Subtle changes in central dopaminergic tone underlie bradykinesia in essential tremor

Colella, Donato; Passaretti, Massimiliano; Frantellizzi, Viviana; Silvia De Feo, Maria; Cannavacciuolo, Antonio; Angelini, Luca; Birreci, Daniele; Costa, Davide; Paparella, Giulia; Guerra, Andrea; De Vincentis, Giuseppe; Berardelli, Alfredo; Bologna, Matteo

doi:10.1016/j.nicl.2023.103526

NeuroImage: Clinical

2023

DOI: 10.1016/j.nicl.2023.103526

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Subtle changes in central dopaminergic tone underlie bradykinesia in essential tremor

Donato Colella,

Massimiliano Passaretti,

Viviana Frantellizzi

et al.

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2024

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Cited by 7 publications

References 59 publications

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Clinical and kinematic characterization of parkinsonian soft signs in essential tremor

Angelini,

Paparella,

Cannavacciuolo

et al. 2024

J Neural Transm

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Background Subtle parkinsonian signs, i.e., rest tremor and bradykinesia, are considered soft signs for defining essential tremor (ET) plus. Objectives Our study aimed to further characterize subtle parkinsonian signs in a relatively large sample of ET patients from a clinical and neurophysiological perspective. Methods We employed clinical scales and kinematic techniques to assess a sample of 82 ET patients. Eighty healthy controls matched for gender and age were also included. The primary focus of our study was to conduct a comparative analysis of ET patients (without any soft signs) and ET-plus patients with rest tremor and/or bradykinesia. Additionally, we investigated the asymmetry and side concordance of these soft signs. Results In ET-plus patients with parkinsonian soft signs (56.10% of the sample), rest tremor was clinically observed in 41.30% of cases, bradykinesia in 30.43%, and rest tremor plus bradykinesia in 28.26%. Patients with rest tremor had more severe and widespread action tremor than other patients. Furthermore, we observed a positive correlation between the amplitude of action and rest tremor. Most ET-plus patients had an asymmetry of rest tremor and bradykinesia. There was no side concordance between these soft signs, as confirmed through both clinical examination and kinematic evaluation. Conclusions Rest tremor and bradykinesia are frequently observed in ET and are often asymmetric but not concordant. Our findings provide a better insight into the phenomenology of ET and suggest that the parkinsonian soft signs (rest tremor and bradykinesia) in ET-plus may originate from distinct pathophysiological mechanisms.

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Clinical and kinematic characterization of parkinsonian soft signs in essential tremor

Angelini,

Paparella,

Cannavacciuolo

et al. 2024

J Neural Transm

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The Role of Cerebellum and Basal Ganglia Functional Connectivity in Altered Voluntary Movement Execution in Essential Tremor

Passaretti,

Piervincenzi,

Baione

et al. 2024

Cerebellum

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Substantial evidence highlights the role of the cerebellum in the pathophysiology of tremor in essential tremor (ET), although its potential involvement in altered movement execution in this condition remains unclear. This study aims to explore potential correlations between the cerebellum and basal ganglia functional connectivity and voluntary movement execution abnormalities in ET, objectively assessed with kinematic techniques. A total of 20 patients diagnosed with ET and 18 healthy subjects were enrolled in this study. Tremor and repetitive finger tapping were recorded using an optoelectronic kinematic system. All participants underwent comprehensive 3T-MRI examinations, including 3D-T1 and blood-oxygen-level dependent (BOLD) sequences during resting state. Morphometric analysis was conducted on the 3D-T1 images, while a seed-based analysis was performed to investigate the resting-state functional connectivity (rsFC) of dorsal and ventral portions of the dentate nucleus and the external and internal segments of the globus pallidus. Finally, potential correlations between rsFC alterations in patients and clinical as well as kinematic scores were assessed. Finger tapping movements were slower in ET than in healthy subjects. Compared to healthy subjects, patients with ET exhibited altered FC of both dentate and globus pallidus with cerebellar, basal ganglia, and cortical areas. Interestingly, both dentate and pallidal FC exhibited positive correlations with movement velocity in patients, differently from that we observed in healthy subjects, indicating the higher the FC, the faster the finger tapping. The findings of this study indicate the possible role of both cerebellum and basal ganglia in the pathophysiology of altered voluntary movement execution in patients with ET.

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Insight into the Relationship Between Motor and Cognitive Symptoms in Essential Tremor

Paparella,

Angelini,

Margiotta

et al. 2024

Cerebellum

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Essential tremor (ET) is a heterogeneous disorder characterized by bilateral upper limbs action tremor and, possibly, neurological signs of uncertain significance, including voluntary movement abnormalities and cognitive disturbances, i.e., the so-called ‘soft’ signs configuring the ET-plus definition. While motor and cognitive disturbances often coexist in ET, their interrelationship remains largely unexplored. Here we aim to further investigate the relationship between motor symptoms, objectively assessed through kinematic analysis, and cognitive dysfunctions in ET. Seventy ET patients underwent clinical examination, as well as kinematic recordings of tremor and finger tapping and a thorough cognitive assessment. We then tested clinic-demographic and kinematic differences between patients with and without cognitive abnormalities, i.e., with mild cognitive impairment (MCI). Correlation analysis served to explore potential associations between kinematic and cognitive data. Forty-three ET patients (61.42%) had MCI. ET-MCI patients exhibited reduced movement velocity during finger tapping compared to those with normal cognition (p < 0.001). Lower movement velocity during finger tapping was associated with poorer cognitive performance. Namely, we observed a correlation between movement velocity and performance on the Babcock Story Immediate and Delayed Recall Test (r = 0.52 and r = 0.45, both p < 0.001), as well as the interference memory task at 10 and 30 s (r = 0.3, p = 0.008 and r = 0.2, p = 0.03). In this study, we have provided data for a better pathophysiological interpretation of motor and cognitive signs in ET, including the role played by the cerebellum or extra-cerebellar areas, which possibly underpin both signs.

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Subtle changes in central dopaminergic tone underlie bradykinesia in essential tremor

Cited by 7 publications

References 59 publications

Clinical and kinematic characterization of parkinsonian soft signs in essential tremor

Clinical and kinematic characterization of parkinsonian soft signs in essential tremor

The Role of Cerebellum and Basal Ganglia Functional Connectivity in Altered Voluntary Movement Execution in Essential Tremor

Insight into the Relationship Between Motor and Cognitive Symptoms in Essential Tremor

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