Showing papers by "Peter D. Schellinger published in 2009"

Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke

Abstract: Background and Purpose—We hypothesized that transcranial laser therapy (TLT) can use near-infrared laser technology to treat acute ischemic stroke. The NeuroThera Effectiveness and Safety Trial–2 (NEST-2) tested the safety and efficacy of TLT in acute ischemic stroke. Methods—This double-blind, randomized study compared TLT treatment to sham control. Patients receiving tissue plasminogen activator and patients with evidence of hemorrhagic infarct were excluded. The primary efficacy end point was a favorable 90-day score of 0 to 2 assessed by the modified Rankin Scale. Other 90-day end points included the overall shift in modified Rankin Scale and assessments of change in the National Institutes of Health Stroke Scale score. Results—We randomized 660 patients: 331 received TLT and 327 received sham; 120 (36.3%) in the TLT group achieved favorable outcome versus 101 (30.9%), in the sham group (P0.094), odds ratio 1.38 (95% CI, 0.95 to 2.00). Comparable results were seen for the other outcome measures. Although no prespecified test achieved significance, a post hoc analysis of patients with a baseline National Institutes of Health Stroke Scale score of 16 showed a favorable outcome at 90 days on the primary end point (P0.044). Mortality rates and serious adverse events did not differ between groups with 17.5% and 17.4% mortality, 37.8% and 41.8% serious adverse events for TLT and sham, respectively. Conclusions—TLT within 24 hours from stroke onset demonstrated safety but did not meet formal statistical significance for efficacy. However, all predefined analyses showed a favorable trend, consistent with the previous clinical trial (NEST-1). Both studies indicate that mortality and adverse event rates were not adversely affected by TLT. A definitive trial with refined baseline National Institutes of Health Stroke Scale exclusion criteria is planned. (Stroke. 2009;40:1359-1364.)

Transcranial ultrasound in clinical sonothrombolysis (TUCSON) trial.

Abstract: Objective Microspheres (microS) reach intracranial occlusions and transmit energy momentum from an ultrasound wave to residual flow to promote recanalization. We report a randomized multicenter phase II trial of microS dose escalation with systemic thrombolysis. Methods Stroke patients receiving 0.9mg/kg tissue plasminogen activator (tPA) with pretreatment proximal intracranial occlusions on transcranial Doppler (TCD) were randomized (2:1 ratio) to microS (MRX-801) infusion over 90 minutes (Cohort 1, 1.4ml; Cohort 2, 2.8ml) with continuous TCD insonation, whereas controls received tPA and brief TCD assessments. The primary endpoint was symptomatic intracerebral hemorrhage (sICH) within 36 hours after tPA. Results Among 35 patients (Cohort 1 = 12, Cohort 2 = 11, controls = 12) no sICH occurred in Cohort 1 and controls, whereas 3 (27%, 2 fatal) sICHs occurred in Cohort 2 (p = 0.028). Sustained complete recanalization/clinical recovery rates (end of TCD monitoring/3 month) were 67%/75% for Cohort 1, 46%/50% for Cohort 2, and 33%/36% for controls (p = 0.255/0.167). The median time to any recanalization tended to be shorter in Cohort 1 (30 min; interquartile range [IQR], 6) and Cohort 2 (30 min; IQR, 69) compared to controls (60 min; IQR, 5; p = 0.054). Although patients with sICH had similar screening and pretreatment systolic blood pressure (SBP) levels in comparison to the rest, higher SBP levels were documented in sICH+ patients at 30 minutes, 60 minutes, 90 minutes, and 24-36 hours following tPA bolus. Interpretation Perflutren lipid microS can be safely combined with systemic tPA and ultrasound at a dose of 1.4ml. Safety concerns in the second dose tier may necessitate extended enrollment and further experiments to determine the mechanisms by which microspheres interact with tissues. In both dose tiers, sonothrombolysis with microS and tPA shows a trend toward higher early recanalization and clinical recovery rates compared to standard intravenous tPA therapy. Ann Neurol 2009;66:28-38.

Therapy of acute basilar artery occlusion: intraarterial thrombolysis alone vs bridging therapy.

Abstract: Background and Purpose— While intravenous recombinant tissue plasminogen activator (rt-PA) has been approved for acute stroke therapy within 3 hours, the optimum management of basilar artery occlusion (BAO) is still a matter of debate. We compared intraarterial thrombolysis with the combined bridging approach of intravenous abciximab and intraarterial thrombolysis with rt-PA (bridging therapy) in an observational, longitudinal, monocenter study. Methods— Between 1998 and 2006, information for 106 patients with acute BAO were prospectively entered into a local database. Patients eligible for treatment received either intraarterial thrombolysis with rt-PA alone (intraarterial thrombolysis) or were treated with intravenous abciximab and intraarterial rt-PA (bridging therapy). Outcome parameters were recanalization of the basilar artery according to Trial in Myocardial Infarction criteria, survival, and reduction of severe disability and death at 3 months. Logistic regression was used to identify independent ...

Safety and outcome after thrombolysis in stroke patients with mild symptoms.

Abstract: Background: Thrombolytic therapy is frequently withheld in patients with minor stroke symptoms. However, recent studies demonstrate that a substantial proportion of these patients d

Abstract 5504: Transient Decrease in Circulating Dendritic Cell Precursors After Acute Stroke - Potential Recruitment Into the Brain

Abstract: Background: The role of dendritic cells (DC) as potent mediators of inflammation has not been sufficiently investigated in stroke. Methods: Circulating myeloid (mDCP), plasmacytoid (pDCP), and total DCP (tDCP) were flow cytometrically analyzed in healthy controls (n=29), patients with asymptomatic A. carotis interna stenosis (ACI-S, n=46), transient ischemic attack (TIA, n=39), acute ischemic stroke (AIS, n=73), and acute hemorrhagic stroke (AHS, n=31). The National Institutes of Health Stroke Scale (NIHSS) and the infarction size in CT scan were evaluated after stroke. In a patient subgroup, postmortem immunohistochemical brain analyses were performed to detect mDC (CD209), pDC (CD123), T cells (CD3), and HLA-DR. Results: In AIS and AHS, circulating mDCP, pDCP, and tDCP (each p Conclusions: Acute stroke leads to a decrease in circulating DCP. Potentially, circulating DCP are recruited from the blood into the infarcted brain, and probably trigger cerebral immune reactions there.

Early Administration of Low Molecular Weight Heparin after Spontaneous Intracerebral Hemorrhage

Abstract: Background: Venous thromboembolism (VTE) is a common complication after stroke. Application of low molecular weight heparins (LMWH) has been proven to be beneficial for the preventi

Acute stroke triage to intravenous thrombolysis and other therapies with advanced CT or MR imaging: pro MR imaging.

Abstract: In this article and the companion piece, two sets of experts present their views on the use of computed tomography (CT) or magnetic resonance (MR) imaging to select patients with acute stroke to undergo available reperfusion therapies. Specifically, in this article, two neurologists provide the clinical background and motivation behind the use of advanced imaging in stroke triage—most notably with regard to major clinical trials—to extend the time window for intravenous thrombolysis beyond the currently recommended 3-hour window after stroke. To date, these trials have focused almost exclusively on the use of MR imaging and MR angiography to determine patient eligibility. In this article, the authors compare the MR and CT methods of triage. In the companion article, three neuroradiologists expand on the benefits and limitations of advanced CT imaging in stroke evaluation and offer their perspective on which modality to choose and why.

Randomized, Placebo-Controlled, Dose-Ranging Clinical Trial of Intravenous Microplasmin in Patients With Acute Ischemic Stroke

Abstract: Background and Purpose-Microplasmin is a recombinant truncated form of human plasmin. It has demonstrated efficacy in experimental animal models of stroke and tolerability in healthy volunteers. We tested the tolerability of microplasmin in patients with acute ischemic stroke. Methods-In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical efficacy. Results-Microplasmin induced reversible effects on markers of systemic thrombolysis and neutralized alpha(2)-antiplasmin by up to 80%. It was well tolerated with one of 30 treated patients developing a fatal symptomatic intracerebral hemorrhage. No significant effect on reperfusion rate or on clinical outcome was observed. Matrix metalloproteinase-2 levels were reduced in microplasmin-treated patients. Conclusions-Microplasmin was well tolerated and achieved neutralization of alpha(2)-antiplasmin. Further studies are warranted to determine whether microplasmin is an effective therapeutic agent for ischemic stroke. (Stroke. 2009; 40: 3789-3795.)

Safety and dose‐escalation study design of Transcranial Ultrasound in Clinical SONolysis for acute ischemic stroke: the TUCSON Trial

Abstract: Rationale Transcranial Doppler (TCD) monitoring during intravenous tissue plasminogen activator (i.v.-tPA) infusion increases recanalization rates in acute ischemic stroke. Addition of perflutren-lipid microspheres MRX-801 (microS) may further enhance the process of recanalization. This article describes the design of the Transcranial Ultrasound in Clinical SONolysis (TUCSON) trial. Aims and Design TUCSON is a phase I-II, randomized, placebo-controlled, open-label, safety, dose-escalation clinical trial of microS+TCD ultrasound (sonolysis). Patients with acute ischemic stroke and arterial intracranial occlusions are enrolled within 3 h of symptom onset. All patients receive standard i.v.-tPA and will be randomized to 90 min of continuous 2-MHz TCD+microS or 90 min of saline+brief TCD vessel assessments. The safety profile of four escalating dose tiers will be assessed. Arterial occlusions and recanalization are defined with the Thrombolysis in Brain Ischemia flow grades. Study Outcomes Safety is determined by the rates of symptomatic intracerebral hemorrhage within 36 h. Neurological deficits and outcomes are measured with the National Institute of Health Stroke Scale and modified Rankin Scale (mRS). The signal-of-efficacy is determined by rates of recanalization, dramatic or early clinical recovery within 2 h, clinical recovery at 24-36 h and independent outcome (mRS 0-2) at 90 days.

Mechanical Ventilation in Guillain-Barré Syndrome: Does Age Influence Functional Outcome?

Abstract: Purpose: To examine the effects of age on differences in the clinical course and functional outcome of mechanically ventilated Guillain-Barre syndrome (GBS) patients. Metho

Bildgebung beim Schlaganfall – eine Übersicht und Empfehlungen des Kompetenznetzes Schlaganfall

Abstract: For the past decades, new technical developments in brain imaging have greatly contributed to a better understanding of the pathophysiology of acute stroke und have paved the way for new possibilities in the diagnosis and treatment of acute stroke. Brain imaging provides indispensable information for a specific and effective management of acute stroke patients. Non-contrast CT is the most widely available technique and has its major impact in the diagnosis or exclusion of intracranial hemorrhage. In addition, early ischaemic signs can be identified on CT in a large number of patients already within the first hours of stroke. Non-contrast CT is the only imaging modality that is required prior to treatment with intravenous thrombolysis. Multiparametric stroke MRI including diffusion-weighted imaging, perfusion imaging, MR angiography and T2*-weighted imaging also detects intracranial haemorrhage with high sensitivity, and provides additional information on the extent of the ischaemic lesion, hypoperfused tissue and on the vessel status. Stroke MRI allows the identification of tissue at risk of infarction, which is the target for reperfusion therapies beyond the 3-hour time window. Multiparametric CT combining perfusion CT and CT angiography likely provides comparable information. Doppler and duplex sonography is a reliable method to screen for pathologies of the extracranial arteries. Transcranial sonography additionally enables one to assess large intracranial vessels in the majority of patients. For the future, multiparametric brain imaging with modern CT or MRI techniques is expected to play an increasing role in the management of acute stroke in the routine clinical setting, as well as in clinical trials.

MR Mismatch Is Useful for Patient Selection for Thrombolysis Yes

Abstract: Geoffrey A. Donnan MD, FRACP Stephen M. Davis MD, FRACP Section Editors: The MR perfusion diffusion (PI/DWI) mismatch concept for the selection of patients for intravenous thrombolysis (IVT) was introduced with several smaller case series in the late 1990s and early 2000s,1 followed by larger series by many international groups over the last 8 years. A potentially salvageable penumbra was operationally defined as a PI/DWI-(volume) mismatch where PI indicates the hypoperfused tissue and DWI shows the more or less severe ischemic core.2 A mismatch volume of 20% (PI>DWI) has been widely accepted as indicator of a penumbral MRI setting. In an ideal world perfusion postprocessing would provide absolute values for cerebral blood flow (CBF). Perfusion maps could then indicate penumbra based on different thresholds for gray and white matter and thus …

Patientenauswahl zur Thrombolyse mittels Perfusions- und Diffusions-MRT

Abstract: Die multiparametrische MRT mit Diffusions- und Perfusionsbildgebung gibt in einem Untersuchungsgang Informationen uber das Ausmas des bereits ischamisch geschadigten Gewebes, die Grose des kritisch minderperfundierten Areals und den Gefasstatus. Uber das Perfusions-Diffusions-Mismatch lasst sich vom Untergang bedrohtes Gewebe identifizieren, das auch noch nach 3 h nach Symptombeginn durch eine erfolgreiche Reperfusionstherapie gerettet werden kann. Neuere Studien zum Mismatch-Konzept haben gezeigt, dass Reperfusion eine entscheidende Bedingung fur ein gutes Ergebnis nach einer Thrombolyse darstellt. Grose Fallserien und nichtrandomisierte Kohortenstudien ergaben, dass bei mittels Perfusions-Diffusions-Mismatch ausgewahlten Patienten eine intravenose Thrombolyse jenseits des 3-Stunden-Zeitfensters sicher und effektiv durchgefuhrt werden kann; randomisierte kontrollierte Studien zur Effektivitat der Mismatch-basierten Thrombolyse jenseits des 3-Stunden-Zeitfensters existieren allerdings bisher nicht. Bis eine solche Studie durchgefuhrt wird, kann in erfahrenen Zentren auch nach 3 h nach Symptombeginn eine Thrombolyse nach individueller Risikoabwagung anhand moderner Bildgebungsbefunde durchgefuhrt werden.

Patient selection for thrombolysis using perfusion and diffusion MRI. An overview

Abstract: Multiparametric MRI including diffusion and perfusion imaging provides information on the extent of irreversibly damaged ischemic and/or critically hypoperfused tissue. Magnetic resonance angiography provides additional information on vessel status. The concept of perfusion-diffusion mismatch allows the estimation of tissue at risk of infarction which might be salvaged by timely reperfusion. In large case series and nonrandomized cohort studies, perfusion-diffusion mismatch-based thrombolysis was performed not less than 3 h after symptom onset with excellent safety and signs of good efficacy. However no randomised controlled trial has confirmed this to date. Recent studies improved the understanding of the mismatch concept and identified reperfusion unequivocally as an important predictor of the clinical response to thrombolysis. At the moment MRI-based thrombolysis can be performed after 3 h based on individual benefit:risk assessment in experienced stroke centers.

The safety and usefulness of low molecular weight heparins and unfractionated heparins in patients with acute stroke.

Abstract: Stroke is a common cause for morbidity and mortality, causing substantial economic costs. Because thrombosis plays a key role in the pathogenesis of ischaemic stroke, heparins, platelet inhibitors and anticoagulants have been used in stroke management. There were high hopes that patients might benefit from the use of heparins. Unfortunately, these expectations have not been met. Instead, thrombolytics have been shown to result in an improvement of outcome in a considerable fraction of patients with ischaemic stroke. Yet, in other areas of stroke management, such as the prevention of venous thromboembolism after stroke, heparins have found their niche. In this review, we report on the currently available literature on heparins for the reduction of stroke-related morbidity and mortality, the prevention of recurrent stroke as well as the prevention of venous thromboembolism in both ischaemic and haemorrhagic stroke with respect to their risks, such as the haemorrhagic transformation of ischaemic strokes.

Malignant hyperthermia and its differential diagnosis

Abstract: Hyperthermia affects almost all endogenous regulatory systems, where especially cardiovascular and central nervous system interactions can result in life threatening complications. This review illustrates signs and symptoms, pathophysiology and therapeutic options of the three most common hyperthermic syndromes in neurology: malignant hyperthermia, serotonine-syndrom and malignant neuroleptic syndrome. The aim of this contribution is to enable the reader to make the differential diagnosis of these three disease entities. Furthermore the association of other specific myopathies and hyperthermia syndromes is discussed.

Bildgebung beim Schlaganfall ± eine Übersicht und Empfehlungen des Kompetenznetzes Schlaganfall Imaging in Stroke ± An Overview and Recommendations from the German Competence Network Stroke

Abstract: Schlaganfall l " Bildgebung l " Computertomografie l " Magnetresonanztomografie " stroke l " imaging l " computed tomography l " magnetic resonance imaging Abstract ! For the past decades, new technical develop- ments in brain imaging have greatly contributed to a better understanding of the pathophysiology of acute stroke und have paved the way for new possibilities in the diagnosis and treatment of acute stroke. Brain imaging provides indispensa- ble information for a specific and effective man- agement of acute stroke patients. Non-contrast CT is the most widely available technique and has its major impact in the diagnosis or exclusion of intracranial hemorrhage. In addition, early ischaemic signs can be identified on CT in a large number of patients already within the first hours of stroke. Non-contrast CT is the only imaging modality that is required prior to treatment with intravenous thrombolysis. Multiparametric stroke MRI including diffusion-weighted imag- ing, perfusion imaging, MR angiography and T2*-weighted imaging also detects intracranial haemorrhage with high sensitivity, and provides additional information on the extent of the ischaemic lesion, hypoperfused tissue and on the vessel status. Stroke MRI allows the identifi- cation of tissue at risk of infarction, which is the target for reperfusion therapies beyond the 3-hour time window. Multiparametric CT com- bining perfusion CT and CT angiography likely provides comparable information. Doppler and duplex sonography is a reliable method to screen for pathologies of the extracranial arteries. Trans- cranial sonography additionally enables one to assess large intracranial vessels in the majority of patients. For the future, multiparametric brain imaging with modern CT or MRI techniques is ex- pected to play an increasing role in the manage- ment of acute stroke in the routine clinical set- ting, as well as in clinical trials.