Periprocedural Safety and Feasibility of the New LVIS EVO Device for Stent-Assisted Coiling of Intracranial Aneurysms: An Observational Multicenter Study.

BACKGROUND AND PURPOSE: Stent-assisted treatment techniques can be an effective treatment option for intracranial aneurysms. The aim of this study was to evaluate the periprocedural feasibility and safety of the new LVIS EVO stent for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with intracranial aneurysms treated with the LVIS EVO in 11 European neurovascular centers were retrospectively reviewed. Patient and aneurysm characteristics, procedural parameters, immediate grade of occlusion, and technical and clinical complications were assessed. RESULTS: Fifty-seven patients with 59 aneurysms were treated with the LVIS EVO device; 57.6% of the aneurysms were incidental; 15.3% were acutely ruptured; 15.3% were recanalized or residual aneurysms; and 11.9% were treated for symptoms other than acute hemorrhage. The most frequent aneurysm locations were the middle cerebral artery (25.4%) and the anterior communicating artery (22.0%). The rate of immediate successful deployment was 93.2%. In 6.8% (n = 4) of cases, additional in-stent angioplasty was needed. The immediate complete occlusion rate was 54.2%, while there was a residual aneurysm in 35.6% and a residual neck in 10.2%. Periprocedural technical complications occurred in 7/59 treatments (11.9%; the most frequent technical complication [n = 3] was thrombus formation), which all resolved completely without clinical sequelae. Postprocedural neurologic complications occurred after 4/59 treatments (6.8%; 2 transient ischemic attacks, 1 minor stroke, 1 major stroke), of which only 1 persistent complication was directly related to the procedure (minor stroke in the vascular territory distal to the stent). CONCLUSIONS: The LVIS EVO stent is a safe, feasible device for the treatment of intracranial aneurysms.

Effect of thrombus size on recanalization by bridging intravenous thrombolysis.

BACKGROUND AND PURPOSE: Thrombus length has been reported as an important predictor of successful recanalization by intravenous thrombolysis but its influence on bridging thrombolysis has not been investigated yet. The effect of thrombus length on recanalization rates evaluated by catheter angiography early after intravenous bridging thrombolysis was analyzed. METHODS: Ninety-six consecutive patients with acute cerebral artery occlusion were included. Occlusion site and thrombus length on initial computed tomography angiography or magnetic resonance angiography were related to recanalization after intravenous bridging thrombolysis on the initial series of catheter angiography. RESULTS: Eleven of 96 patients (11.5%) showed successful recanalization (TICI 2a, 2b or 3) after intravenous bridging thrombolysis. Mean thrombus length in these patients was 10.8 mm as opposed to 15.6 mm in patients without successful recanalization. No thrombus longer than 16 mm showed complete recanalization. Binary logistic regression demonstrated a significant influence of thrombus length on probability of recanalization (odds ratio 0.78, 95% confidence interval 0.65-0.95; P = 0.014). CONCLUSIONS: Thrombus length is a significant predictor of recanalization rates after bridging thrombolysis. Overall recanalization rate within the time frame until interventional treatment is started was 11.5% after bridging thrombolysis.

The LVIS Jr. microstent to assist coil embolization of wide-neck intracranial aneurysms: clinical study to assess safety and efficacy.

INTRODUCTION: This study was aimed to assess clinical safety and efficacy of the LVIS Jr. microstent in stent-assisted coil embolization of wide-neck intracranial aneurysms. METHODS: IRB approved single-center interventional clinical study in 22 patients (10 females, 12 males, mean age 55, age range 33-74 years) for the endovascular treatment of wide-neck aneurysms. After obtaining informed consent, patients were included according to the following criteria: aneurysm fundus-to-neck ratio < 2 or neck diameter > 4 mm, and a parent vessel diameter of ≤3.5 mm. Primary end point for clinical safety was absence of death, absence of major or minor stroke, and absence of transient ischemic attack. Primary end point for treatment efficacy was complete angiographic occlusion according to the Raymond-Roy Occlusion Classification (RROC) immediately after the procedure and at follow-up after 3 and 6 months on magnetic resonance imaging (MRI). RESULTS: In 20/22 (91 %) of patients, the primary end point of safety was reached; in the two remaining patients, transient ischemic attack, but no permanent deficit was observed; in 16/22 (73 %), efficient occlusion (RROC1) was reached, and in 6/22 (27 %), a residual neck remained (RROC2). Single [seven with antegrade, two in crossover configuration, and four with "first-balloon-then-stent" (FBTS) technique] or double-stent (eight patients with Y configuration and one patient with X configuration) deployment was technically successful in all cases. CONCLUSION: Deployment of the LVIS Jr. microstent in various single- or double-stent configurations is safe and effective to assist the treatment of intracranial wide-neck aneurysms.

Prolonged low-dose thrombolysis in posterior circulation stroke.

BACKGROUND: We aimed to investigate the feasibility, preliminary safety, and efficacy of prolonged low-dose intravenous thrombolysis in posterior circulation stroke patients with a thrombus lodged in the basilar artery who were ineligible for standard rtPA administration. METHODS: We retrospectively analyzed consecutively collected patients in our stroke database who suffered from a basilar artery thrombosis and were treated with prolonged (>1 h), intravenous, low-dose (≤20 mg) rtPA between 01/2005 and 11/2012. RESULTS: Patients included in this study (n = 14) were 68.5 years (IQR 55.5; 72.75) of age and presented with a median NIHSS of 2 (1; 5.25). Median time from symptom onset to treatment was 63 h (33; 141). A median dose of 5.21 µg/kg h (4.46; 6.25) rtPA was administered over 24 h (min 10; max 48). No patient experienced symptomatic intracerebral hemorrhage, one patient developed a spinal epidural hematoma, and two elderly patients were switched to comfort care and died. In eight patients (57%) a decrease in thrombus size or no thrombus at all was detected on control imaging. Nine patients (64%) had a favorable outcome (mRS 0-2) at day 90. CONCLUSIONS: Prolonged low-dose thrombolysis with rtPA may be considered as individual treatment option in selected high-risk patients with basilar artery thrombosis. Presented data may lay the groundwork to further investigate safety and efficacy in a prospective trial.

Mechanical thrombectomy with stent retrievers in acute basilar artery occlusion.

BACKGROUND AND PURPOSE: Basilar artery occlusion remains one of the most devastating subtypes of ischemic stroke. The prognosis is poor if early recanalization is not achieved. The purpose of this study was to evaluate the safety and technical feasibility of self-expanding retrievable stents in the endovascular treatment of acute basilar artery occlusion. MATERIALS AND METHODS: Twenty-four patients with acute basilar artery occlusion were treated with Solitaire FR or Revive SE devices between December 2009 and May 2012. Additional treatment included intravenous and/or intra-arterial thrombolysis (21/24) and percutaneous transluminal angioplasty/permanent stent placement (7/24). Recanalization was assessed by means of the TICI score. Clinical outcome was determined at discharge (NIHSS), and at 3 months (mRS). RESULTS: Median NIHSS score on admission was 24; median duration of symptoms was 254 minutes. Successful recanalization (TICI 2b +3) by thrombectomy only was achieved in 18 patients (75%). Intracranial stent deployment after thrombectomy caused by underlying atherosclerotic stenosis was performed in 7 patients. If these patients with intracranial stent placement are included, successful recanalization was achieved in 21 of 24 patients (87.5%). NIHSS improvement ≥10 points was reached in 54% of patients (n = 13/24). Mortality during the first 3 months was 29% (7/24). After 3 months, 8 patients (33%) had a favorable clinical outcome (mRS 0-2). CONCLUSIONS: In our series, application of self-expanding retrievable stents in acute basilar artery occlusion resulted in a high recanalization rate without procedural complications and good clinical outcome in one-third of patients.

Muscle fibers in inflammatory myopathies and cultured myoblasts express the nonclassical major histocompatibility antigen HLA-G.

We demonstrate that HLA-G, a nonclassical major histocompatibility complex class I antigen, is expressed in muscle fibers in various inflammatory myopathies. Further, interferon-gamma induces surface expression and upregulation of mRNA transcripts corresponding to different isoforms of HLA-G in myoblasts cultured from control subjects and patients. HLA-G may have important immunological functions in inflammatory myopathies and other local immune reactions as they occur during vaccination, myoblast transplantation, and gene therapy.

Taking to the road for PI: use the balance scorecard to find your way.

The financial pressures of today's healthcare environment require healthcare professionals to be able to keep all quadrants of quality in check. Tools such as the data card will assist the users of quality data in providing the organization with a catalyst for change. The reproducibility of both the process and the tool has proven to assist an individual organization in creating a clear concise message in the integration of performance measures. This article discusses a methodology and tool for organizations to integrate and evaluate disparate sources of information that can be used to direct priorities for Performance Improvement. The data card is a tool adapted from the Dartmouth Clinical Value Compass used to assist Performance Improvement teams in both the tracking and evaluation of measures related to patient satisfaction, functional status, clinical outcomes, and financial outcomes. The visual enhancement of adding color to the arrows of the compass allows the end users to quickly identify performance improvement opportunities. Examples of the data card are included to assist the readers in identifying specific indicators that can be measured with a specific clinical population as well as adaptation to other uses such as organization-wide indicator measurement Benchmarking is key in defining best practices and has been integrated into the data card.

Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation?

Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4(+) T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.

Human muscle cells express a functional costimulatory molecule distinct from B7.1 (CD80) and B7.2 (CD86) in vitro and in inflammatory lesions.

The B7 family of costimulatory molecules likely includes members distinct from B7.1 (CD80) and B7.2 (CD86). After stimulation with IFN-gamma or TNF-alpha, human myoblasts selectively express BB-1, but not B7.1 or B7.2. BB-1 is detected by anti-BB-1, a mAb cross-reacting with B7.1 (but not B7.2) and an as yet undefined costimulatory molecule. The absence of B7.1 and B7.2 in BB-1-positive myoblasts was confirmed by RT-PCR. The molecule detected by anti-BB-1 is functional, because anti-BB-1 mAb and CTLA4Ig (but not anti-B7.1- or anti-B7.2-specific mAbs) completely inhibit Ag presentation by cytokine-induced myoblasts to HLA-DR-matched Ag-specific CD4+ T cell lines. Stimulation of myoblasts with IL-4 induces B7.1 and B7.2, as well as BB-1, but with different time kinetics. Stimulation of CD40-positive myoblasts with anti-CD40 mAb selectively induces BB-1, whereas stimulation with CD40L-transfected mouse L cells induces BB-1 and B7.1, with different kinetics. To assess whether BB-1 is expressed in muscle tissue, we investigated 23 muscle biopsy specimens from patients with polymyositis, dermatomyositis, inclusion body myositis, Duchenne muscular dystrophy, and nonmyopathic controls by immunohistochemistry and confocal laser microscopy. We found that, in all inflammatory myopathy cases, but not in normal muscle, many muscle fibers strongly react with anti-BB-1. In contrast, muscle fibers did not react with B7.1- or B7.2-monospecific mAbs in any of the pathologic specimens or in normal muscle. Our results demonstrate that human muscle cells can be induced to selectively express BB-1, a functional costimulatory molecule distinct from B7.1 and B7.2. This molecule may play an important role in the immunobiology of muscle.

T-cell heterogeneity in muscle lesions of inclusion body myositis.

In the muscle lesions of inclusion body myositis (IBM), two populations of T cells can morphologically be distinguished, T cells that invade muscle fibers and T cells that remain in interstitial areas. Using combined immunohistochemistry and RT-PCR, we analysed the TCR expressed by these distinct T cell populations. In three of eight IBM muscle specimens, the autoinvasive T cells were stained with one of the available mAbs: anti-Vbeta5.3 in patient 1, anti-Vbeta5.2 in patient 2, and anti-Vbeta3 in patient 3. The corresponding TCR Vbeta mRNAs were amplified by RT-PCR and the PCR products were cloned and sequenced. In all three specimens, the TCRs expressed by the autoinvasive T cells were clonally restricted. Furthermore, in patient 1 two different mAbs labelled two distinct populations of T cells: an autoaggressive population of CD8 + Vbeta5.3 + cells that invaded muscle fibers and a noninvasive interstitial population of CD8 - Vbeta5.1 + cells. TCR sequence analysis revealed that the noninvasive Vbeta5.1 + T cells were clonally diverse, whereas the autoinvasive Vbeta5.3 + T cells were clonally restricted.

Cytotoxic mechanisms in inflammatory myopathies. Co-expression of Fas and protective Bcl-2 in muscle fibres and inflammatory cells.

Expression of the Fas 'death receptor', Fas (CD95/APO-1) renders cells susceptible to programmed cell death ('apoptosis'), whereas Bcl-2 protects cells from apoptosis. Using fluorescence immunohistochemistry, we analysed Fas and Bcl-2 expression in muscle from five patients with polymyositis (PM), four patients with inclusion body myositis (IBM), three patients with dermatomyositis (DM), three patients with Duchenne muscular dystrophy (DMD) and three nonmyopathic controls. Fas (CD95) and Bcl-2 were not detected in control muscle, but expressed in muscle fibres and inflammatory cells in PM, IBM, DM and DMD. The proportion of Fas+ muscle fibres ranged from < 1 to 50%, and was higher in PM and IBM than in DM and DMD. On average, the Fas+ muscle fibres were smaller (median diameter, 10 microns; range, 7-32 microns) than the Fas- fibres (median, 36 microns; range, 10-60 microns). Less than 10% of the Fas+ muscle fibres co-expressed the regeneration marker CD56 (neural cell adhesion molecule N-CAM). In PM and IBM, the proportion of Fas+ muscle fibres was higher among fibres invaded or contacted by T cells than among fibres not contacted by T cells (P < 0.01). The proportion of Fas+ fibres co-expressing Bcl-2 was 76 +/- 16% in PM, 100% in IBM and 63 +/- 23% in DM. Fas and Bcl-2 expression was also noted in inflammatory cells in PM, IBM, DM and DMD. Using the terminal deoxytransferase-catalysed DNA nick end labelling technique for detection of nuclear DNA fragmentation, none of myonuclei, and < 0.1% of inflammatory cell nuclei, showed signs of apoptosis. Our results suggest that, although Fas expression confers susceptibility to Fas-mediated apoptosis, Fas-expressing muscle fibres and inflammatory cells are protected by the anti-apoptotic protein Bcl-2.

Interferon gamma gene expression in sensory neurons: evidence for autocrine gene regulation.

We explored expression and possible function of interferon-gamma (IFN-gamma) in cultured fetal (E15) rat dorsal root ganglion neurons combining whole cell patch-clamp electrophysiology with single cell reverse transcriptase polymerase chain reaction and confocal laser immunocytochemistry. Morphologically, we located IFN-gamma protein in the cytoplasm of the neurons in culture as well as in situ during peri- and postnatal development. Transcripts for classic IFN-gamma and for its receptor were determined in probes of cytoplasm sampled from individual cultured neurons, which had been identified by patch clamp electrophysiology. In addition, the cultured neurons expressed both chains of the IFN-gamma receptor. Locally produced IFN-gamma acts back on its cellular source. Phosphorylation and nuclear translocation of the IFN-inducible transcriptional factor STAT1 as well as IFN-gamma-dependent expression of major histocompatibility complex class I molecules on the neuronal membrane were noted in untreated cultures. However, both processes were substantially blocked in the presence of antibodies neutralizing IFN-gamma. Our findings indicate a role of IFN-gamma in autocrine regulation of sensory neurons.

Cellular immune mechanisms in inflammatory myopathies.

The inflammatory myopathies include dermatomyositis, polymyositis, and inclusion body myositis. In dermatomyositis, muscle fiber injury is secondary to an antibody- or immune-complex-mediated immune response against a vascular-endothelial component. In polymyositis and inclusion body myositis, CD8+ T cells and macrophages invade and eventually destroy initially nonnecrotic muscle fibers. The autoaggressive T cells have the phenotype of activated (HLA-DR+) memory (CD45RO+) cells. T-cell receptor analyses indicate that the autoaggressive T cells are oligoclonal. In inflammatory lesions, muscle fibers express various cytoplasmic and surface molecules that are not detectable in normal fibers. These molecules, which include HLA class I antigens, heat-shock proteins, adhesion molecules, and Fas, are probably induced by locally secreted cytokines. The autoaggressive CD8+ T cells harbor granules containing perforin that aggregate near the contact zone with the target muscle fiber. This is consistent with a perforin- and secretion-dependent mechanism of muscle fiber injury. Many invaded muscle fibers also express the Fas "death receptor," but signs of apoptosis are absent.