Repetitive Transcranial Magnetic Stimulation in Post Stroke Upper Limb Spasticity

Spasticity as Sequela of Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04063995
• Other study ID #: 2019-KAE-0292
• Status: Completed
• Phase: N/A
• Start date: September 9, 2019
• Est. completion date: June 27, 2021

Study information

• Verified date: March 2022
• Source: Izmir Katip Celebi University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: June 27, 2021
• Est. primary completion date: June 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Muscle Spasticity
• Spasticity as Sequela of Stroke
• Stroke

Intervention

Device:
• Repetitive transcranial magnetic stimulation
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.

Locations

Country	Name	City	State
Turkey	Ilker Sengül	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
Izmir Katip Celebi University

Country where clinical trial is conducted

Turkey, 

References & Publications (8)

Bäumer T, Bock F, Koch G, Lange R, Rothwell JC, Siebner HR, Münchau A. Magnetic stimulation of human premotor or motor cortex produces interhemispheric facilitation through distinct pathways. J Physiol. 2006 May 1;572(Pt 3):857-68. — View Citation

Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987 Feb;67(2):206-7. — View Citation

Burke D, Wissel J, Donnan GA. Pathophysiology of spasticity in stroke. Neurology. 2013 Jan 15;80(3 Suppl 2):S20-6. doi: 10.1212/WNL.0b013e31827624a7. Review. — View Citation

Lemon RN. Descending pathways in motor control. Annu Rev Neurosci. 2008;31:195-218. doi: 10.1146/annurev.neuro.31.060407.125547. Review. — View Citation

Li S, Francisco GE. New insights into the pathophysiology of post-stroke spasticity. Front Hum Neurosci. 2015 Apr 10;9:192. doi: 10.3389/fnhum.2015.00192. eCollection 2015. Review. — View Citation

Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14. Review. — View Citation

Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998 Jan;108(1):1-16. — View Citation

Wupuer S, Yamamoto T, Katayama Y, Motohiko H, Sekiguchi S, Matsumura Y, Kobayashi K, Obuchi T, Fukaya C. F-wave suppression induced by suprathreshold high-frequency repetitive trascranial magnetic stimulation in poststroke patients with increased spasticity. Neuromodulation. 2013 May-Jun;16(3):206-11; discussion 211. doi: 10.1111/j.1525-1403.2012.00520.x. Epub 2012 Oct 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Ashworth Scale	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.	Pre-intervention (baseline) and immediately after intervention (post-intervention), up to 45 minutes
Secondary	F wave parameters	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.	Pre-intervention (baseline) and immediately after intervention (post-intervention), up to 45 minutes