Adverse events during endovascular treatment of ruptured aneurysms: A prospective nationwide study on subarachnoid hemorrhage in Sweden.

Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture. Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome. Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale. Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9). Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.

Adverse events associated with microsurgial treatment for ruptured intracerebral aneurysms: a prospective nationwide study on subarachnoid haemorrhage in Sweden.

BACKGROUND: Adverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome. METHODS: Patients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014-2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale. RESULTS: In total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69). CONCLUSION: Intraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.

The impact of previous health on the mortality after aneurysmal subarachnoid hemorrhage: analysis of a prospective Swedish multicenter study.

PURPOSE: There is an an increasing awareness of the importance of health and lifestyle for stroke diseases like spontaneous subarachnoid hemorrhage (SAH). However, the importance of pre-existing medical conditions for clinical course and mortality after SAH has not been studied. The aim of the present study was to identify pre-existing conditions contributing to mortality after SAH. METHODS: Data were extracted from a Swedish national prospective study on patients with SAH. Variables were defined for age, sex, body mass index (BMI), clinical condition at admission, and for 10 pre-existing medical conditions. Models predicting mortality in three time intervals with all possible subsets of these variables were generated, compared and selected using Akaike's information criterion. RESULTS: 1155 patients with ruptured aneurysms were included. The mortality within 1 week was 7.6%, 1 month 14.3%, and 1 year 18.7%. The most common pre-existing medical conditions were smoking (57.6%) and hypertension (38.7%). The model's best predicting mortality within 1 week and from 1 week to 1 month included only the level of consciousness at admission and age, and these two variables were present in all the models among the top 200 in Akaike score for each time period. The most predictive model for mortality between 1 month and 1 year added previous stroke, diabetes, psychiatric disease, and BMI as predictors. CONCLUSION: Mortality within the first month was best predicted simply by initial level of consciousness and age, while mortality within from 1 month to 1 year was significantly influenced by pre-existing medical conditions.

Third Nerve Palsy Due to Intracranial Aneurysms and Recovery after Endovascular Coiling.

INTRODUCTION: The modality of treatment of third nerve palsy (TNP) associated with intracranial aneurysms remains controversial. While treatment varies with the location of the aneurysm, microsurgical clipping of PComm aneurysms has generally been the traditional choice, with endovascular coiling emerging as a reasonable alternative. METHODS: Patients with TNP due to an intracranial aneurysm who subsequently underwent treatment at a mid-sized Canadian neurosurgical center over a 15-year period (2003-2018) were examined. RESULTS: A total of 616 intracranial aneurysms in 538 patients were treated; the majority underwent endovascular coiling with only 24 patients treated with surgical clipping. Only 37 patients (6.9%) presented with either a partial or complete TNP and underwent endovascular embolization; of these, 17 presented with a SAH secondary to intracranial aneurysm rupture. Aneurysms associated with TNP included PComm (64.9%), terminal ICA (29.7%), proximal MCA (2.7%), and basilar tip (2.7%) aneurysms. In general, smaller aneurysms and earlier treatment were provided for patients for ruptured aneurysms with a shorter mean interval to TNP recovery. In the endovascularly treated cohort initially presenting with TNP, seven presented with a complete TNP and the remaining were partial TNPs. TNP resolved completely in 20 patients (55.1%) and partially in 10 patients (27.0%). Neither time to coiling nor SAH at presentation were significantly associated with the recovery status of TNP. CONCLUSION: Endovascular coil embolization is a viable treatment modality for patients presenting with an associated cranial nerve palsy.

Paralysie du troisième nerf en raison d'un anévrisme intracrânien et rétablissement après la pose d'une bobine endovasculaire. INTRODUCTION: Les modalités de traitement de la paralysie du troisième nerf (PTN) associée aux anévrismes intracrâniens demeurent controversées. Bien que les traitements varient selon l'emplacement de l'anévrisme, le clippage (ou clipping) microchirurgical des anévrismes affectant les artères communicantes postérieures (ACP) est généralement apparu comme le choix le plus courant, la pose d'une bobine endovasculaire (endovascular coiling) ayant aussi émergé comme une option raisonnable. MÉTHODES: Nous nous sommes penchés sur les cas de patients atteints de PTN en raison d'un anévrisme intracrânien qui ont ensuite bénéficié d'un traitement dans un centre neurochirurgical canadien de taille moyenne, et ce, sur une période de 15 ans (2003 à 2018). RÉSULTATS: Au total, 616 anévrismes intracrâniens ayant affecté 538 patients ont été traités. La majorité d'entre eux ont bénéficié de la pose d'une bobine endovasculaire alors que seulement 24 patients ont été traités par clippage microchirurgical. Fait à noter, seuls 37 patients (6,9 %) ont donné à voir une PTN partielle ou totale et ont bénéficié d'une embolisation endovasculaire. De ce nombre, 17 ont donné à voir une hémorragie sous-arachnoïdienne (HSA) consécutive à une rupture d'anévrisme intracrânien. Les anévrismes associés à la PTN ont inclus les ACP (64,9 %), l'artère carotide interne terminale (29,7%), l'artère cérébrale moyenne proximale (2,7 %) et la pointe (tip) de l'artère basilaire (2,7 %). En général, un traitement plus précoce a été proposé aux patients victimes de plus petites ruptures d'anévrisme associées à des délais moyens de rétablissement plus courts à la suite d'une PTN. Dans la cohorte de patients ayant donné à voir des signes de PTN et ayant bénéficié d'un traitement endovasculaire, 7 d'entre eux étaient atteints d'une PTN complète alors que les autres étaient atteints d'une PTN partielle. Les signes de PTN ont fini par disparaître complètement chez 20 patients (55,1 %) et partiellement chez 10 autres (27,0 %). Ni les délais dans la pose d'une bobine endovasculaire ni des signes de HSA au moment de consulter n'ont été notablement associés au processus de rétablissement à la suite d'une PTN. CONCLUSION: En somme, il ressort que l'embolisation endovasculaire au moyen de bobines est une modalité de traitement viable pour les patients présentant une paralysie des nerfs crâniens.

Timing of complications during and after elective endovascular intracranial aneurysm coiling.

OBJECTIVE: To determine the time to complications during and after elective endovascular intracranial aneurysm coiling. METHODS: A retrospective chart review of patients undergoing elective endovascular aneurysm coiling between March 2006 and October 2013 in one large Eastern Canadian Neurointerventional Service was performed. Data regarding the incidence, time and type of complication related to the endovascular coiling procedure and clinical outcome at last follow-up were collected. Patient, aneurysm and operation factors were analyzed to determine any factors associated with complication occurrence. RESULTS: Of the 150 patient procedures analyzed, 16% experienced a coiling-related complication, although none resulted in death. 6.7% of patients experienced an intraoperative complication, of which thromboembolism was the most common type. The majority of the complications were detected in the first 6 hours after reversal of anesthesia, and a small proportion the next morning prior to discharge. Only 3.3% of patients had persistent neurological deficit after the procedure on last follow-up. Duration of the operation demonstrated a strong association with the occurrence of procedure-related complications. CONCLUSION: This study demonstrates that coiling-related complications of elective endovascular coiling tend to occur either intraoperatively or are detected shortly after reversal of anesthesia. Further investigation with a larger cohort may help to guide important preoperative communication with patients and identify a select group of patients who may not necessarily require prolonged admission to hospital for observation.

Biopsy versus partial versus gross total resection in older patients with high-grade glioma: a systematic review and meta-analysis.

BACKGROUND: Optimal extent of surgical resection (EOR) of high-grade gliomas (HGGs) remains uncertain in the elderly given the unclear benefits and potentially higher rates of mortality and morbidity associated with more extensive degrees of resection. METHODS: We undertook a meta-analysis according to a predefined protocol and systematically searched literature databases for reports about HGG EOR. Elderly patients (≥60 y) undergoing biopsy, subtotal resection (STR), and gross total resection (GTR) were compared for the outcome measures of overall survival (OS), postoperative karnofsky performance status (KPS), progression-free survival (PFS), mortality, and morbidity. Treatment effects as pooled estimates, mean differences (MDs), or risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were determined using random effects modeling. RESULTS: A total of 12 607 participants from 34 studies met eligibility criteria, including our current cohort of 211 patients. When comparing overall resection (of any extent) with biopsy, in favor of the resection group were OS (MD 3.88 mo, 95% CI: 2.14-5.62, P < .001), postoperative KPS (MD 10.4, 95% CI: 6.58-14.22, P < .001), PFS (MD 2.44 mo, 95% CI: 1.45-3.43, P < .001), mortality (RR = 0.27, 95% CI: 0.12-0.61, P = .002), and morbidity (RR = 0.82, 95% CI: 0.46-1.46, P = .514) . GTR was significantly superior to STR in terms of OS (MD 3.77 mo, 95% CI: 2.26-5.29, P < .001), postoperative KPS (MD 4.91, 95% CI: 0.91-8.92, P = .016), and PFS (MD 2.21 mo, 95% CI: 1.13-3.3, P < .001) with no difference in mortality (RR = 0.53, 95% CI: 0.05-5.71, P = .600) or morbidity (RR = 0.52, 95% CI: 0.18-1.49, P = .223). CONCLUSIONS: Our findings suggest an upward improvement in survival time, functional recovery, and tumor recurrence rate associated with increasing extents of safe resection. These benefits did not result in higher rates of mortality or morbidity if considered in conjunction with known established safety measures when managing elderly patients harboring HGGs.

A cancer stem cell model for studying brain metastases from primary lung cancer.

BACKGROUND: Brain metastases are most common in adults with lung cancer, predicting uniformly poor patient outcome, with a median survival of only months. Despite their frequency and severity, very little is known about tumorigenesis in brain metastases. METHODS: We applied previously developed primary solid tumor-initiating cell models to the study of brain metastases from the lung to evaluate the presence of a cancer stem cell population. Patient-derived brain metastases (n = 20) and the NCI-H1915 cell line were cultured as stem-enriching tumorspheres. We used in vitro limiting-dilution and sphere-forming assays, as well as intracranial human-mouse xenograft models. To determine genes overexpressed in brain metastasis tumorspheres, we performed comparative transcriptome analysis. All statistical analyses were two-sided. RESULTS: Patient-derived brain metastasis tumorspheres had a mean sphere-forming capacity of 33 spheres/2000 cells (SD = 33.40) and median stem-cell frequency of 1/60 (range = 0-1/141), comparable to that of primary brain tumorspheres (P = .53 and P = .20, respectively). Brain metastases also expressed CD15 and CD133, markers suggestive of a stemlike population. Through intracranial xenotransplantation, brain metastasis tumorspheres were found to recapitulate the original patient tumor heterogeneity. We also identified several genes overexpressed in brain metastasis tumorspheres as statistically significant predictors of poor survival in primary lung cancer. CONCLUSIONS: For the first time, we demonstrate the presence of a stemlike population in brain metastases from the lung. We also show that NCI-H1915 tumorspheres could be useful in studying self-renewal and tumor initiation in brain metastases. Our candidate genes may be essential to metastatic stem cell populations, where pathway interference may be able to transform a uniformly fatal disease into a more localized and treatable one.

Bmi1 marks intermediate precursors during differentiation of human brain tumor initiating cells.

The master regulatory gene Bmi1 modulates key stem cell properties in neural precursor cells (NPCs), and has been implicated in brain tumorigenesis. We previously identified a population of CD133+ brain tumor cells possessing stem cell properties, known as brain tumor initiating cells (BTICs). Here, we characterize the expression and role of Bmi1 in primary minimally cultured human glioblastoma (GBM) patient isolates in CD133+ and CD133- sorted populations. We find that Bmi1 expression is increased in CD133- cells, and Bmi1 protein and transcript expression are highest during intermediate stages of differentiation as CD133+ BTICs lose their CD133 expression. Furthermore, in vitro stem cell assays and Bmi1 knockdown show that Bmi1 contributes to self-renewal in CD133+ populations, but regulates proliferation and cell fate determination in CD133- populations. Finally, we test if our in vitro stem cell assays and Bmi1 expression in BTIC patient isolates are predictive of clinical outcome for GBM patients. Bmi1 expression profiles show a marked elevation in the proneural GBM subtype, and stem cell frequency as assessed by tumor sphere assays correlates with patient outcome.

Surgical exposure of the carotid artery for endovascular interventional procedures.

BACKGROUND: Transfemoral approach for endovascular interventions is not always possible in cases of unfavorable anatomy. We report our experience using a transcervical approach with carotid cut down and direct, controlled puncture of the carotid artery. METHODS: Four patients underwent surgical exposure of the carotid artery for endovascular procedures. One patient had retrograde placement of a stent in the common carotid artery, and three patients had coiling of an intracranial aneurysm. After the endovascular procedure, the sheath was removed and the vessel was closed, under direct visualization. RESULTS: The technique allowed access to extracranial and intracranial lesions. There were no access site complications. There were no access site-related cardiac, systemic, or neurologic events. CONCLUSIONS: Transcervical access with surgical exposure of the carotid artery for direct and controlled vascular puncture is an effective alternative for endovascular extracranial and intracranial procedures in patients in whom the femoral route cannot be used.

Treatment of intracranial aneurysms with hydrogel coated expandable coils.

BACKGROUND: Coiling of intracranial aneurysms with platinum coils sometimes results in relatively poor angiographic results which may be is related to low packing volumes achieved. Hydrogel coated expandable coils (HydroCoil) have been shown to achieve better aneurysm volume filling which may potentially result in lower recanalization rates. Currently there is limited clinical data on their safety and efficacy in aneurysm treatment. METHODS: We analyzed data from a prospectively collected database on patients treated at the Toronto Western Hospital. The analysis included the patients' characteristics, aneurysm size, packing, procedure related complications, recanalization and clinical outcome. RESULTS: Twenty-nine aneurysms were treated with HydroCoils only or in combination with other coils. The average calculated filling of the aneurysm volume was 74-76%. On the immediate post treatment angiograms, 44% of the berry type aneurysms were completely obliterated, 33% had a residual neck and, in 20%, a residual aneurysm was seen. Follow-up imaging was available in 23 cases. On imaging follow-up (from 2 days to 11 months) one dissecting aneurysm had recanalized. There were six technical/medical complications with no clinical consequences. Two clinically significant procedural related complications occurred. CONCLUSIONS: HydroCoils can be used effectively to treat intracranial aneurysms. The volume expansion allows for much greater packing than described for bare platinum coils, which may result in better long-term results. The recanalization rate is low but the limited follow-up does not allow for any conclusion regarding the long-term outcome. The complication rate is similar to larger current series using bare platinum coils.

Limitations and technical considerations of endovascular treatment in neonates with high-flow arteriovenous shunts presenting with congestive heart failure: report of two cases.

CASE REPORT: We report two neonatal patients with high-flow intracranial or cervical arteriovenous (AV) shunts who presented with congestive heart failure and were successfully managed with endovascular treatment. One with vein of Galen malformation with body weight of only 2.0 kg is, to our knowledge, the smallest neonate successfully treated with endovascular treatment. The other neonate is, to our knowledge, the first vertebro-vertebral fistula patient presenting with heart failure and treated successfully with endovascular treatment. CONCLUSION: Even in neonates, endovascular treatment is the procedure of choice for high-flow AV shunts presenting with progressive congestive heart failure resistant to medical management. We discuss limitations and technical considerations of endovascular treatments in small neonates with high-flow AV shunts and congestive heart failure.