Biventricular myocardial strain analysis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) using cardiovascular magnetic resonance feature tracking

BACKGROUND: Fibrofatty degeneration of myocardium in ARVC is associated with wall motion abnormalities. The aim of this study was to examine whether Cardiovascular Magnetic Resonance (CMR) based strain analysis using feature tracking (FT) can serve as a quantifiable measure to confirm global and regional ventricular dysfunction in ARVC patients and support the early detection of ARVC. METHODS: We enrolled 20 patients with ARVC, 30 with borderline ARVC and 22 subjects with a positive family history but no clinical signs of a manifest ARVC. 10 healthy volunteers (HV) served as controls. 15 ARVC patients received genotyping for Plakophilin-2 mutation (PKP-2), of which 7 were found to be positive. Cine MR datasets of all subjects were assessed for myocardial strain using FT (TomTec Diogenes Software). Global strain and strain rate in radial, circumferential and longitudinal mode were assessed for the right and left ventricle. In addition strain analysis at a segmental level was performed for the right ventricular free wall. RESULTS: RV global longitudinal strain rates in ARVC (−0.68 ± 0.36 sec(−1)) and borderline ARVC (−0.85 ± 0.36 sec(−1)) were significantly reduced in comparison with HV (−1.38 ± 0.52 sec(−1), p ≤ 0.05). Furthermore, in ARVC patients RV global circumferential strain and strain rates at the basal level were significantly reduced compared with HV (strain: −5.1 ± 2.7 vs. -9.2 ± 3.6%; strain rate: −0.31 ± 0.13 sec(−1) vs. -0.61 ± 0.21 sec(−1)). Even for patients with ARVC or borderline ARVC and normal RV ejection fraction (n=30) global longitudinal strain rate proved to be significantly reduced compared with HV (−0.9 ± 0.3 vs. -1.4 ± 0.5 sec(−1); p < 0.005). In ARVC patients with PKP-2 mutation there was a clear trend towards a more pronounced impairment in RV global longitudinal strain rate. On ROC analysis RV global longitudinal strain rate and circumferential strain rate at the basal level proved to be the best discriminators between ARVC patients and HV (AUC: 0.9 and 0.92, respectively). CONCLUSION: CMR based strain analysis using FT is an objective and useful measure for quantification of wall motion abnormalities in ARVC. It allows differentiation between manifest or borderline ARVC and HV, even if ejection fraction is still normal

Preliminary study of relationships between hypnotic susceptibility and personality disorder functioning styles in healthy volunteers and personality disorder patients

<p>Abstract</p> <p>Background</p> <p>Hypnotic susceptibility is one of the stable characteristics of individuals, but not closely related to the personality traits such as those measured by the five-factor model in the general population. Whether it is related to the personality disorder functioning styles remains unanswered.</p> <p>Methods</p> <p>In 77 patients with personality disorders and 154 healthy volunteers, we administered the Stanford Hypnotic Susceptibility Scale: Form C (SHSSC) and the Parker Personality Measure (PERM) tests.</p> <p>Results</p> <p>Patients with personality disorders showed higher passing rates on SHSSC Dream and Posthypnotic Amnesia items. No significant correlation was found in healthy volunteers. In the patients however, SHSSC Taste hallucination (β = 0.26) and Anosmia to Ammonia (β = -0.23) were significantly correlated with the PERM Borderline style; SHSSC Posthypnotic Amnesia was correlated with the PERM Schizoid style (β = 0.25) but negatively the PERM Narcissistic style (β = -0.23).</p> <p>Conclusions</p> <p>Our results provide limited evidence that could help to understand the abnormal cognitions in personality disorders, such as their hallucination and memory distortions.</p

Trait phenomenological control predicts experience of mirror synaesthesia and the rubber hand illusion

In hypnotic responding, expectancies arising from imaginative suggestion drive striking experiential changes (e.g., hallucinations) — which are experienced as involuntary — according to a normally distributed and stable trait ability (hypnotisability). Such experiences can be triggered by implicit suggestion and occur outside the hypnotic context. In large sample studies (of 156, 404 and 353 participants), we report substantial relationships between hypnotisability and experimental measures of experiential change in mirror-sensory synaesthesia and the rubber hand illusion comparable to relationships between hypnotisability and individual hypnosis scale items. The control of phenomenology to meet expectancies arising from perceived task requirements can account for experiential change in psychological experiments

A novel L1CAM mutation in a fetus detected by prenatal diagnosis

X-linked hydrocephalus is due to mutations in the L1 neuronal cell adhesion molecule (L1CAM) gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. We report on a familial case diagnosed by prenatal ultrasonographic examination, with cerebellar hypoplasia, agenesis of the corpus callosum, and the bilateral overlapping of the second and third fingers of the hand. Sequencing of the L1CAM gene showed a novel missense mutation in exon 14: transition of a guanine to cytosine at position 1777 (c.1777G > C), which led to an amino acid change of alanine to proline at position 593 (Ala593Pro) in the sixth immunoglobulin domain of the L1 protein. The L1CAM mutation testing should be considered in fetuses with ultrasonographic signs of hydrocephalus and a positive family history compatible with X-linked inheritance. We agree with previous reports that suggest also considering limb abnormalities other than adducted thumbs in addition to classical neurological disgenesis, as characteristic for L1-diseas

Customised next-generation sequencing multigene panel to screen a large cohort of individuals with chromatin-related disorder

Background The regulation of the chromatin state by epigenetic mechanisms plays a central role in gene expression, cell function, and maintenance of cell identity. Hereditary disorders of chromatin regulation are a group of conditions caused by abnormalities of the various components of the epigenetic machinery, namely writers, erasers, readers, and chromatin remodelers. Although neurological dysfunction is almost ubiquitous in these disorders, the constellation of additional features characterizing many of these genes and the emerging clinical overlap among them indicate the existence of a community of syndromes. The introduction of high-throughput next generation sequencing (NGS) methods for testing multiple genes simultaneously is a logical step for the implementation of diagnostics of these disorders. Methods We screened a heterogeneous cohort of 263 index patients by an NGS-targeted panel, containing 68 genes associated with more than 40 OMIM entries affecting chromatin function. Results This strategy allowed us to identify clinically relevant variants in 87 patients (32%), including 30 for which an alternative clinical diagnosis was proposed after sequencing analysis and clinical re-evaluation. Conclusion Our findings indicate that this approach is effective not only in disorders with locus heterogeneity, but also in order to anticipate unexpected misdiagnoses due to clinical overlap among cognate disorders. Finally, this work highlights the utility of a prompt diagnosis in such a clinically and genetically heterogeneous group of disorders that we propose to group under the umbrella term of chromatinopathies