**1. Introduction to spinal cord injury: epidemiology and biopsychosocial impact**

Spinal cord injury (SCI), either traumatic or non-traumatic in origin, is a devastating condition that produces long-term effects that persist throughout life and are associated with severe disability and handicap. Reported traumatic SCI annual incidence rates ranges from 12.1 to 57.8 cases per million. Motor vehicle collisions, falls, violence, and sports represent the leading causes. In comparison to traumatic SCI, there is little literature on non-traumatic SCI epidemiology. The etiologies of this type of SCI include vertebral spondylosis (spinal stenosis), tumorous compression, vascular ischemia, congenital diseases and inflammatory conditions [1, 2].

Depending on the level of SCI, patients experience paraplegia or tetraplegia. Paraplegia is defined as the impairment of sensory and/or motor function in lower extremities. Patients with incomplete paraplegia generally have a good prognosis in regaining locomotor ability (around 76% of patients) within a year. Complete paraplegic patients experience limited recovery of lower limb function if their neurological level of injury (NLI) is above T9. An NLI below T9 is associated with 38% chance of regaining some lower extremity function and only 4% chance of recovery to an incomplete status. On the other hand, tetraplegia is defined as partial or total loss of sensory and/or motor function in all four limbs and has a worse prognosis than paraplegia [3].

Spinal cord injury is a leading cause of disability, particularly in young adults. The highest incidences of SCI occur in persons between 20 and 40 years of age [4], being more common in males (82.8%) than females [5]. However, recent reports indicate an increase in SCI prevalence among older people and females. On the other hand, when classifying the types of disabilities caused by SCI, tetraplegia represents around 60%, while paraplegia represents approximately 40% [6]. Among all secondary complications following SCI, pressure ulcers, neurogenic bladder, urinary tract infections, pain, autonomic dysreflexia, osteoporosis, and muscle atrophy represent the majority. Currently, SCI complications management is challenging, and the outcomes are unsatisfactory [5, 7–10]. Moreover, having SCI may increase the risk of developing a health condition that is an indirect consequence of the impairment itself, such as increasing sedentary behaviors that contribute to the development of obesity and diabetes. Psychological factors (depression, anxiety, drug and substance dependency, post-traumatic stress disorders, etc.) may also complicate these chronic health conditions [11]. In addition, SCI leads to an abrupt change in the professional life and future plans of the patients [12] due to the irreversible restriction of functional movement, affecting not only quality of life

but also the ability to live independently. Furthermore, not only economic, educational and social conditions can affect SCI patients. Sexual relationships as well as marriage may be affected in patients who develop a severe disability following SCI [13–15]. These issues have been the most important motivation for the implementation of studies over the last decades that look for novel strategies for SCI. Despite all the progress in both preclinical and clinical studies, new therapies are still needed in order to improve both functional recovery and quality of life following SCI.

Lastly, it is important to mention that disparities between the developing and developed countries capacity to deliver emergency and acute care are evident immediately after a SCI. In many low-resource regions, these disparities can lead to further neurological compromise and poorer first year survival [16]. On the other hand, developed countries have significantly improved survival compared with developing countries. For example, tetraplegics have lower survival rates than paraplegics; however, in developed countries, this gap has narrowed considerably over the last 40 years. Developing countries still have the highest 1-year mortality rates [17].
