Chronic Spinal Cord Injury

Overview

While there are many terrible diseases that industry is trying to find treatments for, traumatic spinal cord injury is particularly devastating for two reasons: one – it can strike anyone, at any time without regard for age, genetics, socio-economic status, and two – there are no treatments available to meaningfully improve quality of life after injury. While we have no control over the former, InVivo is developing therapies to combat the latter. InVivo’s goal is to redefine the life of the spinal cord injury patient.

Spinal cord injuries are defined as damage to the spinal cord, conus medullaris, and cauda equina, and are broadly categorized by origin into either non-traumatic or traumatic injuries. Non-traumatic injuries can result naturally from underlying pathology, such as tumors, infectious diseases, musculo-skeletal diseases, and other congenital conditions. Traumatic injuries, however, can affect anyone and result from sudden injuries such as falls, traffic accidents, sports injuries, and violence.

To fully appreciate the products we are developing for spinal cord injury, it is important to understand not only the basic anatomy and physiology of the spinal cord but also the time progressive nature of the injury.

Anatomy

The spinal cord is an “information super highway” that carries information from the brain to the rest of the body, and relays information from the body back towards the brain. This efficient transfer and integration of ascending and descending information is accomplished through anatomical organization.The spinal cord is divided into neurological segmental levels that correspond to nerve roots that exit the spinal column in between each vertebra. There are 31 pairs of nerve roots that exit either side of the spinal cord: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. Major functions roughly correspond to specific segments of the spinal cord. For example, the muscles of the elbow are controlled by the elements of the C7 segment, while the flexor muscles of the fingers are controlled by the elements of the C8 segment.

spinalCord
Source: World Health Organization and The International Spinal Cord Injury Society1

 

 

CrossSection
Source: Gray, Henry. Anatomy of the Human Body.

 

While the anatomy of each segment is unique, in general each segment can be divided into gray matter and white matter. The gray matter is the highly-vascularized, butterfly shape that houses neural cell bodies, interneurons, and supporting glia cells. The lighter, outer section is called the white matter which is largely responsible for high speed communication between the brain and the spinal segments. The white matter in cross section is lighter in color because of insulating myelin that aids signal transduction.

Time Course of Traumatic Spinal Cord Injury (Acute to Chronic)

In a typical spinal cord injury, a severe traumatic incident (eg, a car crash) leads to the dislocation or fracturing of at least one vertebral body. The vertebral body that once housed and protected the spinal cord can contuse or transect the spinal cord and directly impinge the delicate neuronal tissue within. This primary injury directly disrupts axons, blood vessels, and cell membranes, and it sets off a biological cascade which leads to further damage called the secondary injury. Vascular disruption leads to ischemic destruction of the central area of the spinal cord. The surrounding white matter begins losing myelin, a necessary component for optimal signal transduction. Increased pressure caused by inflammation can also lead to damage and loss of both gray and white matter.

Astrocytes, glial cells surrounding neurons that normally supply physical and metabolic support become reactive in response to the mechanical injury. They migrate to the site of injury and attempt to repair the damage, creating a glial scar. This glial scar in the weeks and months following the initial trauma becomes both a mechanical and chemical barrier, preventing the re-establishment of information flow through the injury site. Signals from the brain cannot get down past the scar and signals from the periphery cannot get up to the brain.

The lack of signal transmission caused by the primary and secondary injury leads to the motor and sensory loss associated with spinal cord injury. The loss of function is level-dependent. For example, an injury at the neck, or cervical, level will result in tetraplegia (aka quadriplegic), or paralysis of both arms and legs. An injury at the chest or thoracic level results in paraplegia, characterized by full control of the arms, but paralysis of the legs.

1. Bickenbach, Jerome E., et al. International perspectives on spinal cord injury. Geneva, Switzerland: World Health Organization, 2013.

2. Gray, Henry. Anatomy of the Human Body. Philadelphia: Lea & Febiger, 1918.