Association of Anticoagulant Use With Hemorrhage Location and Etiology in Incident Spontaneous Intracerebral Hemorrhage.

BACKGROUND: It is unknown whether hypertensive microangiopathy or cerebral amyloid angiopathy (CAA) predisposes more to anticoagulant-associated intracerebral hemorrhage (AA-ICH). The purpose of our study was to determine whether AA-ICH is associated with lobar location and probable CAA. METHODS: This was a cross-sectional analysis of patients with first-ever spontaneous ICH admitted to a tertiary hospital in Boston, between 2008 and 2023. Univariable and multivariable logistic regression were used to investigate the association between anticoagulation use and both lobar hemorrhage location and probable CAA on magnetic resonance imaging (MRI) by Boston Criteria 2.0 or computed tomography by Simplified Edinburgh Criteria. RESULTS: A total of 1104 patients (mean [SD] age, 73 [12]; 499 females [45.0%]) were included. Of the 1104 patients, 268 (24.3%) had AA-ICH: 148 (55.2%) with vitamin K antagonists and 107 (39.9%) with direct oral anticoagulants. Brain MRI was performed in 695 (63.0%) patients. The proportion of patients with lobar hemorrhage was not different between those with and without AA-ICH (121/268 [45.1%] versus 424/836 [50.7%]; odds ratio [OR], 0.80 [95% CI, 0.61-1.05]; P=0.113). Patients with AA-ICH were less likely to have probable CAA on MRI (17/146 [11.6%] versus 127/549 [23.1%]; OR, 0.44 [95% CI, 0.25-0.75]; P=0.002) and probable CAA on MRI or computed tomography if MRI not performed (27/268 [10.0%] versus 200/836 [23.9%]; OR, 0.36 [95% CI, 0.23-0.55]; P<0.001). Among patients with AA-ICH, there were no differences in the proportion with lobar hemorrhage (63/148 [42.6%] versus 46/107 [43.0%]; OR, 1.02 [95% CI, 0.62-1.68]; P=0.946) or probable CAA on MRI (10/72 [13.9%] versus 7/69 [10.1%]; OR, 0.70 [95% CI, 0.25-1.96]; P=0.495) between vitamin K antagonists and direct oral anticoagulant users. CONCLUSIONS: AA-ICH was not associated with lobar hemorrhage location but was associated with reduced odds of probable CAA. These results suggest that hypertensive microangiopathy may predispose more toward incident AA-ICH than CAA and emphasize the importance of blood pressure control among anticoagulant users. These findings require replication in additional cohorts.

Rationale and Design of the Statins Use in Intracerebral Hemorrhage Patients (SATURN) Trial.

INTRODUCTION: The benefits and risks of HMG-CoA reductase inhibitor (statin) drugs in survivors of intracerebral hemorrhage (ICH) are unclear. Observational studies suggest an association between statin use and increased risk of lobar ICH, particularly in patients with apolipoprotein-E (APOE) ε2 and ε4 genotypes. There are no randomized controlled trials (RCTs) addressing the effects of statins after ICH leading to uncertainty as to whether statins should be used in patients with lobar ICH who are at high risk for ICH recurrence. The SATURN trial aims to evaluate the effects of continuation versus discontinuation of statin on the risk of ICH recurrence and ischemic major adverse cerebro-cardio-vascular events (MACCE) in patients with lobar ICH. Secondary aims include the assessment of whether the APOE genotype modifies the effects of statins on ICH recurrence, functional and cognitive outcomes and quality of life. METHODS: The SATURN trial is a multi-center, pragmatic, prospective, randomized, open-label, Phase III clinical trial with blinded end-point assessment. A planned total of 1456 patients with lobar ICH will be recruited from 140 sites in the United States, Canada and Spain. Patients presenting within seven days of a spontaneous lobar ICH that occurred while taking a statin, will be randomized (1:1) to continuation (control) vs. discontinuation (intervention) of the same statin drug and dose that they were using at ICH onset. The primary outcome is the time to recurrent symptomatic ICH within a two-year follow-up period. The primary safety outcome is the occurrence of ischemic MACCE. CONCLUSION: The results will help to determine the best strategy for statin use in survivors of lobar ICH and may help to identify if there is a subset of patients who would benefit from statins.

Investigation on Gender Differences in Leadership of Stroke-Related Clinical Trials.

BACKGROUND: Gender disparities among principal investigators of clinical trials (CT) can have implications regarding the areas of investigation, methods, conduct, trial enrollment, and interpretation of results. An estimation of the gender gap in the leadership of stroke-related CTs from North America has to date not been undertaken. METHODS: We extracted information about stroke-related CTs between 2011 and 2020 from www. CLINICALTRIALS: gov and PubMed. We examined the gender distribution according to the academic credentials and the trial type. The gender of PIs and authors was determined using gender package in R, which identifies gender using historical data from the United States. Additionally, we obtained information from Association of American Medical Colleges and the Accreditation Council for Graduate Medical Education data resource books on the gender composition of full-time neurology faculty, neurology residents and vascular neurology fellows. RESULTS: In these analyses of 821 CTs registered on Clinicaltrials.gov and 110 trials published on PubMed, we found that gender disparity among the PIs, first and last authors have persisted over the last decade without any significant trend toward parity (P>0.05). On examining the gender distribution according to academic credentials and trial type, we found that men were over-represented in the sub-group of PIs with an MD degree (78.11% versus 21.87%; P<0.01) and those leading acute stroke trials (86.04% versus 13.89%; P<0.01). We also found that a lower proportion of women neurology residents pursued a vascular neurology fellowship during this period (33.5% versus 42.5%; P<0.05). CONCLUSIONS: Our results show that the favorable trend toward gender parity seen in Neurology faculty over the last decade has not translated to the same in the leadership of CTs. Our findings merit further investigation and a re-examination of efforts toward inclusion of women as leaders of stroke-related CTs.

Etiology of Primary Cerebellar Intracerebral Hemorrhage Based on Topographic Localization.

BACKGROUND: Cerebellar intracerebral hemorrhage (cICH) is often attributed to hypertension or cerebral amyloid angiopathy (CAA). However, deciphering the exact etiology can be challenging. A recent study reported a topographical etiologic relationship with superficial cICH secondary to CAA. We aimed to reexamine this relationship between topography and etiology in a separate cohort of patients and using the most recent Boston criteria version 2.0. METHODS: We performed a retrospective analysis of consecutive patients with primary cICH admitted to a tertiary academic center between 2000 and 2022. cICH location on brain computed tomography/magnetic resonance imaging scan(s) was divided into strictly superficial (cortex, surrounding white matter, vermis) versus deep (cerebellar nuclei, deep white matter, peduncular region) or mixed (both regions). Magnetic resonance imaging was rated for markers of cerebral small vessel disease. We assigned possible/probable versus absent CAA using Boston criteria 2.0. RESULTS: We included 197 patients; 106 (53.8%) were females, median age was 74 (63-82) years. Fifty-six (28%) patients had superficial cICH and 141 (72%) deep/mixed cICH. Magnetic resonance imaging was available for 112 (57%) patients (30 [26.8%] with superficial and 82 [73.2%] with deep/mixed cICH). Patients with superficial cICH were more likely to have possible/probable CAA (48.3% versus 8.6%; odds ratio [OR], 11.43 [95% CI, 3.26-40.05]; P<0.001), strictly lobar cerebral microbleeds (51.7% versus 6.2%; OR, 14.18 [95% CI, 3.98-50.50]; P<0.001), and cortical superficial siderosis (13.8% versus 1.2%; OR, 7.70 [95% CI, 0.73-80.49]; P=0.08). Patients with deep/mixed cICH were more likely to have deep/mixed cerebral microbleeds (59.2% versus 3.4%; OR, 41.39 [95% CI, 5.01-341.68]; P=0.001), lacunes (54.9% versus 17.2%; OR, 6.14 [95% CI, 1.89-19.91]; P=0.002), severe basal ganglia enlarged perivascular spaces (36.6% versus 7.1%; OR, 7.63 [95% CI, 1.58-36.73]; P=0.01), hypertension (84.4% versus 62.5%; OR, 3.43 [95% CI, 1.61 to -7.30]; P=0.001), and higher admission systolic blood pressure (172 [146-200] versus 146 [124-158] mm Hg, P<0.001). CONCLUSIONS: Our results suggest that superficial cICH is strongly associated with CAA whereas deep/mixed cICH is strongly associated with hypertensive arteriopathy.

An updated systematic review and meta-analysis investigating perihematomal edema and clinical outcome after intracerebral hemorrhage.

OBJECTIVES: The relationship between perihematomal edema (PHE) and intracerebral hemorrhage (ICH) outcomes is uncertain. Given newly published studies, we updated a previous systematic review and meta-analysis assessing the prognostic impact of PHE on ICH outcomes. MATERIALS AND METHODS: Databases were searched through September 2022 using pre-defined keywords. Included studies used regression to examine the association between PHE and functional outcome (assessed by modified Rankin Scale [mRS]) and mortality. The study quality was assessed using the Newcastle-Ottawa Scale. The overall pooled effect, and secondary analyses exploring different subgroups were obtained by entering the log transformed odds ratios and their confidence intervals into a DerSimonian-Laird random effects meta-analysis. RESULTS: Twenty-eight studies (n=8655) were included. The pooled effect size for overall outcome (mRS and mortality) was 1.05 (95% CI 1.03, 1.07; p<0.00). In secondary analyses, PHE volume and growth effect sizes were 1.03 (CI 1.01, 1.05) and 1.12 (CI 1.06, 1.19), respectively. Results of subgroup analyses assessing absolute PHE volume and growth at different time points were: baseline volume 1.02 (CI 0.98, 1.06), 72-hour volume 1.07 (CI 0.99, 1.16), growth at 24 hours 1.30 (CI 0.96, 1.74) and growth at 72 hours 1.10 (CI 1.04, 1.17). Heterogeneity across studies was substantial. CONCLUSIONS: This meta-analysis indicates that PHE growth, especially within the first 24 hours after ictus, has a stronger impact on functional outcome and mortality than PHE volume. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.

Relationship between prior statin therapy and radiological features and clinical outcomes of intracerebral hemorrhage.

OBJECTIVES: A post-hoc analysis of the ICH Deferoxamine (i-DEF) trial was performed to examine any associations pre-ICH statin use may have with ICH volume, PHE volume, and clinical outcomes. MATERIALS AND METHODS: Baseline characteristics were assessed. Various ICH and PHE parameters were measured via a quantitative, semi-automated method at baseline and follow-up CT scans 72-96 h later. A multivariable logistic regression model was created, adjusting for the variables that were significantly different on univariable analyses (p < 0.05), to assess any associations between pre-ICH statin use and measures of ICH and PHE, as well as good clinical outcome (mRS ≤2), at 90 and 180 days. RESULTS: 262 of 291 i-DEF participants had complete data available for analysis. 69 (26.3 %) used statins prior to ICH onset. Pre-ICH statin users had higher prevalences of hypertension, diabetes, and prior ischemic stroke; higher concomitant use of antihypertensives and antiplatelets; and higher blood glucose level at baseline. On univariable analyses, pre-ICH statin users had smaller baseline ICH volume and PHE volume on repeat scan, as well as smaller changes in relative PHE (rPHE) volume and edema extension distance (EED) between the baseline and repeat scans. In the multivariable analysis, none of the ICH and PHE measures or good clinical outcome was significantly associated with pre-ICH statin use. CONCLUSION: Pre-ICH statin use was not associated with measures of ICH or PHE, their growth, or clinical outcomes. These findings do not lend support to either overall protective or deleterious effects from statin use before or after ICH.

The Prognostic Roles of Perihematomal Edema and Ventricular Size in Patients with Intracerebral Hemorrhage.

BACKGROUND: Conflicting data exist regarding the association of perihematomal edema (PHE) with outcomes after intracerebral hemorrhage (ICH). We performed a post hoc analysis of the ICH Deferoxamine trial to examine whether an early change in ventricular size (VS), as a composite measure of PHE growth and mass effect, intraventricular hemorrhage, and hydrocephalus, is a more accurate predictor of outcome than PHE measures alone. METHODS: Computerized tomography scans were performed at baseline and after 72-96 h. We evaluated measures of PHE and change in VS as predictors of outcome, assessed by a dichotomized modified Rankin Scale score (0-2 versus 3-6), primarily at 90 days and secondarily at 30 days. A multivariable logistic regression model was fitted for each predictor, with adjustment for the same confounders. RESULTS: A total of 248 participants were included after we excluded those requiring external ventricular drains. On univariate analyses, older age, female sex, lower Glasgow Coma Scale score and baseline temperature, greater ICH volume, absolute PHE volume, edema extension distance at presentation, lesser changes in relative PHE volume and edema extension distance, and an increase in VS were associated with poor outcome. In multivariable analyses, only the increase in VS was associated with lower odds of modified Rankin Scale scores 0-2 at 90 days (odds ratio 0.927, 95% confidence interval 0.866-0.970, p = 0.001) and 30 days (odds ratio 0.931, 95% confidence interval 0.888-0.975, p = 0.003). CONCLUSIONS: Within the context of a randomized controlled trial with standardized imaging and functional assessments, we did not find significant associations between measures of PHE and outcome but documented an independent association between early increase in VS and lower odds of good clinical outcome.

Predicting Gastrostomy Tube Placement After Intracerebral Hemorrhage: External Validation of the GRAVo Score.

BACKGROUND: Dysphagia is a common consequence of intracerebral hemorrhages (ICH). It can lead to enduring impairments of dietary intake and the requirement for feeding via percutaneous gastrostomy (PEG) tubes. However, variabilities in the course of swallowing recovery after ICH make it difficult to anticipate the need for PEG placement in an individual patient. A new tool called the GRAVo score was recently developed to predict PEG tube placement after an ICH but has not been externally validated. Our study aims were to externally validate the GRAVo score in a multicenter cohort and reexamine the role of race in predicting PEG placement, given the uncertain biological plausibility for this relationship observed in the derivation cohort. METHODS: Patients for this analysis were selected from a previously completed multicenter, randomized, double-blind futility design clinical trial, the Intracerebral Hemorrhage Deferoxamine trial, and underwent a retrospective review of prospectively collected data. The GRAVo scores were computed by using previously established methods using the following variables: Glasgow Coma Scale ≤ 12 (2 points), race (1 point for Black), age > 50 years (2 points), and ICH volume > 30 mL (1 point). Association of GRAVo scores with PEG placement were examined by using logistic regression analysis after adjustment for exposure to deferoxamine. Model performance was estimated by using area under the receiving operating characteristic curve (AUROC). Subsequently, a second model was created by excluding scores for race, and the AUROC of both models were compared. RESULTS: A total of 291 patients with complete data points served as the study cohort; 38 (13%) underwent PEG placement. The median GRAVo score for patients in the PEG and non-PEG groups were 4 (interquartile range 3-4) versus 2 (interquartile range 2-3), respectively (p < 0.0001). External validation of the GRAVo score yielded an AUROC of 0.7008 (95% confidence interval 0.6036-0.78); the model obtained without assignment of scores for the variable race yielded an AUROC of 0.6958 (95% confidence interval 0.6124-0.7891). The receiver operating characteristic curves from both models demonstrated close overlap. CONCLUSIONS: The results of our external validation demonstrate the validity of GRAVo scores for predicting PEG tube placement after an ICH. However, its performance was more modest compared with that of the derivation cohort. Inclusion of the race variable had no measurable effect on model performance. Differences in patient characteristics between these cohorts may have influenced our results. These findings should be taken into consideration when using the GRAVo score to assist clinical decision making on PEG placement after an ICH.

Perihematomal Edema and Clinical Outcome After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

BACKGROUND: Perihematomal edema (PHE) has been proposed as a radiological marker of secondary injury and therapeutic target in intracerebral hemorrhage (ICH). We conducted a systematic review and meta-analysis to assess the prognostic impact of PHE on functional outcome and mortality in patients with ICH. METHODS: We searched major databases through December 2020 using predefined keywords. Any study using logistic regression to examine the association between PHE or its growth and functional outcome was included. We examined the overall pooled effect and conducted secondary analyses to explore the impact of individual PHE measures on various outcomes separately. Study quality was assessed by three independent raters using the Newcastle-Ottawa Scale. Odds ratios (per 1-unit increase in PHE) and their confidence intervals (CIs) were log transformed and entered into a DerSimonian-Laird random-effects meta-analysis to obtain pooled estimates of the effect. RESULTS: Twenty studies (n = 6633 patients) were included in the analysis. The pooled effect size for overall outcome was 1.05 (95% CI 1.02-1.08; p < 0.00). For the following secondary analyses, the effect size was weak: mortality (1.01; 95% CI 0.90-1.14), functional outcome (1.04; 95% CI 1.02-1.07), both 90-day (1.06; 95% CI 1.02-1.11), and in-hospital assessments (1.04; 95% CI 1.00-1.08). The effect sizes for PHE volume and PHE growth were 1.04 (95% CI 1.01-1.07) and 1.14 (95% CI 1.04-1.25), respectively. Heterogeneity across studies was substantial except for PHE growth. CONCLUSIONS: This meta-analysis demonstrates that PHE volume within the first 72 h after ictus has a weak effect on functional outcome and mortality after ICH, whereas PHE growth might have a slightly larger impact during this time frame. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.

Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage.

BACKGROUND: Many patients with acute intracerebral hemorrhages (ICHs) undergo endotracheal intubation with subsequent mechanical ventilation (MV) for "airway protection" with the intent to prevent aspiration, pneumonias, and its related mortality. Conversely, these procedures may independently promote pneumonia, laryngeal trauma, dysphagia, and adversely affect patient outcomes. The net benefit of intubation and MV in this patient cohort has not been systematically investigated. METHODS: We conducted a large single-center observational cohort study to examine the independent association between endotracheal intubation and MV, hospital-acquired pneumonia (HAP), and in-hospital mortality (HM) in patients with ICH. All consecutive patients admitted with a primary diagnosis of a spontaneous ICH to a tertiary care hospital in Boston, Massachusetts, from June 2000 through January 2014, who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Patients with pneumonia on admission, or those having brain or lung neoplasms were excluded. Our exposure of interest was endotracheal intubation and MV during hospitalization; our primary outcomes were incidence of HAP and HM, ascertained using International Classification of Diseases-9 and administrative discharge disposition codes, respectively, in patients who underwent endotracheal intubation and MV versus those who did not. Multivariable logistic regression was used to control for confounders. RESULTS: Of the 2,386 hospital admissions screened, 1,384 patients fulfilled study criteria and were included in the final analysis. A total of 507 (36.6%) patients were intubated. Overall 133 (26.23%) patients in the intubated group developed HAP versus 41 (4.67%) patients in the non-intubated group (p < 0.0001); 195 (38.5%) intubated patients died during hospitalization compared to 48 (5.5%) non-intubated patients (p < 0.0001). After confounder adjustments, OR for HAP and HM, were 4.23 (95% CI 2.48-7.22; p < 0.0001) and 4.32 (95% CI 2.5-7.49; p < 0.0001) with c-statistics of 0.79 and 0.89, in the intubated versus non-intubated patients, respectively. CONCLUSION: In this large hospital-based cohort of patients presenting with an acute spontaneous ICH, endotracheal intubation and MV were associated with increased odds of HAP and HM. These findings urge further examination of the practice of intubation in prospective studies.

Pharyngeal Swallowing Mechanics Secondary to Hemispheric Stroke.

BACKGROUND: Computational analysis of swallowing mechanics (CASM) is a method that utilizes multivariate shape change analysis to uncover covariant elements of pharyngeal swallowing mechanics associated with impairment using videofluoroscopic swallowing studies. The goals of this preliminary study were to (1) characterize swallowing mechanics underlying stroke-related dysphagia, (2) decipher the impact of left and right hemispheric strokes on pharyngeal swallowing mechanics, and (3) determine pharyngeal swallowing mechanics associated with penetration-aspiration status. METHODS: Videofluoroscopic swallowing studies of 18 dysphagic patients with hemispheric infarcts and age- and gender-matched controls were selected from well-controlled data sets. Patient data including laterality and penetration-aspiration status were collected. Coordinates mapping muscle group action during swallowing were collected from videos. Multivariate morphometric analyses of coordinates associated with stroke, affected hemisphere, and penetration-aspiration status were performed. RESULTS: Pharyngeal swallowing mechanics differed significantly in the following comparisons: stroke versus controls (D = 2.19, P < .0001), right hemispheric stroke versus controls (D = 3.64, P < .0001), left hemispheric stroke versus controls (D = 2.06, P < .0001), right hemispheric stroke versus left hemispheric stroke (D = 2.89, P < .0001), and penetration-aspiration versus within normal limits (D = 2.25, P < .0001). Differences in pharyngeal swallowing mechanics associated with each comparison were visualized using eigenvectors. CONCLUSIONS: Whereas current literature focuses on timing changes in stroke-related dysphagia, these data suggest that mechanical changes are also functionally important. Pharyngeal swallowing mechanics differed by the affected hemisphere and the penetration-aspiration status. CASM can be used to identify patient-specific swallowing impairment associated with stroke injury that could help guide rehabilitation strategies to improve swallowing outcomes.

Risk of Stroke-Associated Pneumonia and Oral Hygiene.

BACKGROUND: Pneumonia is a major complication of stroke, but effective prevention strategies are lacking. Since aspiration of oropharyngeal secretions is the primary mechanism for development of stroke-associated pneumonia, strategies that decrease oral colonization with pathogenic bacteria may help curtail pneumonia risk. We therefore hypothesized that systematic oral care protocols can help decrease pneumonia risk in hospitalized stroke patients. In this study, we investigated the impact of a systematic oral hygiene care (OHC) program in reducing hospital-acquired pneumonia in patients with acute-subacute stroke. METHODS: This study compared the proportion of pneumonia cases in hospitalized stroke patients before and after implementation of a systematic OHC intervention. All patients hospitalized with acute ischemic stroke or intracerebral hemorrhage admitted to a large, urban academic medical center in Boston, Mass., USA from May 31, 2008, to June 1, 2010 (epoch prior to implementation of OHC), and from January 1, 2012, to December 31, 2013 (epoch after full implementation of OHC), who were 18 years of age and hospitalized for ≥ 2 days were eligible for inclusion. The cohort in the first epoch constituted the control group whereas the cohort in the second epoch formed the intervention group. Multivariate logistic regression was used to control for confounders. The main outcome measure was hospital-acquired pneumonia, defined via International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: The cohort comprised 1,656 admissions (707 formed historical controls; 949 were in the intervention group). The unadjusted incidence of hospital-acquired pneumonia was lower in the group assigned to OHC compared to controls (14 vs. 10.33%; p = 0.022) with an unadjusted OR of 0.68 (95% CI 0.48-0.95; p = 0.022). After adjustment for influential confounders, the OR of hospital-acquired pneumonia in the intervention group remained significantly lower at 0.71 (95% CI 0.51-0.98; p = 0.041). CONCLUSION: In this large hospital-based cohort of patients admitted with acute stroke, systematic OHC use was associated with decreased odds of hospital-acquired pneumonia.

Acid-suppressive medication use in acute stroke and hospital-acquired pneumonia.

OBJECTIVE: Pneumonia is a morbid complication of stroke, but evidence-based strategies for its prevention are lacking. Acid-suppressive medications have been associated with increased risk for nosocomial pneumonia in hospitalized patients. It is unclear whether these results can be extrapolated to stroke patients, where other factors strongly modulate pneumonia risk. We investigated the association between acid-suppressive medication and hospital-acquired pneumonia in patients with acute stroke. METHODS: All patients hospitalized with acute ischemic stroke or intracerebral hemorrhage in a large, urban academic medical center in Boston, Massachusetts from June 2000 to June 2010 who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Acid-suppressive medication use was defined as any pharmacy charge for a proton-pump inhibitor or histamine-2 receptor antagonist. Multivariate logistic regression was used to control for confounders. The main outcome measure was hospital-acquired pneumonia, defined via International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: The cohort comprised 1,676 admissions. Acid-suppressive medication was ordered in 1,340 (80%) and hospital-acquired pneumonia occurred in 289 (17.2%). The unadjusted incidence of hospital-acquired pneumonia was higher in the group exposed to acid-suppressive medication compared to those unexposed (20.7% vs 3.6%, odds ratio [OR] = 7.0, 95% confidence interval [CI] = 3.9-12.7). After adjustment, the OR of hospital-acquired pneumonia in the exposed group was 2.3 (95% CI = 1.2-4.6). The association was significant for proton-pump inhibitors (OR = 2.7, 95% CI = 1.4-5.4), but not for histamine-2 receptor antagonists (OR = 1.6, 95% CI = 0.8-3.4). INTERPRETATION: In this large hospital-based cohort of patients presenting with acute stroke, acid-suppressive medication use was associated with increased odds of hospital-acquired pneumonia.

Study design for the fostering eating after stroke with transcranial direct current stimulation trial: a randomized controlled intervention for improving Dysphagia after acute ischemic stroke.

GOAL: Dysphagia is a major stroke complication but lacks effective therapy that can promote recovery. Noninvasive brain stimulation with and without peripheral sensorimotor activities may be an attractive treatment option for swallowing recovery but has not been systematically investigated in the stroke population. This article describes the study design of the first prospective, single-center, double-blinded trial of anodal versus sham transcranial direct current stimulation (tDCS) used in combination with swallowing exercises in patients with dysphagia from an acute ischemic stroke. The aim of this study is to gather safety data on cumulative sessions of tDCS in acute-subacute phases of stroke, obtain information about effects of this intervention on important physiologic and clinically relevant swallowing parameters, and examine possible dose effects. METHODS: Ninety-nine consecutive patients with dysphagia from an acute unilateral hemispheric infarction with a Penetration and Aspiration Scale (PAS) score of 4 or more and without other confounding reasons for dysphagia will be enrolled at a single tertiary care center. Subjects will be randomized to either a high or low dose tDCS or a sham group and will undergo 10 sessions over 5 consecutive days concomitantly with effortful swallowing maneuvers. The main efficacy measures are a change in the PAS score before and after treatment; the main safety measures are mortality, seizures, neurologic, motor, and swallowing deterioration. CONCLUSIONS: The knowledge gained from this study will help plan a larger confirmatory trial for treating stroke-related dysphagia and advance our understanding of important covariates influencing swallowing recovery and response to the proposed intervention.

Effects of melodic intonation therapy in patients with chronic nonfluent aphasia.

Patients with large left-hemisphere lesions and post-stroke aphasia often remain nonfluent. Melodic intonation therapy (MIT) may be an effective alternative to traditional speech therapy for facilitating recovery of fluency in those patients. In an open-label, proof-of-concept study, 14 subjects with nonfluent aphasia with large left-hemisphere lesions (171 ± 76 cc) underwent two speech/language assessments before, one at the midpoint, and two after the end of 75 sessions (1.5 h/session) of MIT. Functional MR imaging was done before and after therapy asking subjects to vocalize the same set of 10 bi-syllabic words. We found significant improvements in speech output after a period of intensive MIT (75 sessions for a total of 112.5 h) compared to two pre-therapy assessments. Therapy-induced gains were maintained 4 weeks post-treatment. Imaging changes were seen in a right-hemisphere network that included the posterior superior temporal and inferior frontal gyri, inferior pre- and postcentral gyri, pre-supplementary motor area, and supramarginal gyrus. Functional changes in the posterior right inferior frontal gyri significantly correlated with changes in a measure of fluency. Intense training of intonation-supported auditory-motor coupling and engaging feedforward/feedback control regions in the unaffected hemisphere improves speech-motor functions in subjects with nonfluent aphasia and large left-hemisphere lesions.

Fostering eating after stroke (FEASt) trial for improving post-stroke dysphagia with non-invasive brain stimulation.

Dysphagia is a serious stroke complication but lacks effective therapy. We investigated safety and preliminary efficacy of anodal transcranial direct current stimulation (atDCS) paired with swallowing exercises in improving post-stroke dysphagia from an acute unilateral hemispheric infarction (UHI). We conducted a double-blind, early phase-2 randomized controlled trial, in subjects (n = 42) with moderate-severe dysphagia [Penetration and Aspiration Scale (PAS) score ≥ 4], from an acute-subacute UHI. Subjects were randomized to Low-Dose, High-Dose atDCS or Sham stimulation for 5 consecutive days. Primary safety outcomes were incidence of seizures, neurological, motor, or swallowing function deterioration. Primary efficacy outcome was a change in PAS scores at day-5 of intervention. Main secondary outcome was dietary improvement at 1-month, assessed by Functional Oral Intake (FOIS) score. No differences in pre-defined safety outcomes or adjusted mean changes in PAS, FOIS scores, between groups, were observed. Post-hoc analysis demonstrated that 22 /24 subjects in the combined atDCS group had a clinically meaningful dietary improvement (FOIS score ≥ 5) compared to 8 /14 in Sham (p = 0.037, Fisher-exact). atDCS application in the acute-subacute stroke phase is safe but did not decrease risk of aspiration in this early phase trial. The observed dietary improvement is promising and merits further investigation.

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.

Impairment of speech production predicted by lesion load of the left arcuate fasciculus.

BACKGROUND AND PURPOSE: Previous studies have suggested that patients' potential for poststroke language recovery is related to lesion size; however, lesion location may also be of importance, particularly when fiber tracts that are critical to the sensorimotor mapping of sounds for articulation (eg, the arcuate fasciculus) have been damaged. In this study, we tested the hypothesis that lesion loads of the arcuate fasciculus (ie, volume of arcuate fasciculus that is affected by a patient's lesion) and of 2 other tracts involved in language processing (the extreme capsule and the uncinate fasciculus) are inversely related to the severity of speech production impairments in patients with stroke with aphasia. METHODS: Thirty patients with chronic stroke with residual impairments in speech production underwent high-resolution anatomic MRI and a battery of cognitive and language tests. Impairment was assessed using 3 functional measures of spontaneous speech (eg, rate, informativeness, and overall efficiency) as well as naming ability. To quantitatively analyze the relationship between impairment scores and lesion load along the 3 fiber tracts, we calculated tract-lesion overlap volumes for each patient using probabilistic maps of the tracts derived from diffusion tensor images of 10 age-matched healthy subjects. RESULTS: Regression analyses showed that arcuate fasciculus lesion load, but not extreme capsule or uncinate fasciculus lesion load or overall lesion size, significantly predicted rate, informativeness, and overall efficiency of speech as well as naming ability. CONCLUSIONS: A new variable, arcuate fasciculus lesion load, complements established voxel-based lesion mapping techniques and, in the future, may potentially be used to estimate impairment and recovery potential after stroke and refine inclusion criteria for experimental rehabilitation programs.

The use of non-invasive brain stimulation techniques to facilitate recovery from post-stroke aphasia.

Aphasia is a common symptom after left hemispheric stroke. Neuroimaging techniques over the last 10-15 years have described two general trends: Patients with small left hemisphere strokes tend to recruit perilesional areas, while patients with large left hemisphere lesions recruit mainly homotopic regions in the right hemisphere. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been employed to facilitate recovery by stimulating lesional and contralesional regions. The majority of these brain stimulation studies have attempted to block homotopic regions in the right posterior inferior frontal gyrus (IFG) to affect a presumed disinhibited right IFG (triangular portion). Other studies have used anodal or excitatory tDCS to stimulate the contralesional (right) fronto-temporal region or parts of the intact left IFG and perilesional regions to improve speech-motor output. It remains unclear whether the interhemispheric disinhibition model, which is the basis for motor cortex stimulation studies, also applies to the language system. Future studies could address a number of issues, including: the effect of lesion location on current density distribution, timing of the intervention with regard to stroke onset, whether brain stimulation should be combined with behavioral therapy, and whether multiple brain sites should be stimulated. A better understanding of the predictors of recovery from natural outcome studies would also help to inform study design, and the selection of clinically meaningful outcome measures in future studies.

Transcranial direct current stimulation for post-stroke dysphagia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been investigated as a tool for dysphagia recovery after stroke in several single-center randomized controlled trials (RCT). OBJECTIVE: The aim of this investigation was to quantitatively evaluate the effect of tDCS on dysphagia recovery after a stroke utilizing a systematic review and meta-analysis. METHODS: Major databases were searched through October 2019 using a pre-defined set of criteria. Any RCT investigating the efficacy of tDCS in post-stroke dysphagia using a standardized dysphagia scale as outcome measure was included. Studies were assessed for risk of bias and quality using the Physiotherapy Evidence Database (PEDro) scale. Effect sizes were calculated from extracted data and entered into a random effects analysis to obtain pooled estimates of the effect. RESULTS: Seven RCTs with a total sample size of 217 patients fulfilled the criteria and were included in the analysis. The overall results revealed a small but statistically significant pooled effect size (0.31; CI 0.03, 0.59; p = 0.03). The subgroup which explored the stimulation intensity yielded a moderately significant effect size for the low-intensity stimulation group (g = 0.44; CI = 0.08, 0.81 vs. g = 0.15, CI - 0.30, 0.61). For the other subgroup analyses, neither comparisons of affected vs. unaffected hemisphere or acute vs. chronic stroke phase revealed a significant result. CONCLUSION: This meta-analysis demonstrates a modest but significant beneficial effect of tDCS on improving post-stroke dysphagia. Whether benefits from this intervention are more pronounced in certain patient subgroups and with specific stimulation protocols requires further investigation.