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Purpose: Infections are frequent complications in acute ischemic stroke and may be caused by an altered immune response influencing brain damage. We compared long-term immune responses in stroke patients with or without infections during the recovery period by performing a long-term profiling of clinically relevant inflammatory parameters from stroke onset until day 49. Materials and methods: Thirty-four stroke patients were retrospectively included and divided into two groups depending on infection status. Group 1 had no infections (N = 17) and group 2 had post-admission infection (N = 17). The patients were evaluated carefully for infections and evolution of the peripheral inflammatory response. Neutrophils, monocytes, lymphocytes, total leukocytes and C-reactive protein were evaluated in relation to the occurrence and development of infections. In both patient groups, an acute boost in neutrophils and monocytes were observed whereas the opposite was true for lymphocytes. Results: In Group 1, neutrophils and monocytes approached normal levels after 20–30 days, but remained elevated in Group 2. We found an increase in neutrophils (p = 0.01) and leukocytes (p < 0.01) as well as C-reactive protein (p < 0.01) among infected patients. Lymphocytes remained depressed in Group 2, while Group 1 slowly approached baseline levels. In both groups, CRP levels initially increased with a slow return to baseline levels. From day 0 to 49 after stroke, uninfected patients generally experienced a decline in leukocytes, neutrophils and monocytes (all p < 0.05), while no similar changes happened among infected patients. Conclusions: Our study provides an overview of general immune cell kinetics after stroke related to infection status. Immune cell numbers were severely disturbed for weeks after the insult, independent of infection status, although infected patients achieved the highest cell counts of neutrophils, leukocytes and for C-reactive protein. The sustained depress

Background and Purpose: The computed tomography angiography or contrast-enhanced computed tomography based spot sign has been proposed as a biomarker for identifying on-going hematoma expansion in patients with acute intracerebral hemorrhage. We investigated, if spot-sign positive participants benefit more from tranexamic acid versus placebo as compared to spot-sign negative participants. Methods: TICH-2 trial (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) was a randomized, placebo-controlled clinical trial recruiting acutely hospitalized participants with intracerebral hemorrhage within 8 hours after symptom onset. Local investigators randomized participants to 2 grams of intravenous tranexamic acid or matching placebo (1:1). All participants underwent computed tomography scan on admission and on day 2 (24±12 hours) after randomization. In this sub group analysis, we included all participants from the main trial population with imaging allowing adjudication of spot sign status. Results: Of the 2325 TICH-2 participants, 254 (10.9%) had imaging allowing for spot-sign adjudication. Of these participants, 64 (25.2%) were spot-sign positive. Median (interquartile range) time from symptom onset to administration of the intervention was 225.0 (169.0 to 310.0) minutes. The adjusted percent difference in absolute day-2 hematoma volume between participants allocated to tranexamic versus placebo was 3.7% (95% CI,-12.8% to 23.4%) for spot-sign positive and 1.7% (95% CI,-8.4% to 12.8%) for spot-sign negative participants (Pheterogenity=0.85). No difference was observed in significant hematoma progression (dichotomous composite outcome) between participants allocated to tranexamic versus placebo among spot-sign positive (odds ratio, 0.85 [95% CI, 0.29 to 2.46]) and negative (odds ratio, 0.77 [95% CI, 0.41 to 1.45]) participants (Pheterogenity=0.88). Conclusions: Data from the TICH-2 trial do not support that admission spot sign status

Background: Fatigue is a common and often debilitating stroke sequela, and it is important to accurately define and detect post-stroke fatigue. Often questionnaires are used but a case definition has been developed and proposed as a better tool. Objectives: The aim of the study was to determine validity and inter-rater agreement of the case definition of post-stroke fatigue, and to determine optimal cutoff scores for marked fatigue on the Multidimensional Fatigue Inventory-20 and the Fatigue Severity Scale-7 questionnaires. Methods: Stroke patients were interviewed with the structured interview schedule for the case definition and asked to complete the two questionnaires. To examine the inter-rater agreement of the case definition a second interviewer did another interview blinded to the result of the first interview. Results: Seventy patients were enrolled, 44% women. The median age was 74 years (interquartile range: 67–80) and the median time from stroke to interview was 8 days. The median Fatigue Severity Scale-7 score and the median Multidimensional Fatigue Inventory-20 (General Fatigue subscale) score were higher in the case definition positive than in the negative group (p <.001). The kappa value for the inter-rater agreement was 0.63. A cutoff score of 4.9 for the Fatigue Severity Scale-7 and a cutoff score of 12 on the Multidimensional Fatigue Inventory-20 were optimal to identify marked fatigue according to the case definition. Conclusions: The case definition was valid and had a substantial inter-rater agreement. A score ≥ 5 using the Fatigue Severity Scale-7 or a score ≥ 12 using the Multidimensional Fatigue Inventory-20 (General Fatigue subscale) may be used to detect potentially debilitating post-stroke fatigue in stroke survivors.

OBJECTIVE: Transoesophageal echocardiography (TEE) is the gold standard for the detection of cardiac emboli sources in ischaemic stroke patients, but new computed tomography (CT) scanners are able to visualize the heart. This pilot study aimed to compare findings on TEE with combined cardiovascular scan and cerebral CT angiography in cryptogenic ischaemic stroke patients.METHODS: This pilot study enrolled patients with cryptogenic ischaemic stroke who underwent a combined cardiovascular and cerebral CT angiography scan and a TEE examination, which were interpreted in a blinded manner.RESULTS: Twelve patients with cryptogenic ischaemic stroke were included (mean age 56 years). Of these, 10 patients underwent both a combined cardiovascular and cerebral CT angiography and a TEE examination. All cardiovascular CT scans were readable at sinus rhythm. None of the simultaneous cerebral angiograms were compromised. Thrombi were not detected in any patients. Patent foramen ovale was visualized in five patients by TEE, while cardiovascular CT only identified three. Cardiovascular CT revealed in addition an X-ray negative pulmonary metastasis in one patient, aortic coarctation in another and significant coronary stenosis in four patients.CONCLUSION: The sensitivity for detecting patent foramen ovale was considerably lower for cardiovascular CT than for TEE, however the cardiovascular CT revealed several other very important clinical findings.

Aims Prolonged cardiac monitoring after stroke is recommended though there is no consensus on optimal methods. Short-term ECG recordings with a "thumb-ECG" device have shown promising preliminary results regarding effectiveness and cost benefit. We aimed to examine the performance of thumb-ECG and five days' Holter monitoring in a prospective trial. A secondary endpoint was the inter-observer agreement of the thumb-ECG. Methods Patients older than 65 years with no history of atrial fibrillation who suffered an acute stroke or transient ischemic attack of unknown origin were prospectively included. Patients were monitored for atrial fibrillation with five days' Holter and concurrent 30 s thumb-ECG twice daily, the latter continuing for 30 days. Inter-observer agreement for the thumb-ECG was determined. Results One hundred patients were included and 95 patients were analyzed. Paroxysmal atrial fibrillation was diagnosed in 20 patients with the thumb-ECG recordings and 17 patients on the Holter monitoring. Only 10 were diagnosed with both methods. The difference between the detection rates of the two devices was not significant ( p = 0.63). The inter-observer agreement of the thumb-ECG had a kappa value of 0.65. Conclusion Thirty days' thumb-ECG recordings twice daily for 30 s detect a high proportion of paroxysmal atrial fibrillation in a stroke or transient ischemic attack cohort. The proportion was comparable to five days' Holter monitoring but the agreement between the two methods was poor and the trial was not powered to detect a minor difference between the devices. The inter-observer agreement for the thumb-ECG was substantial. www.clinicalTrials.gov UI: NCT02261766.

BACKGROUND AND PURPOSE: Poststroke fatigue is common and reduces quality of life. Current evidence for intervention is limited, and this is the first placebo-controlled trial to investigate treatment of poststroke fatigue with the wakefulness promoting drug modafinil.METHODS: The trial was randomized, double-blinded, and placebo-controlled. Patients were treated with 400-mg modafinil or placebo for 90 days. Assessments were done at inclusion, 30, 90, and 180 days. The primary end point was fatigue at 90 days measured by the Multidimensional Fatigue Inventory-20 general fatigue domain. Secondary end points included the Fatigue Severity Scale, the Montreal Cognitive Assessment, the modified Rankin Scale and the Stroke-specific quality of Life questionnaire. Adult patients with a recent stroke achieving a score of ≥12 on the Multidimensional Fatigue Inventory-20 general fatigue domain were consecutively included. Exclusion criteria were severe cognitive disabilities and contraindications for modafinil treatment.RESULTS: One thousand one hundred twenty-one patients with stroke were screened and 41 patients included, 21 received modafinil. The primary end point, the Multidimensional Fatigue Inventory-20 general fatigue score, did not differ between groups. Patients in the modafinil group obtained better scores on the Fatigue Severity Scale (P=0.02) and in some subscales of the stroke-specific quality of life questionnaire (0.001

OBJECTIVES: The objective of this study was to examine the effects of d-amphetamine (amph) upon recovery after embolic stroke in rats. METHODS: Ninety-three rats were embolized in the right middle cerebral artery and assigned to: (1) controls; (2) combination (acute amph and later amph-facilitated retraining); (3) late amph (later amph-facilitated retraining alone); and (4) acute amph (acute amph alone). Animals in the combination and in the acute amph groups received a high dose of amph immediately after embolization, while later amph-facilitated retraining in the combination and late amph groups was done by administering a low dose of amph on post-stroke days 2, 5, 8, and 11 followed by retraining in Montoya's Staircase Test. RESULTS: Rats receiving acute amph immediately after embolization achieved an 11% increase in median blood pressure (P<0.05). An investigation of performances with the ipsilateral paws during days 14-21 showed that the acute amph group performed better than the control group (P<0.02). Infarct volumes were lower among animals in the acute amph group than in both the combination and the late amph groups (P<0.05), while the controls did not differ from any group. DISCUSSION: In conclusion, results showed that the acute amph group performed the best, while the late amph and the combination groups performed the worst. Amphetamine treatment in acute stroke may be warranted due to reduced detrimental effects of hypotension and improved brain plasticity.

Udgivelsesdato: 2002-Jun, The therapeutic effect of insulin alone or insulin combined with 30 min delayed thrombolytic therapy was investigated in rats embolized in the right hemisphere with a fibrin clot made from autologous blood. Animals were killed seven days after embolization and the infarct volumes were measured in % of the affected hemisphere. Mortality was calculated as the number of animals dying spontaneously before the scheduled euthanasia. The median infarct volume in control animals (n = 12) was 24%. Insulin (3 IU kg(-1)) was given subcutaneously 15 min, 3 h, and 24 h after embolization (n = 12) and reduced median infarct volume to 11%. Human recombinant tissue plasminogen activator, 8 mg kg(-1), was infused intravenously during 45 min starting 30 min after embolization (n = 14), and the median infarct volume was 18% in this group. When the two treatments were combined, the median infarct volume was reduced to 11% (n = 14). The infarct volumes in the treatment groups were not significantly different from controls (p = 0.62, Kruskal Wallis test). Mortality rates increased from 0% among controls to 47% (p = 0.01) in the insulin alone and 38% (p = 0.02) in the combination therapy group. In conclusion, insulin treatment aiming at blood glucose levels around 2-4 mmol l(-1) was detrimental to clinical outcome causing significantly increased mortality.