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Neurocase Jun 2024Cenobamate (CNB) is one of the newer antiseizure medications for the treatment of focal-onset seizures. The cognitive profile of CNB is not yet known in detail. Here we...
Cenobamate (CNB) is one of the newer antiseizure medications for the treatment of focal-onset seizures. The cognitive profile of CNB is not yet known in detail. Here we present the case of an 18-year-old male high school student with epilepsy who received adjunctive CNB. Under 400 mg/d of CNB in combination with lamotrigine, a neuropsychological reassessment revealed a severe deterioration of the formerly normal episodic memory functions, while executive functions remained unaffected. The de novo memory deficit had already led to a collapse in school performance and he unexpectedly failed to obtain the general qualification for university entrance. Given the beneficial effect of CNB on seizure control, a dose reduction of CNB to 200 mg/d and introduction of valproic acid was performed. This led to a full recovery of objective memory performance. To our knowledge this is the very first report of a dose-dependent, selective and severe decline in episodic memory performance under CNB, potentially impeding academic achievement. The findings call for a cognitive monitoring of CNB which also addresses episodic memory in addition to executive functions. Systematic studies on episodic memory upon CNB treatment would help to appreciate the scope of this apparently reversible adverse effect.
PubMed: 38869048
DOI: 10.1080/13554794.2024.2366472 -
Clinical Laboratory Jun 2024Therapeutic drug monitoring (TDM) involves the measurement of drug concentrations in serum, plasma, whole blood, or other biologic fluids. This study focused on...
BACKGROUND
Therapeutic drug monitoring (TDM) involves the measurement of drug concentrations in serum, plasma, whole blood, or other biologic fluids. This study focused on evaluating the TDM requests of a city hospital over a period of one year, retrospectively.
METHODS
The study retrospectively analyzed TDM requests for carbamazepine, cyclosporine-A, digoxin (DIGOX), lithium (LITH), methotrexate (MTX), phenitoin, tacrolimus, and valproic acid (VALP) from June 1, 2022, to June 1, 2023. Parameters such as the age and the gender of patients, the requesting departments, the measurement results, and the turnaround time (TAT) were assessed. Drug concentrations below the reference values were classified as subtherapeutic, whereas concentrations above the reference values were considered supratherapeutic.
RESULTS
In total, 10,913 drug concentration measurement records were analyzed. The gender distribution was 51.6% male and 48.4% female. Pediatric samples comprised 6.2% and elderly samples 8.6% of the total. Notably, DIGOX, LITH, and VALP levels showed a significant correlation with age (p = < 0.0001, p = < 0.0001, and p = 0.0002, respectively). TAT was maintained at 360 minutes (6 hours) for all tests.
CONCLUSIONS
The study found significant correlations between age and DIGOX, LITH, and VALP levels. TDM plays a critical role in the elderly population, necessitating careful management of these drugs.
Topics: Humans; Drug Monitoring; Male; Female; Retrospective Studies; Middle Aged; Adult; Aged; Child; Adolescent; Young Adult; Child, Preschool; Hospitals, Urban; Infant; Aged, 80 and over; Infant, Newborn; Age Factors
PubMed: 38868874
DOI: 10.7754/Clin.Lab.2024.231223 -
Journal of Cosmetic and Laser Therapy :... Jun 2024We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using...
We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.
PubMed: 38852607
DOI: 10.1080/14764172.2024.2362126 -
Scientific Reports Jun 2024Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social interaction deficits, communication impairments, repetitive behaviors,...
Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism.
Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social interaction deficits, communication impairments, repetitive behaviors, and sensory sensitivities. While the etiology of ASD is multifaceted, abnormalities in glutamatergic neurotransmission and synaptic plasticity have been implicated. This study investigated the role of metabotropic glutamate receptor 8 (mGlu8) in modulating long-term potentiation (LTP) in a rat model of ASD induced by prenatal valproic acid (VPA) exposure. To induce an animal model with autism-like characteristics, pregnant rats received an intraperitoneal injection of 500 mg/kg of sodium valproate (NaVPA) on embryonic day 12.5. High-frequency stimulation was applied to the perforant path-dentate gyrus (PP-DG) synapse to induce LTP, while the mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) was administered into the DG. The results revealed that VPA-exposed rats exhibited reduced LTP compared to controls. DCPG had contrasting effects, inhibiting LTP in controls and enhancing it in VPA-exposed rats. Moreover, reduced social novelty preference index (SNPI) in VPA-exposed rats was reversed by intra-DG administration of S-3,4-DCPG. In conclusion, our study advances our understanding of the complex relationship between glutamatergic neurotransmission, synaptic plasticity, and VPA-induced autism model. The findings suggest that mGlu8 receptor dysfunction plays a role in the impaired synaptic plasticity seen in ASD.
Topics: Animals; Valproic Acid; Long-Term Potentiation; Female; Pregnancy; Rats; Disease Models, Animal; Dentate Gyrus; Synapses; Receptors, Metabotropic Glutamate; Prenatal Exposure Delayed Effects; Perforant Pathway; Autistic Disorder; Glycine; Hippocampus; Rats, Sprague-Dawley; Autism Spectrum Disorder; Male
PubMed: 38849397
DOI: 10.1038/s41598-024-63728-y -
Current Pharmaceutical Design Jun 2024Bipolar disorder is a neuropsychiatric disease characterized by an abundance of undesired ideas and thoughts associated with recurrent episodes of mania or hypomania and...
Bipolar disorder is a neuropsychiatric disease characterized by an abundance of undesired ideas and thoughts associated with recurrent episodes of mania or hypomania and depression. Alterations in the circuits, including the prefrontal cortex, striatum, and limbic system, regulate mood and cause variation in several crucial neurotransmitters, including serotonin, dopamine, GABA, and glutamate. Imbalances in dopamine levels have been implicated in the manic phase, while variance in serotonin is linked to depressive episodes. The precise pathophysiology of bipolar disorder is still unknown. Though different treatments are available, like lithium, risperidone, valproic acid, etc., which are widely used, they come with certain limitations, including narrow therapeutic index, hypothyroidism, weight gain, extrapyramidal symptoms, etc. The interest in herbal- based treatments for bipolar disorder arises from the desire for alternative, potentially more natural, and holistic approaches with fewer side effects. The current review focuses on the potential effects of herbal drugs and their derivatives to alleviate the symptoms of bipolar disorder.
PubMed: 38847247
DOI: 10.2174/0113816128312442240519184440 -
Gut Microbes 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic PS128 (PS128) alleviates ASD symptoms in children. However, the mechanism underlying this improvement in ASD-associated behaviors remains unclear. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of PS128 . Overall, we showed that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, PS128 alters the gut microbiota composition and increases the abundance of spp. and PS128-induced changes in abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.
Topics: Animals; Autism Spectrum Disorder; Mice; Probiotics; Disease Models, Animal; Social Behavior; Female; Male; Valproic Acid; Gastrointestinal Microbiome; Behavior, Animal; Mice, Inbred C57BL; Hippocampus; Pregnancy; Oxytocin; Prefrontal Cortex; Lactobacillus plantarum; Humans
PubMed: 38841895
DOI: 10.1080/19490976.2024.2359501 -
PloS One 2024Epilepsy patients exhibit considerable differences in their response to sodium valproate (VPA) therapy, a phenomenon that might be attributed to individual genetic...
OBJECTIVE
Epilepsy patients exhibit considerable differences in their response to sodium valproate (VPA) therapy, a phenomenon that might be attributed to individual genetic variances. The role of genetic variations, specifically in sodium channels encoded by SCN1A and SCN2A genes, in influencing the effectiveness of VPA in treating epilepsy is still debated. This research focuses on examining the impact of these genetic polymorphisms on the efficacy of VPA therapy among pediatric epilepsy patients in China.
METHODS
Five single nucleotide polymorphisms (SNPs), including SCN1A (rs10188577, rs2298771, rs3812718) and SCN2A (rs2304016, rs17183814), were genotyped in 233 epilepsy patients undergoing VPA therapy. The associations between genotypes and the antiepileptic effects of VPA were assessed, with 128 patients categorized as VPA responders and 105 as VPA non-responders.
RESULTS
In the context of VPA monotherapy, SCN1A rs2298771 and SCN2A rs17183814 were found to be significantly associated with VPA response (P< 0.05).
CONCLUSION
Our study suggests the findings of this investigation indicate that the polymorphisms SCN1A rs2298771 and SCN2A rs17183814 could potentially act as predictive biomarkers for the responsiveness to VPA among Chinese epilepsy patients.
Topics: Humans; NAV1.1 Voltage-Gated Sodium Channel; Valproic Acid; NAV1.2 Voltage-Gated Sodium Channel; Child; Polymorphism, Single Nucleotide; Male; Female; Epilepsy; Anticonvulsants; Child, Preschool; China; Asian People; Adolescent; Treatment Outcome; Genotype; Infant; East Asian People
PubMed: 38837984
DOI: 10.1371/journal.pone.0304869 -
Journal of Medicinal Food Jun 2024Valproic acid is an effective treatment for generalized seizure and related neurological defects. Despite its efficacy and acceptability, its use is associated with...
Valproic acid is an effective treatment for generalized seizure and related neurological defects. Despite its efficacy and acceptability, its use is associated with adverse drug effects. leaves are rich in phytochemical and nutritional components. It has excellent antioxidant and ethnobotanical benefits, thus popular among folk medicines and nutraceuticals. In the present study, 70% ethanol extract of moringa leaves was assessed for its biochemical and histological effects against valproate-induced kidney damage. Female Sprague-Dawley rats were randomly divided into four groups: Group I: control animals given physiological saline ( = 8); Group II: Moringa extract-administered group (0.3 g/kg b.w./day, = 8); Group III: valproate-administered animals (0.5 g/kg b.w./day, = 15); and Group IV: valproate + moringa extract (given similar doses of both valproate and moringa extract, = 12) administered group. Treatments were administered orally for 15 days, the animals were fasted overnight, anesthetized, and then tissue samples harvested. In the valproate-administered experimental group, serum urea and uric acid were elevated. In the kidney tissue of the valproate rats, glutathione was depleted, antioxidant enzyme activities (superoxide dismutase, catalase, glutathione reductase, glutathione -transferase, and glutathione peroxidase) disrupted, while oxidative stress biomarker, inflammatory proteins (Tumor necrosis factor-alpha and interleukin-6), histological damage scores, and the number of PCNA-positive cells were elevated. attenuated all these biochemical defects through its plethora of diverse antioxidant and therapeutic properties.
Topics: Animals; Moringa oleifera; Valproic Acid; Plant Extracts; Rats, Sprague-Dawley; Female; Rats; Kidney; Oxidative Stress; Antioxidants; Superoxide Dismutase; Kidney Diseases; Plant Leaves; Glutathione; Tumor Necrosis Factor-alpha; Humans; Interleukin-6; Catalase; Glutathione Peroxidase
PubMed: 38836511
DOI: 10.1089/jmf.2023.0091 -
Frontiers in Psychiatry 2024This case report describes an exceptionally rare case in which a prior diagnosis of schizophrenia was later determined to be early-onset Fahr's disease, linked to a...
This case report describes an exceptionally rare case in which a prior diagnosis of schizophrenia was later determined to be early-onset Fahr's disease, linked to a genetic mutation in the SLC20A2 gene. Initially, the patient exhibited symptoms resembling schizophrenia, including aggression and hostility, and was highly susceptible to medication side effects such as restlessness and Parkinsonism. Despite maintaining independent activities of daily living, his neurological examinations revealed hidden weakness on the left side. Following adjustments to the medication regimen, stability was achieved with residual psychotic symptoms under treatment with Risperidone 1.5mg/day, Valproic acid 1500mg/day, and Quetiapine 37.5mg/day. This case underscores the importance of conducting comprehensive imaging studies at the time of initial psychiatric diagnosis, regardless of the apparent typicality of the presentation. Additionally, it emphasizes the need for patience and adherence to the "Start Low and Go Slow" approach in medication management to minimize the risk of exacerbating psychiatric symptoms and aggression.
PubMed: 38835553
DOI: 10.3389/fpsyt.2024.1391607 -
JAMA Network Open Jun 2024Concerns exist about teratogenic and long-term neurodevelopmental outcomes of paternal use of valproate during spermatogenesis.
IMPORTANCE
Concerns exist about teratogenic and long-term neurodevelopmental outcomes of paternal use of valproate during spermatogenesis.
OBJECTIVE
To evaluate the association between paternal use of valproate during spermatogenesis and offspring risk of congenital malformations and neurodevelopmental disorders.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide cohort study included 1 235 353 singletons born in Denmark between January 1, 1997, and December 31, 2017, identified in the Medical Birth Register; 1336 children had fathers who had filled prescriptions for valproate during spermatogenesis. Congenital malformations were identified in the first year of life and neurodevelopmental disorders were identified from 1 year of age until December 31, 2018. Statistical analysis was performed March 2024.
EXPOSURES
Paternal valproate exposure was defined as fathers who filled 1 or more prescriptions for valproate immediately before or during the time of spermatogenesis (ie, 3 months prior to conception).
MAIN OUTCOMES AND MEASURES
Children with major congenital malformations in the first year of life and with neurodevelopmental disorders before death or end of follow-up were identified in Danish health registers. Log-binomial regression was used to estimate adjusted relative risks (ARRs) of congenital malformations, and Cox proportional hazards regression was used to estimate adjusted hazards ratios (AHRs) of neurodevelopmental disorders, adjusted for relevant confounders.
RESULTS
Among 1 235 353 live births (634 415 boys [51.4%] and 600 938 girls [48.6%]), 1336 children (0.1%) had fathers who filled prescriptions for valproate during spermatogenesis. The median follow-up was 10.1 years (IQR, 5.1-14.8 years) for valproate-exposed children and 10.3 years (IQR, 5.2-15.6 years) for valproate-unexposed children. A total of 43 903 children (3.6%) received a diagnosis of major congenital malformations in the first year of life, and 51 633 children (4.2%) received a diagnosis of neurodevelopmental disorders during follow-up. When comparing the risk among valproate-exposed children with that among unexposed children, the ARR of major congenital malformations was 0.89 (95% CI, 0.67-1.18), the AHR of neurodevelopmental disorders was 1.10 (95% CI, 0.88-1.37), and the AHR of autism spectrum disorder was 0.92 (95% CI, 0.65-1.30). In analyses addressing the robustness of the findings (ie, dose-response analyses, sibling analyses, analyses restricted to children of fathers with epilepsy, analyses that used children with paternal lamotrigine exposure as active comparator, and analyses that used children with paternal exposure to valproate only before spermatogenesis as a negative control exposure), there still was no increased risk of any of the included end points.
CONCLUSIONS AND RELEVANCE
In all analyses based on this large Danish cohort study, results suggest that exposure to valproate during spermatogenesis was not associated with offspring risk of congenital malformations or neurodevelopmental disorders, including autism spectrum disorder.
Topics: Humans; Valproic Acid; Male; Denmark; Spermatogenesis; Female; Neurodevelopmental Disorders; Infant; Adult; Cohort Studies; Child, Preschool; Child; Paternal Exposure; Anticonvulsants; Registries; Infant, Newborn; Abnormalities, Drug-Induced; Risk Factors; Congenital Abnormalities; Prenatal Exposure Delayed Effects
PubMed: 38833248
DOI: 10.1001/jamanetworkopen.2024.14709