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Since its first clinical description (on his son) by William James West (1793–1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as “West syndrome”, new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances.

CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental and epileptic encephalopathy characterised by severe global developmental impairment and seizures that can begin in the first few months after birth and are often treatment refractory. Ganaxolone, an investigational neuroactive steroid, reduced seizure frequency in an open-label, phase 2 trial that included patients with CDD. We aimed to further assess the efficacy and safety of ganaxolone in patients with CDD-associated refractory epilepsy. In the double-blind phase of this randomised, placebo-controlled, phase 3 trial, done at 39 outpatient clinics in eight countries (Australia, France, Israel, Italy, Poland, Russia, the UK, and the USA), patients were eligible if they were aged 2–21 years with a pathogenic or probably pathogenic CDKL5 variant and at least 16 major motor seizures (defined as bilateral tonic, generalised tonic-clonic, bilateral clonic, atonic, or focal to bilateral tonic-clonic) per 28 days in each 4-week period of an 8-week historical period. After a 6-week prospective baseline period, patients were randomly assigned (1:1) via an interactive web response system to receive either enteral adjunctive ganaxolone or matching enteral adjunctive placebo (maximum dose 63 mg/kg per day for patients weighing ≤28 kg or 1800 mg/day for patients weighing >28 kg) for 17 weeks. Patients, caregivers, investigators (including those analysing data), trial staff, and the sponsor (other than the investigational product manager) were masked to treatment allocation. The primary efficacy endpoint was percentage change in median 28-day major motor seizure frequency from the baseline period to the 17-week double-blind phase and was analysed (using a Wilcoxon-rank sum test) in all patients who received at least one dose of trial treatment and for whom baseline data were available. Safety (compared descriptively across groups) was analysed in all patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov, NCT03572933, and the open-label extension phase is ongoing. Between June 25, 2018, and July 2, 2020, 114 patients were screened for eligibility, of whom 101 (median age 6 years [IQR 3 to 10]) were randomly assigned to receive either ganaxolone (n=50) or placebo (n=51). All patients received at least one dose of a study drug, but seizure frequency for one patient in the ganaxolone group was not recorded at baseline and so the primary endpoint was analysed in a population of 100 patients. There was a median percentage change in 28-day major motor seizure frequency of –30·7% (IQR –49·5 to –1·9) in the ganaxolone group and of –6·9% (–24·1 to 39·7) in the placebo group (p=0·0036). The Hodges–Lehmann estimate of median difference in responses to ganaxolone versus placebo was –27·1% (95% CI –47·9 to – 9·6). Treatment-emergent adverse events occurred in 43 (86%) of 50 patients in the ganaxolone group and in 45 (88%) of 51 patients in the placebo group. Somnolence, pyrexia, and upper respiratory tract infections occurred in at least 10% of patients in the ganaxolone group and more frequently than in the placebo group. Serious adverse events occurred in six (12%) patients in the ganaxolone group and in five (10%) patients in the placebo group. Two (4%) patients in the ganaxolone group and four (8%) patients in the placebo group discontinued the trial. There were no deaths in the double-blind phase. Ganaxolone significantly reduced the frequency of CDD-associated seizures compared with placebo and was generally well tolerated. Results from what is, to our knowledge, the first controlled trial in CDD suggest a potential treatment benefit for ganaxolone. Long-term treatment is being assessed in the ongoing open-label extension phase of this trial. Marinus Pharmaceuticals.

Objectives: The aim of this study was to evaluate the effectiveness of sequential treatments with adrenocorticotropic hormone (ACTH) or ketogenic diet therapy (KDT) in infants with infantile epileptic spasms syndrome (IESS) who did not achieve seizure freedom after initial treatment with either KDT or ACTH. Methods: We conducted a cohort study following a parallel-cohort randomized controlled trial comparing KDT with ACTH as first-line treatment for IESS. Infants who failed to respond were switched per protocol to the alternative treatment (ACTH or KDT) or, if this was not feasible or unsuccessful, to anti-seizure medications (ASMs). The primary outcome was the frequency of sustained seizure freedom at last follow-up. Results: Of 101 infants allocated to the initial treatment phase, N = 67 required further treatment. Of these, 31% (21/67) achieved sustained seizure freedom after the second treatment phase, and 15% (7/46) after rescue treatment with ASMs. KDT as the second treatment achieved sustained seizure freedom in 50% (12/24), compared to 19% (3/16) with ACTH and 9% (2/22) with ASMs. The cumulative response rate after the first and second treatments was 64% for the KDT-ACTH sequence and 68% for the ACTH-KDT sequence. The cumulative response after all three treatment phases was 78% (KDT-ACTH-ASM) and 72% (ACTH-KDT-ASM), respectively. Conclusions: KDT is at least as effective as ACTH as a second treatment and significantly more effective than ASMs in achieving sustained seizure freedom in infants with IESS.

Background and Objectives: Infantile spasms (ISs), or West syndrome (WS), represent an early-onset epileptic encephalopathy in which diverse structural, genetic, metabolic, infectious, and neurocutaneous conditions converge on a shared pattern of hypsarrhythmia, clustered spasms, and later developmental impairment. Growing use of genomic diagnostics has revealed that variants in STXBP1, KCNQ2, GRIN2A, GRIN2B, and TSC-related genes are more common than previously recognized and can be linked to partially actionable pathways. This review aimed to synthesize current evidence on the multifactorial etiology, network-based pathogenesis, and evolving targeted therapies for ISs, with particular attention to TSC-related forms. Materials and Methods: A structured narrative review was undertaken of publications from 1990 to 2025 in PubMed, Scopus, Web of Science, and Embase using terms related to ISs, WS, genetics, mTOR, ACTH, vigabatrin, ketogenic diet, and precision therapies. Authoritative guidance from ILAE and AAN was incorporated. Clinical, molecular, and therapeutic data were grouped under etiological, pathogenetic, and management domains. Results: Structural causes remained the largest group, but combined genetic, genetic–structural, and metabolic etiologies accounted for about one third of contemporary cohorts. Early network disruption involving cortex, thalamus, basal ganglia, and brainstem, together with imbalances in NGF, BDNF, and IGF-1, explained why distinct primary insults produce a uniform electroclinical phenotype. Early treatment with ACTH or high dose prednisolone, with or without vigabatrin, was consistently associated with higher electroclinical remission and better developmental outcome. Everolimus and related mTOR inhibitors showed benefit in TSC-associated ISs, while agents directed at NMDA receptors or KCNQ channels are emerging for genotype defined subgroups. Conclusions: ISs should be approached as a heterogeneous but mechanistically convergent disorder in which rapid diagnosis, parallel genetic testing, and early disease modifying therapy improve prognosis. Integration of molecular profiling with standardized outcome monitoring is likely to move management from symptomatic seizure control to pathway-specific intervention.

Postoperative nausea and vomiting (PONV) frequently occur in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) under general anesthesia. Glycopyrronium bromide, an anticholinergic medication, is believed to not only relieve gastrointestinal spasms but also effectively prevent PONV. To compare the incidence of nausea and vomiting and the effect of relieving spasm between patients administered glycopyrronium bromide and those given anisodamine hydrobromide following endoscopic retrograde cholangiopancreatography (ERCP). This is a monocentric prospective study. Patients eligible for ERCP were randomly assigned to two groups. One group received 0.2 mg glycopyrronium bromide (Group G) intravenously, while the other group received 10 mg anisodamine hydrobromide (Group A) intramuscularly for anesthesia induction. The study assessed duodenal motility during ERCP and the incidence of PONV within 24 hours. The study included 130 patients. Nausea and vomiting within 24 hours post-surgery occurred in nine patients (13.8%) in Group G and 19 patients (29.2%) in Group A, with statistical significance (relative risk (RR), 0.47; 95% confidence interval (CI) [0.02-0.29];  = 0.033). Vomiting specifically was observed in three patients (4.6%) in Group G and 12 patients (18.5%) in Group A, showing statistical significance (RR 0.25; 95% CI [0.03-0.25];  = 0.028). There was no significant difference in duodenal peristalsis between the groups (Group G: 10.9 ± 3.1 times/min; Group A: 11.6 ± 3.1 times/min;  = 0.174). For patients undergoing ERCP under general anesthesia, a subcutaneous injection of 0.2 mg glycopyrronium bromide significantly reduces PONV and provides similar anti-spasmodic effects to 10 mg intramuscular anisodamine hydrobromide.

Infantile spasms constitutes a severe infantile epilepsy syndrome that is difficult to treat and has a high morbidity. Hormonal therapies or vigabatrin are the most commonly used treatments. We aimed to assess whether combining the treatments would be more effective than hormonal therapy alone. In this multicentre, open-label randomised trial, 102 hospitals (Australia [three], Germany [11], New Zealand [two], Switzerland [three], and the UK [83]) enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment. Participants were randomly assigned (1:1) by a secure website to receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents consented, there was an additional randomisation (1:1) of type of hormonal therapy used (prednisolone or tetracosactide depot). Block randomisation was stratified for hormonal treatment and risk of developmental impairment. Parents and clinicians were not masked to therapy, but investigators assessing electro-clinical outcome were masked to treatment allocation. Minimum doses were prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without vigabatrin 100 mg/kg per day. The primary outcome was cessation of spasms, which was defined as no witnessed spasms on and between day 14 and day 42 from trial entry, as recorded by parents and carers in a seizure diary. Analysis was by intention to treat. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 54363174, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2006-000788-27. Between March 7, 2007, and May 22, 2014, 766 infants were screened and, of those, 377 were randomly assigned to hormonal therapy with vigabatrin (186) or hormonal therapy alone (191). All 377 infants were assessed for the primary outcome. Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone (difference 15·0%, 95% CI 5·1–24·9, p=0·002). Serious adverse reactions necessitating hospitalisation occurred in 33 infants (16 on hormonal therapy alone and 17 on hormonal therapy with vigabatrin). The most common serious adverse reaction was infection occurring in five infants on hormonal therapy alone and four on hormonal therapy with vigabatrin. There were no deaths attributable to treatment. Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The 4 week period of spasm cessation required to achieve a primary clinical response to treatment suggests that the effect seen might be sustained, but this needs to be confirmed at the 18 month follow-up. The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, the BRONNER-BENDUNG Stifung/Gernsbach, and University Children's Hospital Zurich.

Neurodevelopmental disorders can have long-lasting effects, causing not only early pediatric symptoms but also a range of neurological issues throughout adulthood. West syndrome is a severe neurodevelopmental disorder marked by infantile spasms, an early symptom that typically subsides with age. However, many patients progress to other seizure forms, known as seizure evolution, which is closely linked to poor long-term outcomes. Despite its clinical significance, the neurobiological mechanisms behind seizure evolution in West syndrome remain poorly understood. Recent genetic studies have consistently identified the CYFIP2 p.Arg87Cys variant in West syndrome patients, and the Cyfip2 + /R87C mouse model carrying this mutation has been shown to recapitulate key symptoms of the disorder, including infantile spasms. In this study, we aimed to gain deeper insight into seizure evolution by conducting longitudinal deep phenotyping of the Cyfip2 + /R87C mouse model from the neonatal stage to seven months of age. We tracked seizure activity through behavioral and EEG recordings and employed multi-omic analyses, including tissue and single-cell level transcriptomics, ultrastructural analysis, proteomics, and lipidomics, to capture a comprehensive view of molecular and cellular changes. Our results showed that after an initial period of neonatal spasms, Cyfip2 + /R87C mice entered a seizure-free phase, followed by spontaneous recurrent seizures in adulthood, ultimately leading to premature death. This progression was associated with synaptic remodeling, sequential activation of different glial cell types, lipid droplet accumulation in astrocytes, and significant proteomic and lipidomic changes in the brain. These findings suggest that seizure evolution in West syndrome involves complex, time-dependent interactions between neurons and glial cells, along with alterations in lipid metabolism. Our study highlights the potential of longitudinal multi-omic approaches to uncover underlying mechanisms of seizure evolution and suggests that targeting these changes could offer novel therapeutic strategies. Additionally, the dataset generated here may provide valuable insights for other epilepsy and neurodevelopmental disorder models.

Background Infantile spasms is the name given to a difficult to treat, severe infantile epilepsy with high morbidity. The United Kingdom Infantile Spasms Study (UKISS) showed that absence of spasms on days 13 and 14 after randomisation was more common in infants allocated hormonal treatments than vigabatrin. At 12–14 months, those with no identified aetiology allocated hormonal treatment had better development. However, epilepsy outcome was not affected by treatment allocated. It is not known if the difference in development persists as the infants grow. Methods Infants in UKISS were followed up blind to treatment allocation by telephone at a mean age of 4 years using the Vineland Adaptive Behaviour Scales (VABS) and an epilepsy questionnaire. Findings 9 of 107 enrolled infants had died. 77 were traced and consented to take part. The median (quartile) VABS scores were 60 (42, 97) for the 39 allocated hormonal treatment and 50 (36, 67) for the 38 allocated vigabatrin (Mann–Whitney U=575; p=0.091; median difference (95% CI): 8 (−1 to 19)). For those with no identified aetiology, VABS scores were 96 (52, 102) for the 21 allocated hormonal treatment and 63 (37, 92) for the 16 allocated vigabatrin (U=98.5; p=0.033; median difference (95% CI): 14 (1 to 42)).The proportions in each treatment group with epilepsy were similar. Interpretation For all 77 infants, development and epilepsy outcomes were not significantly different between the two treatment groups. The better development seen at 14 months in those with no identified aetiology allocated hormonal treatment was seen again at 4 years in this study.

The aim of this study was to investigate the frequency of hemorrhagic side effects of botulinum neurotoxin A injections (BoNT/A) for the treatment of benign essential blepharospasm (BEB) and hemifacial spasm (HFS) in patients taking antithrombotic drugs (ATD). A total of 140 patients were included (female: 65%; BEB: 75%; mean age: 70 ± 12 years). According to their current antithrombotic medication, participants were either assigned to the ATD group (41%), or to the control group (59%). The ATD group was further divided into subgroups depending on the medication administered: acetylsalicylic acid, ADP receptor antagonists, direct oral anticoagulants, vitamin-K antagonists, or dual antiplatelet therapy. The frequency of hemorrhagic side effects was recorded by retrospective analysis of past treatments as documented in the patient’s file set in relation to the number of past treatments (hematoma frequency of past treatments, HFretro) as well as by a prospective survey capturing the side effects of one single treatment (hematoma frequency of actual treatment, HFactual). There was no significant difference in hematoma frequency between the ATD group and the control group, neither for past (HFretro: ATD: 2%; 45/2554; control: 4%; 109/2744) nor for the current BoNT/A treatments (HFactual: ATD: 30%; 16/53; control: 31%; 22/72). Even between ATD subgroups, hematoma frequency did not differ significantly. Overall, hemorrhagic side effects of the BoNT/A treatment for BEB and HFS were mild and non-disabling.

Computed tomography (CT)-guided percutaneous stylomastoid foramen puncture radiofrequency ablation for the treatment of hemifacial spasm has a significant clinical effect; however, related risk factors for recurrence have not been studied. To investigate the risk factors for the recurrence of hemifacial spasm after radiofrequency ablation and construct a model for predicting recurrence. This is a single-center retrospective observational study. The study was conducted at the Pain Department of the Affiliated Hospital of Jiaxing College in Jiaxing, China. A retrospective analysis was performed on 99 patients diagnosed with primary hemifacial spasm (HFS) admitted to the Affiliated Hospital of Jiaxing University between August 2018 and December 2021. All patients underwent CT-guided percutaneous stylomastoid foramen radiofrequency ablation. Kaplan-Meier survival analysis, log-rank test, and Cox proportional risk regression model were used to analyze the clinical factors that affect the recurrence of patients with HFS after radiofrequency ablation, and a recurrence prediction model was established. Follow-up was 3-12 months; recurrence rates were 20.2%, 36.4%, and 71.9% at 3, 6, and 12 months postoperatively, respectively. Univariate analysis showed that puncture approach, operation time, and facial paralysis level were factors influencing recurrence in patients with HFS after radiofrequency ablation (P < 0.05). The multivariate Cox proportional risk regression model showed that the operative time and facial paralysis grade were independent factors for recurrence after radiofrequency ablation in patients with facial spasms. The recurrence risk function model of patients with facial spasms after radiofrequency ablation was expressed as h(t) = h0exp(-0.619X1-2.589X2), where X1 and X2 represent the operation time and facial paralysis grade, respectively. The likelihood ratio of the model was statistically significant (chi squared = 55.769, P < 0.001). We look forward to increasing the sample size in follow-up studies and exploring relevant conclusions in randomized controlled trials. Long operation times and high-grade facial paralysis can reduce the risk of recurrence in patients with facial spasms. The constructed recurrence prediction model could serve as a reference for clinical diagnosis and treatment.