In the borderland of multifocal motor neuropathy and chronic inflammatory demyelinating polyradiculopathy.

Chronic inflammatory demyelinating polyradiculopathy (CIDP) and multifocal motor neuropathy (MMN) are seen as distinct entities with marked differences in pathophysiology and clinical, laboratory, and imaging features. We report a patient with an immune-mediated neuropathy in the borderland of CIDP and MMN, whose magnetic resonance imaging and cerebrospinal fluid (CSF) features strongly resembled CIDP, while the clinical course and treatment response suggested the diagnosis of MMN without conduction blocks. There is strong evidence that MMN is not a variant of CIDP and that these conditions can be separated pathologically. Our case report widens the spectrum of MMN presentations, indicating the existence of a clinical overlap syndrome of MMN and CIDP, and emphasizing the need for more precise criteria regarding CSF and nerve root imaging abnormalities in the differentiation of chronic immune-mediated neuropathies.

De novo arteriovenous shunts after endovascular cure of cerebrospinal macro arteriovenous fistulas. A role for the vasa vasorum?

BACKGROUND AND PURPOSE: Macro-arteriovenous fistulas (MAVFs) are arteriovenous shunts draining into a giant venous ectasia. They can be treated by surgery or embolisation. Angiographic controls are usually performed rapidly after treatment in order to prove the cure of the lesion but no long term angiographies are generally scheduled. We wanted to control the stabilities of such lesions at follow-up. METHOD: Clinical history and imaging of ninety-five patients with high flow shunts draining into venous ectasias (MAVFs, Vein of Galen malformations and dilatations) were reviewed. RESULTS: De novo arteriovenous shunts related to angiogenesis involving vasa vasorum developed in three patients with MAVFs at various intervals. Genetic underlying conditions as HHT or RASA 1 mutations were suspected in each patient. CONCLUSIONS: Neo-angiogenesis can occur after cure of MAVFs. Long term imaging follow-ups should be considered as the natural history of such recurrent shunts is currently unknown.

Does Device Selection Impact Recanalization Rate and Neurological Outcome?: An Analysis of the Save ChildS Study.

Background and Purpose- The recent Save ChildS study provides multicenter evidence for the use of mechanical thrombectomy in children with large vessel occlusion arterial ischemic stroke. However, device selection for thrombectomy may influence rates of recanalization, complications, and neurological outcomes, especially in pediatric patients of different ages. We, therefore, performed additional analyses of the Save ChildS data to investigate a possible association of different thrombectomy techniques and devices with angiographic and clinical outcome parameters. Methods- The Save ChildS cohort study (January 2000-December 2018) analyzed data from 27 European and United States stroke centers and included all pediatric patients (<18 years), diagnosed with arterial ischemic stroke who underwent endovascular recanalization. Patients were grouped into first-line contact aspiration (A Direct Aspiration First Pass Technique [ADAPT]) and non-ADAPT groups as well as different stent retriever size groups. Associations with baseline characteristics, recanalization rates (modified Treatment in Cerebral Infarction), complication rates, and neurological outcome parameters (Pediatric National Institutes of Health Stroke Scale after 24 hours and 7 days; modified Rankin Scale and Pediatric Stroke Outcome Measure at discharge, after 6 and 24 months) were investigated. Results- Seventy-three patients with a median age of 11.3 years were included. Currently available stent retrievers were used in 59 patients (80.8%), of which 4×20 mm (width×length) was the most frequently chosen size (36 patients =61%). A first-line ADAPT approach was used in 7 patients (9.6%), and 7 patients (9.6%) were treated with first-generation thrombectomy devices. In this study, a first-line ADAPT approach was neither associated with the rate of successful recanalization (ADAPT 85.7% versus 87.5% No ADAPT) nor with the complication rate or the neurological outcome. Moreover, there were no associations of stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Conclusions- Our study suggests that neurological outcomes are generally good regardless of any specific device selection and suggests that it is important to offer thrombectomy in eligible children regardless of technique or device selection. Registration- URL: https://www.drks.de/; Unique identifier: DRKS00016528.

Identification of pathogenic YY1AP1 splice variants in siblings with Grange syndrome by whole exome sequencing.

Grange syndrome is an autosomal recessive condition characterized by arterial occlusions and hypertension. Syndactyly, brachydactyly, bone fragility, heart defects, and learning disabilities have also been reported. Loss-of-function variants in YY1AP1 have only recently been associated with Grange syndrome. YY1AP1 encodes for the transcription coactivator yin yang 1-associated protein 1 which regulates smooth muscle cell proliferation and differentiation. We here report on three siblings with steno-occlusive arterial disorder and syndactyly in two of them. Whole exome sequencing including near-splice regions led to the identification of two intronic YY1AP1 variants which were predicted to interfere with normal splicing. Sanger sequencing demonstrated compound-heterozygosity in all affected siblings. RT-PCR analyses confirmed skipping of exon 6 on one allele and exonization of 22 bp in intron 6 on the other. This is the first report of biallelic YY1AP1 variants in noncoding regions and just the second family with multiple affected siblings. Therefore, our report further delineates the phenotypic spectrum of Grange syndrome.

Intradural spinal cord arteriovenous shunts in the pediatric population: natural history, endovascular management, and follow-up.

BACKGROUND: Intradural spinal cord arteriovenous shunts represent a rare entity, particularly in the pediatric population, and clinical diagnosis can be challenging. METHODS: We report the analysis of clinical, angioarchitectural, procedural, and follow-up data in a population of 36 children managed by our team between 2002 and 2017. RESULTS: Hemorrhage occurred in 26 children (72%). Age at onset was 9.22 ± 3.65 years. Lesions were located at the thoracic level in 16 cases, at the cervical level in 15 cases, and the thoraco-lumbar region in 5 cases. A genetic or metameric syndrome was associated in 18 children (50%). Glue embolization provided complete occlusion in 5 children, subtotal in 7, and extensive in 14 without intraprocedural complications. We observed clinical normalization in 11 children, improvement in 11 cases, and stability in 3. Four children worsened during the follow-up, and one child died. CONCLUSIONS: Endovascular staged glue embolization performed in experienced centers is safe in the treatment of pediatric intradural spinal cord arteriovenous shunts. Clinical and neuroradiological follow-up is mandatory, especially for pediatric patients.

Mechanical recanalization in basilar artery occlusion: the ENDOSTROKE study.

OBJECTIVE: A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion. METHODS: ENDOSTROKE is an investigator-initiated multicenter registry for patients undergoing EVT. This analysis includes 148 consecutive patients with BA occlusion, with 59% having received intravenous thrombolysis prior to EVT. Recanalization (defined as Thrombolysis in Cerebral Infarction [TICI] score 2b-3) and collateral status (using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral grading system) were assessed by a blinded core laboratory. Good (moderate) outcome was defined as a modified Rankin Scale score of 0 to 2 (0-3) assessed after at least 3 months (median time to follow-up = 120 days). RESULTS: Thirty-four percent had good and 42% had moderate clinical outcome; mortality was 35%. TICI 2b-3 recanalization was achieved by 79%. Age, hypertension, National Institutes of Health Stroke Scale scores, collateral status, and the use of magnetic resonance imaging prior to EVT predicted clinical outcome, the latter 3 remaining independent predictors in multivariate analysis. Independent predictors of recanalization were better collateral status and the use of a stent retriever. However, recanalization did not significantly predict clinical outcome. INTERPRETATION: Beside initial stroke severity, the collateral status predicts clinical outcome and recanalization in BA occlusion. Our data suggest that the use of a stent retriever is associated with high recanalization rates, but recanalization on its own does not predict outcome. The role of other modifiable factors, including the choice of pretreatment imaging modality and time issues, warrants further investigation.

Age dependency of successful recanalization in anterior circulation stroke: the ENDOSTROKE study.

BACKGROUND: Clinical outcome after endovascular stroke therapy (EVT) for proximal anterior circulation stroke is often disappointing despite high recanalization rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in patients undergoing EVT. Here we focus on the impact of age and recanalization on proximal middle cerebral artery (M1-MCA) or carotid T occlusion. METHODS: ENDOSTROKE is an investigator-initiated, industrially independent multicenter registry launched in January, 2011, for consecutive patients undergoing EVT for large-vessel stroke. This analysis focuses on patients treated in 11 academic and nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) score 2 or 3, and in patients with available Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3 months or later. RESULTS: The median age was 68 years (25th and 75th percentiles: 56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS) score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels. Outcome was highly dependent on patients' age: 60% of the patients within the lowest age quartile (range: 18-56 years) experienced good clinical outcome, decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the highest age quartile (77-94 years). The proportion of patients with poor clinical outcome despite TIMI 2/3 recanalization ('futile recanalization') increased dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and 3rd age quartiles) up to 53% in the highest age quartile. Results were similar in patients with available TICI scores, with 'futile recanalization' rates increasing from 24% to 46% (lowest to highest age quartile). CONCLUSIONS: This study emphasizes the dramatic impact of patients' age on outcome in EVT for M1-MCA or carotid T occlusion, even in the presence of recanalization. Reasons for this age-related decrease in clinically successful recanalization rates urgently need clarification and may comprise patient-related factors (age-related increase in cardioembolic strokes, collateral status, comorbidities) as well as periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent negative impact of general anesthesia in EVT).

Periprocedural aspects in mechanical recanalization for acute stroke: data from the ENDOSTROKE registry.

INTRODUCTION: The ENDOSTROKE registry aims to accompany the spreading use of endovascular stroke treatment (EVT) in academic and non-academic hospitals. This analysis focuses on preprocedural imaging, patient handling and referral, as well as on different treatment modalities in mechanical recanalization. METHODS: Data for this study were from observational registry study in 12 stroke centers in Germany and Austria with online assessment of prespecified variables concerning endovascular stroke therapy. RESULTS: Data from 734 patients undergoing EVT were analyzed. Preferred imaging modality prior to EVT was CT (83 %) and CTA (78 %). In 95 %, EVT was performed under general anesthesia. In 55 % of patients, a combination of intravenous (IV) thrombolysis and EVT was used, followed by pure EVT (25 %), intra-arterial (IA) thrombolysis plus EVT (13 %) and IV + IA thrombolysis plus EVT (7 %). Intrahospital time delay until start of EVT was 91 and 99 min in anterior and vertebrobasilar circulation stroke, respectively. Average duration of EVT was 60 min. Overall thrombolysis in myocardial infarction grade 2/3 recanalization rate was 85 %. Stent retrievers were used in 75 %, being associated with higher recanalization rates than non-stent retrievers. Hemorrhagic complications (symptomatic and asymptomatic) occurred in 12 %. Overall vessel occlusion time was approximately 60 min longer in patients being referred from a primary care hospital for EVT. CONCLUSION: This study gives an overview of procedure-related factors in current EVT practice. It gives estimates on preprocedural imaging modalities, periprocedural handling, and treatment combinations used for EVT. Patient referral for EVT from primary care hospitals is associated with longer vessel occlusion times.

Hyperacute Perfusion Imaging Before Pediatric Thrombectomy: Analysis of the Save ChildS Study.

BACKGROUND AND OBJECTIVES: Perfusion imaging can identify adult patients with salvageable brain tissue who would benefit from thrombectomy in later time windows. The feasibility of obtaining hyperacute perfusion sequences in pediatric stroke is unknown. The aim of this study was to determine whether contrast perfusion imaging delayed time to treatment and to assess perfusion profiles in children with large vessel occlusion stroke. METHODS: The Save ChildS retrospective cohort study (January 2000-December 2018) enrolled children (1 month-18 years) with stroke who underwent thrombectomy from 27 European and U.S. stroke centers. This secondary analysis included patients with anterior circulation occlusion and available imaging for direct review by the neuroimaging core laboratory. Between-group comparisons were performed using the Wilcoxon rank-sum exact test for continuous variables or Fisher exact test for binary variables. Given the small number of patients, evaluation of perfusion imaging parameters was performed descriptively only. RESULTS: Of 33 patients with available neuroimaging, 15 (45.4%) underwent perfusion (CT perfusion n = 6; MR perfusion n = 9); all were technically adequate. The median time from onset to recanalization did not differ between groups {4 hours (interquartile range [IQR] 4-7.5) perfusion+; 3.4 hours (IQR 2.5-6.5) perfusion-, p = 0.158}. Target mismatch criteria were met by 10/15 (66.7%) patients and did not correlate with reperfusion status or functional outcome. The hypoperfusion intensity ratio (HIR) was favorable in 11/15 patients and correlated with older age but not NIHSS, time to recanalization, or stroke etiology. Favorable HIR was associated with better functional outcome at 6 months (Pediatric Stroke Outcome Measure 1.0 [IQR 0.5-2.0] vs 2.0 [1.5-3.0], p = 0.026) and modified Rankin Scale 1.0 [0-1] vs 2.0 [1.5-3.5], p = 0.048) in this small sample. DISCUSSION: Automated perfusion imaging is feasible to obtain acutely in children and does not delay time to recanalization. Larger prospective studies are needed to determine biomarkers of favorable outcome in pediatric ischemic stroke and to establish core and penumbral thresholds in children.

Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma.

Background: The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification. Methods: In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005-2018) and an external validation site in South Korea (44 patients, 2013-2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines. Results: The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64-11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients. Conclusions: The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer.

Complication rates using balloon-expandable and self-expanding stents for the treatment of intracranial atherosclerotic stenoses : analysis of the INTRASTENT multicentric registry.

INTRODUCTION: Using balloon-expandable stents (BES) for treatment of intracranial stenoses, high inflation pressures and rigidity of the device are regarded as major drawbacks limiting feasibility and safety of the procedure. Self-expanding stents (SES) were developed to facilitate lesion access and to allow for less aggressive dilatation. We analyzed data of the INTRASTENT multicentric registry to assess whether self-expanding stents significantly reduced peri-interventional complication rates. METHODS: Records of intracranial stent procedures were entered consecutively into the registry. Datasets were divided into two groups according to the type of stent used. For outcome measurement, we chose three categories: TIA/minor stroke [modified Rankin score (mRS) <2], disabling stroke, and patient death. Clinical outcome was compared between BES and SES. We analyzed types of adverse events occurring in each group in addition. RESULTS: Of 409 atherosclerotic lesions, 254 were treated with BES and 155 with SES. Technical success rates were 97.6% and 98.7%, respectively. Adverse event rates were 4.9%, 3.7%, and 0.8% for TIA/nondisabling stroke, disabling stroke, and death in the BES group compared with 5.3%, 6.0%, and 4.0% in the SES group. The differences were not statistically significant. We observed more perforator strokes after use of BES, but thromboembolic events occurred more often in the SES treatment group. CONCLUSION: Data of the INTRASTENT registry do not support the hypothesis that introduction of SES lowered the overall complication rate of intracranial stent procedures. There might be an advantage using self-expanding stents in vessel segments with important perforating arteries.

Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing.

Evaluation of the Temporal Muscle Thickness as an Independent Prognostic Biomarker in Patients with Primary Central Nervous System Lymphoma.

In this study, we assessed the prognostic relevance of temporal muscle thickness (TMT), likely reflecting patient's frailty, in patients with primary central nervous system lymphoma (PCNSL). In 128 newly diagnosed PCNSL patients TMT was analyzed on cranial magnetic resonance images. Predefined sex-specific TMT cutoff values were used to categorize the patient cohort. Survival analyses, using a log-rank test as well as Cox models adjusted for further prognostic parameters, were performed. The risk of death was significantly increased for PCNSL patients with reduced muscle thickness (hazard ratio of 3.189, 95% CI: 2-097-4.848, p < 0.001). Importantly, the results confirmed that TMT could be used as an independent prognostic marker upon multivariate Cox modeling (hazard ratio of 2.504, 95% CI: 1.608-3.911, p < 0.001) adjusting for sex, age at time of diagnosis, deep brain involvement of the PCNSL lesions, Eastern Cooperative Oncology Group (ECOG) performance status, and methotrexate-based chemotherapy. A TMT value below the sex-related cutoff value at the time of diagnosis is an independent adverse marker in patients with PCNSL. Thus, our results suggest the systematic inclusion of TMT in further translational and clinical studies designed to help validate its role as a prognostic biomarker.

Cerebrovascular Collateral Integrity in Pediatric Large Vessel Occlusion: Analysis of the Save ChildS Study.

BACKGROUND AND OBJECTIVES: Robust cerebrovascular collaterals in adult stroke patients have been associated with longer treatment windows, better recanalization rates, and improved outcomes. No studies have investigated the role of collaterals in pediatric stroke. The primary aim was to determine whether favorable collaterals correlated with better radiographic and clinical outcomes in children with ischemic stroke who underwent thrombectomy. METHODS: This study analyzed a subset of children enrolled in SaveChildS, a retrospective, multi-center, observational cohort study of 73 pediatric stroke patients who underwent thrombectomy between 2000-2018 at 27 US and European centers. Included patients had baseline angiographic imaging and follow-up modified Rankin Scale scores available for review. Posterior circulation occlusions were excluded. Cerebrovascular collaterals were graded on acute neuroimaging by 2 blinded neuroradiologists according to the Tan collateral score, where favorable collaterals are defined as >50% filling and unfavorable collaterals as <50% filling distal to the occluded vessel. Collateral status was correlated with clinical and neuroimaging characteristics and outcomes. Between-group comparisons were performed using the Wilcoxon rank-sum test for continuous variables or Fisher's exact test for binary variables. RESULTS: Thirty-three children (mean age 10.9 [SD±4.9]) years were included; 14 (42.4%) had favorable collaterals. Median final stroke volume as a percent of total brain volume (TBV) was significantly lower in patients with favorable collaterals (1.35% [IQR 1.14-3.76] versus 7.86% [1.54-11.07], p=0.049). Collateral status did not correlate with clinical outcome, infarct growth or final ASPECTS in our cohort. Patients with favorable collaterals had higher baseline ASPECTS (7 [IQR 6-8] versus 5.5 [4-6], p=0.006), smaller baseline ischemic volume (1.57% TBV [IQR 1.09-2.29] versus 3.42% TBV [IQR 1.26-5.33], p=0.035) and slower early infarct growth rate (2.4 mL/hr [IQR 1.5-5.1] versus 10.4 mL/hr [IQR 3.0-30.7], p=0.028). DISCUSSION: Favorable collaterals were associated with smaller final stroke burden and slower early infarct growth rate, but not with better clinical outcome in our study. Prospective studies are needed to determine the impact of collaterals in childhood stroke. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in children with ischemic stroke undergoing thrombectomy, favorable collaterals were associated with improved radiographic outcomes but not with better clinical outcomes.

Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke: An Analysis of the Save ChildS Study.

OBJECTIVE: To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct. METHODS: A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct. RESULTS: Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population. CONCLUSIONS: Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe.

In-hospital complication rates after stent treatment of 388 symptomatic intracranial stenoses: results from the INTRASTENT multicentric registry.

BACKGROUND AND PURPOSE: Stenting is increasingly used as an adjunct to medical therapy in symptomatic intracranial stenoses. High periprocedural adverse event rates are one of the limitations of endovascular treatment. Data from the INTRASTENT multicentric registry should demonstrate in-hospital complications at the current stage of clinical development of the stent procedure. METHODS: Participating centers entered the records of all their consecutive intracranial stent procedures into the database. To determine the clinical outcome in the acute phase, we distinguished transient ischemic attack/nondisabling stroke (modified Rankin Scale <2), disabling stroke, death, and intracranial hemorrhage as clinical complications and analyzed whether they were associated with patient- or stenosis-related risk factors. RESULTS: Data from 372 patients with 388 stenoses proved 4.8% disabling strokes and 2.2% deaths. Transient or minor events were detected in 5.4% of the cases. Hemorrhagic events (3.5%) occurred more frequently after treatment of middle cerebral artery stenoses (P=0.004) and were associated with significantly higher morbidity and mortality rates. Ischemic strokes by compromise of perforating branches were detected mainly in the posterior circulation. However, the overall rate of severe adverse events was not dependent from location, degree, and morphology of the stenosis or from patient's age, gender, vascular risk factors, or type of qualifying event. CONCLUSIONS: The complication rates within the registry are within the limits of previously published data. Severe adverse events were equally distributed between potential risk groups with similar rates but different types of main complications in the anterior and posterior circulation.

Sex-Specific Differences in Primary CNS Lymphoma.

Sex-specific differences have been increasingly recognized in many human diseases including brain cancer, namely glioblastoma. Primary CNS lymphoma (PCNSL) is an exceedingly rare type of brain cancer that tends to have a higher incidence and worse outcomes in male patients. Yet, relatively little is known about the reasons that contribute to these observed sex-specific differences. Using a population-representative cohort of patients with PCNSL with dense magnetic resonance (MR) imaging and digital pathology annotation (n = 74), we performed sex-specific cluster and survival analyses to explore possible associations. We found three prognostically relevant clusters for females and two for males, characterized by differences in (i) patient demographics, (ii) tumor-associated immune response, and (iii) MR imaging phenotypes. Upon a multivariable analysis, an enhanced FoxP3+ lymphocyte-driven immune response was associated with a shorter overall survival particularly in female patients (HR 1.65, p = 0.035), while an increased extent of contrast enhancement emerged as an adverse predictor of outcomes in male patients (HR 1.05, p < 0.01). In conclusion, we found divergent prognostic constellations between female and male patients with PCNSL that suggest differential roles of tumor-associated immune response and MR imaging phenotypes. Our results further underline the importance of continued sex-specific analyses in the field of brain cancer.

Feasibility, Safety, and Outcome of Endovascular Recanalization in Childhood Stroke: The Save ChildS Study.

Importance: Randomized clinical trials have shown the efficacy of thrombectomy of large intracranial vessel occlusions in adults; however, any association of therapy with clinical outcomes in children is unknown. Objective: To evaluate the use of endovascular recanalization in pediatric patients with arterial ischemic stroke. Design, Setting, and Participants: This retrospective, multicenter cohort study, conducted from January 1, 2000, to December 31, 2018, analyzed the databases from 27 stroke centers in Europe and the United States. Included were all pediatric patients (<18 years) with ischemic stroke who underwent endovascular recanalization. Median follow-up time was 16 months. Exposures: Endovascular recanalization. Main Outcomes and Measures: The decrease of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score from admission to day 7 was the primary outcome (score range: 0 [no deficit] to 34 [maximum deficit]). Secondary clinical outcomes included the modified Rankin scale (mRS) (score range: 0 [no deficit] to 6 [death]) at 6 and 24 months and rate of complications. Results: Seventy-three children from 27 participating stroke centers were included. Median age was 11.3 years (interquartile range [IQR], 7.0-15.0); 37 patients (51%) were boys, and 36 patients (49%) were girls. Sixty-three children (86%) received treatment for anterior circulation occlusion and 10 patients (14%) received treatment for posterior circulation occlusion; 16 patients (22%) received concomitant intravenous thrombolysis. Neurologic outcome improved from a median PedNIHSS score of 14.0 (IQR, 9.2-20.0) at admission to 4.0 (IQR, 2.0-7.3) at day 7. Median mRS score was 1.0 (IQR, 0-1.6) at 6 months and 1.0 (IQR, 0-1.0) at 24 months. One patient (1%) developed a postinterventional bleeding complication and 4 patients (5%) developed transient peri-interventional vasospasm. The proportion of symptomatic intracerebral hemorrhage events in the HERMES meta-analysis of trials with adults was 2.79 (95% CI, 0.42-6.66) and in Save ChildS was 1.37 (95% CI, 0.03-7.40). Conclusions and Relevance: The results of this study suggest that the safety profile of thrombectomy in childhood stroke does not differ from the safety profile in randomized clinical trials for adults; most of the treated children had favorable neurologic outcomes. This study may support clinicians' practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.