Imaging of 3D Innervation Zone Distribution in Spastic Muscles From High-density Surface EMG Recordings

• Botulinum neurotoxin (BTX) (Drug), also known as Botox: Each patient will receive BTX injections in 2 sites. 100 units at double dilution will be injected at each site.
• Physical Therapy (Other): Standard physical therapy will be ordered to both groups as part of standard of care for patients after BTX injections to maximize the outcomes.
• Standard BTX injection (ultrasound guided) (Device): For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the innervation zones (IZs) of the entire muscle.
• 3-dimensional innervation zone (3DIZ) guided injection (Device): Simultaneous surface EMG and intramuscular EMG measurements will be acquired from the spastic biceps of the patients. Patients will be seated comfortably on a height-adjustable chair. The arm to be tested will be secured firmly on a customized apparatus with the elbow joint at approximately 90° of flexion and the shoulder at approximately 45° of abduction and 30° of flexion. The 128-channel unipolar surface EMG signals will be recorded with 2 flexible 2-dimensional 64-channel surface electrode array. A coating fine wire electrode will be inserted into the mid-axial section of the biceps to record bipolar intramuscular EMG signals. Ultrasound scan will be performed on the biceps to identify the location of the inserted wire electrode. Patients will be asked to contract their impaired biceps to perform maximum voluntary contraction of elbow flexion against the vertical plates 3 times.

Primary outcomes

• Spasticity as Assessed by Reflex Torque of Elbow Flexors [baseline (1 day prior to BTX injection)]: Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.
• Spasticity as Assessed by Reflex Torque of Elbow Flexors [3 weeks after BTX injection]: Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.
• Spasticity as Assessed by Reflex Torque of Elbow Flexors [3 months after BTX injection]: Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.

Secondary outcomes

• Spasticity as Assessed by the Modified Ashworth Scale (MAS) [baseline (1 day prior to BTX injection)]: The following modified Ashworth scale (MAS) will be used for spasticity assessment: 0 -No increase in muscle tone; 1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension; 1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.
• Spasticity as Assessed by the Modified Ashworth Scale (MAS) [3 weeks after BTX injection]: The following modified Ashworth scale (MAS) will be used for spasticity assessment: 0 -No increase in muscle tone; 1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension; 1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.
• Spasticity as Assessed by the Modified Ashworth Scale (MAS) [3 months after BTX injection]: The following modified Ashworth scale (MAS) will be used for spasticity assessment: 0 -No increase in muscle tone; 1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension; 1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.

Sex: All, ages: 21 Years to 75 Years

Inclusion Criteria:

* a history of not more than one stroke which occurred at least 6 months prior to study enrollment;
* elbow flexor spasticity rated at 2 or 3 on Modified Ashworth scale (MAS);
* receiving repeated botulinum toxin injection every 3-4 months;
* absence of excessive pain in the paretic upper limb;
* capacity to provide informed consent, with Mini-Mental State Examination (MMSE) must be 25 or higher;

The following modified Ashworth scale (MAS) will be used for spasticity assessment:

0 -No increase in muscle tone; 1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension; 1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.

Exclusion Criteria:

* recent botulinum toxin injection < 4 months;
* recent changes in antispastic medications <3 weeks (i.e., the antispastic medication regime is not stable;
* Changes in antispastic medications (such as baclofen, tizanidine, dantrolene etc) during the followup research visits. (NOTE: it is clinically rare for patients who receive repeated injections to change their antispastic medications);
* history of spinal cord injury or traumatic brain damage;
* history of serious medical illness such as cardiovascular or pulmonary complications;
* any condition that, in the judgment of a physician, would prevent the person from participating.

Participant flow

Outcome results

• Spasticity as Assessed by Reflex Torque of Elbow Flexors (Primary), Mean, Newton meter (n-m): Standard BTX Injection (Ultrasound Guided) 2.32 +/- 1.73; 3-dimensional Innervation Zone (3DIZ) Guided Injection 2.04 +/- 1.19
• Spasticity as Assessed by Reflex Torque of Elbow Flexors (Primary), Mean, Newton meter (n-m): Standard BTX Injection (Ultrasound Guided) 2.22 +/- 1.21; 3-dimensional Innervation Zone (3DIZ) Guided Injection 1.47 +/- 0.63
• Spasticity as Assessed by Reflex Torque of Elbow Flexors (Primary), Mean, Newton meter (n-m): Standard BTX Injection (Ultrasound Guided) 2.71 +/- 2.12; 3-dimensional Innervation Zone (3DIZ) Guided Injection 1.89 +/- 0.75
• Spasticity as Assessed by the Modified Ashworth Scale (MAS) (Secondary), Count of participants, Participants: Standard BTX Injection (Ultrasound Guided) 0; 3-dimensional Innervation Zone (3DIZ) Guided Injection 0
• Spasticity as Assessed by the Modified Ashworth Scale (MAS) (Secondary), Count of participants, Participants: Standard BTX Injection (Ultrasound Guided) 0; 3-dimensional Innervation Zone (3DIZ) Guided Injection 0
• Spasticity as Assessed by the Modified Ashworth Scale (MAS) (Secondary), Count of participants, Participants: Standard BTX Injection (Ultrasound Guided) 0; 3-dimensional Innervation Zone (3DIZ) Guided Injection 0

Adverse events

Time frame: 3 months

• Study Protocol and Statistical Analysis Plan (PDF, 2017-03-21)

• Sheng Li, MD, PhD, Principal investigator, The University of Texas Health Science Center, Houston