Expanding the Natural History of SNORD118-Related Ribosomopathy: Hints from an Early-Diagnosed Patient with Leukoencephalopathy with Calcifications and Cysts and Overview of the Literature.

Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive disorder showing a pediatric or adult onset. First described in 1996 by Labrune and colleagues, it was only in 2016 that bi-allelic variants in a non-protein coding gene, SNORD118, were found as the cause for LCC, differentiating this syndrome from coats plus (CP). SNORD118 transcribes for a small nucleolar RNA, which is necessary for correct ribosome biogenesis, hence the classification of LCC among ribosomopathies. The syndrome is characterized by a combination of white matter hyperintensities, calcifications, and cysts on brain MRI with varying neurological signs. Corticosteroids, surgery, and recently bevacizumab, have been tried with unclear results since the natural history of the disease remains elusive. To date, 67 patients with a pediatric onset of disease have been described in the literature, with a clinical-radiological follow-up carried out in only eleven of them. We described the clinical-radiological follow-up from birth to almost five years of age of a late-preterm patient diagnosed with LCC and carried out a thorough overview of pediatric patients described in the literature. It is important to gather serial clinical-radiological data from other patients to depict the natural history of this disease, aiming to deeply depict genotype-phenotype correlations and make the role of new therapeutics clearer.

Visual Function and Neuropsychological Profiling of Idiopathic Infantile Nystagmus.

Though considered a benign condition, idiopathic infantile nystagmus (IIN) may be associated with decreased visual acuity and oculo-motor abnormalities, resulting in developmental delays and poor academic performance. Nevertheless, the specific visual function profile of IIN and its possible impact on neuropsychological development have been poorly investigated. To fill this gap, we retrospectively collected the clinical data of 60 children presenting with IIN over a 10-year period (43 male; mean age of 7 years, range of 2 months-17 years, 9 months). The majority of the subjects in our cohort presented with reduced visual acuity for far distances and normal visual acuity for near distances, associated with oculo-motor abnormalities. The overall scores of cognitive and visual-cognitive tests were in the normal range, but revealed peculiar cognitive and visual-cognitive profiles, defined by specific frailties in processing speed and visual-motor integration. The same neuropsychological profiles characterize many neurodevelopmental disorders and may express a transnosographic vulnerability of the dorsal stream. As the first study to explore the neuropsychologic competencies in children with IIN, our study unveils the presence of subclinical frailties that need to be addressed to sustain academic and social inclusion.

Ketosis and migraine: a systematic review of the literature and meta-analysis.

Introduction: 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 meta-analysis, despite reporting high heterogeneity, found that all interventions had an overall significant effect (Z = 9.07, p < 0.00001; subgroup differences, Chi2 = 9.19, dif = 3, p = 0.03; I2, 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 efficacy. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022330626.