The Effects of Cerebellar Intermittent Theta Burst Stimulation on Gait, Balance, and Disease Anxiety In Stroke Patients

The Effect of Cerebellar Intermittent Theta Burst Stimulation Combined With Conventional Rehabilitation Methods on Gait, Balance, and Disease Anxiety in Patients With Ischemic Stroke

Our study was designed to investigate the effect of cerebellar intermittent theta burst stimulation (iTBS) combined with conventional rehabilitation methods on balance, gait and disease anxiety in patients with ischemic stroke who have residual balance and gait disturbance, using clinical measurement parameters.

Study Overview

• Status: Completed
• Conditions: Hemiplegia Following Ischemic Stroke
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation; Device: Transcranial Magnetic Stimulation Sham

Detailed Description

Loss of balance and gait functions, which are neurological impairments related to stroke, are among the common functional losses depending on the affected brain region. Reduced independence in daily living activities can lead to increased anxiety during ambulation, risk of falling and fear of falling. Studies have shown that applying theta burst stimulation (TBS) to the cerebellum has long-term effects on the excitability of the cerebello-thalamo-cortical pathways and stimulates synaptic plasticity through various mechanisms. In the literature, there are studies examining the effects of cerebellar iTBS on balance and walking functions in stroke patients, but the number of studies are quite limited.

This study was planned as a prospective, randomized, sham-controlled clinical study. According to the statistical analysis 30 patients who were registered at Ankara Bilkent City Hospital Physical Therapy and Rehabilitation Hospital between February 2022 and April 2023 and met the study criteria were included. The patients were divided into two groups: active (n=15) and sham (n=15). Each group received 30 sessions of either active or sham cerebellar iTBS (CRB-iTBS). Additionally, patients received therapeutic interventions from a physiotherapist, including range of motion exercises, stretching, neurophysiological exercises, balance-coordination training, active-assistive mobilization, and exercises for daily living.

The CRB-iTBS treatment targeted the cerebellum on the opposite side to the cerebral lesions, administered in a total of 30 sessions, twice a day with a 5-minute interval between sessions, over a period of 3 weeks. Each stimulation session consisted of 3-burst pulses at a frequency of 50 Hz, with a 10-second repetitive cycle of 2-second stimulations lasting a total of 190 seconds, delivering 600 pulses per session. Each day, a total of 1200 pulses were administered over two sessions, spaced 5 minutes apart. Patients in the sham CRB-iTBS group received the same protocol with a sham coil that visually resembled the active coil.

Clinical evaluations were conducted three times for each patient: Baseline (before treatment), 3rd week (at the and of treatment), and 6th week.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Ankara, Turkey, 06800
    • Ankara Bilkent City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• First ischemic stroke,
• Duration between 2 months to 2 years post-stroke,
• Hemiparesis and residual gait and balance disorders related to the lesion in the MCA area (Berg Balance Scale score < 40),
• Lower extremity Brunnstrom value of at least 3 ,
• Mini Mental State Examination ≥ 24,
• Between 18-80 years old

Exclusion Criteria:

• History of seizures,
• Severe general impairmet or concomittant disease,
• Using benzodiazepines, baclofen or antidepressants,
• Having a cardiac pacemaker, cochlear implant, metallic implants in the brain or skull,
• Pregnancy,
• Under 18 or over 80 years old

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active CRB-iTBS; Patients received a total of 30 sessions active CRB-iTBS targeting contralesional lateral cerebellum, 5 days a week for 3 weeks. The cerebellar region to be targeted, on the opposite side of the cerebral lesion, was determined by measuring 3 cm lateral and 1 cm inferior of the inion, which is the anatomical prominence on the occipital bone (3L1I). Stimulation intensity was set at 80% of the active motor threshold (AMT). AMT was defined as the lowest intensity required for a motor-evoked potentials (MEP) above 200 µV in at least 50% of 10 trials when the patient was contracting targeted muscle 10% on the maximum voluntary contraction. Stimulation was administered as 3-burst pulses at a frequency of 50 Hz, with 2-second stimulation repeated every 10 seconds period. This continued for a total duration of 190 seconds, delivering 600 pulses. Each CRB-iTBS session was performed in 2 sessions before daily rehabilitation programs. Thus, 1200 pulses were applied per day.	Device: Transcranial Magnetic Stimulation; Magstim Rapid2 Magnetic Stimulator (Magstim, Whitland Dyfed, UK), 70 mm Figure-of-eight Coil
Sham Comparator: Sham CRB-iTBS; Patients received a total of 30 sessions sham CRB-iTBS targeting contralesional lateral cerebellum, 5 days a week for 3 weeks. The cerebellar region to be targeted, on the opposite side of the cerebral lesion, was determined by measuring 3 cm lateral and 1 cm inferior of the inion, which is the anatomical prominence on the occipital bone (3L1I). However, sham coil was used for stimulation. Therefore, no real stimulation was applied to the patients. Instead, a sensation mimicking real stimulation was created through the sham coil, with sounds and sensations on the scalp as if stimulation were occurring. Each sham CRB-iTBS session was performed in 2 sessions before daily rehabilitation programs.	Device: Transcranial Magnetic Stimulation Sham; Magstim Rapid2 Magnetic Stimulator (Magstim, Whitland Dyfed, UK), 70 mm Figure-of-eight Sham Coil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Berg Balance Scale (BBS)	This is a scale used to evaluate patients' balance during 14 different activities. These activities include: sitting to standig, standing unsupported, sitting unsupported, standing to sitting, transfers, standing unsupported with eyes closed, standing with feet together, reaching forward while standing, picking up an object from the floor, looking back over the shoulder on both the right and left sides, turning 360 degrees, placing a foot on a stool, standing in a toe-heel position, and standing on one foot. The total score after performing the test determines the predicted risk of falls. The minimum score on the test is 0, and the maximum score is 56. Scores are classified as follows: 0-20 indicates a high risk of falling, 21-40 indicates a moderate risk of falling, and 41-56 indicates a low risk of falling.	Baseline (before treatment), 3rd week (at the end of treatment), 6th week
Gait Analysis- Step Length	The Zebris FDM Type 3 (Zebris Medical GmbH, Germany) device was used to record spatiotemporal data during walking. This system consists of a 3-meter straight platform, with two 1-meter maneuvering platforms at the start and end. It is equipped with sensors and computer software for data analysis. The data collected in the study included step length (cm).	Baseline (before treatment), 3rd week (at the end of treatment), 6th week
Gait Analysis- Step Width	The Zebris FDM Type 3 (Zebris Medical GmbH, Germany) device was used to record spatiotemporal data during walking. This system consists of a 3-meter straight platform, with two 1-meter maneuvering platforms at the start and end. It is equipped with sensors and computer software for data analysis. The data collected in the study included step width (cm).	Baseline (before treatment), 3rd week (at the end of treatment), 6th week
Gait Analysis- Walking Speed	The Zebris FDM Type 3 (Zebris Medical GmbH, Germany) device was used to record spatiotemporal data during walking. This system consists of a 3-meter straight platform, with two 1-meter maneuvering platforms at the start and end. It is equipped with sensors and computer software for data analysis. The data collected in the study included walking speed (km/h).	Baseline (before treatment), 3rd week (at the end of treatment), 6th week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Falls Efficacy Scale (FES-I)	Patients are evaluated for their level of concern about the risk of falling during 16 different activities. A score of 1 reflects no concern, while a score of 4 reflects a high level of concern. Total scores range from 16 to 64, with higher scores indicating greater anxiety about falling and lower self-confidence during activities.	Baseline (before treatment), 3rd week (at the end of treatment), 6th week
Barthel Index for Activities of Daily Living (BI)	The Barthel Index (BI) was used to assess physical independence in daily activities on ten-item scale. These items are: feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfer (bed to chair and back), mobility (on level surfaces). Score of 0 indicating complete dependence and a score of 100 indicating complete independence.	Baseline (before treatment), 3rd week (at the end of treatment), 6th week
Stroke Specific Quality of Life Scale (SS-QOL)	The Stroke-Specific Quality of Life Scale (SS-QOL) assesses the functionality and quality of life in stroke patients through 49 questions across 12 categories. These categories include: thinking, upper extremity functions, vision, work/productivity, social roles, self-care, personality, mood, mobility, language, family roles, and energy. Scoring is done on a scale from 1 to 5, with a total score ranging from 49 to 245. A score of 49 indicates very low quality of life, while a score of 245 indicates high quality of life.	Baseline (before treatment), 3rd week (at the end of treatment), 6th week
Hospital Anxiety and Depression Scale (HADS)	Hospital Anxiety and Depression Scale (HADS) consists of 14 questions, which are to be answered based on the patient's experience over the past few days while hospitalized. Seven of the questions assess depression, and seven assess anxiety levels. Separate scoring is done for anxiety and depression. The score may range between 0 and 21 per subscale. Higher scores indicate higher levels of anxiety and depression.	Baseline (before treatment), 3rd week (at the end of treatment), 6th week

Collaborators and Investigators

• Sponsor: Ankara City Hospital Bilkent
• Investigators: Study Chair: Filiz Acar Sivas, Prof, MD, Ankara Bilkent City Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: November 15, 2024
• First Submitted That Met QC Criteria: November 16, 2024
• First Posted (Estimated): November 20, 2024

Study Record Updates

• Last Update Posted (Estimated): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 16, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Balance; Stroke; Gait; Transcranial Magnetic Stimulation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Paralysis; Ischemic Stroke; Stroke; Hemiplegia
• Other Study ID Numbers: AnkaraCHBilkent-PMR-MK-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No