[It is more than transportation time only: "Drip and ship" delays endovascular thrombectomy in stroke]. / Es ist nicht nur die Transportzeit ­ Das "Drip and ship"-Verfahren kostet Zeit.

BACKGROUND: Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) are acute therapies approved for ischemic stroke. In Germany there are approximately 110 supra-regional stroke units with and approximately 200 regional stroke units without 24 / 7 EVT. Regional stroke units must cooperate with supra-regional stroke units in order to offer EVT if indicated. In the current paper, we discuss the time delay due to secondary transportation from regional to supra-regional stroke units. METHODS: Acute stroke therapy of all patients treated at the regional stroke unit of the SRH Clinics in Sigmaringen in 2016 was analysed retrospectively. Sigmaringen cooperates with the supra-regional stroke units of the Oberschwabenklinik Ravensburg and the University Hospital Tübingen. RESULTS: A total of 299 patients with ischemic stroke and 168 patients with transient ischemic attack (TIA) were treated at the Sigmaringen stroke unit. Of these, 52 patients received IVT and 21 patients were transferred for EVT; of these, 15 patients actually underwent EVT after their cases were reviewed. The CT-to-Groin-times were more than double as long as compared to those in patients directly admitted to the supra-regional stroke units (median 180 minutes vs. 88 minutes). DISCUSSION: Primary admission of patients with acute stroke to regional stroke units without EVT prolongs the CT-to-Groin time. Implications of this knowledge on current and future patient care structures are discussed.

A biochemical marker panel in MRI-proven hyperacute ischemic stroke-a prospective study.

BACKGROUND: Computer tomography (CT) is still the fastest and most robust technique to rule out ICH in acute stroke. However CT-sensitivity for detection of ischemic stroke in the hyperacute phase is still relatively low. Moreover the validity of pure clinical judgment is diminished by several stroke imitating diseases (mimics). The "Triage® Stroke Panel", a biochemical multimarker assay, detects Brain Natriuretic Peptide (BNP), D-Dimers (DD), Matrix-Metalloproteinase-9 (MMP-9), and S100B protein and promptly generates a Multimarkerindex of these values (MMX). This index has been licensed for diagnostic purposes as it might increase the validity of the clinical diagnosis to differentiate between stroke imitating diseases and true ischemic strokes. Our aim was to prove whether the panel is a reliable indicating device for the diagnosis of ischemic stroke in a time window of 6 h to fasten the pre- and intrahospital pathway to fibrinolysis. METHODS: We investigated all consecutive patients admitted to our stroke unit during a time period of 5 months. Only patients with clinical investigation, blood sample collection and MRI within six hours from symptom onset were included. Values of biochemical markers were analyzed according to the results of diffusion weighted MR-imaging. In addition MMX-values in ischemic strokes were correlated with the TOAST-criteria. For statistical analysis the SAS Analyst software was used. Correlation coefficients were analyzed and comparison tests for two or more groups were performed. Statistical significance was assumed in case of p < 0.05. Finally a ROC-analysis was performed for the MMX-Index. RESULTS: In total 174 patients were included into this study (n = 100 strokes, n = 49 mimics, n = 25 transitoric ischemic attacks). In patients with ischemic strokes the mean NIHSS was 7.6 ± 6.2, while the mean DWI-lesion volume was 20.6 ml (range 186.9 to 4.2 ml). According to the MMX or the individual markers there was no statistically significant difference between the group of ischemic strokes and the group of mimics. Moreover the correlation of the index and the DWI-lesion-volume was poor (p = 0.2). CONCLUSIONS: In our setting of acute MRI-proven ischemic stroke the used multimarker-assay (Triage® Stroke Panel) was not of diagnostic validity. We do not recommend to perform this assay as this might lead to a unjustified time delay.

Long-term outcome in transient global amnesia patients with and without focal hyperintensities in the CA1 region of the hippocampus.

Focal hippocampal diffusion-weighted imaging (DWI) lesion patterns are detected in transient global amnesia (TGA) patients in different frequency. It has been speculated that acute diffusion restrictions are associated with a worse outcome. Therefore, we evaluated the influence of acute DWI lesions on the cognitive long-term outcome in TGA patients. Seventeen otherwise healthy patients with the clinical syndrome of TGA, who had MRI investigations on admission as well as 1 day later, were investigated with a comprehensive neuropsychological test battery 2 years later. Acute hippocampal DWI lesions in TGA patients were detected in almost two thirds of the patients. Psychometric evaluation revealed no differences in cognitive performance between patients with and without DWI lesions as well as compared to healthy subjects. In addition, no relapse of the attack has been recognized in either group of TGA patients.

Functional energetics of CD4+-cellular immunity in monoclonal antibody-associated progressive multifocal leukoencephalopathy in autoimmune disorders.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system- (CNS-) infection that typically occurs in a subset of immunocompromised individuals. An increasing incidence of PML has recently been reported in patients receiving monoclonal antibody (mAb) therapy for the treatment of autoimmune diseases, particularly those treated with natalizumab, efalizumab and rituximab. Intracellular CD4(+)-ATP-concentration (iATP) functionally reflects cellular immunocompetence and inversely correlates with risk of infections during immunosuppressive therapy. We investigated whether iATP may assist in individualized risk stratification for opportunistic infections during mAb-treatment. METHODOLOGY/PRINCIPAL FINDINGS: iATP in PHA-stimulated, immunoselected CD4(+)-cells was analyzed using an FDA-approved assay. iATP of mAb-associated PML (natalizumab (n = 8), rituximab (n = 2), efalizumab (n = 1)), or other cases of opportunistic CNS-infections (HIV-associated PML (n = 2), spontaneous PML, PML in a psoriasis patient under fumaric acids, natalizumab-associated herpes simplex encephalitis (n = 1 each)) was reduced by 59% (194.5±29 ng/ml, mean±SEM) in comparison to healthy controls (HC, 479.9±19.8 ng/ml, p<0.0001). iATP in 14 of these 16 patients was at or below 3(rd) percentile of healthy controls, similar to HIV-patients (n = 18). In contrast, CD4(+)-cell numbers were reduced in only 7 of 15 patients, for whom cell counts were available. iATP correlated with mitochondrial transmembrane potential (ΔΨ(m)) (iATP/ΔΨ(m)-correlation:tau = 0.49, p = 0.03). Whereas mean iATP of cross-sectionally analysed natalizumab-treated patients was unaltered (448.7±12 ng/ml, n = 150), iATP was moderately decreased (316.2±26.1 ng/ml, p = 0.04) in patients (n = 7) who had been treated already during the pivotal phase III trials and had received natalizumab for more than 6 years. 2/92 (2%) patients with less than 24 months natalizumab treatment revealed very low iATP at or below the 3(rd) percentile of HC, whereas 10/58 (17%) of the patients treated for more than 24 months had such low iATP-concentrations. CONCLUSION: Our results suggest that bioenergetic parameters such as iATP may assist in risk stratification under mAb-immunotherapy of autoimmune disorders.