Spinal Cord Stimulation in Spinal Muscular Atrophy

Isometric torque: measure the isometric torque produced by the subject at the hip during hip-flexion. Comparison of SCS-on with SCS-off performance. Success Criteria: ≥20% increased torque production over SCS-off baseline as measured during single-joint isometric torque.

Success Criteria: no serious adverse event related to the stimulation or intolerable adverse event reported

Range of Motion (ROM): Meaningful Change: increase of >20% of the hip joint (if available) and the knee joint (if available) during SCS against SCS-off as measured by the HUMAC NORM during single-joint isotonic trials.

Muscle activation: measure surface EMGs produced by the subjects during isometric movements of the hip, knee, and ankle in the HUMAC Norm and compare SCS-on with SCS-off performances. Meaningful Change:<20% EMG RMS compared to SCS-on.

6 minute walk test: perform the 6-minute walk test with SCS-on and SCS-off and distance between SCS-on and SCS-off is set to 24 m. If not ambulatory, any increased ambulation distance from SCS-off condition.

Fatigue will be assessed during motor function tests.

The Revised Hammersmith Functional Scale is a further refined version of the Hammersmith Functional Motor Scale Extended and includes specific items focused on lower-limb motor control such as hip-flexion, standing and walking a that are particularly relevant for the type III population of study. The scale is a 36 item performance evaluation, with a score range from 0-69 in which higher scores indicate better performance.

Meaningful Change: ≥2 point improvement. Compare outcomes between SCS-on and SCS-off. Motor Function Measure 32. The 32 items MFM is often used in trials of neuromuscular disorders, hence it provides a meaningful comparison against outcomes of other trials. Meaningful Change: ≥2 point improvement. Compare outcomes between SCS-on and SCS-off.

Patients will be asked to provide a score from 1 to 10 where a greater number indicates a greater amount of discomfort for each stimulation configuration. Spinal cord stimulation produces tingling sensations and other type of sensory phenomena. It is important to document that stimulation intensities required to improve motor function remain within a range of non-painful sensations.

The investigators will perform High-definition Diffusion Weighted Imaging to quantify Fractional Anisotropy as a measurement of axon density in the brain and spinal cord pre and post study.

The investigators will collect subjects and therapist feedback on how the technology is performing and what they would want to modify using The Clinical Global Impression Scale, a scale of 1-7 where a lower number indicates better performance and a higher number indicates more greatly impacted by their disease.

The investigators will perform High-definition Diffusion Weighted Imaging to quantify Fractional Anisotropy as a measurement of axon integrity in the brain and spinal cord pre and post study.

The investigators will perform resting state and motor-task functional MRI of the brain and spinal cord to quantify neural network activation at rest and during the execution of simple motor task such as leg muscle contraction.

The investigators will measure muscle evoked potential consequent to Transcranial Magnetic Stimulation of the cortico-spinal tract to assess integrity of the cortico-spinal tract.

The investigators will measure H-reflexes of leg muscles to quantify excitability of spinal motoneurons to stimulation of primary sensory afferents pre and post-study. Expected Result: Our main scientific hypothesis is that SCS will restore monosynaptic responses of weak spinal motoneurons, thus increasing H-reflex responses pre and post-study.

The investigators will use high-density EMGs on leg muscles to calculate firing rates of single spinal motoneuron discharge during isometric maximal voluntary contractions.

The investigators will use high-density EMGs on leg muscles to calculate the number of firing rates of single spinal motoneuron discharge during isometric maximal voluntary contractions.