Tongue Acupuncture for the Treatment of Poststroke Aphasia: A Systematic Review and Meta-Analysis

Objective This review evaluated the efficacy of tongue acupuncture for the clinical treatment of poststroke aphasia. Methods PubMed, Medline, Cochrane, Embase, CNKI, VIP, and Wanfang databases were searched from their inception to 1st June 2022. The dataset included randomized controlled trials (RCTs) with tongue acupuncture for the treatment of poststroke aphasia. Data aggregation and risk of bias evaluation were conducted on Review Manager Version 5.4.1 and Stata16.0. The main outcome measures included the Aphasia Battery of Chinese (ABC), the Chinese Functional Communication Profile (CFCP), the Boston Diagnostic Aphasia Examination (BDAE), and clinical efficiency. Then, comparing the effectiveness of tongue acupuncture, tongue acupuncture combined with conventional therapies, conventional therapies with head acupuncture, language training, body acupuncture, and Jie Yu Dan. Results A total of 20 studies with 1355 patients were included. Meta-analysis showed that compared with conventional treatments, tongue acupuncture has a significant improvement in clinical efficacy score (MD = 1.25, 95% CI (1.09, 1.43), P=0.001) and CFCP of poststroke aphasia (MD = 39.78, 95% CI (26.59, 52.97), P < 0.00001), but was not significant in improving ABC (MD = 5.95, 95% CI (2.85, 9.04), P=0.06). Compared to the conventional treatments, tongue acupuncture combined with conventional therapies promoted the ABC (MD = 11.48, 95% CI (2.20, 20.75), P < 0.00001), clinical efficacy score (MD = 1.22, 95% CI (1.14, 1.30), P < 0.00001), and CFCP score (MD = 29.80, 95% CI (19.08, 40.52), P < 0.00001) of poststroke aphasia. Conclusion This systematic review indicated that tongue acupuncture or tongue acupuncture combined with conventional treatments was an effective therapy for treating poststroke aphasia. However, stricter evaluation standards and rigorously designed RCTs are needed.


Background
Stroke is one of the most common neurovascular diseases, with a global prevalence of 101.5 million (2021, latest statistics on heart disease and stroke), among which ischemic stroke accounts for 76 percent (77.2 million) [1]. Ischemic stroke refers to ischemic necrosis or softening of localized cerebral tissue caused by cerebral blood circulation disorder, ischemia, hypoxia, and corresponding symptoms of neurological dysfunction [2]. Ischemic stroke is one of the serious diseases with the highest morbidity and mortality in the world. Stroke is the second leading cause of death among the top ten causes of death in the world, released by the World Health Organization [3]. It is also one of the main causes of severe disability and cognitive impairment worldwide [4].
However, the only effective treatment in the acute phase of ischemic stroke is the application of thrombolytic drugs. Although the emerging endovascular thrombectomy has extended the time window to 24 hours [5], most survived patients still have severe neurological symptoms. Poststroke aphasia (PSA) is one of the most devastating symptoms among the various functional disabilities caused by stroke [6]. More than one-third of stroke survivors suffer from aphasia, in which 30-43% remain chronically affected [7]. e main treatment measures recommended in the "Guidelines for the Diagnosis and Treatment of Cerebral Infarction in China (2017)" include syndrome differentiation and treatment combined with acupuncture and moxibustion [8]; in these guidelines, acupuncture therapy was recommended as a clinical physical therapy method with the exact curative effect on central nervous system diseases [9]. In recent years, acupuncture has made significant progress in the treatment of PSA.
ere are hypoglossal nerve, glossopharyngeal nerve, trigeminal nerve, and facial nerve distributed in the tongue, as well as rich peripheral nerve; the stimulating tongue can enhance the excitability of the central nervous system, promote nerve reflex, regulate the cortexthalamus-cortex, balance the specific conduction and nonspecific conduction of the body, rebuild the neural circuit of language activity, and promote the recovery of language [10]. Many studies have shown that when the tongue is stimulated, the quiescent state of the language function of the cerebral cortex can be activated; then, the local stimulation acts as a communication circuit, which forms conditioned reflexes and improves language ability.
In the theory of traditional Chinese medicine, stroke damages the brain and spinal cord in the blood vessels, and its occurrence and recovery involve the dynamic pathological changes in multiple links of "blood-vessel-heartspirit." e heart opens at the tongue, and the heart is the official of the monarch. e heart area of the tongue is mainly used to treat diseases related to the heart, blood vessels, nerves, and the mental system, such as the Juquan acupoint is in the spleen and the stomach area of the tongue. e spleen manages the transportation and transformation of blood and qi. erefore, stimulating specific acupoints of the tongue may have positive curative effects through the dynamic pathological changes of "blood-pulse-heart-spirit." Tongue acupuncture and its combination therapies (head acupuncture, language training, body acupuncture, and Jie Yu Dan) are gaining more and more attention from researchers, and some clinical studies have also described the clinical application of tongue acupuncture in the treatment of poststroke aphasia, but their quality has not been systematically evaluated. In addition, there was no meta-analysis for tongue acupuncture of poststroke aphasia in the past 10 years.
is study aims to critically evaluate the efficacy and safety of tongue acupuncture in the treatment of poststroke aphasia to provide an evidence base for the clinical practice of acupuncture.

Inclusion Criteria.
e inclusion criteria were as follows: ( For dichotomous variables, the relative risk (RR) and 95% confidence interval (CI) were used to represent the efficacy analysis statistics; for continuous data, weighted mean difference (MD) and 95% confidence interval (CI) were used to express efficacy analysis statistics. Potential publication bias was analyzed by using an "inverted funnel" diagram, and bias in included trials was discussed. Funnel plot and Egger's test were used to analyze the publication bias of the primary outcome indicators.

Quality of the Included Literature.
Cochrane risk of bias assessment was performed on the included literature, as shown in Figures 2 and 3. ree studies [13,17,21] used the random number table method, and the remaining studies [11, 12, 14-16, 18-20, 22-30] did not describe the specific randomization method. Four studies [19,23,29,30] had no follow-up visits and dropouts. None of the studies have published reports, so it is impossible to judge whether the outcome of the choice to report exists. It is not clear whether other biases exist.

Clinical Efficacy.
Fifteen studies [11-14, 16, 19-21, 23-27, 29, 30] reported clinical efficacy, with subgroup analyses by intervention methods. e results of subgroup analysis showed that the difference between tongue acupuncture and conventional treatments [12,27,29] was statistically significant (P � 0.001). e 12 studies that compared tongue acupuncture combined with conventional therapies to conventional therapies [11, 13, 14, 16, 19-21, 23-26, 30] showed good homogeneity (P � 0.96, I 2 � 0%), the difference was statistically significant (MD � 1.23, 95% CI (1.14,1.30), P < 0.00001), and the comparison of the two groups shows that tongue acupuncture combined with conventional therapies improved the clinical efficacy is clear. Details are shown in Figure 6. e results of sensitivity analysis showed that no studies had significantly reversed the results of metaanalysis, indicating that the above results were reliable. See Figure 7 for details.

CFCP Score.
ree studies [13,15,23] reported CFCP scores, and there was heterogeneity between studies (P � 0.29, I 2 � 20%), and subgroup analyses were performed according to different interventions ( Figure 8). e results of   ere were two studies comparing tongue acupuncture combined with conventional therapies to conventional therapies [13,23]. e difference between the studies was statistically significant (MD � 29.80, 95% CI (19.08, 40.52), P < 0.00001), indicating that tongue acupuncture combined with conventional therapies is more effective than conventional treatments in increasing the CFCP score.

Publication Bias Assessment.
In this study, the funnel plot method was used to evaluate the publication bias of the primary outcome indicators, ABC score, and clinical efficacy.

ABC Score Publication Bias.
Publication bias was evaluated for the 9 included studies [13-15, 18, 19, 22, 27, 28, 30]. e funnel plots show that two references comparing tongue acupuncture combined with conventional treatments to conventional treatments may present some publication bias (Figure 9. Egger's test was used for quantitative analysis; In Egger's test, P � 0.135 > 0.05, indicating no publication bias.

Discussion
is systematic review confirmed the effectiveness of tongue acupuncture in the treatment of poststroke aphasia and indicated that tongue acupuncture combined with other therapies is effective in improving ABC scores, CFCP scores, and clinical efficacy.
Tongue acupuncture has a strong acupuncture sensation, and most of the clinical acupoints are mainly tongue acupoints, emphasizing the effect of near treatment. e tongue, as one of the main sound organs, can dredge the meridians and regulate qi and blood by stimulating the meridians and acupoints related to the tongue and sound. Tongue acupuncture is a microneedle therapy based on the theory of acupuncture and moxibustion in traditional Chinese medicine and modern bioholographic theory. It is a special acupuncture method created by Zhengzhou Guan, a famous acupuncture expert, based on the theory of the relationship between tongue and viscera meridians in Huangdi Neijing and his decades of clinical experience [31]. e 24 tongue acupoints relate to certain zang-fu organs. e distribution of tongue acupoints involves the relationship of mutual generation and constraining of five elements. It has become the basic acupoint of tongue acupuncture therapy. e commonly used tongue acupuncture includes the following steps: gargle with 3% hydrogen peroxide solution before acupuncture and ask the patient to extend the tongue naturally. By using disposable sterile acupuncture needles, twist the thumb evenly back and forth 10 times and insert the needles about 1-3 mm. For acupoints on the base of the tongue, the surgeon uses the left hand to fix the anterior 1/3 of the tongue with sterile gauze, so that the tongue is rolled up to expose the acupoints, and routine disinfection is performed. en, use a long needle to puncture Jinjin and Yuye and choose 2 acupoints each time with bleeding.
In clinical application, tongue acupuncture can also be used in conjunction with other treatments, such as head acupuncture. Head acupuncture is a therapy to acupuncture the corresponding head area to treat diseases, which is based on the theory of zang-fu organs and meridians, combined with the functional localization principle of the cerebral cortex. e acupoints are generally emphasized less but more precisely. Head acupuncture can regulate the mind and restore consciousness to speed up the repair of the language function area of the cerebral cortex. Body acupuncture emphasizes holistic treatment and has the characteristics of combining syndrome differentiation with meridian differentiation and regulating the mind and qi. Puncture bloodletting therapy has the characteristics of the

Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias) Selective reporting (reporting bias) Other bias  Evidence-Based Complementary and Alternative Medicine quick effect, remarkable curative effect, low cost, and few adverse reactions, but single bloodletting therapy is difficult to achieve long-term stimulation of the lingual nerve. Language training can re-establish the patient's language function through repeated stimulation from the aspects of oral movements, induced pronunciation, listening comprehension, and word writing. However, a single language training has a very long recovery period and needs to cooperate with clinical interventions to promote the recovery of patients, such as tongue acupuncture. Jie Yu Dan includes Qiang Huo and Quan Xie, which can relieve wind and dredge collaterals [21] and help the monarch medicine Gastrodia elata to dispel wind and phlegm; Quan Xie can also play an antispasmodic effect, which has a better prognosis for patients with cerebral infarction. Tongue acupuncture combined with Jie Yu Dan, the synergistic effect of the two, can enhance the efficacy of the drug to help patients improve speech function. Our results of metaanalysis confirmed that tongue acupuncture combined with the above therapies could make up for the limitations of each method alone, thus improving the clinical efficacy of aphasia patients. e results of this meta-analysis showed that tongue acupuncture is beneficial to PSA. However, the underlying mechanism of tongue acupuncture action against PSA remains unclear. In recent years, many clinical studies and animal experiments have shown that acupuncture significantly improved clinical symptoms and the quality of life of patients by reducing the size of cerebral infarction, improving cerebral blood circulation, inhibiting apoptosis, and promoting cell proliferation and differentiation. Acupuncture therapy also has high safety with few adverse reactions and contraindications [32]. Some studies have suggested [33] that tongue acupuncture can reduce neuronal decay in the hippocampal CA1 region, rebuild cerebral nerve function, and play a positive role in restoring patients' language function. Tongue acupuncture can rapidly establish cerebrovascular collateral circulation [34], increase blood flow, improve cerebral circulation, and rebuild cerebral nerve activity after stroke by regulating the central nervous system. Studies have shown that [35] tongue acupuncture can significantly improve the blood perfusion of brain tissue at the lesion site more than body acupuncture and shrink the lesion site to varying degrees, thereby improving brain function. Tongue acupuncture can also reduce blood viscosity, improve microcirculation, prevent thrombosis, and enhance brain metabolism and blood supply to promote the repair of damaged brain tissue [19]. However, there is still a lack of research on the related signal pathways of tongue acupuncture in the treatment of poststroke aphasia, which should be the goal of future research.
A total of 20 studies were included in this study, and subgroup analysis was performed on CFCP scores [13,15,23] and ABC scores [13-15, 18, 19, 22, 27, 28, 30] according to intervention measures. e results showed that the difference between the tongue acupuncture and the conventional therapy group was statistically significant, but the heterogeneity was high, which may be related to the different acupoint selection and acupuncture intensity of the two groups, and less literature was included; the stability of the results is poor. In the ABC score publication bias, the funnel plots show that two references comparing tongue acupuncture combined with conventional treatments may present some publication bias, which may be due to the small number of cases included in the clinical control and cause shedding. More studies are needed to further analyze and verify the results. e analysis of tongue acupuncture combined with conventional therapy indicated that tongue  Evidence-Based Complementary and Alternative Medicine acupuncture combined with conventional therapy for poststroke aphasia was superior to conventional therapy in improving CFCP score, ABC score, and clinical efficacy. is review had certain limitations. e first limitation is the scarcity of studies, and the methodologically low to moderate quality of the primary data precludes us from drawing confirmative conclusions. Most of the included studies had an unclear risk of bias for blinding, random sequence generation, and allocation concealment; therefore, a preponderance of positive results was observed. e second limitation is that the number of studies is unevenly distributed in the different types of acupuncture, leading to a limited sample size for the CFCP score study. Meanwhile, the included studies also had limitations. e first limitation is that although mentioned randomization in all the 20 included studies, only 4 studies [12,15,16,21] described specific randomization methods, and most of the included studies had unclear bias risks in blinding, random sequence generation, and allocation hiding. Although it is difficult for blind therapists who perform acupuncture, attempts should be made to blind patients, other care providers, and outcome evaluators to minimize trial outcome and evaluation bias. e second limitation is that the sample size included in the study was small, with the largest 120 cases [17] and the smallest 43 cases [19], and no sample size estimation was performed. A third limitation is that we did not perform  Evidence-Based Complementary and Alternative Medicine 7 a subgroup analysis of stroke duration, aphasia type, and treatment course, which may be a potential source of bias. ese potential sources of clinical heterogeneity should be considered in future studies.
is review also has some limitations. e first limitation is the scarcity of studies, and the methodologically low to moderate quality of the primary data precludes us from drawing confirmative conclusions.
Most of the included studies had an unclear risk of bias for       Evidence-Based Complementary and Alternative Medicine randomization method in detail, improve the blind method and allocation concealment, standardize acupuncture therapy, focus on the records of adverse reactions and follow-up, try to select internationally recognized indicators, and improve the repeatability, quality, and reliability of research.

Conclusion
In conclusion, tongue acupuncture is effective and safe in the treatment of poststroke aphasia. Further exploration for tongue acupuncture of poststroke aphasia requires stricter evaluation criteria and high-quality RCT design.
Data Availability e datasets analyzed during the current study are available from the corresponding author upon request.

Disclosure
Shengping Yang and Li Li are the co-first authors.

Conflicts of Interest
e authors declare that they have no conflicts of interest.

Authors' Contributions
YSP and LL participated in the research design. LL screened data extraction. YSP conducted literature search, analyzed the data, performed statistical analysis, and wrote the manuscript. YSP, JR, DHY, XF, KP, and GLL participated in the correction of the manuscript. All authors reviewed, read, and approved the final version of the manuscript.