Regenerative rehabilitation: exploring the synergistic effects of rehabilitation and implantation of a bio-functional scaffold in enhancing nerve regeneration.

Clinically, rehabilitation is one of the most common treatment options for traumatic injuries. Despite that, recovery remains suboptimal and recent breakthroughs in regenerative approaches may potentially improve clinical outcomes. To date, there have been numerous studies on the utilization of either rehabilitative or regenerative strategies for traumatic injury treatment. However, studies that document the combined effects of rehabilitation and regenerative tissue engineering options remain scarce. Here, in the context of traumatic nerve injury treatment, we use a rat spinal cord injury (SCI) model as a proof of concept to evaluate the synergistic effects of regenerative tissue engineering and rehabilitation. Specifically, we implanted a pro-regenerative hybrid fiber-hydrogel scaffold and subjected SCI rats to intensive rehabilitation. Of note, the rehabilitation session was augmented by a novel customized training device that imparts normal hindlimb gait movements to rats. Morphologically, more regenerated axons were observed when rats received rehabilitation (∼2.5 times and ∼2 times enhancement after 4 and 12 weeks of recovery, respectively, p < 0.05). Besides that, we also observed a higher percentage of anti-inflammatory cells (36.1 ± 12.9% in rehab rats vs. 3.31 ± 1.48% in non-rehab rats, p < 0.05) and perineuronal net formation in rehab rats at Week 4. Physically, rehab animals were also able to exert higher ankle flexion force (∼0.779 N vs. ∼0.495 N at Week 4 and ∼1.36 N vs. ∼0.647 N at Week 12 for rehab vs. non-rehab rats, p < 0.001) and performed better than non-rehab rats in the open field test. Taken together, we conclude that coupling rehabilitation with regenerative scaffold implantation strategies can further promote functional recovery after traumatic nerve injuries.

Detection of abnormal muscle activations during walking following spinal cord injury (SCI).

In order to identify optimal rehabilitation strategies for spinal cord injury (SCI) participants, assessment of impaired walking is required to detect, monitor and quantify movement disorders. In the proposed assessment, ten healthy and seven SCI participants were recruited to perform an over-ground walking test at slow walking speeds. SCI participants were given assistance from physiotherapists, if required, while they were walking. In agreement with other research, larger cadence and smaller step length and swing phase of SCI gait were observed as a result of muscle weakness and resultant gait instability. Muscle activation patterns of seven major leg muscles were collected. The EMG signal was processed by the RMS in frequency domain to represent the muscle activation power, and the distribution of muscle activation was compared between healthy and SCI participants. The alternations of muscle activation within the phases of the gait cycle are highlighted to facilitate our understanding of the underlying muscular activation following SCI. Key differences were observed (p-value=0.0006) in the reduced activation of tibialis anterior (TA) in single stance phase and rectus femoris (RF) in swing phase (p-value=0.0011). We can then conclude that the proposed assessment approach of gait provides valuable information that can be used to target and define therapeutic interventions and their evaluation; hence impacting the functional outcome of SCI individuals.

Botulinum toxin type A for refractory neurogenic detrusor overactivity in spinal cord injured patients in Singapore.

INTRODUCTION: Managing neurogenic detrusor overactivity (NDO) successfully in spinal cord-injured patients is a challenge. The aims of preserving kidney function by achieving safe bladder pressures with anticholinergic medication often leave a significant proportion of patients with side effects. Botulinum toxin type A has been shown to be a promising alternative. MATERIALS AND METHODS: Spinal cord injury patients who had NDO, on clean intermittent self-catheterisation, and were refractory to oral medications, were recruited. Three hundred units of botulinum toxin type A (Botox) in 30 mL NaCl solution were injected under cystoscopic guidance into the bladder. RESULTS: Fifteen patients were recruited of whom 9 were tetraplegic and 6 were paraplegic. Eleven (73.3%) had complete injuries. There was a significant reduction in the mean number of leakages from 3.75 +/- 1.79 pre-injection to 0.67 +/- 1.31 and 1.5 +/- 1.5 at 6 and 26 weeks postinjection, respectively (P <0.05). Seventy-five per cent, 37.5% and 50% were completely dry at 6, 26 and 39 weeks post-injection, respectively. The mean maximal catheterisable volume increased from 312.3 +/- 145.6 mL pre-injection to 484.6 +/- 190 mL, 422.3 +/- 157.3 mL and 490.0 +/- 230.4 mL at 6, 26 and 39 weeks post-injection, respectively (P <0.005). Maximum detrusor pressure decreased significantly from 66.3 +/- 22.6 cmH2O to 21.2 +/- 23.1 cmH2O and 33.6 +/- 30.2 cmH2O at 6 and 26 weeks post-injection, respectively (P <0.05). The volume at which reflex detrusor contractions first occurred increased from 127.8 +/- 57.5 mL pre-injury to 305.7 +/- 130.8 mL at 6 weeks and 288.3 +/- 13.0 mL at 26 weeks post-injection (P <0.05). Mean cysometric bladder capacity increased from 187.8 +/- 69.2 mL to 305 +/- 136.4 mL and 288.3 +/- 13.0 mL at 6 and 26 weeks post-injury, respectively (P <0.05). Sixty per cent of patients were completely off medications at 6 and 26 weeks post-injection. One patient had urinary tract infection and 1 experienced autonomic dysreflexia during cystoscopy. Satisfaction levels increased from 4.3 +/- 2.3 pre-injury to 7.2 +/- 1.9 and 7.3 +/- 2.3 at 6 weeks and 26 weeks, respectively. This also correlated with fewer leakages. CONCLUSION: Botulinum toxin type A injected into the detrusor is safe and efficacious for spinal cord injured patients with refractory detrusor overactivity. This effect is maintained at 26 weeks post-injection.

Recovery and regeneration after spinal cord injury: a review and summary of recent literature.

INTRODUCTION: Spinal cord injury (SCI) often results in significant neurologic dysfunction and disability. An annual incidence of 15 to 40 traumatic SCI cases per million population has been reported worldwide, and a conservative estimate for Singapore would be 23 cases per million. With continued improvements in medical care, an increasing prevalence of SCI patients is expected, with corresponding need for comprehensive rehabilitation services led by specialist rehabilitation physicians. METHODS: A literature search, review, and summary of findings of recent studies relating to factors associated with recovery, as well as interventions for rehabilitation and promotion of healing of the injured spinal cord was performed. CONCLUSIONS: Many SCI patients show improvements in motoric and neurologic level, but those with complete injuries have poor chance of improving American Spinal Injury Association (ASIA) scores. SCI of violent aetiology tends to be more neurologic complete, and those without sacral sparing less likely to improve. Older patients generally do well in activities of daily living. Women have better motor score improvement, although men have better Functional Independence Measure (FIM) scores generally. Electrodiagnostic tests such as somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) can help with prognostication, as can imaging techniques such as magnetic resonance imaging (MRI). Immediate surgery for spinal decompression may improve recovery, but whether routine surgery after SCI improves function remains unclear, as does the timing. Methylprednisolone and similar agents appear to help limit secondary injury processes. Rehabilitation interventions such as functional electrical stimulation (FES) and body-weight supported treadmill ambulation training may be effective, as may neural-controlled prostheses and devices. Substances that promote repair and regeneration of the injured spinal cord such as GM-1, 4-AP, BDNG, GDNF, Nogo and MAG-inhibitors, have been studied. Transplanted tissues and cells, such as blood macrophages, bone marrow transplant with GM-CSF, olfactory ensheathing cells, fetal tissues, stem or progenitor cells, have been reported to produce neurological improvements.