Different effects of unilateral versus bilateral subthalamic nucleus stimulation on walking and reaching in Parkinson's disease.

The purpose of this study was to determine the effects of unilateral versus bilateral subthalamic nucleus (STN) stimulation on quantitative measures of walking and reaching in Parkinson's disease (PD). We used kinematic measures and the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale (subscale III) to evaluate the movement of 6 people with PD who had bilateral STN stimulators implanted for at least 6 months and withheld their anti-parkinson medication for at least 8 hours. Subjects were studied with both stimulators off, one on, and both on. Kinematic data were collected as subjects walked, reached to a target, and were rated using the UPDRS motor subscale. STN stimulation improved walking speed and stride length, with the greatest benefit from bilateral stimulation. Reaching speed was improved by unilateral STN stimulation alone, with no additive effect of bilateral stimulation. UPDRS motor subscale ratings paralleled the kinematic findings. STN stimulation did not restore PD subjects' movements to the level of age-matched controls. Overall, these results provide further evidence that the basal ganglia pathways involved in control of walking and reaching may be distinct. We speculate that basal ganglia may influence walking through bilateral pedunculopontine projections and reaching through ipsilateral thalamocortical projections. Our findings also suggest that maximal improvement of walking requires bilateral rather than unilateral STN stimulation.     

Deletion of aldose reductase leads to protection against cerebral ischemic injury.

Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR(-/-) brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR(-/-) brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury.     

Magnetic resonance imaging and clinical correlates of intellectual impairment in myotonic dystrophy

Although intellectual impairment is common in patients with myotonic dystrophy, this aspect of the disease has received relatively little research attention. We examined 41 patients with myotonic dystrophy using objective neuropsychological procedures and magnetic resonance imaging. Ten patients (24%) had severe and generalized intellectual dysfunction, while lesser or no cognitive impairment characterized the remaining patients. Degree of intellectual impairment was not related to neuromuscular status or sex. Patients with severe intellectual disturbance had significantly earlier onset of both myotonia and weakness and were more likely to inherit the disease from their mother. Magnetic resonance imaging findings indicated that while degree of cerebral atrophy was not related to severity of intellectual impairment, skull thickness, focal white matter lesions, and anterior temporal lobe abnormalities were significantly more common in patients with severely disturbed intellect. This study reports a number of previously unreported cerebral magnetic resonance imaging findings associated with intellectual impairment in myotonic dystrophy, but the etiology of these changes awaits neuropathologic examination.     

Dual-source-Computertomographie des Herzens

In a newly developed dual-source computed tomography system (DSCT) the relation of heart rate and image quality and the possible advantages of the system’s superior temporal resolution in the evaluation of left ventricular parameters as compared to results of cardiac magnetic resonance imaging (MRI) were assessed. Coronary CT angiography was performed using a DSCT (Somatom Defintion, Siemens Medical Solutions, Forchheim, Germany) in 21 patients (mean age 62±8; 15 male, 6 female). Image quality of the coronary arteries, the heart valves, and the left ventricular myocardium was assessed using a three-point grading scale. Ten of these patients also underwent cardiac MRI for the assessment of left ventricular function, using a SSFP (steady-state free precession) sequence. Left ventricular ejection fractions (LV-EF), the end-systolic volumes (ESV), and the end-diastolic volumes (EDV) were measured employing MRI and DSCT datasets. The image quality ratings for the coronary arteries at the optimal reconstruction interval were diagnostic even in patients with high heart rates (1.42±0.49). Analysis of global LV function using DSCT quantified from CTA datasets showed a good correlation with results of cardiac MRI [EF: r=0.75 (p=0.01); ESV: r=0.72 (p=0.19); EDV: r=0.71 (p=0.02)]. The dual-source CT system offers robust image quality of the coronary arteries, independent of the heart rate, and provides combined diagnostic imaging of coronary arteries, the heart valves, the myocardium, and the global left ventricular function.