Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps.

BACKGROUND: Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients. METHODS: We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples were functionally analyzed for their formation and clearance of Neutrophil-Extracellular-Traps. The composition of retrieved thrombi has been immunologically analyzed. RESULTS: Peripheral blood of stroke patients showed significantly elevated levels of DNAse-I (p < 0.001), LDG (p = 0.003), CD4 (p = 0.005) as well as the pro-inflammatory cytokines IL-17 (p < 0.001), INF-γ (p < 0.001) and IL-22 (p < 0.001) compared to controls, reflecting a TH1/TH17 response. Increased counts of DNAse-I in sera (p = 0.045) and Neutrophil-Extracellular-Traps in thrombi (p = 0.032) have been observed in patients with onset time of symptoms longer than 4,5 h. Lower values of CD66b in thrombi were independently associated with greater improvement of NIHSS after mechanical thrombectomy (p = 0.045). Stroke-derived neutrophils show higher potential for Neutrophil-Extracellular-Traps formation after stimulation and worse resolution under DNAse-I treatment compared to neutrophils derived from healthy individuals. CONCLUSIONS: Our data provide new insight in the role of activated neutrophils and Neutrophil-Extracellular-Traps in ischemic stroke. Future larger studies are warranted to further investigate the role of immunothrombosis in the cascades of stroke. TRIAL REGISTRATION: DRKS, DRKS00013278, Registered 15 November 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013278.

Distinct Behavior of Traumatic versus Nontraumatic Intracerebral Hematomas: Different Biology or Impact of Age?

BACKGROUND AND STUDY AIMS: Patients with large intracerebral hematomas (ICH) may demonstrate different demographics and underlying brain and systemic diseases, as well as different radiologic courses and distinct outcomes. It remains unclear whether their different behavior attributes to a different biology of the ICH or to the asymmetric characteristics of the two populations. To analyze and adjust for potential sources of selection and treatment bias, our study compared age-matched patients with traumatic and nontraumatic ICH in a single cohort diagnosed and treated in the same surgical department. MATERIAL AND METHODS: We analyzed 135 consecutive patients with traumatic (n = 90) or spontaneous ICH (n = 45) undergoing treatment at a surgical intensive care unit of an urban university hospital. We documented their differences before and after adjustment for age in terms of demographics, the therapies applied, their radiologic (i.e., volume and rate of ICH expansion [HE]) and clinical (patients' outcome at 30 days) course, the length of hospital and ICU stay, as well as the hospital costs. RESULTS: Patients with traumatic ICH demonstrated more favorable clinical and radiologic characteristics at admission, that is, higher Glasgow Coma Scale score (p < 0.001), less frequently dilated pupil (p = 0.028), lower Charlson Comorbidity Index (p < 0.001), smaller ICH volume (p < 0.001), noneloquent (p < 0.001) or nonintraventricular (p = 0.003) ICH locations, as well as underwent fewer neurosurgical interventions (p < 0.001) and showed a better outcome (p = 0.041), defined as Glasgow Outcome Scale 4 and 5. After adjustment for age, no different outcomes were observed. Of note, elderly patients on novel oral anticoagulants (NOACs) were more likely to develop an HE compared with those on vitamin K antagonists (VKAs, p = 0.05) after traumatic brain injury (TBI) but not after spontaneous ICH. CONCLUSION: Our data reveal a significant heterogeneity within the traumatic series. Whereas younger patients show an excellent outcome, the elderly population of the traumatic cases demonstrates a poor outcome similar to that of the nontraumatic cohort. HE under NOACs rather than under VKAs is more likely in the elderly after TBI. Larger prospective trials are warranted to elucidate the potential individual underlying molecular mechanisms for the development of an ICH and HE in these diseases.

Intake of NOAC is associated with hematoma expansion of intracerebral hematomas after traumatic brain injury.

PURPOSE: Novel oral anticoagulants are increasingly replacing vitamin K antagonists in the prophylaxis of thromboembolism as they are associated with lower incidence of spontaneous intracerebral hematomas and they do not require drug level monitoring. However, management dilemmas are apparent in patients on novel oral anticoagulants who have developed intracerebral hematomas after traumatic brain injury, since clinical experience with their reversal strategies is limited. METHODS: We retrospectively studied 90 patients with traumatic intracerebral hematomas undergoing treatment at the surgical intensive care unit of the BG University Clinic Bergmannsheil in Bochum between 2015 and 2018. We analyzed potential prognostic factors for their radiological (expansion of intracerebral hematoma) and clinical (patients' outcome) course, in particular the role of novel oral anticoagulants. RESULTS: 71.1% of patients were male; mean age was 67.3 years. Hematoma's expansion occurred in 35.9% of our patients, whereas 62.2% of our cohort showed a favorable outcome, defined as Glasgow Outcome Scale 4 and 5. Intake of novel oral anticoagulants was associated with a higher rate of hematoma's expansion compared to patients on vitamin K antagonists (p = 0.05) or to patients with normal coagulation status (p = 0.002). A younger age (p < 0.001) was identified as the sole independent prognostic factor for a more favorable outcome, after excluding our cases, who underwent a cardiopulmonary resuscitation. CONCLUSIONS: Our data showed a higher rate of hematoma's expansion in patients with traumatic intracerebral hematomas on novel oral anticoagulants vs. vitamin K antagonists and recommend the consideration of prophylactic reversal of the novel oral anticoagulants at admission. Larger prospective trials are warranted to conclude whether the current specific reversal protocols are safe and effective.

Prognostic value of the preoperative immunological profile in patients with glioblastoma.

BACKGROUND: Aim of our study was to determine the predictive impact of certain serum immunological markers on overall survival (OS) in patients with glioblastoma multiforme (GBM). METHODS: We assayed prospectively values of interleukin 2 (IL-2), immunoglobulin G (IgG), C4, CD3+, CD4+ and CD8+ cells via flow cytometry, enzyme-linked immunosorbent assay (ELISA) and radial immunodiffusion in preoperative sera of adult patients with de novo histologically confirmed supratentorial GBM. Kaplan-Meier method and Cox proportional hazards models were used to assess clinical, laboratory, and treatment prognostic factors for OS. RESULTS: Twenty-six consecutive patients were identified with a mean age of 59.6 years. Median follow up was 12 months. Lower IL-2 values (<7.97 pg/ml vs. ≥7.97 pg/ml, P = 0.029) und CD4+ counts (<200 cells/µl vs. ≥200 cells/µl, P < 0.001) correlated significantly with a shorter OS. The independent prognostic relevance of CD4 + counts was confirmed by the multivariate analysis (HR = 0.010, 95% CI 0.001-0.226, P = 0.011). Further independent prognostic factors for OS were type of resection (resection vs. biopsy) and administration of radiotherapy (yes/no). CONCLUSION: Preoperative values IL-2 and CD4+ cells in sera may carry a prognostic impact. Novel diagnostic models prior to histopathological confirmation may be used to predict prognosis of patients with GBM. Future studies should investigate whether targeting immune factors, such as CD4+ and IL-2, may improve the prognosis of patients with GBM.

Electrode dysfunctions in patients with deep brain stimulation: a clinical retrospective study.

BACKGROUND: Electrode fractures are known hardware problems in patients with deep brain stimulation (DBS) and require surgical revision. Short circuits, loose connections or disconnections of only single contacts of the common quadripolar stimulation electrodes are more subtle dysfunctions and can result in decreased efficacy of DBS. Measuring the impedances of electrodes helps detect such technical dysfunctions. This study evaluates the frequency and clinical implications of abnormal impedance measurements. METHODS: We retrospectively analyzed findings of systematic impedance checks in 591 consecutive patients with DBS for various movement disorders treated in our DBS center between 2005 and 2010. FINDINGS: A technical dysfunction was found in 36 out of 1,142 electrodes (3.2%). Short circuits (22 electrodes) were more frequent than disconnections of single contacts (8 electrodes) or loose contacts (6 electrodes). Moreover, after 109 replacements of impulse generators another 16 electrodes revealed technical dysfunctions, again with short circuits (9 electrodes) exceeding disconnections of single contacts (5 electrodes) and loose contacts (2 electrodes). Most of the short circuits occurred immediately after surgical interventions. In contrast, among dysfunctions occurring later during long-term DBS, disconnections and loose contacts prevailed. Surgical revision was performed in 4 of the overall 52 electrodes with dysfunctions, whereas in the other electrodes adjustment of stimulation parameters resulted in stable and satisfying symptom control. CONCLUSIONS: Technical dysfunctions of stimulation electrodes or extension leads are rare but important sources of unsatisfying DBS efficacy. In the majority of cases DBS programming or reprogramming allows avoiding surgical revision.