Improvement In Bradykinesia Research Articles

Acute Levodopa Challenge in Atypical Parkinsonism: Comprehensive Analysis of Individual Motor Responses.

The acute levodopa challenge is widely used to distinguish Parkinson's disease (PD) from atypical parkinsonian syndromes (APSs) such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). In APSs, very few patients present a clinically relevant response to levodopa. The aim of this study was to determine whether patients with atypical parkinsonism benefit from levodopa in any aspect of their multiple motor deficits despite the generally poor response. This retrospective study analyzed individual motor responses to the acute levodopa challenge using the MDS-UPDRS III in 47 PSP, 26 MSA, and 71 PD patients at Hannover Medical School. Despite the generally poor levodopa response in both PSP and MSA patients, bradykinesia and rigidity were the symptoms most notably affected by levodopa in PSP patients, while MSA patients experienced significant improvements in bradykinesia and action tremor. These findings underscore the variability in levodopa response among PSP and MSA patients and highlight the need for personalized treatment approaches in atypical parkinsonism.

Objective assessment of the effects of opicapone in Parkinson’s disease through kinematic analysis

BackgroundOpicapone (OPC) is a third-generation, selective peripheral COMT inhibitor that improves peripheral L-DOPA bioavailability and reduces OFF time and end-of-dose motor fluctuations in Parkinson’s disease (PD) patients.ObjectivesIn this study, we objectively assessed the effects of adding OPC to L-DOPA on bradykinesia in PD through kinematic analysis of finger movements.MethodsWe enrolled 20 treated patients with PD and motor fluctuations. Patients underwent two experimental sessions (L-DOPA, L-DOPA + OPC), separated by at least 1 week. In each session, patients were clinically evaluated and underwent kinematic movement analysis of repetitive finger movements at four time points: (i) before their usual morning dose of L-DOPA (T0), (ii) 30 min (T1), (iii) 1 h and 30 min (T2), and (iv) 3 h and 30 min after the L-DOPA intake (T3).ResultsMovement velocity and amplitude of finger movements were higher in PD patients during the session with OPC compared to the session without OPC at all the time points tested. Importantly, the variability of finger movement velocity and amplitude across T0–T3 was significantly lower in the L-DOPA + OPC than L-DOPA session.ConclusionsThis study is the first objective assessment of the effects of adding OPC to L-DOPA on bradykinesia in patients with PD and motor fluctuations. OPC, in addition to the standard dopaminergic therapy, leads to significant improvements in bradykinesia during clinically relevant periods associated with peripheral L-DOPA dynamics, i.e., the OFF state in the morning, delayed-ON, and wearing-OFF periods.

Levodopa improved different motor symptoms in patients with Parkinson's disease by reducing the functional connectivity of specific thalamic subregions.

The thalamus is an important relay station for the motor circuit of human. Levodopa can reverse the clinical manifestations by modulating the function of motor circuits, but its detailed mechanisms are still not fully understood. We aimed to explore (1) the mechanism by which levodopa modulates the functional connectivity (FC) in the subregions of the thalamus; (2) the relationship between the changed FC and the improvement of motor symptoms in Parkinson's disease (PD) patients. Resting-state functional MRI was used to scan 36 PD patients and 37 healthy controls. The FC between the subregions in the thalamus and the whole brain was measured and compared under different medication states of PD patients. The correlation between the improvement of motor symptoms and changes in FC in the thalamus subregions was examined. The PD on state exhibited decreased FC between the right pre-motor thalamus and the right postcentral gyrus, as well as the right lateral pre-frontal thalamus and the right postcentral gyrus. These decreases were positively correlated with the improvement of resting tremor. The PD on state also exhibited decreased FC between the left lateral pre-frontal thalamus and right paracentral lobule, which was positively correlated with the improvement of bradykinesia. This study demonstrates that levodopa treats PD by decreasing the FC between the thalamus subregions and pre/post-central cortex. Our results provide a basis for further exploration of the functional activity of thalamic subregions and offer new insights into the precision treatment in PD patients.

A First Methodological Development and Validation of ReTap: An Open-Source UPDRS Finger Tapping Assessment Tool Based on Accelerometer-Data.

Bradykinesia is a cardinal hallmark of Parkinson's disease (PD). Improvement in bradykinesia is an important signature of effective treatment. Finger tapping is commonly used to index bradykinesia, albeit these approaches largely rely on subjective clinical evaluations. Moreover, recently developed automated bradykinesia scoring tools are proprietary and are not suitable for capturing intraday symptom fluctuation. We assessed finger tapping (i.e., Unified Parkinson's Disease Rating Scale (UPDRS) item 3.4) in 37 people with Parkinson's disease (PwP) during routine treatment follow ups and analyzed their 350 sessions of 10-s tapping using index finger accelerometry. Herein, we developed and validated ReTap, an open-source tool for the automated prediction of finger tapping scores. ReTap successfully detected tapping blocks in over 94% of cases and extracted clinically relevant kinematic features per tap. Importantly, based on the kinematic features, ReTap predicted expert-rated UPDRS scores significantly better than chance in a hold out validation sample (n = 102). Moreover, ReTap-predicted UPDRS scores correlated positively with expert ratings in over 70% of the individual subjects in the holdout dataset. ReTap has the potential to provide accessible and reliable finger tapping scores, either in the clinic or at home, and may contribute to open-source and detailed analyses of bradykinesia.

Functional Topography of the Human Subthalamic Nucleus: Relevance for Subthalamotomy in Parkinson's Disease.

The subthalamic nucleus (STN) is considered a key structure in motor, behavioral, and emotional control. Although identification of the functional topography of the STN has therapeutic implications in the treatment of the motor features of Parkinson's disease (PD), the details of its functional and somatotopic organization in humans are not well understood. The aim of this study was to characterize the functional organization of the STN and its correlation with the motor outcomes induced by subthalamotomy. We used diffusion-weighted imaging to assess STN connectivity patterns in 23 healthy control subjects and 86 patients with PD, of whom 39 received unilateral subthalamotomy. Analytical tractography was used to reconstruct structural cortico-subthalamic connectivity. A diffusion-weighted imaging/functional magnetic resonance imaging-driven somatotopic parcellation of the STN was defined to delineate the representation of the upper and lower limb in the STN. We confirmed a connectional gradient to sensorimotor, supplementary-motor, associative, and limbic cortical regions, spanning from posterior-dorsal-lateral to anterior-ventral-medial portions of the STN, with intermediate overlapping zones. Functional magnetic resonance imaging-driven parcellation demonstrated dual segregation of motor cortico-subthalamic projections in humans. Moreover, the relationship between lesion topography and functional anatomy of the STN explains specific improvement in bradykinesia, rigidity, and tremor induced by subthalamotomy. Our results support an interplay between segregation and integration of cortico-subthalamic projections, suggesting the coexistence of parallel and convergent information processing. Identifying the functional topography of the STN will facilitate better definition of the optimal location for functional neurosurgical approaches, that is, electrode placement and lesion location, and improve specific cardinal features in PD. © 2021 International Parkinson and Movement Disorder Society.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Subthalamic beta band suppression reflects effective neuromodulation in chronic recordings

Biomarkers for future adaptive deep brain stimulation still need evaluation in clinical routine. Here, we aimed to assess stimulation-induced modulation of beta-band activity and clinical symptoms in a Parkinson's disease patient during chronic neuronal sensing using a novel implantable pulse generator. Subthalamic activity was recorded OFF and ON medication during a stepwise increase of stimulation amplitude. Off-line fast fourier transfom -based analysis of beta-band activity was correlated with motor performance rated from blinded videos. The stepwise increase of stimulation amplitude resulted in decreased beta oscillatory activity and improvement of bradykinesia. Mean low beta-band (13-20Hz) activity correlated significantly with bradykinesia (ρ= 0.662, p<0.01). Motor improvement is reflected in reduced subthalamic beta-band activity in Parkinson's disease, supporting beta activity as a reliable biomarker. The novel PERCEPT neurostimulator enables chronic neuronal sensing in clinical routine. Our findings pave the way for a personalized precision-medicine approach to neurostimulation.

Modulation of beta bursts in subthalamic sensorimotor circuits predicts improvement in bradykinesia.

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.

Efficacy of lead point using MER with DBS in accurate targeting for persevering subthalamic-nuclei neurons— geometry of the electrode and its implantation in Parkinson‘s

Deep brain stimulation (DBS) is one effectual reliable method to reduce motor symptoms in subjects with neurodegenerative disorder of Parkinson’s disease (PD—Parkinson diseased conditions/patients). However, objective methods for quantifying its efficacy are lacking. Therefore, we present an investigative fusion study for quantifying the effects of DBS in PD by using the microelectrode recording system (MER) to measure the MER signal parameters such as amplitude, frequency, pulse-width, etc. We measured those parameters from the MER signals of subthalamic nuclei (STN) neurons of 46 subjects (92 sides of PD conditions) with DBS stimulator. The channel with maximum recording and the earliest recording were recorded on both sides. Intraoperative test stimulation was performed in all channels from the level at the onset of MER recording. Stimulation was done at 1mv, 3mv to assess the improvement in bradykinesia, rigidity and tremor. Appearance of dyskinesias was considered to be associated with accurate targeting. Side effects were assessed at 5mv and 7mv to ensure that the final channel chosen had maximum improvement with least side effects. Correlation was assessed between the aspects of MER and the final channel chosen in 46 subjects (92 sides, i.e., right and left hemispheres of the brain). Clinical evaluation of subjects showed that their motor symptoms were effectively reduced with DBS. The analysis results showed that the signal characteristics of 46 PD subjects’ subthalamic nuclei (STN) neurons were heterogeneous with DBS on and off. These observations indicate that the DBS with MER technique can be used to objectively quantify the effects of DBS on the neuromuscular function of PD subjects. Further studies are suggested to estimate the clinical and/or diagnostic sensitivity of the method to different types of PD. The measurement parameters in combination of MER with DBS method in acute targeting can be used to quantify the effects

Reliability of Intraoperative Testing During Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is an effective treatment for medically refractory Parkinson's disease (PD). During DBS surgery, intraoperative testing is performed to confirm optimal lead placement by determining the stimulation thresholds for symptom improvement and side effects. However, the reliability of intraoperative testing in predicting distant postoperative thresholds is unknown. In this study, we hypothesized that intraoperative testing reliably estimates postoperative thresholds for both symptom improvement and side effects. We retrospectively analyzed a prospective database with intraoperative and postoperative thresholds for symptom improvement and side effects from a cohort of 66 PD patients who underwent STN DBS. We recorded the stimulation locations relative to the mid-commissural point. Within-patient stimulation pairs were generated by clustering the intraoperative stimulation locations closest to the DBS contacts. We computed the distance between stimulation locations and atlas-based pyramidal tract (PT) and medial lemniscus (ML) masks. A leave-one-out cross-validation analysis was performed to determine the reliability of intraoperative testing in predicting postoperative thresholds while controlling for the distance from the relevant tracks. Intraoperative testing reliably predicted (area under ROC >0.8) postoperative thresholds for tremor and rigidity improvements, as well as stimulation-induced motor contractions and paresthesias. The reliability was poor for improvement in bradykinesia. Intraoperative testing reliably predicts postoperative thresholds. These results are relevant during the informed consent process and patient counseling for DBS surgery. These will also guide the development of future methods for intraoperative feedback, especially during asleep DBS.

Modulation of Nigrofugal and Pallidofugal Pathways in Deep Brain Stimulation for Parkinson Disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical therapy for patients with Parkinson disease (PD). To define the role of adjacent white matter stimulation in the effectiveness of STN-DBS. We retrospectively evaluated 43 patients with PD who received bilateral STN-DBS. The volumes of activated tissue were analyzed to obtain significant stimulation clusters predictive of 4 clinical outcomes: improvements in bradykinesia, rigidity, tremor, and reduction of dopaminergic medication. Tractography of the nigrofugal and pallidofugal pathways was performed. The significant clusters were used to calculate the involvement of the nigrofugal and pallidofugal pathways and the STN. The clusters predictive of rigidity and tremor improvement were dorsal to the STN with most of the clusters outside of the STN. These clusters preferentially involved the pallidofugal pathways. The cluster predictive of bradykinesia improvement was located in the central part of the STN with an extension outside of the STN. The cluster predictive of dopaminergic medication reduction was located ventrolateral and caudal to the STN. These clusters preferentially involved the nigrofugal pathways. Improvements in rigidity and tremor mainly involved the pallidofugal pathways dorsal to the STN. Improvement in bradykinesia mainly involved the central part of the STN and the nigrofugal pathways ventrolateral to the STN. Maximal reduction in dopaminergic medication following STN-DBS was associated with an exclusive involvement of the nigrofugal pathways.

Unsupervised clustering reveals spatially varying single neuronal firing patterns in the subthalamic nucleus of patients with Parkinson's disease

IntroductionSubthalamic nucleus (STN) is an effective target for deep brain stimulation (DBS) to reduce the motor symptoms of Parkinson's disease (PD). It is important to identify firing patterns within the structure for a better understanding of the electro-pathophysiology of the disease. Using recently established metrics, our study aims to autonomously identify the discharge patterns of individual cells and examine their spatial distribution within the STN. MethodsWe recorded single unit activity (SUA) from 12 awake PD patients undergoing a standard clinical DBS surgery. Three extracted features from raw SUA (local variation, bursting index and prominence of peak) were used with k-means clustering to achieve the aforementioned unsupervised grouping of firing patterns. Results279 neurons were isolated and four distinct firing patterns were identified across patients: tonic (11%), irregular (55%), periodic (9%) and non-periodic bursts (25%). The mean firing rates for irregular discharges were significantly lower (p < 0.05) than the rest. Tonic firings were significantly ventral (p < 0.05) while periodic (p < 0.05) and non-periodic (p < 0.01) bursts were dorsal. The percentage of periodically bursting neurons in dorsal region and entire STN were significantly correlated with off state UPDRS tremor scores (r = 0.51, p = 0.04) and improvement in bradykinesia and rigidity (r = 0.57, p = 0.02) respectively. ConclusionStrengthening the application of unsupervised clustering for firing patterns of individual cells, this study shows a unique spatial affinity of tonic activity towards the ventral and bursting activity towards the dorsal region of STN in PD patients. This spatial preference, together with the correlation of clinical scores, can provide a clue towards understanding Parkinsonian symptom generation.

Reader response: Diffuse Lewy body disease manifesting as corticobasal syndrome: A rare form of Lewy body disease

We read with great interest the article by Kasanuki et al.1 that described 11 cases of pathologically confirmed diffuse Lewy body disease, antemortem clinically manifesting as corticobasal syndrome (CBS), in line with previous findings. We recently evaluated a 70-year-old woman referred to our center with possible CBS according to clinical criteria.2 The patient presented with a 3-year history of limb bradykinesia and dystonia prevalent in the right side associated with limb apraxia. Brain MRI detected bilateral parietal cortical atrophy, mainly in the left side, and 18F-fluorodeoxyglucose PET showed left parietal hypometabolism. Additional features suggested an “atypical” atypical parkinsonism3: a slow parkinsonism progression, moderate improvement of bradykinesia with levodopa therapy, and a 10-year history of memory and language impairment associated with mild dysphagia and postural instability. The patient underwent skin biopsy, unveiling abnormal deposition of phosphorylated α-synuclein (p-syn) in skin nerves, unexpected in CBS.

Stimulation of the Tractography-Defined Subthalamic Nucleus Regions Correlates With Clinical Outcomes.

Although deep brain stimulation (DBS) of the dorsolateral subthalamic nucleus (STN) is a well-established surgical treatment for patients with Parkinson disease (PD), there is still controversy about the relationship between the functional segregation of the STN and clinical outcomes. To correlate motor and neuropsychological (NPS) outcomes with the overlap between the volume of activated tissue (VAT) and the tractography-defined regions within the STN. Retrospective study evaluating 13 patients with PD treated with STN-DBS. With the aid of tractography, the STN was segmented into 4 regions: smaSTN (supplementary motor area STN), m1STN (primary motor area STN), mSTN (the sum of the m1STN and the smaSTN segments), and nmSTN (non-motor STN). We computed the overlap coefficients between these STN regions and the patient-specific VAT. The VAT outside of the STN was also calculated. These coefficients were then correlated with motor (Unified Parkinson's Disease Rating Scale, UPDRS III) and NPS outcomes. Stimulation of the mSTN segment was significantly correlated with UPDRS III and bradykinesia improvement. Stimulation of the smaSTN segment, but not the m1STN one, had a positive correlation with bradykinesia improvement. Stimulation of the nmSTN segment was negatively correlated with the improvement in rigidity. Stimulation outside of the STN was correlated with some beneficial NPS effects. Stimulation of the tractography-defined motor STN, mainly the smaSTN segment, is positively correlated with motor outcomes, whereas stimulation of the nmSTN is correlated with poor motor outcomes. Further validation of these results might help individualize and optimize targets prior to STN-DBS.

Distinct subthalamic coupling in the ON state describes motor performance in Parkinson's disease.

Cross-frequency coupling has been reported in the STN of patients with PD, but its significance and functional role are still not well understood. This study investigates pharmacological modulations of subthalamic oscillations and their nonlinear cross-frequency interactions across three consecutive cycles over unique 24-hour-long recordings. Identifying neurobiomarkers for PD can drive the development of novel personalized treatments by providing objective assessment of impairment. In particular, distinct frequency bands in LFP recordings and their interaction with one another have been shown to modulate with dopaminergic medication and thus, proposed as such biomarkers. We recorded local field potentials 3 weeks postoperatively from externalized leads in 9 patients and correlated the neural patterns with improvements in motor signs over three medication intake cycles. We used two modalities to assess symptoms in the unmedicated OFF and the l-dopa-induced motor ON state: a subsection of the UPDRS and a keyboard tapping score measuring bradykinesia. In the OFF state, the amplitude of high-frequency oscillations in the 200- to 300-Hz range was coupled with the phase of low-beta (13-22 Hz) in all patients. After transition to the ON state, three distinct coupling patterns were observed among subjects. Among these, patients showing ON coupling between high-beta (22-30 Hz) and high-frequency oscillations in the 300- to 400-Hz range had significantly greater improvement in bradykinesia, according to the keyboard scores. Observing diminished coupling in the ON state, previous studies have hypothesized that the sole existence of coupling in STN has an "impeding" effect on normal processes, and thus it was considered to be pathological. In contrast, our observation of ON state coupling at distinct frequencies associated with the improvements in motor features suggest that the underlying mechanism of coupling might have impeding or enhancing effects depending on the coupled frequencies. © 2019 International Parkinson and Movement Disorder Society.

Deep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activity

Deep brain stimulation is an established therapy for Parkinson's disease; however, its effectiveness is hindered by limited understanding of therapeutic mechanisms and the lack of a robust feedback signal for tailoring stimulation. We recently reported that subthalamic nucleus deep brain stimulation evokes a neural response resembling a decaying high-frequency (200-500 Hz) oscillation that typically has a duration of at least 10 ms and is localizable to the dorsal sub-region. As the morphology of this response suggests a propensity for the underlying neural circuitry to oscillate at a particular frequency, we have named it evoked resonant neural activity. Here, we determine whether this evoked activity is modulated by therapeutic stimulation – a critical attribute of a feedback signal. Furthermore, we investigated whether any related changes occurred in spontaneous local field potentials. Evoked and spontaneous neural activity was intraoperatively recorded from 19 subthalamic nuclei in patients with Parkinson's disease. Recordings were obtained before therapeutic stimulation and during 130 Hz stimulation at increasing amplitudes (0.67–3.38 mA), ‘washout’ of therapeutic effects, and non-therapeutic 20 Hz stimulation. Therapeutic efficacy was assessed using clinical bradykinesia and rigidity scores. The frequency and amplitude of evoked resonant neural activity varied with the level of 130 Hz stimulation (p < .001). This modulation coincided with improvement in bradykinesia and rigidity (p < .001), and correlated with spontaneous beta band suppression (p < .001). Evoked neural activity occupied a similar frequency band to spontaneous high-frequency oscillations (200-400 Hz), both of which decreased to around twice the 130 Hz stimulation rate. Non-therapeutic stimulation at 20 Hz evoked, but did not modulate, resonant activity. These results indicate that therapeutic deep brain stimulation alters the frequency of evoked and spontaneous oscillations recorded in the subthalamic nucleus that are likely generated by loops within the cortico-basal ganglia-thalamo-cortical network. Evoked resonant neural activity therefore has potential as a tool for providing insight into brain network function and has key attributes of a dynamic feedback signal for optimizing therapy.

The protective effects of citrullus colocynthis on inhibiting oxidative damage and autophagy-associated cell death in Parkinson's disease

• Citrullus colocynthis extract could improve the pathological state of Parkinson's disease in MPP + cell model and MPTP mouse model. • Bioinformatics analysis of the functional network of citrullus colocynthis revealed autophagy might involve in the anti-PD effect of citrullus colocynthis . • Citrullus colocynthis extract induced autophagy associated cell death via inhibited ROS-AMPK-ULK1 pathway in MPP + cell model. Citrullus colocynthis (CC), an ethnic medicine, distributed in Xinjiang Uygur Autonomous Region of China, is a traditional remedy for rheumatic arthritis or diseases caused by abnormal black biliary. Here, we investigated the therapeutic effect of CC on Parkinson's disease (PD) and its protective mechanisms. Firstly, the effects of CC on MPTP-induced PD mouse model were evaluated by a series of behavioral tests. Significant improvement of bradykinesia and memory reduction and reduction of climbing time were observed. Meanwhile, improvement of tyrosine hydroxylase (TH) and α-synuclein was also detected by immunohistochemical and western blot analysis. Additionally, it was also found that CC could relieve the oxidative stress in PD mouse brain tissues by decreasing activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and increasing activity of malondialdehyde (MDA). Moreover, possible protective mechanisms were analyzed by a set of combined bioinformatics methods. Subsequently, the mechanism was verified using immunofluorescence, flow cytometry and western blot. Results showed that CC could reduce oxidative damage by inhibiting the autophagy via ROS-AMPK-ULK1 signaling pathway in MPP + -induced SH-SY5Y cells. In conclusion, the present study validated that CC has a promising neuroprotective effect against PD, which can reduce oxidative stress and inhibiting autophagic cell death.

High-Cadence Cycling Promotes Sustained Improvement in Bradykinesia, Rigidity, and Mobility in Individuals with Mild-Moderate Parkinson's Disease.

Introduction Exercise has been shown to be an important adjunct therapy to medication in Parkinson's disease (PD). However, the optimal type, frequency, and intensity of exercise or physiotherapy are still being debated. An important part of understanding the optimal frequency is to examine how acute bouts of exercise affect motor function and mobility in this population. The purpose of this study is to assess if six bouts of high-cadence cycling improves motor function and mobility in individuals with PD. Methods Sixteen subjects with mild-moderate idiopathic PD were randomized into either a high-cadence cycling or a control (stretching) group. High-cadence cycling was completed on a custom motorized recumbent bicycle at a high cadence between 75 and 85 rpm. Cycling and stretching sessions were separated by 1 day of rest and took place over a 15-day period. Motor function and mobility were assessed after every cycling/stretching bout using the UPDRS Motor III scale, Kinesia ONE, and Timed up and Go (TUG). Results Six bouts of high-cadence cycling improved UPDRS scores (2.5 pts, P=0.002), hand movement amplitude (P=0.013), rapid alternating hand movement speed (P=0.003), gait (P=0.012), and TUG time (1.17 s, P=0.002) from baseline testing to end of treatment. The control group showed no improvements. Conclusions These findings suggest that they are both acute and sustained improvements in motor function and mobility after high-cadence cycling. Future research should examine how exercise type, frequency, and intensity can be optimized for each individual.

Effect of Subthalamic Deep Brain Stimulation on Upper Limb Dexterity in Patients with Parkinson Disease

The efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on dexterity remains controversial despite its recognition as an effective strategy for Parkinson disease. The present study investigated the efficacy of STN-DBS for ameliorating bradykinesia and dexterity compared with dopaminergic medications. Part III of the Unified Parkinson's Disease Rating Scale was used for the evaluation of bradykinesia, whereas the Purdue Pegboard Test and the Box and Block test were selected for dexterity. Our findings indicate that bradykinesia is significantly improved with both DBS and dopaminergic medication, whereas dexterity is improved only with DBS. Dopaminergic medication did not show a satisfactory efficacy on dexterity, and there was little synergistic effect of dopaminergic medication and STN-DBS for improving dexterity associated with Parkinson disease. Our results suggest that DBS is potentially more effective than dopaminergic medications for improving dexterity. The disparities in efficacy for bradykinesia and dexterity between DBS and dopaminergic medication hint at the potential mechanisms of STN-DBS. We speculate that DBS follows at least 2 different mechanisms for improving parkinsonian symptoms: 1) the dopaminergic system, primarily for the improvement of bradykinesia and 2) the nondopaminergic system, for the improvement of dexterity. This hypothesis requires further verification and investigation.

Investigation on the relationship between oxidative stress and cognitive neuropsychology status in patients with MS

The efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on dexterity remains controversial despite its recognition as an effective strategy for Parkinson disease. The present study investigated the efficacy of STN-DBS for ameliorating bradykinesia and dexterity compared with dopaminergic medications.Part III of the Unified Parkinson's Disease Rating Scale was used for the evaluation of bradykinesia, whereas the Purdue Pegboard Test and the Box and Block test were selected for dexterity.Our findings indicate that bradykinesia is significantly improved with both DBS and dopaminergic medication, whereas dexterity is improved only with DBS. Dopaminergic medication did not show a satisfactory efficacy on dexterity, and there was little synergistic effect of dopaminergic medication and STN-DBS for improving dexterity associated with Parkinson disease.Our results suggest that DBS is potentially more effective than dopaminergic medications for improving dexterity. The disparities in efficacy for bradykinesia and dexterity between DBS and dopaminergic medication hint at the potential mechanisms of STN-DBS. We speculate that DBS follows at least 2 different mechanisms for improving parkinsonian symptoms: 1) the dopaminergic system, primarily for the improvement of bradykinesia and 2) the nondopaminergic system, for the improvement of dexterity. This hypothesis requires further verification and investigation.