Enzyme-inducing antiepileptic drugs (EIAEDs) such as carbamazepine, phenytoin, phenobarbital, and primidone are used in the management of epilepsy and can alter hepatic enzymes of the cytochrome P450 (CYP450) system. This can have a significant impact on vitamin D metabolism. We describe the case of a 34-year-old female diagnosed with focal epilepsy who presented to the hospital at 25-weeks gestation with recurrent seizures. On admission, she had multiple generalized tonic-clonic seizures with nystagmus requiring repeated rounds of intravenous (IV) medications. The patient was intubated and sedated and brought for emergency caesarean section due to persistent fetal decelerations in the setting of refractory status epilepticus. Laboratory investigations revealed a serum calcium level of 5.30 mg/dL (SI: 1.32 mmol/L) (reference range, 8.50-10.50 mg/dL [SI: 2.12-2.62 mmol/L]). The patient required numerous antiepileptic infusions for seizure suppression. Further evaluation revealed low 25-hydroxy vitamin D, suggesting significant hypocalcemia and vitamin D deficiency culminating in super-refractory focal status epilepticus due to chronic EIAED use. This case underscores the need to maintain a high index of suspicion for metabolic disturbances in patients on long-term EIAED therapy with regular monitoring of vitamin D and calcium levels to prevent complications.

Experimental data regression and model analyses of micropollutant (MP) degradation kinetics in ultraviolet-based advanced oxidation processes (UV-AOPs) typically assume a constant fluence-based pseudo-first-order rate constant (k'). However, oxidant decay continuously disrupts steady-state concentrations of reactive radicals and repeatedly establishes new equilibria, making k' vary over time-an error source that has not been rigorously assessed. Here, we evaluated these errors and developed refined kinetic analysis methods. Second-order polynomial regression analysis was proposed to quantify both initial and real-time k' values, demonstrating superior accuracy to conventional linear regression analysis, particularly for fast-decaying oxidants (e.g., free chlorine), UV-resistant MPs, and complex water matrices. Furthermore, we established a refined steady-state approximation (rSSA) model incorporating dynamic oxidant decay, which demonstrated enhanced prediction accuracy than the conventional steady-state approximation model. For instance, in a secondary sedimentation effluent at a photon fluence of 1.47 × 10⁻2 einstein m-2, the relative error of model-predicted primidone removal by UV/free chlorine reduced from 98.3% to 12.6%. Additionally, relative deviation framework identified scenarios that violate the constant k' assumption, providing guidance for the selection of kinetic analysis methods. These advancements provide a robust foundation for rigorous experimental design and kinetic interpretation, offering potential value for more rational and energy-efficient operation of UV-AOPs.

Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) represents a rare but severe group of childhood onset epilepsies characterized by sleep-potentiated epileptiform activity, seizures, and developmental stagnation or regression affecting cognition, language, and behavior. Once considered a self-limited electroencephalographic (EEG) phenomenon, D/EE-SWAS is now recognized as a disorder of brain network dysfunction in which persistent epileptiform discharges during non-rapid eye movement sleep disrupt synaptic plasticity, sleep-dependent memory consolidation, and neurodevelopmental trajectories. This review synthesizes recent advances in clinical phenotyping, genetics, neurophysiology, and therapeutics. Etiologically, D/EE-SWAS is highly heterogeneous, with pathogenic variants identified in nearly half of affected individuals, including copy number variants and single-gene disorders involving ion channels, synaptic proteins, and transcriptional regulators. GRIN2A is the most frequently implicated gene, although marked intrafamilial and interfamilial variability underscores the role of modifying genetic and network-level factors. Structural lesions-particularly those affecting thalamocortical circuits-represent another major disease substrate and are critical for treatment stratification. At the mechanistic level, abnormal thalamocortical oscillations, impaired sleep architecture, and disruption of slow-wave and spindle activity provide a pathophysiological framework linking EEG abnormalities to cognitive and behavioral deterioration. Neuroimaging and EEG-functional magnetic resonance imaging studies support a model of widespread network inhibition and disconnection extending beyond the primary epileptogenic zone. Therapeutically, corticosteroids currently represent the most effective first-line treatment, demonstrating superior cognitive outcomes compared with benzodiazepines, although relapse after tapering is common, and optimal dosing strategies remain undefined. Precision medicine approaches, including N-methyl-D-aspartate receptor-targeted therapies for GRIN variants and channel-specific treatments such as primidone for TRPM3 gain of function, offer promising avenues toward disease modification. Epilepsy surgery should be considered early in children with unilateral structural etiologies, where it can provide substantial neurodevelopmental benefit. Future priorities include standardized outcome measures, integration of sleep-based biomarkers, refinement of steroid protocols, and international collaborative trials to improve long-term neurodevelopmental outcomes in this vulnerable population.

Phenobarbital (PB) is historically used for management of seizure disorders but more recently has emerged as a prominent option for the management of alcohol withdrawal syndrome given data suggesting its benefit over benzodiazepines. An important consideration of PB therapy is its induction of cytochrome-P 450 enzymes (CYP450), which may lead to underrecognized drug-drug interactions (DDIs). Knowledge of these PB DDIs, including their onset and offset, is important to better elucidate how to manage these DDIs. To identify published literature evaluating the relevance of DDIs between PB and selected medications, a systematic review was performed including literature published through January 2026, focused on the administration of both PB and a list of medications based on tertiary medication database review as well as clinical relevance, including anticoagulants, antimicrobials, and immunosuppressants. Included articles had to identify outcomes of interest, which were focused on laboratory, pharmacokinetic, and clinical outcomes, and had to be in humans. Data extraction included the onset and offset of PB DDIs and potential PB dose-response and magnitude of induction of target medication. A total of 3271 articles were identified, with 50 studies meeting inclusion criteria, which included both adult and pediatric populations. Thirteen studies evaluated onset of PB induction, which ranged from 6 h to 30 days. Eight studies evaluated offset of PB induction, which ranged from 2 to 8 weeks. Limited data demonstrated a PB dose-response relationship in terms of magnitude of CYP induction. We found that 86% of the included studies demonstrated an impact by PB on outcomes, which were often related to therapeutic drug monitoring. Data suggest that PB does lead to clinically significant DDIs in multiple classes of medications. Future areas of research include focused evaluations on clinical outcomes, as well as studies specifically evaluating single high-dose PB and impact on DDI outcomes.

Trigeminal nerve injury can lead to chronic and difficult-to-treat orofacial neuropathic pain. Here, we uncover a key role for the cation channel TRPM3 in the chronic constriction injury of the infraorbital nerve (IoN-CCI) mouse model of trigeminal neuropathic pain. Wild-type (WT) mice develop spontaneous pain and mechanical allodynia for up to 6 weeks following IoN-CCI, whereas Trpm3[-/-] mice do not develop such symptoms. Using longitudinal RNA sequencing (RNA-seq) analysis, we obtain a detailed time course of transcriptome alterations in trigeminal ganglia during progression of the IoN-CCI model; notably, gene expression regulation is not different between WT and Trpm3[-/-] mice. Two structurally distinct TRPM3 antagonists, primidone and isosakuranetin, effectively reverse spontaneous pain and mechanical allodynia, whereas mavatrep, a potent TRPV1 antagonist, is without analgesic effect. These data indicate that TRPM3 is essential for ongoing pain and allodynia following trigeminal nerve injury, making it a potential target for treating trigeminally mediated neuropathic pain.

Ozone-soil aquifer treatment (O3-SAT) could be employed in land-based treatment systems to achieve improved pharmaceutical and personal care products (PPCPs) and pathogen reduction prior to de-facto recharge of aquifers with reclaimed water. A bench-scale demonstration of O3-SAT was investigated utilizing denitrified effluent to assess attenuation of PPCPs, norovirus (NoV), pepper mild mottle virus (PMMoV), bacteriophage MS2, and tomato brown rugose fruit virus (ToBRFV). Ammonification followed by nitrification evidenced the role of microbial degradation in contaminant removal in the soil columns studied. Ozonation was effective for NoV genetic marker oxidation to below detection (> 4 log removal values), while the PPCPs were removed in the soil columns. Indicator viruses demonstrated limited (ToBRFV and MS2) to negligible (PMMoV) oxidation during ozonation; thus, attenuation via microbial degradation and sorption mechanisms during soil treatment was the governing factor for achieving ∼2 log removal values across treatment conditions. PPCP removal efficiency was compound dependent but followed the categories: 1. Effective oxidation and attenuation, 2. Moderate oxidation and attenuation, 3. Recalcitrant to oxidation and attenuation. Ozonation of characteristically recalcitrant compounds such as sulfamethoxazole, meprobamate, N-N-diethyl-m-toluamide and primidone increased the collective O3-SAT removal compared with SAT alone. Desorption of carbamazepine previously adsorbed to below detection was observed, driven by historical concentrations in soil or modifications to the concentration gradient. These results highlight O3-SAT as a promising enhancement for improving robustness of water reuse treatment systems under a range of operational scenarios.

Neurologic tremors constitute a heterogeneous group of movement disorders that are often challenging to classify due to overlapping clinical presentations. While Parkinsonian, essential, and cerebellar tremors are among the most frequently encountered types, rarer causes such as thalamic infarction may be easily overlooked. We describe a rare case of tremor secondary to thalamic infarction, emphasizing its relevance as an uncommon yet clinically important etiology within the spectrum of neurologic tremors. Focal midbrain lesions can produce a distinctive coarse tremor, referred to as Holmes or rubral tremor, arising from disruption of the dentatorubrothalamic pathway. We report the case of a 53-year-old right-handed woman who presented with a left-sided, 4-Hz coarse tremor evident at rest and with action, demonstrating partial responsiveness to levodopa therapy. The tremor began shortly after a closed head injury at age six, accompanied by left-sided numbness and persistent motor control difficulties beginning within a few weeks. An MRI in 1997 revealed a small infarct-like lesion in the right thalamus, unchanged on a 2022 MRI. Misdiagnosed initially as a conversion reaction, she later received a diagnosis of "essential tremor with Parkinsonian features" and was treated with primidone and intermittent carbidopa-levodopa. The tremor impacts her work as a dental hygienist, but levodopa provides partial relief. Holmes tremor, characterized by low-frequency (2-4 Hz) high-amplitude tremors at rest, with movement, or in posture, is distinct from essential and cerebellar tremors. This case illustrates the rarity of this particular tremor, highlights its distinction from other tremors, and demonstrates potential treatments, including levodopa, thalamotomy, and deep brain stimulation.

Antiepileptic drugs are considered contaminants of emerging concern in water and are resistant to conventional wastewater treatment processes. Therefore, their presence has been detected in surface waters, and their elimination/degradation requires effective treatment methods. In this research, ultrasound-based methods (e.g., sonolysis, sono-Fenton, and sono-photo-Fenton) were addressed in the degradation of antiepileptic drug primidone at laboratory scale. A high-frequency ultrasound (at 578 kHz and 20.4 W) was applied. Then, Fe2+ ions (5 mg l-1) and a UVA lamp (4 W) were added to the sonochemical reactor. After 75 min of treatment, the sono-photo-Fenton method showed better degradation efficiency (93 %) than the sono-Fenton (83 %) and sonolysis (62 %) methods. Finally, the effectiveness of the degradation method by sono-photo-Fenton was tested in simulated pharmaceutical wastewater, degrading 72 % of primidone at 75 min of treatment, indicating matrix effect plays a role in the degradation (which could be a potential application of ultrasound hybridized with the photo-Fenton process).•Three ultrasound-based treatment methods were applied to degrade primidone in water.•The sono-photo-Fenton method degraded 93 % of primidone during 75 min of treatment.•The matrix influence on primidone degradation by sono-photo-Fenton was evaluated.

KCNC1-related disorders encompass a spectrum of neurologic phenotypes that generally include one or more of the following features: developmental delay (DD) / intellectual disability (ID), myoclonus (progressive or nonprogressive), ataxia, and epilepsy. Affected individuals with loss-of-function pathogenic variants with a presumptive dominant-negative action may have myoclonic epilepsy and ataxia due to potassium (K+) channel mutation (MEAK; also known as progressive myoclonus epilepsy (PME) type 7 / EPM7) or developmental and epileptic encephalopathy (DEE) (i.e., intractable epilepsy with DD/ID associated with abnormal interictal EEG activity). Affected individuals with gain-of-function pathogenic variants may present with nonspecific DD/ID and gross motor impairment without myoclonus or epilepsy.

Organic micropollutants (OMP) increasingly enter agricultural soils through irrigation with reclaimed water, raising concerns about their mobility and persistence in soils and their potential to contaminate groundwater. This study investigates the fate of ten OMP in an arable loamy-sand topsoil using a combined experimental and modeling approach. Abiotic/biotic kinetic and isotherm batch experiments were performed to derive process-relevant parameters for sorption and biodegradation. An inverse modeling approach was employed to simultaneously fit the parameters for the different processes to all three data types (i.e., abiotic kinetic, biotic kinetic data, equilibrium data), allowing robust parameter estimation across varying levels of model complexity. The model incorporated equilibrium and kinetic sorption (linear and Freundlich isotherms; one- and two-site kinetic models), first-order biodegradation, and explicitly accounted for vaporization losses due to aerated vessels, extending traditional batch modeling frameworks. Four OMP (adamantan-1-amine, carbamazepine, diclofenac, and sulfamethoxazole) exhibited biphasic sorption behavior, which was best described by a two-site kinetic model. Three OMP (acesulfame, saccharin, and valsartanate) showed negligible sorption but, following lag phases between 4 and 9 days, indicated microbial adaptation. After adaption, rapid biodegradation with half-lives of 0.4, 0.9, and 3.3 days, occurred. The remaining compounds (diatrizoate, trifluoromethanesulfonate, primidone) showed neither sorption nor degradation. The necessity of applying the relatively complex modeling approaches - required to describe the lab experiments - to field conditions was investigated using Hydrus-1D simulations under realistic soil and climate scenarios. The simulations revealed that sorption kinetics and microbial adaptation phases had minimal impacts on OMP transport simulations at field-scale under matrix-dominated flow, despite their importance for laboratory-scale interpretation. The results suggest that simplified equilibrium and immediate-degradation assumptions may be sufficient for risk assessment regarding to OMP in homogeneous soils with predominantly uniform flow conditions. Overall, this study presents a comprehensive framework for bridging laboratory observations with field-scale modeling, offering new insights into OMP fate and guiding efficient parameterization strategies for environmental risk assessment for the management of reclaimed water.

Detecting noxious heat is vital for survival, triggering protective pain responses. The TRPM3 channel is a key nociceptor and a promising therapeutic target for pain and neurological disorders. Here we show that the rabbit TRPM3 is intrinsically dynamic, with its intracellular domain (ICD) sampling both resting and activated states, but favoring the resting state in the absence of stimulation. We reveal that heat and the synthetic agonist CIM0216 shift the equilibrium toward activation by inducing a similar ICD rearrangement. Mutations that facilitate ICD movement enhance sensitivity to both thermal and chemical stimuli, underscoring the central role of the ICD in channel gating. We also show that the antagonist primidone binds the same site as CIM0216 in the S1-S4 domain but inhibits channel activation. This study provides a structural framework for a mechanistic understanding of thermal and chemical gating of TRPM3 and for guiding the rational design of TRPM3-targeted analgesics and neurotherapeutics.

We encountered a case of a neonate diagnosed with essential tongue tremor due to involuntary movements of the tongue and poor oral feeding immediately after birth. Reports of pediatric-onset essential tongue tremor, particularly neonatal-onset, are extremely rare. Neonatal-onset essential tongue tremor can result in feeding difficulties and poor weight gain, potentially affecting subsequent growth and development. Given the importance of early diagnosis and medical intervention, we report our case. A boy born at 40 weeks and 5 days of gestation, weighing 3252 g, normal delivery with an Apgar Score of 8/9. He exhibited poor feeding and tongue tremor since birth. A thorough examination was performed to differentiate involuntary tongue movements. Videofluoroscopic examination of swallowing showed stagnation of contrast medium in the oral cavity, suggesting that it was due to poor tongue movement. Based on clinical findings and various exclusion diagnoses, a diagnosis of essential tongue tremor was made. Primidone, a barbiturate anticonvulsant drug, was started with a therapeutic diagnosis. Treatment resulted in marked improvement in feeding ability, and the primidone was tapered off and discontinued without any side effects after weaning was introduced. We plan to carefully follow up on growth and developmental assessment (especially language development) and continue to provide support to patients and their families.