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Rick C Helmich - One of the best experts on this subject based on the ideXlab platform.
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dopamine responsive and dopamine resistant Resting Tremor in parkinson disease
Neurology, 2020Co-Authors: Heidemarie Zach, Michiel F Dirkx, Dominik Roth, Jaco W Pasman, Bastiaan R Bloem, Rick C HelmichAbstract:Objective We tested the hypothesis that there are 2 distinct phenotypes of Parkinson Tremor, based on interindividual differences in the response of Resting Tremor to dopaminergic medication. We also investigated whether this pattern is specific to Tremor by comparing interindividual differences in the dopamine response of Tremor to that of bradykinesia. Methods In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson Tremor. Clinical scores (Movement Disorders Society–sponsored version of the Unified Parkinson’s Disease Rating Scale part III) were collected “off” and “on” a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, Resting Tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for Resting Tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. Results The dopamine response of Resting Tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of Tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant Tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive Tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. Conclusion Parkinson Resting Tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These Tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.
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author response the nature of postural Tremor in parkinson disease
Neurology, 2018Co-Authors: Rick C Helmich, Mark Hallett, Michiel F DirkxAbstract:We appreciate Dr. Jankovic's comments on our recently published article.1 Our findings suggest that reemergent Tremor is fundamentally the same as Resting Tremor. In our cohort (n = 48), the average latency between movement and Tremor reemergence was 15.9 seconds. The latency varied considerably (1 to >60 seconds) but was not associated with disease or Tremor severity. Recent work suggests that reafference from voluntary movements may reset Tremor,2 but other mechanisms may also apply.3
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cognitive stress reduces the effect of levodopa on parkinson s Resting Tremor
CNS Neuroscience & Therapeutics, 2017Co-Authors: Heidemarie Zach, Michiel F Dirkx, Jaco W Pasman, Bastiaan R Bloem, Rick C HelmichAbstract:AIMS: Resting Tremor in Parkinson's disease (PD) increases markedly during cognitive stress. Dopamine depletion in the basal ganglia is involved in the pathophysiology of Resting Tremor, but it is unclear whether this contribution is altered under cognitive stress. We test the hypothesis that cognitive stress modulates the levodopa effect on Resting Tremor. METHODS: Tremulous PD patients (n = 69) were measured in two treatment conditions (OFF vs. ON levodopa) and in two behavioral contexts (rest vs. cognitive co-activation). Using accelerometry, we tested the effect of both interventions on Tremor intensity and Tremor variability. RESULTS: Levodopa significantly reduced Tremor intensity (across behavioral contexts), while cognitive co-activation increased it (across treatment conditions). Crucially, the levodopa effect was significantly smaller during cognitive co-activation than during rest. Resting Tremor variability increased after levodopa and decreased during cognitive co-activation. CONCLUSION: Cognitive stress reduces the levodopa effect on Parkinson's Tremor. This effect may be explained by a stress-related depletion of dopamine in the basal ganglia motor circuit, by stress-related involvement of nondopaminergic mechanisms in Tremor (e.g., noradrenaline), or both. Targeting these mechanisms may open new windows for treatment. Clinical Tremor assessments under evoked cognitive stress (e.g., counting tasks) may avoid overestimation of treatment effects in real life.
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ep 97 strength lies in peace cognitive stress reduces the effect of levodopa on parkinson s Resting Tremor
Clinical Neurophysiology, 2016Co-Authors: Heidemarie Zach, Michiel F Dirkx, Jaco W Pasman, B R Bloem, Rick C HelmichAbstract: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.
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cerebral causes and consequences of parkinsonian Resting Tremor a tale of two circuits
Brain, 2012Co-Authors: Mark Hallett, Rick C Helmich, Gunther Deuschl, Ivan Toni, Bastiaan R BloemAbstract:Tremor in Parkinson's disease has several mysterious features. Clinically, Tremor is seen in only three out of four patients with Parkinson's disease, and Tremor-dominant patients generally follow a more benign disease course than non-Tremor patients. Pathophysiologically, Tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other Tremors. The purpose of this review is to integrate these clinical and pathophysiological features of Tremor in Parkinson's disease. We first describe clinical and pathological differences between Tremor-dominant and non-Tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of Tremor. We also discuss a newly proposed 'dimmer-switch model' that explains Tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger Tremor episodes and the cerebello-thalamo-cortical circuit that produces the Tremor. Finally, we address several important open questions: why Resting Tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression.
Rita Nisticò - One of the best experts on this subject based on the ideXlab platform.
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development and validation of a new wearable mobile device for the automated detection of Resting Tremor in parkinson s disease and essential Tremor
Diagnostics (Basel Switzerland), 2021Co-Authors: Basilio Vescio, Rita Nisticò, Andrea Quattrone, Marianna Crasa, Antonio Augimeri, Aldo QuattroneAbstract:Involuntary Tremor at rest is observed in patients with Parkinson's disease (PD) or essential Tremor (ET). Electromyography (EMG) studies have shown that phase displacement between antagonistic muscles at prevalent Tremor frequency can accurately differentiate Resting Tremor in PD from that detected in ET. Currently, phase evaluation is qualitative in most cases. The aim of this study is to develop and validate a new mobile tool for the automated and quantitative characterization of phase displacement (Resting Tremor pattern) in ambulatory clinical settings. A new low-cost, wearable mobile device, called µEMG, is described, based on low-end instrumentation amplifiers and simple digital signal processing (DSP) capabilities. Measurements of Resting Tremor characteristics from this new device were compared with standard EMG. A good level of agreement was found in a sample of 21 subjects (14 PD patients with alternating Resting Tremor pattern and 7 ET patients with synchronous Resting Tremor pattern). Our results demonstrate that Tremor analysis using µEMG is easy to perform and it can be used in routine clinical practice for the automated quantification of Resting Tremor patterns. Moreover, the measurement process is handy and operator-independent.
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the placebo effect on Resting Tremor in parkinson s disease an electrophysiological study
Parkinsonism & Related Disorders, 2018Co-Authors: Gaetano Barbagallo, Rita Nisticò, Basilio Vescio, Andrea Quattrone, Antonio Cerasa, Giuseppe Olivadese, Salvatore Nigro, Marianna Crasa, Maria Giovanna Bianco, Maurizio MorelliAbstract:Abstract Introduction The aim of our study was to investigate the effect of apomorphine and placebo on Resting Tremor in Tremor-dominant Parkinson's disease (tPD) patients. Methods Fifteen tPD patients were enrolled. Each patient underwent two treatments on two consecutive days: on day one the patients received a subcutaneous injection of placebo, while on day two they received apomorphine. On each day, the patients underwent three electrophysiological recording sessions: T0, T1, and T2: before, 30 min, and 60 min after the treatment respectively. Electrophysiological changes in Tremor amplitude were evaluated using a triaxial accelerometer. Results Placebo was effective in improving Resting Tremor in all tPD patients (p = 0.009) at T1, but not at T2. Eight out of 15 tPD patients (53.3%) responded to placebo with an at least 70% reduction in Tremor amplitude compared to the basal condition (responders). By contrast, seven out of 15 tPD patients (46.7%) did not show any variation in Tremor amplitude after placebo administration (non-responders). Apomorphine induced a marked reduction in Tremor amplitude at 30 min and 60 min in all investigated tPD patients. Of note, the decrease in Tremor amplitude in placebo responders was similar to that achieved with dopaminergic stimulation induced by apomorphine. Conclusions Our study demonstrates that placebo was very effective in reducing Resting Tremor in about half of patients with tPD. The decrease in Tremor amplitude in placebo responders was similar to that induced by apomorphine. The cerebral mechanisms underlying the placebo effect on Resting Tremor need further investigations.
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structural connectivity differences in essential Tremor with and without Resting Tremor
Journal of Neurology, 2017Co-Authors: Maria Eugenia Caligiuri, Fabiana Novellino, Rita Nisticò, Maria Salsone, Maurizio Morelli, Gennarina Arabia, Gaetano Barbagallo, Angela Lupo, Andrea Quattrone, Basilio VescioAbstract:In this work, we investigated motor network structure in patients affected by essential Tremor (ET) with or without Resting Tremor, using probabilistic tractography of the cerebello-thalamo-basal ganglia-cortical loop. Twenty-five patients with ET, twenty-two patients with ET associated with Resting Tremor (rET), and twenty-five age- and sex-matched healthy controls were included in the study. All participants underwent whole-brain 3D T1-weighted and diffusion-weighted MRI, and DAT-SPECT. Probabilistic tractography was performed on diffusion data in network mode, reconstructing connections between the different structures of the cerebello-thalamo-basal ganglia-cortical loop. All patients with ET, regardless of the presence of Resting Tremor, had normal DAT-SPECT, but showed significantly decreased connectivity in the cerebello-thalamo-precentral cortex network bilaterally, compared to healthy controls. In addition, patients with rET showed reduced connectivity in a pathway connecting globus pallidus, caudate, and supplementary motor area, compared to ET and controls. This latter circuit was significantly damaged in the hemisphere contralateral to the side clinically most affected by Resting Tremor. These findings provide insights upon structural changes underlying the different clinical presentations of ET. Our study demonstrates that ET and rET share common alterations in the cerebello-thalamo-precentral cortex circuit, while rET patients are characterized by specific damage to additional structures of motor network, such as globus pallidus, caudate nucleus, and supplementary motor area. Our findings suggest that ET and rET are different subtypes of the same neurodegenerative disorder.
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Tremor pattern differentiates drug induced Resting Tremor from parkinson disease
Parkinsonism & Related Disorders, 2016Co-Authors: Rita Nisticò, Maurizio Morelli, Gennarina Arabia, A Fratto, Basilio Vescio, Giorgia Sciacca, Angelo LabateAbstract:Abstract Objective DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of Resting Tremor for the differentiation of patients with drug-induced parkinsonism with Resting Tremor (rDIP) from those with Resting Tremor due to PD. Methods This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of Resting Tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. Results Rest Tremor amplitude was higher in PD patients than in rDIP patients (p Conclusions In the absence of DAT-SPECT, the pattern of Resting Tremor can be considered a useful investigation for differentiating rDIP from PD.
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Cerebellar involvement in essential Tremor with and without Resting Tremor: A Diffusion Tensor Imaging study
Parkinsonism & related disorders, 2016Co-Authors: Fabiana Novellino, Giuseppe Nicoletti, Andrea Cherubini, Maria Eugenia Caligiuri, Rita Nisticò, Maria Salsone, Maurizio Morelli, Gennarina Arabia, Salvatore Maria Cavalli, Maria Grazia VaccaroAbstract:Abstract Objective Essential Tremor with Resting Tremor (rET) is a debated and poorly understood clinical phenotype. Converging evidences show that neurodegeneration of the cerebellum underlies the pathophysiology of ET, but it is not known if cerebellar changes also occurs in patients with rET. The aim of our study was to evaluate cerebellar microstructure in patients with ET with- (rET) and without Resting Tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor Imaging (DTI). Methods We studied 67 patients with ET (rET: 29 and ETwr: 38) and 39 age-matched healthy controls (HC). DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in the entire cerebellum and in right and left cerebellar hemispheres. Results MD was significantly higher in the cerebellar GM of ET total group (10.39 ± 0.87) in comparison with HC (9.90 ± 0.71) (p = 0.0027). InteRestingly, MD was significantly different when ETwr (10.48 ± 0.77) were compared with HC (p = 0.0017), whereas a trend toward significance were found between rET (10.29 ± 0.99) and HC (p = 0.067). No differences among groups were found in MD of cerebellar WM and in FA values neither in the WM nor in the GM. Conclusion Our results demonstrate the presence of microstructural changes in the cerebellum of patients with ET. It is noteworthy that rET showed intermediate values compared to HC and ETwr, suggesting that rET shares part of the pathophysiological mechanisms of ETwr, but cerebellar involvement seems do not fully account for rET. In addition to the cerebellar loops, other networks may play a role in rET pathophysiology.
Maurizio Morelli - One of the best experts on this subject based on the ideXlab platform.
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the placebo effect on Resting Tremor in parkinson s disease an electrophysiological study
Parkinsonism & Related Disorders, 2018Co-Authors: Gaetano Barbagallo, Rita Nisticò, Basilio Vescio, Andrea Quattrone, Antonio Cerasa, Giuseppe Olivadese, Salvatore Nigro, Marianna Crasa, Maria Giovanna Bianco, Maurizio MorelliAbstract:Abstract Introduction The aim of our study was to investigate the effect of apomorphine and placebo on Resting Tremor in Tremor-dominant Parkinson's disease (tPD) patients. Methods Fifteen tPD patients were enrolled. Each patient underwent two treatments on two consecutive days: on day one the patients received a subcutaneous injection of placebo, while on day two they received apomorphine. On each day, the patients underwent three electrophysiological recording sessions: T0, T1, and T2: before, 30 min, and 60 min after the treatment respectively. Electrophysiological changes in Tremor amplitude were evaluated using a triaxial accelerometer. Results Placebo was effective in improving Resting Tremor in all tPD patients (p = 0.009) at T1, but not at T2. Eight out of 15 tPD patients (53.3%) responded to placebo with an at least 70% reduction in Tremor amplitude compared to the basal condition (responders). By contrast, seven out of 15 tPD patients (46.7%) did not show any variation in Tremor amplitude after placebo administration (non-responders). Apomorphine induced a marked reduction in Tremor amplitude at 30 min and 60 min in all investigated tPD patients. Of note, the decrease in Tremor amplitude in placebo responders was similar to that achieved with dopaminergic stimulation induced by apomorphine. Conclusions Our study demonstrates that placebo was very effective in reducing Resting Tremor in about half of patients with tPD. The decrease in Tremor amplitude in placebo responders was similar to that induced by apomorphine. The cerebral mechanisms underlying the placebo effect on Resting Tremor need further investigations.
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structural connectivity differences in essential Tremor with and without Resting Tremor
Journal of Neurology, 2017Co-Authors: Maria Eugenia Caligiuri, Fabiana Novellino, Rita Nisticò, Maria Salsone, Maurizio Morelli, Gennarina Arabia, Gaetano Barbagallo, Angela Lupo, Andrea Quattrone, Basilio VescioAbstract:In this work, we investigated motor network structure in patients affected by essential Tremor (ET) with or without Resting Tremor, using probabilistic tractography of the cerebello-thalamo-basal ganglia-cortical loop. Twenty-five patients with ET, twenty-two patients with ET associated with Resting Tremor (rET), and twenty-five age- and sex-matched healthy controls were included in the study. All participants underwent whole-brain 3D T1-weighted and diffusion-weighted MRI, and DAT-SPECT. Probabilistic tractography was performed on diffusion data in network mode, reconstructing connections between the different structures of the cerebello-thalamo-basal ganglia-cortical loop. All patients with ET, regardless of the presence of Resting Tremor, had normal DAT-SPECT, but showed significantly decreased connectivity in the cerebello-thalamo-precentral cortex network bilaterally, compared to healthy controls. In addition, patients with rET showed reduced connectivity in a pathway connecting globus pallidus, caudate, and supplementary motor area, compared to ET and controls. This latter circuit was significantly damaged in the hemisphere contralateral to the side clinically most affected by Resting Tremor. These findings provide insights upon structural changes underlying the different clinical presentations of ET. Our study demonstrates that ET and rET share common alterations in the cerebello-thalamo-precentral cortex circuit, while rET patients are characterized by specific damage to additional structures of motor network, such as globus pallidus, caudate nucleus, and supplementary motor area. Our findings suggest that ET and rET are different subtypes of the same neurodegenerative disorder.
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Tremor pattern differentiates drug induced Resting Tremor from parkinson disease
Parkinsonism & Related Disorders, 2016Co-Authors: Rita Nisticò, Maurizio Morelli, Gennarina Arabia, A Fratto, Basilio Vescio, Giorgia Sciacca, Angelo LabateAbstract:Abstract Objective DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of Resting Tremor for the differentiation of patients with drug-induced parkinsonism with Resting Tremor (rDIP) from those with Resting Tremor due to PD. Methods This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of Resting Tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. Results Rest Tremor amplitude was higher in PD patients than in rDIP patients (p Conclusions In the absence of DAT-SPECT, the pattern of Resting Tremor can be considered a useful investigation for differentiating rDIP from PD.
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Cerebellar involvement in essential Tremor with and without Resting Tremor: A Diffusion Tensor Imaging study
Parkinsonism & related disorders, 2016Co-Authors: Fabiana Novellino, Giuseppe Nicoletti, Andrea Cherubini, Maria Eugenia Caligiuri, Rita Nisticò, Maria Salsone, Maurizio Morelli, Gennarina Arabia, Salvatore Maria Cavalli, Maria Grazia VaccaroAbstract:Abstract Objective Essential Tremor with Resting Tremor (rET) is a debated and poorly understood clinical phenotype. Converging evidences show that neurodegeneration of the cerebellum underlies the pathophysiology of ET, but it is not known if cerebellar changes also occurs in patients with rET. The aim of our study was to evaluate cerebellar microstructure in patients with ET with- (rET) and without Resting Tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor Imaging (DTI). Methods We studied 67 patients with ET (rET: 29 and ETwr: 38) and 39 age-matched healthy controls (HC). DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in the entire cerebellum and in right and left cerebellar hemispheres. Results MD was significantly higher in the cerebellar GM of ET total group (10.39 ± 0.87) in comparison with HC (9.90 ± 0.71) (p = 0.0027). InteRestingly, MD was significantly different when ETwr (10.48 ± 0.77) were compared with HC (p = 0.0017), whereas a trend toward significance were found between rET (10.29 ± 0.99) and HC (p = 0.067). No differences among groups were found in MD of cerebellar WM and in FA values neither in the WM nor in the GM. Conclusion Our results demonstrate the presence of microstructural changes in the cerebellum of patients with ET. It is noteworthy that rET showed intermediate values compared to HC and ETwr, suggesting that rET shares part of the pathophysiological mechanisms of ETwr, but cerebellar involvement seems do not fully account for rET. In addition to the cerebellar loops, other networks may play a role in rET pathophysiology.
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blink reflex recovery cycle distinguishes essential Tremor with Resting Tremor from de novo parkinson s disease an exploratory study
Parkinsonism & Related Disorders, 2014Co-Authors: Rita Nisticò, Maria Salsone, Maurizio Morelli, Gennarina Arabia, Basilio Vescio, Gaetano Barbagallo, Maria Trotta, Aldo QuattroneAbstract:Abstract An increased R2 recovery component of the blink reflex (R2-BRrc) has been observed in Parkinson's disease (PD), cranio-cervical dystonia, dystonic Tremor and essential Tremor with associated Resting Tremor (rET), while the BRrc was reported normal in patients with essential Tremor (ET). Distinguishing rET from Tremor dominant PD (tPD) may be challenging especially in the first stages of the diseases, in the absence of DAT-SPECT investigation. We evaluated the possible usefulness of BRrc for differentiating subjects with de novo tPD from those with rET. We investigated R2-BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 ms in 11 participants with tPD, 10 with rET and 20 healthy controls. All participants underwent DAT-SPECT and cardiac MIBG scintigraphy. R2 recovery was significantly enhanced in tPD compared to controls at all investigated ISIs ( p At ISI 100 R2-BRrc distinguished patients participants with de novo tPD from those with rET with a sensitivity, specificity and accuracy of 100%. Our findings demonstrate the usefulness of BRrc for differentiating de novo tPD from rET.
Heidemarie Zach - One of the best experts on this subject based on the ideXlab platform.
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dopamine responsive and dopamine resistant Resting Tremor in parkinson disease
Neurology, 2020Co-Authors: Heidemarie Zach, Michiel F Dirkx, Dominik Roth, Jaco W Pasman, Bastiaan R Bloem, Rick C HelmichAbstract:Objective We tested the hypothesis that there are 2 distinct phenotypes of Parkinson Tremor, based on interindividual differences in the response of Resting Tremor to dopaminergic medication. We also investigated whether this pattern is specific to Tremor by comparing interindividual differences in the dopamine response of Tremor to that of bradykinesia. Methods In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson Tremor. Clinical scores (Movement Disorders Society–sponsored version of the Unified Parkinson’s Disease Rating Scale part III) were collected “off” and “on” a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, Resting Tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for Resting Tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. Results The dopamine response of Resting Tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of Tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant Tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive Tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. Conclusion Parkinson Resting Tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These Tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.
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cognitive stress reduces the effect of levodopa on parkinson s Resting Tremor
CNS Neuroscience & Therapeutics, 2017Co-Authors: Heidemarie Zach, Michiel F Dirkx, Jaco W Pasman, Bastiaan R Bloem, Rick C HelmichAbstract:AIMS: Resting Tremor in Parkinson's disease (PD) increases markedly during cognitive stress. Dopamine depletion in the basal ganglia is involved in the pathophysiology of Resting Tremor, but it is unclear whether this contribution is altered under cognitive stress. We test the hypothesis that cognitive stress modulates the levodopa effect on Resting Tremor. METHODS: Tremulous PD patients (n = 69) were measured in two treatment conditions (OFF vs. ON levodopa) and in two behavioral contexts (rest vs. cognitive co-activation). Using accelerometry, we tested the effect of both interventions on Tremor intensity and Tremor variability. RESULTS: Levodopa significantly reduced Tremor intensity (across behavioral contexts), while cognitive co-activation increased it (across treatment conditions). Crucially, the levodopa effect was significantly smaller during cognitive co-activation than during rest. Resting Tremor variability increased after levodopa and decreased during cognitive co-activation. CONCLUSION: Cognitive stress reduces the levodopa effect on Parkinson's Tremor. This effect may be explained by a stress-related depletion of dopamine in the basal ganglia motor circuit, by stress-related involvement of nondopaminergic mechanisms in Tremor (e.g., noradrenaline), or both. Targeting these mechanisms may open new windows for treatment. Clinical Tremor assessments under evoked cognitive stress (e.g., counting tasks) may avoid overestimation of treatment effects in real life.
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ep 97 strength lies in peace cognitive stress reduces the effect of levodopa on parkinson s Resting Tremor
Clinical Neurophysiology, 2016Co-Authors: Heidemarie Zach, Michiel F Dirkx, Jaco W Pasman, B R Bloem, Rick C HelmichAbstract: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.
Carl Hermann Lucking - One of the best experts on this subject based on the ideXlab platform.
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thalamic gray matter changes in unilateral parkinsonian Resting Tremor a voxel based morphometric analysis of 3 dimensional magnetic resonance imaging
Neuroscience Letters, 2002Co-Authors: Jan Kassubek, Freimut D Juengling, Bernhard Hellwig, Joachim Spreer, Carl Hermann LuckingAbstract:The thalamus is assumed to be involved in the generation of Parkinsonian Tremor. Ten patients with Tremor-dominant idiopathic Parkinson's disease (IPD) and strictly unilateral Resting Tremor were investigated by cerebral high-resolution 3-dimensional magnetic resonance imaging (MRI). MRI data were analyzed by an observer-independent morphometric technique, voxel-based morphometry (VBM). For VBM, MRI data were automatically normalized and segmented, then gray matter volumes were analyzed on a voxel-by-voxel basis in comparison to an age-matched control group using Statistical Parametric Mapping (SPM99). Highly significant structural changes, i.e. locally increased gray matter concentrations (P<0.001), were found in the nucleus ventralis intermedius (VIM) of the thalamus contralateral to the Tremor side and were significantly covariant with Tremor amplitudes. On the one hand, these changes were localized in close vicinity to a thalamic focal hypermetabolism as revealed by a previous positron emission tomography study in unilateral Parkinsonian Tremor patients. On the other hand, the localization of the focal structural changes in VIM corresponds with the generally accepted target area of Tremor surgery in IPD.
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hypermetabolism in the ventrolateral thalamus in unilateral parkinsonian Resting Tremor a positron emission tomography study
Neuroscience Letters, 2001Co-Authors: Jan Kassubek, Freimut D Juengling, Bernhard Hellwig, Markus Knauff, Joachim Spreer, Carl Hermann LuckingAbstract:Tremorogenesis in Parkinson's disease (PD) is assumed to involve a cerebral network including the thalamus. An imaging study was performed on eight PD patients with strictly unilateral Resting Tremor using fluorodeoxyglucose positron emission tomography coregistered to 3-dimensional magnetic resonance imaging. Increased metabolic activity of high statistical significance (P<0.001) was found in the anterior ventrolateral nuclear group of the thalamus located contralateral to the Tremor side. The metabolic changes significantly covaried with Tremor amplitudes. For the first time, it could be demonstrated that thalamic metabolic changes associated with Tremor in PD are localized in the ventral lateral anterior nucleus (VLa). The results are discussed with respect to previous studies on Tremor generation.