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Background and Objectives: Limited data exist on the safety of IV thrombolysis (IVT) for acute ischemic stroke (AIS) after dabigatran reversal with idarucizumab. We sought to evaluate the safety and efficacy of idarucizumab pretreatment in patients with AIS receiving IVT., Methods: A national registry-based study evaluated the safety and efficacy of IVT in this specific subgroup. We also conducted a systematic review and meta-analysis of cohort studies and case series, aiming to document the pooled rates of (1) symptomatic intracranial hemorrhage (sICH), (2) any intracranial hemorrhage, (3) 3-month mortality, and (4) the proportion of excellent (modified Rankin Scale [mRS] scores 0-1) and (5) good (mRS scores 0-2) functional outcome at 3 months among patients with AIS, who received IVT after dabigatran reversal with idarucizumab. Moreover, we sought to compare these outcomes between IVT-treated patients after dabigatran reversal with idarucizumab and IVT-treated patients without dabigatran pretreatment., Results: Thirteen cohorts including our nation-wide registry-based cohort and 1 case series comprising 553 patients with AIS (mean age: 75 years; male sex: 65%; median baseline NIH Stroke Scale score: 11 points) receiving idarucizumab before IVT were included in this meta-analysis. The pooled rate of sICH after IVT after idarucizumab administration was 4% (95% CI 1-9; I 2 = 26%), while the pooled rates of any intracranial hemorrhage and 3-month mortality were 10% (95% CI 5-16; I 2 = 24%) and 18% (95% CI 10-27; I 2 = 0%), respectively. The pooled rates of excellent and good functional outcomes at 3 months were 56% (95% CI 27-83; I 2 = 69%) and 70% (95% CI 57-81; I 2 = 40%), respectively. The risk of sICH (risk ratio [RR] 1.86; 95% CI 0.91-3.80; I 2 = 0%), any intracranial hemorrhage (RR 1.76; 95% CI 0.99-3.11; I 2 = 8%), and 3-month mortality (RR 1.50; 95% CI 0.91-2.48; I 2 = 0%) did not differ between patients with AIS receiving IVT with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome (RR 1.35; 95% CI 1.11-1.65; I 2 = 27%)., Discussion: IVT for AIS after dabigatran reversal with idarucizumab seems to be safe and effective in observational studies with limited number of patients. Randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of IVT in this specific AIS subgroup.

Introduction: Symptomatic carotid artery disease (CAD) represents an uncommon but treatable cause of corticobasal syndrome., Case Report: We present the clinical details and successful management of a previously healthy 77-year-old patient who presented with 1-year cognitive dysfunction, alien limb syndrome, limb kinetic apraxia, and ipsilateral cortical sensory deficit, fulfilling the criteria of the diagnosis of probable corticobasal syndrome. Imaging modalities, including magnetic resonance imaging and time-of-flight magnetic resonance angiography, revealed acute external borderzone infarcts of the right hemisphere due to symptomatic CAD causing near occlusion of the vessel. The patient underwent a right carotid endarterectomy, leading to a marked improvement in mobility and neuropsychological evaluation., Conclusion: This case highlights the importance of swift diagnosis of symptomatic CAD in patients with corticobasal syndrome. Moreover, it emphasizes the efficacy of carotid endarterectomy in achieving symptom improvement in such cases., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue., Methods: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria., Results: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR ( n = 4), anti-P/Q-VGCC ( n = 3), anti-Hu ( n = 3), anti-Yo ( n = 1), anti-Ma ( n = 1), anti-titin ( n = 1), anti-IgLON5 ( n = 1), and anti-GAD65 ( n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively., Conclusions: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.

Background and purpose: Sporadic cerebral amyloid angiopathy (CAA) is a small vessel disease, resulting from progressive amyloid-β deposition in the media/adventitia of cortical and leptomeningeal arterioles. We sought to assess the prevalence of baseline characteristics, clinical and radiological findings, as well as outcomes among patients with CAA, in the largest study to date conducted in Greece. Methods: Sixty-eight patients fulfilling the Boston Criteria v1.5 for probable/possible CAA were enrolled and followed for at least twelve months. Magnetic Resonance Imaging was used to assess specific neuroimaging markers. Data regarding cerebrospinal fluid biomarker profile and Apolipoprotein-E genotype were collected. Multiple logistic regression analyses were performed to identify predictors of clinical phenotypes. Cox-proportional hazard regression models were used to calculate associations with the risk of recurrent intracerebral hemorrhage (ICH). Results: Focal neurological deficits (75%), cognitive decline (57%), and transient focal neurological episodes (TFNEs; 21%) were the most common clinical manifestations. Hemorrhagic lesions, including lobar cerebral microbleeds (CMBs; 93%), cortical superficial siderosis (cSS; 48%), and lobar ICH (43%) were the most prevalent neuroimaging findings. cSS was independently associated with the likelihood of TFNEs at presentation (OR: 4.504, 95%CI:1.258-19.088), while multiple (>10) lobar CMBs were independently associated with cognitive decline at presentation (OR:5.418, 95%CI:1.316-28.497). cSS emerged as the only risk factor of recurrent ICH (HR:4.238, 95%CI:1.509-11.900) during a median follow-up of 20 months. Conclusions: cSS was independently associated with TFNEs at presentation and ICH recurrence at follow-up, while a higher burden of lobar CMBs with cognitive decline at baseline. These findings highlight the prognostic value of neuroimaging markers, which may influence clinical decision-making.

Stroke is ranked as the second leading cause of death worldwide and a major cause of long-term disability. A potential therapeutic target that could offer favorable outcomes in stroke is the mammalian target of rapamycin (mTOR) pathway. mTOR is a serine/threonine kinase that composes two protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and is regulated by other proteins such as the tuberous sclerosis complex. Through a significant number of signaling pathways, the mTOR pathway can modulate the processes of post-ischemic inflammation and autophagy, both of which play an integral part in the pathophysiological cascade of stroke. Promoting or inhibiting such processes under ischemic conditions can lead to apoptosis or instead sustained viability of neurons. The purpose of this review is to examine the pathophysiological role of mTOR in acute ischemic stroke, while highlighting promising neuroprotective agents such as hamartin for therapeutic modulation of this pathway. The therapeutic potential of mTOR is also discussed, with emphasis on implicated molecules and pathway steps that warrant further elucidation in order for their neuroprotective properties to be efficiently tested in future clinical trials., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Alzheimer's disease is the most common type of dementia, reaching 60-80% of case totals, and is one of the major global causes of the elderly population's decline in functionality concerning daily life activities. Epidemiological research has already indicated that, in addition to several others metabolic factors, diabetes mellitus type 2 is a risk factor of Alzheimer's disease. Many molecular pathways have been described, and at the same time, there are clues that suggest the connection between type 2 diabetes mellitus and Alzheimer's disease, through specific genes, autophagy, and even inflammatory pathways. A systematic review with meta-analysis was conducted, and its main goal was to reveal the multilevel connection between these diseases.

Background:  The human brain, depending on aerobic glycolysis to cover its metabolic needs and having no energy reserves whatsoever, relies on a constant and closely regulated blood supply to maintain its structural and functional integrity. Cerebral autoregulation, that is, the brain's intrinsic ability to regulate its own blood flow independently from the systemic blood pressure and cardiac output, is an important physiological mechanism that offers protection from hypoperfusion injury., Discussion:  Two major independent mechanisms are known to be involved in cerebral autoregulation: (1) flow-metabolism coupling and (2) myogenic responses of cerebral blood vessels to changes in transmural/arterial pressure. A third, less prominent component of cerebral autoregulation comes in the form of neurogenic influences on cerebral vasculature., Conclusion:  Although fragmentation of cerebral autoregulation in separate and distinct from each other mechanisms is somewhat arbitrary, such a scheme is useful for reasons of simplification and to better understand their overall effect. Comprehension of cerebral autoregulation is imperative for clinicians in order for them to mitigate consequences of its impairment in the context of traumatic brain injury, subarachnoid hemorrhage, stroke, or other pathological conditions., Competing Interests: None declared., (Thieme. All rights reserved.)