Investigating Cerebellar Inhibition and Its Clinical Significance in Parkinsonian Tremor and Intention Tremor

NCT05512299 | Unknown DMC

• 1 other identifier: CMUH111-REC3-014
• Study Type: observational
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebellocerebral connection plays an important function in motor control. Nowadays it can be investigated with neuroimaging and physiological methods in humans. Cerebellar inhibition (CBI) is a phenomenon showing a physiological suppression of the motor evoked potential (MEP) evoked from the motor cortex (M1) by delivering a preceding transcranial magnetic stimulation (TMS) on the contralateral cerebellum. Despite the mediated pathway is supposed to be the cerebello-dentato-thalamo-cortical (CDTC) circuit, there is no conclusive evidence. In addition, the clinical significant of CBI remains unclear. Based on our previous studies, we found that the patients with advanced tremor show an impaired Bereitschaftspotential. The findings support a notion that the patients with tremor bear dysfunction of the CDTC circuit. Intriguingly, the pathogenesis of the parkinsonian tremor is highly associated with the CDTC circuit. The "dimmer-switch" model suggests that the basal ganglia-thalamo-cortical circuit dysfunction may initiate the resting tremor, and the following CDTC circuit dysfunction will lead to the large-amplitude resting and postural tremor in Parkinson's disease (PD). The intention tremor is usually found in the patients with cerebellar degeneration, which is also relevant to the CDTC circuit dysfunction. We expect that the clinical significance of CBI and the mediated pathway of CBI will be clarified by this study.

Conditions

Tremor

Keywords

cerebellar inhibition; pallidothalamic tractotomy; thalamotomy; Parkinson's disease; MR-guided focused ultrasound

Outcome Measures

Primary Outcomes (2)

• Change from baseline cerebellar inhibition (CBI) input output curve

  The CBI is recorded with two different TMS coils. The figure-of-eight coil (2X90 mm) is used for the motor cortex stimulation and the double cone coil (2X126 mm) is used for the cerebellar stimulation. The target recording muscle is first dorsal interosseous (FDI). The TMS intensity used to induce an average MEP amplitude of 0.5 mV is also determined. CBI is measured by a paired TMS with an inter-stimulus interval of 6 ms. That is, the test TMS at M1 is delivered 6 ms following the conditional TMS at contralateral cerebellum. There are five TMS intensities used for the conditional cerebellar stimulation: 80%, 90%, 100%, 110% and 120% inion active motor threshold. Ten trials are recorded for each TMS intensity with a pseudorandomized order. The interval between two cerebellum-M1 TMS pairs is 8-seconds with 25% variability (i.e. 6-10 s) to reduce the prediction bias.

  baseline (before the MRgFUS), 1-day, 24-weeks and 48-weeks after the MRgFUS

• Change from baseline functional magnetic resonance imaging

  In this study we mainly adopt diffusion tensor imaging (DTI) to quantify two interested projections: the pallidothalamic pathway and the dentatothalamic pathway. Diffusion tensor imaging of fifty gradient directions is acquired with five non-gradient (B0) images. The B-value is 1500 s/mm2, FOV = 240mm x 240mm, image matrix = 96 x 96, slice thickness = 2.5mm with zero gap. The voxel size is 2.5 x 2.5 x 2.5 mm3 isotopically. The TR was approximately 10000ms which is adjusted to match the slice number of requirements. Image acquired with axial direction, 56 slices to cover the whole brain.

  baseline (before the MRgFUS), 48-weeks after the MRgFUS

Secondary Outcomes (3)

• Change from baseline clinical evaluations

  baseline (before the MRgFUS), 1-day, 24-weeks and 48-weeks after the MRgFUS

• Change from baseline gait analysis

  baseline (before the MRgFUS), 1-day, 24-weeks and 48-weeks after the MRgFUS

• Change from baseline surface electromyography and eye-tracking pattern

  baseline (before the MRgFUS), 1-day, 24-weeks and 48-weeks after the MRgFUS

Study Arms (3)

PD with resting tremor

Parkinson's disease patient with pure resting tremor.

Diagnostic Test: Transcranial Magnetic Stimulation

PD with postural tremor

Parkinson's disease patient with postural tremor.

Diagnostic Test: Transcranial Magnetic Stimulation

Cerebellar degeneration with intention tremor

Cerebellar degeneration patient with intention tremor.

Diagnostic Test: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation DIAGNOSTIC_TEST

The CBI is recorded with two different TMS coils. The figure-of-eight coil (2X90 mm) is used for the motor cortex stimulation and the double cone coil (2X126 mm) is used for the cerebellar stimulation. The target recording muscle is first dorsal interosseous (FDI). The TMS intensity used to induce an average MEP amplitude of 0.5 mV is also determined. CBI is measured by a paired TMS with an inter-stimulus interval of 6 ms. That is, the test TMS at M1 is delivered 6 ms following the conditional TMS at contralateral cerebellum.

Cerebellar degeneration with intention tremor; PD with postural tremor; PD with resting tremor

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult PD patients with pure resting tremor or mixed resting and postural tremor will be studied. Some of them are the patients receiving MR-guided focus ultrasound (MRgFUS). In addition, patients with cerebellar degeneration with intention tremor will be also recruited. Those patients with contraindication to TMS or MRI examination will be excluded.

You may qualify if:

• Patients meet the diagnosis of PD with resting/postural or cerebellar degeneration with intention tremor based on the established consensus criteria.

You may not qualify if:

• Patients with contraindication to TMS or MRI examination.
• Impairment of cognition that leads unable to fully cooperate with the oral commands during examinations.
• Functional III or above congestive heart failure, or cancer with distant metastasis.

Sponsors & Collaborators

• China Medical University Hospital: lead
• Ministry of Science and Technology, Taiwan: collaborator

Study Sites (1)

Department of Neurology, China Medical University Hospital

Taichung, 40447, Taiwan

RECRUITING

MeSH Terms

Conditions

Tremor; Parkinson Disease

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Ming-Kuei Lu, MD, PhD

  Department of Neurology, China Medical University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming-Kuei Lu, MD, PhD

CONTACT

8864-22052121; d4297@mail.cmuh.org.tw

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: August 23, 2022
• Study Start: August 1, 2022
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2024
• Last Updated: August 23, 2022

Record last verified: 2022-08

Locations

TW (1)