Rest Tremor Amplitude Research Articles

Rest Tremor in Parkinson's Disease Is Associated with Ipsilateral Striatal Dopamine Transporter Binding.

The cardinal motor symptoms of Parkinson's disease (PD) include rigidity, bradykinesia, and rest tremor. Rigidity and bradykinesia correlate with contralateral nigrostriatal degeneration and striatal dopamine deficit, but association between striatal dopamine function and rest tremor has remained unclear. The aim of this study was to investigate the possible link between dopamine function and rest tremor using Parkinson's Progression Markers Initiative dataset, the largest prospective neuroimaging cohort of patients with PD. Clinical, [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT), and structural magnetic resonance imaging data from 354 early PD patients and 166 healthy controls were included in this study. We employed a novel approach allowing nonlinear registration of individual scans accurately to a standard space and voxelwise analyses of the association between motor symptoms and striatal dopamine transporter (DAT) binding. Severity of both rigidity and bradykinesia was negatively associated with contralateral striatal DAT binding (PFWE < 0.05 [FWE, family-wise error corrected]). However, rest tremor amplitude was positively associated with increased ipsilateral DAT binding (PFWE < 0.05). The association between rest tremor and binding remained the same controlling for Hoehn & Yahr stage, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, bradykinesia-rigidity score, or motor phenotype. The association between rest tremor and binding was independent of bradykinesia-rigidity and replicated using 2-year follow-up data (PFWE < 0.05). In agreement with the existing literature, we did not find a consistent association between rest tremor and contralateral dopamine defect. However, our results demonstrate a link between rest tremor and increased or less decreased ipsilateral DAT binding. Our findings provide novel information about the association between dopaminergic function and parkinsonian rest tremor. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

P.051 Parkinson’s disease tremor can show entrainment and distractibility with tapping test

Background: Electrophysiological tests such as the tapping test are used to distinguish functional and organic tremors, in which patients with functional tremor commonly show entrainment and amplitude reduction (&gt;50% decrease relative to baseline) of contralateral tremor during tapping. While these features are suggested to be specific to functional tremor, the tapping test in Parkinson’s disease (PD) tremor has not been tested. Methods: We evaluated 18 PD patients (2F, age 64.17±7.30 [mean±SD] years) with rest and postural tremors using surface electromyography and triaxial accelerometry. Patients were recorded while tapping at 1, 3 and 5 Hz with the contralateral arm at rest or outstretched. Tremor amplitude and frequency were calculated using power spectrum analysis from accelerometer recordings. Results: Reduction of rest tremor amplitude was observed in 3/18 patients during 1 and 3 Hz tapping. Reduction was seen in 3/16 and 1/16 patients with postural tremors at 1 and 3 Hz tapping, respectively. Frequency shifts (&gt;1.5 Hz) were observed in 3/18 rest tremors and 6/16 postural tremors. Seven patients exhibited rest and/or postural tremor entrainment during 3 or 5 Hz tapping. Conclusions: Distractibility and entrainment can be found in PD tremor. The tapping test may not reliably distinguish between PD tremor and functional tremor.

Reduced platelet 5-HT content is associated with rest tremor in Parkinson's disease

IntroductionParkinson's disease (PD) is highly heterogeneous in manifestations and pathogenesis. Serotonergic neurotransmitter system dysfunction is frequently implicated in PD tremor. Serotonin (5-HT) content in platelets is highly correlated with that in cerebrospinal fluid. In this study, we aimed to understand whether and how platelet 5-HT content reflects tremor in PD. MethodA total of 139 Chinese PD patients met with inclusion criteria were recruited. Motor and non-motor scores, and disease severity were evaluated. Patients were classified into subtypes of tremor-dominant (TD) and non-tremor-dominant (NTD). Peripheral platelets were isolated, and platelet 5-HT levels were measured. ResultsPlatelet 5-HT content was lower in PD patients of TD subtype than in NTD subtype. Multifactor risk analysis showed that this lower content was independently associated with the TD phenotype. Platelet 5-HT level was inversely correlated with total tremor score, rest tremor amplitude score, rest tremor constancy score, and index of rest tremor, but not with postural tremor score, and kinetic tremor score. ConclusionThe cross-sectional study demonstrates that reduced platelet 5-HT content is associated with PD rest tremor. Our results support the involvement of serotonergic disturbance in PD rest tremor and indicate that 5-HT reduction can be manifested in peripheral platelets.

Evaluation of rest tremor in different positions in Parkinson's disease and essential tremor plus.

Rest tremor (RT) can be observed in several positions (seated, standing, lying down) but it is unknown whether the tremor features may vary across them. This study aimed to compare the RT electrophysiological features across different positions in tremor-dominant Parkinson's disease (PD) and essential tremor plus (ET with RT, rET). We consecutively enrolled 90 tremor-dominant PD and 24 rET patients. The RT presence was evaluated in three positions: with the patient seated, the arm flexed at 90°, the forearm supported against gravity, and the hand hanging down from the chair armrest (hand-hanging position), in lying down supine and in standing position. RT electrophysiological features (amplitude, frequency, burst duration, pattern) were compared between the two patient groups and across the different positions. All PD and rET patients showed RT in hand-hanging position. Supine and standing RT were significantly more common in PD (67.8% and 75.6%, respectively) than in rET patients (37.5% and 45.8%, respectively). RT amplitude, frequency and pattern were significantly different between groups in hand-hanging position whereas only pattern was significantly different between PD and rET in both standing and supine positions. In each patient group, all RT electrophysiological features did not significantly vary across different recording positions (p > 0.05). In our study, PD and rET showed RT in hand-hanging, supine, and standing positions. RT pattern was the only electrophysiological feature significantly different between PD and rET patients in all these positions, enabling clinicians to perform the RT analysis for diagnostic purposes in different tremor positions.

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.

Machine Learning-Based Automatic Rating for Cardinal Symptoms of Parkinson Disease.

We developed and investigated the feasibility of a machine learning-based automated rating for the 2 cardinal symptoms of Parkinson disease (PD): resting tremor and bradykinesia. Using OpenPose, a deep learning-based human pose estimation program, we analyzed video clips for resting tremor and finger tapping of the bilateral upper limbs of 55 patients with PD (110 arms). Key motion parameters, including resting tremor amplitude and finger tapping speed, amplitude, and fatigue, were extracted to develop a machine learning-based automatic Unified Parkinson's Disease Rating Scale (UPDRS) rating using support vector machine (SVM) method. To evaluate the performance of this model, we calculated weighted κ and intraclass correlation coefficients (ICCs) between the model and the gold standard rating by a movement disorder specialist who is trained and certified by the Movement Disorder Society for UPDRS rating. These values were compared to weighted κ and ICC between a nontrained human rater and the gold standard rating. For resting tremors, the SVM model showed a very good to excellent reliability range with the gold standard rating (κ 0.791; ICC 0.927), with both values higher than that of nontrained human rater (κ 0.662; ICC 0.861). For finger tapping, the SVM model showed a very good reliability range with the gold standard rating (κ 0.700 and ICC 0.793), which was comparable to that for nontrained human raters (κ 0.627; ICC 0.797). Machine learning-based algorithms that automatically rate PD cardinal symptoms are feasible, with more accurate results than nontrained human ratings. This study provides Class II evidence that machine learning-based automated rating of resting tremor and bradykinesia in people with PD has very good reliability compared to a rating by a movement disorder specialist.

Effect of eccentric-based rehabilitation on hand tremor intensity in Parkinson disease.

Hand tremor is a disturbing yet sometimes resistant symptom in persons with Parkinson disease (PD). Although many exercise regimens for these people have gained attention in recent years, the effect of resistance training and especially eccentric training on parkinsonian tremor is still uncertain. This study was conducted to investigate the precise effect of upper limb eccentric training on hand tremor in PD. In this randomized controlled trial, a consecutive sample of 21 persons with PD recruited from general hospitals went through 6 weeks of upper limb pure eccentric training as the intervention group (n = 11) or no additional exercise during this period as the control group (n = 10). Resting and postural tremor amplitudes were measured with the cellphone-based accelerometer. Comparing hand tremor amplitudes before and after the trial showed a significant reduction in resting tremor amplitude in the intervention group after exercise sessions (p < 0.05) while detecting no changes in the control group during 6 weeks of study. Meanwhile, postural tremor amplitude remained unchanged in both groups.

Sensitivity and specificity of different hand positions to assess upper limb rest tremor.

Hand position for rest tremor evaluation in PD is not standardized. We evaluated the sensitivity and specificity of different hand positions commonly used to evaluate rest tremor. Twenty patients with PD and rest tremor were included as cases and 20 patients with essential tremor without rest tremor as controls. Video and accelerometric recordings were conducted in semiprone, completely prone, and with hands hanging down from armrest positions. Three movement disorder specialists rated tremor in each different position using Movement Disorder Society UPDRS items 3.17 and 3.18. Hands hanging showed the highest amplitude (P = 0.004) and constancy (P = 0.015) scores. Sensitivity and specificity analysis for each position showed the following sensitivity/specificity results: semiprone, 95%/80%; completely prone, 85%/98.33%; and hands hanging, 96.66%/63.33%, respectively. The hands-hanging position was shown to be the most suitable for evaluating rest tremor amplitude in PD, whereas the completely prone position proved to be more specific to detect rest tremor. The preferred hand position would depend on the purpose of the examination. © 2019 International Parkinson and Movement Disorder Society.

Identifying of factor associated with parkinson’s disease subtypes using random forest

Parkinson’s disease (PD) is a neurodegenerative disorder that caused by the result of lack of dopamine in a specific area of the brain called bangsal ganglia. It is a long term degenerative disorder of the central nervous system that mainly effect the motor system that has some impacts such as difficulty in speech, problem in swallowing, and dressing, trouble with handwriting or even doing some activities, and tremor. Based on this problem, researchers use the Parkinson’s Progression Markers Initiative (PPMI) database to classify subtypes: Tremor Dominant (TD) and Postural Instability Gait Difficulty (PIGD). Identifying the factors of Parkinson’s disease subtypes is crucial in understanding the appropriate therapy for Parkinson’s disease patient. Furthermore, it gives some characteristics of patient that is classified into TD or PIGD. Classification method is used to identify the factors of parkinson’s disease subtypes on 207 patient with PD and 47 variables obtained from Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) part II and part III in event V12. The result is PD patient who is classified to PIGD class have the lower value in constancy of rest tremor, rest tremore amplitude (RUE), tremor, rest tremor amplitude (LUE), and postural tremor of right hand than PD patient with TD and the higher value in postural stability, walking and balance, and freezing than PD patient with TD.

Rest tremor quantification based on fuzzy inference systems and wearable sensors

BackgroundCurrently the most consistent, widely accepted and detailed instrument to rate Parkinson’s disease (PD) is the Movement Disorder Society sponsored Unified Parkinson Disease Rating Scale (MDS-UPDRS). However, the motor examination is based upon subjective human interpretation trying to capture a snapshot of PD status. Wearable sensors and machine learning have been broadly used to analyze PD motor disorder, but still most ratings and examinations lay outside MDS-UPDRS standards. Moreover, logical connections between features and output ratings are not clear and complex to derive from the model, thus limiting the understanding of the structure in the data. MethodsFifty-seven PD patients underwent a full motor examination in accordance to the MDS-UPDRS on twelve different sessions, gathering 123 measurements. Overall, 446 different combinations of limb features correlated to rest tremors amplitude are extracted from gyroscopes, accelerometers, and magnetometers and feed into a fuzzy inference system to yield severity estimations. ResultsA method to perform rest tremor quantification fully adhered to the MDS-UPDRS based on wearable sensors and fuzzy inference system is proposed, which enables a reliable and repeatable assessment while still computing features suggested by clinicians in the scale. This quantification is straightforward and scalable allowing clinicians to improve inference by means of new linguistic statements. In addition, the method is immediately accessible to clinical environments and provides rest tremor amplitude data with respect to the timeline. A better resolution is also achieved in tremors rating by adding a continuous range.

Progression of tremor in early stages of Parkinson's disease: a clinical and neuroimaging study.

Rest tremor is one of the cardinal signs of Parkinson's disease. Kinetic and postural tremors may also occur. The coexistence of these three types of tremor at disease onset and their subsequent progression could have important clinical and therapeutic implications but remain to be fully elucidated. We aimed to: (i) evaluate prevalence and progression of these three types of tremor in early stages of the disease; and (ii) investigate longitudinally the relationship between dopaminergic and serotonergic terminal dysfunction, rest tremor severity and its response to dopaminergic therapy. The Parkinson's Progressive Markers Initiative database provided the baseline and 2-year follow-up clinical ratings and 123ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodophenyltropane (123I-FP-CIT) single photon emission computed tomography images for this study. 123I-FP-CIT measured putamen dopamine transporter and median raphe serotonin transporter availability. A raphe/putamen uptake ratio was calculated for each patient as an index of relative involvement of these structures. Clinical analysis of tremor was conducted on 378 patients: 87.8% presented with tremor at baseline; rest tremor occurred in 69.6% of patients at baseline; and 67.9% at follow-up. Postural and kinetic tremors occurred in about 50% of patients at both baseline and follow-up. Over 20% of patients presenting with tremor did not exhibit a rest component at baseline. The number of patients with isolated rest tremor was halved at follow-up. In tremor predominant patients, rest tremor severity was inversely correlated with raphe serotonin transporter availability both at baseline and follow-up (baseline: constancy P < 0.05, tremor index P < 0.05; follow-up: amplitude P < 0.05, constancy P < 0.05, tremor index P < 0.05). In the entire cohort, more severe tremor scores correlated with lower raphe/putamen uptake ratio values, indicative of more severe raphe dysfunction (baseline: constancy P < 0.01, tremor index P < 0.05; follow-up: amplitude P < 0.01, constancy P < 0.001, tremor index P < 0.001). The percentage of improvement in rest tremor amplitude after acute dopaminergic therapy was smaller in patients with lower raphe/putamen uptake ratio values (P < 0.01). Rest tremor is the most represented type of tremor in early Parkinson's disease. However, postural and kinetic tremor can affect approximately half of these patients and can occur in absence of resting tremor. As disease progresses, both raphe serotonergic dysfunction and putamen dopamine depletion could contribute to the occurrence of rest tremor. The former is linked to more severe tremor scores and poorer response to dopaminergic therapy. Non-dopaminergic treatments might be beneficial for patients whose tremor is associated with a raphe-predominant dysfunction.

EP 97. Strength lies in peace. Cognitive stress reduces the effect of levodopa on Parkinson’s resting tremor

Background Resting tremor in Parkinson’s disease (PD) is markedly increased during cognitive stress. Dopamine depletion in the basal ganglia has a role in the pathophysiology of resting tremor, but it is unclear whether this contribution varies between behavioral settings. Here, we test the hypothesis that levodopa effect on resting tremor amplitude and variability alters during rest and cognitive co-activation. Methods We included 69 PD patients with prominent resting tremor. Patients were measured both OFF medication and after levodopa-benserazide 200/50 mg, using clinical scores (MDS-UPDRS) and accelerometry. We compared two contexts: rest and cognitive co-activation (counting backwards in steps of 7 as fast as possible). We investigated the influence of levodopa and cognitive co-activation, and the interaction between these factors, on resting tremor amplitude and variability. Results Levodopa significantly reduced maximal resting tremor intensity, while cognitive co-activation increased it ( p 0.001 ). Crucially, the levodopa effect was significantly smaller during cognitive co-activation than during rest. In other words, the positive effect of levodopa was counteracted by a negative effect of cognitive stress (sign. TREATMENT × CONTEXT interaction, p = 0.02). Furthermore, levodopa significantly increased resting tremor variability but variability was smaller during cognitive co-activation ( p 0.001 ; here without sign. TREATMENT × CONTEXT interaction). Conclusion Cognitive co-activation reduced the levodopa effect on resting tremor and it reduced tremor variability. This underlines the importance of simple counting tasks in clinical practice, as measurements at rest will overestimate the treatment effect. The reduced levodopa effect during cognitive stress might be caused by non-dopaminergic mechanisms amplifying tremor. Future research aims to identify clinical, electrophysiological and cerebral factors influencing the levodopa effect on resting tremor.

A system to monitor tremors in patients with Parkinson's disease.

In this work the design and development of a system to monitor tremors in patients with Parkinson's disease based on Arduino open-source prototyping platform is presented. For processing data tremors acquired by the sensor device we have developed an Android application which allows an evaluation of the state of PD patients based on three types of tests that are in the Unified Parkinson's Disease Rating Scale recommended by the Movement Disorder Society (MDS-UPDRS); the tests performed in the application are: postural tremor of the hands, kinetic tremors of the hands and resting tremor amplitude. The results of PD Patients showed that despite receiving medication to minimize symptoms of their disease, patients have a considerable tremor amplitude, which affects the normal development of their daily activities. In addition, the spectral analysis of the tremors shows that two of the patients were correctly diagnosed with PD while the third patient showed spectral characteristics which led us to suggest to the treating physician reconsider the diagnosis.

Clinical correlates of raphe serotonergic dysfunction in early Parkinson's disease.

Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous Parkinson's disease subgroup had significantly lower raphe serotonin transporter availability but less severe striatal dopaminergic deficits compared to akinetic-rigid patients with no resting tremor (P < 0.05). In tremulous patients, raphe serotonin transporter availability was also associated with rest tremor constancy (β = -0.380, P < 0.05) and index of rest tremor severity (β = -0.322, P < 0.05). There was no association between raphe serotonin transporter availability and fatigue, depression, excessive daytime sleepiness, or rapid eye movement sleep behaviour disorder in early Parkinson's disease. We conclude that the raphe nuclei are affected in a subgroup of early drug-naïve Parkinson's disease patients and that reduced raphe serotonin transporter availability is associated with the severity of resting tremor but not non-motor symptoms.

Tremor Suppression by Rhythmic Transcranial Current Stimulation

SummaryTremor can dominate Parkinson’s disease and yet responds less well to dopaminergic medications than do other cardinal symptoms of this condition [1, 2]. Deep brain stimulation can provide striking tremor relief, but the introduction of stimulating electrodes deep in the substance of the brain carries significant risks, including those of hemorrhage [3]. Here, we pioneer an alternative approach in which we noninvasively apply transcranial alternating current stimulation (TACS) over the motor cortex [4, 5] to induce phase cancellation of the rest tremor rhythm. We first identify the timing of cortical oscillations responsible for rest tremor in the periphery by delivering tremor-frequency stimulation over motor cortex but do not couple this stimulation to the on-going tremor—instead, the rhythms simply “drift” in and out of phase alignment with one another. Slow alternating periods of phase cancellation and reinforcement result, informing on the phase alignments that induce the greatest change in tremor amplitude. Next, we deliver stimulation at these specified phase alignments to demonstrate controlled suppression of the on-going tremor. With this technique we can achieve almost 50% average reduction in resting tremor amplitude and in so doing form the basis of a closed-loop tremor-suppression therapy that could be extended to other oscillopathies.

Expanded and independent validation of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).

The Movement Disorder Society-UPDRS (MDS-UPDRS) was published in 2008, showing satisfactory clinimetric results and has been proposed as the official benchmark scale for Parkinson's disease. The present study, based on the official MDS-UPDRS Spanish version, performed the first independent testing of the scale and adds information on its clinimetric properties. The cross-culturally adapted MDS-UPDRS Spanish version showed a comparative fit index ≥ 0.90 for each part (I-IV) relative to the English-language version and was accepted as the Official MDS-UPDRS Spanish version. Data from this scale, applied with other assessments to Spanish-speaking Parkinson's disease patients in five countries, were analyzed for an independent and complementary clinimetric evaluation. In total, 435 patients were included. Missing data were negligible and moderate floor effect (30 %) was found for Part IV. Cronbach's α index ranged between 0.79 and 0.93 and only five items did not reach the 0.30 threshold value of item-total correlation. Test-retest reliability was adequate with only two sub-scores of the item 3.17, Rest tremor amplitude, reaching κ values lower than 0.60. The intraclass correlation coefficient was higher than 0.85 for the total score of each part. Correlation of the MDS-UPDRS parts with other measures for related constructs was high (≥ 0.60) and the standard error of measurement lower than one-third baseline standard deviation for all subscales. Results confirm those of the original study and add information on scale reliability, construct validity, and precision. The MDS-UPDRS Spanish version shows satisfactory clinimetric characteristics.

Synchronous pattern distinguishes resting tremor associated with essential tremor from rest tremor of Parkinson’s disease

Rest tremor associated with essential tremor (ET) is a condition that poses challenges in diagnosing Parkinson’s disease (PD). We investigated tremor parameters in PD and ET patients with rest tremor. Fifteen patients with PD and 15 patients with ET underwent electrophysiological examination to evaluate characteristics of muscle bursting in rest postures. Rest tremor amplitude of PD patients was significantly higher than that of patients with ET (p = 0.002), whereas burst duration and frequency were significantly higher in ET than in PD group (p = 0.002, p < 0.001, respectively). Patients with PD, however, showed some overlap of these electrophysiological values with values from patients with ET. By contrast, rest tremor pattern showed no overlap between the two diseases, because all patients with ET presented a synchronous pattern whereas PD patients had an alternating pattern (p < 0.001), a finding that differentiated the patients on an individual basis. The electromyographic pattern of rest tremor may help to differentiate PD from ET.

Tremor amplitude and tremor frequency variability in Parkinson’s disease is dependent on activity and synchronisation of central oscillators in basal ganglia

Rest tremor is one of the four main clinical features of Parkinson's disease (PD), besides rigidity, bradykinesia and postural instability. While rigidity, bradykinesia and postural instability can be explained with changes in neurotransmitter concentrations and neuronal activity in basal ganglia, the pathogenesis of parkinsonian tremor is not fully understood. According to the leading hypothesis tremor is generated by neurons or groups of neurons in the basal ganglia which act as central oscillators and generate repetitive impulses to the muscles of the body parts involved. The exact morphological substrate for central oscillators and the mechanisms leading to their activation are still an object of debate. Peripheral neural structures exert modulatory influence on tremor amplitude, but not on tremor frequency. We hypothesise that rest tremor in PD is the result of two mechanisms: increased activity and increased synchronisation of central oscillators. We tested our hypothesis by demonstrating that the reduction in rest tremor amplitude is accompanied by increased variability of tremor frequency. The reduction of tremor amplitude is attributed to decreased activity and poor synchronisation of central oscillators in basal ganglia; the increased variability of tremor frequency is attributed to poor synchronisation of the central oscillators. In addition, we demonstrated that the recurrence of clinically visible rest tremor is accompanied by a reduction in tremor frequency variability. This reduction is attributed to increased synchronisation of central oscillators in basal ganglia. We argue that both mechanisms, increased activity of central oscillators and increased synchronisation of central oscillators, are equally important and we predict that tremor becomes clinically evident only when both mechanisms are active at the same time. In circumstances when one of the mechanisms is suppressed tremor amplitude becomes markedly reduced. On the one hand, if the number of active central oscillators is very low, the muscle-stimulating impulses are too weak to cause clinically evident tremor. On the other hand, if central oscillator synchronisation is poor, the impulses originating from different central oscillators are not in phase and thus cancel out, again leading to reduced stimulation of muscles and reduced tremor amplitude. Our hypothesis is supported by our measurements on patients with PD and by experimental data cited in the literature. The proposed two mechanisms could have clinical implications. New medical treatments, which would specifically target only one of the proposed mechanisms (oscillator activity or synchronisation), could be effective in reducing tremor amplitude and thus supplement established antiparkinsonian treatments.

Rapid response of parkinsonian tremor to STN‐DBS changes: Direct modulation of oscillatory basal ganglia activity?

Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor and other cardinal symptoms in Parkinson's disease (PD), the precise mechanisms of action of DBS are still unclear. We analyzed the time course of resting tremor amplitude and frequency during discontinuation and subsequent reinitiation of STN-DBS in nine PD patients, using a computerized three-dimensional motion analysis combined with surface electromyography. Following discontinuation of STN-DBS, resting tremor amplitude rapidly increased, reaching maximum amplitude after 2 min (mean +/- 95%CI: 34.3 +/- 13.8 mm; P < 0.01), subsequently stabilizing at a medium level. Reinitiation of stimulation after 30 min resulted in rapid, nearly complete suppression of tremor activity within 1 min (1.4 +/- 1.3 mm; P < 0.01) and, furthermore, increased tremor frequency within a few seconds in seven of nine patients. These findings support the hypothesis that STN-DBS acts by direct interference with the neurotransmission of basal ganglia networks involved in tremor.

Testosterone improves motor function in Parkinson’s disease

In Parkinson’s disease (PD) there is increasing evidence that sex steroids such as estradiol and testosterone modulate, either as a positive or negative effect, the clinical expression of a variety of movement disorders involving the nigrostriatum. Testosterone deficiency is common in the older male population and has an increased prevalence in parkinsonian patients. Testosterone therapy has been shown to improve the non-motor symptoms of PD but evidence for a direct effect of testosterone on motor symptoms is lacking. This case report demonstrates a significant improvement in the resting tremor and fine motor control after testosterone administration in a parkinsonian patient with testosterone deficiency (1 nmol/L). Motor symptom change was shown by serial assessment of the patient’s handwriting, self-reporting using the Unified Parkinson’s Disease Rating Scale and measurement of resting tremor amplitude by an accelerometer. The improvement in motor symptoms correlated with serum testosterone levels. The use of testosterone replacement in those men with decreased levels may improve the motor symptoms as well as increase general wellbeing.