Christian Ovesen

Stroke severity and incidence of acute large vessel occlusions in patients with hyper‐acute cerebral ischemia: results from a prospective cohort study based on CT‐angiography (CTA)

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.

Time Course of Early Postadmission Hematoma Expansion in Spontaneous Intracerebral Hemorrhage

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.

Prediction and observation of post-admission hematoma expansion in patients with intracerebral hemorrhage.

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.

Showing no spot sign is a strong predictor of independent living after intracerebral haemorrhage.

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.

Diagnosing Paroxysmal Atrial Fibrillation in Patients With Ischemic Strokes and Transient Ischemic Attacks Using Echocardiographic Measurements of Left Atrium Function.

Twenty-five to 35 percentage of stroke cases are cryptogenic, and it has been demonstrated that paroxysmal atrial fibrillation (AF) is the causal agent in up to 25% of these incidents. The purpose of this study was to investigate if left atrial (LA) parameters have value for diagnosing paroxysmal AF in patients with ischemic stroke (IS) and transient ischemic attack (TIA). We retrospectively analyzed 219 patients who after acute IS or TIA underwent a transthoracic echocardiographic examination. Patients were designated as patients with paroxysmal AF if they had one or more reported incidents of AF before or after their echocardiographic examination. Patients in the paroxysmal AF group were significantly older and had higher CHA2DS2-VASc score than patients without paroxysmal AF (p <0.05 for both). None of the conventional echocardiographic parameters were significantly associated with paroxysmal AF. However, the atrial measurements evaluating LA function (min LA volume and LA emptying fraction) were significantly different (LA emptying fraction: 45% ± 10% vs 50% ± 10%, p = 0.004; minimal LA volume: 30.2 ml ± 17.3 ml vs 24 ml ± 10 ml, p = 0.035 in patients with paroxysmal AF, even after adjustment for age, gender, CHA2DS2-VASc score, and stroke severity [p <0.05 for both]). By combining the cut-off values of age, LA emptying fraction, and minimal LA volume the diagnostic accuracy of paroxysmal AF was improved, resulting in a sensitivity of 95% and negative predictive value of 97%. In conclusion, in patients with IS and TIA, LA function measurements (minimal LA volume and LA emptying fraction) are independently associated with paroxysmal AF and may improve risk stratification for paroxysmal AF presence after IS or TIA.

External validation of the ability of the DRAGON score to predict outcome after thrombolysis treatment

Easy-to-perform and valid assessment scales for the effect of thrombolysis are essential in hyperacute stroke settings. Because of this we performed an external validation of the DRAGON scale proposed by Strbian et al. in a Danish cohort. All patients treated with intravenous recombinant plasminogen activator between 2009 and 2011 were included. Upon admission all patients underwent physical and neurological examination using the National Institutes of Health Stroke Scale along with non-contrast CT scans and CT angiography. Patients were followed up through the Outpatient Clinic and their modified Rankin Scale (mRS) was assessed after 3 months. Three hundred and three patients were included in the analysis. The DRAGON scale proved to have a good discriminative ability for predicting highly unfavourable outcome (mRS 5-6) (area under the curve-receiver operating characteristic [AUC-ROC]: 0.89; 95% confidence interval [CI] 0.81-0.96; p<0.001) and good outcome (mRS 0-2) (AUC-ROC: 0.79; 95% CI 0.73-0.85; p<0.001). When only patients with M1 occlusions were selected the DRAGON scale provided good discriminative capability (AUC-ROC: 0.89; 95% CI 0.78-1.0; p=0.003) for highly unfavourable outcome. We confirmed the validity of the DRAGON scale in predicting outcome after thrombolysis treatment.

Inducible limb-shaking transitory ischemic attacks: a video-documented case report and review of the literature

BackgroundLimb-shaking transient ischemic attack (TIA) is a well-recognized, but rare observation in contralateral carotid steno-occlusive disease. Consequently, most clinicians have not had the chance to witness an attack.Case presentationWe present the story of a 64-year old gentleman with exercise-induced weakness associated with tremor in his right arm. His left internal carotid artery was occluded at the bifurcation. Administration of statin and antiplatelet did not relieve his symptoms, and his stereotypic, exercise-induced “limb-shaking” episodes persisted. He underwent successful extracranial to intracranial (EC-IC) bypass, which stopped his symptoms. The patient, however, returned to our department and reported that he was able to recreate his original symptoms by compressing the bypass graft manually.ConclusionTo our knowledge, this is the first case with video documentation of the clinical appearance of a limb-shaking TIA. We hope this case report will increase the physicians’ understanding of the clinical nature of limb-shaking TIAs.

Prothrombin complex concentrate versus placebo, no intervention, or other interventions in critically bleeding patients associated with oral anticoagulant administration: a protocol for a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

BackgroundAcute critical bleeding is one of the most feared complications during treatment with oral anticoagulating agents. As more patients undergo treatment with anticoagulating agents, critically bleeding episodes in patients with vitamin K antagonists, thrombin inhibitor, or factor Xa inhibitor-inducted coagulopathy will be encountered frequently by physicians. Hence, an effective treatment capable of reversing the iatrogenic coagulopathy in the acute setting is needed. In randomised clinical trials and observational studies, prothrombin complex concentrate has been reported to be superior to other acute interventions, and many guidelines recommend prothrombin complex concentrate in treatment of critically bleeding patients. The aim of this systematic review is to synthesise the evidence of the effects of prothrombin complex concentrate compared with placebo, no intervention, or other treatment options in critically bleeding patients treated with oral anticoagulants.Methods/designA comprehensive search for relevant published literature will be undertaken in Cochrane Central Register of Controlled Trials, MEDLINE, Embase, WHO International Clinical Trials Registry Platform, Science Citation Index, regulatory databases, and trial registers. We will include randomised clinical trials comparing prothrombin complex concentrate versus placebo, no intervention, or other interventions in critically bleeding patients with oral anticoagulant-induced coagulopathy. Data extraction and risk of bias assessment will be handled by two independent review authors. Meta-analysis will be performed as recommended by Cochrane Handbook for Systematic Reviews of Interventions, bias will be assessed with domains, and trial sequential analysis will be conducted to control random errors. Certainty will be assessed by GRADE.DiscussionAs critical bleeding in patients treated with oral anticoagulants is an increasing problem, an up-to-date systematic review evaluating the benefits and harms of prothrombin complex concentrate is urgently needed. It is the hope that this review will be able to guide best practice in treatment and clinical research of these critically bleeding patients.Systematic review registrationPROSPERO CRD42018084371

Comparison of 3- and 20-Gradient Direction Diffusion-Weighted Imaging in a Clinical Subacute Cohort of Patients with Transient Ischemic Attack: Application of Standard Vendor Protocols for Lesion Detection and Final Infarct Size Projection

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.

Endovascular therapy did not improve expected prognosis after i.v. fibrinolysis: a retrospective analysis based on a nationwide Danish registry

Three randomized clinical trials (RCTs) (1–3) have suggested limited effect on outcome when adding endovascular therapy (EVT) to intravenous (i.v.) fibrinolysis. The DRAGON-score (4) is a prognostic score with a good ability to discriminate patients with a good and miserable three-month outcome [modified Rankin Scale (mRS) 0–2 and mRS 5–6, respectively] in patients treated with i.v fibrinolysis. The score is comprised by six variables: hyperdense artery sign, early infarct changes, prestroke mRS, age, admission glucose level, onset to needle time, and National Institute of Health Stroke Scale (NIHSS). To explore if the RCT results reflected clinical outcome in a nation-wide registry, we compared outcome in patients who received i.v. fibrinolysis + EVT with i.v. fibrinolysis alone adjusted for DRAGON-score. In Denmark, complete national EVT coverage was implemented in 2011. The present analysis is based on data extracted from this Danish Stroke Registry (5) (Data Protection Agency Approval BBH 2012-028). We obtained DRAGON variables and three-months mRS from all patients with an NIHSS >10 receiving i.v. fibrinolysis + plus EVT or i.v. fibrinolysis alone between December 2010 and December 2012. A total of 432 patients (173 treated with EVT) were available. We validated the DRAGON-score and found an acceptable discriminative capability in patients treated with i.v. fibrinolysis only [mRS 0–2: ROC-AUC (receiver operating characteristic – area under the curve) 0·71; 95% confidence interval (CI) 0·65–0·76; P < 0·001] and (mRS 5–6: ROC-AUC 0·77; 95% CI: 0·71–0·83; P < 0·001). Outcome is presented in Fig. 1. In the logistic regression analysis, adjusted for DRAGON-score, adding EVT did not increase the probability of good outcome [odds ratio (OR): 1·16; 95%CI: 0·77– 1·76] or decrease the risk of miserable outcome (OR: 0·852; 95%CI: 0·52–1·38) significantly. These results corroborate results from RCTs.