Search

Background: This study investigated impaired self-awareness of motor deficits in nondemented, nondepressed Parkinson's disease (PD) patients during a defined clinical on state. Methods: Twenty-eight PD patients were examined. Patients' self-ratings and experts' ratings of patients' motor performance were compared. Patient–examiner discrepancies and level of impairment determined severity of impaired self-awareness. Motor exam assessed overall motor functioning, hemibody impairment, and 4 motor phenotypes. Neuropsychological tests were also conducted. Results: Signs of impaired self-awareness were present in 17 patients (60.7%). Higher severity of impaired self-awareness correlated significantly with higher postural-instability and gait-difficulty off scores (r = .575; P = .001), overall motor off scores (r = .569; P = .002), and higher left hemibody off scores (r = .490; P = .008). In multiple linear regression analyses, higher postural-instability and gait-difficulty off scores remained as the only significant predictor of impaired self-awareness severity. Conclusions: Postural instability and gait difficulties, disease severity, and right hemisphere dysfunction seem to contribute to impaired self-awareness. © 2012 Movement Disorder Society

Relatively little is known about patient satisfaction with Parkinson's disease (PD) care and the use of support groups in the United States. We surveyed members of the Muhammad Ali Parkinson's Disease Registry to assess satisfaction with medical care and to evaluate support group use. Satisfaction was measured on a 5-point Likert scale, with high satisfaction defined as a four or five. We used multiple logistic regression to identify factors associated with high satisfaction and support group use. The response rate was 38% (726 of 1923). Most (57%) expressed high satisfaction with PD care. Individuals were most satisfied with the time their provider spent with them (61%) and PD education (56%) but least satisfied with prognostic information (35%) and information about non-drug interventions (28%). Patients seeing a PD specialist were three times more satisfied with their care than those seeing a general neurologist (OR = 3.00, 95% CI: 1.92-4.71; P < 0.0001). Support group use is common, and 61% of survey respondents had attended one at any point. Caucasian race (OR = 2.85, 95% CI: 1.45-5.61), PD duration (OR = 1.05 per year, CI: 1.01-1.10), and PD specialist care (OR = 1.80, CI: 1.16-2.77) were associated with greater support group attendance. Overall, 49% reported high satisfaction with their support group. The greatest concerns were specific needs not being addressed (15%) and insufficient expertise within the group (14%). Most individuals with Parkinson's disease expressed high levels of satisfaction, especially with specialist care. Specialty care and improved education, in the clinic or through support groups, may enhance satisfaction and health care quality.

Hydrogen/deuterium exchange (HDX) using matrix-assisted laser desorption ionization time-of-flight (MALDI-ToF) mass spectrometry is a sensitive, salt-tolerant and high-throughput method useful to probe protein conformation and molecular interactions. However, a drawback of the MALDI HDX technique is that sample preparation methods can typically result in higher levels of artificial deuterium in-exchange and/or hydrogen back-exchange just prior to or during mass analysis; this may impair data reproducibility and impede structural and kinetic data interpretation. While methods to minimize effects of back-exchange during protein analyte deposition on MALDI plates have been reported, this study presents a readily available, highly sensitive protein control set to facilitate rapid MALDI HDX protocol workup. The Ca2+-induced solvent accessible surface area (ASA) changes of calmodulin (CaM) and S100 proteins were employed to monitor and optimize HDX protocol efficiency. Under non-stringent room temperature conditions, the Ca2+-induced deuterium exchange of CaM, ΔDca2+, MH+ shifts −17 Da to −24 Da, while S100 ΔDca2+ MH+ shifts +8 Da to +12 Da. By comparing the divergent CaM and S100 Ca2+-induced deuterium mass shift differences, HDX sample workup and MALDI plate spotting conditions can easily be monitored.

Objective: To determine if future studies of coenzyme Q10 and GPI-1485 in Parkinson disease (PD) may be warranted. Methods: We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold. Results: The primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed. Conclusions: Coenzyme Q10 and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies. NEUROLOGY 2007;68:20-28

Lebiedowska MK, Gaebler-Spira D, Burns RS, Fisk JR. Biomechanic characteristics of patients with spastic and dystonic hypertonia in cerebral palsy. Arch Phys Med Rehabil 2004;85:875–80. Objective To determine what biomechanic characteristics of knee joint motion and walking show potential to quantitatively differentiate spasticity and dystonia in cerebral palsy (CP). Design Descriptive measurement study. Setting University hospital. Participants Seventeen pediatric and adult patients with CP. Interventions Not applicable. Main outcome measures We measured the resistance of the knee joint at different velocities and positions, maximum muscle activation during external motion, amplitude of knee tendon reflexes, maximum isometric flexion and extension torques, velocity of walking, and knee kinematics during the gait cycle. Patients were classified into 2 groups (dystonia or spasticity) if at least 2 of 3 physicians agreed that a prominent component of dystonia was present. Results Patients with dystonia had a greater degree of cocontraction and an increased resistance to external motion at slow velocities. The tendon reflexes were almost normal in patients with dystonia, whereas they were increased in patients with spasticity. Muscle strength was more impaired in patients with dystonia, probably as a result of greater muscle cocontraction. They also walked slower, with smaller knee ranges of motion, during the stance phase of walking. Conclusions The measurement of resistance and of muscle activation during passive motion and tendon reflexes shows potential to differentiate dystonia from spasticity in CP patients with a mixed form of hypertonia. More studies are needed to confirm these results.

Within the aerospace community, health management has mostly been focused on estimating the condition of a vehicle or subsystem for predicting its remaining useful life. Research on using health information to infer effects on the vehicle’s operational capabilities has been gaining momentum over the last decade. These approaches typically perform health assessments on the internal condition of the vehicle; while largely ignoring the external factors and threats that could adversely impact the vehicle’s operational performance. A major technical challenge for increasing autonomy in aerospace systems is improving their state awareness to enable real-time decision making and adaptation. Current aerospace systems lack comprehensive state awareness information making them unable to react to changes in the vehicle states and operational environments. The Air Force Research Laboratory (AFRL) has been investing in Integrated Systems Health Management (ISHM) technologies over the past 15 years to address this issue. AFRL defines ISHM as the integration of internal and external state information for the generation of state awareness and its use for ground management and real-time control of the vehicle. The purpose of this paper is to present AFRL’s ISHM vision, define related terminology, and discuss programmatic research.

To determine what biomechanic characteristics of knee joint motion and walking show potential to quantitatively differentiate spasticity and dystonia in cerebral palsy (CP).Descriptive measurement study.University hospital.Seventeen pediatric and adult patients with CP.Not applicable.We measured the resistance of the knee joint at different velocities and positions, maximum muscle activation during external motion, amplitude of knee tendon reflexes, maximum isometric flexion and extension torques, velocity of walking, and knee kinematics during the gait cycle. Patients were classified into 2 groups (dystonia or spasticity) if at least 2 of 3 physicians agreed that a prominent component of dystonia was present.Patients with dystonia had a greater degree of co-contraction and an increased resistance to external motion at slow velocities. The tendon reflexes were almost normal in patients with dystonia, whereas they were increased in patients with spasticity. Muscle strength was more impaired in patients with dystonia, probably as a result of greater muscle co-contraction. They also walked slower, with smaller knee ranges of motion, during the stance phase of walking.The measurement of resistance and of muscle activation during passive motion and tendon reflexes shows potential to differentiate dystonia from spasticity in CP patients with a mixed form of hypertonia. More studies are needed to confirm these results.

The number of pigmented and non-pigmented neurons in the substantia nigra (SN) of 10 old and six young female Macaca mulatta monkeys and in three old alpha male monkeys were estimated using new stereological cell counting methods. No systematic right-left differences were noted, nor were old animals different from young ones with respect to SN volume (68.9 mm3 vs. 62.8 mm3) or absolute number of nerve cells (320,000 vs. 312,000). However, the total number of pigmented neurons was about eight times higher in old animals compared with young ones (166,000 vs. 21,400) while the total number of non-pigmented SN neurons was less than half in old animals compared with young ones (139,000 vs. 285,000). These differences create difficulties in generalizing experimental results from the rhesus animal model to man. It seems unlikely that a simple correlation can be made between pigmented and tyrosine hydroxylase (TH) positive neurons in SN in monkeys. Instead of estimating the total number of pigmented and non-pigmented cells, only SN neurons positive for TH using immunohistochemical techniques might be used an indicator of the total number of dopaminergic neurons in SN in monkeys.

Explants of canine substantia nigra (SN) and rat mesencephalon (MES), grown in organotypic culture, were incubated with 1-methyl-4-phenylpyridinium (MPP+) and examined for ultrastructural changes. Prolonged exposure (3 days) to doses ranging from 0.1 nM to 10 μM MPP+ resulted in total destruction of all constituents (neuronal and glial) of canine SN cultures. No association was noted between MPP+-induced toxicity and age of canine SN cultures. The first ultrastructural change observed in canine SN cultures incubated with 0.1 nM MPP+ was at 3 h. Grossly swollen mitochondria were noted in large nerve cells. Swollen mitochondria were present in all cells of canine SN cultures by 8 h of incubation with MPP+. Only those rat MES cultures with relatively high preincubation levels of homovanillac acid, determined as an index of viable dopaminergic neurons, incubated with MPP+ (10 μM) for up to 8 days exhibited ultrastructural changes, namely, a swelling of mitochondria within the cytoplasm of large nerve cells. These findings suggest that continual exposure to MPP+in vitro results in a generalized, nonspecific toxicity in those species known to be susceptible to the parent compound 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine in vivo. However, the initial ultrastructural change, i.e., a swelling of mitochondria, may be the same in all species regardless of sensitivity suggesting that the ultimate mechanism underlying MPP+-toxicity relates to mitochondrial function.

Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and (/sup 14/C)methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption.