Association Between Intravenous Thrombolysis and Clinical Outcomes Among Patients With Ischemic Stroke and Unsuccessful Mechanical Reperfusion.

IMPORTANCE Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce. OBJECTIVE To determine whether intravenous thrombolysis (IVT) prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching. INTERVENTIONS Mechanical thrombectomy with or without IVT. MAIN OUTCOMES AND MEASURES Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death. RESULTS After matching, 746 patients were compared by treatment arms (median age, 78 [IQR, 68-84] years; 438 women [58.7%]). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio [AOR], 2.63 [95% CI, 1.41-5.11]; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 [95% CI, 1.35-2.92]; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 [95% CI, 0.29-1.81]; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 [95% CI, 0.34-0.86]; P = .01). CONCLUSIONS AND RELEVANCE These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment

Development of Cortical Lesion Volumes on Double Inversion Recovery MRI in Patients With Relapse-Onset Multiple Sclerosis

Background and Objective: In multiple sclerosis (MS) patients, Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to detect cortical lesions (CL). While the quantity and distribution of CLs seems to be associated with patients' disease course, literature lacks frequent assessments of CL volumes (CL-V) in this context. We investigated the reliability of DIR for the longitudinal assessment of CL-V development with frequent follow-up MRIs and examined the course of CL-V progressions in relation to white-matter lesions (WML), contrast enhancing lesions (CEL) and clinical parameters in patients with Relapsing-Remitting Multiple Sclerosis (RRMS).Methods: In this post-hoc analysis, image- and clinical data of a subset of 24 subjects that were part of a phase IIa clinical trial on the “Safety, Tolerability and Mechanisms of Action of Boswellic Acids in Multiple Sclerosis (SABA)” (ClinicalTrials.gov, NCT01450124) were included. The study was divided in three phases (screening, treatment, study-end). All patients received 12 MRI follow-up-examinations (including DIR) during a 16-months period. CL-Vs were assessed for each patient on each follow-up MRI separately by two experienced neuroradiologists. Results of neurological screening tests, as well as other MRI parameters (WML number and volume and CELs) were included from the SABA investigation data.Results: Inter-rater agreement regarding CL-V assessment over time was good-to-excellent (κ = 0.89). Mean intraobserver variability was 1.1%. In all patients, a total number of 218 CLs was found. Total CL-Vs of all patients increased during the 4 months of baseline screening followed by a continuous and significant decrease from month 5 until study-end (p &lt; 0.001, Kendall'W = 0.413). A positive association between WML volumes and CL-Vs was observed during baseline screening. Decreased CL-V were associated with lower EDSS and also with improvements of SDMT- and SCRIPPS scores.Conclusion: DIR MRI seems to be a reliable tool for the frequent assessment of CL-Vs. Overall CL-Vs decreased during the follow-up period and were associated with improvements of cognitive and disability status scores. Our results suggest the presence of short-term CL-V dynamics in RRMS patients and we presume that the laborious evaluation of lesion volumes may be worthwhile for future investigations.Clinical Trial Numbers:www.ClinicalTrials.gov, “The SABA trial”; number: NCT0145012

Photo of the aneurysm model.

<p>Regions or volumes of interest (inlet, aneurysm, outlet) were chosen at the indicated positions of the model in the corresponding 3D or 2D image data, respectively. The signal within these regions was plotted and analyzed to compare the imaging methods.</p

Multiple frames of dynamic MRI, MPI, and DSA measurements during the passage of a local maximum of contrast agent concentration (see time points 2.5 s-2.8 s in Fig 2).

<p>The passage of the contrast agent bolus through the main vessel of the model can be estimated in MPI and DSA, but not in MRI. A movie showing all frames of the dynamic scans is available as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160097#pone.0160097.s004" target="_blank">S3 Video</a>.</p

Detailed 4D pc-fq imaging parameters.

<p>Detailed 4D pc-fq imaging parameters.</p

Cyclic repetition of the 4D pc-fq MRI (top) shows distinct pulsation and a much lower flow velocity inside the aneurysm.

<p>Dynamic MRI (second top, cubic spline interpolated), MPI (second bottom), and DSA (bottom) also show distinct pulsation and delayed contrast agent dynamics inside the aneurysm. Regions were chosen in the corresponding image data as depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160097#pone.0160097.g001" target="_blank">Fig 1</a>. Pulsations and bolus injections did not perfectly match between the different methods, due to the resetting of the experiments.</p

False color (left) and vector field (right) visualization of the 4D pc-fq MRI at the time point of maximal flow velocity during one pulsation cycle.

<p>Lower flow velocity and different flow directions are clearly visible inside the aneurysm. Movies showing all phases of the pulsation are available as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160097#pone.0160097.s002" target="_blank">S1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160097#pone.0160097.s003" target="_blank">S2</a> Videos.</p

Summary of dynamic measurement analysis (mean ± standard deviation).

<p>Summary of dynamic measurement analysis (mean ± standard deviation).</p

Effect of Intravenous Alteplase on Functional Outcome and Secondary Injury Volumes in Stroke Patients with Complete Endovascular Recanalization

Intravenous thrombolytic therapy with alteplase (IVT) is a standard of care in ischemic stroke, while recent trials investigating direct endovascular thrombectomy (EVT) approaches showed conflicting results. Yet, the effect of IVT on secondary injury volumes in patients with complete recanalization has not been analyzed. We hypothesized that IVT is associated with worse functional outcome and aggravated secondary injury volumes when administered to patients who subsequently attained complete reperfusion after EVT. Anterior circulation ischemic stroke patients with complete reperfusion after thrombectomy defined as thrombolysis in cerebral infarctions (TICI) scale 3 after thrombectomy admitted between January 2013&ndash;January 2021 were analyzed. Primary endpoints were the proportion of patients with functional independence defined as modified Rankin Scale (mRS) score 0&ndash;2 at day 90, and secondary injury volumes: Edema volume in follow-up imaging measured using quantitative net water uptake (NWU), and the rate of symptomatic intracerebral hemorrhage (sICH). A total of 219 patients were included and 128 (58%) patients received bridging IVT before thrombectomy. The proportion of patients with functional independence was 28% for patients with bridging IVT, and 34% for patients with direct thrombectomy (p = 0.35). The rate of sICH was significantly higher after bridging IVT (20% versus 7.7%, p = 0.01). Multivariable logistic and linear regression analysis confirmed the independent association of bridging IVT with sICH (aOR: 2.78, 95% CI: 1.02&ndash;7.56, p = 0.046), and edema volume (aOR: 8.70, 95% CI: 2.57&ndash;14.85, p = 0.006). Bridging IVT was associated with increased edema volume and risk for sICH as secondary injury volumes. The results of this study encourage direct EVT approaches, particularly in patients with higher likelihood of successful EVT