Influence of Hospital Type on Outcomes of Patients With Acute Spontaneous Intracerebral Hemorrhage: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Whether the outcome of patients with spontaneous intracerebral hemorrhage (ICH) differs depending on the type of hospital where they are admitted is uncertain. The objective of this study was to determine influence of hospital type at admission (telestroke center [TSC], primary stroke center [PSC], or comprehensive stroke center [CSC]) on outcome for patients with ICH. We hypothesized that outcomes may be better for patients admitted to a CSC. METHODS: This is a multicenter prospective observational and population-based study of a cohort of consecutively recruited patients with ICH (March 2020-March 2022). We included all patients with spontaneous ICH in Catalonia (Spain) who had a pre-ICH modified Rankin scale (mRS) score of 0-3 and who were admitted to the hospital within 24 hours of onset. We compared patients admitted to a TSC/PSC (n = 641) or a CSC (n = 1,320) and also analyzed the subgroup of patients transferred (n = 331) or not transferred (n = 310) from a TSC/PSC to a CSC. The main outcome was the 3-month mRS score obtained by blinded investigators. Outcomes were compared using adjusted ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI for a shift in mRS scores. A propensity score matching (PSM) analysis was performed for the subgroup of transferred patients. RESULTS: Relevant data were obtained from 1961 of a total of 2,230 patients, with the mean (SD) age of 70 (14.1) years, and 713 (38%) patients were women. After adjusting for confounders (age, NIH Stroke Scale score, intraventricular hemorrhage, hematoma volume, and pre-ICH mRS score), type of hospital of initial admission (CSC vs TSC/PSC) was not associated with outcome (adjusted common OR 1.13, 95% CI 0.93-1.38). A PSM analysis indicated that transfer to a CSC was not associated with more favorable outcomes (OR 0.77, 95% CI 0.55-1.10; p = 0.16). DISCUSSION: In this population-based study, we found that, after adjusting for confounders, hospital types were not associated with functional outcomes. In addition, for patients who were transferred from a TSC/PSC to a CSC, PSM indicated that outcomes were similar to nontransferred patients. Our findings suggest that patient characteristics are more important than hospital characteristics in determining outcome after ICH. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03956485.

Clinical impact of microbleeds in patients with Alzheimer's disease.

INTRODUCTION: Cerebral microbleeds (CMBs) are more frequent in patients with Alzheimer's disease (AD) than in the general population. However, their clinical significance remains poorly understood. We carried out a multimodal approach to evaluate the impact of CMBs at a clinical, neuropsychological, and survival level, as well as on core AD biomarkers in the cerebrospinal fluid (CSF) in AD patients. METHODS: We prospectively recruited 98 patients with mild-moderate AD. At baseline, they underwent brain MRI, and AD CSF biomarkers and APOE genotypes were analysed. An extensive neuropsychological battery was performed at baseline and after 1 year of follow-up. We analysed the stroke incidence and mortality with survival analyses. RESULTS: Forty-eight (48.5%) patients had at least one CMBs. Eight (8.2%) patients had strictly nonlobar CMBs, 39 (40.2%) had any lobar CMB locations. The incidence of stroke was higher in AD patients with lobar CMBs than in those without CMBs (p < 0.05). Mortality did not differ among groups (p > 0.05). At the cognitive level, CMBs patients deteriorated more rapidly at 12 months according to MMSE scores, with no differences observed at 24 months. We did not observe differences in the other tests, except for an increase in caregiver burden in the CMBs group. The presence of cerebral amyloidosis and APOE ε4 were associated with a greater presence of CMBs. CONCLUSION: CMBs are associated with an increased risk of ischemic stroke in AD patients without differences in mortality. Patients with CMBs did not seem to have different consequences associated with cognitive decline except for an increase in caregiver overload.

Risk of New-Diagnosed Atrial Fibrillation After Transient Ischemic Attack.

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.

Sex-Related Differences in Clinical Features, Neuroimaging, and Long-Term Prognosis After Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Differences in sex in the incidence, presentation, and outcome of events after ischemic stroke have been studied in depth. In contrast, only limited data are available after transient ischemic attack (TIA). We aim to assess sex-related differences in the presentation, cause, neuroimaging features, and predictors of long-term prognosis in patients with TIA. METHODS: We carried out a prospective cohort study of consecutive patients with TIA from January 2006 to June 2010. Nondefinitive TIA events were defined by the presence of isolated atypical symptoms. The risk of stroke recurrence (SR) and composite of major vascular events were stratified by sex after a median follow-up time of 6.5 (interquartile range, 5.0-9.6) years. RESULTS: Among the 723 patients studied, 302 (41.8%) were female and 79 (10.9%) suffered a nondefinitive TIA event. Vascular territory diffusion-weighted imaging patterns (odds ratio, 1.61 [95% CI, 0.94-2.77]), and nondefinitive TIA events (odds ratio, 2.66 [95% CI, 1.55-4.59]) were associated with women, whereas active smoking (odds ratio, 0.30 [95% CI, 0.15-0.58]) and large artery atherosclerosis causes (odds ratio, 0.50 [95% CI, 0.29-0.83]) were related to men. The risk of SR was similar in both sexes (12.6% [95% CI, 8.9-16.3] for women versus 14.3% [95% CI, 11.0-17.6] for men). In contrast, the risk of major vascular events was significantly lower in women than in men (17.5% [95% CI, 13.2-21.8] versus 23.8% [95% CI, 19.7-27.9]). In both sexes, after adjusting for age, large artery atherosclerosis was associated with SR (hazard ratio, 3.22 [95% CI, 1.42-7.24] and hazard ratio, 2.00 [95% CI, 1.14-3.51]). In a Kaplan-Meier analysis, females with positive diffusion-weighted imaging (P=0.014) and definitive TIA (log-rank test P=0.022) had a significantly higher risk of SR. CONCLUSIONS: Despite similar risks of SR, there were sex-related differences in baseline characteristics, presenting symptoms, patterns of acute ischemic lesions, cause, and outcomes. These findings encourage further research into optimal preventive strategies that take into account these differences.

REMOTE Ischemic Perconditioning Among Acute Ischemic Stroke Patients in Catalonia: REMOTE-CAT PROJECT.

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.

Induced neuroprotection by remote ischemic perconditioning as a new paradigm in ischemic stroke at the acute phase, a systematic review.

BACKGROUND: Remote ischemic conditioning during cerebral ischemia (remote ischemic perconditioning, RIPerC) refers to the application of several cycles of brief ischemia and reperfusion (I/R) commonly to a limb, and it represents a new paradigm in neuroprotection with multiple mechanisms of action in ischemic stroke (IS) patients during acute phase. Some clinical trials just finished, and a few others are still ongoing; gather the current knowledge and pull it down to influence the present and future studies was the goal of this paper. METHODS: A systematic review of published research papers and/or registered clinical trials since 2000 was performed. RESULTS: Nineteen studies were identified and only four studies were completed. All of them have demonstrated that RIPerC is safe, feasible and well tolerated in IS patients. However, a high heterogeneity of clinical trial characteristics was observed: five (26.3%) randomized clinical trials (RCTs) included only thrombolytic-treated patients, three (15.8%) RCTs only thrombectomy-treated patients, and five (26.3%) RCTs required radiological confirmation of IS. Temporal inclusion criteria vary from 4 h to 48 h. Most of the clinical trials used 4 cycles of RIPerC in the upper non-affected limb. Interestingly, only three (16.7%) RCTs applied RIPerC during the transportation in the ambulance. Neuroimaging outputs were the main endpoints when endovascular therapy was applied; functional outcome is also the main endpoint in large-medium size studies. CONCLUSIONS: This review summarizes the completed and ongoing clinical trials on RIPerC in IS patients, where RIPerC has been used alone or in combination with recanalization therapies. Ongoing clinical trials will provide new information on the best RIPerC intervention strategy and potentially improve the functional outcome of IS patients; definition of new RIPerC strategies would ideally aim at enhancing tissue preservation, promoting neurological recovery, and stratify patients to improve treatment feasibility.

Mitochondrial m.13513G>A Point Mutation in ND5 in a 16-Year-Old Man with Leber Hereditary Optic Neuropathy Detected by Next-Generation Sequencing.

This article reports a Leber hereditary optic neuropathy (LHON) case associated for the first time with mitochondrial m.13513G>A mutation. We present a 16-year-old man who complained of subacute, painless, visual loss. Ocular examination showed optic nerve atrophy, papillary pseudoedema, and optic disc pallor. Extraocular manifestations included hypertrophic myocardiopathy and myopathy. Initial genetic analysis excluded the three most common LHON mutations. Sanger sequencing of the whole mitochondrial deoxyribonucleic acid showed no mutation. Next-generation sequencing (NGS) revealed m.13513G>A mutation in the NADH dehydrogenase (ND5) subunit gene ( MT-ND5 ). The m.13513G>A mutation has never been associated with LHON phenotype without Leigh/mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes features. NGS techniques should be considered when this diagnosis is strongly suspected.