The first decade of flow diversion for intracranial aneurysms with the Pipeline embolization device.

OBJECTIVE: Flow diverter devices have revolutionized the treatment of intracranial aneurysms (IAs) since their approval in 2011 and have continued to evolve. The devices have been widely adopted across institutions and centers over the past decade; however, long-term follow-up after treatment with the Pipeline embolization device (PED) is not well described in the literature. The authors' institution was among the first to begin using PEDs, allowing them to report their series of patients treated with flow diverters ≥ 10 years ago. In this study, the authors aimed to evaluate the long-term angiographic and clinical outcomes of these patients and review lessons learned along the way. METHODS: The authors performed a retrospective review of their institution's IA database from January 2007 to July 2012. All patients with IAs treated with a PED prior to July 2012 were included. Clinical and angiographic characteristics were extracted. Available angiographic follow-up at 1, 3, 5, and 10 years was reported. RESULTS: A total of 83 patients with 92 aneurysms treated with a PED ≥ 10 years ago were identified and included in the study. The mean aneurysm dome diameter was 9.2 (SD 5.7) mm, the mean aneurysm height was 10.4 (SD 6.8) mm, and the mean neck width was 4.1 (SD 2.4) mm. Only 1 (1.1%) aneurysm was ruptured at presentation. Eight (8.7%) aneurysms were recurrences of previous treatment modalities. The morphology was saccular in 77 (83.7%) aneurysms, fusiform in 14 (15.2%), and blister-like in 1 (1.1%). Among saccular aneurysms, 60 (77.9%) were wide-necked. Seventy-five (81.5%) aneurysms were in the internal carotid artery, 12 (13.0%) were vertebrobasilar, 3 (3.3%) were in the middle cerebral artery, and 2 (2.2%) were in the posterior cerebral artery. Angiographic follow-up at 1, 3, 5, and 10 years was available for 75, 59, 50, and 15 patients, respectively. The complete occlusion rates at 1, 3, 5, and 10 years were 94.7%, 96.6%, 96.0%, and 100%, respectively. The retreatment rates at 1, 3, 5, and 10 years were 8.0%, 6.8%, 8.0%, and 6.7%, respectively. CONCLUSIONS: The authors provide their single-institution series of IA patients treated with a PED ≥ 10 years ago, with the first report of 10-year follow-up for the available patients.

Post-partum posterior reversible encephalopathy syndrome requiring decompressive craniectomy: case report and review of the literature.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon but potentially devastating syndrome if not recognized and treated appropriately. As the name implies, recognition of the condition and proper management may reverse the clinical and radiological findings. However, diagnosis is not always straightforward. We present the case of a 24-year-old female who was 4 days post-partum and presented with headache, neck pain, and new-onset seizures. She had undergone epidural anesthesia during labor, and initial imaging was suggestive of intracranial hypotension versus pachymeningitis. Despite initial conservative therapy including anti-epileptic drugs, magnesium therapy, empiric antibiotics, and Trendelenburg positioning, the patient continued to deteriorate. Follow-up imaging was suggestive of PRES with signs of intracranial hypertension. The patient underwent a decompressive suboccipital craniectomy for refractory and severe PRES and later fully recovered. This case highlights the sometimes difficult diagnosis of PRES, possible association with pregnancy, eclampsia/preeclampsia and/or cerebrospinal fluid drainage, and the rare but life-saving need for decompression in severe cases.

Unexpected Hurdle in the Race: Hypophosphatasia Unmasked by the Female Athlete Triad.

Hypophosphatasia should be considered for any patient who presents with multiple metatarsal stress fractures and a low alkaline phosphatase.

Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial.

BACKGROUND: Diffuse intrinsic pontine glioma is one of the deadliest central nervous system tumours of childhood, with a median overall survival of less than 12 months. Convection-enhanced delivery has been proposed as a means to efficiently deliver therapeutic agents directly into the brainstem while minimising systemic exposure and associated toxic effects. We did this study to evaluate the safety of convection-enhanced delivery of a radioimmunotherapy agent targeting the glioma-associated B7-H3 antigen in children with diffuse intrinsic pontine glioma. METHODS: We did a phase 1, single-arm, single-centre, dose-escalation study at the Memorial Sloan Kettering Cancer Center (New York, NY, USA). Eligible patients were aged 3-21 years and had diffuse intrinsic pontine glioma as diagnosed by consensus of a multidisciplinary paediatric neuro-oncology team; a Lansky (patients <16 years of age) or Karnofsky (patients ≥16 years) performance score of at least 50 at study entry; a minimum weight of 8 kg; and had completed external beam radiation therapy (54·0-59·4 Gy at 1·8 Gy per fraction over 30-33 fractions) at least 4 weeks but no more than 14 weeks before enrolment. Seven dose-escalation cohorts were planned based on standard 3 + 3 rules: patients received a single infusion of 9·25, 18·5, 27·75, 37, 92·5, 120·25, or 148 MBq, respectively, at a concentration of about 37 MBq/mL by convection-enhanced delivery of the radiolabelled antibody [124I]-8H9. The primary endpoint was identification of the maximum tolerated dose. The analysis of the primary endpoint was done in the per-protocol population (patients who received the full planned dose of treatment), and all patients who received any dose of study treatment were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01502917, and is ongoing with an expanded cohort. FINDINGS: From April 5, 2012, to Oct 8, 2016, 28 children were enrolled and treated in the trial, of whom 25 were evaluable for the primary endpoint. The maximum tolerated dose was not reached as no dose-limiting toxicities were observed. One (4%) of 28 patients had treatment-related transient grade 3 hemiparesis and one (4%) had grade 3 skin infection. No treatment-related grade 4 adverse events or deaths occurred. Estimated volumes of distribution (Vd) were linearly dependent on volumes of infusion (Vi) and ranged from 1·5 to 20·1 cm3, with a mean Vd/Vi ratio of 3·4 (SD 1·2). The mean lesion absorbed dose was 0·39 Gy/MBq 124I (SD 0·20). Systemic exposure was negligible, with an average lesion-to-whole body ratio of radiation absorbed dose higher than 1200. INTERPRETATION: Convection-enhanced delivery in the brainstem of children with diffuse intrinsic pontine glioma who have previously received radiation therapy seems to be a rational and safe therapeutic strategy. PET-based dosimetry of the radiolabelled antibody [124I]-8H9 validated the principle of using convection-enhanced delivery in the brain to achieve high intra-lesional dosing with negligible systemic exposure. This therapeutic strategy warrants further development for children with diffuse intrinsic pontine glioma. FUNDING: National Institutes of Health, The Dana Foundation, The Cure Starts Now, Solving Kids' Cancer, The Lyla Nsouli Foundation, Cookies for Kids' Cancer, The Cristian Rivera Foundation, Battle for a Cure, Cole Foundation, Meryl & Charles Witmer Charitable Foundation, Tuesdays with Mitch Charitable Foundation, and Memorial Sloan Kettering Cancer Center.

Structured Reporting for Findings of Spontaneous Intracranial Hypotension on Brain MRI.

A voluntary structured reporting template (based on the Bern score) for brain MRI examinations performed for suspected spontaneous intracranial hypotension (SIH) was associated with an increase in reporting of intracranial MRI findings of SIH and a reduction in discordant assessments with respect to a reference reader.

Supplements, nutrition, and alternative therapies for the treatment of traumatic brain injury.

Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild injury, researchers now look to pharmaceutical supplementation in an attempt to foster success in human clinical trials. Non-traditional therapies, such as acupuncture and even music therapy are being considered to combat the neuropsychiatric symptoms of TBI. In this review, we highlight alternative approaches that have been studied in clinical and pre-clinical studies of TBI, and other related forms of neural injury. The purpose of this review is to stimulate further investigation into novel and innovative approaches that can be used to treat the mechanisms and symptoms of mild TBI.

Elucidating the role of compression waves and impact duration for generating mild traumatic brain injury in rats.

BACKGROUND: In total, 3.8 million concussions occur each year in the US leading to acute functional deficits, but the underlying histopathologic changes that occur are relatively unknown. In order to improve understanding of acute injury mechanisms, appropriately designed pre-clinical models must be utilized. METHODS: The clinical relevance of compression wave injury models revolves around the ability to produce consistent histopathologic deficits. Mild traumatic brain injuries activate similar neuroinflammatory cascades, cell death markers and increases in amyloid precursor protein in both humans and rodents. Humans, however, infrequently succumb to mild traumatic brain injuries and, therefore, the intensity and magnitude of impacts must be inferred. Understanding compression wave properties and mechanical loading could help link the histopathologic deficits seen in rodents to what might be happening in human brains following concussions. RESULTS: While the concept of linking duration and intensity of impact to subsequent histopathologic deficits makes sense, numerical modelling of compression waves has not been performed in this context. In this interdisciplinary work, numerical simulations were performed to study the creation of compression waves in an experimental model. CONCLUSION: This work was conducted in conjunction with a repetitive compression wave injury paradigm in rats in order to better understand how the wave generation correlates with histopathologic deficits.

Adenocarcinoma of the Cecum with Rare Splenic Metastasis.

Isolated splenic metasisis is a rare finding in colorectal carcinoma. We report a case of metastatic cecal adenocarcinoma to the spleen. In spring 2011, a 53-yearold woman underwent en bloc right hemicolectomy with partial omentectomy. The tumor was Stage III pT3 pN2a M0. She received four months of modified FOLFOX6 chemotherapy and one month of capecitabine. In spring 2012, a PET/CT revealed a low attenuation focus in the spleen consistent with metastatic adenocarcinoma, so she underwent splenectomy. Additional imaging has revealed no disease recurrence. There are only a small number of case reports for isolated splenic metastasis; thus, no standardized treatment course has been developed.

Stereotactic radiosurgery planning based on time-resolved CTA for arteriovenous malformation: a case report and review of the literature.

Stereotactic radiosurgery has long been recognized as the optimal form of management for high-grade arteriovenous malformations not amenable to surgical resection. Radiosurgical plans have generally relied upon the integration of stereotactic magnetic resonance angiography (MRA), standard contrast-enhanced magnetic resonance imaging (MRI), or computed tomography angiography (CTA) with biplane digital subtraction angiography (DSA). Current options are disadvantageous in that catheter-based biplane DSA is an invasive test associated with a small risk of complications and perhaps more importantly, the two-dimensional nature of DSA is an inherent limitation in creating radiosurgical contours. The necessity of multiple scans to create DSA contours for radiosurgical planning puts patients at increased risk. Furthermore, the inability to import two-dimensional plans into some radiosurgery programs, such as Cyberknife TPS, limits treatment options for patients. Defining the nidus itself is sometimes difficult in any of the traditional modalities as all draining veins and feeding arteries are included in the images. This sometimes necessitates targeting a larger volume, than strictly necessary, with stereotactic radiosurgery for treatment of the AVM. In this case report, we show the ability to use a less-invasive and three-dimensional form of angiography based on time-lapsed CTA (4D-CTA) rather than traditional DSA for radiosurgical planning. 4D-CTA may allow generation of a series of images, which can show the flow of contrast through the AVM. A review of these series may allow the surgeon to pick and use a volume set that best outlines the nidus with least interference from feeding arteries or draining veins. In addition, 4D-CTA scans can be uploaded into radiosurgery programs and allow three-dimensional targeting. This is the first reported case demonstrating the use of a 4D CTA and an MRI to delineate the AVM nidus for Gamma Knife radiosurgery, with complete obliteration of the nidus over time and subsequent management of associated radiation necrosis with bevacizumab.

Osteopathia striata with cranial sclerosis (OSCS): review of the literature and case report demonstrating challenges of spinal fusion after trauma.

Osteopathia striata with cranial sclerosis (OSCS) is a rare but well-described pathology characterized by abnormalities in bone deposition in the axial and cranial skeleton as well as other abnormalities and associated deficits. These skeletal abnormalities can lead to significant intra-operative challenges for the surgeon and influence outcomes for the patient. In this report, we present a case of a patient with OSCS who was involved in a traumatic motor vehicle crash and underwent posterior cervico-thoracic fusion for a T4 chance fracture. Bony abnormalities in the cervico-thoracic spine presented a significant operative challenge due to alterations in bony anatomy and bone architecture. This case serves as an example of the challenges that the spine surgeon faces when dealing with OSCS, and highlights the differences between OSCS and commoner skeletal hyperplasias such as osteopetrosis.

Alzheimer's disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities.

BACKGROUND: Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE) have long been recognized as sharing some similar neuropathological features, mainly the presence of neurofibrilary tangles and hyperphosphorylated tau, but have generally been described as distinct entities. Evidence indicates that neurotrauma increases the risk of developing dementia and accelerates the progression of disease. Findings are emerging that CTE and AD may be present in the same patients. CLINICAL PRESENTATION: This study presents a series of previously unpublished cases, with one case demonstrating possible neurotrauma-related AD, one pure CTE, and an example of a case exhibiting features of both AD and CTE. The future significance of this work lies not only in the confirmation of AD-CTE co-existence, but, more importantly, ways of generating a hypothesis about the possibility that CTE may accelerate AD development. Understanding the relationship between neurotrauma and neurodegenerative disease will help elucidate how distinct disease entities can co-exist in the same patient. It will ultimately require the use of pre-clinical animal models and repeat injury paradigms to investigate clinically relevant injury mechanisms. These models should produce a CTE-like phenotype that must be both neuropathologically and behaviourally similar to human disease. CONCLUSION: This case series and review of the literature presents a discussion of AD and CTE in the context of neurotrauma. It highlights recent work from repetitive neurotrauma models with an emphasis on those exhibiting a CTE-like phenotype. Potential mechanisms of interest shared amongst AD and CTE are briefly addressed and future experiments are advocated for to enhance understanding of CTE pathophysiology and the relationship between CTE and AD.

Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review.

Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes including vasospasm, cognitive decline, and even death. Currently, treatment options are limited for this potentially life threatening injury. Recent evidence suggests that neuroinflammation plays a critical role in injury expansion and brain damage. Red blood cell breakdown products can lead to the release of inflammatory cytokines that trigger vasospasm and tissue injury. Preclinical models have been used successfully to improve understanding about neuroinflammation following aneurysmal rupture. The focus of this review is to provide an overview of how neuroinflammation relates to secondary outcomes such as vasospasm after aneurysmal rupture and to critically discuss pharmaceutical agents that warrant further investigation for the treatment of subarachnoid hemorrhage. We provide a concise overview of the neuroinflammatory pathways that are upregulated following aneurysmal rupture and how these pathways correlate to long-term outcomes. Treatment of aneurysm rupture is limited and few pharmaceutical drugs are available. Through improved understanding of biochemical mechanisms of injury, novel treatment solutions are being developed that target neuroinflammation. In the final sections of this review, we highlight a few of these novel treatment approaches and emphasize why targeting neuroinflammation following aneurysmal subarachnoid hemorrhage may improve patient care. We encourage ongoing research into the pathophysiology of aneurysmal subarachnoid hemorrhage, especially in regards to neuroinflammatory cascades and the translation to randomized clinical trials.

Irrigated greywater in an urban sub-division as a potential source of metals to soil, groundwater and surface water.

Increased water demands in dry countries such as Australia, have led to increased adoption of various water reuse practices. Irrigation of greywater (all water discharged from the bathrooms, laundry and kitchen apart from toilet waste) is seen as a potential means of easing water demands; however, there is limited knowledge of how greywater irrigation impacts terrestrial and aquatic environments. This study compared four greywater irrigated residential lots to adjacent non-irrigated lots that acted as controls. Accumulation and potential impacts of metals in soil, groundwater and surface water, as a result of greywater irrigation, were assessed by comparing measured concentrations to national and international guidelines. Greywater increased concentrations of some metals in irrigated soil and resulted in As, B, Cr and Cu exceeding guidelines after only four years of irrigation. Movement of metals from the irrigation areas resulted in metal concentrations in groundwater (Al, As, Cr, Cu, Fe, Mn, Ni and Zn) and surface water (Cu, Fe and Zn) exceeding environmental quality guidelines again within four years. These results are unlikely to be universally applicable but indicate the need to consider metals in greywater in order to minimize potential adverse environmental effects from greywater irrigation.

National utilization patterns of Mohs micrographic surgery for invasive melanoma and melanoma in situ.

BACKGROUND: Although wide local excision continues to be commonly used for melanoma treatment, Mohs micrographic surgery (MMS) for the treatment of melanomas remains controversial. OBJECTIVE: We sought to determine national utilization patterns for MMS in the treatment of invasive melanoma and melanoma in situ. METHODS: A retrospective analysis of patients receiving surgical excision (MMS or wide local excision) for the treatment of invasive melanoma and melanoma in situ was performed using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. RESULTS: A total of 195,768 melanomas were diagnosed from 2003 through 2009 from the 17 SEER registries. Utilization of MMS for invasive melanoma and melanoma in situ increased by 60% from 2003 to 2008. Of all SEER-captured lesions treated by surgical excision in this time period, 3.5% (6872) were excised by MMS. LIMITATIONS: Patient insurance status, physician reimbursement practices, and health care provider type were not addressed in this article. CONCLUSION: Use of MMS for melanoma appears to be increasing. Future studies should explore whether this is associated with better outcomes.

Continuous Intrathecal Medication Delivery With the IRRA flow Catheter: Pearls and Early Experience.

BACKGROUND AND OBJECTIVES: Intrathecal (IT) medications are routinely introduced through catheterization of the intraventricular space or subarachnoid space. There has been sporadic use of IT medications delivered directly to the ventricle either by intermittent injection through an external ventricular drain (EVD) or by an Ommaya reservoir with a ventricular catheter. IT medication delivery through EVD has many drawbacks, including the necessary opening of a sterile system, delivery of medication in a bolus form, and requirements to clamp the EVD after medication delivery. Despite these setbacks, IT medications delivered through EVD have been used across a wide range of applications, including antibiotic delivery treatment of vasospasm with nicardipine and delivery of tissue plasminogen activator. METHODS: We used a newly developed active fluid exchange device to treat various severe conditions involved in the cerebral ventricles. Here, we present our treatment protocols and advice on the techniques related to successful active fluid exchange therapy. RESULTS: Seventy patients have been treated with our system with various conditions, including subarachnoid hemorrhage, intraventricular hemorrhage, ventriculitis, and cerebral abscess. Total complication rate was 14% with only 1 catheter occlusion and low rates of hemorrhage, infection, and spinal fluid leak. CONCLUSION: Current continuous IT medication dosages and protocols are based on reports and consensus statements evaluating intermittent instillation of medication boluses. The pharmacokinetics of continuous dosing and the therapeutic and safety profiles of the medications need to be studied in a prospective manner to evaluate the true optimal dosing standards. Furthermore, the ability to deliver continuous, sterile medications directly through an IT route will open new avenues of pharmacotherapy that were previously closed. This report serves as a basic guide for the safe and effective use of the IRRA flow active fluid exchange catheter to deliver IT medications.

Ecotoxicity threshold values for 4-hydroxychlorothalonil, carbendazim, dimethoate and methoxyfenozide in fresh and marine waters: Part 1. Derivation of threshold values.

Pesticide active ingredients are frequently detected in the rivers, creeks, wetlands, estuaries, and marine waters of the Great Barrier Reef (GBR) region and are one of the main contributors to poor water quality. Pesticide concentrations detected in the environment through water quality monitoring programs can be compared against estimates of ecologically "safe" concentrations (i.e., water quality guidelines) to assess the potential hazard and risk posed to aquatic ecosystems. Water quality guidelines are also required to estimate the aquatic risk posed by pesticide mixtures, which is used for the Reef 2050 Water Quality Improvement Plan pesticide target. Seventy-four pesticide active ingredients and their degradates are frequently detected in GBR catchment waterways, however many do not have water quality guidelines in the Australian and New Zealand Guidelines for Fresh and Marine Water Quality. The current study derives ecotoxicity threshold values (ETVs) as unendorsed guideline values for active ingredients in two fungicides (4-hydroxychlorothalonil (fungicide degradate) and carbendazim) and two insecticides (dimethoate and methoxyfenozide) that are commonly detected in GBR catchment waterways. The proposed ETVs have been derived using species sensitivity distributions, as recommended in the Australian and New Zealand nationally endorsed method for deriving water quality guidelines for aquatic ecosystem protection. Four ETVs were derived for each chemical with values that should theoretically protect 99, 95, 90 and 80 % of species (i.e., PC99, PC95, PC90, PC80, respectively). The PC99 and PC95 values for 4-hydroxychlorothalonil, carbendazim, dimethoate and methoxyfenozide were 0.49 µg/L and 4 µg/L, 0.029 µg/L and 0.45 µg/L, 0.11 µg/L and 5.8 µg/L and 0.19 µg/L and 2 µg/L, respectively. The ETVs will be used in an ecological hazard and risk assessment across GBR waterways in part two of this study. The ETVs can also be used to assess potential risk across Australia and internationally where monitoring data are available.

An International, Multicenter Feasibility Study on Active and Continuous Irrigation With Cerebrospinal Fluid Exchange for Improving Outcomes in Cerebral Ventriculitis.

BACKGROUND AND OBJECTIVES: Cerebral ventriculitis remains a challenging neurosurgical condition because of poor outcomes including mortality rates of nearly 80% and a prolonged course of treatment in survivors. Despite current conventional management, outcomes in some cases remain unsatisfactory, with no definitive therapeutic guidelines. This feasibility study aims to explore the use of a novel active, continuous irrigation and drainage system (IRRAflow [IRRAS AB]) combined with intraventricular drug delivery for patients with cerebral ventriculitis. METHODS: We conducted a multicenter, international, retrospective study of patients with ventriculitis who were treated with use of the IRRAflow system. Data collected included patient demographics, comorbidities, admission Glasgow Coma Scale score, baseline modified Rankin Scale (mRS) score, and imaging findings. Catheter occlusions, infections, and shunt placement were recorded for outcome assessment, along with discharge mRS scores and in-hospital deaths. RESULTS: Four centers contributed data for a total of 21 patients who had IRRAflow placement for treatment of ventriculitis. Thirteen (61.9%) were men (mean age = 49.8 ± 14.87 years). The median baseline mRS score was 1. The median Glasgow Coma Scale score at admission was 13. The etiology of ventriculitis was iatrogenic in 12 (57.1%) patients and secondary to an abscess in 9 (42.9%). No cases reported hemorrhage or failure of IRRAflow placement. Antibiotics were administered through the IRRAflow system in 13 (61.9%) cases in addition to systemic dosing. Sixteen (76.2%) patients had significant clinical improvement and resolution of ventriculitis. Seven (33.3%) patients required shunt placement after resolution because of persistent hydrocephalus. There were 6 (28.6%) in-hospital deaths. CONCLUSION: The use of active irrigation with drainage for continuous delivery of intraventricular irrigation fluid with antibiotics led to dramatically low mortality. In our case series, it led to a marked improvement in neurological status, imaging findings, and cerebrospinal fluid profiles, making it a technically feasible and safe treatment for ventriculitis.

A propensity score-matched comparative study of balloon guide catheters versus conventional guide catheters for concurrent mechanical thrombectomy with carotid stenting in tandem strokes: comparison of first pass effect, symptomatic intracranial hemorrhage, and 90-day functional outcomes.

BACKGROUND: Extensive clot burden in tandem strokes accounts for poor mechanical thrombectomy (MT) outcomes. Several studies have shown the benefit of balloon guide catheters (BGCs) in MT and carotid artery stenting. OBJECTIVE: In view of this potential benefit, to investigate the safety and effectiveness of proximal flow arrest using a BGC during concurrent MT and carotid revascularization for tandem stroke treatment in a comparative, propensity score-matched (PSM) study. METHODS: Patients with a tandem stroke identified from our endovascular database were dichotomized into groups treated with BGCs versus conventional guide catheters. One-to-one PSM adjustment for baseline demographics and treatment selection bias using nearest-neighbor matching was performed. Patient demographics, presentation characteristics, and procedural details were recorded. Outcomes assessed were final modified Thrombolysis in Cerebral Infarction (mTICI) grade, periprocedural symptomatic intracranial hemorrhage (sICH) rate, in-hospital mortality, and 90-day modified Rankin Scale (mRS) score. Mann-Whitney U test and multivariate logistic regression were performed to compare procedural parameters and clinical outcomes. RESULTS: Concurrent carotid revascularization (stenting with/without angioplasty) and MT was performed in 125 cases (BGC: 85; no BGC: 40). After PSM (40 patients/group), the BGC group had a significantly shorter procedure duration (77.9 vs 61.5 min; OR=0.996; P=0.006), lower discharge National Institutes of Health Stroke Scale score (8.0 vs 11.0; OR=0.987; P=0.042), and higher odds of 90-day mRS 0-2 score (52.3% vs 27.5%; OR=0.34; P=0.040). On multivariate regression, the BGC group had a significantly higher first pass effect rate (mTICI 2b or 3)(OR=1.115, 95% CI 1.015 to 1.432; P=0.013) and lower periprocedural sICH rate (OR=0.615, 95% CI 0.406 to 0.932; P=0.025). No difference in in-hospital mortality was observed (OR=1.591, 95% CI 0.976 to 2.593; P=0.067). CONCLUSION: BGCs used for concurrent MT-carotid revascularization with flow arrest were safe and resulted in superior clinical and angiographic outcomes in patients with a tandem stroke.

Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke.

BACKGROUND AND PURPOSE: Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator reperfusion in aged rats. METHODS: Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18- to 20-month-old female Sprague-Dawley rats using an autologous blood clot with tissue plasminogen activator-mediated reperfusion. Bryostatin was administered at 6 hours post-MCAO, then at 3, 6, 9, 12, 15, and 18 days after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 days after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 days post-MCAO. Histological assessment of PKC isozymes was performed at 24 hours post-MCAO. RESULTS: Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 days. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 days post-MCAO. Changes in αPKC expression and εPKC expression in neurons were noted in bryostatin-treated rats at 24 hours post-MCAO. CONCLUSIONS: Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome after MCAO.

Neuroprotection for ischemic stroke: moving past shortcomings and identifying promising directions.

The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with preliminary success of ongoing clinical trials for anti-inflammatory compounds such as minocycline. We review the role of inflammation in stroke and in particular, the role of inflammatory cell recruitment and macrophage phenotype in the inflammatory process. Emerging evidence indicates an increasing role of neuro-immune crosstalk, which has led to increased interest in identification of peripheral biomarkers indicative of neural injury. It is our hope that identification and investigation of factors influencing stroke pathophysiology may lead to improved therapeutics.