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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.

The demand for noninvasive methods to assess postural defections is increasing because back alterations are more common among the healthy population. We propose a combined infrared method of rasterstereography and thermography to assess the back without harmful effects. This study aims to provide reference data on rasterstereography and thermography to evaluate the back of a healthy population and to further study the correlation between these two methods. This cross-sectional research involved 175 healthy individuals (85 males and 90 females) aged 22 to 35 years. There is a large Cohen’s d effect size in the cervical depth (males = 43.77 ± 10.96 mm vs. females = 34.29 ± 7.04 mm, d = 1.03), and in the lumbar lordosis angle (males = 37.69 ± 8.89° vs. females = 46.49 ± 8.25°, d = − 1.03). The back temperature was different for gender in the cervical area (males = 33.83 ± 0.63 °C vs. females = 34.26 ± 0.84 °C, d = − 0.58) and dorsal area (males = 33.13 ± 0.71 °C vs. females = 33.59 ± 0.97 °C, d = − 0.55). Furthermore, in the female group there was a moderate correlation of lumbar temperature with lumbar lordosis angle (r = − 0.50) and dorsal temperature with shoulders torsion (r = 0.43). Males showed a moderate correlation for vertebral surface rotation RMS with cervical (r = − 0.46), dorsal (r = − 0.60), and lumbar (r = − 0.50) areas and cervical temperature with shoulders obliquity (r = 0.58). These results highlight a possible correlation between rasterstereography and thermography, which may elucidate the underlying mechanics of spinal alterations and thermal muscle response. Our findings may represent reference data for other studies using noninvasive methods to assess postural alterations.

Background The diagnosis of mitochondrial disorders (MDs) in pediatric patients is complex and often delayed due to heterogeneous clinical presentations and limited access to invasive confirmation tests such as muscle biopsy. Objective To evaluate the diagnostic sensitivity and specificity of a targeted next-generation sequencing (NGS) panel (Blueprint Genetics ® “FLEX Comprehensive Epilepsy Panel Plus”) for detecting MDs in a cohort of pediatric patients with neurological symptoms compared with gold standard tissue biopsy and clinical follow-up. The primary endpoint was the diagnostic accuracy of targeted NGS panel testing for pediatric MDs. The secondary endpoints were the identification of clinical predictors and biochemical correlations associated with increased diagnostic yield and the assessment of age-dependent diagnostic patterns. Methods We enrolled 36 pediatric patients between May 2022 and July 2023 on the basis of predefined clinical criteria suggestive of MDs. All patients underwent buccal swab-based targeted NGS testing. Confirmatory tissue biopsies and functional studies were performed in selected cases as the gold standard reference. True positives were defined as pathogenic/likely pathogenic variants confirmed by tissue biopsy and/or strong clinical correlation. Statistical analyses included Pearson correlation, Fisher’s exact test, and univariate logistic regression, stratifying data by age of onset and clinical features. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to ensure methodological rigor and transparency. This was a convenience sample without a priori power calculation. Results Five patients (5/34 out of 36 patients who completed the study, 14.7%) harbored variants in MD-associated genes. Pathogenic or likely pathogenic variants were confirmed in three cases through tissue biopsy, acting as true positives. The sensitivity was 100% (95% CI: 29.2–100%), the specificity was 94% (95% CI: 79.6–99.3%), the accuracy was 94% (95% CI: 80.3–99.3%), and the positive predictive value was 60% (95% CI: 14.7–94.7%). The positive predictive value reflects the presence of variants of uncertain significance (VUS) requiring further validation. Statistically significant correlations were observed between the presence of MD variants and elevated blood lactate ( R  = 0.51, p  < 0.05) and GGT levels ( R  = 0.46, p  < 0.05) and reduced hemoglobin ( R =-0.42, p  < 0.05). Eight specific clinical signs, occurring at < 12 months of age, strongly predicted MD-related variants with statistical significance ( p  < 0.05). Conclusion Targeted NGS via buccal swabs demonstrates high accuracy and specificity in diagnosing pediatric MDs when guided by a structured clinical phenotype and confirmed by tissue analysis. Early onset of specific clinical signs should prompt NGS testing and may reduce unnecessary invasive procedures. Early diagnosis enables improved patient management and family counseling.

Epileptic and developmental encephalopathies (EDEs) are a group of severe, genetically various neurological conditions characterized by early-onset seizures and developmental impairments. Recent advances in molecular genetics and diagnostic tools have led to the development of precision therapies, aiming to address the deep causes of these disorders. Examples, such as pyridoxine for pyridoxine-dependent epilepsy and the ketogenic diet for GLUT1 deficiency syndrome illustrate the potential of presumed tailored treatments. However, challenges persist, as current therapies often fail to fully mitigate neurodevelopmental impairments. Moreover, traditional phenotype-based management strategies, while effective for seizure control, do not address the root causes of these disorders, underscoring the limitations of existing approaches. This article explores the evolving landscape of precision medicine in EDEs, emphasizing the importance of genetic insights in therapy design and the need for a multidisciplinary approach. It also highlights the barriers to widespread implementation, including diagnostic delays, accessibility, and a lack of robust clinical evidence. To fully realize the potential of precision therapies, comprehensive genetic integration, innovation in treatment, and global collaboration are essential. The future of EDE management lies in therapies that not only control symptoms but also correct genetic and molecular defects, offering a more effective, individualized approach to care.

Background/Objectives: Child abuse is a pervasive global issue with significant implications for the physical, emotional, and psychological well-being of victims. This review highlights the clinical, molecular, and therapeutic dimensions of child abuse, emphasizing its long-term impact and the need for interdisciplinary approaches. Early exposure to abuse activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to chronic cortisol release and subsequent neuroplastic changes in brain regions such as the hippocampus, amygdala, and prefrontal cortex. These molecular alterations, including epigenetic modifications and inflammatory responses, contribute to the heightened risk of psychiatric disorders and chronic illnesses in survivors. Clinically, child abuse presents with diverse manifestations ranging from physical injuries to psychological and developmental disorders, making timely diagnosis challenging. Methods: A multidisciplinary approach involving thorough clinical evaluation, detailed histories, and collaboration with child protection services is essential for accurate diagnosis and effective intervention. Results: Recent advances in molecular biology have identified biomarkers, such as stress-related hormones and epigenetic changes, which provide novel insights into the physiological impact of abuse and potential targets for therapeutic intervention. Current treatment strategies prioritize the child’s safety, psychological well-being, and prevention of further abuse. Trauma-focused cognitive behavioral therapy and family-centered interventions are pivotal in promoting recovery and resilience. Conclusions: Emerging research focuses on integrating molecular findings with clinical practice, utilizing digital health tools, and leveraging big data to develop predictive models and personalized treatments. Interdisciplinary collaboration remains crucial to translating research into policy and practice, ultimately aiming to mitigate the impact of child abuse and improve outcomes for survivors.

Background Wilson disease (WD) is an Autosomal-Recessive disorder due to mutations of ATP7B gene on chromosome 13q14.3 . Inadequate protein function leads to low ceruloplasmin blood levels and copper accumulation in liver, basal ganglia and chornea. Main clinical manifestations are hypertransaminasemia, tremors, dysarthria, dystonia and psychiatric symptoms. The phenotypic variability in WD is considerable and its onset can be heterogeneous: the most common type in childhood is the hepatic involvement, followed by the neurological one or others. The presence of a genotype-phenotype correlation has not yet been fully demonstrated. The phenotypic variability may be explained by the intervention of other modifier genes regulating copper metabolism in the presence of mutations ATP7B. Case presentation A streaking phenotypic variability was observed in two Sicilian sisters carrying the same genotype for ATB7B gene [ c.3207C > A / c. 3904-2A > G ]. Although both started to present signs at age 10 years, onset was characterized by neurological signs in the first (tremors, motor incoordination, language and cognitive impairment), while liver involvement has been the only sign in the other. They started the same chelation therapy. After a 20-year follow-up the former is severely affected (MRI evidence of basal ganglia copper deposits and hyperchogenic liver, thrombocytopenia), while the latter presents only a moderate liver enlargement. In literature, the splice mutation c. 3904-2A > G is also reported in Egypt population, associated with acute liver failure or chronic hepatic disease, and it could be typical of Mediterranean area, not being reported in other geographical zones. Conclusion Based on our clinical experience in Eastern Sicily, there is a considerable phenotypic variability in WD, even in the presence of an identical genotype. The mutation c. 3904-2A > G could be associated with this phenotypic variability in Mediterranean population, but further studies should be conducted. This condition could be explained by the intervention of modifier genes regulating copper metabolism in the presence of defective ATP7B protein function. Further investigations on their role by Next Generation Sequencing or Whole Exome Analysis might have a profound impact on patients’ management and in particular on therapy.

Background: Developmental dysplasia of the hip (DDH) is one of the most common pediatric conditions. The current gold-standard treatment for children under six months of age with a reducible hip is bracing, but the orthopedic literature features several splint options, and each one has many advantages and disadvantages. The aim of this review is to analyze the available literature to document the up-to-date evidence on DDH conservative treatment. Methods: A systematic review of PubMed and Science Direct databases was performed by two independent authors (C.d.C. and A.V.) using the keywords “developmental dysplasia hip”, “brace”, “harness”, “splint”, “abduction brace” to evaluate studies of any level of evidence that reported clinical or preclinical results and dealt with conservative DDH treatment. The result of every stage was reviewed and approved by the senior investigators (V.P. and G.T.). Results: A total of 1411 articles were found. After the exclusion of duplicates, 367 articles were selected. At the end of the first screening, following the previously described selection criteria, we selected 29 articles eligible for full text reading. The included articles mainly focus on the Pavlik harness, Frejka, and Tubingen among the dynamic splint applications as well as the rhino-style brace, Ilfeld and generic abduction brace among the static splint applications. The main findings of the included articles were summarized. Conclusions: Dynamic splinting for DDH represents a valid therapeutic option in cases of instability and dislocation, especially if applied within 4–5 months of life. Dynamic splinting has a low contraindication. Static bracing is an effective option too, but only for stable hips or residual acetabular dysplasia.

CDKL5 deficiency disorder (CDD) is a complex clinical condition resulting from non-functional or absent CDKL5 protein, a serine–threonine kinase pivotal for neural maturation and synaptogenesis. The disorder manifests primarily as developmental epileptic encephalopathy, with associated neurological phenotypes, such as hypotonia, movement disorders, visual impairment, and gastrointestinal issues. Its prevalence is estimated at 1 in 40,000–60,000 live births, and it is more prevalent in females due to the lethality of germline mutations in males during fetal development. This Italian multi-center observational study focused on 34 patients with CDKL5-related epileptic encephalopathy, aiming to enhance the understanding of the clinical and molecular aspects of CDD. The study, conducted across 14 pediatric neurology tertiary care centers in Italy, covered various aspects, including phenotypic presentations, seizure types, EEG patterns, treatments, neuroimaging findings, severity of psychomotor delay, and variant-phenotype correlations. The results highlighted the heterogeneity of seizure patterns, with hypermotor-tonic-spasms sequence seizures (HTSS) noted in 17.6% of patients. The study revealed a lack of clear genotype–phenotype correlation within the cohort. The presence of HTSS or HTSS-like at onset resulted a negative prognostic factor for the presence of daily seizures at long-term follow-up in CDD patients. Despite extensive polypharmacotherapy, including medications such as valproic acid, clobazam, cannabidiol, and others, sustained seizure freedom proved elusive, affirming the inherent drug-resistant nature of CDD. The findings underscored the need for further research to explore response rates to different treatments and the potential role of non-pharmacological interventions in managing this challenging disorder.

Recent studies have shown that neurologic inflammation may both precipitate and sustain seizures, suggesting that inflammation may be involved not only in epileptogenesis but also in determining the drug-resistant profile. Extensive literature data during these last years have identified a number of inflammatory markers involved in these processes of \"neuroimmunoinflammation\" in epilepsy, with key roles for pro-inflammatory cytokines such as: IL-6, IL-17 and IL-17 Receptor (IL-17R) axis, Tumor-Necrosis-Factor Alpha (TNF-α) and Transforming-Growth-Factor Beta (TGF-β), all responsible for the induction of processes of blood-brain barrier (BBB) disruption and inflammation of the Central Nervous System (CNS) itself. Nevertheless, many of these inflammatory biomarkers have also been implicated in the pathophysiologic process of other neurological diseases. Future studies will be needed to identify the disease-specific biomarkers in order to distinguish epilepsies from other neurological diseases, as well as recognize different epileptic semiology. In this context, biological markers of BBB disruption, as well as those reflecting its integrity, can be useful tools to determine the pathological process of a variety of neurological diseases. However; how these molecules may help in the diagnosis and prognostication of epileptic disorders remains yet to be determined. Herein, authors present an extensive literature review on the involvement of both, systemic and neuronal immune systems, in the early onset of epileptic encephalopathy.

Background/Objectives: Cutaneous hypopigmentation is a common clinical sign observed in a variety of disorders. It may be congenital or acquired, localized or diffuse, and can range from benign to being associated with systemic conditions, including those affecting the central nervous system. Recognition of the key clinical features associated with each disorder is essential for accurate diagnosis and for differentiating one condition from another. Methods: PubMed, Embase, and Scopus databases were used to prepare a systematic review. Search terms were: “congenital”, “cutaneous”, “localized”, “diffuse”, “hypopigmentation” and “neurological disorders/signs”. The focus was on congenital cutaneous hypopigmentation, distinguishing between localized and diffuse presentations, with emphasis on neurological involvement. Peer-reviewed articles, case series, and original studies with neurological manifestations of the disease were reviewed. Cutaneous hypopigmentation disorders associated with diffuse cerebral involvement include syndromes such as Chediak–Higashi, Griscelli, Elejalde, Cross, Tietz albinism-deafness, Prader–Willi, Angelman, and several congenital metabolic disorders. In contrast, the ‘localized’ group comprises syndromes such as Waardenburg, Incontinentia pigmenti, and the phacomatoses, including hypomelanosis of Ito and tuberous sclerosis complex. Results: Overlapping phenotypes and genetic heterogeneity lead to diagnostic challenges and potential errors suggesting multiple specialists. The main clinical features of each disorder are discussed, with particular attention paid to neurological signs. A practical flowchart is provided to help distinguish between ‘diffuse’ and ‘localized’ forms with neurological involvement. Conclusions: Early identification of cutaneous features, followed by comprehensive clinical and instrumental evaluation, enables timely and accurate diagnosis, ultimately improving the clinical outcomes for affected children.