Spasticity After Spinal Cord Injury

Very often, people who have a SCI have difficulty doing things with their arms or hands as a result of muscle stiffness , or spasticity. Spastacity can cause problems performing even the simplest of everyday tasks. This research will help us understand how the body recovers and changes neurologically after SCI.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Behavioral: Acoustic stimuli (Startle)

Detailed Description

After spinal cord injury (SCI), damage to descending motor pathways has been associated with the development of spasticity (Frigon and Rossignol, 2006; Trompetto et al., 2014). Self-reported questionnaires and clinical exams indicate that individuals with incomplete SCI, who showed residual descending connectivity, have a high prevalence of spasticity compared to individuals with complete SCI (Little et al., 1989; Holtz et al., 2017). In agreement, our recent electrophysiological and spinal cord imaging data in humans with a diagnosis of a clinically motor complete SCI showed the presence of descending motor pathway connectivity in individuals with spasticity compared to those without spasticity (Sangari et al., 2019). However, which descending motor pathways influence spasticity following SCI, and to what extent, remains poorly understood. This proposal has two main goals: 1) to examine the contribution of cortico- and reticulo-spinal pathways to spasticity in upper and lower limb muscles, and 2) to develop strategies to promote functional recovery of upper and lower limb spastic muscles in humans with chronic incomplete SCI. The aims below will test two main hypotheses.

In Aim 1, we will use transcranial magnetic stimulation and startle acoustic stimuli to examine the contribution of the cortico- and reticulo-spinal pathway to upper and/or lower limb muscles electromyographic activity. Spinal cord atrophy and morphological characterization of cortico- and reticulo-spinal pathways will be assessed with high-resolution magnetic resonance imaging. Physiological and neuroimaging outcomes will be associated with clinical assessment of spasticity.

In Aim 2, we propose to enhance cortico- and reticulo-spinal contribution to upper and/or lower limb function in spastic muscles by using a novel intervention combining startle acoustic stimuli with motor training.

This research will provide new knowledge about the contribution of descending motor pathways to the control of spasticity in upper and lower limb muscles following incomplete cervical SCI (Aim1) and might lead to the development of a novel rehabilitation intervention to improve upper and lower limb motor function recovery by enhancing residual descending control over spinal networks (Aim 2).

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sina Sangari, PhD; Phone Number: 312.238.1365; Email: ssangari@rsralab.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Shirley Ryan AbilityLab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for individuals with SCI

• Chronic SCI (≥1 year of injury)
• Incomplete spinal cord injury at T12 or above
• Males and Females
• Ages 18-75 years

Inclusion criteria for non-spastic individuals with SCI

-MAS scores of 0 and 1

Inclusion criteria for spastic individuals with SCI

• MAS scores of 2, 3 and 4
• The ability to perform a voluntary flexion and extension of the elbow and/or knee or ankle
• The ability to reach and grasp an object

Inclusion criteria for health controls

• Males and females
• Ages 18-75 years
• Right-handed
• Able to perform elbow and/or knee or ankle flexion and extension

Exclusion Criteria for individuals with SCI and healthy controls:

• Uncontrolled medical problems including pulmonary, cardiovascular, or orthopedic disease
• Any debilitating disease prior to the SCI that caused exercise intolerance
• Premorbid, ongoing major depression or psychosis, altered cognitive status
• History of head injury or stroke
• Pacemaker
• Metal plate in skull
• History of seizures
• Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants
• Pregnant females
• Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, or herniated cervical disk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aim 1; To accomplish this aim, we will conduct one experiment in two sessions separated by 2- 3 days using a crossover design. Participants will be assigned into one of three groups: spastic SCI, non-spastic SCI, and controls. We expect that people enrolled in Aim 1 will complete 2 visits within 1 week. Visit 1 Measurements: MVCs; MEP Recruitment Curves; iMEPs; StartReact Visit 2 Measurements: Participant Reported Spasticity; MAS; PSAD; KINARM; MRI of brain and spinal cord	Behavioral: Acoustic stimuli (Startle); A startle stimulus (120 dB, 500 Hz, 50 ms) will be delivered through headphones
Experimental: Aim 2; To accomplish this aim, we will use a randomized crossover design study with spastic SCI participants receiving a single intervention combining non-invasive acoustic stimuli (Startle) or sham-Startle with motor training to enhance cortico- and reticulo-spinal contribution, separated by ~2 weeks. Visit 1 and Visit 2 Single intervention of: Startle + exercise training OR sham-Startle + exercise training Pre and post measurements: MVCs; MEP recruitment curves; iMEPs; StartReact; Participant reported spasticity; MAS; PSAD; KINARM; Neuromechanical hand and/or leg testing; GRASSP; TRI-HFT; 10-meter walk test; Pendulum Test	Behavioral: Acoustic stimuli (Startle); A startle stimulus (120 dB, 500 Hz, 50 ms) will be delivered through headphones

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MEP recruitment curves	Ten stimuli (0.2 Hz) will be delivered at each intensity to plot the mean peak-to-peak amplitude of the MEP from the non-rectified response against the TMS intensity in each subject (MEP recruitment curve).	3-4 hours
Ipsilateral MEPs (iMEPs)	Ten stimuli will be delivered during head straight and ten stimuli will be delivered during lateral head rotation, randomly alternated (0.2 Hz).	3-4 hours
StartReact	Here, participants will be asked to observe a light-emitting diode (LED) located in front of their head. When the LED will illuminate, individuals will be asked to move their arm or leg. In some trials, the LED will be presented with either a quiet acoustic stimulus (80 dB, 500 Hz, 50 ms) or a startling acoustic stimulus (SAS, 120 dB, 500 Hz, 50 ms) delivered through a headphone.	3-4 hours
Participant reported spasticity	Spasticity questionnaire	3-4 hours
Modified Ashworth Scale (MAS)	This scale measures resistance encountered during manual passive muscle stretching using a six-point ordinal scale.	3-4 hours
Portable Spasticity Assessment Device (PSAD)'	The PSAD combine biomechanical and electrophysiological measurements for an objective quantification of active and passive component of muscle stiffness	3-4 hours
Pendulum Test	As part of the physical exam, we will use the pendulum test to measure muscle tone at the knee by using gravity to provoke muscle stretch reflexes during passive swinging of the lower limb.	3-4 hours
10-meter walk test	10-meter walk test will be used to assess walking speed	3-4 hours
Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP).	This exam measures clinical impairment that incorporates three domains vital to upper-limb function: sensation, strength, and prehension.	3-4 hours
Toronto Rehabilitation Institute-Hand Function Test (TRI-HFT)	This exam measures gross motor function frequently used to manipulate objects that participants may encounter in their daily lives.	3-4 hours

Collaborators and Investigators

• Sponsor: Shirley Ryan AbilityLab

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2020
• Primary Completion (Anticipated): June 18, 2023
• Study Completion (Anticipated): May 18, 2024

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 20, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Spinal cord injury, Spasticity, TMS
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Muscle Hypertonia; Wounds and Injuries; Spinal Cord Injuries; Muscle Spasticity
• Other Study ID Numbers: STU00212201

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