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Parkinson's disease is a debilitating neurodegenerative disease for which there is no cure. It is characterized by bradykinesia, resting tremor, rigidity and postural instability, due to impairment of function of the basal ganglia which is involved in the coordination of body movement. Neuro-inflammation is pathogenesis of development in early Parkinson's disease. High-sensitivity C-reactive protein level is a useful non-specific biochemical marker of inflammation. Objective of this study was to analyze the symptoms of Parkinson disease and it's correlation with high sensitive CRP. Seventy-six Parkinson's disease patients were enrolled in this Cross-sectional observational study that was attended in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from September 2014 to March 2016. Analysis of the symptoms of Parkinson disease and it's correlation with high sensitive CRP were done among these patients. This study was performed on 76 Parkinson disease patients with presented early with symptoms. a positive and highly significant correlation were seen in between duration of tremor and High sensitivity CRP (r=0.430, p<0.001) and between duration of bradykinesia and High sensitivity CRP (r=0.426, p<0.001) which indicate increase duration causes increase level of high-sensitivity C-reactive protein value. The neuro-inflammation plays a significant role in the pathogenesis of symptoms development in early Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders worldwide. Current identification and monitoring of its motor symptoms depends on the clinical expertise. Repetitive finger tapping is one of the most common clinical maneuvers to assess for bradykinesia. Despite the increasing use of technology aids to quantitatively characterize the motor symptoms of PD, there is still a relative lack of clinical evidence to support their widespread use, particularly in low-resource settings. In this pilot study, we used a low-cost design prototype coupled with an inertial sensor is coupled to quantify the frequency of the finger tapping movements in four participants with PD. Repetitive finger tapping was performed using both hands before and after taking levodopa as part of their clinical treatment. The proposed 3D design allowed repetitive movements to be performed without issues. The maximum frequency of finger tapping was in the range of 0.1 to 4.3 Hz. Levodopa was associated with variable changes in the maximum frequency of finger tapping. This pilot study shows the feasibility for low-cost technology to quantitatively characterize repetitive movements in people living with PD.Clinical relevance- In this pilot study, a low-cost inertial sensor coupled to a design prototype was feasible to characterize the frequency of repetitive finger tapping movements in four participants with PD. This method could be used to quantitatively identify and monitor bradykinesia in people living with PD.

Objective: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long-term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13-30 Hz) dynamics or a wider bilateral network dysfunction., Methods: Twenty-one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist-flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN-STN beta coherence., Results: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN-STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia., Interpretation: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029-1039., (© 2023 American Neurological Association.)

Reduced expression of a platelet protein protects against thrombosis during chronic immobilization.

Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.

Background: Bradykinesia is a cardinal feature in parkinsonisms. No study has assessed the differential features of bradykinesia in patients with pathology-proven synucleinopathies and tauopathies., Objective: We examined whether bradykinesia features (speed, amplitude, rhythm, and sequence effect) may differ between pathology-proven synucleinopathies and tauopathies., Methods: Forty-two cases who underwent autopsy were included and divided into synucleinopathies (Parkinson's disease and dementia with Lewy bodies) and tauopathies (progressive supranuclear palsy). Two raters blinded to the diagnosis retrospectively scored the Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III and Modified Bradykinesia Rating Scale on standardized videotaped neurological examinations. Bradykinesia scores were compared using the Mann-Whitney test and logistic regression models to adjust for disease duration., Results: Demographic and clinical parameters were similar between synucleinopathies and tauopathies. There were no differences between speed, amplitude, rhythm, and sequence effect in synucleinopathies and tauopathies in unadjusted comparisons and adjusted models (all P > 0.05)., Conclusions: Clinical bradykinesia features do not distinguish the underlying neuropathology in neurodegenerative parkinsonisms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Patients who require antipsychotic drug treatment are at increased risk of fractures, including osteoporosis-related fragility fractures, for reasons related to demographics, illness-related factors, and treatment-related factors. As examples, patients with dementia may be vulnerable to falls due to cognitive and psychomotor impairment, patients with schizophrenia may be vulnerable to injury related to physical restlessness or physical aggression, and patients receiving antipsychotics may suffer falls related to sedation, psychomotor impairment, bradykinesia, or postural hypotension. Antipsychotics may also increase the risk of fracture through long-term hyperprolactinemia and resultant osteoporosis. A meta-analysis of 36 observational studies conducted in mostly elderly samples found that antipsychotic exposure was associated with an increased risk of hip fracture as well as increased risk of any fracture; the findings were consistent in almost all subgroup analyses. An observational study that controlled for confounding by indication and illness severity found that fragility fractures in patients with schizophrenia were associated with higher daily doses, higher cumulative doses, longer duration of treatment, and prolactin-raising rather than prolactin-sparing antipsychotics; in patients receiving prolactin-raising antipsychotics, the concurrent use of aripiprazole appeared protective. The absolute risks of fracture are unknown and could vary depending on patient age, patient sex, indication for antipsychotic use, nature of the antipsychotic (and associated risk of sedation, psychomotor impairment, bradykinesia, and postural hypotension), daily dose prescribed, duration of antipsychotic exposure, baseline risk of fracture, and other risk factors. Patients should therefore be individually evaluated for risk factors for falls and fractures related to sociodemographic, clinical, and treatment-related risk factors. Patients identified to be at risk should be advised about risk-mitigating strategies. If prolactin-raising antipsychotics are required in the long term, prolactin levels should be monitored and prolactin-lowering strategies should be considered. Osteoporosis should be investigated and managed, if identified, to prevent fragility fractures., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

No biomarker of Parkinson's disease exists that allows clinicians to adjust chronic therapy, either medication or deep brain stimulation, with real-time feedback. Consequently, clinicians rely on time-intensive, empirical, and subjective clinical assessments of motor behaviour and adverse events to adjust therapies. Accumulating evidence suggests that hypokinetic aspects of Parkinson's disease and their improvement with therapy are related to pathological neural activity in the beta band (beta oscillopathy) in the subthalamic nucleus. Additionally, effectiveness of deep brain stimulation may depend on modulation of the dorsolateral sensorimotor region of the subthalamic nucleus, which is the primary site of this beta oscillopathy. Despite the feasibility of utilizing this information to provide integrated, biomarker-driven precise deep brain stimulation, these measures have not been brought together in awake freely moving individuals. We sought to directly test whether stimulation-related improvements in bradykinesia were contingent on reduction of beta power and burst durations, and/or the volume of the sensorimotor subthalamic nucleus that was modulated. We recorded synchronized local field potentials and kinematic data in 16 subthalamic nuclei of individuals with Parkinson's disease chronically implanted with neurostimulators during a repetitive wrist-flexion extension task, while administering randomized different intensities of high frequency stimulation. Increased intensities of deep brain stimulation improved movement velocity and were associated with an intensity-dependent reduction in beta power and mean burst duration, measured during movement. The degree of reduction in this beta oscillopathy was associated with the improvement in movement velocity. Moreover, the reduction in beta power and beta burst durations was dependent on the theoretical degree of tissue modulated in the sensorimotor region of the subthalamic nucleus. Finally, the degree of attenuation of both beta power and beta burst durations, together with the degree of overlap of stimulation with the sensorimotor subthalamic nucleus significantly explained the stimulation-related improvement in movement velocity. The above results provide direct evidence that subthalamic nucleus deep brain stimulation-related improvements in bradykinesia are related to the reduction in beta oscillopathy within the sensorimotor region. With the advent of sensing neurostimulators, this beta oscillopathy combined with lead location could be used as a marker for real-time feedback to adjust clinical settings or to drive closed-loop deep brain stimulation in freely moving individuals with Parkinson's disease., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Alzheimer's disease is primarily characterized by cognitive decline; recent studies, however, emphasize the occurrence of motor impairment in this condition. Here, we investigate whether motor impairment, objectively evaluated with kinematic techniques, correlates with neurophysiological measures of the primary motor cortex in Alzheimer's disease., Methods: Twenty patients and 20 healthy subjects were enrolled. Repetitive finger tapping was assessed by means of a motion analysis system. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and short-latency afferent inhibition. Plasticity-like mechanisms were indexed according to changes in motor-evoked potential amplitude induced by the intermittent theta-burst stimulation., Results: Patients displayed slowness and altered rhythm during finger tapping. Movement slowness correlated with reduced short-latency afferent inhibition in patients, thus suggesting that degeneration of the cholinergic system may also be involved in motor impairment in Alzheimer's disease. Moreover, altered movement rhythm in patients correlated with worse scores in the Frontal Assessment Battery., Conclusion: This study provides new information on the pathophysiology of altered voluntary movements in Alzheimer's disease., Significance: The study results suggest that a cortical cholinergic deficit may underlie movement slowness in Alzheimer's disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the pathophysiological mechanisms underlying bradykinesia are, however, still unclear. In this article, we review clinical and experimental studies on bradykinesia performed in patients with Parkinson's disease and atypical parkinsonism. We also review studies on animal experiments dealing with pathophysiological aspects of the parkinsonian state. In Parkinson's disease, bradykinesia is characterized by slowness, the reduced amplitude of movement, and sequence effect. These features are also present in atypical parkinsonisms, but the sequence effect is not common. Levodopa therapy improves bradykinesia, but treatment variably affects the bradykinesia features and does not significantly modify the sequence effect. Findings from animal and patients demonstrate the role of the basal ganglia and other interconnected structures, such as the primary motor cortex and cerebellum, as well as the contribution of abnormal sensorimotor processing. Bradykinesia should be interpreted as arising from network dysfunction. A better understanding of bradykinesia pathophysiology will serve as the new starting point for clinical and experimental purposes., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We studied the effect of hypokinesia combined with cold exposure on morphological parameters of the heart in Wistar-Kyoto rats and rats with spontaneous genetically determined hypertension (SHR). The pathological processes developing in the heart of white laboratory rats significantly affected cardiac function and manifested in the deterioration of the morphological structure of the heart: reduction of heart weight, thinning of the free wall of the left ventricle. These changes indicate transition to a lower energy level of functioning. At the same time, hypertrophy of the right free wall develops in both rat lines. Combined effect of hypokinesia and cold is probably a factor indirectly promoting the development of pulmonary heart.

Objective: Quantification of bradykinesia (slowness of movement) is crucial for the treatment and monitoring of Parkinson's disease. Subjective observational techniques are the de-facto 'gold standard', but such clinical rating scales suffer from poor sensitivity and inter-rater variability. Although various technologies have been developed for assessing bradykinesia in recent years, most still require considerable expertise and effort to operate. Here we present a novel method to utilize an inexpensive off-the-shelf hand-tracker (Leap Motion) to quantify bradykinesia., Approach: Eight participants with Parkinson's disease receiving benefit from deep brain stimulation were recruited for the study. Participants were assessed 'on' and 'off' stimulation, with the 'on' condition repeated to evaluate reliability. Participants performed wrist pronation/supination, hand open/close, and finger-tapping tasks during each condition. Tasks were simultaneously captured by our software and rated by three clinicians. A linear regression model was developed to predict clinical scores and its performance was assessed with leave-one-subject-out cross validation., Main Results: Aggregate bradykinesia scores predicted by our method were in strong agreement (R  =  0.86) with clinical scores. The model was able to differentiate therapeutic states and comparison between the test-retest conditions yielded no significant difference (p   =  0.50)., Significance: These findings demonstrate that our method can objectively quantify bradykinesia in agreement with clinical observation and provide reliable measurements over time. The hardware is readily accessible, requiring only a modest computer and our software to perform assessments, thus making it suitable for both clinic- and home-based symptom tracking.

A professional violinist reported increasing difficulties playing the violin. He executed the initial half of the musical piece well, but produced an increasing number of mistakes during the second half. Neurological examination was remarkable for bradykinesia and tremor. Formal acoustic analysis of finger taps and pronation-supination showed a decrement in sound intensity and number of taps over time. Oscillations in performance correlated with a parkinsonian tremor. We interpret these findings as the audible equivalent of bradykinesia and tremor. Listening to bradykinesia and quantifying its decrement using acoustic analysis may offer a simple, objective, and reliable supplement to the neurological examination. Ann Neurol 2018;84:931-933., (© 2018 American Neurological Association.)

Background: Clinical and anecdotal observations propose that patients with Parkinson's disease (PD) may show drug-induced dyskinesia (DID) concomitantly with cardinal motor features. However, the extent of the concomitant presence of DID and cardinal features remains to be determined., Objectives: This cross-sectional study measured peak-dose choreic-type DID in a quantitative manner in patients diagnosed with PD, and determined whether symptoms such as tremor, bradykinesia, rigidity, postural instability or freezing of gait (FoG) were still detectable in these patients., Methods: 89 patients diagnosed with PD were recruited and assessed using a combination of quantitative measures using inertial measurement units to capture DID, tremor, bradykinesia, and FoG. Clinical evaluations were also used to assess rigidity and postural instability. Motor symptoms of PD were assessed 3 times during the testing period, and a series of activities of daily living were repeated twice, in between clinical tests, during which the level of DID was quantified. Peak-dose was identified as the period during which patients had the highest levels of DID. Levels of tremor, rigidity, bradykinesia, postural instability, and FoG were used to determine the percentage of patients showing these motor symptoms simultaneously with DID., Results: 72.4% of patients tested presented with measurable DID during the experiment. Rest, postural and kinetic tremor (12.7% , 38.1% , and 15.9% respectively), bradykinesia (28.6% ), rigidity (55.6% ), postural instability (71.4% ) and FoG (9.5% ) were detected simultaneously with DID., Conclusions: PD symptomatology remains present in patients showing peak-dose choreic-type DID, illustrating the challenge facing physicians when trying to avoid dyskinesia while attempting to alleviate motor symptoms.

Hospitalized patients are at risk of venous thromboembolism (VTE) and prophylaxis is often suboptimal due to difficulty in identifying at-risk patients. Simple and validated risk-assessment models (RAMs) are available to assist clinicians in identifying patients who have a high risk for developing VTE. Despite the well-documented association of immobility with increased risk of thrombosis, immobility is not consistently defined in clinical studies. We conducted a systematic review of published VTE RAMs and used objective criteria to determine how the term immobility is defined in RAMs. We identified 17 RAMs with six being externally validated. The concept of immobility is vaguely described in different RAMs, impacting the validity of these models in clinical practice. The wide variability in defining mobility in RAMs precluded its accurate clinical application, further limiting generalization of published RAMs. Externally validated RAMs with clearly defined qualitative or quantitative terms of immobility are needed to assess VTE risk in real-time at the point-of-care.

Parkinsonian signs are common in patients with Alzheimer's disease (AD) of mild degree and predict functional decline, but their relationship with gait speed and balance is unclear. The aims of this study were to describe characteristics of patients with parkinsonian signs among 98 patients with AD of mild degree (with no comorbid Parkinson's disease), and to examine associations between parkinsonian signs with gait speed and balance. A cross sectional study at a memory clinic was conducted. Presence of each parkinsonian sign (bradykinesia, rigidity and tremor) was derived from the UPDRS, regular gait speed was recorded over 10m and balance were assessed using the Mini-Balance Evaluation Systems Test (Mini-BESTest). Bradykinesia was present in 30.6% of the sample, rigidity in 13.3% and tremor only in one patient. Patients with bradykinesia were older, had worse cognitive impairment and worse gait and balance performance than those without bradykinesia. More men than women had rigidity. Bradykinesia was significantly associated with mini-BESTest after adjusting for demographic factors (p<0.001, explaining 13.3% of the variance), but was not significantly associated with gait speed. Rigidity was not associated with either gait speed or balance. We conclude that assessment of bradykinesia should be included in examination of balance control in patients with AD of mild degree., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Gait freezing as a presenting and relatively restricted condition is uncommon but a distinctive disorder. This entity was initially defined as "pure akinesia with gait freezing", and later a neuropathological substrate of progressive supranuclear palsy has been recognized. Limited studies have reported the clinical evolution after presentation, which is important for patient counseling. The objective of this study was to assess the demographic and clinical features, treatment-response, neuroimaging, and evolution of pure akinesia with gait freezing. A retrospective review of patients with this phenotype as previously defined was performed. Patients included had no or minimal limb rigidity and/or bradykinesia and no resting tremor, and all underwent neuroimaging of the brain after onset. Inclusion criteria were met by 30 patients, who were followed up to 21 years after symptom onset. During their course, 28 patients had falls (93 %), 12 patients had dysarthria (40 %), and 13 had handwriting changes (43 %). All patients had progression of their gait disorder over time, but with a variable interval until falls occurred. None of the patients developed vertical gaze palsy or met diagnostic criteria for an alternative parkinsonian disorder. Pure akinesia with gait freezing is a distinctive disorder that can be recognized in the clinic. Despite the previously reported progressive supranuclear palsy-like neuropathology, the clinical course is much less aggressive and disabling than classic Richardson syndrome, although fall risk eventually develops in nearly all patients. Bradykinesia, tremor, and rigidity do not develop, distinguishing pure akinesia with gait freezing from Parkinson's disease and other parkinsonian disorders.

Introduction: Anosognosia or impaired self-awareness of motor symptoms (ISAm) has been rarely investigated in Parkinson's disease (PD). We here studied the relationship between ISAm during periods with and without dopaminergic medication (ON- and OFF-state), and clinical, neuropsychological, and neuroimaging data to further elucidate behavioural aspects and the neurobiological underpinnings of ISAm., Methods: Thirty-one right-handed, non-demented, non-depressed PD patients were included. ISAm was evaluated using a recently developed scale that assesses awareness of dyskinesia, resting tremor, and bradykinesia. The test was applied during both ON- and OFF-states. Multiple correlation analyses between ISAm and behavioural data were conducted. In addition, imaging of glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was performed to investigate the neural basis of ISAm. A multiple regression approach was applied to investigate metabolism alterations related to ISAm., Results: In the OFF-state, higher ISAm was associated with left-sided disease onset, older age, and shorter disease duration. Concerning FDG-PET data, there was a significant negative correlation between higher OFF-state ISAm and decreased glucose metabolism in the right inferior frontal gyrus (IFG). In the ON-state, ISAm was not significantly correlated with clinical or behavioural data. However, there was a significant correlation between higher ISAm and an increased metabolism in the bilateral medial frontal gyrus, left IFG, right superior frontal gyrus and right precentral gyrus., Conclusion: The results support the role of the right hemisphere in awareness of motor symptoms in the OFF-state. In the ON-state, dopaminergic medication and dyskinesia influence ISAm and relate to metabolism changes in bilateral frontal regions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Several risk assessment models include infection and immobility among the items to be considered for venous thromboembolism (VTE) prevention. However, information on patients with infection leading to immobility and developing VTE are limited, as well as on the role of specific types of infection. Data were collected from the worldwide RIETE registry, including patients with symptomatic objectively confirmed VTE, and followed-up for at least 3 months. The overall population of RIETE at June 2013 (n = 47,390) was considered. Acute infection leading to immobility was reported in 3.9 % of non-surgical patients. Compared with patients immobilized due to dementia, patients with infection had a shorter duration of immobilization prior to VTE (less than 4 weeks in 94.2 vs. 25.9 % of cases; p < 0.001). During the 3-month follow-up, VTE patients with infection versus those with dementia had a lower rate of fatal bleeding (0.5 vs. 1.1 %; p < 0.05) or fatal PE (1.7 vs. 3.5 %; p < 0.01). Patients with respiratory tract infections had more likely PE as initial VTE presentation than other types of infection (62.3 vs. 37.7 %; p < 0.001). Significantly more patients with pneumonia than those with other respiratory infections had received VTE prophylaxis (50.2 vs. 30.6 %; p < 0.001). Following VTE, patients with sepsis showed a significantly higher risk of fatal bleeding. Based on our real-world data, infection seems to contribute to the pathogenesis of VTE by accelerating the effects of immobility. Its role as VTE risk factor probably deserves further attention and specific assessment in order to optimize VTE prophylaxis and treatment.

Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover., (© 2015 American Society for Bone and Mineral Research.)

An age-associated loss of muscle mass and strength--sarcopenia--begins at around the fifth decade of life, with mass being lost at ~0.5-1.2% per year and strength at ~3% per year. Sarcopenia can contribute to a variety of negative health outcomes, including an increased risk for falls and fractures, the development of metabolic diseases like type 2 diabetes mellitus, and increase the chance of requiring assisted living. Linear sarcopenic declines in muscle mass and strength are, however, punctuated by transient periods of muscle disuse that can accelerate losses of muscle and strength, which could result in increased risk for the aforementioned conditions. Muscle disuse is recognizable with bed rest or immobilization (for example, due to surgery or acute illness requiring hospitalization); however, recent work has shown that even a relative reduction in ambulation (reduced daily steps) results in significant reductions in muscle mass, strength and possibly an increase in disease risk. Although reduced ambulation is a seemingly "benign" form of disuse, compared to bed rest and immobilization, reports have documented that 2-3 weeks of reduced daily steps may induce: negative changes in body composition, reductions in muscle strength and quality, anabolic resistance, and decrements in glycemic control in older adults. Importantly, periods of reduced ambulation likely occur fairly frequently and appear more difficult to fully recover from, in older adults. Here we explore the consequences of muscle disuse due to reduced ambulatory activity in older adults, with frequent comparisons to established models of disuse: bed rest and immobilization.

A challenge for the clinical management of advanced Parkinson's disease (PD) patients is the emergence of fluctuations in motor performance, which represents a significant source of disability during activities of daily living of the patients. There is a lack of objective measurement of treatment effects for in-clinic and at-home use that can provide an overview of the treatment response. The objective of this paper was to develop a method for objective quantification of advanced PD motor symptoms related to off episodes and peak dose dyskinesia, using spiral data gathered by a touch screen telemetry device. More specifically, the aim was to objectively characterize motor symptoms (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Digitized upper limb movement data of 65 advanced PD patients and 10 healthy (HE) subjects were recorded as they performed spiral drawing tasks on a touch screen device in their home environment settings. Several spatiotemporal features were extracted from the time series and used as inputs to machine learning methods. The methods were validated against ratings on animated spirals scored by four movement disorder specialists who visually assessed a set of kinematic features and the motor symptom. The ability of the method to discriminate between PD patients and HE subjects and the test-retest reliability of the computed scores were also evaluated. Computed scores correlated well with mean visual ratings of individual kinematic features. The best performing classifier (Multilayer Perceptron) classified the motor symptom (bradykinesia or dyskinesia) with an accuracy of 84% and area under the receiver operating characteristics curve of 0.86 in relation to visual classifications of the raters. In addition, the method provided high discriminating power when distinguishing between PD patients and HE subjects as well as had good test-retest reliability. This study demonstrated the potential of using digital spiral analysis for objective quantification of PD-specific and/or treatment-induced motor symptoms.

Fall injuries in people with Parkinson's disease (PD) are a major health problem. Increased sway while walking is a risk factor and further understanding of this destabilizing gait change may assist with rehabilitation and help prevent falls.Here, stride-to-stride head oscillations are used to help characterise different aspects of gait impairment in 10 people with PD on medication (67 years, SD 4), 10 healthy age-matched (HAM) participants (66 years, SD 7), and 10 young (30 years, SD 7). A wearable accelerometer was used to analyse head oscillations during five repeat 17 m walks by each participant.People with PD had significantly faster transverse plane head oscillations than the HAM or young groups; both along mediolateral (PD 47.2 cm s(-1), HAM 32.5 cm s(-1), and young 32.7 cm s(-1)) and anterioposterior axes (PD 33.3 cm s(-1), HAM 24.5 cm s(-1), and young 20.6 cm s(-1)). These differences were uncorrelated with reduced vertical oscillation velocity (PD 15.5 cm s(-1), HAM 18.8 cm s(-1), and young 20.1 cm s(-1)) and reduced walking speed (PD 1.2 m s(-1), HAM 1.4 m s(-1), and young 1.4 m s(-1)).Increased transverse plane head oscillations in people with PD may reflect motor impairment and the inability to respond sufficiently to perturbations while walking, which appears to be distinct from gait hyperkinesia, reduced vertical oscillations, step length, and walking speed.

Substantia nigra (SN) hyperechogenicity can be detected by transcranial sonography (TCS) to assist the early diagnosis of idiopathic Parkinson's disease (IPD). This study prospectively investigated whether SN hyperechogenicity is also present in Huntington's disease (HD) patients with symptoms of hypokinesia and/or rigidity. All patients recruited to the study (n = 15) were characterised by hypokinesia and/or rigidity while nine of these patients also displayed chorea and/or dystonia. The control group included 15 individuals. Clinical examination was documented using the Unified Huntington's Disease Rating Scale (UHDRS). TCS examination revealed SN hyperechogenicity in 14/15 (93.3 %) patients (9/14 unilateral, 5/14 bilateral). Hyperechogenicity of the caudate and lentiform nuclei (CN, LN) was less frequent (CN: 80 % total, LN: 53.3 % total). This is the first study to assess SN hyperechogenicity in hypokinetic HD patients. Assuming that the primary sites of pathology in IPD and HD are the SN and the striatum, respectively, our observations suggest a functional impairment of the nigrostriatal system in HD, an effect that is potentially independent of the primarily-affected basal ganglia nucleus.

Background/aims: Large epidemiological prospective studies represent an important opportunity for investigating risk factors for rare diseases such as Parkinson's disease (PD). Here we describe the procedures we used for ascertaining PD cases in the EPIC (European Prospective Investigation into Cancer and Nutrition) study., Methods: The following three-phase procedure was used: (1) elaboration of a NeuroEPIC4PD template for clinical data collection, (2) identification of all potential PD cases via record linkage and (3) validation of the diagnosis through clinical record revision, in a population of 220,494 subjects recruited in 7 European countries. All cases were labelled with the NeuroEPIC4PD diagnoses of 'definite', 'very likely', 'probable', or 'possible' PD., Results: A total of 881 PD cases were identified, with over 2,741,780 person-years of follow-up (199 definite, 275 very likely, 146 probable, and 261 possible). Of these, 734 were incident cases. The mean age at diagnosis was 67.9 years (SD 9.2) and 458 patients (52.0%) were men. Bradykinesia was the most frequent presenting motor sign (76.5%). Tremor-dominant and akinetic rigid forms of PD were the most common types of PD. A total of 289 patients (32.8%) were dead at the time of the last follow-up., Conclusions: This exercise proved that it is feasible to ascertain PD in large population-based cohort studies and offers a potential framework to be replicated in similar studies., (© 2015 S. Karger AG, Basel.)

The aim of this study was to develop regression models for the quantification of parkinsonian bradykinesia. Forty patients with Parkinson's disease participated in this study. Angular velocity was measured using gyro sensor during finger tapping, forearm-rotation, and toe tapping tasks and the severity of bradykinesia was rated by two independent neurologists. Various characteristic variables were derived from the sensor signal. Stepwise multiple linear regression analysis was performed to develop models predicting the bradykinesia score with the characteristic variables as input. To evaluate the ability of the regression models to discriminate different bradykinesia scores, ANOVA and post hoc test were performed. Major determinants of the bradykinesia score differed among clinical tasks and between raters. The regression models were better than any single characteristic variable in terms of the ability to differentiate bradykinesia scores. Specifically, the regression models could differentiate all pairs of the bradykinesia scores (p<0.05) except for one pair in the finger tapping task and one pair in the toe tapping task. In contrast, any single characteristic variable was found not sensitive enough to discriminate many of the pairs, especially in case of the toe tapping task. The results suggest that the multiple regression models reflecting these differences would be beneficial for the quantification of bradykinesia because the cardinal features included in the determination of bradykinesia score differ among tasks as well as among the raters.

Background: Fatigue is a common nonmotor symptom of Parkinson's disease (PD). Although the causes of fatigue were estimated in the previous reports, fatigue is not fully understood. To determine the frequency of and factors related to fatigue in patients with PD, we carried out clinical assessments in our university hospital., Methods: We used the Japanese version of the Parkinson Fatigue Scale (J-PFS). The J-PFS was administered to 110 patients with PD, and a cutoff point of 3.3 was used for the diagnosis of fatigue. Subsequently, demographic characteristics, clinical features, and medications utilized were evaluated to elucidate the factors related to fatigue. In particular, we focused on the relationship between fatigue and gait disorder assessed via the portable gait rhythmogram., Results: The frequency of fatigue in patients with PD was 52.7%. Univariate analysis revealed that factors significantly associated with fatigue were many motor symptoms and nonmotor symptoms. In addition, multivariate analysis revealed that gait disorder and constipation were independent factors related to fatigue. Furthermore, short-step walking and bradykinesia in gait disorder had especially a relationship with fatigue., Conclusions: More than half of our patients were judged having fatigue. Several factors, including motor and nonmotor symptoms, might be related to fatigue in patients with PD.

Objective: Impaired gait initiation (GI) in patients with advanced Parkinson's disease (PD) is a typical functional sign of akinesia. Failure to initiate the first step is frequently presented by patients with freezing of gait (FOG) and is often considered a sub-type of freezing. The literature on the effects of cueing of GI preparation and execution remains controversial. Our objective was to establish whether auditory cueing improves the preparation and/or execution of GI in PD patients with a history of FOG., Methods: We recorded first-step preparation and execution in 30 PD patients with confirmed FOG under two randomised conditions: self-triggered (ST) gait and gait cued by a sound beep in off- and on-dopa conditions. Anticipatory postural adjustments (APAs) were evaluated by monitoring the trajectory of the centre of pressure., Results: We compared the patients with 30 patients without history of FOG and 30 healthy controls (HCs). l-Dopa only slightly improved the characteristics of APAs in freezers but was effective to improve gait hypokinesia. Auditory cueing was effective in improving step preparation in freezers, who showed adequate APAs more frequently. As seen with HCs and patients without FOG, patients released their APAs more quickly when auditory cueing was applied. However, cueing did not have a significant effect on step length. Clinically, auditory cueing also improved start hesitation in freezers., Conclusions: Auditory cueing improved step preparation but not step execution in PD patients., Significance: A failure to link step preparation and execution during GI may explain the poor first-step execution seen in PD freezers., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Bradykinesia is a cardinal symptom of Parkinson's disease (PD). Both aging and disease are shown to be associated with decreased adaptability to environmental stresses characterized by reduced complexity (or increased regularity) of biorhythms. The purpose of this study was to investigate the regularity of movement in individuals with PD, and the effect of dopaminergic medication. Nine subjects with PD and eight controls performed wrist flexion/extension movements at maximal velocity and range of motion. Subjects with PD were tested under two medication conditions. Approximate entropy (ApEn) was calculated to assess the regularity of the movement, with the smaller value associated with the greater regularity. Data revealed that subjects with PD had lower ApEn values than controls. Medication did not alter the ApEn values. These findings demonstrate that impaired voluntary movement in individuals with PD is associated with increased regularity of movement and this exaggerated regularity appears less sensitive to anti-PD medication.

Background: The Bradykinesia Akinesia Incoordination (BRAIN) test is a computer keyboard-tapping task that was developed for use in assessing the effect of symptomatic treatment on motor function in Parkinson's disease (PD). An online version has now been designed for use in a wider clinical context and the research setting., Methods: Validation of the online BRAIN test was undertaken in 58 patients with Parkinson's disease (PD) and 93 age-matched, non-neurological controls. Kinesia scores (KS30, number of key taps in 30 seconds), akinesia times (AT30, mean dwell time on each key in milliseconds), incoordination scores (IS30, variance of travelling time between key presses) and dysmetria scores (DS30, accuracy of key presses) were compared between groups. These parameters were correlated against total motor scores and sub-scores from the Unified Parkinson's Disease Rating Scale (UPDRS)., Results: Mean KS30, AT30 and IS30 were significantly different between PD patients and controls (p≤0.0001). Sensitivity for 85% specificity was 50% for KS30, 40% for AT30 and 29% for IS30. KS30, AT30 and IS30 correlated significantly with UPDRS total motor scores (r = -0.53, r = 0.27 and r = 0.28 respectively) and motor UPDRS sub-scores. The reliability of KS30, AT30 and DS30 was good on repeated testing., Conclusions: The BRAIN test is a reliable, convenient test of upper limb motor function that can be used routinely in the outpatient clinic, at home and in clinical trials. In addition, it can be used as an objective longitudinal measurement of emerging motor dysfunction for the prediction of PD in at-risk cohorts.

High-frequency stimulation of the subthalamic nucleus (STN-HFS) is widely used as therapeutic intervention in patients suffering from advanced Parkinson's disease. STN-HFS exerts a powerful modulatory effect on cortical motor control by orthodromic modulation of basal ganglia outflow and via antidromic activation of corticofugal fibers. However, STN-HFS-induced changes of the sensorimotor cortex are hitherto unexplored. To address this question at a genomic level, we performed mRNA expression analyses using Affymetrix microarray gene chips and real-time RT-PCR in sensorimotor cortex of parkinsonian and control rats following STN-HFS. Experimental parkinsonism was induced in Brown Norway rats by bilateral nigral injections of 6-hydroxydopamine and was assessed histologically, behaviorally, and electrophysiologically. We applied prolonged (23h) unilateral STN-HFS in awake and freely moving animals, with the non-stimulated hemisphere serving as an internal control for gene expression analyses. Gene enrichment analysis revealed strongest regulation in major histocompatibility complex (MHC) related genes. STN-HFS led to a cortical downregulation of several MHC class II (RT1-Da, Db1, Ba, and Cd74) and MHC class I (RT1CE) encoding genes. The same set of genes showed increased expression levels in a comparison addressing the effect of 6-hydroxydopamine lesioning. Hence, our data suggest the possible association of altered microglial activity and synaptic transmission by STN-HFS within the sensorimotor cortex of 6-hydroxydopamine treated rats.

Clinical assessment of orofacial muscle tone is of interest for differential diagnosis of the dysarthrias, but standardized procedures and normative data are lacking. In this study, perceptual ratings of tone were compared with instrumental measures of tissue stiffness for facial, lingual, and masticatory muscles in 70 individuals with dysarthria. Perceptual and instrumental tone data were discordant and failed to discriminate between five dysarthria types. These results raised concerns about the validity of Myoton-3 stiffness measures in the orofacial muscles. Therefore, a second study evaluated contracted and relaxed orofacial muscles in 10 neurotypical adults. Results for the cheek, masseter, and lateral tongue surface followed predictions, with significantly higher tissue stiffness during contraction. In contradiction, stiffness measures from the superior surface of the tongue were lower during contraction. Superior-to-inferior tongue thickness was notably increased during contraction. A third study revealed that tissue thickness up to ~10 mm significantly affected Myoton-3 measures. Altered tissue thickness due to neuromuscular conditions like spasticity and atrophy may have undermined the detection of group differences in the original sample of dysarthric speakers. These experiments underscore the challenges of assessing orofacial muscle tone and identify considerations for quantification of tone-related differences across dysarthria groups in future studies.

Purpose: Contractures are common problems for the elderly with far reaching functional and medical consequences. The aim of this systematic literature review was to give an overview of contracture and to identify potential risk factors associated with contractures., Methods: A systematic literature search with two objectives limited to the last 10 years was performed to identify studies dealing with definition of contracture (objective 1 = O1) and with risk factors (objective 2 = O2). Predefined information including age, sample size, study design, setting, condition, joint, definition of contracture, mode of measurement, and whether inter- and/or intra-rater reliability were assessed, as well as risk factors of contracture were extracted., Results: One hundred and sixty one and 25 studies were retrieved. After applying exclusion criteria 47 studies (O1) and 3 studies (O2) remained. Only 9 studies (O1) provided a definition of contracture. In 3 studies (O2) several potential risk factors were identified., Conclusions: In most of the studies it seems that the presence of a contracture is equivalent with the presence of restriction in the range of motion (ROM) of a joint. Very little is known about risk factors for contractures. But it seems that immobility may play a pivotal role in the development of this condition. IMPLICATION FOR REHABILITATION: The prevalence of contractures in nursing home residents is estimated at 55% with significant functional and medical consequences. In most studies, which were published in the last 10 years, the presence of a contracture is equivalent with the presence of restriction in the range of motion of a joint. Immobility seems to play a role in the development of contractures. Potential avenues to prevention of contractures and subsequent functional limitations are exercise programmes for and maintenance of mobility of the elderly.

Expectation contributes to placebo and nocebo responses in Parkinson's disease (PD). While there is evidence for expectation-induced modulations of bradykinesia, little is known about the impact of expectation on resting tremor. Subthalamic nucleus (STN) deep brain stimulation (DBS) improves cardinal PD motor symptoms including tremor whereas impairment of verbal fluency (VF) has been observed as a potential side-effect. Here we investigated how expectation modulates the effect of STN-DBS on resting tremor and its interaction with VF. In a within-subject-design, expectation of 24 tremor-dominant PD patients regarding the impact of STN-DBS on motor symptoms was manipulated by verbal suggestions (positive [placebo], negative [nocebo], neutral [control]). Patients participated with (MedON) and without (MedOFF) antiparkinsonian medication. Resting tremor was recorded by accelerometry and bradykinesia of finger tapping and diadochokinesia were assessed by a 3D ultrasound motion detection system. VF was quantified by lexical and semantic tests. In a subgroup of patients, the effect of STN-DBS on tremor was modulated by expectation, i.e. tremor decreased (placebo response) or increased (nocebo response) by at least 10% as compared to the control condition while no significant effect was observed for the overall group. Interestingly, nocebo responders in MedON were additionally characterized by significant impairment in semantic verbal fluency. In contrast, bradykinesia was not affected by expectation. These results indicate that the therapeutic effect of STN-DBS on tremor can be modulated by expectation in a subgroup of patients and suggests that tremor is also among the parkinsonian symptoms responsive to placebo and nocebo interventions. While positive expectations enhanced the effect of STN-DBS by further decreasing the magnitude of tremor, negative expectations counteracted the therapeutic effect and at the same time exacerbated a side-effect often associated with STN-DBS. The present findings underscore the potency of patients' expectation and its relevance for therapeutic outcomes.

The present study investigated the effects of sequence complexity, defined in terms of phonemic similarity and phonotoactic probability, on the timing and accuracy of serial ordering for speech production in healthy speakers and speakers with either hypokinetic or ataxic dysarthria. Sequences were comprised of strings of consonant-vowel (CV) syllables with each syllable containing the same vowel, /a/, paired with a different consonant. High complexity sequences contained phonemically similar consonants, and sounds and syllables that had low phonotactic probabilities; low complexity sequences contained phonemically dissimilar consonants and high probability sounds and syllables. Sequence complexity effects were evaluated by analyzing speech error rates and within-syllable vowel and pause durations. This analysis revealed that speech error rates were significantly higher and speech duration measures were significantly longer during production of high complexity sequences than during production of low complexity sequences. Although speakers with dysarthria produced longer overall speech durations than healthy speakers, the effects of sequence complexity on error rates and speech durations were comparable across all groups. These findings indicate that the duration and accuracy of processes for selecting items in a speech sequence is influenced by their phonemic similarity and/or phonotactic probability. Moreover, this robust complexity effect is present even in speakers with damage to subcortical circuits involved in serial control for speech.

Background: Understanding the relation between predominantly choreatic and hypokinetic-rigid motor subtypes and cognitive and general functioning may contribute to knowledge about different motor phenotypes in Huntington's disease., Methods: In the European Huntington's Disease Network Registry study, 1882 subjects were classified as being predominantly choreatic (n=528) or hypokinetic-rigid (n=432), according to their scores on items of the total motor score a priori labeled as choreatic or hypokinetic-rigid; the other 922 patients were of a mixed type. The relationship between motor type and cognitive (verbal fluency, symbol digit modalities, Stroop color, word and interference tests) and functional (total functional capacity) capacity was investigated using multiple linear regression., Results: Motor subtype contributed significantly to the total functional capacity score (partial r(2) : 7.8%; P<.001) and to the 5 cognitive scores (partial r(2) ranged from 2.0% to 8.4%; all P<.001)., Conclusions: Patients with a predominantly choreatic motor phenotype performing better in all areas than patients with a hypokinetic-rigid motor phenotype., (Copyright © 2013 Movement Disorder Society.)

Repetitive finger tapping is a well-established clinical test for the evaluation of parkinsonian bradykinesia, but few studies have investigated other finger movement modalities. We compared the kinematic changes (movement rate and amplitude) and response to levodopa during a conventional index finger-thumb-tapping task and an unconstrained index finger flexion-extension task performed at maximal voluntary rate (MVR) for 20 s in 11 individuals with levodopa-responsive Parkinson's disease (OFF and ON) and 10 healthy age-matched controls. Between-task comparisons showed that for all conditions, the initial movement rate was greater for the unconstrained flexion-extension task than the tapping task. Movement rate in the OFF state was slower than in controls for both tasks and normalized in the ON state. The movement amplitude was also reduced for both tasks in OFF and increased in the ON state but did not reach control levels. The rate and amplitude of movement declined significantly for both tasks under all conditions (OFF/ON and controls). The time course of rate decline was comparable for both tasks and was similar in OFF/ON and controls, whereas the tapping task was associated with a greater decline in MA, both in controls and ON, but not OFF. The findings indicate that both finger movement tasks show similar kinematic changes during a 20-s sustained MVR, but that movement amplitude is less well sustained during the tapping task than the unconstrained finger movement task. Both movement rate and amplitude improved with levodopa; however, movement rate was more levodopa responsive than amplitude.

Background: Coordination between the upper and lower extremities is important to providing dynamic stability during human gait. Though limited, previous research has suggested that interlimb coordination may be impaired in persons with Parkinson's disease. We extend this previous work using continuous analytical techniques to enhance our understanding of interlimb coordination during gait in persons with Parkinson's disease., Methods: Eighteen adults with Parkinson's disease and fifteen healthy older adults walked overground while undergoing three-dimensional motion capture. Ipsilateral and contralateral interlimb coordination between the sagittal shoulder and hip angles was assessed using cross-covariance techniques. Independent samples and paired samples t-tests compared measures of interlimb coordination between groups and between sides within the participants with Parkinson's disease, respectively. Pearson's correlations were applied to investigate associations between interlimb coordination measures and subscores of gait, posture, and bradykinesia on the Unified Parkinson's Disease Rating Scale., Findings: Ipsilateral and contralateral interlimb coordination was reduced in persons with Parkinson's disease compared to the healthy older adults. Ipsilateral coordination between the upper and lower extremities more affected by disease was found to be negatively associated with clinical scores of gait and posture. Interlimb coordination was not significantly associated with clinical measures of bradykinesia., Interpretation: Persons with Parkinson's disease exhibit reduced interlimb coordination during gait when compared to healthy older adults. These reductions in coordination are related to clinically-meaningful worsening of gait and posture in persons with PD and coordination of arm and leg movements should be considered in future research on gait therapy in this population., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Previous studies based on coronary angiography or computed tomography coronary angiography have demonstrated a high prevalence of coronary stenosis in patients with cerebral infarction and no prior history of coronary artery disease (CAD). The purpose of the present study was to compare the coronary angiographic findings of patients with prior cerebral infarction with those of patients with no prior cerebral infarction. Consecutive patients (n = 126) who underwent a first coronary angiography for suspected CAD but had no prior history of CAD were classified into 2 groups, those with a clinical history of cerebral infarction (cerebral infarction group) and those without a clinical history of cerebral infarction (noncerebral infarction group). The incidences of diabetes mellitus, peripheral artery disease, coronary stenosis, and multivessel disease were significantly higher in the cerebral infarction group than in the noncerebral infarction group. Multiple logistic regression analysis relating to coronary stenosis identifi ed prior cerebral infarction (P = 0.0027, odds ratio = 4.414) and diabetes mellitus (P = 0.0446, odds ratio = 2.619) as explanatory factors. Thirty-four of 78 patients (44%) with coronary stenosis did not have angina symptoms. Multiple logistic regression analysis regarding the lack of angina symptoms identified motor dysfunction (modified Rankin scale ≥ 2) (P = 0.0028, odds ratio = 8.323) as an explanatory factor. The results of the present study suggest that compared with patients without cerebral infarction those with the disorder have a high prevalence of coronary stenosis, and indicate that the development of angina symptoms is influenced by the severity of motor dysfunction.

Recent studies suggest that Parkinson's disease (PD) is associated with pathological synchronous oscillatory activity in the basal ganglia. Beta frequency band (β-FB) oscillations likely contribute to bradykinesia and rigidity in PD; however, details of the relationship between these two phenomena remain unclear. To explore β-FB oscillatory activity in relation to motor signs of bradykinesia and rigidity, we studied 17 patients with akinetic-rigid type PD who had electrodes implanted into the subthalamic nucleus (STN) for deep brain stimulation therapy. Microelectrode recordings were obtained in the STN during surgery and neuronal activity was analyzed offline. The spectral characteristics were calculated. Of 155 neurons from 30 STN, 56 (36.1%) had β-FB oscillatory activity. Neurons with oscillatory activity were localized in the dorsal two-thirds of the STN. These data indicate that β-FB oscillatory activity may be of particular importance in the generation of motor deficits in PD., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background and Aims: (1) To establish the prevalence of mild cognitive impairment (MCI) in newly diagnosed drug-naive patients with Parkinson's disease adopting recently proposed and more conservative preliminary research criteria. (2) To investigate the relation between cognitive performances, MCI and motor dysfunction., Methods: 132 consecutive newly diagnosed drug-naive PD patients and 100 healthy controls (HCs) underwent a neuropsychological evaluation covering different cognitive domains. Moreover, on the basis of the Unified Parkinson's Disease Rating Scale II/III, different motor scores were calculated and patients were classified in motor subtypes. 11 patients were excluded from the analysis during clinical follow-up which was continued at least 3 years from the diagnosis; therefore, the final sample included 121 patients., Results: MCI prevalence was higher in PD (14.8%) patients than in HCs (7.0%). PD patients reported lower cognitive performances than HCs in several cognitive domains; HCs also outperformed cognitively preserved PD patients in tasks of episodic verbal memory and in a screening task of executive functions. MCI-PD patients presented a more severe bradykinesia score than non-MCI PD patients and patients mainly characterised by tremor had better performances in some cognitive domains, and specific cognitive-motor relationships emerged., Conclusions: Although the adoption of more conservative diagnostic criteria identified a lower MCI prevalence, we found evidence that newly diagnosed drug-naive PD patients present a higher risk of MCI in comparison with HCs. Axial symptoms and bradykinesia represent risk factors for MCI in PD patients and a classification of PD patients that highlights the presence/absence of tremor, as proposed in this study, is probably better tailored for the early stages of PD than classifications proposed for more advanced PD stages.

Manganese (Mn) is a nutrient and neurotoxicant sometimes associated with mood, motor and neurological effects. Reports of health effects from occupational exposure to Mn are well known, but the reported links to environmental airborne Mn (Mn-Air) are less conclusive. Marietta, OH (USA) is a previously identified community with elevated Mn-Air from industrial emissions. Households were randomly selected in Marietta and the comparison town (Mount Vernon, OH). The responders were used to recruit on a voluntary basis 30- to 75-year-old residents, i.e. 100 in Marietta and 90 in Mount Vernon. They were administered the Unified Parkinson's Disease Rating Scale (UPDRS), motor efficiency, and mood tests, along with a comprehensive questionnaire including demographics, health and work history. Blood Mn (MnB), serum ferritin, and hepatic enzymes were measured. Results were compared with those of 90 residents from a demographically similar comparison town, Mount Vernon, OH, where Mn-Air from industrial emissions was not of concern. Mn-Air exposure indices were modeled for Marietta residents. The Mn-exposed participants resided on average 4.75 miles (range 1-11) from the Mn point source. Their modeled residential Mn-Air estimate ranged from 0.04 to 0.96 μg/m(3) and was on average 0.18 μg/m(3). The group means of MnB were similar for the Mn-exposed (9.65 μg/L) and comparison (9.48 μg/L) participants. The Marietta group reported more generalized anxiety on the Symptom Checklist-90-Revised (SCL-90-R) than the comparison group (p=0.035). Generalized anxiety in Marietta was related to a cumulative exposure index (p=0.002), based on modeled Mn-Air concentration and length of residence. Higher generalized anxiety scores were related to poorer performance on UPDRS tests [adjusted relative risk (95%CI): 2.18 (1.46-3.25) for motor-related activities of daily living, 3.44 (1.48-7.98) for bradykinesia, and 1.63 (1.06-2.53) for motor/movement]. Group differences in SCL-90-R generalized anxiety between the two towns and the observed relationship between exposure indices and generalized anxiety suggest an association between environmental Mn exposure and anxiety states. Whether this association is due to direct neurotoxic effects of Mn-Air or concern about the health effects of air pollution remains an open question. The results highlight the importance of measuring anxiety in relation to neuropsychological and neurological endpoints, and should be validated in other studies of Mn-exposed communities., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Brachial plexus injuries can occur as a result of various mechanisms such as stretching, direct and indirect trauma or following childbirth. Bilateral brachial plexus injuries are uncommon and associated with a poor functional outcome. We report a case of bilateral brachial plexus injury resulting from prolonged immobilization of the arms in hyper-abducted position resulting in compression of the brachial plexus on both sides. The injuries were treated conservatively and following 4 months of active rehabilitation in our unit, the patient still had poor arm functions and required care and support in the community on discharge.

Introduction: Global left ventricular (LV) hypokinesis is considered to be the cause of stroke, while the significance of segmental wall motion abnormalities is still unknown., Objectives: The aim of the study was to determine the frequency of embolic signals in the middle cerebral artery in patients with segmental LV wall hypokinesis in the course of coronary artery disease (CAD) with and without stroke., Patients and Methods: The study included 68 patients (aged 21-87 years) with segmental LV wall hypokinesis (33 patients without and 35 with stroke). The reference group comprised 30 patients (aged 43-76 years) with atherosclerotic risk factors; the control group comprised 37 healthy volunteers (aged 41-71 years). All subjects underwent echocardiography and carotid and transcranial Doppler ultrasound with the detection of microembolic signals., Results: Embolic signals were observed significantly more often in patients with segmental LV wall hypokinesis than in the control and reference groups. In patients with CAD and stroke, an increased number of embolic signals (≥3) was observed significantly more often compared with patients without stroke. Compared with other locations, interventricular septum and apex hypokinesis was associated with a higher frequency of embolic signals in the middle cerebral arteries., Conclusions: Segmental LV motion abnormalities in the form of hypokinesis in patients with CAD are associated with the presence of embolic signals in the middle cerebral arteries, which may have clinical significance as a risk factor for stroke.

Objective: The authors' intention was to evaluate the incidence of the three subtypes of delirium, the risk factors of the subtypes in cardiac surgery, and the impact of the subtypes on clinical outcomes., Design: A prospective study., Setting: A university hospital., Participants: A total population of 506 patients undergoing cardiac surgery was screened for delirium., Interventions: None., Measurement and Main Results: Patients undergoing cardiac surgery were screened by using the Intensive Care Delirium Screening Checklist (ICDSC) and the Richmond Agitation and Sedation Scale (RASS). Patients with hypoactive delirium were compared with nondelirious patients. Outcomes measured were the duration of mechanical ventilation and the length of stay in the intensive care unit. The overall delirium incidence was 11.6%, whereas the incidence of the hypoactive subtype was 9%. Age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01-1.09, p = 0.02), a history of depression (OR = 3.57; 95% CI, 1.04-10.74; p = 0.03), preoperative therapy with diuretics (OR = 2.85; 95% CI, 1.36-6.35; p < 0.01), aortic clamping times (OR = 1.01; 95% CI, 1.00-1.02; p < 0.01) and blood transfusions (OR = 1.18; 95% CI, 1.05-1.34; p < 0.01) were predictors for the development of hypoactive delirium. Preoperative therapy with β-blockers (OR = 0.32; 95% CI, 0.16-0.65; p < 0.01) and higher hemoglobin before surgery (OR = 0.73; 95% CI, 0.60-0.91; p < 0.01) were associated with a lower prevalence of hypoactive delirium. Hypoactive delirium is an independent predictor for prolonged mechanical ventilation time (OR = 1.56; 95% CI, 1.25-1.92; p < 0.01) and the length of stay in the ICU (OR = 1.42; 95% CI, 1.22-1.65, p < 0.01)., Conclusion: Hypoactive delirium itself is a strong predictor for a longer ICU stay and a prolonged period of mechanical ventilation. Some of the risk factors related to the intraoperative and postoperative setting are suitable for preventive action., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study aimed to analyze quantitatively videofluoroscopic (VF) images of patients with Parkinson's disease (PD), to evaluate if the predicted factors of the oral phase of swallowing deteriorated with PD progression, and to demonstrate a relationship between the abnormal movements of the tongue and food transportation. Thirty PD patients were recruited and divided into mild/moderate (Hoehn & Yahr stages II and III) and advanced (stages IV and V) groups. They underwent measurement of tongue strength and VF using 5 ml of barium gelatin jelly as a test food. We measured the speed of bolus movement and the range of tongue and mandible movements during oropharyngeal transit time. The maximum tongue pressure of the mild/moderate group was significantly larger than that of advanced group (p = 0.047). The oropharyngeal transit time of the mild/moderate group was significantly shorter than that of the advanced group (p = 0.045). There was a significant negative correlation between the speed of tongue movement and the oropharyngeal transit time (p = 0.003, R = -0.527). Prolonged mealtimes and the ejection of insufficiently masticated food from the oral cavity into oropharynx were associated with PD progression. These results indicate the importance of the oral phase of swallowing in PD patients.

Paradoxical kinesia (PK) is the sudden resolution of a previously stabilized akinesia in an advanced idiopathic Parkinson's disease (IPD) patient facing an immediate threat. We are reporting the effect of PK, as a consequence of a life threatening event (earthquake), in a group of 14 patients with parkinsonism and dementia in Hoehn/Yahr (H/Y) stage 3-5. All the patients presented an extraordinary motor response during the earthquake that has recently stricken the Italian city of L'Aquila. All of them were able to safely escape unaided and, in some cases, to assist their families, despite they suffered before from severe night time akinesia and gait difficulties with postural instability requiring assistance. In five patients, the improvement of motor disabilities, particularly of freezing, lasted for 2-5 months.

Objective: To investigate the frequency of bradykinesia in patients with obsessive-compulsive disorder (OCD) and to see whether patients with OCD who also have bradykinesia display distinctive neuropsychological and neuropsychiatric features., Methods: We studied 23 antipsychotic-free patients with OCD and 13 healthy controls. Bradykinesia was assessed with section III of the Unified Parkinson Disease Rating Scale. The Wechsler Adult Intelligent Scales-Revised (WAIS-R) was used to assess the Full Scale IQ and to measure visuospatial, visuoconstructional ability and psychomotor speed/mental slowness., Results: Of the 23 patients with OCD studied, 8 (34%) had mild symptoms of bradykinesia. No relationship was found between bradykinesia and the sociodemographic variables assessed but this motor symptom was significantly associated with the severity of compulsions. Patients with bradykinesia differed from those without: they had a higher frequency of repeating compulsions, and lower IQ scores, performance scores, and WAIS-R subtest scores for similarities and picture completion. No significant differences were found between patients without bradykinesia and healthy controls in any test., Conclusions: Clinical assessment of motor symptoms in adult patients with OCD often discloses mild bradykinesia sometimes associated with repeating compulsions and poor WAIS-R performance scores., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)