Spinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy - Upper Limb

Spinal cord stimulation (SCS) has shown remarkable efficacy in restoring motor function in people with spinal cord injury by recruiting afferent input to enhance the responsiveness of spared neural circuits to residual cortical inputs. This pilot will test if SCS can show evidence to improve motor deficits in people with Type 2, 3, or 4 spinal muscular atrophy (SMA). The investigators will enroll up to six subjects with Type 2, 3, or 4 SMA aged 16 or older that show quantifiable motor deficits of the upper body. The investigators will then implant the subjects with percutaneous, linear spinal leads near the cervical spinal cord for a period of up to 29 days. Although these leads are not optimized for motor function but rather for their clinically approved indication of treating pain, the investigators believe they provide a safe technology enabling our team to perform scientific measurement necessary to evaluate potential for effects of SCS in motor paralysis with SMA. After the end of the study, the leads will be explanted.

The investigators plan to 1. verify that spinal cord stimulation increases elbow muscle strength in subjects with SMA, 2. verify that spinal cord stimulation improves motor control in subjects with SMA, 3. verify that spinal cord stimulation induces measurable changes in spinal circuits and motoneuron recruitment properties in the 29 day course of implantation.

Eligibility Criteria:
SMA Participant Inclusion Criteria:

1. Subject has a diagnosis of 5q-autosomal recessive SMA confirmed by determination of a genetic deletion in the SMN1 gene (5q12.2-q13.3).
2. Subject is diagnosed as being non-ambulatory SMA based on the following criteria:

   a. Can't stand independently.
3. Subject is ≥16 years of age and \< 65 years of age.
4. Subject is able to sit independently.
5. A minimum score of 1 for Entry Item "A" of the Revised Upper Limb Module (RULM) scale for SMA: "Can use hands to hold pencil or pick up a coin/token or drive a powered chair, use phone key pad"
6. Subject (and subject's parent or legal guardian if subject is a minor) is willing and able to comply with scheduled visits and study procedures
7. Participants must have started SMN inducing therapies (Spinraza or risdisplam) at least 6 months prior to enrollment. (They must have either gotten their first injection at at least 6 months prior, or they started daily intake of risdisplam at least 6 months prior to the study)

Healthy Control Participant Inclusion Criteria:

1. Subject is ≥18 years of age and \< 65 years of age.
2. Subject is able to stand independently for ≥3 seconds.
3. Subject is willing and able to comply with scheduled visits and study procedures.

SMA Participant Exclusion Criteria:

1. Subject has deformation of the spinal canal preventing lead implantation as judged by the study neurosurgeon
2. Subject has size of spinal canal that is insufficient for lead implantation as judged by the study neurosurgeon
3. Subject has moderate or severe joint contractures that would affect ability to perform study measures, determined by the study physician
4. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator
5. Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety of anesthesia or the procedures, make it unlikely that intervention or follow-up will be correctly completed or impair the assessment of study results, in the opinion of the investigator
6. Female subjects are pregnant or breastfeeding, as established by self-report.
7. Subject has severe claustrophobia
8. Subject is on anticoagulant, anti-spasticity or anti-seizure medication within 4 weeks of lead implantation or requires these medications during the treatment phase of the study
9. Subject has medical implant that precludes magnetic resonance imaging
10. Subject has a deconditioned respiratory system, per the discretion of the physician investigator.
11. Subjects with renal insufficiency at the discretion of the physician investigator.
12. Subjects requiring any form of sedation for MRI will be excluded.

Healthy Control Participant Exclusion Criteria:

1. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator would impact participation in the study.
2. Participants who have any serious disease or disorder (e.g. cancer, severe cardiac or respiratory disease, neurological conditions other than stroke, etc.) or cognitive impairments that could affect their ability to participate in this study.
3. Female subjects are pregnant or breastfeeding, as established by self-report.
4. Subjects requiring sedation for MRI will be excluded.