1. Introduction

Epilepsy is a chronic disease in which sudden abnormal discharge of brain neurons leads to transient brain dysfunction [1]. Each epileptic seizure of the patient is unpredictable, which not only seriously reduces the quality of life, but also causes different degrees of cognitive dysfunction, manifested as a functional decline in attention, memory, abstract thinking ability, reasoning ability, etc. even lost [2, 3]. Epidemiological studies revealed that the global prevalence of epilepsy has surpassed 70 million, with approximately 700,000 new cases reported annually [2]. Numerous experimental models have demonstrated that cognitive dysfunction is a common comorbidity in epilepsy. For instance, Kumar et al. discovered that all rats with pentetrazole-induced epilepsy exhibited cognitive deficits [4]. In clinical practice, the prevalence of cognitive impairment in epilepsy patients varies from 30% to 40%, depending on the assessment method and population under evaluation [5]. Cognitive impairment significantly impacts the quality of life for individuals with epilepsy, emphasizing the significance of early prediction and intervention in managing cognitive dysfunction. With the promotion and application of the “biology-psychology-social” medical model, in the process of clinical diagnosis and treatment of epilepsy, it is necessary to pay attention not only to the control of epileptic seizures but also to the accompanying cognitive impairment of patients.

The earliest records of epilepsy in China can be traced back to 2000 years ago in the Huang Di Nai Jing of traditional Chinese medicine. Traditional Chinese medicine has a long history and rich experience in the treatment of epilepsy. It has the advantages of a stable curative effect, few side effects, and can promote the recovery of brain cell function, and is expected to be applied in antiepileptic therapy [6, 7]. Acupuncture is another important traditional healing method, which has been used and applied for more than 2000 years in China. In recent years, acupuncture has shown positive therapeutic effects in improving overall effectiveness of epilepsy treatment, reducing the severity of epileptic seizures, and minimizing adverse reactions. Research has confirmed that electroacupuncture stimulation of “Zu-san-li” and “Shang-ju-xu” for 6 weeks significantly reduces the level of cyclooxygenase-2 (COX-2) in the hippocampus of epileptic rats, resulting in an anti-inflammatory effect [8]. Furthermore, electroacupuncture intervention has been found to upregulate the expression of Nuclear factor erythroid2-related factor 2 (Nrf-2) and its downstream antioxidant factors, activating the Nrf-2-ARE signaling pathway to protect brain tissue against oxidative stress damage [9]. In summary, acupuncture’ s mechanism in treating epilepsy encompasses various aspects of the condition’ s pathogenesis, including apoptosis inhibition, inflammatory response suppression, oxidative stress reduction, ion channel regulation, and modulation of intestinal flora. However, high-quality evidence from relevant studies is lacking. Therefore, we carried out a meta-analysis of randomized controlled trials (RCTs) to reach a solid conclusion with a larger sample size. We aimed to determine the effects of acupuncture for epilepsy patients with cognitive impairment and provide evidence-based recommendations for patients with epilepsy.

2. Methods

2.3 Data sources and search strategies

All published RCTs in the following databases will be searched from their inception to April 2023: PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, the Cochrane Central Register of Controlled Trials (CENTRAL), Wanfang database, and the China National Knowledge Infrastructure (CNKI), without language restrictions.

The search terms included “epilepsy”, “Epilepsies”, “Seizure Disorder”, “Seizure Disorders”, “Cognitive Dysfunctions”, “Cognitive Impairments”, “Cognitive Impairment”, “Cognitive Disorder”, “Cognitive Decline”, “Cognitive Declines”, “Mental Deterioration”, “Acupuncture Therapy”, “Acupuncture”, “Traditional Chinese medicine”, “Traditional Chinese herbs”. An example of the search strategy for PubMed is summarized in Table 1.

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Table 1. Search strategy for PubMed.

https://doi.org/10.1371/journal.pone.0297410.t001

2.4 Study selection and data extraction

We will import all identified literature into EndNote X9 software to delete any duplicates. Two authors will screen the titles/abstracts of all potential studies to remove studies that are not related to the topic. Then, the full text of the remaining studies will be read carefully to further determine whether they fulfill all eligible criteria. If necessary, a third author will help to solve any divergence between the two authors. The following data were extracted from the included studies: (1) basic information of the study including the first author’s name, year of publication, sample sizes, participant’s age, and disease duration; (2) interventions details; (3) control details; (4) primary outcome indicators, secondary outcome indicators before and after the intervention; (5) adverse events. If available data could not be obtained directly from the article, the corresponding author was contacted and clarification of ambiguities and missing information was provided by phone or email. Details of the selection process will be presented in the PRISMA flow chart (Fig 1).

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Fig 1. Flowchart of trial selection process for this systematic review.

“n” represents the number of studies.

https://doi.org/10.1371/journal.pone.0297410.g001

3. Discussion

At present, the influencing factors of cognitive dysfunction in epilepsy patients have been basically clarified, but the pathogenesis has not yet been fully clarified. Studies have found that epilepsy-related cognitive impairment may be related to damage such as hippocampal sclerosis, abnormal transmitter transmission, inflammatory factors and oxidative stress [10–14]. D’Avila et al. discovered that activated microglia release various inflammatory mediators, which can lead to tissue damage and neurotoxicity through mechanisms like oxidative stress and synaptic remodeling [15]. These processes have been linked to cognitive impairment. Mishra et al. conducted a study using a mouse model of epilepsy and found that reducing lipid peroxidation levels and increasing antioxidant mechanisms resulted in shorter seizure duration and improved cognitive function [16]. The existence of cognitive impairment will bring a certain burden to the life of epilepsy patients. Therefore, it is of great significance to diagnose and treat cognitive impairment in time to reduce the burden on patients and their families.

Modern pharmacological studies have shown that some traditional Chinese medicines (such as Gastrodia elata, Polygala tenuifolia, Acorus tatarinowii, Nardostachys chinensis, Safflower, etc.) have the effects of inhibiting platelet aggregation, prolonging thrombin time, protecting neurons, nourishing blood and calming the nerves, antiepileptic, sedative, antispasmodic, and analgesic [17–20]. Acupuncture and moxibustion treat epilepsy mainly by disrupting brain waves, inhibiting seizures, affecting the neuroendocrine immune system, and protecting neurons, thereby reducing seizures and improving the quality of life of patients with epilepsy. Acupuncture acts on acupoints through physical stimulation, stimulates related nerve veins, affects the secretion and release of neurotransmitters in the brain, and regulates the electrical activity of brain nerve cells [9, 21].

However, there is no studies have not been systematically organized on the efficacy of acupuncture for primary epilepsy patients with cognitive impairment. Thus, it is necessary to organize evidence that has been proven by RCTs, so that it can be used.

Supporting information