Medicine and Health Sciences Commons^™

Associations Between Performance On The Rey-Osterrieth Complex Figure And Regional Brain Volumes In Children With And Without Velocardiofacial Syndrome, Kevin Antshel, Jena Peebles, Nuria Abdulsabur, Anne Marie Higgins, Nancy Roizen, Robert Shprintzen, Wanda Fremont, Robert Natasi, Wendy Kates

Robert J. Shprintzen

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race, and gender-ratio comparable sample of 59 control participants were included in the project. Participants received an MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white …

Kyphotic Progression After Thoracolumbar Burst Fractures Treated Conservatively, With Mis, Or Via Open Approach, Mark Rivkin, Howard Eisenbrock

Mark Rivkin

Management of thoracolumbar burst fractures (AO A3) without neurological deficit is subject to debate in the literature. While TLICS provides guidance for injuries necessitating intervention, it makes little mention of best surgical approaches. Furthermore, intact patients with suspected posterior ligamentous complex injury (TLICS 4) compose an additional level of management uncertainty. Present study examined outcomes for TL burst fractures in neurologically intact patients with suspected disruption of the PLC treated with bracing, MIS, or open fixation and fusion.

G-Csf, Rt-Pa And Combination Therapy After Experimental Thromboembolic Stroke, Rainer Kollmar, Nils Henninger, Christian Urbanek, Stefan Schwab

Nils Henninger

BACKGROUND: Granulocyte Colony-Stimulating Factor (G-CSF) has remarkable neuroprotective properties. Due to its proven safety profile, G-CSF is currently used in clinical stroke trials. As neuroprotectants are considered to be more effective in the early phase of cerebral ischemia and during reperfusion, G-CSF should to be tested in combination with thrombolysis. Therefore, combination therapy was investigated in an experimental model of thromboembolic stroke. METHODS: Male Wistar rats (n = 72) were subjected to a model of thromboembolic occlusion (TE) of the middle cerebral artery. Different groups (n = 12 each) treated by recombinant tissue-plasminogen activator (rt-PA) or/and G-CSF: group control (control), …

Use Of Telemedicine To Increase Thrombolysis And Advance Care In Acute Ischemic Stroke, Nils Henninger, Nabi Chowdhury, Marc Fisher, Majaz Moonis

Nils Henninger

The use of the only proven therapy for acute ischemic stroke, intravenous tissue plasminogen activator (tPA), remains disappointingly low. One potential way to increase the use of tPA is by the implementation of telemedicine stroke care networks. Preliminary data from several studies indicate that the safe and expanded use of tPA for ischemic stroke can be accomplished with the help of telemedicine. Telemedicine stroke care networks can also be used in the future to enhance stroke diagnosis with advanced CT and MRI technology and to potentially increase the number of patients referred to tertiary stroke centers for intra-arterial therapies. It …

Leukoaraiosis And Sex Predict The Hyperacute Ischemic Core Volume, Nils Henninger, Eugene Lin, Diogo Haussen, Laura Lehman, Deepak Takhtani, Magdy Selim, Majaz Moonis

Nils Henninger

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) and male sex have been associated with decreased cerebrovascular reactivity, which potentially adversely affects tissue viability in acute stroke. Therefore, we aimed to elucidate the contribution of LA-severity and sex to the extent of the hyperacute ischemic core volume after intracranial large artery occlusion. METHODS: We analyzed data from 87 patients with acute intracranial large artery occlusion who had acute multimodal computed tomography-imaging. LA-severity was assessed using the van Swieten scale on noncontrast computed tomography. Computed tomography perfusion data were analyzed using automatic calculation of the mean transit time and hyperacute cerebral blood volume defects. …

Severity Of Pre-Existing Cerebral Small Vessel Disease Is Associated With Outcome After Traumatic Brain Injury, Nils Heninger, Saef Izzy, Raphael Carandang, Wiley Hall, Susanne Muehlschlegel

Nils Henninger

Background and purpose: It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of pre-existing white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of pre-existing cerebral small vessel disease related white matter rarefaction (leukoaraiosis) is independently associated with outcome after TBI. Methods: We retrospectively analyzed consecutive, prospectively enrolled patients of ≥50 years (n=136) that were admitted to a single neurological-trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range …

Normobaric Hyperoxia Delays Perfusion/Diffusion Mismatch Evolution, Reduces Infarct Volume, And Differentially Affects Neuronal Cell Death Pathways After Suture Middle Cerebral Artery Occlusion In Rats, Nils Henninger, James Bouley, Julia Nelligan, Kenneth Sicard, Marc Fisher

Nils Henninger

Normobaric hyperoxia (NBO) has been shown to extend the reperfusion window after focal cerebral ischemia. Employing diffusion (DWI)- and perfusion (PWI)-weighted magnetic resonance imaging (MRI), the effect of NBO (100% started at 30 mins after middle cerebral artery occlusion (MCAO)) on the spatiotemporal evolution of ischemia during and after permanent (pMCAO) and transient suture middle cerebral artery occlusion (tMCAO) was investigated (experiment 3). In two additional experiments, time window (experiment 1) and cell death pathways (experiment 2) were investigated in the pMCAO model. In experiment 1, NBO treatment reduced infarct volume at 24 h after pMCAO by 10% when administered …

Characterizing Tissue Fate After Transient Cerebral Ischemia Of Varying Duration Using Quantitative Diffusion And Perfusion Imaging, Juergen Bardutzky, Qiang Shen, Nils Henninger, Stefan Schwab, Timothy Duong, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects of reperfusion on ischemic lesion evolution and pixel-by-pixel apparent diffusion coefficient-cerebral blood flow (ADC-CBF) dynamics of core and mismatch tissues after 35, 60, and 95 minutes of transient focal ischemia in rats (n=28). METHODS: Serial diffusion-, perfusion-, and T2-weighted imaging were performed up to 24 hours. The evolution of the magnetic resonance image-derived lesion volume was investigated and ADC-CBF scatterplots were performed to prospectively characterize the ADC and CBF dynamics of core and mismatch tissues with different fates. For comparison, similar analysis was performed on a historical …

Comparison Of Ischemic Lesion Evolution In Embolic Versus Mechanical Middle Cerebral Artery Occlusion In Sprague Dawley Rats Using Diffusion And Perfusion Imaging, Nils Henninger, Kenneth Sicard, Karl Schmidt, Juergen Bardutzky, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague Dawley rats after permanent suture MCAO (sMCAO; n=8) and embolic MCAO (eMCAO; n=8).

METHODS: Serial measurements of quantitative cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) were performed up to 180 minutes after MCAO. ADC and CBF values within 5 different brain regions were analyzed. ADC and CBF lesion volumes were calculated by using previously …

Ischemic Lesion Volume Determination On Diffusion Weighted Images Vs. Apparent Diffusion Coefficient Maps, Bernt Bratane, Birgül Bastan, Marc Fisher, James Bouley, Nils Henninger

Nils Henninger

Though diffusion weighted imaging (DWI) is frequently used for identifying the ischemic lesion in focal cerebral ischemia, the understanding of spatiotemporal evolution patterns observed with different analysis methods remains imprecise. DWI and calculated apparent diffusion coefficient (ADC) maps were serially obtained in rat stroke models (MCAO): permanent, 90 min, and 180 min temporary MCAO. Lesion volumes were analyzed in a blinded and randomized manner by 2 investigators using (i) a previously validated ADC threshold, (ii) visual determination of hypointense regions on ADC maps, and (iii) visual determination of hyperintense regions on DWI. Lesion volumes were correlated with 24 hour 2,3,5-triphenyltetrazoliumchloride …

The Proteasome Inhibitor Velcade Reduces Infarction In Rat Models Of Focal Cerebral Ischemia, Nils Henninger, Kenneth Sicard, James Bouley, Marc Fisher, Nancy Stagliano

Nils Henninger

The potential neuroprotective effects of VELCADE were investigated in two different models of focal cerebral ischemia. For time-window assessment, male Wistar-Kyoto rats were treated with 0.2 mg/kg VELCADE at 1, 2, or 3 h after the induction of permanent middle cerebral artery occlusion (MCAO) using the suture occlusion method (experiment 1). To evaluate effects in a different model, male Sprague-Dawley rats received 0.2 mg/kg VELCADE after embolic MCAO (experiment 2). Infarct volume was calculated based on TTC-staining 24 h postischemia and whole blood proteasome activity was fluorometrically determined in both experiments at baseline, 1 and 24 h post-MCAO. In experiment …

Laser Doppler Flowmetry Predicts Occlusion But Not Tpa-Mediated Reperfusion Success After Rat Embolic Stroke, Nils Henninger, James Bouley, Bernt Bratane, Birgül Bastan, Meghan Shea, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: Laser Doppler flowmetry (LDF) is increasingly used to assess adequate occlusion after embolic stroke (ES) in rats. METHODS: Employing LDF, relative regional cerebral blood flow (rCBF) was continuously monitored during the first 2 h following ES and correlated with 24 h 2,3,5-triphenyltetrazolium chloride (TTC)-staining of corrected infarct volume. In a preliminary experiment (n=18), it was demonstrated that rCBF-reduction to 37% or less of baseline correctly identified occlusion success in the suture middle cerebral artery occlusion (sMCAO) model. Using the same methodology, we then assessed whether LDF allowed for identification of animals with successful ES (experiment 2, n=26) …

Visualization Of Clot Lysis In A Rat Embolic Stroke Model: Application To Comparative Lytic Efficacy, Ronn Walvick, Bernt Bratane, Nils Henninger, Kenneth Sicard, James Bouley, Zhanyang Yu, Eng Lo, Xiaoying Wang, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model and to compare tissue plasminogen activator (tPA)-based clot lysis with and without recombinant Annexin-2 (rA2). METHODS: In experiment 1 we used in vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50 muL in 250 muL blood. In experiment 2, we used in vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot …

Differences In Ischemic Lesion Evolution In Different Rat Strains Using Diffusion And Perfusion Imaging, Juergen Bardutzky, Qiang Shen, Nils Henninger, James Bouley, Timothy Duong, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: Interstrain differences in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. We investigated, in 2 commonly used rat strains (Sprague-Dawley [SD] and Wistar-Kyoto [WK]), the spatiotemporal evolution of ischemia after permanent suture MCAO using diffusion and perfusion imaging.

METHODS: Serial measurements of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were performed up to 210 min after MCAO. Lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after …

Differential Recovery Of Behavioral Status And Brain Function Assessed With Functional Magnetic Resonance Imaging After Mild Traumatic Brain Injury In The Rat, Nils Henninger, Kenneth Sicard, Zhixin Li, Praveen Kulkarni, Stephan Dutzmann, Christian Urbanek, Stefan Schwab, Marc Fisher

Nils Henninger

OBJECTIVE: The relationship between cerebral integrity, recovery of brain function, and neurologic status after mild traumatic brain injury is incompletely characterized.

DESIGN: Prospective and randomized study in rodents.

SETTING: University laboratory.

SUBJECTS: Male Wistar rats (290-310 g).

INTERVENTIONS: In rats, quantitative diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), T2-weighted imaging (T2WI), and functional magnetic resonance imaging (fMRI) were performed up to 21 days after weight-induced, closed-head, mild traumatic brain injury (MTBI, n = 6) or sham operation (n = 6). Pixel-by-pixel analysis and region of interest analysis were used to evaluate structural (apparent diffusion coefficient [ADC] and basal cerebral …

Normobaric Hyperoxia And Delayed Tpa Treatment In A Rat Embolic Stroke Model, Nils Henninger, Bernt Bratane, Birgül Bastan, James Bouley, Marc Fisher

Nils Henninger

In a rat embolic stroke (eMCAO) model, the effects of 100% normobaric hyperoxia (NBO) with delayed recombinant tissue plasminogen activator (tPA) administration on ischemic lesion size and safety were assessed by diffusion- and perfusion (PWI)-weighted magnetic resonance imaging. NBO or room air (Air) by a face mask was started at 30 mins posteMCAO and continued for 3.5 h. Tissue plasminogen activator or saline was started at 3 h posteMCAO. Types and location of hemorrhagic transformation were assessed at 24 h and a spectrophotometric hemoglobin assay quantified hemorrhage volume at 10 h. In NBO-treated animals the apparent diffusion coefficient/PWI mismatch persisted …

Translational Research In Stroke: Taking Advances In The Pathophysiology And Treatment Of Stroke From The Experimental Setting To Clinical Trials, Marc Fisher, Nils Henninger

Nils Henninger

Many advances have occurred regarding an increased understanding of the basic pathophysiology of ischemic brain injury that could lead to enhanced therapy for this disorder. Among the more important basic science advances are enhanced knowledge of the components of the ischemic cascade, the phenomenon of ischemic preconditioning, the potential relevance of hibernation, studies on gene expression in ischemic tissue, and imaging identification of the ischemic penumbra. The large number of unsuccessful prior clinical trials with a wide range of purported acute stroke therapies has provided many insights and lessons regarding how to perform better trials in the future. Translating these …

Traumatic Brain Injury: Translation From Animal Models And Genetics To Improving Outcomes, Susanne Muehlschlegel, Nils Henninger, Raphael Carandang, Constance Moore

Nils Henninger

This presentation offers background information on traumatic brain injury (TBI), a public health problem which affects approximately 1.7 million Americans each year. The presentation is part of a mini-symposium highlighting the interdisciplinary and translational nature of TBI research at the University of Massachusetts Medical School.

Long-Term Changes Of Functional Mri-Based Brain Function, Behavioral Status, And Histopathology After Transient Focal Cerebral Ischemia In Rats, Kenneth Sicard, Nils Henninger, Marc Fisher, Timothy Duong, Craig Ferris

Nils Henninger

BACKGROUND AND PURPOSE: The relation between recovery of brain function and neurological status after clinical and experimental cerebral ischemia is incompletely characterized. We assessed the evolution of ischemic injury, behavioral status, and brain activity at acute to chronic periods after transient middle cerebral artery occlusion (tMCAO) in rats. METHODS: Male Sprague-Dawley rats were subjected to 20-minute tMCAO (n=10) or sham operation (n=10). Sensorimotor behavioral testing and multimodal (diffusion, perfusion, T2, and functional) MRI, as well as postmortem hematoxylin-eosin staining, were performed before and up to 21 days after tMCAO. MRI and histological parameters were evaluated in 5 regions of interest …

Stimulating Circle Of Willis Nerve Fibers Preserves The Diffusion-Perfusion Mismatch In Experimental Stroke, Nils Henninger, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: Stimulation of the nerves traversing the ethmoidal foramen (including postsynaptic, parasympathetic projections from the sphenopalatine ganglion [SPG], henceforth referred to as "SPG-stimulation") has been shown to elevate cerebral blood flow (CBF) and to be neuroprotective after permanent, middle cerebral artery occlusion (pMCAO). METHODS: Employing diffusion (DWI)- and perfusion (PWI) weighted MRI, the effect of SPG-stimulation (started at 60 minutes post-MCAO) on the spatiotemporal evolution of ischemia during and after pMCAO was investigated. In an additional experiment, regional CBF changes were investigated in the nonischemic brain. RESULTS: In the nonischemic brain, SPG stimulation significantly elevated CBF predominantly within …

Acute Ischemic Stroke Therapy, Nils Henninger, Rajat Kumar, Marc Fisher

Nils Henninger

Data from the European Cooperative Acute Stroke Study (ECASS) III trial demonstrated that tissue plasminogen activator given up to 4.5 h after stroke onset improves outcome and treatment guidelines support its use during this time window. Intra-arterial therapy with tissue plasminogen activator or devices is commonly used at large tertiary centers up to 6-8 h after stroke onset, but conclusive evidence of efficacy remains lacking. During the acute phase after stroke onset, blood pressure elevations should be reduced as should substantial elevations in blood glucose. Statins are recommended in essentially all non-cardioembolic stroke patients. The most important future directions for …

Differential Recovery Of Multimodal Mri And Behavior After Transient Focal Cerebral Ischemia In Rats, Kenneth Sicard, Nils Henninger, Marc Fisher, Timothy Duong, Craig Ferris

Nils Henninger

The association between recovery of brain function and behavior after transient cerebral ischemia in animals and humans is incompletely characterized. Quantitative diffusion- (DWI), perfusion- (PWI), T(2)-weighted (T(2)WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 1 day after 20-mins transient middle cerebral artery occlusion (tMCAO; n=6) or sham operation (n=6) in male Sprague-Dawley rats. Viability thresholds were employed to calculate diffusion, perfusion, and T(2) lesion volumes. Region of interest analysis was used to evaluate structural and functional MR signal changes within the sensorimotor network, which were then related to corresponding behavioral measures. Post-mortem 2,3,5-triphenyltetrazolium chloride …

Leukoaraiosis Predicts Poor 90-Day Outcome After Acute Large Cerebral Artery Occlusion, Nils Henninger, Eugene Lin, Stephen Baker, Ajay Wakhloo, Deepak Takhtani, Majaz Moonis

Nils Henninger

BACKGROUND: To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. METHODS: We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007-2010) at a single academic …

Spectacular Shrinking Deficit: Insights From Multimodal Magnetic Resonance Imaging After Embolic Middle Cerebral Artery Occlusion In Sprague-Dawley Rats, Nils Henninger, Kenneth Sicard, Marc Fisher

Nils Henninger

Almost no data is available on the serial changes in the brain after spectacular shrinking deficit (SSD) that may help understand this relatively rare clinical phenomenon. Quantitative diffusion-(DWI), perfusion-(PWI), T(1)-(T1WI), T(2)-weighted (T2WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 7 days after embolic middle cerebral artery occlusion (eMCAO) in male Sprague-Dawley rats (n=9). Region of interest (ROI) analysis was used to evaluate structural and functional MR signal changes within three ROIs defined by the apparent diffusion coefficient (ADC), cerebral blood flow (CBF) signatures, and final tissue viability. DWI, PWI, and T2WI lesion volumes were …

Therapeutic Medical Hypothermia--A Multispecialty Approach, Sudip Nanda, Nainesh Patel, Surya Bhatt, Claranne Mathiesen, John Castaldo, Shree Sharma, Santo Longo

Nainesh C Patel MD

No abstract provided.

Gaps And Opportunities In Refractory Status Epilepticus Research In Children: A Multi-Center Approach By The Pediatric Status Epilepticus Research Group (Pserg), Ivan Fernandez, Nicholas Abend, Satish Agadi, Sookee An, Ravindra Arya, Jessica Carpenter, Kevin Chapman, William Gaillard, Tracy Glauser, David Golstein, Joshua Goldstein, Howard Goodkin, Cecil Hahn, Erin Heinzen, Mohamad Mikati, Katrina Peariso, John Pestian, Margie Ream, James Riviello, Robert Tasker, Korwyn Williams, Tobias Loddenkemper

Ivan J. Fernandez

PURPOSE: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG). METHODS: A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. RESULTS: The care of pediatric …