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To evaluate the effects of 12-week polestriding intervention on gait and disease severity in people with mild to moderate Parkinson disease (PD).A-B-A withdrawal study design.Outpatient movement disorder center and community facility.Individuals (N=17; 9 women [53%] and 8 men [47%]; mean age, 63.7±4.9y; range, 53-72y) with mild to moderate PD according to United Kingdom brain bank criteria with HoehnYahr score ranging from 2.5 to 3.0 with a stable medication regimen and ability to tolerate "off" medication state.Twelve-week polestriding intervention with 12-week follow-up.Gait was evaluated using several quantitative temporal, spatial, and variability measures. In addition, disease severity was assessed using clinical scales such as Unified Parkinson's Disease Rating Scale (UPDRS), HoehnYahr scale, and Parkinson's Disease Questionnaire-39.Step and stride lengths, gait speed, and step-time variability were improved significantly (P.05) because of 12-week polestriding intervention. Also, the UPDRS motor score, the UPDRS axial score, and the scores of UPDRS subscales on walking and balance improved significantly after the intervention.Because increased step-time variability and decreased step and stride lengths are associated with PD severity and an increased risk of falls in PD, the observed improvements suggest that regular practice of polestriding may reduce the risk of falls and improve mobility in people with PD.

OBJECT Recent studies show that deep brain stimulation can be performed safely and accurately without microelectrode recording ortest stimulation but with the patient under general anesthesia. The procedure couples techniques for direct anatomical targeting on MRI with intraoperative imaging to verify stereotactic accuracy. However, few authors have examined the clinical outcomes of Parkinson’s disease (PD) patients after this procedure. The purpose of this study was to evaluate PD outcomes following “asleep” deep brain stimulation in the globus pallidus internus (GPi). METHODS The authors prospectively examined all consecutive patients with advanced PD who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson’s Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson’s Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented. RESULTS Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events. CONCLUSIONS Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after surgery.

Alison Conovaloff,1 Narayanan Krishnamurthi,1 Padma Mahant,2 Johan Samanta,2 James Abbas11Center for Adaptive Neural Systems, School of Biological and Health Systems Engineering, Ira A Fulton School of Engineering, Arizona State University, Tempe, AZ, USA, 2Movement Disorders Clinic, Banner Good Samaritan Medical Center, Phoenix, AZ, USABackground: The efficacy of deep brain stimulation (DBS) in Parkinson’s disease has been convincingly demonstrated in studies comparing motor performance with and without stimulation, but characterization of the stimulation dose-response curves has been limited.Methods: In a series of case studies, eight subjects with Parkinson’s disease and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS) and at three reduced amplitudes, ie, approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively). Performance was assessed using the motor section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), which includes subscores for tremor, bradykinesia, gait, posture, and tapping. Data at the reduced settings were analyzed to determine if individual subjects demonstrated a threshold-like response, which was defined as a dose-response curve in which one decrement in stimulation accounted for ≥70% of the maximum change observed. Day-to-day variability was assessed using the CDS data from the three different days.Results: In the dose-response curves, two subjects exhibited a threshold-like response, four exhibited a graded change, and two did not exhibit substantial changes. For some subjects, variability in CDS performance across the three days exceeded the change observed when reducing amplitude to the MOD setting. Comparisons across this set of eight subjects demonstrated that the mean UPDRS-III and all but one subscore significantly increased (performance degraded) when amplitude was reduced from CDS to the LOW and OFF conditions, but there were no significant changes when amplitude was reduced from CDS to the MOD condition.Conclusion: Individual differences in the DBS dose-response curves may provide opportunities to optimize clinical performance. Day-to-day variability in motor performance cautions against the use of a single UPDRS measurement in clinical selection of DBS settings.Keywords: deep brain stimulation, Parkinson’s disease, Unified Parkinson’s disease rating scale, motor performance

Background and purpose:To characterize patients with benign essential blepharospasm (BEB) by diagnosis, environmental risk factors, and family history. Methods:Two hundred and forty patients with BEB were evaluated through a clinical examination and questionnaire. The questionnaire reviewed personal medical history, demographic factors, risk factors for the development of blepharospasm and family history of dystonia and other neurological conditions. Results:Benign essential blepharospasm was more commonly found in women (2.8:1) and 93% of the patients were Caucasian. Fifty percent had pure BEB, 31% had BEB/Meige!s syndrome, and 4% had BEB and eyelid opening apraxia (+/)Meige!s syndrome). A minority of patients reported preceding photophobia (25%) or other eye conditions (22%). The majority were non-smokers, had no exposure to anti-emetic or antipsychotic agents, had a normal birth history, and had no history of head trauma. Seventy-two percent did report a stressful event immediately prior to the development of symptoms. Treatments reported included botulinum toxin (BoNT), oral medications, surgical procedures, and acupuncture. Thirty-two percent of patients reported a family history of focal dystonia, and BEB was the most commonly reported. Conclusion:This study confirms previous reports of usual age, sex, ca!eine and tobacco use, and family history in patients with blepharospasm. New findings include a report on occupation, lower reports of preceding eye conditions and photophobia, and higher reported stressful events. Further, this study shows a change in treatment with an increase in BoNT use and decrease in surgical procedures.

For people with Parkinson's disease (PD), gait and postural impairments can significantly affect their ability to perform activities of daily living. Presentation of appropriate cues has been shown to improve gait in PD. Based on this, a treadmill-based system and experimental paradigm were developed to determine if people with PD can utilize real-time feedback (RTFB) of step length or back angle (uprightness) to improve gait and posture. Eleven subjects (mean age 67 ± 8 years) with mild-to-moderate PD (Hoehn and Yahr stage I–III) were evaluated regarding their ability to successfully utilize RTFB of back angle or step length during quiet standing and treadmill walking tasks during a single session in their medication-on state. Changes in back angle and step length due to feedback were compared using Friedman nonparametric tests with Wilcoxon Signed-Rank tests for post-hoc comparisons. Improvements in uprightness were observed as an increase in back angle during quiet standing ( $p = 0.005$ ) and during treadmill walking ( $p = 0.005$ ) with back angle feedback when compared to corresponding tasks without feedback. Improvements in gait were also observed as an increase in step length ( $p = 0.005$ ) during step length feedback compared to tasks without feedback. These results indicate that people with mild-to-moderate PD can utilize RTFB to improve upright posture and gait. Future work will investigate the long-term effects of this RTFB paradigm and the development of systems for clinical or home-based use.

In view of the evidence that thyroid hormone administration has angiogenic effects on the hypertrophic myocardium, we tested the hypothesis that the capillary supply in the hypertrophic myocardium surviving infarction would be improved by administration of the thyroid hormone analog, diiodothyroproprionic acid (DITPA). We administered DITPA (MI-DITPA) or saline (MI-saline), s.c., to rats for 10 days following experimental infarction of the left ventricle (LV). Morphometric methods were used to assess capillarity and myocyte cross-sectional area in three regions of the left ventricle: (1) border (next to the scar of infarction); (2) adjacent (next to the border); and (3) remote (interventricular septum). Infarct size ranged from 20–85% of the LV free-wall, and both groups had similar mean infarct size. Capillary length density (L v ) was significantly higher in the remote region of the treated group than in the MI-saline rats. L v in the border region, which experienced the most marked increase in cardiocyte cross-sectional area, was not significantly lower than in the other regions, indicating a more marked angiogenic response. In hearts with large infarcts (≥40%) L v in the border region was higher in the DITPA group than in the non-treated rats. In the MI-DITPA group, cardiocyte size in the border region was positively correlated with that of the other regions, which contrasts with the negative correlations noted for the MI-saline rats. These data suggest that DITPA therapy (1) may improve maximal perfusion potential of the hypertrophied myocardium surviving a myocardial infarction, and (2) is selectively effective in the border region of hearts with large infarcts.

Objective Our overall aims were to elucidate the temporal and spatial sequence of coronary vascularization during development in the rat, and to determine whether basic fibroblast growth factor expression corresponds to any phase of the vascularization process. Methods Immunohistochemical, histochemical, morphometric and in situ hybridization analyses were performed on prenatal and postnatal hearts of various ages. Results Coronary vascularization, which begins at embryonic day 13 (E13) with blood island-like structures in the epicardium, progresses from this layer toward the endocardium as indicated by a transmural gradient of vascular volume throughout the ventricles. Vascular smooth muscle first appears in E17 hearts at the time a capillary-like plexus coalesces and penetrates the aorta to form the main coronary arteries. These vessels maintain an anastomatic morphology and must undergo subsequent remodeling in order to assume adult branching characteristics. The early postnatal period is characterized by development of the arterial tree and the enzymatic differentiation of the arteriolar and venular ends of the capillary bed. Although bFGF is expressed both prenatally and postnatally, the highest mRNA expression was noted during the early period of vascularization (E14 and E15), and the early neonatal period (1–6 days) which corresponds to a period of substantial microvascular growth. Conclusions Coronary vascularization follows a temporal sequence which includes transmural expansion of the capillary bed, arteriolar formation subsequent to vascular penetration of the aorta, and postnatal growth, differentiation, and remodeling. Since high levels of bFGF expression are correlated with key time points in coronary vascular growth, bFGF may play an important role in this process.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is now widely used to alleviate symptoms of Parkinson’s disease (PD). The specific aim of this study was to identify posture control measures that may be used to improve selection of DBS parameters in the clinic and this was carried out by changing the DBS stimulation amplitude. A dynamic posture shift paradigm was used to assess posture control in 4 PD STN-DBS subjects. Each subject was tested at 4 stimulation amplitude settings. Movements of the center of pressure and the position of the pelvis were monitored and several quantitative indices were calculated. The presence of any statistically significant changes in several normalized indices due to reduced/no stimulation was tested using the one-sample t test. The peak velocity and the average movement velocity during the initial and mid phases of movement towards the target posture were substantially reduced. These results may be explained in terms of increased akinesia and bradykinesia due to altered stimulation conditions. Thus, the dynamic posture shift paradigm may be an effective tool to quantitatively characterize the effects of DBS on posture control and should be further investigated as a tool for selection of DBS parameters in the clinic.

Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is now widely used to alleviate symptoms of Parkinson's disease (PD). The long-term goal is to develop a quantitative tool to facilitate selection of DBS settings in the clinic since the typical parameter selection process may not adequately consider the effects of DBS on posture control. The aim of this study was to characterize the effects of changing the stimulation amplitude of DBS on posture control in PD. A dynamic posture shift paradigm involving target acquisition was used to assess posture control in 4 PD STN-DBS subjects. Each subject was tested at 4 stimulation amplitude settings: Clinically-determined (CD) settings, moderate (approx. 70% CD), low (approx. 30% CD), and off (no stimulation). Movements of the center of pressure and the position of the pelvis were monitored and several quantitative indices were calculated. The most substantial change was reductions in the peak velocity and the average movement velocity during the initial and mid phases of movement towards the target posture. These results may be explained in terms of increased akinesia and bradykinesia in the altered stimulation conditions. Thus, the dynamic posture shift paradigm can reveal changes in posture control capabilities, as evidenced by changes in movement velocity, due to alterations in DBS stimulation settings.

We sought to define quantitative electroencephalographic (EEG) measures as biomarkers of both early and late cognitive decline in Parkinson's disease (PD). PD subjects classified as cognitively normal (PD-CogNL), mild cognitive impairment (PD-MCI), and dementia (PD-D) were studied. Cognitive status and neuropsychological testing was correlated with background rhythm and frequency band EEG power across five frequency bands. We conclude that global EEG measures have potential use as biomarkers in the study of both early and late cognitive deterioration in PD, including for evaluating its treatment. PD-MCI has mean quantitative EEG characteristics that represent an intermediate electrophysiological state between PD-CogNL and PD-D.

Objectives: To systematically investigate the ability of Parkinson’s disease patients to discretely and dynamically scale the size of continuous movements and to assess the impact of movement size on outcome variability. Methods: Ten patients with Parkinson’s disease (mean age 72 years) were compared with 12 healthy elderly controls (mean age 70 years). The subjects wrote with a stylus on a graphics tablet. In experiment 1 they drew circles, matching the size of five target circles ranging in magnitude from a radius of 0.5 cm up to 2.5 cm. In experiment 2 they drew spirals with a radius of at least 2 cm. In both experiments the drawings were initially performed as accurately as possible then as fast and accurately as possible. Results: In both experiments the patients and controls drew at a similar speed. The within trial variability of the pen trajectory was greater for patients than controls, and increased disproportionately with the size of the movement. When the emphasis was on size rather than variability (circles), the patients’ drawing movements were the same size as controls. When the emphasis was on accuracy of pen trajectory (that is, minimum variability) rather than size (spirals), the patients’ drawing movements were smaller than controls. Conclusions: The movements made by Parkinson’s disease patients are hypometric partly as an adaptive strategy used to reduce movement variability. This strategy is used primarily when the requirement to make accurate movements outweighs the need to make large movements.

We tested the hypothesis that early vascularization of the embryonic heart is enhanced after bolus injections of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) into the vitelline vein before the onset of myocardial vasculogenesis (3.5 days, stage 21). Electron and light microscopy were utilized to obtain morphometric data. At stages 29 and 31, myocardial vessel volume or numerical density were higher in embryos injected with 50 ng bFGF than in the saline-injected controls. A VEGF injection increased vascular volume density at stage 29 and both volume and numerical density at stage 31. bFGF, but not VEGF, was associated with an enhancement of the sinusoidal system (spongy layer of the ventricle) at stage 29. This effect disappeared by stage 31. In conclusion, 1) enhancement of bFGF or VEGF before myocardial vascularization increases vascular growth, but the initial effect of bFGF is greater; 2) the effects of these growth factors on vascular volume and numerical density are temporally dependent; and 3) bFGF, in addition to its effects on the coronary vasculature, influences ventricular modeling by apparently acting on myocytes as well as endothelial cells.