Integrative-interpersonal dynamic therapy for poststroke depression (INID): study protocol of a randomised controlled pilot trial.

INTRODUCTION: Depression is the most frequent psychiatric disorder following stroke, affecting about one-third of stroke survivors. Patients experience poorer recovery, lower quality of life and higher mortality compared with stroke survivors without depression. Despite these well-known malign consequences, poststroke depression (PSD) is regarded underdiagnosed and undertreated. Evidence of beneficial effects of psychotherapy to treat PSD remains scarce and inconclusive and is limited by heterogeneity in design, content and timing of the intervention. This pilot study aims to assess the feasibility of a newly developed integrative-interpersonal dynamic PSD intervention in an outpatient setting and provide a first estimation of the potential effect size as basis for the sample size estimation for a subsequent definite trial. METHOD AND ANALYSIS: Patients will be recruited from two German stroke units. After discharge from inpatient rehabilitation, depressed stroke survivors will be randomised to short-term psychotherapy (12 weeks, ≤16 sessions) or enhanced treatment as usual. The manualised psychotherapy integrates key features of the Unified Psychodynamic and Cognitive-Behavioural Unified Protocol for emotional disorders and was adapted for PSD. Primary endpoints are recruitment feasibility and treatment acceptability, defined as a recruitment rate of ≥20% for eligible patients consenting to randomisation and ≥70% completion-rate of patients participating in the treatment condition. A preliminary estimation of the treatment effect based on the mean difference in Patient Health Questionnaire-9 (PHQ-9) scores between intervention and control group six months poststroke is calculated. Secondary endpoints include changes in depression (PHQ-9/Hamilton Depression Scale) and anxiety (Generalised Anxiety Disorder 7) of all participants across all follow-ups during the first year poststroke. ETHICS AND DISSEMINATION: The INID pilot study received full ethical approval (S-321/2019; 2022-2286_1). Trial results will be published in a peer-reviewed journal in the first half of 2025. One-year follow-ups are planned to be carried out until summer 2025. TRIAL REGISTRATION NUMBER: DRKS00030378.

Aortic Arch Variations and Supra-aortic Arterial Tortuosity in Stroke Patients Undergoing Thrombectomy : Retrospective Analysis of 1705 Cases.

PURPOSE: Unfavorable vascular anatomy can impede thrombectomy in patients with acute ischemic stroke. The aim of this study was to determine the prevalence of aortic arch types, aortic arch branching patterns and supra-aortic arterial tortuosity in stroke patients with large vessel occlusion. METHODS: Computed tomography (CT) and magnetic resonance (MR) images of all stroke patients in an institutional thrombectomy registry were retrospectively reviewed. Aortic arch types and branching patterns of all patients were determined. In patients with anterior circulation stroke, the prevalence of tortuosity (elongation, kinking or coiling) of the supra-aortic arteries of the affected side was additionally assessed. RESULTS: A total of 1705 aortic arches were evaluated. Frequency of aortic arch types I, II and III were 777 (45.6%), 585 (34.3%) and 340 (19.9%), respectively. In 1232 cases (72.3%), there was a normal branching pattern of the aortic arch. The brachiocephalic trunk and the left common carotid artery had a common origin in 258 cases (15.1%). In 209 cases (12.3%), the left common carotid artery arose from the brachiocephalic trunk. Of 1598 analyzed brachiocephalic trunks and/or common carotid arteries, 844 (52.8%) had no vessel tortuosity, 592 (37.0%) had elongation, 155 (9.7%) had kinking, and 7 (0.4%) had coiling. Of 1311 analyzed internal carotid arteries, 471 (35.9%) had no vessel tortuosity, 589 (44.9%) had elongation, 150 (11.4%) had kinking, and 101 (7.7%) had coiling. CONCLUSION: With 20%, type III aortic arches are found in a relevant proportion of stroke patients eligible for mechanical thrombectomy. Nearly half of the stroke patients present with supra-aortic arterial tortuosity, mostly arterial elongation.

"But it's a nice compromise" - Qualitative multi-centre study of barriers and facilitators to acute telestroke cooperation in a regional stroke network.

BACKGROUND: Telemedical services can be used to complement on-site services when demand for specialists exceeds supply or when specialists are not evenly distributed across health systems. Using stroke as an example, this study aimed to explore how patients and staff experience telestroke cooperation in a stroke network in Germany. METHODS: We conducted a qualitative multi-method and multi-centre study combining 32 non-participant observations at one hub and four spoke hospitals with 26 semi-structured interviews with hub and spoke staff as well as stroke patients and relatives. Observation protocols and interview transcripts were analysed to identify barriers and facilitators to telestroke cooperation from the perspectives of staff, patients and relatives. RESULTS: In terms of barriers to telestroke cooperation, we found technological problems, providing the treatment for one patient from two sites, competing priorities between telestroke and in-house duties in the spoke hospitals, as well as difficulties in participating in the teleneurological examination via a videoconferencing system for older and disabled patients. In terms of facilitators, we found an overall very positive perception of telestroke provision by patients, good professional relationships within the network, and sharing of neurological expertise to be experienced as helpful for telestroke cooperation. CONCLUSIONS: We recommend better integration of telemedical services into the care pathway, fostering relationships within the network, improved technological support and resources, and more emphasis within networks, in public awareness efforts as well as in academia on the evaluation of telemedical services from the perspectives of patients and relatives, especially older patients and patients with disabilities.

Accuracy and reliability of PBV ASPECTS, CBV ASPECTS and NCCT ASPECTS in acute ischaemic stroke: a matched-pair analysis.

BACKGROUND AND PURPOSE: To investigate the reliability and accuracy of Alberta Stroke Program Early Computed Tomography Scores (ASPECTS) derived from flatpanel detector computed tomography pooled blood volume maps compared to non-contrast computed tomography and multidetector computed tomography perfusion cerebral blood volume maps. METHODS: ASPECTS from pooled blood volume maps were evaluated retrospectively by two experienced readers for 37 consecutive patients with acute middle cerebral artery (MCA) M1 occlusion who underwent flatpanel detector computed tomography perfusion imaging before mechanical thrombectomy between November 2016 and February 2019. For comparison with ASPECTS from non-contrast computed tomography and cerebral blood volume maps, a matched-pair analysis according to pre-stroke modified Rankin scale, age, stroke severity, site of occlusion, time from stroke onset to imaging and final modified thrombolysis in cerebral infarction (mTICI) was performed in a separate group of patients who underwent multimodal computed tomography prior to mechanical thrombectomy between June 2015 and February 2019. Follow-up ASPECTS were derived from either non-contrast computed tomography or from magnetic resonance imaging (in seven patients) one day after mechanical thrombectomy. RESULTS: Interrater agreement was best for non-contrast computed tomography ASPECTS (w-kappa = 0.74, vs. w-kappa = 0.63 for cerebral blood volume ASPECTS and w-kappa = 0.53 for pooled blood volume ASPECTS). Also, accuracy, defined as correlation between acute and follow-up ASPECTS, was best for non-contrast computed tomography ASPECTS (Spearman ρ = 0.86 (0.65-0.97), P < 0.001), while it was lower and comparable for pooled blood volume ASPECTS (ρ = 0.58 (0.32-0.79), P < 0.001) and cerebral blood volume ASPECTS (ρ = 0.52 (0.17-0.80), P = 0.001). It was noteworthy that cases of relevant infarct overestimation by two or more ASPECTS regions (compared to follow-up imaging) were observed for both acute pooled blood volume and cerebral blood volume ASPECTS but occurred more often for acute pooled blood volume ASPECTS (25% vs. 5%, P = 0.02). CONCLUSION: Non-contrast computed tomography ASPECTS outperformed both pooled blood volume ASPECTS and cerebral blood volume ASPECTS in accuracy and reliability. Importantly, relevant infarct overestimation was observed more often in pooled blood volume ASPECTS than cerebral blood volume ASPECTS, limiting its present clinical applicability for acute stroke imaging.

Trimethylamine-N-Oxide Levels Are Similar in Asymptomatic vs. Symptomatic Cerebrovascular Atherosclerosis.

Introduction: Trimethylamine-N-oxide (TMAO) is correlated with atherosclerosis and vascular diseases such as coronary heart disease and ischemic stroke. The aim of the study was to investigate whether TMAO levels are different in symptomatic vs. asymptomatic cerebrovascular atherosclerosis. Methods: This was a prospective, case-control study, conducted at a tertiary care university hospital. Patients were included if they had large-artery atherosclerosis (TOAST criteria). Symptomatic patients with ischemic stroke were compared with asymptomatic patients. As primary endpoint, TMAO levels on admission were compared between symptomatic and asymptomatic patients. Univariable analysis was performed using Mann-Whitney U test and multivariable analysis using binary logistic regression. TMAO values were adjusted for glomerular filtration rate (GFR), age, and smoking. Results: Between 2018 and 2020, 82 symptomatic and asymptomatic patients were recruited. Median age was 70 years; 65% were male. Comparing symptomatic (n = 42) and asymptomatic (n = 40) patients, no significant differences were found in univariable analysis in TMAO [3.96 (IQR 2.30-6.73) vs. 5.36 (3.59-8.68) µmol/L; p = 0.055], GFR [87 (72-97) vs. 82 (71-90) ml/min*1.73 m2; p = 0.189] and age [71 (60-79) vs. 69 (67-75) years; p = 0.756]. In multivariable analysis, TMAO was not a predictor of symptomatic cerebrovascular disease after adjusting for age and GFR [OR 1.003 (95% CI: 0.941-1.070); p = 0.920]. In a sensitivity analysis, we only analyzed patients with symptomatic stenosis and excluded patients with occlusion of brain-supplying arteries. Again, TMAO was not a significant predictor of symptomatic stenosis [OR 1.039 (0.965-1.120), p = 0.311]. Conclusion: TMAO levels could not be used to differentiate between symptomatic and asymptomatic cerebrovascular disease in our study.

Age-Dependent Differences in the Rate and Symptoms of TIA Mimics in Patients Presenting With a Suspected TIA to a Neurological Emergency Room.

Background: Transient ischemic attack (TIA) needs further diagnostic evaluation to prevent future ischemic stroke. However, prophylaxis can be harmful in elderly if the diagnosis is wrong. We aimed at characterizing differences in TIA mimics in younger and older patients to enhance diagnostic accuracy in elderly patients. Methods: In a dedicated neurological emergency room (nER) of a tertiary care University hospital, patients with transient neurological symptoms suspicious of TIA (<24 h) were retrospectively analyzed regarding their final diagnoses and their symptoms. These parameters were compared between patients aged 18-70 and >70 years using descriptive, univariable, and multivariable statistics. Results: From November 2018 until August 2019, 386 consecutive patients were included. 271 (70%) had cardiovascular risk factors and all patients received cerebral imaging, mostly CT [376 (97%)]. There was no difference in the rate of diagnosed TIA between the age groups [85 (46%) vs. 58 (39%); p = 0.213].TIA mimics in the elderly were more often internal medicine diseases [35 (19%) vs. 7 (5%); p < 0.001] and epileptic seizures [48 (26%) vs. 24 (16%); p = 0.032] but less often migraine [2 (1%) vs. 20 (13%); p < 0.001]. The most frequent symptoms in all patients were aphasia and dysarthria [107 (28%) and 92 (24%)]. Sensory impairments were less frequent in elderly patients [23 (11%) vs. 54 (30%); p < 0.001]. Impaired consciousness and orientation were independent predictors for TIA mimics (p < 0.001) whereas facial palsy (p < 0.001) motor weakness (p < 0.001), dysarthria (p = 0.022) and sensory impairment (p < 0.001) were independent predictors of TIA. Conclusion: TIA mimics in elderly patients are more likely to be internal medicine diseases and epilepsy compared to younger patients. Excluding internal medicine diseases seems to be important in elderly patients. Facial palsy, motor weakness, dysarthria and sensory impairment are associated with TIA.

Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy.

Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41-1.4) min-1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56-0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10-0.82]) compared to hyperperfusion (PPV = 0.93 [0.68-1.0]) or unaffected perfusion (PPV = 1.0 [0.75-1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression.

Differential effects of the SARS-CoV-2 pandemic on patients presenting to a neurological emergency room depending on their triage score in an area with low COVID-19 incidence.

BACKGROUND: We analyzed the effects of the SARS-CoV-2 pandemic on neurologic emergencies, depending on the patients' triage score in a setting with relatively few COVID-19 cases and without lack of resources. METHODS: Consecutive patients of a tertiary care center with a dedicated neurologic emergency room (nER) were analyzed. The time period of the first lockdown in Germany (calendar weeks 12-17, 2020) was retrospectively compared to the corresponding period in 2019 regarding the number of patients presenting to the nER, the number of patients with specific triage scores (Heidelberg Neurological Triage Score), the number of patients with stroke, and the quality of stroke care. RESULTS: A total of 4330 patients were included. Fewer patients presented themselves in 2020 compared to 2019 (median [interquartile range] per week: 134 [118-143] vs. 187 [182-192]; p = 0.015). The median numbers of patients per week with triage 1 (emergent) and 4 (non-urgent) were comparable (51 [43-58] vs. 59 [54-62]; p = 0.132, and 10 [4-16] vs. 16 [7-18]; p = 0.310, respectively).The median number of patients per week declined in categories 2 and 3 in 2020 (41 [37-45] vs. 57 [52-61]; p = 0.004, and 28 [23-35] vs. 61 [52-63]; p = 0.002, respectively. No change was observed in the absolute number of strokes (138 in 2019 and 141 in 2020). Quality metrics of stroke revascularization therapies (symptom-to-door time, door-to-needle time or relative number of therapies) and stroke severity remained constant. CONCLUSION: During the lockdown period in 2020, the number of patients with emergent symptoms remained constant, while fewer patients with urgent symptoms presented to the nER. This may imply behavioral changes in care-seeking behavior.

Safety of Mechanical Thrombectomy with Combined Intravenous Thrombolysis in Stroke Treatment 4.5 to 9 Hours from Symptom Onset.

BACKGROUND: An extended time window for intravenous thrombolysis (IVT) for acute stroke patients up to 9 hours from symptom onset has been established in recent trials, excluding patients who received mechanical thrombectomy (MT). We therefore investigated whether combined therapy with IVT and MT (IVT+MT) is safe in patients with ischemic stroke and large vessel occlusion (LVO) in an extended time window. METHODS: We retrospectively analyzed patients with anterior circulation ischemic stroke and LVO who were treated within 4.5 to 9 hours after symptom onset using MT with or without IVT. Primary endpoint was the occurrence of any intracranial hemorrhage (ICH). Multivariable logistic regression was used to adjust for potential confounders. RESULTS: In total, 168 patients were included in the study, 44 (26%) were treated with IVT+ MT. 133 (79%) patients had a M1-/distal carotid artery occlusion. Median ASPECT-Score was 8 (IQR 7-10) and complete reperfusion (mTICI 2b-3) was achieved in 132 (79%) patients. 18 (41%) of the patients in the IVT+MT group developed any ICH vs. 45 (36%) patients in the direct MT group (p=0.587). Symptomatic ICH occurred in 5 (11%) patients with IVT+MT vs. 8 (6%) patients receiving direct MT (p=0.295). In multivariable analysis, IVT+MT was not an independent predictor of ICH (adjusted for NIHSS, degree of reperfusion, symptom-onset-to-treatment time and therapy with tirofiban; OR 0.95 [95% CI 0.43-2.08], p=0.896). CONCLUSION: Mechanical thrombectomy in stroke patients seems to be safe with combined intravenous thrombolysis within 4.5 to 9 hours after onset as it did not significantly increase the risk for intracranial hemorrhage.

Distal arterial occlusions in patients with mild strokes - is endovascular therapy superior to thrombolysis alone?

BACKGROUND AND PURPOSE: Safety and efficacy of endovascular thrombectomy (EVT) in patients with mild stroke syndromes is unclear, especially in distal vessel occlusions. METHODS: We analysed in our stroke database (HeiReKa) between 2002 and April 2019 safety and efficacy of EVT compared to intravenous thrombolysis (IVT) in patients with occlusions distal to the M1 segment of the middle cerebral artery and the top of the basilar artery who presented with a National Institute of Health Stroke Scale (NIHSS) below 6. Excellent (good) outcome was defined as modified rankin scale (mRS) 0-1 (0-2) or return to baseline mRS (good) after 3 months. Safety endpoints were mortality after 3 months and intracranial hemorrhage according to the Heidelberg Bleeding Classification (HBC). RESULTS: Of 4167 patients 94 met the inclusion criteria. Sixty-four patients were allocated to the IVT group and 30 to the EVT group of which 15 also received IVT; three patients (4.6%) in the IVT group received rescue EVT. Baseline characteristics did not differ but more M2 occlusions were found in the EVT group (93.3% vs. 64.1%, p = 0.02). Intracranial bleeding occurred more often in EVT patients (HBC class 2: 13.3% vs. 1.6%, p = 0.01). Excellent and good outcome were not significantly different (75% vs. 70%, p = 0.65 and 87.5% vs. 73.3%, p = 0.14). Mortality was significantly lower in IVT patients (1.6% vs. 13.3%, p = 0.04). CONCLUSION: Rates of excellent and good outcome after IVT or EVT were almost similar, but safety parameters were increased after EVT. EVT may be considered in selected patients after careful risk/benefit analysis.

High-normal PaCO2 values might be associated with worse outcome in patients with subarachnoid hemorrhage - a retrospective cohort study.

BACKGROUND: While both hypercapnia and hypocapnia are harmful in patients with subarachnoid hemorrhage (SAH), it is unknown whether high-normal PaCO2 values are better than low-normal values. We hypothesized that high-normal PaCO2 values have more detrimental than beneficial effects on outcome. METHODS: Consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH) requiring mechanical ventilation treated in a tertiary care university hospital were retrospectively analyzed regarding the influence of PaCO2 on favorable outcome, defined as modified Rankin scale score < 3 at discharge. Primary endpoint was the difference in the proportion of PaCO2 values above 40 mmHg in relation to all measured PaCO2 values between patients with favorable and unfavorable outcome. RESULTS: 150 patients were included. Median age was 57 years (p25:50, p75:64), median Hunt-Hess score was 4 (p25:3, p75:5). PaCO2 values were mainly within normal range (median 39.0, p25:37.5, p75:41.4). Patients with favorable outcome had a lower proportion of high-normal PaCO2 values above 40 mmHg compared to patients with unfavorable outcome (0.21 (p25:0.13, p75:0.50) vs. 0.4 (p25:0.29, p75:0.59)) resulting in a lower chance for favorable outcome (OR 0.04, 95% CI 0.00-0.55, p = 0.017). In multivariable analysis adjusted for Hunt-Hess score, pneumonia and length of stay, elevated PaCO2 remained an independent predictor of outcome (OR 0.05, 95% CI 0.00-0.81, p = 0.035). CONCLUSIONS: A higher proportion of PaCO2 values above 40 mmHg was an independent predictor of outcome in patients with aSAH in our study. The results need to be confirmed in a prospective trial.

Development and validation of the Heidelberg Neurological Triage System (HEINTS).

BACKGROUND/OBJECTIVE: Neurological syndromes are underrepresented in existing triage systems which are not validated for neurological patients; therefore, we developed and validated the new Heidelberg Neurological Triage System (HEINTS) in a prospective, single-center observational study. METHODS: Patients were triaged according to the new triage system by nurses and physicians (stage 1) as well as trained nurses (stage 2). In stage 1, all patients presenting to the neurological emergency room (ER) were triaged by nurses and physicians. In stage 2, three specially trained nurses triaged patients according to HEINTS. The main outcomes comprised interrater agreement between nurses' and physicians' triage (stage 1), sensitivity and specificity to detect emergencies (stages 1 and 2), and improvement in triage quality as a result of training (stage 2), as well as correlation of HEINTS with hospital admissions and resource utilization. RESULTS: In stage 1 (n = 2423 patients), sensitivity and specificity to detect neurological emergencies were 84.2% (SD 0.8%) and 85.4% (SD 0.8%) for nurses, as well as 92.4% (SD 0.6%) and 84.1% (SD 0.9%) for physicians, respectively. The interrater-reliability between nurses and physicians in stage 1 was moderate [Cohen's kappa 0.44, standard deviation (SD) 0.02]. In stage 2 (n = 506 patients), sensitivity of trained nurses increased to 94.3% (SD 1.0%), while specificity decreased to 74.8% (SD 1.9%). Correlation of HEINTS triage with hospital admission and resource utilization in both stages was highly significant. CONCLUSIONS: HEINTS predicted hospital admissions and resource utilization. Agreement between nurses and physicians was moderate. HEINTS, applied by physicians and by nurses after training, reliably detected neurological emergencies.

Correlation of Tmax volumes with clinical outcome in anterior circulation stroke.

BACKGROUND AND PURPOSE: The recent thrombectomy trials have shown that perfusion imaging is helpful in proper patient selection in thromboembolic stroke. In this study, we analyzed the correlation of pretreatment Tmax volumes in MR and CT perfusion with clinical outcome after thrombectomy. METHODS: Forty-one consecutive patients with middle cerebral artery occlusion (MCA) or carotid T occlusion treated with thrombectomy were included. Tmax volumes at delays of >4, 6, 8, and 10 s as well as infarct core and mismatch ratio were automatically estimated in preinterventional MRI or CT perfusion using RAPID software. These perfusion parameters were correlated with clinical outcome. Outcome was assessed using modified Rankin scale at 90 days. RESULTS: In patients with successful recanalization of MCA occlusion, Tmax > 8 and 10 s showed the best linear correlation with clinical outcome (r = 0.75; p = .0139 and r = 0.73; p = .0139), better than infarct core (r = 0.43; p = .2592). In terminal internal carotid artery occlusions, none of the perfusion parameters showed a significant correlation with clinical outcome. CONCLUSIONS: Tmax at delays of >8 and 10 s is a good predictor for clinical outcome in MCA occlusions. In carotid T occlusion, however, Tmax volumes do not correlate with outcome.

Outcome of patients with proximal vessel occlusion of the anterior circulation and DWI-PWI mismatch is time-dependent.

BACKGROUND AND PURPOSE: Patients with ischemic stroke and large vessel occlusion are assumed to benefit from endovascular therapy (ET) independent of the symptom onset-to-treatment time (OTT) if they present with a mismatch of diffusion- and perfusion-weighted imaging (DWI-PWI mismatch). We aimed at studying the influence of OTT on clinical outcome in these patients. METHODS: Retrospective database review in a tertiary care university hospital. All patients presented with proximal vessel occlusion of the anterior circulation and DWI-PWI mismatch. Primary outcome was the influence of OTT on modified Rankin scale (mRS) score three months after treatment, dichotomized in favourable (0-2) and unfavourable outcome (3-6). Secondary outcome was the effect of OTT on the shift of the mRS score. Patients treated within an early time window (<340min) and a late time window (≥340min) were compared. RESULTS: 139 patients were included. The rate of favourable outcome was significantly higher in patients who were treated in an early compared to those treated in a late time window (31 [49%] vs. 20 patients [27%], p=0.005). Adjusted multivariate logistic regression revealed that late treatment was an independent negative predictor of favourable outcome (odds ratio 0.39, confidence interval [0.18-0.84]; p=0.016). A shift towards higher mRS scores for late treatment was evident (p=0.015). In sensitivity analysis, OTT remained an independent predictor when evaluated as continuous variable. These findings were confirmed in patients with a comparable DWI-PWI mismatch according to the definitions from large trials (DEFUSE 2, DEFUSE 3, SWIFT-PRIME, EXTEND-IA). CONCLUSION: Outcome of patients with comparable DWI-PWI mismatch is time-dependent.

T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain.

Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P < .0001). Conclusion T1ρ-weighted DGE MR imaging in healthy volunteers and patients with newly diagnosed, untreated glioblastoma enabled visualization of brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue. © RSNA, 2017 Online supplemental material is available for this article.

Tumor Infiltration in Enhancing and Non-Enhancing Parts of Glioblastoma: A Correlation with Histopathology.

PURPOSE: To correlate histopathologic findings from biopsy specimens with their corresponding location within enhancing areas, non-enhancing areas and necrotic areas on contrast enhanced T1-weighted MRI scans (cT1). MATERIALS AND METHODS: In 37 patients with newly diagnosed glioblastoma who underwent stereotactic biopsy, we obtained a correlation of 561 1mm3 biopsy specimens with their corresponding position on the intraoperative cT1 image at 1.5 Tesla. Biopsy points were categorized as enhancing (CE), non-enhancing (NE) or necrotic (NEC) on cT1 and tissue samples were categorized as "viable tumor cells", "blood" or "necrotic tissue (with or without cellular component)". Cell counting was done semi-automatically. RESULTS: NE had the highest content of tissue categorized as viable tumor cells (89% vs. 60% in CE and 30% NEC, respectively). Besides, the average cell density for NE (3764 ± 2893 cells/mm2) was comparable to CE (3506 ± 3116 cells/mm2), while NEC had a lower cell density with 2713 ± 3239 cells/mm2. If necrotic parts and bleeds were excluded, cell density in biopsies categorized as "viable tumor tissue" decreased from the center of the tumor (NEC, 5804 ± 3480 cells/mm2) to CE (4495 ± 3209 cells/mm2) and NE (4130 ± 2817 cells/mm2). DISCUSSION: The appearance of a glioblastoma on a cT1 image (circular enhancement, central necrosis, peritumoral edema) does not correspond to its diffuse histopathological composition. Cell density is elevated in both CE and NE parts. Hence, our study suggests that NE contains considerable amounts of infiltrative tumor with a high cellularity which might be considered in resection planning.

Endovascular stroke therapy may be safe in patients with elevated international normalized ratio.

INTRODUCTION: Endovascular therapy in acute ischemic stroke is safe and efficient. However, patients receiving oral anticoagulation were excluded in the larger trials. OBJECTIVE: To analyze the safety of endovascular therapy in patients with acute ischemic stroke and elevated international normalized ratio (INR) values. METHODS: Retrospective database review of a tertiary care university hospital for patients with anterior circulation stroke treated with endovascular therapy. Patients with anticoagulation other than vitamin K antagonists were excluded. The primary safety endpoint was defined as symptomatic intracranial hemorrhage (sICH; ECASS II definition). The efficacy endpoint was the modified Rankin scale (mRS) score after 3 months, dichotomized into favorable outcome (mRS 0-2) and unfavorable outcome (mRS 3-6). RESULTS: 435 patients were included. 90% were treated with stent retriever. 27 (6.2%) patients with an INR of 1.2-1.7 and 21 (4.8%) with an INR >1.7. 33 (7.6%) had sICH and 149 patients (34.3%) had a favorable outcome. Patients with an elevated INR did not have an increased risk for sICH or unfavorable outcome in multivariable analysis. The additional use of IV thrombolysis in patients with an INR of 1.2-1.7 did not increase the risk of sICH or unfavorable outcome. These results were replicated in a sensitivity analysis introducing an error of the INR of ±5%. They were also confirmed using other sICH definitions (Safe Implementation of Thrombolysis in Stroke (SITS), National Institute of neurological Disorders and Stroke (NINDS), Heidelberg bleeding classification). CONCLUSIONS: Endovascular therapy in patients with an elevated INR is safe and efficient. Patients with an INR of 1.2-1.7 may be treated with combined IV thrombolysis and endovascular therapy.

Adiabatically prepared spin-lock approach for T1ρ-based dynamic glucose enhanced MRI at ultrahigh fields.

PURPOSE: Chemical exchange sensitive spin-lock and related techniques allow to observe the uptake of administered D-glucose in vivo. The exchange-weighting increases with the magnetic field strength, but inhomogeneities in the radiofrequency (RF) field at ultrahigh field whole-body scanners lead to artifacts in conventional spin-lock experiments. Thus, our aim was the development of an adiabatically prepared T1ρ -based imaging sequence applicable to studies of glucose metabolism in tumor patients at ultrahigh field strengths. METHODS: An adiabatically prepared on-resonant spin-lock approach was realized at a 7 Tesla whole-body scanner and compared with conventional spin-lock. The insensitivity to RF field inhomogeneities as well as the chemical exchange sensitivity of the approach was investigated in simulations, model solutions and in the human brain. RESULTS: The suggested spin-lock approach was shown to be feasible for in vivo application at ultrahigh field whole-body scanners and showed substantially improved image quality compared with conventional spin-lock. The sensitivity of the presented method to glucose was verified in model solutions and a glucose contrast was observed in a glioblastoma patient after intravenous administration of glucose solution. CONCLUSION: An adiabatically prepared spin-lock preparation was presented that enables a homogeneous and chemical exchange sensitive T1ρ -based imaging at ultra-high field whole-body scanners, e.g., for T1ρ -based dynamic glucose enhanced MRI. Magn Reson Med 78:215-225, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial.

Importance: Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from randomized trials. Objective: To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy. Design, Setting, and Participants: SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment), a single-center, randomized, parallel-group, open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany (April 2014-February 2016) included 150 patients with acute ischemic stroke in the anterior circulation, higher National Institutes of Health Stroke Scale (NIHSS) score (>10), and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery. Intervention: Patients were randomly assigned to an intubated general anesthesia group (n = 73) or a nonintubated conscious sedation group (n = 77) during stroke thrombectomy. Main Outcomes and Measures: Primary outcome was early neurological improvement on the NIHSS after 24 hours (0-42 [none to most severe neurological deficits; a 4-point difference considered clinically relevant]). Secondary outcomes were functional outcome by modified Rankin Scale (mRS) after 3 months (0-6 [symptom free to dead]), mortality, and peri-interventional parameters of feasibility and safety. Results: Among 150 patients (60 women [40%]; mean age, 71.5 years; median NIHSS score, 17), primary outcome was not significantly different between the general anesthesia group (mean NIHSS score, 16.8 at admission vs 13.6 after 24 hours; difference, -3.2 points [95% CI, -5.6 to -0.8]) vs the conscious sedation group (mean NIHSS score, 17.2 at admission vs 13.6 after 24 hour; difference, -3.6 points [95% CI, -5.5 to -1.7]); mean difference between groups, -0.4 (95% CI, -3.4 to 2.7; P = .82). Of 47 prespecified secondary outcomes analyzed, 41 showed no significant differences. In the general anesthesia vs the conscious sedation group, substantial patient movement was less frequent (0% vs 9.1%; difference, 9.1%; P = .008), but postinterventional complications were more frequent for hypothermia (32.9% vs 9.1%; P < .001), delayed extubation (49.3% vs 6.5%; P < .001), and pneumonia (13.7% vs 3.9%; P = .03). More patients were functionally independent (unadjusted mRS score, 0 to 2 after 3 months [37.0% in the general anesthesia group vs 18.2% in the conscious sedation group P = .01]). There were no differences in mortality at 3 months (24.7% in both groups). Conclusions and Relevance: Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy, conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours. The study findings do not support an advantage for the use of conscious sedation. Trial Registration: clinicaltrials.gov Identifier: NCT02126085.

Capillary Transit Time Heterogeneity Is Associated with Modified Rankin Scale Score at Discharge in Patients with Bilateral High Grade Internal Carotid Artery Stenosis.

BACKGROUND AND PURPOSE: Perfusion weighted imaging (PWI) is inherently unreliable in patients with severe perfusion abnormalities. We compared the diagnostic accuracy of a novel index of microvascular flow-patterns, so-called capillary transit time heterogeneity (CTH) to that of the commonly used delay parameter Tmax in patients with bilateral high grade internal carotid artery stenosis (ICAS). METHODS: Consecutive patients with bilateral ICAS ≥ 70%NASCET who underwent PWI were retrospectively examined. Maps of CTH and Tmax were analyzed with a volumetric approach using several thresholds. Predictors of favorable outcome (modified Rankin scale at discharge 0-2) were identified using univariate and receiver operating characteristic (ROC) curve analysis. RESULTS: Eighteen patients were included. CTH ≥ 30s differentiated best between patients with favorable and unfavorable outcome when both hemispheres were taken into account (sensitivity 83%, specificity 73%, area under the curve [AUC] 0.833 [confidence interval (CI) 0.635; 1.000]; p = 0.027). The best discrimination using Tmax was achieved with a threshold of ≥ 4s (sensitivity 83%, specificity 64%, AUC 0.803 [CI 0.585;1.000]; p = 0.044). The highest AUC was found for left sided volume with CTH ≥ 15s (sensitivity 83%, specificity 91%, AUC 0.924 [CI 0.791;1.000]; p = 0.005). CONCLUSION: The study suggests that CTH is superior to Tmax in discriminating ICAS patients with favorable from non-favorable outcome. This finding may reflect the simultaneous involvement of large vessels and microvessels in ICAS and underscore the need to diagnose and manage both aspects of the disease.