Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.

Editorial: «Interventional Neuroradiology: a Neuroscience sub-specialty?¼.

Interventional Neuroradiology (INR) is not bound by the classical limits of a speciality, and is not restricted by standard formats of teaching and education. Open and naturally linked towards neurosciences, INR has become a unique source of novel ideas for research, development and progress allowing new and improved approaches to challenging pathologies resulting in better anatomo-clinical results. Opening INR to Neurosciences is the best way to keep it alive and growing. Anchored in Neuroradiology, at the crossroad of neurosciences, INR will further participate to progress and innovation as it has often been in the past.

«Interventional Neuroradiology: a neuroscience sub-specialty?¼.

Interventional Neuroradiology (INR) is not bound by the classical limits of a specialty, and is not restricted by standard formats of teaching and education. Open and naturally linked towards neurosciences, INR has become a unique source of novel ideas for research, development and progress allowing new and improved approaches to challenging pathologies resulting in better anatomo-clinical results. Opening INR to Neurosciences is the best way to keep it alive and growing. Anchored in Neuroradiology, at the crossroad of neurosciences, INR will further participate to progress and innovation as it has often been in the past.

Doença ateromatosa intracraniana (DAIC) e angioplastia com stent: um seguimento a longo prazo / Intracranial atheromatosis disease (ICAD) and stent supported angioplasty: a long-term follow-up

Objetivos: A doença ateromatosa intracraniana sintomática possui prognóstico desfavorável. A indicação do tratamento endovascular com angioplastia transluminal percutânea (ATP) assistida com stent deve ser realizada de acordo com: a eficácia, segurança, complicações e o risco de re-estenose a longo prazo. Material e Métodos: Estudo realizado entre 1996 e 2008, inclui 28 pacientes com estenoses localizadas na artéria carótida interna (11), artéria basilar (14) e artéria vertebral (5). Todos sintomáticos mesmo sob tratamento anticoagulante e estenose >60% (média de 83,5%). Resultados: Houve uma redução significativa do grau de estenose (inferior a 50%), com estenose média residual de 36,8%. Ocorreram duas complicações, com hematomas de reperfusão(6,6%). No seguimento a longo prazo, encontrouse um único caso de reestenose e nenhum paciente apresentou acidente vascular cerebral isquêmico transitório ou definitivo. Conclusão: O tratamento das estenoses intracranianas com angioplastia assistida com stent é eficiente, com baixo índice de complicação e de reestenose nesta série.

Endovascular coil occlusion of 152 middle cerebral artery aneurysms: initial and midterm angiographic and clinical results.

OBJECT: The object of this study was to evaluate the initial and mid-term angiographic and clinical results after endovascular coil occlusion of middle cerebral artery (MCA) aneurysms at the authors' institution. METHODS: The authors conducted a retrospective analysis of a consecutive series of 152 MCA aneurysms (73 ruptured) treated by endovascular coiling in 140 patients. Angiographic and clinical data at initial and midterm follow-up as well as procedure-related complications were prospectively registered. RESULTS: At discharge, favorable clinical outcomes (Glasgow Outcome Scale score of 1 or 2) were obtained in 89.3% of patients (125/140). Seven patients (5%) were in a vegetative state or had died. Complications were encountered in association with 11.8% of the procedures (18/152), and most (13/18) involved thromboembolic events (which led to permanent ischemia in 4 cases and death in 1). The overall procedure-related mortality rate was 0.7%, and the rates of permanent and transient morbidity were 2.6 and 2%, respectively. At a mean follow-up duration of 4.3 years there had been 4 cases of rebleeding: early rebleeding occurred during the initial postoperative period in 3 cases and later in 1. Total or subtotal occlusion was obtained in 84.2% of aneurysms (128/152). At follow-up, this satisfactory occlusion persisted in 83.3% of aneurysms (110/132) at 1 year posttreatment, 79.5% (89/112) at 3 years, and 80.2% (73/91) at 5 years. CONCLUSIONS: Risks and initial and midterm angiographic and clinical results after endovascular treatment of MCA aneurysms are nearly identical to other locations. Endovascular treatment may thus be proposed as an alternative to surgical clipping at this location. Nevertheless, a longer follow-up period is necessary to determine its efficacy, particularly in cases of unruptured aneurysms.

[Interventional neuroradiology. Current status--future prospects]. / Neuroradiologie interventionnelle. Etat actuel--perspectives d'avenir.

First developed in the 1960s, interventional neuroradiology has vastly improved the management of patients with vascular diseases of the brain and spine, including vascular malformations and stroke. Gradually replacing open-skull neurosurgical approaches, endovascular occlusion of ruptured intracranial aneurysms has improved the post-bleed prognosis. With the increasing number of fortuitously discovered aneurysms, international randomized studies are being organized to determine whether preventive treatment is better than abstention. A wide range of therapeutic strategies are available for brain arteriovenous malformations, including hyperselective embolization, open-skull surgery, radiosurgery, and abstention. The choice depends on multiple parameters, including symptoms, clinical status, the angioarchitecture of the malformation, and the patient's psychology and wishes (...).

Treatment of hemorrhagic intracranial dissections.

OBJECTIVE: To analyze the treatment options in hemorrhagic intracranial dissections. METHODS: This study involved a retrospective review of 27 patients with 29 dissections treated during a 16-year period, mainly by endovascular treatment (EVT). RESULTS: EVT was performed in the acute stage in 12 of the 29 dissections, and occlusion was performed using coils at the dissection site in six dissections and with proximal balloon occlusion in six dissections. Wrapping was performed in one case. In the remaining 16 dissections, which were not treated, mainly for anatomic reasons, three patients died, one from rebleeding. Angiographic follow-up performed in the 13 surviving patients demonstrated an initially misdiagnosed lesion in one and worsening lesions in five that led to delayed EVT in five and surgical clipping in one. One of these dissections, which was located on a dominant vertebral artery, was treated after subsequent rupture using a stent and coils to preserve the patency of the parent vessel. Four ischemic complications related to EVT resulted in a moderate disability in two patients. No rebleeding occurred after EVT, but one patient died because of a poor initial clinical status; the other patients improved. In the 10 patients treated conservatively, four died, three from a poor initial clinical status and one from rebleeding, and six patients had a good clinical outcome. Of the 27 patients, three had rebleeding and one died as a result of that rebleeding. Seventeen patients (63%) had a good recovery, six (22%) had a moderate disability, and four (15%) died. CONCLUSION: EVT provides effective protection against rebleeding. When possible, occlusion with coils at the dissection site is the current method of choice. Another option is parent artery occlusion with balloons, and the use of a stent may preserve vessel permeability in specific cases.

A methodology for validating a 3D imaging modality for brain AVM delineation: application to 3DRA.

A general methodology is described to validate a 3D imaging modality with respect to 2D digital subtracted angiography (DSA) for brain AVMs (BAVM) delineation. It relies on the assessment of the statistical compatibility of the radiosurgical target delineated in 3D with its delineations in 2D. This methodology is demonstrated through a preliminary evaluation of 3D rotational angiography (3DRA). Generally speaking, BAVM delineation cannot be performed on 3DRA alone. However, in our study, 3DRA showed similar performances to DSA for rather easy cases, and even better for three patients. Conversely, three problematic cases are identified and discussed.

Current diagnostic modalities for intracranial aneurysms.

Aneurysm diagnosis has evolved considerably over the last years. Technological advances have brought CT angiography and MR angiography to the forefront of ruptured and nonruptured intracranial aneurysm diagnosis. This article highlights current diagnostic modalities for intracranial aneurysms.

Efficacy and morbidity of arc-therapy radiosurgery for cerebral arteriovenous malformations: a comparison with the natural history.

PURPOSE: To report the results of arc-therapy radiosurgery for cerebral arteriovenous malformation (AVM) and to compare the adverse event rate with the rate expected from the natural history. METHODS AND MATERIALS: We performed a retrospective study of our 118 first patients with a mean follow-up of 46 months (range, 5-105 months). The AVMs had features indicating a poor prognosis at initial presentation and had already been treated by previous embolizations in 88% of patients. The mean volume of the targets was 7.4 cm3 (range, 0.3-28.3 cm3). The mean minimal and maximal dose was 17.7 Gy (range, 10-25 Gy) and 24.5 Gy (range, 17-36 Gy), respectively. RESULTS: The crude and 5-year actuarial rate of cure (total obstruction of the AVM shunt at angiography) was 54% (60 of 112) and 77%, respectively. The only independent prognostic factor of cure was the AVM volume (crude cure rate 67% for <7 cm3 vs. 35% for > or =7 cm3; p = 0.001). No patient died. Transient and permanent complications and hemorrhage occurred in 5%, 1.7%, and 6% of patients, respectively. The annual risk of an adverse event (hemorrhage or complication) was 3.9%. CONCLUSION: The results of our series showed that radiosurgery, performed alone or after prior shrinkage of the AVM by embolization, is both effective and well tolerated, with a rate of adverse events comparable to that expected from the natural history.

Treatment of hemorrhagic intracranial dissections.

OBJECTIVE: To analyze the treatment options in hemorrhagic intracranial dissections. METHODS: This study involved a retrospective review of 27 patients with 29 dissections treated during a 16-year period, mainly by endovascular treatment (EVT). RESULTS: EVT was performed in the acute stage in 12 of the 29 dissections, and occlusion was performed using coils at the dissection site in six dissections and with proximal balloon occlusion in six dissections. Wrapping was performed in one case. In the remaining 16 dissections, which were not treated, mainly for anatomic reasons, three patients died, one from rebleeding. Angiographic follow-up performed in the 13 surviving patients demonstrated an initially misdiagnosed lesion in one and worsening lesions in five that led to delayed EVT in five and surgical clipping in one. One of these dissections, which was located on a dominant vertebral artery, was treated after subsequent rupture using a stent and coils to preserve the patency of the parent vessel. Four ischemic complications related to EVT resulted in a moderate disability in two patients. No rebleeding occurred after EVT, but one patient died because of a poor initial clinical status; the other patients improved. In the 10 patients treated conservatively, four died, three from a poor initial clinical status and one from rebleeding, and six patients had a good clinical outcome. Of the 27 patients, three had rebleeding and one died as a result of that rebleeding. Seventeen patients (63%) had a good recovery, six (22%) had a moderate disability, and four (15%) died. CONCLUSION: EVT provides effective protection against rebleeding. When possible, occlusion with coils at the dissection site is the current method of choice. Another option is parent artery occlusion with balloons, and the use of a stent may preserve vessel permeability in specific cases.

Sarcoplasmic reticulum K(+) channels from human and sheep atrial cells display a specific electro-pharmacological profile.

It has recently been proposed that the Ca(2+) uptake by the SR is inhibited by blocking Cl(-) and/or K(+) movements across this intracellular membrane. We have characterised the functional and pharmacological profile of the SR K(+) channel derived from human and sheep atrial cells. Mammalian atrial SR preparations were subjected to [(3)H]-ryanodine binding assays, SDS-PAGE analysis and channel protein reconstitution into planar lipid bilayers. Assessment of [(3)H]-ryanodine binding on the SR Ca(2+) release channel revealed that it was inhibited by both Ruthenium Red and Mg(2+) with IC(50) values of 4.11 microM and 9.12 m M, respectively. In crude populations as well as in all SR-enriched fractions, activity of K(+) selective channels was recorded. This channel displayed a high conductance value of 193 and 185 pS for human and sheep preparations respectively. Gating and conducting behaviours of this channel were unaffected by the addition of up to 5m M 4-Aminopyridine (4-AP), 100 n M Iberiotoxin (IbTX), 10 microM E-4031 and 30 microM amiodarone. However, 100n M Dendrotoxin (gamma-DTX) largely increase the occurrence of the SR K(+) channel subconducting states without an effect on the main unitary conductance. These results demonstrate that the SR K(+) channel, present in all mammalian atrial SR membranes tested (as assessed by [(3)H]-ryanodine binding and its typical inhibition by ruthenium red and the magnesium), displays different properties than those classically described for cardiac sarcolemmal K(+) channels. Despite the fact that the biophysical properties of the SR K(+) channel are well known, its molecular identity remains to be ascertained.

Endovascular treatment of Hunt and Hess grade IV and V aneuryms.

BACKGROUND AND PURPOSE: Controversy still surrounds the question of when and how to manage cases of subarachnoid hemorrhage of Hunt and Hess grade IV and V aneurysms. Several authors are in favor of surgical treatment, reporting improved clinical outcomes and lower mortality rates. Considering that endovascular procedures are currently being increasingly used to treat aneurysms, we investigated their use in the management of subarachnoid bleeding in a retrospective review of 80 patients. METHODS: Eighty patients were admitted to our hospital between October 1992 and October 1998 with subarachnoid hemorrhage of Hunt and Hess grade IV and V aneurysms. Patients received standard resuscitation treatment, nimodipine to prevent vasospasm, CSF shunt when necessary, and selective occlusion with Guglielmi detachable coil. They were subsequently followed up for at least 1 year. Aneurysm occlusion was monitored with MR angiography and/or angiography at 6 months and at 1 year. RESULTS: Of the 80 patients, 42 (52.5%) did well (Glasgow Outcome Scale score of 1 or 2) (62% of the 56 patients with grade IV and 25% of the 24 patients with grade V aneurysms), seven (8.75%) presented with poor neurologic status (Glasgow Outcome Scale score of 3), and 30 (37.5%) died during the first 6 months (26.7% of the patients with grade IV and 62% of the patients with grade V aneurysms). One patient was lost to follow-up. The main causes of death were consequences of initial bleeding in the patients with grade V aneurysms and vasospasm in the patients with grade IV aneurysms. CONCLUSION: The results are at least as encouraging as the outcomes reported for the surgical series and suggest that early endovascular treatment of high grade hemorrhage is a feasible option, especially because endovascular maneuvers can be performed at any time, even during vasospasm.