Exploring the relationship between lesion morphology and pathogenesis in acute small subcortical infarction.

Introduction Acute small subcortical infarctions (SSIs) result from occlusions of small penetrating arteries, and the underlying pathological factors can have different clinical implications. The objective of this study was to assess the clinical relevance of acute SSIs based on their sizes and morphologies. Methods This retrospective case-control study analyzed clinical and imaging data of stroke patients with acute SSIs in penetrating artery territories who underwent MRI within 5 days of stroke onset, registered between 2016 and 2020. We categorized these patients into three groups based on size and morphology: diameter < 20mm, diameter ≧ 20mm, and separated lesions. We then evaluated their clinical characteristics and outcomes. Results We analyzed 726 stroke patients with SSIs, among whom 573 had a diameter <20mm, 99 had a diameter ≥20mm, and 54 had separated lesions. The patients had a median age of 70 years and a median National Institutes of Health Stroke Scale (NIHSS) score of 4 on arrival. Patients who experienced early neurological deterioration (END) had a significantly lower chance of good functional outcomes (27.3% vs. 64.4%, p<0.001). Patients with a diameter ≧20mm had the most severe NIHSS on arrival and at day 3, the highest rate of END, and the lowest rate of good outcome at 3 months. The incidence of cardioembolism did not differ between patients with diameters of ≥20mm and <20mm. However, multiple logistic regression analysis revealed that separated lesions were more likely to be associated with cardioembolic stroke (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 2.0-28.5) and parent artery stenosis >50% (aOR, 3.8; 95% CI, 2.1-7.0) than a diameter of <20mm. Moreover, SSIs with a diameter of ≥20mm was found to be associated with an increased risk of END compared to that with a diameter of <20mm (aOR, 2.9; 95% CI, 1.7-5.2). Conclusion Our study suggests that the sizes and morphologies of acute SSIs may indicate different underlying pathologies and be linked to diverse clinical outcomes. Our findings also challenge the current imaging criteria for embolic stroke of undetermined source, as we did not find a link between large subcortical infarction and cardioembolic stroke.

Human thirst behavior requires transformation of sensory inputs by intrinsic brain networks.

BACKGROUND: To survive and thrive, many animals, including humans, have evolved goal-directed behaviors that can respond to specific physiological needs. An example is thirst, where the physiological need to maintain water balance drives the behavioral basic instinct to drink. Determining the neural basis of such behaviors, including thirst response, can provide insights into the way brain-wide systems transform sensory inputs into behavioral outputs. However, the neural basis underlying this spontaneous behavior remains unclear. Here, we provide a model of the neural basis of human thirst behavior. RESULTS: We used fMRI, coupled with functional connectivity analysis and serial-multiple mediation analysis, we found that the physiological need for water is first detected by the median preoptic nucleus (MnPO), which then regulates the intention of drinking via serial large-scale spontaneous thought-related intrinsic network interactions that include the default mode network, salience network, and frontal-parietal control network. CONCLUSIONS: Our study demonstrates that the transformation in humans of sensory inputs for a single physiological need, such as to maintain water balance, requires large-scale intrinsic brain networks to transform this input into a spontaneous human behavioral response.

Do initially non-dehydrated patients with acute ischemic stroke need fluid supplement?

Background: We previously found that dehydration is an independent predictor of early deterioration after acute ischemic stroke and rehydration helps to improve outcomes. There is limited evidence of how to treat patients who are initially non-dehydrated. In this study, we tested the hypothesis that rehydration therapy, based on the daily urine specific gravity, will improve the outcome of ischemic stroke patients who are initially non-dehydrated. Methods: We conducted a single-arm prospective study of patients with acute ischemic stroke with historical controls. For the first 5 days of study group, a daily urine specific gravity of > 1.020 g/ml was taken as indication for rehydration and patients were advised to drink water via oral or tubal feeding with a dose of 5 ml/kg body weight right away and after dinner. Control group patients were rehydrated without reference to urine specific gravity. An increase in National Institutes of Health Stroke Scale score of ≥ 4 within three days was defined as having stroke-in-evolution. Scores of ≤ 1 on the modified Rankin scale at 3 months were considered to indicate a favorable outcome. Results: A total of 125 patients were analyzed, 46 in the study group and 79 in the control group. The groups did not significantly differ in the stroke-in-evolution rate (4.3% vs. 8.2%, P = 0.474). The rate of favorable outcome at 3 months was significantly higher in the study group than in the control group (56.5% vs. 27.8%, P = 0.001). Conclusions: Urine specific gravity-based hydration might be a useful method to improve functional outcomes of patients with acute ischemic stroke who were non-dehydrated at admission.

The influence of dehydration on the prognosis of acute ischemic stroke for patients treated with tissue plasminogen activator.

BACKGROUND: Many studies have determined that dehydration is an independent predictor of outcome after ischemic stroke (IS); however, none have determined if the use of thrombolytic therapy modifies the negative impact of poor hydration. To inform the stroke registry established at our institution, we conducted a retrospective study to determine if dehydration remains a negative prognostic factor after IS patients treated with tissue plasminogen activator (tPA). METHODS: Between 2007 and 2012, we recruited 382 subjects; 346 had data available and were divided into 2 groups on the basis of their blood urea nitrogen/creatinine (BUN/Cr) ratio. Dehydrated subjects had a BUN/Cr ratio ≥ 15; hydrated subjects had a BUN/Cr < 15. The primary outcome was impairment at discharge as graded by the Barthel Index (BI) and the modified Rankin Scale (mRS). RESULTS: The dehydration group had a greater mean age; more women; lower mean levels of hemoglobin, triglycerides, and sodium; and higher mean potassium and glucose levels. A favorable outcome as assessed by the mRS (≤2) was significantly less frequent among dehydrated subjects, but a favorable outcome by the BI (≥60) was not. Logistic regression and multivariate models confirmed that dehydration is an independent predictor of poor outcome by both the mRS and the BI; however, it was not predictive when patients were stratified by Trial of Org 10,172 in Acute Stroke Treatment subtype. CONCLUSIONS: Our findings indicate that use of thrombolytic therapy does not eliminate the need to closely monitor hydration status in patients with IS.

Urine-Specific Gravity-Based Hydration Prevents Stroke in Evolution in Patients with Acute Ischemic Stroke.

BACKGROUND: Early neurological deterioration after ischemic stroke (stroke-in-evolution [SIE]) is associated with poorer outcomes. Previous studies have demonstrated a link between hydration status and the development of SIE. In this study, we tested the hypothesis that rehydration therapy, administered on the basis of urine-specific gravity (USG) findings, might reduce the development of SIE. METHODS: We conducted a single-arm prospective study of patients with acute ischemic stroke with historical controls. For the study group, a USG higher than 1.010 was taken as an indication for rehydration. Control group patients were rehydrated without referring to USG. An increase in National Institutes of Health Stroke Scale (NIHSS) score of 4 or higher within 3 days was defined as having SIE. RESULTS: A total of 445 patients were analyzed, 167 in the study group and 278 in the control group. The proportion of patients who developed SIE was numerically, but not significantly, lower in the study group (5.9%; 10 of 167) compared with the control group (11.5%; 32 of 278). Among patients with a USG higher than 1.010 at admission, the SIE rate was significantly reduced in the study group compared with the control group (6.1% versus 16.0%; P = .021), while the rate of SIE was similar in those with a USG of 1.010 or lower at admission. Multivariate logistic regression analysis confirmed that USG-based hydration was an independent factor associated with reducing SIE. CONCLUSIONS: USG might be a convenient and useful method for guiding fluid therapy in patients with acute ischemic stroke. USG-based hydration reduced the incidence of SIE among patients with a USG higher than 1.010 at admission.

Initial blood pressure is associated with stroke severity and is predictive of admission cost and one-year outcome in different stroke subtypes: a SRICHS registry study.

BACKGROUND: To investigate if initial blood pressure (BP) on admission is associated with stroke severity and predictive of admission costs and one-year-outcome in acute ischemic (IS) and hemorrhagic stroke (HS). METHODS: This is a single-center retrospective cohort study. Stroke patients admitted within 3 days after onset between January 1st and December 31st in 2009 were recruited. The initial BP on admission was subdivided into high (systolic BP ≥ 211 mmHg or diastolic BP ≥ 111 mmHg), medium (systolic BP 111-210 mmHg or diastolic BP 71-110 mmHg), and low (systolic BP ≤ 110 mmHg or diastolic BP ≤ 70 mmHg) groups and further subgrouped with 25 mmHg difference in systole and 10 mmHg difference in diastole for the correlation analysis with demographics, admission cost and one-year modified Rankin scale (mRS). RESULTS: In 1173 IS patients (mean age: 67.8 ± 12.8 years old, 61.4% male), low diastolic BP group had higher frequency of heart disease (p =0.001), dehydration (p =0.03) and lower hemoglobin level (p <0.001). The extremely high and low systolic BP subgroups had worse National Institutes of Health Stroke Scale (NIHSS) score (p =0.03), higher admission cost (p <0.001), and worse one-year mRS (p =0.03), while extremely high and low diastolic BP subgroups had higher admission cost (p <0.01). In 282 HS patients (mean age: 62.4 ± 15.4 years old, 60.6% male), both low systolic and diastolic BP groups had lower hemoglobin level (systole: p =0.05; diastole: p <0.001). The extremely high and low BP subgroups had worse NIHSS score (p =0.01 and p <0.001, respectively), worse one-year mRS (p =0.002 and p =0.001, respectively), and higher admission cost (diastole: p <0.002). CONCLUSIONS: Stroke patients with extremely high and low BP on admission have not only worse stroke severity but also higher admission cost and/or worse one-year outcome. In those patients with low BP, low admission hemoglobin might be a contributing factor.

Favorable outcome of blood urea nitrogen/creatinine-based hydration therapy 3 months after acute ischemic stroke.

BACKGROUND: Dehydration is associated with acute ischemic stroke. However, the relationship between hydration therapy given during acute ischemic stroke and clinical outcomes remains unclear. AIMS: We determined whether hydration therapy in patients with a blood urea nitrogen/creatinine (BUN/Cr) ratio of at least 15 improved clinical outcome. METHODS: We conducted a nonblinded, phase II, single-arm, prospective study of patients with acute ischemic stroke and BUN/Cr ratio of at least 15 with historical controls. The hydration group received intravenous bolus (300-500 mL) saline followed by maintenance saline infusion (40-80 mL/h for the first 72 hours), whereas the control group received maintenance saline infusion (40-60 mL/h for the first 24 hours and 0-60 mL/h for 24-72 hours after stroke). The study end point was the percentage of patients with a favorable outcome defined as modified Rankin scale score of 2 or lower at 3 months after stroke. RESULTS: A total of 237 patients were enrolled (hydration, n = 134; control, n = 103). The mean volume of saline infused within the first 72 hours was significantly larger (P < .001), and the rate of favorable outcome at 3 months after stroke was significantly higher (P = .016) in the hydration group than in the controls. Further analysis revealed that the difference was significant in the lacunar stroke subtype (P = .020) but not in the nonlacunar subtype. CONCLUSIONS: Blood urea nitrogen/Cr ratio-based saline hydration therapy in patients with acute ischemic stroke significantly increased the rate of favorable clinical outcome with functional independence at 3 months after stroke.

To Load or Not to Load? Aspirin Loading in Acute Ischemic Stroke: A Study of Clinical Outcomes.

BACKGROUND AND PURPOSE: Aspirin is known to reduce mortality and recurrent vascular events. However, there are no reports about the dose-response of loading aspirin in treating acute ischemic stroke. The objective of this study was to compare the effectiveness of different loading doses of aspirin in acute ischemic stroke presenting within 48 hours of symptom onset. METHODS: This was a retrospective, hospital-based cohort study. Patients were classified as high dose (160-325 mg) or low dose (<160 mg) based on the initial loading dose of aspirin at the emergency department. The primary outcome measure was a favorable modified Rankin Scale (mRS) score of 1 or lower on discharge. Secondary outcomes included in-hospital mortality, stroke progression during admission, and bleeding events. A propensity score with 1:3 matching was used to balance baseline characteristics, and stepwise multiple logistic regression was performed for variable adjustment. RESULTS: From a total of 7738 available patients, 3802 patients were included. Among them, 750 patients were in the high-dose group. Multiple logistic regression after matching revealed that the high-dose group was significantly associated with a favorable clinical outcome on discharge (odds ratio: 1.49, 95% confidence interval: 1.17-1.89, P <.01), but not mortality or stroke progression. The high-dose group also experienced more minor bleeding events. CONCLUSIONS: A higher loading dose of aspirin (160-325 mg) can be beneficial in treating acute ischemic stroke, although there is an increased risk of minor bleeding.

Preliminary Prospective Study to Assess the Effect of Early Blood Urea Nitrogen/Creatinine Ratio-Based Hydration Therapy on Poststroke Infection Rate and Length of Stay in Acute Ischemic Stroke.

BACKGROUND: This study aimed to determine whether blood urea nitrogen (BUN)/creatinine (Cr)-based hydration therapy can decrease the rate of poststroke infection and length of stay (LOS) in the neurology ward. METHODS: This was a nonblinded, phase II single-arm prospective study with a historical control group of patients with acute ischemic stroke and a BUN/Cr ratio of 15 or higher. The study group (n = 134) received an intravenous saline bolus (300-500 mL) followed by maintenance saline (40-80 mL/hour) for the first 72 hours. The control group (n = 103) received maintenance saline infusions (40-60 mL/hour for the first 24 hours and 0-60 mL/hour for the next 24-72 hours). RESULTS: The hydration group had a significantly lower poststroke infection rate than did the control group (7.5% versus 17.5%, P = .018) and significantly shorter LOS in the neurology ward (13.5 ± 11.6 versus 19.6 ± 14.6 days, P < .01). With regard to adverse events, two patients in each group had cerebral edema. CONCLUSIONS: The findings suggest that the BUN/Cr ratio needs to be corrected in a timely manner in patients with acute ischemic stroke. Providing prompt saline hydration therapy based on the daily BUN/Cr ratio might decrease the poststroke infection rate and shorten LOS.

Bun/creatinine ratio-based hydration for preventing stroke-in-evolution after acute ischemic stroke.

BACKGROUND: Blood urea nitrogen (BUN)/creatinine (Cr) ratio was recently reported to be an independent predictor of stroke-in-evolution (SIE) among patients who had suffered acute ischemic stroke. We aim to determine if providing hydration therapy to patients with a BUN/Cr ≥15 reduces the occurrence of SIE after acute ischemic stroke. METHODS: This prospective interventional study included 189 patients (hydration group, n = 92; control group, n = 97) with acute ischemic stroke and a BUN/Cr ≥15. Hydration group received intravenous bolus (300-500 mL) saline followed by a maintenance saline infusion (40-80 mL/h for the first 72 h), while control group received maintenance saline infusion (40-60 mL/h for the first 24 h and 0-60 mL/h for 24-72 h). The study endpoint was the proportion of patients who developed SIE within the first three days of emergency department admission. RESULTS: There were no significant differences in demographic or clinical characteristics between both groups. Patients in the hydration group received a significantly larger (all P < 0.001) median volume of infused saline than patients in the control group on Days 1 (2400 vs 1440 mL), 2 (1440 vs 0 mL), and 3 (1000 vs 0 mL). The proportion of patients who experienced SIE was significantly lower in the hydration group (9/92; 9.8%) compared with the control group (21/97; 21.6%) (Fig. 1, P = 0.026). CONCLUSIONS: Our preliminary findings suggest that providing patients with acute ischemic stroke hydration therapy on the basis of their presenting BUN/Cr ratio may help reduce the occurrence of SIE and therefore improve prognosis.

Hypertensive patients using thiazide diuretics as primary stroke prevention make better functional outcome after ischemic stroke.

BACKGROUND: Thiazides have been used for the control of blood pressure and primary prevention of ischemic stroke. No previous studies have assessed the influence of thiazides on functional prognosis after ischemic stroke. METHODS: Demographics, prestroke conditions, poststroke National Institutes of Health Stroke Scale score, and clinical and laboratory parameters were prospectively registered in 216 Taiwanese patients. One hundred forty patients who completed follow-up 3 months after experiencing ischemic stroke were assessed with the modified Rankin scale as functional prognoses. RESULTS: Twenty-one patients used thiazide to control hypertension before experiencing ischemic stroke. No differences of stroke subtypes and comorbidities before stroke were observed between the 2 groups. The emergency department National Institutes of Health Stroke Scale was lesser among thiazide users (4 [2-7] versus 6 [4-16], P = .02). Among 140 patients who completed follow-up in 90 days, thiazide users had more favorable functional status (modified Rankin scale ≤2: 42.4% versus 26.9%, P = .02, odds ratio 3.34, 95%, confidence interval .130-.862). CONCLUSION: Hypertensive patients treated with thiazides long term had a lesser severity of stroke and better functional outcomes after ischemic stroke.

Enhanced versus standard hydration in acute ischaemic stroke: REVIVE - a randomised clinical trial.

RATIONALE: Early neurological deterioration (END) within 72 hours of stroke onset is associated with poor prognosis. Optimising hydration might reduce the risk of END. AIMS: To determine in acute ischaemic stroke patients if enhanced hydration versus standard hydration reduced the incidence of major (primary) and minor (secondary) END, as whether it increased the incidence of early neurological improvement (secondary), at 72 hours after admissionSample Size Estimate: 244 participants per arm. METHODS AND DESIGN: A prospective, double-blinded, multicentre, parallel-group, randomised controlled trial conducted at 4 hospitals from April 2014 to July 2020, with data analysed in August 2020. The sample size estimated was 488 participants (244 per arm). Ischaemic stroke patients with measurable neurological deficits of onset within 12 hours of emergency department presentation and blood urea nitrogen/creatinine (BUN/Cr) ratio ≥15 at point of admission were enrolled and randomised to 0.9% sodium chloride infusions of varying rates - enhanced hydration (20 mL/kg body weight, one-third given via bolus and remainder over 8 hours) versus standard hydration (60 mL/hour for 8 hours), followed by maintenance infusion of 40-80 mL/hour for the subsequent 64 hours. The primary outcome measure was the incidence of major early neurological deterioration at 72 hours after admission, defined as an increase in National Institutes of Health Stroke Scale of ≥4 points from baseline. RESULTS: 487 participants were randomised (median age 67 years; 287 females). At 72 hours: 7 (2.9%) in the enhanced-hydration arm and 5(2.0%) in the standard-hydration developed major early neurological deterioration (p=0.54). The incidence of minor early neurological deterioration and early neurological improvement did not differ between treatment arms. CONCLUSIONS AND RELEVANCE: Enhanced hydration ratio did not reduce END or improve short term outcomes in acute ischaemic stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02099383, https://clinicaltrials.gov/study/NCT02099383).

The impact factors on the cost and length of stay among acute ischemic stroke.

BACKGROUND: Understanding hospital costs and length of stay (LOS) can optimize the in-hospital management of acute stroke. We investigated cost and LOS in first-ever and recurrent stroke patients in Taiwan. METHODS: Data were examined in patients at Chang Gung Memorial Hospital in Chiayi County of Taiwan from April 1, 2008, to March 31, 2010 [corrected]. Predictors of hospital cost and LOS in these patients were studied. RESULTS: The study included 1021 patients with 1084 stroke episodes. Mean age was 68.1 ± 10.8 years (range: 32-93). The average cost was NTD$45,709.30 ± NTD$66,697.40 (US$1408.70 ± US$2084.30; US$1 = NTD$32) and average LOS was 13.9 ± 14.1 days (range: 1-129). After multivariate regression analysis, the significant predictive factors for cost were LOS, smoking, and medication for secondary prevention. The significant predictive factors for LOS were diabetes mellitus, atrial fibrillation, recurrence, and stroke subtype. CONCLUSIONS: Age 65 and over, atrial fibrillation, stroke treatment, and subtypes were the significant predictive factors affecting hospital costs and LOS. Compared to other countries, Taiwan spent the least while Canada had the highest expense. The United States had the shortest LOS (6 days) in contrast to Canada with the longest LOS (34-47 days). Regarding mean daily cost of stroke, the United States had the highest cost per day while China spent the least.

An observational study on salivary conductivity for fluid status assessment and clinical relevance in acute ischemic stroke during intravenous fluid hydration.

The body fluid status in acute stroke is a crucial determinant in early stroke recovery but a real-time method to monitor body fluid status is not available. This study aims to evaluate the relationship between salivary conductivity and body fluid status during the period of intravenous fluid hydration. Between June 2020 to August 2022, patients presenting with clinical signs of stroke at the emergency department were enrolled. Salivary conductivities were measured before and 3 h after intravenous hydration. Patients were considered responsive if their salivary conductivities at 3 h decreased by more than 20% compared to their baseline values. Stroke severity was assessed using the National Institutes of Health Stroke Scale, and early neurological improvement was defined as a decrease of ≥ 2 points within 72 h of admission. Among 108 recruited patients, there were 35 of stroke mimics, 6 of transient ischemic attack and 67 of acute ischemic stroke. Salivary conductivity was significantly decreased after hydration in all patients (9008 versus 8118 µs/cm, p = 0.030). Among patients with acute ischemic stroke, the responsive group, showed a higher rate of early neurological improvement within 3 days compared to the non-responsive group (37% versus 10%, p = 0.009). In a multivariate logistic regression model, a decrease in salivary conductivity of 20% or more was found to be an independent factor associated with early neurological improvement (odds ratio 5.42, 95% confidence interval 1.31-22.5, p = 0.020). Real-time salivary conductivity might be a potential indicator of hydration status of the patient with acute ischemic stroke.

Predictors of clinical deterioration during hospitalization following acute ischemic stroke.

BACKGROUND/AIMS: A number of risk factors for early worsening of neurological symptoms have been identified. We aimed to evaluate the influence of hemorheologic, biochemical, and metabolic factors on neurological deterioration during hospitalization following acute ischemic stroke and develop a model of neurological deterioration. METHODS: Worsening of stroke was defined as a deleterious increase in NIH Stroke Scale (NIHSS) score of ≥4 points during hospitalization. We performed multivariate logistic regression analysis and constructed a prediction model based on chart data of 2,398 patients admitted at five medical centers; 203 of the patients had worsening of stroke and 2,186 had not. RESULTS: The results of multivariate logistic regression analysis showed that hemoglobin (odds ratio: 0.529) and albumin (odds ratio: 0.024) were significantly associated with stroke deterioration, as were the modified Rankin Scale on emergency department admission (odds ratio: 4.956) and length of hospitalization (odds ratio: 1.201). After adjusting for age, gender and NIHSS on emergency department admission, only hemoglobin (odds ratio: 0.894, 95% confidence interval: 0.814-0.981, p = 0.018) was associated with worsening. CONCLUSION: Hemoglobin and albumin were found to be risk factors for persistent neurological deterioration during hospitalization following acute ischemic stroke, suggesting that blood viscosity may be related to neurological deterioration.

PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging.

INTRODUCTION: Dual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase subtilisin-kexin type 9 and effectively lower low-density lipoprotein cholesterol levels with less side effects than statins. We hypothesise that alirocumab treatment in addition to statin therapy could stabilise intracranial plaque and reduce arterial stenosis. METHODS AND ANALYSIS: In this prospective, randomised, open-label, blinded end-point study, we will use high-resolution vessel-wall MRI to evaluate the efficacy and safety of alirocumab in patients who had an acute ischaemic stroke from ICAS. We will recruit 66 patients who had an acute ischaemic stroke within 7 days of symptom onset, who had symptomatic intracranial artery stenosis (>30%) at the middle cerebral artery, basilar artery or intracranial internal carotid artery. Among them, 22 patients will be randomised to the intervention group to receive treatment with 75 mg alirocumab subcutaneously every 2 weeks for a total of 26 weeks, while those in the control group will not. All patients in both groups will receive antiplatelet agents and high-intensity statins, including 20 mg rosuvastatin or 40-80 mg atorvastatin or at the maximum tolerated dose. All of them will undergo MRI at recruitment and after 26 weeks. The primary outcomes are changes in intracranial atherosclerotic plaques in the MRI before and after 6 months treatment. This trial is being conducted at Chang Gung Memorial Hospital at Chiayi, Taiwan. ETHICS AND DISSEMINATION: This trial has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (approval no. 202 002 482A3). Written informed consent will be obtained from all research participants. Study results will be published as peer-reviewed articles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, Identifier: NCT05001984; Pre-results.

Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study.

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.

Effects of Early Rehydration on Brain Perfusion and Infarct Core after Middle Cerebral Artery Occlusion in Rats.

Imaging evidence for the effect of rehydration on cerebral perfusion and brain ischemia has never been proposed in the literature. This study aimed to test the hypothesis that early rehydration treatment can improve cerebral perfusion and decrease infarct volume, consequently reducing mortality of dehydrated stroke animals. METHODS: Thirty dehydrated experimental rats were randomly assigned to either a rehydration or control group after middle cerebral artery occlusion (MCAO). Diffusion-weighted imaging and dynamic contrast enhancement perfusion imaging were performed at 30 min and 6 h after MCAO using a 9.4T MR imaging scanner to measure the infarct volume and brain perfusion. RESULTS: The survival rates after the first MRI scan were 91.7% for the rehydration group and 58.3% for the control group (p = 0.059). The survival rates after the second MRI scan were 66.7% for the rehydration group, and 8.3% of the control group survived (p = 0.003). The infarct volume of the rehydration group was significantly smaller than control group at 30 min after MCAO (p = 0.007). The delay time and time to maximum were significantly shorter in the rehydration group at 30 min (p = 0.004 and 0.035, respectively). CONCLUSIONS: The findings suggest that early rehydration therapy can decrease the infarct volume, shorten the delay time of cerebral perfusion, and increase survival of dehydrated ischemic-stroke rats. This preliminary study provided imaging evidence that more intensive early hydration therapies and reperfusion strategies may be necessary for acute stroke patients with dehydrated status.

Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison.

INTRODUCTION: Branch atheromatous disease (BAD) contributes to small-vessel occlusion in cases of occlusion or stenosis of large calibre penetrating arteries, and it is associated with a higher possibility of early neurological deterioration (END) and recurrent stroke in acute ischaemic stroke. As the pathology of BAD is due to atherosclerosis, we postulate that early intensive medical treatment with dual antiplatelet therapy (DAPT) and high-intensity statins may prevent END and recurrent stroke in acute small subcortical infarction caused by BAD. METHODS AND ANALYSIS: In this prospective, single-centre, open-label, non-randomised, single-arm study using a historical control, we will compare early DAPT and high-intensity statin treatment with a historical control group of patients with BAD who were treated with single antiplatelet therapy without high-intensity statin treatment. Patients will be eligible for enrolment if they are admitted for acute ischaemic stroke within 24 hours, have a National Institutes of Health Stroke Scale (NIHSS) score of 1-8 and are diagnosed with BAD by MRI. Patients will take aspirin, clopidogrel and high-intensity statins (atorvastatin or rosuvastatin) within 24 hours of stroke onset, followed by aspirin or clopidogrel alone from day 22. The primary endpoint is the percentage of patients who develop END within 7 days of stroke onset (defined as an increase in the NIHSS score ≥2 points) and recurrent stroke within 30 days. The total sample sizes will be 138 for the intervention group and 277 for the control group. A historical control group will be drawn from previous prospective observation studies. ETHICS AND DISSEMINATION: The protocol of this study has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (202001386A3). All participants will have to sign and date an informed consent form. The findings arising from this study will be disseminated in peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT04824911.