## 4 Discussion  
[PERSON] et al. reported a domestic phase 3 trial of condoliase for the treatment of protrusion type and sub-ligamentous extrusion type of LDH, in which an improvement in visual analog scale (VAS) score (improvement of VAS of leg pain \(\geq\)50% 12 weeks after administration of condoliase) was seen in 59/81 patients (72%) [26]. We used the NRS score for the evaluation of leg pain and defined improvement in NRS score \(\geq\) 50% as good. This is similar to [PERSON]'s evaluation. The improvement rate in our study was 21/34 patients (61.8%). This was inferior to that in [PERSON]'s report. One of the reasons for this difference could be that [PERSON]'s study might have had a high rate of spontaneous remission, because a high rate of improvement (50%) was also observed in the placebo group. [PERSON] et al. also reported that chemonucleolysis with condoliase was effective in 34/47 patients (70.2%); however, they defined a more than 20 mm decrease in the VAS score as effective. There is also a possibility of the inclusion of cases with trans-ligamentous extrusion that might have contributed to the good outcome in Table 3 of [PERSON]'s report [30; 31]. Comparing the data of previous studies and our study, at least 60% of the cases with extrusion and sub-ligamentous extrusion type of LDH might respond to chemonucleolysis. From this study, it can be suggested that the size of the protruded NP might be a predictive factor for the improvement of leg pain. Chemonucleolysis with condoliase might be less effective in cases with protrusion type and the small subligamentous extrusion type; however, it is difficult to  
Figure 6: A patient of herniation with spondylosis in whom low back pain worsened significantly after chemonucleolysis. The decrease in the intervertebral disc height (blue arrow) might cause mechanical stress to the pars interarticularis defect (yellow arrows). \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Leg Pain** & **Group G (_n = 21_)** & **Group P (_n = 13_)** & _p-Value_ \\ \hline disc height decreases \(\geq\) 25\% & 15 & 6 & 0.168 \({}^{\dagger}\) \\ HIC of protruded NP on MRI & 14 & 4 & **0.042 \({}^{\dagger}\)** \\ the spinal canal occupying ratio \(\geq\) 40\% & 13 & 3 & **0.028 \({}^{\dagger}\)** \\ Pfirrmann classification & & & 0.591 \({}^{\dagger}\) \\ Grade II & 7 & 6 & \\ Grade III & 13 & 7 & \\ Grade IV & 1 & 0 & \\ \hline \hline \end{tabular} \({}^{\dagger}\): \(\chi^{2}\) test. HIC = high-intensity change, NP = nucleus pulposus, MRI = magnetic resonance imaging. _p \(<\)_ 0.05 is shown in bold.  
\end{table} 
Table 5: Comparison of imaging findings of patients with leg pain between the G and P groups. precisely distinguish between the two on MRI. Nevertheless, a spinal canal occupancy ratio \(\geq\) 40% is highly predictive of improvement in leg pain. Various surgical approaches from decompression alone to fixation, have been reported for the treatment of large central LDHs, which are difficult to treat [32; 33; 34; 35; 36]. In recent years, transforaminal disectomy by FESS has been reported to have good results for large central LDHs [37; 38; 39]. However, chemonucleolysis with condoliase seems to be a less invasive treatment than FESS and is suitable for large central LDH. We show below, representative images of a patient with a large LDH treated by chemonucleolysis with condoliase in Figure 7. An 18-year-old man with L4/5 LDH complaining of low back pain and left leg pain was first treated conservatively for more than 12 months. There was no improvement, and chemonucleolysis was performed. The improvement in low back pain and leg pain was gradually seen 4 weeks after chemonucleolysis without any adverse events. The NRS scores for both, low back and leg pains improved significantly from 7 to 0 and from 3 to 0, respectively, at 6 months after the treatment (Figure 7). [PERSON] et al. investigated the signal intensity of the protruded NP and reported that patients with high intensity on T2-weighted MRI showed a better response to chemonucleolysis with condoliase [30].