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Stroke affects up to one in five people during their lifetime in some high-income countries, and up to almost one in two in low-income countries. Globally, it is the second leading cause of death. Clinically, the disease is characterised by sudden neurological deficits. Vascular aetiologies contribute to the most common causes of ischaemic stroke, including large artery disease, cardioembolism, and small vessel disease. Small vessel disease is also the most frequent cause of intracerebral haemorrhage, followed by macrovascular causes. For acute ischaemic stroke, multimodal CT or MRI reveal infarct core, ischaemic penumbra, and site of vascular occlusion. For intracerebral haemorrhage, neuroimaging identifies early radiological markers of haematoma expansion and probable underlying cause. For intravenous thrombolysis in ischaemic stroke, tenecteplase is now a safe and effective alternative to alteplase. In patients with strokes caused by large vessel occlusion, the indications for endovascular thrombectomy have been extended to include larger core infarcts and basilar artery occlusion, and the treatment time window has increased to up to 24 h from stroke onset. Regarding intracerebral haemorrhage, prompt delivery of bundled care consisting of immediate anticoagulation reversal, simultaneous blood pressure lowering, and prespecified stroke unit protocols can improve clinical outcomes. Guided by underlying stroke mechanisms, secondary prevention encompasses pharmacological, vascular, or endovascular interventions and lifestyle modifications. [ABSTRACT FROM AUTHOR]

Background: Although anxiety is common in several neurological conditions, it has been poorly investigated after spontaneous intracerebral hemorrhage (ICH). Aims: In consecutive ICH survivors, we assessed the long-term prevalence of anxiety and its clinical and radiological determinants. Methods: Using the Hospital Anxiety and Depression Scale (HADS), we evaluated ICH survivors enrolled in the prospective, single-center Prognosis of Intracerebral Hemorrhage (PITCH) study. The prevalence of anxiety (defined as a HADS-anxiety subscale score >7) was evaluated at three time points (1–2, 3–5, and 6–8 years after ICH), along with neurological symptoms severity, functional disability, and cognitive impairment scores. Clinical and radiological characteristics associated with anxiety were evaluated in univariate and multivariable models. Results: Of 560 patients with spontaneous ICH, 255 were alive 1 year later, 179 of whom completed the HADS questionnaire and were included in the study. Thirty-one patients (17%; 95% confidence interval (CI) = 12–23) had anxiety 1–2 years, 38 (27%; 95% CI = 19–34) 3–5 years, and 18 (21%; 95% CI = 12–30) 6–8 years after ICH. In patients with anxiety, the prevalence of associated depressive symptoms was 48% 1–2 years, 61% 3–5 years, and 56% 6–8 years after ICH. Among clinical and radiological baseline characteristics, only lobar ICH location was significantly associated with anxiety 1–2 years after ICH (odds ratio = 2.8; 95% CI = 1.2–6.5). Anxiety was not associated with concomitant neurological symptoms severity, functional disability, or cognitive impairment. Conclusion: Anxiety is frequent in ICH survivors, often in association with depressive symptoms, even many years after the index event. [ABSTRACT FROM AUTHOR]

Background: Factors associated with long-term mortality after spontaneous intracerebral hemorrhage (ICH) have been poorly investigated. Aim: Our objective was to identify variables associated with long-term mortality in a prospective cohort of 30-day ICH survivors. Methods: We prospectively included consecutive 30-day spontaneous ICH survivors. We evaluated baseline and follow-up clinical characteristics and magnetic resonance imaging (MRI) markers of chronic brain injury as variables associated with long-term mortality using univariate and multivariable Cox proportional hazard regression models. Results: Of 560 patients with spontaneous ICH, 304 (54.2%) survived more than 30 days and consented for follow-up. During a median follow-up of 10 years (interquartile range: 8.0–10.5), 176 patients died. The cumulative survival rate at 10 years was 38%. In multivariable analysis, variables independently associated with long-term mortality were age (hazard ratio (HR) per 10-year increase: 1.68, 95% confidence interval (CI): 1.45–1.95), male gender (HR: 1.41, CI: 1.02–1.95), prestroke dependency (HR: 1.66, CI: 1.15–2.39), National Institutes of Health Stroke Scale score (HR per 1-point increase: 1.03, CI: 1.01–1.04), occurrence of any stroke (HR: 2.24, CI: 1.39–3.60), and dementia (HR: 1.51, CI: 1.06–2.16) during follow-up. Among MRI markers, only cerebral atrophy (HR per 1-point increase: 1.50, CI: 1.13–2.00) was independently associated with long-term mortality. Conclusions: Preexisting comorbidities, clinical severity at presentation, and significant clinical event during follow-up are associated with long-term mortality. Among MRI markers of chronic brain injury, only cerebral atrophy is associated with long-term mortality. [ABSTRACT FROM AUTHOR]

Background: The epileptogenicity of recombinant tissue-plasminogen activator (rt-PA) has been suggested, but seizures were not evaluated in randomised controlled trials. Objective: To evaluate whether rt-PA was associated with early seizures in a cohort of consecutive patients with cerebral ischaemia. Method: We included consecutive adults with ischaemic stroke due to large-vessel occlusion from the North-of-France stroke network selected for a mechanical thrombectomy (MT). Patients without contraindication received i.v. rt-PA. We evaluated stroke severity with the National Institutes of Health Stroke Scale (NIHSS), and functional status with the modified Rankin scale (mRS), and recorded epileptic seizures occurring between the end of imaging and day 7. We performed statistics using propensity analyses. Results: We included 1638 patients (783 men, 47.8%; median age 71 years; median NIHSS score 16; 1007 treated by rt-PA, 61.5%), in whom 60 (3.7%) developed early epileptic seizures. After adjustment on propensity scores, early seizures were associated with infections [adjusted odds ratio (adjOR) 2.86; 95% confidence interval (CI) 1.37–5.95] and delay between stroke recognition and end of MT (adjOR 1.04 for 10 min more; 95% CI 1.01–1.08), but not with rt-PA (adjOR 1.35; 95% CI 0.55–3.33). The propensity-matched analysis of 343 pairs of patients found no difference in the occurrence of early seizures between those with and without rt-PA (p = 0.386). Conclusion: We found no significant association between rt-PA and early epileptic seizures. If rt-PA has the potential for epileptogenicity, the magnitude of the effect should be modest compared to its favourable effect on functional outcome. [ABSTRACT FROM AUTHOR]

Background and purpose: Guidelines help physicians to provide optimal care for stroke patients, but implementation is challenging due to the quantity of recommendations. Therefore a practical overview related to applicability of recommendations can be of assistance. Methods: A systematic review was performed on ischaemic stroke guidelines published in scientific journals, covering the whole acute care process for patients with ischaemic stroke. After data extraction, experts rated the recommendations on dimensions of applicability, that is, actionability, feasibility and validity, on a 9‐point Likert scale. Agreement was defined as a score of ≥8 by ≥80% of the experts. Results: Eighteen articles were identified and 48 recommendations were ultimately extracted. Papers were included only if they described the whole acute care process for patients with ischaemic stroke. Data extraction and analysis revealed variation in terms of both content and comprehensiveness of this description. Experts reached agreement on 34 of 48 (70.8%) recommendations in the dimension actionability, for 16 (33.3%) in feasibility and for 15 (31.3%) in validity. Agreement on all three dimensions was reached for seven (14.6%) recommendations: use of a stroke unit, exclusion of intracerebral haemorrhage as differential diagnosis, administration of intravenous thrombolysis, performance of electrocardiography/cardiac evaluation, non‐invasive vascular examination, deep venous thrombosis prophylaxis and administration of statins if needed. Discussion and conclusion: Substantial variation in agreement was revealed on the three dimensions of the applicability of recommendations. This overview can guide stroke physicians in improving the care process and removing barriers where implementation may be hampered by validity and feasibility. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is frequent after stroke, and several studies have suggested that biological and imaging characteristics present before stroke are associated with the development of post-stroke cognitive impairment. Objective: The aim of our study was to systematically review biological and imaging predictors of cognitive impairment after stroke. Method: Studies were identified from bibliographic databases and reference lists, and were included if conducted in patients with acute stroke, with at least 30 patients, and a follow-up of at least 3 months. We included articles on potential biomarkers of cognitive impairment that pre-existed to stroke. Results: We identified 22,169 articles, including 20,349 with abstract. After analysis, 66 studies conducted in 42 cohorts met selection criteria. They included 30–9522 patients [median 170; interquartile range (IQR) 104–251] with a median follow-up of 12 months (IQR 3–36). All studies met quality criteria for description of the study population and standardization of biomarkers. Twenty-nine studies met all quality criteria. There was no convincing evidence that any biological marker may predict cognitive impairment. The most consistent predictors of cognitive impairment after stroke were global atrophy and medial temporal lobe atrophy. Conclusion: Pre-existing cerebral atrophy is the most consistent predictor of cognitive impairment that can be identified in patients with an acute stroke. [ABSTRACT FROM AUTHOR]

While being increasingly recognized in clinical routine, brain microbleeds remain a puzzling finding for physicians. These small dot-like lesions are thought to be old perivascular collections of hemosiderin deposits. They can be found in different neurological settings such as cerebrovascular or neurodegenerative diseases. While their microscopic size would suggest considering these lesions as anecdotal, they are now regarded as biomarkers of severity of an underlying cerebrovascular disease. Their natural history and the interactions with surrounding brain cells remain unknown. However, their presence may impact therapeutic decisions. Deciphering the biological mechanisms leading to, or following microbleeds would enable us to address a key question: do microbleeds arise and impact the surrounding parenchyma like a miniature version of intracerebral hemorrhages or do they represent a different kind of injury? We hereby discuss, based on both clinical and experimental literature, the gap between the definition of microbleeds coming from neuroimaging and the pathophysiological hypotheses raised from histopathological and experimental data. Our analysis supports the need for a convergent effort from clinicians and basic scientists to go beyond the current "macro" view and disclose the cellular and molecular insights of these cerebral hemorrhagic microlesions. [ABSTRACT FROM AUTHOR]

The clinical picture of moderate-to-severe thrombocytopenia and thrombotic complications at unusual sites occurring within 4-28 days of vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford/AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) has been named vaccine-induced immune thrombotic thrombocytopenia (VITT), and several publications have followed the first case reports on 28 March 2021 [1-5]. However, there are similarities with the heparin-induced thrombocytopenia syndrome (HIT), and researchers have identified circulating platelet-activating platelet factor 4 antibodies in these patients. Cerebral venous sinus thrombosis associated with COVID-19 vaccine-induced thrombocytopenia: Improvement in mortality rate over time. [Extracted from the article]

Subarachnoid haemorrhage (SAH) accounts for 5% of all strokes. To date, treatment of intracranial hypertension still represents a major therapeutic target for improving outcome in patients with SAH [3]. Patients with small DC flap extent (<75 cm SP 2 sp ) were more likely to require prolonged (>3 days, aOR 3.60, 95% CI 1.37-9.42) and enhanced (aOR 2.31, 95% CI 1.12-4.74) postoperative intracranial hypertension treatment. [Extracted from the article]

Pre-hospital notification enhances thrombolysis rate and improves intra-hospital delays, but the impact of the notification to the neurologist by the emergency medical system (EMS) call centre remains unknown. Our objective was to compare pre-hospital and in-hospital delays in stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA), with and without pre-hospital notification. We compared baseline characteristics and in-hospital delays in stroke patients treated by rt-PA with a high-level notification (call to EMS and EMS-neurologist discussion), a low-level notification (call to EMS without EMS-neurologist discussion ) and no pre-hospital notification. Of 302 consecutive patients [165 women, 54.6 %; median age 74 years, interquartile range (IQR) 59-83], patients with high-level, low-level and no notification differed for the severity at admission (median National Institutes of Health Stroke Scale scores, respectively, of: 12, IQR 7-17; 9, IQR 6-15, and 8, IQR 6-14, p = 0.029). Patients with high-level notification had shorter (1) admission-to-completion of imaging times (27 min, IQR 14-35) than patients with low-level notification (35 min, IQR 17-54) or no notification (36 min, IQR 30-58) ( p < 0.01); (2) door-to-needle times (49 min, IQR 39-62 vs. 57 min, IQR 39-81 vs. 63 min, IQR 51-97; p = 0.003); and (3) onset-to-needle times (140 min, IQR 110-175 vs. 155 min, IQR 106-230 vs. 182 min, IQR 131-234; p < 0.001). They did not differ for onset-to-admission time and imaging-to-needle time. Pre-hospital notification by the EMS reduces intra-hospital delays in patients eligible for rt-PA, but the benefit is higher in the case of discussion between the EMS and the neurologist before admission. [ABSTRACT FROM AUTHOR]

The delayed conditioned eyeblink reflex, in which an individual learns to close the eyelid in response to a conditioned stimulus (e.g. a tone) relies entirely on the functional integrity of a cerebellar motor circuitry that involves the contingent activation of Purkinje cells by parallel and climbing fibres. Molecular changes that disrupt the function of this circuitry, in particular a loss of type-1 metabotropic glutamate receptors (mGlu1 receptors), occur in Purkinje cells of patients with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis as a result of neuroinflammation. mGlu1 receptors are required for cerebellar motor learning associated with the conditioned eyeblink reflex. We propose that the delayed paradigm of the eyeblink conditioning might be particularly valuable for the detection of subtle abnormalities of cerebellar motor learning that are clinically silent and are not associated with demyelinating lesions or axonal damage. In addition, the test might have predictive value following a clinically isolated syndrome, and might be helpful for the evaluation of the efficacy of drug treatment in multiple sclerosis. [ABSTRACT FROM AUTHOR]

Objective: Stroke is the leading cause of death and disability. Timely differentiation between ischemic stroke, hemorrhagic stroke, and stroke mimics is critical for tailored treatment and triage. To accelerate the identification of stroke's subtype, we propose to use the levels of circulating tPA as a biomarker. Methods: Biostroke is an observational study performed at the Caen Hospital. We quantified tPA levels in 110 patients with ischemic strokes, 30 patients with hemorrhagic strokes, and 67 stroke mimic patients upon their arrival at the emergency. Two logistic regression models were formulated: one with parameters measurable in an ambulance (Model A) and one with parameters measurable at the hospital (Model H). These models were both tested with or without plasma tPA measurements. Our initial assessment involved evaluating the effectiveness of both models in distinguishing between hemorrhagic strokes, ischemic strokes, and stroke mimics within our study cohort. Results: Plasmatic tPA levels exhibit significant distinctions between hemorrhagic, ischemic, and mimic stroke patients (1.8; 2.5; 2.4 ng/mL, respectively). The inclusion of tPA in model A significantly enhances the classification accuracy of hemorrhagic patients only, increasing identification from 0.67 (95% CI, 0.59 to 0.75) to 0.78 (95% CI, 0.7 to 0.85) (p = 0.0098). Similarly, in model H, classification accuracy of hemorrhagic patients significantly increased with the addition of tPA, rising from 0.75 (95% CI, 0.67 to 0.83) without tPA to 0.86 (95% CI, 0.81 to 0.91) with tPA (p = 0.024). Interpretations: Our findings underscore the valuable role of tPA levels in distinguishing between stroke subtypes. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Decompressive hemicraniectomy (DH) improves survival and functional outcome in large middle cerebral artery (MCA) infarcts. However, long‐term cognitive outcomes after DH remain underexplored. In a cohort of patients with large right‐hemisphere MCA infarction undergoing DH, we assessed the rates of long‐term cognitive impairment over 3‐year follow‐up.We prospectively evaluated consecutive patients included in the Lille Decompressive Surgery Database (May 2005–April 2022) undergoing DH according to existing guidelines for large hemisphere MCA infarction. We included patients with right‐sided stroke and screened with the Mini‐Mental State Examination (MMSE) in at least one of the prespecified follow‐ups (3‐month, 1‐year, 3‐year). Cognitive impairment was defined as an MMSE score < 24. We included only right‐hemisphere strokes to avoid testing biases related to severe aphasia. We compared clinical and neuroimaging data in patients with and without cognitive impairment.Three hundred four patients underwent DH during the study period. Among 3‐month survivors, 95 had a right‐hemisphere stroke and underwent at least one cognitive screening (median age = 51 years, 56.8% men). Forty‐four patients (46.3%) exhibited cognitive impairment at least once during the 3‐year follow‐up. Baseline characteristics did not significantly differ between patients with and without cognitive impairment. Regarding long‐term temporal trends, cognitive impairment was observed in 23 of 76 (30.3%), 25 of 80 (31.3%), and 19 of 66 (28.8%) patients at 3‐month, 1‐year, and 3‐year follow‐up, respectively, and it was associated with higher rates of functional disability (all p < 0.05).The persistently high rates of cognitive impairment after DH highlight the importance of cognitive monitoring to improve the long‐term management of survivors. [ABSTRACT FROM AUTHOR]

Distal medium vessel occlusions (DMVOs) are increasingly recognized as a next target for endovascular thrombectomy (EVT). Our objective was to investigate safety and clinical outcomes of EVT for DMVO of the middle cerebral artery (MCA). We analyzed data of the Lille Reperfusion Registry from January 2017 to September 2020. Patients with a primary or secondary DMVO of the MCA seen on pretreatment angiogram were included. Only patients with a eTICI score 2b50–2b67 on initial angiogram were considered. Baseline characteristics, angiographic clinical, and safety outcomes were compared between patients treated with EVT or standard medical treatment (no-EVT). Of the 171 patients included, 96 received EVT (46.9% male, 68.7 ± 15.8 years) and 75 received standard medical treatment (44% male, 73.9 ± 13.1 years). EVT patients had a better improvement of the NIHSS score at discharge (adjusted mean difference: 3.71; 95% CI: 1.18–6.24). In the distal M2 occlusions subgroup, EVT was significantly associated with a higher rate of early neurologic improvement (adjusted OR: 3.62 95% CI: 1.31–10.03), NIHSS improvement at discharge (adjusted mean difference: 5.23; 95% CI: 2.18–8.29), and improved modified Rankin Scale score at 3 months (adjusted common OR for 1 point improvement: 3.06; 95% CI: 1.30 to 7.23). Symptomatic intracranial hemorrhage occurred in 3.1% in the EVT group and in 9.5% in the no-EVT group. EVT for DMVO of the MCA appears to be safe and may lead to improved clinical outcomes. This effect was especially pronounced in patients with distal M2 occlusions, warranting randomized trials to validate this result. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a major complaint in stroke survivors, but data focusing on intracerebral haemorrhage (ICH) survivors are scarce. In a cohort of spontaneous ICH survivors, we assessed the long-term prevalence of fatigue and its associated factors. Methods: We included consecutive 1-year ICH survivors from the prospective, observational, single-centre Prognosis of Intracerebral Haemorrhage (PITCH) study. We evaluated fatigue (defined as a score ≥ 4 in Chalder Fatigue Scale); the severity of neurological, depressive, and anxiety symptoms; and functional disability 1, 3, and 6 years after ICH. We performed univariable and multivariable models to evaluate clinical factors and brain magnetic resonance imaging (MRI) small vessel disease (SVD) markers associated with fatigue. Results: Of 255 1-year ICH survivors, 153 (60%) underwent fatigue screening and were included in this study. Seventy-eight patients (51%) reported fatigue at 1-year, 56/110 (51%) at 3-year, and 27/67 (40%) at 6-year follow-up. Patients with fatigue exhibited more severe concomitant depressive/anxiety symptoms, but the severity of depressive symptoms was the only clinical factor significantly associated with 1-year fatigue in multivariable analysis (adjusted odds ratio 1.4 for one-point increase; 95% confidence interval 1.2–1.6). Patients with severe cortical atrophy at baseline had increased risk of fatigue at 1-year follow-up compared to patients with mild/no cortical atrophy (adjusted odds ratio 2.5; 95% confidence interval 1.1–5.8). Conclusions: Fatigue after ICH is frequent and long-lasting, and it is associated with cortical atrophy (but not with other MRI markers of cerebral SVD). The link between fatigue and depressive symptoms may represent a potential therapeutic target. [ABSTRACT FROM AUTHOR]

We report a case of neurosyphilis presenting with meningitis and subacute multicranial neuropathy in a young immune-competent man. Signs of primary and secondary stages of syphilitic infection occurred almost contemporarily in our patient. MRI revealed the involvement of several cranial nerves. CSF examination proved to be diagnostic. Syphilitic meningitis should be considered among the differential diagnoses of subacute, multicranial neuropathy, or skull base meningitis. The clinical course of this patient shows that early diagnosis and treatment warrant a good neurological outcome. [ABSTRACT FROM AUTHOR]

Background: Patients treated at off-hours for acute conditions have increased mortality rates. This effect has been poorly evaluated in patients treated by mechanical thrombectomy (MT). Objective: This study aimed at comparing outcomes between patients treated at off-hours and at working hours by MT for acute stroke due to large-vessel occlusion in the anterior circulation, in a well-organised network. Method: We included consecutive adults who underwent MT for large-vessel occlusion in the anterior circulation over a 51-month period, in the network of 16 hospitals from the North-of-France area, sharing similar protocols. Patients underwent magnetic resonance imaging-scans at admission and then 22–36 h later. We compared 3-month outcomes of patients treated at off-hours and at working time, the primary outcome being a modified Rankin scale (mRS) 0 to 2. Results: The study population consisted of 1,179 patients (631 women, 53.5%; mean age 72 years; median baseline National Institutes of Stroke Scale 17; 639 at off-hours, 54.2%; 734 treated with rt-PA, 62.3%; median delay stroke recognition to end of MT 281 min). No patient was lost to follow-up. The outcomes did not differ between the two groups: adjusted odds ratio (adjOR) for mRS 0–2: 0.89; 95% confidence interval (CI) 0.67–1.18; adjOR for mRS 0–1: 0.91; 95% CI 0.68–1.21; adjOR for death 1.12; 95% CI 0.81–1.55). Conclusion: Our study did not show worse outcomes in patients treated at off-hours. This result suggests that the off-hours effect reported in other studies can be minimized by a coordinated organisation of stroke care providing similar levels of care at off-hours. [ABSTRACT FROM AUTHOR]

Background: CEA is associated with peri-operative risk of brain ischemia, due both to emboli production caused by manipulation of the plaque and to potentially noxious reduction of cerebral blood flow by carotid clamping. Mild hypothermia (34–35°C) is probably the most effective approach to protect brain from ischemic insult. It is therefore a substantial hypothesis that hypothermia lowers the risk of ischemic brain damage potentially associated with CEA. Purpose of the study is to test whether systemic endovascular cooling to a target of 34.5–35°C, initiated before and maintained during CEA, is feasible and safe. Methods: The study was carried out in 7 consecutive patients referred to the Vascular Surgery Unit and judged eligible for CEA. Cooling was initiated 60–90 min before CEA, by endovascular approach (Zoll system). The target temperature was maintained during CEA, followed by passive, controlled rewarming (0.4°C/h). The whole procedure was carried out under anesthesia. Results: All the patients enrolled had no adverse events. Two patients exhibited a transient bradycardia (heart rate 30 beats/min). There were no significant differences in the clinical status, laboratory and physiological data measured before and after CEA. Conclusions: Systemic cooling to 34.5–35.0°C, initiated before and maintained during carotid clamping, is feasible and safe. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Objective: This study aimed at identifying the incidence, predictors, and impact on long-term mortality and dementia of early-onset delirium in a cohort of patients with spontaneous intracerebral hemorrhage. Methods: We prospectively recruited consecutive patients in the Prognosis of InTra-Cerebral Hemorrhage (PITCH) cohort and analyzed incidence rate of early-onset delirium (i.e. during the first seven days after intracerebral hemorrhage onset) with a competing risk model. We used a multivariable Fine-Gray model to identify baseline predictors, a Cox regression model to study its impact on the long-term mortality risk, and a Fine-Gray model adjusted for pre-specified confounders to analyze its impact on new-onset dementia. Results: The study population consisted of 248 patients (mean age 70 years, 54% males). Early-onset delirium incidence rate was 29.8% (95% confidence interval (CI) 24.3–35.6). Multivariate analysis showed that pre-existing dementia (subhazard ratio (SHR) 2.08, 95%CI 1.32–3.32, p = 0.002), heavy alcohol intake (SHR 1.79, 95%CI 1.13–2.82, p = 0.013), and intracerebral hemorrhage lobar location (SHR 1.56, 95%CI 1.01–2.42, p = 0.049) independently predicted early-onset delirium. Median follow-up was 9.5 years. Early-onset delirium was associated with higher mortality rates during the first five years of follow-up (HR 1.52, 95%CI 1.00–2.31, p = 0.049), but did not predict new-onset dementia (SHR 1.31, 95%CI 0.60–2.87). Conclusion: Early-onset delirium is a frequent complication after intracerebral hemorrhage; it is associated with markers of pre-existing brain vulnerability and with higher mortality risk, but not with higher dementia rates during long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations.Methods: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy.Findings: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard.Interpretation: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations.Funding: US National Institutes of Health (R01 AG26484). [ABSTRACT FROM AUTHOR]

Background: Patients with anterior circulation ischemic strokes due to large vessel occlusion (AIS-LVO) and very severe neurological deficits (National Institutes of Health Stroke Scale (NIHSS) score > 25) were under-represented in clinical trials on endovascular treatment (EVT). We aimed to evaluate safety and outcomes of EVT in patients with very severe vs. severe (NIHSS score 15–25) neurological deficits. Methods: We included consecutive patients undergoing EVT for AIS-LVO between January 2015 and December 2019 at Lille University Hospital. We compared rates of parenchymal hemorrhage (PH), symptomatic intracranial hemorrhage (SICH), procedural complications, and 90-day mortality between patients with very severe vs. severe neurological deficit using univariable and multivariable logistic regression analyses. Functional outcome (90-days modified Rankin Scale) was compared between groups using ordinal logistic regression analysis. Results: Among 1484 patients treated with EVT, 108 (7%) had pre-treatment NIHSS scores > 25, 873 (59%) with NIHSS scores 15–25 and 503 (34%) with NIHSS scores < 15. Rates of PH, SICH, successful recanalization, and procedural complications were similar in patients with NIHSS scores > 25 and NIHSS 15–25. Patients with NIHSS > 25 had a lower likelihood of improved functional outcome (adjcommon OR 0.31[95% CI 0.21–0.47]) and higher odds of mortality at 90 days (adjOR 2.3 [95% CI 1.5–3.7]) compared to patients with NIHSS 15–25. Successful recanalization was associated with better functional outcome (adjcommon OR 3.8 [95% CI 1.4–10.4]), and lower odds of mortality (adjOR 0.3 [95% CI 0.1–0.9]) in patients with very severe stroke. The therapeutic effect of recanalization on functional outcome and mortality was similar in both groups. Conclusions: In patients with very severe neurological deficit, EVT was safe and successful recanalization was strongly associated with better functional outcome at 90 days. [ABSTRACT FROM AUTHOR]

Cyclooxygenase-2-derived prostaglandin E2 (PGE2) contributes to excitotoxic and ischemic neuronal cell death by engaging neuronal PGE2 type 1 receptors (EP1R). Our previous studies have shown that EP1R signaling resulted in disturbances of intracellular Ca2+ homeostasis and suppression of the pro-survival protein kinase AKT. The aim of this study was to investigate whether these pathophysiological mechanism have a role in the neuronal cell death after transient forebrain ischemia. Mice were subjected to ischemia/reperfusion by bilateral common carotid artery occlusion. Hippocampal cornu ammonis area 1 (CA1) neuronal cell death was determined 5 days after reperfusion. Animals treated with the EP1R antagonist SC51089 or EP1R-deficient mice (EP1−/−) showed significantly less neuronal injury as compared to vehicle-treated wild-type controls. Benefits of EP1R blockage were still evident 14 days after injury. Better neuronal survival was correlated with reduced neuronal caspase-3 activity and decreased nuclear translocation of the apoptosis-inducing factor . Neuroprotection could be reverted by intracerebroventricular administration of the phosphoinositide 3-kinase inhibitor LY294002 and was not further increased by the calcineurin inhibitor FK506. These data implicate EP1R in postischemic neuronal apoptosis possibly by facilitating AKT inhibition. [ABSTRACT FROM AUTHOR]

Background. Endarterectomy (CEA) or stenting (CAS) of a stenotic carotid artery is currently undertaken to reduce stroke risk. In addition removal of the arterial narrowing has been hypothesized to improve cerebral hemodynamics and provide benefits in cognitive functions, by supposedly resolving a "hypoperfusion" condition. Methods. In this study we sought to test whether resolution of a carotid stenosis is followed bymeasurable changes in cognitive functions in 22 subjects with "asymptomatic" stenosis. Results. A main finding of the study was the statistically significant pre-post difference observed in the performance of phonological verbal fluency and Rey's 15-word immediate recall. Remarkably, there was a significant interaction between phonological verbal fluency performance and side of the carotid intervention, as the improvement in the verbal performance, a typical "lateralized" skill, was associated with resolution of the left carotid stenosis. Conclusion.The results reflect a substantial equivalence of the overall performance at the before- and after- CEA or CAS tests. In two domains, however, the postintervention performance resulted improved.The findings support the hypothesis that recanalization of a stenotic carotid could improve brain functions by resolving hypothetical "hypoperfusion" states, associated with the narrowing of the vessels. [ABSTRACT FROM AUTHOR]

Background: Transient ischemic attacks (TIAs) bear a presumed high risk of early recurrence of stroke. Data in the literature, however, are inconsistent, as recurrence rates range from 9.5 to 20%, at 90 days. Aims: The study was designed to determine the risk of stroke after TIA. Methods: 94 consecutive patients referred to a Stroke Unit for TIA or minor stroke, within 24 h of symptom onset, were recruited. Eleven of the 94 patients (12%, 95% CI: 7-20%) had a relapse within 90 days. The relapse consisted of a TIA for 9 patients (10%, 95% CI: 5-17%), or of a stroke for 2 subjects (1%, 95% CI: 0-8%). More than a quarter of the relapses occurred within 1 week from the first TIA. ABCD2, ABCD2-I and ABCD-E+ scores were similar among people with or without relapse. Conclusions: The data seem to confirm previous reports on the relatively low relapse rate for stroke, when TIA patients are promptly assisted in dedicated structures. The findings stress the potential benefit of early intervention in subjects with TIA. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and purpose: Decompressive hemicraniectomy (DH) reduces mortality of large middle cerebral artery (MCA) territory infarcts. Survivors are at high risk of poststroke seizures (PSSs). This study aims to describe the incidence of PSSs, to identify associated factors, and to assess their impact on long‐term outcomes. Methods: We included consecutive patients who underwent DH for large MCA infarcts from May 2005 to December 2019 at Lille University Hospital. Patients were followed up at 3 months, 1 year, and 3 years. We analysed (i) the incidence and associated factors of early onset PSSs (EPSSs) with logistic regression models; (ii) the incidence and associated factors of late onset PSSs (LPSSs) in survivors at 7 days with a univariate Cox proportional hazard regression model for interval‐censored data; and (iii) the impact of PSSs (EPSSs and LPSSs) on mortality with univariate and multivariate Cox proportional hazard regression models and modified Rankin Scale at 1 and 3 years, with univariate and adjusted multivariate ordinal logistic regression analyses. Results: Of 248 patients (150 men, 60.5%; mean age = 50.4 ± 9.6 years), 106 (42.7%) presented PSSs (six inaugural seizures, 22 EPSSs, 78 LPSSs) during follow‐up. The PSS cumulative incidence was 12.3% at 7 days, 24.9% at 3 months, 49.8% at 1 years, and 54.8% at 3 years. No predictor was significantly associated with either EPSSs or LPSSs. PSSs did not significantly impact mortality and long‐term functional outcome. Conclusions: The incidence of PSSs after DH is high, reaching more than 50% 3 years after stroke, but PSSs did not influence long‐term mortality or functional outcome. [ABSTRACT FROM AUTHOR]

Introduction: I ntracranial vertebral dissections have polymorphs clinical presentations and can lead to haemorrhagic complications if they are intracranial. We here describe a case of a thrombosed dissecting aneurysm of postero-inferior cerebellar artery (PICA) revealed by a Wallenberg syndrome preceded by headaches.Case: A 23-year-old patient, without neurological or vascular past medical history, was admitted for dizziness preceded by headache. The clinical examination on admission revealed an incomplete Wallenberg syndrome, associating hemiface sensitive deficit, Horner's syndrome, dysmetria and nystagmus. The brain MRI showed a latero-medullary infarct with a homolateral PICA thrombosed dissecting aneurysm.Conclusion: The diagnosis of intracranial dissecting aneurysms needs particular caution because aneurysm sac thrombosis can give false reassurance on angiographic MR sequences. Moreover, the anatomic features of intracranial artery walls make them prone to sub-adventitial dissection and subsequent subarachnoid haemorrhages. Therefore, antithrombotic therapy should be used with caution, due to the risk of bleeding in these intracranial dissections. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dickkopf-1 (DKK1) is an inhibitor of the canonical Wnt pathway, which is known to be impaired in both psychotic and neurodegenerative disorders. Here, we examined serum DKK1 levels as an indicator of ongoing neurodegeneration in psychotic patients, with or without a recent or current history of drug abuse. Methods: We measured serum DKK1 levels by ELISA in 22 inpatients with psychosis and no history of drug abuse, 22 with psychosis and drug abuse, and 16 controls. We rated psychopathology using the following rating scales: the Positive and Negative Syndrome Scale (PANSS); the Clinical Global Impressions (CGI) severity scale; and the Global Assessment of Functioning (GAF) scale. Extrapyramidal motor symptoms were assessed by the Simpson-Angus Neurological Rating Scale (NRS). Results: Inpatients with psychosis and comorbid substance abuse showed significantly higher serum DKK1 levels than inpatients with psychosis and no comorbid substance abuse or controls. Comorbid patients had earlier onset, longer duration of psychosis, and more severe extrapyramidal motor symptoms. However, we did not find any significant correlation between DKK1 levels and rating scale scores. Conclusion: Psychosis led to elevated serum DKK1 levels, and substance abuse led to a further increase. Knowing that there is a correlation between brain and blood levels of DKK1, we speculate that the observed increase in DKK1 levels reflects drug-induced neurotoxicity in our patients. [Copyright &y& Elsevier]

Abstract: Background and objectives: Current liquid chromatographic tandem mass spectrometry (LC–MS/MS) methods to measure serum levels of aripiprazole (Ar) and dehydroaripiprazole (DHAr) are sensitive, but difficult to use in a hospital context. We aimed to develop a rapid LC–MS/MS method allowing reliable level measurement in the presence of co-administered drugs, withdrawing samples from 22 patients with acute agitation receiving 9.75mg aripiprazole IM injection. Method: We developed a sensitive and selective HPLC–MS/MS method to measure serum Ar and DHAr levels in a hospital laboratory, requiring minimal sample preparation and inferior sample volume compared to previous LC–MS/MS methods. Analytes were separated on a reversed-phase HPLC (run-time, 10min). A triple quadrupole tandem mass spectrometer was used for quantitative analysis in positive mode by a multiple reaction monitoring. Samples were drawn 2, 4, 6, and 24h post-injection. Results: Calibration curves (2–1000ng/mL for Ar and 3.5–500ng/mL for DHAr) were linear, with mean correlation coefficient >0.9998. Within- and between-day precision and accuracy were within 10%. Mean recovery was 95.2±4.5% for Ar and 97.6±7.2% for DHAr. Ar and DHAr peaks were not affected by other co-administered psychotropic drugs. Conclusion: Our method measured Ar and DHAr concentrations reliably, simply and rapidly without employing many reagents, as currently existing methods. [Copyright &y& Elsevier]

Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Tr p values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention. • The Kynurenine:Tryptophan ratio is an activation biomarker of the kynurenine pathway. • The kynurenine pathway has a key role in the regulation of the immune system. • The Kyn:Trp ratio is significantly increased in SARS-CoV2-postive patients. • The increase is more prominent in males than in females' SARS-CoV2-positive patients. • Increased Kyn:Trp ratio is associated with lymphopenia and COVID-19 severity. [ABSTRACT FROM AUTHOR]