Targeting neuroendocrine abnormalities in Parkinson’s disease with exercise

Parkinson’s Disease (PD) is a prevalent and complex age-related neurodegenerative condition for which there are no disease-modifying treatments currently available. The pathophysiological process underlying PD remains incompletely understood but increasing evidence points to multiple system dysfunction. Interestingly, the past decade has produced evidence that exercise not only reduces signs and symptoms of PD but is also potentially neuroprotective. Characterizing the mechanistic pathways that are triggered by exercise and lead to positive outcomes will improve understanding of how to counter disease progression and symptomatology. In this review, we highlight how exercise regulates the neuroendocrine system, whose primary role is to respond to stress, maintain homeostasis and improve resilience to aging. We focus on a group of hormones – cortisol, melatonin, insulin, klotho, and vitamin D – that have been shown to associate with various non-motor symptoms of PD, such as mood, cognition, and sleep/circadian rhythm disorder. These hormones may represent important biomarkers to track in clinical trials evaluating effects of exercise in PD with the aim of providing evidence that patients can exert some behavioral-induced control over their disease

Kinematic Foot Types in Youth with Equinovarus Secondary to Hemiplegia

Background Elevated kinematic variability of the foot and ankle segments exists during gait among individuals with equinovarus secondary to hemiplegic cerebral palsy (CP). Clinicians have previously addressed such variability by developing classification schemes to identify subgroups of individuals based on their kinematics. Objective To identify kinematic subgroups among youth with equinovarus secondary to CP using 3-dimensional multi-segment foot and ankle kinematics during locomotion as inputs for principal component analysis (PCA), and K-means cluster analysis. Methods In a single assessment session, multi-segment foot and ankle kinematics using the Milwaukee Foot Model (MFM) were collected in 24 children/adolescents with equinovarus and 20 typically developing children/adolescents. Results PCA was used as a data reduction technique on 40 variables. K-means cluster analysis was performed on the first six principal components (PCs) which accounted for 92% of the variance of the dataset. The PCs described the location and plane of involvement in the foot and ankle. Five distinct kinematic subgroups were identified using K-means clustering. Participants with equinovarus presented with variable involvement ranging from primary hindfoot or forefoot deviations to deformtiy that included both segments in multiple planes. Conclusion This study provides further evidence of the variability in foot characteristics associated with equinovarus secondary to hemiplegic CP. These findings would not have been detected using a single segment foot model. The identification of multiple kinematic subgroups with unique foot and ankle characteristics has the potential to improve treatment since similar patients within a subgroup are likely to benefit from the same intervention(s)

Effect of Fine Wire Electrode Insertion on Gait Patterns in Children with Hemiplegic Cerebral Palsy

Background Fine wire electromyography (EMG) is commonly used for surgical decision making in equinovarus foot deformity. However, this invasive technique may have the unwanted effect of altering the gait of children with cerebral palsy (CP). The purpose of this study was to determine if fine wire insertion into the posterior tibialis muscle affects temporal-spatial parameters and hindfoot kinematics during gait in children with equinovarus secondary to hemiplegic CP. Methods 12 children with hemiplegic CP who presented with an equinovarus foot (mean age 12.5 yrs, four right-sided, eight left-sided) were recruited. Temporal-spatial parameters and 3-D segmental foot and ankle kinematic gait data were collected utilizing standard gait analysis and the Milwaukee Foot Model (MFM). Three representative trials with and without fine wire electrode insertion were compared to determine the effect of electrode placement in the posterior tibialis on temporal spatial-parameters and hindfoot sagittal, coronal and transverse plane kinematic peaks, timing of kinematic peaks, and excursions. Results No significant differences in any temporal-spatial or kinematic parameters were observed between “with wire” and “without wire” conditions. Strong correlations were observed among the gait parameters, with the exception of cadence, for the two conditions. Discussion Fine wire insertion into the posterior tibialis had no measurable effect on the gait of individuals with equinovarus secondary to hemiplegic CP. This suggests that the simultaneous collection of segmental foot and ankle kinematics and fine wire EMG data of the posterior tibialis is acceptable for surgical decision making in this patient population

Progressive Resistance Exercise and Parkinson's Disease: A Review of Potential Mechanisms

This paper reviews the therapeutically beneficial effects of progressive resistance exercise (PRE) on Parkinson's disease (PD). First, this paper discusses the rationale for PRE in PD. Within the first section, the review discusses the central mechanisms that underlie bradykinesia and muscle weakness, highlights findings related to the central changes that accompany PRE in healthy individuals, and extends these findings to individuals with PD. It then illustrates the hypothesized positive effects of PRE on nigro-striatal-thalamo-cortical activation and connectivity. Second, it reviews recent findings of the use of PRE in individuals with PD. Finally, knowledge gaps of using PRE on individuals with PD are discussed along with suggestions for future research

Combining high dose therapy, bilateral motor priming, and vagus nerve stimulation to treat the hemiparetic upper limb in chronic stroke survivors: a perspective on enhancing recovery

Stroke is a leading cause of disability worldwide and upper limb hemiparesis is the most common post-stroke disability. Recent studies suggest that clinically significant motor recovery is possible in chronic stroke survivors with severe impairment of the upper limb. Three promising strategies that have been investigated are (1) high dose rehabilitation therapy (2) bilateral motor priming and (3) vagus nerve stimulation. We propose that the future of effective and efficient upper limb rehabilitation will likely require a combination of these approaches

Control of interjoint coordination during the swing phase of normal gait at different speeds

BACKGROUND: It has been suggested that the control of unconstrained movements is simplified via the imposition of a kinetic constraint that produces dynamic torques at each moving joint such that they are a linear function of a single motor command. The linear relationship between dynamic torques at each joint has been demonstrated for multijoint upper limb movements. The purpose of the current study was to test the applicability of such a control scheme to the unconstrained portion of the gait cycle – the swing phase. METHODS: Twenty-eight neurologically normal individuals walked along a track at three different speeds. Angular displacements and dynamic torques produced at each of the three lower limb joints (hip, knee and ankle) were calculated from segmental position data recorded during each trial. We employed principal component (PC) analysis to determine (1) the similarity of kinematic and kinetic time series at the ankle, knee and hip during the swing phase of gait, and (2) the effect of walking speed on the range of joint displacement and torque. RESULTS: The angular displacements of the three joints were accounted for by two PCs during the swing phase (Variance accounted for – PC1: 75.1 ± 1.4%, PC2: 23.2 ± 1.3%), whereas the dynamic joint torques were described by a single PC (Variance accounted for – PC1: 93.8 ± 0.9%). Increases in walking speed were associated with increases in the range of motion and magnitude of torque at each joint although the ratio describing the relative magnitude of torque at each joint remained constant. CONCLUSION: Our results support the idea that the control of leg swing during gait is simplified in two ways: (1) the pattern of dynamic torque at each lower limb joint is produced by appropriately scaling a single motor command and (2) the magnitude of dynamic torque at all three joints can be specified with knowledge of the magnitude of torque at a single joint. Walking speed could therefore be altered by modifying a single value related to the magnitude of torque at one joint

The Interrelated Multifactorial Actions of Cortisol and Klotho: Potential Implications in the Pathogenesis of Parkinson’s Disease

The pathogenesis of Parkinson’s disease (PD) is complex, multilayered, and not fully understood, resulting in a lack of effective disease-modifying treatments for this prevalent neurodegenerative condition. Symptoms of PD are heterogenous, including motor impairment as well as non-motor symptoms such as depression, cognitive impairment, and circadian disruption. Aging and stress are important risk factors for PD, leading us to explore pathways that may either accelerate or protect against cellular aging and the detrimental effects of stress. Cortisol is a much-studied hormone that can disrupt mitochondrial function and increase oxidative stress and neuroinflammation, which are recognized as key underlying disease mechanisms in PD. The more recently discovered klotho protein, considered a general aging-suppressor, has a similarly wide range of actions but in the opposite direction to cortisol: promoting mitochondrial function while reducing oxidative stress and inflammation. Both hormones also converge on pathways of vitamin D metabolism and insulin resistance, also implicated to play a role in PD. Interestingly, aging, stress and PD associate with an increase in cortisol and decrease in klotho, while physical exercise and certain genetic variations lead to a decrease in cortisol response and increased klotho. Here, we review the interrelated opposite actions of cortisol and klotho in the pathogenesis of PD. Together they impact powerful and divergent mechanisms that may go on to influence PD-related symptoms. Better understanding of these hormones in PD would facilitate the design of effective interventions that can simultaneously impact the multiple systems involved in the pathogenesis of PD