fluoxetine (EDG005)

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.

From Visceral Pain to Emotional Distress: Comparative Effectiveness of Antispasmodics and Antidepressants in Irritable Bowel Syndrome - Systematic Review and Network Meta-analysis.

Ismaiel Abdulrahman A, Leucuta Daniel-Corneliu DC, Boitos Irina I, Foucambert Paul P et al.

Antispasmodics and antidepressants are standard therapies for managing both the gastrointestinal symptoms and psychological comorbidities associated with irritable bowel syndrome (IBS). However, direct comparative evidence regarding their efficacy across different symptom domains is scarce. This systematic review and network meta-analysis aimed to assess the relative effectiveness of these agents on abdominal pain, psychological outcomes, overall IBS symptom severity, and quality of life (QoL). We conducted a comprehensive search of PubMed, EMBASE, and Scopus to identify relevant randomized controlled trials evaluating antispasmodics and antidepressants for IBS. Eligible studies underwent quality assessment and were synthesized using network meta-analysis. We calculated standardized mean differences (SMDs) with 95% confidence intervals (CIs) for pain outcomes (VAS), anxiety, depression, the IBS Severity Scoring System (IBS-SSS), and QoL. Twenty-nine studies were included in the analysis. Significant reductions in pain (VAS) were observed with imipramine (SMD -34.06; 95%CI -51.89 to -16.22) and the alverine/simethicone combination (SMD -6.23; 95%CI -9.93 to -2.53), while mebeverine and anise oil showed benefits in specific IBS subgroups. The most substantial improvements in anxiety occurred with flupentixol-melitracen (SMD -6.63; 95%CI -10.13 to -3.13), followed by small-intestinal release peppermint oil, fluoxetine, and vortioxetine. Imipramine was most effective for depressive symptoms (SMD -9.40; 95%CI -10.29 to -8.51), followed by venlafaxine, flupentixol-melitracen, desipramine, and vortioxetine. Amitriptyline was the only agent to show significant improvement in IBS-SSS scores (SMD -23.70; 95%CI -43.27 to -4.13). The largest gains in QoL were associated with otilonium bromide (SMD 30.90; 95%CI 26.62 to 35.18), followed by venlafaxine, amitriptyline, and cumin sofouf. Imipramine and alverine/simethicone were superior for reducing abdominal pain, whereas flupentixol-melitracen, peppermint oil, fluoxetine, and vortioxetine demonstrated the strongest anxiolytic effects. Effective options for depression included imipramine, venlafaxine, flupentixol-melitracen, desipramine, and vortioxetine. Notably, amitriptyline uniquely improved overall IBS severity scores, while otilonium bromide, venlafaxine, amitriptyline, and cumin sofouf provided the greatest benefits for QoL. These findings clarify comparative efficacy and may guide tailored pharmacotherapy strategies for IBS patients.