Detection of Parkinsonian Motor Symptoms Using Non-Invasive Motion Sensing Technology

Parkinson’s Disease (PD) is characterized by impaired movement, resting tremor, and muscle rigidity. The Unified PD Rating Scale (UPDRS) is a standardized protocol used by neurologists to measure progression of disease as well as evaluation of treatments. However, this examination is subjective, time consuming, and results can be affected by stress, diet, or sleep. Our goal is to develop a non-invasive device that can record objective clinically-relevant measurements during subtasks of the UPDRS to allow for remote evaluations, which would be beneficial considering the frequency of clinical visits for medication adjustments. Five healthy individuals (ages 21-59) completed UPDRS tasks 3.6 (pronation/supination of hands) and 3.17 (rest tremor amplitude). Participants performed these tasks twice, first normally and second simulating PD patients (tremor, bradykinesia, reduction of movement amplitude) after viewing example videos. Motion data including linear and angular accelerations in 3 dimensions was acquired using a lightweight wrist-mounted motion sensor. Three features were extracted: (1) Power of higher frequency components of the linear acceleration signal (rest task), as a measure of resting tremor amplitude. (2) Power of higher frequency components of the rotational acceleration signal (pronation/supination task), as a measure of bradykinesia. (3) Standard deviation of the local maxima of the rotational acceleration (pronation/supination task), as a measure of reduction in movement speed and amplitude. These features were used to correctly differentiate trials completed with and without simulated PD symptoms, using an SVM classifier with leave-one-out cross validation accuracy of 95%. These findings suggest it is possible to capture clinical features of PD using motion sensors. Future work in PD patients will examine how these measures correlate with UPDRS evaluations and whether they will be helpful in providing a quick, objective telehealth measure of progression and treatment response that can supplement current tools.

Identifying and modulating distinct tremor states through peripheral nerve stimulation in Parkinsonian rest tremor

Background Resting tremor is one of the most common symptoms of Parkinson’s disease. Despite its high prevalence, resting tremor may not be as effectively treated with dopaminergic medication as other symptoms, and surgical treatments such as deep brain stimulation, which are effective in reducing tremor, have limited availability. Therefore, there is a clinical need for non-invasive interventions in order to provide tremor relief to a larger number of people with Parkinson’s disease. Here, we explore whether peripheral nerve stimulation can modulate resting tremor, and under what circumstances this might lead to tremor suppression. Methods We studied 10 people with Parkinson’s disease and rest tremor, to whom we delivered brief electrical pulses non-invasively to the median nerve of the most tremulous hand. Stimulation was phase-locked to limb acceleration in the axis with the biggest tremor-related excursion. Results We demonstrated that rest tremor in the hand could change from one pattern of oscillation to another in space. Median nerve stimulation was able to significantly reduce (− 36%) and amplify (117%) tremor when delivered at a certain phase. When the peripheral manifestation of tremor spontaneously changed, stimulation timing-dependent change in tremor severity could also alter during phase-locked peripheral nerve stimulation. Conclusions These results highlight that phase-locked peripheral nerve stimulation has the potential to reduce tremor. However, there can be multiple independent tremor oscillation patterns even within the same limb. Parameters of peripheral stimulation such as stimulation phase may need to be adjusted continuously in order to sustain systematic suppression of tremor amplitude.

Safety and Tolerability of a Wearable, Vibrotactile Stimulation Device for Parkinson’s Disease

Background: Resting tremor is a cardinal symptom of Parkinson’s disease (PD) that contributes to the physical, emotional, and economic burden of the disease.Objective: The goal of this study was to investigate the safety, tolerability, and preliminary effectiveness of a novel wearable vibrotactile stimulation device on resting tremor in individuals with PD.Methods: Using a randomized cross-over design, subjects received two different vibrotactile stimulation paradigms (high amplitude patterned and low amplitude continuous) on two separate laboratory visits. On each visit, resting tremor was video recorded for 10 min at baseline and while the vibrotactile stimulation was applied. Tremor severity was scored by a blinded clinician.Results: Both vibration paradigms were well safe and well tolerated and resulted in a reduction in resting tremor severity with a moderate effect size (n = 44, p < 0.001, r = 0.37–0.54). There was no significant difference between the two vibration paradigms (p = 0.14).Conclusion: Short durations of vibrotactile stimulation delivered via wearable devices were safe and well tolerated and may attenuate resting tremor severity in individuals with PD. The sample size as well as the potential preliminary effectiveness revealed by two arms of the study could not eliminate the potential for a placebo effect.

Medicinal plants possessed anti-Parkinsonian effects with emphasis on their mechanisms of action

Parkinsonʼs disease is a progressive neurodegenerative dysfunction characterized by the loss of dopaminergic neurons of the nigrostriatal system. Dopamine is important to maintain normal movement patterns. The cardinal physical signs of the disease are distal resting tremor, rigidity, bradykinesia, and asymmetric onset. Treatment aims to improve these motor symptoms. Many medicinal plants possessed Parkinsonian effects by different mechanisms, included inhibition of α-synuclein condensation, reduction of oxidative stress and neuro-inflammation, increase of dopaminergic neurons survival, blockade of the adenosine A2A receptor and regulation of molecular pathways involved in neuronal survival such as MAPK, Nrf2, and NF-κB, thus exerted neuroprotective actions. In the present review, we highlight the medicinal plants with potential anti-Parkinsonian effects with discussing the mechanisms of their beneficial effects.

Comprehensive analysis of resting tremor based on acceleration signals of patients with Parkinson’s disease

BACKGROUND: Resting tremor is an essential characteristic in patients suffering from Parkinson’s disease (PD). OBJECTIVE: Quantification and monitoring of tremor severity is clinically important to help achieve medication or rehabilitation guidance in daily monitoring. METHODS: Wrist-worn tri-axial accelerometers were utilized to record the long-term acceleration signals of PD patients with different tremor severities rated by Unified Parkinson’s Disease Rating Scale (UPDRS). Based on the extracted features, three kinds of classifiers were used to identify different tremor severities. Statistical tests were further designed for the feature analysis. RESULTS: The support vector machine (SVM) achieved the best performance with an overall accuracy of 94.84%. Additional feature analysis indicated the validity of the proposed feature combination and revealed the importance of different features in differentiating tremor severities. CONCLUSION: The present work obtains a high-accuracy classification in tremor severity, which is expected to play a crucial role in PD treatment and symptom monitoring in real life.

Detection and Quantification of Resting Tremor in Parkinson’s Disease Using Long-Term Acceleration Data

Long-term monitoring of resting tremor is key to assess the status of patients suffering from Parkinson’s disease (PD), which is of vital importance for reasonable medication. The detection and quantification of resting tremor in reported works rely heavily on specified movements and are not appropriate for long-term monitoring in real-life condition. The purpose of this study is to develop a detection model for long-term monitoring of resting tremor and explore an effective indicator for tremor quantification. This study included long-term acceleration data from PD patients and proposed a resting tremor detection model based on machine learning classifiers and Synthetic Minority Oversampling Technique (SMOTE). Four machine learning classifiers, K-Nearest Neighbor (KNN), Random Forest (RF), Adaptive Boosting (AdaBoost), and Support Vector Machine (SVM), were compared. Furthermore, an indicator called tremor timing ratio (TTR) was defined and calculated for tremor quantification. The detection model with RF classifier achieved the highest overall accuracy of 94.81%. The sample entropy of the acceleration signal was proved most influential in the classification by exploring the feature importance. Through the Kruskal-Wallis test and the Mann-Whitney U test, the TTR had a strong correlation with the subscore of resting tremor in Unified Parkinson Disease Rating Scale (UPDRS). Such two-step evaluation process for resting tremor can detect the tremor effectively and is expected to be applied in long-term monitoring of PD patients in daily life to realize a more comprehensive assessment of PD.

LRRK2 along the Golgi and lysosome connection: a jamming situation

Parkinson's disease (PD) is an age-related neurodegenerative disorder, clinically characterized by bradykinesia, rigidity, and resting tremor. Leucine-Rich Repeat Kinase 2 (LRRK2) is a large, multidomain protein containing two enzymatic domains. Missense mutations in its coding sequence are amongst the most common causes of familial PD. The physiological and pathological impact of LRRK2 is still obscure, but accumulating evidence supports a role for LRRK2 in membrane and vesicle trafficking, mainly functioning in the endosome-recycling system, (synaptic) vesicle trafficking, autophagy, and lysosome biology. LRRK2 binds and phosphorylates key regulators of the endomembrane systems and is dynamically localized at the Golgi. The impact of LRRK2 on the Golgi may reverberate throughout the entire endomembrane system and occur in multiple intersecting pathways, including endocytosis, autophagy, and lysosomal function. This would lead to overall dysregulation of cellular homeostasis and protein catabolism, leading to neuronal dysfunction and accumulation of toxic protein species, thus underlying the possible neurotoxic effect of LRRK2 mutations causing PD.

A Case Report on Late-onset Friedrich's Ataxia and Response on Parkinsonism Treatment

Friedrich's ataxia is a progressive neurodegenerative disease that affects the posterior cord of the spinal tract. We present a case of an 83-year-old male with resting tremor and rigidity that had gradually worsened over the past few years. The patient has been diagnosed with Friedrich's ataxia. Unlike typical Friedrich ataxia, this patient does not have a shortened life expectancy. There is a small percentage of atypical patients demonstrate late-onset of disease, isolated spastic paraparesis without ataxia, and retained or exacerbated deep tendon reflex. Although there is no association between Parkinson's disease and Friedrich's ataxia; in our case, treatment of tremor and rigidity improves the patient's quality of life.

Increasing Serotonin to Reduce Parkinsonian Tremor

While current dopamine-based drugs seem to be effective for most Parkinson's disease (PD) motor dysfunctions, they produce variable responsiveness for resting tremor. This lack of consistency could be explained by considering recent evidence suggesting that PD resting tremor can be divided into different partially overlapping phenotypes based on the dopamine response. These phenotypes may be associated with different pathophysiological mechanisms produced by a cortical-subcortical network involving even non-dopaminergic areas traditionally not directly related to PD. In this study, we propose a bio-constrained computational model to study the neural mechanisms underlying a possible type of PD tremor: the one mainly involving the serotoninergic system. The simulations run with the model demonstrate that a physiological serotonin increase can partially recover dopamine levels at the early stages of the disease before the manifestation of overt tremor. This result suggests that monitoring serotonin concentration changes could be critical for early diagnosis. The simulations also show the effectiveness of a new pharmacological treatment for tremor that acts on serotonin to recover dopamine levels. This latter result has been validated by reproducing existing data collected with human patients.

Immunotherapies for Parkinson’s disease: Progression of Clinical Development

: Parkinson’s disease is a common neurodegenerative disease affecting the movement and wellbeing of most elderlies. The manifestations of Parkinson’s disease often include resting tremor, stiffness, bradykinesia and muscular rigidity. The typical hallmark of Parkinson’s disease is the destruction of neurons in the substantia nigra and the presence of Lewy bodies in different compartments of the central nervous system. Due to various limitations to the currently available treatments, immunotherapies have emerged to be the new approach to Parkinson’s disease treatment. This approach shows some positive outcomes on the efficacy in removing the aggregated species of alpha-synuclein, which is believed to be one of the causes of Parkinson’s disease. In this review, an overview of how alpha-synuclein contributes to Parkinson’s disease and the effects of a few new immunotherapeutic treatments, including BIIB054 (cinpanemab), MEDI1341, AFFITOPE and PRX002 (prasinezumab) that are currently under clinical development, will be discussed.