Name of journal: World Journal of Transplantation esps manuscript no: 18452 Manuscript Type: Original Article Retrospective Study

Evaluation HSCS and HPS transplantation efficiency in SCI patients with ASIA, FIM and ISCISCI-92

The functional repair of spinal cord was analyzed for 72 chronic SCI cases; it was measured with ASIA, ISCISCI-92 and FIM indexes at all stages of HSCs and HPSs transplantation. The evaluation with ASIA index demonstrated regress of neurologic symptoms only in 23 cases. Two patients with complete SCI (ASIA A) showed restoration of the locomotion below neurologic level of injury with muscle force of no less than 3 points (ASIA C) after HSCs and HPs transplantation, and over 3 points (1 patient, ASIA D). The ASIA B patient after HSCs and HPs transplantation showed neurologic restoration to ASIA C.

Nevertheless, the above shown analysis of clinical regress of neurologic symptoms demonstrates inefficiency of the ASIA impairment scale that was used to evaluate restoration of the spinal cord functions. On the one hand, it is associated with the specific features of restoration of spinal cord functions, and on the other, with low sensitivity of the index that gives only general estimation of regress of the neurologic damage. According to Belova^[11] the ASIA index is applicable only for screening of the spinal functions during acute period of SCI. To evaluate neurologic progress in SCI, the more detailed characterization of locomotion, sensation and urination is required in every individual case.

As shown above, the sensation recovered after the manifestations of the restoration of motor functions analysis, especially in S4-S5 segments. The sensation restored mosaically, frequently after the development of passive or active movements, and involved the segments only partially. Absence of sensation in S4-S5 segments conditioned ASIA A level of impairment, even if motor functions of certain muscles below injury level were preserved to a certain extent. In this respect, 10 patients observed restoration of muscle force in most of the muscles below the level of injury that enabled their walking with assisting devices after 4-8 transplantations, while currently, two patients are able to cover short distances independently. However, only one of these patients demonstrated restoration of sensation in S4-S5 segments.

Hence, the ASIA impairment scale is effective to assess the degree of disability, but is ineffective, when used to assess the restoration of spinal cord functions in chronic SCI after HSCs and HPs transplantation.

Motor progress was also assessed with the ISCISCI-92 motor and sensory scores, and the data coincided with those received in evaluation of motor functions by the specifically developed scale. The number of the patients with the signs of locomotive repair was 56.9%. Moreover, the motor activity rates increased from baseline 32.7 points to 37.1 after the first transplantation and to 39.9 after repeated transplantation of HSCs and HPs (P < 0.05, at each stage of transplantation) (Figure 14C).

In spite of clinical restoration of sensation in 38.6% of the patients, the ISCISCI-92 scores did not confirm these data. This is conditioned by the absence of evaluation of deep sensation in ISCISCI-92, and, as noted before, by the “ceiling effect”, when the neurologic status changes within the partial restoration of sensation.

Hence, the assessment of motor restoration with the ISCISCI-92 scores demonstrated effectiveness of the HSCs and HPs transplantation in chronic SCI patients. The ISCISCI-92 score confirms the data of our specifically developed scale to assess the clinical motor restoration of spinal cord, thus, demonstrating its applicability in practice. The advantage of our evaluation scale of clinical motor restoration over the ISCISCI-92 lies in the multi-factor analysis of the motor activity, based on standard neurologic examination. Absence of changes in sensation as measured by ISCISCI-92 scores that, however, are accompanied by the clinical signs of restoration, demands development of new tools to measure changes both in surface sensation (touch and pain) and deep sensation. Despite partial solution of this issue in the specifically developed scale of clinical motor restoration, the “ceiling effect” was not overcome in partial restoration of this function.

We would like to focus on the restoration of the functional independence after HSCs and HPs transplantation that was evaluated in 64 patients with the Functional Independence Measurement (FIM) scale. The signs of the restoration of life activity was observed in 36.2% patients and were minimal (from baseline 50.1 points to 50.5 points after the first transplantation, and to 50.7 points after repeated HSCs and HPs transplantation; P < 0.05 at all stages of therapy, respectively) (Figure 15). It is associated with moderate restoration of the spinal functions after the first HSCs and HPs transplantations that manifested mostly in locomotion. However, as shown above, further transplantations resulted in more profound clinical progress. Besides, the FIM scale, when applied to chronic SCI cases has significant disadvantage: in the cases of considerable disorders of nerve impulse conductance, the FIM displayed very low sensitivity, due to absence of detailed functional evaluation. Accordingly, the analysis of the obtained data showed very slight improvement of the FIM scores, demonstrating improvement of the functional independence conditioned by the motor function of spinal cord.