rTMS Therapy for Primary Orthostatic Tremor
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 30 - 75 |
| Updated: | 6/2/2018 |
| Start Date: | August 2015 |
| End Date: | May 2019 |
| Contact: | Aparna Wagle-Shukla, M.D. |
| Email: | aparna.shukla@neurology.ufl.edu |
| Phone: | 352-294-5400 |
rTMS Therapy for Primary Orthostatic Tremor: A Novel Treatment Approach
Primary orthostatic tremor(POT) is a rare progressive functionally disabling tremor disorder.
The characteristic features of POT are symptoms of unsteadiness in legs reported by patients
when they are standing and improvement of symptoms upon walking and sitting. Due to the
limited success of other treatment options there is a clear merit in continuing efforts to
explore and investigate novel treatment modalities. Transcranial magnetic stimulation (TMS)
is a well-established physiological tool to understand brain function. When repetitious TMS
pulses are delivered to a specific target at predefined stimulation parameters, it is
referred to as rTMS therapy.The investigators propose a novel approach to investigate the
clinical and physiological effects of low frequency rTMS therapy in POT. The overarching
hypothesis of this study is that low frequency rTMS therapy delivered to the cerebellum will
modulate the cerebellar excitability and result in clinical improvements.In order to
determine the physiological effects related to rTMS, the tremor physiology will also be
recorded with surface electromyography (EMG). The investigator will also record the changes
in cerebellum excitability in response to rTMS using cerebello-cortical inhibition (CBI), a
well-established TMS parameter.
The characteristic features of POT are symptoms of unsteadiness in legs reported by patients
when they are standing and improvement of symptoms upon walking and sitting. Due to the
limited success of other treatment options there is a clear merit in continuing efforts to
explore and investigate novel treatment modalities. Transcranial magnetic stimulation (TMS)
is a well-established physiological tool to understand brain function. When repetitious TMS
pulses are delivered to a specific target at predefined stimulation parameters, it is
referred to as rTMS therapy.The investigators propose a novel approach to investigate the
clinical and physiological effects of low frequency rTMS therapy in POT. The overarching
hypothesis of this study is that low frequency rTMS therapy delivered to the cerebellum will
modulate the cerebellar excitability and result in clinical improvements.In order to
determine the physiological effects related to rTMS, the tremor physiology will also be
recorded with surface electromyography (EMG). The investigator will also record the changes
in cerebellum excitability in response to rTMS using cerebello-cortical inhibition (CBI), a
well-established TMS parameter.
POT tremors recorded on surface electromyography (EMG) reveal distinct high frequency bursts
of 13-18 Hz tremors in the leg muscles. POT was first described in 1984 at the University of
Florida. Since then several clinical descriptions have been published however despite this
knowledge for thirty years, treatment opportunities for POT have remained poor. Several
medications have been tried, but the results have been disappointing. Thalamic deep brain
stimulation (DBS) surgery, which is an invasive therapy approved by the FDA for treatment of
essential tremor, was recently investigated in POT but the early results have only been
partially successful. In clinical descriptions, POT has been observed to be associated with
clinical features of cerebellar dysfunction such as dysmetria and gait ataxia. Positron
emission tomography (PET) imaging has shown an increased activation of bilateral cerebellum
related either to a mismatch between the peripheral afferent and the cerebellar efferent
traffic or to a primary disorder of the cerebellum. MRI study has confirmed a cerebellar
atrophy in POT and finally transcranial magnetic stimulation (TMS), has shown POT can be
reset by stimulation of the cerebellum. The primary goal of this study is to test the
efficacy of low frequency rTMS therapy in POT. The first aim of the study is to determine the
clinical impact of 1-Hz rTMS therapy in POT when delivered to the cerebellum. This impact
will be evaluated by the clinical scoring of leg tremors in standing posture, and the
functional assessment of gait mobility. The second aim of this study is to determine the
physiological effects of 1-Hz rTMS therapy in POT when delivered to the cerebellum. The
investigator will determine the effects on the amplitude and frequency of tremors recorded
with surface EMG. They will also determine the effects on the cerebello-cortical inhibition
measured with TMS. Comparisons will be drawn between before rTMS therapy, immediately or +5
minutes after and 60+ minutes after assessments to determine the time course of effects. In
this application, subjects with POT will be enrolled based on clinical history, physical exam
and a 13-18 Hz tremor recorded on the surface EMG in accordance with the Consensus Statement
of the Movement Disorder Society. Data will be presented as mean (SD) unless otherwise
indicated. For each of the outcome variables, the statistical analyst will conduct a mixed
model analysis using time and stimulation arm as repeated factors adjusted for baseline
values, and subjects as the random factor.
of 13-18 Hz tremors in the leg muscles. POT was first described in 1984 at the University of
Florida. Since then several clinical descriptions have been published however despite this
knowledge for thirty years, treatment opportunities for POT have remained poor. Several
medications have been tried, but the results have been disappointing. Thalamic deep brain
stimulation (DBS) surgery, which is an invasive therapy approved by the FDA for treatment of
essential tremor, was recently investigated in POT but the early results have only been
partially successful. In clinical descriptions, POT has been observed to be associated with
clinical features of cerebellar dysfunction such as dysmetria and gait ataxia. Positron
emission tomography (PET) imaging has shown an increased activation of bilateral cerebellum
related either to a mismatch between the peripheral afferent and the cerebellar efferent
traffic or to a primary disorder of the cerebellum. MRI study has confirmed a cerebellar
atrophy in POT and finally transcranial magnetic stimulation (TMS), has shown POT can be
reset by stimulation of the cerebellum. The primary goal of this study is to test the
efficacy of low frequency rTMS therapy in POT. The first aim of the study is to determine the
clinical impact of 1-Hz rTMS therapy in POT when delivered to the cerebellum. This impact
will be evaluated by the clinical scoring of leg tremors in standing posture, and the
functional assessment of gait mobility. The second aim of this study is to determine the
physiological effects of 1-Hz rTMS therapy in POT when delivered to the cerebellum. The
investigator will determine the effects on the amplitude and frequency of tremors recorded
with surface EMG. They will also determine the effects on the cerebello-cortical inhibition
measured with TMS. Comparisons will be drawn between before rTMS therapy, immediately or +5
minutes after and 60+ minutes after assessments to determine the time course of effects. In
this application, subjects with POT will be enrolled based on clinical history, physical exam
and a 13-18 Hz tremor recorded on the surface EMG in accordance with the Consensus Statement
of the Movement Disorder Society. Data will be presented as mean (SD) unless otherwise
indicated. For each of the outcome variables, the statistical analyst will conduct a mixed
model analysis using time and stimulation arm as repeated factors adjusted for baseline
values, and subjects as the random factor.
Inclusion Criteria:
- Potential participants will be diagnosed with Primary orthostatic tremor (POT) and be
recruited through IRB approved database maintained by the Movement Disorders Center
Exclusion Criteria:
- Pregnancy
- Active seizure disorder
- Significant cognitive impairment
- Presence of a metallic body such as pacemaker, implants, prosthesis,artificial limb or
joint, shunt, metal rods and hearing aid
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