Brief Title
Repetitive Transcranial Magnetic Stimulation (TMS) for Progressive Supranuclear Palsy and Corticobasal Degeneration
Official Title
Noninvasive Cortical Stimulation (rTMS) for Motor and Non-Motor Features of Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD)
Brief Summary
Drug therapy of atypical parkinsonism is generally considered either ineffective or minimal
1. Therefore, there is an urgent need to find alternative therapies to treat atypical
parkinsonian disorders. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive
tool that modulates cortical excitability with minimal discomfort and holds therapeutic
promise in treating neurological and psychiatric disorders.
The basal ganglia-thalamocortical circuits that are affected in Progressive Supranuclear
Palsy (PSP) and Corticocbasal Ganglionic Degeneration (CBGD) are likely structurally and
functionally segregated. The 'motor' circuit is implicated in parkinsonian akinesia and
hypokinesia; a 'prefrontal' circuit is implicated in working memory and mood regulation, and
linked with non-motor symptoms such as depression and apathy. In this proposal, we
characterize motor and prefrontal network dysfunction in PSP and CBGD patients, and propose
that high-frequency and low-frequency rTMS directed over separate motor and prefrontal
cortical targets of each network may show specific and selective beneficial effects on motor
vs. cognitive function in PSP and CBGD patients, respectively. Quantitative motor outcome
measures include timed finger tapping tasks. Quantitative cognitive outcome measures comprise
a visual analogue scale (VAS).
If successful, this pilot study will provide proof of principle data to suggest potential
benefits for rTMS in PSP/CBGD patients, and provide sufficient data and experience to support
future PSP/CBGD studies that include the use of rTMS to investigate the pathophysiology of
motor and non-motor features of PSP and CBGD patients.
Detailed Description
Background: Drug therapy of atypical parkinsonism is generally ineffective or minimal, and
novel therapy approaches for atypical parkinsonian disorders are needed. Repetitive
transcranial magnetic stimulation (rTMS) is a noninvasive tool that modulates cortical
excitability and holds promise in treating neurological/psychiatric disorders. The 'motor'
basal ganglia-cortical circuit is implicated in parkinsonian akinesia and hypokinesia; a
'prefrontal' circuit is implicated in working memory (WM) and mood regulation, possibly
linked to depression and apathy.
Hypothesis: Motor deficits in Progressive Supranuclear Palsy (PSP) and Corticobasal
Ganglionic Degeneration (CBGD) are associated with a dysfunctional motor network; emotional
deficits in PSP/CBGD are associated with a dysfunctional prefrontal network. We hypothesize
that high-frequency and low-frequency rTMS over cortical targets will selectively and
specifically improve tasks and symptoms relevant to that target in PSP and CBGD patients,
respectively.
Aims: To contrast cortical excitability characteristics and motor and emotional function
between PSP and CBGD patients. To determine selective and specific beneficial rTMS effects
over primary motor (M1) and dorsolateral prefrontal (DLPFC) cortex on cortical excitability
characteristics and motor and emotional function in PSP and CBGD patients.
Design: Ten individuals with PSP and ten with CBGD will participate in a within-subject
cross-sectional design. Motor outcome measures include a timed finger tapping task at
comfortable and maximal speed. Quantitative cognitive outcome measures comprise a visual
analogue scale of mood states (VAS). After a first baseline visit, PSP patients will receive
high-frequency 5 Hz rTMS in two separate visits to two site conditions (left DLPFC vs. the
more affected side of M1) across subjects with two within-session task conditions (motor vs.
cognitive). They will also receive sham stimulation in a separate visit. These three
stimulation visits will be randomized. CBGD patients will receive the same treatment with the
only difference that they will receive low-frequency 1 Hz rTMS instead.
Relevance: If successful, we will demonstrate a double-dissociation and causal functional
significance between rTMS modulation of M1 in motor tasks and DLPFC in emotional function in
PSP Vs. CBGD. Exploratory aims will be conducted. Sufficient data and experience for future
PSP/CBGD intervention studies will help identify candidate TMS parameters that are optimal
for given symptoms.
Study Type
Observational
Primary Outcome
Cortical excitability (CE) measures expressed in motor evoked potentials (MEP)
Secondary Outcome
visual analog scale (VAS)
Condition
Progressive Supranuclear Palsy
Study Arms / Comparison Groups
PSP patients
Description: People that have been clinically diagnosed with atypical parkinsonism, i.e., PSP
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
30
Start Date
October 2008
Completion Date
February 2012
Primary Completion Date
December 2011
Eligibility Criteria
Inclusion Criteria:
If you are an adult with PSP or CBGD:
1. Must be in good physical health.
If you are neurologically healthy volunteers:
1. Must be older than 35 years
Exclusion Criteria:
1. Must have no implanted metal. Dental fillings are acceptable.
2. Must have no personal seizure or 1st degree relative with history of seizures
3. Must not take any medication that lowers seizure threshold.
Gender
All
Ages
35 Years - N/A
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Allan Wu, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01174771
Organization ID
UCaliforniaLA
Secondary IDs
CurePSP
Responsible Party
Principal Investigator
Study Sponsor
University of California, Los Angeles
Study Sponsor
Allan Wu, M.D., Principal Investigator, UCLA Neurology
Verification Date
May 2014