Morphine tolerance limits its long-term clinical utility, and neuroinflammation is a key underlying mechanism. This study investigated whether zonisamide, an antiepileptic drug with anti-inflammatory properties, attenuates morphine-induced neuroinflammation and morphine tolerance.

Antiseizure medications (ASMs) are the mainstay of epilepsy treatment but may adversely affect cognitive functions, deepening the cognitive and psychosocial burden intrinsic to epilepsy. Cognitive side effects vary widely across drug classes, doses, treatment regimens, and individual susceptibility, typically affecting attention, processing speed, memory, language, and executive function. This narrative review provides an updated synthesis of the clinical evidence on the cognitive effects of ASMs, mostly in adults, building on a prior 2009 review and focusing on agents introduced into clinical practice since then. A literature search of PubMed identified studies published between January 2009 and December 2025, yielding data from randomised controlled trials, observational studies, meta-analyses, and systematic reviews. Overall, newer-generation ASMs, including rufinamide, lacosamide, brivaracetam, cannabidiol, fenfluramine, and ganaxolone, demonstrate generally favourable cognitive profiles when used at recommended doses, particularly in monotherapy or rational polytherapy. Eslicarbazepine and cenobamate may be associated with mild, dose-dependent cognitive effects, occurring only at the upper end of the recommended dose range. In contrast, old ASMs and certain second-generation agents, notably topiramate and zonisamide, remain consistently associated with higher cognitive risks. Special populations, including older adults and individuals with intellectual disabilities, are particularly vulnerable to cognitive adverse effects and benefit from agents with low interaction potential and benign neuropsychological profiles. Cognitive dysfunction in epilepsy is multifactorial, reflecting the interaction between disease-related neurobiological mechanisms and treatment effects. Optimal management requires balancing seizure control with cognitive preservation through individualised drug selection, cautious titration, and minimisation of polytherapy to achieve the best functional and quality-of-life outcomes.

To report the occurrence of rebound phenomenon in a dog with phenobarbital and zonisamide toxicosis treated with intermittent hemodialysis.

Stroke-like Migraine Attacks after Radiation Therapy (SMART) syndrome is a rare, delayed complication of cerebral irradiation characterized by stroke-like symptoms, seizures, and/or headaches, with mean latency period of 11.2 years. It is most associated with gliomas and medulloblastomas and diagnosis is challenging due to symptom overlap with recurrent neurologic deficits. We present a 59-year-old male with history of right frontal convexity anaplastic meningioma complicated by seizure disorder and Todd's paralysis, status post tumor resection, adjuvant radiation to 6000cGy, craniotomy and cranioplasty complicated by subdural abscess/empyema. Four years later, he presented with an epileptic seizure followed by progressive left facial and hand numbness with facial droop over 24 hours. Vitals, blood work, lumbar puncture and head computed tomography (CT) were unremarkable. CT angiography demonstrated asymmetric gyral enhancement and sulcal effacement within the right frontal lobe. Brain magnetic resonance imaging (MRI) demonstrated right hemispheric sulcal enhancement within the prior radiation field with cortical/leptomeningeal FLAIR hyperintensity and subtle diffusion restriction Electroencephalography revealed nonspecific right temporal and paracentral lateralized rhythmic discharges. Following multidisciplinary evaluation, the patient required a prolonged dexamethasone taper due to failed initial steroid taper and was initiated on amlodipine with continuation of levetiracetam, zonisamide, and clobazam. MRI at three months showed enhancement resolution with clinical improvement and no recurrent seizures. This case highlights SMART syndrome as a diagnosis of exclusion, notable for its shortened latency in comparison to the reported mean and rare association with meningioma, emphasizing the need for heightened clinical suspicion in patients with prior cerebral irradiation presenting with progressive neurologic deficits.

We present the case of a child with myoclonus-dystonia (MD) who was mistaken for having stuttering and responded to oral zonisamide therapy. An 11-year-old boy presented with a 3-month history of speech-induced myoclonus, dystonia, and speech disfluency, with a positive family history in his father. A final diagnosis of MD was made, and the child responded to zonisamide. MD is a treatable form of neurogenic stuttering. It may mimic stuttering, and detailed analysis of the phenomenology and the evaluation of family history may help establish the diagnosis. A trial of zonisamide may be considered in the treatment of this disabling condition.

Carbonic anhydrase (CA, EC 4.2.1.1) inhibitors of the sulfonamide/sulfamate type, such as acetazolamide, thiazides/high-ceiling diuretics, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, antiepileptics (sulthiame, topiramate, zonisamide), or non-steroidal anti-inflammatory agents such as celecoxib and polmacoxib, are effective inhibitors of most CA isoforms present in vertebrates but their clinical use in various pathologies is associated with side effects. Significant efforts were done in the last decades for developing isoform-selective inhibitors for all 12 catalytically active mammalian isoforms, with important results being obtained by using the tail approach or by the discovery of new inhibitory chemotypes, such as the coumarins and their derivatives, the boron/selenium-containing compounds, etc. SLC-0111, an antitumor sulfonamide in clinical development is an example of a successful strategy emerged by using the tail approach, this compound being a selective inhibitor of the tumor-associated isoforms CA IX and XII. Coumarins, sulfocoumarins and some boron-containing compounds show significant levels of isoform-selective inhibition against many CA isoforms too. Few compounds, on the other hand, show selectivity for inhibiting microbial over vertebrate isoforms, which is a considerable challenge for developing anti-infectives based on CA inhibitors. At the moment, only coumarins act as class-selective inhibitors for α- and η-CAs, not inhibiting significantly other CA classes (β-, γ-, δ-, ζ-, θ- and ι-CAs). Selective CA activators for the mammalian isoforms are not available yet, although they might lead to relevant pharmacological applications for the management of neurodegenerations, emotional memory disorders, obsessive-compulsive disorders, phobias, post-traumatic stress. Finding more effective isoform-selective and more importantly, class-selective modulators of activity for vertebrate CAs might afford opportunities for innovative therapeutic/pharmacological applications.

Carbonic anhydrase (CA, EC 4.2.1.1) isoforms I (CA I) and II (CA II) are widespread cytosolic proteins in most vertebrates. They are abundant in the red blood cells and many other tissues, being involved in physiological processes such as pH regulation, CO₂/bicarbonate homeostasis, respiration, and secretion of electrolytes rich in acid or bicarbonate in the stomach, kidneys, cerebrospinal fluid, eyes, and bones. The genetics, biochemistry, expression, localization in tissues and organs, kinetic properties, and catalytic mechanisms of these enzymes are well understood at the molecular level. At least five different inhibition mechanisms were described with more than 50 chemotypes acting as inhibitors. The activation with amine/amino acid activators was also well studied. The physiological role of CA I is poorly understood, whereas CA II is a physiologically dominant isoform, playing crucial functions in a host of tissues/organs. Interfering with its activity by means of inhibitors has been and is currently exploited in therapy for the management of edema, glaucoma, epilepsy, obesity, acute mountain sickness, and idiopathic intracranial hypertension. Promising preclinical data pointed to the potential use of CA II inhibitors for the management of other conditions, such as neuropathic pain, cerebral ischemia, rheumatoid arthritis, Alzheimer's disease, osteoporosis, and obstructive sleep apnea. Many CA inhibitors are in clinical use for the management of such conditions, among which are acetazolamide, thiazides and high-ceiling diuretics, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, and antiepileptics such as sulthiame, topiramate and zonisamide, whereas SLC-0111 is in clinical development as an antitumor agent. CA activators are not yet used clinically, but they might have pharmacological applications in the management of neurodegeneration, emotional memory disorders, obsessive-compulsive disorders, phobias, generalized anxiety, and post-traumatic stress. Finding novel modulators of activity for these enzymes may lead to innovative therapeutic applications and deepen our understanding of enzymes, their inhibitors, and their activators.