Gillespie syndrome (GLSP) is a rare congenital disorder characterized by partial aniridia, hypotonia, progressive cerebellar hypoplasia, nonprogressive ataxia, and intellectual disability. All ...causative variants to date affect the central or the 3ʹ‐terminal domains of ITPR1 gene and exhibit autosomal recessive or dominant inheritance pattern. We investigated by exome sequencing the molecular cause of GLSP in a family composed by consanguineous healthy parents, two affected siblings and one healthy son. We found the novel splice site variant c.278_279 + 2delACGT located at the 5ʹ‐end of ITPR1. The affected siblings were homozygotes, their parents heterozygous carriers and the variant was absent in the healthy son, indicating a recessive inheritance pattern. The deletion abolished the splice‐donor site at exon 5/intron 5 junction, causing the skipping of exon 5 and the generation of a premature STOP codon. The mutation is predicted to result in the synthesis of a 64‐amino acids nonfunctional protein. The mutant transcript comprised >96% of ITPR1 mRNA in the affected siblings, indicating that a small amount of wild‐type transcript was still present. The novel autosomal recessive mutation here reported is the first variant affecting the ITPR1 N‐terminal suppressor domain, thus extending the spectrum of the pathogenetic variants in GLSP and the range of the associated clinical manifestations.
We describe the case of a 63-year-old woman who developed a coronavirus disease 2019-associated acute encephalopathy with perivascular gadolinium enhancement.
Imaging is fundamental to assessing the acoustic pathway in infants with congenital deafness. We describe our depiction of the membranous labyrinth in infants using the heavily T2-weighted 3D FLAIR ...sequence without a contrast agent.
We retrospectively reviewed 10 infants (20 ears) (median term equivalent age: 2 weeks; IQR: 1-5 weeks) who had undergone brain MR imaging including a noncontrast heavily T2-weighted 3D FLAIR scan of the temporal bone. For each ear, 3 observers analyzed, in consensus, the saccule, the utricle, and the 3 ampullae, assessing the visibility (score 0, not appreciable; score 1, visible without well-defined boundaries; score 2, visible with well-defined boundaries) and morphology ("expected" or "unexpected" compared with adults). The heavily T2-weighted 3D FLAIR sequence was scored for overall quality (score 0, inadequate; score 1, adequate but with the presence of image degradation; score 2, adequate).
Six (60%) MR examinations were considered adequate (score 1 or 2). The saccule was visible in 10 ears (83.3%) with an expected morphology in 9 ears (90%). In 1 ear of an infant with congenital deafness, the saccule showed an unexpected morphology. The utricle was visible as expected in 12 ears (100%). The lateral ampulla was visible in 5 ears (41.6%), the superior ampulla was visible in 6 ears (50.0%), and the posterior ampulla was visible in 6 ears (50.0%), always with expected morphology (100%).
MR imaging can depict the membranous labyrinth in infants using heavily T2-weighted 3D FLAIR without an injected contrast agent, but the sequence acquisition time reduces its feasibility in infants undergoing MR studies during natural sleep.
Abstract Background Bipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been ...reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET). Methods Twenty-seven BD type I psychotic patients with ( n = 10) or without ( n = 17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired. Results Gray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients. Conclusions These findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis.
Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, ...first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings.
Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution.
MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients.
Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.
•Cri-du-Chat Syndrome (CdCS) is a clinically recognizable syndrome ascribed to deletions in the short arm of chromosome 5.•Structural brain malformations have been reported in CdCS patients, but their presence has not been studied systematically.•The most common findings are: isolated pontine hypoplasia, vermian hypoplasia, ventricular and corpus callosum anomalies.•The study confirms the presence of polymicrogyria (reported once) and optical nerves hypoplasia (never reported).•The study suggests a genotype-phenotype correlations, finding a smallest region of overlap, linked with pontine hypoplasia.
Abstract In schizophrenia, paliperidone palmitate (PP) long acting injectable (LAI) has been reported to sustain plasma concentrations and improve clinical symptoms. Moreover, it has also been ...demonstrated the important role of total gray matter (GM) volumes in predicting the clinical outcome. However, no studies investigating the association between PP-LAI treatment and brain morphometry has been published so far. Therefore, the main aim of our 24 weeks prospective observational exploratory study was to investigate the relation between brain anatomy and clinical outcome in seven patients with acute psychosis treated with PP-LAI. At baseline and every month (from T0 to T6) patients were clinically evaluated with the Brief Psychiatric Rating Scale (BPRS). 3 T Magnetic Resonance Imaging at baseline was acquired and total GM and intracranial volumes were extracted to explore their predictive values on BPRS scores. After 24 weeks of treatment with PP-LAI, patients showed statistically significant improvements in BPRS scores. Moreover, subjects with higher total GM volumes had a significantly higher BPRS improvement at 24 weeks compared to patients with lower total GM volumes. Our findings confirm the effectiveness of PP-LAI in treating acute psychosis and suggest that greater GM volumes predict drug response, potentially supporting a favourable prognosis.
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