Stroke-related sleep disorder (SSD) refers to a group of clinical syndromes that appear for the first time after stroke or pre-existing sleep disorder before stroke persists or worsens after stroke, and meets the diagnostic criteria for sleep disorder. SSD is divided into two types: sleep disorder after stroke and sleep disorder with stroke, that is, sleep disorder has existed in the past, but persisted or worsened after stroke.
Epidemiological studies have shown that the prevalence of sleep disorders in the elderly is as high as 50%, including insomnia, daytime sleepiness (EDS), sleep breathing disorder (SDB), central sleep apnea (CSA), obstructive Sleep apnea (OSA), rapid eye movement sleep behavior disorders (RBD), circadian rhythm sleep-wake disorders (CRSWs), restless legs syndrome (RLS). Foreign research reports that the prevalence of SSD is 44% to 78%, while the research report in my country is 62% to 80%.
It can be seen that the prevalence of SSD in my country is significantly higher than that in foreign countries, among which insomnia is the most common. Due to physical, psychological and environmental changes, stroke patients are prone to sleep disorders, especially in the acute phase of stroke. Studies have found that there is a two-way effect between sleep disorders and stroke. Sleep disorders such as long-term insomnia, SDB and restless legs syndrome (RLS) are both risk factors for stroke and can affect the recovery effect of stroke patients, thereby aggravating the patient The condition increases stroke recurrence and mortality, resulting in a vicious circle between the two.
However, stroke patients and caregivers often ignore sleep problems, believing that it is a natural process of aging or a manifestation of mental and physical diseases. Therefore, it is very important for medical staff to evaluate the sleep disorders of stroke patients early and to manage their symptoms in a targeted manner. There are two main treatment methods for SSD: drugs and non-drugs. However, studies have found that the use of hypnotic drugs can produce a variety of adverse reactions, such as sleep structure disorders, memory decline, cognitive impairment, and motor dysfunction.
As a result, non-drug intervention has attracted more and more attention, and domestic research on non-drug intervention to promote sleep in stroke patients is relatively limited. This review summarizes the current status of non-pharmacological interventions for SSDs to provide a basis for formulating personalized non-pharmacological interventions for SSDs, and to provide a reference for promoting the physical and mental recovery of stroke patients.
1、SSD non-pharmacological intervention measures
Compared with drug therapy, non-pharmaceutical interventions have the outstanding advantage of avoiding adverse reactions and dependence caused by drugs. The short-term therapeutic effect of some interventions is not only similar to that of drug therapy, but also lasts longer than drug therapy. The Chinese Guidelines for Diagnosis and Treatment of Insomnia point out that psychological and behavioral therapy is the preferred treatment method for patients with insomnia. Among them, cognitive behavioral therapy (CBT-I) is the most effective and safe, and has a high degree of applicability. Currently, non-pharmacological intervention methods are divided into two categories, one is psychological and behavioral therapy, and the other is complementary and alternative therapy (CAM).
1.1 Psychological and behavioral therapy
Sleep disorders in stroke patients are closely related to their psychological factors and wrong beliefs and attitudes. Therefore, medical staff should correct the poor cognition and behavior of stroke patients, so that the patient can face the disease correctly, reconstruct the cognitive model that helps sleep, and eliminate the patient's anxiety and depression caused by the disease. Psychological and behavioral treatment methods include sleep hygiene education, cognitive behavioral therapy, and music therapy.
1.1.1 Sleep hygiene education
Sleep hygiene education is to guide patients with stroke on their sleep hygiene knowledge and sleep habits, change or eliminate bad factors that affect patients’ sleep, so as to improve the behavior and environment of patients’ sleep quality. Expert consensus recommends that patients should be guided to work and rest regularly and maintain good sleep hygiene. For patients with stroke complicated with sleep disorders, medical staff should inform the related information of diseases with sleep disorders and proper sleep health education.
In order to explore the impact of sleep health education on the quality of sleep and quality of life of SSD patients, 70 inpatients with stroke were selected as the research objects. The experimental group and the control group were given admission education, discharge guidance, and rehabilitation training every night according to the doctor’s instructions. Oral Zolpidem tartrate tablets (Sinos) 10mg, the experimental group added systematic sleep hygiene education intervention on this basis. The forms of education include nurses using one-to-one oral explanations, patients and their families participating in sleep missions, and issuing health education manuals.
The content of education includes the causes of SSD; the influence of sleep disorders on the recovery from stroke; the correct way to take sedatives and sleeping habits and develop good sleeping habits. The results showed that after 2 months of sleep hygiene education, the sleep quality of patients in the test group was better than that in the control group. Therefore, systematic and standardized sleep health education can improve the sleep quality of stroke patients. The Chinese Guidelines for Diagnosis and Treatment of Insomnia suggest that there is not enough evidence to prove that sleep hygiene education alone has a definite effect, and it needs to be used in combination with other psycho-behavioral treatment methods. Although following correct sleep hygiene education does not mean that SSD patients can be cured, the guidance of correct sleep behavior and living habits can improve sleep and provide help and protection for other treatment options.
1.1.2 Cognitive behavior therapy
Cognitive behavioral therapy is a psychological treatment method that analyzes the patient's thinking activities and strategies for coping with the disease based on the patient's behavior and emotions, and finds out and corrects the wrong cognition. It has a high cure rate and a wide range of applications. And other advantages. The American Medical Association guidelines have recommended cognitive behavioral therapy as the first-line treatment for insomnia. In 2017, Nguyen et al., in order to evaluate the efficacy of individual cognitive behavioral therapy (CBT) and conventional therapy (TAU) on post-stroke fatigue and sleep disorders, conducted a 4-month randomized controlled trial for 15 stroke patients.
Six patients in the control group received conventional nursing and rehabilitation, and nine patients in the experimental group received adaptive CBT treatment 8 times a week. CBT interventions are provided based on a standardized treatment manual that includes 6 modules to deal with fatigue and sleep in 8 separate treatment sessions. The treatment content includes the core CBT principles of psychological education, behavior activation, behavior testing, cognitive reconstruction, problem solving and prevention of recurrence. The course follows the traditional CBT structure, including agenda setting, homework task review, introduction of new concepts or new technologies, and collaborative discussions on how to implement these strategies in the participants’ daily environment.
In the evaluation after 4 months, the test group significantly reduced fatigue compared with the control group. Significant differences between the groups also appeared in terms of sleep quality and depression. The experimental group was more dominant. Sleep disturbance and quality of life improved immediately after treatment, but they were no longer superior to the control group during follow-up. In general, cognitive behavioral therapy is a promising treatment that can improve stroke-related fatigue, sleep quality, and depression. In recent years, my country has gradually applied and promoted it, but there are still few clinical studies on sleep disorders related to stroke patients. In order for cognitive behavioral therapy to truly work in my country, targeted localized research is essential. In the future, the research field of cognitive behavioral therapy should mainly focus on improving the treatment effect and transforming to the community, as well as strengthening the training and dissemination of cognitive behavioral therapy for medical staff.
1.1.3 Music therapy
The American Music Therapy Association (AMTA) believes that music therapy is a method of using music or performing music-related activities to improve an individual's specific physical, emotional, cognitive, and social needs. As we all know, music can produce a sense of pleasure. There are reports in the literature that music has the ability to vent emotions, improve cognitive performance and affect awakening. Music therapy can be used as another way to activate the injured brain, induce neuroplasticity, and potentially reduce or repair the injured brain.
Music therapy is currently a new type of fringe subject. Since the 1980s, some scholars in my country have combined music therapy and Chinese medicine culture in clinical practice, resulting in five element music and music current therapy. Fu Meiting and others conducted a 14-day randomized controlled trial on 70 SSD patients. The control group received conventional treatment and nursing care, and the experimental group received Kaitianmen and Five Elements music therapy on this basis. The results show that Kaitianmen combined with five elements music therapy can improve the sleep quality of SSD patients and improve the quality of life of patients. Studies by Zhuo Yewen and others have shown that the intervention of meditation music therapy for patients with ischemic stroke sleep disorders can improve the patient’s sleep quality, increase patient satisfaction, and reduce the risk of stroke recurrence. Music therapy guides the patient to perform breathing and muscle relaxation training by playing gentle and pleasant music, so that the patient can relax physically and mentally, reduce the body's oxygen consumption, promote the patient's emotional calm, and effectively improve the patient's sleep quality. However, due to too many types of music, patients will be more inclined to their favorite music, which may affect the expected results of the study. Follow-up research can pay more attention to the individuality of patients, so as to choose suitable music.
1.2 Complementary and Alternative Therapy
In the non-pharmaceutical intervention measures of SSD, it is difficult for patients to implement related psychological and behavioral intervention measures such as behavior regulation and sleep hygiene technical guidance. Some patients will actively seek complementary and alternative treatments to improve their sleep status. Although complementary and alternative treatments are not the content of mainstream and orthodox medicine, they can make up for their shortcomings and provide a comprehensive combination of diagnosis, treatment and prevention methods that it cannot achieve. At present, it has been widely used in clinical and research at home and abroad. A South Korean study showed that 54% of stroke patients used complementary and alternative therapies, and 16% of them believed that it can effectively achieve psychological relaxation. Complementary and alternative therapies commonly used for SSD patients include exercise therapy, physical therapy, and acupuncture.
1.2.1 Exercise therapy
Modern medical research has proved that exercise therapy has obvious therapeutic effects in treating SSD patients, and can help them relax physically and mentally, and make the patients sleep as soon as possible. Long-term exercise can enable patients to have a more objective assessment of their physical fitness, help patients adjust their work and rest time, make the patient work and rest regular, and improve the patient's sleep time and quality.
However, the method, form, intensity and timing of exercise therapy will affect the efficacy of sleep disorders. Common SSD prevention and intervention exercise methods include aerobic training, resistance training and joint training. There are supervised team sports, one-on-one personal guidance, and home sports. Ni Xiaohong et al. conducted a 4-week randomized controlled trial on 82 SSD patients. The experimental group was given exercise therapy combined with psychotherapy, and exercise therapy was divided into three parts.
The first part is the passive movement therapy of the patient's limbs. The medical staff performs passive movement of the patient's limbs such as joint activities. Twice a day, 40 min each time. The second part is aerobic exercise therapy. The aerobic exercise methods include slow walking, Tai Chi, etc., once a day, and at the same time, the patient is trained to walk for 20 minutes each time. The third part is medical gymnastics and exercise therapy. If the patient cannot leave the ward due to illness, exercise treadmill training can be carried out in the department. Take the patient’s fatigue as the degree, twice a day, 30 min each time. There are two main aspects of psychotherapy. The first is to pay close attention to the patient's emotional changes, strengthen communication skills, and establish a good nurse-patient relationship with the patient, so that the patient can trust the medical staff, actively talk about their inner feelings, and encourage the patient more.
The second is to carry out health education for patients, such as issuing health handbooks, to strengthen patients’ understanding of the disease, and to formulate targeted psychological rehabilitation treatments for them to reduce their psychological burden. The control group was given exercise therapy only. The results showed that the sleep quality of the control group and the test group were improved compared to before the intervention, and the test group's score was significantly lower than that of the control group, suggesting that exercise therapy combined with psychotherapy can significantly improve the patient's sleep quality. Due to the small side effects and low cost, exercise therapy is often the preferred and easy treatment method, but the observation of the curative effect may be affected by the patient's subjective feelings. Therefore, it can be used in combination with other treatment methods in future clinical studies to design more rigorous treatment plans.
1.2.2 Physical Therapy
Physical therapy, as a non-drug treatment that is painless, non-invasive, safe, and easy to be accepted by patients, has been widely used in clinical treatment. At present, with regard to SSD, commonly used physical therapies include transcranial electrical stimulation (CES) and repetitive transcranial magnetic stimulation (rTMS). Transcranial electrical stimulation mainly uses micro currents to adjust the activity of cerebral cortical nerve cells, thereby changing their excitability, which is beneficial to the recovery of the nerve function of the affected brain tissue of stroke patients. Repetitive transcranial magnetic stimulation mainly uses low-frequency (1-5 Hz) pulsed magnetic fields to directly hyperpolarize nerve cells, reduce the metabolic function of local brain tissue, and thereby inhibit the hyperexcited state of the cerebral cortex. Chinese scholars such as Li Chunzhen, in order to explore the effect of applying transcranial electrical stimulation and motor imaging therapy to improve upper limb function and sleep status of stroke patients, selected 77 stroke patients for a three-week randomized controlled trial.
The experimental group was given a combination of transcranial electrical stimulation and motor imaging therapy. Transcranial electrical stimulation was treated once a day for 20 minutes each time. The control group only used transcranial electrical stimulation, and the method was the same as that of the experimental group. The results showed that the Pittsburgh sleep quality scores of the two groups of patients decreased after treatment, and the test group was lower than the control group. This shows that transcranial electrical stimulation combined with motor imaging therapy to treat stroke patients has a better effect on the patient's sleep quality. He Yugong et al. selected 90 patients with post-stroke depression and divided them into 3 groups for an 8-week randomized controlled trial. The three groups of patients were given basic treatment and comprehensive rehabilitation training, the control group was given escitalopram, the treatment group was given rT-MS treatment, and the combined treatment group was a combination treatment of the control group and the treatment group.
The results showed that the degree of depression, sleep quality, neurological impairment, and ADL ability of the three groups of patients were improved compared to before treatment, but there was no statistically significant difference between the groups. Therefore, it can be judged that rTMS treatment has the same effect of improving sleep quality as escitalopram. Although physical therapy has the advantages of good therapeutic effect and small side effects, its clinical application depends on the patient's wishes. In the current research, we can see that most researchers use physical therapy combined with other treatment methods to intervene in the research subjects. If only physical therapy is used, the method is relatively simple and easily affected by the patient's disease and age.
1.2.3 Acupuncture
Acupuncture and moxibustion is also called acupuncture therapy. It is a treatment method of traditional Chinese medicine. It is a kind of mechanical stimulation. The essence of its effect is to stimulate and promote the body's own regulatory function and self-healing ability to treat diseases. The advantage of acupuncture is that it has no side effects of drugs. . Acupuncture has the functions of dredging the meridians, coordinating yin and yang, and regulating the viscera. It can stimulate the patient's own meridians to resist evil and balance the body's blood, yin and yang. According to the results of related trials and research, the main mechanism of acupuncture treatment of SSD may be related to reducing the damage of arousal functional area and regulating the neurotransmitters and cytokines related to arousal.
Cao Yan and others selected 84 elderly patients with insomnia after ischemic stroke for a 4-week randomized controlled trial. The test group took the acupuncture points Shenting, Baihui, Anmian, Yintang, Shenmen, Sanyinjiao and Zusanli for acupuncture treatment, while the control group took the same acupuncture points and received sham acupuncture treatment. The needle tip did not pierce the skin. The results showed that the sleep quality index of both groups of Pittsburgh decreased after 4 weeks, and the test group was significantly lower than the control group. It can be seen from this that acupuncture and moxibustion have a certain helpful effect on improving the sleep quality of patients. Although studies have shown that acupuncture has a certain effect in the treatment of post-stroke insomnia patients, there is still a lack of relevant research in other types of stroke sleep disorders. Therefore, future research should focus on other types of SSD and strengthen the improvement of SSD. Refined understanding.
2 、Outlook
Different SSD non-drug treatment methods can improve the patient's sleep quality to varying degrees, but the key to the choice of method depends on the patient's choice. There is no uniform standard for the intervention dose, frequency, and time of various intervention methods, so there is a lack of exploration of the best evidence. In the final effect evaluation of the patient's sleep quality, objective evaluation indicators can be added, and qualitative research can be added at the same time, to explore the true experience of the patient, and to improve the comprehensiveness and rigor of the research.
At the same time, patient compliance is also the key to observing the effect of research. However, the above clinical studies lack the monitoring and description of this indicator. In the future research field, researchers can add this observation indicator to continuously explore and improve the SSD. Non-pharmaceutical intervention methods provide a theoretical basis for improving the sleep quality of stroke patients and for clinical medical staff to effectively manage the physical and mental rehabilitation of stroke patients.
At the same time, national policies are actively supporting the development of more innovative drugs.
In order to accelerate the development of China's innovative drug industry, the state has issued a series of policies covering the priority review of innovative drugs and subsequent medical insurance reimbursements, and strong support for innovative drugs from drug registration to drug terminal use. With the effective establishment of a dynamic adjustment mechanism for the scope of basic medical insurance drugs, more innovative drugs will have the opportunity to be added to the national medical insurance catalog in the future, helping the development of innovative drugs from an economic perspective.
From the clinical demand-oriented research and development path, because the current market commonly used thrombolytic drugs such as recombinant urokinase and rt-PA have a short half-life of only 4-8 minutes, which cannot alleviate the incidence of acute thrombosis, patients and doctors are looking forward to more With the emergence of many new drugs or new therapies that effectively relieve and treat acute thrombosis, the industry is also welcoming a group of biotech companies to compete on the research and development track of innovative thrombolytic drugs.
For example, the industry market has recently noticed that the oncolytic bacterial carrier YB1 developed by an oncolytic bacterial therapy company can carry the thrombolytic enzyme rt-PA to accumulate in the thrombus and can be released at a fixed point, which solves the problem of its short half-life.
According to the data, the company has deployed the YB1 thrombolytic product pipeline: YB1-rt-PA, which is its first-generation targeted thrombus ablation product. The main feature is that it is carried by YB1 and releases Urokinase at the thrombus position. , Can achieve the role of rapid fixed-point release of thrombolytic drugs.
It is reported that this company has two other thrombolytic drug pipelines under development, namely YB1-rt-DE, which combines YB1 with defibrase, and YB1-rt-PL, which combines YB1 with plasmin, both of which are currently in the design and development stage. It is hoped that these innovative thrombolytic drugs can be marketed as soon as possible, so that more stroke patients will benefit from this and improve their health.
