Focal Dystonia
Conditions
Keywords
focal hand dystonia (FHD), repetitive transcranial magnetic stimulation (rTMS), sensorimotor retraining
Brief summary
This study is exploring a new experimental procedure in dystonia called repetitive transcranial magnetic brain stimulation (TMS) combined with rehabilitation. The purpose of the study is to determine whether repetitive TMS is effective as a treatment to reduce symptoms in dystonia as demonstrated by improved motor performance.
Detailed description
BACKGROUND: Though the etiology of focal hand dystonia (FHD) is uncertain, two primary factors implicated in the development of dystonic symptoms are excessive cortical excitability and impaired sensorimotor processing. OBJECTIVE: The purpose of this study was to determine the functional efficacy and neural effects of a Dual intervention of rTMS and sensorimotor retraining. Our working hypothesis is: subjects receiving the combined intervention will (1) display significantly improved handwriting measures; (2) report significant improvement in daily functional ability; (3) display reduced hand cramping compared; and (4) demonstrate reduced corticospinal excitability after the Dual intervention when compared to the rTMS+ stretching and massage (Sham) intervention. METHODS: A randomized, single-subject, multiple baseline design with crossover is used for this study that will examine ten subjects with FHD with two interventions: five days of low-frequency 1 Hz rTMS + sensorimotor retraining (Dual intervention) vs. rTMS + stretching and massage (Sham). The rTMS is applied to the premotor cortex at 1 Hz at 90% resting motor threshold for 1200 pulses. For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed.
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation
Applied to the premotor cortex at 1 Hz at 90% resting motor threshold for 1200 pulses.
BEHAVIORALSensorimotor Retraining
For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed
BEHAVIORALNon-specific Therapy
A non-specific massage and stretching program directed to the hand, wrist and forearm
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Greater than 18 years of age * Symptoms of focal hand dystonia or writer's cramp
Exclusion criteria
* History of seizure or other neurologic disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Global Rating of Change at Posttest (Day 5) | Baseline and Posttest | Symptom severity was assessed using the global rating of change (GROC). For the GROC, participants were asked to identify between one to three functions most impacted by focal hand dystonia. At posttest 1 they were then asked to select a rating of perceived change that represented the level of function compared to baseline. Perceived change consisted of a ±7 point Likert scale (+7= a very great deal better, 0= no change, -7= a very great deal worse). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Sensation at Posttest (Day 5) | Baseline and Posttest | Examinations included two point discrimination. Two-point discrimination threshold was completed using a Disk-Criminator™. Participants were asked to reply one or two after each presentation. Static and dynamic stimuli were presented to the index and ring fingers bilaterally, meaning it was presented as a static stimuli or it was slowly swept across the skin (dynamic). |
| Change From Baseline in Cortical Silent Period at Posttest (Day 5) | Baseline and Posttest | Cortical silent period (CSP) testing was completed during an isometric contraction of the target muscle whereby the motor evoked potential is followed by a short duration of electromyographic quiescence. The maximal voluntary contraction for finger abduction was recorded using a custom strain gauge placed around the index finger. Real-time visual feedback was given on a laptop screen to project the force produced by the participant and 20% of the maximum of three trials was calculated and displayed on a target line. For the CSP, participants were asked to contract until the target line was met, then a single transcranial magnetic stimulation pulse was delivered to the motor cortex. Ten trials were collected with a short rest period to prevent fatigue. CSP duration was calculated in milliseconds (ms). CSP EMG data were first rectified, and then a 10-ms moving average calculation was applied to the data. The onset of the CSP was set as the time point of the delivery of the TM |
| Change From Baseline in Arm Dystonia Disability Scale at Posttest (Day 5) | Baseline and Posttest | The Arm Dystonia Disability Scale (ADDS) is a survey where participants rate task difficulty for activities such as writing, handling utensils, and buttoning on a scale of 1-4 (1 = no difficulty ,4 = not able or marked difficulty). This is a subjective assessment of impairment due to focal hand dystonia. Scores are determined using an equation: total points scored, divided by the maximum possible (23), multiplied by the quotient by 90 and subtract from 90%. Scores range from 0%-90% with higher scores indicating more function. |
| Change From Baseline for Physician Rated Impairment at Posttest (Day 5) | Baseline and Posttest | Video recordings were made as participants wrote on a pad of paper with pen. Participants were asked to draw a series of 10 loops across the pad of paper followed by The dog is barking and their signature, each repeated four times. A physician blinded to participant allocation rated recordings. Scoring criteria were adapted from a standardized writer's cramp rating scale (WCRS) (Wissel et al., 1996), rating pathological flexion or extension at the wrist, fingers and elbow, presence of tremor, dystonic posture, writing speed and latency of dystonic symptoms. Final scores are expressed as a rating listed as a movement score. |
| Change From Baseline in Physical Function at Posttest (Day 5) | Baseline and Posttest | Participants completed the full SF-36 assessment with subsection of interest: physical functioning. |
| Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) | Baseline and Posttest | Digitized handwriting was assessed using a computerized tablet (WACOM Co., Ltd., japan) with MovAlyzeR® (Neuroscript LLC, Tempe, AZ) hardware and software. Participants used a custom modified digitized pen (Kiko Software, Netherlands) to write in a self-selected pace and style on the tablet with real-time visual feedback. Writing tasks included My country tis of thee at a self-selected pace, repeated eight times. Data were sampled at 215 Hz (resolution: 5080 lpi, accuracy: ±0.01 pressure range: 0-800 g). Writing samples were segmented by points of minimal velocity into single strokes for analysis. Pressure for each stroke was automatically calculated within the software. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rTMS + Sensorimotor Retraining, rTMS + CTL Repetitive transcranial magnetic (rTMS) stimulation and sensorimotor retraining for the first phase, then rTMS with control therapy (CTL). CTL therapy was non-specific therapy that includes stretching, massage, range of motion.
Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed | 5 |
| rTMS + CTL, rTMS + Sensorimotor Retraining Repetitive transcranial magnetic stimulation (rTMS) with control therapy (CTL). CTL therapy was non-specific therapy that includes stretching, massage, range of motion for the first phase, then rTMS with sensorimotor retraining.
Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | rTMS + Sensorimotor Retraining, rTMS + CTL | rTMS + CTL, rTMS + Sensorimotor Retraining | Total |
|---|---|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 13.55359731 | 44 years STANDARD_DEVIATION 6.751543034 | 46 years STANDARD_DEVIATION 10.64320336 |
| Region of Enrollment United States | 5 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 5 | 2 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 |
Outcome results
Primary
Change From Baseline in Global Rating of Change at Posttest (Day 5)
Symptom severity was assessed using the global rating of change (GROC). For the GROC, participants were asked to identify between one to three functions most impacted by focal hand dystonia. At posttest 1 they were then asked to select a rating of perceived change that represented the level of function compared to baseline. Perceived change consisted of a ±7 point Likert scale (+7= a very great deal better, 0= no change, -7= a very great deal worse).
Time frame: Baseline and Posttest
Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rTMS With Sensorimotor Retraining | Change From Baseline in Global Rating of Change at Posttest (Day 5) | 1.3 units on a scale |
| rTMS With Control Therapy | Change From Baseline in Global Rating of Change at Posttest (Day 5) | 1.2 units on a scale |
Secondary
Change From Baseline for Physician Rated Impairment at Posttest (Day 5)
Video recordings were made as participants wrote on a pad of paper with pen. Participants were asked to draw a series of 10 loops across the pad of paper followed by The dog is barking and their signature, each repeated four times. A physician blinded to participant allocation rated recordings. Scoring criteria were adapted from a standardized writer's cramp rating scale (WCRS) (Wissel et al., 1996), rating pathological flexion or extension at the wrist, fingers and elbow, presence of tremor, dystonic posture, writing speed and latency of dystonic symptoms. Final scores are expressed as a rating listed as a movement score.
Time frame: Baseline and Posttest
Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rTMS With Sensorimotor Retraining | Change From Baseline for Physician Rated Impairment at Posttest (Day 5) | Improvement | 2 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline for Physician Rated Impairment at Posttest (Day 5) | No Change | 3 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline for Physician Rated Impairment at Posttest (Day 5) | Worsening | 0 Participants |
| rTMS With Control Therapy | Change From Baseline for Physician Rated Impairment at Posttest (Day 5) | Improvement | 0 Participants |
| rTMS With Control Therapy | Change From Baseline for Physician Rated Impairment at Posttest (Day 5) | No Change | 3 Participants |
| rTMS With Control Therapy | Change From Baseline for Physician Rated Impairment at Posttest (Day 5) | Worsening | 1 Participants |
Secondary
Change From Baseline for Pressure During Hand Writing at Posttest (Day 5)
Digitized handwriting was assessed using a computerized tablet (WACOM Co., Ltd., japan) with MovAlyzeR® (Neuroscript LLC, Tempe, AZ) hardware and software. Participants used a custom modified digitized pen (Kiko Software, Netherlands) to write in a self-selected pace and style on the tablet with real-time visual feedback. Writing tasks included My country tis of thee at a self-selected pace, repeated eight times. Data were sampled at 215 Hz (resolution: 5080 lpi, accuracy: ±0.01 pressure range: 0-800 g). Writing samples were segmented by points of minimal velocity into single strokes for analysis. Pressure for each stroke was automatically calculated within the software.
Time frame: Baseline and Posttest
Population: One participant that did not display symptoms affecting handwriting and did not participate in the handwriting analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rTMS With Sensorimotor Retraining | Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) | Improvement | 2 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) | No Change | 3 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) | Worsening | 0 Participants |
| rTMS With Control Therapy | Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) | Improvement | 2 Participants |
| rTMS With Control Therapy | Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) | No Change | 1 Participants |
| rTMS With Control Therapy | Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) | Worsening | 0 Participants |
Secondary
Change From Baseline in Arm Dystonia Disability Scale at Posttest (Day 5)
The Arm Dystonia Disability Scale (ADDS) is a survey where participants rate task difficulty for activities such as writing, handling utensils, and buttoning on a scale of 1-4 (1 = no difficulty ,4 = not able or marked difficulty). This is a subjective assessment of impairment due to focal hand dystonia. Scores are determined using an equation: total points scored, divided by the maximum possible (23), multiplied by the quotient by 90 and subtract from 90%. Scores range from 0%-90% with higher scores indicating more function.
Time frame: Baseline and Posttest
Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rTMS With Sensorimotor Retraining | Change From Baseline in Arm Dystonia Disability Scale at Posttest (Day 5) | 71.98 percentage of function | Standard Deviation 7.031320694 |
| rTMS With Control Therapy | Change From Baseline in Arm Dystonia Disability Scale at Posttest (Day 5) | 71.42 percentage of function | Standard Deviation 8.464086657 |
Secondary
Change From Baseline in Cortical Silent Period at Posttest (Day 5)
Cortical silent period (CSP) testing was completed during an isometric contraction of the target muscle whereby the motor evoked potential is followed by a short duration of electromyographic quiescence. The maximal voluntary contraction for finger abduction was recorded using a custom strain gauge placed around the index finger. Real-time visual feedback was given on a laptop screen to project the force produced by the participant and 20% of the maximum of three trials was calculated and displayed on a target line. For the CSP, participants were asked to contract until the target line was met, then a single transcranial magnetic stimulation pulse was delivered to the motor cortex. Ten trials were collected with a short rest period to prevent fatigue. CSP duration was calculated in milliseconds (ms). CSP EMG data were first rectified, and then a 10-ms moving average calculation was applied to the data. The onset of the CSP was set as the time point of the delivery of the TM
Time frame: Baseline and Posttest
Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rTMS With Sensorimotor Retraining | Change From Baseline in Cortical Silent Period at Posttest (Day 5) | Improvement | 2 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline in Cortical Silent Period at Posttest (Day 5) | No Change | 2 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline in Cortical Silent Period at Posttest (Day 5) | Worsening | 1 Participants |
| rTMS With Control Therapy | Change From Baseline in Cortical Silent Period at Posttest (Day 5) | Improvement | 1 Participants |
| rTMS With Control Therapy | Change From Baseline in Cortical Silent Period at Posttest (Day 5) | No Change | 1 Participants |
| rTMS With Control Therapy | Change From Baseline in Cortical Silent Period at Posttest (Day 5) | Worsening | 2 Participants |
Secondary
Change From Baseline in Physical Function at Posttest (Day 5)
Participants completed the full SF-36 assessment with subsection of interest: physical functioning.
Time frame: Baseline and Posttest
Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rTMS With Sensorimotor Retraining | Change From Baseline in Physical Function at Posttest (Day 5) | No Change | 4 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline in Physical Function at Posttest (Day 5) | Improvement | 1 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline in Physical Function at Posttest (Day 5) | Worsening | 0 Participants |
| rTMS With Control Therapy | Change From Baseline in Physical Function at Posttest (Day 5) | Improvement | 0 Participants |
| rTMS With Control Therapy | Change From Baseline in Physical Function at Posttest (Day 5) | No Change | 2 Participants |
| rTMS With Control Therapy | Change From Baseline in Physical Function at Posttest (Day 5) | Worsening | 2 Participants |
Secondary
Change From Baseline in Sensation at Posttest (Day 5)
Examinations included two point discrimination. Two-point discrimination threshold was completed using a Disk-Criminator™. Participants were asked to reply one or two after each presentation. Static and dynamic stimuli were presented to the index and ring fingers bilaterally, meaning it was presented as a static stimuli or it was slowly swept across the skin (dynamic).
Time frame: Baseline and Posttest
Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rTMS With Sensorimotor Retraining | Change From Baseline in Sensation at Posttest (Day 5) | Worsening | 0 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline in Sensation at Posttest (Day 5) | Improvement | 3 Participants |
| rTMS With Sensorimotor Retraining | Change From Baseline in Sensation at Posttest (Day 5) | No Change | 2 Participants |
| rTMS With Control Therapy | Change From Baseline in Sensation at Posttest (Day 5) | No Change | 1 Participants |
| rTMS With Control Therapy | Change From Baseline in Sensation at Posttest (Day 5) | Improvement | 2 Participants |
| rTMS With Control Therapy | Change From Baseline in Sensation at Posttest (Day 5) | Worsening | 1 Participants |