To unravel the cerebral mechanisms of re-emergent postural tremor in PD and understand to what extent these mechanisms overlap with those involved in resting tremor. A secondary objective is to understand how cerebral tremor-related mechanisms…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Re-emergent postural tremor-related cerebral activity, as measured by combined
electrophysiology-fMRI. This robust technique has already been widely applied
to several different tremor syndromes, including Parkinsonian resting tremor,
essential tremor, and dystonic tremor.
Secondary outcome
Clinical assessments: disease severity using MDS-UPDRS Part III (motor
examination), most-affected side, most-tremulous side, handedness (Edinburgh
Handedness Inventory), and cognitive function (MoCA).
Structural MRI: T1 and T2-weighted structural images, diffusion-tensor imaging
(DTI) scan, and neuromelanin scan. The anatomical T1-image will be used for
registration of the fMRI-scans and the T2-image for improved cerebellar
segmentation. The DTI and neuromelanin scans will be used to look for the
integrity of the substantia nigra and locus coeruleus (LC). These measures are
then correlated to clinical and electrophysiological tremor characteristics, as
well as cerebral tremor-related activity (see below).
Functional MRI: the fMRI experiment will be used to investigate and localize
cerebral tremor-related activity. Moreover, within-subject differences in
cerebral activity patterns and connectivity strengths between resting tremor
and re-emergent postural tremor will be investigated. The extent of activity
and effective connectivity parameters of the tremor-circuit will be correlated
with electrophysiological tremor characteristics (e.g., tremor amplitude, the
duration of the latency, etc).
Electrophysiology: tremor will be measured from surface-electromyography (EMG)
and accelerometery. Surface EMG electrodes will be placed on the first dorsal
interosseus, abductor pollicis brevis, extensor carpi radialis, flexor carpi
radialis, biceps, and triceps on the most-tremulous side. In case of clear leg
tremor, surface EMG-electrode may be placed on the gastrocnemius and/or
tibialis anterior muscles. A tri-axial accelerometer will be placed on both the
most and least-tremulous side (dorsum of the hand). These peripheral tremor
measures will be used to characterize tremor, assess tremor-specific
eligibility for the fMRI session, and during scanning to compute scan-by-scan
fluctuations of tremor power, which will be used to obtain cerebral
tremor-related activity, as done before.
Behavioural assessments: subjects will perform a mental arithmetic task during
part of the trials (e.g., 100-3, 100-6, 100-7, 100-9). Such a cognitive
co-activation task is known to induce tremor, increase its (variations in)
amplitude and shorten the latency duration. This task is added to increase the
odds of capturing clear tremor episodes before the trial ends. Pupil diameter
and heart rate will be recorded as a proxy of cognitive effort during scanning,
similar to previous studies.
Participant characteristics: date of birth, biological sex, disease duration
since diagnosis, disease duration since subjective symptom onset, relevant
comorbidities, and medication use.
Background summary
Tremor (trembling) is one of the cardinal motor symptoms of Parkinson*s disease
(PD) and patients report tremor to be one of the main symptoms they wish to see
improvement upon. Parkinsonian tremor often occurs at rest in the hands, which
is called a resting tremor. However, tremor is often suppressed during
voluntary movement and may re-emerge several seconds later after adopting a
stable posture against gravity. This is called re-emergent postural tremor.
Unfortunately, usual dopaminergic medication (e.g., levodopa) is not or
moderately effective in alleviating resting tremor and medication effects are
even worse for re-emergent postural tremor. Limited knowledge regarding the
cerebral mechanisms of re-emergent tremor hinders development of novel
therapies.
Study objective
To unravel the cerebral mechanisms of re-emergent postural tremor in PD and
understand to what extent these mechanisms overlap with those involved in
resting tremor. A secondary objective is to understand how cerebral
tremor-related mechanisms relate to MRI correlates of nigrostriatal
(dopaminergic) cell loss.
Study design
This study involves an observational fMRI study in PD patients exhibiting both
resting and re-emergent postural tremor (n=40).
Clinical, electrophysiological, and MRI measures will be collected. This study
will involve two sessions on separate days with the second visit preferably
scheduled <1 month after the first visit. The first visit will not involve fMRI
and will mainly be used to characterize re-emergent postural tremor and confirm
tremor-specific eligibility criteria for the second (fMRI) visit. These
eligibility criteria are based on two main factors: 1) there is clear tremor
suppression after abrupt voluntary movement, and 2) tremor suppression does not
last more than 20 seconds.
The study will take place at the Donders Centre for Cognitive Neuroimaging
(DCCN) and the sponsor is the Radboud University Medical Center (Radboudumc).
Study burden and risks
The burden on the patients mainly consist of the time spent during this study
(two sessions of ~95 minutes, 3 hours total) and potentially a worsening
Parkinsonian symptoms as a result of withholding medication on the morning
before the study assessments. All measurements are non-invasive, painless, and
without ionizing radiation. Patients do not directly benefit from participating
in this study. However, we are convinced that this study will provide novel
insights into the mechanisms of Parkinsonian tremor which will improve future
research regarding novel therapeutic targets for tremor treatment.
Reinier Postlaan 4
Nijmegen 6525 GC
NL
Reinier Postlaan 4
Nijmegen 6525 GC
NL
Listed location countries
Age
Inclusion criteria
- A diagnosis of idiopathic PD made by a movement disorder specialist
- PD disease duration of 7 years or less, defined as time since diagnosis by a
neurologist
- A history of both resting and re-emergent postural tremor in the same arm
Exclusion criteria
- Severe neurological co-morbidity
- Co-existing other tremor (e.g., functional tremor, dystonic tremor, essential
tremor)
- Significant cognitive impairment: Montreal Cognitive Assessment (MoCA) <21
points
- Contra-indications for MRI
- Moderate to severe head tremor
- Tremor latency duration >20 seconds after abrupt voluntary movement
- Unclear tremor suppression after voluntary movement
- Taking dopamine-agonists with a levodopa equivalent dose of more than 150mg
per day
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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In other registers
| Register | ID |
|---|---|
| CCMO | NL85143.091.24 |