SCI influences not only conduction of sensory and motor signals across the site of lesion, but also the autonomic nervous system. According to American Spinal Injury Association Impairment Scale, the degree of SCI can be divided into A—Complete, B—Incomplete, C, D—Incomplete, E—Normal. In this study, SCI in the included studies mainly caused by traumatic and nontraumatic injuries, such as accident, gunshot, vehicular, fall, violence. The indicators of efficacy and safety of different regimens in the included studies were measured by LEMS, WISCI, constipation rate, headache, and urinary tract infection altogether. Through the comparison of these five indicators, this study evaluated the efficacy and safety of 9 nonoperative regimens, including placebo, pregabalin, GM-1 ganglioside, venlafaxine XR, fampridine, conventional OT, BWSTT, RAGT + OT, and BWSOT, using direct pairwise meta-analysis and network meta-analysis.
The results of pairwise meta-analysis showed that the efficacies of RAGT + OT and BWSOT were relatively better, while the efficacy of conventional OT was relatively poorer, and the results of SUCRA values further confirmed this point. RAGT focused on improving the activity of spinal interneurons on the basis of the function of the central pattern generator through supplying sensory-motor stimulation to ameliorate neural plasticity. RAGT also has the merits of repeatedly performing a preprogrammed gait pattern, and RAGT has been reported to promote motor recovery as well as functional improvement.[32,38] Meanwhile, RAGT can also improve confidence in walking performance, promote intralimb and interlimb coordination, as well as alter synergistic contraction of the antagonistic muscles of the knee joint and the ankle joint. However, RAGT cannot reflect an immediate feedback, and RAGT combined with conventional OT can yield more benefits in ambulatory function than conventional OT alone do, thus improving walking ability and muscle strength in SCI patients. For BWSOT in SCI patients, it can be a more task-specific form of gait training when compared with treadmill training, which may also relieve the transition from walking in the process of therapy to walking in a real-life environment. BWSOT is also appealing for the reason that it is inexpensive and also does not require costly treadmills, which is a particularly significant consideration for patients who in the low and middle-income countries. Moreover, BWSOT is better than conventional OT for the following aspects: it frees the doctors from physically supporting patients in the process of gait training, it decreases the need for personnel to build a safe environment for gait training, and it provides the doctors with the choice to step back, observe and further analyses the patient's gait.
The results of pairwise meta-analysis also showed that the safeties of venlafaxine XR and GM-1 ganglioside were relatively higher, while the safety of fampridine was relatively lower, and the results of SUCRA values further confirmed this point. Venlafaxine has been tested extensively and has reported to be both safe and well tolerated. Additionally, venlafaxine seems to be effective for obsessive–compulsive disorder (OCD), and it causes fewer side effects than other medications. Compared with placebo controls, patients who treated with venlafaxine XR showed greater improvement in SCI-related disability, especially in the areas of home responsibilities or family life and social life. GM-1 ganglioside is an infrequent autosomal recessive lysosomal storage disorder which is attributable to a deficiency of β-galactosidase enzyme activity. GM-1 is often used in clinical practice and it is also described as a well-established drug in SCI medical interventions. The administration of GM-1 ganglioside could improve nerve functions with the mechanisms of activity reservation of Ca2+-ATPase and Na+-K+-ATPase; antagonism of excitatory amino acid toxicity; promotion of multiple nerve growth factors; prevention of lactic acidosis; prevention of intracellular calcium accumulation; direct restoration of damaged nerve cell membranes; blockage of nerve cell apoptosis. There are also studies showed an effective result of GM-1 ganglioside in treating SCI patients.[48–50] However, since fampridine could significantly improve walking speed in patients with multiple sclerosis when compared with placebo, the role of fampridine as a contributory factor to the clinical efficacy was unclear, which is consistent with the results of our meta-analysis.
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