Clinical neuroscience
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Galvanic vestibular stimulation may improve anterior bending posture in Parkinson’s disease Yohei Okadaa,b, Yorihiro Kitaa,c, Junji Nakamuraa,c, Hiroshi Kataokad, Takao Kiriyamad, Satoshi Uenod, Makoto Hiyamizua,b, Shu Moriokaa,b and Koji Shomotoa This study investigated the effects of binaural monopolar galvanic vestibular stimulation (GVS), which likely stimulates the bilateral vestibular system, on the anterior bending angle in patients with Parkinson’s disease (PD) with anterior bending posture in a single-blind, randomized sham-controlled crossover trial. The seven PD patients completed two types of stimulation (binaural monopolar GVS and sham stimulation) applied in a random order 1 week apart. We measured each patient’s anterior bending angles while he or she stood with eyes open and eyes closed before/after the stimulations. The anterior bending angles in both the eyes-open and the eyes-closed conditions were significantly reduced after the GVS. The amount of change in the eyes-closed condition post-GVS was significantly larger than that by sham stimulation. The amount of change in anterior bending angles in the GVS condition was not significantly correlated with Unified Parkinson’s Disease Rating Scale motor score, disease duration, the duration of the postural deformities, and the
Introduction Anterior bending posture is a major problem for patients with Parkinson’s disease (PD). Camptocormia is defined as a severe (minimum 45°) anterior bending posture. Possible mechanisms involved in camptocormia are abdominal muscle dystonia and paraspinal myopathy [1]. Various treatments such as levodopa [2], deep brain stimulation [3], lidocaine injection [4], botulinum toxin injection [5], spinal magnetic stimulation [6], and orthosis and physiotherapy [7,8] have been administered in attempts to improve camptocormia. However, there is insufficient evidence on the effectiveness of these treatments for camptocormia and mild to moderate anterior bending posture in PD patients. It was reported that vestibular function is impaired in PD patients with lateral flexion [9]. By investigating the vestibular evoked myogenic potentials, Pollak et al. [10] found that vestibulocollic reflexes in PD patients were absent unilaterally or bilaterally, which was associated with unilateral or bilateral dysfunction of the vestibulospinal tract. However, they did not describe any relationships between these deficits and postural deformities. The vestibulospinal tract is associated with the control of antigravity muscles and is important in the postural control in the sagittal plane. We hypothesized 0959-4965 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
anterior bending angles before the GVS. Binaural monopolar GVS might improve anterior bending posture in PD patients, irrespective of the duration and the severity of disease and postural deformities. Binaural monopolar GVS might be a novel treatment strategy to improve anterior bending posture in PD. NeuroReport 26:405–410 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. NeuroReport 2015, 26:405–410 Keywords: anterior bending posture, galvanic vestibular stimulation, Parkinson’s disease, postural deformities, randomized clinical trial a Graduate School of Health Science, Kio University, bNeurorehabilitation Research Center of Kio University, cDepartment of Rehabilitation, Nishiyamato Rehabilitation Hospital and dDepartment of Neurology, Nara Medical University, Nara, Japan
Correspondence to Yohei Okada, PhD, Department of Physical Therapy, Faculty of Health Science, Kio University, 4-2-2 Umami-naka, Koryo-cho, Kitakatsuragigun, Nara 635 0832, Japan Tel: + 81 745 54 1601; fax: + 81 745 54 1600; e-mail: [email protected] Received 18 February 2015 accepted 20 February 2015
that the function of the bilateral vestibulospinal tract is impaired in PD patients with anterior bending posture, causing underactivity of the antigravity muscles. Galvanic vestibular stimulation (GVS) is a method that stimulates vestibular organs [11] and influences the function of the vestibulospinal tract [12]. In GVS, electrodes are attached to the mastoids behind the patient’s ears to stimulate the vestibular system by low direct current. GVS has been used in neurophysiological experiments and otological tests, and there have been some reports in which GVS was used as an intervention strategy in PD patients and stroke patients with unilateral spatial neglect or pushing symptoms [13–15]. We hypothesized that binaural monopolar GVS, which likely stimulates the bilateral vestibular system, might activate the bilateral vestibulospinal tract and improve the anterior bending posture in PD patients. The effects of binaural monopolar GVS on anterior bending posture in PD patients have not been clarified. Here, we thus investigated the effects of binaural monopolar GVS on anterior bending posture in PD patients.
Patients and methods Patients
Seven PD outpatients with anterior bending posture were recruited. All patients fulfilled the UK Parkinson’s Disease DOI: 10.1097/WNR.0000000000000360
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Society Brain Bank criteria [16]. Detailed clinical information of these patients is presented in Table 1. All of the patients were being treated with antiparkinson drugs, and their treatment remained unchanged during the study. The patients had not undergone any brain surgery such as deep brain stimulation, and they had no history of neurological or vestibular disorders other than PD. The protocol of this study was approved by the Medical Ethics Committees of Kio University (H25-11) and Nara Medical University (H25-703), and written informed consent was obtained from all patients. The study conformed to the principles outlined in the Declaration of Helsinki. The study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000010896). Stimulation protocols
The single-blind randomized sham-controlled crossover design was used. All seven patients were assigned randomly to one of two groups: GVS-sham (the immediate group) or sham-GVS (the delayed group). One of two types of stimulation (binaural monopolar GVS and sham) was assigned randomly to each patient as the first stimulation. The other procedure was performed in the same patient at the same time of day 1 week after the first procedure. Patients A, B, C, and D were assigned to the immediate group. Patients E, F, and G were assigned to the delayed group. The patients were blinded in terms of the type of stimulation. All of the experiments were conducted while the patients were in an ‘on’ state, that is, ∼ 1 h after taking their antiparkinson medication. Both the binaural monopolar GVS and the sham stimulation were applied using an electrical stimulation system Table 1
(Chattanooga Intelect Advanced Combo; DJO Global, Vista, California, USA) and self-adhesive electrodes (32 mm × 32 mm). In both types of stimulation, two electrode pairs were located with the cathode electrode of each pair over the mastoid process and the anode electrode over the trapezius muscle on the same side. Both types of stimulation were applied to the patients in the supine position for 20 min. During the binaural monopolar GVS in patients C–F, the current intensity was ramped up until 0.7 mA was reached, and this current was maintained until the end of the stimulation. In patients A and B, the current intensity was ramped up to only 0.2 and 0.5 mA, respectively, because of the patients’ complaint of pain at both sides of the mastoid process. For the sham stimulation, the first part of the procedure was the same, and subsequently, the current intensity was ramped down to 0 mA over a 10-s period, and this absence of current was maintained until the end of the stimulation. Studies using transcranial direct current stimulation indicated a quick habituation to cutaneous sensation and showed that patients were unable to distinguish between real and sham stimulation [17]. Outcome measures and data analysis
The outcome measures were the average anterior bending angles while standing with eyes open and eyes closed for 30 s each and the Unified Parkinson’s Disease Rating Scale (UPDRS) gait subscore. In the postural evaluation, the patients were instructed to stand comfortably with their feet 10 cm apart and with their arms along the trunk. To evaluate the anterior bending angles, we captured the patients’ sagittal posture by a digital video camera and
Patients’ characteristics Immediate group (n = 4)
Age Sex Disease duration (years) Hoehn–Yahr stage UPDRS part 3 Duration of the postural deformities (years) Antiparkinson drugs (mg/day) Levodopa Rotigotine Bromocriptine Cabergoline Pramipexole Ropinirole Selegiline Entacapone Amantadine Zonisamide Trihexyphenidyl Droxidopa Clonazepam Istradefylline
Delayed group (n = 3)
Patient A
Patient B
Patient C
Patient D
Patient E
Patient F
Patient G
75 Female 10 3 13 4
63 Female 8 3 6 0.8
65 Male 4 3 32 2
66 Female 14 3 29 5
83 Female 17 3 16 6
72 Male 12 4 27 2
74 Male 14 4 24 2
300 − − 2 − − 5 − − 50 − − − −
300 9 − − − − 5 300 − 25 − − − −
300 9 − − 1.5 − − − − 100 2 − − −
550 − 2.5 − 3 − − − − − 2 − − −
450 4.5 − − − − − − − 25 − 600 − −
500 − − − − 4 5 300 200 50 − − 1 40
600 − − − 3 − 5 100 − 25 − 300 − −
UPDRS, Unified Parkinson’s Disease Rating Scale.
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GVS for anterior bending posture in PD Okada et al. 407
We used Spearman’s correlation test to examine the relationship between the amounts of change of the angles in the GVS condition and disease duration, the UPDRS motor score, the duration of the postural deformities, and the anterior bending angles while standing before the GVS. The α level was set at 0.05. To investigate the trends in the sustained effects of the GVS on the anterior bending angles in the eyes-open and eyes-closed conditions, we compared the angles before and after the GVS and before the sham stimulation (1 week post-GVS) in the immediate group.
carried out a frame-by-frame video analysis. The anterior bending angle was calculated as the angle formed between the line joining the marker positioned on the C7 spinous process and the midpoint of the right and left posterior superior iliac spine and a vertical reference line every 30 frames, and then averaged (Fig. 1a). The data are presented as the mean (SEM). The Wilcoxon signed-rank test was used to assess the difference between anterior bending angles in the eyes-open and eyes-closed conditions, the difference between these angles and the UPDRS-gait subscore before the GVS and sham stimulation, the difference between these angles and the UPDRS-gait subscore before and after the stimulation (in both the GVS and the sham conditions), and the difference between the amounts of change of the angles in the GVS and sham conditions.
Results All patients completed the GVS and the sham stimulation sessions without any adverse effects such as vertigo, nausea, or nystagmus. The anterior bending angle in the eyes-closed condition was significantly larger than that in
Fig. 1
(a)
Before the GVS
40
38.0 32.5
34.0 29.6
30
20
10
0
Pre
Post GVS
Pre
Post
Sham
∗
10
60
∗
∗ 50
43.9
40
35.7
36.4
32.2
30 20 10 0
Pre
Post GVS
Pre
Post Sham
Amount of change of the anterior bending angles (deg.)
50
Anterior bending angles in the eyes-closed condition (deg.)
Anterior bending angles in the eyes-open condition (deg.)
(b)
Immediately after the GVS
8.2 8 6
5.4 4.4
4
3.3
2 0
GVS
Sham
Eyes-open
GVS
Sham
Eyes-closed
(a) Measurement of the anterior bending angle before and immediately after the binaural monopolar galvanic vestibular stimulation (GVS) in a representative patient. (b) Anterior bending angles before and immediately after the binaural monopolar GVS and sham stimulation. Data columns indicate the mean, and error bars indicate the SEM. *P < 0.05, significant difference.
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the eyes-open condition at all of the time points, except before the sham stimulation [pre-GVS: eyes-open, 38.0 (7.1), eyes-closed, 43.9 (7.8), Z = − 2.28, P = 0.018; postGVS: eyes-open, 32.5 (6.3), eyes-closed, 35.7 (7.1), Z = − 1.94, P = 0.043; pre-sham: eyes-open, 34.0 (6.6), eye-closed, 36.4 (6.8), Z = − 1.61, P = 0.091; post-sham: eyes-open, 29.6 (6.1), eyes-closed, 33.2 (6.4), Z = − 2.28, P = 0.018]. The anterior bending angles in the eyes-open and eyes-closed conditions before the GVS were not significantly different from those before the sham stimulation (eyes-open, Z = − 1.10, P = 0.24; eyes-closed, Z = − 1.61, P = 0.091). After the GVS, anterior bending angles in both the eyesclosed and the eyes-closed conditions were reduced in all seven patients. The anterior bending angles in both the eyes-open and the eyes-closed conditions were significantly reduced after the GVS (eyes-open, Z = − 2.28, P = 0.018; eyes-closed, Z = − 2.28, P = 0.018) (Fig. 1b). The angles were also reduced in both conditions after the sham stimulation in five of the seven patients, but the reduction was not significant (eyes-open, Z = − 1.77, P = 0.063; eyes-closed, Z = − 1.77, P = 0.063). The amount of change of the anterior bending angle in the eyes-open condition following GVS was not significantly different from that following the sham stimulation [GVS, 5.4 (1.5); sham, 4.4 (2.4); Z = − 0.85; P = 0.74]. However, the amount of change in the eyesclosed condition following GVS was significantly larger than that following the sham stimulation [GVS, 8.2 (1.2); sham, 3.3 (1.3); Z = − 1.94; P = 0.043]. The amount of change of anterior bending angles in the eyes-open and eyes-closed conditions in the GVS condition was not significantly correlated with the disease duration (eyesopen, P = 0.53; eyes-closed, P = 0.13), the UPDRS motor score (eyes-open, P = 0.59; eyes-closed, P = 0.43), the duration of the postural deformities (eyes-open, P = 0.63; eyes-closed, P = 0.87), and the anterior bending angle (eyes-open, P = 0.12, eyes-closed, P = 0.12). Anterior bending angles in the eyes-open and eyesclosed condition 1 week after GVS were smaller than those before the GVS in patients A and B. Patient A: eyes-open condition: pre-GVS, 18.8; post-GVS, 17.7; 1 week post-GVS, 17.1; eyes-closed condition: pre-GVS, 21.5; post-GVS, 16.4; 1 week post-GVS, 18.2. Patient B: eyes-open condition: pre-GVS, 10.3; post-GVS, 8.0; 1 week post-GVS, 6.0; eyes-closed condition: pre-GVS, 13.5; post-GVS, 8.3; 1 week post-GVS, 8.9. The anterior bending angle in the eyes-open condition 1 week after GVS in patient C was larger than that before the GVS, but the angle in the eyes-closed condition after 1 week post-GVS was smaller than that before the GVS: eyes-open condition: pre-GVS, 47.3; post-GVS, 42.3; 1 week post-GVS, 49.1; eyes-closed condition: pre-GVS, 51.2; post-GVS, 44.8; 1 week post-GVS, 46.7.
In patient D, the anterior bending angles in the eyesopen and eyes-closed conditions after 1 week post-GVS were larger than that before the GVS: eyes-open condition: pre-GVS, 36.6; post-GVS, 34.6; 1 week post-GVS, 48.3; eyes-closed condition: pre-GVS, 45.0; post-GVS, 37.7, 1 week post-GVS, 49.7. The patients’ UPDRS-gait subscores before the GVS were not significantly different from those before the sham stimulation (Z = − 1.36, P = 0.50). The UPDRS-gait subscores did not change significantly after the GVS or the sham stimulation compared with before the stimulations: pre-GVS, 1.3 (0.3), post-GVS, 1.4 (0.4), Z = − 0.89, P = 1.00; pre-sham, 1.6 (0.4), post-sham, 1.3 (0.3), Z = − 1.36, P =0.50.
Discussion To the best of our knowledge, this is the first study to investigate the effects of binaural monopolar GVS on anterior bending posture in PD patients. All seven of our patients completed the binaural monopolar GVS without adverse effects such as vertigo, nausea, or nystagmus. The results of this study suggest that a single session of binaural monopolar GVS is feasible. The patients’ anterior bending angles in the eyes-open and eyes-closed conditions were significantly reduced after the GVS, whereas the tendency toward decreasing anterior bending angles after the sham stimulation was not significant. These results suggested that binaural monopolar GVS immediately improved the anterior bending posture in these PD patients. The amount of change in the eyes-closed condition by the GVS was significantly larger than that by sham stimulation, although that in the eyes-open condition was not significantly different between both types of stimulation. These results indicate that in PD patients, binaural monopolar GVS might improve sagittal postural control with vestibular and proprioceptive senses. One possible mechanism of the effects of binaural monopolar GVS is the activation of the bilateral vestibulospinal tract. The activation of the bilateral vestibulospinal tract by binaural monopolar GVS might cause an activation of the antigravity muscles and improve the anterior bending posture. The function of the vestibulospinal tract and the effects of the binaural monopolar GVS on the vestibulospinal tract in PD patients with anterior bending posture remains to be further clarified. Another possible mechanism of the effects of binaural monopolar GVS is the influence on the body schema and/ or vertical perception. The body schema and vertical perception are integrated with visual, proprioceptive, and vestibular sensations, and are important for postural control. We observed that PD patients’ anterior bending angle in the eyes-closed condition was larger than the angle in the eyes-open condition at almost all time points
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GVS for anterior bending posture in PD Okada et al. 409
in the present study. This phenomenon indicated that the visual dependence in the postural control was increased and that postural control with vestibular and somatosensory sensation might be impaired in PD patients with an anterior bending posture. The anterior bending posture in PD patients might be related to body schema impairment and/or vertical misperception caused by a disintegration of proprioceptive and vestibular information. Body schema and vertical perception are processed in the temporoparietal cortex, including the posterior parietal cortex and the vestibular cortex [18,19]. GVS activates the temporoparietal junction, the central sulcus, and the intraparietal sulcus, including the parietoinsular vestibular cortex [20], and GVS modifies the body schema [21] and vertical perception [22]. In the present study, the binaural monopolar GVS might have affected the body schema and/or vertical perception integrated with vestibular and proprioceptive senses in the temporoparietal cortex and thus improved the patients’ sagittal postural control. Further investigations are needed to determine the characteristics of body schema and vertical perception in PD patients with an anterior bending posture and to determine the mechanism of binaural monopolar GVS. In addition, we observed that the amount of change in the anterior bending angle in the eyes-open and eyesclosed conditions was not significantly correlated with the disease duration, UPDRS motor score, duration of postural deformities, or the anterior bending angles while standing. The duration and severity of PD and postural deformities might not affect the amount of change in the anterior bending angles induced by the binaural monopolar GVS. The anterior bending angles in the eyes-open and eyesclosed conditions 1 week after GVS were smaller than those before the GVS in patients A and B, whose anterior bending postures were mild to moderate. However, the anterior bending angles 1 week after GVS in patients C and D, whose anterior bending postures were severe, were larger than those before the GVS. The effects of the GVS might be sustained for at least 1 week in PD patients with a mild to moderate anterior bending posture. The UPDRS-gait subscores did not change significantly after the GVS or the sham stimulation, indicating that a single session of the binaural monopolar GVS might not affect gait disorders. Future studies should also evaluate gait and balance and determine the effects of binaural monopolar GVS on gait and balance in more detail. The small sample size and lack of a long follow-up period were a limitation of this study. Larger sample sizes and a longer follow-up period are needed to determine whether binaural monopolar GVS can improve anterior bending
posture and other symptoms in PD patients with an anterior bending posture.
Conclusion The present study investigated the effects of binaural monopolar GVS on anterior bending posture in PD patients in a single-blind randomized sham-controlled cross-over trial. Binaural monopolar GVS might improve the anterior bending posture in PD patients. Binaural monopolar GVS may be a novel treatment strategy to improve the anterior bending posture in PD.
Acknowledgements The authors are extremely grateful to Dr Kazuma Sugie and Dr Mari Tearashima (Nara Medical University, Department of Neurology) for the recruitment of participants. This work was supported by a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science (No. 25750246). Conflicts of interest
There are no conflicts of interest.
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405
Galvanic vestibular stimulation may improve anterior bending posture in Parkinson’s disease Yohei Okadaa,b, Yorihiro Kitaa,c, Junji Nakamuraa,c, Hiroshi Kataokad, Takao Kiriyamad, Satoshi Uenod, Makoto Hiyamizua,b, Shu Moriokaa,b and Koji Shomotoa This study investigated the effects of binaural monopolar galvanic vestibular stimulation (GVS), which likely stimulates the bilateral vestibular system, on the anterior bending angle in patients with Parkinson’s disease (PD) with anterior bending posture in a single-blind, randomized sham-controlled crossover trial. The seven PD patients completed two types of stimulation (binaural monopolar GVS and sham stimulation) applied in a random order 1 week apart. We measured each patient’s anterior bending angles while he or she stood with eyes open and eyes closed before/after the stimulations. The anterior bending angles in both the eyes-open and the eyes-closed conditions were significantly reduced after the GVS. The amount of change in the eyes-closed condition post-GVS was significantly larger than that by sham stimulation. The amount of change in anterior bending angles in the GVS condition was not significantly correlated with Unified Parkinson’s Disease Rating Scale motor score, disease duration, the duration of the postural deformities, and the
Introduction Anterior bending posture is a major problem for patients with Parkinson’s disease (PD). Camptocormia is defined as a severe (minimum 45°) anterior bending posture. Possible mechanisms involved in camptocormia are abdominal muscle dystonia and paraspinal myopathy [1]. Various treatments such as levodopa [2], deep brain stimulation [3], lidocaine injection [4], botulinum toxin injection [5], spinal magnetic stimulation [6], and orthosis and physiotherapy [7,8] have been administered in attempts to improve camptocormia. However, there is insufficient evidence on the effectiveness of these treatments for camptocormia and mild to moderate anterior bending posture in PD patients. It was reported that vestibular function is impaired in PD patients with lateral flexion [9]. By investigating the vestibular evoked myogenic potentials, Pollak et al. [10] found that vestibulocollic reflexes in PD patients were absent unilaterally or bilaterally, which was associated with unilateral or bilateral dysfunction of the vestibulospinal tract. However, they did not describe any relationships between these deficits and postural deformities. The vestibulospinal tract is associated with the control of antigravity muscles and is important in the postural control in the sagittal plane. We hypothesized 0959-4965 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
anterior bending angles before the GVS. Binaural monopolar GVS might improve anterior bending posture in PD patients, irrespective of the duration and the severity of disease and postural deformities. Binaural monopolar GVS might be a novel treatment strategy to improve anterior bending posture in PD. NeuroReport 26:405–410 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. NeuroReport 2015, 26:405–410 Keywords: anterior bending posture, galvanic vestibular stimulation, Parkinson’s disease, postural deformities, randomized clinical trial a Graduate School of Health Science, Kio University, bNeurorehabilitation Research Center of Kio University, cDepartment of Rehabilitation, Nishiyamato Rehabilitation Hospital and dDepartment of Neurology, Nara Medical University, Nara, Japan
Correspondence to Yohei Okada, PhD, Department of Physical Therapy, Faculty of Health Science, Kio University, 4-2-2 Umami-naka, Koryo-cho, Kitakatsuragigun, Nara 635 0832, Japan Tel: + 81 745 54 1601; fax: + 81 745 54 1600; e-mail: [email protected] Received 18 February 2015 accepted 20 February 2015
that the function of the bilateral vestibulospinal tract is impaired in PD patients with anterior bending posture, causing underactivity of the antigravity muscles. Galvanic vestibular stimulation (GVS) is a method that stimulates vestibular organs [11] and influences the function of the vestibulospinal tract [12]. In GVS, electrodes are attached to the mastoids behind the patient’s ears to stimulate the vestibular system by low direct current. GVS has been used in neurophysiological experiments and otological tests, and there have been some reports in which GVS was used as an intervention strategy in PD patients and stroke patients with unilateral spatial neglect or pushing symptoms [13–15]. We hypothesized that binaural monopolar GVS, which likely stimulates the bilateral vestibular system, might activate the bilateral vestibulospinal tract and improve the anterior bending posture in PD patients. The effects of binaural monopolar GVS on anterior bending posture in PD patients have not been clarified. Here, we thus investigated the effects of binaural monopolar GVS on anterior bending posture in PD patients.
Patients and methods Patients
Seven PD outpatients with anterior bending posture were recruited. All patients fulfilled the UK Parkinson’s Disease DOI: 10.1097/WNR.0000000000000360
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of the article is prohibited.
406
NeuroReport 2015, Vol 26 No 7
Society Brain Bank criteria [16]. Detailed clinical information of these patients is presented in Table 1. All of the patients were being treated with antiparkinson drugs, and their treatment remained unchanged during the study. The patients had not undergone any brain surgery such as deep brain stimulation, and they had no history of neurological or vestibular disorders other than PD. The protocol of this study was approved by the Medical Ethics Committees of Kio University (H25-11) and Nara Medical University (H25-703), and written informed consent was obtained from all patients. The study conformed to the principles outlined in the Declaration of Helsinki. The study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000010896). Stimulation protocols
The single-blind randomized sham-controlled crossover design was used. All seven patients were assigned randomly to one of two groups: GVS-sham (the immediate group) or sham-GVS (the delayed group). One of two types of stimulation (binaural monopolar GVS and sham) was assigned randomly to each patient as the first stimulation. The other procedure was performed in the same patient at the same time of day 1 week after the first procedure. Patients A, B, C, and D were assigned to the immediate group. Patients E, F, and G were assigned to the delayed group. The patients were blinded in terms of the type of stimulation. All of the experiments were conducted while the patients were in an ‘on’ state, that is, ∼ 1 h after taking their antiparkinson medication. Both the binaural monopolar GVS and the sham stimulation were applied using an electrical stimulation system Table 1
(Chattanooga Intelect Advanced Combo; DJO Global, Vista, California, USA) and self-adhesive electrodes (32 mm × 32 mm). In both types of stimulation, two electrode pairs were located with the cathode electrode of each pair over the mastoid process and the anode electrode over the trapezius muscle on the same side. Both types of stimulation were applied to the patients in the supine position for 20 min. During the binaural monopolar GVS in patients C–F, the current intensity was ramped up until 0.7 mA was reached, and this current was maintained until the end of the stimulation. In patients A and B, the current intensity was ramped up to only 0.2 and 0.5 mA, respectively, because of the patients’ complaint of pain at both sides of the mastoid process. For the sham stimulation, the first part of the procedure was the same, and subsequently, the current intensity was ramped down to 0 mA over a 10-s period, and this absence of current was maintained until the end of the stimulation. Studies using transcranial direct current stimulation indicated a quick habituation to cutaneous sensation and showed that patients were unable to distinguish between real and sham stimulation [17]. Outcome measures and data analysis
The outcome measures were the average anterior bending angles while standing with eyes open and eyes closed for 30 s each and the Unified Parkinson’s Disease Rating Scale (UPDRS) gait subscore. In the postural evaluation, the patients were instructed to stand comfortably with their feet 10 cm apart and with their arms along the trunk. To evaluate the anterior bending angles, we captured the patients’ sagittal posture by a digital video camera and
Patients’ characteristics Immediate group (n = 4)
Age Sex Disease duration (years) Hoehn–Yahr stage UPDRS part 3 Duration of the postural deformities (years) Antiparkinson drugs (mg/day) Levodopa Rotigotine Bromocriptine Cabergoline Pramipexole Ropinirole Selegiline Entacapone Amantadine Zonisamide Trihexyphenidyl Droxidopa Clonazepam Istradefylline
Delayed group (n = 3)
Patient A
Patient B
Patient C
Patient D
Patient E
Patient F
Patient G
75 Female 10 3 13 4
63 Female 8 3 6 0.8
65 Male 4 3 32 2
66 Female 14 3 29 5
83 Female 17 3 16 6
72 Male 12 4 27 2
74 Male 14 4 24 2
300 − − 2 − − 5 − − 50 − − − −
300 9 − − − − 5 300 − 25 − − − −
300 9 − − 1.5 − − − − 100 2 − − −
550 − 2.5 − 3 − − − − − 2 − − −
450 4.5 − − − − − − − 25 − 600 − −
500 − − − − 4 5 300 200 50 − − 1 40
600 − − − 3 − 5 100 − 25 − 300 − −
UPDRS, Unified Parkinson’s Disease Rating Scale.
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GVS for anterior bending posture in PD Okada et al. 407
We used Spearman’s correlation test to examine the relationship between the amounts of change of the angles in the GVS condition and disease duration, the UPDRS motor score, the duration of the postural deformities, and the anterior bending angles while standing before the GVS. The α level was set at 0.05. To investigate the trends in the sustained effects of the GVS on the anterior bending angles in the eyes-open and eyes-closed conditions, we compared the angles before and after the GVS and before the sham stimulation (1 week post-GVS) in the immediate group.
carried out a frame-by-frame video analysis. The anterior bending angle was calculated as the angle formed between the line joining the marker positioned on the C7 spinous process and the midpoint of the right and left posterior superior iliac spine and a vertical reference line every 30 frames, and then averaged (Fig. 1a). The data are presented as the mean (SEM). The Wilcoxon signed-rank test was used to assess the difference between anterior bending angles in the eyes-open and eyes-closed conditions, the difference between these angles and the UPDRS-gait subscore before the GVS and sham stimulation, the difference between these angles and the UPDRS-gait subscore before and after the stimulation (in both the GVS and the sham conditions), and the difference between the amounts of change of the angles in the GVS and sham conditions.
Results All patients completed the GVS and the sham stimulation sessions without any adverse effects such as vertigo, nausea, or nystagmus. The anterior bending angle in the eyes-closed condition was significantly larger than that in
Fig. 1
(a)
Before the GVS
40
38.0 32.5
34.0 29.6
30
20
10
0
Pre
Post GVS
Pre
Post
Sham
∗
10
60
∗
∗ 50
43.9
40
35.7
36.4
32.2
30 20 10 0
Pre
Post GVS
Pre
Post Sham
Amount of change of the anterior bending angles (deg.)
50
Anterior bending angles in the eyes-closed condition (deg.)
Anterior bending angles in the eyes-open condition (deg.)
(b)
Immediately after the GVS
8.2 8 6
5.4 4.4
4
3.3
2 0
GVS
Sham
Eyes-open
GVS
Sham
Eyes-closed
(a) Measurement of the anterior bending angle before and immediately after the binaural monopolar galvanic vestibular stimulation (GVS) in a representative patient. (b) Anterior bending angles before and immediately after the binaural monopolar GVS and sham stimulation. Data columns indicate the mean, and error bars indicate the SEM. *P < 0.05, significant difference.
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NeuroReport 2015, Vol 26 No 7
the eyes-open condition at all of the time points, except before the sham stimulation [pre-GVS: eyes-open, 38.0 (7.1), eyes-closed, 43.9 (7.8), Z = − 2.28, P = 0.018; postGVS: eyes-open, 32.5 (6.3), eyes-closed, 35.7 (7.1), Z = − 1.94, P = 0.043; pre-sham: eyes-open, 34.0 (6.6), eye-closed, 36.4 (6.8), Z = − 1.61, P = 0.091; post-sham: eyes-open, 29.6 (6.1), eyes-closed, 33.2 (6.4), Z = − 2.28, P = 0.018]. The anterior bending angles in the eyes-open and eyes-closed conditions before the GVS were not significantly different from those before the sham stimulation (eyes-open, Z = − 1.10, P = 0.24; eyes-closed, Z = − 1.61, P = 0.091). After the GVS, anterior bending angles in both the eyesclosed and the eyes-closed conditions were reduced in all seven patients. The anterior bending angles in both the eyes-open and the eyes-closed conditions were significantly reduced after the GVS (eyes-open, Z = − 2.28, P = 0.018; eyes-closed, Z = − 2.28, P = 0.018) (Fig. 1b). The angles were also reduced in both conditions after the sham stimulation in five of the seven patients, but the reduction was not significant (eyes-open, Z = − 1.77, P = 0.063; eyes-closed, Z = − 1.77, P = 0.063). The amount of change of the anterior bending angle in the eyes-open condition following GVS was not significantly different from that following the sham stimulation [GVS, 5.4 (1.5); sham, 4.4 (2.4); Z = − 0.85; P = 0.74]. However, the amount of change in the eyesclosed condition following GVS was significantly larger than that following the sham stimulation [GVS, 8.2 (1.2); sham, 3.3 (1.3); Z = − 1.94; P = 0.043]. The amount of change of anterior bending angles in the eyes-open and eyes-closed conditions in the GVS condition was not significantly correlated with the disease duration (eyesopen, P = 0.53; eyes-closed, P = 0.13), the UPDRS motor score (eyes-open, P = 0.59; eyes-closed, P = 0.43), the duration of the postural deformities (eyes-open, P = 0.63; eyes-closed, P = 0.87), and the anterior bending angle (eyes-open, P = 0.12, eyes-closed, P = 0.12). Anterior bending angles in the eyes-open and eyesclosed condition 1 week after GVS were smaller than those before the GVS in patients A and B. Patient A: eyes-open condition: pre-GVS, 18.8; post-GVS, 17.7; 1 week post-GVS, 17.1; eyes-closed condition: pre-GVS, 21.5; post-GVS, 16.4; 1 week post-GVS, 18.2. Patient B: eyes-open condition: pre-GVS, 10.3; post-GVS, 8.0; 1 week post-GVS, 6.0; eyes-closed condition: pre-GVS, 13.5; post-GVS, 8.3; 1 week post-GVS, 8.9. The anterior bending angle in the eyes-open condition 1 week after GVS in patient C was larger than that before the GVS, but the angle in the eyes-closed condition after 1 week post-GVS was smaller than that before the GVS: eyes-open condition: pre-GVS, 47.3; post-GVS, 42.3; 1 week post-GVS, 49.1; eyes-closed condition: pre-GVS, 51.2; post-GVS, 44.8; 1 week post-GVS, 46.7.
In patient D, the anterior bending angles in the eyesopen and eyes-closed conditions after 1 week post-GVS were larger than that before the GVS: eyes-open condition: pre-GVS, 36.6; post-GVS, 34.6; 1 week post-GVS, 48.3; eyes-closed condition: pre-GVS, 45.0; post-GVS, 37.7, 1 week post-GVS, 49.7. The patients’ UPDRS-gait subscores before the GVS were not significantly different from those before the sham stimulation (Z = − 1.36, P = 0.50). The UPDRS-gait subscores did not change significantly after the GVS or the sham stimulation compared with before the stimulations: pre-GVS, 1.3 (0.3), post-GVS, 1.4 (0.4), Z = − 0.89, P = 1.00; pre-sham, 1.6 (0.4), post-sham, 1.3 (0.3), Z = − 1.36, P =0.50.
Discussion To the best of our knowledge, this is the first study to investigate the effects of binaural monopolar GVS on anterior bending posture in PD patients. All seven of our patients completed the binaural monopolar GVS without adverse effects such as vertigo, nausea, or nystagmus. The results of this study suggest that a single session of binaural monopolar GVS is feasible. The patients’ anterior bending angles in the eyes-open and eyes-closed conditions were significantly reduced after the GVS, whereas the tendency toward decreasing anterior bending angles after the sham stimulation was not significant. These results suggested that binaural monopolar GVS immediately improved the anterior bending posture in these PD patients. The amount of change in the eyes-closed condition by the GVS was significantly larger than that by sham stimulation, although that in the eyes-open condition was not significantly different between both types of stimulation. These results indicate that in PD patients, binaural monopolar GVS might improve sagittal postural control with vestibular and proprioceptive senses. One possible mechanism of the effects of binaural monopolar GVS is the activation of the bilateral vestibulospinal tract. The activation of the bilateral vestibulospinal tract by binaural monopolar GVS might cause an activation of the antigravity muscles and improve the anterior bending posture. The function of the vestibulospinal tract and the effects of the binaural monopolar GVS on the vestibulospinal tract in PD patients with anterior bending posture remains to be further clarified. Another possible mechanism of the effects of binaural monopolar GVS is the influence on the body schema and/ or vertical perception. The body schema and vertical perception are integrated with visual, proprioceptive, and vestibular sensations, and are important for postural control. We observed that PD patients’ anterior bending angle in the eyes-closed condition was larger than the angle in the eyes-open condition at almost all time points
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GVS for anterior bending posture in PD Okada et al. 409
in the present study. This phenomenon indicated that the visual dependence in the postural control was increased and that postural control with vestibular and somatosensory sensation might be impaired in PD patients with an anterior bending posture. The anterior bending posture in PD patients might be related to body schema impairment and/or vertical misperception caused by a disintegration of proprioceptive and vestibular information. Body schema and vertical perception are processed in the temporoparietal cortex, including the posterior parietal cortex and the vestibular cortex [18,19]. GVS activates the temporoparietal junction, the central sulcus, and the intraparietal sulcus, including the parietoinsular vestibular cortex [20], and GVS modifies the body schema [21] and vertical perception [22]. In the present study, the binaural monopolar GVS might have affected the body schema and/or vertical perception integrated with vestibular and proprioceptive senses in the temporoparietal cortex and thus improved the patients’ sagittal postural control. Further investigations are needed to determine the characteristics of body schema and vertical perception in PD patients with an anterior bending posture and to determine the mechanism of binaural monopolar GVS. In addition, we observed that the amount of change in the anterior bending angle in the eyes-open and eyesclosed conditions was not significantly correlated with the disease duration, UPDRS motor score, duration of postural deformities, or the anterior bending angles while standing. The duration and severity of PD and postural deformities might not affect the amount of change in the anterior bending angles induced by the binaural monopolar GVS. The anterior bending angles in the eyes-open and eyesclosed conditions 1 week after GVS were smaller than those before the GVS in patients A and B, whose anterior bending postures were mild to moderate. However, the anterior bending angles 1 week after GVS in patients C and D, whose anterior bending postures were severe, were larger than those before the GVS. The effects of the GVS might be sustained for at least 1 week in PD patients with a mild to moderate anterior bending posture. The UPDRS-gait subscores did not change significantly after the GVS or the sham stimulation, indicating that a single session of the binaural monopolar GVS might not affect gait disorders. Future studies should also evaluate gait and balance and determine the effects of binaural monopolar GVS on gait and balance in more detail. The small sample size and lack of a long follow-up period were a limitation of this study. Larger sample sizes and a longer follow-up period are needed to determine whether binaural monopolar GVS can improve anterior bending
posture and other symptoms in PD patients with an anterior bending posture.
Conclusion The present study investigated the effects of binaural monopolar GVS on anterior bending posture in PD patients in a single-blind randomized sham-controlled cross-over trial. Binaural monopolar GVS might improve the anterior bending posture in PD patients. Binaural monopolar GVS may be a novel treatment strategy to improve the anterior bending posture in PD.
Acknowledgements The authors are extremely grateful to Dr Kazuma Sugie and Dr Mari Tearashima (Nara Medical University, Department of Neurology) for the recruitment of participants. This work was supported by a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science (No. 25750246). Conflicts of interest
There are no conflicts of interest.
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