전체메뉴
Search
Article Search

JoP

Research article

Split Viewer

Related articles in JAMS

More Related Articles

Article

Research article

2017; 10(1): 33-38

Published online February 1, 2017 https://doi.org/10.1016/j.jams.2016.12.007

Copyright © Medical Association of Pharmacopuncture Institute.

Acupuncture as Adjuvant Therapy for Sleep Disorders in Parkinson’s Disease

Fábio Henrique de Amorim Aroxa1, Ihana Thaís Guerra de Oliveira Gondim2, Elba Lúcia Wanderley Santos2, Maria das Graças Wanderley de Sales Coriolano2, Amdore Guescel C. Asano2, Nadja Maria Jorge Asano3*

1Academic of Medicine graduation of Federal University of Pernambuco – Recife, Pernambuco (PE), Brazil
2Pro-Parkinson Program of Clinical Hospital of Federal University of Pernambuco – Recife (PE), Brazil
3Clinical Medicine Department of Federal University Pernambuco – Recife (PE), Brazil

Correspondence to:Nadja Maria Jorge Asano

Received: May 3, 2016; Revised: December 15, 2016; Accepted: December 20, 2016

http://creativecommons.org/licenses/by-nc-nd/4.0/

Abstract

There are few studies which attest the efficacy of acupuncture on treatment of sleep disturbs in Parkinson disease. The aimed of this randomized clinical trial was to evaluate the effects of acupuncture on sleep disturbs of 22 patients with diagnosis of idiopathic Parkinson disease (Hoehn–Yahr 1 to 3) who have assistance on the Pro-Parkinson Program of Clinical Hospital at Federal University of Pernambuco in Brazil. All participants were evaluated by Parkinson Disease Sleep Scale (PDSS) before and after 8 weeks. The experimental group was submitted to 8 sections (once a week) which had duration of 30 minutes. The control group had no intervention. The intervention was executed using the acupuncture points LR3 (Taichong), SP6 (Sanyinjiao), LI4 (Hegu), TE5 (Wai-Guan), HT7 (Shenmen), PC6 (Neiguan), LI11 (Quchi), GB20 (Fengchi). Paired analyses were obtained by Wilcoxon test and independent analyses were made according to Mann–Whitney test. This study presented a potential therapeutic benefit of acupuncture on sleep disturbs of Parkinson's disease patients. This study showed a possible therapeutic benefit through acupuncture in sleep disorders in patients with PD. However, we propose new studies related to the effects of acupuncture on the clinical symptoms and evolution of the disease.

Keywords: Acupuncture, Parkinson Disease, Sleep Disorders

1. Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder with a high prevalence in older people, affecting 1 in 1000 people aged >60 years. Although it has been widely accepted that is has a relationship with dopaminergic neuron death, its etiology remains unknown [1, 2]. Sleep disturbance is often a nonmotor symptom in PD, which includes excessive daytime sleepiness and insomnia [3-6]. Such sleep disturbance occurs as part of the disease course of the evolution of PD, and as a side effect of antiparkinsonian medication [7, 8].

Acupuncture is a method in Traditional Chinese Medicine that was developed in the 1st century bce [9, 10]. With regards to PD, some studies have suggested promising results, such as relief of a wide range of symptoms and a reduction in adverse drug effects [11, 12]. Acupuncture has been shown to improve scoring on the Parkinson’s Disease Sleep Scale (PDSS) [13]. This result may reflect neuromodulation by substances like γ-aminobutyric acid, melatonin, and β-endorphins [14].

The present study evaluated the effects of acupuncture on sleep disturbance in patients participating in the Pro-Parkinson Program at the Clinical Hospital, Federal University of Pernambuco, Brazil.

2. Materials and methods

2.1. Ethics statement

This was a randomized clinical trial conducted according to the CONSORT 2010 checklist. All patients signed an informed consent form, and the study was approved by the Ethics Committee for Research with Humans at the Center of Health Sciences of Federal University of Pernambuco (Protocol CAAE: 49662915.4.0000.5208). This trial was registered at ClinicalTrials.gov NCT: 02731677.

2.2. Participants

Twenty-two PD patients diagnosed by a neurologist entered the study. Patients were recruited during their routine outpatient visit to the Neurology Clinic (Pro-Parkinson Program) at the Clinical Hospital, Federal University of Pernambuco. Inclusion criteria were: (1) patients with idiopathic PD according to the UK Parkinson’s Disease Society Brain Bank criteria [15]; (2) Stage I–III PD, according to the Hoehn–Yahr (HY) scale [16]; (3) age 35–80 years; (4) minimum score of 18 on the Mini Mental State Examination (MMSE) for low academic level or a minimum score of 26 for high academic level [17]; and (5) a stable dose of antiparkinsonian medication for ≥ 2 months. We excluded patients who had another neurological condition or who had received physiotherapy. The patients were enumerated and allocated to experimental or control groups according a simple raffle.

The Pro-Parkinson Program promotes multidisciplinary assistance for patients with PD. It also offers educational activities for patients and their caregivers. Currently, the program receives an average of 250 patients annually, and comprises of professors and undergraduate and postgraduate students in medicine, physiotherapy, odontology, psychology, speech therapy, and occupational therapy, as well as a support team.

2.3. Clinical assessment

All patients were clinically evaluated prior to starting the study with the following instruments: MMSE, HY scale, and PDSS, and after eight sessions, only PDSS was applied.

2.3.1. HY scale

The HY scale was developed by Hoehn and Yahr [16]. The original version consists of five stages that evaluate the severity of PD by analyzing global signals and symptoms, which classifies individuals according to their incapacity. Stage I: patients present with unilateral symptoms (tremor, stiffness, and bradykinesia) but can have autonomy. Stage II: bilateral symptoms together with abnormal speech, bent posture, and the well-known “en-bloc gait”. Stage III: addition of characteristic postural instability; until this stage, autonomy can be preserved. Stage IV: patients are dependent on caregivers. Stage V: patients are restricted to bed or a wheelchair.

2.3.2. MMSE

MMSE is a useful tool for screening for cognitive disturbance because of its ease of application and that fact that it only requires 5–10 minutes. It comprises of 11 items that can accumulate a total score of 30 points. The first part of the test evaluates memory and executive function (attention and concentration), and the second part evaluates cortical function. The cutoff is according to academic achievement: analphabetism or low academic achievement, 18 points; ≥ 8 years of schooling, 26 points [17].

2.3.3. PDSS

PDSS is a visual analog and self-administered scale comprising 15 items that address the following domains: (1) overall quality of sleep; (2) sleep onset and maintenance insomnia; (3) nocturnal restlessness; (4) nocturnal psychosis; (5) nocturia; (6) nocturnal motor symptoms; (7) sleep refreshment; and (8) daytime dozing. It is administered during the ON phase, which means under antiparkinsonian drug action. The severity of symptoms is registered by the patient, based on the experiences of the last seven days by marking a 10 cm line. The line is subdivided into 10 parts from 0 (intense symptoms) to 10 (without symptoms). The maximum score is 150 points, which suggests a patient free of symptoms [18].

2.4. Intervention

The experimental group was submitted to eight weekly sessions of 30 minutes. The control group had no intervention. The intervention was executed using the acupuncture points LR3 (Taichong), SP6 (Sanyinjiao), LI4 (Hegu), TE5 (Wai-Guan), HT7 (Shenmen), PC6 (Neiguan), LI11 (Quchi), and GB20 (Fengchi). All the acupuncture points had been selected according to data from previous studies [19, 20, 21, 22, 23, 24, 25, 26, 27].

This study was a randomized controlled clinical trial, in which PD patients were divided into two groups. One group received acupuncture treatment with the current drug treatment unchanged (acupuncture and drug), and another group maintained the prescribed antiparkinsonian drugs (drug alone). The patients were treated with a stable dose of antiparkinsonian medication for ≥ 2 months and did not report any adverse events before the study.

2.5. Statistical analysis

Statistical analysis was performed using software BioEstat version 5.3 (Amazonas, Brazil), and p < 0.05 indicated statistical significance. The data were analyzed following a descriptive statistic on the measure of dispersion and central tend (median and interquartile range). Paired analyses were obtained by Wilcoxon test and independent analyses were made according to the Mann–Whitney test.

3. Results

The study sample consisted of 22 patients who were enrolled in the Pro-Parkinson Program at the Clinical Hospital, Federal University of Pernambuco (Fig. 1). Table 1 shows the general characteristics of the patients. There was no significant difference between the groups regarding age, despite the difference of 9 years between the groups (56 vs. 65 years).

CG = control group; EG = experimental group; HY = Hoehn–Yahr; PDSS = Parkinson’s Disease Sleep Scale..

*Data expressed as average ± standard deviation, independent t test..

Data expressed in median (interquartile range). Mann–Whitney test..

&md=tbl&idx=1' data-target="#file-modal"">Table 1

General characteristics of study population..

CGEGp
Sex7♂ e 4♀7♂ e 4♀
Age (y)*56 (12)65 (10)0.07
Stage (HY)20 (0.5)10 (1)0.05
PDSS97 (58)87 (33)0.94

CG = control group; EG = experimental group; HY = Hoehn–Yahr; PDSS = Parkinson’s Disease Sleep Scale..

*Data expressed as average ± standard deviation, independent t test..

Data expressed in median (interquartile range). Mann–Whitney test..


Figure 1. Sample constitution flow diagram.

There was no difference in the total PDSS score between the experimental and control groups before intervention. However, there was a significant improvement in the experimental group after intervention (Table 2). The median PDSS scores increased after re-evaluation (after acupuncture) in almost all domains, however, there was no significant difference in: sleep onset and maintenance, nocturnal agitation, nocturia, relaxing sleep, and daytime sleepiness. Significant differences were observed in the domains: general sleep quality, nocturnal psychosis, and nocturnal motor symptoms (Table 3). Table 4 expresses the median (interquartile range) of PDSS domains. The median values (indicative of improvement) were observed in the experimental group in the following domains: nocturnal motor symptoms and daytime sleepiness. However, for all other domains there were no significant differences between the groups.

Results presented as median (interquartile range)..

* p < 0.05, Wilcoxon test..

CG = control group; EG = experimental group; PDSS = Parkinson’s Disease Sleep Scale..

&md=tbl&idx=2' data-target="#file-modal"">Table 2

PDSS score before and after intervention..

PDSSWilcoxon p

EvaluationRe-evaluation
CG97 (58)124 (57)0.13
EG87 (33)126 (25)0.02*
Mann–Whitney p0.940.66

Results presented as median (interquartile range)..

* p < 0.05, Wilcoxon test..

CG = control group; EG = experimental group; PDSS = Parkinson’s Disease Sleep Scale..


Results presented as median (interquartile range)..

* p < 0.05, Wilcoxon test..

Tendency for improvement..

PDSS = Parkinson’s Disease Sleep Scale..

&md=tbl&idx=3' data-target="#file-modal"">Table 3

PDSS scores before and after intervention in experimental group..

DomainsEvaluationRe-evaluationp
Overall quality of sleep (Item 1)50 (4)80 (3)0.01*
Sleep onset and maintenance insomnia (Items 2 & 3)10 (5)15 (10)0.12
Nocturnal restlessness (Items 4 & 5)10 (10)17 (6)0.09
Nocturnal psychosis (Items 6 & 7)20 (10)20 (1)0.04*
Nocturia (Items 8 & 9)10 (8)10 (13)0.34
Nocturnal motor symptoms (Items 10–13)30 (11)36 (8)0.01*
Sleep refreshment (Item 14)50 (10)10 (4)0.09
Daytime dozing (Item 15)90 (7)10 (3)0.12

Results presented as median (interquartile range)..

* p < 0.05, Wilcoxon test..

Tendency for improvement..

PDSS = Parkinson’s Disease Sleep Scale..


Results presented as median (interquartile range), Mann–Whitney test..

CG = control group; EG = experimental group; PDSS = Parkinson’s Disease Sleep Scale..

&md=tbl&idx=4' data-target="#file-modal"">Table 4

PDSS scores after intervention..

DomainsCGEGp
Overall quality of sleep (Item 1)10 (10)80 (3)0.86
Sleep onset and maintenance insomnia (Items 2 & 3)19 (12)15 (10)0.84
Nocturnal restlessness (Items 4 & 5)20 (16)17 (6)0.81
Nocturnal psychosis (Items 6 & 7)20 (0)20 (1)0.53
Nocturia (Items 8 & 9)15 (9)10 (13)0.74
Nocturnal motor symptoms (Items 10–13)30 (14)36 (8)0.21
Sleep refreshment (Item 14)10 (5)10 (4)0.94
Daytime dozing (Item 15)90 (4)10 (3)0.39

Results presented as median (interquartile range), Mann–Whitney test..

CG = control group; EG = experimental group; PDSS = Parkinson’s Disease Sleep Scale..


4. Discussion

The purpose of this study was to evaluate the effects of acupuncture on sleep disorders in patients with PD, using the PDSS, which is a specific instrument for sleep evaluation in this disease.

The results showed that acupuncture significantly improved quality of nocturnal sleep, nocturnal psychosis, and nocturnal motor symptoms. These findings are important because sleep disturbance is one of the most common nonmotor symptoms in PD, compromising the quality of life of these patients [28]. There is a high prevalence of daytime sleepiness and insomnia in PD, affecting nearly 50% of patients [29, 30]. Sleep disturbance is usually present at an advanced stage of the disease [31].

Many PD patients have reported using acupuncture as an alternative treatment at some point in their life, improving some aspects of the disease [31]. A systematic review and meta-analysis by Zhang et al [32] confirmed the tolerability of this adjuvant therapy, which could reduce the adverse effects caused by conventional medication.

Although onset and maintenance of sleep, nocturnal agitation, nocturia, relaxing sleep, and daytime sleepiness did not show any significant differences, there was a tendency towards improvement in the experimental group. It is curious to note that these patients showed subjective improvement in their activities of daily living during acupuncture, due to the improvement in nocturnal sleep. They reported improvement in daytime sleepiness, fatigue, and mood and requested more acupuncture sessions. These results reinforce the conclusion of Zhang et al [32] that Traditional Chinese Medicine is suitable for long-term use in these patients. The authors reported that patients undergoing Traditional Chinese Medicine associated with antiparkinsonian medication exhibited significant improvement in symptoms, as demonstrated by the Unified Parkinson’s Disease Rating Scale score.

Shulman et al [23] also conducted a pilot study with 20 patients with PD to evaluate the efficacy and tolerability of acupuncture. In 85% of the patients there was some subjective improvement in at least one of the following symptoms: sleep and rest, tremor, writing, depression, and bradykinesia. However, that study differed from ours in that other instruments not specifically focused on sleep disorders or some not specific for the evaluation of PD itself were used. Cristian et al [19] conducted a randomized pilot study that comprised two groups of 14 PD patients. They found no significant difference in functional scales and motricity. Nevertheless, the results suggested an improvement in daily activities, quality of life, and sleep disturbance in the group treated with acupuncture.

Although complementary therapy is promising, there are few studies in the literature that prove the efficacy of acupuncture in the treatment of sleep problems in patients with PD.

The present study had some limitations: heterogeneous groups and differences in patient age and stage of PD, which could have influenced the results. It is important to consider that the results were based on a subjective scale based on the patients’ self-perception about the general state of their sleep, and more objective evaluations such as polysomnography and the multiple sleep latency test are needed for a more accurate assessment.

The present study showed a possible therapeutic benefit of acupuncture in sleep disorders in patients with PD. We propose further studies of the effects of acupuncture on the clinical symptoms and evolution of PD.

Acknowledgments

The study was developed in the Department of Clinical Medicine in partnership with the Pro-Parkinson Program of the Clinical Hospital, Federal University of Pernambuco – Recife (PE), Brazil. Funding for the present study was obtained from Edictal 2015, PIBEX-Grande Recife, PROEXC, Federal University of Pernambuco – Recife (PE), Brazil.

Disclosure statement

The authors declare that they have no conflicts of interest and no financial interests related to the material of this manuscript.

Fig 1.

Figure 1.Sample constitution flow diagram.
Journal of Acupuncture and Meridian Studies 2017; 10: 33-38https://doi.org/10.1016/j.jams.2016.12.007

Table 1 . General characteristics of study population..

CGEGp
Sex7♂ e 4♀7♂ e 4♀
Age (y)*56 (12)65 (10)0.07
Stage (HY)20 (0.5)10 (1)0.05
PDSS97 (58)87 (33)0.94

CG = control group; EG = experimental group; HY = Hoehn–Yahr; PDSS = Parkinson’s Disease Sleep Scale..

*Data expressed as average ± standard deviation, independent t test..

Data expressed in median (interquartile range). Mann–Whitney test..


Table 2 . PDSS score before and after intervention..

PDSSWilcoxon p

EvaluationRe-evaluation
CG97 (58)124 (57)0.13
EG87 (33)126 (25)0.02*
Mann–Whitney p0.940.66

Results presented as median (interquartile range)..

* p < 0.05, Wilcoxon test..

CG = control group; EG = experimental group; PDSS = Parkinson’s Disease Sleep Scale..


Table 3 . PDSS scores before and after intervention in experimental group..

DomainsEvaluationRe-evaluationp
Overall quality of sleep (Item 1)50 (4)80 (3)0.01*
Sleep onset and maintenance insomnia (Items 2 & 3)10 (5)15 (10)0.12
Nocturnal restlessness (Items 4 & 5)10 (10)17 (6)0.09
Nocturnal psychosis (Items 6 & 7)20 (10)20 (1)0.04*
Nocturia (Items 8 & 9)10 (8)10 (13)0.34
Nocturnal motor symptoms (Items 10–13)30 (11)36 (8)0.01*
Sleep refreshment (Item 14)50 (10)10 (4)0.09
Daytime dozing (Item 15)90 (7)10 (3)0.12

Results presented as median (interquartile range)..

* p < 0.05, Wilcoxon test..

Tendency for improvement..

PDSS = Parkinson’s Disease Sleep Scale..


Table 4 . PDSS scores after intervention..

DomainsCGEGp
Overall quality of sleep (Item 1)10 (10)80 (3)0.86
Sleep onset and maintenance insomnia (Items 2 & 3)19 (12)15 (10)0.84
Nocturnal restlessness (Items 4 & 5)20 (16)17 (6)0.81
Nocturnal psychosis (Items 6 & 7)20 (0)20 (1)0.53
Nocturia (Items 8 & 9)15 (9)10 (13)0.74
Nocturnal motor symptoms (Items 10–13)30 (14)36 (8)0.21
Sleep refreshment (Item 14)10 (5)10 (4)0.94
Daytime dozing (Item 15)90 (4)10 (3)0.39

Results presented as median (interquartile range), Mann–Whitney test..

CG = control group; EG = experimental group; PDSS = Parkinson’s Disease Sleep Scale..


References

  1. Hornykiewicz O. Chemical neuroanatomy of the basal ganglia e normal and in Parkinson's disease. J Chem Neuroanat. 2001;22:3-12.
    CrossRef
  2. Obeso JA, Marin C, Rodriguez-Oroz C, Blesa J, Benitez-Temiño B, Mena-Segovia J, et al. The basal ganglia in Parkinson's disease: current concepts and unexplained observations. Ann Neurol. 2008;64(Suppl 2):S30-S46.
    Pubmed CrossRef
  3. Chaudhuri KR, Yates L, Martinez-Martin P. The non-motor symptom complex of Parkinson's disease: a comprehensive assessment is essential. Curr Neurol Neurosci Rep. 2005;5:275-283.
    Pubmed CrossRef
  4. Chaudhuri KR, Martinez-Martin P, Schapira AHV, Stocchi F, Sethi K, Odin P, et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMS Quest study. Mov Disord. 2006;21:916-923.
    Pubmed CrossRef
  5. Pal PK, Calne S, Samii A, Fleming JAE. A review of normal sleep and its disturbances in Parkinson's disease. Parkinsonism Relat Disord. 1999;5:1-17.
    Pubmed CrossRef
  6. Arnulf I. Excessive daytime sleepiness in parkinsonism. Sleep Med Rev. 2005;9:185-200.
    Pubmed CrossRef
  7. Askenasy JJ. Sleep disturbances in Parkinsonism. J Neural Transm. 2003;110:125-150.
    Pubmed CrossRef
  8. Chaudhuri KR, Logishetty K. Dopamine receptor agonists and sleep disturbances in Parkinson's disease. Parkinsonism Relat Disord. 2009;15(Suppl 4):S101-S104.
    Pubmed CrossRef
  9. Kaptchuk TJ. Acupuncture: theory, efficacy, and practice. Ann Intern Med. 2002;136:374-383.
    Pubmed CrossRef
  10. Zhang A, Sun H, Yan G, Cheng W, Wang X. Systems biology approach opens door to essence of acupuncture. Complement Ther Med. 2013;21:253-259.
    Pubmed CrossRef
  11. Zhuang X, Wang L. Acupuncture treatment of Parkinson's diseaseda report of 29 cases. J Trad Chin Med. 2000;20:265-267.
  12. Lam YC, Kum WF, Durairajan SS, Lu JH, Man SC, Xu M, et al. Efficacy and safety of acupuncture for idiopathic Parkinson's disease: a systematic review. J Altern Complement Med. 2008;14:663-671.
    Pubmed CrossRef
  13. Liang X, Chen F. The effects of the seven acupoints of the cranial base on health-related quality of life for patients with Parkinson's disease: a randomized controlled trial. Int J Trad Chin Med. 2014;36:613-616.
  14. Zhao K. Acupuncture for the treatment of insomnia. Int Rev Neurobiol. 2013;111:217-234.
    Pubmed CrossRef
  15. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinicopathological study of 100 cases. J Neurol Neurocirg Psychiatry. 1992;55:181-184.
    Pubmed CrossRef
  16. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17:427-442.
    Pubmed CrossRef
  17. Folstein MF, Folstein SE, Mchugh PR. Mini-mental State. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189-198.
    CrossRef
  18. Chaudhuri KH, Paul S, Dimarco A, Whately-Smith C, Bridgman K, Mathew R, et al. The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2002;73:629-635.
    Pubmed KoreaMed CrossRef
  19. Cristian A, Katz M, Cutrone E, Walker RH. Evaluation of acupuncture in the treatment of Parkinson's disease: a double-blind pilot study. Mov Disord. 2005;20:1185-1188.
    Pubmed CrossRef
  20. Jung JC, Kim KH, Park YC, Kim HB, Lee SH, Chang DI, et al. The study on the effect of acupuncture on UPDRS and heart rate variability in the patients with idiopathic Parkinson's disease. J Korean Acupunct Moxibust Soc. 2006;23:143-153.
  21. Park YC, Chang DI, Lee YH, Park DS. The study on the effect of acupuncture treatment in patients with idiopathic Parkinson's disease. J Korean Acupunct Moxibust Soc. 2007;24:43-54.
  22. Cho SY, Shim SR, Rhee HY, Park HJ, Jung WS, Moon SK, et al. Effectiveness of acupuncture and bee venom acupuncture in idiopathic Parkinson's disease. Parkinsonism Relat Disord. 2012;18:948-952.
    Pubmed CrossRef
  23. Shulman LM, Wen X, Weiner WJ, Bateman D, Minagar A, Duncan R, et al. Acupuncture therapy for the symptoms of Parkinson's disease. Mov Disord. 2002;17:799-802.
    Pubmed CrossRef
  24. Ha JY, Lee SH, Yin CS, Park SM, Kang JW, Chang DI, et al. The effect of manual acupuncture therapy on symptoms of the patients with idiopathic Parkinson's disease. J Korean Orient Med. 2003;24:172-183.
  25. Kang MK, Lee SH, Hong JM, Park SM, Kang JW, Park HJ, et al. Effect of electroacupuncture on patients with idiopathic Parkinson's disease. J Korean Acupunct Moxibust Soc. 2004;21:59-68.
  26. Eng ML, Lyons KE, Greene MS, Pahwa R. Open-label trial regarding the use of acupuncture and yin tui na in Parkinson's disease outpatients: a pilot study on efficacy, tolerability, and quality of life. J Altern Complement Med. 2006;12:395-399.
    Pubmed CrossRef
  27. Chae Y, Lee H, Kim H, Kim CH, Chang DI, Kim KM, et al. Parsing brain activity associated with acupuncture treatment in Parkinson's diseases. Mov Disord. 2009;24:1794-1802.
    Pubmed CrossRef
  28. Wang F, Sun L, Zhang XZ, Jia J, Liu Z, Huang XY, et al. Effect and potential mechanism of electroacupuncture add-on treatment in patients with Parkinson's Disease. Evid Based Complement Alternat Med. 2015;2015:692795.
    Pubmed KoreaMed CrossRef
  29. Chaudhuri KR, Odin P, Antonini A, Martinez-Martin P. Parkinson's disease: the non-motor issues. Parkinsonism Relat Disord. 2011;17:717-723.
    Pubmed CrossRef
  30. Bonnet AM, Jutras MF, Czernecki V, Corvol JC, Vidailhet M. Nonmotor symptoms in Parkinson's disease in 2012: relevant clinical aspects. Parkinsons Dis. 2012;2012. 198316.
    Pubmed KoreaMed CrossRef
  31. Zeng BY, Zhao K. Effect of acupuncture on the motor and nonmotor symptoms in Parkinson's diseaseda review of clinical studies. CNS Neurosci Ther. 2016;22:333-341.
    Pubmed CrossRef
  32. Zhang G, Xiong N, Zhang Z, Liu L, Huang J, Yang J, et al. Effectiveness of traditional Chinese medicine as an adjunct therapy for Parkinson's disease: a systematic review and meta-analysis. PLoS One. 2015;10.
    Pubmed KoreaMed CrossRef