Cerebellar rTMS and Physical Therapy for Cerebellar Ataxia

Study Overview
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Brief Summary
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The present study investigated the efficacy and safety of combination treatment of repetitive transcranial magnetic stimulation (rTMS) and physical therapy (PT) in patients with cerebellar variant of multiple system atrophy (MSA-C) and spinocerebellar ataxia.

Official Title
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Effect of Repetitive Transcranial Magnetic Stimulation With Intensive Physical Therapy in Cerebellar Ataxia: A Pilot Study

Conditions
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Multiple System Atrophy, Cerebellar Variant (Disorder), Spinocerebellar Ataxias

Intervention / Treatment
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* Device: Cerebellar repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients with probable MSA-C and spinocerebellar ataxia (SCA) cerebellar ataxia as main clinical presenting feature and able to walk independently without walking devices aged over 20 presence of cerebellar atrophy proven by brain MRI. Exclusion Criteria: secondary cerebellar ataxia peripheral neuropathy, radiculopathy, or decreased visual acuity that can cause peripheral ataxia musculoskeletal disease affecting gait or balance other neurologic symptoms, including symptomatic parkinsonism (two or more rigidity and/or bradykinesia scores in one limb by Unified Parkinson's disease Rating Scale part 3) or spasticity (20) psychiatric symptoms requiring medication or with cognitive decline (Mini-mental state examination [MMSE] < 20) taking any sedative medications or anti-parkinsonian medications such as benzodiazepine, levodopa or dopamine agonist history of seizure or metallic brain implants; (8) cardiopulmonary diseases causing dyspnea during exercise.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cerebellar rTMS + Physical therapy<br>rTMS was delivered on the scalp for over 2 cm under the inion, which is the scalp over the cerebellum area, using a double-cone coil connected to a Magstim Rapid2® stimulator with two Booster Modules (Magstim, Spring Gardens, Wales, UK) in accordance with safety recommendations. Stimulation was delivered to the cerebellum at 10 Hz with 90% of the mean resting motor threshold intensity for 5 seconds at 55 second intervals to deliver 1000 pulses in 20 minutes. Immediately after rTMS, the combination treatment group received balance and gait training by a physical therapist for 30 minutes/day and underwent aerobic exercise using a stationary bicycle at moderate intensity (12 to 14 rating of perceived exertion) for 30 minutes/day and 5 days/week for two weeks. In the control group, no participants received physical therapy or rTMS for two weeks. | Device: Cerebellar repetitive transcranial magnetic stimulation<br>* rTMS was delivered on the scalp for over 2 cm under the inion, which is the scalp over the cerebellum area, using a double-cone coil connected to a Magstim Rapid2® stimulator with two Booster Modules (Magstim, Spring Gardens, Wales, UK) in accordance with safety recommendations. Stimulation was delivered to the cerebellum at 10 Hz with 90% of the mean resting motor threshold intensity for 5 seconds at 55 second intervals to deliver 1000 pulses in 20 minutes. Immediately after rTMS, the combination treatment group received balance and gait training by a physical therapist for 30 minutes/day and underwent aerobic exercise using a stationary bicycle at moderate intensity (12 to 14 rating of perceived exertion) for 30 minutes/day and 5 days/week for two weeks. In the control group, no participants received physical therapy or rTMS for two weeks.<br>|
| Sham Comparator: Sham stimulation + Physical therapy<br>Sham stimulation was delivered on the scalp for over 2 cm under the inion, which is the scalp over the cerebellum area, using a double-cone coil connected to a Magstim Rapid2® stimulator. Sham stimulation was delivered to the cerebellum for 5 seconds at 55 second intervals in 20 minutes. Immediately after rTMS, the combination treatment group received balance and gait training by a physical therapist for 30 minutes/day and underwent aerobic exercise using a stationary bicycle at moderate intensity (12 to 14 rating of perceived exertion) for 30 minutes/day and 5 days/week for two weeks. In the control group, no participants received physical therapy or rTMS for two weeks. | Device: Cerebellar repetitive transcranial magnetic stimulation<br>* rTMS was delivered on the scalp for over 2 cm under the inion, which is the scalp over the cerebellum area, using a double-cone coil connected to a Magstim Rapid2® stimulator with two Booster Modules (Magstim, Spring Gardens, Wales, UK) in accordance with safety recommendations. Stimulation was delivered to the cerebellum at 10 Hz with 90% of the mean resting motor threshold intensity for 5 seconds at 55 second intervals to deliver 1000 pulses in 20 minutes. Immediately after rTMS, the combination treatment group received balance and gait training by a physical therapist for 30 minutes/day and underwent aerobic exercise using a stationary bicycle at moderate intensity (12 to 14 rating of perceived exertion) for 30 minutes/day and 5 days/week for two weeks. In the control group, no participants received physical therapy or rTMS for two weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Cooperative Ataxia Rating Scale (ICARS) | The scale is scored out of 100 with 19 items and 4 subscales of postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. Higher scores indicate higher levels of impairment. | The change of ICARS score between baseline (T0) and immediately after (T1) treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from temporospatial parameters of gait | Gait parameters measured by GAITRite system | The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention. | 
| Change from posturography | Posturography measured by Pedoscan system | The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention. | 
| Change from Mini-Mental State Examination (MMSE) | Measurement of cognitive function | The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention. | 
| Change from Beck depression inventory (BDI) | Measurement of symptoms of depression | The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention. | 
| Change from Barthel Index for Activities of Daily Living | Measurement of activities of daily living | The clinical scales were evaluated by blinded raters at baseline (T0) and immediately after (T1), 4 weeks after (T2), and 12 weeks (T3) after intervention. | 
| Change from International Cooperative Ataxia Rating Scale (ICARS) | The scale is scored out of 100 with 19 items and 4 subscales of postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. Higher scores indicate higher levels of impairment. | The clinical scales were evaluated by blinded raters at baseline (T0) and 4 weeks after (T2), and 12 weeks (T3) after intervention. |