DISCUSSION

Multiple sessions of 1-Hz rTMS facilitated the effects of RFEs in improving the motor function of the affected upper limb, but did not change spasticity in chronic stroke patients. Significantly larger improvements were observed in the ARAT score compared with sham rTMS. The FMA, ARAT and STEF scores improved significantly during the motor rTMS sessions, but the trend did not reach statistical significance during sham rTMS sessions. The MAS score and F/M ratio of the affected side did not change significantly. These results demonstrated that priming by rTMS enhanced the improvement in the affected hand function through a motor-training effect in chronic patients after stroke. Combining 1-Hz rTMS to the unaffected motor cortex with RFEs produced significantly greater improvement than sham rTMS.

The present study extends the findings of previous studies. This study was based on the hypothesis that the application of 1-Hz rTMS to the unaffected motor cortex decreased the transcallosal inhibition (2) and increased the local excitability of the affected motor cortex, which could represent an increase in synaptic efficacy. Previous studies reported that 1-Hz rTMS to the unaffected motor cortex improved the function of affected upper limbs in chronic stroke patients. Single sessions of 1-Hz rTMS for 25 min (1,500 pulses) improved the pinch acceleration (2). Stimulation at 1 Hz (600 pulses) decreased single and choice reaction time (4). Single sessions of 1-Hz rTMS for 25 min (1,500 pulses) enhanced the effect of motor training on pinch force in stroke patients (3). Multiple sessions of 1-Hz rTMS for 25 min (1,500 pulses) for 10 days boosted the effect of physiotherapy in chronic stroke patients (10). In the present study, 1-Hz rTMS for 4 min (240 pulses) facilitated the effect of RFEs, supporting and extending the findings of previous studies.

Although high correlations have previously been documented for the FMA and ARAT (18), there was a difference in gain between sessions for FMA and ARAT in this study. STEF was designed to evaluate the speed of carrying objects, which might be difficult to differentiate among subjects with moderate impairment. The small size of the study group might prevent us from detecting a clear difference in gain between sessions for FMA, STEF and ARAT.

Short duration (4 min, 240 pulses) 1-Hz rTMS facilitated the effect of RFEs on hemiplegic upper-limb function in our study. The effects would have been greater if the period of rTMS was longer. But there were two reasons why we used 4 min 1-Hz rTMS, even though many previous studies have used 25 min. First, previous studies reported the effect of short duration of 1-Hz rTMS. MEPs were significantly reduced after 1-Hz rTMS for 4 min (240 pulses) (19). Significant inhibition continued for 5 min after 150 pulses of 1-Hz rTMS (20). Short duration 1-Hz rTMS could affect the excitability of the motor cortex. Stimulation at 1 Hz, 10 min (600 pulses) decreased single and choice reaction time in stroke patients (4). Thus, it might be possible to induce a temporary state in which motor learning was optimized even after short duration 1-Hz rTMS. Secondly, short-lasting effects of 1-Hz rTMS were considered sufficient for enhancing the effect of RFEs, because the RFEs were able to facilitate and directly repeat isolated movements in the hemiplegic upper limb over a relatively short time-period. If the minimum period of effective rTMS was known, it might be of great benefit to stroke patients. Koganemaru et al. (21) reported that combining motor training with 5-Hz rTMS could facilitate use-dependent plasticity and achieve functional recovery of motor impairments. RFEs can repeat and improve target movements, such as finger extension, thumb abduction and elbow extension. Combining rTMS and RFEs might facilitate use-dependent plasticity. Short-duration of 1-Hz rTMS to the unaffected motor cortex and RFEs could therefore be an effective rehabilitative approach for patients with hemiplegic stroke.

F-waves can be used to study long-pathway nerve conduction and motor neurone excitability. We used MAS scores and F-waves to measure spasticity. Although we expected 1-Hz rTMS to reduce spasticity and F-wave amplitudes, the MAS score and F/M ratio of the affected upper limb did not change during our study. We put forward 3 reasons why the MAS and F/M ratio of the affected upper limb did not change. First, the adequacy of MAS is not conclusive, although the MAS is often used to assess spasticity (22). Secondly, the range of MAS scores before the first session were 0–2, thus we only measured mild-to-moderate spasticity. MAS scores might change after rTMS sessions in patients with severe spasticity. Thirdly, the rTMS conditions are different from other reports. Valle et al. (23) showed that there was a significant reduction in spasticity after multiple sessions of 5-Hz rTMS, but not 1-Hz. Mally & Dinya (24) showed that multiple sessions of 1-Hz rTMS using a circular coil significantly reduced the spasticity of affected limbs in chronic stroke patients. Kondo et al. (25) reported that a single session of 1-Hz rTMS significantly decreased the F/M ratio in affected upper limbs. Reducing spasticity after rTMS in stroke patients might thus depend on the stimulated area or the duration and frequency of rTMS.

Some limitations of the current study should be noted. First, we did not measure neurophysiological data except for upper-limb F-waves. We were unable to investigate whether 1-Hz rTMS decreased excitability in the intact hemisphere and increased excitability in the affected hemisphere. Secondly, our sham rTMS may affect the sensory cortex, because the position 5 cm posterior of the motor cortex is close to the sensory cortex. Thus, the motor cortex may be influenced indirectly through the sensory cortex. Thirdly, the small size of the study group prevented us from examining the effects of differences in the severity of hemiplegia using subgroup analysis. Further research is needed to confirm the effectiveness of combining 1-Hz rTMS and RFEs.

In conclusion, this study shows that multiple sessions of 1-Hz rTMS of the unaffected motor cortex facilitates the effects of RFEs on hemiplegic upper-limb function in chronic stroke patients.

REFERENCES