Table 4.
Approaches Used in Chronic Spinal Cord Injury
| Study | Study phase | Approach | Classification | Mechanism | Outcome measure (clinical Neurological nnd/or motor performance) | Comparison/control | Direction of results | Follow-up | SC integrity | SC connectivity |
|---|---|---|---|---|---|---|---|---|---|---|
| Lima et al, 2006 | Phase I | Olfactory mucosal autografts | Cell therapy | Neural regeneration | AIS scores | N/A | N/A | 6, 12, and 18 months | MRI | Absent |
| Chhabra et al, 2009 | Phase I | Olfactory ensheathing cells | Cell therapy | Neural regeneration | AIS scores, WISCI, SCIM | N/A | N/A | 6, 12 and 18 months | MRI (only included lesions 2–3 cm) | MEPs |
| Wirz et al, 2005 | Phase I | Locomotor training (gait-driven orthosis) | Rehabilitation | Plasticity | LEMS, 6-min walk test, 10 meter walk, timed up and go, WISCI-II | N/A | N/A | Post-intervention (8 weeks) | Absent | Absent |
| Yazdani et al, 2013 | Phase I | Bone-marrow mesenchymal stromal cells, Schwann cells and rehabilitation | Combination of cell therapy + rehabilitation | Neural regeneration+plasticity | AIS scores | N/A | N/A | 24 months | MRI-excluded stenosis and tethering of the spinal cord | Absent |
| Field-Fote et al, 2001 | Phase I | Body-weight supported treadmill training + electrical stimulation | Combination of rehabilitation+ electrical stimulation/neuroelectric device | Plasticity | 2 min walk (speed), LEMS | N/A | N/A | Post-intervention (12 weeks) | Absent | Absent |
| Fleerkote et al, 2014 | Phase I | Body-weight supported treadmill training (AAN-RO) | Combination of rehabilitation+ electrical stimulation/neuroelectric device | Plasticity | 10 meter walk† (distance), WISCI, TUG†, 6 min walk†, LEMS† | N/A | N/A | 8 weeks | Absent | Absent |
| Segal et al, 1999 | Phase II | 4-amynopiridine (low, high dose) | Pharmacology | Plasticity | AIS motor scores† | Comparison (unblinded high dose) | † = groups collapsed | 3 months | Absent | Absent |
| Buehner et al, 2012 | Phase II | Manual facilitated body weight-supported step training on a treadmill + community reintegration | Combination of rehabilitation + other | Plasticity | LEMS,† UEMS,† 6-min walk (speed and distance),† and 10-meter walk (speed)† | N/A | † = pre-post difference | Mean of 60.3 ± 53.24 sessions (approximately 5 months) | Absent | Absent |
| Bunday et al, 2012 | Phase II | Transcranial magnetic stimulation paired with electrical stimulation | Combination of electrical stimulation/neuroelectric device | Plasticity | NHPT* | Comparison group | * = ↑ TMS + stim | post-test (single session) | Absent | MEPs |
| Beekhuizen et al, 2005 | Phase III | Upper extremity task-specific training and submotor threshold electrical stimulation (TST + stim vs. TST) | Combination of Electrical stimulation/neuroelectric device + rehabilitation | Plasticity | JTT,* WMFT,* pinch strength* | Comparison group (TST) | Between-group difference = * ↑ TST+stim | 3 weeks | Absent | MEPs |
| Beekhuizen et al, 2008 | Phase III | Upper extremity task-specific training and submotor threshold electrical stimulation (TST+stim, TST, stim and wait-list control) | Combination of electrical stimulation/neuroelectric device + rehabilitation | Plasticity | JTT,* WMFT,* pinch strength* | Control group (wait-list) | Between-group difference = * ↑ TST + stim | 3 weeks | Absent | MEPs |
| Hoffman et al, 2010 | Phase III | Upper extremity task-specific training (unimanual, bimanual) and electrical stimulation (submotor threshold and FES), and wait-list control | Combination of electrical stimulation/neuroelectric device + rehabilitation | Plasticity | JTT,† | Rehabilitation in isolation | † = pre-post difference (groups collapsed) | 3 weeks | Absent | MEPs |
| Sadowsky et al, 2013 | Phase III | FES cycling | Combination of rehabilitation + electrical stimulation/neuroelectric device | Plasticity | AIS scores†, AIS motor† scores, FIM† | Control (no intervention) | † = FES | Mean of 29.1 months | Absent | Absent |
| Field-Fote et al, 2005 | Phase III | Body-weight supported treadmill training + electrical stimulation (TM, OG, TS, and LR) | Combination of rehabilitation + electrical stimulation/neuroelectric device | Plasticity | 6 min walk,† 2 min walk † | Comparison group | † = pre-post difference (groups collapsed) | 12 weeks | Absent | Absent |
| Field-Fote et al, 2011 | Phase III | Body-weight supported treadmill training + electrical stimulation (TM, OG, TS, and LR) | Combination of rehabilitation+ electrical stimulation/neuroelectric device | Plasticity | 10 meter walk (distance)* | Comparison group | Between-group difference = * ↑ OG | 12 weeks | Absent | Absent |
| Jones et al, 2014 | Phase III | ABT | Rehabilitation | Plasticity | AIS motor score, * LEMS, * 10 meter walk, * 6 min walk, * TUG, SCIM-III, SCI-FAI, * RNL index, | Wait-list control | * = ↑ ABT | 24 weeks | Absent | Absent |
| Dai et al, 2013 | Phase III | Mesenchymal stem cells (OS, CT, control) | Cell therapy | Neural regeneration | AIS scores†1, MEPs, AIS motor scores†2 | Control (no intervention) |
†1 = OS, CT †2 = CT |
6 months | MRI (guided injection site) | MEP |
| Mackay-Sim et al, 2008 | Phase III | Olfactory ensheathing cell transplant | Cell therapy | Neural renegeration | AIS scores, FIM, IADL, COVS | Control group | No differences | 3 years | MRI | MEPs |
| Lima et al, 2010 | Phase III | Olfactory mucosal autografts + locomotor training | Combination of cell therapy + rehabilitation | Plasticity + neural regeneration | LEMS,† FIM† and WISCI† | Comparison group | † = pre-post difference (groups collapsed) | Mean of 27.7 months | MRI (only included lesions 3–4 cm) | Absent |
| Larson et al, 2013 | Phase III | Locomotor training (olfactory mucosal transplant and control) | Combination of cell therapy + rehabilitation | Plasticity + neural regeneration | AIS scores† | Control group | † = pre-post difference (groups collapsed) | 60 days | Absent | Absent |
| Kishk et al, 2010 | Phase III | Bone-marrow + rehabilitation | Combination of cell therapy + rehabilitation | Plasticity + Neural regeneration | AIS scores | Control group | No differences | 1 year | MRI | Absent |
| Hayes et al, 2014 | Phase III | Daih + LT (Daih, Sham-Daih, Daih+LT, Sham-Daih+LT) | Combination of pharmacology + rehabilitation | Plasticity | 10 meter walk (time) †, * 6 min walk†,†1,†2,*1 |
Sham-Daih, Sham-Daih+LT (crossover design) |
† = Daih * = ↑ Daih †1 = Sham-Daih †2 = Daih + LT *1 = ↑ Daih + LT |
Day 1, Day 5, 1 week and 2 weeks | Absent | Absent |
*
Refers to between-group differences and †refers to pre-post differences.
SC, spinal cord; AIS, American Spinal Cord Injury Impairment Scale; MRI, magnetic resonance imaging; WISCI, walking index for spinal cord injury; SCIM, Spinal Cord Independence Measure; MEP, motor evoked potentials; LEMS, lower extremity motor scores obtained from AIS assessment; AAN-RO, assist-as-needed robotic orthosis; TUG, timed up and go; UEMS, upper extremity motor scores obtained from AIS assessment; TMS, transcranial magnetic stimulation; NHPT, nine-hole peg test; stim, electrical stimulation; TST, task-specific training; WMFT, wolf motor function test; FES, functional electrical stimulation; FIM, Functional Independence Measure; TM, treadmill training with manual assistance; OG, overground training; TS, treadmill training with electrical stimulation; LR, locomat robotic orthosis training; SCI-FAI, Spinal Cord Injury Functional Ambulation Index; RNL Index, Reintegration to Normal Living; ABT, activity-based therapy; OS, open surgery; CT, computed tomography-guided; IADL, Lawton's instrumental activities of daily living; COVS, clinical outcomes variable scale; daily acute intermittent hypoxia; LT, locomotor training.