heteromeric nAChRs are central players in epileptogenesis. Evidence is wide for autosomal dominant sleep-related hypermotor epilepsy (ADSHE). Studies of ADSHE-linked nAChR subunits in expression systems suggest that the epileptogenic process is promoted by overactive receptors. Investigation in animal models of ADSHE indicates that expression of mutant nAChRs can lead to lifelong hyperexcitability by altering i) the function of GABAergic populations in the mature neocortex and thalamus, ii) synaptic architecture during synaptogenesis. Understanding the balance of the epileptogenic effects in adult and developing networks is essential to plan rational therapy at different ages. Combining this knowledge with a deeper understanding of the functional and pharmacological properties of individual mutations will advance precision and personalized medicine in nAChR-dependent epilepsy.
Topics: Animals; Receptors, Nicotinic; Nicotinic Agonists; Seizures; Phenotype; Epilepsy
PubMed: 36796465
DOI: 10.1016/j.phrs.2023.106698 -
Frontiers in Molecular Neuroscience 2022The gene, predominantly distributed in neurons, plays an essential role in controlling the resting membrane potential and regulating cellular excitability. Previously,...
The gene, predominantly distributed in neurons, plays an essential role in controlling the resting membrane potential and regulating cellular excitability. Previously, only two variants were identified to be associated with human disease, facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth (FHEIG) syndrome. In this study, we performed trio-based whole exon sequencing (WES) in a cohort of patients with epilepsy. Two likely pathogenic variants were identified in two unrelated cases with heterogeneous phenotypes, including one with Rolandic epilepsy and one with the FHEIG syndrome. The two variants were predicted to be damaged by the majority of algorithms. These variants showed no allele frequencies in controls and presented statistically higher frequencies in the case cohort than that in controls. The FHEIG syndrome-related variants were all located in the region with vital functions in stabilizing the conductive conformation, while the Rolandic epilepsy-related variant was distributed in the area with less impact on the conductive conformation. This study expanded the genetic and phenotypic spectrum of . Phenotypic variations of are potentially associated with the molecular sub-regional effects. Carbamazepine/oxcarbazepine and valproate may be effective antiepileptic drugs for patients with variants.
PubMed: 36683851
DOI: 10.3389/fnmol.2022.1081097 -
Pharmaceutics Jan 2023Oxcarbazepine (OXC) is an anticonvulsant drug, indicated for the treatment of the neurological disorder, epilepsy. The objective of the present study was to evaluate the...
Oxcarbazepine (OXC) is an anticonvulsant drug, indicated for the treatment of the neurological disorder, epilepsy. The objective of the present study was to evaluate the transdermal delivery of OXC from microemulsions using different penetration enhancers. Transcutol® P (TRC), oleic acid (OA), cineole (cin), Labrasol (LS), Tween 80 (T80) and N-Methyl-Pyrrolidone (NMP) were used as penetration enhancers as well as microemulsion components. Simple formulations of OXC in propylene glycol (PG) incorporating various penetration enhancers and combination of penetration enhancers were also evaluated for transdermal delivery. Drug delivery and penetration enhancement were studied using human cadaver skin on Franz diffusion cells. The results showed that all penetration enhancers improved the rate of permeation of OXC compared to the control. The flux of drug delivery from the various formulations was found to be, in decreasing order, cin > OA + TRC > NMP > TRC > OA. Overall, microemulsions prepared using cineole, Tween 80 and Transcutol® P (TRC) were shown to be provide the best penetration enhancement for OXC.
PubMed: 36678811
DOI: 10.3390/pharmaceutics15010183 -
Journal of Clinical Neurology (Seoul,... Jan 2023This study aimed to determine the effects of oxcarbazepine (OXC) on the language function of patients with pediatric epilepsy.
BACKGROUND AND PURPOSE
This study aimed to determine the effects of oxcarbazepine (OXC) on the language function of patients with pediatric epilepsy.
METHODS
We assessed the language abilities of patients aged 5-17 years with newly diagnosed focal epilepsy and the same number of age-matched healthy children using the Test of Problem Solving (TOPS) and the Receptive and Expressive Vocabulary Test-Receptive (REVT-R). The Mean Length of Utterance-words (MLU-w) was used to estimate linguistic productivity before and after OXC initiation. All patients received OXC monotherapy with a starting dosage of 10 mg/kg/day for 1 week, which in some cases was increased to 30 mg/kg/day (or 1,200 mg/day).
RESULTS
The study finally included 41 pediatric patients (22 males and 19 females; age 9.9±3.0 years, mean±standard deviation). All language parameters of the TOPS improved significantly after initiating OXC (determining cause, 12.5±4.8-13.7±4.1 [=0.016]; making inference, 15.6±5.6-17.4±6.4 [<0.001]; and predicting, 9.8±5.0-11.6±4.5 [=0.001]). However, patients who received OXC did not exhibit a significantly extended MLU-w (determining cause, =0.493; making inference, =0.386; and predicting, =0.341). Receptive language scores also significantly increased after taking OXC (REVT-R: 121.0±43.1-129.4±43.8, =0.002), but the percentage of development age to chronological age did not vary (REVT-developmental quotient: =0.075).
CONCLUSIONS
Our results suggest that OXC is safe and preserves language function in patients with pediatric epilepsy.
PubMed: 36606649
DOI: 10.3988/jcn.2023.19.1.76 -
Frontiers in Pharmacology 2022In this study, we intended to compare and rank the efficacy and acceptability of antiseizure medications (ASMs) for adjunctive treatment of children with drug-resistant...
In this study, we intended to compare and rank the efficacy and acceptability of antiseizure medications (ASMs) for adjunctive treatment of children with drug-resistant focal-onset seizures. We conducted a computerized search of PubMed, EMBASE, Cochrane Library, Web of Science, and Google Scholar to identify eligible randomized controlled trials (RCTs) published before 31 May 2022. We included studies evaluating the efficacy and tolerability of antiseizure medications for children with drug-resistant focal-onset seizures. The efficacy and safety were reported in terms of responder and dropout rate along with serious adverse events, the outcomes were ranked with the surface under the cumulative ranking curve (SUCRA). A total of 14 studies (16 trials) with 2,464 patients were included, involving 10 active antiseizure medications. For the primary endpoint of at least 50% reduction in focal-onset seizures, the surface under the cumulative ranking curve ranking suggested that lamotrigine and levetiracetam were more effective as compared with other antiseizure medications; moreover, levetiracetam had the highest probability of rank first for achieving seizure freedom. Concerning tolerability, oxcarbazepine and eslicarbazepine acetate were associated with higher dropout rates relative to other antiseizure medications and placebo, and topiramate was associated with higher occurrence of side effects. No significant differences were found between active antiseizure medications concerning dropout for side effects. According to the surface under the cumulative ranking curve ranking, lamotrigine, levetiracetam, and oxcarbazepine were more efficacious than other active antiseizure medications in terms of responder rate. Concerning tolerability, oxcarbazepine was more likely to lead to dropout and topiramate was associated with higher occurrence of side effects.
PubMed: 36588743
DOI: 10.3389/fphar.2022.978876