PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications.

BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). MATERIALS AND METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

Need for palliative care from birth to infancy in pediatric patients with neurological diseases.

BACKGROUND: Palliative care is a comprehensive treatment approach that guarantees comfort for pediatric patients and their families from diagnosis to death. The techniques used for neurological patients in the field of palliative care can enhance the quality of care provided to patients with neurological disorders and support their families. PURPOSE: This study aimed to analyze the palliative care protocols in use in our department, describe the palliative course in the clinical setting, and propose the implementation of hospital palliative care for long-term prognosis of patients with neurological diseases. METHODS: This retrospective observational study examined the application of palliative care from birth to early infancy in neurological patients. We studied 34 newborns with diseases affecting the nervous system impairing prognosis. The study was conducted from 2016 to 2020 at the Neonatology Intensive Care Unit and the Pediatric Unit of the San Marco University Hospital in Catania, Sicily, Italy. RESULTS: Despite current legislation in Italy, no palliative care network has been activated to meet the needs of the population. In our center, given the vast number of patients with neurological conditions requiring palliative care, we should activate a straightforward departmental unit for neurologic pediatric palliative care. CONCLUSION: The establishment of specialized reference centers that manage significant neurological illnesses is due to neuroscience research progress in recent decades. Integration with specialized palliative care is sparse but now seems essential.

Epileptic spasms in infants: can video-EEG reveal the disease's etiology? A retrospective study and literature review.

Objective: Epileptic spasms are a type of seizure defined as a sudden flexion or extension predominantly of axial and/or truncal limb muscles that occur with a noticeable periodicity. Routine electroencephalogram supports the diagnosis of epileptic spasms, which can occur due to different causes. The present study aimed to evaluate a possible association between the electro-clinical pattern and the underlying etiology of epileptic spasms in infants. Materials and methods: We retrospectively reviewed the clinical and video-EEG data on 104 patients (aged from 1 to 22 months), admitted to our tertiary hospital in Catania and the tertiary hospital in Buenos Aires, from January 2013 to December 2020, with a confirmed diagnosis of epileptic spasms. We divided the patient sample into structural, genetic, infectious, metabolic, immune, and unknown, based on etiology. Fleiss' kappa (К) was used to assess agreement among raters in the electroencephalographic interpretation of hypsarrhythmia. A multivariate and bivariate analysis was conducted to understand the role of the different video-EEG variables on the etiology of epileptic spasms. Furthermore, decision trees were constructed for the classification of variables. Results: The results showed a statistically significant correlation between epileptic spasms semiology and etiology: flexor spasms were associated with spasms due to genetic cause (87.5%; OR < 1); whereas mixed spasms were associated with spasms from a structural cause (40%; OR < 1). The results showed a relationship between ictal and interictal EEG and epileptic spasms etiology: 73% of patients with slow waves and sharp waves or slow waves on the ictal EEG, and asymmetric hypsarrhythmia or hemi hypsarrhythmia on the interictal EEG, had spasms with structural etiology, whereas 69% of patients with genetic etiology presented typical interictal hypsarrhythmia with high-amplitude polymorphic delta with multifocal spike or modified hypsarrhythmia on interictal EEG and slow waves on the ictal EEG. Conclusion: This study confirms that video-EEG is a key element for the diagnosis of epileptic spasms, also playing an important role in the clinical practice to determine the etiology.

Impressive efficacy of the ketogenic diet in a KCNQ2 encephalopathy infant: a case report and exhaustive literature review.

Background: KCNQ2 encephalopathy is characterized by neonatal-onset epilepsy and developmental impairment, due to "de novo" KCNQ2 pathogenic variants. According to literature data, sodium channel blocking agents appear to be the best treatment options for the disease. Reports describing the use of ketogenic diet (KD) in the KCNQ2 pediatric population are limited. The non-conservative amino acid substitution p.Ser122Leu in KCNQ2 is associated with a broad spectrum of inheritance modalities, clinical phenotypes and outcomes; no previous reports of the same variant treated with KD are available in literature. Case Description: We described a 22-month-old female with seizure onset on day 2 of life. At three months of age, she presented refractory status epilepticus (SE) that did not respond to midazolam and carbamazepine, which was added once a "de novo" p.Ser122Leu KCNQ2 variant was demonstrated. KD was the only treatment that led to cessation of seizures. The baby maintained seizures remission and achieved neurodevelopmental milestones. Conclusions: To define an overt genotype-phenotype correlation for KCNQ2 pathogenic variants is a challenge; we propose the KD as a valuable treatment for refractory seizures and impaired neurodevelopment in infants harboring "de novo" mutations in the KCNQ2 gene.

Neonatal neurologic emergencies requiring access to paediatric emergency units: a retrospective observational study.

Herein, authors present a retrospective, multi-center study to determine the number of accesses to Pediatric Emergency Unit (PEU) of patients within 28 days of life, admitted to (1) the Acute and Emergency Pediatric Unit, San Marco University Hospital, Catania, Italy; (2) Garibaldi Hospital for Emergency Care, Catania, Italy; (3) Cannizzaro Hospital for Emergency Care, Catania, Italy. We included neonates admitted for neurologic problems, from January 2015 to December 2020, to the 1-Acute and Emergency Access of the San Marco University Hospital, Catania, Italy [observation center 1 (OC1)]; 2-Garibaldi Hospital for Emergency Care, Catania, Italy (Observation Center 2-OC2); 3-Cannizzaro Hospital for Emergency Care, Catania, Italy (Observation Center 3-OC3). For each patient, we evaluated the severity of urgency, by studying the admission triage-coloured codes, the clinical data at admission and the discharge diagnosis. Neonates who had access to PEU were 812 in the OC1, 3720 in the OC2, and 748 in the OC3 respectively; 69 (8.4%), 138 (3.7%), and 55 (7.4%) was the proportion of neonatal accesses for neurological conditions. We observed that in the study period, the three hospitals had an important decrease of pediatric accesses to their PEU, but the proportion of neonates who had access to the OC1 for neurologic diseases, with respect to the total neonatal accesses, remained stable. We found that the most frequent neurologic disease for which newborns had access to PEU was Cyanosis, (46.1% of all neonatal accesses). Apnea was the second most frequent cause, with a number of 76 accesses (29%). In the literature there are numerous studies on the assessment of diseases that most frequently concern the pediatric patient in an emergency room, but there are very few references on neonatal accesses for urgent neurologic diseases. Therefore, appropriate training is required to avoid unnecessary tests without overlooking potentially serious conditions.

Measurement of nitric oxide and assessment of airway diseases in children: an update.

INTRODUCTION: Nitric oxide (NO) is a gas synthesized by the inducible NO synthase enzyme in airway cells and it is thought to make important functions in the airway inflammation of several respiratory diseases. EVIDENCE ACQUISITION: This current study is a review of the literature from 1990 to present about NO and its use in clinical practice. The databases used were PubMed, Scopus, and Cochrane Library. EVIDENCE SYNTHESIS: At the respiratory level there are three different measurements sites of NO: nNO (nasal nitric oxide), FeNO (exhaled fraction of nitric oxide), CaNO (alveolar nitric oxide). Each of them is produced at different levels of the respiratory tract and is involved in various diseases. nNO finds its use, principally, in the allergic rhinitis in fact it can be used as a measure of therapeutic efficacy, but not for the evaluation of the severity; also in primary ciliary dyskinesia (PCD), where high levels exclude the disease, and in chronic rhinosinusitis, but it is not currently used as a diagnostic or prognostic marker. FeNO has a greatest use in bronchial asthma, particularly, it is considered a non-invasive biomarker to identify and to monitor airway inflammation but currently, there is not a consensus on the use of the FeNO in the management of asthma treatment. Finally, CaNO is the least used in clinical practice, because lack of standardization of measurement techniques. CONCLUSIONS: Nitric oxide is a sensitive indicator of the presence of airway inflammation and ciliary dysfunction, although some studies have shown varying or conflicting results.

Omalizumab treatment in a 12 year-old girl with chronic spontaneous urticaria.

Background: Omalizumab is a recombinant humanized IgG monoclonal antibody, which binds the Fc region of free IgE prevent its binding to its high-affinity receptor (FcεR1) on mast cells and basophils. Omalizumab was approved as add-on therapy for moderate-to-severe persistent allergic asthma and for patients with chronic spontaneous urticaria resistant to antihistamine treatment. Patient and results: This article reports effective and safe treatment of a 12 years old girl with add-on omalizumab. On an initial dose of omalizumab of 300 mg once every 4 weeks, the patient experienced resolution of symptoms to a degree that exceeded the effect of previous treatments. Conclusion: Convincing evidence in support of the efficacy and safety of Omalizumab in the treatment of CSU in adolescent has accumulated over the past few years.

Minor pulmonary malformations in a child.

Can you diagnose this child with minor pulmonary malformations and recurrent pulmonary symptoms? http://ow.ly/6zQB30jHZAP.

Exhaled markers of antioxidant activity and oxidative stress in stable cystic fibrosis patients with moderate lung disease.

The sustained imbalance between oxidant and antioxidant species contributes to lung damage in patients with cystic fibrosis (CF). Glutathione (GSH) is an important component of the antioxidant defense in the airways epithelial lining fluid and its transportation out of the cells may be altered in CF. The aim of this study was to assess the oxidants/antioxidants balance in the airways of patients with CF. We measured the concentrations of GSH, the total antioxidant capacity and the concentration of 8-iso-prostaglandin F2α (8-isoprostane), a marker of oxidative stress, in the exhaled breath condensate of 17 non-smoking patients with CF, in stable phase, and in 17 age-matched healthy subjects. The levels of GSH and total antioxidant capacity in patients with CF were significantly lower than in healthy subjects (0.66 ± 0.07 µM versus 1.30 ± 0.08 µM, p < 0.001, respectively for GSH; 0.157 ± 0.02 mM and 0.32 ± 0.01 mM, p < 0.05, respectively for antioxidant capacity). The concentration of 8-isoprostane was higher in CF than in healthy controls (26.5 ± 0.1 pg ml-1 versus 10.8 ± 0.1 pg ml-1; p < 0.05). A low concentration of antioxidant agents, particularly glutathione, and increased levels of 8-isoprostane in the exhaled breath suggest an altered oxidizing environment in the airways of patients with CF. This altered redox environment in the epithelial liquid surface may contribute to progressive lung disease.

HMGB1 values and response to HBV vaccine in children with celiac disease.

OBJECTIVES: In addition to its wide clinical variability, celiac disease (CD) can also cause a lower response to the hepatitis B virus (HBV) than healthy individuals. The aim of this study was to examine high mobility group box 1 (HMGB1) as a new potential marker of an inadequate response to HBV vaccine in children with CD at diagnosis before starting a gluten-free diet. METHODS: We recruited 49 children with CD who were tested at admission for immunization against HBV. Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay test. RESULTS: Serum HMGB1 levels were significantly higher in nonresponders than in responders (P < 0.05). In the responders group in particular, with reference to the titer of vaccine response, we found a significantly higher serum HMGB1 level in the low responders (P < 0.001). We detected statistically significant higher values of HMGB1 in the typical form of disease presentation than in the atypical or silent form (P < 0.05). In the typical form, we showed even significantly higher HMGB1 values in low responders than in high responders (P < 0.001). With regard to the HLA haplotype and serum HMGB1 levels, any statistically significant difference was detected (P > 0.05). CONCLUSIONS: In patients with CD, HMGB1 could represent a new marker that is able to reflect the immune impairment that results in failure of the HBV vaccination.

HMGB1 as a new biomarker of celiac disease in children: A multicenter study.

OBJECTIVE: Despite the availability of specific sierology and point-of-care tests, the phenotypic heterogeneity and the symptoms fluctuation as well as the "open-window" existing among the late and silent forms cause often a delayed celiac disease (CD) diagnosis. Recently, it has been reported that high mobility group box 1 (HMGB1) mediates inflammation and gastrointestinal barrier failure. The aim of this study was to detect serum HMGB1 levels at CD diagnosis and to evaluate the relationship between serum HMGB1 levels and clinical and histologic phenotypes. METHODS: 49 CD children and 44 healthy children were enrolled. Specific antitissue transglutaminase type 2, antideaminated form of gliadin antibodies, serum HMGB1 levels, and typical histopathological changes in duodenal mucosa were performed in all patients. Mucosal lesions were classified according to Marsh classification. In relation to clinical presentation, we classified patients into: typical, atypical and silent forms. RESULTS: Serum HMGB1 levels were significantly higher in those with CD than those in the healthy control group (P < 0.001). Significant differences in serum HMGB1 levels were detected in children with typical CD form compared to both children with atypical CD form (P < 0.001) and children with silent CD form (P < 0.001). By using the Marsh classification, significant differences were found between subjects with grade 3 B-B1 and 3 C-B2 and villous atrophy, respectively (P < 0.05). On the contrary, no significant differences in serum HMGB1 levels in subgroups of children with grade 3 A compared to grade 3 B-B1 were detected. CONCLUSIONS: HMGB1 is upregulated at diagnosis in all CD children, especially in typical form, and reflecting the histologic severity of disease.

Breastfeeding and IL-10 levels in children affected by cow's milk protein allergy: A restrospective study.

AIM: To assess the protective role of breast-feeding in infants with CMPA-related AEDS as well as IL-10 utility as marker of disease evolution. METHODS: 64 breast-feeding children with CMPA-related AEDS (31 males and 33 females; mean age 5.56±2.41months; 21 mild AEDS; 25 moderate AEDS; 18 severe AEDS) and 60 artificial feeding babies (33 males and 27 females; mean age 6.01±2.08months; 26 mild AEDS; 19 moderate AEDS; 15 severe AEDS) were evaluated. In all patients serum IL-10 levels were detected. RESULTS: Significant Score Atopic Dermatitis (SCORAD) index point differences between breastfed and not breastfed children (p<0.001) have been detected. The serum IL-10 levels were lower in children with CMPA-related AEDS as compared to the healthy control group (p<0.001). Moreover, a significant inverse correlation between serum IL-10 levels and SCORAD in both enrolled groups has been also noted. In particular, IL-10 levels, in both groups, were significantly lower in children with severe symptoms. Conversely, serum IL-10 levels were significantly increased in children with mild-severe symptoms in both groups. Furthermore, breastfed children, with lower severe symptoms, had higher serum IL-10 levels. Finally, serum total IgE levels were negatively correlated with serum IL-10 levels in both breastfed and non-breastfed children with CMPA-related AEDS (p<0.001). CONCLUSIONS: We reported that exclusive breast-feeding induces hyposensitization in children with CMPA-related AEDS and it is associated with minor disease severity and higher serum IL-10 levels, resulting as useful disease-monitor marker.

Severe disease in Cystic Fibrosis and fecal calprotectin levels.

Fecal calprotectin (FC) is used to asses the presence of intestinal inflammation also in patients with Cystic Fibrosis (CF) and recent studies showed a correlation between bowel and lung disease in these patients. The aim of this study was to analyze the levels of FC in CF and correlate them with different phenotypes of disease. We enrolled a cohort of 54 CF patients and 50 healthy controls. In these patients, calprotectin has been assayed on a stools sample using an ELISA kit. In all patients we analyzed, FC levels were elevated above the cut-off value and significantly higher than in healthy controls. Among CF patients, FC was significantly higher in patients older than 18 years, with pancreatic insufficiency, underweight status, Pseudomonas Aeruginosa airways colonization, CF-related diabetes mellitus, reduced lung function, or high number of pulmonary exacerbations. These results suggest that in patients with CF, FC levels are not only influenced by the CF enteropathy but also by the severity of the genetic disease. Since we found higher FC levels in patients with a severe phenotype (P. Aeruginosa airways colonization, FEV1<50% of predicted, pancreatic insufficiency, underweight status,) we suggest that this marker could be useful to monitor longitudinally a clinical worsening.

Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis.

AIM: To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS: Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS: The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION: This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.