Combination treatment of low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy for upper limb hemiparesis after stroke: clinical results in more than a thousand patients

Abstract

Objectives: Application of repetitive transcranial magnetic stimulation (rTMS) influences neural excitability of selected brain areas noninvasively. Low-frequency rTMS suppresses local neural activity while high-frequency rTMS increases the activity. Low-frequency rTMS applied to the non-lesional hemisphere has proved to improve motor function of the paretic upper limb after stroke, with the reduction of inter-hemispheric inhibition towards the lesional hemisphere. On the other hand, some clinical studies have confirmed the beneficial effect of intensive occupational therapy (OT) for upper limb hemiparesis after stroke. Therefore, this study originally developed a combined protocol of these two interventions, expecting that motor recovery would be facilitated. The purpose of this study was to clarify the safety, feasibility and efficacy of the combined protocol for poststroke patients with upper limb hemiparesis. Furthermore, this study investigated the influence of age at the intervention on the extent of motor recovery with the protocol using linear regression analysis. Methods: The study subjects were 1008 post-stroke patients with upper limb hemiparesis (mean age=61.1 ± 12.4 years, mean time after stroke onset=81.5 ± 88.5 months) from eight institutions in Japan. Prior to the intervention, medical doctors and occupational therapists from each institution received a training programme for standardizing the protocol. During 15-day hospitalization, each patient was scheduled to receive 22 treatment sessions of 20-minutes low-frequency rTMS followed by 120-minutes of intensive OT daily. Low-frequency pulses of 1 Hz were applied to the motor cortex of the non-lesional hemisphere. The intensity of the stimulation was set at 90% of resting motor threshold of the first dorsal interosseous muscle of the unaffected upper limb. The programme of intensive OT is composed of one-to-one training and self-exercise. In oneto- one training, shaping and repetitive task practice techniques were mainly involved. Fugl-Meyer Assessment (FMA), log performance time of Wolf Motor Function Test (WMFT) and Functional Ability Score (FAS) of WMFT were evaluated on the days of admission and discharge. Results: The protocol was completed by all patients without any adverse effects. The FMA score significantly increased from 45.3 ± 12.1 to 49.7 ± 10.4 points (p<0.001). Similarly, log performance time of WMFT significantly decreased from 2.78 ± 1.07 to 2.43 ± 1.22 (p<0.001). In addition, the intervention significantly increased FAS of WMFT from 45.6 ± 13.8 to 49.7 ± 14.1 points (p<0.001). Linear regression analysis indicated that the response to the treatment was significantly influenced by severity and side of hemiparesis. However, the age at the intervention did not influence the response. The extent of motor recovery did not differ between patients aged 70 years or over and those aged under 70 years. Conclusions: The proposed combination treatment is safe and feasible. The treatment seems to improve motor function of the paretic upper limb after stroke, although the efficacy of the treatment needs to be confirmed in a further study.