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Clinical analysis of the polymorphism of clopidogrel and aspirin-related genes

Journal of Clinical Neurology.2018;31(6):414-417. doi:10.3969/j.issn.1004-1648.2018.06.005

Objective To analyse the polymorphisms of CYP2C19,GPⅢa,PTGS1,GP1BA genes.Methods The basic information of 159 patients in the department of neurology of our hospital during January 2017 to November 2017 was collected. CYP2C19、GPⅢa、PTGS1、GP1BA genes were detected. Results The average age of the patients was (65.32 +12.71)years old,including 112 men (70.4%)and 47 female (29.6%). As for the CYP2C19*2G681Apolymorphism,there were 58 GG-genotype carriers,82 GA-genotype carriers and 19 AC-genotype carriers. For the CYP2C19*3G636Apolymorphism,there were 141 GG-genotype carriers and 18 GA-genotype carriers,for the CYP2C19*17C806Tpolymorphism,there were 155 CC-genotype carriers and 4 CT-genotype carriers. For the GPⅢa polymorphism,the TT genotype had 157 carriers,and the TC genotype had two carriers. For the PTGS1 polymorphism,there were 159 AA-genotype carriers.For the GP1BA polymorphism,the CC genotype had 136 carriers and the CT genotype had 23 carriers. The distribution of genotypes fitted the Hardy-Weinberg equilibrium for all the polymorphisms,except those of PTGS1.Phenotypes:there were 2 clopidogrel ultra metabolizer (1.3%),47 extensive metabolizer (29.6%),82 intermediate metabolizer (51.6%),and 28 poormetabolizer (17.6%). For aspirin,2 resistance (1.3%)and 157 sensitive (98.7%).Conclusion Clopidogrel poor metabolizer is significantly higher than aspirin resistance.

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Utility of single fiber electromyography in the differential diagnosis of hyperthyroidism associated with ocular myasthenia gravis and Graves ophthalmopathy

Wen-Juan LI ; Yu-Kai WANG ; Jian XIE

Journal of Clinical Neurology.2018;31(6):422-424. doi:10.3969/j.issn.1004-1648.2018.06.007

Objective To assess the utility of single fiber EMG (SFEMG)in the differential diagnosis of hyperthyroidism associated with ocular myasthenia gravis (OMG)and Graves ophthalmopathy.Methods SFEMG was performed in orbicularis oculi muscle of 2 groups of patients.including 32 patients with hyperthyroidism associated with OMG,and 35 patients with Graves ophthalmopathy.The parameters of SFEMG between different groups were compared.Results The mean jitter was (96.2 ± 23.7),(42.8 ± 12.6)μs in hyperthyroidism associated with OMG and patients with Graves Orbitopathy. M50of the percentage of jitter ＞55 μs was 92% and 5% in the 2 groups respectively.M50of the percentage of block was 25% and 0 in the 2 groups respectively.Fiber density was (1.9 ± 0.4)and (1.7 ± 0.5)in the 2 groups respectively.There was significant difference in those parameters of SFEMG between the patients in 2 groups(t＝15.56,Z＝9.26,Z＝7.35,all P＜0.01).Conclusion SFEMG of orbicularis oculi muscle shows significantly increased jitter and block in hyperthyroidism associated with OMG,which can help to differentiate hyperthyroidism associated with OMG from Graves ophthalmopathy.

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Effects of downregulated pregnane X receptor on glutamate-induced expression and activity of P-glycoprotein in the mouse brain microvascular endothelial cells

Yong-Fei CHENG ; Nian YU ; Qing DI

Journal of Clinical Neurology.2018;31(6):450-455. doi:10.3969/j.issn.1004-1648.2018.06.015

Objective To investigate the effects of downregulated pregnane X receptor (PXR)on expression and activity of P-glycoprotein(P-gp)in mouse brain microvascular endothelial cells (mBMEC)exposed to glutamate (GLU)to mimic conditions during seizures. Methods The bEnd.3 cells,were cultured in vitro and treated with culture medium containing 0 μmol,10 μmol,50 μmol,100 μmol GLU for 30 min and exposed to 100 μM GLU for different durations (0 min,15 min,30 min). With PXR knockdown using siRNA,the cells were divided into NC siRNA plus GLU group and siRNA-PXR plus GLU group. Western blotting was used to detect the protein expressions of P-gp and PXR in each group. Immunofluorescence assay was used to detect localization of PXR in cells. The expression of P-gp mRNA was detected by RT-qPCR. Rhodamine123 (Rh123)accumulation assay was used to study the activity of the P-gp in cells.Results PXR and P-gp protein expressions in the 50 μmol and 100 μmol GLU group were significantly higher than that in the blank group(P＜0.05),especially maximal expressions occurred in the 100 μmol GLU group. GLU exposures as short as 15 min and 30 min significantly increased PXR expressions(all P＜0.05);P-gp expression in the 30 min groups was higher than that in the blank group (P＜0.05 ). The data of immunofluorescence analysis suggested that the PXR nuclear accumulation increased in the 100 μM GLU group, compared with the blank group(P＜0.05). Compared with NC siRNA plus GLU group,the protein level of PXR was decreased by approximately 37%[(1.00 ± 0.00)vs(0.63 ± 0.18);t＝3.41,P＝0.02]and the levels of P-gp protein and mRNA were respectively decreased by 43%[(1.00 ± 0.00)vs (0.57 ± 0.09);t＝7.94,P＝0.00] and 52%[(1.00 ± 0.04)vs (0.48 ± 0.08);t ＝10.98,P＝0.00]in the siRNA-PXR plus GLU group. The fluorescence intensity of intracellular Rh123 in the GLU group (0.72 ± 0.01)was lower than that in the blank group [(1.00 ± 0.03);t ＝9.66,P＝0.00]. The fluorescence intensity of Rh123 in the GLU plus verapamil (P-gp inhibitor)group (1.07 ± 0.04)was higher than that in the GLU group (t＝－11.93,P＝0.00). The fluorescence intensity of Rh123 in the siRNA-PXR plus GLU group (0.91 ± 0.03)was higher than that in the NC siRNA plus GLU group[(0.69 ± 0.05);t＝－7.52,P＝0.00]. Conclusions Downregulation of PXR expression results in the inhibition of P-gp expression and activity in the mBMEC exposed to GLU to mimic seizures. PXR may play an important role in the regulation of seizure-induced expression and activity of P-gp in the blood-brain barrier.

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The Clinical and prognosis of PRRT2 gene-related paroxysmal disorders (Report of 1 case)

Chao LIANG ; Dan WANG ; Hu GUO

Journal of Clinical Neurology.2018;31(6):469-471. doi:10.3969/j.issn.1004-1648.2018.06.019

Objective To investigate the clinical features and prognosis of PRRT2-related paroxysmal disorders. Methods Retrospected clinical data of one cases of benign infantile epilepsy diagnosed by gene diagnosis. Results The clinical manifestations of this Children were recurrent convulsions,cluster seizures,and no obvious abnormalities in physical examination. Genetic examination showed mutation of PRRT2 frameshift. Her mother had a history of paroxysmal motor-induced dyskinesia,and her uncle and cousin had a history of convulsions when they were young. The patient did not convulse after oral oxcarbazepine. Conclusions PRRT2 gene-related paroxysmal diseases are characterized by self-limited infantile epilepsy and paroxysmal motor-induced dyskinesia. Genetic diagnosis is needed for definitive diagnosis.The main treatment of this disease is to control epilepsy,and the prognosis is good.

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Determination of serum miR-128 level in patients with first-visit Parkinson’s disease and its related study

Jianying GE ; Wenli ZHU

Journal of Clinical Neurology.2019;32(5):333-336. doi:10.3969/j.issn.1004-1648.2019.05.008

To study the changes of serum miR-128 in patients with first-visit Parkinson’s disease (PD) before and after treatment, and the correlation between serum miR-128 and unified PD rating scale (UPDRS) scores and inflammatory factors in patients with PD. It is helpful to explore the diagnostic value and pathogenesis of miR-128 in PD. Methods Serum miR-128 levels were measured in 54 patients with first-visit PD ( first-visit PD group) before and after treatment, and were compared with 50 cases of healthy controls (healthy control group). The UPDRS scale was evaluated and the serum levels of IL-1β and TNF-α were measured, and the results were analyzed. Results The level of serum miR-128 in first-visit PD group was significantly lower than that in healthy control group (t = 8. 87, P< 0.01 ). After two months of treatment, the level of serum miR-128 in first-visit PD group was significantly higher than that before treatment (t= -5.13, P<0.01), and the UPDRS score was significantly lower than that before treatment (t=9.67, P<0.01). There was a negative correlation between serum miR-128 level and UPDRS score, IL-1β and TNF-α levels in first-visit PD group, respectively ( r= -0.763, r= -0.656, r= -0.674; all P<0.01). The area under the working characteristic curve of serum miR128 was 0.882 (95% CI:0.776-0. 952, P<0.01 ). The sensitivity of diagnosis of PD was 72. 0% , and the specificity was 88. 9%. Conclusion Among the first first-visit PD patients, the level of serum miR-128 is abnormal, and it can be used as a better index of peripheral blood for evaluating the condition and auxiliary diagnosis of PD, which plays an important role in the pathogenesis of depression.

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Autonomic dysfuction and its correlation research in patients with Parkinson’s disease combined with orthostatic hypotension

Hongmei MA ; Shouhua MA

Journal of Clinical Neurology.2019;32(5):337-340. doi:10.3969/j.issn.1004-1648.2019.05.010

To investigate the autonomic dysfunction in patients with Parkinson’s disease ( PD) combined with orthostatic hypotension (OH). Methods Seventy-six PD patients were selected and divided into PD-OH group (n=40) and non-OH group (n=36) after the measurement of blood pressure in the supine to standing position. The scales for outcomes in PD-autonomic test (SCOPA-AUT) was used to evaluate the patients in the two groups. Results There were significant differences in age, duration and Hoehn-Yahr stage between the two groups (all P<0.05). The total value of SCOPA-AUT in the PD-OH group was significantly higher than that in the non-OH group ( P< 0.05 ). The scores of digestive system, urinary system, cardiovascular system, sympathetic/parasympathetic system and sexual function of SCOPA-AUT in the PD-OH group were all significantly higher than those in the non-OH group (all P<0.05). Conclusion The autonomic dysfunction of PD patients with OH is more serious than that of PD patients without OH, and clinical diagnosis and management of PD patients with OH should be strengthened.

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The expression characteristics and significance of peripheral blood lymphocyte programmed death-1 in patients with aneurysmal subarachnoid hemorrhage

Yi GAO ; Yuhang AI

Journal of Clinical Neurology.2019;32(5):368-371. doi:10.3969/j.issn.1004-1648.2019.05.022

By observing the expression of peripheral blood lymphocyte programmed death-1 (PD-1) in patients with aneurysm subarachnoid hemorrhage (aSAH), the expression characteristics and significance in patients with aSAH were explored. Methods A total of 21 patients with aSAH were selected and were divided into neurological symptoms group [ Glaskow Coma Scale ( GCS) <15, 10 cases] and non-neurological symptoms group (GCS=15, 11 cases) according to GCS. And 6 health human were selected as the control group. The expression of CD4 + and CD8 + T lymphocytes in peripheral blood of patients in each group was detected by flow cytometry, and its characteristics and significance were analyzed. Results The percentages of PD-1 + CD4 + T lymphocyte and PD-1 +CD8 + T lymphocytein of non-neurological symptoms group were significantly higher than those in control group, while significantly lower than those in neurological symptoms group ( all P< 0.05 ). The percentages of PD-1 +CD4 + T lymphocyte and PD-1 +CD8 + T lymphocytein were significantly correlated with the GCS score, and the Spearson coefficients were 0.87 and 0.83, respectively (all P<0.05). In the aSAH patients, the incidence of pulmonary infection in neurological symptoms group was significantly higher than that in non-neurological symptoms group (P<0.05), and the percentages of PD-1 +CD4 + T lymphocyte and PD-1 +CD8 + T lymphocytein in pulmonary infection group was significantly higher than that in non-pulmonary infection group ( all P< 0.05 ). Conclusion In patients with aSAH, especially those with neurological symptoms, the expression intensity of CD4 +and CD8 + T lymphocyte PD-1 is significantly increased, which is correlated with the severity of neurological symptoms after aSAH and pulmonary infection after hemorrhage.

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Research progress on diagnosis and application value of CSF exosome in CNS disease

Xiaoxu GE ; Qiuhong JI

Journal of Clinical Neurology.2019;32(5):383-386. doi:10.3969/j.issn.1004-1648.2019.05.028

Exosomes are vesicles released into extracellular cells by fusion of intracellular polyvesicles and cell membranes. Exosomes are secreted by a variety of cells and exist in a variety of body fluids. Exosomes contain proteins, lipids and nucleic acids, which can participate in the information exchange between cells. Exosomes secreted by CNS cells are involved in the occurrence and development of CNS diseases. Recent studies have shown that exosomes can not only serve as early diagnostic markers for CNS diseases, but also have therapeutic potential for CNS diseases. In this paper, the development, diagnosis and treatment of CSF exosomes in CNS diseases were reviewed.

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Research progress of repetitive transcranial magnetic stimulation in the treatment of hemiplegia after cerebral infarction

Di SHAO ; Hanyan LUO

Journal of Clinical Neurology.2019;32(5):394-397. doi:10.3969/j.issn.1004-1648.2019.05.031

Cerebral infarction, also known as ischemic stroke, is a cerebrovascular disease with high disability and fatality rate worldwide. Despite comprehensive rehabilitation therapy on neural function, considerable patients may still suffer from motor functional disabilities, which directly affect their quality of life, ability of daily life, as well as increase the economic burden of patients’ families and society. Therefore, promoting the recovery of motor function is particularly important in patients with cerebral infarction, and this requires more novel therapeutic options in clinical practice. Repetitive transcranial magnetic stimulation is a painless and non-invasive therapy. Accumulating evidences suggest that repetitive transcranial magnetic stimulation can effectively improve the motor function of hemiplegic limb after stroke, and thus improving the patients quality of life. At present, new progress has been made in the basic and clinical studies of repetitive transcranial magnetic stimulation treatment. This review summarized these advances in this field in order to be beneficial to clinical work.

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Effect of carotid atherosclerotic plaque on severity and recurrence of patients with cerebral infarction

Zhanghong XIAO ; Lidong DING ; Kaifu KE

Journal of Clinical Neurology.2015;(4):269-272,280.

Objective To explore the effect of carotid atherosclerotic plaque ( CAP) on severity and recurrence of patients with cerebral infarction ( CI ) .Methods The prospective cohort study was utilized in this research. Existence and type of CAP were detected by Doppler ultrasound, and patients were divided into plaque group and without plaque group.The patients was evaluated by NIHSS on admission and 7 d, 14 d after admission, and patients were followed up for 1 year.The condition of CI recurrence was be observed.Results According to the Doppler ultrasound, patients were divided into plaque group ( 173 cases, 70.3%) and without plaque group ( 73 cases, 29.7%) .Compared with without plaque group, age, NIHSS score and incidences of hypertension, diabetes, hyperlipidemia, hyperfibrinogenemia were significantly increased (P<0.05 -0.01).In the patients who were conducted follow-up, cerebral infarction recurrence was in 39 cases (24.84%) in plaque group, recurrence time was 10.12 month.The recurrence time was 11.82 month in patient with non-vulnerable plaque, it was 10.62 month in patient with mixed plaque, and it was 9.13 month in patient with vulnerable plaque.Cerebral infarct recurrence was in 7 cases (10.45%) in without plaque group, recurrence time was 11.56 month.The recurrence rate in plaque group was significant increased than that in without plaque, however, the recurrence time for without plaque group was longer than that for plaque group ( all P<0.05 ) .The recurrence rate and recurrence time in patient with vulnerable plaque was significantly earlier than that in patient with non-vulnerable plaque (P=0.034).Conclusion The CAP in patients with acute CI can exacerbate the disease, and increase recurrence rate.It is especially in patients with vulnerable plaque.

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