Sönke Langner

Analysis of Lymphocyte Subsets in Patients With Stroke and Their Influence on Infection After Stroke

Background and Purpose— Recent studies have attributed the increased infection vulnerability of patients with stroke to stroke-induced immunosuppression. We have therefore explored the immunological changes in patients with ischemic stroke. Methods— Blood from 46 patients with stroke was analyzed by fluorescent-activated cell sorter to determine leukocyte subsets. To identify changes that represent clinically relevant immunosuppression, we compared patients who developed infection within 14 days after stroke with those who did not. Results— Stroke induced a dramatic and immediate loss of T-lymphocytes, most pronounced within 12 hours after stroke onset. Only patients with subsequent infection exhibited a delay in the recovery of CD4+ T-lymphocyte counts. Conclusions— Our data suggest that a loss of CD4+ T cell function contributes to the stroke-induced immunosuppression. The CD4+ T cell count on the day after stroke may emerge as a predictive marker for poststroke infection allowing, early identification of patients at risk.

Chronic Back Pain Is Associated With Decreased Prefrontal and Anterior Insular Gray Matter: Results From a Population-Based Cohort Study

UNLABELLED Chronic back pain (CBP) is associated with circumscribed atrophy in gray matter (GM) predominantly localized in areas of the so-called pain matrix and the prefrontal cortex (PFC). Previous studies applying voxel-based morphometry (VBM) for identifying structural brain alterations related to CBP have reported inconsistent results, were limited to small sample sizes, and often did not control for medication. We therefore used VBM for high-resolution magnetic resonance images to investigate the association of CBP and regional GM volume in 111 individuals with CBP and 432 pain-free controls derived from the representative Study of Health in Pomerania, controlling for effects of medication. CBP was associated with decreased regional GM in the ventrolateral PFC and dorsolateral PFC, both the ventral and dorsal medial PFC, and the anterior insula. Pain intensity showed a weak negative correlation with GM volume in the left dorsolateral PFC, ventrolateral PFC, and anterior cingulate cortex. The CBP sample showed alterations in regions commonly associated with pain processing and emotional demands. To our knowledge, this is the first VBM study reporting decreased regional GM volume in the medial PFC in a CBP sample. We were unable to confirm alterations in regions other than the dorsolateral PFC and the insula. PERSPECTIVE Previous studies reported inconsistent results for brain areas altered in chronic pain conditions, which may be in part attributable to small sample sizes, medication use, or emotional comorbidities. This study in a large and representative cohort helps to clarify these issues.

Comparison between cold plasma, electrochemotherapy and combined therapy in a melanoma mouse model.

The study was undertaken to compare antitumor efficacy of electrochemotherapy (ECT) with cold plasma therapy (CP) in a melanoma mouse model. After melanoma implantation into the flank of C57BL/6N mice, CP by two different plasma sources (APPJ and DBD) was applied directly to the tumor surface. ECT was performed with bleomycin intravenously at a field strength of 1000 V/cm without or combined with CP. Primary endpoints were tumor growth acceleration (TGA), daily volume progression (DVP) and survival after treatment. Both plasma sources as single treatment showed a significant TGA delay, which proved less effective than ECT. CP (APPJ) combined with ECT (ECJ) significantly improved per cent mouse survival, with significant superiority compared with ECT. Plasma therapy alone albeit less effective seems a potential alternative to ECT in patients with melanoma and can be applied manifold in a session without general anaesthesia. Accordingly, CP alone and combined with ECT may serve as new option in palliative skin melanoma therapy.

Endovaskuläre Therapie des akut ischämischen Schlaganfalls unter Analgosedierung im Vergleich zur Intubationsnarkose – Durchführbarkeit, periprozedurale Sicherheit, klinisches und radiologisches Outcome

PURPOSE Vessel recanalization is an important predictor of clinical outcome in the treatment of acute ischemic stroke. Endovascular therapies are used with increasing frequency. There is no general agreement on the policy of anesthesia during endovascular therapy, ranging from general anesthesia (GA) to local anesthesia at the puncture site with conscious sedation (CS) as needed. The aim of the study was to evaluate the safety and feasibility and radiological and clinical outcome of endovascular stroke therapy under CS. MATERIALS AND METHODS We retrospectively included all patients with acute ischemic stroke who were treated with endovascular therapy over a five-year period. Data was evaluated with respect to type of sedation, conversion from CS to GA, recanalization rate, infarct volume and peri- and post-procedural complications. RESULTS There was a technical failure in 7 patients. Of the remaining 124 patients (mean age 68.8 ± 14.6 years), 65 were female (52 %). The site of occlusion was located in the anterior circulation in 94 patients (76 %) and in the posterior circulation in 30 cases (24 %). 105 patients (85 %) were treated under CS and 16 cases (13 %) primarily under GA. In 3 cases (2 %) peri-procedural conversion to GA was necessary. Primary intra-arterial thrombolysis, mechanical recanalization only, and combination therapy were performed in 60 (48 %), 27 (22 %) and 37 (30 %) patients, respectively. There were no significant differences for recanalization rate and complications between GA and CS. The mean procedure time was significantly shorter in patients treated under CS (p < 0.01). CONCLUSION Endovascular stroke therapy with CS is feasible, can be performed safely and is faster than with GA.

T1 bias in chemical shift-encoded liver fat-fraction: Role of the flip angle

To investigate flip angle (FA)‐dependent T1 bias in chemical shift‐encoded fat‐fraction (FF) and to evaluate a strategy for correcting this bias to achieve accurate MRI‐based estimates of liver fat with optimized signal‐to‐noise ratio (SNR).

Erratum to: Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years.

Purpose To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey.

Stroke Alters Respiratory Burst in Neutrophils and Monocytes

Background and Purpose— Stroke-induced immune alterations predispose patients to infections. Although the relationship between stroke and the adaptive immune system has been investigated in detail, to date it is unknown whether the innate immune system, which forms the first line of antibacterial defense, is also impaired in patients with stroke. Therefore, we investigated whether chemotaxis, phagocytosis, oxidative burst, degranulation of defensins, and NETosis in monocytes and in neutrophil granulocytes are altered in patients with stroke compared with controls. Methods— Sixty-three patients having acute ischemic stroke were recruited within 12 hours of symptom onset; blood was sampled on admission and on days 1, 3, 5, and 7. Thirty-seven age-matched controls were also recruited. Cell migration, phagocytosis, and oxidative burst of phagocytes were determined in vitro. Human neutrophil peptides 1 to 3 and serum metanephrine levels were measured by enzyme-linked immunosorbent assay, and NETosis was quantified by immunohistochemistry. Results— The key mechanisms required for bacterial killing, oxidative burst, and NETosis were significantly reduced in samples taken from patients with stroke compared with controls, whereas migration, phagocytic function, and defensin production remained unimpaired in monocytes and granulocytes from patients with stroke. Conclusions— Stroke-induced immune alterations include impairment of the first-line defense performed by specialized phagocytes against bacteria. The hypothesis that these changes enhance susceptibility to acquired infections is supported by our observation that on admission oxidative burst in monocytes was more impaired in patients with stroke with subsequent stroke-associated infections.

Neural correlates of impaired emotional face recognition in cerebellar lesions

Clinical and neuroimaging data indicate a cerebellar contribution to emotional processing, which may account for affective-behavioral disturbances in patients with cerebellar lesions. We studied the neurophysiology of cerebellar involvement in recognition of emotional facial expression. Participants comprised eight patients with discrete ischemic cerebellar lesions and eight control patients without any cerebrovascular stroke. Event-related potentials (ERP) were used to measure responses to faces from the Karolinska Directed Emotional Faces Database (KDEF), interspersed in a stream of images with salient contents. Images of faces augmented N170 in both groups, but increased late positive potential (LPP) only in control patients without brain lesions. Dipole analysis revealed altered activation patterns for negative emotions in patients with cerebellar lesions, including activation of the left inferior prefrontal area to images of faces showing fear, contralateral to controls. Correlation analysis indicated that lesions of cerebellar area Crus I contribute to ERP deviations. Overall, our results implicate the cerebellum in integrating emotional information at different higher order stages, suggesting distinct cerebellar contributions to the proposed large-scale cerebral network of emotional face recognition.

Comparison of Parameter Threshold Combinations for Diffusion Tensor Tractography in Chronic Stroke Patients and Healthy Subjects

Background Although quantitative evaluation of diffusion tensor imaging (DTI) data seemed to be extremely important for clinical research its application is under debate. Besides fractional anisotropy (FA) the quantitative comparison between hemispheres of the number of fibers reconstructed by means of diffusion tensor tractography (DTT) is commonly used. However, the tractography-related parameters FA, minimum tract length (LENGTH) and the angle between two contiguous tracking steps (ANGLE) are inconsistently applied. Using 18 combinations we tested for the influence of parameter thresholds on the amount of reconstructed fibers for the posterior pyramidal tract in both hemispheres in order to obtain meaningful thresholds for DTT. Results In 14 chronic stroke patients with unilateral lesions of the pyramidal tract around the height of the internal capsule and considerable motor deficits a 3-way repeated-measures ANOVA showed a significant interaction between the effects of FA and ANGLE level on reconstructed fiber lateralization, F (2.9, 37.67) = 3.01, p = 0.044, and a significant main effect FA, F (1.4, 18.1) = 11.58, p = 0.001. Post-hoc pairwise comparisons showed that this interaction was completely driven by FA. In 22 right-handed healthy subjects no significant interactions or main effects could be found. Conclusion The parameter threshold combinations with highest FA showed highest effect. ANGLE and LENGTH insofar influenced the lateralization effect when selected as liberal as possible, short LENGTH and large ANGLE thresholds. The DTT approach should be used with great care since results are highly dependent on the thresholds applied.

Diffusion-sensitized ophthalmic magnetic resonance imaging free of geometric distortion at 3.0 and 7.0 T: a feasibility study in healthy subjects and patients with intraocular masses.

ObjectivesThis study is designed to examine the feasibility of diffusion-sensitized multishot split-echo rapid acquisition with relaxation enhancement (RARE) for diffusion-weighted ophthalmic imaging free of geometric distortions at 3.0 and 7.0 T in healthy volunteers and patients with intraocular masses. Materials and MethodsA diffusion-sensitized multishot split-echo RARE (ms-RARE) variant is proposed as an alternative imaging strategy for diffusion-weighted imaging. It is compared with standard single-shot echo planar imaging (EPI) and readout-segmented EPI in terms of geometric distortions in a structure phantom as well as in vivo at 3.0 and 7.0 T. To quantify geometric distortions, center of gravity analysis was carried out. Apparent diffusion coefficient (ADC) mapping in a diffusion phantom was performed to verify the diffusion sensitization within ms-RARE. An in vivo feasibility study in healthy volunteers (n = 10; mean age, 31 ± 7 years; mean body mass index, 22.6 ± 1.7 kg/m2) was conducted at 3.0 and 7.0 T to evaluate clinical feasibility of ms-RARE. As a precursor to a broader clinical study, patients (n = 6; mean age, 55 ± 12 years; mean body mass index, 27.5 ± 4.7 kg/m2) with an uveal melanoma and/or retinal detachment were examined at 3.0 and 7.0 T. In 1 case, the diseased eye was enucleated as part of the therapy and imaged afterward with magnetic resonance microscopy at 9.4 T. Macrophotography and histological investigation was carried out. For qualitative assessment of the image distortion, 3 independent readers reviewed and scored ms-RARE in vivo images for all subjects in a blinded reading session. Statistical significance in the difference of the scores (a) obtained for the pooled ms-RARE data with b = 0 and 300 s/mm2 and (b) for the 3 readers was analyzed using the nonparametric Mann-Whitney test. ResultsThe assessment of geometric integrity in phantom imaging revealed the ability of ms-RARE to produce distortion-free images. Unlike ms-RARE, modest displacements (2.3 ± 1.4 pixels) from the fast low angle shot imaging reference were observed for readout-segmented EPI, which were aggravated for single-shot EPI (8.3 ± 5.7 pixels). These observations were confirmed in the in vivo feasibility study including distortion-free diffusion-weighted ophthalmic images with a 0.5 × 0.5 × 5 mm3 spatial resolution at 3.0 T and as good as 0.2 × 0.2 × 2 mm3 at 7.0 T. The latter represents a factor of 40 enhancement in spatial resolution versus clinical protocols recently reported for diffusion-weighted imaging of the eye at 1.5 T. Mean ADC values within the vitreous body were (2.91 ± 0.14) × 10−3 mm2/s at 3.0 T and (2.93 ± 0.41) × 10−3 mm2/s at 7.0 T. Patient data showed severe retinal detachment in the anatomical images. Whereas the tumor remained undetected in T1-weighted and T2-weighted imaging at 3.0/7.0 T, in vivo ADC mapping using ms-RARE revealed the presence of a uveal melanoma with a significant contrast versus the surrounding subretinal hemorrhage. This observation was confirmed by high-resolution ex vivo magnetic resonance microscopy and histology. Qualitative analysis of image distortion in ms-RARE images obtained for all subjects yielded a mean ± SD image quality score of 1.06 ± 0.25 for b = 0 s/mm2 and of 1.17 ± 0.49 for b = 300 s/mm2. No significant interreader differences were observed for ms-RARE with a diffusion sensitization of b = 0 s/mm2 and 300 s/mm2. ConclusionsThis work demonstrates the capability of diffusion-sensitized ms-RARE to acquire high-contrast, high–spatial resolution, distortion-free images of the eye and the orbit at 3.0 and 7.0 T. Geometric distortions that are observed for EPI-based imaging approaches even at lower field strengths are offset by fast spin-echo–based imaging techniques. The benefits of this improvement can be translated into the assessment of spatial arrangements of the eye segments and their masses with the ultimate goal to provide guidance during diagnostic treatment of ophthalmological diseases.