Controlled trial on the effect of 10 days low‐frequency repetitive transcranial magnetic stimulation (rTMS) on motor signs in Parkinson's disease

Abstract

We evaluated the effect of low-frequency rTMS on motor signs in Parkinson's disease (PD), under a double-blind placebo-controlled trial design. PD patients were randomly assigned to received either real (n = 9) or sham (n = 9) rTMS for 10 days. Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90% of daily rest motor threshold using a large circular coil over the vertex. The effect of the stimulation, delivered during the ON-period, was evaluated during both ON and OFF periods. Tests were carried out before and after the stimulation period, and again 1 week after. The effect of the stimulation was evaluated through several gait variables (cadence, step amplitude, velocity, the CV(stride-time), and the turn time), hand dexterity, and also the total and motor sections of the UPDRS. Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation, the effect appearing during either ON or OFF evaluation, and most importantly, equally displayed in both real and sham group. The rest of the variables were not influenced. We conclude the protocol of stimulation used, different from most protocols that apply larger amount of stimuli, but very similar to some previously reported to have excellent results, has no therapeutic value and should be abandoned. This contrasts with the positive reported effects using higher frequency and focal coils. Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS.

Transcranial Magnetic Stimulation Treatment for Motor Symptoms in Parkinson’s Disease: A Review of Two Decades of Studies

“…Overall, there is growing evidence of potential beneficial effects of rTMS treatment for motor symptoms in PD: of the 40 studies reviewed, only 12 [31,32,36,43,45,47,54,60,[61][62][63]68] did not find any improvement and one of these reported a symptoms worsening after stimulation [54]. Nevertheless, the magnitude of effects varied significantly across studies, probably due to the heterogeneity between stimulation protocols (in terms of frequency, intensity, duration) and targeted regions.…”

“…Nevertheless, the magnitude of effects varied significantly across studies, probably due to the heterogeneity between stimulation protocols (in terms of frequency, intensity, duration) and targeted regions. Moreover, many studies were not sham-controlled and for sham-controlled studies, different methods of sham stimulation have been used: tilted [33,37,54,56,60,62], sham [39,47,63] and inactive coils [50,66,68] have been used, as well as occipital stimulation [40,49,61], coil back surface [41] and realistic sham [51,57,58]. A very recent review [69] examined 20 RCTs of rTMS treatment for motor dysfunction in PD to evaluate the efficacy of treatment and identify protocols factors that moderate the effects of treatment.…”

“…We decided to include only studies focusing on motor symptoms, therefore studies employing neuropsychological testing, mood rating scales, voice and speech rating scales and cortical excitability or neurotransmitter levels measures were excluded. Most studies focused on three regions: M1, SMA and DLPFC [ Table 1-3], while fewer targeted other areas [36,61,[64][65][66][67][68][ Table 4]. Nine studies [32][33][34]39,45,52,54,55,63] tested the effects of only one rTMS session, while the remaining administered a higher number of sessions, ranging from 2 to 20.…”

“…Sample sizes were generally under 30 subjects, except for five studies [36,40,57,58,64]. In regard to outcome measures, the Unified Parkinson's Disease Rating Scale -Section III (UPDRS-III) was the most employed measure (33 of 40 studies) [32][33][34][36][37][38][39][40][41][42][43][44][47][48][49][50][51][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68], yet some studies employed other motor function measures such as movement and reaction time [29,30,35], Grooved Pegboard test for fine movement [31], pointing, pronation supination, Purdue Pegboard Test [45], movement frequency [46] and gait kinematics [52].…”

“…All studies except for the abovementioned one [61] delivered a low number of pulses, ranging from 30 to 100, although in repeated sessions. Three studies [64][65]68] targeted the vertex of the skull: the first 2 studies [64][65], conducted by the same authors, reported significant improvements in motor symptoms as suggested by the decrease in UPDRS scores, while the latter [68] found no differences between real and sham stimulation groups and suggested the lack of therapeutic value of this stimulation protocol, which should have been abandoned.…”