Nirav J. Patel

Organization of a United States County System for Comprehensive Acute Stroke Care

Background and Purpose— Organized systems of care have the potential to improve acute stroke care delivery. The current report describes the experience of implementing a county-wide system of spoke-and-hub stroke neurology receiving centers (SNRC) that incorporated several comprehensive stroke center recommendations. Methods— Observational study of patients with suspected stroke of <5 hours duration transported by emergency medical system personnel to an SNRC during the first year of this system. Results— A total of 1360 patients with suspected stroke were evaluated at 9 hub SNRC, of which 553 (40.7%) had a discharge diagnosis of ischemic stroke. Of these 553, intravenous tissue-type plasminogen activator was administered to 110 patients (19.9% of ischemic strokes). Care at the 6 neurointerventional-ready SNRC was a major focus in which 25.1% (99/395) of the patients with ischemic stroke received acute intravenous or intra-arterial reperfusion therapy, and in which provision of such therapies was less common with milder stroke, older age, and Hispanic origin. The door-to-needle time for intravenous tissue-type plasminogen activator met the <60-minute target in only 25% of patients and was 37% longer (P=0.0001) when SNRC were neurointerventional-ready. Conclusions— A stroke system that incorporates features of comprehensive stroke centers can be effectively implemented with substantial rates of acute reperfusion therapy administration. Experiences potentially useful to broader implementation of comprehensive stroke centers are considered.

SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome

Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes.

Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor

The function of melatonin as a protective agent against newborn hypoxic‐ischemic (H‐I) brain injury is not yet well studied, and the mechanisms by which melatonin causes neuroprotection in neurological diseases are still evolving. This study was designed to investigate whether expression of MT1 receptors is reduced in newborn H‐I brain injury and whether the protective action of melatonin is by alterations of the MT1 receptors. We demonstrated that there was significant reduction in MT1 receptors in ischemic brain of mouse pups in vivo following H‐I brain injury and that melatonin offers neuroprotection through upregulation of MT1 receptors. The role of MT1 receptors was further supported by observation of increased mortality in MT1 knockout mice following H‐I brain injury and the reversal of the inhibitory role of melatonin on mitochondrial cell death pathways by the melatonin receptor antagonist, luzindole. These data demonstrate that melatonin mediates its neuroprotective effect in mouse models of newborn H‐I brain injury, at least in part, by the restoration of MT1 receptors, the inhibition of mitochondrial cell death pathways and the suppression of astrocytic and microglial activation.

Angiographic, hemodynamic, and histological changes in an animal model of brain arteriovenous malformations treated with Gamma Knife radiosurgery

OBJECT Brain arteriovenous malformations (AVMs) are a major cause of stroke. Many AVMs are effectively obliterated by stereotactic radiosurgery, but such treatment for lesions larger than 3 cm is not as effective. Understanding the responses to radiosurgery may lead to new biological enhancements to this treatment modality. The aim of the present study was to investigate the hemodynamic, morphological, and histological effects of Gamma Knife surgery (GKS) in an animal model of brain AVM. METHODS An arteriovenous fistula was created by anastomosing the left external jugular vein to the side of the common carotid artery in 64 male Sprague-Dawley rats (weight 345 ± 8.8 g). Six weeks after AVM creation, 32 rats were treated with a single dose of GKS (20 Gy); 32 animals received sham radiation. Eight irradiated and 8 control animals were studied at each specified time point (1, 3, 6, and 12 weeks) for hemodynamic, morphological, and histological characterization. RESULTS Two AVMs showed partial angiographic obliteration at 6 weeks. Angiography revealed complete obliteration in 3 irradiated rats at 12 weeks. Blood flow in the ipsilateral proximal carotid artery (p < 0.001) and arterialized jugular vein (p < 0.05) was significantly lower in the irradiated group than in the control group. The arterialized veins external diameter was significantly smaller in GKS-treated animals at 6 (p < 0.05) and 12 (p < 0.001) weeks. Histological changes included subendothelial cellular proliferation and luminal narrowing in GKS-treated animals. Neither luminal obliteration nor thrombus formation was identified at any of the time points in either irradiated or nonirradiated animals. CONCLUSIONS GKS produced morphological, angiographic, and histological changes in the model of AVM as early as 6 weeks after treatment. These results support the use of this model for studying methods to enhance radiation response in AVMs.

Self-assessment of the training of vascular fellows: survey results of 219 vascular fellows from 2004 through 2007.

Introduction. In an attempt to identify the concerns of vascular fellows regarding their training in vascular surgery, we conducted a survey consisting of 22 questions at an annual national meeting from 2004 to 2007. Methods. The fellows were asked to assess various aspects of their training as excellent, satisfactory, or mixed. Results. 76% were satisfied with their endovascular experience during their fellowship while 82% were satisfied with their experience with open cases. The distribution of non-learning cases was felt to be excellent, satisfactory, or required some or much improvement in: 45%, 44%, 8%, and 2% respectively. However, only 61% felt that their vascular laboratory experience was excellent or satisfactory. Only 36% actually performed the vascular duplex exam, and only 49% felt that they would feel comfortable in managing a vascular laboratory. Conclusions. The results of this Survey suggest that several significant issues are reflected in the minds of vascular trainees.

Spontaneous Recanalization of an Occluded Internal Carotid Artery

Recanalization after extracranial internal carotid artery (ICA) occlusion is a rare phenomenon and the natural history of the disease is largely unknown. There have been few cases reported in the published data, including early recanalization after a cerebrovascular accident (CVA). We report a case of a 74-year-old man who presented with a CVA and a history of multiple CVAs in the past, the last episode being a year ago. Multiple imaging modalities, including duplex scans, computerized tomographic angiograms, and fluoroscopy-guided angiogram of bilateral carotid arteries, showed occlusion of the left ICA in the past. The duplex scan performed 8 months later demonstrated late spontaneous recanalization of the occluded left ICA. The patient underwent successful carotid endarterectomy. The pathophysiology, natural history, and possible surveillance strategy are discussed in this case report.

Stent deployment protocol for optimized real-time visualization during endovascular neurosurgery

Successful application of endovascular neurosurgery depends on high-quality imaging to define the pathology and the devices as they are being deployed. This is especially challenging in the treatment of complex cases, particularly in proximity to the skull base or in patients who have undergone prior endovascular treatment. The authors sought to optimize real-time image guidance using a simple algorithm that can be applied to any existing fluoroscopy system. Exposure management (exposure level, pulse management) and image post-processing parameters (edge enhancement) were modified from traditional fluoroscopy to improve visualization of device position and material density during deployment. Examples include the deployment of coils in small aneurysms, coils in giant aneurysms, the Pipeline embolization device (PED), the Woven EndoBridge (WEB) device, and carotid artery stents. The authors report on the development of the protocol and their experience using representative cases. The stent deployment protocol is an image capture and post-processing algorithm that can be applied to existing fluoroscopy systems to improve real-time visualization of device deployment without hardware modifications. Improved image guidance facilitates aneurysm coil packing and proper positioning and deployment of carotid artery stents, flow diverters, and the WEB device, especially in the context of complex anatomy and an obscured field of view.

Refinement of the Hybrid Neuroendovascular Operating Suite: Current and Future Applications

OBJECTIVE In early-generation hybrid biplane endovascular operating rooms, switching from surgical to angiographic position is cumbersome. In this report, we highlight the unique design of a new hybrid neuroendovascular operating suite that allows surgical access to the head while keeping the biplane system over the lower body of the patient. Current and future hybrid neuroendovascular operating suite applications are discussed. METHODS We collaborated with engineers to implement the following modifications to the design of the angiographic system: translation of the bed toward the feet to allow biplane cerebral imaging in the head-side position and the biplane left-side position; translation of the base of the A-plane C-arm away from the feet to allow increased operator space at the head of the bed and to allow cerebral imaging in both the head-side and left-side positions; use of a specialized boom mount for the display panel to increase mobility; and use of a radiolucent tabletop with attachments for the headrest or radiolucent head clamp system. RESULTS The modified hybrid neuroendovascular operating suite allows for seamless transition between surgical and angiographic positions within seconds, improving workflow efficiency and decreasing procedure time as compared with early-generation hybrid rooms. CONCLUSIONS Combined endovascular and surgical applications are facilitated by co-locating their respective technologies and refining the ergonomics of the system to ease transition between both sets of technologies. In so doing, hybrid neuroendovascular operating suites can be anticipated to improve patient outcomes, generate novel treatment paradigms, and improve time and cost efficiency.

Chapter 63 – Inferior Vena Cava Filter Placement

Your body can develop a blood clot in the vein in your legs which is called a deep vein thrombosis (DVT). This blood clot, or a piece of this clot, can move from your leg to your heart and lungs. A clot in your lung is called a pulmonary embolism. If you have one or two of these problems and cannot take blood thinners, you are a candidate for an inferior vena cava (IVC) filter. The filter will trap any clot or pieces of the clot to keep them from your heart or lungs.

Results of Surgery for Low-Grade Brain Arteriovenous Malformation Resection by Early Career Neurosurgeons: An Observational Study

BACKGROUND For sustainability of arteriovenous malformation (AVM) surgery, results from early career cerebrovascular neurosurgeons (ECCNs) must be acceptably safe. OBJECTIVE To determine whether ECCNs performance of Spetzler-Ponce Class A AVM (SPC A) resection can be acceptably safe. METHODS ECCNs completing a cerebrovascular fellowship (2004-2015) with the last author were included. Inclusion of the ECCN cases occurred if they: had a prospective database of all AVM cases since commencing independent practice; were the primary surgeon on SPC A; and had made the significant management decisions. All SPC A surgical cases from the beginning of the ECCNs independent surgical practice to a maximum of 8 yr were included. An adverse outcome was considered a complication of surgery leading to a new permanent neurological deficit with a last modified Rankin Scale score >1. A cumulative summation (Cusum) plot examined the performance of each surgery. The highest acceptable level of adverse outcomes for the Cusum was 3.3%, derived from the upper 95% confidence interval of the last authors reported series. RESULTS Six ECCNs contributed 110 cases for analysis. The median number of SPC A cases operated by each ECCN was 16.5 (range 4-40). Preoperative embolization was performed in 5 (4.5%). The incidence of adverse outcomes was 1.8% (95% confidence interval: <0.01%-6.8%). At no point during the accumulated series did the combined cohort become unacceptable by the Cusum plot. CONCLUSION ECCNs with appropriate training appointed to large-volume cerebrovascular centers can achieve results for surgery for SPC A that are not appreciably worse than those published from high-volume neurosurgeons.