The clinical benefits of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) remain controversial. We performed a comprehensive study to examine whether rTMS is a safe and effective treatment for PD. Twelve PD patients received rTMS once a week. The crossover study design consisted of 4-week sham rTMS followed by 4-week real rTMS. The Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn and Yahr Stage, Schwab and England ADL Scale, Actigraph, Mini-Mental State Examination, Hamilton Depression Scale, Wechsler Adult Intelligence Scale-revised, and cerebral blood flow (CBF) and cerebrospinal fluid (CSF) examinations were used to evaluate the rTMS effects. Under both drug-on and drug-off conditions, the real rTMS improved the UPDRS scores significantly, while the sham rTMS did not. There were no significant changes in the results of the neuropsychological tests, CBF and CSF. rTMS seems to be a safe and effective therapeutic option for PD patients, especially in a wearing-off state. 1. Introduction Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. The prevalence of PD in Japan has been estimated to be about 100 per 100,000 population [1]. The exact etiology and pathogenesis of PD remain unknown at present [2–5]. The treatments for PD consist of antiparkinsonian drugs, such as L-dopa, and stereotactic brain surgery. Although these treatments are effective for PD symptoms, there are several therapeutic problems, such as the on-and-off phenomenon. Therefore, to overcome the problems, some therapeutic trials for PD are being conducted. Among them, repetitive transcranial magnetic stimulation (rTMS) has been used with some PD patients. In 1994, Pascual-Leone et al. reported that rTMS improved the fine movement of the upper extremities in patients with PD [6]. Since then, clinical trials of rTMS for PD have been reported, many of which indicated the efficacy of rTMS on the symptoms of PD [7–11]; however, others did not [12–14]. Moreover, no study has performed a comprehensive analysis including examinations of neuropsychological status, cerebral blood flow (CBF), and cerebrospinal fluid (CSF). Here, we report a comprehensive clinical trial of rTMS for PD with blind tests of motor functions. 2. Patients and Methods 2.1. Patients Twelve PD patients (seven men and five women) with a mean age of 69.2 years (range: 57–78 years) were included in this study (Table 1). We used the diagnostic criteria recommended by the “Multicentric Research Study on the Skill and Indication of
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