Effect of Acupuncture on NSE and Hcy Levels and Magnetic Resonance Spectrum in Cerebral Infarction Patients

Zheng Su, Xu Jing, Wang Peng, Luo Qiang

Taihe Hospital Affiliated to Hubei Medical College, Shiyan 442000, China

Effect of Acupuncture on NSE and Hcy Levels and Magnetic Resonance Spectrum in Cerebral Infarction Patients

Zheng Su, Xu Jing, Wang Peng, Luo Qiang

Taihe Hospital Affiliated to Hubei Medical College, Shiyan 442000, China

Objective: To observe the effect of stage-based acupuncture on neuron specific enolase (NSE), homocysteine (Hcy) levels and magnetic resonance spectrum in patients with cerebral infarction.

Methods: Ninety eligible subjects were randomized into two groups, 45 in each. The control group was intervened by conventional neurological medication, while the treatment group was by acupuncture according to different stages in addition to the conventional neurological medication. The therapeutic efficacy was evaluated after a treatment course.

Results: The total effective rate was 97.8% in the treatment group versus 77.8% in the control group, and the treatment group was significantly superior to the control (P＜0.01). In comparing the National Institutes of Health stroke scale (NIHSS) score, NSE and Hcy levels, the treatment group was lower than the control group, and the differences were statistically significant (P＜0.01). The analysis of magnetic resonance spectrum revealed that the treatment group had a markedly higher N-acetyle-aspartate (NAA) concentration and lower lactic acid (Lac)concentration than the control group (P＜0.01).

Conclusion: Stage-based acupuncture significantly increases clinical efficacy and heals neurological function deficit, and its mechanism is possibly related to the decrease of NSE and Hcy levels, increase of NAA, and elimination of Lac.

Acupuncture Therapy; Electroacupunture; Cerebral Infarction; Stroke; Homocysteine; Magnetic Resonance Spectroscopy

Cerebral infarction refers to necrosis of local brain tissue resulting from the narrowing or blockage of the blood vessels supplying blood to the brain, majorly manifested by hemiplegia and hemianesthesia. With high disability and fatality rates, it severely damages people’s health and quality of life. Currently, the Western medicine normally manages this condition with supportive and symptomatic treatments including anti-hypertension, lipid modulation, anti-coagulants, and nourishing brain cells. However, it doesn’t have a satisfactory efficacy for limb dysfunction. Traditional Chinese medicine (TCM) usually adopts acupuncture, moxibustion, external medicinal application, and Chinese herbal medicines to treat this disease[1-5]. In this study, the cerebral infarction patients were given stage-based acupuncture, to observe the effect of acupuncture on the levels of neuron specific enolase (NSE) and homocysteine (Hcy), and the magnetic resonance spectrum was also adopted to determine the changes of the metabolism in brain.

1 Clinical Study

1.1 Diagnostic criteria

1.1.1 Diagnostic criteria of TCM

The diagnostic criteria of TCM were based on theStandard for Diagnosis and Therapeutic Effect Evaluation of Stroke(Trial)[6]revised by the Collaborative Group of Acute Encephalopathy of State Administration of Traditional Chinese Medicine.

1.1.2 Diagnostic criteria of Western medicine

The diagnostic criteria of Western medicine were made according to theChina Diagnostic and Treatment Guidelines for Acute Ischemic Stroke(2010)[7].

1.2 Inclusion criteria

In conformity with the above diagnostic criteria of both TCM and Western medicine, and diagnosed with cerebral infarction by CT or MRI test; disease duration＜72 h; age 38-74 years old, with clear consciousness; without any habits (smoking, and drinking wine or thick tea, etc.) that may influence the metabolism of Hcy; without any diseases which may influence the metabolism of Hcy, N-acetyl aspartate (NAA), and lactic acid (Lac), and without taking any drugs which may affect the concentrations.

1.3 Exclusion criteria

Against any of the above inclusion criteria; hemiplegia induced by brain trauma, tumor, parasitic encephalopathy, craniocerebral surgeries, or metabolism disturbance, as well as cerebral embolism and embolism of brain stem; accompanied by severe primary diseases of heart, liver, kidney, hematopoietic system, or endocrine system, severe hypertension, psychological or intelligence disturbance; allergic to or intolerant of acupuncture.

1.4 General data

Ninety eligible subjects were enrolled from the inpatient department of our hospital. Of them, there were 46 males and 44 females, aged 38-74 years old with the mean age of (53.8±4.5) years old. They were randomized into a treatment group and a control group by random number table, 45 in each. There were no significant differences in the general data of age, gender, and disease duration between the two groups (P＞0.05), indicating the comparability (table 1).

Table 1. Comparison of general data

The clinical managements of the two groups are shown in Fig.1.

Fig.1 Clinical management flow chart

2 Treatment Methods

2.1 Treatment group

In addition to the basic treatment, the treatment group also received stage-based acupuncture.

2.1.1 Early stage of flaccid stage

Acupoints: Neiguan (PC 6), Shuigou (GV 26), Sanyinjiao (SP 6), Jiquan (HT 1), Weizhong (BL 40), and Chize (LU 5).

Operation: After standard sterilization for local skin, disposable filiform needles of 0.3 mm in diameter and 40 mm in length were used for acupuncture referring to the brain-refreshing and orifice-opening acupuncture method. Bilateral Neiguan (PC 6) points were initially punctured perpendicularly for 0.5-1.0 cun, with lifting-thrusting and twisting reducing techniques for 1 min; Shuigou (GV 26) was then needled obliquely towards the nasal septum, with bird-pecking reducing technique till tears produced and eyeballs moisturized;Sanyinjiao (SP 6) was punctured along the tibia with an angle of 45° between the needle and skin for 0.5-1 cun, with lifting-thrusting tonifying technique till there was an involuntary twitching of lower limbs; Jiquan (HT 1) was perpendicularly punctured 2 cun below the standard location on the Heart Meridian for 0.5-0.8 cun avoiding armpit hair, with lifting-thrusting and twisting reducing techniques; Weizhong (BL 40) was punctured perpendicularly for 0.5-1 cun when the patient was in a supine position with the leg straightly raised; Chize (LU 5) was perpendicularly punctured for 1 cun with the elbow bent by 120°, with lifting-thrusting reducing techniques till there were twitching movements of the forearm and fingers[8].

2.1.2 Last stage of flaccid paralysis

Acupoints: Waiguan (TE 5), Hegu (LI 4), Jianyu (LI 15), Shousanli (LI 10), Quchi (LI 11), Zusanli (ST 36), Yanglingquan (GB 34), Fengshi (GB 31), Sanyinjiao (SP 6), Fenglong (ST 40), Xuanzhong (GB 39), and Jiaji (EX-B 2) of neck and lumbar.

Operation: After standard sterilization for local skin, disposable filiform needles of 0.3 mm in diameter and 40 mm in length were used and connected to G6805-2 electroacupuncture apparatus [for the upper limbs, Jianyu (LI 15) and Shousanli (LI 10) as a pair, Waiguan (TE 5) and Quchi (LI 11) as a pair; for the lower limbs, Zusanli (ST 36) and Yanglingquan (GB 34) as a pair, Fenglong (ST 40) and Xuanzhong (GB 39) as a pair], with sparse-dense wave, frequency at 1.2 Hz, making rhythmic twitching of limbs, for 25-30 min each time. 2.1.3 Spastic stage

Acupoints: Jianyu (LI 15), Naoshu (SI 10), Binao (LI 14), Yangxi (LI 5), Tianjing (TE 10), Waiguan (TE 5), Yinlingquan (SP 9), Taixi (KI 3), Sanyinjiao (SP 6), Yanglingquan (GB 34), and Zusanli (ST 36).

Operation: After routine sterilization for skin, disposable acupuncture needles of 0.3 mm in diameter and 40 mm in length were used for deep acupuncture. Points from the yang meridians of upper limb, Binao (LI 14), Jianyu (LI 15), and Tianjing (TE 10) were punctured with lifting-thrusting tonifying techniques, and Neiguan (PC 6), the point from the yin meridian, was punctured with twisting reducing technique. Points from the yin meridians of lower limb, Taichong (LR 3), Sanyinjiao (SP 6), and Yinlingquan (SP 9) were punctured with lifting-thrusting tonifying technique, and the acupoints from the yang meridians, Yanglingquan (GB 34), and Zusanli (ST 36), were punctured with lifting-thrusting reducing techniques.

2.1.4 Recovery stage

Acupoints: Jianjing (GB 21), Shousanli (LI 10), Jianyu (LI 15), Hegu (LI 4), Waiguan (TE 5), Huantiao (GB 30), Shenmai (BL 62), Shenshu (BL 23), Zhaohai (KI 6), Xuanzhong (GB 39), Yanglingquan (GB 34), Zusanli (ST 36), Kunlun (BL 60), Sanyinjiao (SP 6), and Taichong (LR 3).

Operation: After standard sterilization, disposable acupuncture needles of 0.3 mm in diameter and 40 mm in length were used, with sparse-dense wave and frequency at 1.2 Hz, to make rhythmic twitching to the limbs.

Needles were retained for 30 min each time, one session per day. The treatment protocol was adjusted according to disease condition.

2.2 Control group

The control group received the same basic treatment as that in the treatment group.

The two groups received treatment once every day, 30 d as a treatment course, and were evaluated after a course.

3 Observation on Therapeutic Efficacy

3.1 Observation indexes

3.1.1 NSE and Hcy levels

In both groups, patients all received morning blood test before and after treatment, 3 mL each tube, 2 tubes each time. After centrifugation, one tube of blood was used to determine serum NSE by enzyme-linked immunosorbent assay (ELISA)[9], and the other tube was used to determine Hcy by fluorescence-linked immunosorbent assay (FLISA)[10].

3.1.2 Determination of neurological function deficit

Neurological function deficit was evaluated by using the National Institutes of Health Stroke Scale (NIHSS) before and after treatment[11].

3.1.3 Examination of magnetic resonance spectrum[12]

The 1.5T MRI scanner (Simens Avanto Erlangen, Germany) was adopted to determine the concentrations of creatine (Cr), NAA, and Lac, and to calculate the ratio of Lac/Cr and NAA/Cr before and after treatment[12].

3.2 Evaluation of therapeutic efficacy

The therapeutic efficacy was evaluated by theClinical Scale for Neurological Function Deficit of Stroke Patients[13].

Basic recovery: Limb function is completely or substantially restored; patient can live independently, muscle strength is restored to ≥grade 4; neurological function deficit decreases by over 90%; and disability is evaluated as grade 0.

Marked effect: Limb function is obviously improved; muscle strength is restored to ≥grade 2; neurological function deficit decreases by ＞45% but ≤90%; and disability is evaluated as grade 1-3.

Improvement: Limb function and other symptoms have some improvement; muscle strength is grade 1;and neurological function deficit decreases by ＞17% but≤45%.

Invalid: Symptoms are not improved; and neurological function deficit decreases by ≤17%.

3.3 Statistical analysis

All data were processed by using SPSS 17.0 statistical software. Measurement data were expressed by (), inter-group comparison was analyzed by usingt-test, numeration data were compared by using Chi-square test, and the rank data were compared by theRidittest.P＜0.05 indicates a statistical significance.

3.4 Results

3.4.1 Comparison of clinical efficacy

The total effective rate was 97.8% in the treatment group versus 77.8% in the control group. TheRiditanalysis showed that the difference was statistically significant (P＜0.01). It indicates that stage-based acupuncture can obviously increase the clinical efficacy (table 2).

3.4.2 Comparison of NIHSS score and concentrations of NSE and Hcy

There were no significant differences between the two groups in comparing NIHSS score, and NSE and Hcy concentrations (P＞0.05). After treatment, NIHSS score, and NSE and Hcy concentrations all dropped markedly in both groups, and the differences were statistically significant (P＜0.05). The decreases in the treatment group were more obvious than those in the control group (P＜0.01 orP＜0.05). It indicates that stage-based acupuncture can decrease the NSE and Hcy levels in cerebral infarction patients, and can heal the neurological function deficit (table 3).

3.4.3 Comparison of metabolites NAA and Lac

There were no significant differences between the two groups in comparing NAA and Lac before treatment (P＞0.05). After treatment, the level of Lac decreased markedly and NAA increased notably in the treatment group (P＜0.01); the differences between the two groups after treatment were statistically significant (P＜0.05), (table 4).

Table 2. Comparison of clinical efficacy (case)

Table 3. Comparison of NIHSS score and NSE and Hcy concentrations ()

Table 3. Comparison of NIHSS score and NSE and Hcy concentrations ()

Note: Intra-group comparison, 1)P＜0.05; compared to the control group after treatment, 2)P＜0.05, 3)P＜0.01

Hcy (μmol/L) Pre-treatment Post-treatment 24.11±5.16 16.28±2.101)3)25.01±4.38 20.19±6.151)

Table 4. Comparison of NAA and Lac ()

Table 4. Comparison of NAA and Lac ()

Note: Intra-group comparison, 1)P＜0.01; compared to the control group after treatment, 2)P＜0.05

GroupsnNAA/Cr Lac/Cr Pre-treatment Post-treatment Pre-treatment Post-treatment Treatment 45 1.23±0.01 3.16±1.521)2)2.71±0.31 1.20±1.011)2)Control 45 1.21±0.07 1.87±0.83 2.73±0.27 2.21±0.35

4 Discussion

Cerebral infarction is a commonly encountered disease caused by blockage of cerebral vessels and subsequent cerebral neurological dysfunctions, with various risk factors, and high disability and relapse rates. It’s majorly manifested by hemiplegia and hemianesthesia. TCM holds that, when a weak constitution is stimulated by risk factors, it will induce imbalance between yin and yang, and the disordered qi and blood will go up to interfere with the brain, and the disease will then develop. With the progress of study on the pathogenesis of cerebral infarction, more and more experts believe that Hcy is a novel independent risk factor in the development of cerebral infarction[14], and it’s closely related to the formation of atherosclerosis[15]. The latest research shows that NSE mainly exists in the brain’s neurons and neuroendocrine cells, with a very low concentration in normal condition. However, with occurrence of cerebral infarction, NSE will leak out from damaged neural cells into the intercellular space, and then take part in body fluid circulation. Therefore, the determination of NSE can be considered as a sensitive index for damage of neurons, and an index for telling the prognosis of the damaged neurons[9]. Magnetic resonance spectrum is a new functionalimaging detective method. It can noninvasively observe the changes of cellular metabolites in cerebral infarction and provide evidences of the happening and development of cerebral infarction[16]. NAA is predominantly present in functional neurons, reflecting the densities and functional status of neuron and neuraxis, and sensitively reporting the function of residual status of neurons[17]. The determination of NAA can be taken as an important index for foretelling the prognosis of cerebral infarction[18]. Under normal circumstances, Lac has a very low concentration. However, it can significantly increase when there are pathological changes in skull base, e.g. cerebral infarction, and the concentration changes sensitively and accordingly with the development of cerebral infarction, which is a dynamic process[19].

Modern medicine holds that post-stroke hemiplegia happens when the advanced motor function, which is controlled by the brain, is inhibited, and the basic motor function, which is controlled by the spinal cord, including associated reaction, associated movement, and postural reflex, etc., are released due to the damage of brain[20]. Its pathogenesis follows the early stage of flaccid paralysis, last stage of flaccid paralysis, spastic stage, and recovery stage. Stage-based acupuncture is a treatment method built up upon the syndrome differentiation of TCM, combining with the modern rehabilitation. It has changed the traditional theory that to treat flaccidity by selecting acupoints from the Yangming Meridians alone.

The early stage of flaccid paralysis: The patient is in a spinal shock, a decreased or loss of muscular tension or sensation. TCM holds that the pathogenesis of this stage should be the blocked orifices and failure of brain to conduct qi flow. Therefore, Shi’s brain-activating and orifice-opening needling method is adopted. Shuigou (GV 26) works to open orifices, activate brain, and regulate the function of Zang-fu organs. Neiguan (PC 6) is for calming mind and regulating blood. Sanyinjiao (SP 6) can warm and tonify the Liver, Spleen and Kidney Meridians, for regulating qi and blood, supplementing brain and marrow, and calming mind. Chize (LU 5), Weizhong (BL 40), and Jiquan (HT 1) can unblock and dredge meridians and collaterals, promote the flow of qi and blood, and improve limb functions. Strong stimulation to the above points can evoke and strengthen the muscular tension and sensation.

The end stage of flaccid paralysis: At this stage, patient’s muscular tension is improved, and associated movement occurs. For the treatment of this stage, points from the Hand and Foot Yangming Meridians are selected to use with the Jiaji (EX-B 2) points. As a meridian with profound qi and blood, the Yangming Meridians can be punctured to dredge and unblock meridians and collaterals, and to regulate qi and blood. When qi and blood are sufficient, tendons and vessels can be nourished, and thus flaccidity can be healed. The Jiaji (EX-B 2) points reside on both sides of the Governor Vessel and are close to the Back-Shu acupoints. Therefore, they are punctured to regulate the function of Zang-fu organs and yin-yang, activate qi and promote the blood circulation, and strengthen tendons and bones with the help of other points.

Spastic stage: There appear synergic movements of the flexor muscles of upper limb and extensor muscles of lower limb, and increased or even hyperactive muscular tension. The affected upper limb is present with spastic flexor muscles and flaccid extensor muscles. The affected lower limb is present with external rotation and over extension of extensor muscles and spastic and flexed flexor muscles. This stage should be treated by reducing the excess and tonifying the deficiency. For the upper limb, acupoints from the yang meridians including Jianyu (LI 15), Tianjing (TE 10), and Naoshu (SI 10) are selected to tonify the deficient yang. With the help of Neiguan (PC 6), the yang aspects can be produced profoundly with the help of yin aspect. For the lower limb, points from yin meridians including Taichong (LR 3), Sanyinjiao (SP 6), and Taixi (KI 3) are selected to tonify the deficient yin, with the help of points from yang meridians, Yanglingquan (GB 34) and Xuanzhong (GB 39), the yin aspects can be generated profoundly. The above points work together to unblock meridians and collaterals, promote the flow of qi and blood, harmonize yin and yang, inhibit the dominant muscles, and activate the non-dominant muscles, and finally achieve the balance between the flexor and extensor muscles.

Recovery stage: The patient has abandoned comovement through the above treatments, spasticity starts to show improvement, limb function, speech function and sensation are substantially improved, but there are still sequelae such as weakness of limbs, slurred speech, and hemiplegia. At this time, there is an imbalance between yin and yang, qi and blood, because of the disharmony between qi and blood, and blocked meridians and collaterals. Therefore, acupoints are used together to balance yin and yang, unblock meridians and collaterals, lubricate joints, and promote the recovery of limb function, sensation, and speech function.

This study shows that stage-based acupuncture can significantly increase the therapeutic efficacy, decrease Hcy and NSE levels, and heal the neurological function deficit in patients with cerebral infarction. The magnetic resonance spectrum also reveals that stage-based acupuncture can boost the release of NAA, and the elimination of Lac, and promote the reconstruction of neurological function. Therefore, stage-based acupuncture is worth promotion in clinic as an effective approach in treating cerebral infarction.

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Translator: Hong Jue

Received Date: April 10, 2013

R246.6

A

roups of patients all

the same basic treatment, including blood pressure control, anti-coagulation, reducing fibrinogen, and modulating cerebral edema.

Author: Zheng Su, M.M., physician

Luo Qiang, M.M., associate chief physician.

E-mail: taihemzb@163.com