Implantation of 3D-Printed Patient-Specific Aneurysm Models into Cadaveric Specimens: A New Training Paradigm to Allow for Improvements in Cerebrovascular Surgery and Research.

AimTo evaluate the feasibility of implanting 3D-printed brain aneurysm model in human cadavers and to assess their utility in neurosurgical research, complex case management/planning, and operative training.MethodsTwo 3D-printed aneurysm models, basilar apex and middle cerebral artery, were generated and implanted in four cadaveric specimens. The aneurysms were implanted at the same anatomical region as the modeled patient. Pterional and orbitozygomatic approaches were done on each specimen. The aneurysm implant, manipulation capabilities, and surgical clipping were evaluated.ResultsThe 3D aneurysm models were successfully implanted to the cadaveric specimens' arterial circulation in all cases. The features of the neck in terms of flexibility and its relationship with other arterial branches allowed for the practice of surgical maneuvering characteristic to aneurysm clipping. Furthermore, the relationship of the aneurysm dome with the surrounding structures allowed for better understanding of the aneurysmal local mass effect. Noticeably, all of these observations were done in a realistic environment provided by our customized embalming model for neurosurgical simulation.Conclusion3D aneurysms models implanted in cadaveric specimens may represent an untapped training method for replicating clip technique; for practicing certain approaches to aneurysms specific to a particular patient; and for improving neurosurgical research

Diagnosis and evaluation of intracranial arteriovenous malformations

BACKGROUND: Ideal management of intracranial arteriovenous malformations (AVMs) remains poorly defined. Decisions regarding management of AVMs are based on the expected natural history of the lesion and risk prediction for peritreatment morbidity. Microsurgical resection, stereotactic radiosurgery, and endovascular embolization alone or in combination are all viable treatment options, each with different risks. The authors attempt to clarify the existing literature's understanding of the natural history of intracranial AVMs, and risk-assessment grading scales for each of the three treatment modalities. METHODS: The authors conducted a literature review of the existing AVM natural history studies and studies that clarify the utility of existing grading scales available for the assessment of peritreatment risk for all three treatment modalities. RESULTS: The authors systematically outline the diagnosis and evaluation of patients with intracranial AVMs and clarify estimation of the expected natural history and predicted risk of treatment for intracranial AVMs. CONCLUSION: AVMs are a heterogenous pathology with three different options for treatment. Accurate assessment of risk of observation and risk of treatment is essential for achieving the best outcome for each patient

Parkinson's disease subtypes in the Oxford Parkinson disease centre (OPDC) discovery cohort

Background: Within Parkinson’s there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Objective: Use a data-driven approach to unravel any heterogeneity in the Parkinson’s phenotype in a well-characterised, population-based incidence cohort. Methods: 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Results: Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Conclusion: Our approach identified several Parkinson’s phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson’s

Implantation of 3D-Printed Patient-Specific Aneurysm Models into Cadaveric Specimens: A New Training Paradigm to Allow for Improvements in Cerebrovascular Surgery and Research

Aim. To evaluate the feasibility of implanting 3D-printed brain aneurysm model in human cadavers and to assess their utility in neurosurgical research, complex case management/planning, and operative training. Methods. Two 3D-printed aneurysm models, basilar apex and middle cerebral artery, were generated and implanted in four cadaveric specimens. The aneurysms were implanted at the same anatomical region as the modeled patient. Pterional and orbitozygomatic approaches were done on each specimen. The aneurysm implant, manipulation capabilities, and surgical clipping were evaluated. Results. The 3D aneurysm models were successfully implanted to the cadaveric specimens’ arterial circulation in all cases. The features of the neck in terms of flexibility and its relationship with other arterial branches allowed for the practice of surgical maneuvering characteristic to aneurysm clipping. Furthermore, the relationship of the aneurysm dome with the surrounding structures allowed for better understanding of the aneurysmal local mass effect. Noticeably, all of these observations were done in a realistic environment provided by our customized embalming model for neurosurgical simulation. Conclusion. 3D aneurysms models implanted in cadaveric specimens may represent an untapped training method for replicating clip technique; for practicing certain approaches to aneurysms specific to a particular patient; and for improving neurosurgical research

The Application of the Novel Grading Scale (Lawton-Young Grading System) to Predict the Outcome of Brain Arteriovenous Malformation

BACKGROUND: A supplementary grading scale (Supplemented Spetzler-Martin grade, Supp-SM) was introduced in 2010 as a refinement of the SM system to improve preoperative risk prediction of brain arteriovenous malformations (AVMs). OBJECTIVE: To determine the ability to predict surgical outcomes using the Supp-SM grading scale. METHODS: This retrospective study was conducted on 200 patients admitted to the Helsinki University Hospital between 2000 and 2014. The validity of the Supp-SM and SM grading systems was compared using the area under the receiver operating characteristic (AUROC) curves, with respect to the change between preoperative and early (3-4 mo) as well as final postoperative modified Rankin Scale (mRS) scores. RESULTS: The performance of the Supp-SM was superior to that of the SM grading scale in the early follow-up (3-4 mo): AUROC = 0.57 (95% confidence interval [CI]: 0.49-0.65) for SM and AUROC = 0.67 (95% CI: 0.60-0.75) for Supp-SM. The Supp-SM performance continued improving over SM at the late follow-up: AUROC = 0.63 (95% CI: 0.55-0.71) for SM and AUROC = 0.70 (95% CI: 0.62-0.77) for Supp-SM. The perforating artery supply, which is not part of either grading system, plays an important role in the early follow-up outcome (P = .008; odds ratio: 2.95; 95% CI: 1.32-6.55) and in the late follow-up outcome (P <.001; odds ratio: 5.89; 95% CI: 2.49-13.91). CONCLUSION: The Supp-SM grading system improves the outcome prediction accuracy and is a feasible alternative to the SMS, even for series with higher proportion of high-grade AVMs. However, perforators play important role on the outcome.Peer reviewe

Constitutively active Notch4 receptor elicits brain arteriovenous malformations through enlargement of capillary-like vessels

Arteriovenous (AV) malformation (AVM) is a devastating condition characterized by focal lesions of enlarged, tangled vessels that shunt blood from arteries directly to veins. AVMs can form anywhere in the body and can cause debilitating ischemia and life-threatening hemorrhagic stroke. The mechanisms that underlie AVM formation remain poorly understood. Here, we examined the cellular and hemodynamic changes at the earliest stages of brain AVM formation by time-lapse two-photon imaging through cranial windows of mice expressing constitutively active Notch4 (Notch4*). AVMs arose from enlargement of preexisting microvessels with capillary diameter and blood flow and no smooth muscle cell coverage. AV shunting began promptly after Notch4* expression in endothelial cells (ECs), accompanied by increased individual EC areas, rather than increased EC number or proliferation. Alterations in Notch signaling in ECs of all vessels, but not arteries alone, affected AVM formation, suggesting that Notch functions in the microvasculature and/or veins to induce AVM. Increased Notch signaling interfered with the normal biological control of hemodynamics, permitting a positive feedback loop of increasing blood flow and vessel diameter and driving focal AVM growth from AV connections with higher blood velocity at the expense of adjacent AV connections with lower velocity. Endothelial expression of constitutively active Notch1 also led to brain AVMs in mice. Our data shed light on cellular and hemodynamic mechanisms underlying AVM pathogenesis elicited by increased Notch signaling in the endothelium.American Heart Association (Grant 0715062Y)Tobacco-Related Disease Research Program (Predoctoral Fellowship 18DT-0009

Optic Foraminotomy for Clipping of Superior Carotid-Ophthalmic Aneurysms

Background: Carotid-ophthalmic aneurysms usually cause visual problems. Its surgical treatment is challenging because of its anatomically close relations to the optic nerve, carotid artery, ophthalmic artery, anterior clinoid process, and cavernous sinus, which hinder direct access. Despite recent technical advancements enabling risk reduction of this complication, postoperative deterioration of visual function remains a significant problem. Therefore, the goal of preserving and/or improving the visual outcome persists as a paramount concern. Objective: We propose optic foraminotomy as an alternative microsurgical technique for dorsal carotid-ophthalmic aneurysms clipping. As a secondary objective, the step by step of that technique and its benefits are compared to the current approach of anterior clinoidectomy. Methods: We present as an example two patients with superior carotid-ophthalmic aneurysms in which the standard pterional craniotomy, transsylvian approach, and optic foraminotomy were performed. Surgical techniques are presented and discussed in detail with the use of skull base dissections, microsurgical images, and original drawings. Results: Extensive opening of the optic canal and optic nerve sheath was successfully achieved in all patients allowing a working angle with the carotid artery for correct visualization of the aneurysm and further clipping. Significant visual acuity improvement occurred in both patients because of decompression of the optic nerve. Conclusion: Optic foraminotomy is an easy and recommended technique for exposing and treating superior carotid-ophthalmic aneurysms and allowing optic nerve decompression during the first stages of the procedure. It shows several advantages over the current anterior clinoidectomy technique regarding surgical exposure and facilitating visual improvement

Bringing high-grade arteriovenous malformations under control: clinical outcomes following multimodality treatment in children.

OBJECTIVE:Brain arteriovenous malformations (AVMs) consist of dysplastic blood vessels with direct arteriovenous shunts that can hemorrhage spontaneously. In children, a higher lifetime hemorrhage risk must be balanced with treatment-related morbidity. The authors describe a collaborative, multimodal strategy resulting in effective and safe treatment of pediatric AVMs. METHODS:A retrospective analysis of a prospectively maintained database was performed in children with treated and nontreated pediatric AVMs at the University of California, San Francisco, from 1998 to 2017. Inclusion criteria were age ≤ 18 years at time of diagnosis and an AVM confirmed by a catheter angiogram. RESULTS:The authors evaluated 189 pediatric patients with AVMs over the study period, including 119 ruptured (63%) and 70 unruptured (37%) AVMs. The mean age at diagnosis was 11.6 ± 4.3 years. With respect to Spetzler-Martin (SM) grade, there were 38 (20.1%) grade I, 40 (21.2%) grade II, 62 (32.8%) grade III, 40 (21.2%) grade IV, and 9 (4.8%) grade V lesions. Six patients were managed conservatively, and 183 patients underwent treatment, including 120 resections, 82 stereotactic radiosurgery (SRS), and 37 endovascular embolizations. Forty-four of 49 (89.8%) high-grade AVMs (SM grade IV or V) were treated. Multiple treatment modalities were used in 29.5% of low-grade and 27.3% of high-grade AVMs. Complete angiographic obliteration was obtained in 73.4% of low-grade lesions (SM grade I-III) and in 45.2% of high-grade lesions. A periprocedural stroke occurred in a single patient (0.5%), and there was 1 treatment-related death. The mean clinical follow-up for the cohort was 4.1 ± 4.6 years, and 96.6% and 84.3% of patients neurologically improved or remained unchanged in the ruptured and unruptured AVM groups following treatment, respectively. There were 16 bleeding events following initiation of AVM treatment (annual rate: 0.02 events per person-year). CONCLUSIONS:Coordinated multidisciplinary evaluation and individualized planning can result in safe and effective treatment of children with AVMs. In particular, it is possible to treat the majority of high-grade AVMs with an acceptable safety profile. Judicious use of multimodality therapy should be limited to appropriately selected patients after thorough team-based discussions to avoid additive morbidity. Future multicenter studies are required to better design predictive models to aid with patient selection for multimodal pediatric care, especially with high-grade AVMs