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NCT Number: NCT04063995

Repetitive Transcranial Magnetic Stimulation in Post Stroke Upper Limb Spasticity

The reticulospinal pathway (RSP) is at the center of spasticity mechanism. The RSP indirectly synapses with motor neurons via interneurons in the ventromedial intermediate zone in both halves of the spinal cord, and directly synapses with motor neurons of proximal extremity muscles. The main motor cortex region controlling unilateral RSP is the premotor cortex. That is, a single limb is represented in both premotor cortices. This suggests theoretically that if the corticoreticular pathway controlling RSP is modulated by dorsal premotor cortex stimulation, there may be a change in the regulation of the intraspinal network regulating the stretch reflex. Therefore, the hypothesis in this study is that the application of repetitive transcranial magnetic stimulation (rTMS) over the contralesional dorsal premotor cortex in chronic stroke patients changes the severity of spasticity.

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Key information

About this study

Spasticity is a disorder characterized by increase in velocity-related muscle tone as a part of upper motor neuron syndrome. Although the mechanisms underlying stroke-related spasticity have not been fully understood, the current view is that spasticity is related to an imbalance between descending excitatory and inhibitory systems that regulate spinal stretch reflex and associated with abnormal intraspinal processes. The reticulospinal pathway (RSP) is at the center of this mechanism called cortical disinhibition. The dorsal RSP, which has an inhibitory effect on the spinal stretch reflex, originates from the medullary reticular formation and is under cortical control. In contrast to dorsal RSP, medial RSP which is not under the control of motor cortex originates from pontine reticular formation,and has an excitatory effect on spinal stretch reflex. The main motor cortex region controlling unilateral dorsal RSP is the premotor cortex. Unilateral RSP indirectly synapses with motor neurons via interneurons in the ventromedial intermediate zone in both halves of the spinal cord, and directly synapses with motor neurons of proximal extremity muscles. That is, a single limb is represented in both premotor cortices. This suggests theoretically that if the corticoreticular pathway controlling dorsal RSP is modulated by dorsal premotor cortex stimulation, there may be a change in the regulation of the intraspinal network regulating the stretch reflex. Furthermore, in stroke patients with severe motor impairment, the relationship between high cortical centers and the primary motor cortex is more in the form of facilitation rather than interhemispheric inhibition between the primary motor cortices. In other words, stimulation of one side premotor cortex may affect motor impairment and spasticity by affecting primary and high motor cortical centers of both hemispheres and both halves of the spinal cord. Therefore, the hypothesis in this study is that the application of repetitive transcranial magnetic stimulation (rTMS) over the contralesional dorsal premotor cortex in chronic stroke patients changes the severity of spasticity. Based on this hypothesis, our aim is to investigate the effect of rTMS over the contralesional dorsal premotor cortex on the severity of spasticity in patients with chronic stroke with moderate to severe upper extremity spasticity.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • ≥ 18 years
  • Stroke history ≥ 1 year
  • Having a first stroke
  • Grade 2 or 3 muscle tone according to the Modified Ashworth Scale (MAS) assessment in at least one of the elbow, wrist and finger flexors
  • Signed consent to participate in the study

Exclusion criteria

  • To have a clinical condition (metallic implant, cardiac pace, pregnancy, breastfeeding, claustrophobia, epilepsy, head trauma, cranial operation history) that will constitute a contraindication to transcranial magnetic stimulation
  • Presence of malignancy
  • Pregnancy or breastfeeding
  • Non-stroke disease or lesion affecting the sensorimotor system
  • Presence of pump/shunt
  • Advanced cognitive impairment
  • To have been rehabilitated in the last 3 months
  • Botulinum toxin injection in the last 3 months
  • Taking systemic antispastic drugs (Patients taking these drugs may be included in the study after a period of at least 3 times the half-life of the drug used if they agree to quit)
  • Previously treated with TMS

Treatment and study plan

repetitive transcranial magnetic stimulation

Device

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive intervention that uses magnetic fields to stimulate nerve cells to improve the symptoms of a variety of disorders, including stroke-related motor impairment.

Primary outcomes

  1. Modified Ashworth Scale

    Time frame: Pre-intervention (baseline) and immediately after intervention (post-intervention), up to 45 minutes

    The modified Ashworth Scale is a scale that clinically evaluates the presence and severity of muscle tone increase. It is an ordinal scale that evaluates spasticity at six levels between 0 and 4 (0, 1, 1+, 2, 3, 4). The severity of spasticity increases as the score increases. Score 0 indicates no increase in muscle tone, while score 4 indicates that the affected part is rigid. Six levels between 0 and 5 (0, 1, 2, 3, 4, 5) will be used in statistical analysis. The score of 1+ will be treated as 2, 2 as 3, 3 as 4 and 4 as 5.

Secondary outcomes

  1. F wave parameters

    Time frame: Pre-intervention (baseline) and immediately after intervention (post-intervention), up to 45 minutes

    F-wave is one of the late responses caused by antidromic stimulation of alpha motor neurons. It occurs following supramaximal electrical stimulation of peripheral motor nerves following M response. The F wave indicates the transmission from the stimulated point to the motor neuron and back to the recording electrode. Increased F wave frequency, increased F / M ratio and amplitude has been considered to indicate the increased motor neuron excitability.

Sponsors and collaborators

Lead sponsor

Izmir Katip Celebi University

Other

Registry information

Official study title

Effect of Repetitive Transcranial Magnetic Stimulation Over Contralesional Dorsal Premotor Cortex on Post Stroke Upper Limb Spasticity

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Aug 21, 2019
Registry last updated
Apr 1, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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