Does abnormal interhemispheric inhibition play a role in mirror dystonia?

The presence of mirror dystonia (dystonic movement induced by a specific task performed by the unaffected hand) in the dominant hand of writer's cramp patients when the nondominant hand is moved suggests an abnormal interaction between the 2 hemispheres. In this study we compare the level of interhemispheric inhibition (IHI) in 2 groups of patients with writer's cramp, one with the presence of a mirror dystonia and the other without as well as a control group. The level of bidirectional IHI was measured in wrist muscles with dual‐site transcranial magnetic stimulation with a 10‐millisecond (short IHI) and a 40‐millisecond (long IHI) interstimulus interval during rest and while holding a pen in 9 patients with mirror dystonia 7 without mirror dystonia, and 13 controls. The group of patients without mirror dystonia did not differ from the controls in their IHI level. In contrast, IHI was significantly decreased in the group of patients with mirror dystonia in comparison with the group without mirror dystonia and the controls in both wrist muscles of both the dystonic and unaffected hand whatever the resting or active condition (P = 0.001). The decrease of IHI level in the group of patients with mirror dystonia was negatively correlated with the severity and the duration of the disease: the weaker the level of IHI, the more severe was the disease and the longer its duration. Interhemispheric inhibition disturbances are most likely involved in the occurrence of mirror dystonia. This bilateral deficient inhibition further suggests the involvement of the unaffected hemisphere in the pathophysiology of unilateral dystonia. © 2013 International Parkinson and Movement Disorder Society     

Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI

Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus (³¹P) magnetic resonance spectroscopy (³¹P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.     

Monitoring stroke progression: in vivo imaging of cortical perfusion,blood–brain barrier permeability and cellular damage in the rat photothrombosis model

Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood–brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood–brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.     

Pulse inversion sonography in the early phase of the sonographic contrast agent Levovist: differentiation between benign and malignant focal liver lesions.

OBJECTIVE: To determine whether examination of focal liver lesions by pulse inversion sonography in the early perfusion phase of the contrast agent Levovist (SH U 508A; Schering AG, Berlin, Germany) enables distinction between benign and malignant lesions. METHODS: Seventy-two patients were examined. The cause of the lesion was confirmed by liver biopsy, computed tomography, or both or by hepatic iminodiacetic acid-enhanced scintigraphy. Forty-two patients had malignant liver lesions, and 30 had benign liver lesions. After injection of 2 g of Levovist intravenously, analysis of Levovist arrival was performed by the interval delay imaging technique for 60 seconds. RESULTS: The early arrival of Levovist less than 30 seconds after injection was used as an indicator for malignancy and had specificity of 67% and sensitivity of 60% (P < .05). The central starlike fill-in as a sign for focal nodular hyperplasia had specificity of 100% and sensitivity of 67% (P < .001). The rimlike pattern followed by centripetal fill-in as a sign for hemangioma had specificity of 100% and sensitivity of 18% (P < .01). In contrast, the early diffuse stippled arrival pattern was found in 60% of malignant lesions and also in 33% of cases of focal nodular hyperplasia and in 1 patient with an adenoma. CONCLUSIONS: Analysis of Levovist arrival time cannot distinguish between a malignant or benign lesion in individual cases. However, the central starlike arrival pattern is characteristic of focal nodular hyperplasia.     

Neuroprotective effect of ischemic preconditioning in focal cerebral infarction：relationship with upregulation of vascular endothelial growth factor

Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.     

康柏西普玻璃体内注射治疗特发性脉络膜新生血管

目的　探究康柏西普玻璃体内注射治疗特发性脉络膜新生血管（idiopathic choroidal neovascularization,ICNV）的疗效。方法　选择2016年1月至2018年1月我院眼科收治的ICNV患者146例（146眼）纳入研究,所有患者均行玻璃体内注射康柏西普治疗,测量治疗前后最佳矫正视力（BCVA）、眼压、黄斑中心凹脉络膜厚度（subfoveal choroidal thickness,SFCT）及上侧脉络膜厚度（superior choroidal thickness,SCT）、下侧脉络膜厚度（inferior choroidal thickness,ICT）、鼻侧脉络膜厚度（nasal choroidal thickness,NCT）、颞侧脉络膜厚度（temporal choroidal thickness,TCT）,观察并评价脉络膜新生血管（CNV）渗漏情况,比较患眼治疗前后BCVA、眼压及各区域脉络膜厚度,以及患眼及对侧眼脉络膜厚度差异。结果　与治疗前比较,患眼治疗后 1 d、1个月时BCVA均显著提高(均为P<0.05）。患眼治疗前后眼压比较差异均无统计学意义（均为P>0.05）。随访12个月时患眼渗漏区面积较治疗前均有下降,CNV渗漏治疗有效率为80.82%。治疗前患眼SFCT、NCT 2.2 mm、TCT 2.2 mm、TCT 3.45 mm均显著高于对侧眼（均为P<0.05）;治疗后12个月患眼各部位脉络膜厚度均较治疗前显著降低,差异均有统计学意义（均为P<0.05）。治疗过程中及治疗后均未见严重不良反应发生。结论　玻璃体内注射康柏西普可改善ICNV患者视力,减少视网膜渗漏症状,降低SFCT,效果较好。     

早期“强制性使用”运动疗法对局灶性脑梗死大鼠行为学评分及神经生长因子的影响

目的：探讨脑卒中后早期强制性使用单侧肢体对局灶性脑梗死大鼠行为学评分及大脑皮质梗死周围（NGF）表达的影响。方法：健康雄性Sprague-Dawley（SD）大鼠,用大鼠大脑中动脉线栓法（MCAO）建立永久性缺血模型,按照Zea-Longa的方法对动物的行为缺陷进行评分,选取1—3分者60只,将60只大鼠随机分为2组,健侧前肢固定组（A组）30只,未固定组（B组）30只,7d时解除固定,再采用随机区组法分为14d时处死组和21d处死组,各组动物在7d时和处死前做神经功能评分（Longa评分）,采用免疫组织化学（SP）方法观察NGF蛋白的表达;采用（POD法）原位杂交方法检测NGF mRNA表达。结果：固定组与未固定组相比,早期“强制性使用”运动疗法可以改善14d及21d的行为学评分,有显著性意义（P〈0.05）;在梗死周围皮质NGF蛋白和NGF mRNA的表达,固定组14d时表达均明显高于非固定组（P〈0.05）,而在21d时无显著性意义。结论：早期“强制性使用”运动疗法可以改善神经功能的恢复,从基因水平来提高NGF的表达可能为其发挥作用的机制之一。     

Can noncontact mapping distinguish between endo- and epicardial foci?

Objectives  Noncontact mapping has been demonstrated to facilitate RF ablation of ventricular arrhythmias, but the reproducibility in the localization of endocardial exit sites during focal ventricular tachycardia (“VT”) originating from defined myocardial layers has not been systematically studied. Furthermore, it remains unclear whether noncontact mapping can distinguish between endo- and epicardial foci. Methods  In six dogs, constant pacing was applied through octopolar needle electrodes in the left ventricle to mimic VT of subendocardial, midmyocardial (mid1; mid2) or subepicardial origin. Using noncontact mapping, the site of origin was determined for each of 50 consecutive beats of all “VTs” and the variation between respective exit sites was measured. Exit sites were reconstructed for 50 consecutive beats of each “VT” and the time span between site of origin and exit site was measured as a parameter of intramural conduction. Results  While subendocardial and midmyocardial (mid1, mid2) foci were pinpointed with a variation of ≤2 mm, a variation of 4 mm was encountered for subepicardial foci. A gradual increase in intramural conduction was evident from endocardial towards epicardial foci, with significant differences between subendocardial (4.8 ± 0.9 ms), midmyocardial (mid1 = 11.1 ± 4.6 ms; mid2 = 11.8 ± 3.5 ms) and subepicardial (16.8 ± 3.6 ms) foci (P < 0.005). Systematic differences in the morphology of virtual waveforms depending on the site of origin could not be detected. Conclusions  Except for subepicardial foci, noncontact mapping localized focal activity in the LV with high reproducibility. In contrast to morphological parameters, the determination of intramural conduction provides a fair estimate of the depth of foci and is proposed as a novel parameter to identify a subepicardial origin. Dr. Frederik Voss and Dr. Alexander Bauer contributed equally to this work.