Search

Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion.Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes.Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048).In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

International audience; Background and purpose: Studies on long-term nonmotor outcomes of subthalamic nucleus stimulation in Parkinson disease (PD) are scarce. This study reports on very long-term non-motor and motor outcomes in one of the largest cohorts of people with advanced PD, treated for >10 years with subthalamic nucleus stimulation. The main outcome was to document the evolution of independence in activities of daily living. The secondary outcomes were to measure the change in quality of life, as well as non-motor and motor outcomes.Methods: Patients were studied preoperatively, at 1 year, and beyond 10 years after subthalamic stimulation with an established protocol including motor, non-motor, and neuropsychological assessments.Results: Eighty-five people with PD were included. Independence scores in the off-medication condition (measured with the Schwab & England Activities of Daily Living Scale) as well as quality of life (measured with the Parkinson's Disease Questionnaire [PDQ]-37) remained improved at longest follow-up compared to preoperatively (respectively, p < 0.001, p = 0.015). Cognitive scores, measured with the Mattis Dementia Rating Scale, significantly worsened compared to before and 1 year after surgery (p < 0.001), without significant change in depression, measured with the Beck Depression Inventory. Motor fluctuations, dyskinesias, and off dystonia remained improved at longest follow-up (p < 0.001), with a significant reduction in dopaminergic treatment (45%, p < 0.001).Conclusions: This study highlights the long-term improvement of subthalamic stimulation on independence and quality of life, despite the progression of disease and the occurrence of levodopa-resistant symptoms.

In eukaryotes and in archaea late steps of translation initiation involve the two initiation factors e/aIF5B and e/aIF1A. In eukaryotes, the role of eIF5B in ribosomal subunit joining is established and structural data showing eIF5B bound to the full ribosome were obtained. To achieve its function, eIF5B collaborates with eIF1A. However, structural data illustrating how these two factors interact on the small ribosomal subunit have long been awaited. The role of the archaeal counterparts, aIF5B and aIF1A, remains to be extensively addressed. Here, we study the late steps of Pyrococcus abyssi translation initiation. Using in vitro reconstituted initiation complexes and light scattering, we show that aIF5B bound to GTP accelerates subunit joining without the need for GTP hydrolysis. We report the crystallographic structures of aIF5B bound to GDP and GTP and analyze domain movements associated to these two nucleotide states. Finally, we present the cryo-EM structure of an initiation complex containing 30S bound to mRNA, Met-tRNAiMet, aIF5B and aIF1A at 2.7 Å resolution. Structural data shows how archaeal 5B and 1A factors cooperate to induce a conformation of the initiator tRNA favorable to subunit joining. Archaeal and eukaryotic features of late steps of translation initiation are discussed.

Aberrantly slow mRNA translation leads to ribosome stalling and subsequent collision with the trailing neighbor. Ribosome collisions have recently been shown to act as stress sensors in the cell, with the ability to trigger stress responses balancing survival and apoptotic cell-fate decisions depending on the stress level. However, we lack a molecular understanding of the reorganization of translation processes over time in mammalian cells exposed to an unresolved collision stress. Here we visualize the effect of a persistent collision stress on translation usingin situcryo electron tomography. We observe that low dose anisomycin collision stress leads to the stabilization of Z-site bound tRNA on elongating 80S ribosomes, as well as to the accumulation of an off-pathway 80S complex possibly resulting from collision splitting events. We visualize collided disomesin situ, occurring on compressed polysomes and revealing a stabilized geometry involving the Z-tRNA and L1 stalk on the stalled ribosome, and eEF2 bound to its collided rotated-2 neighbor. In addition, non-functional post-splitting 60S complexes accumulate in the stressed cells, indicating a limiting Ribosome associated Quality Control clearing rate. Finally, we observe the apparition of tRNA-bound aberrant 40S complexes shifting with the stress timepoint, suggesting a succession of different initiation inhibition mechanisms over time. Altogether, our work visualizes the changes of translation complexes under persistent collision stress in mammalian cells, indicating how perturbations in initiation, elongation and quality control processes contribute to an overall reduced protein synthesis.SummaryUsingin situcryo electron tomography we visualized the reorganization of mammalian translation processes during a persistent collision stress.

De novo Parkinson's disease (PD) patients with apathy exhibit prominent limbic serotonergic dysfunction and microstructural disarray. Whether this distinctive lesion profile at diagnosis entails different prognosis remains unknown.To investigate the progression of dopaminergic and serotonergic dysfunction and their relation to motor and nonmotor impairment in PD patients with or without apathy at diagnosis.Thirteen de novo apathetic and 13 nonapathetic PD patients were recruited in a longitudinal double-tracer positron emission tomography cohort study. We quantified the progression of presynaptic dopaminergic and serotonergic pathology using [After the initiation of dopamine replacement therapy, apathy, depression, and anxiety improved at follow-up in patients with apathy at diagnosis (n = 10) to the level of patients without apathy (n = 11). Patients had similar progression of motor impairment, whereas mild impulsive behaviors developed in both groups. Striato-pallidal and mesocorticolimbic presynaptic dopaminergic loss progressed similarly in both groups, as did serotonergic pathology in the putamen, caudate nucleus, and pallidum. Contrastingly, serotonergic innervation selectively increased in the ventral striatum and anterior cingulate cortex in apathetic patients, contributing to the reversal of apathy besides dopamine replacement therapy.Patients suffering from apathy at diagnosis exhibit compensatory changes in limbic serotonergic innervation within 5 years of diagnosis, with promising evidence that serotonergic plasticity contributes to the reversal of apathy. The relationship between serotonergic plasticity and dopaminergic treatments warrants further longitudinal investigations. © 2022 International Parkinson and Movement Disorder Society.

Background and Purpose: In the settings of thrombectomy, the first-pass effect (FPE), defined by a complete recanalization after one pass with no rescue therapy, has been shown to be associated with an improved outcome. As this phenomenon has been predominantly described in anterior circulation strokes, we aimed to study the prevalence, outcomes, and predictors of FPE in patients with a basilar artery occlusion. Methods: From a prospective multicentric registry, we collected the data of all consecutive basilar artery occlusion patients who underwent thrombectomy and compared the outcomes of patients who achieved FPE and those who did not. We also compared FPE patients with those who achieved a complete recanalization with >1 pass. Finally, a multivariate analysis was performed to determine the predictors of FPE. Results: Data from 280 patients were analyzed in our study, including 84 of 280 patients (30%) with an atheromatous etiology. An FPE was achieved in 93 patients (33.2%), with a significantly higher proportion of good outcomes (modified Rankin Scale score 0-2 at 3 months) and lower mortality than non-FPE patients. An FPE was also associated with improved outcomes compared with patients who went on to have full recanalization with >1 pass. Contact aspiration as first-line strategy was a strong predictor of FPE, whereas baseline antiplatelets and atheromatous etiology were negative predictors. Conclusions: In our study, an FPE was achieved in approximately one-third of patients with a basilar artery occlusion and was associated with improved outcomes. More research is needed to improve devices and techniques to increase the incidence of FPE. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03776877.

Aminoacyl-tRNA synthetases (aaRS) are ubiquitously expressed enzymes responsible for ligating amino acids to their cognate tRNA molecules through an aminoacylation reaction. The resulting aminoacyl-tRNA is delivered to ribosome elongation factors to participate in protein synthesis. Seryl-tRNA synthetase (SARS1) is one of the cytosolic aaRSs and catalyzes serine attachment to tRNASer . SARS1 deficiency has already been associated with moderate intellectual disability, ataxia, muscle weakness, and seizure in one family. We describe here a new clinical presentation including developmental delay, central deafness, cardiomyopathy, and metabolic decompensation during fever leading to death, in a consanguineous Turkish family, with biallelic variants (c.638G>T, p.(Arg213Leu)) in SARS1. This missense variant was shown to lead to protein instability, resulting in reduced protein level and enzymatic activity. Our results describe a new clinical entity and expand the clinical and mutational spectrum of SARS1 and aaRS deficiencies.

Amino acids (AAs) with a noncanonical backbone would be a valuable tool for protein engineering, enabling new structural motifs and building blocks. To incorporate them into an expanded genetic code, the first, key step is to obtain an appropriate aminoacyl-tRNA synthetase (aaRS). Currently, directed evolution is not available to optimize such AAs, since an appropriate selective pressure is not available. Computational protein design (CPD) is an alternative. We used a new CPD method to redesign MetRS and increase its activity towardsβ-Met, which has an extra backbone methylene. The new method considered a few active site positions for design and used a Monte Carlo exploration of the corresponding sequence space. During the exploration, a bias energy was adaptively learned, such that the free energy landscape of the apo enzyme was flattened. Enzyme variants could then be sampled, in the presence of the ligand and the bias energy, according to theirβ-Met binding affinities. Eleven predicted variants were chosen for experimental testing; all exhibited detectable activity forβ-Met adenylation. Top predicted hits were characterized experimentally in detail. Dissociation constants, catalytic rates, and Michaelis constants for bothα-Met andβ-Met were measured. The best mutant retained a preference forα-Met overβ-Met; however, the preference was reduced, compared to the wildtype, by a factor of 29. For this mutant, high resolution crystal structures were obtained in complex with bothα-Met andβ-Met, indicating that the predicted, active conformation ofβ-Met in the active site was retained.Author summaryAmino acids (AAs) with a noncanonical backbone would be valuable for protein engineering, enabling new structural motifs. To incorporate them into an expanded genetic code, the key step is to obtain an appropriate aminoacyl-tRNA synthetase (aaRS). Currently, directed evolution is not available to optimize such AAs. Computational protein design is an alternative. We used a new method to redesign MetRS and increase its activity towardsβ-Met, which has an extra backbone methylene. The method considered a few active site positions for design and used a Monte Carlo exploration of sequence space, during which a bias energy was adaptively learned, such that the free energy landscape of the apo enzyme was flattened. Enzyme variants could then be sampled, in the presence of the ligand and the bias energy, according to theirβ-Met binding affinities. Eleven predicted variants were chosen for experimental testing; all exhibited detectableβ-Met adenylation activity. Top hits were characterized experimentally in detail. The best mutant had its preference forα-Met overβ-Met reduced by a factor of 29. Crystal structures indicated that the predicted, active conformation ofβ-Met in the active site was retained.

Background: Management of extracranial internal carotid artery steno-occlusive lesion during endovascular therapy remains debated. Stent occlusion within 24 hours of endovascular therapy is a frequent event after acute carotid artery stenting, and we currently lack large population results. We investigated the incidence, predictors, and clinical impact of stent occlusion after acute carotid artery stenting in current clinical practice. Methods: Patients treated by endovascular therapy with acute carotid artery stenting between 2015 and 2019 in 5 large-volume endovascular-capable centers were retrospectively analyzed. Patients were separated in 2 groups according to the stent patency at 24 hours after carotid artery stenting. We compared baseline characteristics, treatment modalities, and clinical outcome depending on 24-hour stent patency. Primary end point was favorable outcome, defined as a modified Rankin Scale score 0–2 at 3 months. Results: A stent occlusion was observed in 47/225 patients (20.9%). Patients with stent patency had a lower baseline National Institutes of Health Stroke Scale (median [interquartile range]: 13 [7–17] versus 18 [12–21]) and had more often stroke of atherothrombotic origin (77.0% versus 53.2%). A higher stent patency rate was found for patients treated with P2Y 12 antagonists at the acute phase (odds ratio [OR]‚ 2.95 [95% CI‚ 1.10–7.91]; P =0.026) and treated with angioplasty (OR‚ 2.42 [95% CI‚ 1.24–4.67]; P =0.008). A better intracranial angiographic reperfusion was observed in patients with 24-hour stent patency compared with patients without stent patency (OR‚ 8.38 [95% CI‚ 3.07–22.78]; P P P =0.009). Conclusions: One out of 5 patients treated with carotid artery stenting during endovascular therapy presented a stent occlusion within 24 hours. This event was associated with worse functional outcome. Stroke etiology, P2Y 12 antagonist administration, quality of intracranial reperfusion, and angioplasty were associated with 24-hour stent patency.

International audience; INTRODUCTION: There is a growing interest in personality evaluation in Parkinson's disease (PD), following observations of specific temperaments in PD patients. Therefore, our objective was to evaluate personality dimensions from the Temperament and Character Inventory (TCI) in a cohort of fluctuating PD patients considered for deep brain stimulation. METHODS: Fluctuating PD patients from the PREDISTIM cohort were included. Description of TCI dimensions and comparison with a French normative cohort were performed. Pearson correlations between TCI dimensions and motor, behavioral and cognitive variables were investigated. Structural and internal consistency analysis of the TCI were further assessed. RESULTS: The 570 PD patients presented significant higher scores in Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness and significant lower scores in Self-Transcendence compared to the French normative cohort; only Novelty Seeking scores were not different. Harm Avoidance and Self-directedness scores were correlated with PDQ-39 total, HAMD, HAMA scores, and anxiolytic/antidepressant treatment. Novelty Seeking scores were correlated with impulsivity. Pearson correlations between TCI dimensions, principal component analysis of TCI sub-dimensions and Cronbach's alpha coefficients showed adequate psychometric proprieties. CONCLUSION: The TCI seems to be an adequate tool to evaluate personality dimensions in PD with good structural and internal consistencies. These fluctuating PD patients also have specific personality dimensions compared to normative French population. Moreover, Harm Avoidance and Self-Directedness scores are associated with anxio-depressive state or quality of life and, and Novelty Seeking scores with impulsivity.

Resume L’hypotension intracrânienne spontanee (HIS) est une anomalie de repartition des volumes intracrâniens, due a une fuite rachidienne de liquide cephalorachidien (LCR), au depend des espaces sous-arachnoidiens qui ne peuvent plus assurer l’interface entre le nevraxe et l’enveloppe osteomeningee. La definition par la Classification Internationale des Cephalees 3e edition (ICHD-3) demontre qu’il s’agit d’un challenge diagnostique pour le praticien. Elle s’appuie sur des signes cliniques peu specifiques qui doivent etre confirmes par des signes radiologiques difficiles a identifier, prouvant une fuite meningee de LCR. Il en decoule une strategie therapeutique encore peu etablie. A partir d’une discussion de cette definition, afin d’ameliorer le diagnostic d’HIS, il apparait crucial de chercher dans l’enquete etiologique des patients presentant des cephalees, le caractere orthostatique, permanent ou non, dans l’anamnese des symptomes. Qu’il soit present ou non, il faudra ensuite verifier sur l’IRM cerebrale des signes indirects de fuite du LCR sous la forme d’un deplacement cranio caudal du nevraxe, d’un engorgement veineux, ou d’un decollement sous-dural. En cas de diagnostic etabli, un traitement medical associe a un blood patch epidural lombaire pouvant etre repete, constitue la premiere ligne therapeutique. L’identification de la fuite de LCR est plus difficile et inconstante, necessitant le recours au myelo-TDM. Elle sera reservee aux cas pour lesquels le diagnostic reste incertain apres l’IRM cerebro-medullaire, et pour lesquels une therapie ciblee sur la breche est indispensable. L’amelioration des strategies diagnostiques de l’HIS est d’autant plus importante que le pronostic est extremement favorable grâce a un traitement bien conduit.

BackgroundWe report the first case series of spontaneous intracranial hypotension (SIH) patients who underwent CT-guided percutaneous cyanoacrylate injection targeting the cerebrospinal fluid (CSF) leak.MethodsA retrospective analysis was performed for all consecutive cases of SIH patients with CSF leak confirmed on CT myelography, treated by CT-guided percutaneous cyanoacrylate injection at our institution from 2016 to 2022. On pretreatment brain and spine MRIs, we analyzed signs of SIH according to the Bern score, and dichotomized cases into positive/negative for spinal longitudinal extradural CSF collection (SLEC-P or SLEC-N). The leaks detected on CT myelography were classified into three types according to Schievinket al. We collected the Headache Impact Test 6 (HIT-6) scores throughout a 6-month follow-up, with a brain CT scan at each visit.Results11 patients were included (mean age 48.4 years, six men). Five SLEC-P type 1, three SLEC-P type 2, and three SLEC-N type 3 leaks were identified. All patients had significant signs of SIH on pretreatment brain MRI (mean Bern score 7.8±1.1). Six patients underwent a foraminal puncture, and five patients had a cervical epidural approach. Two patients experienced mild and transient locoregional pain after cervical epidural injection. Mean HIT-6 score at baseline was 66.8±3.2 and at the 6-month follow-up was 38±3.6 (PConclusionsCT-guided percutaneous cyanoacrylate injection may be a potential therapeutic option for the different types of CSF leak causing SIH.

Background: Previous studies described a parkinsonian personality characterized as rigid, introverted, and cautious; however, little is known about personality traits in de novo Parkinson’s disease (PD) patients and their relationships with motor and neuropsychiatric symptoms. Objective: To investigate personality in de novo PD and explore its relationship with PD symptoms. Methods: Using Cloninger’s biosocial model, we assessed personality in 193 de novo PD patients. Motor and non-motor symptoms were measured using several validated scales. Cluster analysis was conducted to investigate the interrelationship of personality traits, motor, and non-motor symptoms. Results: PD patients showed low novelty seeking, high harm avoidance, and normal reward dependence and persistence scores. Harm avoidance was positively correlated with the severity of depression, anxiety, and apathy (rs = [0.435, 0.676], p

Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the electron-density difference between solubilized biomacromolecules and the buffer, and provides information on molecular masses, particle dimensions and interactions, low-resolution conformations and pair distance-distribution functions. When SAXS data are recorded at multiple contrasts, i.e. at different solvent electron densities, it is possible to probe, in addition to their overall shape, the internal electron-density profile of biomacromolecular assemblies. Unfortunately, contrast-variation SAXS has been limited by the range of solvent electron densities attainable using conventional co-solutes (for example sugars, glycerol and salt) and by the fact that some biological systems are destabilized in their presence. Here, SAXS contrast data from an oligomeric protein and a protein–RNA complex are presented in the presence of iohexol and Gd-HPDO3A, two electron-rich molecules that are used in biomedical imaging and that belong to the families of iodinated and lanthanide-based complexes, respectively. Moderate concentrations of both molecules allowed solvent electron densities matching those of proteins to be attained. While iohexol yielded higher solvent electron densities (per mole), it interacted specifically with the oligomeric protein and precipitated the protein–RNA complex. Gd-HPDO3A, while less efficient (per mole), did not disrupt the structural integrity of either system, and atomic models could be compared with the SAXS data. Due to their elevated solubility and electron density, their chemical inertness, as well as the possibility of altering their physico-chemical properties, lanthanide-based complexes represent a class of molecules with promising potential for contrast-variation SAXS experiments on diverse biomacromolecular systems.

Background: Fatigue is a frequent and troublesome symptom present from the early stages of Parkinson’s disease (PD). Objective: To examine the relationship between fatigue and the neuropsychiatric triad, which includes apathy, depression, and anxiety, in de novo PD. Methods: We performed a cross-sectional study including 197 patients with de novo PD and assessed fatigue using the Parkinson’s Disease Fatigue Scale (PDFS-16). We evaluated motor status using the Unified Parkinson’s Disease Rating Scale (UPDRS) part III score and evaluated neuropsychiatric status using the Ardouin Scale of Behavior in Parkinson’s Disease (ASBPD). We carried out univariate and multivariate analyses to model association between motor signs, non-motor signs, and fatigue risk. Results: Frequency of fatigue (28.9%) was of the same order of magnitude as that of apathy. PD patients with fatigue reported a lower quality of life than patients without fatigue (p

ObjectivesTo assess the prevalence and the cumulative incidence of dementia at short-, medium- and long-term follow-up after deep brain stimulation (DBS) of the subthalamic nucleus (STN) (at 1, 5, and 10 years) and to evaluate potential risk factors for postoperative dementia.MethodsThe presence of dementia (according to the DSM-V) was retrospectively evaluated at each postoperative follow-up in patients with Parkinson disease (PD) who underwent bilateral STN-DBS. Preoperative and perioperative risk factors of developing postoperative dementia were also investigated. Demographic data, disease features, medications, comorbidities, nonmotor symptoms, PD motor scales, neuropsychological scales at baseline, and perioperative complications were collected for each patient.ResultsA total of 175 patients were included, and 104 were available at 10-year follow-up. Dementia prevalence was 2.3% at 1 year, 8.5% at 5 years, and 29.8% at 10 years. Dementia cumulative incidence at 1, 5, and 10 years was 2.3%, 10.9%, and 25.7%, respectively. The corresponding dementia incidence rate was 35.6 per 1,000 person-years. Male sex, higher age, hallucinations, lower frontal score at baseline, and perioperative cerebral hemorrhage were predictors of dementia.ConclusionsIn patients with PD with longstanding STN-DBS, dementia prevalence and incidence are not higher than those reported in the general PD population. Except for few patients with perioperative cerebral hemorrhage, STN-DBS is cognitively safe, and does not provide dementia risk factors in addition to those reported for PD itself. Identification of dementia predictors in this population may improve patient selection and information concerning the risk of poor cognitive outcome.

BACKGROUND: HIT-SKK protocol is used for the treatment of low risk medulloblastomas in young children with the aim of eliminating cranial irradiation and its long-term side effects, in particular neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders.The objectives are to describe the risk factors and the course of LE, and to investigate its impact on long-term neurocognitive and behavioural outcome. METHODS: A French retrospective, multicenter study including 35 children under 5 years of age, treated between 2009 and 2017, with a median follow up of 72 months. All follow-up MRIs including assessment of the severity of the LE (Fazekas and CTCAE grading) and all NP evaluations were centrally rewieved. RESULTS: 25/34 evaluable patients presented a LE during follow up, in a median delay of 2 months (1 - 17 months) after the start of chemotherapy. Grade 2 and 3 abnormalities were correlated with higher cumulative dose of ITV -MTX (p=0,01). Full Scale IQ (FSIQ) and Wechsler indexes were in the average or low average of the reference population. FSIQ was deficient in 7/20 evaluable patients. Processing speed (PSI) was the most frequently impaired neurocognitive domain: 9/20 patients with borderline or very low score, all having received a significantly higher cumulative dose of ITV-MTX (p=0,04). A decrease in overall NP scores was observed in patients for whom grade 2 or 3 LE persisted at the end of follow-up with an average FSIQ estimated at 82.1 (SD 16.9) versus 94.2 (SD 20.6). This decrease was significant for PSI (p=0,049). LE and neurocognitive impairments were not correlated with a younger age at diagnosis. CONCLUSION: This study confirmed the responsibility of MTX, and in particular ITV-MTX therapy in the onset and, most often, persistence of LE and its association with neurocognitive disorders.

Background and Purpose: Approximately half of the patients with acute ischemic stroke due to anterior circulation large vessel occlusion do not achieve functional independence despite successful reperfusion. We aimed to determine influence of reperfusion strategy (bridging therapy, intravenous thrombolysis alone, or mechanical thrombectomy alone) on clinical outcomes in this population. Methods: From ongoing, prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke registry in France, all patients with anterior circulation large vessel occlusion who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3) following reperfusion therapy were included. Primary end point was favorable outcome, defined as 90-day modified Rankin Scale score ≤2. Patient groups were compared using those treated with bridging therapy as reference. Differences in baseline characteristics were reduced after propensity score-matching, with a maximum absolute standardized difference of 14% for occlusion site. Results: Among 1872 patients included, 970 (51.8%) received bridging therapy, 128 (6.8%) received intravenous thrombolysis alone, and the remaining 774 (41.4%) received MT alone. The rate of favorable outcome was comparable between groups. Excellent outcome (90-day modified Rankin Scale score 0–1) was achieved more frequently in the bridging therapy group compared with the MT alone (odds ratio after propensity score-matching, 0.70 [95% CI, 0.50–0.96]). Regarding safety outcomes, hemorrhagic complications were similar between the groups, but 90-day mortality was significantly higher in the MT alone group compared with the bridging therapy group (odds ratio, 1.60 [95% CI, 1.09–2.37]). Conclusions: This real-world observational study of patients with anterior circulation large vessel occlusion demonstrated a similar rate of favorable outcome following successful reperfusion with different therapeutic strategies. However, our results suggest that bridging therapy compared with MT alone is significantly associated with excellent clinical outcome and lower mortality. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03776877.

BackgroundRuptured basilar artery perforator aneurysms (BAPAs), defined as microaneurysms which develop in basilar perforator arteries without direct involvement of the basilar trunk, represent a rare cause of subarachnoid hemorrhage (SAH). The diagnosis of BAPAs is difficult because of their small size, with high rates of negative angiography. The development of high-resolution MRI could increase the diagnostic performance. In this study we describe the usefulness of susceptibility weighted imaging (SWI) for the diagnosis of ruptured BAPAs.MethodsIn a case series, we retrospectively collected data of patients admitted to our institution from 2018 to 2021 for SAH with negative CT angiography who underwent MRI (including SWI) and DSA during hospitalization.ResultsEight patients with a definitive diagnosis of ruptured BAPA and five patients with a definitive diagnosis of angiogram-negative SAH were included. In all of the patients with BAPAs MRI showed a focal, thick, semi-circumferential SWI hypointensity covering the vessel wall at the level of the BAPA subsequently revealed on DSA; this phenomen is known as ‘SWI capping’. No SWI capping was observed in the five patients with a definitive diagnosis of angiogram-negative SAH.ConclusionSWI capping appears to be a reliable indirect sign for the diagnosis and localization of ruptured BAPAs, a rare form of microaneurysm easily misdiagnosed on DSA in initial angiogram-negative SAH.

Resume Introduction Les occlusions du tronc basilaire, representent 20 % des accidents vasculaires ischemiques cerebraux et sont de mauvais pronostic. La thrombectomie mecanique, traitement de reference pour les occlusions proximales de la circulation anterieure est egalement indiquee dans ce type d’occlusion malgre l’absence de consensus. Donnees recentes Selon les donnees recentes de la litterature, une recanalisation satisfaisante est obtenue dans 79 % des cas sans difference significative selon la technique employee. La reperfusion semble meilleure et plus rapide en cas d’aspiration premiere. L’echec de recanalisation est independamment associe a une evolution clinique defavorable. La mortalite a 3 mois est associe a l’âge ≥60 ans, un score NIHSS ≥13 a l’admission, l’absence de thrombolyse intraveineuse, l’angioplastie et/ou stenting et un score pc-ASPECTS bas. Conclusion La recanalisation efficace est l’objectif premier de la prise en charge initiale, et les techniques endovasculaires recentes ont demontre leur efficacite angiographique avec une superiorite pour l’aspiration distale. Cependant, la mortalite de ces patients depasse encore les 40 % malgre les dernieres avancees techniques.

Recently, we observed the first example of a left‐handed G‐quadruplex structure formed by natural DNA, named Z‐G4 . We analysed the Z‐G4 structure and inspected its primary 28‐nt sequence in order to identify motifs that convey the unique left‐handed twist. Using circular dichroism spectroscopy, NMR spectroscopy, and X‐ray crystallography, we revealed a minimal sequence motif of 12 nt (GTGGTGGTGGTG) for formation of the left‐handed DNA G‐quadruplex, which is found to be highly abundant in the human genome. A systematic analysis of thymine loop mutations revealed a moderate sequence tolerance, which would further broaden the space of sequences prone to left‐handed G‐quadruplex formation. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version