1,720,989 research outputs found
Deep phenotyping in brain malformations: from disease trajectories to the development of new networks of rare neuropediatric diseases
Full text linkDeep phenotyping is pivotal in the study of rare neuropediatric diseases, as it enables a precise and comprehensive characterization of clinical features and improves disease understanding.
Subjects with rare neuropediatric diseases exhibit unique and highly heterogeneous functioning, and therefore require individualized interventions, updated outcome evaluation, and adapted tools. By leveraging advanced imaging, detailed neuropsychological assessments, and integrative bioinformatics, deep phenotyping may serve as a link to specific genotypes, enhancing diagnostic accuracy and promoting the discovery of disease mechanisms and therapeutic targets.
On the premise that current research in the field of rare neuropediatric diseases should not overlook deep phenotyping, my PhD program was structured around the development of an innovative tool for deep phenotyping and the characterization of neuroradiological and behavioral patterns associated with specific brain malformations.
Grounded in a constant interplay between clinical care and research, the development of an innovative registry for diagnosed and undiagnosed rare neuropediatric diseases was undertaken within the framework of a multicenter network project. Chapter II outlines the development process, the structure of the platform, and its underlying philosophy.
Chapter III presents all the studies conducted, focusing on the deep phenotyping of midline and posterior cranial fossa malformations. Regarding the former, biological pathways leading to septo-optic dysplasia were analyzed, and both subjective and objective assessments of sleep were performed in patients with septo-optic dysplasia and corpus callosum agenesis. Concerning the latter, abnormal fetal neuroradiological findings are correlated with long-term clinical outcomes, and the phenotypic patterns of posterior cranial fossa malformations are described and linked to both clinical prognosis and genotype.Deep phenotyping is pivotal in the study of rare neuropediatric diseases, as it enables a precise and comprehensive characterization of clinical features and improves disease understanding.
Subjects with rare neuropediatric diseases exhibit unique and highly heterogeneous functioning, and therefore require individualized interventions, updated outcome evaluation, and adapted tools. By leveraging advanced imaging, detailed neuropsychological assessments, and integrative bioinformatics, deep phenotyping may serve as a link to specific genotypes, enhancing diagnostic accuracy and promoting the discovery of disease mechanisms and therapeutic targets.
On the premise that current research in the field of rare neuropediatric diseases should not overlook deep phenotyping, my PhD program was structured around the development of an innovative tool for deep phenotyping and the characterization of neuroradiological and behavioral patterns associated with specific brain malformations.
Grounded in a constant interplay between clinical care and research, the development of an innovative registry for diagnosed and undiagnosed rare neuropediatric diseases was undertaken within the framework of a multicenter network project. Chapter II outlines the development process, the structure of the platform, and its underlying philosophy.
Chapter III presents all the studies conducted, focusing on the deep phenotyping of midline and posterior cranial fossa malformations. Regarding the former, biological pathways leading to septo-optic dysplasia were analyzed, and both subjective and objective assessments of sleep were performed in patients with septo-optic dysplasia and corpus callosum agenesis. Concerning the latter, abnormal fetal neuroradiological findings are correlated with long-term clinical outcomes, and the phenotypic patterns of posterior cranial fossa malformations are described and linked to both clinical prognosis and genotype
The changing face of dietary therapy for epilepsy
No full textKetogenic diet is an established and effective non-pharmacologic treatment for drug-resistant epilepsy. Ketogenic diet represents the treatment of choice for GLUT-1 deficiency syndrome and pyruvate dehydrogenase complex deficiency. Infantile spasms, Dravet syndrome and myoclonic-astatic epilepsy are epilepsy syndromes for which ketogenic diet should be considered early in the therapeutic pathway. Recently, clinical indications for ketogenic diet have been increasing, as there is emerging evidence regarding safety and effectiveness. Specifically, ketogenic diet response has been investigated in refractory status epilepticus and encephalopathy with status epilepticus during sleep. New targets in neuropharmacology, such as mitochondrial permeability transition, are being studied and might lead to using it effectively in other neurological diseases. But, inefficient connectivity and impaired ketogenic diet proposal limit ideal availability of this therapeutic option. Ketogenic diet in Italy is not yet considered as standard of care, not even as a therapeutic option for many child neurologists and epileptologists.
CONCLUSIONS:
The aim of this review is to revisit ketogenic diet effectiveness and safety in order to highlight its importance in drug-resistant epilepsy and other neurological disorders.
WHAT IS KNOWN:
• Ketogenic diet efficacy is now described in large case series, with adequate diet compliance and side effects control. • Ketogenic diet is far from being attempted as a first line therapy. Its availability varies worldwide. What is New: • New pharmacological targets such as mitochondrial permeability transition and new epileptic syndromes and etiologies responding to the diet such as refractory status epilepticus are being pointed out. • Ketogenic diet can function at its best when used as a tailor-made therapy. Fine tuning is crucial
The effects of ketogenic dietary therapies on sleep: A scoping review
No full textSleep problems are common in neurological conditions for which ketogenic dietary therapies (KDTs) are recognised as an effective intervention (drug-resistant epilepsy, autism spectrum disorder, and migraine). Given the composite framework of action of ketogenic dietary therapies, the prevalence of sleep disturbance, and the importance of sleep regulation, the present scoping review aimed at identifying and mapping available evidence of the effects of ketogenic dietary therapies on sleep. A comprehensive web-based literature search was performed retrieving publications published to June 2023 using PubMed and Scopus, yielding to 277 records. Twenty papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study design and sleep outcome evaluation among the selected studies. Several changes in sleep quality and sleep structure under ketogenic dietary therapies were found, namely an improvement of overall sleep quality, improvement in the difficulty falling asleep and nighttime awakenings, improvement in daytime sleepiness and an increase of REM sleep. The relevance and possible physiological explanations of these changes, clinical recommendations, and future directions in the field are discussed
Ketosis and migraine: a systematic review of the literature and meta-analysis
No full textIntroduction: Headaches are a prevalent disorder worldwide, and there is
compelling evidence that certain dietary interventions could provide relief from
attacks. One promising approach is ketogenic therapy, which replaces the brain’s
glucose fuel source with ketone bodies, potentially reducing the frequency or
severity of headaches.
Aim: This study aims to conduct a systematic review of the scientific literature
on the impact of ketosis on migraine, using the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) method.
Results: After a careful selection process and bias evaluation, 10 articles were
included in the review, primarily from Italy. The bias assessment indicated that
50% of the selected articles had a low risk of bias in all domains, with the
randomization process being the most problematic domain. Unfortunately, the
evaluation of ketosis was inconsistent between articles, with some assessing
ketonuria, some assessing ketonemia, and some not assessing ketosis levels at
all. Therefore, no association could be made between the level of ketosis and
the prevention or reduction of migraine attacks. The ketogenic therapies tested
in migraine treatments included the very low-calorie ketogenic diet (VLCKD, n =
4), modified Atkins diet (MAD, n = 3), classic ketogenic diet (cKDT, n = 2), and the
administration of an exogenous source of beta-hydroxybutyrate (BHB). The metaanalysis, despite reporting high heterogeneity, found that all interventions had an
overall significant eect (Z = 9.07, p < 0.00001; subgroup dierences, Chi2 = 9.19,
dif = 3, p = 0.03; I
2
, 67.4%), regardless of the type of endogenous or exogenous
induction of ketosis.
Conclusion: The initial findings of this study suggest that metabolic ketogenic
therapy may provide some benefit in treating migraines and encourage further
studies, especially randomized clinical trials with appropriate and standardized
methodologies. The review strongly recommends the use of the adequate
measurement of ketone levels during ketogenic therapy to monitor adherence to
the treatment and improve knowledge of the relationship between ketone bodies
and e cacy.
Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier:
CRD4202233062
A novel variant in NEUROD2 in a patient with Rett-like phenotype points to Glu130 codon as a mutational hotspot
No full textNEUROD2, encoding the neurogenic differentiation factor 2, is essential for neurodevelopment. To date, heterozygous missense variants in this gene have been identified in eight patients (from six unrelated families) with epileptic encephalopathy and developmental delay
Case report: KETOLAND the psychoeducation program for ketogenic diet
No full textGlucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare neurological disorder characterized by a wide spectrum of symptoms: epilepsy, movement disorders and neurocognitive impairment. The gold standard treatment for GLUT1DS are ketogenic dietary therapies (KDTs), specifically classical ketogenic diet (CKD). Despite the benefits, CKD often represents a challenge for patients and their families since meal preparation is extremely demanding and deviates a lot from normal diet. To assure an optimal compliance to CKD a psychological support for parents and patients with GLUT1DS is highly recommended. Specifically, a psychoeducational intervention that ameliorates the knowledge about the illness and its therapy improves treatment' s adherence and efficacy. The aim of this case report is to investigate the effectiveness of a psychoeducational program, partially implemented through telepsychology, based on the theoretical model of Cognitive Behavioral Play Therapy (CBPT) to support KDT knowledge and adherence in a patient with GLUT1DS who presented a worsening of her clinical picture due to a sparse knowledge of KDTs principles which determined a low adherence. Thus, with this case report we propose a model of intervention with psychoeducation in a patient with a complex chronic disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Adherence to ketogenic dietary therapies in epilepsy: A systematic review of literature
No full textTreatment adherence, defined as the degree to which the patient actively follows the plan of care, is very difficult for subjects undergoing ketogenic dietary therapies (KDTs). This is a relevant issue because adherence to dietary therapies is considered 1 of the primary determinants of the treatment's success. This paper aimed to review the literature evidence about KDT adherence according to age and diagnosis of patients. Performed based on the Preferred Reporting Items for Systematic Reviews and Meta -Analyses method, this systematic review included clinical trials and observational studies. The risk of bias was assessed by the RoB 2.0 Cochrane tool and the quality of evidence according to the Mixed Methods Appraisal Tool system. Twenty-two articles were included, with more than half ( n = 12) having average quality (2-3 stars). The studies' heterogeneity in measuring adherence and diagnosis made it difficult to compare results. Mean adherence rates were 71.5%, 66%, and 63.9% for children, adolescents, and adults, respectively. Adherence and compliance rates varied according to the follow-up period (79.7%, 66.7%, and 37.7% at 6, 24, and 36 months, respectively). The most frequent reasons for low adherence were linked to inefficacy in seizure control, adverse effects, food refusal, difficulty in preparing KDT meals or diet restrictiveness, lack of motivation, poor parental compliance, or cost of the diet. To conclude, there is a lack of standardized tools to measure adherence. Several studies highlighted the families' challenges in adhering to KDTs. These factors should be considered when creating strategies and resources on family education. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY -NC -ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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