Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Basilar artery perforator aneurysms: a comparison with non-perforator saccular aneurysms.

BACKGROUND: Basilar artery perforator aneurysms (BAPAs) are rare. There is no systematic description of their presentation, imaging, natural history and outcomes and how these compare to conventional non-perforator aneurysms. Thus, the authors in this study aimed to compare BAPAs to non-perforator aneurysms. METHODS: Cases were identified from a prospective neurovascular database, notes and imaging retrospectively reviewed and compared to a consecutive series of patients with non-perforator aneurysms. Blood volume on CT and vessel wall imaging (VWI) were compared to controls. RESULTS: 9/739 patients with aneurysmal subarachnoid haemorrhage (aSAH) harboured BAPAs. Compared to 103 with aSAH from posterior circulation aneurysms, they were more likely to be male (6/9, p = 0.008), but of equal severity (4/9 poor grade, p = 0.736) and need of CSF drainage (5/9, p = 0.154). Blood volume was similar to controls (30.2 ml vs 26.7 ml, p = 0.716). 6/9 BAPAs were initially missed on CTA. VWI showed thick (2.9 mm ± 2.7) bright enhancement (stalk ratio 1.05 ± 0.12), similar to controls with ruptured aneurysms (0.95 ± 0.23, p = 0.551), and greater than unruptured aneurysms (0.43 ± 0.11, p < 0.001). All were initially managed conservatively. Six thrombosed spontaneously. Three grew and had difficult access with few good endovascular options and were treated through a subtemporal craniotomy without complication. None rebled. At 3 months, all presenting in poor grade were mRS 3-4 and those in good grade mRS 1-2. CONCLUSIONS: Despite their small size, BAPAs present with similar volume SAH, WFNS grade and hydrocephalus to other aneurysms. They are difficult to identify on CTA but enhance strikingly on VWI. The majority thrombosed. Initial conservative management reserving treatment for growth was associated with no rebleeds or complications.

A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging.

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown.

Mechanistic and Synthetic Implications of the Diol-Ritter Reaction: Unexpected Yet Reversible Pathways in the Regioselective Synthesis of Vicinal-Aminoalcohols.

The Ritter reaction of 1,2-diolmonoesters with nitriles to 1- vic-amido-2-esters proceeds through dioxonium and nitrilium cation intermediates. To provide the basis for the reaction mechanism, novel forms of these cations were isolated, characterized, and studied by spectroscopic methods and single crystal X-ray analysis. Ground and transition state energies were determined both experimentally and theoretically. Taken together, these data suggest that the reaction proceeds via rapid formation of the dioxonium cation 9, followed by rate determining yet reversible ring opening by acetonitrile to the corresponding nitrilium cation 10 (computed Δ G⧧ = 24.7 kcal at 50 °C). Rapid, irreversible hydration of the latter affords the corresponding vic-acetamido ester. Controlled addition of H2O to the dioxonium cation 9 in acetonitrile- d3 results in near-quantitative production of deuterated acetamido ester 13a. Kinetics of this conversion (9 to 13a) are biphasic, and the slow phase is ascribed to either direct cation 9 attack by acetamide to form cation 16 via O-alkylation or by reversible ether formation. Deuterium labeling studies suggest O-alkylated cation 16 does not directly isomerize to N-alkylated cation 18; instead, it reverts to vic-amidoester 13a via the nitrilium pathway. Preliminary results indicate high regioselectivity for primary amide formation in the diol-Ritter sequence.

Intravenous Thrombolysis in Patients With Cervical Artery Dissection: A Secondary Analysis of the STOP-CAD Study.

OBJECTIVES: Cervical artery dissection (CeAD) accounts for 25% of ischemic strokes in young adults. This study evaluated the benefits and harms of intravenous thrombolysis (IVT) in patients presenting with spontaneous CeAD and acute ischemic stroke symptoms. METHODS: This analysis used data from the retrospective STOP-CAD study and included patients with spontaneous CeAD who presented within 1 day of acute ischemic stroke symptoms. Patients were dichotomized into those who received IVT and those managed without IVT. We assessed the association between IVT and 90-day functional independence (modified Rankin Scale scores 0-2) and the incidence of symptomatic intracranial hemorrhage (ICH, defined as ICH causing new or worsening neurologic symptoms within 72 hours after CeAD diagnosis). RESULTS: This study included 1,653 patients from the original STOP-CAD cohort of 4,023. The median age was 49 years, and 35.1% were women; 512 (31.0%) received IVT. IVT was associated with 90-day functional independence (adjusted odds ratio [aOR] = 1.67, 95% CI 1.23-2.28, p = 0.001), but not with symptomatic ICH (aOR = 1.52, 95% CI 0.79-2.92, p = 0.215). DISCUSSION: In patients with spontaneous CeAD and suspected ischemic stroke, IVT improved functional outcomes, without increasing symptomatic ICH risk. These findings support current guideline recommendations to consider thrombolysis for otherwise eligible patients with CeAD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IVT significantly increases the probability of 90-day functional independence in patients with CeAD.

Changing the channel: a qualitative analysis of an innovative video intervention to explore resident attitudes towards interprofessional collaboration on a Geriatric Medicine Unit.

Background: Medical learners develop a more positive attitude toward Interprofessional Collaboration (IPC) following Interprofessional Education (IPE) programs. However, IPE is not standardized, and the most effective teaching tool is unclear. The purpose of our study was to develop an IPE teaching tool for medical residents during an inpatient geriatric medicine rotation at an academic hospital, evaluate and explore the impact of the program on resident attitudes towards teamwork, and identify barriers and facilitators to interprofessional collaboration. Methods: An innovative video was developed which simulated a common IPC scenario. Near the start of the rotation, learners watched the video then participated in a facilitated discussion around principles of IPE, using the Canadian Interprofessional Health Collaborative (CIHC) framework, which highlights interprofessional communication, patient-centered care, role clarification, team functioning, collaborative leadership, and interprofessional conflict resolution. At the end of their four-week rotation, focus groups were conducted to explore resident attitudes towards IPE. The Theoretical Domain Framework (TDF) was used for qualitative analysis. Results: Data from 23 participants in five focus groups were analyzed using the TDF framework. Residents were able to identify barriers and facilitators to IPC in five TDF domains: environmental context and resources, social/professional role and identity, knowledge, social influences, and skills. Their observations correlated with the CIHC framework. Conclusion: The use of a scripted video and facilitated group discussion gave insights into residents' attitudes, perceived barriers, and facilitators towards IPC on a geriatric medicine unit. Future research could explore the use of this video intervention in other hospital services where team-based care is important.

Contexte: Les apprenants en médecine développent une attitude plus positive à l'égard de la collaboration interprofessionnelle (CIP) après avoir suivi un programme de formation interprofessionnelle (FIP). Toutefois, la FIP n'est pas standardisée et on ne sait pas quel outil d'enseignement est le plus efficace. Le but de notre étude était d'élaborer un outil de FIP pour les résidents en stage de gériatrie dans un hôpital universitaire, d'évaluer et d'explorer les effets du programme sur les attitudes des résidents à l'égard du travail d'équipe, et de recenser les facteurs qui entravent ou facilitent la collaboration interprofessionnelle. Méthodes: Une capsule vidéo innovante simulant un scénario courant de CIP a été créée. Au début de leur stage de résidence, les apprenants ont regardé la capsule et participé à une discussion animée sur les principes de la CIP, conformément au référentiel du Consortium pancanadien pour l'interprofessionnalisme en santé (CPIS), qui prône notamment la communication interprofessionnelle, les soins centrés sur le patient, la clarification des rôles, le fonctionnement de l'équipe, le leadership collaboratif et la résolution des conflits interprofessionnels. À la fin de leur stage de quatre semaines, des groupes de discussion ont été organisés pour explorer les attitudes des résidents à l'égard de la CIP. Un cadre de domaines théoriques (Theoretical Domains Framework) a été appliqué pour réaliser l'analyse qualitative. Conclusion: Au moyen d'une capsule scénarisée et d'une discussion de groupe dirigée, nous avons pu cerner les attitudes des résidents d'une unité de gériatrie par rapport à la CIP ainsi que leurs perceptions quant aux facteurs qui peuvent l'entraver ou la faciliter. Des travaux futurs pourraient explorer le recours à cette formule d'enseignement de la CIP dans d'autres services hospitaliers où les soins en équipe sont importants.

Endovascular treatment of cranial dural arteriovenous fistulae: a single-centre, 14-year experience and the impact of Onyx on local practise.

INTRODUCTION: Dural arteriovenous fistulae (DAVFs) are a potentially dangerous group of intracranial arteriovenous shunts with significant morbidity and mortality. Treatment has traditionally included transvenous and/or transarterial embolisation, which may be followed by surgical ligation. This study assesses the impact of Onyx on treatment. METHODS: Forty-nine consecutive patients referred for endovascular management of DAVFs between 1994 and 2008 were included in a retrospective, intention-to-treat analysis. DAVFs managed conservatively or purely surgically were excluded. Success rates and complications were compared between patients treated by transvenous, transarterial Onyx and transarterial non-Onyx material embolisation. RESULTS: Fifty-six separate DAVFs were detected in 49 patients. Embolisation of 52 DAVFs was performed or attempted. Transvenous sinus occlusion of ten type I or II DAVFs resulted in cure but was unsuccessful in a single type IV fistula and three of the four indirect carotico-cavernous fistulae treated in this way. Two type I and nine type III/IV were identified in the transarterial, non-Onyx group and three of 11 (27.3%) were cured. Amongst the six type II and 20 type III/IV DAVFs belonging to the transarterial Onyx group, cure was achieved in 17 of 26 (65.4%) rising to 72.7%, considering only those cases where the fistula could be accessed and Onyx was injected. CONCLUSIONS: The introduction of Onyx has improved the endovascular cure rate of DAVFs, particularly types III and IV. Advances in technology have made an endovascular approach the management of choice for the majority of DAVFs requiring treatment. Low complication rates are achievable.

Vessel Wall Imaging After Subarachnoid Hemorrhage in Patients with Multiple Intracranial Aneurysms: A Cautionary Case.

BACKGROUND: Almost 30% of patients with subarachnoid hemorrhage (SAH) are found to have multiple aneurysms. This can potentially present a serious management dilemma when planning treatment. Magnetic resonance imaging vessel wall imaging (VWI) has been proposed as a reliable technique in differentiating between ruptured and unruptured aneurysms in patients with multiple intracranial aneurysms who present with SAH. Expert consensus now supports this as a possible use for the technique. CASE DESCRIPTION: Here we present a patient presenting a particular clinical dilemma with SAH and a left third nerve palsy and transient speech disturbance who had circumferential enhancement in the left larger 3.5-mm irregular middle cerebral artery aneurysm and no detectable enhancement in what was angiographically either a 1.5-mm smooth noncompressive left posterior communicating artery aneurysm or infundibulum, but was proved at surgery to be the culprit aneurysm. CONCLUSION: Although a case of concurrent false positive and false negative in the same patient has not previously been reported, the positive predictive value of VWI for rupture status is known to be much lower than its negative predictive value, and a case like this might be expected to occur in 0.6% of patients. Therefore, whereas VWI is a valuable tool, it should be used in conjunction with, and not in lieu of, traditional indicators of aneurysm rupture.

The Resolution of Oculomotor Nerve Palsy Caused by Unruptured Posterior Communicating Artery Aneurysms: A Cohort Study and Narrative Review.

OBJECTIVE: Recovery of oculomotor nerve palsy after microsurgical and endovascular treatment has been studied in numerous small series of predominantly ruptured aneurysms. Little consideration has been given to the distinction between ruptured and unruptured aneurysms. This study examines the influence of treatment modality on oculomotor palsy recovery as a result of unruptured posterior communicating artery aneurysms. METHODS: Patients who presented between 2003 and 2015 with an oculomotor palsy secondary to an unruptured posterior communicating artery aneurysm were identified from the hospital database. A keyword search for "posterior communicating artery aneurysm" and "oculomotor nerve palsy OR third nerve palsy" using the PubMed database was performed for the narrative review. RESULTS: The cohort study and narrative review identified 15 and 179 eligible patients, respectively. Surgically treated patients in the cohort study did not have a significantly better rate of complete palsy resolution than those who had been coiled (P = 0.08). In the review, clipping of the aneurysm resulted in a higher rate of complete palsy resolution (70.0%; 95% confidence interval [CI], 60.7%-79.3%) than did coiling (46.5%; 95% CI, 36.0%-57.0%). Patients who presented with an aneurysm <7 mm had a higher rate of complete palsy resolution compared with aneurysms >7 mm (68.6%; 95% CI, 57.7%-79.5% vs. 44.3%; 95% CI, 32.7%-55.9%). Patients presenting with a complete palsy (49.4%; 95% CI, 38.6%-60.2%) had a lower rate of recovery than did those with a partial palsy (71.4%; 95% CI, 60.2%-82.6%). CONCLUSIONS: In this narrative review, surgical clipping of unruptured posterior communicating artery aneurysms was associated with a higher rate of associated oculomotor palsy recovery than was endovascular treatment.

Lessons to be learned: a case study approach. Sunshine-induced hypercalcaemia?

A man of 56 years presented with severe hypercalcaemia shortly after returning from a holiday in the sun. The final diagnosis was sarcoidosis. Measurement of the metabolites of vitamin D did not support sunshine exposure as being a contributory factor to the hypercalcaemia. The effects of sarcoid tissue on calcium metabolism are discussed.

Varicella zoster virus central nervous system immune reconstitution inflammatory syndrome presenting in a child.

A HIV-positive child presented with acute onset of right hemiplegia, facial palsy and dysphasia 4 weeks after commencing highly active antiretroviral therapy. Magnetic resonance imaging confirmed a left-sided cerebral infarct. Cerebrospinal fluid polymerase chain reaction was positive for varicella zoster virus. This is the first reported pediatric case of varicella zoster virus-related immune reconstitution inflammatory syndrome involving the central nervous system.