[Characteristics of autonomic neuropathy in patients with vestibular migraine].

Objective: To investigate the characteristics of autonomic neuropathy in patients with vestibular migraine (VM) by sympathetic skin reflex (SSR) and R-R interval variation (RRIV). Methods: Seventy-three patients with interseizure VM and 36 healthy controls in the Department of Neurology affiliated to Shanghai Fourth People's Hospital of Tongji University from November 1, 2019 to December 31, 2021 were prospectively enrolled. SSR and RRIV were performed and relevant parameters were recorded, including SSR latency, SSR amplitude, RRIV during calm breathing (R%), RRIV during deep breathing (D%), RRIV difference between deep breathing and calm breathing (D%-R%), RRIV ratio between deep breathing and calm breathing (D%/R%), and the difference and correlation of various parameters between VM patients and healthy controls were analyzed. Results: Among the 73 patients with VM, there were 12 males and 61 females, and aged (46±13) years. While among 36 healthy controls, there were 6 males and 30 females, and aged (46±7) years. Among the 73 VM patients, abnormal SSR, abnormal RRIV, abnormal SSR and RRIV, and abnormal SSR or RRIV was detected in 38 cases (52%), 17 cases (23%), 11 cases (15%) and 44 cases (60%), respectively. Compared with healthy controls, the lower extremity SSR latency [(1 719±289) ms] in VM patients was longer than that in control group [(1 500±349) ms] (P=0.001), but the upper extremity SSR amplitude [1.6 (0.8, 3.0) mV] was lower than that in control group [2.6 (1.8, 4.2) mV] (P=0.006). SSR amplitude, R% and D% were negatively correlated with age in VM patients (rs=-0.311, P=0.007; rs=-0.237, P=0.043; rs=-0.263, P=0.024, respectively). SSR of lower extremity in VM patients was longer than that of upper extremity [(1 719±289) ms vs (1 244±185) ms, P<0.001], but the amplitude of lower extremity was lower than that of upper extremity [0.8 (0.3, 1.7) mV vs 1.6 (0.8, 3.0) mV, P<0.001]. SSR latency of upper limb was positively correlated with SSR latency of lower limb (r=0.436, P<0.001), the amplitude of upper limb was positively correlated with amplitude of lower limb (rs=0.456, P<0.001), and D% was positively correlated with R% (rs=0.357, P=0.002). Conclusion: The autonomic neuropathy during VM interphase features with imbalance between sympathetic and parasympathetic nervous system, and the sympathetic nerve function is mainly impaired.

[Estradiol regulates the expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats].

Objective: To observe the effects of estradiol on expression of plasma membrane Ca2+-ATPase isoform 2 in inner ear of rats. Methods: Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group. Results: There was no significant difference in serum estradiol and progesterone levels among the five groups before operated(P>0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group (P<0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group (P>0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group (P<0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group (P<0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group (P<0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group (P<0.05) while the expression levels underwent no significantly change in E2 and E2+P groups (P<0.05). Conclusion: The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.

[Changes of serum E2 and Otolin-1 levels in postmenopausal women with BPPV].

Objective:To investigate the changes of serum estradiol（E2） and otolith structural protein Otolin-1 levels in postmenopausal women with benign paroxysmal positional vertigo（BPPV）. Method:Forty postmenopausal women diagnosed as primary BPPV were selected as the experimental group. Meanwhile, 40 postmenopausal women without vertigo during the same time were selected as the control group. 4 ml of fasting peripheral venous blood was extracted in the morning, and E2 and Otolin-1 protein levels in serum of the two groups were detected by electrochemiluminescence（ECL） and ELISA, respectively. Result:①The serum level of E2 in the experimental group was（29.11±15.11） pg/ml, which was lower than that in the control group（37.18±12.24） pg/ml（P=0.010）. ②The serum level of Otolin-1 in the experimental group was（361.55±186.14） pg/ml, which was significantly higher than that in the control group（282.61±139.98） pg/ml（P=0.035）. ③Spearman correlation analysis was carried out on the serum levels of Otolin-1 and E2 in the experimental group and the control group, respectively, and no correlation was found between them（P=0.403 and 0.363, respectively）. ④In the control group, age was negatively correlated with serum E2 level（P=0.044, r=-0.320）, suggesting that age was only weakly correlated with E2 level. However, in the experimental group, there was no correlation between the two（P=0.148）. ⑤There was no correlation between age and serum Otolin-1 level in the two groups（P=0.705 and 0.076, respectively）. Conclusion:Compared with postmenopausal patients without vertigo, the level of E2 in postmenopausal BPPV patients decreased, but the level of Otolin-1 increased significantly. Therefore, the serum level of Otolin-1 may be used as a bio-marker to assist the diagnosis and efficacy evaluation of postmenopausal women with BPPV.

[Analysis of the difference between the results of caloric tests and video head pulse tests in patients with vestibular migraine and vestibular neuritis].

Objective:To compare the results of caloric tests and video head impulse tests (VHIT) in patients with vestibular migraine (VM) and vestibular neuritis (VN), so as to provide help for the differential diagnosis of the two patients. Method:Retrospectively analyze VM and VN patients within 2 weeks of onset from August 1, 2016 to December 31, 2017 in neurology clinic of the Changzheng Hospital of Second Military Medical University, all patients were examined by caloric tests and VHIT, and the results of the two groups were compared and analyzed.Result:The 40 cases of VM patients， among them, 23 cases were abnormal in caloric test, 17 cases showed unilateral canal paresis, 6 cases showed bilateral weakness, the unilateral abnormality rate was higher than that of bilateral abnormality（P<0.01）. 8 cases were abnormal in VHIT, 3 cases had unilateral vestibulo-ocular reflex (VOR) gain decline, 5 cases had bilateral VOR gain decline, unilateral and bilateral VHIT abnormal rate had no difference (P>0.05). The 45 cases of VN patients. Among them, 45 cases were abnormal in caloric test, 37cases showed unilateral canal paresis, 8 cases showed bilateral weakness, the unilateral abnormality rate was higher than that of bilateral abnormality（P<0.001). 35 cases were abnormal in VHIT, 21 cases had unilateral VOR gain decline, 14 cases had bilateral VOR gain decline, unilateral and bilateral VHIT abnormal rate had no difference (P> 0.05). By statistical analysis, the abnormal rate of caloric test of VN and VM were higher than that of VHIT, and the abnormal rate of caloric test and VHIT in VM patients were lower than that of VN. The slow phase velocity (SPV) and the VHIT gain of the three group of semicircular canals of strong and weak caloric response sides in the VM patients were higher than those of the corresponding canals in the VN patients.Conclusion:The low frequency damage of vestibule function of semicircular canals in VN and VM patients is more than that of high frequency. Compared with VM, the high and low frequency damage of the semicircular canals in VN patients are more common(P<0.05), and prone to high and low frequency simultaneous involvement (P<0.001). From the SPV of caloric test and VHIT gain values, the degree of damage to the high and low frequency semicircular canals of in VN patients was more serious than that in VM patients.

[Misdiagnosis and associated costs of benign paroxysmal positional vertigo].

Objective: The aims of this study were to investigate the misdiagnosis of benign paroxysmal positional vertigo (BPPV) and to estimate the associated costs. Methods: During October 2015 to December 2015, eighty patients were diagnosed with BPPV in the outpatient dizziness clinic of Shanghai Changzheng Hospital and the clinical data of all the 80 patients were collected including the demographic and clinical characteristics, the history of diagnosis, inappropriate diagnostic tests, costs of the medical tests, transportation and accommodation. All the data were investigated to estimate the misdiagnosis of benign paroxysmal positional vertigo and the associated costs in Shanghai, China. Results: This study showed that the misdiagnosis rate of BPPV was 60.0% (48/80) and the common inappropriate diagnostic tests for BPPV included Cranial CT and MRI test, cervical MRI, cervical and cerebrovascular investigations et al. There was no significant difference between the misdiagnosis patients (48) and patients without misdiagnosis (32) in gender, age, duration of symptom, involved canal and type of BPPV.Complications were significantly more frequent in the misdiagnosis group than for those without[81.3%(39 /48) vs 34.4%(11 /32)]. The estimated costs for each misdiagnosed individual were 8 502.98 China Yuan (CNY) and one-year economic burden associated with the misdiagnosis of BPPV in Shanghai was 13.184 7-78.862 1 million CNY. Conclusions: Our study suggests that the misdiagnosis rate of BPPV is high and the financial impact on patients and society with this disease is huge. The cost-effective Dix-Hallpike or supine roll test maneuver should be used before applying other expensive medical tests in order to minimize misdiagnosis and the waste of health care resources.

[Etiological analysis on patients in department of vertigo and dizziness oriented outpatient].

Objective: We aimed to explore the spectrum of causes for patients in department of vertigo and dizziness oriented outpatient, in order to provide a reference for diagnosis and treatment of patients with vertigo or dizziness. Methods: Retrospective analysis were carried out with clinical data of patients in our department of vertigo and dizziness oriented outpatient. The target group under study was diagnosed based on the uniform diagnostic criteria, and re-visiting patients were excluded. Results: This clinical study was conducted on 5 348 cases, who visited our vertigo and dizziness oriented outpatient from December 2012 to July 2015. The ratio of male to female was 1∶1.48, the age range was between 16 and 93. The frequencies of different etiology were: benign paroxysmal positional vertigo 1 902(35.56%), Chronic subjective dizziness 1 329(24.85%), vestibular migraine 624(11.67%), Meniere's disease 378(7.07%), multi-sensory neuropathy 231(4.32%), vestibular paroxysmia 177(3.31%), benign recurrent vestibulopathy 171(3.20%), presyncope 66(1.23%), posterior circulation ischemia 57(1.07%), vestibular neuritis 54(1.01%), sudden deafness complicated vertigo 36(0.67%), other reasons 68(1.27%), unknown 255(4.77%). Conclusions: Our study indicates that the precedent three causes for vertigo or dizziness are benign paroxysmal positional vertigo, chronic subjective dizziness and vestibular migraine, followed by Meniere's disease、multi-sensory neuropathy, vestibular paroxysmia and benign recurrent vestibulopathy. Presyncope, posterior circulation ischemia, vestibular neuritis and sudden deafness complicated vertigo are relatively infrequent. There are still a certain proportion of patients undetermined.

[Research status of vestibular migraine].

Pathogenesis, clinical characteristics and treatments of vestibular migraine(VM) in recent years were retrospectively analyzed. The results showed that VM had diversified vestibular symptoms. VM may show a mild central and peripheral vestibular dysfunction during ictal and interictal period. Although no specificity, it could provide important references to identify VM. The pathogenesis of VM, which depended upon the clues of migraine, had been supposed to be probably related to genetic susceptibility, neurotransmitter changes induced by trigeminal nerve, and abnormal integration of central signal, and further exploration of functional abnormalities in brain-related areas showed by functional imaging technology may shed light on the pathogenesis of VM. Until now, the pharmacotherapies of VM have been still based on the treatment of migraine and the efficacy remains to be clarified.

Correlation between endothelial dysfunction, Rho-associated protein kinase activity, C-reactive protein and obstructive sleep apnoea syndrome in male patients.

OBJECTIVE: This study investigated the association between obstructive sleep apnoea syndrome (OSAS) and flow-mediated dilatation (FMD), Rho-associated protein kinase (ROCK) activity, and C-reactive protein (CRP) concentrations in male patients. METHODS: Consecutive patients with symptoms suggestive of OSAS were recruited and divided into non-OSAS (n = 18) and OSAS (n = 32) groups. FMD was measured in the brachial artery; blood samples were taken to measure ROCK activity and CRP concentrations. RESULTS: ROCK activity and CRP concentrations were significantly higher, and FMD was significantly lower, in the OSAS group than in the non-OSAS group. There was a correlation between ROCK activity and FMD. In stepwise multiple regression analyses, the proportion of sleep time spent with an oxygen saturation < 90% was a significant determinant of ROCK activity, while body mass index was the only significant determinant of CRP concentration. The oxygen desaturation index was a significant determinant of FMD. CONCLUSIONS: OSAS increased ROCK activity and was a major determinant of endothelial dysfunction.

Topiramate as an adjunctive treatment for refractory partial epilepsy in the elderly.

This double-blind, placebo-controlled study investigated the efficacy and tolerability of adjunctive topiramate in 86 elderly Chinese patients with refractory partial epilepsy. Patients who had at least four seizures per 4 weeks during an 8-week baseline period, despite medication with up to three standard antiepileptic drugs (AEDs), were randomly assigned to receive topiramate (n = 46) or placebo (n = 40). Topiramate dosages were titrated (target dose 200 mg/day orally) for 8 weeks and maintained at stable levels for another 12 weeks; concomitant AEDs continued at original dosages. All patients completed the study: 47.8% in the topiramate group and 7.5% on placebo reached ≥ 50% reduction in complex partial seizures. In the topiramate group, the most common adverse events were dizziness, somnolence, fatigue, headache and difficulty with memory; most events were transient and mild or moderate in severity. It was concluded that 200 mg/day topiramate was effective and well-tolerated in elderly patients with refractory partial epilepsy.

The influence of mutation at Glu44 and Glu56 of cytochrome b5 on the protein's stabilization and interaction between cytochrome c and cytochrome b5.

To characterize the roles played by Glu44 and Glu56 of cytochrome b5 in the formation of the electrostatic complex between cytochrome c and cytochrome b5, the Glu44, Glu56, or both sites were changed to alanine by site-directed mutagenesis. The influence of these two residues on the protein stability was probed by investigating the kinetic behaviors of protein denaturation in urea or upon heating and the heme-transfer reactions between apo-myoglobin and the variants of cytochrome b5. It has been found that when the Glu44 and/or Glu56 are mutated to alanine, the protein stability increases slightly due to the fact that the hydrophilic residue is changed to a hydrophobic one, resulting in the two pairs of helices surrounding the heme taking a more compact conformation. The difference in voltammetric behavior of cytochrome c, cytochrome b5, and its three mutants, Cyt b5 E44A, E56A, and E44/56A, alone and in 1:1 protein complexes demonstrates that both Glu44 and Glu56 of cytochrome b5 take part in the electrostatic interaction with cytochrome c. The entropy changes, DeltaS degreesrc and enthalpy changes, DeltaH degrees, derived from the temperature dependence of the formal reduction potentials of each protein in different protein systems suggest that, because of the mutual interaction with cytochrome c, cytochrome b5 mutants, especially the E44A-containing mutants, in the protein complexes suffer greater conformational changes upon reduction than that of the wild type. The variation of these thermodynamic parameters indicates that the strength of mutual interactions between cytochrome c and cytochrome b5 or its mutants has the following order: Cyt c/Cyt b5 > Cyt c/Cyt b5 E56A > Cyt c/Cyt b5 E44A > Cyt c/Cyt b5 E44/56A.

Synthesis of the 5'-half molecule of yeast alanine tRNA.

In this paper, we report the synthesis of the 5'-half molecule of yeast alanine tRNA (tRNAAlay) by ligating three oligonucleotide fragments corresponding to the nucleotide sequences 1-13, 14-22 and 23-35 respectively under the catalysis of T4 RNA ligase (Fig. 1). Because of the high purity of the oligonucleotide fragments and the excellent quality of T4RNA ligase and polynucleotide kinase we prepared, the isolation steps were simplified and the overall yields were much higher. The ligating yield of the docosamer (IV) was 75%, that of the pentatriacontamer (V), 90%, and the isolated yield of the final product was 21% calculated on the basis of the tridecamer (III) used in the first reaction. Under the action of T4 RNA ligase the synthetic 5'-half molecule was joined with the natural 3'-half molecule forming a semi-synthetic tRNAAlay, which possessed the biological activities of both accepting (3H)-alanine and incorporating it into proteins. The correctness of the structure of the synthetic 5'-half molecule was verified by both chemical analysis and biological activity assay.