Hemimegalencephaly is a rare congenital malformation of cortical development involving hamartomatous overgrowth of part or all of one cerebral hemisphere. It commonly presents during infancy with early-onset, drug-resistant seizures, developmental impairment, and contralateral motor deficits. Infantile epileptic spasms may be an initial manifestation. Brain magnetic resonance imaging (MRI) is central to diagnosis and surgical planning. We report the case of an 11-month-old boy with West syndrome and severe developmental delay whose epileptic spasms persisted despite treatment with vigabatrin, sodium valproate, and levetiracetam. Brain MRI demonstrated marked asymmetric enlargement of the left cerebral hemisphere, diffuse cortical thickening, blurring of the gray-white matter differentiation, enlargement and morphological distortion of the left lateral ventricle, shallow sulcation, and extensive pachygyria with areas approaching an agyric appearance. The right cerebral hemisphere was structurally preserved. These findings were consistent with left hemimegalencephaly associated with an extensive malformation of cortical development. An anterior corpus callosotomy was performed as a palliative disconnective procedure; however, the epileptic spasms persisted, and the patient was subsequently referred for evaluation of definitive left hemispherotomy. This case illustrates the characteristic MRI appearance of hemimegalencephaly with diffuse cortical malformation and highlights the limitations of anterior corpus callosotomy when the epileptogenic substrate involves an entire malformed hemisphere. It also emphasizes the role of imaging in guiding escalation to definitive hemispheric disconnection when seizures remain drug-resistant.

Cerebral arteriovenous malformations (AVMs) are rare during pregnancy, when the haemodynamic and hormonal changes of gestation may increase the risk of rupture. Lesions that are large, located in eloquent regions, and drained by deep venous channels represent a surgically high-risk subtype, carry substantial surgical morbidity, and are frequently managed conservatively when unruptured. We describe a 33-year-old G3P1L1A1 parturient at 36 weeks and six days of gestation with an untreated right parieto-temporo-occipital AVM, who declined intervention across three encounters and underwent an elective lower-segment Caesarean section (LSCS) with bilateral tubal ligation. The anaesthetic approach chosen was a graded epidural technique: fractionated bupivacaine boluses with real-time haemodynamic monitoring between increments. This allowed the rate of sympathectomy to be controlled, avoiding the abrupt sympathectomy associated with a subarachnoid block. Carbetocin was used as the uterotonic agent. Levetiracetam was continued perioperatively. A healthy male infant was delivered, and the mother was discharged neurologically intact on day seven, with no AVM rupture, seizure, or new deficit.

Pseudohypoparathyroidism (PHP) type 1A is a rare inherited disorder characterized by resistance to parathyroid hormone and, typically, features of Albright hereditary osteodystrophy. We report a late-onset case in a 59-year-old woman who presented with cognitive decline, behavioral and psychiatric symptoms, gait instability, and seizure-like episodes. Laboratory tests showed hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone levels. Brain imaging revealed symmetrical calcifications in the bilateral basal ganglia, thalami, and periventricular regions, while electroencephalography showed epileptiform discharges. Genetic testing identified a heterozygous missense variant in GNAS, c.285C>G: p.Ser95Arg, which has not been previously reported. Based on the clinical manifestations, biochemical abnormalities, neuroimaging findings, and genetic results, the patient was diagnosed with late-onset atypical PHP type 1A. After treatment with calcium supplementation, calcitriol, and levetiracetam, no further seizures occurred, and serum calcium returned to the normal range, although cognitive improvement was limited. This case suggests that calcium-phosphate metabolism and parathyroid hormone levels should be assessed in adults presenting with symmetrical intracranial calcifications, seizures, or cognitive impairment. Genetic testing may further support early diagnosis and help reduce misdiagnosis.

Synaptic vesicle glycoprotein 2C (SV2C) is a vesicular protein enriched in dopaminergic neurons of the basal ganglia that modulates dopamine storage and release, and its disruption is implicated in Parkinson's disease (PD). Despite strong genetic and pathological links to PD, there are no selective small-molecule probes for SV2C. Here, we describe an AI-enhanced virtual screening (VS) and experimental campaign that identified multiple novel chemotypes with low-micromolar affinity and marked selectivity for SV2C over SV2A and SV2B, starting from a large, general-purpose commercial library. Because no full-length high-resolution SV2C structure was available, we built a homology model using SV2A cryo-EM structures as templates and characterized its conformational landscape by molecular dynamics (MD) and Gaussian accelerated MD (GaMD) simulations in apo form and in complex with known SV2 ligands (plosaracetam, levetiracetam, brivaracetam, and padsevonil). A convolutional neural network-based scoring function (CNN_VS), retrospectively validated on a manually curated 39-ligand SV2A benchmark (r = 0.72 vs experimental pIC50), was then applied in a multi-stage funnel to 5.96 million Mcule in-stock compounds, which were sequentially filtered to 3.19 million CNS-relevant molecules before docking and rescoring. From 94 VS-prioritized candidates, 71 compounds were experimentally profiled in an orthogonal primary assay cascade combining a thermal shift assay (TSA) with a [3H]-padsevonil scintillation proximity assay (SPA), followed by Ki determination and isoform selectivity profiling for key hits. This campaign yielded 22 active molecules (31% hit rate) that naturally segregated into two categories: compounds that showed primary site competition, and compounds that did not show primary site competition with [3H]-padsevonil. A subset of competitor compounds also showed thermostabilization activity. Among these, compounds 36 and 56 emerged as particularly attractive leads, with Ki values of 24.6 uM and 3.25 uM at SV2C, respectively, and greater than 10-fold selectivity versus SV2A; compound 56 also maintained approximately 12-fold selectivity relative to SV2B. A complementary subset of SV2C-selective hits behaved as padsevonil-site competitors, providing a lead set that will serve as a template for functional characterization and future drug development for conditions that affect dopaminergic signaling. Docking analysis suggests a common binding mode anchored by conserved tryptophan residues in the SV2 pocket, a prediction independently confirmed by an unpublished SV2A-plosaracetam cryo-EM structure showing 0.76 Angstrom binding-site C-alpha RMSD relative to the SV2C model and complete conservation of the tryptophan cage. Subtle differences in the luminal domain and transmembrane region point to the structural determinants underlying isoform selectivity. Collectively, these results demonstrate that an AI-driven VS pipeline, tightly integrated with medium-throughput biophysical assays, can deliver selective SV2C binders from a general chemical library on a structurally under-characterized membrane target. The identified hits provide multiple starting points for hit-to-lead optimization and tools for probing SV2C biology and its role in PD.

The patient was a woman in her 20s. In June of a certain year, she experienced cardiopulmonary arrest due to acute epiglottitis and was admitted to the ICU and required mechanical ventilation. From the first day of hospitalization, she exhibited generalized seizures and was diagnosed with acute symptomatic seizures following hypoxic brain injury. Treatment with diazepam and levetiracetam was initiated, leading to symptom resolution. However, around the seventh day of hospitalization, she began experiencing episodic limb muscle hypertonia and fever. Based on diagnostic criteria, she was diagnosed with paroxysmal sympathetic hyperactivity on the 20th day of hospitalization. Although treatment with propranolol, gabapentin, and baclofen was initiated, her symptoms persisted. On the 38th day of hospitalization, morphine hydrochloride and methylprednisolone were administered, resulting in remarkable improvement. The present case shows that accurate diagnosis of paroxysmal sympathetic hyperactivity following hypoxic brain injury, particularly its differentiation from acute symptomatic seizures, is essential for appropriate management.

Levetiracetam (LEV) is commonly used as an adjunctive antiseizure medication (ASM) in dogs because of its favorable pharmacokinetic profile and limited hepatic metabolism. However, because LEV is predominantly eliminated through renal excretion, prospective clinical evidence regarding its effects on renal function in dogs remains limited. This prospective study evaluated short-term changes in renal biomarkers and urinalysis parameters in 12 client-owned dogs with idiopathic epilepsy (IE) receiving concurrent phenobarbital (PB) and adjunctive LEV. All 12 dogs were evaluated at baseline (day 0), day 14, and day 28. Renal assessment included serum symmetric dimethylarginine (SDMA), serum creatinine, blood urea nitrogen (BUN), phosphorus, albumin, and urinalysis; glomerular filtration rate (GFR) was not directly measured. Changes in SDMA over time were analyzed using the Friedman test, whereas serum creatinine, BUN, phosphorus, and albumin were analyzed using repeated-measures ANOVA with the Geisser-Greenhouse correction. No statistically significant changes were detected in SDMA, serum creatinine, BUN, phosphorus, or albumin during the 4-week study period. Urinalysis showed no consistent progressive abnormalities, including proteinuria, glucosuria, or urinary casts. Sedation was the most frequently observed clinical adverse event, occurring in 83% (10/12) of dogs, although it was generally mild and did not require treatment discontinuation. Overall, no detectable short-term deterioration in the assessed renal biomarkers or urinalysis parameters was identified during the 4-week study period in non-azotemic dogs receiving concurrent PB and adjunctive LEV. However, the absence of statistically significant or clinically detectable changes does not exclude subtle alterations in renal function or subclinical renal injury. Larger controlled studies with longer follow-up periods and direct assessment of GFR are warranted.

Background/Objectives: Antiseizure drugs (ASDs) are the primary therapeutic approach for epilepsy in small animals. Although ASDs are primarily used to modulate central neuronal excitability, they are commonly administered systemically, most often by the oral route, and may therefore influence neuronal populations outside the central nervous system. Nevertheless, their functional effects on peripheral neuronal populations, including enteric and dorsal root ganglion (DRG) neurons, remain incompletely characterized at a comparative pharmacological level. This study aimed to perform a comparative functional neuropharmacological profiling of commonly used ASDs in primary cultured myenteric and DRG neurons. Methods: Changes in neuronal activity were assessed in primary cultured guinea pig myenteric and DRG neurons using voltage-sensitive dye imaging with Di-8-ANEPPS following direct ASD application under standardized in vitro conditions. Results: ASDs exerted distinct drug- and neuron-type-specific effects on peripheral neuronal excitability. Topiramate induced the most pronounced reduction in neuronal excitability in myenteric neurons, whereas phenobarbital and levetiracetam produced only minor changes compared with buffer control. Potassium bromide induced mainly excitatory effects in both enteric and DRG neurons. Overall, most ASDs predominantly increased neuronal excitability in DRG neurons. Conclusions: These findings demonstrate distinct functional response profiles of ASDs in enteric and sensory neuronal populations. This comparative in vitro approach may provide a basis for future studies investigating peripheral neuronal drug effects and may help relate experimental pharmacological profiling to clinically relevant challenges associated with ASD treatment across different disorders.

Oxidative stress is implicated in epilepsy, but seizures, disease severity, diet, comorbidity and treatment all influence circulating redox biomarkers. We systematically reviewed human evidence on levetiracetam (LEV) under three estimands: within-person change, LEV-treated epilepsy versus healthy controls, and LEV versus other antiseizure medications. PubMed/MEDLINE, Cochrane Library, Web of Science and Scopus were searched from inception to 15 July 2026 (PROSPERO CRD420261448016; OSF HXA4U). Eleven non-randomized studies contributed 297 participants-the sum of LEV subgroups with analysable biomarker data, not the total enrolled populations. Effect estimates with 95% confidence intervals were calculated here wherever reporting permitted; none could be derived for four studies, and those derived are wide, inconsistent in direction, or from designs that cannot attribute change to LEV. Meta-analysis was inappropriate: definitions, matrices, assays, estimands and variance reporting were incompatible. Certainty was very low for every outcome-domain/comparator body, and a sensitivity analysis excluding one report failing a post hoc source-verifiability check (10 studies, 265 participants) changed no conclusion. This review's contribution is not an estimate of LEV's redox effect but a demonstration of why the literature cannot establish one: the human evidence is not of sufficient validity to support or refute such an effect.