# Corticospinal Intermittent Theta Burst Stimulation Propelling Sensorimotor Function Recovery in Complete Spinal Cord Injury: Protocol for a Randomized Controlled Trial

## TL;DR

This study tests if intermittent theta burst stimulation can help people with complete spinal cord injuries regain motor and sensory functions.

## Contribution

The study introduces a novel protocol using iTBS to assess corticospinal tract recovery in complete spinal cord injury patients.

## Key findings

- iTBS may improve corticospinal tract integrity and synaptic transmission in cSCI patients.
- The study will evaluate iTBS's impact on motor recovery, pain modulation, and quality of life.
- Electrophysiological and biomarker assessments will quantify iTBS's effects on neurological recovery.

## Abstract

Intermittent theta burst stimulation (iTBS) is a noninvasive stimulation technique to induce neuronal and synaptic plasticity. The induced cortical plasticity is imperative in the recovery of motor and sensory functions. Spinal cord injury (SCI) causes damage to neurons and results in sensorimotor dysfunction. The effect of iTBS on recovery of motor and sensory dysfunction in complete SCI (cSCI) is still elusive.

This study aims to assess the effect of iTBS on corticospinal tract integrity, plasticity, and regaining of motor and sensory function in patients with cSCI. The rationale behind using an iTBS protocol is to modify and augment the communication between spared neurons of the corticospinal tract and strengthen the synaptic transmission, which will improve motor function in underlying muscles.

A total of 40 patients with cSCI with American Spinal Injury Association (ASIA) grade A, aged 18-60 years, were randomly assigned to 5 groups. To evaluate the efficacy of iTBS versus traditional repetitive transcranial magnetic stimulation, patients were categorized into placebo, repetitive transcranial magnetic stimulation, and iTBS. In addition, to determine the optimal site for stimulation, groups were further subdivided into motor cortex, spinal cord, and combined. Each patient underwent 10 iTBS sessions twice daily for 5 consecutive days. Neurological outcomes and functional outcome parameters will be assessed. Electrophysiological evaluations included transcranial magnetic stimulation single-pulse and paired-pulse parameters. The effect of iTBS intervention on biomarkers will be quantified using the enzyme-linked immunosorbent assay, while neurotransmitters will be quantified by liquid chromatography and tandem mass spectrometry. Measurements will be done before and after the intervention, with follow-ups at 1, 2, and 3 months.

The outcome of the study will be defined by electrophysiological parameters elicited by single- and paired-pulse stimulation, ASIA score, pain, activities of daily life, quality of life, anxiety, depression, and biomarkers related to SCI. The results of this study will uncover the effectiveness of iTBS stimulation on (1) recovery of motor and sensory function in cSCI, (2) excitability of the corticospinal tract, (3) neurological recovery and modulation of pain, and (4) cortical reorganization after injury.

iTBS in conjunction with an individualized rehabilitation program may serve as an integrated strategy to rejuvenate locomotor abilities and improve the overall quality of life for people with cSCI.

Clinical Trials Registry- India CTRI/2022/11/047038; https://ctri.nic.in/Clinicaltrials/main1.php?EncHid=13361.98443

DERR1-10.2196/66531