Publications by authors named "Alberto Verrotti"

371 Publications

Using social robot NAO for emotional support to children at a paediatric emergency department: a randomised clinical trial.

J Med Internet Res 2021 Nov 9. Epub 2021 Nov 9.

Department of life, health & Environmental sciences- MESVA-School of Emergency and Urgency Medicine, University of L'Aquila, via spennati L'aquila 67100, L'Aquila, IT.

Background: Social robots have been used for improving anxiety in children in stressful clinical situations, as during painful procedures. No studies have been performed yet to assess their effect in children while waiting for emergency room consultations.

Objective: To assess the impact of social robots in managing stress in children waiting for an emergency room procedure through the assessment of salivary cortisol levels.

Methods: This was an open randomised clinical trial in children attending a paediatric emergency department. Children accessing the emergency room were randomised to one of three groups: 1) playing with a NAO social robot; 2) playing with a study nurse; 3) waiting with parents. All children were measured salivary cortisol levels through a swab. Salivary cortisol levels before and after the intervention were compared in the three groups. We calculated the effect size of our interventions through the Cohen's d-based effect size correlation (r).

Results: A total of 109 children aged 3 to 10 years were enrolled in the study and 94 had complete data for the analyses. Salivary cortisol levels decreased significantly more in the group exposed to robot interaction than in the other two groups (r=0.75). Cortisol levels decreased more in girls (r=0.92) than boys (r=0.57).

Conclusions: Social robots are efficacious in decreasing stress in children accessing the emergency room and may be considered as a tool for improving emotional perceptions of children and their families in such a critical setting.

Clinicaltrial: Robot Therapy in Pediatric Emergency, NCT04627909, https://clinicaltrials.gov/ct2/show/study/NCT04627909.
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http://dx.doi.org/10.2196/29656DOI Listing
November 2021

Gastrointestinal and hepatic involvement during COVID-19 pandemic: A focus on pediatric population and possible future implications.

World J Gastroenterol 2021 Oct;27(40):7000-7004

Department of Pediatrics, University of Perugia, Perugia 06132, PG, Italy.

Since the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, there is still limited knowledge about this condition and its natural history. Children have been relatively spared during COVID-19 pandemic but a novel syndrome known as multisystem inflammatory syndrome (MIS-C) has emerged, following a SARS-CoV-2 infection in children and adolescents. This syndrome can lead to shock and multiple organ failure requiring intensive care. Although COVID-19 clinical research focuses on respiratory symptoms, extrapulmonary involvement such as gastrointestinal (GI) and hepatic manifestations should also be considered. In fact, GI and hepatic involvement play an important role among the most common presenting symptoms of both pediatric and adult COVID-19 and MIS-C. This involvement can not only be one of the most common presenting clinical features but also one of the sequelae of these syndromes. Abdominal ultrasonography monitoring could be very useful to identify a potential involvement of the GI tract and liver. Moreover, long-term follow-up is needed and would be essential to define the long-term outcomes of these patients.
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http://dx.doi.org/10.3748/wjg.v27.i40.7000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567473PMC
October 2021

Promelaxin Microenemas Are Non-inferior to Oral Polyethylene Glycol for the Treatment of Functional Constipation in Young Children: A Randomized Clinical Trial.

Front Pediatr 2021 29;9:753938. Epub 2021 Oct 29.

Department of Translational Medical Sciences, Section of Pediatric, University of Naples Federico II, Naples, Italy.

Polyethylene glycol (PEG) is recommended as first-line treatment of pediatric functional constipation. However, the oral route of administration is often poorly feasible in children mostly due to poor palatability. Promelaxin microenemas exert a topical evacuative action and may offer a valuable option in pediatric FC. To assess whether Promelaxin microenemas would be non-inferior to PEG 4000 in young children with FC. This is a randomized, open-label, multi-centric, non-inferiority trial enrolling infants and young children aged 6-48 months, with FC according to Rome III criteria. After 1 week of run in, children were randomized to 2 weeks of Promelaxin or PEG, followed by a 6-week on-demand treatment period. Primary endpoint was response rate to randomized treatment, with "response" defined as at least 3 evacuations per week and an average increase of at least one evacuation per week as compared to baseline. Safety, stool consistency and the analysis of fecal microbiota were secondary endpoints. Out of the 158 patients who entered the trial, 153 patients were treated (77 and 76, PEG and Promelaxin arm, respectively). In the primary analysis, the 95% confidence interval (CI) for the treatment's effect lay entirely above the non-inferiority margin in both Full Set (FAS) and Per Protocol (PP) analyses, providing evidence of the non-inferiority of Promelaxin vs. PEG 4000 [response rate difference: 16.5% (CI 1.55-31.49%) and 11.03% (CI -5.58 to 27.64%), FAS and PP analyses, respectively]. Mean compliance to the randomized treatment was >80% in both arms. Secondary endpoints did not significantly differ between the two arms, except for the average number of total days of on-demand treatment that was significantly lower in the Promelaxin arm [14.6 (12.7) vs. 9.8 (9.1), mean (SD); primary endpoint responders in PEG and Promelaxin arm, respectively; = 0.027]. Microbiota evenness significantly increased in the PEG 4000 arm at V4 as compared to the Promelaxin arm ( < 0.05). In addition, at V5, patients treated with PEG showed a significantly decreased microbiota density as compared to patients treated with Promelaxin ( = 0.036). Promelaxin microenemas are non-inferior to oral PEG in children with FC. www.ClinicalTrials.gov, identifier: NCT02751411.
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http://dx.doi.org/10.3389/fped.2021.753938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586088PMC
October 2021

A nationwide study on Sydenham's chorea: Clinical features, treatment and prognostic factors.

Eur J Paediatr Neurol 2021 Nov 6;36:1-6. Epub 2021 Nov 6.

Pediatric Rheumatology, Pediatric University Department, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy.

Objectives: Sydenham's Chorea (SC) is a neuropsychiatric disorder and a major manifestation of acute rheumatic fever. The erroneous assumption that SC is a benign and self-limiting disease, has led to a lack of high-quality scientific evidence of the therapeutical and prognostic features of SC.

Study Design: We retrospectively analyzed the medical records of patients <18-years old with SC in 17 Italian pediatric centers. Recorded data included clinical, instrumental and laboratory parameters. Prognostic risk factors including treatment regimens were assessed with univariate and multivariate sub-analysis.

Results: We included 171 patients with SC. 66% had generalized chorea, and 34% hemichorea. 81% had carditis (subclinical in 65%). Additional neurological symptoms were reported in 60% of the patients, mainly dysarthria and dysgraphia. 51% had neuropsychiatric symptoms at onset, which persisted after 12 months in 10%. Among psychiatric manifestations, the most common was anxiety disorder/depression (77%). Neurological remission was reached by 93% of the patients at 6 months; 9% relapsed. Patients were treated as follows: 11% penicillin alone, 37% immunomodulatory therapy, 16% symptomatic drugs (i.e. anti-seizure medication, dopamine antagonists) and 37% both symptomatic and immunomodulatory treatment. Neurological outcome did not differ between groups. Patients receiving symptomatic drugs had a higher risk of relapse on multivariate analysis (p = 0.045).

Conclusions: Treatment of SC was largely heterogeneous. Based on our results, immunomodulatory therapy did not show higher efficacy at medium term, although it was associated to a slightly lower risk of relapse compared to symptomatic therapy. Longitudinal studies are needed to assess specific risk factors and best treatment options.
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http://dx.doi.org/10.1016/j.ejpn.2021.11.002DOI Listing
November 2021

Paracetamol and Ibuprofen in the Treatment of Fever and Acute Mild-Moderate Pain in Children: Italian Experts' Consensus Statements.

Children (Basel) 2021 Sep 30;8(10). Epub 2021 Sep 30.

Department of Pediatrics, University of Perugia, 06100 Perugia, Italy.

Fever and pain are challenging symptoms in children and adolescents and are common reasons for consultations in primary care and hospital. Paracetamol and ibuprofen are currently the only recommended drugs for treating fever in Italy, but the therapeutic approaches are discrepant in the different settings. In Italy, paracetamol and ibuprofen are the most prescribed analgesics for acute mild-moderate pain in children; however, their use is often inappropriate in that fever is over-treated and pain is under-treated. An Italian board of experts analyzed the motivations for the misalignment between daily practice and guidelines of fever and acute mild-moderate pain management of the territory and hospitals. The expert opinion consensus process underscored the appropriate use of paracetamol and ibuprofen according to clinical scenarios, patients' profiles, and the safety features of the drugs. Although patients' profiles can indicate different benefits from paracetamol or ibuprofen, critical issues of fever and acute mild-moderate pain management persist in primary care and hospitals. These expert opinion consensus statements can be an across-the-board tool to harmonize the routine practice between the territory and hospitals, especially under special conditions (at-risk for dehydration, coagulation disorder patients, etc.). It can also promote educational activity about fever and acute mild-moderate pain management to enhance the milestones already achieved by Italian pediatricians.
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http://dx.doi.org/10.3390/children8100873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534871PMC
September 2021

Epilepsy in "Sunflower syndrome": electroclinical features, therapeutic response, and long-term follow-up.

Seizure 2021 Dec 2;93:8-12. Epub 2021 Oct 2.

Department of Pediatrics, University of Perugia, Italy.

Background: Sunflower syndrome (SFS) is a rare childhood-onset generalized epilepsy characterized by photosensitivity, heliotropism, and drug-resistant stereotyped seizures maybe self-induced by hand-waving maneuvers. Data on the long-term prognosis are scantly and evidence over best treatment strategies is lacking.

Methods: We retrospectively describe the electroclinical features, and therapeutic response in a group of 21 patients with SFS, without intellectual disability.

Results: 16 patients were female (67%), with a median age at onset of 7 years. In all patients, ictal episodes began with sun-staring, and hand-waving in front of the sunlight, accompanied by brief typical absence seizures. 17 patients (81%) showed interictal EEG abnormalities, mainly characterized by spike and polyspike-and-wave discharges. Ictal epileptiform activity occurred approximately less than one second after the start of hand-waving. At the last follow-up (median length 8.2 years), 12 patients (57%) were drug-resistant. Nine of them (75%) achieved seizure control with the use of tainted lenses, either alone or compared with anti-seizure medications (ASM). Disappearance of seizures was associated with EEG improvement/normalization when tinted glasses were used during EEG recordings.

Conclusion: While the clinical and EEG characteristics of SFS are well defined, the best therapeutic approaches are still under debate. Our data confirms a high rate of drug-resistance and frequent need of polytherapy. Of note, in drug-resistant patients, lenses (but not ASM) were able to suppress PPR in our patients while wearing lenses. Regarding the role of lenses, we do not only rely on the PPR reduction but also clinically by the reduction of seizures. Although additional data are needed, lenses seem to have a powerful potential role for the management of SFS.
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http://dx.doi.org/10.1016/j.seizure.2021.09.021DOI Listing
December 2021

Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants.

Ital J Pediatr 2021 Oct 12;47(1):208. Epub 2021 Oct 12.

Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Background: Heterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features.

Case-report: A 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe).

Conclusion: This case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding.
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http://dx.doi.org/10.1186/s13052-021-01162-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507175PMC
October 2021

A Rare Case of Brachyolmia with Amelogenesis Imperfecta Caused by a New Pathogenic Splicing Variant in .

Genes (Basel) 2021 Sep 12;12(9). Epub 2021 Sep 12.

Medical Genetics Unit, University and Hospital of Perugia, 06129 Perugia, Italy.

In recent years, a rare form of autosomal recessive brachyolmia associated with amelogenesis imperfecta (AI) has been described as a novel nosologic entity. This disorder is characterized by skeletal dysplasia (e.g., platyspondyly, short trunk, scoliosis, broad ilia, elongated femoral necks with coxa valga) and severe enamel and dental anomalies. Pathogenic variants in the latent transforming growth factor-β binding protein 3 () gene have been found implicated in the pathogenesis of this disorder. So far, biallelic pathogenic variants have been identified in less than 10 families. We here report a young boy born from consanguineous parents with a complex phenotype including skeletal dysplasia associated with aortic stenosis, hypertrophic cardiomyopathy, hypodontia and amelogenesis imperfecta caused by a previously unreported homozygous splice site variant. We also compare the genotypes and phenotypes of patients reported to date. This work provides further evidence that brachyolmia with amelogenesis imperfecta is a distinct nosologic entity and that variations in are involved in its pathogenesis.
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http://dx.doi.org/10.3390/genes12091406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470690PMC
September 2021

Headache in progressive facial hemiatrophy (Parry-Romberg syndrome): A paradigmatic case and systematic review of the literature.

Cephalalgia 2021 Sep 26:3331024211043452. Epub 2021 Sep 26.

Pediatric Clinic, Maggiore Hospital, ASST Crema, Crema, Italy.

Background: Parry-Romberg syndrome is a neuro-cutaneous disease characterized by progressive hemifacial atrophy. Although common, headache in this population is scarcely reported in the literature.

Objective: To evaluate the clinical features of headache in pediatric and adult patients with Parry-Romberg syndrome, and to discuss diagnostic and treatment approaches of headache in Parry-Romberg syndrome.

Methods: We conducted a systematic review in accordance with PRISMA guidelines. We searched the MEDLINE database to identify eligible studies and identified patients with Parry-Romberg syndrome and headache. We further reported a paradigmatic case with a complex headache disorder and described its management and outcome.

Results: We identified 74 articles, 41 of which were included in the analysis. A total of 52 patients (55.8% female) were included for data analysis. The main age at onset of headache was 20 years (SD 15.2; range 3-56). A diagnosis of migraine was made in 53.9%. Abnormal brain imaging was found in 82.2% of patients.

Conclusion: Long-term follow-up of patients is required, because headache may develop (and evolve) at any time over the course of the disease. Primary and secondary headaches often co-occur in patients with Parry-Romberg syndrome. Further research into the underlying etiopathogenesis and therapeutic targets would be recommended.
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http://dx.doi.org/10.1177/03331024211043452DOI Listing
September 2021

Epilepsy, electroclinical features, and long-term outcomes in Pitt-Hopkins syndrome due to pathogenic variants in the TCF4 gene.

Eur J Neurol 2021 Sep 14. Epub 2021 Sep 14.

Department of Paediatrics, University of Perugia, Perugia, Italy.

Background And Purpose: Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by deletions/variants in the TCF4 gene. Seizures may be present in up to half of the patients, leading to a more severe disease burden. This study aims to analyse the electroclinical phenotype, treatment options, and long-term outcomes of epilepsy in PTHS.

Methods: A multicentre observational cohort study was performed, and the electroclinical data of PTHS individuals affected by epileptic seizures were retrospectively reviewed and analysed.

Results: The series includes 21 patients (11 female) with a median age at seizure onset of 2 years (range = 0.5-8). The median time of follow-up was 7.9 years (range = 2-27). Both generalized and focal epilepsies were present at the same prevalence (42.8%), whereas a minority of patients presented developmental and epileptic encephalopathies (14.4%). At the long-term follow-up, 42.8% achieved seizure freedom, whereas 42.8% developed drug-resistant epilepsy (DRE). The age at seizure onset was found to be an independent predictor for seizure outcome; in this regard, patients having seizure onset after the age of 2 years were more prone to achieve seizure freedom (odds ratio = 0.04, 95% confidence interval = 0.003-0.53; p = 0.01). During evolution, seizures tended to settle down, and even in patients with DRE, seizures tended to persist at a lower frequency and appeared to be more easily manageable over time.

Conclusions: This study provides new insight into the natural history of epilepsy in PTHS. Better characterization of epileptic phenotype and prompt tailored treatment improve overall management and quality of life.
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http://dx.doi.org/10.1111/ene.15104DOI Listing
September 2021

Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome.

Int J Mol Sci 2021 Aug 10;22(16). Epub 2021 Aug 10.

Medical Genetics Unit, Maternal-Infantile Department, University and Hospital of Perugia, 06129 Perugia, Italy.

The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20-40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS.
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http://dx.doi.org/10.3390/ijms22168611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395258PMC
August 2021

Case Report: Remdesivir and Convalescent Plasma in a Newly Acute B Lymphoblastic Leukemia Diagnosis With Concomitant Sars-CoV-2 Infection.

Front Pediatr 2021 2;9:712603. Epub 2021 Aug 2.

Pediatric Onco-Hematology With Bone Marrow Transplantation Unit, Azienda Ospedaliera di Perugia, Perugia, Italy.

The spread of Covid-19 has worsened the prognosis of oncology patients, interrupting or delaying life-saving therapies and contextually increasing the risk of severe SARS-CoV-2 infections. Acute lymphoblastic leukemia (ALL) is the most frequent cancer in pediatric age and the management of this disease with concomitant SARS-COV-2 infection represents a challenging situation. We present the case of a 6-year-old female newly diagnosed with ALL during a documented SARS-CoV-2 infection. Our patient was admitted 20 days after SARS-CoV-2 detection for evening-rise fever. Laboratory testing showed severe neutropenia while chest x-ray detected moderate pulmonary involvement. Acute lymphoblastic leukemia diagnosis was made through morphological and molecular analysis on bone marrow aspirate. Given the stability of the blood count and clinical conditions, antiviral therapy with Remdesivir and Convalescent Plasma was started before antileukemic treatment, obtaining a rapid resolution of the infection. In our experience, the treatment with Remdesivir and Convalescent Plasma led to a rapid resolution of Sars-Cov-2 infection. Our case did not present any adverse event to the therapy. Thus, this treatment could be considered in patients with malignancies, in order to accelerate the resolution of the infection and begin immunosuppressive treatment safely. Further studies are required to confirm this hypothesis.
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http://dx.doi.org/10.3389/fped.2021.712603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365506PMC
August 2021

The Pharmacoresistant Epilepsy: An Overview on Existant and New Emerging Therapies.

Front Neurol 2021 22;12:674483. Epub 2021 Jun 22.

Department of Medicine and Surgery, Pediatric Clinic, University of Perugia, Perugia, Italy.

Epilepsy is one of the most common neurological chronic disorders, with an estimated prevalence of 0. 5 - 1%. Currently, treatment options for epilepsy are predominantly based on the administration of symptomatic therapy. Most patients are able to achieve seizure freedom by the first two appropriate drug trials. Thus, patients who cannot reach a satisfactory response after that are defined as pharmacoresistant. However, despite the availability of more than 20 antiseizure medications (ASMs), about one-third of epilepsies remain drug-resistant. The heterogeneity of seizures and epilepsies, the coexistence of comorbidities, and the broad spectrum of efficacy, safety, and tolerability related to the ASMs, make the management of these patients actually challenging. In this review, we analyze the most relevant clinical and pathogenetic issues related to drug-resistant epilepsy, and then we discuss the current evidence about the use of available ASMs and the alternative non-pharmacological approaches.
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http://dx.doi.org/10.3389/fneur.2021.674483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258148PMC
June 2021

New Onset of Hepatic Steatosis Post-Severe Multisystem Inflammatory Syndrome in Children (MIS-C): A Case Report.

Int J Environ Res Public Health 2021 06 29;18(13). Epub 2021 Jun 29.

Department of Pediatrics, University of Perugia, 06132 Perugia, Italy.

The emergence of Multisystem Inflammatory Syndrome (MIS-C) following SARS-CoV-2 infection in children and adolescents provided a new diagnostic and management challenge as there is limited knowledge about this condition and its natural history. In existing literature on MIS-C, there are currently no data about long-term outcomes. We report the case of a 14-year-old boy, with no significant past medical history, who presented a condition of multiorgan dysfunction due to MIS-C, after a SARS CoV-2 infection, and subsequent clinical-laboratory signs of hepatic steatosis at short-term follow-up. The case suggests how hepatic steatosis may be a possible sequela following SARS-CoV-2 infection, MIS-C and its medical treatment. Therefore, a close and long-term follow-up is needed to establish the pathophysiology and the evolution of this condition in patients following MIS-C.
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http://dx.doi.org/10.3390/ijerph18136961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297213PMC
June 2021

Prevalence of allergic rhinitis with lower airways inflammation: A new endotype with high risk of asthma development?

J Paediatr Child Health 2021 Jun 29. Epub 2021 Jun 29.

Pediatric Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Aim: Asthma and allergic rhinitis share common pathophysiological mechanisms. However, while asthma phenotypes and endotypes are defined basing on both clinical and immunological features, rhinitis classification is still based on severity and frequency of symptoms. Recently, fractional exhaled nitric oxide (FeNO) has been suggested as a possible biomarker of rhinitis to asthma development. The aim of our study was to define the prevalence of a high FeNO allergic rhinitis endotype in a paediatric population of children with allergic rhinitis in order to quantify the impact of such patients in general practice.

Methods: A total of 159 children (aged 7-16 years) with allergic rhinitis and no asthmatic symptoms were enrolled in our study. Severity assessment of rhinitis and asthma was evaluated in accordance with ARIA and GINA guidelines. All patients performed the following assessments: skin prick test (SPT), spirometry and FeNO measurement.

Results: FeNO was increased in 54 (33.9%) of 159 patients. No significant correlation with age, severity and frequency of rhinitis was evidenced. Positive SPT for house dust mites was related with a higher prevalence of high FeNO (P = 0.04), with no significant correlation with other sensitisations. All patients showed normal spirometric values.

Conclusion: A possible new endotype of allergic rhinitis and lower airways inflammation showed to be significantly present in our population. The lack of correlation with allergic rhinitis severity assessment suggests that FeNO could be considered as an independent variable, possibly linked to a higher risk of asthma development in children with no lower airways symptoms and normal spirometry.
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http://dx.doi.org/10.1111/jpc.15626DOI Listing
June 2021

Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy.

Neurology 2021 08 2;97(6):e577-e586. Epub 2021 Jun 2.

From IRCCS Istituto Giannina Gaslini (A.A., M.S., M.I., A.R., B.C., P.S., S.B., V.D.S., C.M., F.Z., P.S.); Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI) (A.A., M.S., P.S., V.D.S., C.M., F.Z., P.S.), University of Genoa, Italy; Neuropediatrics Section of the Department of Pediatrics (G.W.), Asklepios Clinic Hamburg Nord-Heidberg, Hamburg; Department of Pediatric and Adolescent Medicine II (Neuropediatrics, Social Pediatrics) (G.W.), University Medical Centre Schleswig-Holstein, Kiel, Germany; Department of Neurosciences (C.C., C.D.L.), Pediatric Neurology Unit, Tor Vergata University, Roma; Human Genetics (L.C., F. Brancati), Department of Life, Health, and Environmental Sciences, and Department of Pediatrics (A.V.), University of L'Aquila; Child Neuropsychiatry Unit (V.B.), Department of Mental Health, ASST-LARIANA, Como; Medical Genetics Unit (P.P.), "S. Maria della Misericordia" Hospital, Perugia, Italy; Department of Pediatric Neurology (A.F.-J.), Hospital Universitario Quirónsalud and Universidad Europea de Madrid, Madrid, Spain; Istanbul University Istanbul Faculty of Medicine (N.B.), Department of Neurology, Turkey; Department of Biomedicine and Prevention (G.N.), Tor Vergata University of Rome; IRCCS Neuromed (G.N.), Pozzilli, Italy; Department of Pharmacology (G.N.), School of Medicine, University of Nevada, Reno; Department of Pediatrics (C.v.S.), University Hospital Munich, Germany; Paracelsus Medical University (C.v.S.), Salzburg, Austria; Epilepsy Center for Children and Adolescents (F.K., G.J.K.), Vogtareuth, Germany; Department of Neuropediatrics (G.C.W., G.R.), University Children's Hospital Zurich, Switzerland; Translational and Clinical Research Institute (D.L.-S., R.H.T., M.L.), Newcastle University; Department of Clinical Neurosciences (D.L.-S., R.H.T., M.L.), Newcastle Upon Tyne Hospitals National Health Service Foundation Trust, UK; Epilepsy Center (S.S.), Federico II University, Napoli, Italy; Institute of Human Genetics (C.D.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Institut du Cerveau et de la Moelle épinière (ICM) (C.D.), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, Paris, France; Center for Synaptic Neuroscience and Technology (F.Benfenati), Istituto Italiano di Tecnologia; IRCCS Ospedale Policlinico San Martino (F. Benfenati), Genoa; and Human Functional Genomics (F. Brancati), IRCCS San Raffaele Pisana, Rome, Italy.

Objective: To describe the clinical and genetic findings in a cohort of individuals with bathing epilepsy, a rare form of reflex epilepsy.

Methods: We investigated by Sanger and targeted resequencing the gene in 12 individuals from 10 different families presenting with seizures triggered primarily by bathing or showering. An additional 12 individuals with hot-water epilepsy were also screened.

Results: In all families with bathing epilepsy, we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in , 9 of which are novel. Conversely, none of the individuals with hot-water epilepsy displayed variants. In mutated individuals, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail clipping, haircutting, or watching someone take a shower. Unprovoked seizures and a variable degree of developmental delay were also common.

Conclusion: Bathing epilepsy is genetically distinct reflex epilepsy caused mainly by mutations.
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http://dx.doi.org/10.1212/WNL.0000000000012298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424500PMC
August 2021

An Open Retrospective Study of a Standardized Cannabidiol Based-Oil in Treatment-Resistant Epilepsy.

Cannabis Cannabinoid Res 2020 Jul 21. Epub 2020 Jul 21.

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.

Cannabidiol (CBD) has antiseizure properties but no psychoactive effects. Randomized controlled trials of an oral, pharmaceutical formulation of highly purified CBD are promising; however, data regarding other formulations are sparse and anecdotal. We evaluated the effectiveness of add-on therapy with a standardized CBD-based oil in treatment-resistant epilepsy (TRE) patients. An open retrospective study was carried out on patients with refractory epilepsy of different etiology. We reviewed clinical data from medical charts and caregiver's information. Participants received add-on with 24% CBD-based oil, sublingually administered, at the starting dose of 5-10 mg/[kg·day] up to the maximum dose of 50 mg/[kg·day], based on clinical efficacy. Efficacy was evaluated based on patients being seizure free or experiencing at ≥50% improvement on seizure frequency. Tolerability and suspected adverse drug reaction data were also analyzed. We included 37 patients (46% female) with a median age of 16.1 (range: 2-54) years. Twenty-two (60%) patients suffered from epileptic encephalopathy, 9 (24%) from focal epilepsy, and 6 (16%) from generalized epilepsy. Mean follow-up duration was 68 (range: 24-72) weeks. The average age at seizure onset was 3.8±2.1 years (range: 7 days-21 years). The median achieved CBD-based oil dose was 4.2±11.4 (range: 0.6-50) mg/[kg·day]. At 40-month follow-up, 7 (19%) patients were seizure free, 27 (73%) reported >50% improvement, 2 (5%) patients reported <50% improvement, and 1 patient discontinued therapy due to lack of efficacy. Weaning from concomitant antiepileptic drugs was obtained after 24 weeks from CBD introduction in 10 subjects. Mild and transitory adverse events, including somnolence or loss of appetite, occurred in nine (25%) patients. We showed the efficacy of a CBD-based oil formulation with few significant side effects in patients with TRE of various etiologies.
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http://dx.doi.org/10.1089/can.2019.0082DOI Listing
July 2020

An update on brivaracetam for the treatment of pediatric partial epilepsy.

Expert Opin Pharmacother 2021 Aug 12;22(11):1387-1395. Epub 2021 May 12.

Department of Pediatrics, University of Perugia, Perugia, Italy.

: Brivaracetam (BRV) is an antiseizure medication (ASM), which has been approved as an adjunctive treatment in adults and pediatric patients aged four years and older with focal onset seizures. It is a second-generation levetiracetam (LEV) derivative, sharing the same mechanism of action, binding synaptic vesicles 2A (SV2A). BRV shows higher binding affinity and selectivity and higher brain permeability than LEV.: This article reviews randomized controlled trials, retrospective and prospective studies published up to December 2020, searched in electronic databases MEDLINE, EMBASE and the Clinical Trial Database and provide an overview of efficacy, safety and tolerability of BRV in pediatric patients with partial epilepsy. Furthermore, the authors provide their expert opinion on the drug and give their future perspectives.: The analysis of the literature data has demonstrated the safety and efficacy of BRV in pediatric patients, with more evidence in children aged 4 to 16 years with an onset of focal seizures. However, a positive response was also achieved in patients affected by some encephalopathic epilepsies. Comparative efficacy studies between BRV and other ASMs, in addition to well-designed RCTs that include larger pediatric populations are needed to better define the role and potentiality of this ASM.
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http://dx.doi.org/10.1080/14656566.2021.1921151DOI Listing
August 2021

Perampanel Improves Cortical Myoclonus and Disability in Progressive Myoclonic Epilepsies: A Case Series and a Systematic Review of the Literature.

Front Neurol 2021 24;12:630366. Epub 2021 Mar 24.

Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Naples, Italy.

Progressive myoclonic epilepsies (PMEs) are a heterogenous group of genetic diseases presenting with epilepsy, cognitive impairment, and severe action myoclonus, which can severely affect daily life activities and independent walking ability. Perampanel is a recent commercially available antiseizure medication with high efficacy against generalized seizures. Some reports supported the role of perampanel in ameliorating action myoclonus in PMEs. Here, we aimed to describe a case series and provide a systematic literature review on perampanel effects on PMEs. We report the perampanel effectiveness on myoclonus, daily life activities, and seizures on an original Italian multicenter case series of 11 individuals with PMEs. Then, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we performed a systematic review on perampanel effect on myoclonus and disability in PMEs. We searched PubMed, Scopus, and Google Scholar articles on perampanel and PMEs up to June 2020. No prospective trials were found. We reviewed 11 case series manuscripts reporting 104 cases of different PMEs. Here, we are reporting the effectiveness of perampanel in five individuals affected by Unverricht-Lundborg disease, three by Lafora disease, two by sialidosis, and one by an undetermined PME. Nine out of 11 individuals improved their disability related to the action myoclonus (two with Lafora disease did not). Among the 104 persons with PMEs collected by the systematic review, we found that more than half of the patients receiving perampanel exhibited an amelioration of action myoclonus and, consequently, of their independence in daily life activities. The Unverricht-Lundborg disease seemed to show the best clinical response to perampanel, in comparison with the other more severe PMEs. A significant seizure reduction was achieved by almost all persons with active epilepsy. Only 11% of PME patients dropped out due to inefficacy. Perampanel demonstrated a beneficial effect with regard to action myoclonus, disability, and seizures and was well-tolerated in people with PMEs, independently from their genetic diagnosis. Given the limited scientific evidence, broader prospective trials should be encouraged.
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http://dx.doi.org/10.3389/fneur.2021.630366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024635PMC
March 2021

Electroclinical features of MEF2C haploinsufficiency-related epilepsy: A multicenter European study.

Seizure 2021 May 30;88:60-72. Epub 2021 Mar 30.

Maternal and Pediatric Department, Fondazione IRCCS Casa Sollievo della Sofferenza, Poliambulatorio "Giovanni Paolo II", Viale Padre Pio, snc, San Giovanni Rotondo (FG) 71013, Italy.

Purpose: Epilepsy is a main manifestation in the autosomal dominant mental retardation syndrome caused by heterozygous variants in MEF2C. We aimed to delineate the electro-clinical features and refine the genotype-phenotype correlations in patients with MEF2C haploinsufficiency.

Methods: We thoroughly investigated 25 patients with genetically confirmed MEF2C-syndrome across 12 different European Genetics and Epilepsy Centers, focusing on the epileptic phenotype. Clinical features (seizure types, onset, evolution, and response to therapy), EEG recordings during waking/sleep, and neuroimaging findings were analyzed. We also performed a detailed literature review using the terms "MEF2C", "seizures", and "epilepsy".

Results: Epilepsy was diagnosed in 19 out of 25 (~80%) subjects, with age at onset <30 months. Ten individuals (40%) presented with febrile seizures and myoclonic seizures occurred in ~50% of patients. Epileptiform abnormalities were observed in 20/25 patients (80%) and hypoplasia/partial agenesis of the corpus callosum was detected in 12/25 patients (~50%). Nine patients harbored a 5q14.3 deletion encompassing MEF2C and at least one other gene. In 7 out of 10 patients with myoclonic seizures, MIR9-2 and LINC00461 were also deleted, whereas ADGRV1 was involved in 3/4 patients with spasms.

Conclusion: The epileptic phenotype of MEF2C-syndrome is variable. Febrile and myoclonic seizures are the most frequent, usually associated with a slowing of the background activity and irregular diffuse discharges of frontally dominant, symmetric or asymmetric, slow theta waves with interposed spike-and-waves complexes. The haploinsufficiency of ADGRV1, MIR9-2, and LINC00461 likely contributes to myoclonic seizures and spasms in patients with MEF2C syndrome.
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http://dx.doi.org/10.1016/j.seizure.2021.03.025DOI Listing
May 2021

Genotype-phenotype correlations in patients with de novo pathogenic variants.

Neurol Genet 2020 Dec 30;6(6):e528. Epub 2020 Nov 30.

Department of Neurosciences (F. Malerba, G.B., E.A., A. Riva, V.S., L.N., C. Minetti, F.Z., P.S.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova; Pediatric Neurology and Muscular Diseases Unit (F. Malerba, G.B., F. Marchese, E.A., A. Riva, M.S.V., V.S., C. Minetti, P.S.), IRCCS Istituto G. Gaslini; Center for Synaptic Neuroscience and Technology ([email protected]) (G.A., L.M., F.B.), Istituto Italiano di Tecnologia; Department of Experimental Medicine (G.A.), Università degli Studi di Genova; Laboratory of Human Genetics (E.G.); Unit of Medical Genetics (F. Madia, F.Z.), IRCCS Istituto G. Gaslini, Genova, Italy; Child Neurology and Neurorehabilitation Unit (M.A.), Department of Pediatrics, Central Hospital of Bolzano, Bolzano; Child Neurology and Psychiatry Unit (L.G., P.A., P.M.), ASST Spedali Civili, Brescia; Neurology Unit (M. Trivisano, N.S.), Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Roma; Child Neurology Unit (A. Russo, G.G.), IRCCS, Institute of Neurological Sciences of Bologna; Child Neuropsychiatry Unit (F.R.), U.O.N.P.I.A. ASST-Rhodense, Rho, Milano; Neurology Unit and Laboratories (T.P.), A. Meyer Children's Hospital, Firenze; Child Neurology and Psychiatric Unit (C. Marini), Pediatric Hospital G. Salesi, United Hospital of Ancona; Child Neuropsychiatry Unit (M.M.M., L.N.), IRCCS Istituto G. Gaslini, Genova; Department of Pediatric Neuroscience (E.F.), Fondazione IRCCS Istituto Neurologico Carlo Besta; Unit of Genetics of Neurodegenerative and Metabolic Diseases (B. Castellotti), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano; Department of Child Neuropsychiatry (G.C.), Epilepsy Center, C. Poma Hospital, Mantova; Fondazione Poliambulanza Brescia (G.C.); Epilepsy Center (A.C.), Department of Neuroscience, Reproductive and Odontostomatological Sciences, Università degli Studi di Napoli Federico II, Napoli; Department of Pediatrics (A.V.), University of Perugia; Section of Pharmacology (F. Miceli, M. Taglialatela), Department of Neuroscience, Reproductive and Odontostomatological Sciences, Università degli Studi di Napoli Federico II, Napoli; IRCCS Ospedale Policlinico San Martino (L.M., F.B.), Genova, Italy; Division of Pediatric Neurology (M.R.C.), Saint-Luc University Hospital, and Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium; Department of Epilepsy Genetics and Personalized Treatment (K.M.J., R.S.M.), The Danish Epilepsy Center Filadelfia, Dianalund, Denmark; Institute for Regional Health Services (K.M.J., R.S.M.), University of Southern Denmark, Odense, Denmark; Department of Neurology (B. Ceulemans, S.W.), University Hospital Antwerp; Applied & Translational Neurogenomics Group (S.W.), VIB-Center for Molecular Neurology; Laboratory of Neurogenetics (S.W.), Institute Born-Bunge, University of Antwerp, Belgium; and Department of Life and Environmental Sciences (L.M.), Polytechnic University of Marche, Ancona, Italy.

Objective: Early identification of de novo variants in patients with epilepsy raises prognostic issues toward optimal management. We analyzed the clinical and genetic information from a cohort of patients with de novo pathogenic variants to dissect genotype-phenotype correlations.

Methods: Patients with de novo pathogenic variants were identified from Italy, Denmark, and Belgium. Atomic resolution Kv7.2 structures were also generated using homology modeling to map the variants.

Results: We included 34 patients with a mean age of 4.7 years. Median seizure onset was 2 days, mainly with focal seizures with autonomic signs. Twenty-two patients (65%) were seizure free at the mean age of 1.2 years. More than half of the patients (17/32) displayed severe/profound intellectual disability; however, 4 (13%) of them had a normal cognitive outcome.A total of 28 de novo pathogenic variants were identified, most missense (25/28), and clustered in conserved regions of the protein; 6 variants recurred, and 7 were novel. We did not identify a relationship between variant position and seizure offset or cognitive outcome in patients harboring missense variants. Besides, recurrent variants were associated with overlapping epilepsy features but also variable evolution regarding the intellectual outcome.

Conclusions: We highlight the complexity of variant interpretation to assess the impact of a class of de novo mutations. Genetic modifiers could be implicated, but the study paradigms to successfully address the impact of each single mutation need to be developed.
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http://dx.doi.org/10.1212/NXG.0000000000000528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803337PMC
December 2020

Definitive pathognomonic signs and symptoms of paediatric neurological COVID-19 are still emerging.

Acta Paediatr 2021 06 21;110(6):1774-1777. Epub 2021 Mar 21.

Department of Paediatrics, University of Rome, Rome, Italy.

Children with COVID-19 tend to show milder symptoms than adults during the pandemic, but growing evidence of neurological involvement has emerged. Some studies have reported neurological symptoms in children with COVID-19, which include multisystem inflammatory syndrome, a disease that shares some, but not all, of the characteristics of Kawasaki disease. This review presents, and discusses, the evidence to date. Our initial findings suggest that neurological manifestations can be considered to be the direct result of central nervous system viral invasion or post-infection immuno-mediated disease.
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http://dx.doi.org/10.1111/apa.15827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013208PMC
June 2021

A Case of Salt-Wasting Congenital Adrenal Hyperplasia with Triple Homozygous Mutation: Review of Literature.

J Pediatr Genet 2021 Mar 9;10(1):57-62. Epub 2020 Mar 9.

Department of Pediatrics, University of L'Aquila, L'Aquila, Italy.

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency represents a group of autosomal recessive disorders characterized by impaired cortisol production due to altered upstream steroid conversions, subclassified as classic and nonclassic forms. The genotype-phenotype correlation is possible in the most frequent case but not in all. Despite in literature many mutations are known, there is the possibility of finding a new genetic pattern in patients with CAH.
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http://dx.doi.org/10.1055/s-0040-1705110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853915PMC
March 2021

The Ketogenic Diet for the Treatment of Mood Disorders in Comorbidity With Epilepsy in Children and Adolescents.

Front Pharmacol 2020 24;11:578396. Epub 2020 Nov 24.

Department of Medicine, Surgery, and Odontoiatry, Child and Adolescent Neuropsychiatry, University of Salerno, Salerno, Italy.

The ketogenic diet, used for over a century as an alternative therapy for the control of drug-resistant seizures in both children and adults, has recently drawn increasing interest in various neurological or psychiatric disorders other than epilepsy. In particular, there are a few preliminary studies in mood and neurodevelopmental disorders such as anxiety, depression and autism spectrum disorders. Mood disorders in comorbidity with epilepsy are commonly seen in adolescents and young adults both at the onset and during the course of the epileptic disorder. The rationale for the use of the ketogenic diet is based on the potential mood stabilizing effects through level modifications of metabolites such as dopamine and serotonin and the regulation of GABA/glutamatergic neurotransmission, mitochondrial function and oxidative stress. In this review, epilepsies with a higher risk of mood disorders in adolescents will be considered. A brief overview of the various types of ketogenic diet that can currently be offered to young patients in order to improve palatability and compliance with the diet, is also included. The efficacy and tolerability of the ketogenic diet options for the treatment of mood disorders, with or without drug therapy including mood stabilizers and antidepressant drugs, are as well discussed.
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http://dx.doi.org/10.3389/fphar.2020.578396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768824PMC
November 2020

Novel therapeutic options for Dravet and Lennox-Gastaut syndrome.

Expert Rev Neurother 2021 Nov 11;21(11):1191-1194. Epub 2021 Jan 11.

Pediatric Neurology and Muscular Diseases Unit, IRRCS Istituto Giannina Gaslini, Genova, Italy.

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http://dx.doi.org/10.1080/14737175.2020.1862651DOI Listing
November 2021

Cyclic Vomiting Syndrome in Children.

Front Neurol 2020 2;11:583425. Epub 2020 Nov 2.

Chair of Pediatrics, Department of Neuroscience, Mental Health and Sense Organs (NESMOS), Faculty of Medicine & Psychology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.

Cyclic Vomiting Syndrome (CVS) is an underdiagnosed episodic syndrome characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. It is often misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. CVS mainly occurs in pre-school or early school-age, but infants and elderly onset have been also described. The etiopathogenesis is largely unknown, but it is likely to be multifactorial. Recent evidence suggests that aberrant brain-gut pathways, mitochondrial enzymopathies, gastrointestinal motility disorders, calcium channel abnormalities, and hyperactivity of the hypothalamic-pituitary-adrenal axis in response to a triggering environmental stimulus are involved. CVS is characterized by acute, stereotyped and recurrent episodes of intense nausea and incoercible vomiting with predictable periodicity and return to baseline health between episodes. A distinction with other differential diagnoses is a challenge for clinicians. Although extensive and invasive investigations should be avoided, baseline testing toward identifying organic causes is recommended in all children with CVS. The management of CVS requires an individually tailored therapy. Management of acute phase is mainly based on supportive and symptomatic care. Early intervention with abortive agents during the brief prodromal phase can be used to attempt to terminate the attack. During the interictal period, non-pharmacologic measures as lifestyle changes and the use of reassurance and anticipatory guidance seem to be effective as a preventive treatment. The indication for prophylactic pharmacotherapy depends on attack intensity and severity, the impairment of the QoL and if attack treatments are ineffective or cause side effects. When children remain refractory to acute or prophylactic treatment, or the episode differs from previous ones, the clinician should consider the possibility of an underlying disease and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities and specific sub-phenotype. This review was developed by a joint task force of the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) to identify relevant current issues and to propose future research directions on pediatric CVS.
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http://dx.doi.org/10.3389/fneur.2020.583425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667239PMC
November 2020

Exploring treatments for drooling in children with neurological disorders.

Expert Rev Neurother 2021 02 6;21(2):179-187. Epub 2020 Dec 6.

Pediatric Neurology and Muscular Diseases Unit, IRRCS Istituto Giannina Gaslini , Genova, Italy.

: Drooling represents a major problem in the every-day life of pediatric patients with neurological disorders. The significant burden, both physical and socio-psychological, of the disorder requires adequate clinical evaluation and proper management. However, treating drooling remains a challenge for clinicians. This is a review of the most up-to-date therapeutic options for the treatment of drooling in the pediatric population, hence both conservative, pharmacological, and surgical approaches are discussed. : Randomized clinical trials (RCTs), structured reviews, and case reports are included. Special focus is paid on the methods used to evaluate the efficacy and safety outcomes in the selected RCTs, trying to promote the use of more validated scales to assess drooling in the future. : The lack of reliable metrics to assess efficacy and safety outcomes in drooling limits researchers from identifying the best patient-suitable treatment. The relatively small number of clinical trials carried out over the last two decades is also due to the difficulty in assessing drooling using subjective scales. A key enabler for new efficient therapies stands in the introduction of accurate and robust metrics to measure treatment effectiveness on drooling.
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http://dx.doi.org/10.1080/14737175.2021.1855146DOI Listing
February 2021

Posterior Reversible Encephalopathy Syndrome in infants and young children.

Eur J Paediatr Neurol 2021 Jan 28;30:128-133. Epub 2020 Oct 28.

Unit of Pediatric Oncology and Haematology "Lalla Seràgnoli", Department of Pediatrics, Sant'Orsola Hospital, University of Bologna, Bologna, Italy. Electronic address:

Aim: The aim of this study was to describe the characteristics of Posterior Reversible Encephalopathy Syndrome (PRES) in infants and young children (<6 years) and to compare them with the older pediatric population affected by PRES.

Methods: we retrospectively reviewed records of 111 children (0-17 years) diagnosed with PRES from 2000 to 2018 in 6 referral pediatric hospitals in Italy. The clinical, radiological and EEG features, as well as intensive care unit (ICU) admission rate and outcome of children aged <6 years were compared to those of older children (6-17 years). Factors associated with ICU admission in the whole pediatric cohort with PRES were also evaluated.

Results: Twenty-nine patients younger than 6 years (26%) were enrolled with a median age at onset of PRES of 4 years (range: 6 months-5 years). Epileptic seizures were the most frequent presentation at the disease onset (27/29 patients). Status epilepticus (SE) was observed in 21/29 patients: in detail, 11 developed convulsive SE and 10 presented nonconvulsive SE (NCSE). SE was more frequent in children <6 years compared with older children (72% vs 45%) as well as NCSE (35% vs 10%). Seventeen children aged <6 years required ICU admission. Prevalence of ICU admissions was higher within younger population compared to older (59% vs 37%). In the whole study population SE was significantly associated with ICU admission (p = 0.001).

Conclusions: PRES in children < 6 years differs from older children in clinical presentation suggesting a more severe presentation at younger age.
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http://dx.doi.org/10.1016/j.ejpn.2020.10.009DOI Listing
January 2021

Potential role of brivaracetam in pediatric epilepsy.

Acta Neurol Scand 2021 Jan 13;143(1):19-26. Epub 2020 Oct 13.

Paediatric Neurology and Muscular Diseases Unit, IRCCS 'G. Gaslini' Institute, Genoa, Italy.

Brivaracetam (BRV) is a new antiseizure medication (ASM) that is currently approved for adjunctive treatment in patients with focal onset seizures. Similarly to levetiracetam (LEV), BRV works by binding SV2A vesicles with a high affinity and a linear pharmacokinetic profile. Retrospective studies and randomized clinical trials have already proven the efficacy of BRV, even in patients who failed treatment with LEV. Most studies about the efficacy and tolerability conducted so far were performed in adult cohorts, whereas few studies have been performed in children; however, BRV was proven to be a useful ASM for pediatric focal epilepsies, with fewer studies and conflicting results among patients with generalized epilepsies and epileptic syndromes. Retention rates were high in the cohorts analyzed, and no serious treatment-emergent adverse events were reported in the majority of patients, with somnolence, drowsiness, irritability, aggression, and decreased appetite being the most frequently reported side effects. Although there are few original papers published on the subject so far, the analysis of the literature data demonstrated the efficacy and safety of BRV in pediatric patients, with more evidence for children aged 4-16 years with an onset of focal seizures. However, a positive response was also achieved in patients affected by encephalopathic epilepsies (eg, Jeavons' epilepsy, Dravet syndrome, Lennox-Gastaut syndrome, and juvenile myoclonic epilepsy), and ongoing studies are now testing BRV in order to widen its application to other forms of epilepsy and to test its effectiveness when used in monotherapy. This review aims to provide a comprehensive analysis of the literature surrounding the efficacy and tolerability of BRV for pediatric patients.
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http://dx.doi.org/10.1111/ane.13347DOI Listing
January 2021

Cognitive, adaptive, and behavioral effects of adjunctive rufinamide in Lennox-Gastaut syndrome: A prospective observational clinical study.

Epilepsy Behav 2020 11 10;112:107445. Epub 2020 Sep 10.

Oasi Research Institute (IRCCS), Unit of Neurology and Clinical Neurophysiopathology, Troina, Italy.

Introduction: Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by multiple drug-resistant seizure types. Children with LGS usually experience cognitive regression, and LGS is almost always associated with moderate to severe cognitive impairment. Rufinamide (RFM) was approved by the European Medicines Agency in 2007 for the adjunctive treatment of seizures associated with LGS in patients ≥4 years of age. The primary objective of our study was to assess cognitive, adaptive, and behavior functioning of patients with LGS after 12 months of RFM therapy.

Methods: This was an observational, multicenter, prospective study involving 16 patients diagnosed with LGS aged between 7 and 58 years (mean = 22 ± 16.3). Fourteen of 16 patients were already on therapy with 3 antiseizure drugs and 2/16 with 4 antiseizure drugs; RFM has been added with 100 mg/week increments up to a dose of 300-2400 mg/day. The participants and their parents underwent a neuropsychological evaluation for the assessment of intellectual, adaptive, and emotional/behavioral functioning (Leiter International Performance Scale-Revised (LEITER-R), Vineland, and Child Behavior CheckList (CBCL), respectively) before the RFM introduction (baseline) and 12 months after the RFM therapy (T2). Physical and neurological examination, electroencephalography (EEG) recording, seizure type and frequency, and adverse reactions were also considered.

Results: After 12 months, the total intelligence quotient (IQ) assessed by LEITER-R did not show statistical significant changes, such as there were no statistically significant changes in adaptive functions, assessed by Vineland. Furthermore, there were no statistically significant changes in internalizing and externalizing problems assessed by CBCL.

Conclusion: Adjunctive treatment with RFM did not negatively affect cognitive, adaptive function, and emotional profile in patients with LGS after 1 year of follow-up.
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http://dx.doi.org/10.1016/j.yebeh.2020.107445DOI Listing
November 2020
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