TCCD Fusion Imaging to Estimate Intracranial Pressure and Tissue Displacement with Large Hemispheric Infarction.

BACKGROUND: Despite breakthroughs in stroke treatment, some patients still experience large infarctions of the cerebral hemispheres resulting in mass effect and tissue displacement. The evolution of mass effect is currently monitored using serial computed tomography (CT) imaging. However, there are patients who are ineligible for transport, and there are limited options for bedside monitoring of unilateral tissue shift. METHODS: We used fusion imaging for overlaying transcranial color duplex with CT angiography. This method allows overlay of live ultrasound on top of CT or magnetic resonance imaging scans. Patients with large hemispheric infarctions were eligible to participate. Position data from the source files were used and matched with live imaging and correlation to magnetic probes on the patient's forehead and ultrasound probe. Shift of cerebral parenchyma, displacement of the anterior cerebral arteries, basilary artery and third ventricle were analyzed, as well as pressure on the midbrain, and the displacement of the basilar artery on the head were analyzed. Patients received multiple examinations in addition to standard care of treatment with CT imaging. RESULTS: The sensitivity for diagnosing a shift of 3 mm with fusion imaging was 100%, with a specificity of 95%. No side effects or interactions with critical care equipment were recorded. CONCLUSIONS: Fusion imaging is an easy method to access and acquire measurements for critical care patients and follow-up of tissue and vascular displacement after stroke. Fusion imaging may be a decisive support for indicating hemicraniectomy.

The Downside of Botulinum Injections for Anterocollis: A Case Series and a Review of the Literature.

OBJECTIVES: This is a case series and a review of the literature of therapeutic outcomes of botulinum toxin (BT) injections for anterocollis. METHODS: Data collected included gender, age, age at onset, muscles targeted, and doses injected. Routine forms were filled out during each visit: Patient Global Impression of Change, Clinician Global Impression of Severity, Tsui scale. The effect duration and side effects (SEs) of the previous treatment were noted. RESULTS: We described 4 patients (3 men, 13 visits) with anterocollis, as primary postural abnormality of the neck, emphasizing the therapeutic response to BT injection. Mean age at onset was 75.3 ± 7.0 years, age at first injection was 80.7 ± 3.5 years. The mean total dose per treatment was 290.0 ± 95.6 units. Patient Global Impression of Change with any grade of favorable effect was reported in 27.3% of the treatments. In objective assessment, Global Impression of Severity and Tsui scores did not show a consistent tendency of improvement. Neck weakness was prevalent in 18.2% of the visits of the anterocollis group while no other SEs were noted. We found 15 articles describing experience with BT for anterocollis in 67 patients (19 in deep and 48 in superficial neck muscles). CONCLUSIONS: This case series describes the poor outcome of BT treatment for anterocollis, with low efficacy and bothersome SE. Levator scapulae injection for anterocollis is not effective and is highly associated with head drop and should perhaps be abandoned. Injection to the longus colli might give some benefit in non-responders.

In-thrombus thrombin secretion: a new diagnostic marker of atrial fibrillation in cryptogenic stroke.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Flexible endoscopic evaluation of swallowing (FEES) to determine neurological intensive care patients' oral diet.

PURPOSE: Dysphagia is common in critically ill neurological patients and is associated with a high mortality and morbidity. Data on the usefulness of flexible endoscopic examination of swallowing (FEES) in neurological intensive care unit (ICU) patients are lacking, raising the need for evaluation. METHOD: FEES was performed in neurological intensive care patients suspected of dysphagia. We correlated findings with baseline data, disability status, pneumonia and duration of hospitalisation, as well as a need for mechanical ventilation or tracheotomy. RESULT: This analysis consisted of 125 patients with suspected dysphagia. Most of the patients (81; 64,8%) suffered from acute stroke. Dysphagia was diagnosed using FEES in 90 patients (72%). FEES results led to dietary modifications in 80 patients (64%). The outcome at discharge was worse in dysphagic stroke patients diagnosed by FEES as compared to non-dysphagic stroke patients (p = 0.009). Patients without oral diet had higher need for intubation (p = 0.007), tracheotomy (p = 0.032) and higher mortality (p < 0.001) in comparison to patients with at least small amounts of oral intake. CONCLUSION: As the clinical assessment of the patients often classified the dysphagia incorrectly, the broad use of FEES in ICU patients might help to adequately adjust patients' oral diet. This knowledge might contribute to lower mortality and morbidity.

In-thrombus thrombin secretion: a new diagnostic marker of atrial fibrillation in cryptogenic stroke.

BACKGROUND: Endovascularly retrieved clots are a potential resource for diagnosing stroke etiology, which may influence secondary prevention treatment. In this study we measured thrombin activity eluted by serially washing clots. METHODS: Clots were retrieved from 68 patients with acute ischemic stroke, freshly frozen and classified by standard criteria into proven atrial fibrillation (AF, 18 patients), atherosclerotic origin (AS, 15 patients), cryptogenic stroke (Cr, 17 patients) and other known causes (18 patients). Thawed clot samples were washed by transferring them into 1 mL buffer in seven hourly cycles and a fluorescent substrate assay was used to measure secreted thrombin activity. The clots were also examined histologically. Artificial fibrin and red blood cell-rich clots were similarly assayed for wash-eluted thrombin activity as an external control. RESULTS: Thrombin activity eluted from clots of AF origin decreased significantly with time in contrast to steady levels eluted from AS origin thrombi (P<0.0001 by repeated measures ANOVA). The Cr stroke group was indistinguishable from the AF group and differed statistically from the AS group (P=0.017 by repeated measures ANOVA). In artificial clots we found a biphasic activity pattern, with initially decreasing levels of eluted thrombin (AF pattern) and then, with continuing washes, steady eluted thrombin levels (AS pattern). CONCLUSIONS: An assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Pre-admission CHA2DS2-VASc score and outcome of patients with acute cerebrovascular events.

BACKGROUND: The CHA2DS2-VASc score has been recommended for the assessment of thromboembolic risk in patients with atrial fibrillation. Data regarding the association between the pre-admission CHA2DS2-VASc score and the outcome of patients with stroke and TIA are scarce. We aimed to assess the predictive value of pre-admission CHA2DS2-VASc score for early risk stratification of patients with acute cerebrovascular event. METHODS: The study group consisted of 8309 patients (53% males, mean age of 70±13.3years) with acute stroke and TIA included in the prospective National Acute Stroke Israeli (NASIS) registry. The two-primary end-points were in-hospital mortality and severe disability at discharge. We divided the study population into 4 groups according to their pre-admission CHA2DS2-VASc score (0-1, 2-3, 4-5, >5). RESULTS: Following a multivariate analysis odds ratios (OR) for all-cause mortality increased for CHA2DS2-VASc score >1 (OR=2.1 95% CI=1.2-3.6, OR=1.8 95% CI=1.1-3.2, OR=1.8 95% CI 1.1-3.3, for patients with CHA2DS2-VASc score of 2-3, 4-5 and >5, respectively, p<0.001). OR for severe disability (mRS 4-5) at discharge increased significantly in direct association with the CHA2DS2-VASc score (OR=1.55 95% CI=1.14-2.12, OR=2.42 95% CI=1.8-3.3, OR=3 95% CI 2.19-4.27, for patients with CHA2DS2-VASc score of 2-3, 4-5 and >5, respectively as compared with 0-1, p<0.001). Each 1-point increase in the CHA2DS2-VASc score was associated with a 21% increase in the risk for severe disability. CONCLUSIONS: High-risk pre-admission CHA2DS2-VASc score among patients with acute cerebrovascular events is associated with higher in-hospital mortality and severe disability at discharge.

Cytokine Interferon-γ suppresses the function of capsule myofibroblasts and induces cell apoptosis.

Myofibroblasts (MFs), a contractile subset of fibroblasts, play a pivotal role in physiological wound healing and in the development of many fibroconnective disorders. The complex cytokine network regulating the function of MFs in joint stiffness is still poorly understood. In this in vitro study, we investigated the effect of the cytokine Interferon-gamma (IFN-γ) on MFs isolated from human joint capsules. MFs were cultivated either in the presence of increasing concentrations of IFN-γ alone or in combination with IFN-γ neutralizing antibodies. Cell viability, cytotoxicity, apoptosis, and mRNA gene expression of the MF markers alpha-smooth muscle actin (α-SMA) and collagen type I were analyzed in MF cultures. Contraction potential was analyzed in an established collagen gel contraction assay simulating the extracellular matrix. Using immunofluorescence staining, we could verify that MFs express IFN-γ-receptor (R)-1 on their membrane. IFN-γ decreased MF viability and significantly elevated the apoptosis rate in a dose-dependent manner. IFN-γ down-regulated α-SMA and collagen type I mRNA expression which was associated with a diminished MF mediated contraction of the gel matrices. These effects were suppressed by simultaneous treatment of cells with a neutralizing IFN-γ antibody. Our experiments confirm the hypothesis that the cytokine IFN-γ is a crucial component of the regulatory network of capsule MFs. IFN-γ notably influences the ability of MFs to contract collagen matrices by suppressing α-SMA gene expression. IFN-γ is toxic for MFs in high concentrations and may negatively regulate the number of pro-fibrotic MFs during the healing process via induction of cell apoptosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2524-2533, 2017.

Influence of the anti-inflammatory cytokine interleukin-4 on human joint capsule myofibroblasts.

Post-traumatic joint contracture was reported to be associated with elevated numbers of contractile myofibroblasts (MFs) in the healing capsule. During the physiological healing process, the number of MFs declines; however, in fibroconnective disorders, MFs persist. The manifold interaction of the cytokines regulating the appearance and persistence of MFs in the pathogenesis of joint contracture remains to be elucidated. The objective of our current study was to analyze the impact of the anti-inflammatory cytokine interleukin (IL)-4 on functional behavior of MFs. Cells were isolated from human joint capsule specimens and challenged with three different concentrations of IL-4 with or without its neutralizing antibody. MF viability, contractile properties, and the gene expression of both alpha-smooth muscle actin (α-SMA) and collagen type I were examined. Immunofluorescence staining revealed the presence of IL-4 receptor (R)-alpha (α) on the membrane of cultured MFs. The cytokine IL-4 promoted MF viability and enhanced MF modulated contraction of collagen gels. Moreover, IL-4 intervened in gene expression by up-regulation of α-SMA and collagen type I mRNA. These effects could be specifically lowered by the neutralizing IL-4 antibody. On the basis of our findings we conclude that the anti-inflammatory cytokine IL-4 specifically regulates viability and the contractile properties of MFs via up-regulating the gene expression of α-SMA and collagen type I. IL-4 may be a helpful target in developing anti-fibrotic therapeutics for post-traumatic joint contracture in human. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1290-1298, 2017.