Subacute Phase Of Ischemic Stroke Research Articles

L-arginine pathway metabolites can discriminate paroxysmal from permanent atrial fibrillation in acute ischemic stroke.

Atrial fibrillation (AF) is the most common arrhythmia diagnosed in clinical practice. We aimed to measure the L-arginine pathway metabolites as well as their ratios in patients with different types of AF or sinus rhythm and to explore the relationship among the markers and clinical variables in the subacute phase of acute ischemic stroke (AIS). A total of 46 patients with AIS were prospectively enrolled. The patients were divided into three groups based on diagnosis of either sinus rhythm, paroxysmal or permanent AF. Plasma concentration of the L-arginine pathway metabolites were analyzed at post-stroke 24 hours in the three rhythm groups. Besides, clinical variables and laboratory data were recorded. Asymmetric dimetylarginine (ADMA) was significantly higher in patients with permanent AF compared to sinus rhythm (p<0.001). Both ADMA (p<0.001) and symmetric dimethylarginine (SDMA) (p<0.002) at 24 hours were significantly higher among patients with permanent AF compared to those with paroxysmal AF. The L-arginine/SDMA (p<0.031) ratios at 24 hours were significantly higher among patients with sinus rhythm compared to those with permanent AF. ROC analysis also revealed that plasma SDMA cut-off level over 0.639 μmol/L discriminated permanent AF from paroxysmal AF or sinus rhythm with a 90.9% sensitivity and 77.1% specificity. Neutrophil-lymphocyte ratio also showed significantly higher value in individuals with both paroxysmal and permanent AF (p=0.029). Plasma level of SDMA could discriminate permanent from paroxysmal AF in the subacute phase of ischemic stroke. In addition, an increased neutrophil-lymphocyte ratio may suggest inflammatory process in the evolution of atrial fibrillation.

Post-Stroke Depression.

Introduction:The depression is a common mental disorder, especially after a stroke, which further aggravates the recovery.Aim:To analyze depression within 48 hours and fifteen days after ischemic stroke in relation to gender and location (brain hemisphere and brain circulation).Methods:We analyzed 40 patients (65.3±10.3 years), half of them were women. Mean age of women was 66.35±7.31 years and men 64.2±12.68 years (p= 0.5). Ischemic stroke was verified by computed tomography. Levels of depression were measured with self-estimated Zung’s scale. On the tests, score of 50 and higher verified depression. Criteria made by Domasio were used to determine location of the IS.Results:Mean value on depression scale in acute phase of ischemic stroke was 46.85 ± 8.6 and in subacute phase 43.4 ± 8 (p =0.06). In 19 (47.5%) patients (55% of women, 40% of men; p=0.3) depression was found during the first and in 10 (25%) patients (35% of women, 15 % of men; p=0.06) during the second evaluation (p<0.019). Mean value on depression in acute phase of illness in women was 49.1 ± 7.38, as well as in men 44.6 ± 9.22 (p=0.088) and in subacute phase in women 45.25 ± 8.04, as well as in men 41.5 ± 7.75 (p=0.16). Concerning location of ischemic stroke, there were no significant differences in levels of depression.Conclusion:Number of patients with post-stroke depression is significantly lower in subacute phase of ischemic stroke. Although the number of depressive women and their depression scores are higher, gender differences are not statistically significant. There is no correlation between post-stroke depression and location of lesion in acute and subacute phase of illness.

Acupuncture efficacy on ischemic stroke recovery: multicenter randomized controlled trial in China.

Acupuncture is a frequently used complementary treatment for ischemic stroke in China but the evidence available from previous randomized trials is inconclusive. The objective of this study was to assess the efficacy and safety of acupuncture in a more robustly designed larger scale trial. This is a multicenter, single-blinded, randomized controlled trial. Eight hundred sixty-two hospitalized patients with limb paralysis between 3 to 10 days after ischemic stroke onset were allocated acupuncture plus standard care or standard care alone. The acupuncture was applied 5 times per week for 3 to 4 weeks. The primary outcomes were defined as follows: (1) death/disability according to Barthel index and (2) death/institutional care at 6 months. There was a tendency of fewer patients being dead or dependent in acupuncture group (80/385, 20.7%) than in control group (102/396, 25.8%) at 6 months (odds ratio, 0.75; 95% confidence interval, 0.54-1.05). The benefit was noted in subgroup receiving ≥10 sessions of acupuncture (odds ratio, 0.68; 95% confidence interval, 0.47-0.98). There was no statistical difference in death or institutional care between the 2 groups (odds ratio, 1.06; 95% confidence interval, 0.63-1.79). Severe adverse events occurred in 7.6% and 8.3% of patients in the 2 groups, respectively. Acupuncture seemed to be safe in the subacute phase of ischemic stroke. If the potential benefits observed are confirmed in future larger study, the health gain from wider use of the treatment could be substantial. URL: http://www.chictr.org/en/. Unique identifier: ChiCTR-TRC-11001353.

Concurrent use of granulocyte-colony stimulating factor with repetitive transcranial magnetic stimulation did not enhance recovery of function in the early subacute stroke in rats.

We investigated the additive effect of repetitive transcranial magnetic stimulation (rTMS) combined with granulocyte-colony stimulating factor (G-CSF) on functional outcome in the early subacute phase of stroke. Seven-week-old male rats were subjected to permanent middle cerebral artery occlusion (MCAo) and were divided into four groups: normal saline administration with sham rTMS (group 1, n = 15), G-CSF administration with sham rTMS (group 2, n = 15), G-CSF with 1 Hz rTMS (group 3, n = 14), and G-CSF with 20 Hz rTMS (group 4, n = 15). Animals received G-CSF or saline for 5 days from the day of MCAo and were concurrently treated with 20-min rTMS on their lesioned hemisphere for 2 weeks. Neurological functional score was worse in group 4 compared to that in group 2 on day 15. In Western blots conducted on day 25, phosphorylation of endothelial nitric oxide synthase was markedly lower in groups 2, 3, and 4 than that in group 1 in the ischemic border zone. PECAM-1 expression at ischemic core was lower in groups 4 than in group 2. Caspase-3 expression was markedly higher in groups 4 than in group 1, 2, 3 at ischemic core. Iba1 expression was higher in groups 4 than in group 1, 2 at ischemic core. G-CSF combined with rTMS administered in the early subacute phase of ischemic stroke may exert a hazardous effect on functional recovery, possibly due to impaired angiogenic mechanism, decreased cell survival, and increased inflammation.

Transcranial Magnetic Stimulation Combined with Speech and Language Training in Early Aphasia Rehabilitation: A Randomized Double-Blind Controlled Pilot Study

Background: Functional neuroimaging studies with poststroke aphasia patients have shown increased activation of the unaffected hemisphere, which hypothetically reflects a maladaptive strategy of brain reorganization. Objective: We investigated whether repetitive transcranial magnetic stimulation (rTMS) inhibiting the right-hemisphere homologue of Broca’s area improves language restitution if combined with speech/language therapy. Methods: Forty aphasic patients during the subacute phase of ischemic stroke were randomized to a 3-week aphasia rehabilitation protocol in combination with real or sham rTMS. Naming, repetition, and comprehension were assessed using the Boston Diagnostic Aphasia Examination at baseline, immediately after therapy, and 15 weeks after completing treatment. Results: Although language functions improved in both experimental and control groups after 3 weeks, only slight group differences in degree of recovery were revealed between patients receiving rTMS and control participants. Follow-up revealed that severely aphasic rTMS patients demonstrated significantly greater improvement than patients receiving sham stimulation in repetition. Conclusions: Inhibitory rTMS applied to the right frontal language homologue is not effective for all poststroke aphasia patients, although it might benefit selected patients.

Abstract TP61: Elevated CRP Between Day 1 And 7 and not Admission CRP Is An Independent Predictor For Outcome at 3 Months In Thrombolized Acute Stroke Patients

Background: The value of CRP in stroke patients undergoing thrombolysis, in the acute and subacute phase of ischemic stroke as a prognostic tool for outcome is unclear, since conflicting reports exist. Aim of our study was to explore the role of admission CRP and follow-up CRP between day 1 and 7, for outcome and mortality in stroke patients treated with rtPa. Methods: From March 1998 to 2011 all patients admitted to our hospital and undergoing thrombolysis for acute ischemic stroke were included into an open, prospective database. Stroke severity was assessed using the NIHSS. In all patients CRP levels was measured upon admission in the emergency room, after 24 hours from the acute event and in the following days. CT scan before treatment and routine brain CT scan 24-36 h after thrombolysis were performed. Symptomatic haemorrhage (sICH) was defined according to ECASS II criteria. Functional outcome was assed by mRS at three months and divided into independent (mRS0-2) and dependent (mRS 3-5). Results: In total, 1292 patients were registered in our database. About 70% of patients had an increase of CRP values in the first 7 days after admission. Infection occurred in 22% of patients and about 25% had a large brain infarction (&gt;1/3 of vessel territory). sICH occurred in 6.7% of patients. Follow-up CRP levels between day 1 and 7 were significantly associated with cardio embolic stroke (p=0.033), infarct size (p&lt;0.001), infection (p&lt;0.001), symptomatic haemorrhage (p&lt;0.001), independent (p&lt;0.001), dependent outcome (p&lt;0.001) and mortality (p&lt;0.001). CRP values between day 1 and 7 (OR 2.824 CI95%; 1.534 - 5.201, p=0.001), infarct size (OR 2.254; CI95% 1.480 - 3.432, p&lt;0.001), infection (OR1.752; CI95% 1.100 - 2.789, p=0.018) and NIHSS (OR 1.043; CI95% 1.016 - 1.069, p=0.001) were independent predictors for dependent outcome. Admission CRP values were not independently associated with outcome and mortality after multivariate logistic regression analysis. Conclusion: Together with know predictors like infarct size, NIHSS and infections, maximally elevated CRP levels within day 1 and 7 were strongly and independently associated with long-term outcome in thrombolyzed stroke patients after correction for baseline variables.

Effect of blood pressure on 3-month functional outcome in the subacute stage of ischemic stroke

We aimed to study various measures of blood pressure (BP) in the subacute phase of ischemic stroke to determine whether any of them predicted clinical outcome. In this retrospective observational study, a consecutive series of patients hospitalized for ischemic stroke within 48 hours of onset were enrolled. The subacute stage of stroke was defined as the time period from 72 hours of symptom onset to discharge or transfer. During this period, mean, maximum, maximum - minimum, SD, and coefficient of variation of systolic BP (SBP) and diastolic BP (DBP) were determined. A baseline severity-adjusted analysis was performed using each patient's 3-month modified Rankin Scale score as the primary outcome. Among a total of 2,271 patients, the median number of BP measurements was 34 per person and the median interval from onset to discharge was 8.7 days. Measures of variability of BP were associated with poor outcome. One SD increase of maximum - minimum (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12-1.42), SD (OR, 1.20; 95% CI, 1.07-1.34), or coefficient of variation (OR, 1.21; 95% CI, 1.09-1.35) for SBP, but not mean level of SBP (OR, 0.92; 95% CI, 0.79-1.07), was independently associated with poor outcome. Results were similar for DBP. This study shows that variability of BP, but not average BP in the subacute stage of ischemic stroke, is associated with functional outcome at 3 months after stroke onset.

Intrinsic Activated Microglia Map to the Peri-infarct Zone in the Subacute Phase of Ischemic Stroke

Microglial activation is an important component of the neuroinflammatory response to ischemic stroke. Experimental studies have outlined such patterns temporally and spatially. In vivo studies in stroke patients have relied on positron emission tomography and (R)-PK11195, a ligand that binds peripheral benzodiazepine binding sites. In this study we sought to establish temporal and spatial patterns of microglial activation in ischemic stroke with particular emphasis on a defined peri-infarct zone. Using this technique, we studied carotid territory ischemic stroke patients in 3 time windows up to 30 days after ictus. Controls were studied in a single session. [11C](R)-PK11195 injection was followed by 3-dimensional acquisition over 60 minutes. Cerebral blood volume (CBV) was measured afterward with the use of standard C15O paradigms. Analysis employed the reference tissue model in which ipsilateral cerebellum was used to generate parametric binding potential maps corrected for CBV. Data were coregistered to T1-based MRI. Using control data to identify 99% confidence limits, a region of interest analysis was applied to identify significant binding in core infarction, contralateral hemisphere, and within a defined peri-infarct zone. Four patients (mean age, 66 years) were imaged across 9 sessions. Four age-matched controls were studied. Within this model, ipsilateral cerebellum was validated as a reference tissue. With the use of control-derived confidence limits and correction for CBV, significant binding potential rises were identified beyond 72 hours and extending to 30 days in core infarction, contralateral hemisphere, and peri-infarct zone. In ischemic stroke patients, minimal activation of microglia is seen before 72 hours. Beyond this, binding potential rises in core infarction, peri-infarct zone, and contralateral hemisphere to 30 days. This may represent a therapeutic opportunity that extends beyond time windows traditionally reserved for neuroprotection.

Leakage of brain-originated proteins in peripheral blood: temporal profile and diagnostic value in early ischemic stroke

The clinical value of determination of CNS-specific proteins in peripheral blood at the acute phase of ischemic stroke is unclear. S-100 protein and neurone specific enolase were serially quantified in peripheral blood at the acute and subacute phase of ischemic stroke (hours 4, 8, 10, 24 and 72 after onset of symptoms). Whereas S-100 protein was detected in none of the matched control subjects, this protein was observed in 17/24 of the stroke patients. Patients with detectable S-100 protein had significantly larger infarctions. Cortical infarctions had already significantly increased S-100 concentrations at days 1 and 3 compared to subcortical or brainstem infarctions. Patients with volumes of brain lesion of >5 ccm exhibited significantly increased serum levels of S-100 at hours 10, 24 and 72 compared to those with lesion volumes of <5 ccm. At hours 10, 24 and 72, concentrations of S-100 correlated with scores of neurological outcome. Although kinetics of release of neurone specific enolase showed a similar pattern of release in blood, no significant association to outcome or extent of brain damage was observed. These results suggest that S-100 protein and not NSE may represent a useful serum marker of brain damage in acute stroke.

脳梗塞亜急性期の｀１２３´Ｉ‐ＩＭＰ ＳＰＥＣＴにみられる病巣高集積について

脳梗塞亜急性期の｀１２３´Ｉ‐ＩＭＰ ＳＰＥＣＴにみられる病巣高集積について