fluoxetine (EDG005)

A3 adenosine receptor regulates depression-like behaviors through astrocyte-nourished excitatory synapse formation.

Li Bai B, Zeng Meng M, Liu Jiahui J, Huang Wanqing W et al.

Abnormal excitatory synaptic function plays a critical role in major depressive disorder. In this study, we investigated the role of the A3 adenosine receptor (A3AR), previously implicated in affective disorders, in excitatory synapse formation within prefrontal cortical circuits. Using a corticosterone-induced mouse model of depression, we found that the adenosine receptor activator 3'-deoxyadenosine (3'dA) produced antidepressant-like effects and selectively increased A3AR expression, whereas fluoxetine did not. 3'dA also restored the synaptic organizers neuroligin-2 (NLGN2) and neurexin-2 and elevated BDNF, excitatory synaptic markers (synapsin-1, PSD-95, and GluR1), and dendritic spine density in the PFC. Notably, enhanced NLGN2 immunoreactivity co-localized with astrocytes exclusively in 3'dA-treated mice but not in fluoxetine-treated mice. Pharmacological blockade of A3AR with MRS-1191 prevented the 3'dA-induced behavioral and molecular changes in this corticosterone-induced depressive-like mouse model. Together, our findings identify A3AR as a key regulator of NLGN2 expression and excitatory synapse formation and suggest a potential target for antidepressant therapies.

Epilepsy of infancy with migrating focal seizures: A scoping review of clinical features, diagnostic testing including genetics, long-term outcomes, mortality, and current and emerging therapeutic strategies.

Samanta Debopam D

Epilepsy of infancy with migrating focal seizures (EIMFS) is among the most severe developmental and epileptic encephalopathies (DEEs), marked by intractable multifocal seizures migrating across both hemispheres, profound developmental arrest, and high early mortality. Advances in next-generation sequencing have revealed a heterogeneous genetic architecture dominated by KCNT1 gain-of-function variants across more than 30 implicated genes, creating opportunities for precision therapeutics. To systematically map published evidence on the clinical, electrophysiological, neuroimaging, genetic, and therapeutic landscape of EIMFS, and to delineate critical knowledge gaps and future research priorities. A scoping review was conducted following the Arksey and O'Malley framework, searching PubMed, Ovid MEDLINE, Embase, Cochrane Library/CENTRAL, and ClinicalTrials.gov. Of 643 articles screened, 89 met inclusion criteria. Beyond confirmation of the canonical electroclinical phenotype, several gaps emerged: neonatal versus post-neonatal onset stratification by genetic etiology remains largely uncharacterized; genotype-specific EEG biomarkers are lacking except for a single small KCNT1 study; and the clinical significance of atypical EEG features-including burst suppression and hypsarrhythmia-is undefined. Neuroimaging literature documents progressive cerebral atrophy and myelination abnormalities without quantitative volumetry, diffusion tractography markers, or attribution to seizure burden, medication effects, or underlying etiology. Genetic diagnostic yield was 70-80%, with KCNT1 accounting for 30-50% of solved cases; however, genotype-outcome stratification is limited. Seizures were broadly refractory; potassium bromide, ketogenic diet, cannabidiol, and quinidine (in KCNT1-confirmed cases) showed partial efficacy. Emerging precision approaches include sodium channel blockers for SCN2A gain-of-function variants, novel small molecules, fluoxetine, antisense oligonucleotides, and divalent siRNA targeting KCNT1. Systemic-to-pulmonary collateral circulation causing severe cardiopulmonary complications was reported across multiple cases, yet no consensus screening protocol exists. EIMFS remains one of the most refractory epilepsy syndromes of infancy. Precision genetic diagnosis is essential to guide targeted therapy. International collaborative registries, standardized outcome measures, genotype-stratified biomarker studies, and rapid point-of-care genomic testing are urgently needed to advance evidence-based care for this highly vulnerable population.

Oculogyric Crisis and Torticollis Temporally Associated With Short-Term Coadministration of Fluoxetine and Hydroxyzine in a Child With Attention-Deficit/Hyperactivity Disorder.

Çobaner Mustafa M, Tufan Ali Evren AE

Second- and third-line treatment options for refractory monosymptomatic enuresis in children: a scoping review.

Selvi Ismail I, Marco Beatriz Banuelos BB, Dönmez M İrfan Mİ, Baydilli Numan N et al.

Around one-third of patients with monosymptomatic nocturnal enuresis (MNE) do not respond to conventional first-line treatments. Although international guidelines outline second- and third-line treatment options, these recommendations may not fully address the needs of every case encountered in daily practice. Therefore, the question of which treatment strategy should be used for refractory cases remains unanswered. We conducted a scoping review (PROSPERO CRD420251171197) following PRISMA Extension for Scoping Reviews (PRISMA-ScR), searching the PubMed, Embase, Ovid MEDLINE, Scopus, Web of Science, Google Scholar, CINAHL and the Cochrane Library databases to identify all published reports of treatment for refractory MNE in paediatric patients up to March 2026. Eligible studies included randomized controlled trials and prospective or retrospective observational cohort studies written in English. The primary outcome was the number of wet nights (classified as complete, partial or no response according to the ICCS criteria). Secondary outcomes included a comparison of the efficacy of second- and third-line treatment options if enough data could be found. The Cochrane RoB 2 tool was used to assess the risk of bias in randomized clinical trials, and the Methodological Index for Non-Randomized Studies (MINORS) was used for non-randomized cohort studies. Following screening and eligibility assessment, 17 out of 2578 articles met the PICO inclusion criteria. The included studies enrolled a total of 1348 children and adolescents with mean ages ranging from approximately 8 to 17 years. Many of the second- or third-line treatments described in the literature were excluded due to incorrect methodology, study design or patient population. The results showed that, following first-line treatment, a combination of biofeedback, electrical nerve stimulations, anticholinergics (e.g. oxybutynin, tolterodine, solifenacin), β3-adrenoceptor agonists (e.g. vibegron), tricyclic antidepressants (e.g. imipramine) and selective serotonin reuptake inhibitor (e.g. fluoxetine) improved both partial response (PR) and complete response (CR) at varying rates across highly heterogeneous interventions and study populations. However, the evidence does not strongly support a treatment algorithm. Furthermore, reports on electro-acupuncture, furosemide, onabotulinumtoxin A injections or the herbal medicine 'shokenchuto' were considered unreliable for pure refractory MNE, despite improvements in PR and CR occurring at different rates. Conclusion: The question of which treatment strategy should be used for refractory cases remains unanswered due to a lack of sufficiently unbiased, prospective, randomized, controlled studies involving long-term follow-up. Some second- and third-line treatment options may improve PR and CR rates, despite the limited available evidence to support a treatment algorithm. However, further research is needed to confirm these benefits.