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Lesion Volume (lesion + volume)
Selected AbstractsSubcortical lesions after transient thread occlusion in the rat: T2 -weighted magnetic resonance imaging findings without corresponding sensorimotor deficitsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2005Susanne Wegener MD Abstract Purpose To investigate infarct evolution and functional consequences of exclusive subcortical or cortico-subcortical strokes, transient middle cerebral artery occlusion (MCAO) was conducted in Wistar rats. Materials and Methods MCAO was induced in male Wistar rats (260,300 g) for 60 minutes. Lesion volumes and absolute T2 times on magnetic resonance imaging (MRI) were assessed 1 and 14 days after MCAO using a 4.7-T MRI animal scanner in conjunction with functional testing (adhesive tape removal, cylinder test, and ledged beam walking). Results Functional test scores were not distinguishable between sham-operated animals (N = 5) and those with exclusive caudoputaminal infarct (N = 8; group cp), but showed significant deficits in animals with cortico-subcortical infarction (N = 10; group cp+). The cp group had lower absolute T2 times and a more pronounced reduction in T2 lesion volume over time than the subcortical component in the cp+ group. There was no correlation of T2 lesion size or absolute T2 times and functional impairment in either group. Conclusion When judged from functional tests alone, subcortical ischemic lesions may not be diagnosed reliably. Furthermore, T2 -weighted (T2 -w) MRI does not well anticipate functional deficits in primarily striatal lesions. J. Magn. Reson. Imaging 2005;21:340,346. © 2005 Wiley-Liss, Inc. [source] The Virtual International Stroke Trials Archive (VISTA): results and impact on future stroke trials and management of stroke patientsINTERNATIONAL JOURNAL OF STROKE, Issue 2 2010C. Weimar Background The Virtual International Stroke Trials Archive was established to improve stroke care and trial design through the collation, categorization and potential access to data sets from clinical trials for the treatment of stroke. Methods Virtual International Stroke Trials Archive currently provides access to a combined data set of 29 anonymised acute stroke trials and one acute stroke registry with data on >27 500 patients aged between 18 and 103 (mean 71) years. Results Virtual International Stroke Trials Archive has facilitated research across a broad canvas. The prognosis was poor in patients with very high blood pressure at the time of admission or with a wide variability of systolic blood pressure during the acute phase. The late occurrence of hyperthermia following an ischaemic stroke worsens the prognosis. Stroke lateralisation is not an important predictor of cardiac adverse events or 90-day mortality. Haemorrhagic transformation is seen frequently in patients with cardio-embolic strokes and is associated with a poor prognosis when occurring after the acute phase. Virtual International Stroke Trials Archive has allowed various prognostic models for patients with ischaemic or haemorrhagic stroke to be established and validated. More direct outcomes such as lesion volume can be useful in phase II clinical trials for determining whether a phase III trial should be undertaken. New outcome measures such as ,home time' may also strengthen future trials. On a worldwide level, the prognosis of stroke patients differs considerably between various countries. Conclusion Virtual International Stroke Trials Archive provides an excellent opportunity for analysis of natural history data and prognosis. It has the potential to influence clinical trial design and implementation through exploratory data analyses. [source] Subcortical lesions after transient thread occlusion in the rat: T2 -weighted magnetic resonance imaging findings without corresponding sensorimotor deficitsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2005Susanne Wegener MD Abstract Purpose To investigate infarct evolution and functional consequences of exclusive subcortical or cortico-subcortical strokes, transient middle cerebral artery occlusion (MCAO) was conducted in Wistar rats. Materials and Methods MCAO was induced in male Wistar rats (260,300 g) for 60 minutes. Lesion volumes and absolute T2 times on magnetic resonance imaging (MRI) were assessed 1 and 14 days after MCAO using a 4.7-T MRI animal scanner in conjunction with functional testing (adhesive tape removal, cylinder test, and ledged beam walking). Results Functional test scores were not distinguishable between sham-operated animals (N = 5) and those with exclusive caudoputaminal infarct (N = 8; group cp), but showed significant deficits in animals with cortico-subcortical infarction (N = 10; group cp+). The cp group had lower absolute T2 times and a more pronounced reduction in T2 lesion volume over time than the subcortical component in the cp+ group. There was no correlation of T2 lesion size or absolute T2 times and functional impairment in either group. Conclusion When judged from functional tests alone, subcortical ischemic lesions may not be diagnosed reliably. Furthermore, T2 -weighted (T2 -w) MRI does not well anticipate functional deficits in primarily striatal lesions. J. Magn. Reson. Imaging 2005;21:340,346. © 2005 Wiley-Liss, Inc. [source] Magnetic resonance image registration in multiple sclerosis: Comparison with repositioning error and observer-based variabilityJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2002I Leng Tan MD Abstract Purpose To study the use of image registration in the analysis of multiple sclerosis (MS) lesion volume and compare this with repositioning error and observer-based variability. Materials and Methods The normalized mutual information (NMI) algorithm is evaluated in an accuracy study using a phantom, followed by a validation study on magnetic resonance (MR) data of MS patients. Further, using scan-rescan MR data, the effect of registration on MS lesion volume compared with repositioning error and observer-based variability is assessed. Results The registration accuracy was near perfect in the phantom study, while the in vivo validation study demonstrated an accuracy on the order of 0.2,0.3 mm. In the scan-rescan study, quantification accounted for 15.6% of the relative variance, repositioning for 44.4%, and registration for 40.0%. Conclusion NMI resulted in robust and accurate alignment of MR brain images of MS patients. Its use in the detection of changes in MS using large serial MR imaging (MRI) data warrants future evaluation. J. Magn. Reson. Imaging 2002;15:505,510. © 2002 Wiley-Liss, Inc. [source] Time evolution of cerebral perfusion and apparent diffusion coefficient measured by magnetic resonance imaging in a porcine stroke modelJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2002Lisbeth Røhl MD Abstract Purpose To demonstrate the feasibility of sequential diffusion-weighted (DW) and perfusion-weighted (PW) magnetic resonance imaging (MRI) of a recently developed porcine stroke model and to evaluate the evolution of cerebral perfusion and the apparent diffusion coefficient (ADC) over time. Materials and Methods In five pigs, DW imaging (DWI) and PW imaging (PWI) was carried out for 7 hours after stroke onset, starting 1 hour after middle cerebral artery occlusion (MCAO). Results The DWI lesion volume increased significantly with time, and final DWI lesion volume correlated well with lesion area on histological sections (r = 0.910). T2 changes could be recognized 3 hours after stroke onset. At 1 hour the ADC ratio (ischemic lesion/contralateral side) was reduced to 0.81 in the caudate-putamen and to 0.87 in the cortex, and the cerebral blood flow ratio was reduced to 0.40 in the caudate-putamen and 0.51 in the cortex. Conclusion The level of flow reduction in the caudate-putamen and the cortex after 1 hour is in good correlation with human thresholds of irreversible and reversible ischemic damage, and accordingly, this model might be a model for mechanisms of infarct evolution and therapeutic intervention. J. Magn. Reson. Imaging 2002;15:123,129. © 2002 Wiley-Liss, Inc. [source] Progressive Cerebral Disease in Lymphomatoid Granulomatosis Causes Anterograde Amnesia and Neuropsychiatric DisorderJOURNAL OF NEUROIMAGING, Issue 2 2006Dominic A. Carone PhD ABSTRACT The authors report neuropsychological (NP) and serial quantitative magnetic resonance imaging (MRI) findings of a 29-year-old woman with lymphomatoid granulomatosis (LG). Disease course was characterized by acute psychosis, tremor, fever, seizures, and progressive cognitive impairment. At the time of symptom onset, brain MRI revealed mild lesion volume and normal parenchymal volume. This was followed by dramatic progression of brain lesions and atrophy over 2 years, at which point the patient expired. Atrophy was most prominent in the mesial temporal lobes. NP testing revealed marked amnesia and mild impairments in other cognitive domains. To our knowledge, this is the first recorded case of LG in which bilateral temporal lobe atrophy is evident and accompanied by anterograde amnesia. We speculate that temporal lobe atrophy was influenced by the established susceptibility of this region in various neurological diseases. [source] Clinical,Magnetic Resonance Imaging Correlations in Multiple SclerosisJOURNAL OF NEUROIMAGING, Issue 2005Robert Zivadinov MD ABSTRACT Conventional magnetic resonance imaging (MRI) has routinely been used to improve the accuracy of multiple sclerosis (MS) diagnosis and monitoring, detect the effects of diseasemodifying therapy, and refine the utility of clinical assessments. However, conventional MRI measures, such as the use of lesion volume and count of gadolinium-enhancing and T2 lesions, have insufficient sensitivity and specificity to reveal the true degree of pathological changes occurring in MS. Newer metrics of MRI analysis, including T1-weighted hypointense lesions (black holes) and central nervous system (CNS) atrophy measures, are able to capture a more global picture of the range of tissue alterations caused by inflammation, demyelination, axonal loss, and neurodegeneration. There is mounting evidence that these MRI measures correlate well with existing and developing neurological impairment and disability. In so doing, these MRI techniques can help elucidate the mechanisms underlying the pathophysiology and natural history of MS. The current understanding is that T1 black holes and CNS atrophy more accurately reflect the neurodegenerative and destructive components of the MS disease process. Therefore, the shortand long-term studies that aim to measure the degree and severity of the neurodegenerative MS disease process should incorporate these MRI metrics as part of their standard routine MRI protocols. [source] Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2005Eric Anthony Sribnick Abstract Spinal cord injury (SCI) is a devastating neurologic injury with functional deficits for which the only currently recommended pharmacotherapy is high-dose methylprednisolone, which has limited efficacy. Estrogen is a multiactive steroid that has shown antiinflammatory and antioxidant effects, and estrogen may modulate intracellular Ca2+ and attenuate apoptosis. For this study, male rats were divided into three groups. Sham group animals received a laminectomy at T12. Injured rats received both laminectomy and 40 g · cm force SCI. Estrogen-group rats received 4 mg/kg 17,-estradiol (estrogen) at 15 min and 24 hr post-injury, and vehicle-group rats received equal volumes of dimethyl sulfoxide (vehicle). Animals were sacrificed at 48 hr post-injury, and 1-cm-long segments of the lesion, rostral penumbra, and caudal penumbra were excised. Inflammation was assessed by examining tissue edema, infiltration of macrophages/microglia, and levels of cytosolic and nuclear NF,B and inhibitor of kappa B (I,B,). Myelin integrity was examined using Luxol fast blue staining. When compared to sham, vehicle-treated animals revealed increased tissue edema, increased infiltration of inflammatory cells, decreased cytosolic levels of NF,B and I,B,, increased levels of nuclear NF,B, and increased myelin loss. Treatment of SCI rats with estrogen reduced edema and decreased inflammation and myelin loss in the lesion and penumbral areas, suggesting its potential as a therapeutic agent. Further work needs to be done, however, to elucidate the neuroprotective mechanism of estrogen. © 2005 Wiley-Liss, Inc. [source] Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosisMAGNETIC RESONANCE IN MEDICINE, Issue 5 2008F. Agosta Abstract Functional MRI (fMRI) was used to assess proprioceptive-associated cervical cord activity in 24 relapsing multiple sclerosis (MS) patients and 10 controls. Cord and brain conventional and diffusion tensor (DT) MRI were also acquired. fMRI was performed using a block design during a proprioceptive stimulation consisting of a passive flexion-extension of the right upper limb. Cord lesion number, cross-sectional area, mean diffusivity (MD) and fractional anisotropy (FA), whole brain and left corticospinal tract lesion volume (LV), gray matter (GM) MD, and normal-appearing white matter (NAWM) MD and FA were calculated. MS patients had higher average cord fMRI signal changes than controls (3.4% vs. 2.7%, P = 0.03). Compared to controls, MS patients also had a higher average signal change in the anterior section of the right cord at C5 (P = 0.005) and left cord at C5,C6 (P = 0.03), whereas no difference was found in the other cord sections. Cord average signal change correlated significantly with cord FA and brain left corticospinal tract LV, GM-MD, and NAWM-FA. This study shows an abnormal pattern of activations in the cervical cord of MS patients following proprioceptive stimulation. Cord fMRI changes might have a role in limiting the clinical consequences of MS associated with irreversible tissue damage. Magn Reson Med 59:1035,1042, 2008. © 2008 Wiley-Liss, Inc. [source] Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and induces axonal regrowth of injured spinal cordNEUROPATHOLOGY, Issue 3 2010Weidong Gu It has been demonstrated that transplantation of bone marrow mesenchymal stem cells (BMSCs) improves recovery of injured spinal cord in animal models. However, the mechanism of how BMSCs promote repair of injured spinal cord remains under investigation. The present study investigated the neural differentiation of BMSCs, the lesion volume and axonal regrowth of injured spinal cord after transplantation. Seven days after spinal cord injury, 3 × 105 BMSCs or PBS (control) was delivered into the injury epicenter of the spinal cord. At 8 weeks after spinal cord injury, transplantation of BMSCs reduced the volume of cavity and increased spared white matter as compared to the control. BMSCs did not express the cell marker of neurons, astrocytes and oligodendrocytes in injured spinal cord. Transmission electron microscopic examination displayed an increase in the number of axons in BMSC rats. The effect of BMSCs on growth of neuronal process was further investigated by using a coculture system. The length and the number of neurites from spinal neurons significantly increased when they cocultured with BMSCs. PCR and immunochemical analysis showed that BMSCs expressed brain-derived neurotrophic factor (BDNF) and glia cell line-derived neurotrophic factor (GDNF). These findings demonstrate that transplantation of BMSCs reduces lesion volume and promotes axonal regrowth of injured spinal cord. [source] MRI monitoring of focal cerebral ischemia in peroxisome proliferator-activated receptor (PPAR)-deficient miceNMR IN BIOMEDICINE, Issue 3 2007Jean-Baptiste Pialat Abstract Peroxisome proliferator-activated receptors (PPARs) are a potential target for neuroprotection in focal ischemic stroke. These nuclear receptors have major effects in lipid metabolism, but they are also involved in inflammatory processes. Three PPAR isotypes have been identified: ,, , (or ,) and ,. The development of PPAR transgenic mice offers a promising tool for prospective therapeutic studies. This study used MRI to assess the role of PPAR, and PPAR, in the development of stroke. Permanent middle cerebral artery occlusion induced focal ischemia in wild-type, PPAR, -null mice and PPAR, -null mice. T2 -weighted MRI was performed with a 7 T MRI scan on day 0, 1, 3, 7 and 14 to monitor lesion growth in the various genotypes. General Linear Model statistical analysis found a significant difference in lesion volume between wild-type and PPAR-null mice for both , and , isotypes. These data validate high-resolution MRI for monitoring cerebral ischemic lesions, and confirm the neuroprotective role of PPAR, and PPAR, in the brain. Copyright © 2007 John Wiley & Sons, Ltd. [source] Determinants of Lesion Sizes and Tissue Temperatures During Catheter CryoablationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2007MARK A. WOOD M.D. Background:Factors which influence lesion size from catheter-based cryoablation have not been well described. This study describes factors which influence lesion size during catheter cryoablation. Methods and Results:Cryoablation was delivered to porcine left ventricular myocardium in a saline bath using 4- or 8-mm electrode catheters. Ablation was delivered with the electrodes either vertical or horizontal to the tissue and both with and without superfusate flow over the electrode. The effect of electrode contact pressure was tested. Lesion dimensions were measured. All experiments were duplicated to measure tissue temperatures at 1-, 2-, 3-, and 5-mm deep to the ablation electrode. The 8-mm electrode produced lower tissue temperatures and larger lesion volumes when compared with the 4-mm electrode (all P < 0.05). Superfusate flow slowed the rate of tissue cooling, markedly warmed tissue temperatures, and reduced lesion volume when compared with no flow conditions. By linear regression modeling, lesion sizes and tissue temperatures were related to the presence of superfusate flow, electrode orientation, contact pressure and electrode size, or catheter refrigerant flow rate (r2 for models = 0.90,0.96, all P < 0.001). Electrode temperature predicted lesion size or tissue temperatures only when analyzed independent of electrode size or refrigerant flow rate. Conclusions:Lesion sizes and tissue temperatures during catheter cryoablation are related to convective warming, electrode orientation, electrode contact pressure, and any of the following: electrode size, catheter refrigerant flow rate or electrode temperature. However, electrode temperature may be a poor predictor of lesion size and tissue temperature for a given catheter size. [source] A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosisANNALS OF NEUROLOGY, Issue 3 2010Massimiliano Calabrese MD Objective We assessed the occurrence, extent, and frequency of formation of cortical lesions (CLs) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS), and their relationship with cortical atrophy and disability progression. Methods One-hundred seven MS patients (76 RRMS and 31 SPMS), enrolled in a prospective, longitudinal magnetic resonance imaging (MRI) study, were assessed clinically and by brain MRI (including a double inversion recovery sequence) 3 years after study initiation. CL number and volume, T2 white matter (WM) lesion volume, gray matter fraction, and expanded disability status scale (EDSS) were measured. Results At baseline, CLs were detected in 64.4% of RRMS and 74.2% of SPMS patients. During follow-up, 132 new CLs were found in 44 RRMS patients (57.9%; 0.8 new CL/patient/yr) and 61 in 15 SPMS patients (48.4%; 1.0 new CL/patient/yr). Among these patients, only 31 also showed at least 1 new WM lesion. CL number and volume increases were higher in the 52 patients with a clinical worsening compared with those without (p < 0.001). Baseline CL volume correlated with baseline EDSS (r = 0.36, p < 0.001) and EDSS changes over time (r = 0.51, p < 0.001). Baseline CL volume was an independent predictor of EDSS accumulation and GM volume change at follow-up in both patient groups. In SPMS patients, baseline T2 WM lesion volume was another independent predictor of EDSS worsening. Interpretation In relapse-onset MS, CLs accumulate over time and are associated with disability progression. The quantification of CLs might represent an additional useful paraclinical tool to monitor MS evolution. ANN NEUROL 2010;67:376,383 [source] Slowed progression in models of huntington disease by adipose stem cell transplantation,ANNALS OF NEUROLOGY, Issue 5 2009Soon-Tae Lee MD Objective Adipose-derived stem cells (ASCs) are readily accessible and secrete multiple growth factors. Here, we show that ASC transplantation rescues the striatal pathology of Huntington disease (HD) models. Methods ASCs were isolated from human subcutaneous adipose tissue. In a quinolinic acid (QA)-induced rat model of striatal degeneration, human ASCs (1 million cells) were transplanted into the ipsilateral striatal border immediately after the QA injection. In 60-day-old R6/2 mice transgenic for HD, ASCs (0.5 million cells) were transplanted into each bilateral striata. In in vitro experiments, we treated mutant huntingtin gene-transfected cerebral neurons with ASC-conditioned media. Results In the QA model, human ASCs reduced apomorphine-induced rotation behavior, lesion volume, and striatal apoptosis. In R6/2 transgenic mice, transplantation of ASCs improved Rota-Rod performance and limb clasping, increased survival, attenuated the loss of striatal neurons, and reduced the huntingtin aggregates. ASC-transplanted R6/2 mice expressed elevated levels of peroxisome proliferator-activated receptor , coactivator-1, (PGC-1,) and reactive oxygen defense enzymes and showed activation of the Akt/cAMP-response element-binding proteins. ASC-conditioned media decreased the level of N-terminal fragments of mutant huntingtin and associated apoptosis, and increased PGC-1, expression. Interpretation Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors. Ann Neurol 2009;66:671,681 [source] Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial,ANNALS OF NEUROLOGY, Issue 4 2009Kathleen Hawker MD Objective Rituximab, a monoclonal antibody selectively depleting CD20+ B cells, has demonstrated efficacy in reducing disease activity in relapsing-remitting multiple sclerosis (MS). We evaluated rituximab in adults with primary progressive MS (PPMS) through 96 weeks and safety through 122 weeks. Methods Using 2:1 randomization, 439 PPMS patients received two 1,000mg intravenous rituximab or placebo infusions every 24 weeks, through 96 weeks (4 courses). The primary endpoint was time to confirmed disease progression (CDP), a prespecified increase in Expanded Disability Status Scale sustained for 12 weeks. Secondary endpoints were change from baseline to week 96 in T2 lesion volume and total brain volume on magnetic resonance imaging scans. Results Differences in time to CDP between rituximab and placebo did not reach significance (96-week rates: 38.5% placebo, 30.2% rituximab; p = 0.14). From baseline to week 96, rituximab patients had less (p < 0.001) increase in T2 lesion volume; brain volume change was similar (p = 0.62) to placebo. Subgroup analysis showed time to CDP was delayed in rituximab-treated patients aged <51 years (hazard ratio [HR] = 0.52; p = 0.010), those with gadolinium-enhancing lesions (HR = 0.41; p = 0.007), and those aged <51 years with gadolinium-enhancing lesions (HR = 0.33; p = 0.009) compared with placebo. Adverse events were comparable between groups; 16.1% of rituximab and 13.6% of placebo patients reported serious events. Serious infections occurred in 4.5% of rituximab and <1.0% of placebo patients. Infusion-related events, predominantly mild to moderate, were more common with rituximab during the first course, and decreased to rates comparable to placebo on successive courses. Interpretation Although time to CDP between groups was not significant, overall subgroup analyses suggest selective B-cell depletion may affect disease progression in younger patients, particularly those with inflammatory lesions. Ann Neurol 2009;66:460,471 [source] Postischemic treatment of neonatal cerebral ischemia should target autophagy,ANNALS OF NEUROLOGY, Issue 3 2009Julien Puyal PhD Objective To evaluate the contributions of autophagic, necrotic, and apoptotic cell death mechanisms after neonatal cerebral ischemia and hence define the most appropriate neuroprotective approach for postischemic therapy. Methods Rats were exposed to transient focal cerebral ischemia on postnatal day 12. Some rats were treated by postischemic administration of pan-caspase or autophagy inhibitors. The ischemic brain tissue was studied histologically, biochemically, and ultrastructurally for autophagic, apoptotic, and necrotic markers. Results Lysosomal and autophagic activities were increased in neurons in the ischemic area from 6 to 24 hours postinjury, as shown by immunohistochemistry against lysosomal-associated membrane protein 1 and cathepsin D, by acid phosphatase histochemistry, by increased expression of autophagosome-specific LC3-II and by punctate LC3 staining. Electron microscopy confirmed the presence of large autolysosomes and putative autophagosomes in neurons. The increases in lysosomal activity and autophagosome formation together demonstrate increased autophagy, which occurred mainly in the border of the lesion, suggesting its involvement in delayed cell death. We also provide evidence for necrosis near the center of the lesion and apoptotic-like cell death in its border, but in nonautophagic cells. Postischemic intracerebroventricular injections of autophagy inhibitor 3-methyladenine strongly reduced the lesion volume (by 46%) even when given >4 hours after the beginning of the ischemia, whereas pan-caspase inhibitors, carbobenzoxy-valyl-alanyl-aspartyl(OMe)-fluoromethylketone and quinoline-val-asp(OMe)-Ch2-O-phenoxy, provided no protection. Interpretation The prominence of autophagic neuronal death in the ischemic penumbra and the neuroprotective efficacy of postischemic autophagy inhibition indicate that autophagy should be a primary target in the treatment of neonatal cerebral ischemia. Ann Neurol 2009 [source] Activation of metabotropic glutamate receptor 5 improves recovery after spinal cord injury in rodents,ANNALS OF NEUROLOGY, Issue 1 2009Kimberly R. Byrnes PhD Objective Activation of metabotropic glutamate receptor 5 (mGluR5) has neuroprotective properties in vitro and has been reported to limit postischemic lesion volume in vivo. Previously, mGluR5 has been identified on microglia in vitro, but the effects of mGluR5 activation on inflammation in vivo or on recovery after spinal cord injury is unknown. Methods Rats received intrathecal infusion of the selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) for 7 days after moderate impact spinal cord injury at T9. Complementary studies examined CHPG effects on activated spinal microglia cultures. Results Functional motor recovery was significantly increased by CHPG treatment up to 28 days after injury, with improvements in weight bearing, step taking, and coordination of stepping behavior. CHPG treatment significantly reduced lesion volume and increased white matter sparing at 28 days after injury. Administration of CHPG attenuated microglial-associated inflammatory responses in a dose-dependent fashion, including expression of ED1, Iba-1, Galectin-3, NADPH oxidase components, tumor necrosis factor-,, and inducible nitric oxide synthase. Because mGluR5 is expressed by microglial cells in the rat spinal cord, such effects may be mediated by direct action on microglial cells. mGluR5 stimulation also reduced microglial activation and decreased microglial-induced neurotoxicity in spinal cord microglia cultures; the latter effects were blocked by the selective mGluR5 antagonist MTEP. Interpretation These data demonstrate that mGluR5 activation can reduce microglial-associated inflammation, suggesting that the protective effects of mGluR5 agonists may reflect this action. Ann Neurol 2009;66:63,74 [source] Early imaging correlates of subsequent motor recovery after stroke,ANNALS OF NEUROLOGY, Issue 5 2009Randolph S. Marshall MS Objective To determine whether functional magnetic resonance imaging activation obtained in the first few days after stroke correlates with subsequent motor recovery. Methods Twenty-three patients with hemiparesis after first-time stroke were scanned at 2.0 ± 0.9 days while performing a simple motor task. We defined recovery as the change in Fugl,Meyer score from time of scan to approximately 3 months later (90 ± 8 days). We performed three different tests to assess correlations between brain activation and change in Fugl,Meyer score: (1) multivariate (most sensitive to spatially diffuse activation); (2) voxel-wise Statistical Parametric Mapping (most sensitive to focal activation), and (3) primary motor cortex region-of-interest analysis (most sensitive to average activation within this region). All tests controlled for initial stroke severity and lesion volume, as well as other established clinical variables. Results The multivariate test was significant [F (595, 4,934) = 1.93; p < 0.001]. The Statistical Parametric Mapping test detected two small clusters of focal activity located in the ipsilesional postcentral gyrus and cingulate cortex (p < 0.05, corrected). The region-of-interest test was not significant. Interpretation There is a pattern of brain activation present in the first few days after stroke, of which the postcentral gyrus and cingulate cortex are a part, that correlates with subsequent motor recovery. This result suggests that there are recovery processes engaged early after stroke that could provide a target for intervention. Ann Neurol 2009;65:596,602 [source] Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesionsANNALS OF NEUROLOGY, Issue 2 2008Jacqueline T. Chen PhD Objective To assess demyelination and remyelination in vivo in acute gadolinium (Gd)-enhancing lesions of multiple sclerosis (MS). Methods We measured significant changes in magnetization transfer ratio (MTR) consistent with demyelination and remyelination of individual lesion voxels, as well as the mean normalized MTR over all lesion voxels during and after contrast enhancement, in MS patients participating in a 3-year Canadian trial assessing immunoablation and autologous stem cell transplantation for treatment of MS. Results The average mean normalized lesion MTR over all lesions exhibited partial recovery over 2 to 4 months after Gd enhancement. Voxel-based analysis demonstrated that approximately 70% of the initially enhancing lesion volume (GdLV) was left with stably low MTR over 39 months of evaluation. The percentage of the GdLV undergoing significant increases in MTR consistent with remyelination increased for approximately 7 months after enhancement and then stabilized at 21 %GdLV. Significant decreases in MTR consistent with demyelination were ongoing for approximately 33 months after enhancement, stabilizing at 9 %GdLV. The estimated error of these measurements, based on scan/rescan analysis, was less than 0.4 %GdLV. Interpretation We found significant changes in MTR consistent with demyelination and remyelination that followed different temporal evolutions and were ongoing in different lesion regions for at least 3 years after lesion formation. Ann Neurol 2008 [source] Characterizing the diffusion/perfusion mismatch in experimental focal cerebral ischemiaANNALS OF NEUROLOGY, Issue 2 2004Xiangjun Meng MD Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) can rapidly detect lesions in acute ischemic stroke patients. The PWI volume is typically substantially larger than the DWI volume shortly after onset, that is, a diffusion/ perfusion mismatch. The aims of this study were to follow the evolution of the diffusion/ perfusion mismatch in permanent and 60- minute temporary focal experimental ischemia models in Sprague-Dawley rats using the intraluminal middle cerebral artery occlusion (MCAO) method. DWI and arterial spin-labeled PWI were performed at 30, 60, 90, 120, and 180 minutes after occlusion and lesion volumes (mm3) calculated At 24 hours after MCAO, and infarct volume was determined using triphenyltetrazolium chloride staining. In the permanent MCAO group, the lesion volume on the ADC maps was significantly smaller than that on the cerebral blood flow maps through the first 60 minutes after MCAO; but not after 90 minutes of occlusion. With 60 minutes of transient ischemia, the diffusion/perfusion mismatch was similar, but after reperfusion, the lesion volumes on ADC and cerebral blood flow maps became much smaller. There was a significant difference in 24- hour infarct volumes between the permanent and temporary occlusion groups. [source] Early magnetic resonance imaging findings in patients receiving tissue plasminogen activator predict outcome: Insights into the pathophysiology of acute stroke in the thrombolysis era,ANNALS OF NEUROLOGY, Issue 1 2004Julio A. Chalela MD We measured ischemic brain changes with diffusion and perfusion MRI in 42 ischemic stroke patients before and 2 hours (range approximately 1.5 to 4.5 hours) after standard intravenous tissue plasminogen activator (tPA) therapy. The median time from stroke onset to tPA was 131 minutes. Clinical and MRI variables (change in perfusion and/or diffusion weighted lesion volume) were compared between those with excellent outcome defined as 3-month modified Rankin score (mRS) of 0 to 1 and those with incomplete recovery (mRS >1). In multivariate logististic regression analysis, the most powerful independent predictor for excellent outcome was improved brain perfusion: hypoperfusion volume on mean transit time (MTT) map decrease >30% from baseline to 2-hour post tPA scan (p=0.009; odds ratio [95% confidence interval], 20.7 [2.1-203.9]). Except for age < 70 years, no other baseline clinical or imaging variable was an independent predictor of outcome. We propose MTT lesion volume decrease more than 30% 2 hours after tPA as an early marker of long-term clinical benefit of thrombolytic therapy. [source] Black holes in multiple sclerosis: definition, evolution, and clinical correlationsACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010M. A. Sahraian Sahraian MA, Radue E-W, Haller S, Kappos L. Black holes in multiple sclerosis: definition, evolution, and clinical correlations. Acta Neurol Scand: 2010: 122: 1,8. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Magnetic resonance imaging (MRI) is a sensitive paraclinical test for diagnosis and assessment of disease progression in multiple sclerosis (MS) and is often used to evaluate therapeutic efficacy. The formation of new T2-hyperintense MRI lesions is commonly used to measure disease activity, but lacks specificity because edema, inflammation, gliosis, and axonal loss all contribute to T2 lesion formation. As the role of neurodegeneration in the pathophysiology of MS has become more prominent, the formation and evolution of chronic or persistent Tl-hypointense lesions (black holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. Despite the use of various detection methods, including advanced imaging techniques such as magnetization transfer imaging and magnetic resonance spectroscopy, correlation of persistent black holes with clinical outcomes in patients with MS remains uncertain. Furthermore, although axonal loss and neuronal tissue destruction are known to contribute to irreversible disability in patients with MS, there are limited data on the effect of therapy on longitudinal change in Tl-hypointense lesion volume. Measurement of black holes in clinical studies may elucidate the underlying pathophysiology of MS and may be an additional method of evaluating therapeutic efficacy. [source] Basilar artery atherosclerotic disease is related to subacute lesion volume increase in pontine base infarctionACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009J. S. Kim Background,,, Although basilar artery atherosclerotic disease (BAD) is frequent in patients with pontine base infarction, it remains unknown whether BAD is related to the lesion size or clinical outcome. Methods,,, We studied 56 patients with unilateral pontine base infarction who underwent (i) diffusion-weighted MRI within 48 h after stroke onset and (ii) follow-up MRI and MR angiography in the subacute stage. Neurologic progression was defined as increased National Institutes of Health Stroke Scale score by , 2 during admission. Clinical outcome was dichotomized as good and poor (, 3) according to the modified Rankin Scale at 1 month after stroke onset. Results,,, Twenty-two patients (39%) had BAD and 15 patients (27%) had neurologic progression. Follow-up MRI performed at median 3.5 ± 1.1 days after the initial MRI showed the lesion volume significantly increased (P < 0.001). The BAD was not significantly related to demographic characteristics, risk factors, initial and follow-up lesion volume, neurologic progression and clinical outcome, but was closely related to the subacute increase in lesion volume (P = 0.004 for 20% increase, P = 0.029 for 50% increase). Conclusions,,, BAD is related to subacute increase in lesion volume, but not to ultimate poor clinical outcome in patients with pontine base infarction. [source] Short/long heterozygotes at 5HTTLPR and white matter lesions in geriatric depressionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2008David C. Steffens Abstract Objective We examined the relationship between 5HTTLPR genotype and volume of magnetic resonance imaging (MRI) brain lesions. Method We studied 217 older depressed patients and 141 individuals in the comparison group using a standard brain MRI protocol to calculate lesion volumes. Genotype at 5HTTLPR was determined for each subject. Results In age-adjusted models, the l/s genotype was associated with increased volume of total and white-matter lesions among depressed patients. This relationship lost significance in models controlling for reported hypertension. Conclusions The finding that 5HTTLPR heterozygotes have higher vascular lesion volumes may be related to development of hypertension. Copyright © 2007 John Wiley & Sons, Ltd. [source] Effect of Exogenous and Endogenous Antioxidants on 3-Nitropionic Acid-Inducedin vivo Oxidative Stress and Striatal LesionsJOURNAL OF NEUROCHEMISTRY, Issue 4 2000Insights into Huntington's Disease Abstract: 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of complex II in the mitochondria. 3-NP toxicity has gained acceptance as an animal model of Huntington's disease (HD). In the present study, we confirmed that rats injected with 3-NP (20 mg/kg, i.p., daily for 4 days) exhibit increased oxidative stress in both striatum and cortical synaptosomes as well as lesions in the striatum. Synaptosomal membrane proteins from rats injected with 3-NP exhibited a decrease in W/S ratio, the relevant electron paramagnetic resonance (EPR) parameter used to determine levels of protein oxidation, and western blot analysis for protein carbonyls revealed direct evidence of increased synaptosomal protein oxidation. Treatment of rats with the brain-accessible free radical spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N -oxide (DEPMPO; 30 mg/kg, i.p., daily 2 h before 3-NP injection) or with N -acetylcysteine (NAC; 100 mg/kg, i.p., daily 2 h before 3-NP injection), a known glutathione precursor, before 3-NP treatments protects against oxidative damage induced by 3-NP as measured by EPR and western blot analysis for protein carbonyls. Furthermore, both DEMPMPO and NAC treatments before 3-NP administration significantly reduce striatal lesion volumes. These data suggest oxidative damage is a prerequisite for striatal lesion formation and that antioxidant treatment may be a useful therapeutic strategy against 3-NP neurotoxicity and perhaps against HD as well. [source] Determinants of Lesion Sizes and Tissue Temperatures During Catheter CryoablationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2007MARK A. WOOD M.D. Background:Factors which influence lesion size from catheter-based cryoablation have not been well described. This study describes factors which influence lesion size during catheter cryoablation. Methods and Results:Cryoablation was delivered to porcine left ventricular myocardium in a saline bath using 4- or 8-mm electrode catheters. Ablation was delivered with the electrodes either vertical or horizontal to the tissue and both with and without superfusate flow over the electrode. The effect of electrode contact pressure was tested. Lesion dimensions were measured. All experiments were duplicated to measure tissue temperatures at 1-, 2-, 3-, and 5-mm deep to the ablation electrode. The 8-mm electrode produced lower tissue temperatures and larger lesion volumes when compared with the 4-mm electrode (all P < 0.05). Superfusate flow slowed the rate of tissue cooling, markedly warmed tissue temperatures, and reduced lesion volume when compared with no flow conditions. By linear regression modeling, lesion sizes and tissue temperatures were related to the presence of superfusate flow, electrode orientation, contact pressure and electrode size, or catheter refrigerant flow rate (r2 for models = 0.90,0.96, all P < 0.001). Electrode temperature predicted lesion size or tissue temperatures only when analyzed independent of electrode size or refrigerant flow rate. Conclusions:Lesion sizes and tissue temperatures during catheter cryoablation are related to convective warming, electrode orientation, electrode contact pressure, and any of the following: electrode size, catheter refrigerant flow rate or electrode temperature. However, electrode temperature may be a poor predictor of lesion size and tissue temperature for a given catheter size. [source] Characterizing the diffusion/perfusion mismatch in experimental focal cerebral ischemiaANNALS OF NEUROLOGY, Issue 2 2004Xiangjun Meng MD Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) can rapidly detect lesions in acute ischemic stroke patients. The PWI volume is typically substantially larger than the DWI volume shortly after onset, that is, a diffusion/ perfusion mismatch. The aims of this study were to follow the evolution of the diffusion/ perfusion mismatch in permanent and 60- minute temporary focal experimental ischemia models in Sprague-Dawley rats using the intraluminal middle cerebral artery occlusion (MCAO) method. DWI and arterial spin-labeled PWI were performed at 30, 60, 90, 120, and 180 minutes after occlusion and lesion volumes (mm3) calculated At 24 hours after MCAO, and infarct volume was determined using triphenyltetrazolium chloride staining. In the permanent MCAO group, the lesion volume on the ADC maps was significantly smaller than that on the cerebral blood flow maps through the first 60 minutes after MCAO; but not after 90 minutes of occlusion. With 60 minutes of transient ischemia, the diffusion/perfusion mismatch was similar, but after reperfusion, the lesion volumes on ADC and cerebral blood flow maps became much smaller. There was a significant difference in 24- hour infarct volumes between the permanent and temporary occlusion groups. [source] White matter lesions volume and motor performances in the elderly,ANNALS OF NEUROLOGY, Issue 6 2009Aïcha Soumaré MSc Objectives To investigate the cross-sectional and longitudinal associations between performance-based measures of motor function and volume of white matter lesions (WMLs), and to examine the influence of the localization of these lesions. Methods At baseline, motor performances (maximum walking speed, Tinetti gait and balance subscales) were assessed in 1,702 subjects aged 80 years or younger from the Dijon (France), France center of the Three-City study. Volumes of WMLs lesions (total, periventricular, deep) were measured using an automated method of tissue segmentation and quantification of lesion size. At 8-year follow-up, walking speed was evaluated in 1,086 subjects. Results At baseline, mean and 95% confidence interval (CI) walking speed was lower in subjects with total volumes of WMLs ,90th percentile (1.50 [1.45,1.55] m/s) than in subjects with lower volumes (1.56 [1.55,1.58] m/s; p = 0.004). Baseline total volumes of WMLs above the 90th percentile predicted walking speed decline during follow-up (odds ratio [95% CI] for having the greatest walking speed decline = 2.3 [1.3,4.1], p = 0.006). Moreover, high volumes of periventricular but not deep WMLs were associated with slower walking speed at baseline (p = 0.005) and over time (p = 0.001), and with lower Tinetti gait subscore (p = 0.02). Interpretation Our study shows a cross-sectional and longitudinal association between high total volumes of WMLs, in particular volumes above the 90th percentile, and impaired mobility. These associations were independent of several confounders, including cognition, and were mainly accounted for by volumes of periventricular WMLs. These findings support the hypothesis of a vascular contribution to motor decline in the elderly. Ann Neurol 2009;65:706,715 [source] | ||||||||||||||||||||||||||||