Μέτρηση μορίων απόπτωσης στον ορό του αίματος παιδιών με σπασμούς

Στην παρούσα μελέτη διερευνήσαμε τα επίπεδα της αντιαποπτωτικής πρωτεΐνης Bcl-2 και της προαποπτωτικής κασπάσης-9 στον ορό του αίματος 118 παιδιών και εφήβων, εκ των οποίων 82 ασθενείς έπασχαν από ιδιοπαθή επιληψία και 36 ασθενείς είχαν εκδηλώσει ένα ή δύο πρώτα επεισόδια κρίσεων τον τελευταίο μήνα πριν την αιμοληψία. Οι ασθενείς κατηγοριοποιήθηκαν βάσει του τύπου των κρίσεων, αριθμού κρίσεων, έλεγχο ή μη αυτών. Tα επίπεδα ορού αίματος στους ασθενείς συγκρίθηκαν με αυτά ομάδας 30 υγιών μαρτύρων και διαπιστώθηκε στατιστικά σημαντική αύξηση της Bcl-2 (p=0,0001) αλλά όχι της κασπάσης-9 (p=0,987). Για κάθε αύξηση της Bcl-2 κατά 1ng/ml πάνω από την τιμή 12,76 ng/ml (πάνω από δύο σταθερές αποκλίσεις από τη μέση τιμη της Bcl-2 στην ομάδα των μαρτύρων) η πιθανότητα του παιδιού να ανήκει στην ομάδα των ασθενών αυξάνεται κατά 12%. Τα επίπεδα της Bcl-2 στο αίμα αποτελούν συνεπώς ενα δυνητικό διαγνωστικό μοριακό βιολογικό δείκτη (βιοδείκτη) για τους ενεργούς σπασμούς και την επιληψία. Τετραπλάσια τιμή των επιπέδων της Bcl-2 στο αίμα διαπιστώθηκε στις γενικευμένες και στις εστιακές σύνθετες εξωκροταφικές κρίσεις σε σύγκριση με τους άλλους τύπους κρίσεων, αν και στατιστικά μη σημαντική η διαφορά λόγω του μεγάλου μεγέθους των τυπικών αποκλίσεων. Στατιστικά σημαντική διαφορά των επιπέδων της Βcl-2 αλλά όχι της κασπάσης-9 διαπιστώθηκε στη σύγκριση μεταξύ των εστιακών σύνθετων εξωκροταφικών κρίσεων και των εστιακών απλών κινητικών κρίσεων (p=0,047), όπως επίσης στη σύγκριση μεταξύ των εστιακών σύνθετων εξωκροταφικών κρίσεων και όλων των κροταφικών κρίσεων μαζί (p=0,034). Δε διαπιστώθηκε συσχέτιση μεταξύ των επιπέδων Bcl-2 και κασπάσης-9 στον ορό του αίματος των ασθενών με το φύλο, ηλικία, διάρκεια επιληψίας, αριθμό κρίσεων ανά μήνα και συνολικό αριθμό κρίσεων ανεξαρτήτως διάρκειας. Τα επίπεδα της κασπάσης-9 ήταν στατιστικά σημαντικά αυξημένα στους ασθενείς με δύο ή περισσότερα επεισόδια κρίσεων το μήνα σε σύγκριση με εκείνους με ένα επεισόδιο τον μήνα (p=0,048). Μετά από υποτροπή κρίσεως (σε ασθενείς προηγουμένως υπό έλεγχο), τα επίπεδα των Bcl-2 και κασπάσης-9 αυξήθηκαν οξέως και παράλληλα σε σύγκριση με τους χωρίς έλεγχο κρίσεων ασθενείς. Δε διαπιστώθηκε στατιστικά σημαντική διαφορά στα επίπεδα της Bcl-2 και της κασπάσης-9 μεταξύ των ασθενών χωρίς έλεγχο των κρίσεων, με έλεγχο των κρίσεων και σε αυτούς με μονήρη υποτροπή μετά από έλεγχο. Δε διαπιστώθηκε στατιστικά σημαντική διαφορά μεταξύ των ασθενών υπό και χωρίς φαρμακοθεραπεία (p=0,170 και p=0,072 αντίστοιχα).This study investigates the blood serum levels of antiapoptotic Bcl-2 and proapoptotic caspase-9 proteins in 118 children and adolescents, of which 82 suffered from idiopathic epilepsy and 36 had, for the first time, one or two seizures in the last month before the blood sampling. Patients were categorized according to type, number of seizures, control of seizures. Mean serum levels of Bcl-2 and caspase-9 in patients were compared to those of 30 healthy controls and were found significantly higher for Bcl-2 (p<0,0001) but not caspase-9 (p=0,987). Data analysis showed that for every 1ng/ml of increased Bcl-2 above 12,76ng/ml (more than 2 standard deviations above mean value of Bcl-2 in control’s group) there is a 12% higher possibility in the prediction for the child to be classified in the patient’s group. Therefore Bcl-2 serum level can be regarded as a potential diagnostic molecular biomarker for epilepsy and active seizures. Higher mean serum levels of Bcl-2 and caspase-9 (fourfold) were observed in generalized seizures as well as in focal complex extratemporal seizures but there was no statistically significant difference compared to the other types of seizures, possibly due to the large size of standard deviations. Significantly increased levels of Bcl-2 but not caspase-9 were found in the focal complex extratemporal seizures compared to simple focal motor seizures (p=0,047) and also in the focal complex extratemporal seizures compared to all types of temporals added together (p=0,034). No correlations were found between Bcl-2 and caspase-9 serum levels concerning the gender, age, seizure duration, number of seizures per month and the total number of seizures independently of duration. Serum levels of caspase-9 were statistically significantly increased in patients with two or more seizures per month compared to those with one seizure per month (p=0,048). After a single relapse (in previously controlled patients), Bcl-2 and caspase-9 serum levels were increased acutely and in parallel compared to controlled patients. There was no statistically significant difference of Bcl-2 and caspase-9 serum levels between uncontrolled patients, controlled patients and controlled single-relapse patients. Levels of Bcl-2 and caspase-9 presented with no significant difference between patients with and without treatment (p=0,170 and p=0,072 respectively)

Serum levels of apoptosis molecules in children with seizures

This study investigates the blood serum levels of antiapoptotic Bcl-2 and proapoptotic caspase-9 proteins in 118 children and adolescents, of which 82 suffered from idiopathic epilepsy and 36 had, for the first time, one or two seizures in the last month before the blood sampling. Patients were categorized according to type, number of seizures, control of seizures. Mean serum levels of Bcl-2 and caspase-9 in patients were compared to those of 30 healthy controls and were found significantly higher for Bcl-2 (p<0,0001) but not caspase-9 (p=0,987). Data analysis showed that for every 1ng/ml of increased Bcl-2 above 12,76ng/ml (more than 2 standard deviations above mean value of Bcl-2 in control’s group) there is a 12% higher possibility in the prediction for the child to be classified in the patient’s group. Therefore Bcl-2 serum level can be regarded as a potential diagnostic molecular biomarker for epilepsy and active seizures. Higher mean serum levels of Bcl-2 and caspase-9 (fourfold) were observed in generalized seizures as well as in focal complex extratemporal seizures but there was no statistically significant difference compared to the other types of seizures, possibly due to the large size of standard deviations. Significantly increased levels of Bcl-2 but not caspase-9 were found in the focal complex extratemporal seizures compared to simple focal motor seizures (p=0,047) and also in the focal complex extratemporal seizures compared to all types of temporals added together (p=0,034). No correlations were found between Bcl-2 and caspase-9 serum levels concerning the gender, age, seizure duration, number of seizures per month and the total number of seizures independently of duration. Serum levels of caspase-9 were statistically significantly increased in patients with two or more seizures per month compared to those with one seizure per month (p=0,048). After a single relapse (in previously controlled patients), Bcl-2 and caspase-9 serum levels were increased acutely and in parallel compared to controlled patients. There was no statistically significant difference of Bcl-2 and caspase-9 serum levels between uncontrolled patients, controlled patients and controlled single-relapse patients. Levels of Bcl-2 and caspase-9 presented with no significant difference between patients with and without treatment (p=0,170 and p=0,072 respectively).Στην παρούσα μελέτη διερευνήσαμε τα επίπεδα της αντιαποπτωτικής πρωτεΐνης Bcl-2 και της προαποπτωτικής κασπάσης-9 στον ορό του αίματος 118 παιδιών και εφήβων, εκ των οποίων 82 ασθενείς έπασχαν από ιδιοπαθή επιληψία και 36 ασθενείς είχαν εκδηλώσει ένα ή δύο πρώτα επεισόδια κρίσεων τον τελευταίο μήνα πριν την αιμοληψία. Οι ασθενείς κατηγοριοποιήθηκαν βάσει του τύπου των κρίσεων, αριθμού κρίσεων, έλεγχο ή μη αυτών. Tα επίπεδα ορού αίματος στους ασθενείς συγκρίθηκαν με αυτά ομάδας 30 υγιών μαρτύρων και διαπιστώθηκε στατιστικά σημαντική αύξηση της Bcl-2 (p=0,0001) αλλά όχι της κασπάσης-9 (p=0,987). Για κάθε αύξηση της Bcl-2 κατά 1ng/ml πάνω από την τιμή 12,76 ng/ml (πάνω από δύο σταθερές αποκλίσεις από τη μέση τιμή της Bcl-2 στην ομάδα των μαρτύρων) η πιθανότητα του παιδιού να ανήκει στην ομάδα των ασθενών αυξάνεται κατά 12%. Τα επίπεδα της Bcl-2 στο αίμα αποτελούν συνεπώς ένα δυνητικό διαγνωστικό μοριακό βιολογικό δείκτη (βιοδείκτη) για τους ενεργούς σπασμούς και την επιληψία. Τετραπλάσια τιμή των επιπέδων της Bcl-2 στο αίμα διαπιστώθηκε στις γενικευμένες και στις εστιακές σύνθετες εξωκροταφικές κρίσεις σε σύγκριση με τους άλλους τύπους κρίσεων, αν και στατιστικά μη σημαντική η διαφορά λόγω του μεγάλου μεγέθους των τυπικών αποκλίσεων. Στατιστικά σημαντική διαφορά των επιπέδων της Βcl-2 αλλά όχι της κασπάσης-9 διαπιστώθηκε στη σύγκριση μεταξύ των εστιακών σύνθετων εξωκροταφικών κρίσεων και των εστιακών απλών κινητικών κρίσεων (p=0,047), όπως επίσης στη σύγκριση μεταξύ των εστιακών σύνθετων εξωκροταφικών κρίσεων και όλων των κροταφικών κρίσεων μαζί (p=0,034). Δε διαπιστώθηκε συσχέτιση μεταξύ των επιπέδων Bcl-2 και κασπάσης-9 στον ορό του αίματος των ασθενών με το φύλο, ηλικία, διάρκεια επιληψίας, αριθμό κρίσεων ανά μήνα και συνολικό αριθμό κρίσεων ανεξαρτήτως διάρκειας. Τα επίπεδα της κασπάσης-9 ήταν στατιστικά σημαντικά αυξημένα στους ασθενείς με δύο ή περισσότερα επεισόδια κρίσεων το μήνα σε σύγκριση με εκείνους με ένα επεισόδιο τον μήνα (p=0,048). Μετά από υποτροπή κρίσεως (σε ασθενείς προηγουμένως υπό έλεγχο), τα επίπεδα των Bcl-2 και κασπάσης-9 αυξήθηκαν οξέως και παράλληλα σε σύγκριση με τους χωρίς έλεγχο κρίσεων ασθενείς. Δε διαπιστώθηκε στατιστικά σημαντική διαφορά στα επίπεδα της Bcl-2 και της κασπάσης-9 μεταξύ των ασθενών χωρίς έλεγχο των κρίσεων, με έλεγχο των κρίσεων και σε αυτούς με μονήρη υποτροπή μετά από έλεγχο. Δε διαπιστώθηκε στατιστικά σημαντική διαφορά μεταξύ των ασθενών υπό και χωρίς φαρμακοθεραπεία (p=0,170 και p=0,072 αντίστοιχα)

Endosaccular flow disruption with the Contour Neurovascular System: angiographic and clinical results in a single-center study of 60 unruptured intracranial aneurysms

International audienceBackground The Contour Neurovascular System is a novel device designed to treat intracranial aneurysms by intrasaccular flow disruption. We report our experience and mid-term follow-up in a series of patients treated with the Contour. Methods The patients were divided into an intention to treat and a per protocol population, the latter defined by the successful implantation of the Contour device. The intention to treat population included 53 patients (30 women, mean age 56 years) with 60 unruptured intracranial aneurysms (53 in the anterior circulation and seven in the posterior circulation). There was clinical and angiographic follow-up immediate postoperatively and at 24 hours, 3 months and 1 year using the Raymond–Roy classification and the O’Kelly–Marotta grading scale. Results The Contour was successfully implanted in 54/60 (90%) aneurysms. With regard to the angiographic follow-up, there was adequate occlusion (defined as complete occlusion or presence of a neck remnant) in 31.5% of 54 aneurysms immediately postoperatively, 62.3% (in 53/54 aneurysms) at 24 hours, 81.4% (in 43/54 aneurysms) at 3 months, and 89.3% (in 28/54 aneurysms) at 1 year. Technical complications in 60 aneurysms of the intention to treat population included two (3.3%) inadvertent detachments of the device. Thromboembolic events were observed in four of the 60 aneurysms (6.7%), with no clinical symptoms in three patients and transient morbidity in one (1.7%). No aneurysm bleeding was observed and no patient was retreated during the 1-year follow-up period. There was no permanent morbidity or mortality. Conclusions The Contour device is effective and safe in the treatment of intracranial aneurysms. However, more experience and long-term follow-up are needed

Review on the current treatment status of vein of Galen malformations and future directions in research and treatment

Introduction Vein of Galen malformations (VOGMs) represent a rare pathologic entity with often catastrophic natural history. The advances in endovascular treatment in recent years have allowed for a paradigm shift in the treatment and outcome of these high-flow shunts, even though their pathogenetic mechanisms and evolution remain in part obscure. Areas covered The overall management of VOGMs requires a tailored case-to-case approach, starting with in utero detection and reserving endovascular treatment for indicated cases. Lately, the advances in translational research with whole-genome sequencing and the coupling with cellular-level hemodynamics attempt to shed more light in the pathogenesis and evolution of these lesions. At the same time the advances in endovascular techniques allow for more safety and tailored technical strategy planning. Furthermore, the advances in MRI techniques allow a better understanding of their vascular anatomy. In view of these recent advances and by performing a PUBMED literature review of the last 15 years, we attempt a review of the evolutions in the imaging, management, endovascular treatment and understanding of underlying mechanisms for VOGMs. Expert opinion The progress in the fields detailed in this review appears very promising in better understanding VOGMs and expanding the available therapeutic arsenal

Bcl-2 and caspase-9 serum levels in children and adolescents with idiopathic epilepsy and active seizures.

BACKGROUND: In the present study we investigated the levels of proapoptotic caspase-9 and antiapoptotic Bcl-2 proteins in the sera of children and adolescents with idiopathic epilepsy and tried to relate the findings to the patients&apos; clinical parameters. METHODS: This retrospective study consisted of 118 children and adolescents with idiopathic epilepsy, categorized according to type and number of seizures, duration of the disease and the control of seizures and 30 age- and sex-matched controls. The relapse of seizures was taken into consideration. RESULTS: Mean serum level between Bcl-2 and caspase-9 was significantly higher only in Bcl-2 patients, compared to controls (P≤0.0001) and (P=0.987) respectively. Significant difference in Bcl-2 level was found among the different types of focal seizures. Caspase-9 level was statistically different in patients with two or more seizures per month compared to those with one seizure per month (P=0.048). No correlation was found between Bcl-2 and caspase-9 levels and age, gender, seizure frequency, total number of seizures and the duration of epilepsy. No significant difference was found in patients with and without drug treatment. CONCLUSIONS: Bcl-2 displays an association with apoptosis and highlights the potential of being a surrogate biomarker for active seizures and epilepsy. There is a significant difference in Bcl-2 serum level among the different types of focal seizures. Proapoptotic caspase-9 cannot act as a marker of active seizures and epilepsy. Caspase-9 serum level is increased acutely in controlled cases after a single relapse

Pre-Interventional 3D-Printing-Assisted Planning of Flow Disrupter Implantation for the Treatment of an Intracranial Aneurysm

International audienceIntrasaccular flow disrupter devices (ISFD) have opened up new ways to treat intracranial aneurysms but choosing the correct size of ISFD can be challenging. We describe the first use of 3D printing to assist in the choice of ISFD, and we report an illustrative case. We developed a technique that uses preoperative angiography to make a plastic model of the aneurysm. We tested the deployment of different sizes of intrasaccular flow disruptor on the 3D model under fluoroscopy. The best devices were then used as the first-line strategy to treat the patient. The preoperative 3D printing helped in the successful selection of a first-line ISFD, which was not the one recommended by the manufacturer. Three-dimensional printing can provide interesting information regarding the treatment of intracranial aneurysms using ISFD. Further studies are needed to fully assess its benefits

Direct transfer to angiosuite for patients with severe acute stroke treated with thrombectomy: the multicentre randomised controlled DIRECT ANGIO trial protocol

Introduction Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT.Methods and analysis DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0–2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0–2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment.Ethics and dissemination The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal.Trial registration number NCT03969511

European Multicenter Study of ET-COVID-19

International audienceBackground and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090

Mechanical Thrombectomy for Acute Ischemic Stroke Amid the COVID-19 Outbreak

International audienceBackground and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P <0.001) in MT case volumes during the epidemic period, and a significant increase in delays between imaging and groin puncture, overall (mean 144.9±SD 86.8 minutes versus 126.2±70.9; P <0.001 in 2019) and in transferred patients (mean 182.6±SD 82.0 minutes versus 153.25±67; P <0.001). After the instatement of strict epidemic mitigation measures, there was a significant negative correlation between the number of hospitalizations for COVID and the number of MT cases ( R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P <0.05). Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution