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Background: Transient ischemic attack (TIA) provides a unique opportunity to optimize secondary preventive treatments to avoid subsequent ischemic stroke (SIS). Although atrial fibrillation (AF) is the leading cause of cardioembolism in IS and anticoagulation prevents stroke recurrence (SR), limited data exists about the risk of new-diagnosed AF (NDAF) after TIA and the consequences of the diagnostic delay. The aim of our study was to determine this risk in a cohort of TIA patients with long-term follow-up. Methods: We carried out a prospective cohort study of 723 consecutive TIA patients from January 2006 to June 2010. Median follow-up was 6.5 (5.0-9.6) years. In a subgroup of 204 (28.2%) consecutive patients, a panel of biomarkers was assessed during the first 24 h of the onset of symptoms. Multivariate analyses were performed to find out the associated factors of NDAF. Kaplan-Meier analysis was also performed to analyzed risk of SIS. Results: NDAF was indentified in 116 (16.0%) patients: 42 (36.2%) during admission, 18 (15.5%) within first year, 29 (25%) between one and five years and 27 (23.3%) beyond 5 years. NDAF was associated with sex (female) [hazard ratio (HR) 1.61 (95% CI, 1.07-2.41)], age [[HR 1.05 (95% CI, 1.03-1.07)], previous ischemic heart disease (IHD) [HR 1.84, (95% CI 1.15-2.97)] and cortical DWI pattern [HR 2.81 (95% CI, 1.87-4.21)]. In the Kaplan-Meier analysis, NT-proBNP ≥ 218.2 pg/ml (log-rank test P < 0.001) was associated with significant risk of NDAF during the first 5 years of follow-up. Patients with NDAF after admission and before 5 years of follow-up had the highest risk of SIS (P = 0.002). Conclusion: The risk of NDAF after TIA is clinically relevant. We identified clinical and neuroimaging factors of NDAF. In addition, NT-proBNP was related to NDAF. Our results can be used to evaluate the benefit of long-term cardiac monitoring in selected patients. [ABSTRACT FROM AUTHOR]

Introduction: Ischemic tolerance (IT) refers to a state where cells are resistant to the damaging effects caused by periods of ischemia. In a clinical scenario, the IT phenomenon would be activated by a recent transient ischemic attack (TIA) before an ischemic stroke (IS). The characterization of inflammatory protein expression patterns will contribute to improved understanding of IT. Methods: A total of 477 IS patients from nine hospitals, recruited between January 2011 and January 2016, were included in the current study and divided in three groups: 438 (91.9%) patients without previous TIA (group 1), 22 (4.6%) patients who suffered TIA 24 h before IS (group 2), and 17 (3.5%) patients who suffered TIA between 24 h and 7 days prior to IS (group 3). An inflammatory biomarker panel (IL-6, NT-proBNP, hsCRP, hs-Troponin, NSE, and S-100b) on plasma and a cytokine antibody array was performed to achieve the preconditioning signature potentially induced by TIA phenomena. Primary outcome was modified rankin scale (mRs) score at 90 days. Results: Recent previous TIA was associated with better clinical outcome at 90 days (median mRS of group 1: 2.0 [1.0–4.0]; group 2: 2.0 [0.0–3.0]; group 3: 1.0 [0–2.5]; p = 0.086) and smaller brain lesion (group 1: 3.7 [0.7–18.3]; group 2: 0.8 [0.3–8.9]; group 3: 0.6 [0.1–5.5] mL; p = 0.006). All inflammation biomarkers were down regulated in the groups of recent TIA prior to IS compared to those who did not suffer a TIA events. Moreover, a cytokine antibody array revealed 30 differentially expressed proteins between the three groups. Among them, HRG1-alpha (Fold change 74.4 between group 1 and 2; 74.2 between group 1 and 3) and MAC-1 (Fold change 0.05 between group 1 and 2; 0.06 between group 1 and 3) expression levels would better stratify patients with TIA 7 days before IS. These two proteins showed an earlier inflammation profile that was not detectable by the biomarker panel. Conclusion: Inflammatory pathways were activated by transient ischemic attack, however the period of time between this event and a further ischemic stroke could be determined by a protein signature that would contribute to define the role of ischemic tolerance induced by TIA. [ABSTRACT FROM AUTHOR]

Rationale: Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection. Aim and/or Hypothesis: To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care. Sample Size Estimates: A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%. Methods and Design: We aim to conduct a multicentre study of pre-hospital RIPerC application in AIS patients. A total of 572 adult patients diagnosed of suspected clinical stroke within 8 h of symptom onset and clinical deficit >0 according to prehospital rapid arterial occlusion evaluation (RACE) scale score will be randomized, in blocks of size 4, to RIPerC or sham. Patients will be stratified by RACE score scale. RIPerC will be started in the ambulance before hospital admission and continued in the hospital if necessary. It will consist of five cycles of electronic tourniquet inflation and deflation (5 min each). The cuff pressure for RIPerC will be 200 mmHg during inflation. Sham will only simulate vibration of the device. Study Outcome(s): The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days. Discussion: Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03375762. [ABSTRACT FROM AUTHOR]

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene ( FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments. [ABSTRACT FROM AUTHOR]

Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system. [ABSTRACT FROM AUTHOR]