THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 18, Number 4, 2012, pp. 1–6 ª Mary Ann Liebert, Inc. DOI: 10.1089/acm.2011.0131
Original Article
Clinical Effects of Scalp Electrical Acupuncture in Stroke: A Sham-Controlled Randomized Clinical Trial Wu Tu Hsing, MD, PhD,1 Marta Imamura, MD, PhD,2 Kayleen Weaver, BA,3 Felipe Fregni, MD, PhD,3,4 and Raymundo S. Azevedo Neto, MD, PhD1
Abstract
Objectives: The majority of individuals who survive a stroke are disabled because of persisting neurological impairments. The objective of this study was to evaluate the efficacy of subcutaneous electrical stimulation of the scalp in spontaneous functional recovery of patients with chronic ischemic stroke, by evaluating clinical, neurological, and functional findings. Subjects and methods: Sixty-two (62) subjects who were at least 18 months postdiagnosis of ischemic stroke were randomized to receive 10 sessions of placebo or active low-frequency electrical stimulation (2/100 Hz) using subcutaneous acupuncture needles over the scalp. Functional and neurological evaluations were indexed by the Barthel, Rankin, and National Institutes of Health Stroke Scale (NIHSS). Results: Results show that there was a significant difference in functional improvement between the sham and active group as indexed by NIHSS scale. The active group had a larger functional improvement after 10 sessions of scalp electrical acupuncture. The other two functional scales (Rankin and Barthel) failed to show significant differences between the two treatment groups. Conclusions: These results support further testing of scalp electrical acupuncture for the treatment of stroke as well further mechanistic studies to understand mechanisms associated with the observed improvement. Further studies need to consider longer follow-up assessments to investigate potential functional changes associated with electrical acupuncture.
This method consists of the introduction of needles in the subcutaneous tissue of the scalp at corresponding functional areas of the cerebral cortex.2 Various studies have shown the possibility of clinical and functional improvement in ischemic stroke using nonscalp acupuncture techniques,3,4 though evidence is mixed and a recent review concluded that there was not enough evidence supporting the effects of acupuncture for acute and subacute stroke.5 On the other hand, other authors have evaluated the efficacy of electroacupuncture for treatment of stroke sequelae and showed some beneficial results.6 Naeser et al. (1994) compared manual acupuncture’s effect associated with electroacupuncture with a control group for the treatment of paralysis in patients who have had an acute stroke and who are undergoing physiotherapy.6 As results are still mixed and there are no definite answers on the effects of electroacupuncture for chronic stroke, a sham-controlled randomized trial was conducted to evaluate
Introduction
A
mong all disabling entities, stroke plays an important role in means of number of involved patients and impact on health services. Despite the high incidence and resultant sequelae, there are still few treatment alternatives for these patients during the chronic stage to recover motor and other cognitive functions. Spontaneous recovery using standard rehabilitation procedures can be achieved up to on average 6 months to 1 year after the initial ictus. In fact, about one third to half of patients remain with moderate to severe functional deficits.1 Aside from traditional forms of physical therapy, alternative forms of rehabilitation, such as acupuncture, may be beneficial in promoting long-term spontaneous recovery in patients who have had a stroke. Scalp acupuncture appears to be an innovative therapeutic method capable of treating cerebral or visceral diseases related to the cerebral cortex. 1
Department of Pathology, University of Sa˜o Paulo School of Medicine, Sa˜o Paulo, Brazil. Division of Physical Medicine, Institute of Orthopaedics and Traumatology, University of Sa˜o Paulo School of Medicine, Sa˜o Paulo, Brazil. 3 Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA. 4 Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 2
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HSING ET AL. Table 1. Trial Characteristics According to STRICTA Guidelines
Section/topic
Trial characteristics
1. Acupuncture rationale (Explanations and examples) 1a. Style of acupuncture (e.g., Traditional Chinese Medicine, Japanese, Korean, Western medical, Five Element, ear acupuncture, etc.) 1b. Reasoning for treatment provided, based on historical context, literature sources, and/or consensus methods, with references where appropriate
1c. Extent to which treatment was varied
2. Details of needling 2a. Number of needle insertions per subject per session (mean and range where relevant) (Explanations and examples) 2a. Number of needle insertions per subject per session (mean and range where relevant) 2b. Names (or location if no standard name) of points used (uni/bilateral)
2c. Depth of insertion, based on a specified unit of measurement, or on a particular tissue level
2d. Response sought (e.g., de qi or muscle twitch response) 2e. Needle stimulation (e.g. manual, electrical) 2f. Needle retention time 2g. Needle type (diameter, length, and manufacturer or material) 3. Treatment regimen (Explanations and examples) 3a. Number of treatment sessions 3b. Frequency and duration of treatment sessions 4. Other components of treatment (Explanations and examples) 4a. Details of other interventions administered to the acupuncture group (e.g. moxibustion, cupping, herbs, exercises, lifestyle advice) 4b. Setting and context of treatment, including instructions to practitioners, and information and explanations to patients
The reasoning for the treatment is based on scalp acupuncture theory in which needling of scalp areas correlated with lesioned brain areas could increase activity in these areas and therefore enhance local neuroplasticity in the lesioned cortex. We therefore used the method of scalp acupuncture as described by Tom Sintan Wen, MD, PhD—using a Western medical style based on underlying neuroanatomy.a,b Treatment was standardized; the only difference was that for left-sided strokes, we also added 3 needles in the scalp areas related to language. —
There were 11 needles placed in left-hemiplegic patients (right sided stroke), and 14 in right hemiplegic (left-sided stroke, based on areas of language) The following areas were stimulated contralaterally: (a) motor area of the face, upper limb, lower limb, (3 needles); (b) sensory correspondent areas, face, upper limb, lower limb (3 needles); (c) sensory-motor area of the lower limbs (bilateral) (2 needles); (d) supplementary motor area (3 needles); (e) area of language (only right hemiplegia) ( + 3 needles) Needles applied to the subcutaneous tissues of the scalp, prior to hitting the periosteum, in the projection of motor and sensitive areas of Penfield homunculus as well as frontal and temporal associative areas There was no qi or muscle-twitch-only sensation due to needling; placement only based on anatomy Electric 30 minutes per session Stainless-steel disposable needles 0.3-mm diameter and 40-mm long
Patients received 10 sessions of low-frequency electrical stimulation (2/100 Hz alternated) Twice-a-week sessions, 30 minutes per session
No other interventions The interventions were conducted at the Orthopaedics and Traumatology Institute of the University of Sao Paulo. Only one experienced practitioner conducted the interventions. Patients were informed about the research, and read and signed the informed consent form (continued)
SCALP ELECTRICAL ACUPUNCTURE IN STROKE
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Table 1. (Continued) Section/topic
Trial characteristics
5. Practitioner background (Explanations and examples) 5. Description of participating acupuncturists (qualification or professional affiliation, years in acupuncture practice, other relevant experience)
Dr. Wu was the acupuncturist in this study. He is a physiatrist, who studied acupuncture at Veteran’s General Hospital Taiwan in 1989. He has more than 20 years of experience, and is a university professor of the University of Sao Paulo (USP), and the director of the specialization course in acupuncture of the Clinics Hospital of University of Sa˜o Paulo School of Medicine.
6. Control or comparator interventions (Explanations and examples) 6a. Rationale for the control or comparator in the context of the research question, with sources that justify this choice 6b. Precise description of the control or comparator. If sham acupuncture or any other type of acupuncture-like control is used, provide details as for Items 1 to 3 above.
As there may be an important placebo effect associated with motor improvement, a sham condition was well-justified. For sham stimulation, patients received 10 sessions of placebo electrical stimulation, through disconnected cables applied to the scalp, using the same parameters of treatment (duration of sessions and location of stimulation). During placebo stimulation, audiovisual feedback was given to patients.
a
Hu HH, Chung C, Liu TJ, et al. A randomized controlled trial on the treatment for acute partial ischemic stroke with acupuncture. Neuroepidemiology 1993;12:106–113. b Sa¨llstro¨m S, Kjendahl, A, Osten PE, et al. Acupuncture in the treatment of stroke patients in the subacute stage: A randomized, controlled study. Compl Ther Med 1996;4:193–197.
the clinical effect of subcutaneous electrical stimulation of the scalp in patients with chronic ischemic stroke in a relatively large trial in 62 patients with chronic stroke. Materials and Methods Study population Sixty two (62) subjects, 44 male and 18 female, with ages ranging from 24 to 65 years (mean = 51.27 – 8.96), with definite diagnosis of ischemic stroke with at least 18 months of duration, from 1.5 to 16 years from the ictus (mean = 7.88 – 4.35), 38 with right and 24 with left hemiplegia were studied. Patients with unstable or severe clinical conditions, significant perceptual and cognitive disturbances, including memory deficits and deficits that inhibit understanding of the proposed treatment, were excluded. Therefore, patients with a score of 21 or higher on the National Institutes of Health Stroke Scale (NIHSS) scale were excluded. Subjects were allowed to participate in the study only after signing the informed consent, and all study procedures were approved by the local ethics committee board and were compliant with the Declaration of Helsinki. After consent, subjects were randomly allocated into two groups. Group analysis at baseline shows that both groups were matched for age, duration postictus, gender, and baseline functional and neurological assessments. Intervention: Scalp electrical acupuncture stimulation Patients received 10 sessions of low-frequency electrical stimulation (2/100 Hz) applied through subcutaneous needles at the projection of the motor, sensory, frontal, and temporal associative areas of Penfield homunculus in the
scalp, for 30 minutes, twice a week for 5 weeks. Electrical stimulation intensity was discriminative but bearable to the subject. Needles of 0.3-mm diameter and 40-mm long were applied to the subcutaneous tissues of the scalp in the projection of motor and sensitive areas of Penfield homunculus as well as frontal and temporal associative areas. For sham stimulation, patients received 10 sessions of placebo electrical stimulation, through disconnected cables applied to the scalp, using the same parameters of treatment (duration of sessions and location of stimulation). During placebo stimulation, audiovisual feedback was evident to patients. See additional details regarding acupuncture in Table 1 using STRICTA guidelines and Figure 1 and Figure 2 for additional details on location of needles. Assessments Subjects were evaluated before and immediately after 10 treatment sessions by examiners blinded to treatment group. Because there was interest in assessing clinical effects, blinded examiners evaluated neurological and functional outcomes including Barthel index, modified Rankin scale, and the NIHSS (for more information on NIHSS, go to: www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf). Statistical analysis For statistical analysis, STATA was used (StataCorp., College Station, TX). For the NIH and Barthel scales, mixed analysis of variance (ANOVA) models were conducted to assess whether there was a differential improvement when comparing active versus sham group. For Rankin scale, Fisher’s exact test was used for this analysis. A significance level of 5% was adopted (a = 0.05).
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HSING ET AL.
FIG. 1. Diagram showing localization of acupuncture points using scalp landmarks such as Cz (GV20). Using these landmarks, it is possible to localize the primary motor and sensory cortex as well as supplementary and language areas.
Results Subjects tolerated treatment well, and there were no adverse effects reported. There were no dropouts during the trial. There were 62 patients enrolled who were randomized to the two treatment groups. At baseline, the two treatment groups were similar regarding demographic and clinical characteristics. Table 2 shows a summary of these data. Mixed ANOVA models were initially conducted so as to assess interaction effects between group and treatment for the Barthel and NIHSS scales. Significant interaction effects were found between group and time of stimulation for the NIHSS scale only (F1,60 = 4.92, p = 0.03). For the Barthel scale, this analysis was not significant (F1,60 = 1.73, p = 0.19). Results are shown in Table 3. The pre- versus post-treatment were then compared in the active and control group for NIH scale and it was found that functional improvement was observed in the active group
FIG. 2. Patient receiving scalp electrical acupuncture as used in the trial. Six cables were attached to electrodes. In this case because it was a left-sided stroke, two electrodes were attached at the motor area, two electrodes were attached at the supplementary motor area, and two electrodes were attached at the language area.
( p = 0.0023) but not in the control group ( p = 0.86). For the Rankin scale, group results were compared using a Fisher t test because this scale is categorical. No significant differences were found for either group or time effects ( p > 0.05 in all analyses). Finally, correlations were performed to assess whether the significant functional improvements were correlated with age or duration of stroke, and no significant results were found ( p > 0.05 for all the analyses), showing that these variables are not correlated with the outcome. Discussion In this study, a differential effect of active versus sham electrical stimulation was found only for NIHSS. The other two functional scales—Rankin and Barthel scales—did not show differential results. The first important point to discuss is the conflicting results between the clinical neurological scale (NIHSS) and the
SCALP ELECTRICAL ACUPUNCTURE IN STROKE
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Table 2. Descriptive Data for Study Groups
the study assessing scalp electrical acupuncture for chronic stroke showed a significant positive correlation between clinical changes in the affected upper limb and cortical activity in the ipsilesional motor cortex.8 Finally, body electrical acupuncture resulted in a smaller effect (only for patients who were compliant with the protocol) in chronic stroke.9 These results, in addition to the current results, suggest that the electrical component might be critical during acupuncture treatment for chronic stroke. Future studies should compare in the same trial regular acupuncture versus electrical acupuncture versus regular peripheral electrical stimulation in order to detangle the effects of this treatment because electrical stimulation might be the main component to explain the significant clinical effects.10 Some limitations should be discussed. Because the intention was to increase external generalizability in this study, the population of this study was heterogeneous. Although this study had a relatively large population, it is possible that by increasing the number of subjects studied, it may change the significance in the other scales, though the authors were interested in meaningful clinical changes. Additionally, it is emphasized that the functional rating evaluation scales— Rankin and Barthel—did not show enough sensitivity to detect short-term changes. Some patients already presented near maximum functional scores in all evaluations performed. Therefore, further improvements could not be detected in those patients. Asymptomatic and severely disabled patients were excluded from the study; therefore, major changes would not occur. It is also possible that the results from Rankin and Barthel scales may be due to a type II error. However, post-hoc power calculation shows that effect size (given power of 80% and a of 5% and 62 patients) is 0.035, which is a small effect size, therefore making less likely this hypothesis. Further investigations should employ other scales capable of detecting minor improvements, including quality of life and patient’s satisfaction level. The clinical observation in this study demonstrated that patients from the control group reported improvement in subjective issues such as dizziness. The therapeutic group, however, reported subjective improvement during activities such as range of motion, muscle strength, and mainly that movements were easier to perform. This phenomenon may suggest a reduction in spasticity, which was not directly evaluated through those scales. Further investigations should specifically evaluate spasticity, including gait analysis and surface electroneuromyographic studies, and also should study the neural mechanisms associated with this intervention so as to understand and optimize the effects of scalp electrical acupuncture for chronic stroke.
Study sample data Active scalp electroacupuncture
M SD MAX MIN N
Sham scalp electroacupuncture
Agea
Time post-strokea
Age
Time post-stroke
50 9.1 65 34 35
8.06 4.56 25 2 35
52 8.65 64 24 27
7.65 4.15 16 1.5 27
a
Measured in years. M, mean; SD, standard deviation; MAX, maximum value; MIN, minimum value; N, number of cases.
functional scales (Rankin and Barthel). The NIHSS is an assessment of neurological function as a result of the stroke (e.g., level of consciousness, motor strength, etc.). The Barthel and Rankin scales measure functional outcomes (level of assistance in activities of daily living [ADLs]) dependent on the level of stroke. In addition, the NIHSS has more scale items than the Rankin or Barthel scales, and may be more sensitive with respect to scoring. One potential explanation for the significant results in the NIHSS assessment only is that this scale measures changes that can be detected acutely (i.e., during short-term assessment), whereas the Rankin and Barthel scales can detect the level of assistance needed or competence in ADLs as a result of the neurological changes in a larger time-frame. As a result, there may be subtle changes detected in the NIHSS scale that might not be reflected in the Rankin or Barthel scales. Because assessments were performed only immediately after treatment, it is not clear whether the improvements seen in NIHSS would be detected in the Rankin and Barthel scales, had assessment been done at a later time. Another important issue to be discussed is the potential mechanisms underlying the improvement detected in this study. Because the intervention was electrical acupuncture, it is possible that both components—acupuncture and electrical stimulation—were involved in the therapeutic improvement. In order to compare these results with previous studies, results were analyzed from the three randomized clinical trials on acupuncture in chronic stroke as selected by a recent review that included only trials with rigorous methods.5 Interestingly, the study using acupuncture only showed no significant effect of real acupuncture for spasticity,7 whereas Table 3. Functional and Neurological Scales Measured Pre- and Postacupuncture (Mean [SD])
Disclosure Statement
Treatment condition Active Pre
No competing financial interests exist.
Sham Post
Pre
Post
Barthel 102.8 (7.86) 103.6 (6.53) 103.7 (10.5) 103.3 (10.9) Rankin 2.24 (0.79) 2.17 (0.76) 2.04 (0.68) 2.00 (0.82) NIH 4.36 (2.78)* 3.75 (2.30)* 4.27 (2.15) 4.27 (2.39) *Significant difference noted; p = 0.03; a < 0.05. SD, standard deviation; NIH, National Institutes of Health.
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6 3. Chou P, Chu H, Lin JG. Effects of electroacupuncture treatment on impaired cognition and quality of life in Taiwanese stroke patients. J Altern Complement Med 2009;15:1067–1073. 4. Lu JY, Tu WZ, Zheng DY, et al. Effects of acupuncture on different acupoints in combination with rehabilitation on hemiplegic muscle spasticity in hemiplegia patients [in Mandarin Chinese]. Zhongguo Zhen Jiu 2010;30:542–546. 5. Kong JC, Lee MS, Shin BC, et al. Acupuncture for functional recovery after stroke: A systematic review of sham-controlled randomized clinical trials. CMAJ 2010; 182:1723–1729. 6. Naeser MA, Alexander MP, Stiassny-Eder D, et al. Acupuncture in the treatment of paralysis in chronic and acute stroke patients: Improvement correlated with specific CT scan lesion sites. Acupunct Electrother Res 1994;19:227–249. 7. Fink M, Rollnik JD, Bijak M, et al. Needle acupuncture in chronic poststroke leg spasticity. Arch Phys Med Rehabil 2004;85:667–672. 8. Schaechter JD, Connell BD, Stason WB, et al. Correlated change in upper limb function and motor cortex activation
HSING ET AL. after verum and sham acupuncture in patients with chronic stroke. J Altern Complement Med 2007;13:527–532. 9. Wayne PM, Krebs DE, Macklin EA, et al. Acupuncture for upper-extremity rehabilitation in chronic stroke: A randomized sham-controlled study. Arch Phys Med Rehabil 2005;86:2248–2255. 10. Zaghi S, Acar M, Hultgren B, et al. Noninvasive brain stimulation with low-intensity electrical currents: Putative mechanisms of action for direct and alternating current stimulation. Neuroscientist 2010;16:285–307.
Address correspondence to: Wu Tu Hsing, MD, PhD Department of Pathology University of Sa˜o Paulo School of Medicine Avenida Dr. Arnaldo, 455 sala 1349 01246-903 Sa˜o Paulo, S.P. Brazil E-mail:
[email protected]
