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BACKGROUND Patent Foramen Ovale (PFO) has a high estimated prevalence (25% of the general population) and has been implicated in the pathogenesis of cryptogenic stroke and transient ischemic attack (TIA), as well as in the pathogenesis of migraine headache. This study evaluated the effectiveness of percutaneous transcatheter PFO closure with Amplatzer devices, from a large single-center experience. METHODS from January 1998 to December 2014, 577 patients (243 males and 334 females, mean age 50 years, range 11-82 years) with documented PFO and history of at least one episode of cryptogenic stroke/TIA (n=356) or occasional finding of previous ischemic lesions on MRI (n=221) underwent percutaneous transcatheter closure of PFO using an Amplatzer™ Occluder. All the procedures were performed under general anesthesia or mild sedation, and were assisted by transesophageal or intracardiac echocardiography. RESULTS Procedural success was 100%. After a median follow-up period of 2.7 years with echocardiographic evaluations, the rate of recurrent adverse cerebral events was 0.4%. Two patients (0.4%) required a secondary procedure for significant residual shunt. Of 36 patients with minor residual shunt, 30 (83%) showed spontaneous shunt regression at follow-up. There was a consistent decrease after procedure in headache migraine, Platypnea-Orthodeoxia, fainting episodes, syncope, and Coenaesthesia Phenomena. CONCLUSIONS Transcatheter PFO closure is an effective and safe therapy for the prevention of thromboembolic events in the patients with cryptogenic stroke/TIA or an occasional finding of a positive cerebral MRI. Late follow-up shows device stability and clinical improvement in the majority of patients.

Objectives: Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy marked by cortical hyperexcitability. Recent neuroimaging data suggested also a thalamic role in sustaining epileptic propensity in JME. However, thalamic hyperexcitability was not demonstrated so far. Low-frequency (LF-SEPs) and high-frequency somatosensory evoked potentials (HF-SEPs) are very sensitive to thalamic (early HF-SEPs burst, eHFO) and cortical (late HF-SEPs burst, lHFO) excitability. The aim of our experiment was to explore and discern the role of thalamic and cortical excitability in epileptic susceptibility of JME through a LF-SEPs and HF-SEPs study. Methods: Twenty-three subjects with JME (11 females, 30.2 ± 9.8-year-old) and 23 healthy control subjects (12 females, age: 34.7 ± 7.7-year-old) underwent right median LF-SEPs scalp recordings. Cp3′-Fz traces were filtered (400–800 Hz) to reveal HF-SEPs. All JME patients were on drug treatment and seizure free, except for sporadic myoclonus. Results: N20 LF-SEPs amplitude (p < 0.009), areas of totHFO, eHFO and lHFO (all p < 0.005) and totHFO duration (p = 0.013) were increased in JME respect to healthy subjects. totHFO area was negatively correlated with the number of antiepileptic drugs (rho = -0.505, sig.: 0.027), while eHFO area was positively correlated with the myoclonus frequency (rho = 0.555, sig = 0.014). Conclusions: We demonstrated that in JME the thalamic hyperexcitability assists the cortical one in sustaining epileptic susceptibility. Significance: Our results support the concept of JME as a network and genetic disorder.

Objective To determine the predictive power for seizure-freedom of 19-channels EEG, measured both before and after three months the initiation of the use of Levetiracetam (LEV), in a cohort of people after a new diagnosis of temporal-lobe epilepsy (TLE) using a machine-learning approach. Methods Twenty-three individuals with TLE were examined. We dichotomized clinical outcome into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG effective power in different frequency bands was compared using baseline EEG (T0) and the EEG after three months of LEV therapy (T1) between SF and NSF patients. Partial Least Square (PLS) analysis was used to test and validate the prediction of the model for clinical outcome. Results A total of 152 features were extracted from the EEG recordings. When considering only the features calculated at T1, a predictive power for seizure-freedom (AUC = 0.750) was obtained. When employing both T0 and T1 features, an AUC = 0.800 was obtained. Conclusions This study provides a proof-of-concept pipeline for predicting the clinical response to anti-seizure medications in people with epilepsy. Significance Future studies may benefit from the pipeline proposed in this study in order to develop a model that can match each patient to the most effective anti-seizure medication.

Objective Quantitative Encephalography (qEEG) depicts synthetically the features of EEG signal and represents a promising tool in the assessment of neurophysiological changes brought about by Anti-Seizure Medications (ASMs). In this study we characterized qEEG alterations related to add-on therapy with Perampanel (PER). PER is the only ASM presenting a direct glutamatergic antagonism, hence the characterization of PER induced EEG changes could help to better understand its large spectrum of efficacy. Methods We analysed standard-19 channel-EEG from 25 People with Epilepsy (PwE) both before (T0) and after (T1) the introduction of PER as add-on treatment. Normal values were obtained in 30 healthy controls (HC) matched for sex and age. EEGs were analysed using Matlab™ and the EEGlab and Brainstorm toolkits. We extracted spectral power and connectivity (Phase locking Value) of EEG signal and then compared these features between T0 and T1 and across groups (PwE, HC), we also evaluated the correlations with clinical features. Results PwE showed increased theta power (p = 0.036) after the introduction of PER but no significant change of EEG connectivity. We also found that PwE have reduced beta power (p = 0.012) and increased connectivity in delta (p = 0.013) and theta (p = 0.007) range as compared to HC, but no significant change was observed between T0 and T1 in PwE. Finally, we found that PwE classified as drug responders to PER have greater alpha power both at T0 and at T1 (p = 0.024) suggesting that this parameter may predict response to treatment. Conclusions PER causes slight increase of theta activity and does not alter connectivity as assessed by standard EEG. Moreover, greater alpha power could be a good marker of response to PER therapy, and potentially ASM therapy in general. Significance Our results corroborate the hypothesis that pharmaco-EEG is a viable tool to study neurophysiological changes induced by ASM. Additionally, our work highlights the role of alpha power as a marker of ASM therapeutic response.

Isolated intrauterine growth restriction (IUGR) and preeclampsia (PE) share common placental pathogenesis. Differently from IUGR, PE is a systemic disorder which may also affect liver and brain. Early diagnosis of these conditions may optimize maternal and fetal management. Aim of this study was to assess whether Epidermal Growth Factor-Like domain 7 (EGFL7) dosage in maternal blood discriminates between isolated IUGR and PE. A total of 116 women were enrolled in this case–control study: 12 non-pregnant women, 34 healthy pregnant women, 34 women presenting with isolated IUGR and 36 presenting with PE. Levels of circulating EGFL7 and other known pro- and anti-angiogenic factors were measured by ELISA at different gestational ages (GA). Between 22–25 weeks of gestation, EGFL7 levels in early-onset PE (e-PE) plasma samples were significantly higher than those measured in controls or isolated IUGR samples (69.86 ± 6.17 vs. 19.8 ± 2.5 or 18.8 ± 2.8 µg/ml, respectively). Between 26–34 weeks, EGFL7 levels remained significantly higher in e-PE compared to IUGR. At term, circulating and placental EGFL7 levels were comparable between IUGR and late-onset PE (l-PE). In contrast, circulating levels of PlGF were decreased in both IUGR- and PE- complicated pregnancies, while levels of both sFLT-1 and sENDOGLIN were increased in both conditions. In conclusion, EGFL7 significantly discriminates between isolated IUGR and PE.

Objective We designed a longitudinal cohort study on People with Epilepsy (PwE) with the aim of assessing the effect of Perampanel (PER) on cortico-subcortical networks, as measured by high-frequency oscillations of somatosensory evoked potentials (SEP-HFOs). SEP-HFOs measure the excitability of both thalamo-cortical projections (early HFOs) and intracortical GABAergic synapses (late HFOs), thus they could be used to study the anti-glutamatergic action of PER, a selective antagonist of the AMPA receptor. Methods 15 PwE eligible for PER add-on therapy, were enrolled prospectively. Subjects underwent SEPs recording from the dominant hand at two times: PwET0 (baseline, before PER titration) and PwET1 (therapeutic dose of 4 mg). HFOs were obtained by filtering N20 scalp response in the 400–800 Hz range. Patients were compared with a normative population of 15 healthy controls (HC) matched for age and sex. Results We found a significant reduction of Total HFOs and mostly early HFOs area between PwET0 and PwET1 (p = 0.05 and p = 0.045 respectively) and between HC and PwET1 (p = 0.01). Furthermore, we found a significant reduction of P24/N24 Amplitude between PwET0 and HC and between PwET0 and PwET1 (p = 0.006 and p = 0.032, respectively). Conclusions Introduction of PER as add-on therapy reduced the area of total HFOs, acting mainly on the early burst, related to thalamo-cortical pathways. Furthermore P24/N24 amplitude, which seems to reflect a form of cortico-subcortical integration, resulted increased in PwE at T0 and normalized at T1. Significance Our findings suggest that PER acts on cortico-subcortical excitability. This could explain the broad spectrum of PER and its success in forms of epilepsy characterized by thalamo-cortical hyperexcitability.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography. Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

WOS:000613461600006 PubMed ID: 32926494 Objectives To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251(27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.

OBJECTIVE To establish consistent normal reference values for fetal anterior cerebral artery (ACA) and posterior cerebral artery (PCA) pulsatility index (PI) in prolonged pregnancy. METHODS This prospective cross-sectional observational study included singleton normal prolonged pregnancies into two study groups according to the gestational age: from 40 + 0 to 40 + 6 and from 41 + 0 to 41 + 6 weeks. The PI was assessed in both anatomical segments of ACA (ACA-S1 and ACA-S2) and of PCA (PCA-S1 and PCA-S2) with color Doppler imaging and pulsed Doppler examination, and reference centiles charts were generated. PI values from the two investigated segments of each vessel were also compared. RESULTS Data were obtained in 771 patients: n = 448 in the 40 + 0 and 40 + 6 weeks group, and n = 323 in the 41 + 0 and 41 + 6 weeks group. A moderate decrease in PI was observed as pregnancy progressed. No differences in PI values were found between the two anatomical segments of ACA and PCA. CONCLUSION This study provides Doppler reference values for the fetal ACA and PCA PI. It also shows that Doppler examination could be performed indifferently in one of the two anatomical segments of these arteries.

We conducted an international multicenter retrospective cohort study, PregOuTCOV, to examine the eff ect of gestational age at time of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on obstetric and neonatal outcomes. We included all singleton pregnancies with a live fetus at 10 weeks' gestation in which pregnancy outcomes were known. The exposed group consisted of patients infected with SARS-CoV-2, whereas the unexposed group consisted of all remaining patients during the same period. Primary outcomes were defi ned as composite adverse obstetric outcomes and composite adverse neonatal outcomes. Of 10,925 pregnant women, 393 (3.60%) were infected with SARSCoV- 2 (exposed group). After matching for possible confounders, we identifi ed statistically signifi cant increases in the exposed group of composite adverse obstetric outcomes at >20 weeks' gestation and of composite adverse neonatal outcomes at >26 weeks' gestation (p, SCOPUS: ar.j, info:eu-repo/semantics/published

Preterm delivery (PTD) represents the leading cause of neonatal death and disability. Among risk factors for PTD, maternal obesity (MO) is becoming an ever more relevant condition in developed countries, although the mechanisms relating this condition to higher risk of PTD is not clear. Aim of this narrative review is to summarize evidences from clinical and translational research showing how MO might negatively impact on pregnancy and neonatal outcomes, particularly, by increasing the risk of PTD.We performed comprehensive review of the literature in PubMed and Google Scholar databases for studies from 1998 to 2018 linking MO to PTD and inflammation.Chronic inflammatory status associated to increased synthesis of adipokines and cytokines from fat tissue has been shown in obesity. Obese women have a higher risk of both spontaneous and medically induced PTD. In about 50% of cases of spontaneous PTD, an infection-induced chorion amnionitis can be detected while in the remaining 50% a sterile inflammatory response has been described. Activation of uterine innate immunity system in intra-amniotic cavity and in chorioamniotic membranes might represent the missing link between MO and the pathogenesis of PTD.Tissue inflammation might represent the pathogenic link between MO and increased occurrence of PTD. The achievement of pre-pregnancy normal maternal weight and body mass index is a fundamental aim of public health to reduce the incidence of PTD and get optimal reproductive outcomes.

COVID-19 pandemic is representing a serious challenge to worldwide public health. Lung Ultrasonography (LUS) has been signaled as a potential useful tool in this pandemic contest either to intercept viral pneumonia or to foster alternative paths. LUS could be useful in determining early lung involvement suggestive or not of COVID-19 pneumonia and potentially plays a role in managing decisions for hospitalization in isolation or admission in general ward. In order to face pandemic, in a period in which a large number of emergency room accesses with suspicious symptoms are expected, physicians need a standardized ultrasonographic approach, fast educational processes in order to be able to recognize both suggestive and not suggestive echographic signs and shared algorithms for LUS role in early management of patients.

Under certain circumstances, such as during the current COVID-19 outbreak, pregnant women can be a target for respiratory infection, and lung examination may be required as part of their clinical evaluation, ideally while avoiding exposure to radiation. We propose a practical approach for obstetricians/gynecologists to perform lung ultrasound examination, discussing potential applications, semiology and practical aspects, which could be of particular importance in emergency situations, such as the current pandemic infection of COVID-19. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

The aim of the present study is to investigate the correlation between pregnancies complicated by morphological or chromosomal fetal anomalies and an obstetric history of two or more pregnancy losses, analyzing the association with any maternal risk factor.Retrospective analysis of women who had access to the Day Hospital Clinic of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from 2012 to 2018 for a pregnancy complicated by fetal malformation and/or abnormal karyotype, and who had an obstetric history of at least one pregnancy loss. Patients were divided into four groups depending on the number of miscarriages and the presence of a genetic anomaly: Group 0 included women with2 miscarriages and fetal malformations, Group 1 included women with ≥2 miscarriages and fetal malformations, Group 2 included women with2 abortion, fetal malformations and the presence of genetic anomalies; Group 3 included women with 2 ≥ abortions, fetal malformations and genetic anomalies. Statistical analysis was performed using the SAS v. 9.4 (SAS Institute Inc., Cary, NC, USA).A total of 466 patients were included in the present analysis. Out of these, 379 patients belonged to Group 0; 40 patients entered in Group 1; Group 2 included 42 patients, and 5 patients were part of Group 3. Pregnancies complicated by fetal congenital malformations in patients with two or more pregnancy losses were significantly associated with maternal trombophilic disease and previous birth defects. Recurrent miscarriage and fetal structural anomalies were also significantly correlated with advanced maternal age.An adequate periconceptional counseling regarding the risk of fetal congenital anomalies may be indicated in patients affected by thrombophilic disease, as well as in those of advanced maternal age and with a pregnancy history of fetal malformations. The screening for thrombophilia may be advisable in patients with an obstetric history of congenital birth defects.

Background: Cardiology divisions reshaped their activities during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to analyze the organization of echocardiographic laboratories and echocardiography practice during the second wave of the COVID-19 pandemic in Italy, and the expectations for the post-COVID era. Methods: We analyzed two different time periods: the month of November during the second wave of the COVID-19 pandemic (2020) and the identical month during 2019 (November 2019). Results: During the second wave of the COVID-19 pandemic, the hospital activity was partially reduced in 42 (60%) and wholly interrupted in 3 (4%) echocardiographic laboratories, whereas outpatient echocardiographic activity was partially reduced in 41 (59%) and completely interrupted in 7 (10%) laboratories. We observed an important change in the organization of activities in the echocardiography laboratory which reduced the operator-risk and improved self-protection of operators by using appropriate personal protection equipment. Operators wore FFP2 in 58 centers (83%) during trans-thoracic echocardiography (TTE), in 65 centers (93%) during transesophageal echocardiography (TEE) and 63 centers (90%) during stress echocardiography. The second wave caused a significant reduction in number of echocardiographic exams, compared to November 2019 (from 513 ± 539 to 341 ± 299 exams per center, −34%, p &lt, 0.001). On average, there was a significant increase in the outpatient waiting list for elective echocardiographic exams (from 32.0 ± 28.1 to 45.5 ± 44.9 days, +41%, p &lt, 0.001), with a reduction of in-hospital waiting list (2.9 ± 2.4 to 2.4 ± 2.0 days, −17%, p &lt, 0.001). We observed a large diffusion of point-of-care cardiac ultrasound (88%), with a significant increase of lung ultrasound usage in 30 centers (43%) during 2019, extended to all centers in 2020. Carbon dioxide production by examination is an indicator of the environmental impact of technology (100-fold less with echocardiography compared to other cardiac imaging techniques). It was ignored in 2019 by 100% of centers, and currently it is considered potentially crucial for decision-making in cardiac imaging by 65 centers (93%). Conclusions: In one year, major changes occurred in echocardiography practice and culture. The examination structure changed with extensive usage of point-of-care cardiac ultrasound and with lung ultrasound embedded by default in the TTE examination, as well as the COVID-19 testing.

OBJECTIVES The aim of this study is to develop a Machine Learning (ML) algorithm for an automatic classification of fetal occiput position at transperineal ultrasound (TPU) during the second stage of labor. METHODS Prospective cohort study including singleton term pregnancies (> 37 weeks of gestation) in the second stage of labor, with the fetus in cephalic presentation. Transabdominal ultrasound was preliminarily performed to assess the actual fetal occiput position, which was labeled as occiput anterior (OA) or non-occiput anterior (non-OA). Subsequently, for each case, one sonographic image of the fetal head was acquired on the axial plane using TPU and archived on a cloud for remote analysis. Using the transabdominal sonographic diagnosis as the gold standard, a ML algorithm based on a pattern recognition feed-forward neural network was trained on the transperineal images to discriminate between OA and non-OA cases. In the training phase the model tuned its parameters in order to approximate correctly the training data - i.e., the training dataset - in order to correctly assess the fetal head position, by exploiting geometric, morphological and intensity-based features of the images. In the testing phase, the diagnostic performance of the algorithm was evaluated on unlabeled data, which represented the testing dataset. On this group the ability of the ML algorithm to differentiate the OA from the non-OA fetal positions was assessed in terms of diagnostic accuracy. The F1 -score and Precision-Recall Area Under the Curve (PR-AUC) were also calculated to assess the algorithm's performance. The Cohen's kappa (k) was finally added to evaluate the agreement between the algorithm and the gold standard. RESULTS Over a period of 24 months, 1219 women in the second stage of labor were enrolled. They were classified as OA (n=801 or 65.7%) or non-OA (n=418 or 34.3%) on the basis of transabdominal ultrasound. From both the sub-groups (OA and non-OA), 70% of the patients were randomly assigned to the training dataset (824 patients) while the remaining 30% (395 patients) were used as testing dataset. On the latter group the ML based algorithm yielded a correct classification of the fetal occiput position in 90.6% of cases (357 out of 395), including 224 out of 246 OA (91.0%) and of 133 out of 149 non-OA images (89.3%). Moreover, for the evaluation the algorithm's performance we found a F1 -score=88.7% and PR-AUC=85.4%. The algorithm showed a balanced performance in the recognition of both anterior and non-anterior occiput positions. Eventually, the robustness of the proposed algorithm was confirmed by a high agreement with the gold standard method (k = 0.81; p

Objectives: To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild or moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound evaluation of the fetal brain. Methods: This was a multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, the UK and Spain. Inclusion criteria were fetuses affected by isolated mild (ventricular atrial diameter, 10.0–11.9 mm) or moderate (ventricular atrial diameter, 12.0–14.9 mm) VM on ultrasound, defined as VM with normal karyotype and no other additional central nervous system (CNS) or extra-CNS anomalies on ultrasound, undergoing detailed assessment of the fetal brain using a multiplanar approach as suggested by the International Society of Ultrasound in Obstetrics and Gynecology guidelines for the fetal neurosonogram, followed by fetal MRI. The primary outcome of the study was to report the incidence of additional CNS anomalies detected exclusively on prenatal MRI and missed on ultrasound, while the secondary aim was to estimate the incidence of additional anomalies detected exclusively after birth and missed on prenatal imaging (ultrasound and MRI). Subgroup analysis according to gestational age at MRI (< 24 vs ≥ 24 weeks), laterality of VM (unilateral vs bilateral) and severity of dilatation (mild vs moderate VM) were also performed. Results: Five hundred and fifty-six fetuses with a prenatal diagnosis of isolated mild or moderate VM on ultrasound were included in the analysis. Additional structural anomalies were detected on prenatal MRI and missed on ultrasound in 5.4% (95% CI, 3.8–7.6%) of cases. When considering the type of anomaly, supratentorial intracranial hemorrhage was detected on MRI in 26.7% of fetuses, while polymicrogyria and lissencephaly were detected in 20.0% and 13.3% of cases, respectively. Hypoplasia of the corpus callosum was detected on MRI in 6.7% of cases, while dysgenesis was detected in 3.3%. Fetuses with an associated anomaly detected only on MRI were more likely to have moderate than mild VM (60.0% vs 17.7%; P < 0.001), while there was no significant difference in the proportion of cases with bilateral VM between the two groups (P = 0.2). Logistic regression analysis showed that lower maternal body mass index (adjusted odds ratio (aOR), 0.85 (95% CI, 0.7–0.99); P = 0.030), the presence of moderate VM (aOR, 5.8 (95% CI, 2.6–13.4); P < 0.001) and gestational age at MRI ≥ 24 weeks (aOR, 4.1 (95% CI, 1.1–15.3); P = 0.038) were associated independently with the probability of detecting an associated anomaly on MRI. Associated anomalies were detected exclusively at birth and missed on prenatal imaging in 3.8% of cases. Conclusions: The incidence of an associated fetal anomaly missed on ultrasound and detected only on fetal MRI in fetuses with isolated mild or moderate VM undergoing neurosonography is lower than that reported previously. The large majority of these anomalies are difficult to detect on ultrasound. The findings from this study support the practice of MRI assessment in every fetus with a prenatal diagnosis of VM, although parents can be reassured of the low risk of an associated anomaly when VM is isolated on neurosonography. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Introduction: Progressive myoclonic epilepsies (PMEs) are a heterogenous group of genetic diseases presenting with epilepsy, cognitive impairment, and severe action myoclonus, which can severely affect daily life activities and independent walking ability. Perampanel is a recent commercially available antiseizure medication with high efficacy against generalized seizures. Some reports supported the role of perampanel in ameliorating action myoclonus in PMEs. Here, we aimed to describe a case series and provide a systematic literature review on perampanel effects on PMEs.Methods: We report the perampanel effectiveness on myoclonus, daily life activities, and seizures on an original Italian multicenter case series of 11 individuals with PMEs. Then, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we performed a systematic review on perampanel effect on myoclonus and disability in PMEs. We searched PubMed, Scopus, and Google Scholar articles on perampanel and PMEs up to June 2020. No prospective trials were found. We reviewed 11 case series manuscripts reporting 104 cases of different PMEs.Results: Here, we are reporting the effectiveness of perampanel in five individuals affected by Unverricht–Lundborg disease, three by Lafora disease, two by sialidosis, and one by an undetermined PME. Nine out of 11 individuals improved their disability related to the action myoclonus (two with Lafora disease did not). Among the 104 persons with PMEs collected by the systematic review, we found that more than half of the patients receiving perampanel exhibited an amelioration of action myoclonus and, consequently, of their independence in daily life activities. The Unverricht–Lundborg disease seemed to show the best clinical response to perampanel, in comparison with the other more severe PMEs. A significant seizure reduction was achieved by almost all persons with active epilepsy. Only 11% of PME patients dropped out due to inefficacy.Conclusions: Perampanel demonstrated a beneficial effect with regard to action myoclonus, disability, and seizures and was well-tolerated in people with PMEs, independently from their genetic diagnosis. Given the limited scientific evidence, broader prospective trials should be encouraged.

Dual-axis rotational coronary angiography (DARCA) has already been shown to reduce both the amount of contrast medium and radiation exposure compared with conventional coronary angiography (CCA). However, a clinical benefit of such imaging modality has never been demonstrated. The aim of this study was to evaluate the efficacy of DARCA to prevent acute kidney injury (AKI) compared with CCA. Consecutive patients who underwent coronary angiography were enrolled to DARCA (n = 80) or CCA (n = 80). Patients presenting with ST-segment elevation myocardial infarction or previously underwent coronary artery bypass graft were excluded. The 2 groups were homogeneous in terms of both clinical and procedural characteristics. Total x-ray time and total amount of contrast medium were significantly lower in the DARCA group compared with the CCA group (x-ray time 3.2 minutes [1.8 to 7.0] vs 5.1 minutes [2.6 to 9.9], p = 0.002; contrast medium amount 40 ml [31 to 116] vs 80 ml [50 to 150], p

Background Polycystic ovary syndrome (PCOS) is a low-grade inflammatory disease characterized by anovulation and hyperandrogenism, associated with insulin-resistance. The aim of our study was to investigate the effects of a treatment with alpha-lipoic acid on clinical, endocrine and metabolic features of women affected by PCOS. Methods In this pilot cohort study, 60 women (30 hyperinsulinemic and 30 normoinsulinemic patients; age 15-34 years) were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months treatment with alpha-lipoic acid 800 mg/daily. Investigations were performed during the early follicular phase of the menstrual cycles (spontaneous or progestin-induced cycles): after fasting overnight for 10-12 h, blood samples were collected for hormonal and metabolic assays and oral glucose tolerance test and pelvic ultrasound were performed. Total Antioxidant Capacity was expressed as LAG time. Results The treatment was able to increase the number of menstrual cycles during the 6 months considered in all patients and to reduce BMI in the normoinsulinemic population. In hyperinsulinemic patients we observed a statistically significant reduction in AUC-I as well as an increase of total antioxidant capacity. Conclusions The relevant results in restoring menstrual cyclicity in both groups, in addition to the antioxidant effect, confirm that hyperinsulinemia influences only the metabolic response to the treatment, without predict the ovarian function. Even if alpha-lipoic acid mechanisms of action is not clear and further studies are needed to confirm these results, it could be considered a valid therapeutic alternative to traditional drugs, without side effects as reported.

Introduction: The current COVID-19 pandemic has been associated with high rates of mortality and significant morbidity. Both the risk of infection for pregnant women and the risk of vertical transmission have been evaluated, and the presence of the SARS-CoV-2 virus has been demonstrated both in the placenta and in the amniochorionic membranes. However, the actual effects of this pathogen on pregnancy and on placental morphology are still unclear.Objective: To describe histopathologic findings in the placentas of women with SARS-CoV-2 infection during pregnancy and their correlation with clinical signs and perinatal outcome.Methods: Placental tissues from pregnant women with SARS-CoV-2 infection delivering between March 2020 and February 2021 were analyzed.Results: One hundred six placentas from women with SARS-CoV-2 infection during pregnancy who delivered in Fondazione Policlinico A. Gemelli were examined. Most of them were asymptomatic. All neonates had available test results for SARS-CoV-2 and only one resulted positive. Placental tissues mainly showed signs of maternal vascular malperfusion and of placenta injury in terms of syncytial node increase (96.2%), villar agglutination (77.3%), neointimal hyperplasia (76.4%), excessive fibrin deposition (43.3%), and chorangiosis (35.8%). No significant differences in the frequency of the histopathological lesions were observed according to maternal symptoms.Conclusion: Looking to placental tissues from SARS-CoV-2 positive women at the screening performed close to delivery, placental injuries could be detected without any correlation with fetal and neonatal outcomes. We hypothesize that short latency between SARS-CoV-2 infection and delivery is the main reason for these observations.

Uterine myomas or uterine fibroids are the most common benign uterine masses affecting women. The management of large myoma during pregnancy is challenging, and surgical treatment is a possible option. We report nine cases of pregnant women affected by uterine masses larger than 10 cm, who underwent surgical treatment during the second trimester of pregnancy. In all cases, the masses were preconceptionally unknown and diagnosed during the first trimester. In eight cases, no maternal and fetal complications arose during or after surgical treatment and delivery occurred at full term of pregnancy. In one case, spontaneous abortion was recorded. In all cases, histologic diagnosis demonstrated the benign nature. Women affected by large uterine masses diagnosed for the first time in pregnancy could be taken into consideration for surgical treatment in a referral center during the second trimester.

BACKGROUND The posterior quadratus lumborum block (pQLB) has been used in postoperative pain management after cesarean section (CS). However, clinicians have no data about pQLB safety in pregnants, at increased risk of local anesthetic systemic toxicity (LAST). The purpose of the present study was to explore the efficacy and the safety of adding epinephrine to ropivacaine for bilateral pQLB vs. bilateral pQLB performed with ropivacaine alone in CS. METHODS In this prospective trial 52 pregnants, ASA 2 physiological status, were consecutively allocated to one of two groups, e-pQLB and pQLB; e-pQLB group received 0.375% ropivacaine+100 mcg epinephrine, 20 mL each side; pQLB received 0.375% ropivacaine alone, 20 mL each side. The primary and secondary outcomes were to evaluate if the adjunct of epinephrine to ropivacaine increases efficacy and safety of pQLB, respectively. RESULTS Authors found in e-pQLB group vs. p-QLB group: a total mean morphine consumption statistically lower during the first 24 postoperative hours (5.08±3.12, vs. 9.11±4.67 SD mg, P=0.0002); NRS values statistically lower at six hours from block, both at rest (1.73±1.88 SD vs. 2.88±2.53, P=0.03) and with movement (3.03±1.98 SD vs. 4.23±2.87, P=0.04); a longer time between block and the first opioid request (5.92±2.48 vs. 3.78±2.68 SD hrs, P

Autoimmune diseases (AIDs) are associated with strong female preponderance and often present before or during the reproductive years; consequently, pregnancy and breastfeeding are topics of major interest for these patients. AIDs show different responses to pregnancy: some ameliorate, while others remain unchanged, and several AIDs aggravate. The response of the AIDs to the hormonal and immunological alterations of pregnancy reflects the different pathophysiology of each disease. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with multiple autoantibodies, multiorgan involvement, more aggressive therapy, and increased impact on pregnancy outcome. For the management of pregnancy in patients with SLE and/or APS, it is important to individuate the correct risk profile for each woman and timing for treatment. The optimal timing for starting or modulating treatment is at preconception assessment to influence the placentation. In this chapter, we discuss the management of pregnancy in patients with AIDs.

Classic lissencephaly is a rare and serious brain malformation classified in type 1 and type 2. Type 1 is associated with mutations in the human LIS1 gene, which are numerous and constantly discovered. We present a case of isolated fetal ventriculomegaly with subsequent and unexpected diagnosis of neonatal lissencephaly. The clinical manifestation does not match the genotype, often associated with cerebellar hypoplasia.

Objective: In the last decades, childbearing has moved to higher ages, displaying adverse outcomes related to advanced maternal age at birth. Accordingly, the aim was to perform a cost analysis in ...

BackgroundPre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women.Methodsperipheral venous blood was collected from 22 women with PE and 22 normal pregnant women. Circulating STBEVs were collected by ultra-centrifugation (120000 g) and analyzed for the expression of HLA-DR and placental alkaline phosphatase (PLAP), a specific marker of the placenta, by Western blot analysis and flow cytometry.Resultscirculating STBEVs positive for HLA-DR were observed in 64% of PE women while no HLA-DR positivity was detected in any of the controls (PConclusionsAberrant expression of HLA-DR in circulating STBEVs is specifically associated to PE. Further studies are required: a) to define the role of aberrant placental expression of HLA-DR molecules in the pathogenesis of PE; b) evaluate a possible application of detecting circulating HLA-DR positive STBEVs in the diagnosis and prediction of PE in the first and second trimester of pregnancy.

BackgroundQuantitative EEG (qEEG) can capture changes in brain activity that follow a stroke. Accordingly, EEG metrics could be used to monitor patients’ state and recovery. Although qEEG metrics traditionally focus on oscillatory activity, recent findings highlight the importance of aperiodic (power-law) structure in characterizing pathological brain states.ObjectiveTo assess neurophysiological impairment and recovery from mono-hemispheric stroke by means of the Spectral Exponent (SE), a metric that reflects EEG slowing and quantifies the power-law decay of the EEG Power Spectral Density (PSD). To relate neurophysiological recovery with patient’s functional outcome.MethodsEighteen patients (n=18) with Middle Cerebral Artery (MCA) ischaemic stroke were retrospectively enrolled for this study. Patients underwent EEG recording in the sub-acute phase (T0) and after 2 months of physical rehabilitation (T1). Sixteen healthy controls (HC; n=16) matched by age and sex were enrolled as a normative group. SE values and narrow-band PSD were estimated for each recording. We compared SE and band-power between patients and HC, and between the affected (AH) and unaffected hemisphere (UH) at T0 and T1 in patients.ResultsAt T0, stroke patients showed significantly more negative SE values than HC (p=0.003), reflecting broad-band EEG slowing. Moreover, SE over the AH was consistently more negative compared to the UH and showed a renormalization at T1 in our patient sample. This SE renormalization significantly correlated with NIHSS improvement (R= 0.63, p=0.005).ConclusionsSE is a reliable readout of the electric changes occurring in the brain after an ischaemic cortical lesion. Moreover, SE holds the promise to be a robust method to assess stroke impairment as well as to monitor and predict functional outcome.

Background: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics. Methods: we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups. Results: PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60′ or 120′ glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60′ or 120′ glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score &lt, 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, p = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, p = 0.05). Conclusion: placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes.

Increasing evidence coming from both experimental and humans’ studies strongly suggest the existence of a link between epilepsy, in particular temporal lobe epilepsy (TLE), and Alzheimer’s disease (AD). Patients with mild cognitive impairment and AD are more prone to have seizures, and seizures seem to facilitate amyloid-β and tau deposits, thus promoting neurodegenerative processes. Consistent with this view, long-lasting drug-resistant TLE and AD have been shown to share several pathological and neuroimaging features. Even if studies addressing prevalence of interictal and subclinical epileptiform activity in these patients are not yet conclusive, their findings raise the possibility that epileptiform activity might negatively impact memory and hasten cognitive decline, either directly or by association with unrecognized silent seizures. In addition, data about detrimental effect of network hyperexcitability in temporal regions in the premorbid and early stages ofADopen up newtherapeutic opportunities for antiseizure medications and/or antiepileptic strategies that might complement or enhance existing therapies, and potentially modify disease progression. Here we provide a review of evidence linking epileptiform activity, network hyperexcitability, and AD, and their role promoting and accelerating neurodegenerative process. Finally, the effects of antiseizure medications on cognition and their optimal administration in patients with AD are summarized.

Introduction: The primary aim of this study was to ascertain the strength of association between cerebral blood flow assessed in anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries and the following clinical outcomes: small for gestational age (SGA), induction of labor (IOL) for oligohydramnios and caesarean section (CS) for nonreassuring fetal status (NRFS) during labor. Material and methods: Retrospective analysis of prospectively collected data on consecutive singleton pregnancies from 40 0/7 to 41 6/7 week of gestation. UA, ACA, MCA, PCA pulsatility index (PI) were measured from 40 weeks of gestations. Furthermore, the ratios between cerebral blood flow and UA (CPR, ACA/UA and PCA/UA) were calculated and correlated with the observed outcomes. Results: Two hundred twenty-four singleton pregnancies were included in the study. Mean PI of either ACA (p = .04), MCA (p = .008), and PCA (p = .003) were lower in the SGA compared to non-SGA group; furthermore, mean PCA PI was significantly lower than MCA PI (p = .04). Furthermore, CPR (p = .016), ACA/UA (p = .02), and PCA/UA (p = .003) were significantly lower in the SGA group compared to controls. UA, ACA, MCA, and PCA PI were higher in women undergoing IOL for oligohydramnios compared to controls. Logistic regression analysis showed that CPR and PCA/UA ratio were independently associated with SGA. SGA, ACA PI, and ACA/UA were independently associated with CS for NRFS. Finally, birthweight centile, were independently associated with IOL oligohydramnios. Despite this, the predictive accuracy of Doppler in detecting any of the explored outcome was only poor to moderate. Conclusion: Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor. However, the predictive accuracy of Doppler at term is only poor to moderate, thus advising against its use in clinical practice as a standalone screening test for adverse perinatal outcome in pregnancies at term. Key Message Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor.

Introduction Insulin resistance (IR) is associated with polycystic ovary syndrome (PCOS). Oxidative stress (OS) is, in turn, related to IR. Studies in PCOS evidenced an increase in OS markers, but they are mainly performed in obese patients, while the complex picture of normal weight PCOS is still poorly investigated. Matherials and Methods To investigate OS in PCOS and relationship with hormonal and metabolic picture, we performed a case-control study in 2 PCOS groups: normal weight (N-PCOS, n=21, age 18–25 ys, mean±SEM BMI 20.7±0.2 kg/m2) and obese (OB-PCOS, n=15, 20–30 ys, BMI 32.8±1.1), compared with control groups matched for BMI: normal (N-C, n=10, 20–30 ys, BMI 21.6±0.9) and obese (OB-C, n=20, 21–31ys, BMI 36.8±1.0). Malondialdehyde (MDA) in blood plasma and peripheral mononuclear cells, obtained by density-gradient centrifugation, was assayed spectrophotometrically by TBARS assay. CoenzymeQ10 (CoQ10) in plasma and cells was assayed by HPLC. Plasma Total Antioxidant Capacity (TAC) was also measured by spectrophotometric method. Results PCOS patients exhibited higher Testosterone levels than controls, but OB-PCOS had highest HOMA (Homeostasis Model Assessment) index, suggesting marked insulin resistance. Despite plasma MDA levels were not significantly different (N-PCOS 3380±346.94 vs. N-C 7 120±541.66; OB-PCOS 5 517.5±853.9 vs. OB. 3 939.66±311.2 pmol/ml), intracellular MDA levels were significantly higher in N-PCOS than controls (mean 3 259±821.5 vs. 458±43.2 pmol/106/cells) and higher than OB-PCOS, although not significantly (1363.1±412.8 pmol/106/cells). Intracellular CoenzymeQ10 was higher in N-PCOS than in N-C, but the highest levels were found in OB-C. Conclusions Our data, while confirming the presence of OS in obese PCOS patients in agreement with literature, suggest that OS could be present also in normal weight PCOS, but it can be revealed in tissue rather than in plasma. The relationship with metabolic status remains to be established, but could be a physiopathological basis for antioxidant treatment in such patients.

Objective: In early 2020, Italy struggled with an unprecedented health emergency related to the COVID-19 pandemic. Medical care of chronic neurological diseases, such as epilepsy, is being sorely neglected. In this national survey, we aimed at understanding the impact of COVID-19 lockdown on the care of people with epilepsy (PwE) and identifying PwE risk factors for seizure worsening to direct telemedicine efforts.Methods: We administered a 48-items online survey (published on April 11, 2020) including socio-demographic, epilepsy-related, and psychometric variables (BDI-II for depression, GAD-7 for anxiety, and PSQI for sleep) to PwE and people without epilepsy (PwoE). Regression analysis identified predictors of seizure worsening.Results: We collected responses from 456 PwE (344 females) and 472 PwoE (347 females). Outpatient examinations of PwE were postponed in 95% of cases. One-third of PwE complained of issues with epilepsy management, but only 71% of them reached the treating physician and solved their problems. PwE had worse depressive and anxiety symptoms (higher BDI-II and GAD-7 scores; p < 0.001) than PwoE. Sleep quality was equally compromised in both groups (47 and 42%). Sixty-seven PwE (18%) reported seizure worsening, which was best explained by the number of anti-seizure medications (ASM) of chronic therapy and the severity of sleep disorder.Conclusions: During the current COVID-19 pandemic, a significant percentage of PwE experienced difficulties in follow-up and a seizure number increase, in particular those chronically taking more ASMs and with poor sleep quality. This dramatic experience outlines the urgent need for validation and implementation of telemedicine services for epileptic patients in order to provide regular follow-up.

BACKGROUND: Despite the well-known second trimester ultrasound signs, current possibilities of in utero surgical repair of open spina bifida require a timely detection of the spine defect. OBJECTIVE: To evaluate the diagnostic accuracy of the ratio between brain stem (BS) diameter and its distance to the occipital bone (BSOB) (BS/BSOB ratio) in the detection of fetuses with open spina bifida at first trimester ultrasound. METHODS: A systematic review and meta-analysis of diagnostic accuracy was performed by searching seven electronic databases from their inception to February 2019 for all studies assessing the association between BS/BSOB ratio and diagnosis of spine bifida. Diagnostic accuracy of BS/BSOB ratio in prenatal diagnosis of spine bifida was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR + and LR-), and area under the curve (AUC) on SROC curves. RESULTS: Four studies, including 17,598 fetuses with 23 cases of open spina bifida, were included in the meta-analysis. BS/BSOB ratio showed pooled sensitivity of 0.70 (95% CI 0.47-0.87; I2 = 78.3%), specificity of 1.00 (95% CI 0.99-1.0; I2 = 99.2%), LR + and LR- of 51.44 (95% CI 9.53-277.64; I2 = 85.5%) and 0.23 (95% CI 0.04-1.17; I2 = 64.8%), respectively, and an AUC of 0.9649. CONCLUSION: First trimester BS/BSOB ratio has a high diagnostic accuracy in detecting fetuses with open spina bifida.

Background: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients. Material and methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included. Results: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies. Conclusions: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.

Most vaccinations are recommended within the 15th month of life, in order to reduce risks and to protect children from the initial stages of their lives. A vaccination training session was carried out during the birthing preparation course, aimed at increasing the attitude toward vaccination in maternal-child age. A questionnaire on vaccination awareness was administered before and after the training session and on-site flu vaccination was offered to women and their companions. The percentage of participants who consider the preparatory course a useful tool to obtain information about vaccines increases significantly from 30.34% at pre-intervention to 64.56% at post-intervention (p &lt, 0.001). There is a significant increase in the mean number of vaccinations that the participants want their children to get. The number of participants believing that there is no relationship between vaccination and autism rose from 41.05 to 72.97% (p &lt, 0.001). In total, 48 out of 119 (40.34%) pregnant women participating in the course and 39 companions were vaccinated for influenza. Vaccination knowledge and attitude significantly increased after a training session dedicated to vaccination as a part of the pregnant pre-birth course, whose aim can be therefore extended to the management of the health of the child, well beyond the period of pregnancy, according to the life-course approach to health.

Continuous glucose monitoring (CGM) might be an effective tool to improve glycemic control in gestational diabetes mellitus (GDM). Few data are available about its utilization as a diagnostic tool to find potential alterations of glycemia in subjects with normal oral glucose tolerance test (OGTT). In this preliminary prospective real-life observational study, we aimed to analyze the glycemic pattern in normal and gestational diabetes mellitus (GDM) women by continuous glucose monitoring (CGM) in order to detect potential differences between the two groups and glycemic alterations despite a normal OGTT. After the screening for GDM, subjects were connected to a CGM system for seven consecutive days. The areas under the curve of the first 60 minutes after each meal and 60 minutes before breakfast were analyzed. Women with normal OGTT that during CGM showed impaired glycemic values (more than 95 fasting or more than 140 one hour after meals or more than 120 two hours after meals) performed one week of self-monitoring of blood glucose (SMBG). After OGTT, 53 women considered normal and 46 affected by GDM were included. CGM parameters did not show any differences between the two groups with impaired glycemic excursions found in both groups. After CGM period, 33 women with normal OGTT showed abnormal glycemic patterns. These 33 women then performed one week of SMBG. After evaluation of one week of SMBG, 21 required diet therapy and 12 required insulin treatment and were followed until the delivery. An increase in gestational weight gain was observed in normal women with normal OGTT but this was not significant. No significant data were found regarding neonatal outcomes in the two groups of women. In conclusion, CGM use in pregnancy might help to detect glycemic fluctuations in women with normal OGTT, improving their treatment and outcomes.

Introduction: This study aimed to test the hypothesis that cardiac size is maintained in small fetuses presenting with cardiomegaly. Materials and Methods: We identified singleton fetuses with estimated fetal weight Z-scores for cardiac and thoracic circumferences normalized for gestational age (GA), biparietal diameter (BPD), head circumference (HC), and femur length (FL), obtained from 188 normally grown fetuses. Results: When comparing chest size, small fetuses had significantly lower thoracic circumferences median Z-scores (IQR) for GA = −4.82 (−6.15 to −3.51), BPD = −2.42 (−4.04 to −1.48), HC = −2.72 (−4.53 to −1.90), and FL = −1.60 (−2.87 to −0.71); p < 0.001 for all. When comparing heart size, small fetuses showed lower cardiac circumferences median Z-scores (IQR) for GA = −1.59 (−2.79 to −0.16); p < 0.001, similar cardiac circumferences Z-scores for BPD = 0.29 (−0.65 to 1.28); p = 0.284 and HC = 0.11 (−1.13 to 0.96); p = 0.953, and higher cardiac circumferences Z-scores for FL = 0.94 (−0.05 to 2.13); p < 0.001. Conclusions: Our results show that in small fetuses with cardiomegaly, the heart maintains normal dimensions when normalized to cranial diameters and higher dimensions when normalized to long bones. This provides insight into cardiac adaptation to adverse intrauterine environment.

To serially assess fetal cardiac dimensions in congenital diaphragmatic hernia (CDH) and their relation to disease severity. Retrospective analysis of CDH cases and matched controls. Mitral (MVd) and tricuspid (TVd) valve diameters, left (LV) and right (RV) ventricular length and area, Z-scores, were serially assessed at 24–26, 30–32, and 35–37 weeks gestational age (GA). In CDH cases MVd, MVd Z-score, and LV area were significantly reduced at 24–26 and 35–37 weeks GA. TVd, TVd Z-score, and RV area were significantly reduced at 24–26 weeks. RV area Z-score increased with advancing GA. MVd and MVd Z-score were significantly lower at 24–26 weeks GA in CDH who had a combined outcome of death and/or ECMO. LV hypoplasia in CDH is characterized by reduced MVd from 24 weeks GA. MVd, and the ratio of mitral and tricuspid valve diameters at later gestations, may be potential predictors of disease severity.

The myocardial performance index (MPI) has been proposed to evaluate cardiac dysfunction in newborns from diabetic mothers. Although MPI is routinely assessed in newborns, its role in the evaluation of fetuses from women with hyperglycemia in pregnancy (HIP) is still under evaluation. We aimed to evaluate the differences in third trimester fetal MPI in pregnant women with hyperglycemia compared to healthy controls. Seven electronic databases were searched for all studies assessing women with HIP who underwent evaluation of fetal left MPI during pregnancy compared to a control group. The summary measures were reported as mean differences (MD) in the mean fetal left MPI between women with HIP and healthy controls, with a 95 % confidence interval (CI). A post hoc subgroup analysis based on the type of HIP - pregestational diabetes, GDM, or gestational impaired glucose tolerance (GIGT) - was performed as an additional analysis. 14 studies assessing 1326 fetuses (580 from women with HIP and 746 from controls) were included. Women with HIP had a significantly higher mean left fetal MPI compared to controls (MD 0.08; 95 %CI: 0.05 to 0.11; p 0.00 001). Subgroup analysis according to the type of HIP concurred with the overall analysis for women with DM (MD 0.07; 95 %CI: 0.01 to 0.13; p = 0.02) and for women with GDM (MD 0.012; 95 %CI: 0.07 to 0.17; p 0.00 001) but not for women with GIGT (MD -0.01, 95 % CI -0.28 to 0.27; p = 0.96). Fetal left MPI is increased in pregnancies with HIP appearing as a potential marker of cardiac dysfunction.ZIEL: Der myokardiale Performance-Index (MPI) wurde vorgeschlagen, um die kardiale Dysfunktion bei Neugeborenen von Müttern mit Diabetes zu beurteilen. Obwohl der MPI routinemäßig bei Neugeborenen bestimmt wird, ist seine Rolle bei der Beurteilung von Föten von Schwangeren mit Hyperglykämie (HIP) noch in der Evaluierung. Unser Ziel war es, die Unterschiede im fetalen MPI im dritten Trimester bei schwangeren Frauen mit Hyperglykämie im Vergleich zu gesunden Kontrollen zu bewerten. Sieben elektronische Datenbanken wurden nach allen Studien durchsucht, in denen Frauen mit HIP untersucht wurden, bei denen während der Schwangerschaft eine Bewertung des fetalen linken MPI im Vergleich zu einer Kontrollgruppe durchgeführt wurde. Die zusammenfassenden Messungen wurden als mittlere Differenzen (MD) des mittleren fetalen linken MPI zwischen Frauen mit HIP und gesunden Kontrollen mit einem 95 %-Konfidenzintervall (KI) angegeben. Eine Post-hoc-Subgruppenanalyse basierend auf dem HIP-Typ – präkonzeptioneller Diabetes, Gestationsdiabetes mellitus (GDM) oder Gestations-bedingte Glukosetoleranzstörung (GIGT) – wurde als zusätzliche Analyse durchgeführt. 14 Studien mit 1326 Föten (580 von Frauen mit HIP und 746 von Kontrollpersonen) wurden eingeschlossen. Frauen mit HIP hatten einen signifikant höheren mittleren linken fetalen MPI im Vergleich zu den Kontrollen (MD 0,08; 95 %-KI 0,05–0,11; p 0,00 001). Die Subgruppenanalyse nach dem HIP-Typ stimmte mit der Gesamtanalyse für Frauen mit DM (MD 0,07; 95 %-KI 0,01–0,13; p = 0,02) und für Frauen mit GDM (MD 0,012; 95 %-KI 0,07–0,17; p 0,00 001) überein, nicht aber für Frauen mit GIGT (MD –0,01; 95 %-KI –0,28–0,27; p = 0,96). Der fetale linke MPI ist bei Schwangerschaften mit HIP erhöht und könnte sich somit als potenzieller Marker für die kardiale Dysfunktion erweisen.

The goal of this study is to understand how very elderly patients (VEP) after ischemic stroke are currently treated in a Stroke Unit (SU) Hub in Italy. We designed a retrospective monocentric study on patients admitted in the SU of "AO San Camillo Forlanini" over an 8-year period.Data were collected among patients with acute ischemic stroke admitted to SU between January 2012 and December 2019. Patients were divided into three sub-groups: Adults (18-65 years); Elderly (66-85 years); and VEP (85 years). Vascular risk factors and clinical variables as predictors of short-term clinical outcome were compared among age groups.A total of 1979 patients were enrolled, 254 were VEP (12.8%). The proportion of VEP showed no significant modifications during the 8-year period (11.9% in 2012-2015 and 13.7% in 2016-2019; p=0.93). The proportion of women, hypertension and atrial fibrillation was significantly higher in VEP compared to other age groups (p0.001). The rate of VEP being treated with rt-PA increased from 2012-2015 to 2016-2019 (from 12.8% to 25.5%, p0.001). Endovascular thrombectomy was rarely performed in VEP (1.5% of VEP). Rt-PA treatment was associated with favorable outcome for all three age groups (p0.05).We showed that VEP present different vascular risk factor profiles, clinical features, and prognostic elements for short-term stroke outcome. Future studies will reveal whether we will observe an increasing trend in the use of rt-PA and endovascular thrombectomy and whether it will result in improved functional outcome for VEP.

Objectives: Restrictive measures adopted during the COVID-19 pandemic, in order to limit contagion, have had a severe impact on mental health. The burden of lockdown has been particularly heavy on patients with chronic neurologic diseases such as People with Epilepsy (PwE). Our survey aims to describe the struggles and needs of Drug-Resistant (DR) PwE with implanted Vagal Nerve Stimulator (VNS) during the first wave of the COVID-19 lockdown in order to find strategies that help patients cope with present or future periods of restriction.Methods: We collected answers from 30 respondents who underwent an online survey including socio-demographic and clinical information and COVID-19-related information. Depression, anxiety symptoms, and sleep quality were investigated in patients through BDI II, GAD-7, and the PSQI scale.Results: In all, 46% of our sample reported an increase in the number of seizures; the entire sample complained of epilepsy-related issues (medication availability, VSN adjustments, anxiety, sleep disturbance); one out of three participants reported major epilepsy issues felt urgent; 30% had to postpone scheduled examination. Significantly higher scores for depression and anxiety scales were found in patients who perceived seizure frequency worsening and reported major epilepsy-related issues.Conclusion: Preliminary findings showed that the first lockdown influenced the clinical and psychological status of PwE and was related to seizures worsening. The lack of medical assistance and control on VNS therapy left patients to cope with the situation without a chance to contact a specialist. We discuss how a wider implementation of telemedicine programs could facilitate remote assistance of PwE with a VNS implant.

Improvements in medical technologies have seen over-medicalization of childbirth. Caesarean section (CS) is a lifesaving procedure proven effective in reducing maternal and perinatal mortality across the globe. However, as with any medical procedure, the CS intrinsically carries some risk to its beneficiaries. In recent years, CS rates have risen alarmingly in high-income countries. Many exceeding the World Health Organisation (WHO) recommendation of a 10 to 15% annual CS rate. While this situation poses an increased risk to women and their children, it also represents an excess human and financial burden on health systems. Therefore, from a health system perspective this study systematically summarizes existing evidence relevant to the factors driving the phenomenon of increasing CS rates using Italy as a case study.Employing the WHO Health System Framework (WHOHSF), this systematic review used the PRISMA guidelines to report findings. PubMed, SCOPUS, MEDLINE, Cochrane Library and Google Scholar databases were searched up until April 1, 2020. Findings were organised through the six dimensions of the WHOHSF framework: service delivery, health workforce, health system information; medical products vaccine and technologies, financing; and leadership and governance.CS rates in Italy are affected by complex interactions among several stakeholder groups and contextual factors such as the hyper-medicalisation of delivery, differences in policy and practice across units and the national context, issues pertaining to the legal and social environment, and women's attitudes towards pregnancy and childbirth.Mitigating the high rates of CS will require a synergistic multi-stakeholder intervention. Specifically, with processes able to attract the official endorsement of policy makers, encourage concensus between regional authorities and local governments and guide the systematic compliance of delivery units with its clinical guidelines.La cesárea (CS) es un procedimiento que salva vidas y que ha demostrado su eficacia en la reducción de la mortalidad materna y perinatal en todo el mundo. Sin embargo, como cualquier procedimiento médico, la cesárea intrínsecamente conlleva cierto riesgo para sus beneficiarias, especialmente para aquellas que clínicamente no la requieren. La OMS recomienda una tasa de 10–15% de CS como estándar de buena práctica obstétrica. Sin embargo, en muchos países desarrollados el número de CS realizado por año continúa aumentando exponencialmente presionando los recursos limitados de los sistemas de salud. Si bien esta situación expone a las mujeres y a sus fetos a un mayor riesgo quirúrgico, también representa una excesiva carga financiera para los sistemas de salud. TEMA: Utilizando el Framework del Sistema de Salud de la OMS (WHOHSF) y utilizando a Italia como referencia, esta revisión tiene como objetivo resaltar las circunstancias que determinan la excesiva tasa de CS observada en muchos países desarrollados. Analizamos el problema a través de las seis dimensiones del WHOHSF: prestación de servicios, personal sanitario, información del sistema de salud; productos médicos, vacunas y tecnologías, financiación; y liderazgo y gobernanza. Las tasas de CS en Italia se ven afectadas por una compleja interacción entre varios grupos de interés y factores como la ‘hiper-medicalización’ de la prestación, las diferencias en las políticas y prácticas entre las unidades y en el contexto nacional, cuestiones relativas al entorno legal y social junto con las actitudes de las mujeres hacia el embarazo y el parto. CONCLUSIóN: La reducción de las altas tasas de CS requerirá una intervención sinérgica que incluya a las partes interesadas en todos los niveles. Específicamente, intervenciones capaces de atraer el respaldo oficial de los responsables políticos, una alineación de puntos de vista entre las autoridades regionales y los gobiernos locales, y un cumplimiento sistemático de las directrices clínicas por parte de las unidades de prestación de servicios.HINTERGRUND: Der Kaiserschnitt (CS) ist ein lebensrettendes Verfahren, das sich als wirksam erwiesen hat, um die mütterliche und perinatale Sterblichkeit weltweit zu reduzieren. Wie bei jedem medizinischen Verfahren birgt die CS jedoch ein gewisses Risiko für die Betroffenen, insbesondere für diejenigen, die sie medizinisch nicht benötigen. Die WHO empfiehlt eine Rate von 10–15% CS als Standard für gute geburtshilfliche Praxis. In vielen entwickelten Ländern steigt die Zahl der jährlich durchgeführten CS jedoch weiterhin exponentiell an und setzt die begrenzten Ressourcen der Gesundheitssysteme unter Druck. Während diese Situation Frauen und ihre ungeborenen Babys einem erhöhten Operationsrisiko aussetzt, stellt sie auch eine übermäßige finanzielle Belastung für die Gesundheitssysteme dar.Unter Anwendung des WHO Health System Framework (WHOHSF) und am Beispiel Italiens soll diese Übersicht die Umstände aufzeigen, die der in vielen Industrieländern beobachteten übermäßigen CS-Anzahl zugrunde liegen. Wir analysieren das Problem anhand der sechs Dimensionen des WHOHSF: Leistungserbringung, Gesundheitspersonal, Informationen über das Gesundheitssystem; medizinische Produkte, Impfstoffe und Technologien, Finanzierung sowie Führung und Kontrolle. In Italien werden die CS-Raten durch ein komplexes Zusammenspiel verschiedener Interessengruppen und Faktoren beeinflusst, wie z.B. die “Hyper-Medizinalisierung” der Entbindung, Abweichungen in Theroie und Praxis zwischen den Abteilungen und im nationalen Kontext, Fragen des rechtlichen und sozialen Umfelds sowie die Einstellung der Frauen zu Schwangerschaft und Geburt.Um die hohen Raten der CS zu verringern, ist ein synergetisches Vorgehen unter Einbeziehung der Beteiligten auf allen Ebenen erforderlich. Insbesondere sind Interventionen erforderlich, die die offizielle Zustimmung der politischen Entscheidungsträger finden, eine Abstimmung der Standpunkte zwischen regionalen und lokalen Behörden und eine systematische Einhaltung der klinischen Leitlinien durch die Geburtenstationen.

ispartof: JOURNAL OF ULTRASOUND IN MEDICINE vol:40 issue:9 pages:1991-1996 ispartof: location:England status: published

Transcutaneous vagus nerve stimulation (tVNS) is an alternative non-invasive method for the electrical stimulation of the vagus nerve with the goal of treating several neuropsychiatric disorders. The objective of this study is to assess the effects of tVNS on cerebral cortex activity in healthy volunteers using resting-state microstates and power spectrum electroencephalography (EEG) analysis. Eight male subjects aged 25–45 years were recruited in this randomized sham-controlled double-blind study with cross-over design. Real tVNS was administered at the left external acoustic meatus, while sham stimulation was performed at the left ear lobe, both of them for 60 min. The EEG recording lasted 5 min and was performed before and 60 min following the tVNS experimental session. We observed that real tVNS induced an increase in the metrics of microstate A mean duration (p = 0.039) and an increase in EEG power spectrum activity in the delta frequency band (p < 0.01). This study confirms that tVNS is an effective way to stimulate the vagus nerve, and the mechanisms of action of this activation can be successfully studied using scalp EEG quantitative metrics. Future studies are warranted to explore the clinical implications of these findings and to focus the research of the prognostic biomarkers of tVNS therapy for neuropsychiatric diseases.

To assess quality of life (QoL) in adult people with epilepsy (PWE) and identify the main factors affecting it. We enrolled consecutively 122 PWE. They were interviewed for a careful collection of demographic and clinical data. Patients completed dedicated questionnaires for the assessment of the quality of life (Quality of Life in Epilepsy Scale-31) (Q31) as well as psychosocial features: depressive symptoms (DS) (Beck Depression Inventory-II/BDI-II), difficulties of emotion regulation (Difficulties of Emotion Regulation Scale/DERS), and stigma related to epilepsy (Stigma Scale of Epilepsy/SSE and Jacoby’s Stigma Scale/JSS). The results of Q31 and their subscales were correlated with clinical details of PWE, as well as the other scores. A stepwise multiple regression analysis was applied to identify the main factors affecting QoL. Quality of life is inversely correlated mostly with psychosocial features, as DS, emotion dysregulation, and stigma perception, as well as with epilepsy-related factors, as the seizure frequency and number of antiseizure medications (ASMs). The combination of DS, perceived stigma, and number of ASMs best explained the QoL. Worse features of QoL were detected in females and in patients with age of epilepsy onset in adulthood. Quality of life in adult PWE is predominantly affected by psychosocial factors more than epilepsy-related ones. These findings suggest that effective epilepsy management requires more than seizure control, and early detection of psychological dysfunction and tailored interventions to improve the QoL should be considered.