Structural characterization of antibody-responses from Zolgensma treatment provides the blueprint for the engineering of an AAV capsid suitable for redosing.

Monoclonal antibodies (mAbs) are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids used as gene therapy delivery vectors. This study structurally characterizes the interactions of 21 human-derived antibodies from patients treated with the AAV9 vector, Zolgensma ® , utilizing high-resolution cryo-electron microscopy. The majority of the bound antibodies do not conform to the icosahedral symmetry of the capsid, thus requiring localized reconstructions. These complex structures provide unprecedented details of the mAbs binding interfaces, with some antibodies inducing structural perturbations of the capsid upon binding. Key surface capsid amino acid residues were identified facilitating the design of capsid variants with an antibody escape phenotype, with the potential to expand the patient cohort treatable with AAV9 vectors to include those that were previously excluded due to their pre-existing neutralizing antibodies, and possibly also to those requiring redosing.

Outcomes of Mechanical Thrombectomy in Patients With Neurological Disorders: A National Inpatient Sample Database Analysis.

INTRODUCTION: Mechanical thrombectomy (MT) has changed the standard of care for patients presenting with acute ischemic stroke (AIS). The window of treatment has significantly increased the number of patients who would benefit from intervention and operators may be confronted with patients harboring preexistent neurological disorders. Still, the epidemiology of patients with AIS and neurological disorders has not been established. METHODS: This is a retrospective study, which utilizes data from the National Inpatient Sample (NIS) between 2012 and 2016. Patients with the major neurological comorbidities in the study were included: Alzheimer's dementia (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and myasthenia gravis (MG). These patients were divided into groups and analyzed based on discharged home status, length of hospital stay (LOS), and inpatient mortality. These outcomes were also compared between patients who underwent MT versus those who did not. RESULTS: In this study, 460,070 patients with AIS were identified and included. MT was performed less often when the patient had a neurological diagnosis compared to those without a neurological disease (p<0.0001). However, patients with AIS who have underlying neurological disorders such as AD, PD, and MS have shown similar outcomes after MT to those who do not have these disorders. CONCLUSION: Patients with preexisting neurological disorders were less likely to undergo MT. Further studies are required to elucidate the implications of having a neurological disorder in the setting of an AIS.

Abnormal Neurologic Findings in Patients With Sickle Cell Disease Without a History of Major Neurologic Events.

Background and Objectives: Patients with sickle cell disease (SCD) are prone to symptomatic neurologic complications. Previous studies reported accrual of neural injury starting at early age, even without having symptomatic neurologic events. The aim of this study was to assess the prevalence and risk factors of abnormal neurologic findings in patients with SCD with no history of major symptomatic neurologic events. Methods: Our study extracted patients diagnosed with SCD from the Cooperative Study of Sickle Cell Disease. Patients who underwent a neurologic evaluation were included in our analysis. Patients with previous documented major symptomatic neurologic events were excluded. We compared patients with SCD with abnormal neurologic findings with those without in terms of clinical and laboratory parameters using multivariate binary logistic regression. Results: A total of 3,573 patients with SCD were included (median age = 11 [IQR = 19] years, male = 1719 [48.1%]). 519 (14.5%) patients had at least one abnormal neurologic finding. The most common findings in descending order were abnormal reflexes, gait abnormalities, cerebellar dysfunction, language deficits, nystagmus, abnormal muscle tone and strength, Romberg sign, Horner syndrome, and intellectual impairment. History of eye disease (odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.63-4.68) and history of osteomyelitis (OR = 2.55, 95% CI 1.34-4.84) were the strongest predictors of abnormal neurologic findings, followed by smoking (OR = 1.59, 95% CI 1.08-2.33), aseptic necrosis (OR = 1.57, 95% CI 1.06-2.33), hand-foot syndrome (OR = 1.48, 95% CI 1.04-2.12), and male sex (OR = 1.42, 95% CI 1.01-2.02). Discussion: Neurologic deficits are relatively common in patients with SCD, even without documented major neurologic insults. They range from peripheral and ophthalmic deficits to central and cognitive disabilities. Patients with SCD should have early regular neurologic evaluations and risk factor modification, particularly actively promoting smoking cessation.

A Comparative Study of Hemorrhagic Conversion Patterns After Stroke Thrombolysis With Alteplase Versus Tenecteplase.

BACKGROUND AND PURPOSE: Tenecteplase is the thrombolytic drug of choice for acute ischemic stroke (AIS) as it has unique pharmacologic properties, along with results demonstrating its non-inferiority compared to alteplase. However, there are contradictory data concerning the risk of intracranial hemorrhage. The purpose of the study was to report the rate and patterns of symptomatic intracranial hemorrhage (sICH) in AIS patients after thrombolysis with tenecteplase compared to alteplase. METHODS: This is a retrospective cohort study with data collected 90 days before and after the change from alteplase to tenecteplase from 15 Texas stroke centers. The primary endpoint is the incidence of sICH according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) and European Cooperative Acute Stroke Study III (ECASS-3) criteria. The secondary endpoints are the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBC). RESULTS: A total of 431 patients were eligible for thrombolytic therapy. Half of the cohort received alteplase (n=216), and the other half received tenecteplase (n=215). The average age of the alteplase group was 62.94 years old (SD=15.12) and 64.45 years old (SD=14.51) for the tenecteplase group. Seven patients in the alteplase group (3.2%) and 14 (6.5%) in the tenecteplase group had sICH, with an odds ratio of 1.44 (95% CI 0.60-3.43; P=0.41). An increased National Institutes of Health Stroke Scale (NIHSS) score on arrival (1.06; 95% CI 1.0004-1.131; P=0.04) was a statistically significant predictor of sICH. Tenecteplase was associated with a statistically significant increase in HBC-3 (P=0.040) over alteplase. CONCLUSIONS: Compared with alteplase, our study revealed a higher rate of sICH with tenecteplase that was not statistically significant and a higher rate of HBC-3 hemorrhages that was statistically significant. The proposed mechanism of bleeding is hemorrhagic conversion in clinically silent infarcts and contusions underlying the lesions. Further studies are needed to confirm our findings and determine predictive risk factors.

Impact of pre-treatment cerebral microbleeds on the outcomes of endovascular thrombectomy: A systematic review and meta-analysis.

OBJECTIVE/AIM: To investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic review and meta-analysis. We included observational studies that recruited AIS-LVO patients, used susceptibility-sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The extracted data included study and population characteristics, risk of bias domains, and outcome measures. The outcomes of interest included functional independence, revascularization success, procedural and hemorrhagic adverse events. We conducted a meta-analysis using the Mantel-Haenszel method and calculated the risk ratios. RESULTS: Four studies with a total of 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome was observed in patients with CMBs (Risk ratio (RR) 0.69, 95% confidence interval (CI): 0.52 to 0.91, P=0.01). No significant differences were observed between the CMBs and no CMBs groups in terms of successful revascularization, mortality, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and parenchymal hematoma. CONCLUSIONS: The presence of CMBs significantly reduced the likelihood of achieving functional independence post-EVT in AIS-LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic events. Future research should explore the mechanisms of this association and strategies to mitigate its impact.

The Effect of COVID-19 Vaccines on Stroke Outcomes: A Single-Center Study.

BACKGROUND: One of the defining narratives of the COVID-19 pandemic has been the acceptance and distribution of vaccine. To compare the outcomes of COVID-19 positive vaccinated and unvaccinated stroke patients. METHODS: This is a single-center retrospective study of COVID-19-vaccinated and unvaccinated stroke patients between April 2020 and March 2022. All patients presenting with stroke regardless of treatment modalities were included. National Institutes of Health Stroke Scale was used to assess stroke severity. The primary outcome was functional capacity of the patients at discharge. RESULTS: The study cohort comprised 203 COVID-19 positive stroke patients divided into 139 unvaccinated and 64 fully vaccinated patients. At discharge, the modified Rankin scale score was significantly lower in the vaccinated cohort (3[1-4] vs. 4[2-5], odds ratio = 0.508, P = 0.011). At 3 months of follow-up, the median modified Rankin scale score was comparable between both cohorts. CONCLUSIONS: Although vaccination did not show any significant difference in stroke patient outcomes on follow-up, vaccines were associated with lower rates of morbidity and mortality at discharge among stroke patients during the pandemic.

Cerebral Ischemic Reperfusion Injury: Preventative and Therapeutic Strategies.

Acute ischemic stroke is a leading cause of morbidity and mortality in the United States. Treatment goals remain focused on restoring blood flow to compromised areas. However, a major concern arises after reperfusion occurs. Cerebral ischemic reperfusion injury is defined as damage to otherwise salvageable brain tissue occurring with the reestablishment of the vascular supply to that region. The pool of eligible patients for revascularization continues to grow, especially with the recently expanded endovascular therapeutic window. Neurointensivists should understand and manage complications of successful recanalization. In this review, we examine the pathophysiology, diagnosis, and potential management strategies in cerebral ischemic reperfusion injury.

Intravenous thrombolysis plus mechanical thrombectomy versus mechanical thrombectomy alone for acute ischemic stroke: A systematic review and updated meta-analysis of clinical trials.

BACKGROUND: Mechanical thrombectomy (MT) is the gold standard treatment for large vessel occlusion (LVO). A vital factor that might influence MT outcomes is the use of intravenous thrombolysis (IVT). A few clinical trials in this domain thus far have not yielded consistent outcomes. We conducted this meta-analysis to synthesize collective evidence in this regard. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines were followed, and we performed a comprehensive literature search of four databases (PubMed, Scopus, Web of Science, Cochrane CENTRAL). For outcomes constituting continuous data, the mean difference (MD) and its standard deviation (SD) were pooled. For outcomes constituting dichotomous data, the frequency of events and the total number of patients were pooled as the risk ratio (RR). RESULTS: Seven clinical trials with a total of 2317 patients are included in this meta-analysis. Six trials are randomized, and one trial was nonrandomized. No significant differences were found between MT plus IVT and MT alone in successful recanalization (RR 1.04, 95% Confidence Interval (CI) [0.92 to 1.17], P = 0.53), 90-day functional independence (RR 1.03, 95% CI [0.90 to 1.19], P = 0.65), symptomatic intracranial hemorrhage (sICH) (RR 1.22, 95% CI [0.84 to 1.75], P = 0.30), or mortality (RR 0.94, 95% CI [0.76 to 1.18], P = 0.61). CONCLUSION: The current evidence does not favor either MT plus IVT or MT alone for LVO except for the procedural time. More trials are needed in this regard, and certain factors should be considered when comparing the two approaches.

Ultra-Short-Term Dual Antiplatelet Therapy in Treating Unruptured Brain Aneurysm With the Pipeline Flex-Shield Embolization Device.

Ruptured cerebral aneurysms can cause significant morbidity and mortality. Endoluminal devices to treat aneurysms such as the Pipeline™ Flex Embolization Device with Shield Technology (PFES) (Medtronic, Dublin, Ireland) integrate phosphorylcholine on the surface of the device in order to reduce platelet adherence that causes periprocedural thromboembolic events and subsequent long-term intrastent stenosis. In addition to the Shield Technology, patients are commonly placed on dual antiplatelet therapy (DAPT) for six months to reduce thromboembolic events and subsequent long-term intrastent stenosis. There is a strong positive correlation between the length of DAPT use and bleeding. Here, we present a case of a 66-year-old female with a right supraclinoid internal carotid artery (ICA) aneurysm treated with a PFES who was placed on dual antiplatelet therapy for the first 31 days postoperative and subsequently maintained on aspirin (ASA) 81 mg monotherapy. At two months, a follow-up diagnostic cerebral angiogram showed complete occlusion of the aneurysm with a patent stent. Our case sets the stage for further research into the optimal length of dual antiplatelet therapy required in PFES to prevent short and long-term thromboembolic events. This report indicates that it may be safe for patients with PFES to intermittently halt the use of DAPT to manage bleeding complications or perform surgery.

Relation between brain natriuretic peptide and delayed cerebral ischemia in patients with aneurysmalsubarachnoid hemorrhage.

BACKGROUND: Brain natriuretic peptide (BNP), often used to evaluate degree of heart failure, has been implicated in fluid dysregulation and inflammation in critically-ill patients. Twenty to 30% of patients with aneurysmal subarachnoid hemorrhage (aSAH) will develop some degree of neurogenic stress cardiomyopathy (NSC) and in turn elevation of BNP levels. We sought to explore the association between BNP levels and development of delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: We retrospectively evaluated the records of 149 patients admitted to the Neurological Intensive Care Unit between 2006 and 2015 and enrolled in an existing prospectively maintained aSAH database. Demographic data, treatment and outcomes, and BNP levels at admission and throughout the hospital admission were noted. RESULTS: Of the 149 patients included in the analysis, 79 developed DCI during their hospital course. We found a statistically significant association between DCI and the highest recorded BNP (OR 1.001, 95% CI-1.001-1.002, p = 0.002). The ROC curve analysis for DCI based on BNP showed that the highest BNP level during hospital admission (AUC 0.78) was the strongest predictor of DCI compared to the change in BNP over time (AUC 0.776) or the admission BNP (AUC 0.632). CONCLUSION: Our study shows that DCI is associated not only with higher baseline BNP values (admission BNP), but also with the highest BNP level attained during the hospital course and the rapidity of change or increase in BNP over time. Prospective studies are needed to evaluate whether routine measurement of BNP may help identify SAH patients at high risk of DCI.

Neurocritical care management of poor-grade subarachnoid hemorrhage: Unjustified nihilism to reasonable optimism.

BACKGROUND AND PURPOSE: Historically, overall outcomes for patients with high-grade subarachnoid hemorrhage (SAH) have been poor. Generally, between physicians, either reluctance to treat, or selectivity in treating such patients has been the paradigm. Recent studies have shown that early and aggressive care leads to significant improvement in survival rates and favorable outcomes of grade V SAH patients. With advancements in both neurocritical care and end-of-life care, non-treatment or selective treatment of grade V SAH patients is rarely justified. Current paradigm shifts towards early and aggressive care in such cases may lead to improved outcomes for many more patients. MATERIALS AND METHODS: We performed a detailed review of the current literature regarding neurointensive management strategies in high-grade SAH, discussing multiple aspects. We discussed the neurointensive care management protocols for grade V SAH patients. RESULTS: Acutely, intracranial pressure control is of utmost importance with external ventricular drain placement, sedation, optimization of cerebral perfusion pressure, osmotherapy and hyperventilation, as well as cardiopulmonary support through management of hypotension and hypertension. CONCLUSIONS: Advancements of care in SAH patients make it unethical to deny treatment to poor Hunt and Hess grade patients. Early and aggressive treatment results in a significant improvement in survival rate and favorable outcome in such patients.

Dramatic rise in seroprevalence rates of SARS-CoV-2 antibodies among healthy blood donors: The evolution of a pandemic.

BACKGROUND: Seroprevalence studies of SARS-CoV-2 antibodies are useful in assessing the epidemiological status in the community, and the degree of spread. OBJECTIVE: To study the seroprevalence rates of SARS-CoV-2 antibodies among healthy blood donors in Jordan, at various points of time and as the pandemic evolves in the community. METHODS: In total, 1374 blood donor samples, from three groups, were tested for SARS-CoV-2 total immunoglobulin antibodies. In the first group, samples from 734 individuals (from donations made between January and June 2020) were tested in June. In the second group, 348 individuals were tested in September 2020. The third group of 292 individuals was tested in February 2021. A qualitative assay was used for testing (specificity 99.8%, sensitivity 100%). RESULTS: The first two groups, from January-June and September 2020, when confirmed Covid-19 cases numbered between several hundred and 3000, showed a seroprevalence rate of 0% (95% CI 0.00-0.51%). The third group (early February 2021), when the number of confirmed cases had reached 100 times that of September 2020, revealed a seroprevalence of 27.4% (95% CI 22.5-32.9%). CONCLUSIONS: A dramatic rise in seroprevalence of SARS-CoV-2 antibodies was seen among healthy blood donors in Jordan, in parallel with widespread intracommunity transmission of the disease. This information is useful for assessing the degree of herd immunity, and provides for better understanding of the pandemic.

Carotid Cavernous Fistula Treatment via Flow Diversion: A Systematic Review of the Literature.

BACKGROUND: Carotid cavernous fistulas (CCFs) are pathologic connections between the carotid arteries and the cavernous sinus and have been classically treated with endovascular coil embolization, although flow diverters have been used for treatment successfully multiple times. The aim of this study is to systematically review the literature for efficacy of flow diverters in treating CCFs. METHODS: A systematic review was conducted using the PRISMA guidelines. PubMed, PubMed Central, Cochrane Library, and Embase databases were searched. Combinations and variations of "carotid cavernous fistula," "flow diversion," "pipeline embolization device," "Surpass," "Silk," "p64," "FRED," and "flow redirection endoluminal device" in both AND and OR configurations were used to gather relevant articles. Citations of included articles from the systematic review were also screened for possible inclusion as a part of manual review. Included studies were full-text publications written in English that had patients with diagnosed CCFs and treatment with flow diversion. RESULTS: Eighteen full-text publications were relevant to this systematic review. A total of 41 patients underwent flow-diverting therapy alone or in conjunction with coil embolization, liquid embolization, and/or stenting for treatment of a diagnosed CCF. Twenty-nine patients (70.7%) needed 1 procedure alone, 11 patients (26.8%) required a second procedure, and 1 patient (2.4%) required a third procedure. Six patients (14.6%) had lasting symptoms despite intervention; however, all 41 patients had clinical improvement compared with initial presentation. Flow diversion was a useful solitary treatment or adjunctive treatment in all patients. CONCLUSIONS: Flow diversion is a useful adjunct in combination with coil embolization for the treatment of CCFs but long-term outcomes remain to be seen.

Lower complication rates associated with transradial versus transfemoral flow diverting stent placement.

BACKGROUND: Currently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion. METHODS: We retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches. RESULTS: A total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035). CONCLUSION: TRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.

Body Mass Index and Overall Outcome Following Subarachnoid Hemorrhage: An Obesity Paradox?

BACKGROUND: Conventional understanding of obesity demonstrates negative consequences for overall health, whereas more modern studies have found that it can provide certain advantages. The current literature on the effect of body mass index (BMI) in subarachnoid hemorrhage (SAH) is similarly inconsistent. METHODS: cohort of 406 patients with SAH were retrospectively reviewed and stratified into 3 BMI categories: normal weight, 18.5-24.9 kg/m2; overweight, 25-29.9 kg/m2; and obese, >30 kg/m2. Neurologic status, the presence of clinical cerebral vasospasm, and outcome as assessed by the modified Rankin scale (mRS) were obtained. RESULTS: Statistical differences were evident for all outcome categories. A categorical analysis of the different groups revealed that compared with the normal weight group, the overweight group had an odds ratio (OR) for mortality of 0.415 (P = 0.023), an OR for poor mRS score at 90 days of 0.432 (P = 0.014), and an OR for poor mRS score at 180 days of 0.311 (P = 0.001), and the obese group had statistically significant ORs for poor mRS score at 90 days of 2.067 (P = 0.041) and at 180 days of 1.947 (P = 0.049). These significant ORs persisted in a multivariable model controlling for age and Hunt and Hess grade. CONCLUSIONS: The overweight group exhibited strikingly lower odds of death and poor outcome compared with the normal weight group, whereas the obese group demonstrated the opposite. These associations persisted in a multivariable model; thus, BMI can be considered an important predictor of outcome after SAH.

HTRA1-Related Cerebral Small Vessel Disease: A Review of the Literature.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is clinically characterized by early-onset dementia, stroke, spondylosis deformans, and alopecia. In CARASIL cases, brain magnetic resonance imaging reveals severe white matter hyperintensities (WMHs), lacunar infarctions, and microbleeds. CARASIL is caused by a homozygous mutation in high-temperature requirement A serine peptidase 1 (HTRA1). Recently, it was reported that several heterozygous mutations in HTRA1 also cause cerebral small vessel disease (CSVD). Although patients with heterozygous HTRA1-related CSVD (symptomatic carriers) are reported to have a milder form of CARASIL, little is known about the clinical and genetic differences between the two diseases. Given this gap in the literature, we collected clinical information on HTRA1-related CSVD from a review of the literature to help clarify the differences between symptomatic carriers and CARASIL and the features of both diseases. Forty-six symptomatic carriers and 28 patients with CARASIL were investigated. Twenty-eight mutations in symptomatic carriers and 22 mutations in CARASIL were identified. Missense mutations in symptomatic carriers are more frequently identified in the linker or loop 3 (L3)/loop D (LD) domains, which are critical sites in activating protease activity. The ages at onset of neurological symptoms/signs were significantly higher in symptomatic carriers than in CARASIL, and the frequency of characteristic extraneurological findings and confluent WMHs were significantly higher in CARASIL than in symptomatic carriers. As previously reported, heterozygous HTRA1-related CSVD has a milder clinical presentation of CARASIL. It seems that haploinsufficiency can cause CSVD among symptomatic carriers according to the several patients with heterozygous nonsense/frameshift mutations. However, the differing locations of mutations found in the two diseases indicate that distinct molecular mechanisms influence the development of CSVD in patients with HTRA1-related CSVD. These findings further support continued careful examination of the pathogenicity of mutations located outside the linker or LD/L3 domain in symptomatic carriers.

Bailout Strategies and Complications Associated with the Use of Flow-Diverting Stents for Treating Intracranial Aneurysms.

BACKGROUND: Flow-diverting stents (FDS) have revolutionized the endovascular management of unruptured, complex, wide-necked, and giant aneurysms. There is no consensus on management of complications associated with the placement of these devices. This review focuses on the management of complications of FDS for the treatment of intracranial aneurysms. SUMMARY: We performed a systematic, qualitative review using electronic databases MEDLINE and Google Scholar. Complications of FDS placement generally occur during the perioperative period. KEY MESSAGE: Complications associated with FDS may be divided into periprocedural complications, immediate postprocedural complications, and delayed complications. We sought to review these complications and novel management strategies that have been reported in the literature.

Mandatory Neuroendovascular Evolution: Meeting the New Demands.

BACKGROUND: Traditionally, patients undergoing acute ischemic strokes were candidates for mechanical thrombectomy if they were within the 6-h window from onset of symptoms. This timeframe would exclude many patient populations, such as wake-up strokes. However, the most recent clinical trials, DAWN and DEFUSE3, have expanded the window of endovascular treatment for acute ischemic stroke patients to within 24 h from symptom onset. This expanded window increases the number of potential candidates for endovascular intervention for emergent large vessel occlusions and raises the question of how to efficiently screen and triage this increase of patients. SUMMARY: Abbreviated pre-hospital stroke scales can be used to guide EMS personnel in quickly deciding if a patient is undergoing a stroke. Telestroke networks connect remote hospitals to stroke specialists to improve the transportation time of the patient to a comprehensive stroke center for the appropriate level of care. Mobile stroke units, mobile interventional units, and helistroke reverse the traditional hub-and-spoke model by bringing imaging, tPA, and expertise to the patient. Smartphone applications and social media aid in educating patients and the public regarding acute and long-term stroke care. KEY MESSAGES: The DAWN and DEFUSE3 trials have expanded the treatment window for certain acute ischemic stroke patients with mechanical thrombectomy and subsequently have increased the number of potential candidates for endovascular intervention. This expansion brings patient screening and triaging to greater importance, as reducing the time from symptom onset to decision-to-treat and groin puncture can better stroke patient outcomes. Several strategies have been employed to address this issue by reducing the time of symptom onset to decision-to-treat time.

Significance of 18F-FDG PET/CT in Characterization of Equivocal Lesions in High-Risk Testicular Carcinoma in Restaging Setting.

OBJECTIVES: The present study aims to evaluate the role of Positron emission tomography (PET) -computed tomography (CT) with 18F-fluorodeoxyglucose (18F-FDG) in the restaging of high-risk testicular cancer. METHODS: Forty-five patients (mean age of 38.1±11.3 years and range 23-81 years) with testicular carcinoma, underwent 18F-FDG PET-CT during their clinical course were prospectively selected. PET positivity was defined as a site of abnormal 18F-FDG uptake in tissue histologically proven or clinically or radiographically suspected to represent tissue involvement. The sites of disease were characterized as either nodal or extranodal. All patients were followed-up for at least 12 months with a diagnostic and/or functional imaging modality. RESULTS: Of the 45 patients 38 (84%) patient presented with seminoma and 7 (16%) were Non-seminomatous germ cell tumors. Analysis of secondary disease spectrum showed nodal involvement in 65%, osseous involvement in 23% and mixed visceral/soft tissue lesions in 12% of patients. Nineteen (42%) were negative for any metastatic disease. All negative patients remain disease free in the follow-up of one year. Out of the positive 26/45 patients, PET-CT showed progressive disease in 3/26, stable disease 1/26 and partial response in 2/26 and complete metabolic resolution in 20/26 patients. 18F-FDG PET-CT was able to characterize all patients leading to significant change of primary decision of wait and watch to go for treatment and vice versa. CONCLUSION: 18F-FDG PET-CT scan is potentially an excellent tool for characterization of equivocal lesions on CT scan in the restaging settings and follow up of high-risk testicular cancer patients.

Management Strategies for Intracranial Pressure Crises in Subarachnoid Hemorrhage.

Objectives: Standard management strategies for lowering intracranial pressure (ICP) in traumatic brain injury has been well-studied, but the use of lesser known interventions for ICP in subarachnoid hemorrhage (SAH) remains elusive. Searches were performed in PubMed and EBSCO Host to identify best available evidence for evaluation and management of medically refractory ICP in SAH. The role of standard management strategies such as head elevation, hyperventilation, mannitol and hypertonic saline as well as lesser known management such as sodium bicarbonate, indomethacin, tromethamine, decompressive craniectomy, decompressive laparotomy, hypothermia, and barbiturate coma are reviewed. We also included dose concentrations, dose frequency, infusion volume, and infusion rate for these lesser known strategies. Nonetheless, there is still a gap in the evidence to recommend optimal dosing, timing and its role in the improvement of outcomes but early diagnosis and appropriate management reduce adverse outcomes.