BACKGROUND:Growing evidence suggests that thrombus composition may influences embolic stroke severity, treatment response, and patient outcomes. While previous studies have characterized histopathological differences between cardioembolic stroke (CES) and atheroembolic stroke (AES), less is known about embolic strokes of undetermined source (ESUS). This study examines the relationship between embolic stroke etiology, thrombus composition, and clinical outcomes to improve classification and guide therapeutic strategies. METHODS:This retrospective study included 323 patients with acute embolic ischemic stroke treated with mechanical thrombectomy. Stroke etiology was classified as CES (n = 151), AES (n = 71), or ESUS (n = 81). Histopathological examination was performed on 127 retrieved thrombi, assessing fibrin architecture, platelet distribution, neutrophil content, and red blood cell integrity. Clinical parameters, including National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), length of hospital stay, and in-hospital mortality, were analyzed. Statistical models examined associations between thrombus characteristics, stroke etiology, and functional recovery. RESULTS:CES thrombi exhibited higher platelet and neutrophil content, with a dense, centrally concentrated platelet distribution consistent with fibrin-rich, compact thrombi. In contrast, AES thrombi showed a more diffuse, net-like distribution of platelets, aligning with high-shear conditions in stenotic arteries. ESUS thrombi closely resembled AES but contained a heterogeneous fibrin profile, including the highest proportion of compact fibrin, suggesting alternative thrombus maturation mechanisms. Patients with AES exhibited the poorest functional recovery (lowest NIHSS and mRS improvement), despite successful recanalization. ESUS had the highest in-hospital mortality. Stroke mechanism was significantly associated with both thrombus composition and patient outcomes in this study. CONCLUSIONS:Thrombus histopathology varies significantly by stroke etiology, with platelet distribution emerging as a strong classifier. ESUS thrombi exhibit hybrid features, emphasizing the need for improved classification. Clinical outcomes differed across etiologies, with AES patients experiencing the slowest recovery and ESUS patients exhibiting the highest in-hospital mortality. Integrating thrombus characteristics into risk stratification models, secondary prevention strategies, and artificial intelligence-driven classification may enhance acute stroke management.

Endovascular treatment of strokes caused by large vessel occlusion enables the histopathological investigation of the retrieved embolus, possibly providing a novel opportunity to contribute to the diagnostic workup of etiology and to define secondary prevention measures in strokes with uncertain genesis. We aimed to develop a classification rule based on pathophysiological considerations and adjustment to reference thrombi for distinction between cardiac and arteriosclerotic emboli and to validate this classification rule on a patient cohort. From 125 patients with stroke due to large vessel occlusion and thrombectomy, 82 patients with known etiology (55 cardioembolic and 27 arterioembolic strokes) were included. The corresponding emboli were histologically evaluated by two raters blinded to the etiology of stroke by means of a novel classification rule. Presumed etiology and classification results were compared. Agreement concerning cardiac emboli was 72.2% (95% CI: 58.4–83.5) for rater I and 78.2% (95% CI: 65.0–88.2) for rater II. Agreement concerning arteriosclerotic emboli was 70.4% (95% CI: 49.8–86.3) for rater I and 74.1% (95% CI: 53.7–88.9) for rater II. Overall agreement reached 71.6% (95% CI: 60.5–81.1) for rater I and 76.8% (95% CI: 66.2–85.4) for rater II. Within the limits of generally restricted accuracy of histological evaluations, the classification rule differentiates between cardiac and arteriosclerotic emboli of acute ischemic stroke patients. Further improvement is needed to provide valuable complementary data for stroke etiology workup.

Background Thrombus histology has become a potential diagnostic tool for the etiology assessment of patients with ischemic stroke caused by embolic proximal vessel occlusion. We validated a classification rule that differentiates between cardiac and arteriosclerotic emboli in individual stroke patients. We aim to describe in detail the development of this classification rule and disclose its reliability. Methods The classification rule is based on the hypothesis that cardiac emboli arise out of separation thrombi and arteriosclerotic emboli result from agglutinative thrombi. 125 emboli recovered by thrombectomy from stroke patients and 11 thrombi serving as references for cardiac (n = 5) and arteriosclerotic emboli (n = 6) were Hematoxylin and eosin, Elastica-van Gieson and CD61 stained and rated independently by two histopathologists blinded to the presumed etiology by several pre-defined criteria. Intra- and interobserver reliabilities of all criteria were determined. Out of the different criteria, three criteria with the most satisfactory reliability values were selected to compose the classification rule that was finally adjusted to the reference thrombi. Reliabilities of the classification rule were calculated by using the emboli of stroke patients. Results The classification rule reached intraobserver reliabilities for the two raters of 92.9% and 68.2%, respectively. Interobserver reliability was 69.9%. Conclusions A new classification rule for emboli obtained from thrombectomy was established. Within the limitations of histological investigations, it is reliable and able to distinguish between cardioembolic and arteriosclerotic emboli.

We present two cases of ChAdOx1 nCov-19 (AstraZeneca)-associated thrombotic thrombocytopenia syndrome (TTS) and cerebral venous sinus thrombosis (CVST). At the time of emergency room presentation due to persistent headache, blood serum levels revealed reduced platelet counts. Yet, 1 or 4 days after the onset of the symptom, the first MR-angiography provided no evidence of CVST. Follow-up imaging, performed upon headache refractory to nonsteroidal pain medication verified CVST 2–10 days after initial negative MRI. Both the patients received combined treatment with intravenous immunoglobulins and parenteral anticoagulation leading to an increase of platelet concentration in both the individuals and resolution of the occluded cerebral sinus in one patient.

Background: Optimizing thrombolytic therapy is vital for improving stroke outcomes. We aimed to evaluate the efficacy of tenecteplase (TNK) compared to the current gold standard rt-PA (alteplase), with and without additional ultrasound treatment. Methods: In vitro clots that are similar to ex vivo clots concerning their histological condition and their durability were generated from whole blood. For five treatment groups we compared relative clot weight loss (each n=60) and fibrin fiber density in transmission electron microscopy (TEM) (each n=5). The control group (A) was treated only with plasma. Two groups were designated for each rt-PA (B+C) and TNK (D+E). Groups C and E were additionally treated with ultrasound. Dosages were 50µg/ml for rt-PA and 30µg/ml for TNK. Results were evaluated by using analyses of variance (ANOVA) and post-hoc t-tests. Results: Weight loss was increased significantly for all groups compared to the control group. Both TNK groups showed significantly increased weight loss compared to their counterpart rt-PA group (p≤0.001). For TEM only group D showed significantly decreased fibrin fiber density (p<0.05) compared to both rt-PA groups. Ultrasound did not significantly increase dissolution of clots with either method (best p=0.16). Conclusions: Tenecteplase dissolved clots more effectively than rt-PA with and without ultrasound. A higher sample size could provide more convincing results for TEM. Keywords: Stroke, thrombolysis, tenecteplase, ultrasound, transmission electron microscopy.

Objectives: Endovascular treatment (ET), in addition to a therapy with intravenous recombinant tissue plasminogen activator IV rt-PA in patients with acute ischemic stroke, has been found to improve outcome. However, data about ET in patients who have not received therapy with rt-PA due to contraindications for IV rt-PA are sparse. Comparison of ET with IV rt-PA versus ET alone in patients with stroke is done using a proximal intracranial arterial occlusion (internal carotid artery, middle cerebral artery (M1-Segment)). Methods: During a 5-year period (2011-2016), 236 patients (mean age, 69 +/- 14years; 46% women; median NIHSS score 13 +/- 5) who were treated at the Department of Neurology and Neuroradiology at the University of Lubeck, undergoing ET with or without IV rt-PA were included and analyzed. Results: A total of 144 patients (61%) underwent ET + IV rt-PA, and 92 patients (39%) underwent ET only. The ET with IV rt-PA is associated with a higher rate of favorable functional outcomes (mRS2) at discharge from hospital (51.4% vs. 23.1%, p < .001) and lower rate of in-hospital mortality (9% vs. 19.6%, rho = .019) and symptomatic intracerebral hemorrhage [sICH] (2.1% vs. 8.7%; rho = .019) compared to ET, whereas the modified treatment in cerebral infarction score (mTICI) did not differ between the groups. In the adjusted logistic regression analysis, the ET + IV rt-PA was associated with an increased probability of favorable functional outcome (OR, 4.3; 95% confidence interval [CI], 2.2-8.5; rho < .001). For the in-hospital mortality (OR, 0.74; 95% CI, 0.29-1.9; rho = .76) and sICH (OR, 0.3; 95% CI, 0.07-1.2; rho = .09), no differences were found. Conclusion: Recanalization results after endovascular treatment are not relevantly improved in patients receiving rt-PA. However, an additional therapy with IV rt-PA has a positive impact on functional outcome.

Cerebrospinal fluid (CSF) flow is sensitive to many cerebral disorders. We aimed to develop a noninvasive bedside method to detect physiological and pathological CSF phenomena by measuring pulsation patterns of the third ventricle. By transcranial B-mode ultrasound, electrocardiography (ECG)-gated video loops of the third ventricle were acquired. "Speckle tracking" software was used to quantify the relative change of its width. We conducted measurements of nine cardiac cycles in 11 healthy subjects in sitting and in supine position during Valsalva maneuver to investigate the influence of an increased intracranial pressure on the relative deformation of the third ventricle. In one patient with occlusive hydrocephalus, 19 cardiac cycles were measured in sitting position before and after removal of a tumorous obstruction of the aqueduct of Sylvius. Healthy subjects expressed a pulse-related increased width of the third ventricle ([Formula: see text]: +5.69, 95% confidence interval [CI] = [4.38, 7.00]). No significant difference was found between the sitting and the supine position in healthy adults. In the preoperative state of occlusive hydrocephalus, we found a negative, pulse-related deformation ([Formula: see text]: -1.86, 95% CI = [-2.15, -1.58]) with delayed onset. After surgery, the deformation pattern resembled that of our healthy controls. The difference between pre- and postoperative condition was significant (p < 0.001). Transcranial B-mode sonography can be used to record small movements of the sidewalls of the third ventricle. This noninvasive bedside method is suitable to assess CSF pulsatility within the third ventricle and might be able to distinguish between physiological and pathological flows.

Background Visualisation of nigrosome 1, a substructure of the healthy substantia nigra, was restricted in susceptibility weighted MR imaging in almost all patients with Parkinson's disease studied so far. The purpose of this study was to determine the degree of visibility of this substructure in subjects without Parkinson's disease and to examine the potential link between increasing brain iron accumulation with age and its detectability. Methods In 46 subjects ( 21 women, 25 men; 19 to 75 y; mean age: 44.5; SD: 15.6) examined with susceptibility weighted MR imaging at 7T visibility of nigrosome 1 was rated and classified. We assessed differences related to age and to signal intensities in the substantia nigra, red nucleus and putamen as correlates of the individual iron concentration. Results In 93% nigrosome 1was at least unilaterally clearly present. In 24% at least one-sided limited visibility was observed. Using predefined classification criteria the specificity of the visibility across all age groups reached approximately 94%. We found no correlation with increasing iron concentrations with age. Conclusion Aging with a related increase in iron concentration probably does not affect the visibility of nigrosome 1 at 7T SWI MRI. Our results support the role of this feature as a future differential diagnostic tool but further large-scale prospective studies are needed to better define the extent of a "limited visibility" to which an individual can be considered healthy.

The mechanics of cerebrospinal fluid (CSF) circulation is complex and technical limitations in measuring CSF flow prevent a complete understanding of its physiology. On the other hand, CSF flow is vulnerable to many cerebral disorders. It was our aim to develop a non-invasive and favorable method to detect pathological and physiological CSF phenomena by measuring the wall movement of the third ventricle. By diagnostical transcranial B-mode ultrasound the cardiac related pulsatile deformation of the third ventricle was measured over time. ECG-gated video loops were saved and analyzed off-line to quantify the relative change of its width. We conducted measurements of 9 cardiac cycles in 11 healthy volunteers. In one patient with occlusive hydrocephalus 19 cardiac cycles were measured, each before and after removal of a tumorous obstruction of the aqueduct of Sylvius. Healthy volunteers expressed a pulse related increased width of the third ventricle (max +5.69 ± 2.54%). The deformation courses were in accordance with known literature about CSF dynamics. In case of occlusive hydrocephalus, we found a negative pulse related deformation (min −1.84 ± 0.21%) with delayed onset for the preoperative state. After surgery, the deformation pattern resembled that of our healthy controls. The difference between pre- and postoperative condition was significant (p<0.001). Conventional transcranial B-mode-sonography can be used to record small movements of the sidewalls of the third ventricle. Therefore, this non-invasive bedside-method is suitable to assess CSF pulsatility within the third ventricle and might be able to distinguish between physiological and pathophysiological flow conditions. Further investigations should prove the reliability of this technique.

Prevalence of cobalamin deficiency is high especially in older patients and an immediate therapy start is necessary to prevent irreversible neurological damages. Unfortunately, the diagnosis of cobalamin deficiency is difficult and at present, there is no consensus for diagnosis of this deficiency. Therefore, we aim to elucidate a meaningful diagnostic pathway by a case report with an initially misleading medical history.

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Background: Patients with acute ischemic strokes frequently take an acetylsalicylic acid (ASA) premedication. We determined the impact of ASA on different thrombolysis strategies in vitro. Methods: For two clot types made from platelet-rich plasma (one with and one without ASA) lysis rates were measured by weight loss after 1 h for five different groups: in control group A clots were solely placed in plasma; in groups B and C clots were treated with rt-PA (60 kU/ml), and in groups D and E clots were treated with desmoteplase (DSPA; 2 µg/ml). Ultrasound (2 MHz, 0.179 W/cm2) was included in groups C and E. The fibrin mesh structures of the clots were investigated by electron microscopy. Results: For both clot types lysis rates increased significantly for all treatment strategies compared to their control group (each p < 0.001). The addition of ASA significantly increased the lysis rate in all 5 groups (each p < 0.001) and led to a ceiling effect concerning the treatment. A semiquantitative analysis of transmission electron micrographs revealed a decreased fibrin density for clots with ASA. For both clot types DSPA and ultrasound led to a significant dissolution of the fibrin mesh (both p = 0.029). Conclusions: In vitro ASA pretreatment leads to significantly increased lysis rates due to a weaker fibrin mesh in platelet-rich plasma clots.

Background: Moyamoya syndrome is a vasculopathy characterised by progressive occlusion of the cerebral arteries resulting in the development of abnormal collateral circulation. To diagnose this syndrome, imaging of the cerebral arteries is required including CT- or MR-angiography and conventional angiography. We present a case of moyamoya disease with typical findings detected in the sonography. The diagnosis was suspected after reviewing the initial ultrasound images of the cerebral arteries with evidence for obliterated intracranial arteries and the detection of an existing collateral circulation network.Case presentation: A 62 years old male patient presented in the hospital's emergency department with symptoms indicating a subacute cerebrovascular event. Immediate sonographic studies showed a right-sided pulsatile Doppler-signal in the common and internal carotid arteries, suggestive of distal stenoses. In addition, the transcranial examination indicated obliteration of both middle cerebral arteries. Numerous arterial vessels suggestive of leptomeningeal collateral arteries revealed a strong arterial leptomeningeal flow. At this stage of the diagnostic work-up, the collateral circulation network, characteristic of moyamoya disease, was indicated by sonography. Moyamoya syndrome was verified by conventional angiography. The aetiological work remained empty, so the diagnosis of moyamoya disease was established.Conclusion: Our case report indicates that sonography can be a useful tool for detecting the vaculopathy in moyamoya syndrome. In case routine procedures, such as the CT- or MR-angiography, with evidence for obliterated intracerebral arteries, ultrasound studies might provide important information regarding an existing collateral network in the scope of a moyamoya syndrome.

The aim of the study described here was to evaluate the thrombolytic efficacy of combined treatment with the fibrin-selective plasminogen activator desmoteplase (DSPA) and therapeutic ultrasound (sonothrombolysis [STL]) compared with conventional rt-PA (recombinant tissue plasminogen activator) treatment in vitro. Lysis rates were determined by the weight loss of platelet-rich plasma (PRP) clots treated with rt-PA (60 kU/mL) or DSPA (2 μg/mL) combined with pulsed wave ultrasound (2 MHz, 0.179 W/cm(2)). To reveal the individual effects of medication and ultrasound, lysis rates were also determined for DSPA monotherapy and for combined treatment with rt-PA and ultrasound. Clots solely placed in plasma served as the control group. Lysis increased significantly with rt-PA (26.5 ± 7.8%) and DSPA (30.5 ± 6%) compared with the control group (18.2 ± 5.9%) (each p < 0.001). DSPA lysis was more effective than rt-PA lysis (without STL: p = 0.015, with STL: p = 0.01). Combined treatment with DSPA and 2-MHz STL significantly exceeded rt-PA lysis (32.8% vs. 26.5%, p < 0.001).

Background and purpose: This study aimed to determine the frequency and associated factors of acute brain infarction (ABI) detected by noncontrast cranial computed tomography (CCT) in patients with transient ischemic attack (TIA) of symptom duration <1 h and to investigate the association between evidence of ABI and short-term risk of stroke. Methods: During a 54-month period (starting November 2007), consecutive patients with TIA (symptom duration <1 h) admitted and imaged with CCT were prospectively evaluated. Adjusted logistic regression was used to estimate odds ratios (ORs). Results: Of 1021 patients (mean age, 74.5 ± 11 years; 52% female) with TIA (symptom duration <1 h) imaged with CCT at admission, 68 patients (6.7%; 95% CI, 5.3–8.3%) exhibited TIA-related ABI. Adjusted logistic regression showed that ABI was independently correlated with atrial fibrillation (AF) (OR, 3.3; 95% CI, 1.4–7.9; p = 0.006) and time between onset and CT assessment >6 h (OR, 2.5; 95% CI, 1.1–6.1; p = 0.034). During hospitalization (5 ± 3 d), 22 patients (2.2%; 95% CI, 1.4–3.1%) developed a stroke. Patients with ABI had higher stroke rates than those without (10.3% and 1.6%, respectively; p < 0.001). Adjusted logistic regression revealed that stroke risk was independently correlated with ABI (OR, 5.3; 95% CI, 1.8–15.0; p = 0.002) and AF (OR, 2.6; 95% CI, 1.1–6.4; p = 0.026). Conclusions: Detection of ABI by CCT in TIA patients with symptom duration <1 h may depend on timing of CCT assessment and presence of AF. Evidence of ABI indicates an elevated stroke risk during hospitalization.

Background: Agreement about the most suitable clot formation protocol for sonothrombolysis investigations is lacking. Lysis rates vary strongly owing to different test conditions and, thus, cannot be compared. We aim to establish a simple but physiologically grounded protocol for in vitro coagulation to enable standardized sonothrombolysis investigations.Method: Clots were generated from platelet-rich plasma (PRP) obtained by centrifugation (10 min, 180 x g) of human venous blood (VB). PRP was mixed with the boundary layer formed between the supernatant and the erythrocyte layer. To achieve clots with different platelet counts, PRP was gradually substituted with platelet-free plasma (PFP), harvested from the supernatant of VB after centrifugation (10 mm, 2570 x g). Clot types were examined for histological appearance, hydrodynamic resistance under physiological flows, and lysis rate measured by weight loss after a 2-h treatment with recombinant tissue plasminogen activator (rt-PA) (60 kU/ml). Lysis rates of the most suitable clot were measured after a 1-h treatment with rt-PA (60 kU/ml), and combined treatment with rt-PA and 2-MHz transcranial color-coded sonography (TCCS) (0.179 W/cm(2)) or 2-MHz transcranial Doppler (TCD) (0.457 W/cm(2)).Results: With increased platelet count, the hydrodynamic resistance of the artificial clots increased, their histological appearance became more physiological, and lysis rates decreased. The most suitable clots consisted of 1.5-ml PRP, 2.0-ml PFP, and 0.5-ml boundary layer. Their lysis rates were 36.7 +/- 7.8% (rt-PA), 40.8 +/- 8.6% (rt-PA +TCCS), and 40.4 +/- 8.3% (rt-PA+TCD). Comparison with existing methods: These systemic investigations were conducted for the first time.Conclusion: This protocol should be used for standardized sonothrombolysis investigations. (C) 2014 Elsevier B.V. All rights reserved.

“Speckle tracking” is a new quantification software that allows to measure and to monitor the movement of two selected points (speckles), individually and relative to one another. We applied this technique in order to study the pulsation of the third ventricle and to evaluate the diagnostic potential of this new technique.

ABSTRACTBACKGROUNDMicrovascular imaging (MVI), a new ultrasound technology, is used to analyze brain perfusion at the patient's bedside. This study aims to evaluate the diagnostic and prognostic value of MVI in patients with acute ischemic stroke (AIS).METHODSNineteen patients suffering from AIS (mean age, 70.9 ± 12.2 years; 47% female; mean NIHSS‐score, 12 ± 8) were investigated within the first 12 hours after symptom onset. We used the iU22 (Philips) system (S5–1 probe; low‐mechanical index; depth, 13 cm), and 2 bolus injections of an ultrasound contrast agent (2.4 mL SonoVue™ per injection). The area of maximal perfusion deficit (AMPD) was compared with infarction on follow‐up cranial computed tomography (CT) and NIHSS score 24 hours after stroke onset.RESULTSOf 19 patients, 15 patients (79%) had sufficient insonation conditions. Of these patients, 12 had infarctions. The sensitivity and specificity of detecting infarctions with ultrasound perfusion imaging were 91% and 67%, respectively. A significant correlation existed between the AMPD and NIHSS score at 24 hours after symptom onset (P= .023), and with occlusion of the internal carotid artery (P= .005).CONCLUSIONPerforming bedside MVI in the early phase of AIS provides information on brain parenchyma perfusion and prognosis of AIS.