Frequency, clinical presentation and outcome of vigilance impairment in patients with uni- and bilateral ischemic infarction of the paramedian thalamus

Ischemic stroke of the paramedian thalamus is a rare differential diagnosis in sudden altered vigilance states. While efforts to describe clinical symptomatology exist, data on the frequency of paramedian thalamic stroke as a cause of sudden impaired vigilance and on accompanying clinical signs and outcome are scarce. We retrospectively analyzed consecutive patients admitted to a tertiary stroke center between 2010 and 2019 diagnosed with paramedian thalamic stroke. We evaluated frequency of vigilance impairment (VI) due to paramedian thalamic stroke, accompanying clinical signs and short-term outcome in uni- versus bilateral paramedian lesion location. Of 3896 ischemic stroke patients, 53 showed a paramedian thalamic stroke location (1.4%). VI was seen in 29/53 patients with paramedian thalamic stroke and in 414/3896 with any stroke (10.6%). Paramedian thalamic stroke was identified as causal to VI in 3.4% of all patients with initial VI in the emergency department and in 0.7% of all ischemic stroke patients treated in our center. Accompanying clinical signs were detected in 21 of these 29 patients (72.4%) and facilitated a timely diagnosis. VI was significantly more common after bilateral than unilateral lesions (92.0% vs. 21.4%; p < 0.001). Patients with bilateral paramedian lesions were more severely affected, had longer hospital stays and more frequently required in-patient rehabilitation. Paramedian thalamic lesions account for about 1 in 15 stroke patients presenting with impaired vigilance. Bilateral paramedian lesion location is associated with worse stroke severity and short-term outcome. Paying attention to accompanying clinical signs is of importance as they may facilitate a timely diagnosis

Can intracranial time-of-flight-MR angiography predict extracranial carotid artery stenosis?

Objectives: Extracranial stenosis of the internal carotid artery (ICA) is an important cause of ischemic stroke and transient ischemic attack (TIA). It can be diagnosed using contrast-enhanced CT or MR angiography (MRA) as well as Doppler ultrasound. In this study, we assessed the diagnostic value of intracranial time-of-flight (TOF) MRA to predict extracranial ICA stenosis (ICAS). Methods: We retrospectively analyzed consecutive patients with acute ischemic stroke or TIA and middle- (50-69%) or high-grade (70-99%) unilateral extracranial ICAS according to NASCET criteria assessed by ultrasound between January 2016 and August 2018. The control group consisted of patients without extracranial ICAS. Intraluminal signal intensities (SI) of the intracranial ICA on the side of the extracranial stenosis were compared to the contralesional side on TOF-MRA source images. SI ratios (SIR) of contralesional:lesional side were compared between groups. Results: In total, 151 patients were included in the main analysis. Contralesional:lesional SIR in the intracranial C4-segment was significantly higher in patients with ipsilateral extracranial ICA stenosis (n = 51, median 74 years, 57% male) compared to the control group (n = 100, median 68 years, 48% male). Mean SIR was 1.463 vs. 1.035 (p < 0.001) for right-sided stenosis and 1.362 vs. 1.000 (p < 0.001) for left-sided stenosis. Receiver-operating characteristic curve demonstrated a cut-off value of 1.086 for right-sided [sensitivity/specificity 75%/81%; area under the curve (AUC) 0.81] and 1.104 for left-sided stenosis (sensitivity/specificity 70%/84%; AUC 0.80) in C4 as a good predictor for high-grade extracranial ICAS. Conclusions: SIR on TOF-MRA can be a marker of extracranial ICAS

Frequency of silent brain infarction in transient global amnesia

Background: and purpose To determine the frequency and distribution pattern of acute DWI lesions outside the hippocampus in patients clinically presenting with Transient Global Amnesia (TGA). Methods: Consecutive patients clinically presenting with TGA between January 2010 and January 2017 admitted to our hospital were retrospectively evaluated. All patients fulfilled diagnostic criteria of TGA. We analyzed imaging and clinical data of all patients undergoing MRI with high-resolution diffusion-weighted imaging within 72 h from symptom onset. Results: A total of 126 cases were included into the study. Fifty-three percent (n = 71/126) presented with one or more acute lesions in hippocampal CA1-area. Additional acute DWI lesions in other cortical regions were found in 11% (n = 14/126). All patients with DWI lesions outside the hippocampus presented with neurological symptoms typical for TGA (without additional symptoms.) Conclusions: In a relevant proportion of clinical TGA patients, MRI reveals acute ischemic cerebral lesions. Therefore, cerebral MRI should be performed in patients with TGA to identify a possible cardiac involvement and to detect stroke chameleons

Validation as New Imaging Biomarker

Background In order to select patients most likely to benefit for thrombolysis and to predict patient outcome in acute ischemic stroke, the volumetric assessment of the infarcted tissue is used. However, infarct volume estimation on Diffusion weighted imaging (DWI) has moderate interrater variability despite the excellent contrast between ischemic lesion and healthy tissue. In this study, we compared volumetric measurements of DWI hyperintensity to a simple maximum orthogonal diameter approach to identify thresholds indicating infarct size >70 ml and >100 ml. Methods Patients presenting with ischemic stroke with an NIHSS of ≥ 8 were examined with stroke MRI within 24 h after symptom onset. For assessment of the orthogonal DWI lesion diameters (od- values) the image with the largest lesion appearance was chosen. The maximal diameter of the lesion was determined and a second diameter was measured perpendicular. Both diameters were multiplied. Od-values were compared to volumetric measurement and od-value thresholds identifying a lesion size of > 70 ml and > 100 ml were determined. In a selected dataset with an even distribution of lesion sizes we compared the results of the od value thresholds with results of the ABC/2 and estimations of lesion volumes made by two resident physicians. Results For 108 included patients (53 female, mean age 71.36 years) with a median infarct volume of 13.4 ml we found an excellent correlation between volumetric measures and od-values (r2 = 0.951). Infarct volume >100 ml corresponds to an od-value cut off of 42; > 70 ml corresponds to an od-value of 32. In the compiled dataset (n = 50) od-value thresholds identified infarcts > 100 ml / > 70 ml with a sensitivity of 90%/ 93% and with a specificity of 98%/ 89%. The od-value offered a higher accuracy in identifying large infarctions compared to both visual estimations and the ABC/2 method. Conclusion The simple od-value enables identification of large DWI lesions in acute stroke. The cutoff of 42 is useful to identify large infarctions with volume larger than 100 ml. Further studies can analyze the therapeutic utility of this new method

Cardiac Troponin and Recurrent Major Vascular Events after Minor Stroke or Transient Ischemic Attack

Objective: This study was undertaken to investigate whether high-sensitivity cardiac troponin T (hs-cTnT) is associated with major adverse cardiovascular events (MACE) in patients with minor stroke or transient ischemic attack (TIA), and whether this association differs after risk stratification based on the Age, Blood Pressure, Clinical Features, Duration of Symptoms, Diabetes (ABCD2 ) score. Methods: INSPiRE-TMS was a randomized controlled trial allocating patients with minor stroke or TIA to an intensified support program or conventional care. In this post hoc analysis, participants were categorized using hs-cTnT levels (5th generation; Roche Diagnostics, Manheim, Germany; 99th percentile upper reference limit [URL] = 14ng/l). Vascular risk was stratified using the ABCD2 score (lower risk = 0-5 vs higher risk = 6-7). Cox proportional hazard regression was performed using covariate adjustment and propensity score matching (PSM) for the association between hs-cTnT and MACE (stroke/nonfatal coronary event/vascular death). Results: Among 889 patients (mean age = 70 years, 37% female), MACE occurred in 153 patients (17.2%) during a mean follow-up of 3.2 years. hs-cTnT was associated with MACE (9.3%/yr, >URL vs 4.4%/yr, ≤URL, adjusted hazard ratio [HR] = 1.63 [95% confidence interval (CI) = 1.13-2.35], adjusted HR [Q4 vs Q1 ] = 2.57 [95% CI = 1.35-4.97], adjusted HR [log-transformed] = 2.31 [95% CI = 1.37-3.89]). This association remained after PSM (adjusted HR = 1.76 [95% CI = 1.14-2.72]). There was a significant interaction between hs-cTnT and ABCD2 category for MACE occurrence (pinteraction = 0.04). In the lower risk category, MACE rate was 9.5%/yr in patients with hs-cTnT > URL, which was higher than in those ≤URL (3.8%/yr) and similar to the overall rate in the higher risk category. Interpretation: hs-cTnT levels are associated with incident MACE within 3 years after minor stroke or TIA and may help to identify high-risk individuals otherwise deemed at lower risk based on the ABCD2 score. If confirmed in independent validation studies, this might warrant intensified secondary prevention measures and cardiac diagnostics in stroke patients with elevated hs-cTnT

HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology

We present HepatoNet1, a manually curated large-scale metabolic network of the human hepatocyte that encompasses >2500 reactions in six intracellular and two extracellular compartments.Using constraint-based modeling techniques, the network has been validated to replicate numerous metabolic functions of hepatocytes corresponding to a reference set of diverse physiological liver functions.Taking the detoxification of ammonia and the formation of bile acids as examples, we show how these liver-specific metabolic objectives can be achieved by the variable interplay of various metabolic pathways under varying conditions of nutrients and oxygen availability

High‐Sensitivity Cardiac Troponin T and Recurrent Vascular Events After First Ischemic Stroke

Background: Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with recurrent vascular events and death in patients with first-ever, mild to moderate ischemic stroke. Methods and Results: We used data from the PROSCIS-B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs-cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all-cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs-cTnT above upper reference limit, 39.2%). During a mean follow-up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all-cause death. The primary outcome occurred more often in patients with hs-cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3-3.3), with a dose-response relationship when the highest and lowest hs-cTnT quartiles were compared (15.2 versus 1.8 events per 100 person-years; adjusted hazard ratio, 4.8; 95% CI, 1.9-11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions: Hs-cTnT is dose-dependently associated with an increased risk of recurrent vascular events and death within 3 years after first-ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs-cTnT for individualized risk stratification after stroke. Registration URL: ; Unique identifier: NCT01363856

Assessment of thrombus length in acute ischemic stroke by post-contrast magnetic resonance angiography

Hintergrund: Für die erfolgreiche Rekanalisation beim akuten ischämischen Schlaganfall ist die Thrombuslänge ein wesentlicher Faktor. Die Post-Kontrastmittel (KM) Magnetresonanz-Angiographie (MRA) erlaubt über leptomeningealen Kollateralfluss die Darstellung von Gefäßabschnitten distal des intrakraniellen arteriellen Thrombus beim akuten ischämischen Schlaganfall. In dieser Arbeit untersuchen wir die Hypothese, dass die Post-KM MRA eine präzise Quantifizierung der Thrombuslänge in verschiedenen intrakraniellen Gefäßen ermöglicht. Methoden: Patienten mit MR-tomographischem Nachweis eines ischämischen Hirninfarkts mit intrakraniellem Gefäßverschluss, die sich innerhalb von 24h nach Symptombeginn in unserem Krankenhaus vorstellten, wurden prospektiv evaluiert. Die Post-KM MRA wurde zu einem standardgemäßen Schlaganfall-MRT Protokoll hinzugefügt. Eine Dickschicht-3D-Rekonstruktion der Maximalen Intensitätsprojektion wurde verwendet, um die Thrombuslänge zu messen. Das klinische Outcome bei Entlassung wurde mit der modifizierten Rankin Skala (mRS) ermittelt. Ergebnisse: Insgesamt wurden 34 Patienten (medianes Alter 72 Jahre) mit einem medianen National Institutes of Health Stroke Scale score von 11 und einem medianen Zeitintervall von 116 min. zwischen Symptombeginn und Bildgebung eingeschlossen. Die Post-KM MRA ermöglichte die Darstellung des proximalen und distalen Endes des Thrombus in 31 Patienten (91%). In drei Patienten (9%) stellte sich in der Post-KM MRA ein partieller Verschluss dar. Die mediane Thrombuslänge bei Patienten mit vollständigem Gefäßverschluss betrug 9,9 mm (Interquartilsabstände [IQR] 1.6-14.0 mm). Patienten mit schlechten klinischen Outcome (mRS größer-gleich 3) hatten signifikant längere Thromben als Patienten mit gutem klinischen Outcome, definiert als mRS kleiner-gleich 2 (median 11.3 mm [IQR 7.15-16.6] versus median 5.5 mm [IQR 2.8-8.8]; P = 0.011). Schlussfolgerung: Die Post-KM MRA ermöglicht die adäquate Quantifizierung der intrakraniellen, arteriellen Thrombuslänge in verschiedenen Gefäßterritorien. Die Thrombuslänge ist dabei mit einem schlechteren klinischen Outcome assoziiert.Background and Purpose: Intra-arterial thrombus length is an important predictor for recanalization success in patients with acute ischemic stroke. Postcontrast magnetic resonance angiography (MRA) with leptomeningeal flow enables visualization of vessel segments distal to an intracranial arterial thrombus in acute ischemic stroke. We hypothesized that postcontrast MRA allows precise assessment of clot length in different intracranial vessels. Methods: Patients with MRI-confirmed ischemic stroke and intracranial artery occlusion at different vessel sites admitted to our hospital within 24 hours of symptom onset were prospectively evaluated. Postcontrast MRA was added to a standard stroke MRI protocol. Thrombus length was measured on thick slab maximum intensity projection images. Clinical outcome at hospital discharge was assessed by modified Rankin Scale (mRS). Results: Overall, thirty-four patients (median age 72 years) presenting with a median National Institutes of Health Stroke Scale score of 11 and a median onset to imaging time of 116 minutes were included. Postcontrast MRA enabled depiction of proximal and distal terminus of the thrombus in 31 patients (91%), whereas in three patients (9%) postcontrast MRA presented a partial occlusion. Median thrombus length in patients with complete occlusion was 9.9 mm (Interquartile range 1.6-14.0 mm). In patients with poor outcome (mRS 3) median thrombus length was significantly longer than in those with good outcome, defined as mRS 2 (median 11.3 mm [IQR 7.15-16.6] versus median 5.5 mm [IQR 2.8-8.8]; P = 0.011;). Conclusions: Postcontrast MRA accurately demonstrates intraarterial thrombus length at different vessel occlusion sites. Thrombus length is associated with poor clinical outcome

Frequency, clinical presentation and outcome of vigilance impairment in patients with uni- and bilateral ischemic infarction of the paramedian thalamus

Ischemic stroke of the paramedian thalamus is a rare differential diagnosis in sudden altered vigilance states. While efforts to describe clinical symptomatology exist, data on the frequency of paramedian thalamic stroke as a cause of sudden impaired vigilance and on accompanying clinical signs and outcome are scarce. We retrospectively analyzed consecutive patients admitted to a tertiary stroke center between 2010 and 2019 diagnosed with paramedian thalamic stroke. We evaluated frequency of vigilance impairment (VI) due to paramedian thalamic stroke, accompanying clinical signs and short-term outcome in uni- versus bilateral paramedian lesion location. Of 3896 ischemic stroke patients, 53 showed a paramedian thalamic stroke location (1.4%). VI was seen in 29/53 patients with paramedian thalamic stroke and in 414/3896 with any stroke (10.6%). Paramedian thalamic stroke was identified as causal to VI in 3.4% of all patients with initial VI in the emergency department and in 0.7% of all ischemic stroke patients treated in our center. Accompanying clinical signs were detected in 21 of these 29 patients (72.4%) and facilitated a timely diagnosis. VI was significantly more common after bilateral than unilateral lesions (92.0% vs. 21.4%; p &amp;lt; 0.001). Patients with bilateral paramedian lesions were more severely affected, had longer hospital stays and more frequently required in-patient rehabilitation. Paramedian thalamic lesions account for about 1 in 15 stroke patients presenting with impaired vigilance. Bilateral paramedian lesion location is associated with worse stroke severity and short-term outcome. Paying attention to accompanying clinical signs is of importance as they may facilitate a timely diagnosis

Adapting the Computed Tomography Criteria of Hemorrhagic Transformation to Stroke Magnetic Resonance Imaging

Background: The main safety aspect in the use of stroke thrombolysis and in clinical trials of new pharmaceutical or interventional stroke therapies is the incidence of hemorrhagic transformation (HT) after treatment. The computed tomography (CT)-based classification of the European Cooperative Acute Stroke Study (ECASS) distinguishes four categories of HTs. An HT can range from a harmless spot of blood accumulation to a symptomatic space-occupying parenchymal bleeding associated with a massive deterioration of symptoms and clinical prognosis. In magnetic resonance imaging (MRI) HTs are often categorized using the ECASS criteria although this classification has not been validated in MRI. We developed MRI-specific criteria for the categorization of HT and sought to assess its diagnostic reliability in a retrospective study. Methods: Consecutive acute ischemic stroke patients, who had received a 3-tesla MRI before and 12-36 h after thrombolysis, were screened retrospectively for an HT of any kind in post-treatment MRI. Intravenous tissue plasminogen activator was given to all patients within 4.5 h. HT categorization was based on a simultaneous read of 3 different MRI sequences (fluid-attenuated inversion recovery, diffusion-weighted imaging and T2* gradient-recalled echo). Categorization of HT in MRI accounted for the various aspects of the imaging pattern as the shape of the bleeding area and signal intensity on each sequence. All data sets were independently categorized in a blinded fashion by 3 expert and 3 resident observers. Interobserver reliability of this classification was determined for all observers together and for each group separately by calculating Kendall's coefficient of concordance (W). Results: Of the 186 patients screened, 39 patients (21%) had an HT in post-treatment MRI and were included for the categorization of HT by experts and residents. The overall agreement of HT categorization according to the modified classification was substantial for all observers (W = 0.79). The degrees of agreement between experts (W = 0.81) and between residents (W = 0.87) were almost perfect. For the distinction between parenchymal hematoma and hemorrhagic infarction, the interobserver agreement was almost perfect for all observers taken together (W = 0.82) as well as when experts (W = 0.82) and residents (W = 0.91) were analyzed separately. Conclusion: The ECASS CT classification of HT was successfully adapted for usage in MRI. It leads to a substantial to almost perfect interobserver agreement and can be used for safety assessment in clinical trials