What is a complete spinal cord injury?
Patients in the ongoing Neuro-Spinal ScaffoldTM study are required to have a complete spinal cord injury. These patients have no motor or sensory function below the level of their spinal cord injury including the sacral (lower) segments at S4-5. Patients with incomplete spinal cord injury have partial sensory and/or motor function below the level of injury. The specific method of assessing injury status (complete versus incomplete) is described below.
The spinal cord is comprised of cervical, thoracic, lumbar and sacral/coccygeal segments.
The following representative examples indicate what functions are lost with spinal cord injury at various neurological levels:
C5 – loss of function at the elbow, wrist and fingers, trunk and lower extremities
C8 – loss of function of the finger trunk and lower extremities
T8 – loss of function of some abdominal, back muscles and lower extremities
L3 – loss of function at the knee, ankle and toes
S1 – loss of function at the ankle and toes
Additionally, spinal cord injuries can lead to significant problems with bowel, bladder and sexual function.
How is the degree of spinal cord injury assessed in the InVivo clinical trials?
The ASIA Impairment Scale: The American Spinal Injury Association (ASIA) in collaboration with the International Spinal Cord Society (ISCOS) has developed a neurologic examination tool for assessing spinal cord injury known as the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Results of the ISNCSCI examination are used to determine the ASIA Impairment Scale (AIS) classification.
Patients with complete spinal cord injury are classified as AIS A. Patients with incomplete spinal cord injury have partial sensory and/or motor function below the level of injury and are classified as AIS B (partial sensory function), AIS C (partial sensory and motor function) or AIS D (partial sensory and increased motor function, i.e. can move at least half of the muscles against gravity). Patients who have a complete return of sensory and motor function are classified as AIS E.
These classifications are based upon the ISNCSCI examination in which the examiner performs a neurologic examination to assess sensory function of the entire body and motor function of the upper and lower extremities. The assessments are based on the following point system (simplified definitions; see http://asia-spinalinjury.org/wp-content/uploads/2016/02/International_Stds_Diagram_Worksheet.pdf for complete definitions)
Muscle function grading
0 = total paralysis
1 = palpable or visible contraction
2 = active movement, full range of motion with gravity eliminated
3 = active movement, full range of motion against gravity
4 = active movement, full range of motion against gravity and moderate resistance (patient exerts force against resistance by the examiner) in muscle specific position
5 = normal
0 = absent
1 = altered, either decreased/impaired sensation or hypersensitivity
2 = normal
Below is an example of the sensory examination of a sample patient who is AIS A (complete spinal cord injury) at the T6 spinal cord (neurologic) level (green is normal function and red is absence of function) and the full ISNCSCI scoring system for this sample patient.
The InVivo Pilot Study of the Neuro-Spinal ScaffoldTM (InVivo-100-101)
This study enrolls only patients with complete, thoracic spinal cord injury (AIS A). These patients have the most severe injury and experience the least neurologic recovery over time. The odds of improving motor function below the level of their injury (AIS C, D or E) are low. Patients in this study have experienced an injury in the thoracic (trunk) region from T3 – T12/L1.
Below are statistics from the European Multicenter Study about Spinal Cord Injury (EMSCI) database outlining the low rate of motor recovery from injuries in the thoracic region.
In sum, fewer than 6% of patients recover to a grade C or D at 3 months and by 12 months, fewer than 11% have recovered to a grade C or D.
|T2-T12||Baseline||4 weeks||12 weeks||24 weeks||48 weeks|
|N (no. of patients)||237||366||346||256||209|
Data from Zariffa, et al, Spinal Cord (2011) 49, 463-471 (EMSCI database)