Summary
This study aimed to evaluate the prevalence and the relationship of sleep breathing disorders (SBDs) and laryngeal motility alterations in patients with drug‐resistant epilepsy after vagus ...nerve stimulator (VNS) implantation. Twenty‐three consecutive patients with medically refractory epilepsy underwent out‐of‐center sleep testing before and after VNS implantation. Eighteen eligible subjects underwent endoscopic laryngeal examination post‐VNS implantation. Statistical analysis was carried out to assess an association between laryngeal motility alterations and the onset/worsening of SBDs. After VNS implantation, 11 patients showed a new‐onset mild/moderate SBD. Half of the patients already affected by obstructive sleep apnea (OSA) showed worsening of SBD. All of the patients with a new‐onset OSA had a laryngeal pattern with left vocal cord adduction (LVCA) during VNS stimulation. The association between VNS‐induced LVCA and SBD was statistically significant. This study suggests an association between VNS and SBD, hinting to a pivotal role of laryngeal motility alterations. The relationship between SBD and VNS‐induced LVCA supports the need to routinely investigate sleep respiratory and laryngeal motility patterns before and after VNS implantation.
Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear ...correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches.
Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a ...constant pressure overload. Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH.The aim of this study is to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating pathological from physiological LVH in the middle-aged population.
we selected a group of 80 master athletes, a group of 80 sedentary subjects with essential hypertension and an apparent normal diastolic function at standard PW Doppler analysis. The two groups were comparable for increased left ventricular wall thickness and mass index (134.4 +/- 19.7 vs 134.5 +/- 22.1 gr/m2; p > .05). Diastolic function indexes using the PW technique were in the normal range for both.
Pulsed Wave TDI study of diastolic function immediately distinguished the two groups. While in master athletes the diastolic TDI-derived parameters remained within normal range (E' 9.4 +/- 3.1 cm/sec; E/E' 7.8 +/- 2.1), in the hypertensive group these parameters were found to be constantly altered, with mean values and variation ranges always outside normal validated limits (E' 7.2 +/- 2.4 cm/sec; E/E' 10.6 +/- 3.2), and with E' and E/E' statistically different in the two groups (p < .001).
Our study showed that the TDI technique can be an easy and validated method to assess diastolic function in differentiating normal from pseudonormal diastolic patterns and it can distinguish physiological from pathological LVH emphasizing the eligibility certification required by legal medical legislation as in Italy.
IRF2BPL has recently been described as a novel cause of neurodevelopmental disorders with multisystemic regression, epilepsy, cerebellar symptoms, dysphagia, dystonia, and pyramidal signs. We ...describe a novel IRF2BPL phenotype consistent with progressive myoclonus epilepsy (PME) in three novel subjects and review the features of the 31 subjects with IRF2BPL‐related disorders previously reported. Our three probands, aged 28–40 years, harbored de novo nonsense variants in IRF2BPL (c.370C > T, p.Gln124* and c.364C > T; p.Gln122*, respectively). From late childhood/adolescence, they presented with severe myoclonus epilepsy, stimulus‐sensitive myoclonus, and progressive cognitive, speech, and cerebellar impairment, consistent with a typical PME syndrome. The skin biopsy revealed massive intracellular glycogen inclusions in one proband, suggesting a similar pathogenic pathway to other storage disorders. Whereas the two older probands were severely affected, the younger proband had a milder PME phenotype, partially overlapping with some of the previously reported IRF2BPL cases, suggesting that some of them might be unrecognized PME. Interestingly, all three patients harbored protein‐truncating variants clustered in a proximal, highly conserved gene region around the “coiled‐coil” domain. Our data show that PME can be an additional phenotype within the spectrum of IRF2BPL‐related disorders and suggest IRF2BPL as a novel causative gene for PME.
Obstructive sleep apnea syndrome (OSAS) is a sleep disorder characterized by repetitive episodes of upper airway obstruction. The aim of this study was to evaluate whether continuous positive airway ...pressure (CPAP) treatment is linked to improvements in cognitive abilities and emotional functions of patients with OSAS. Following the exclusion of four subjects for non-adherence to CPAP treatment, the final study sample was composed of 16 patients with moderate-to-severe OSAS, who were assessed both prior to and after 3 months of CPAP treatment, using a neuropsychological battery and questionnaires to assess mood and anxiety disorders, irritability, quality of life, quality of sleep and daytime sleepiness. We observed significant improvements in Digit Span Backward, Short Story and Corsi Span performances after 3 months of CPAP treatment. Questionnaires showed a significant reduction in daytime sleepiness and improvements in the subjective perception of sleep quality and sleep efficiency, and reduced daytime dysfunction. CPAP treatment has significant effects on different cognitive domains in patients with OSAS, especially working memory, long-term verbal memory, and short-term visuospatial memory.
•Perinatal depression (PND) is a highly prevalent complication of pregnancy.•It is difficult to predict which women will experience depression during the peripartum.•Machine learning techniques may ...help identifying predictors of PND during early pregnancy.•We developed a data-driven ML model to quantify the risk of developing PND symptoms.•Besides psychosocial factors, sleep alterations were found to be a strong predictor of PND.
Perinatal depression (PND) is a common complication of pregnancy associated with serious health consequences for both mothers and their babies. Identifying risk factors for PND is key to early detect women at increased risk of developing this condition. We applied a machine learning (ML) approach to data from a multicenter cohort study on sleep and mood changes during the perinatal period (“Life-ON”) to derive models for PND risk prediction in a cross-validation setting. A wide range of sociodemographic variables, blood-based biomarkers, sleep, medical, and psychological data collected from 439 pregnant women, as well as polysomnographic parameters recorded from 353 women, were considered for model building. These covariates were correlated with the risk of future depression, as assessed by regularly administering the Edinburgh Postnatal Depression Scale across the perinatal period. The ML model indicated the mood status of pregnant women in the first trimester, previous depressive episodes and marital status, as the most important predictors of PND. Sleep quality, insomnia symptoms, age, previous miscarriages, and stressful life events also added to the model performance. Besides other predictors, sleep changes during early pregnancy should therefore assessed to identify women at higher risk of PND and support them with appropriate therapeutic strategies.
Abstract A 70-year-old man experienced an amoxycillin-induced anaphylactic reaction complicated by acute inferior myocardial infarction with transient ST-segment elevation. There was a spontaneous ...resolution of ST-segment elevation and the patient was treated for anaphylaxis. Coronary angiography showed severe obstructive coronary atherosclerosis, but not involving the infarct-related artery. Percutaneous coronary intervention of the affected artery was then performed and the patient was discharged three days later. Acute ST-elevation myocardial infarction has been described as one of the severe, still rare cardiovascular complications of anaphylaxis. In the present case, according to the previous reports, the main pathogenetic mechanism involved appears to have been coronary vasospasm probably caused by the release of potent vasoactive mast cell derived mediators in the setting of anaphylaxis.
This study aimed to assess the concordance of various psychometric scales in detecting Perinatal Depression (PND) risk and diagnosis. A cohort of 432 women was assessed at 10-15th and 23-25th ...gestational weeks, 33-40 days and 180-195 days after delivery using the Edinburgh Postnatal Depression Scale (EPDS), Visual Analogue Scale (VAS), Hamilton Depression Rating Scale (HDRS), Montgomery-Åsberg Depression Rating Scale (MADRS), and Mini International Neuropsychiatric Interview (MINI). Spearman's rank correlation coefficient was used to assess agreement across instruments, and multivariable classification models were developed to predict the values of a binary scale using the other scales. Moderate agreement was shown between the EPDS and VAS and between the HDRS and MADRS throughout the perinatal period. However, agreement between the EPDS and HDRS decreased postpartum. A well-performing model for the estimation of current depression risk (EPDS > 9) was obtained with the VAS and MADRS, and a less robust one for the estimation of current major depressive episode (MDE) diagnosis (MINI) with the VAS and HDRS. When the EPDS is not feasible, the VAS may be used for rapid and comprehensive postpartum screening with reliability. However, a thorough structured interview or clinical examination remains necessary to diagnose a MDE.
Pathogenic
variants cause a severe early-onset developmental and epileptic encephalopathy (STXBP1-DEE). We aimed to investigate the natural history of STXBP1-DEE in adults focusing on seizure ...evolution, the presence of movement disorders, and the level of functional (in)dependence.
In this observational study, patients with a minimum age of 18 years carrying a (likely) pathogenic
variant were recruited through medical genetics departments and epilepsy centers. Treating clinicians completed clinical questionnaires and performed semistructured video examinations while performing tasks from the (modified) Unified Parkinson Disease Rating Scale when possible.
Thirty adult patients were included for summary statistics, with video recordings available for 19 patients. The median age at last follow-up was 24 years (range 18-58 years). All patients had epilepsy, with a median onset age of 3.5 months. At last follow-up, 80% of adults had treatment-resistant seizures despite long periods of seizure freedom in 37%. Tonic-clonic, focal, and tonic seizures were most frequent in adults. Epileptic spasms, an unusual feature beyond infancy, were present in 3 adults. All individuals had developmental impairment. Periods of regression were present in 59% and did not always correlate with flare-ups in seizure activity. Eighty-seven percent had severe or profound intellectual disability, 42% had autistic features, and 65% had significant behavioral problems. Video examinations showed gait disorders in all 12 patients able to walk, including postural abnormalities with external rotation of the feet, broad-based gait, and asymmetric posture/dystonia. Tremor, present in 56%, was predominantly of the intention/action type. Stereotypies were seen in 63%. Functional outcome concerning mobility was variable ranging from independent walking (50%) to wheelchair dependence (39%). Seventy-one percent of adults were nonverbal, and all were dependent on caregivers for most activities of daily living.
STXBP1-DEE warrants continuous monitoring for seizures in adult life. Periods of regression are more frequent than previously established and can occur into adulthood. Movement disorders are often present and involve multiple systems. Although functional mobility is variable in adulthood, STXBP1-DEE frequently leads to severe cognitive impairments and a high level of functional dependence. Understanding the natural history of STXBP1-DEE is important for prognostication and will inform future therapeutic trials.
Transradial access (TRA) emerged in the last two decades as a valid alternative to the standard transfemoral access (TFA) for cardiac catheterization and percutaneous coronary intervention (PCI). Due ...to contrasting results, the penetration and uptake of TRA in real-world clinical practice has been slow and still limited to high experienced center.
We performed an updated systematic review and study-level meta-analysis of randomized controlled trials (RCTs) that investigated the efficacy and safety of TRA versus TFA for PCI in patients with ACS. MEDLINE, Scopus, the Cochrane Library, and TCTMD.org were searched for abstracts, manuscripts, and conference reports published until April 31, 2016. The three pre-specified primary endpoints of interest were: all-cause mortality, major bleeding and major adverse cardiac events (MACE), at 30 days of follow-up. Primary analytic approach was according the intention-to-treat principle using inverse variance weighted random effect models.
Study level data from 12 RCTs were extracted and analyzed. TRA compared with TFA in ACS patients undergoing invasive management was associated with a significant reduction in the risk of mortality (RR=0.72; 95% CI: 0.59-0.88; P=0.002), major bleeding (RR 0.48; 95% CI: 0.37-0.61; P<0.00001) and MACE (RR 0.81; 95% CI: 0.69-0.96; P=0.01), with similar procedural rate of success. In addition, TRA was associated with reduced in-hospital length of stay. There were no differences in the risk of stroke, myocardial infarction and target vessel or target lesion revascularization.
The results of the present study confirm TRA as the preferred routine upfront strategy for ACS patients undergoing PCI.
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