Objective-To assess the eVects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson's disease (PD). Methods-The eYcacy of STN stimulation on total motor disability score (unified Parkinson's disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson's disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the "oV" and "on" drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the "activities of daily living" (ADL)-that is, speech, swallowing, turning in bed, falling, walking, and freezing-was obtained from each patient's questionnaire (UPDRS, part II). Results-Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. Conclusion-These findings suggest that bilateral STN stimulation improves most axial features of Parkinson's disease and that a synergistic eVect can be obtained when stimulation is used in conjunction with levodopa treatment. (J Neurol Neurosurg Psychiatry 2000;68:595-600)

E ssential hypertension is characterized by sustained elevations of blood pressure (BP) that can lead to target organ damage and an increased risk for cardiovascular disease. 1Potential life-threatening outcomes of hypertension, such as stroke, renal insufficiency, and cardiac hypertrophy, had been initially perceived as a result of macrovascular alterations. These macrovascular events, however, do not occur independently of microvascular derangement. [2][3][4] Studies have shown that alterations in microvascular structure (rarefaction), vasomotor tonus (enhanced vasoconstriction or blunted vasodilation), and endothelial dysfunction are principal processes in the pathogenesis of hypertension and are evident in several organs/tissue types. [5][6][7][8] In the skeletal muscle, microvascularization is important for oxygen and nutrient supply and for effective metabolite clearance. Studies in hypertension have shown structural or functional impairments in the microvasculature within skeletal muscles, 8 implying a reduced capacity for oxygen delivery and exchange. Furthermore, animal studies using experimental models of hypertension suggested that mitochondrial dysfunction (ie, decreased expression of mitochondrial components and defects in respiratory complexes) and increased oxidative stress result in impaired oxidative capacity and reduced mitochondrial ATP production.9,10 Importantly, in these animals, the mitochondrial dysfunction and the reduced oxidative capacity were present before the development of hypertension, suggesting a possible role of these processes to the pathogenesis of hypertension.11 However, information on skeletal muscle microvascular alterations and oxidative Abstract-This study examined in vivo (1) skeletal muscle oxygenation and microvascular function, at rest and during handgrip exercise, and (2) their association with macrovascular function and exercise blood pressure (BP), in newly diagnosed, never-treated patients with hypertension and normotensive individuals. Ninety-one individuals (51 hypertensives and 40 normotensives) underwent office and 24-hour ambulatory BP, arterial stiffness, and central aortic BP assessment, followed by a 5-minute arterial occlusion and a 3-minute submaximal handgrip exercise. Changes in muscle oxygenated and deoxygenated hemoglobin and tissue oxygen saturation were continuously monitored by nearinfrared spectroscopy and beat-by-beat BP by Finapres. Hypertensives had higher (P<0.001) central aortic BP and pulse wave velocity versus normotensives and exhibited (1) a blunted tissue oxygen saturation response during occlusion, with slower (P=0.006) deoxygenation rate, suggesting reduced muscle oxidative capacity, and (2) a slower reoxygenation rate and blunted hyperemic response (P<0.05), showing reduced microvascular reactivity. Muscle oxygenation responses were correlated with aortic systolic and pulse pressure and augmentation index (P<0.05; age and body mass index (BMI) adjusted). When exercising at the same submaximal intensity, hypertensives required a sig...

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Twenty males ran either on a level treadmill (nonmuscle-damaging condition) or on a downhill treadmill (muscle-damaging condition). Blood and urine samples were collected before and after exercise (immediately after, 1h, 4h, 24h, 48h, and 96h). The following assays were performed: F(2)-isoprostanes in urine, protein carbonyls in plasma, glutathione, superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes. The main finding was that monophasic redox responses were detected after nonmuscle-damaging exercise compared to the biphasic responses detected after muscle-damaging exercise. Based on these findings, muscle-damaging exercise may be a more appropriate experimental model to induce physiological oxidative stress.