Direct Versus Indirect Revascularization for Moyamoya: a Large Multicenter Study.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.

Increasing fire and the decline of fire adapted black spruce in the boreal forest.

Intensifying wildfire activity and climate change can drive rapid forest compositional shifts. In boreal North America, black spruce shapes forest flammability and depends on fire for regeneration. This relationship has helped black spruce maintain its dominance through much of the Holocene. However, with climate change and more frequent and severe fires, shifts away from black spruce dominance to broadleaf or pine species are emerging, with implications for ecosystem functions including carbon sequestration, water and energy fluxes, and wildlife habitat. Here, we predict that such reductions in black spruce after fire may already be widespread given current trends in climate and fire. To test this, we synthesize data from 1,538 field sites across boreal North America to evaluate compositional changes in tree species following 58 recent fires (1989 to 2014). While black spruce was resilient following most fires (62%), loss of resilience was common, and spruce regeneration failed completely in 18% of 1,140 black spruce sites. In contrast, postfire regeneration never failed in forests dominated by jack pine, which also possesses an aerial seed bank, or broad-leaved trees. More complete combustion of the soil organic layer, which often occurs in better-drained landscape positions and in dryer duff, promoted compositional changes throughout boreal North America. Forests in western North America, however, were more vulnerable to change due to greater long-term climate moisture deficits. While we find considerable remaining resilience in black spruce forests, predicted increases in climate moisture deficits and fire activity will erode this resilience, pushing the system toward a tipping point that has not been crossed in several thousand years.

Oculomotor nerve cavernous malformation: case report and operative video.

BACKGROUND: Cavernous malformations (CMs) are clusters of thin-walled sinusoidal vessels without well-defined walls. Though they can occur anywhere in the neuroaxis, cranial nerve (CN) CMs are rare. METHOD: We report a 47-year-old male with gradual CN III palsy. Initial imaging showed no significant findings, but a follow-up MRI revealed a growing lesion along CN III. Intraoperative findings confirmed a CN III CM. Diagnosing and treating CN III CM are complex. Radiological findings lack specificity, requiring consideration of various diagnoses for patients with isolated CN III palsy and abnormal radiological findings. CONCLUSION: Surgery is the gold standard, aiming for complete lesion removal while minimizing neurological complications.

Comparative Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke Patients with ASPECTS 2-3 vs. 4-5.

BACKGROUND: The influence of Alberta Stroke Program Early CT Score (ASPECTS) on outcomes following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients with low ASPECTS remains unknown. In this study, we compared the outcomes of AIS patients treated with MT for large vessel occlusion (LVO) categorized by ASPECTS value. METHODS: We conducted a retrospective analysis involving 305 patients with AIS caused by LVO, defined as the occlusion of the internal carotid artery and/or the M1 segments of the middle cerebral artery, stratified into two groups: ASPECTS 2-3 and 4-5. The primary outcome was favorable outcome defined as a 90-day modified Rankin Scale (mRS) score of 0-3. Secondary outcomes were 90-day mRS 0-2, 90-day mortality, any intracerebral hemorrhage (ICH), and symptomatic ICH (sICH). We performed multivariable logistic regression analysis to evaluate the impact of ASPECTS 2-3 vs. 4-5 on outcomes. RESULTS: Fifty-nine patients (19.3%) had ASPECTS 2-3 and 246 (80.7%) had ASPECTS 4-5. Favorable outcomes showed no significant difference between the two groups (adjusted odds ratio [aOR]= 1.13, 95% confidence interval [CI]: 0.52-2.41, p=0.80). There were also no significant differences in 90-day mRS 0-2 (aOR= 1.65, 95% CI: 0.66-3.99, p=0.30), 90-day mortality (aOR= 1.14, 95% CI: 0.58-2.20, p=0.70), any ICH (aOR= 0.54, 95% CI: 0.28-1.00, p=0.06), and sICH (aOR= 0.70, 95% CI: 0.27-1.63, p = 0.40) between the groups. CONCLUSIONS: AIS patients with LVO undergoing MT with ASPECTS 2-3 had similar outcomes compared to ASPECTS 4-5.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Predictors of Clinical and Radiographic Failure from 636 Embolizations.

Background Knowledge regarding predictors of clinical and radiographic failures of middle meningeal artery (MMA) embolization (MMAE) treatment for chronic subdural hematoma (CSDH) is limited. Purpose To identify predictors of MMAE treatment failure for CSDH. Materials and Methods In this retrospective study, consecutive patients who underwent MMAE for CSDH from February 2018 to April 2022 at 13 U.S. centers were included. Clinical failure was defined as hematoma reaccumulation and/or neurologic deterioration requiring rescue surgery. Radiographic failure was defined as a maximal hematoma thickness reduction less than 50% at last imaging (minimum 2 weeks of head CT follow-up). Multivariable logistic regression models were constructed to identify independent failure predictors, controlling for age, sex, concurrent surgical evacuation, midline shift, hematoma thickness, and pretreatment baseline antiplatelet and anticoagulation therapy. Results Overall, 530 patients (mean age, 71.9 years ± 12.8 [SD]; 386 men; 106 with bilateral lesions) underwent 636 MMAE procedures. At presentation, the median CSDH thickness was 15 mm and 31.3% (166 of 530) and 21.7% (115 of 530) of patients were receiving antiplatelet and anticoagulation medications, respectively. Clinical failure occurred in 36 of 530 patients (6.8%, over a median follow-up of 4.1 months) and radiographic failure occurred in 26.3% (137 of 522) of procedures. At multivariable analysis, independent predictors of clinical failure were pretreatment anticoagulation therapy (odds ratio [OR], 3.23; P = .007) and an MMA diameter less than 1.5 mm (OR, 2.52; P = .027), while liquid embolic agents were associated with nonfailure (OR, 0.32; P = .011). For radiographic failure, female sex (OR, 0.36; P = .001), concurrent surgical evacuation (OR, 0.43; P = .009), and a longer imaging follow-up time were associated with nonfailure. Conversely, MMA diameter less than 1.5 mm (OR, 1.7; P = .044), midline shift (OR, 1.1; P = .02), and superselective MMA catheterization (without targeting the main MMA trunk) (OR, 2; P = .029) were associated with radiographic failure. Sensitivity analyses retained these associations. Conclusion Multiple independent predictors of failure of MMAE treatment for chronic subdural hematomas were identified, with small diameter (<1.5 mm) being the only factor independently associated with both clinical and radiographic failures. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chaudhary and Gemmete in this issue.

Active upper aerodigestive tract hemorrhage in patients with head and neck cancers: the "dot-in-sludge" sign.

Active extravasation into the upper aerodigestive tract is a dramatic and potentially life-threatening complication in patients with head and neck cancers. It prompts presentation to the emergency room and subsequent urgent imaging to identify the source of hemorrhage. Imaging of these patients may be complicated by treatment-altered anatomy, posing a challenge to the emergency radiologist who needs to rapidly identify the presence of active hemorrhage and the potential source vessel. This retrospective review summarizes the clinical and imaging findings of 6 oropharyngeal and oral cavity squamous cell cancer (SCC) patients with active upper aerodigestive tract hemorrhage. Most patients had advanced stage disease and prior radiation therapy. All CECT or CTA exams on presentation demonstrated the "dot-in-sludge" sign of active extravasation, as demonstrated by a "dot" of avidly enhancing extravasated contrast material layered against a background "sludge" of non-enhancing debris in the lumen of the upper aerodigestive tract. Common sources of hemorrhage included the lingual, facial, and superior thyroidal arteries. Familiarity with these findings will help radiologists increase their accuracy and confidence in interpreting these urgent, complex examinations.

Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred.

INTRODUCTION: Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations. METHODS: A genetic association study was conducted to examine ADAD AAO in 340 individuals with the PSEN1 E280A mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early-onset AD study and four late-onset AD studies. RESULTS: 13 variants had p<1×10-7 or p<1×10-5 with replication including three independent loci with candidate associations with clusterin including near CLU. Other suggestive associations were identified in or near HS3ST1, HSPG2, ACE, LRP1B, TSPAN10, and TSPAN14. DISCUSSION: Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate, and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforces their potentially impactful role.

Causal Associations Between Modifiable Risk Factors and the Alzheimer's Phenome.

OBJECTIVE: The purpose of this study was to infer causal relationships between 22 previously reported risk factors for Alzheimer's disease (AD) and the "AD phenome": AD, AD age of onset (AAOS), hippocampal volume, cortical surface area and thickness, cerebrospinal fluid (CSF) levels of amyloid-ß (Aß42 ), tau, and ptau181 , and the neuropathological burden of neuritic plaques, neurofibrillary tangles (NFTs), and vascular brain injury (VBI). METHODS: Polygenic risk scores (PRS) for the 22 risk factors were computed in 26,431 AD cases/controls and the association with AD was evaluated using logistic regression. Two-sample Mendelian randomization (MR) was used to infer the causal effect of risk factors on the AD phenome. RESULTS: PRS for increased education and diastolic blood pressure were associated with reduced risk for AD. MR indicated that only education was causally associated with reduced risk of AD, delayed AAOS, and increased cortical surface area and thickness. Total- and LDL-cholesterol levels were causally associated with increased neuritic plaque burden, although the effects were driven by single nucleotide polymorphisms (SNPs) within the APOE locus. Diastolic blood pressure and pulse pressure are causally associated with increased risk of VBI. Furthermore, total cholesterol was associated with decreased hippocampal volume; smoking initiation with decreased cortical thickness; type 2 diabetes with an earlier AAOS; and sleep duration with increased cortical thickness. INTERPRETATION: Our comprehensive examination of the genetic evidence for the causal relationships between previously reported risk factors in AD using PRS and MR supports a causal role for education, blood pressure, cholesterol levels, smoking, and diabetes with the AD phenome. ANN NEUROL 2021;89:54-65.

Genome-wide association study and functional validation implicates JADE1 in tauopathy.

Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-ß (Aß) plaques. The pathogenesis of PART is not known, but evidence suggests an association with genes that promote tau pathology and others that protect from Aß toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n = 647) using Braak neurofibrillary tangle stage as a quantitative trait. We found some significant associations with candidate loci associated with AD (SLC24A4, MS4A6A, HS3ST1) and progressive supranuclear palsy (MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brains with four microtubule-binding domain repeats (4R) isoforms and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation in post-mortem human PART brain tissue revealed a specific binding of JADE1 protein to four repeat tau lacking N-terminal inserts (0N4R). Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model, as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a modifier of neurofibrillary degeneration.

Imaging Intracranial Aneurysms in the Endovascular Era: Surveillance and Posttreatment Follow-up.

While most intracranial aneurysms (IAs) remain asymptomatic over a patient's lifetime, those that rupture can cause devastating outcomes. The increased usage and quality of neuroimaging has increased detection of unruptured IAs and driven an increase in surveillance and treatment of these lesions. Standard practice is to treat incidentally discovered unruptured IAs that confer high rupture risk as well as ruptured IAs to prevent rehemorrhage. IAs are increasingly treated with coil embolization instead of microsurgical clipping; more recently, flow diversion and intrasaccular flow disruption have further expanded the versatility and utility of endovascular IA treatment. Imaging is increasingly used for posttreatment IA follow-up in the endovascular era. While cerebral angiography remains the standard for IA characterization and treatment planning, advances in CT and CT angiography and MR angiography have improved the diagnostic accuracy of noninvasive imaging for initial diagnosis and surveillance. IA features including size, dome-to-neck ratio, location, and orientation allow rupture risk stratification and determination of optimal treatment strategy and timing. The radiologist should be familiar with the imaging appearance of common IA treatment devices and the expected imaging findings following treatment. In distinction to clipping and coil embolization, flow diversion and intrasaccular flow disruption induce progressive aneurysm obliteration over months to years. Careful assessment of the device; the treated IA; adjacent brain, bone, meninges; and involved extracranial and intracranial vasculature is crucial at posttreatment follow-up imaging to confirm aneurysm obliteration and identify short-term and long-term posttreatment complications. An invited commentary by Chatterjee is available online. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. ©RSNA, 2022.

Diffuse Angiogram-Negative Subarachnoid Hemorrhage is Associated with an Intermediate Clinical Course.

BACKGROUND: The cerebral angiography result is negative for an underlying vascular lesion in 15-20% of patients with nontraumatic subarachnoid hemorrhage (SAH). Patients with angiogram-negative SAH include those with perimesencephalic SAH and diffuse SAH. Consensus suggests that perimesencephalic SAH confers a more favorable prognosis than diffuse SAH. Limited data exist to contextualize the clinical course and prognosis of diffuse SAH in relation to aneurysmal SAH in terms of critical care complications, neurologic complications, and functional outcomes. Here we compare the clinical course and functional outcomes of patients with perimesencephalic SAH, diffuse SAH, and aneurysmal SAH to better characterize the prognostic implications of each SAH subtype. METHODS: We conducted a retrospective cohort study that included all patients with nontraumatic SAH admitted to a tertiary care referral center between January 1, 2012, and December 31, 2017. Bleed patterns were radiographically adjudicated, and patients were assigned to three groups: perimesencephalic SAH, diffuse SAH, and aneurysmal SAH. Patient demographics, complications, and clinical outcomes were reported and compared. RESULTS: Eighty-six patients with perimesencephalic SAH, 174 with diffuse SAH, and 998 with aneurysmal SAH presented during the study period. Patients with aneurysmal SAH were significantly more likely to be female, White, and active smokers. There were no significant differences between patients with diffuse SAH and perimesencephalic SAH patterns. Critical care complications were compared across all three groups, with significant between-group differences in hypotension and shock (3.5% vs. 16.1% vs. 38.4% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01) and endotracheal intubation (0% vs. 26.4% vs. 48.8% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01). Similar trends were noted with long-term supportive care with tracheostomy and gastrostomy tubes and length of stay. Cerebrospinal fluid diversion was increasingly required across bleed types (9.3% vs. 54.6% vs. 76.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively, p < 0.001). Vasospasm and delayed cerebral ischemia were comparable between perimesencephalic SAH and diffuse SAH but significantly lower than aneurysmal SAH. Patients with diffuse SAH had intermediate functional outcomes, with significant rates of nonhome discharge (23.0%) and poor functional status on discharge (26.4%), significantly higher than patients with perimesencephalic SAH and lower than patients with aneurysmal SAH. Diffuse SAH similarly conferred an intermediate rate of good functional outcomes at 1-6 months post discharge (92.3% vs. 78.6% vs. 47.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.016). CONCLUSIONS: We confirm the consensus data that perimesencephalic SAH is associated with a more benign clinical course but demonstrate that diffuse SAH confers an intermediate prognosis, more malignant than perimesencephalic SAH but not as morbid as aneurysmal SAH. These results highlight the significant morbidity associated with diffuse SAH and emphasize need for vigilance in the acute care of these patients. These patients will likely benefit from continued high-acuity observation and potential support to avert significant risk of morbidity and neurologic compromise.

A globally diverse reference alignment and panel for imputation of mitochondrial DNA variants.

BACKGROUND: Variation in mitochondrial DNA (mtDNA) identified by genotyping microarrays or by sequencing only the hypervariable regions of the genome may be insufficient to reliably assign mitochondrial genomes to phylogenetic lineages or haplogroups. This lack of resolution can limit functional and clinical interpretation of a substantial body of existing mtDNA data. To address this limitation, we developed and evaluated a large, curated reference alignment of complete mtDNA sequences as part of a pipeline for imputing missing mtDNA single nucleotide variants (mtSNVs). We call our reference alignment and pipeline MitoImpute. RESULTS: We aligned the sequences of 36,960 complete human mitochondrial genomes downloaded from GenBank, filtered and controlled for quality. These sequences were reformatted for use in imputation software, IMPUTE2. We assessed the imputation accuracy of MitoImpute by measuring haplogroup and genotype concordance in data from the 1000 Genomes Project and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The mean improvement of haplogroup assignment in the 1000 Genomes samples was 42.7% (Matthew's correlation coefficient = 0.64). In the ADNI cohort, we imputed missing single nucleotide variants. CONCLUSION: These results show that our reference alignment and panel can be used to impute missing mtSNVs in existing data obtained from using microarrays, thereby broadening the scope of functional and clinical investigation of mtDNA. This improvement may be particularly useful in studies where participants have been recruited over time and mtDNA data obtained using different methods, enabling better integration of early data collected using less accurate methods with more recent sequence data.

Safety and chronic lesion characterization of pulsed field ablation in a Porcine model.

BACKGROUND: Pulsed field ablation (PFA) has been identified as an alternative to thermal-based ablation systems for treatment of atrial fibrillation patients. The objective of this Good Laboratory Practice (GLP) study was to characterize the chronic effects and safety of overlapping lesions created by a PFA system at intracardiac locations in a porcine model. METHODS: A circular catheter with nine gold electrodes was used for overlapping low- or high-dose PFA deliveries in the superior vena cava (SVC), right atrial appendage (RAA), and right superior pulmonary vein (RSPV) in six pigs. Electrical isolation was evaluated acutely and chronic lesions were assessed via necropsy and histopathology after 4-week survival. Acute and chronic safety data were recorded peri- and post-procedurally. RESULTS: No animal experienced ventricular arrhythmia during PFA delivery, and there was no evidence of periprocedural PFA-related adverse events. Lesions created in all anatomies resulted in electrical isolation postprocedure. Lesions were circumferential, contiguous, and transmural, with all converting into consistent lines of chronic replacement fibrosis, regardless of trabeculated or smooth endocardial surface structure. Ablations were non-thermally generated with only minimal post-delivery temperature rises recorded at the electrodes. There was no evidence of extracardiac damage, stenosis, aneurysms, endocardial disruption, or thrombus. CONCLUSION: PFA deliveries to the SVC, RAA, and RSPV resulted in complete circumferential replacement fibrosis at 4-week postablation with an excellent chronic myocardial and collateral tissue safety profile. This GLP study evaluated the safety and efficacy of a dosage range in preparation for a clinical trial and characterized the non-thermal nature of PFA.

Characterization of the microbiome in the infant diapered area: Insights from healthy and damaged skin.

It has been recognized for nearly a century that human beings are inhabited by a remarkably dense and diverse microbial ecosystem, yet we are only just beginning to understand and appreciate the many roles that these microbes play in human health and development. Establishment of the microbiome begins at birth, but many previous studies on infant skin health have focused on Candida species. Little is known on the full microbial composition across different areas and even less is known on how these communities change during disease/inflammatory states. In this clinical study, infants were recruited during periods of diaper dermatitis (DD) and health to characterize the skin microbiome in these two states. Substantial shifts in the skin microbiome were observed across four sites in the diapered area (genitals, intertriginous, buttocks and perianal), as well as during periods of DD. As DD scores increased, there was a shift in relative abundance that demonstrated higher community percentages of faecal coliforms, such as Enterococcus, and lower percentages of Staphylococcus strains. In high-rash samples, the predominant Staphylococcus species is S aureus, potentially implicating S aureus as a DD aetiological agent. This study provides new information related to the microbiome on infant skin in the diapered area and provides insights into the role of the microbiome in the development of DD.

Endovascular treatment of anterior cranial fossa dural arteriovenous fistula: a multicenter series.

PURPOSE: We report a multicenter experience using endovascular embolization as the first line approach for treatment of anterior cranial fossa (ACF) dural arteriovenous fistula (DAVF). METHODS: All patients with DAVFs located in the anterior cranial fossa who were treated with endovascular technique as a first line approach were included. Demographics, clinical presentation, angioarchitecture, strategy, complications, immediate angiographic, and follow-up results were included in the analysis. RESULTS: Twenty-three patients met the inclusion criteria (18 male and 5 female). Age ranged from 14 to 79 years (mean 53 years). Twelve patients presented with hemorrhage. Twenty-eight endovascular procedures were performed. The overall immediate angiographic cure rate after endovascular treatment was 82.6% (19/23 patients). The angiographic cure rate of the transvenous strategy was significantly superior to the transarterial strategy (p ≤ 0.001). There was 1 complication in 28 total procedures (3.6%). Angiographic follow-up was available in 21 out of the 23 patients with a mean of 25 months (range 2 to 108 months). In these 21 patients, the DAVF was completely cured in 20 (95%). At last follow-up, all patients had a modified Rankin scale (mRS) 0 to 2. CONCLUSION: Our experience suggests that endovascular treatment for ACF DAVFs has an acceptable safety profile with high rates of complete occlusion, particularly with transvenous approach. Whenever possible, transvenous approach should be preferred over transarterial approach as first line strategy.

Multiple intracranial aneurysms in a patient with type I Gaucher disease: a case report and literature review.

Multiple intracranial aneurysms (IAs) have never been reported in a patient with Gaucher disease (GD). A 69-year-old-female with type I GD presented with a left sixth nerve palsy due to a large posterior inferior cerebellar artery (PICA) aneurysm. Cerebral angiography demonstrated fifteen unruptured IAs (UIAs).

Induced functional modulations of isolated large mammalian hearts.

In this study we used Visible Heart® methodologies featuring cyclic temperature modulation of porcine hearts in order to establish characteristic temperature responses. This isolated and perfused model is a more predictable and modifiable analog for human heart preservation and isolates the response of the cardiac tissue. We comprehensively monitored isolated porcine hearts undergoing temperature change and demonstrated optimization of isolated cardiac function under mild hypothermia. We tracked metrics of cardiac function as continuous variables during temperature changes (~ 31 to 39 °C), eliciting a well-defined reduction in metabolic demand and in heart rate modulation. Optimization of function appeared to occur around 34.7 ± 0.9 °C (n = 13). Cardiac response was further investigated in the presence of active pacing in order to assess pacing capture and the heart's functional response without a means of regulating rate. Our results may have direct clinical implications for emerging heart preservation methods prior to transplantation, as well as benefits for investigators using isolated heart models for preclinical device testing. Clinically, this porcine model is a basis for finding new ways to extend the window of viability for transplantable organs, thereby restoring or improving graft function and potentially enhancing recipient outcomes.

Comprehensive review of imaging of intracranial aneurysms and angiographically negative subarachnoid hemorrhage.

Intracranial aneurysms confer the risk of subarachnoid hemorrhage (SAH), a potentially devastating condition, though most aneurysms will remain asymptomatic for the lifetime of the patient. Imaging is critical to all stages of patient care for those who harbor an unruptured intracranial aneurysm (UIA), including to establish the diagnosis, to determine therapeutic options, to undertake surveillance in patients who elect not to undergo treatment or whose aneurysm(s) portends such a low risk that treatment is not indicated, and to perform follow-up after treatment. Neuroimaging is equally as important in patients who suffer an SAH. DSA remains the reference standard for imaging of intracranial aneurysms due to its high spatial and temporal resolution. As noninvasive imaging technology, such as CTA and MRA, improves, the diagnostic accuracy of such tests continues to increasingly approximate that of DSA. In cases of angiographically negative SAH, imaging protocols are necessary not only for diagnosis but also to search for an initially occult vascular lesion, such as a thrombosed, ruptured aneurysm that might be detected in a delayed fashion. Given the crucial role of neuroimaging in all aspects of care for patients with UIAs and SAH, it is incumbent on those who care for these patients, including cerebrovascular neurosurgeons, interventional neurologists and neuroradiologists, and diagnostic radiologists and neurointensivists, to understand the role of imaging in this disease and how individual members of the multispecialty team use imaging to ensure best practices to deliver cutting-edge care to these often complex cases. This review expounds on the role of imaging in the management of UIAs and ruptured intracranial aneurysms and in the workup of angiographically negative subarachnoid hemorrhage.

The use of contrast-enhanced, time-resolved magnetic resonance angiography in cerebrovascular pathology.

Digital subtraction angiography (DSA) has long been the imaging gold standard in the evaluation, treatment, and follow-up of cerebro- and spinovascular disorders. However, DSA has the disadvantages of invasiveness, contrast allergy or nephropathy, the impracticality of procedural preparation and recovery, and expense. Contrast-enhanced (CE), time-resolved (TR) magnetic resonance angiography (CE TR-MRA) is a sophisticated, relatively novel imaging modality that provides multiphasic contrast-enhanced visualization of the neurovasculature. Given the crucial role of angiography in all aspects of care for patients with complex neurovascular disorders, it is incumbent on those who care for these patients to understand the usefulness and pitfalls of novel imaging in this arena to ensure best practices, and to deliver cutting edge care to these patients in a way that minimizes cost, but does not compromise quality. CE TR-MRA has the potential to play an expanded role in the workup and follow-up across the spectrum of neurovascular disease, and this review is aimed to help neurosurgeons better understand how CE TR-MRA can be used to better manage patients in this cohort.

Combined reconstructive and deconstructive endovascular approach for bilateral vertebral artery dissection with subarachnoid hemorrhage.

The video highlights a challenging case of bilateral vertebral artery dissection presenting with subarachnoid hemorrhage. The patient was found to have a critical flow-limiting stenosis in his dominant right vertebral artery and a ruptured pseudoaneurysm in his left vertebral artery. A single-stage endovascular treatment with stent reconstruction of the right vertebral artery and coil embolization sacrifice of the left side was performed. The case highlights the rationale for treatment and potential alternative strategies.The video can be found here: https://youtu.be/e0U_JE2jISw.