Effects of 4-AP on Functional SCI Recovery

Electrical stimulation will be performed placing the cathode on the upper thoracic between the spinal processes between T3 and T4 vertebrae and the anode at ~10 cm above

Individuals will perform a maximum voluntary contraction (MVC) of each targeted muscle (quadriceps femoris, tibialis anterior or soleus) through surface electrodes secured to the skin over the belly of each muscle.

Transcranial magnetic stimuli (TMS) will be delivered to the optimal scalp position for activation of quadriceps femoris and tibialis anterior muscles. The optimal scalp position will be determined by moving the coil in small steps along the hand/arm/leg representation of the primary motor cortex to find the region where the largest MEP can be evoked with the minimum intensity in the targeted muscles.

We will use the 10-meter walk test to quantify walking speed in meters per second. The same percentage of body-weight support will be used during pre- and post-assessments. Less time to walk 10-meter indicates better outcome.

We will measure the distance walked over 6 minutes. The same percentage of body-weight support will be used as in 10-meter walk test. The longer distance walked during 6 minutes indicates better outcome.

Motor part of the exam is completed through the testing of key muscle functions corresponding to 10 myotomes (C5-T1 and L2-S1) for right and left side separately. The strength of each muscle function is graded on a six-point scale ranging from 0 meaning complete paralysis to 5 meaning full strength. The total motor score is sum of all motor scores range from 0-100. Sensory part of the exam is completed through the testing of a key point in each of the 28 dermatomes (from C2 to S4-5) on the right and left sides of the body. At each of these key points, two aspects of sensation are examined: light touch and pin prick. Appreciation of light touch and pin prick sensation at each of the key points is separately scored on a three-point scale; 0-absent, 1-altered, and 2-normal or intact. 56 is the maximum score for both light touch and pin prick and the total sensory score ranges from 0 to 112. Higher scores represent better outcome for motor and sensory scores.

The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Ambulation and basic mobility subdomains assess the ability to engage in walking activities in different locations that vary based on speed, time and condition and the ability to manage stairs under different conditions. Bowel management difficulties subdomain measures an ability to carry out a bowel program; concerns about incontinence and bowel accidents; and the impact of bowel management on everyday living. Bladder management difficulties subdomain measures ability to carry out a bladder program; worry about bladder accidents; concerns about implementing one's bladder program; and impact on everyday living. Higher scores on all subdomains represent better outcome.

In order to identify descending motor tract, brainstem and C2 cervical spinal cord images will be acquired on a MAGNETOM Prisma 3T system using a 64-channel birdcage head/neck coil. To quantify the effect of atrophy in oblique directions, we will measure the radius from the cord shape center of mass to its border, R(α), for angles α over the whole circle with an angular resolution of 6°. Mean measures of all 5 axial slices will be used for statistical from nerve roots, noise, and other confounding effects.