Effect of Qiangli Dingxuan Tablet on Cerebral Hemodynamics and Brainstem Auditory Evoked Potentials in Vertigo Patients with Posterior Circulation Ischemia

Deng Lijun (邓立军)

ABSTRACT OBJECTIVE: To observe the effect of Qiangli Dingxuan Tablet on cerebral hemodynamics and brainstem auditory evoked potentials in vertigo patients with posterior circulation ischemia. METHODS: A total of 120 vertigo patients with posterior circulation ischemia were randomly divided into observation group and control group. 60 patients in the control group were treated with conventional western medicine. 60 patients in the observation group were treated with Qiangli Dingxuan Tablet on the basis of the control group. After 2 weeks of treatment, the improvement of vertigo(dizziness handicap inventory (DHI), dizziness handicap inventory (DHI)), the hemodynamic index (Basilar artery blood flow velocity (BA), left vertebroarterial artery (LVA), and the average blood flow velocity of right vertebroarterial artery(RVA)) and the changes in brain stem auditory evoked potential (BAEP) of two groups were observed. And statistical analysis was conducted for the clinical efficacy and adverse reactions during treatment of two groups. RESULTS: The total effective rate of the observation group was significantly higher than that of the control group (P ＜ 0.05). The DHI and DARS scores of the two groups were significantly lower than those before treatment (P ＜ 0.05), and the degree of reduction was more obvious in the observation group (P ＜ 0.05). The levels of BA, LVA and RVA in the two groups were significantly higher than those before treatment (P ＜ 0.05), and the levels of BA, LVA and RVA in the observation group were significantly higher than those in the control group (P ＜ 0.05). The indexes of BAEP latency I, II, III and indexes of BAEP peak latency I -III, III-V, IV were obviously lower than those before treatment (P ＜ 0.05). Besides, the decrease of BAEP index in the observation group was significantly lower than that in the control group (P ＜ 0.05). No adverse reactions occurred during the treatment of the two groups. CONCLUSION: Qiangli Dingxuan Tablet is able to significantly improve the cerebral hemodynamics and brainstem auditory evoked potentials of patients with PCIV, and quickly relieve vertigo. It is safe and reliable and worthy of clinical application.

KEYWORDS: Posterior circulation ischemic vertigo; Qiangli Dingxuan Tablet; Cerebral hemodynamics; Brain stem auditory evoked potential

Posterior circulation ischemia vertigo (PCIV) is a common type of ischemic cerebrovascular disease,and the incidence rate accounts for about 20% of all ischemic cerebrovascular diseases. PCIV disease is clinically prevalent in elderly patients, and its clinical manifestations are complex and diverse, which may cause severe cognitive dysfunction and motor dysfunction.In severe cases, death probably occurs and the clinical prognosis is poor. Vertigo is a typical symptom of patients with posterior circulation ischemia. Among patients with vertigo, the proportion of patients with posterior circulation ischemia disease is as high as 59.89%[1].Symptoms of vertigo caused by posterior circulation ischemia are often recurrent with rapidly onset. Patients are often accompanied by focal neurological deficits. If the treatment is not timely received, severe cerebrovascular events such as cerebral infarction can be induced[2]. At present, there are various therapies in Western medicine to treat PCIV, including anticoagulation, lipid-lowering,angioplasty, aortic stenosis stent implantation and surgical treatment. Although there is effect in short-term therapy,the individual differences are large, and the long-term recurrence rate is also high. In recent years, therapy of integrative Chinese and Western medicine has gradually become a sensible choice for clinical treatment of various diseases. It significantly shorten the treatment cycle,reduce the toxic and side effects caused by Western medicine on the body, improve the long-term clinical efficacy, and promote the patient's treatment compliance.Qiangli Dingxuan Tablet is purely consisting of Chinese medicine preparation. The components are Rhizoma Gastrodiae, Cortex Eucommiae, Cortex Eucommiae leaf,Rhizoma Chuanxiong, Flos Chrysanthemi Indici, which have the function of reducing blood pressure and blood fat and reliving the feeling of vertigo. Qiangli Dingxuan Tablet has good curative effects on dizziness, headache and vertigo caused by hypertension, hyperlipidemia and arteriosclerosis. From February 2017 to January 2018,the author has treated 60 PCIV patients with Qiangli Dingxuan Tablet combined with conventional Western medicine, which has showed satisfactory results. The following report is now available.

CLINICAL INFORMATION

General information

A total of 120 patients with PCIV were admitted to our hospital during the above period. The diagnosis of Western medicine met the requirements of PCIV in Chinese Expert Consensus for Posterior Circulation Ischemia[3]: ① Vertigo is the main complaint symptoms,accompanied by tinnitus, headache, eye movement disorders, limb fibrillation, ataxia and other symptoms and signs; ② Ultrasound examination demonstrates vertebral basilar artery occlusion or stenosis;③ Transcranial Doppler examination (TCD) suggests insufficient blood supply to the vertebral basilar artery system; ④ Positive cervical spine test. The classification of TCM diseases' names and syndromes refers to Chinese Internal Medicine[4]. It is hyperactivity of the liver yang characterized by dizziness, tinnitus, distention of eyes, insomnia, dreaminess, irritability, limb tremors,even falling down, flushed face, red tongue, yellow tongue coating, string-like pulse or rapid pulse. Exclude those with organ dysfunction such as liver and kidney,those with severe primary disease, vertigo caused by brain tumor, cerebral hemorrhage, benign paroxysmal positional vertigo and vestibular neuritis, those who were neurological substance abuser, and those with cognitive dysfunction and mental illness. The included patients were randomly divided into 2 groups: 60 patients in the observation group, 26 males and 32 females; aged 45-70 (58.2±4.3) years old; The course of disease was 3-14 (6.5±0.8) months. 60 patients in the control group,26 males and 34 females; aged 48-70 (58.7±4.4) years old; The course of disease was 2-13 (6.1±1.0) months;25 cases of hypertension, 18 cases of hyperlipemia, 17 cases of diabetes. There was no significant difference in the general data between the two groups (P ＞ 0.05).

Treatment methods

The control group was treated with conventional Western medicine, including anti-platelet aggregation therapy with aspirin enteric-coated tablets (Bayer Health Care Co., Ltd., SFDA approval number: J20080078,specification: 100mg), 100mg/time, oral, 1 time/d; Lipidlowering therapy with Atorvastatin calcium tablets(Pfizer Pharmaceutical Co., Ltd., SFDA approval number H20051407, Specification: 10mg), oral, 20mg/d, 1 time/d; Antihypertensive treatment with Valsartan dispersible tablets (Lunan Beite Pharmaceutical Co., Ltd., SFDA approval number H20051350, specification: 40mg), oral,40mg/d, 1 time/d; Hypoglycemic therapy with Metformin Hydrochloride Tablets (Kanto Pharmaceutical Co., Ltd.,SFDA approval number H22021373, Specification:0.25g), oral, 0.25g/d, 3 times/d; And gave the treatment of flunarizine hydrochloride capsule (Harbin Pharmaceutical Group, SFDA approval number H19993926, specification:5mg), oral, 5mg/time, 1 time/d. The above medication was continuously treated for 2 weeks. On the basis of the treatment of the control group, the observation group was treated with Qiangli Dingxuan Tablet (Shanxi Hanwang Chinese Medicine Co., Ltd., SFDA approval number Z61020139, Specification: 0.35g), each time orally administered 2.1g, 3 times/d, with 2 weeks as a course of treatment. There was a total of 1 course for treatment.

Observation index

① Clinical efficacy: Refer to Guiding Principles for Clinical Research of New Drugs in Traditional Chinese Medicine[5], Recovery: clinical symptoms and signs completely subsided, and related physical and chemical indexes basically returned to normal level; Excellent effective: clinical symptoms and signs were significantly relieved, still accompanied by mild dizziness without the sense of sway and rotation of oneself. Daily life and work are not affected, and related physical and chemical indexes are significantly improved; Effective: clinical symptoms and signs are alleviated. Dizziness is improved,while still accompanied with slight sense of sway and rotation of oneself. The daily work and life are affected.The relevant physical and chemical indexes are improved.Ineffective: clinical symptoms, signs and related physical and chemical indexes have not been improved or even aggravated. Recovery + excellent effective +Effective = Total Effective. ② Vertigo improvement:The improvements of vertigo before and after treatment were assessed by dizziness handicap inventory (DHI) and dizziness assessment rating scale (DARS) respectively.DHI assessed the severity of subjective symptoms of vertigo from the overall evaluation. There were 25 questions, including physical, emotion, and function aspects. The higher the score was, the more severe the vertigo disorder would be. The DARS mainly evaluated balance of walking, existing dizziness, directional vertigo,and the overall impression of the doctor and patient. The higher the score was, the more severe the patient's vertigo would be. ③ Hemodynamic index: TCD was used to test the changes of average blood velocity of basilar artery (BA),left vertebroarterial artery (LVA) and right vertebroarterial artery (RVA). ④ Brain stem auditory evoked potential(BAEP): The electroencephalogram evoked potential meter was used to detect the changes of BAEP index before and after treatment. The specific operation steps: the patient lay in supine position. Recording electrode was connected to the top of the head following with nipples. The electrode grounding was connected to forehead. The skin electrode impedance was kept below 5kΩ. Short-term sound was used to stimulate one ear, and intensity was +60d.Another ear was masked by 40-50dB and the intensity was maintained at 11.1Hz. The left and right were repeated detections for 2-3 rounds. The values of the latency and inter-wave latency of the patient were compared and measured. ⑤ Safety analysis: The adverse reactions during the treatment of the two groups were counted.

Statistical methods

Statistical analysis was performed using SSPS 22.0 statistical software. Measurement data were expressed as (x–±S) and compared by t test. The count data is represented by n (%), and the comparison is performed by the X2test. P ＜ 0.05 is considered statistically significant.

RESULTS

Comparison of clinical effects after treatment in 2 groups

After treatment, the total effective rate of the observation group was 91.7%, and the total effective rate of the control group was 75.0%. The observation group was significantly higher than the control group (P ＜ 0.05).See Table 1.

Comparison of vertigo before and after treatment in 2 groups

There were no significant differences in DHI and DARS scores between the two groups before treatment(P ＞ 0.05). After treatment, the DHI and DARS scores of the two groups were significantly lower than those before treatment (P ＜ 0.05), and the degree of reduction was more obvious in the observation group (P ＜ 0.05).See Table 2.

Comparison of 2 groups' average blood flow velocity of basilar artery and vertebral artery before and after treatment

There was no significant difference in BA, LVA and RVA between the two groups before treatment (P ＞ 0.05).After treatment, the levels of BA, LVA and RVA in the two groups were significantly higher than those before treatment (P ＜ 0.05), and BA, LVA and RVA levels of observation group were significantly higher than those of control group (P ＜ 0.05). See Table 3.

Table 1. Comparison of clinical effects after treatment in 2 groups (n (%))

Table 2. Comparison of vertigo before and after treatment in 2 groups (x–±S, score)

Table 3. Comparison of 2 groups' average blood flow velocity of basilar artery and vertebral artery before and after treatment (x–±S, cm/s)

Table 4. Comparison of changes of BAEP indexes in latency before and after treatment in 2 groups (x–±S, ms)

Table 5. Comparison of changes of BAEP indexes in peak latency before and after treatment in 2 groups (x–±S, ms)

Comparison of changes of BAEP indexes before and after treatment in 2 groups

There were no significant differences of indexes of BAEP's latency I, II, III and BAEP's peak latency I-III,III-V, and IV between the two groups before treatment(P ＞ 0.05). After treatment, indexes of BAEP's latency I,II, III and BAEP's peak latency I-III, III-V, and IV were significantly lower than those before treatment (P ＜ 0.05).Besides, the decrease of BAEP index in the observation group was significantly lower than that in the control group (P ＜ 0.05). See Table 4 and Table 5.

Safety analysis

There were mild sleepiness and diarrhea symptoms in two groups. There were 2 cases in the observation group and 3 cases in the control group. No special treatment was given. These symptoms disappeared after suspending the drug. The routine blood and urine tests electrocardiogram, liver and kidney function did not appear any significant abnormal situations.

DISCUSSION

The posterior circulation system consists of the vertebral artery, basilar artery and posterior cerebral artery. It is also known as the vertebrobasilar system,which is the main source of blood supply for the vestibular system such as the vestibular nerve, vestibular nucleus and vestibular receptor. Posterior circulation ischemia refers to the persistent or transient symptoms of vertebral basilar artery system caused by insufficient blood supply due to embolism, atherosclerosis, etc.According to the duration of ischemia and the degree of ischemia, it can be divided into cerebellar infarction,brain stem infarction and transient ischemic attack[6].Dizziness is an important clinical manifestation and diagnosis basis for patients with posterior circulation ischemia. It demonstrates the spatial relationship caused by positional or motor illusion, the reaction distortion of the surrounding environment in the cortex followed by the illusion of dumping, rotation and undulation[7].The pathogenesis of posterior circulation ischemia is complicated. Modern medical research believes that its occurrence is mainly related to atherosclerosis and embolus. Atherosclerosis is the most common cause of posterior circulation ischemia. The main pathological mechanism is aortic stenosis or some complications caused by occlusion such as arterial embolism and thrombosis. The vertebral artery initial segment and intracranial segment are prone to atherosclerosis.Posterior circulation ischemia caused by emboli detachment is also a common clinical pathogenesis.Most of the emboli are derived from the aorta, heart and basilar artery, and the prone position is the distal part of the basilar artery and the intracranial segment of the vertebral artery[8]. In recent years, the clinical incidence of PCIV is on the rise. It seriously affects the quality of patients' life. The treating principles of Western medicine are anticoagulation, prevention of vasospasm and improvement of hemodynamics. In this study, the control group was treated with flunarizine hydrochloride capsules on the basis of anti-platelet aggregation, lipid-lowering,antihypertensive and other conventional treatments.Flunarizine hydrochloride capsule is a selective calcium channel antagonist. There is a significant blocking effect on open calcium channel under pathological conditions such as ischemia. It is widely used in the treatment of cerebrovascular diseases such as vertigo and migraine and neurological diseases. After the treatment with flunarizine hydrochloride capsules, the total effective rate was 73.8%, and the patients' DHI score, DARS score, cerebral hemodynamics index and BAEP index were significantly improved, which indicated that flunarizine hydrochloride capsule perform well in treating PCIV. However, clinical studies have confirmed that long-term use of flunarizine hydrochloride capsules is prone to fatigue, drowsiness,weight gain, depression and other adverse reactions[9].Thus the clinical application of the drug dose should be strictly monitored, and closely observe the patient's adverse reactions.

PCIV belongs to the concept of "dizziness" of traditional Chinese medicine (TCM). "Dizziness" firstly appeared in The Inner Canon of Huangdi, meaning vertigo and dazzle. Patient's main manifestations are dizziness, vertigo, tinnitus, nausea, vomiting and sweating. The position of dizziness is in the brain. Its cause is closely related to the dysfunction of liver, kidney and spleen. The pathogenesis is related to diet, emotion,body weakness and external sensation. Hyperactivity of the liver yang, deficiency of the kidney essence,interior retention of phlegm dampness, deficiency of qi and blood and blood stasis obstructing orifices are the common TCM syndromes of dizziness. Treatment should be based the principle of reinforcing the deficiency and reduce the excess, regulating yin and yang. In this study,the hyperactivity of the liver yang was regarded as the research object. Liver is the organ of wind and wood,which is predisposed to flourishing growth and mobile.If there is yin deficiency of liver and kidney, yin fails to preserve yang, water failing to moisten wood. Yang is upper hyperactivity and there is a feeling of vertigo. The treatment should be based on calming the liver to stop the wind with the combination of tonifying liver and kidney, promoting circulation and reliving the feeling of vertigo. Qiangli Dingxuan Tablet is a commonly used medication for clinical treatment of cardiovascular and cerebrovascular diseases. It has the functions of lowering blood pressure, and lowering lipid and reliving glare. It can quickly relieve and treat dizziness, limb numbness,hyperlipemia, hypertension and other diseases caused by various reasons. Besides, it has a good effect on the sequelae of stroke and the improvement of blood supply of cardiovascular[10]. Modern research has confirmed that Qiangli Dingxue Tablet can multi-directionally activate the deformability of red blood cells, fight against platelet aggregation, inhibit thrombus formation, reduce blood viscosity, and act on the hypothalamus to adjust autonomic nerve function to achieve stun and calm[11]. The main components of Qiangli Dingxuan Tablet are Rhizoma Gastrodiae, Cortex Eucommiae, Cortex Eucommiae leaf, Rhizoma Chuanxiong, Flos Chrysanthemi Indici.Rhizoma Gastrodiae can sooth the liver and subdue yang,relieve convulsion and spasm. Cortex Eucommiae can strengthen bones and muscles, tonify liver and kidney.Flos Chrysanthemi Indici can dispel wind and heat, whose indications are headache, dizziness. Rhizoma Chuanxiong can promote flow of qi and relieve pain, activate the blood circulation to eliminate blood stasis. This prescription can activate the blood circulation and relieve the feeling of vertigo, tonify liver and kidney, calming liver to check endogenous wind and relieve convulsion. Modern pharmacological studies have shown that gastrodin can effectively improve headache, dizziness, nausea,vomiting and other symptoms in patients with ischemic vertigo. In addition, gastrodin plays a role in inhibiting platelet aggregation and anti-thrombosis within a certain range, which helps to improve hemodynamics[12].Cortex Eucommiae has functions of antihypertensive,hypoglycemic, hypolipidemic and enhanced nonspecific immune[13]. Flos Chrysanthemi Indici has antihypertensive, analgesic, anti-oxidant effects[14]. The active ingredient of Cortex Eucommiae leaf is roughly the same as that of Cortex Eucommiae. It has the functions of blood pressure reduction, lipid regulation, hypoglycemic,sedative, soothing and relieving fatigue[15]. Ligustrazine has the functions of inhibiting platelet aggregation,vasodilation, and fighting atherosclerosis[16]. Therefore,the various drug components in Qiangli Dingxuan Tablet can pose anti-platelet aggregation, antithrombotic,sedative, tranquillizing, non-dizziness, lipid-lowering,antihypertensive, hypoglycemic and other effects through different routes. Qiangli Dingxuan Tablet has a significant improvement on vertigo caused by posterior circulation ischemia.

Although PCIV patients show fewer symptoms of hearing loss in clinical practice, studies have shown that the blood supply disorder of the posterior circulation system can cause changes in the microcirculation of the cochlea. The vertebral basilar artery supplies blood to the brainstem, inner ear, cerebellum and other positions through branches. When there is stenosis or spasm,ischemia occurs in the cochlear nerve, brainstem central nervous system and vestibular nerve, which impairs the auditory conduction pathway and induces BAEP abnormalities[17]. BAEP is a sensitive index demonstrating the degree of brain stem damage, which can effectively reflect the electrical activity of nerve impulses caused by various stimuli in the brainstem auditory conduction pathway, and reflect the brainstem function from the electrophysiological point of view. The wave I of BAEP is produced at the junction of the cochlea and the auditory nerve, which is related to the electrical activity of the extracranial segment of the auditory nerve The wave III of BAEP is produced in the upper olive nucleus, which is related to the electrical activity above the medial nucleus. The wave V of BAEP originates from the central nucleus at hypothalamus of the middle brain,which is related to the electrical activity of the upper nucleus and the central nucleus of the hypothalamus.Therefore, by analyzing the data of each wave's latency, it is helpful to understand the abnormalities of brainstem auditory conduction function[18]. In this study, the indexes of BAEP latency I, II, III and indexes of BAEP peak latency I -III, III-V, IV were obviously lower than those before treatment (P ＜ 0.05). Besides,the decrease of BAEP index in the observation group was significantly lower than that in the control group(P ＜ 0.05). Therefore, Qiangli Dingxuan Tablet is able to greatly improve brainstem auditory conduction function.In addition, the total effective rate of the observation group was significantly higher than that of the control group. The improvement of vertigo (DHI score, DARS score) and hemodynamic parameters (BA, LVA, RVA)of observation group were significantly better than that of the control group. No serious adverse reactions occurred during the treatment period in the two groups.This study indicates that Qiangli Dingxuan Tablet can effectively relieve the symptoms of vertigo, improve brain hemodynamics, and remain good drug safety. In summary, Qiangli Dingxuan Tablet can significantly improve the cerebral hemodynamics and brainstem auditory evoked potentials of patients with PCIV, and quickly relieve the symptoms of vertigo, which is safe and reliable, and worthy of clinical application.