Subacute Phase Of Ischemic Stroke Research Articles

Dynamic susceptibility contrast-enhanced MRI with USPIO in evaluating angiogenesis of the peri-infarction zones in subacute ischemic stroke in a permanent middle cerebral artery occlusion rat model.

Dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) can reflect the angiogenesis of ischemic stroke. To investigate the value of DSC-MRI with ultrasmall superparamagnetic particles of iron oxides (USPIO) in evaluating angiogenesis in the peri-infarction zones in subacute ischemic stroke in a permanent middle cerebral artery occlusion (pMCAO) rat model. A total of 21 Sprague-Dawley rats were randomly divided into the pMCAO and sham operation groups. Every rat in each group underwent DSC-MRI with USPIO at 3, 5, and 7 days. DSC-MRI parameters of the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), relative mean transit time (rMTT), and relative time to peak (rTTP) were measured, calculated, and compared among the different times. Sequential correlations were analyzed among the histopathological indexes with the microvascular density (MVD) and percentage of vascular area (%VA), the serum factors with vascular endothelial growth factor (VEGF), vascular cell adhesion molecule 1 (VCAM-1), and perfusion parameters, respectively. The rCBV and rCBF in the peri-infarction area of pMCAO rats were significantly higher on day 7 than on day 3, whereas no significant changes in rMTT and rTTP were observed at 3, 5, and 7 days. Significantly positive correlations were found between rCBV and MVD, %VA, VEGF, VCAM-1, between rCBF and MVD, %VA, VEGF, and VCAM-1 at 3, 5, and 7 days in the pMCAO group. The rCBV and rCBF deriving from USPIO-DSC may be potentially useful for evaluating the angiogenesis of the peri-infarction zones in the subacute phase of ischemic stroke.

Neuroprotection of Transcranial Cortical and Peripheral Somatosensory Electrical Stimulation by Modulating a Common Neuronal Death Pathway in Mice with Ischemic Stroke.

Therapeutic electrical stimulation, such as transcranial cortical stimulation and peripheral somatosensory stimulation, is used to improve motor function in patients with stroke. We hypothesized that these stimulations exert neuroprotective effects during the subacute phase of ischemic stroke by regulating novel common signaling pathways. Male C57BL/6J mouse models of ischemic stroke were treated with high-definition (HD)-transcranial alternating current stimulation (tACS; 20 Hz, 89.1 A/mm2), HD-transcranial direct current stimulation (tDCS; intensity, 55 A/mm2; charge density, 66,000 C/m2), or electroacupuncture (EA, 2 Hz, 1 mA) in the early stages of stroke. The therapeutic effects were assessed using behavioral motor function tests. The underlying mechanisms were determined using transcriptomic and other biomedical analyses. All therapeutic electrical tools alleviated the motor dysfunction caused by ischemic stroke insults. We focused on electrically stimulating common genes involved in apoptosis and cell death using transcriptome analysis and chose 11 of the most potent targets (Trem2, S100a9, Lgals3, Tlr4, Myd88, NF-kB, STAT1, IL-6, IL-1β, TNF-α, and Iba1). Subsequent investigations revealed that electrical stimulation modulated inflammatory cytokines, including IL-1β and TNF-α, by regulating STAT1 and NF-kB activation, especially in amoeboid microglia; moreover, electrical stimulation enhanced neuronal survival by activating neurotrophic factors, including BDNF and FGF9. Therapeutic electrical stimulation applied to the transcranial cortical- or periphery-nerve level to promote functional recovery may improve neuroprotection by modulating a common neuronal death pathway and upregulating neurotrophic factors. Therefore, combining transcranial cortical and peripheral somatosensory stimulation may exert a synergistic neuroprotective effect, further enhancing the beneficial effects on motor deficits in patients with ischemic stroke.

PERIPHERAL ARTERIAL STIFFNESS PREDICTS INDEPENDENTLY FUNCTIONAL OUTCOME AFTER ISCHEMIC STROKE

Objective: Aortic stiffness is a strong predictor of morbidity in various clinical conditions, including ischemic stroke. However, the prognostic significance of the peripheral arterial stiffness, defined as radial -carotid pulse wave velocity - for functional outcome in ischemic stroke remains unknown. Design and method: We enrolled 189 patients (126 males, age 62.9±11.9 years, mean±SD) with acute ischemic stroke (NIHSS score at admission 6.4±5.1 points). Radial-carotid pulse wave velocity (CR PWV), peripheral blood pressure (BP) and heart rate (HR) were measured (SphygmoCor®) within several (6±2) days after stroke onset. Functional outcome was evaluated 90 days after stroke using the modified Rankin Scale (mRS) with an mRS score of 0 to 1 considered as an excellent outcome. Results: In univariate analysis, age, severity of stroke, heart rate, previous stroke, predicted stroke functional outcome. By contrast, CR PWV had no significant predictive value for stroke outcome (8.91±1.66 vs 8.56±1.50 m/s; p=0.14). In a multivariate analysis, the predictive value of CR PWV was significantly associated with functional outcome (OR, 1.34; 95% CI, 1.77–1.01; p=0.04) after adjustment for covariates, with higher values of CR PWV being associated with better prognosis. Conclusions: We found that the CR PWV in patients in the subacute phase of ischemic stroke is associated with functional outcome independently of traditional neurologic and hemodynamic factors. This PWV index might be useful in clinical practice, including therapeutic decisions, but needs broader studies in patient populations of stroke subtypes.

Measurement of non-invasive cardiac output during cycling exercise in ischemic stroke inpatients: A pilot study.

Cardiac dysfunction accompanies acute ischemic stroke and affects the effective implementation of early rehabilitation interventions. There is a lack of reference hemodynamic data on cardiac function in the subacute phase of ischemic stroke. In this study, we aimed to identify appropriate cardiac parameters for exercise training utilizing a pilot study. We used a transthoracic electrical bioimpedance non-invasive cardiac output measurement (NICOM) device to monitor cardiac function in real time for two groups [i.e., subacute ischemic stroke inpatients group (n= 10) and healthy control group (n= 11)] using a cycling exercise experiment. The parameters of both groups were compared to highlight the cardiac dysfunction in the subacute phase in patients with ischemic stroke. We considered stroke volume index (SVI) and systemic vascular resistance index (SVRi) as the primary outcomes, and there was significant intragroup difference (stroke group: P< 0.001; control group: P< 0.001, using one-way ANOVA) and significant intergroup difference at each individual time segment (P< 0.01, using independent t-test). Among the secondary outcomes, i.e., cardiac index (CI), ejection fraction (EF), end-diastolic volume (EDV), and cardiac contraction index (CTI), we found significant intergroup differences in CI, EF, and CTI scores (P< 0.01, using independent t-test). Significant interaction with respect to time and group were seen only in the SVRi and CI scores (P< 0.01, using two-way ANOVA). There was no significant inter- or intra-group differences in EDV scores. SVRI, SVI, and CI values highlight cardiac dysfunction in stroke patients the most. At the same time, these parameters suggest that cardiac dysfunction in stroke patients may be closely related to the increased peripheral vascular resistance caused by infarction and the limitation of myocardial systolic function.

Flow-augmentation STA-MCA bypass for acute and subacute ischemic stroke due to internal carotid artery occlusion and the role of advanced neuroimaging with hemodynamic and flow-measurement in the decision-making: preliminary data.

A major clinical challenge is the adequate identification of patients with acute (<1 week) and subacute (1-6 weeks) ischemic stroke due to internal carotid artery (ICA) occlusion who could benefit from a surgical revascularization after a failure of endovascular and/or medical treatment. Recently, two novel quantitative imaging modalities have been introduced: (I) quantitative magnetic resonance angiography (qMRA) with non-invasive optimal vessel analysis (NOVA) for quantification of blood flow in major cerebral arteries (in mL/min), and (II) blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess cerebrovascular reactivity (CVR). The aim of this study is to present our cohort of patients who underwent surgical revascularization in the acute and subacute phase of ischemic stroke as well as to demonstrate the importance of hemodynamic and flow assessment for the decision-making regarding surgical revascularization in patients with acute and subacute stroke and ICA-occlusion. Symptomatic patients with acute and subacute ischemic stroke because of persistent ICA-occlusion despite optimal medical/endovascular recanalization therapy who were treated at the Neuroscience Clinical Center of the University Hospital Zurich underwent both BOLD-CVR and qMRA-NOVA to study the hemodynamic and collateral vessel status. Patients selected for surgical revascularization according to our previously published flowchart were included in this prospective cohort study. Repeated NOVA and BOLD-CVR investigations were done after bypass surgery as follow up as well as clinical follow up. Continuous BOLD-CVR and qMRA-NOVA variables were compared using paired Student t-test. Between May 2019 and September 2022, superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery was performed in 12 patients with acute and subacute stroke because of ICA-occlusion despite of optimal endovascular and/or medical treatment prior to the surgery. Impaired BOLD-CVR in the occluded vascular territory [MCA territory: ipsilateral vs. contralateral: -0.03±0.07 vs. 0.11±0.07 %BOLD/mmHgCO2, P<0.001] as well as reduced hemispheric flow with qMRA-NOVA (ipsilateral vs. contralateral: 228.00±54.62 vs. 384.50±70.99 mL/min, P=0.01) were measured indicating insufficient collateralization. Post-operative qMRA-NOVA showed improved hemispheric flow (via bypass) (pre-bypass vs. post-bypass: 236.60±76.45 vs. 334.20±131.33 mL/min, P=0.02) and the 3-month-follow-up with BOLD-CVR showed improved cerebral hemodynamics (MCA territory: pre-bypass vs. post-bypass: -0.01±0.05 vs. 0.06±0.03 %BOLD/mmHgCO2, P=0.02) in all patients studied. Quantitative assessment with BOLD-CVR and qMRA-NOVA allows us to evaluate the pre- and post-operative cerebral hemodynamics and collateral vessel status in patients with acute/subacute stroke due to ICA occlusion who may benefit from surgical revascularization after failure of endovascular/medical treatment.

DAYTIME SUPINE BLOOD PRESSURE NORMALIZED BY 24-HOUR VALUES INDEPENDENTLY PREDICTS FUNCTIONAL OUTCOME AFTER ISCHEMIC STROKE

Objective: Blood pressure (BP) after ischemic stroke (IS) may follow various patterns. Post-event acute BP alterations mirror both stroke and patient characteristics, and resolve over time, yet their clinical significance is low or uncertain. Whether individual BP variations, based on a single standardized measurement normalized by a background BP course, have a distinct significance for stroke outcome remains unknown. We hypothesized that the BP difference index (BPD) between daytime supine resting and a series of surrounding BP values (daytime, 24-hour (24h)) in the subacute phase of IS is associated with functional outcome. Design and method: we included 131 IS patients [age 60.8 ± 12.5 years, median (NIHSS) score 5 (3-8)]. Office BP measurements and continuous 24-hour BP monitoring were performed on day 7 after stroke onset. The daytime period was defined as the interval from 6 a.m. to 10 p.m. Functional outcome was evaluated 90 days after stroke using the modified Rankin Scale (mRS) with an mRS score of 3 to 6 (dependency or death) considered as a poor outcome. Results: In a univariate analysis, high BPD was significantly associated with a poor stroke outcome (p = 0.001, 0.003, and 0.002 for systolic, diastolic, and mean BP, respectively, irrespective of the normalization subperiod (daytime, 24h). In a multivariate analysis, the predictive value of BPD remained significant only for systolic BP [SBP] normalized by daytime or 24h mean (OR, 1.06; 95% CI, 1.01-1.11; p = 0.02) after adjustment for covariates. Moreover, the relationship was stronger in a subgroup of patients able to walk independently (mRS 0-2) on day 7 after stroke onset (adjusted OR, 1.08; 95% CI, 1.01-1.17; p = 0.049 for SBP normalized by daytime or adjusted OR, 1.09; 95% CI, 1.01-1.18; p = 0.03 for SBP normalized by 24h mean). Conclusions: We found that the higher difference between supine resting and daytime or diurnal mean BP in patients in the subacute phase of ischemic stroke is independently associated with a poor outcome. This BP index might be useful in clinical practice, including therapeutic decisions, but needs broader studies in patient populations of stroke subtypes.

The frequency and determinants of executive dysfunction among patients with subacute phase of ischemic stroke in West Nusa Tenggara, Indonesia

Background: Executive dysfunction is a common form of intellectual weakening that interferes with the functional activity of the stroke survivors. Detection of executive dysfunction in the subacute segment of ischemic stroke allows the patients to receive appropriate interventions for optimal clinical outcomes. This study aims to investigate the frequency and determinants of executive dysfunction among subacute ischemic stroke patients in West Nusa Tenggara. Methods: This study involved 192 subjects divided into two groups: ischemic stroke (n=96) and control groups (n=96). Categorical data collected from both ischemic stroke and control subjects were age, gender, education level, occupation, hypertension, diabetes mellitus, Trail Making Test Part B, verbal fluency test, backward digit span scores and executive function status. Besides the data previously mentioned, clinical data that were also collected in ischemic stroke subjects was infarct size. The significant difference in the frequency of executive dysfunction between ischemic stroke and control groups was analyzed using chi-square test. The association between the determinants of executive dysfunction and the frequency of this executive dysfunction was analyzed using logistic regression. Results: This study discovered that the frequency of executive dysfunction among subjects with subacute phase of ischemic stroke was 52.1% and it was significantly higher compared with controls (p&lt;0.0001). Further, lower education level was the only determinant significantly correlated with the increased risk of executive dysfunction in the subjects (Odds ratio [OR] =3.47; 95% confidence interval [CI] = 1.47 – 10.26). Conclusion: There was high frequency of subacute ischemic stroke-associated executive dysfunction associated with lower education level.

Adherence to positive airway pressure therapy initiated in the early subacute phase of ischemic stroke: a PRESS study follow-up.

BackgroundSleep-disordered breathing (SDB) is frequent in stroke patients and negatively affects stroke outcomes. Positive airway pressure (PAP) is the standard first-line treatment for patients with moderate-to-severe SDB. Despite a strong link between PAP adherence and therapeutic response, rates of post-stroke PAP adherence remain underexplored. Our study aimed to determine PAP adherence in patients undergoing comprehensive sleep apnea assessment and in-lab PAP titration in the early subacute phase of stroke.MethodsIn-hospital screening pulse oximetry was performed in consecutive patients with imaging-confirmed acute ischemic stroke. Subjects with desaturation index ≥ 15.3/h were selected as PAP candidates, and polysomnography was recommended. In a sleep laboratory setting, subjects underwent a diagnostic night followed by a titration night, and PAP therapy was initiated in subjects with apnea–hypopnea index ≥ 15/h. Adherence to PAP therapy was assessed at a 6-month follow-up visit.ResultsOf 225 consecutive patients with acute ischemic stroke, 116 were PAP candidates and 52 were able to undergo polysomnography. PAP therapy was initiated in 35 subjects. At a 6-month follow-up visit, out of 34 stroke survivors, PAP adherence (PAP use of > 4 h per night) was present in 47%. Except for the significantly lower minimal nocturnal O2 saturation determined from the polysomnography (74.6 ± 11.7% vs. 81.8 ± 5.2%, p = 0.025), no other significant difference in characteristics of the groups with PAP adherence and PAP non-adherence was found.ConclusionsLess than half of the stroke subjects remained adherent to PAP therapy at 6 months post-PAP initiation. Special attention to support adaptation and adherence to PAP treatment is needed in this group of patients.

The effect of bi-hemispheric transcranial direct current stimulation on verbal function in Broca's aphasia

Aphasia is one of the most common deficits occurring after stroke that remains, at least in part, even after speech therapy and medication treatment. Non-invasive direct current transcranial stimulation (tDCS) is used to improve brain function by induction of neural plasticity. This study investigated the effect of bi-hemispheric tDCS on verbal function in patients with stroke-induced Broca's aphasia. Thirty patients with Broca's aphasia due to ischemic stroke, referred to an academic hospital in Guilan Province, Iran, in 2019-20, were studied. Patients were divided into two groups receiving seven sessions of either active or sham tDCS. The tDCS sessions began 10–20 days after stroke onset. The severity of aphasia before and after the intervention and a 3-month follow-up were assessed by the Persian version of the Western Battery-1 test (P-WAB-1). T-test, ANOVA, and Repeated Measurement were used for data analyses. The mean P-WAB-1 score was significantly higher in the intervention group both early after tDCS (P ≤ 0.0001) and on the 3-months follow-up (P ≤ 0001). Linear regression analysis indicated that tDCS had a positive effect on verbal performance scores independent of age, sex, and lesion volume (Regression coefficient = −33.3). Bi-hemispheric tDCS effectively improves verbal function in Broca's aphasia in the sub-acute phase of ischemic stroke.

Self-assembling Molecular Medicine for the Subacute Phase of Ischemic Stroke

Ischemic stroke leads to acute neuron death and forms an injured core, triggering delayed cell death at the penumbra. The impaired brain functions after ischemic stroke are hardly recovered because of the limited regenerative properties. However, recent rodent intervention studies manipulating the extracellular environments at the subacute phase shed new light on the regenerative potency of the injured brain. This review introduces the rational design of artificial extracellular matrix (ECM) mimics using supramolecular peptidic scaffolds, which self-assemble via non-covalent bonds and form hydrogels. The facile customizability of the peptide structures allows tuning the hydrogels' physical and biochemical properties, such as charge states, hydrophobicity, cell adhesiveness, stiffness, and stimuli responses. Supramolecular peptidic materials can create safer and more economical drugs than polymer materials and cell transplantation. We also discuss the importance of activating developmental programs for the recovery at the subacute phase of ischemic stroke. Self-assembling molecular medicine mimicking the ECMs and activating developmental programs may stand as a new drug modality of regenerative medicine in various tissues.

ARTERIAL STIFFNESS GRADIENT PREDICTS INDEPENDENTLY FUNCTIONAL OUTCOME AFTER ISCHEMIC STROKE

Objective: Arterial stiffness is a strong predictor of morbidity in various clinical conditions, including ischemic stroke. However, the prognostic significance of the newly emerged aortic–brachial arterial stiffness gradient, defined as carotid–femoral/radial -carotid pulse wave velocity (PWV ratio) for functional outcome in ischemic stroke remains unknown. Design and method: We enrolled 144 patients (114 males, age 63.1 ± 12.4 years, mean ± SD) with acute ischemic stroke (NIHSS score at admission 6.6 ± 5.3 points). Carotid-femoral pulse wave velocity (PWV), radial –carotid PWV and peripheral blood pressure (BP) were measured (SphygmoCorâ) within several (6 ± 2) days after stroke onset. Functional outcome was evaluated 90 days after stroke using the modified Rankin Scale (mRS) with an mRS score of 3 to 6 (dependency or death) considered as a poor outcome. Results: PWV ratio was higher in patients with a poor stroke outcome than in patients of the reference group (1.34 ± 0.58 vs 1.17 ± 0.30; p = 0.017). In a multivariate analysis, the predictive value of PWV ratio remained significant (OR, 3.62; 95% CI, 1.04–12.75; p = 0.044) after adjustment for covariates. In contrast, CF PWV had no significant predictive value for stroke poor outcome. Conclusions: We found that the higher PWV ratio in patients in the subacute phase of ischemic stroke is independently associated with a poor outcome. This PWV index might be useful in clinical practice, including therapeutic decisions, but needs broader studies in patient populations of stroke subtypes.

Glial cell line derived neurotrophic factor in brain repair after focal ischemic stroke.

Glial cell line derived neurotrophic factor in brain repair after focal ischemic stroke.

Characteristics of Cognitive Status in Sub-Population of Sub-Acute Stage of Ischemic Stroke Patients in West Nusa Tenggara, Indonesia

Cognitive decline is a significant complication that affects most stroke survivors. Early detection of cognitive decline in ischemic stroke patients and identification of risk factors improves their clinical outcomes. This study aimed to determine the characteristics of cognitive status in the sub-acute phase of ischemic stroke. A cross-sectional study was conducted on 89 sub-acute ischemic stroke patients in three hospitals in West Nusa Tenggara recruited consecutively from August 2019 to April 2020. The data collected were demographic and clinical characteristics, cognitive status, and functional outcome. The association between clinical and demographic characteristics and cognitive decline was analyzed using logistic regression. In addition, the relationship between cognitive status and functional outcomes of these patients was examined using the chi-square test. This study revealed that the prevalence of cognitive decline in these subjects was 71.9%. Multiple logistic regression showed that age was the only characteristic associated with cognitive decline in the subjects (OR = 5.12,95% CI = 1.08-24.28). Furthermore, the frequency of cognitive decline in these subjects was significantly associated with functional outcomes (p-value =0.014). Thus, there was a high prevalence of cognitive decline in sub-acute ischemic stroke patients associated with increasing age and poor functional outcomes.

Magnetic resonance imaging-based changes in vascular morphology and cerebral perfusion in subacute ischemic stroke

MRI-based vessel size imaging (VSI) allows for in-vivo assessment of cerebral microvasculature and perfusion. This exploratory analysis of vessel size (VS) and density (Q; both assessed via VSI) in the subacute phase of ischemic stroke involved sixty-two patients from the BAPTISe cohort (‘Biomarkers And Perfusion--Training-Induced changes after Stroke’) nested within a randomized controlled trial (intervention: 4-week training vs. relaxation). Relative VS, Q, cerebral blood volume (rCBV) and –flow (rCBF) were calculated for: ischemic lesion, perilesional tissue, and region corresponding to ischemic lesion on the contralateral side (mirrored lesion). Linear mixed-models detected significantly increased rVS and decreased rQ within the ischemic lesion compared to the mirrored lesion (coefficient[standard error]: 0.2[0.08] p = 0.03 and −1.0[0.3] p = 0.02, respectively); lesion rCBF and rCBV were also significantly reduced. Mixed-models did not identify time-to-MRI, nor training as modifying factors in terms of rVS or rQ up to two months post-stroke. Larger lesion VS was associated with larger lesion volumes (β 34, 95%CI 6.2–62; p = 0.02) and higher baseline NIHSS (β 3.0, 95%CI 0.49–5.3;p = 0.02), but was not predictive of six-month outcome. In summary, VSI can assess the cerebral microvasculature and tissue perfusion in the subacute phases of ischemic stroke, and may carry relevant prognostic value in terms of lesion volume and stroke severity.

Clinical correlates of social cognition after an ischemic stroke: preliminary findings.

ABSTRACT.The co-occurrence of post-stroke behavioral disorders and cognitive impairment has been extensively investigated. However, studies usually do not include social cognition among the assessed cognitive domains.Objective: To investigate the potential association between facial emotion recognition, a measure of social cognition, and behavioral and cognitive symptoms in the subacute phase of ischemic stroke.Methods: Patients admitted to a Stroke Unit with ischemic stroke were followed up to 60 days. At this time point, they were evaluated with the following tools: Mini-Mental State Examination (MMSE); Frontal Assessment Battery (FAB); Visual Memory Test of the Brief Cognitive Battery (VMT); Phonemic Verbal Fluency (F-A-S Test); Digit Span; Facial Emotion Recognition Test (FERT) and Hospital Anxiety and Depression Scale (HADS). A control group composed of 21 healthy individuals also underwent the same evaluation.Results: Eighteen patients with ischemic stroke were enrolled in this study. They had similar age, sex and schooling years compared to controls. Depression symptoms and episodic memory deficits were significantly more frequent in patients compared to controls. The recognition of sadness expression positively correlated with the levels of anxiety and depression, while and the recognition of fear expression negatively correlated with depression in the stroke group.Conclusions: After an ischemic stroke, patients exhibit impairment in social cognition skills, specifically facial emotion recognition, in association with behavioral symptoms.

Spleen is not required for therapeutic effects of 4OH-GTS-21, a selective α7 nAChR agonist, in the sub-acute phase of ischemic stroke in rats

Acute ischemic stroke (AIS) causes both central and peripheral inflammation, while activation of α7 nicotinic acetylcholine receptors (nAChRs) provides both central and peripheral anti-inflammatory and anti-apoptotic effects. Here, we provide evidence that 4OH-GTS-21, a selective α7 agonist, produces its therapeutic effects via primarily central sites of action because 4OH-GTS-21 was found equally effective in splenectomized and non-spenectomized rats in the sub-acute phase of ischemic stroke (≤1 week). However, the spleen may boost the therapeutic efficacy of 4OH-GTS-21 in certain behavioral tasks as our data also indicated. In our tests, AIS was modeled by transient middle cerebral artery occlusion (tMCAO). Splenectomy was done 2 weeks before tMCAO. We determined that: 1) Daily 4OH-GTS-21 treatments for 7 days after tMCAO significantly reduced neurological deficits and brain injury in both splenectomized and non-spelenectomized rats demonstrating that the spleen is not required for therapeutic benefits of 4OH-GTS-21; 2) The effects of 4OH-GTS-21 in the adhesive sticker removal test were significantly weaker in splenectomized animals suggesting that the spleen boosts the efficacy of 4OH-GTS-21 in the first week after tMCAO; and 3) Ischemic brain injury was not significantly affected by splenectomy in both vehicle-treated and 4OH-GTS-21-treated animals. These data support the hypothesis that the therapeutic efficacy of sub-chronic (≤1 week) 4OH-GTS-21 primarily originates from central sites of action. These results validate brain availability as a critical factor for developing novel α7 ligands for AIS.

Effective Tools to Predict Depression in Acute and Subacute Phase of Ischemic Stroke.

Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke. Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke. The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.

Increased blood pressure variability during the subacute phase of ischemic stroke is associated with poor functional outcomes at 3 months

Thus far, it is well known that increased blood pressure variability may exacerbate stroke outcomes. Blood pressure in the acute phase would be influenced by both reactive hypertension to stroke and intrinsic blood pressure reactivity. Thus, we aimed to evaluate the association between blood pressure variability and outcomes at 3 months using ambulatory blood pressure monitoring in ischemic stroke patients in the subacute phase after reactive hypertension subsided. We retrospectively examined 626 consecutive patients with acute ischemic stroke who underwent 24-hour ambulatory blood pressure monitoring during the subacute phase of stroke (median, 9 days from onset). The variability in blood pressure was evaluated by assessing the standard deviation and coefficient of variation of systolic and diastolic blood pressure. The primary outcome was functional status at 3 months. A poor outcome was defined as a modified Rankin scale score of 3 or more and a good outcome as 2 or less. We assessed the functional outcome at 3 months in 497 patients (79.4%). The mean systolic and diastolic blood pressure levels were not associated with functional outcome. The multivariable analysis revealed that increases in the standard deviations of systolic and diastolic blood pressure, coefficient of variation of diastolic blood pressure, and morning blood pressure surge were associated with poor outcome. Blood pressure variability during the subacute phase of ischemic stroke can be a useful prognostic indicator of poor functional outcome at 3 months in patients with acute ischemic stroke.

Abstract TP370: Increased Blood Pressure Variability During the Subacute Phase is Associated With 3-month Functional Poor Outcome in Patients With Acute Ischemic Stroke

Background: The increased blood pressure (BP) variability may influence on the stroke outcome. However, in the acute phase of large stroke, reactive hypertension would occur and sustain for a few days. Therefore, in this phase, it is difficult to understand a cause of BP variability whether it is from reactive hypertension or original blood pressure reactivity. Thus, we aimed to evaluate the association of BP variability using ambulatory blood pressure monitoring (ABPM) in the subacute phase of ischemic stroke, when restoration from reactive hypertension can be observed, with 3-month outcomes. Method: We retrospectively enrolled a consecutive series of 840 patients hospitalized for acute ischemic stroke (55.2% males, age: 76 ± 12 years) performing 24-hour ABPM during the subacute phase of stroke (median 9 days from onset). Variability in BP was evaluated with the standard deviation (SD) and with the coefficient of variation (CV) of systolic (SBP) and diastolic BP (DBP). The primary outcome was evaluated from the 3-month functional status: poor outcome as a modified Rankin Scale score of 3 or more and good outcome as 2 or less. Results: Patients with dipper, non-dipper and riser type were 11.4%, 50.5%, and 38.1%, respectively among the total enrolled cohort. Of these, 651 patients (77.5 %) were assessed for the functional outcomes at 3 months. The rates of patients with poor functional outcome were higher in patients with non-dipper or riser type than in the dipper type (47.7%, 57.1%, and 35.1%, respectively). The mean level of SBP and DBP were not associated with functional outcome. The variability of SBP and DBP was significantly associated with poor functional outcome in univariate analysis. After adjusting for age, sex and initial stroke severity, one increase of SD value (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.03 to 1.13, P&lt;0.001), CV value (OR 1.06, 95% CI 1.01 to 1.12, P = 0.02) for SBP, and SD value (OR 1.07, 95% CI 1.04 to 1.10, P&lt;0.001), CV value (OR 1.05, 95% CI 1.02 to 1.08, P&lt;0.001) for DBP were independently associated with poor outcome. Conclusion: The variability of BP in the subacute phase of ischemic stroke is expected to be a useful prognostic factor of a 3-month functional outcome.

“Code-Stroke” CT Perfusion; Challenges and Pitfalls

Regarding the most recent ischemic stroke treatment guideline, perfusion imaging has been recommended up to 24 hours after initial symptoms of brain infarction. Patients with a significant amount of salvageable peri-infarct ischemia and no contraindications benefit from delayed thrombolysis and intra-arterial thrombectomy. This approach causes increasingly more CT perfusion to be done in the subacute phase of ischemic stroke. CT perfusion findings in this "subacute phase" are slightly different from "hyper-acute" ischemic stroke. The interpreting radiologist must be confident in reporting the CT perfusion study in an urgent setting since these studies are under the umbrella of "code-stroke" and should be read in minutes. In addition, results of the CT perfusion have a critical effect on the patient's outcome and misinterpretation can be fatal in that underestimation of the salvageable ischemia excludes the patient from potential effective treatment. Underestimation of infarct volume may cause unnecessary thrombolysis/thrombectomy and potentially fatal intracranial hemorrhage. In this review, we are trying to explain the basic concept of "code-stroke" CT perfusion, typical findings, and pitfalls in a practical way.