Acute Intermittent Hypoxia and Body Weight Supported Treadmill Training for Incomplete Spinal Cord Injury Patients

Spinal cord injury (SCI) interrupts descending synaptic pathways from brainstem premotor neurons to spinal motor neurons, thereby paralyzing muscles below the neurological level. In recent years, considerable evidence has demonstrated that acute intermittent hypoxia (AIH) elicits plasticity in the spinal cord and strengthens spare synaptic pathways which is expressed as respiratory and somatic functional recovery in animals and humans suffering from incomplete SCI. The fundamental hypothesis guiding this project is that AIH-induced motor plasticity can be "harnessed" to improve walking capacity in incomplete SCI patients, classified as C and D categories according to International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). The inclusion criteria include patients > 18 years-old, with traumatic or non-traumatic, non-progressive incomplete SCI, onset > 6 months, neurological level C5-T12, with walking ability with or without assistive devices, without joint contractures, orthopedic injuries, osteoporosis, cutaneous lesions, cardiopulmonary complications and a body weight below 150 Kg. A randomized, triple-blind, placebo-controlled parallel design study will be done including 100% of patients fulfilling the criteria. Participants will receive repetitive acute intermittent hypoxia (rAIH: 15 episodes of 90 second 9% inspired oxygen interspersed with 90-second normoxia) or repetitive continued normoxia (rSham: 21% inspired oxygen) combined with 45 minutes body weight-supported treadmill training on 5 consecutive days and then three times per week for 3 weeks. Primary outcome measurement will be the 10-meter walking test. Secondary outcome measurements include the 6-minute walking test, timed up and go test, body/weight load, modified ashworth scale and visual analog scale. All outcomes will be measured before beginning the protocol (baseline), after five days of AIH/Sham (D5), weekly up to the end of the study (W2-W4), and a post-study follow-up for 2 weeks (F1-F2). Aditionally, cognitive assesment before and after the study will be performed using the "Figura compleja de Rey-Osterrieth" and the "Test de aprendizaje verbal España Complutense (TAVEC)". Repetitive AIH and body weight-supported treadmill training may represent a novel, safe, and noninvasive potential therapy to partially restore walking function in incomplete sub-acute and chronic SCI patients, a population with limited, if any, potential for improved function.