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Aims To evaluate the extent of left atrial (LA) fibrosis in patients with a recent stroke without atrial fibrillation and controls without established cardiovascular disease. Methods and results This prospectively designed study used cardiac magnetic resonance to detect LA late gadolinium enhancement as a proxy for LA fibrosis. Between 2019 and 2021, we consecutively included 100 patients free of atrial fibrillation with recent ischaemic stroke ( Conclusion LA fibrosis was more extensive in patients with stroke than in age- and sex-matched controls. A similar extent of LA fibrosis was observed in patients with stroke of undetermined aetiology and stroke classified as attributable to large- or small-vessel disease. Our findings suggest that LA structural abnormality is more frequent in patients with stroke than in controls independent of aetiological classification.

Introduction Non-vitamin K-antagonist oral anticoagulants (NOAC) have become first choice oral anticoagulant (OAC) with decreasing use of vitamin K antagonists (VKA), partly due to lower risk of intracerebral hemorrhage (ICH). Aim: to identify trends in sale of OACs and relate them to trends in OAC-related ICH (OAC-ICH). Patients and methods Study was based on the population in the Capital Region of Denmark (1.8 million inhabitants). We identified all patients admitted with a non-traumatic OAC-ICH in 2010–2017 and ascertained diagnosis and drug use through medical charts. We used information available in the public domain on sale of defined daily doses (DDD) of OAC in the Capital Region of Denmark. Results 453 patients with OAC-ICH out of a total of 2877 ICH-events were identified. From 2010 to 2017 sale of NOAC rose from 0.1 to 11.8 DDD/1000 inhabitants/day (p Discussion In Denmark, the population on OACs has increased; resulting from increased use of NOACs. Parallel to this development, the proportion of OAC-ICH overall has increased based on an increasing trend in NOAC-related ICH. Conclusion Our findings document a need for further research on prevention and treatment of this complication.

IntroductionDespite workup for the aetiology of ischaemic stroke, about 25% of cases remain unexplained. Paroxysmal atrial fibrillation is typically suspected but often not detected. Even if atrial fibrillation (AF) is detected, the quantitative threshold of clinically relevant AF remains unclear. Emerging evidence suggests that left atrial (LA) functional and structural abnormalities may convey a risk of ischaemic stroke in which AF is only one of several features. These abnormalities have been termed ‘atrial cardiomyopathy’. This study uses cardiac magnetic resonance (CMR) to evaluate atrial cardiomyopathy among patients with stroke of undetermined aetiology compared with those with an attributable mechanism and controls without established cardiovascular disease.Methods and analysisThis cross-sectional and prospective cohort study included 100 patients with recent ischaemic stroke and 50 controls with no established cardiovascular disease. The study will assess LA structural and functional abnormalities with CMR. Inclusion began in March 2019, and follow-up is planned to be complete in January 2023. There are two scheduled follow-ups: (1) 18 months after individual inclusion, counting from the index diagnostic MRI of the brain, (2) end of study follow-up at 18 months after inclusion of the last patient, assessing the incidence of recurrent ischaemic stroke, AF and cardiovascular death. The primary endpoint is the extent of CMR-assessed atrial fibrosis in the LA at baseline. The study is powered to detect a difference of 6% fibrosis between stroke of undetermined aetiology and stroke of known mechanism with a SD of 9%, a significance level of 0.05, and power of 80%.Ethics and disseminationThis study has been approved by the Danish National Committee on Health Research Ethics (H-18055313). All participants in the study signed informed consent. Results from the study will be published in peer-reviewed journals regardless of the outcome.Trial registration numberNCT03830983.

Introduction and AimData remain limited on sex-differences in patients with oral anticoagulant (OAC)-related intracerebral hemorrhage (ICH). We aim to explore similarities and differences in risk factors, acute presentation, treatments, and outcome in men and women admitted with OAC-related ICH.MethodThis study was a retrospective observational study based on 401 consecutive patients with OAC-related ICH admitted within 24 h of symptom onset. The study was registered on osf.io. We performed logarithmic regression and cox-regression adjusting for age, hematoma volume, Charlson Comorbidity Index (CCI), and pre-stroke modified Ranking Scale (mRS). Gender and age were excluded from CHA2DS2-VASc and CCI was not adjusted for age.ResultsA total of 226 men and 175 women were identified. More men were pre-treated with vitamin K-antagonists (73.5% men vs. 60.6% women) and more women with non-vitamin K-antagonist oral anticoagulants (26.5% men vs. 39.4% women), p = 0.009. Women were older (mean age 81.9 vs. 76.9 years, p < 0.001). CHA2DS2-VASc and CCI were similar in men and women.Hematoma volumes (22.1 ml in men and 19.1 ml in women) and National Institute of Health Stroke Scale (NIHSS) scores (13 vs. 13) were not statistically different, while median Glasgow Coma Scale (GCS) was lower in women, (14 [8;15] vs. 14 [10;15] p = 0.003).Women's probability of receiving reversal agents was significantly lower (adjusted odds ratio [aOR] = 0.52, p = 0.007) but not for surgical clot removal (aOR = 0.56, p = 0.25). Women had higher odds of receiving do-not-resuscitate (DNR) orders within a week (aOR = 1.67, p = 0.04). There were no sex-differences in neurological deterioration (aOR = 1.48, p = 0.10), ability to walk at 3 months (aOR = 0.69, p = 0.21) or 1-year mortality (adjusted hazard ratio = 1.18, p = 0.27).ConclusionSignificant sex-differences were observed in age, risk factors, access to treatment, and DNRs while no significant differences were observed in comorbidity burden, stroke severity, or hematoma volume. Outcomes, such as adjusted mortality, ability to walk, and neurological deterioration, were comparable. This study supports the presence of sex-differences in risk factors and care but not in presentation and outcomes.

Early Neurological Deterioration (END) occur in up to 25% of patients with ischaemic stroke receiving stroke-unit-care and in 11-13.8% of patients treated with iv-tissue-Plasmniogen-Activator (iv-tPA). The aim of the study was to establish and compare the prevalence of END and symptomatic Intracranial Hemorrhage (sICH) in a prospectively designed registry of consecutive patients treated with iv-tPA to a historic cohort of iv-tPA eligible patients whom were hospitalized prior to implementation of iv-tPA-treatment but receiving otherwise comparable acute stroke care.Single center registry from a public Danish stroke-unit. Three-hundred-sixty-one unselected consecutive iv-tPA-treated patients admitted within 4.5 h from symptom-onset with symptoms of acute stroke and17 years of age. The iv-tPA-treated cohort was compared to a pre-tPA cohort of 246 iv-tPA-eligible patients who were admitted to the same stroke center from 1998 to 2001. Acute stroke care apart from iv-tPA was comparable. Outcome measures was assessed on admission and at 24 h; END as any increase in National Institute of Health Stroke Scale (NIHSS) and symptomatic Intracranial Hemorrhage (sICH) with use of CT-head-scan.END was observed in 27 (7.5%) of the 361 patients in the tPA-cohort and 43 (17.5%) of 246 in the pre-tPA-cohort, p 0.0001. Any ICH was detected in 23 (6.4%) and sICH in 3 (0.8%) of the iv-tPA-treated patients.END is significantly less frequent in acute stroke patients treated with iv-tPA. Deterioration due to ICH was rare and of limited severity in this population. END though remains a significant complication after stroke why more detailed knowledge on the various causes of END is needed to further improve patient outcome.

Objectives Perfusion through leptomeningeal collateral vessels is a likely pivotal factor in the outcome of stroke patients. We aimed to investigate the effect of collateral status on outcome in a cohort of unselected, consecutive stroke patients with middle cerebral artery occlusion undergoing reperfusion therapy. Materials and methods This retrospectively planned analysis was passed on prospectively collected data from 187 consecutive patients with middle cerebral artery occlusion admitted within 4.5 hours to one center and treated with intravenous thrombolysis alone (N = 126), mechanical thrombectomy alone (N = 5), or both (N = 56) from May 2009 to April 2014. Non-contrast CT (NCCT) and computed tomography angiography (CTA) were provided on admission and NCCT repeated at 24 hours. Collateral status was assessed based on the initial CTA. Hemorrhagic transformation was evaluated on the 24-hour NCCT and according to European Cooperative Acute Stroke Study (ECASS) criteria. Modified Rankin Scale score was assessed at 90 days, and mortality at 1 year. Results At 90 days, median (IQR) modified Rankin Scale score in patients with poor collateral status was 4 (3-6) compared to 2 (1-4) in patients with good collateral status (P

Objectives Door-Needle-times (DNT) of 20 min are feasible when Computer Tomography (CT) is used for first-line brain-imaging to assess stroke-patients’ eligibility for intravenous-tissue-Plasminogen-Activator (iv-tPA), but the more time-consuming Magnetic Resonance Imaging (MRI)-based-evaluation is superior in detecting acute ischaemia.

Objectives: The purpose of this pilot study was to investigate the feasibility and effects of computer-based cognitive rehabilitation (CBCR) in patients with symptoms of visuospatial neglect or homonymous hemianopia in the subacute phase following stroke. Method: A randomized, controlled, unblinded cross-over design was completed with early versus late CBCR including 7 patients in the early intervention group (EI) and 7 patients in the late intervention group (LI). EI received CBCR training immediately after inclusion (m = 19 days after stroke onset) for 3 weeks and LI waited for 3 weeks after inclusion before receiving CBCR training for 3 weeks (m = 44 days after stroke onset). Results: CBCR improved visuospatial symptoms after stroke significantly when administered early in the subacute phase after stroke. The same significant effect was not found when CBCR was administered later in the rehabilitation. The difference in the development of the EI and LI groups during the first 3 weeks was not significant, which could be due to a lack of statistical power. CBCR did not impact mental well-being negatively in any of the groups. In the LI group, the anticipation of CBCR seemed to have a positive impact of mental well-being. Conclusion: CBCR is feasible and has a positive effect on symptoms in patients with visuospatial symptoms in the subacute phase after stroke. The study was small and confirmation in larger samples with blinded outcome assessors is needed.

Background In a prospective cohort of patients with transient ischemic attack (TIA), we investigated usefulness and feasibility of arterial spin labeling (ASL) perfusion and susceptibility weighted imaging (SWI) alone and in combination with standard diffusion weighted (DWI) imaging in subacute diagnostic work-up. We investigated rates of ASL and SWI changes and their potential correlation to lasting infarction 8 weeks after ictus. Methods Patients with TIA underwent 3T-MRI including DWI, ASL and SWI within 72 h of symptom onset. We defined lasting infarction as presence of 8-week MRI T2-fluid attenuated inversion recovery (FLAIR) hyperintensity or atrophy in the area of initial DWI-lesion. Results We included 116 patients. Diffusion and perfusion together identified more patients with ischemia than either alone (59% vs. 40%, p

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging perfusion method based on changes in net-magnetization of blood water. The absence of contrast use and ionizing radiation, renders ASL valuable in hyper-acute settings as a monitoring tool for repeated dynamical measurements during and after intervention, and for patients with known co-morbidities. This text provides a short methodological introduction to ASL and contrasts it with traditional contrast-enhanced perfusion imaging. The review focused on sequence usefulness in the clinical setting of acute cerebral ischemia investigation.

Objective: Diffusion tensor imaging may aid brain ischemia assessment but is more time consuming than conventional diffusion-weighted imaging (DWI). We compared 3-gradient direction DWI (3DWI) and 20-gradient direction DWI (20DWI) standard vendor protocols in a hospital-based prospective cohort of patients with transient ischemic attack (TIA) for lesion detection, lesion brightness, predictability of persisting infarction, and final infarct size.Methods: We performed 3T-magnetic resonance imaging including diffusion and T2-fluid attenuated inversion recovery (FLAIR) within 72 h and 8 weeks after ictus. Qualitative lesion brightness was assessed by visual inspection. We measured lesion area and brightness with manual regions of interest and compared with homologous normal tissue.Results: 117 patients with clinical TIA showed 78 DWI lesions. 2 lesions showed only on 3DWI. No lesions were uniquely 20DWI positive. 3DWI was visually brightest for 34 lesions. 12 lesions were brightest on 20DWI. The median 3DWI lesion area was larger for lesions equally bright, or brightest on 20DWI [median (IQR) 39 (18-95) versus 18 (10-34) mm2, P = 0.007]. 3DWI showed highest measured relative lesion signal intensity [median (IQR) 0.77 (0.48-1.17) versus 0.58 (0.34-0.81), P = 0.0006]. 3DWI relative lesion signal intensity was not correlated to absolute signal intensity, but 20DWI performed less well for low-contrast lesions. 3DWI lesion size was an independent predictor of persistent infarction. 3-gradient direction apparent diffusion coefficient areas were closest to 8-week FLAIR infarct size.Conclusion: 3DWI detected more lesions and had higher relative lesion SI than 20DWI. 20DWI appeared blurred and did not add information.Clinical Trial Registration: http://www.clinicaltrials.gov. Unique Identifier NCT01531946.

Central sensitization is a condition in which there is an abnormal responsiveness to nociceptive stimuli. As such, the process may contribute to the development and maintenance of pain. Factors influencing the propensity for development of central sensitization have been a subject of intense debate and remain elusive. Injury-induced secondary hyperalgesia can be elicited by experimental pain models in humans, and is believed to be a result of central sensitization. Secondary hyperalgesia may thus reflect the individual level of central sensitization. The objective of this study was to investigate possible associations between increasing size of secondary hyperalgesia area and brain connectivity in known resting-state networks. We recruited 121 healthy participants (male, age 22, SD 3.35) who underwent resting-state functional magnetic resonance imaging. Prior to the scan session, areas of secondary hyperalgesia following brief thermal sensitization (3 min. 45 °C heat stimulation) were evaluated in all participants. 115 participants were included in the final analysis. We found a positive correlation (increasing connectivity) with increasing area of secondary hyperalgesia in the sensorimotor- and default mode networks. We also observed a negative correlation (decreasing connectivity) with increasing secondary hyperalgesia area in the sensorimotor-, fronto-parietal-, and default mode networks. Our findings indicate that increasing area of secondary hyperalgesia is associated with increasing and decreasing connectivity in multiple networks, suggesting that differences in the propensity for central sensitization, assessed as secondary hyperalgesia areas, may be expressed as differences in the resting-state central neuronal activity.

Movement artifacts compromise image quality and may interfere with interpretation, especially in magnetic resonance imaging (MRI) applications with low signal-to-noise ratio such as functional MRI or diffusion tensor imaging, and when imaging small lesions. High image resolution has high sensitivity to motion artifacts and often prolongs scan time that again aggravates movement artifacts. During the scan fast imaging techniques and sequences, optimal receiver coils, careful patient positioning, and instruction may minimize movement artifacts. Physiological noise sources are motion from respiration, flow and pulse coupled to cardiac cycles, from the swallowing reflex and small spontaneous head movements. Par example, in resting-state functional MRI spontaneous neuronal activity adds 1-2% of signal change, even under optimal conditions signal contributions from physiological noise remain a considerable fraction hereof. Movement tracking during imaging may allow for prospective correction or postprocessing steps separating signal and noise.

Background Door-to-needle time of 20 minutes to stroke patients with intravenous tissue plasminogen activator (iv-tPA) is feasible when computed tomography (CT) is used as first-line of brain imaging. Magnetic resonance imaging (MRI)-based assessment is more time-consuming but superior in detecting acute ischemia. The certainty with which stroke physicians prescribe or refrain from giving iv-tPA treatment to CT- versus MRI-examined patients has not previously been studied. The aim of the present study was to determine the effect of a primary imaging strategy of CT or MRI on clinicians' certainty to prescribe or refrain from giving iv-tPA to patients with suspected acute stroke. Method Consecutive patients with suspected stroke were quasi-randomized to either CT- or MRI-based assessment before potential iv-tPA treatment. The influence of (1) the clinical findings and (2) the image findings, and (3) the certainty with which the stroke physician prescribed or refrained from giving iv-tPA treatment were assessed with visual analog scales (VAS). Predictors of treatment certainty were identified with a random-effect model. Results Four-hundred forty-four consecutive patients were quasi-randomized. MRI influenced the final treatment decision more than CT (P = .002). Compared with CT-examined patients (mean VAS score 8.6, SD ±1.6) stroke physicians were significantly more certain when prescribing or refraining from giving iv-tPA to MRI-examined patients (mean VAS score 9.0, SD ±1.2) (P = .014). No differences in modified Rankin scale or mortality were detected at 3 months in CT- versus MRI-examined iv–tPA-treated patients. Conclusions Stroke physicians were significantly more certain when prescribing iv-tPA to MRI-examined stroke patients, and MRI influences the final treatment decision significantly more compared with CT, although no difference in mortality and functional outcome at 3 months was detected between CT- and MRI-examined patients treated with iv-tPA.

Background and Purpose— Early hematoma expansion (EHE) in patients with intracerebral hematoma is a promising treatment target. To date, the time course of EHE has remained poorly described. We prospectively investigated the time course of EHE. Methods— We included consecutive patients presenting spontaneous intracerebral hematoma within 4.5 hours. On admission, patients underwent noncontrast computed tomography (CT) and CT angiography. Serial hematoma volume estimations by transcranial B-mode ultrasound were effected through the contralateral transtemporal bone window by obtaining sagittal, transversal, and coronal diameter and calculating the ABC/2-formula. National Institute of Health Stroke Scale and transcranial B-mode ultrasound were performed consecutively every 30 minutes during the first 6 hours and from 6 to 12 hours every 2 hours. Follow-up CT and ultrasound were performed after ≈24 hours. Results— Twenty-five patients with intracerebral hematoma were included; mean (SD) time from onset to CT was 108.6 (45.7) minutes. Ten (40%) patients had EHE. In patients with a final clinically significant hematoma expansion >12.5 mL, all EHE occurred within 6 hours after admission scan. EHE in spot sign positive patients continued during the first 5 hours after CT angiography. In spot sign–negative patients, no significant EHE was observed (Friedman test, P =0.476). Neurological deterioration occurred in 5 (20%) patients and was well temporally correlated with EHE. Transcranial B-mode ultrasound demonstrated good volume estimation compared with the follow-up CT with a maximum absolute volume deviation within 7 mL and minimal systematic error (mean deviation, 1.3 [confidence interval, −0.1 to 2.6] mL). Conclusions— EHE was reliably reflected by transcranial B-mode ultrasound and mainly occurred within the first 7 to 8 hours after symptom onset. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01472224.

Introduction: Vascular pathology in the extracranial vertebral arteries remains among the possible causes in cryptogenic stroke. However, the diagnosis is challenged by the great variety in the anatomy of the vertebral arteries, clinical symptoms and difficulties in the radiological assessments. The aim of this study was to assess the prevalence of CT angiography (CTA)-detected pathological findings in the extracranial vertebral arteries in an acute stroke population and secondly to determine the frequency of posterior pathology as probable cause in patients with otherwise cryptogenic stroke. Method: The analysis was based on 657 consecutive patients with symptoms of acute stroke and a final diagnosis of ischemic stroke or transient ischemic attack. On admission, a noncontrast CT cerebrum and CTA were performed. A senior consultant neuroradiologist, blinded to clinical data, reviewed all CTA scans systematically, assessing the four segments of the extracranial vertebral arteries. First, the frequency of pathological findings including stenosis, plaques, dissection, kinked artery and coiling was assessed. Subsequently, we explored the extent of the pathological findings that were the most plausible causes of stroke, namely either a possible dissection or a kinked artery. Results: Findings in the extracranial vertebral arteries included significant stenosis (0.8%), atherosclerotic plaque types (3.8%), possible dissections (2.6%), kinked arteries (2.6%) and coiling (32.0%). Eighteen patients (2.8%) with pathological findings had an unknown cause of stroke, likely posterior symptoms and no clinical stroke symptoms from the anterior circuit. Of these, 3 cases were kinked arteries (0.5%) and 15 cases (2.3%) were possible dissections. Conclusion: We found that in approximately 3% of the study population, the most plausible cause of the cryptogenic strokes was due to a pathological finding in the posterior extracranial vertebral arteries, being either a possible dissection or a kinked artery. In general, posterior vascular pathology is not uncommon, and CTA is a useful modality in the detection of changes based on characteristics and locations of findings in the extracranial vertebral arteries. Ultrasound examination can be a useful supplementary tool in deciding the consequence of vascular findings on CTA.

Introduction: The issue if Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) are ‘best’ in evaluation of patients with symptoms of acute stroke prior to intravenous-tissue-plasminogen-activator treatment (iv-tPA) has been widely discussed; CT-based door-to-needle-times of 20 minutes are feasible and motivated by time-dependent efficacy of iv-tPA, but the more time consuming MRI-based evaluation likely provides additional information on hyper-acute cerebral ischemia and iv-tPA-contraindicating stroke mimicking pathology. Aim: The aim of this study was to compare the delay of iv-tPA-treatment and the level of diagnostic information obtained for patients randomized to CT and MRI-based acute stroke evaluation. Method: Three-hundred-sixty-nine consecutive patients admitted with symptoms of stroke within 4.5 hours from symptom-onset were quasi-randomized to CT or MRI-based evaluation as part of an ongoing single-center trial and treated with iv-tPA if eligible. Door-to-needle-times for patients, allocated to CT and MRI, were compared. Imaging of diagnostic quality and stroke mimicking detected pathology were registered for the two modalities. Results: Door-to-needle-times for CT evaluated patients (median 26 (7-55) min) were significantly faster than for MRI-examined patients (median 36 (11-71) min), p=0.007. Imaging of adequate diagnostic quality was acquired for all patients examined with CT and for 96.4% of patients, without inherent MRI-contraindications, examined with MRI. All patients with discharge diagnoses of intracerebral hemorrhage and intracerebral oncological pathology were identified by the primary scan at admission, regardless if CT or MRI were performed. Conclusion: CT-based evaluation prior to iv-tPA-treatment is faster and as presice as MRI-based evaluation of patients with acute stroke.

Background Computed tomographic angiography (CTA) is widely available in emergency rooms to assess acute stroke patients. To standardize readings and educate new readers, we developed a 3-step e-learning tool based on the test-teach-retest methodology in 2 acute stroke scenarios: vascular occlusion and "spot sign" in acute intracerebral hemorrhage. We hypothesized that an e-learning program enhances reading skills in physicians of varying experience. Methods We developed an HTML-based program with a teaching segment and 2 matching test segments. Tests were taken before and after the teaching segment; the test size was 40% of the teaching segment size. We assessed diagnostic accuracy and readers' confidence. Results were compared using the Wilcoxon rank sum test. Results Four neurologic consultants and four radiologic residents completed the program. The vascular occlusion teaching segment increased diagnostic accuracy from 42% to 68% ( P = .005). The neurologic consultants showed significant progress, with average scores of 50% versus 75% ( P = .027). The radiologic residents showed trend with progress, with average scores of 33% versus 60% ( P = .081). The entire group detected spot sign correctly 69% before versus 92% after teaching ( P = .009) and reported a median self-perceived diagnostic certainty of 50% versus 75% ( P = .030). Self-perceived diagnostic certainty revealed no significant increase for vascular occlusion. Conclusions The e-learning program is a useful educational tool for users of varying experience, and it enhances diagnostic confidence.

Introduction Central sensitization plays a pivotal role in maintenance of pain and is believed to be intricately involved in several chronic pain conditions. One clinical manifestation of central sensitization is secondary hyperalgesia. The degree of secondary hyperalgesia presumably reflects individual levels of central sensitization. The objective of this study was to investigate the association between areas of secondary hyperalgesia and volumes of the caudate nuclei and other brain structures involved in pain processing. Materials and methods We recruited 121 healthy male participants; 118 were included in the final analysis. All participants underwent whole brain magnetic resonance imaging (MRI). Prior to MRI, all participants underwent pain testing. Secondary hyperalgesia was induced by brief thermal sensitization. Additionally, we recorded heat pain detection thresholds (HPDT), pain during one minute thermal stimulation (p-TS) and results of the Pain Catastrophizing Scale (PCS) and Hospital Anxiety and Depression score (HADS). Results We found no significant associations between the size of the area of secondary hyperalgesia and the volume of the caudate nuclei or of the following structures: primary somatosensory cortex, anterior and mid cingulate cortex, putamen, nucleus accumbens, globus pallidus, insula and the cerebellum. Likewise, we found no significant associations between the volume of the caudate nuclei and HPDTs, p-TS, PCS and HADS. Conclusions Our findings indicate that the size of the secondary hyperalgesia area is not associated with the volume of brain structures relevant for pain processing, suggesting that the propensity to develop central sensitization, assessed as secondary hyperalgesia, is not correlated to brain structure volume. (Less)

Background: Studies have reported neurological detoriation at 24 hours in 20- 40% of patients with symptoms of ischemic stroke. Aim: To asses the frequency of neurological deterioration in patients after fibrinolysis. Methods: A prospective single hospital registry was based on 481 unselected consecutive patients admitted from July 2009- December 2011 with symptoms of acute ischemic stroke within 4.5 hours from symptom onset. Patients fulfilling international guidelines were treated with i.v tPA. Clinical status was assessed by National Institute of Health Stroke Scale (NIHSS) and Computerized Tomography was conducted at admission in all 481 patients and at 24 hours in patients treated with i.v tPA to assess neurological as well as radiological status. Patients were stratified as having neurological deterioration of 1, 2, 3 or > 3 NIHSS points. Results: Three-hundred and twenty three (67.2%) of the admitted stroke patients were treated with i.v tPA (median NIHSS 7, 1-42). At 24 hours, neurological detoriation was observed in 24 of the treated patients (7.4 %) (ΔNIHSS median +2; 1-9). Eleven patients had ΔNIHSS=+1, 3 patients had ΔNIHSS=+2, 4 patients had ΔNIHSS=+3 and 6 patients had ΔNIHSS>+3.Any degree of haemorrhagic transformation was detected in 28 (8.7 %) of the patients treated with i.v tPA (median ΔNIHSS -1.5; -10 - +4), of which 3 were symptomatic (0.9%) (median ΔNIHSS +2, 1-4). Neurological deterioration occurred significantly more often in patients admitted with moderat-severe stroke (p=0.003) and in patients with large vessel occlusions (p=0.041). Conclusion: The neurological deterioration observed in patients treated with i.v tPA was modest and less frequent than previous reported in patients with symptoms of acute stroke prior to general implementation of thrombolysis. Deteriation due to haemorrhagic transformation was rare and of limited scale in this population. If this phenomena is due to better care, selection of patients for treatment in accordance with international guidelines or due to an unknown effect caused by tPA is uncertain.

OBJECTIVES: To find determining factors for persistent infarction signs in patients with transient ischaemic attack (TIA), herein initial diffusion lesion size, visibility on apparent diffusion coefficient (ADC) or fluid-attenuated inversion recovery (FLAIR) and location.DESIGN: Prospective cohort study of patients with clinical TIA receiving 3T-MRI within 72 hours of symptom onset and at 8-week follow-up.SETTING: Clinical workflow in a single tertiary stroke centre between February 2012 and June 2014.PARTICIPANTS: 199 candidate patients were recruited, 64 patients were excluded due to non-TIA discharge diagnosis or no 8-week MRI. 122 patients completed the study.PRIMARY OUTCOME MEASURES: The primary outcome was visible persistent infarction defined as 8-week FLAIR hyperintensity or atrophy corresponding to the initial diffusion-weighted imaging (DWI) lesion.RESULTS: 50 patients showed 84 initial DWI lesions. 29 (35%) DWI lesions did not result in infarction signs on 8-week FLAIR. 26 (90%, P30% of initial DWI-area, OR 14.10, 95% CI 3.61 to 54.72), adjusted for FLAIR-visibility, DWI-area, ADC-confirmation and time to scan (TTS) from symptom onset to baseline MRI. Acute FLAIR-visibility was a strong associated factor for persistent infarction signs (OR 33.06, 95% CI 2.94 to 1432.34). For cGM lesions area size was sole associated factor for persistent infarction signs with a 0.31 cm2 (area under the curve (AUC), 0.97) threshold. In eight (16%) DWI-positive patients, all lesions reversed fully.CONCLUSIONS: 16% of DWI-positive patients and one-third of acute DWI lesions caused no persistent infarction signs, especially small cGM lesions were not followed by development of persistent infarction signs. Late MRI after TIA is likely to be less useful in the clinical setting, and it is dubious if the absence of old vascular lesions can be taken as evidence of no prior ischaemic attacks.TRIAL REGISTRATION NUMBER: NCT01531946; Results.

Summary Background The aim of this study was to describe and validate a method to obtain reproducible and comparable results concerning extension of a specific skin area, unaffected by individual differences in body surface area. Methods A phantom simulating the human torso was equipped with three irregular areas representing the increasing extension of an affected skin area over time. A large sheet of flexible calques paper was placed at the phantom, and five clinicians copied the three irregular shapes two times, resulting in 60 copies. Subsequently, a digital photograph was taken of the calques papers with a clinical ruler placed at the margin. The images were postprocessed and measured in the program ‘ImageJ’ by two observers. An exact area measurement of the three irregular shapes was performed for comparison. Results We found an interobserver variation of 0·36% when comparing the measurements of all three areas. Comparing observer measurements with the exact areas size, we found an underestimate of 2·52%. We observed a tendency that the discrepancy in measurement increases when the measured area decreases. Conclusion We find this method accurate, reproducible and easy to use. The presented method can be of help when documenting psoriasis and other dermatologic conditions as well as when exploring the effects of new types and variations of ultrasound-guided peripheral nerve blocks – especially in study volunteers.

Background Incidental findings of suspect lung opacities are common in computed tomography (CT)–based thorax examinations, especially in high-risk patients, such as stroke patients. Screening with CT of the thorax has detected lung cancer in approximately .31%-1.20% of high-risk populations. The aim of the present study was to report the frequency of suspect lung opacities on routine acute stroke imaging. Methods Seven hundred and fifty-seven consecutive stroke patients evaluated for intravenous thrombolysis treatment within 4.5 hours of symptom debut, from June 2009 to December 2011, were included in a prospective registry on which this analysis was based. On admission, CT angiography from the aortic arch to vertex was performed, including the lung apices, corresponding to 1/3 of the total lung volume. A senior neuroradiologist reviewed all scans registering suspect lung opacities, which subsequently were characterized as either malignant, presumed malignant, presumed benign or benign, based on radiologic parameters of malignancy, positron emission tomography scan, histology, and clinical features. Results Suspect lung opacities appeared on the CT angiography in 20 patients (2.6%). Five suspect lung opacities were categorized as malignant and 3 suspect lung opacities were categorized as presumed malignant. This corresponds to an incidence of 1.1% (8 of 750). Conclusions Malignant lung opacities were found in approximately 1% of this high-risk population, whereas our findings do not support full CT of the thorax as routine on stroke patients.

Background Is computed tomography (CT)–verified leukoaraiosis (LA) a risk factor for post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage? Methods (1) Retrospective analysis based on a prospectively planned single-center registry of consecutive tissue plasminogen activator (tPA)–treated patients within 4.5 hours from symptom onset. Standard work-up included baseline noncontrast CT and CT angiography and next day follow-up noncontrast CT. Baseline noncontrast CT LA was graded using Fazekas' score and dichotomized as the absence (Fazekas, 0) or the presence (Fazekas, 1-3). Hemorrhagic transformation was rated using European Cooperative Acute Stroke Study (ECASS) criteria. Symptomatic intracerebral hemorrhage was defined as hemorrhage and deterioration of National Institutes of Health Stroke Scale (NIHSS) of 4 or greater within 36 hours from symptom onset. Endovascularly treated patients were excluded. (2) Pooled analysis with 1312 tPA-treated patients from literature. Results In all, 311 tPA-treated patients were included between April 2009 and July 2012. LA was present in 113 (36%). Twenty-three (7%) showed hemorrhagic transformation. LA positive patients had significantly higher hemorrhagic transformation frequency (11.5%, P = .04). LA doubled hemorrhagic transformation risk (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4-5.8). Only 4 patients developed symptomatic intracerebral hemorrhage, 3 with LA. LA was not an independent risk factor for hemorrhagic transformation ( P = .2). Pooled analysis of 1623 patients in total, hereof 479 LA positive patients, showed significantly higher symptomatic intracerebral hemorrhage frequency in 35 (7.3%) LA positive than that in 44 (3.8%) LA negative patients, ( P = .005) and doubled symptomatic intracerebral hemorrhage risk in LA positives (OR, 1.97; 95% CI 1.22-3.19). Conclusions LA doubles the risk of post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage; this finding does not support withholding thrombolysis from patients with LA.

Post-admission hematoma expansion in patients with intracerebral hemorrhage (ICH) comprises a simultaneous major clinical problem and a possible target for medical intervention. In any case, the ability to predict and observe hematoma expansion is of great clinical importance. We review radiological concepts in predicting and observing post-admission hematoma expansion. Hematoma expansion can be observed within the first 24 h after symptom onset, but predominantly occurs in the early hours. Thus capturing markers of on-going bleeding on imaging techniques could predict hematoma expansion. The spot sign observed on computed tomography angiography is believed to represent on-going bleeding and is to date the most well investigated and reliable radiological predictor of hematoma expansion as well as functional outcome and mortality. On non-contrast CT, the presence of foci of hypoattenuation within the hematoma along with the hematoma-size is reported to be predictive of hematoma expansion and outcome. Because patients tend to arrive earlier to the hospital, a larger fraction of acute ICH-patients must be expected to undergo hematoma expansion. This renders observation and radiological follow-up investigations increasingly relevant. Transcranial duplex sonography has in recent years proven to be able to estimate hematoma volume with good precision and could be a valuable tool in bedside serial observation of acute ICH-patients. Future studies will elucidate, if better prediction and observation of post-admission hematoma expansion can help select patients, who will benefit from hemostatic treatment.

Background The frequency of acute large vessel occlusions in relation to clinical severity has not yet been established in a comprehensive, consecutive and unselected cohort of patients with hyper-acute cerebral ischemia. Aim The aim of this study was to establish the frequency of acute large vessel occlusions and describe the relations to the National Institutes of Health Stroke Scale (NIHSS), lesion site and time from symptom onset in unselected consecutive patients with hyper-acute cerebral ischemia. Methods A prospective single hospital registry was based on consecutive unselected patients admitted from July 2009 to December 2011 with symptoms of acute cerebral ischemia within 4·5 h from symptom onset. ICA, M1, M2, ACA, PCA, BA and VA were assed for occlusions. Best NIHSS-cut-off values were calculated based on sensitivity and specificity for detecting any, anterior and posterior occlusions and the effect of time after symptom onset was assessed. Results Six hundred thirty-seven patients, with admission NIHSS: 1–42, were included; 183 patients presented with acute vessel occlusions (28·7%) in 15 different combinations of occlusions. The best NIHSS-cut-off for detecting any occlusion was 6. NIHSS is highly depending on lesion site, highest values being observed in relation to combined and M1 occlusions. Conclusion Acute vessel occlusions are frequent in unselected patients. Occlusions occurred in all NIHSS score values but a NIHSS cut-off value of 6 most optimally predicted acute vessel occlusion, even though accuracy was low.

Background: Spot sign on computed tomography angiography (CTA) is a marker of on-going bleeding and poor outcome in ICH patients. CTA is not as widely available as non-contrast CT (NCCT). The swirl sign is a less well described marker of on-going bleeding on NCCT. We investigated, if the swirl sign can predict spot sign on CTA and as well as its ability to predict poor outcome in ultra-early ICH patients. Method: We included 137 patients with spontaneous ICH admitted within 4.5 hours from symptom onset from April 2009 to January 2013. Standard work up included NCCT and CTA. The swirl sign on NCCT was defined as regions of hypo- or isodensity located within the hyperdens haematoma with brain parenchyma as reference. Modified Rankin Scale (mRS) was assessed at 3 months (out-patient clinic or by telephone). Results: Of the 35 (25.5%) patients with a swirl sign on NCCT, 27 (77%) also had spot sign on CTA. This yields a high specificity and negative predictive value (0.92 and 0.86 respectably) and a slightly lower sensitivity and positive predictive value (0.66 and 0.77 respectably). The swirl sign emerged as a highly significant predictor of the spot sign (OR 15.5 CI: 5.6-42.8), adjusted for admission haematoma volume and time to scan. Swirl sign was associated with poorer median [IQR] outcome after 3 months (5 [4-6] vs. 3 [2-5], p < 0.0001). Swirl sign was an independent predictor of poor outcome (mRS 5-6) (OR 3.28 CI: 1.15-9.34) adjusted for age, admission NIHSS, and admission haematoma volume. The presence of both spot and swirl sign did not add to the prediction of poor outcome. Conclusion: Swirl sign is a valid marker for the presence of spot sign. The swirl sign entails poor outcome irrespective of other independent predictors. Further studies are needed to evaluate the value of the swirl sign in clinical decision-making and trials.

Objectives We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation. Design This study presents data from a prospective cohort of patients admitted to our stroke unit for thrombolysis evaluation. Setting and participants We included 652 with a final diagnosis of ischaemic stroke or transient ischaemic attack (TIA) from April 2009 to December 2011. All patients were acutely evaluated with cerebral CT and CT angiography (CTA). Acute radiological examinations were screened for intracranial arterial stenosis (IAS) or intracranial arterial calcifications (IAC). Intracranial stenosis was grouped into 30–50%, 50–70% and >70% lumen reduction. The extent of IAC was graded as number of vessels affected. Primary and secondary outcome measure Patients were followed until July 2013. Recurrence of an ischaemic event (stroke, ischaemic heart disease (IHD) and TIA) was documented through the national chart system. Poor outcome was defined as death or recurrence of ischaemic event. Results 101 (15.5%) patients showed IAS (70: 30–50%, 29: 50–70% and 16: >70%). Two-hundred and fifteen (33%) patients had no IAC, 339 (52%) in 1–2 vessels and 102 (16%) in >2 vessels. During follow-up, 53 strokes, 20 TIA and 14 IHD occurred, and 95 patients died. The risk of poor outcome was significantly different among different extents of IAS as well as IAC (log-rank test p

Background: A spot sign on computed tomography angiography (CTA) is a potentially strong predictor of poor outcome on ultra-early radiological imaging. The aim of this study was to assess the spot sign as a predictor of functional outcome at 3 months as well as long-term mortality, with a focus on the ability to identify patients with a spontaneous, acceptable outcome. Methods: In a prospective, consecutive single-centre registry of acute stroke patients, we investigated patients with spontaneous intracerebral haemorrhage (ICH) admitted within 4.5 h after symptom onset from April 2009 to January 2013. The standard work-up in our centre included CTA for spot sign status, unless a contraindication was present. Modified Rankin Scale (mRS) scores were assessed at 3 months in the outpatient clinic or by telephone interviews. Long-term mortality was assessed by electronic chart follow-up for up to 1,500 days. Results: Of the 128 patients, 37 (28.9%) had a spot sign on admission CTA. The presence of a spot sign was associated with larger median admission haematoma volume [38.0 ml (IQR 18.0-78.0) vs. 12.0 ml (5.0-24.0); p < 0.0001] and higher median National Institutes of Health Stroke Scale score [19 (IQR 12-23) vs. 12 (6-16); p < 0.0001]. Three months after stroke, the median functional outcome was considerably better in patients without spot sign [mRS score 3 (IQR 2-4) vs. 6 (4-6); p < 0.0001]. The absence of a spot sign showed a sensitivity and specificity for good outcome (mRS scores 0-2) of 0.91 and 0.36, respectively. The presence of a spot sign was, in multivariate models, an independent inverse predictor of good 3-month outcome (OR 0.17; 95% CI: 0.03-0.88) as well as a prominent independent predictor of poor 3-month outcome (mRS scores 5-6; OR 3.40; 95% CI: 1.10-10.5) and death during follow-up (HR 3.04; 95% CI: 1.45-6.34). Patients with a spot sign surviving the acute phase had long-term survival comparable to patients with no spot sign. Conclusion: The absence or presence of a spot sign is a reliable ultra-early predictor of long-term mortality and functional outcome in patients with spontaneous ICH.

Stroke remains the most frequent cause of handicap in adult life and according to the WHO the second cause of death in the Western world. In the peracute phase, intravenous thrombolysis and in some cases endovascular therapy may induce early revascularization and hereby improve prognosis. However, only up to 20-25% of patients are eligible to causal treatment. Further, care in a specialized stroke unit improves prognosis in all patients independent of age and stroke severity. Even when it is not possible to prevent tissue loss, the surviving brain areas of functional brain networks have a substantial capacity to reorganize after a focal ischemic (or hemorrhagic) brain lesion. This functional reorganization contributes to functional recovery after stroke. Functional magnetic resonance imaging (fMRI) provides a valuable tool to capture the spatial and temporal activity changes in response to an acute ischemic lesion. Task-related as well as resting-state fMRI have been successfully applied to elucidate post-stroke remodeling of functional brain networks. This includes regional changes in neuronal activation as well as distributed changes in functional brain connectivity. Since fMRI is readily available and does not pose any adverse effects, repeated fMRI measurements provide unprecedented possibilities to prospectively assess the time course of reorganization in functional neural networks after stroke and relate the temporospatial dynamics of reorganization at the systems level to functional recovery. Here we review the current status and future perspectives of fMRI as a means of studying functional brain reorganization after stroke. We summarize (a) how fMRI has advanced our knowledge regarding the recovery mechanisms after stroke, and (b) how fMRI has been applied to document the effects of therapeutical interventions on post-stroke functional reorganization.

Stroke remains the most frequent cause of handicap in adult life and according to the WHO the second cause of death in the Western world. In the peracute phase, intravenous thrombolysis and in some cases endovascular therapy may induce early revascularization and hereby improve prognosis. However, only up to 20-25% of patients are eligible to causal treatment. Further, care in a specialized stroke unit improves prognosis in all patients independent of age and stroke severity. Even when it is not possible to prevent tissue loss, the surviving brain areas of functional brain networks have a substantial capacity to reorganize after a focal ischemic (or hemorrhagic) brain lesion. This functional reorganization contributes to functional recovery after stroke. Functional magnetic resonance imaging (fMRI) provides a valuable tool to capture the spatial and temporal activity changes in response to an acute ischemic lesion. Task-related as well as resting-state fMRI have been successfully applied to elucidate post-stroke remodeling of functional brain networks. This includes regional changes in neuronal activation as well as distributed changes in functional brain connectivity. Since fMRI is readily available and does not pose any adverse effects, repeated fMRI measurements provide unprecedented possibilities to prospectively assess the time course of reorganization in functional neural networks after stroke and relate the temporospatial dynamics of reorganization at the systems level to functional recovery. Here we review the current status and future perspectives of fMRI as a means of studying functional brain reorganization after stroke. We summarize (a) how fMRI has advanced our knowledge regarding the recovery mechanisms after stroke, and (b) how fMRI has been applied to document the effects of therapeutical interventions on post-stroke functional reorganization.

Persistent lower back pain after instrumental posterolateral desis may arise from incomplete fusion. We investigate the impact of experience on interobserver agreement in fusion estimation.Four independent observers, two residents and two musculoskeletal radiologists, reviewed dedicated lumbar 64-MDCT scans and scored vertebral levels 1-5 after Glassman's grades, 1: solid bilateral fusion, 2: solid unilateral fusion, 3: partial bilateral fusion, 4: partial unilateral fusion, 5: non-fusion. We investigated two simplifying dichotomizations, solid bilateral fusion (Glassman 1) versus all others and uni- or bilateral fusion (Glassman 1-2) versus partial or non-fusion.Thirty-six patients with 61 operated lumbar levels were included. Interobserver agreement rates for four observers using Glassman's system were fair (kappa 0.32), either dichotomization showed moderate agreement (kappa 0.53 and 0.59). Observer pairs had comparable prevalence adjusted interobserver agreement rates (residents: PABAK 0.67 and 0.54; consultants: PABAK 0.57 and 0.71).Difference in observer experience seems of minor impact.

Objective Patients with intracerebral haemorrhage (ICH) are at high risk of neurological deterioration (ND). We aimed at establishing predictors of early ND (END) as well as late ND (LND) and at exploring the impact of neurological stability during the first week on long-term prognosis. Design We conducted this study as a retrospective cohort study. ND was evaluated based on the consciousness and severity of neurological symptoms. ND during the first 24 h after admission was defined as early ND and from 24 h to 7 days as LND. Patients were followed up until February 2015. Participants We included 300 patients with acute ICH (≤4.5 h from symptom onset) who were admitted to our institution from March 2009 to January 2015. Setting Section of Acute Neurology, Department of Neurology, Bispebjerg Hospital is a specialised referral centre receiving patients with acute stroke from the entire capital region of Denmark. Results We found that a spot sign on CT angiography (OR 10.7 CI 4.79 to 24.3) and extensive degree of interventricular haemorrhage (IVH) (OR 8.73 CI 2.87 to 26.5) were independent predictors of END, whereas a degree of comorbidity (Charlton Index), admission stroke severity and degree of IVH predicted LND. On follow-up imaging, haematoma expansion was independently associated with END (OR 6.1 CI 2.2 to 17.3), and expansion of IVH was independently associated with both END (OR 1.7 CI 1.2 to 2.3 per point increase) and LND (OR 2.3 CI 1.3 to 4.2 per point increase). ND during the first week was associated with a 1-year mortality of 60.5%, compared with 9.2% among the patients who remained stable. Conclusions These results suggest that stability during the first week entails an optimistic prognosis. A relatively easy and effective risk stratification of END and LND is possible on admission based on the spot sign, IVH and clinical parameters.

Background Primary ICH expands in up to 50% of cases and in these treatment with haemostatic compounds can be potentially beneficial. Spot detection on multi-detector CTangiography (MDCTA) studies may identify ongoing bleeding and thus predict haematoma expansion. Aim was to assess the frequency, the prognostic impact and haematoma volume increase in patients with positive spot sign in comparison to no spot sign.