Kersten Villringer

Prehospital thrombolysis in acute stroke Results of the PHANTOM-S pilot study

Objective: Beneficial effects of IV tissue plasminogen activator (tPA) in acute ischemic stroke are strongly time-dependent. In the Pre-Hospital Acute Neurological Treatment and Optimization of Medical care in Stroke (PHANTOM-S) study, we undertook stroke treatment using a specialized ambulance, the stroke emergency mobile unit (STEMO), to shorten call-to-treatment time. Methods: The ambulance was staffed with a neurologist, paramedic, and radiographer and equipped with a CT scanner, point-of-care laboratory, and a teleradiology system. It was deployed by the dispatch center whenever a specific emergency call algorithm indicated an acute stroke situation. Study-specific procedures were restricted to patients able to give informed consent. We report feasibility, safety, and duration of procedures regarding prehospital tPA administration. Results: From February 8 to April 30, 2011, 152 subjects were treated in STEMO. Informed consent was given by 77 patients. Forty-five (58%) had an acute ischemic stroke and 23 (51%) of these patients received tPA. The mean call-to-needle time was 62 minutes compared with 98 minutes in 50 consecutive patients treated in 2010. Two (9%) of the tPA-treated patients had a symptomatic intracranial hemorrhage and 1 of these patients (4%) died in hospital. Technical failures encountered were 1 CT dysfunction and 2 delayed CT image transmissions. Conclusions: The data suggest that prehospital stroke care in STEMO is feasible. No safety concerns have been raised so far. This new approach using prehospital tPA may be effective in reducing call-to-needle times, but this is currently being scrutinized in a prospective controlled study.

Silent new DWI lesions within the first week after stroke.

Background: The rate of cerebral infarct recurrence is determined by clinical examination. Routine neurological examination is less sensitive than cerebral imaging in detecting new cerebral lesions. We aimed to determine the rate of new diffusion-weighted imaging (DWI) lesions at 2 time points after stroke and to identify factors associated with them. Methods: Patients who were hospitalized with acute ischemic stroke underwent DWI at 3 time points (within 24, 48 and 144 h after stroke onset, respectively). Scans were made anonymous and reviewed in a random order. Lesions on DWI were delineated manually by blinded investigators. Then, coregistered DWI templates were analyzed for new ischemic lesions on the corresponding follow-up DWI. New lesions had to be separate and lesion growth was not considered. Univariate and multivariable logistic regression analyses were performed to define predictors of new DWI lesions. Results: A total of 159 patients were enrolled in the study. Clinical stroke recurrence was detected in 2.5% of patients. A new cerebral lesion was detected in 5.7% of patients between first and second imaging (first interval) and 23.3% between second and third imaging (second interval). In univariate analyses, thrombolysis and multiple lesion pattern were associated with new lesions within the first interval. Ipsilateral carotid stenosis, multiple lesion pattern, vessel recanalization, atrial fibrillation, older age and higher NIHSS were associated with new lesions within the second interval. In multivariable analysis, ipsilateral carotid stenosis, recanalization and multiple lesion pattern remained independently associated with any new lesions. Conclusions: New DWI lesions occur more often than routine neurological examination suggests. Thrombolysis was associated with very early new DWI lesions within the first interval, ipsilateral carotid stenosis and spontaneous recanalization with new DWI lesions within the second interval.

Vessel size imaging reveals pathological changes of microvessel density and size in acute ischemia

The aim of this study was to test the feasibility of vessel size imaging with precise evaluation of apparent diffusion coefficient and cerebral blood volume and to apply this novel technique in acute stroke patients within a pilot group to observe the microvascular responses in acute ischemic tissue. Microvessel density-related quantity Q and mean vessel size index (VSI) were assessed in 9 healthy volunteers and 13 acute stroke patients with vessel occlusion within 6hours after symptom onset. Our results in healthy volunteers matched with general anatomical observations. Given the limitation of a small patient cohort, the median VSI in the ischemic area was higher than that in the mirrored region in the contralateral hemisphere (P < 0.05). Decreased Q was observed in the ischemic region in 2 patients, whereas no obvious changes of Q were found in the remaining 11 patients. In a patient without recanalization, the VSI hyperintensity in the subcortical area matched well with the final infarct. These data reveal that different observations of microvascular response in the acute ischemic tissue seem to emerge and vessel size imaging may provide useful information for the definition of ischemic penumbra and have an impact on future therapeutic approaches.

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 Kendalls 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.

The Potential of Microvessel Density in Prediction of Infarct Growth: A Two-Month Experimental Study in Vessel Size Imaging

Objectives: Vessel size imaging is a novel technique to evaluate pathological changes of the microvessel density quantity Q and the mean vessel size index (VSI). As a follow-up study, we assessed these parameters for microscopic description of ischemic penumbra and their potentials in predicting lesion growth. Methods: Seventy-five patients with a perfusion-diffusion mismatch were examined within 24 h from symptom onset. We defined three regions of interest: the initial infarct (INF), the ischemic penumbra (IPE), and the healthy region (HEA) symmetric to the IPE. For 23 patients with a 6th-day follow-up, IPE regions were divided into areas of infarct growth and areas of oligemia. Result: The median values of Q and VSI were: for INF 0.29 s-1/3 and 15.8 µm, for IPE 0.33 s-1/3 and 20.6 µm and for HEA 0.36 s-1/3 and 17.4 µm. The Q in the IPE was significantly smaller than in HEA, and VSI was significantly larger. The Q with a threshold of 0.32 s-1/3 predicted the final infarction with a sensitivity of 69% and a specificity of 64%. Conclusions: The reduced Q and increased VSI in the IPE confirmed our previous pilot results. Although Q showed a trend to identify the severity of ischemia in an overall voxel population, its potential in predicting infarct growth needs to be further tested in a larger cohort including a clear status of reperfusion and recanalization.

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

Objectives Post-contrast magnetic resonance angiography (PC-MRA) enables visualization of vessel segments distal to an intra-arterial thrombus in acute ischemic stroke. We hypothesized that PC-MRA also allows clot length measurement in different intracranial vessels. Methods Patients with MRI-confirmed ischemic stroke and intracranial artery occlusion within 24 hours of symptom onset were prospectively evaluated. PC-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 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 min were included. PC-MRA enabled precise depiction of proximal and distal terminus of the thrombus in 31 patients (91%), whereas in three patients (9%) PC-MRA presented a partial occlusion. Median thrombus length in patients with complete occlusion was 9.9 mm. In patients with poor outcome (mRS ≥3) median thrombus length was significantly longer than in those with good outcome (mRS ≤2;P=0.011). Conclusions PC-MRA demonstrates intra-arterial thrombus length at different vessel occlusion sites. Longer thrombus length is associated with poor clinical outcome. Clinical trial registration NCT02077582; Results.

MRI follow-up after 24 h is an accurate surrogate parameter for treatment success after thrombolysis.

Eleven patients had no initial vessel occlusion, 19 showed re-canalization at 1–6 h (early recanalizers), and 6 additional patients showed recanalization at 24 h (late recanalizers). Four patients were nonrecanalizers. Age, gender and time to treatment did not differ between the subgroups. At baseline, nonrecanalizers had significantly larger perfusion deficits (p = 0.011) and patients with no initial occlusion had significantly smaller DWI and hypoperfu-sion volumes. Median lesion growth until 1–6 h was not signifi-cantly different between the groups (p = 0.167). The median lesion growth from baseline until 24 h was significantly larger in the nonrecanalizers compared to the other groups (71.4 vs. 2.8 ml, p < 0.05). The median perfusion deficit at 24 h and final lesion size did not differ between early and late recanalizers; both were sig-nificantly larger in nonrecanalizers. A modified Rankin Scale score of 0–2 at 3 months was reached by 66% of the recanalizers while no nonrecanalizer reached an independent outcome (p = 0.02).