Physician Approaches to Antithrombotic Therapies for Recently Symptomatic Carotid Stenosis.

BACKGROUND: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. METHODS: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. RESULTS: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. CONCLUSION: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

Autologous hematopoietic stem cell transplant for the treatment of refractory myasthenia gravis with anti-muscle specific kinase antibodies.

INTRODUCTION/AIMS: Up to 25% of patients with myasthenia gravis (MG) have refractory disease despite trials of multiple immunosuppressants. Several case series describe acetylcholine receptor antibody-positive (AChR) MG patients treated with autologous hematopoietic stem cell transplant (HSCT). In this report, we describe three patients with anti-muscle-specific kinase (MuSK) MG treated with HSCT. METHODS: We included all patients who had undergone HSCT with anti-MuSK myasthenia gravis identified through the records of the Alberta Blood and Marrow Transplant Program. We collected demographic and clinical data including validated MG scales as well as questionnaire data. RESULTS: All 3 patients had severe disease (Myasthenia Gravis Foundation of America score IVb-V) and were refractory to multiple treatments, including rituximab. All patients improved with no clinical manifestations or mild symptoms and remained as such for 2, 3.5, and 5.5 y. Adverse events ranged from treatable infections and transient dyspnea to persistent fatigue and premature menopause. The average worst Myasthenia Gravis Activities of Daily Living (MG-ADL) scores improved from 14.7 before to 0.3 after HSCT. The mean worst Myasthenia Gravis Quality of Life Questionnaire (MG-QoL15) scores improved from 26.7 to 0. All patients reported they would undergo transplant again for their MG. DISCUSSION: We describe three patients with anti-MuSK MG treated with HSCT, all of whom became symptom free from MG with a tolerable side effect profile. In patients with severe refractory anti-MuSK MG, it may be reasonable to consider HSCT.

Prevalence of high-risk aortic arch atherosclerosis features on computed tomography angiography in embolic stroke of undetermined source.

INTRODUCTION: Embolic stroke of undetermined source (ESUS) comprises a heterogenous group. There is a need to further identify etiologies within this group to guide management strategies. We examined the prevalence of aortic arch atherosclerosis (AAA) on CT angiography (CTA) in patients with embolic stroke of undetermined source (ESUS) to characterize high-risk plaque features. METHODS: All patients from two prospective multicenter acute ischemic stroke studies (INTERRSeCT and PRove-IT) were included if the CTA adequately imaged the proximal aortic arch and the stroke etiology was recorded. Three readers blinded to stroke etiology analyzed the following AAA plaque features on baseline CTA at the time of stroke: 1) thickness in millimetres (mm); 2) morphology (none, smooth, ulcerated, or protruding); 3) location within the aortic arch (proximal, transverse, or distal); and 4) calcification (none, single small, multiple small, single large, or diffuse extensive). RESULTS: We included 1063 patients, of which 293 (27.6%) had ESUS (mean age 67.5 years; 46.4% men; median NIHSS 12; 80.6% large vessel occlusion). Mean AAA thickness was significantly larger in ESUS patients (3.8 mm) compared to non-ESUS patients (3.0 mm; p<0.0001) and to a subgroup of patients with large artery atherosclerosis (2.9 mm; p=0.003). ESUS patients had a significantly higher proportion of ulcerated or protruding plaques (17.4% vs 10.3%; risk ratio 1.7, 95% C.I. 1.2-2.4, p=0.002). The location of AAA in the ESUS group was the ascending aorta in 37.9%, transverse arch in 42.3%, and descending aorta in 84.6%. Although AAA was mostly located in the distal aortic arch, ulcerated or protruding plaques were least common in the distal arch (p=0.002). There was no difference between ESUS and non-ESUS patients in plaque location (p=0.23) or calcification grade (p=0.092). CONCLUSION: ESUS patients in our study had thicker AAA and a higher prevalence of ulcerated or protruding plaques located more proximally within the aortic arch. High-risk plaque features may suggest a causal role of AAA in the ESUS population with visible intracranial occlusions.

Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability: A Meta-Analysis.

BACKGROUND: Randomized controlled trials for the use of alteplase in acute ischemic stroke have excluded or had little representation of patients with prestroke disability, and the benefit of alteplase in this population remains uncertain. We performed a systematic review and meta-analysis to examine the outcomes of thrombolysis in patients with premorbid disability. METHODS: We performed a systematic review in accordance with the Meta-Analysis of Observational Studies in Epidemiology guidelines and retrieved studies reporting intravenous thrombolysis (IVT) in patients with prestroke disability (modified Rankin Scale score, 3-5) with acute ischemic stroke, either compared with untreated patients or treated patients without premorbid disability. The primary outcome was the return to premorbid disability at 90 days. Secondary outcomes included rate and odds ratio of favorable functional outcome at 90 days (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: Eight articles were included involving 103 988 patients. Patients with disability treated with IVT had better odds of returning to baseline function compared with those who did not receive IVT (odds ratio, 7.26 [95% CI, 2.51-21.02]). Mortality and rates of sICH were not significantly different between patients with disability treated with IVT and those not treated, although there were numerically more sICHs in the IVT group. Return to baseline function was not significantly different between patients with and without prestroke disability (odds ratio, 1.46 [95% CI, 0.75-2.83]). The rates of sICH were not significantly different in patients with and without premorbid disability. However, mortality was 3× higher in patients with premorbid disability than in those without premorbid disability (38.2% versus 12.6%). CONCLUSIONS: The use of IVT in patients with disability was associated with better outcomes compared with patients who did not receive IVT without statistically significant added risks of sICH or mortality. When compared with those without disability, there was no significant difference in the return to baseline function or sICH. High-quality data comparing treated versus untreated patients with premorbid disability are needed to clarify this issue. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.

Gold Coast criteria expand clinical trial eligibility in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Consensus criteria to formalize the diagnosis of amyotrophic lateral sclerosis (ALS) and refine clinical trial populations have evolved. The recently proposed Gold Coast consensus criteria are intended to simplify use and increase sensitivity. We aimed to evaluate the potential impact of these criteria on clinical trial eligibility. METHODS: We performed a single-center, retrospective study of people diagnosed with ALS between 2016 and 2021 to determine the numbers of those meeting Gold Coast, revised El Escorial (rEEC) criteria, and Awaji criteria. We identified the proportion of those who would have been eligible for participation in three major ALS clinical trials if Gold Coast were used in place of rEEC definite/probable criteria. (rEEC D/P). RESULTS: Two hundred six people with ALS were included in our study. 48.5% met Gold Coast criteria but not rEEC D/P. Using the Gold Coast criteria would result in higher rates of clinical trial eligibility after other inclusion criteria were met: 95.2% vs 42.5% (P < .001) in a phase III study of riluzole; 100% vs 31.0% (P = .002) in a phase III study of edaravone; and 95.6% vs 45.3% (P < .001) in an ongoing phase III study of sodium phenylbutyrate and taurursodiol. The sensitivity of the Gold Coast criteria (96.1%; 95% confidence interval [CI], 92.2%-98.2%) was significantly higher than that of rEEC D/P (47.6%; 95% CI, 40.6%-54.6%; for difference, χ2  = 117.6; P < .001). DISCUSSION: Until robust biomarkers are available to diagnose ALS, consensus diagnostic criteria remain necessary. Gold Coast criteria would expand research and clinical trial eligibility and improve external validity of clinical trial results.

Validation of a machine learning software tool for automated large vessel occlusion detection in patients with suspected acute stroke.

PURPOSE: CT angiography (CTA) is the imaging standard for large vessel occlusion (LVO) detection in patients with acute ischemic stroke. StrokeSENS LVO is an automated tool that utilizes a machine learning algorithm to identify anterior large vessel occlusions (LVO) on CTA. The aim of this study was to test the algorithm's performance in LVO detection in an independent dataset. METHODS: A total of 400 studies (217 LVO, 183 other/no occlusion) read by expert consensus were used for retrospective analysis. The LVO was defined as intracranial internal carotid artery (ICA) occlusion and M1 middle cerebral artery (MCA) occlusion. Software performance in detecting anterior LVO was evaluated using receiver operator characteristics (ROC) analysis, reporting area under the curve (AUC), sensitivity, and specificity. Subgroup analyses were performed to evaluate if performance in detecting LVO differed by subgroups, namely M1 MCA and ICA occlusion sites, and in data stratified by patient age, sex, and CTA acquisition characteristics (slice thickness, kilovoltage tube peak, and scanner manufacturer). RESULTS: AUC, sensitivity, and specificity overall were as follows: 0.939, 0.894, and 0.874, respectively, in the full cohort; 0.927, 0.857, and 0.874, respectively, in the ICA occlusion cohort; 0.945, 0.914, and 0.874, respectively, in the M1 MCA occlusion cohort. Performance did not differ significantly by patient age, sex, or CTA acquisition characteristics. CONCLUSION: The StrokeSENS LVO machine learning algorithm detects anterior LVO with high accuracy from a range of scans in a large dataset.

Determinants of hyponatremia following a traumatic brain injury.

BACKGROUND: Hyponatremia is common in patients with central nervous system disease. It may prolong hospitalization and increase morbidity and mortality. However, the incidence and risks factors remain largely unknown in traumatic brain injury (TBI). The objectives of this study are to characterize hyponatremia in TBI patients and find its main risk factors. METHODS: All patients admitted with a diagnosis of acute TBI over a 1-year period were included, except patients with known chronic hyponatremia, those who died within 72 h, and those receiving hyperosmolar therapy to treat their intracranial hypertension. Sodium levels throughout hospitalization were collected. Post-traumatic hyponatremia was defined as follows: borderline (1-2 points below normal and 1-2 days duration) and significant (more than 2 points below normal and/or more than 2 days duration). Demographic data, GCS, mechanism of injury, and CT findings were collected. These factors were correlated to the incidence of hyponatremia. RESULTS: Hyponatremia was found in 29% of the 283 included patients and was significant in 2/3 of the cases. Significant hyponatremia had a narrower peak, between 7 and 11 days, while borderline hyponatremia started earlier and was more distributed in time. Factors associated with hyponatremia were greater age (p = 0.004), worse ISS (p = 0.017), worse Marshall Grade on CT (p = 0.007), and a diffuse pattern of injury on CT (p < 0.001). Significant hyponatremia was associated with: a diffuse pattern of injury on CT (p = 0.032), the presence of intracerebral hemorrhage (p = 0.027), and multiple lesions on CT (p = 0.043). CONCLUSIONS: Post-traumatic hyponatremia is common and can lead to serious consequences in TBI patients. Adequate monitoring and treatment are therefore important. Older patients and those with more significant injury on CT are more at risk.

Pediatric versus adult meningioma: comparison of epidemiology, treatments, and outcomes using the Surveillance, Epidemiology, and End Results database.

Pediatric meningiomas, which account for < 1% of all meningiomas, are thought to have unique features, including being more aggressive than their adult counterparts. The goal of this investigation was to compare pediatric and adult meningiomas in a large head-to-head comparison. We used the Surveillance, Epidemiology, and End Result (SEER) datasets to compare meningioma demographics, first treatments, and outcomes among children/adolescents (0-21 years), young adults (22-45 years), and older adults (> 45 years). During 2004-2012, SEER contained 59148 patients age 0-107 years diagnosed with meningioma, with children/adolescents accounting for 381 (0.64%) patients. Unlike older and young adults, children/adolescents with meningioma did not demonstrate female predominance, and had an equal 1:1 male-to-female ratio. Children/adolescents also had almost three-times as many spinal tumors (13.1%) than young adults (4.2%) and older adults (4.4%). Both children/adolescents and young adults had undergone more gross total resections (both 43%) versus older adults (25%), and were treated more with radiation (14.6%, and 12.0% respectively) than their older counterparts (8.5%). In addition, both children/adolescents and young adults had significantly lower all-cause mortality (4.5% in both) than older adults (24.6%), during median 35-month follow-up. Inherent limitations of the SEER datasets restrict our ability to answer important questions regarding comparisons of tumor grading, histological diagnosis, cause-specific mortality, and neurofibromatosis status. Pediatric meningiomas appear distinct from their adult counterparts as they do not display the typical female predominance and include more clinically relevant spinal tumors. More extensive surgeries, greater use of radiation therapy, and lower all-cause mortality were seen in both children/adolescents and young adults, which raises questions regarding the perceived uniquely aggressive nature of pediatric meningiomas. However, due to the significant limitations of the SEER datasets, our results must be interpreted cautiously and stand only to foster novel questions, which would be better answered in well-designed, prospective studies.

The State of Technology in Craniosynostosis.

INTRODUCTION: Craniosynostosis, the premature fusion of ≥1 cranial sutures, is the leading cause of pediatric skull deformities, affecting 1 of every 2000 to 2500 live births worldwide. Technologies used for the management of craniofacial conditions, specifically in craniosynostosis, have been advancing dramatically. This article highlights the most recent technological advances in craniosynostosis surgery through a systematic review of the literature. METHODS: A systematic electronic search was performed using the PubMed database. Search terms used were "craniosynostosis" AND "technology" OR "innovation" OR "novel.' Two independent reviewers subsequently reviewed the resultant articles based on strict inclusion and exclusion criteria. Selected manuscripts deemed novel by the senior authors were grouped by procedure categories. RESULTS: Following review of the PubMed database, 28 of 536 articles were retained. Of the 28 articles, 20 articles consisting of 21 technologies were deemed as being novel by the senior authors. The technologies were categorized as diagnostic imaging (n = 6), surgical planning (n = 4), cranial vault evaluation (n = 4), machine learning (n = 3), ultrasound pinning (n = 3), and near-infrared spectroscopy (n = 1). CONCLUSION: Multiple technological advances have impacted the treatment of craniosynostosis. These innovations include improvement in diagnosis and objective measurement of craniosynostosis, preoperative planning, intraoperative procedures, communication between both surgeons and patients, and surgical education.

Reperfusion therapies for ischemic stroke in dementia and cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) have an unclear benefit in those with pre-stroke dementia or cognitive impairment, as these patients were often excluded from landmark stroke trials. We performed a systematic review and meta-analysis to assess the outcomes of IVT and EVT in these populations. AIMS: Our systematic review, conforming to the Meta-Analysis of Observational Studies in Epidemiology guidelines, investigated studies on acute ischemic stroke patients with pre-stroke dementia or cognitive impairment treated with IVT or EVT. Primary outcome was favorable 90-day outcome (mRS 0-2). Secondary outcomes included 90-day mortality, symptomatic intracranial hemorrhage (SICH), and radiographic intracranial hemorrhage (ICH). SUMMARY OF REVIEW: Nine articles were identified, with five observational studies of IVT use in patients with (n = 1078) and without dementia (n = 2805) being selected for the meta-analysis. There were no significant differences in favorable outcome (adjusted OR: 0.61, 95% CI 0.24-1.59), mortality (unadjusted OR: 1.19, 95% CI 0.86-1.64), ICH (unadjusted OR: 1.32, 95% CI 0.79-2.19), and symptomatic ICH (unadjusted OR: 0.94, 95% CI 0.70-1.25) for patients undergoing IVT with pre-stroke dementia versus those without. One EVT study (n = 615 with dementia vs n = 9600 without) found no significant differences in outcomes apart from an increased odds of ICH for those with pre-existing dementia (adjusted OR: 1.57, 95% CI 1.03-2.40). A pooled analysis of three IVT studies showed no significant association of cognitive impairment (n = 93 vs n = 211 without) with all assessed outcomes, whereas a study of EVT found that pre-stroke cognitive impairment was associated with poor 90-day outcomes (mRS 3-6). CONCLUSION: These results suggest no substantial safety issues in the use of IVT or EVT for patients with pre-existing dementia or cognitive impairment compared to those without. However, the efficacy of these therapies in this demographic remains uncertain. Further rigorous studies that include a more nuanced outcome measurement approach are warranted. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.

Endovascular treatment of acute ischemic stroke in patients with pre-morbid disability: a meta-analysis.

BACKGROUND: Trials of endovascular thrombectomy (EVT) for acute stroke have excluded patients with pre-morbid disability. Observational studies may help inform consideration of EVT in this population. We aimed to assess the effectiveness and safety of EVT in patients with pre-morbid disability. METHODS: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched MEDLINE and Embase for studies describing outcomes in patients with pre-morbid disability (modified Rankin Scale (mRS) 2-5), treated with EVT or medical management (MM). Random-effects meta-analysis was used to pool outcomes including 90-day return to baseline mRS, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: We analyzed 14 studies of patients with pre-morbid disability (mRS 2-5, 1373 EVT and 253 MM). The rate of return to baseline mRS was 30.0% (95% CI 25.3% to 34.7%) in patients treated with EVT. Compared with medical therapy, EVT was associated with a higher likelihood of return to baseline mRS (OR 2.37, 95% CI 1.39 to 4.04) and a trend towards lower mortality (OR 0.68, 95% CI 0.46 to 1.02), with similar odds of sICH (OR 1.01, 95% CI 0.49 to 2.08). In studies comparing patients with versus without pre-morbid disability treated with EVT, similar results were found except that pre-morbid disability, when defined more strictly as mRS 3-5, was associated with mortality (OR 3.49, p<0.001). CONCLUSION: In eligible patients with pre-morbid disability, observational studies suggest that EVT carries a higher chance of return to baseline mRS compared with patients treated with MM or without pre-morbid disability, although with higher mortality than patients without pre-morbid disability. These findings argue against the routine exclusion of such patients from EVT and merit validation with randomized trials.

Clinical outcomes in pediatric hydrocephalus patients treated with endoscopic third ventriculostomy and choroid plexus cauterization: a systematic review and meta-analysis.

OBJECTIVE: Endoscopic third ventriculostomy and choroid plexus cauterization (ETV+CPC) is a novel procedure for infant hydrocephalus that was developed in sub-Saharan Africa to mitigate the risks associated with permanent implanted shunt hardware. This study summarizes the hydrocephalus literature surrounding the ETV+CPC intraoperative abandonment rate, perioperative mortality rate, cerebrospinal fluid infection rate, and failure rate. METHODS: This systematic review and meta-analysis followed a prespecified protocol and abides by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy using MEDLINE, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 2019. Studies included controlled trials, cohort studies, and case-control studies of patients with hydrocephalus younger than 18 years of age treated with ETV+CPC. Pooled estimates were calculated using DerSimonian and Laird random-effects modeling, and the significance of subgroup analyses was tested using meta-regression. The quality of the pooled outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: After screening and reviewing 12,321 citations, the authors found 16 articles that met the inclusion criteria. The pooled estimate for the ETV+CPC failure rate was 0.44 (95% CI 0.37-0.51). Subgroup analysis by geographic income level showed statistical significance (p < 0.01), with lower-middle-income countries having a lower failure rate (0.32, 95% CI 0.28-0.36) than high-income countries (0.53, 95% CI 0.47-0.60). No difference in failure rate was found between hydrocephalus etiology (p = 0.09) or definition of failure (p = 0.24). The pooled estimate for perioperative mortality rate (n = 7 studies) was 0.001 (95% CI 0.00-0.004), the intraoperative abandonment rate (n = 5 studies) was 0.04 (95% CI 0.01-0.08), and the postoperative CSF infection rate (n = 5 studies) was 0.0004 (95% CI 0.00-0.003). All pooled outcomes were found to be low-quality evidence. CONCLUSIONS: This systematic review and meta-analysis provides the most comprehensive pooled estimate for the ETV+CPC failure rate to date and demonstrates, for the first time, a statistically significant difference in failure rate by geographic income level. It also provides the first reported pooled estimates for the risk of ETV+CPC perioperative mortality, intraoperative abandonment, and CSF infection. The low quality of this evidence highlights the need for further research to improve the understanding of these critical clinical outcomes and their relevant explanatory variables and thus to appreciate which patients may benefit most from an ETV+CPC. Systematic review registration no.: CRD42020160149 (https://www.crd.york.ac.uk/prospero/).

Supramaximal resection: A systematic review of its safety, efficacy and feasibility in glioblastoma.

The philosophy of 'supramaximal resection' (SMR) beyond the T1-enhanced margin holds some potential in glioblastoma surgery, but the quality of available literature has not been elucidated. A systematic review of published studies of SMR in glioblastoma surgery was performed. Articles were sought in MEDLINE, EMBASE, Scopus and Cochrane Central Register for Clinical Trials. The search items were grouped into three themes; supramaximal resection, glioblastoma and outcomes. Cases were included wherein the initial extent of resection was described as exceeding gross total resection, that is to say, beyond the area of T1-enhancement on MRI. Only newly diagnosed glioblastoma was considered. Articles containing primary patient data, including outcome data, were included; reviews, editorials, descriptive articles and systematic reviews were excluded. Subsequently, 1123 unique articles were initially retrieved. After screening article titles and abstracts for relevance to SMR in glioblastoma, seven articles remained, and were all included post-full text review. No randomized controlled trials were discovered. Almost all studies were of Level 4 quality, according to Oxford Center for Evidence-Based Medicine guidelines. The included articles yielded a total of 2019 surgically treated glioblastoma patients, 13.5% of whom underwent SMR. Preliminary results suggest SMR of glioblastoma positively impacts overall and progression free survival. However, the contemporaneous literature supporting glioblastoma SMR is of low quality, with neither anatomical nor radiographic definitional consensus for what constitutes SMR. Prospective studies of larger pooled populations with standardized technical, radiological and outcome measures in designated centers would help minimize bias and validate SMR in appropriately selected glioblastoma patients.