Transmission des voies olfactives aux cellules réticulospinales de la lamproie

Les informations olfactives sont connues pour leur capacité à induire des comportements moteurs spécifiques. En dépit de nombreuses observations comportementales chez les vertébrés, on ne connaît toujours pas les mécanismes et les voies nerveuses qui sous-tendent ces phénomènes de transformation olfacto-locomotrices. Chez la lamproie, des travaux récents ont permis de décrire cette voie, et les mécanismes responsables de la transformation des entrées olfactives en activité locomotrice (Derjean et al., 2010). Cette voie prend origine dans la partie médiane du bulbe olfactif, et envoie des projections vers le tubercule postérieur, une région qui se trouve dans le diencéphale. De là, les neurones projettent directement vers la Région Locomotrice Mésencéphalique, connue pour envoyer des connexions vers les neurones réticulospinaux, et activer la locomotion. L’objectif de cette étude était d’établir si l’ensemble des neurones réticulospinaux répond aux stimulations olfactives. Pour ce faire, nous avons utilisé sur une préparation de cerveau isolé de lamproie des techniques d’électrophysiologie et d’imagerie calcique. La stimulation électrique des nerfs olfactifs, de la région médiane du bulbe olfactif ou du tubercule postérieur a provoqué une activation de toutes les cellules réticulospinales qui se retrouvent dans les quatre noyaux réticulaires (ARRN : Noyau Réticulaire Rhombencéphalique Antérieur; MRN : Noyau Réticulaire Mésencéphalique; MRRN : Noyau Réticulaire Rhombencéphalique Moyen; PRRN : Noyau Réticulaire Rhombencéphalique Postérieur). Seule la partie médiane du bulbe olfactif est impliquée dans le passage de l’information olfactive vers les neurones réticulospinaux. Nous avons aussi découvert que le blocage des récepteurs GABAergiques dans la partie médiane du bulbe olfactif augmentait les réponses olfactives de façon considérable dans les cellules réticulospinales. Nous avons montré ainsi qu’il existe un tonus inhibiteur impliqué dans la dépression modulatrice de la voie olfacto-locomotrice. Ce travail a permis de montrer que la stimulation des afférences sensorielles olfactives active simultanément l’ensemble des populations de neurones réticulospinaux qui commandent la locomotion. De plus, il existerait un tonus inhibiteur GABAergique, au niveau de la partie médiane du bulbe olfactif, responsable d’une dépression modulatrice dans la voie olfacto-locomotrice.Olfactory inputs are known for their ability to induce specific motor behaviors. Despite numerous behavioral observations in vertebrates, the mechanisms and the neural pathways underlying the olfactory-locomotor transformation are still unknown. In lamprey, recent studies have described this pathway and the mechanism underlying the transformation of olfactory input into a locomotor activity (Derjean et al., 2010). This pathway originates in the medial part of the olfactory bulb, sends projections to the posterior tuberculum, a diencephalic region. From there, the neurons project directly to the mesencephalic locomotor region that is known to send projections to the reticulospinal neurons to activate locomotion. Using lamprey brain preparation, electrophysiology and calcium imaging, the aim of this study was to establish whether all reticulospinal neurons respond to olfactory stimuli. Electrical stimulation of the olfactory nerves, the medial part of the olfactory bulb or the posterior tuberculum activates all reticulospinal cells in the four reticular nuclei (ARRN: Anterior rhombencephalic reticular nucleus; MRN: middle mesencephalic reticular nucleus; MRRN: middle rhombencephalic reticular nucleus; PRRN: posterior rhombencephalic reticular nucleus). The medial part of the olfactory bulb is the only region that is implicated in transmitting the olfactory information to reticulospinal neurons. We also discovered that when blocking the GABAergic receptors in the medial part of the olfactory bulb, the reticulospinal neurons have a stronger response to olfactory stimulation. Thus we showed that a tonic inhibition is involved in the modulating depression of the olfacto-locomotor pathway. Altogether, this work shows that stimulation of the olfactory sensory inputs activates simultaneously the entire population of reticulospinal neurons that control locomotion. In addition, there is a GABAergic tonic inhibition at the level of the medial part of the olfactory bulb that causes a modulating depression in the olfacto-locomotor pathway

Assessing a 600-mg Loading Dose of Clopidogrel 24 Hours Prior to Pipeline Embolization Device Treatment

Background: Clopidogrel/aspirin antiplatelet therapy routinely is administered 7-10 days before pipeline aneurysm treatment. Our study assessed the safety and efficacy of a 600-mg loading dose of clopidogrel 24 hours before Pipeline Embolization Device (PED) treatment. Methods: In this retrospective cohort study, we included patients treated with PED from October 2010 to May 2016. A total of 39.7% (n = 158) of patients were dispensed a loading dose of 650 mg of aspirin plus at least 600 mg of clopidogrel 24 hours preceding PED deployment, compared to 60.3% (n = 240) of patients who received 81-325 mg of aspirin daily for 10 days with 75 mg of clopidogrel daily preprocedurally. The mean follow-up was 15.8 months (standard deviation [SD] 12.4 months). modified Rankin Scale (mRS) was registered before the discharge and at each follow-up visit. To control confounding, we used multivariable logistic regression and propensity score conditioning. Results: Of 398 patients, the proportion of female patients was ~16.5% (41/240) in both groups and shared the same mean of age ~56.46 years. ~12.2% (mean = 0.09; SD = 0.30) had a subarachnoid hemorrhage. 92% (mean = 0.29; SD = 0.70) from the pretreatment group and 85.7% (mean = 0.44; SD = 0.91) of the bolus group had a mRS ≤2. In multivariate analysis, bolus did not affect the mRS score, P = 0.24. Seven patients had a long-term recurrence, 2 (0.83%; mean = 0.01; SD = 0.10) of which from the pretreatment group. In a multivariable logistic regression, bolus was not associated with a long-term recurrence rate (odds ratio [OR] 1.91; 95% confidence interval [CI] 0.27-13.50; P = 0.52) or with thromboembolic accidents (OR 0.99; 95% CI 0.96-1.03; P = 0.83) nor with hemorrhagic events (OR 1.00; 95% CI 0.97-1.03; P = 0.99). Three patients died: one who received a bolus had an acute subarachnoid hemorrhage. The mean mortality rate was parallel in both groups ~0.25 (SD = 0.16). Bolus was not associated with mortality (OR 1.11; 95% CI 0.26-4.65; P = 0.89). The same associations were present in propensity score-adjusted models. Conclusions: In a cohort receiving PED, a 600-mg loading dose of clopidogrel should be safe and efficacious in those off the standard protocol or showing \u3c30% platelet inhibition before treatment

The Use of Prasugrel and Ticagrelor in Pipeline Flow Diversion

Background: Despite the routine clopidogrel/aspirin anti-platelet therapy, complications like thromboembolism, continue to be encountered with PED. We studied the safety and the efficacy of prasugrel in the management of clopidogrel non-responders treated for intracranial aneurysms. Methods: 437 consecutive neurosurgery patients were identified between January 2011 and May 2016. Patients allergic or having \u3c30% platelet-inhibition with a daily 75mg of clopidogrel were dispensed 10mg of prasugrel daily (n=20) or 90mg of ticagrelor twice daily (n=2). The average follow-up was 15.8 months (SD=12.4 months). Patient clinical well being was evaluated with the modified Rankin Scale (mRS) registered before the discharge and at each follow-up visit. To control confounding we used multivariable mixed-effects logistic regression and propensity score conditioning. Results: 26 of 437(5.9%) patients (mean of age 56.3 years; 62 women [14,2%]) presented with a sub-arachnoid hemorrhage. 1 patient was allergic to clopidogrel and prasugrel simultaneously. All the patients receiving prasugrel (n=22) had a mRS\u3c2 on their latest follow-up visit (mean=0.67; SD=1.15). In a multivariate analysis, clopidogrel did not affect the mRS on last follow-up, p=0.14. Multivariable logistic regression showed that clopidogrel was not associated with an increased long-term recurrence rate (odds ratio[OR], 0.17; 95%Confidence Interval [CI95%], 0.01-2.70; p=0.21) neither with an increased thromboembolic accident rate (OR, 0.46; CI95%, 0.12-1.67; p=0.36) nor with an increased hemorrhagic event rate (OR, 0.39; CI95%,0.91-1.64; p=0.20). None of the patients receiving prasugrel deceased or had a long-term recurrence nor a hemorrhagic event, only 1 patient suffered from mild aphasia subsequent to a thromboembolic event. 3 patients on clopidogrel passed during the study: (2) from acute SAH and (1) from intra-parenchymal hemorrhage. Clopidogrel was not associated with an increased mortality rate (OR, 2.18; CI95%,0.11-43.27; p=0.61). The same associations were present in propensity score adjusted models. Conclusion: In a cohort of patients treated with PED for their intracranial aneurysms, prasugrel (10mg/day) is a safe alternative to clopidogrel resistant, allergic or non-responders

Clinical Applications of the Pipeline Embolization Device

No abstract availabl

Rare Case of Diffuse Spinal Arachnoiditis Following a Complicated Vertebral Artery Dissection

Spinal arachnoiditis (SA) is an extremely rare and delayed complication of intracranial subarachnoid hemorrhage (SAH). SA is an inflammatory process leading to chronic fibrosis of the spinal cord. Possible pathophysiology is a two-staged disease of initial inflammatory reaction secondary to SAH, followed by a “free interval phase” prior to delayed adhesive phase (i.e. SA). The clinical course can be complicated and is the cause of major morbidity.https://jdc.jefferson.edu/neurosurgeryposters/1009/thumbnail.jp

Gastric Perforation From a Migrating Ventriculoperitoneal Shunt: A Case Report and Review of Literature

Ventriculoperitoneal (VP) shunts represent a surgical option for patients affected by increased intracranial hypertension when medical management fails or is contraindicated. Complications following implantation include shunt obstruction, infection, over and under drainage, migration or disconnection of the tube, formation of a pseudocyst, and allergy to the silicone tube. We report the case of a 31-year-old woman who presented to the emergency room with nausea and generalized malaise, found to have the distal segment of the VP catheter perforating her gastric wall into the stomach lumen which required surgical intervention. In this report, we describe a rare complication associated with the implantation of ventriculoperitoneal shunt (VPS) catheters and the subsequent management plan

Hypoglossal Nerve Injury With C1 Lateral Mass Screw Placement: A Case Report and Review of the Literature

We report the case of a 62-year-old man who presented with a progressive myelopathy secondary to spinal cord compression from an odontoid process fracture and subaxial central canal stenosis. The patient underwent a C1-T2 posterior decompression and instrumented fusion (PCDF) and did well immediately postoperatively. However, on POD1, he developed a right hypoglossal nerve (HN) palsy attributed to direct mechanical compression or injury from the C1 lateral mass screw (LMS), which improved following a revision and screw replacement. While HN injury is a known complication of high anterior and anterolateral cervical spine approaches as well as transcondylar screw fixation, this case aims to expand on the limited reports available regarding hypoglossal nerve injury following placement of bicortical C1 LMS. Furthermore, the use of fluoroscopic guidance in addition to anatomic landmarks and triggered electromyography of the tongue are offered as potential solutions to prevent HN injury intraoperatively

A Phase 2 Study of Coltuximab Ravtansine (SAR3419) Monotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

International audienceBackground Long-term disease-free survival in adult patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory, and treatment options are limited for those patients who relapse or fail to respond following initial therapy. We conducted a dose-escalation/expansion phase 2, multicenter, single-arm study to determine the optimal dose of coltuximab ravtansine (SAR3419), an anti-CD19 antibody-drug conjugate, in this setting. Patients and Methods The dose-escalation part of the study determined the selected dose of coltuximab ravtansine for evaluation of efficacy and safety in the dose-expansion phase. Patients received coltuximab ravtansine induction therapy (up to 8 weekly doses); responding patients were eligible for maintenance therapy (biweekly administrations for up to 24 weeks). Three dose levels of coltuximab ravtansine were examined: 55, 70, and 90 mg/m2. The primary endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DOR) and safety. Results A total of 36 patients were treated: 19 during dose escalation; 17 during dose expansion. One dose-limiting toxicity was observed at 90 mg/m2 (grade 3 peripheral motor neuropathy), and therefore 70 mg/m2 was selected for the dose-expansion phase. Five patients discontinued therapy due to adverse events (AEs). The most common AEs were pyrexia, diarrhea, and nausea. Of 17 evaluable patients treated at the selected dose, 4 responded (estimated ORR using Bayesian methodology: 25.47% [80% confidence interval: 14.18-39.6%]); DOR was 1.94 (range: 1-5.6) months. Based on these results, the study was prematurely discontinued. Conclusions Coltuximab ravtansine is well tolerated but is associated with a low clinical response rate in patients with relapsed/refractory AL

Efficient convexity and domination algorithms for fine- and medium-grain hypercube computers

This paper gives hypercube algorithms for some simple problems involving geometric properties of sets of points. The properties considered emphasize aspects of convexity and domination. Efficient algorithms are given for both fine- and medium-grain hypercube computers, including a discussion of implementation, running times and results on an Intel iPSC hypercube, as well as theoretical results. For both serial and parallel computers, sorting plays an important role in geometric algorithms for determining simple properties, often being the dominant component of the running time. Since the time required to sort data on a hypercube computer is still not fully understood, the running times of some of our algorithms for unsorted data are not completely determined. For both the fine- and medium-grain models, we show that faster expected-case running time algorithms are possible for point sets generated randomly. Our algorithms are developed for sets of planar points, with several of them extending to sets of points in spaces of higher dimension.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41352/1/453_2005_Article_BF01758751.pd