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Neurological outcome after ischemic stroke depends on residual salvageable brain tissue at the time of recanalization. Head down tilt 15° (HDT15) was proven effective in reducing infarct size and improving functional outcome in rats with transient middle cerebral artery occlusion (t‐MCAO) by increasing cerebral perfusion within the ischemic penumbra. In this pooled analysis, individual animal‐level data from three experimental series were combined in a study population of 104 t‐MCAO rats (45 in HDT15 group and 59 in flat position group). Co‐primary outcomes were infarct size and functional outcome at 24 h in both groups. The secondary outcome was hemodynamic change induced by HDT15 in ischemic and non‐ischemic hemispheres in a subgroup of animals. Infarct size at 24 h was smaller in HDT15 group than in flat position group (absolute mean difference 31.69 mm3, 95% CI 9.1–54.2, Cohen's d 0.56, p = 0.006). Functional outcome at 24 h was better in HDT15 group than in flat position group (median [IQR]: 13[10–16] vs. 11), with a shift in the distribution of the neurobehavioural scores in favour of HDT15. Mean cerebral perfusion in the ischemic hemisphere was higher during HDT15 than before its application (Perfusion Unit [P.U.], mean ± SD: 52.5 ± 19.52 P.U. vs. 41.25 ± 14.54 P.U., mean of differences 13.36, 95% CI 7.5–19.18, p = 0.0002). Mean cerebral perfusion in the non‐ischemic hemisphere before and during HDT15 was unchanged (P.U., mean ± SD: 94.1 ± 33.8 P.U. vs. 100.25 ± 25.34 P.U., mean of differences 3.95, 95%, CI −1.9 to 9.6, p = 0.1576). This study confirmed that HDT15 improves the outcome in t‐MCAO rats by promoting cerebral perfusion in the ischemic territory, without disrupting hemodynamics in non‐ischemic areas. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies. Sample Size Estimates: A sample size of 80 patients (40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at p = 0.05, two sided. Methods and Design: TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm. Study Outcomes: The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1α, and HSP27 at 24 h and 72 h. Discussion/Conclusion: RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04400981. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disease, with chameleon presentations and several mimics. Considering the poor prognosis of ALS, their precise and timely identification is pivotal. Affection of the cervical spine represents one potential source of ALS mimics that should never be missed, since it is potentially treatable. We hereby present 5 cases initially diagnosed as ALS but eventually found to have different kinds of cervical spine affection, from a common compressive myelopathy to a rare space-occupying cystic fluid collection. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) patients often express cognitive and behavioral dysfunctions within the so-called "frontotemporal spectrum disorders." Guidelines recommend screening of such dysfunctions, albeit only ALS dedicated tools are eventually suitable, due to the profound motor limitations induced by the disease. ALS Cognitive Behavioral Screen (ALS-CBS) is such a screening tool but normative data are not available, limiting its widespread implementation. Our aim consisted in producing normative data for the Italian version of the ALS-CBS. The scale was administered to n = 458 healthy controls with different age and education. Following translation and back translation of the original version of the test, normative data and correction scores for the ALS-CBS cognitive subtest (ALS-CBSci) were generated. Furthermore, n = 100 ALS consecutive outpatients with a wide range of cognitive and motor severity underwent to the ALS-CBS, besides FAB and Weigl sorting test (WST), in order to check its usability. Completion rate was 100% for ALS-CBS and WST, and 68% for the FAB. Corrected ALS-CBS scores showed 12% detection rate of significant cognitive dysfunction with a moderate kappa with FAB and WST. For the ALS-CBS behavioral subtest (ALS-CBSbi), a caregiver was available for n = 81 ALS patients and asked to complete the subset. The detection rate for behavioral dysfunction was 55.5%, and a mild correlation between with the Caregiver Burden Inventory was present (r = - 0.26, p = 0.04). In conclusion, we offer here normative data for the ALS-CBS, a handy tool for screening frontotemporal spectrum dysfunctions in ALS patients, and confirm its usability and validity in an outpatient setting. [ABSTRACT FROM AUTHOR]

Headache is a milestone in cerebrovascular disorders; indeed, it may represent the only symptom at onset or predominates over the other neurological features. Unfortunately, headache associated with cerebrovascular diseases lacks clear-cut characteristics as it may resemble a migraine attack, tension-type headache, or cluster headache; pain localization is also misleading along with drug (analgesic) response. However, in this review, we have analyzed and described the most common patterns of headache for different vascular disorders: it is known that headache due to subarachnoid aneurysmal hemorrhage presents peculiar characteristics (thunderclap, acute presentation, and high intensity), whereas in cerebral vasoconstriction syndrome, the short duration and the relapsing-remitting course of the thunderclap headache are key points for the diagnosis; in cervicocerebral artery, dissection pain is most commonly ipsilateral to the dissected vessel and is mainly perceived in the temporal area in case of carotid artery dissection and in the occipital area in case of vertebral artery dissection; in cerebral venous thrombosis, pain is often acute or subacute and severe; unfortunately, it may resemble a typical migraine attack or a tension-type episode; by the contrary, in primary angiitis of the central nervous system, pain is always subacute or chronic with mild-to-moderate intensity; finally, in brain arteriovenous shunts such as malformation or fistula, pain is more frequently a clue for disease complication such as hemorrhage from the malformation or thrombosis of the draining vein. [ABSTRACT FROM AUTHOR]

Background: Epileptiform activity, including status epilepticus (SE), occurs in up to one-third of comatose survivors of cardiac arrest and may predict poor outcome. The relationship between SE and hypoxic-ischemic brain injury (HIBI) is not established., Methods: This is a single-center retrospective study on consecutive patients with post-anoxic super-refractory SE. HIBI was graded as non-widespread (group 1) or widespread (group 2) by qualitative analysis of DWI/ADC and T2w-FLAIR. Between-group differences in the rate of poor neurological outcome at 6 months (primary outcome), SE resolution and consciousness recovery before discharge, and mortality at 6 months (secondary outcomes) were investigated., Results: From January 2011 to February 2023, 40 patients were included. HIBI was widespread in 45% of patients and non-widespread in 55%. The rate of poor neurological outcome at 6 months was 27% in group 1 and 83% in group 2 (OR 12.8, CI 95% [2.5-64.3], p = 0.002). The rate of consciousness recovery before discharge was 73% in group 1 versus 22% in group 2 (OR 8.8, CI 95% [1.9-40.3], p = 0.005). SE resolved in 95% of patients in group 1 versus 67% in group 2 (OR 10.5, CI 95% [1.1-97.9], p = 0.039). Mortality rate at 6 months was 27% in group 1 versus 50% in group 2 (OR 0.4, CI 95% [0.1-1.9], p = 0.303)., Conclusion: Patients with widespread HIBI had higher odds of poor outcome at 6 months, lower probability of SE resolution and of consciousness recovery before discharge compared to those with non-widespread HIBI. Mortality at 6 months did not differ significantly between the two groups., (© 2025 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Short-term dual antiplatelet treatment (DAPT) is superior to single antiplatelet treatment (SAPT) for secondary prevention in non-cardioembolic minor ischemic stroke and high-risk transient ischemic attack (TIA). As the real-world use of DAPT is broader than in trials, it is important to clarify its benefit/risk profile in a diverse population., Methods: Post hoc analysis of prospectively collected data from the READAPT cohort and three prospective stroke registries including patients with mild-to-moderate (National Institute of Health Stroke Scale (NIHSS) score 0-10) ischemic stroke receiving early DAPT or SAPT. The primary effectiveness outcome was 90-day return to pre-stroke neurological functioning using modified Rankin Scale (mRS) score. Secondary effectiveness outcomes were 90-day mRS shift, new ischemic stroke/TIA, vascular and all-cause death, 24 h early neurological improvement or deterioration. The safety outcome was 90-day intracranial hemorrhage., Results: We matched 1008 patients treated with DAPT and 1008 treated with SAPT. Compared to SAPT, patients treated with DAPT showed higher likelihood of 90-day primary effectiveness outcome (87.5% vs. 84.4%, risk difference 3.1% (95% confidence interval (CI): 0.1%-6.1%); p = 0.047, risk ratio 1.03 (95% CI: 1.01-1.07); p = 0.043) and higher rate of 24-h early neurological improvement (25.3% vs. 15.4%, risk difference 9.9% (95% CI: 6.4%-13.4%); p < 0.001, risk ratio 1.65 (95% CI: 1.37-1.97); p < 0.001). No differences were observed for other study outcomes. Subgroup analysis confirmed benefit of DAPT over SAPT for primary effectiveness outcome in patients with moderate stroke, those treated with intravenous thrombolysis, and those who received antiplatelet loading dose., Conclusion: Our findings suggest that DAPT use might be safe and more effective than SAPT even in the real world and in patients who do not strictly fulfill the criteria of landmark large clinical trials., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AZ reports compensation from Angels Initiative, Boehringer-Ingelheim, Daiichi Sankyo for consultant services; from Angels Initiative, Boehringer-Ingelheim, CSL Behring for speaking honoraria or other education services; from Daiichi Sankyo for meeting; from Bayer, and Astra Zeneca for participation on a Data Safety, Monitoring or Advisory Board; he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. RO reports grants from Novartis and Allergan; compensation from Teva Pharmaceutical Industries, Eli Lilly and Company, and Novartis for other services; and travel support from Teva Pharmaceutical Industries. SS reports compensation from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc, Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada for consultant services; compensation from Novartis for other services. MP reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc., for consultant services. The other authors report no conflicts.

Background: According to the literature, about one third of patients with brain ischemic symptoms lasting <24 h, which are classified as Transient ischemic attacks (TIAs) according to the traditional "time-based" definition, show the presence of acute ischemic lesions at neuroimaging. Recent evidence has shown that the presence of acute ischemic lesions at neuroimaging may impact on the outcome of patients with transient ischemic symptoms treated with dual antiplatelet treatment (DAPT). This uncertainty is even more compelling in recent years as short-term DAPT has become the standard treatment for any non-cardioembolic TIA or minor ischemic stroke., Methods: This is a pre-specified subgroup analysis from a prospective multicenter real-world study (READAPT). The analysis included patients with time-based TIA-that is, those with ischemic symptoms lasting <24 h-who started DAPT. In the whole population, we assessed the presence of acute brain ischemic lesions at neuroimaging and their association with the ABCD 2 score. To assess the impact of acute brain ischemic lesions on 90-day prognosis, we performed a propensity score matching of patients with and without those lesions. We adopted a primary effectiveness outcome which was a composite of new stroke/TIA events and death due to vascular causes at 90 days., Results: We included 517 patients-324 (62.7%) male-with a median (interquartile range-IQR) age of 74 (IQR = 65-81) years; 144 patients (27.9%) had acute brain ischemic lesions at neuroimaging. The proportion of patients with brain ischemic lesions did not vary according to the ABCD 2 score. At follow-up, 4 patients with brain ischemic lesions (2.8%) and 21 patients without lesions (5.6%) reported the primary effectiveness outcome, which was similar between the groups before ( p  = 0.178) and after matching ( p  = 0.518)., Conclusions: In our population, patients with transient ischemic symptoms and acute ischemic lesions at brain magnetic resonance imaging (MRI) had a risk of recurrent ischemic events similar to those without lesions. The risk of recurrent ischemic events was low in both groups., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.Z. reports compensation from Angels Initiative, Boehringer-Ingelheim, and Daiichi Sankyo for consultant services; from Angels Initiative, Boehringer-Ingelheim, and CSL Behring for speaking honoraria or other education services; from Daiichi Sankyo for meeting; from Bayer and Astra Zeneca for participation on a Data Safety, Monitoring Board or Advisory Board; and he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. R.O. reports grants from Novartis and Allergan; compensation from Teva Pharmaceutical Industries, Eli Lilly and Company, and Novartis for other services; and travel support from Teva Pharmaceutical Industries. S.S. reports compensation from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc., Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada for consultant services; employment by Università degli Studi dell’Aquila; and compensation from Novartis for other services. MP reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc., for consultant services. DT reports compensation from Alexion, Astra Zeneca, Medtronic, and Pfizer for consultant services and participation on a Data Safety, Monitoring Board or Advisory Board. The other authors report no conflicts.

Background and Purpose: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs., Methods: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD 2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment., Results: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding., Conclusions: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AZ reports compensation from Angels Initiative, Boehringer-Ingelheim, Daiichi Sankyo, CSL Behring, Bayer, and Astra Zeneca; and he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. RO reports compensations from Novartis and Allergan, Teva Pharmaceutical Industries, Eli Lilly and Company, SS reports compensations from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc, Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada; employment by Università degli Studi dell’Aquila. MPa reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc. DT reports compensation from Alexion, AstraZeneca, Medtronic, and Pfizer. The other authors report no conflicts.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Introduction: Multicentre preclinical randomised controlled trials (pRCT) are emerging as a necessary step to confirm efficacy and improve translation into the clinic. The aim of this project is to perform two multicentre pRCTs (one in rats and one in mice) to investigate the efficacy of remote ischaemic conditioning (RIC) in an experimental model of severe ischaemic stroke., Methods and Analysis: Seven research laboratories within the Italian Stroke Organization (ISO) Basic Science network will participate in the study. Transient endovascular occlusion of the proximal right middle cerebral artery will be performed in two species (rats and mice) and in both sexes. Animals will be randomised to receive RIC by transient surgical occlusion of the right femoral artery, or sham surgery, after reperfusion. Blinded outcome assessment will be performed for dichotomised functional neuroscore (primary endpoint) and infarct volume (secondary endpoint) at 48 hours. A sample size of 80 animals per species will yield 82% power to detect a significant difference of 30% in the primary outcome in both pRCTs. Analyses will be performed in a blind status and according to an intention-to-treat paradigm. The results of this study will provide robust, translationally oriented, high-quality evidence on the efficacy of RIC in multiple species of rodents with large ischaemic stroke., Ethics and Dissemination: This is approved by the Animal Welfare Regulatory Body of the University of Milano Bicocca, under project license from the Italian Ministry of Health. Trial results will be subject to publication according to the definition of the outcome presented in this protocol., Trial Registration Number: PCTE0000177., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)