中枢γ—氨基丁酸对大鼠烫伤早期心血管功能的影响

目的：通过阻断烫伤早期大鼠中枢和下丘脑室旁核γ－氨基丁酸的作用，观察大鼠心血管指标和存活时间的改变。方法：制备大鼠３０％总体表面积Ⅲ度烫伤模型；借助脑立体定向仪行中枢内注射；运用四导生理仪记录血压和心肌力学指标。结果：烫伤早期大鼠中枢和下丘脑室旁核γ－氨基丁酸作用的阻断可明显回升其血压、左心室收缩压、左心室内压最大变化速率和延长存活时间。结论：提示中枢γ－氨基丁酸对大鼠烫伤早期心血管功能有影响，部     

双侧丘脑底核电刺激治疗原发性肌张力障碍

目的 研究双侧丘脑底核（STN）脑深部电刺激术（DBS）治疗原发性肌张力障碍的长期疗效：方法 比较15例行舣侧STN—DBS治疗的原发性肌张力障碍患者，手术前后的Burke—Fahn—Marsden肌张力障碍评分改善程度及长期改善效果。结果 15例原发性肌张力障碍患者中12例在开启刺激器后症状即刻得到部分缓解，以不自主运动、异常姿势及躯体的扭转改善为主，其中9例在刺激1—3d后、3例刺激1，周后改善75％以上，6个月后平均改善92％；1例在2个月后开始改善，6个月后改善90％以上；2例在1个月开始出现轻微改善，6个月后改善了76％：15例患者的长期随访结果显示其疗效稳定，经过1—3次程控后不需经常调整刺激参数：所有患者未出现手术相关并发症及永久性副作用。结论 双侧丘脑底核脑深部电刺激术对原发性肌张力障碍有显著的治疗效果，且疗效持久、稳定，无并发症及永久性副作用。比较GPi—DBS而言，STN—DBS起效快、最件刺激化点及参数易于确定、刺激参数水平低、长期疗效稳定，可能是原发性肌张力障碍DBS治疗的理想靶点。     

Excitatory amino acid receptor regulation after subthalamic nucleus lesions in the rat

The subthalamic nucleus plays a pivotal role in the regulation of basal ganglia output. Recent electrophysiologic, lesion and immunocytochemical studies suggest that the subthalamic nucleus uses an excitatory amino acid as a neurotransmitter. After complete ablation of the subthalamic nucleus, we have examined the NMDA, AMPA, kainate and metabotropic subtypes of excitatory amino acid receptors in two major subthalamic projection areas (globus pallidus and substantia nigra pars reticulata) with quantitative autoradiography. Two weeks after ablation, binding sites for [³H]AMPA and [³H]kainate increased in substantia nigra pars reticulata ipsilateral to the lesion. In globus pallidus on the lesioned side, [³H]glutamate binding to the NMDA recognition site decreased. The results suggest that glutamate receptors regulate after interruption of subthalamic nucleus output.     

Unilateral dopamine depletion paradoxically enhances amphetamine-induced Fos expression in basal ganglia output structures

The ability of amphetamine to induce expression of the immediate early gene protein, Fos, was examined by immunocytochemistry in animals with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle. Amphetamine induced Fos expression in the globus pallidus (GP) on the intact side of the brain, but this response was greatly attenuated on the dopamine-depleted side. In contrast, amphetamine induced little Fos expression in the entopeduncular nucleus (EPN) and the substantia nigra pars reticulata (SNpr) on the intact side of the brain, but resulted in pronounced expression in these structures on the lesioned side. These findings demonstrate that unilateral dopamine depletion results in a pathophysiological state in which some responses to amphetamine are attenuated while others are paradoxically potentiated. One explanation of these effects is that amphetamine may indirectly activate excitatory inputs to the SNpr and the EPN on both sides of the brain. On the intact side, these effects would be opposed by the simultaneous activation of inhibitory pathways arising in the striatum and the GP, with the result that little Fos expression would be seen. On the dopamine-depleted side, however, engagement of these inhibitory pathways would be attenuated and the unopposed effects of the excitatory inputs mobilized by amphetamine would result in exaggerated Fos synthesis.     

Subthalamic influences on the cardiorespiratory functions in the cat

The electrical stimulation of the subthalamic nucleus (STN) caused a conspicuous increase in arterial blood pressure (BP), heart rate (HR) and respiratory rate (RR) in freely moving cats. The pulse pressure (PP) increased significantly following an initial decrease at the beginning of the 10 s long stimulation. A rebound bradycardia occurred after switching off the stimulation. Cardiorespiratory responses might be elicited also during ketamine-induced anaesthesia. The BP responses reduced highly under the blockade of the alpha(1)-adrenergic receptors. The neurotoxic lesions of the ipsilateral globus pallidus caused no significant alterations in the cardiorespiratory responses to STN stimulation. It is concluded that, besides its role in the motor control, STN is also involved in adjusting the cardiorespiratory functions to the somatomotor activity.     

Effect of subthalamic nucleus deep brain stimulation on balance in Parkinson’s disease: A static posturographic analysis

BackgroundThe effect of subthalamic deep brain stimulation on balance in Parkinson’s disease remains unclear.ObjectiveTo evaluate the effect of subthalamic nucleus stimulation on balance in Parkinson’s disease using posturography.Methods16 patients (9 women) who underwent subthalamic deep brain stimulation [mean age 59.6 years (46–70); mean disease duration 15.6 years (7–25); mean duration of subthalamic stimulation 32.1 months (3.0–69.6)] and 13 healthy age-matched controls were evaluated using a static posturography analysis. Patients were assessed under four conditions: 1) off medication/off stimulation; 2) off medication/on stimulation; 3) on medication/off stimulation and 4) on medication/on stimulation in ten experimental paradigms, some reproducing common situations of daily living. The displacement of the centre of pressure was analyzed using 14 posturographic parameters. The Mann-Whitney test was used to compare patients with controls. The Wilcoxon signed rank test was used to compare patients under different clinical conditions.ResultsPatients off medication/off stimulation showed larger and more rapid displacements of the centre of pressure than controls in most paradigms (p < 0.05), particularly when performing a dual task. Subthalamic stimulation alone reduced the lateral excursion and anterior-posterior velocity of the centre of pressure in quite stance paradigms (p < 0.05). Subthalamic stimulation combined with antiparkinsonian medication did not induce statistically significant changes in posturagraphic measures in any experimental paradigm.ConclusionsAlthough subthalamic stimulation alone may induce some positive effect on balance, subthalamic stimulation in addition to antiparkinsonian medication, which is the usual treatment in clinical practice, did not modify balance as assessed by static posturography in patients with Parkinson’s disease.     

Image-based biophysical modeling predicts cortical potentials evoked with subthalamic deep brain stimulation

BackgroundSubthalamic deep brain stimulation (DBS) is an effective surgical treatment for Parkinson’s disease and continues to advance technologically with an enormous parameter space. As such, in-silico DBS modeling systems have become common tools for research and development, but their underlying methods have yet to be standardized and validated.ObjectiveEvaluate the accuracy of patient-specific estimates of neural pathway activations in the subthalamic region against intracranial, cortical evoked potential (EP) recordings.MethodsPathway activations were modeled in eleven patients using the latest advances in connectomic modeling of subthalamic DBS, focusing on the hyperdirect pathway (HDP) and corticospinal/bulbar tract (CSBT) for their relevance in human research studies. Correlations between pathway activations and respective EP amplitudes were quantified.ResultsGood model performance required accurate lead localization and image fusions, as well as appropriate selection of fiber diameter in the biophysical model. While optimal model parameters varied across patients, good performance could be achieved using a global set of parameters that explained 60% and 73% of electrophysiologic activations of CSBT and HDP, respectively. Moreover, restricted models fit to only EP amplitudes of eight standard (monopolar and bipolar) electrode configurations were able to extrapolate variation in EP amplitudes across other directional electrode configurations and stimulation parameters, with no significant reduction in model performance across the cohort.ConclusionsOur findings demonstrate that connectomic models of DBS with sufficient anatomical and electrical details can predict recruitment dynamics of white matter. These results will help to define connectomic modeling standards for preoperative surgical targeting and postoperative patient programming applications.     

Subthalamic nucleus stimulation and gait in Parkinson’s Disease: a not always fruitful relationship

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides efficient treatment for the alleviation of motor signs in patients with advanced Parkinson’s disease (PD), but its specific effects on gait is sometimes less successful as it may even lead to an aggravation of freezing of gait. To better understand when axial symptoms can be expected to improve and when they may worsen or be resistant to STN-DBS, we propose here a narrative review that considers the recent literature evidences based on instrumental gait analysis data. Our aim is to report about the efficacy of STN-DBS on PD gait, analyzing the clinical and procedural factors involved, and discussing the strategies for optimizing such effectiveness in patients with advanced PD.     

Long-term directional deep brain stimulation: Monopolar review vs. local field potential guided programming

BackgroundDirectional subthalamic stimulation in Parkinson's disease can increase stimulation threshold for adverse effects and widen the therapeutic window. However, selection of programming settings is time consuming, requiring a thorough monopolar clinical review. To overcome this, programming may be guided by intraoperatively recording local field potential beta oscillations (13–35 Hz).Objectives1) Evaluate whether the power of beta oscillations recorded intraoperatively can predict the clinically most effective directional contacts; and 2) assess long-term directional stimulation outcomes between patients programmed based on clinical monopolar review and patients programmed based on beta activity.MethodsWe conducted a non-randomized, prospective study with 24 Parkinson's disease patients divided into two groups. In group A (14 patients, 2016–2018), we investigated whether beta activity in the directional contacts correlated with clinical efficacy. Stimulating parameters were selected according to clinical monopolar review and mean follow-up was 27 months. In group B (10 patients, 2018–2019), stimulating parameters were selected according to beta activity and mean follow-up was 13 months.ResultsNeurophysiological results showed a strong correlation between clinical efficacy and the low-beta sub-band. Contacts with highest beta peaks increased the therapeutic window by 25%. Selecting the two contacts with highest beta peaks provided an 82% probability of selecting the best clinical contact. Clinical results showed similar improvements in group A (motor score, 72% reduction; levodopa-equivalent daily dose, 65% reduction) and B (72% and 63% reduction, respectively), maintained at long-term follow-up.ConclusionsOur results validate the long-term efficacy of directional stimulation guided by intraoperative local field potential beta oscillations.