Zhongxin Zhao

A population-based survey of multiple sclerosis in Shanghai, China.

Objective: To conduct a large population-based survey on multiple sclerosis (MS) prevalence in Shanghai, China. Methods: We established a network of physicians, mainly neurologists, for identifying prevalent patients with MS and systematically checked inpatient registers at each hospital in the study area for patients with a diagnosis of MS, neuromyelitis optica, or other demyelinating disorders. MS diagnosis in patients was validated by senior neurologists according to the McDonald criteria. Results: In total, 123 patients with a validated MS diagnosis from the study population, 8.86 million inhabitants with permanent residence in Shanghai, were alive on the prevalence day. The crude MS prevalence rate was 1.39 cases per 100,000 inhabitants (95% CI: 1.16 to 1.66 cases) in the study population in Shanghai. There were 79 female and 44 male patients with MS, a female-to-male ratio of 1.8. Nearly all (96%) of the patients with validated MS had been examined by MRI. Conclusion: Multiple sclerosis prevalence in Shanghai is in line with that reported for other Asian populations.

Clusterin in Alzheimer’s disease: a player in the biological behavior of amyloid-beta

Alzheimer’s disease (AD) remains a major killer, and although its pathogenesis varies, one dominant feature is an increase in the expression, formation, and sedimentation of senile plaques of amyloid-beta (Aβ) peptides in the brain. The chaperone protein clusterin has, since its first discovery at the end of the 20th century, been labeled as a cytoprotector. However, epigenetic studies showing that clusterin is associated with the severity and risk of AD, especially in the hippocampus, triggered studies to clarify its role in the pathogenesis of AD. It is true that clusterin can inhibit the aggregation of Aβ and therefore prevent further formation of senile plaques in the AD brain, yet it induces the formation of soluble forms of Aβ which are toxic to neurons. Another problematic finding is that clusterin is involved in a pathway through which Aβ has neurodegenerative effects intracellularly. Although the role of clusterin in the pathogenesis of AD is still not clear, this review specifically discusses the interactions between clusterin and Aβ, to open up the possibility of a potential therapeutic approach for treating AD.

Clinical features of patients with multiple sclerosis from a survey in Shanghai, China

Objective To describe clinical features of patients with multiple sclerosis (MS) in Shanghai, China. Methods Prevalent patients with MS were identified and investigated by a network of physicians in 11 districts of Shanghai during the period from 1 September 2004 to 31 August 2005. Admission registries of each hospital in the study area were checked systematically for patients with a diagnosis of MS, neuromyelitis optica or other demyelinating disorders. All patients with collected information were evaluated by four senior neurologists according to the McDonald criteria. Results There were 249 (146 female and 103 male) patients with a confirmed MS diagnosis, at a female-to-male ratio of 1.4. The mean age at onset of MS was 37.4 years for the 249 patients with MS and, on the prevalence day, 42.7 years. The most frequent location of clinical MS lesions in the central nervous system was the spinal cord (61%), followed by the cerebrum (55%) and optic nerves (41%). Nearly all (96%) of the patients with MS had been examined by magnetic resonance imaging, and 226 (94%) patients of those examined were suggestive of MS. No family history of MS was found in any of the patients. Most (86%) of the patients had no or mild disability on the prevalence day (31 December 2004). Almost all (96%) patients with MS had been treated with corticosteroids. Conclusion Clinical features of patients with MS are described based on the information from the largest case series reported among Chinese. Comparisons and discussions are made with findings from the other populations.

Calcineurin contributes to spatial memory impairment induced by rapid eye movement sleep deprivation.

Recent evidence suggests that rapid eye movement (REM) sleep deprivation (REMSD) causes learning and memory deficits. However, the mechanism of REMSD-induced memory impairment remains unclear. Calcineurin (CaN) is involved in synaptic plasticity and is known as a negative constraint on learning and memory. Here we report that 72 h REMSD by the modified multiple platform method in rats resulted in spatial memory impairment in the Morris water maze and elevated hippocampal cytosolic CaN activity, both of which were reversed after 18 h sleep recovery. CaN expression in the whole-tissue homogenate of the hippocampus was not altered by REMSD. The results suggest that elevated hippocampal CaN activity is involved in REMSD-induced spatial memory impairment.

Neuropeptide S mitigates spatial memory impairment induced by rapid eye movement sleep deprivation in rats.

Rapid eye movement (REM) sleep deprivation causes learning and memory deficits. Neuropeptide S, a newly discovered neuropeptide, has been shown to regulate arousal, anxiety, and may enhance long-term memory formation and spatial memory. However, it is unknown whether neuropeptide S could improve the REM sleep deprivation-induced memory impairment. Here, we report that 72-h REM sleep deprivation in rats resulted in spatial memory impairment and reduced phosphorylation level of cAMP-response element binding protein in the hippocampus, both of which were reversed by central administration of neuropeptide S. The results suggest that neuropeptide S mitigates spatial memory impairment in rats induced by 72-h REM sleep deprivation, possibly through activating cAMP-response element binding protein phosphorylation in the hippocampus.

Symptoms and occurrences of narcolepsy: a retrospective study of 162 patients during a 10-year period in eastern China.

OBJECTIVE Our study was designed to assess symptomatology and occurrences of narcolepsy in eastern China between 2003 and 2012. Herein we report the substantial changes in the occurrence and clinical features of narcolepsy over the last decade in China. METHODS We performed a retrospective analysis of 162 Han Chinese patients with narcolepsy at Changzheng Hospital, Shanghai, China. Clinical histories and precipitating factors were recorded, in addition to narcolepsy and H1N1 winter flu pandemic (pH1N1) occurrences at Changzheng Hospital. The occurrences also were compared between the Changzheng Hospital and the Peoples Hospital, Beijing, China. RESULTS In our sample, narcolepsy occurred 1.73 times more frequently in men than in women. Most of the participants were children, which peaked to 91% in 2010. Excessive daytime sleepiness (EDS), disrupted nocturnal sleep, cataplexy, and weight gain were the four major symptoms. We found that 40% of patients had identifiable precipitating factors. The occurrence of narcolepsy in 2010 showed an approximate three-fold difference from the baseline levels at the Changzheng Hospital, which showed positive relationships with occurrences of pH1N1 in Shanghai and the occurrence of narcolepsy at the Peoples Hospital. CONCLUSIONS Our findings show the interactive effects of geography and H1N1 disease in relation to narcolepsy in Han Chinese populations, and strengthen the theoretic hypothesis that immune and mental factors facilitate the onset of narcolepsy.

Serum level of interleukin-6 in Chinese patients with multiple sclerosis

The aim of this study was to investigate the serum concentration of interleukin (IL)-6 in patients with relapsing-remitting MS (RR-MS), compare the difference between males and females, and explore the correlation between the serum concentration of IL-6 and clinical parameters like the current age, the age at onset, disease duration, disability (expanded disability status scale, EDSS), and the number of relapse. We compared the serum concentration of IL-6 in 39 patients with MS and 39 healthy controls matched with sex and age. The serum IL-6 concentration was measured by FlowCytomix. Compared to healthy controls, both the frequency of subjects with detectable level of IL-6 (P=0.005) and the serum concentration of IL-6 (P=0.004) were significantly higher in MS patients. When data were analyzed by gender, statistical significances between MS patients and healthy controls were observed only in females, although the frequency with detectable level and the serum concentration of IL-6 were higher in male MS patients than male controls. The serum level of IL-6 was found to be significantly positively correlated with the number of relapse for female MS patients (r(s)=0.511, P=0.009), with the current age for male MS patients (r(s)=0.700, P=0.005), and with the age at onset for all MS patients (r(s)=0.351, P=0.028). Our results may support that IL-6 is involved in the pathogenesis of MS and indicate that differences exist between male and female patients.

Validation of the rapid eye movement sleep behavior disorder screening questionnaire in China

We validated the Chinese version of the rapid eye movement sleep behavior disorder (RBD) screening questionnaire (RBDSQ) and calculated its cut-off value for idiopathic or symptomatic sleep behavior disorders (iRBD or sRBD) in Chinese people. Patients with RBD (n=63) and controls (n=165) were enrolled. After all subjects had completed a structured interview, the Chinese version of the RBDSQ and the video polysomnography test, we evaluated the reliability, areas under the curves and the best cut-off values of the RBDSQ and investigated the utility of RBDSQ for iRBD and sRBD in China. We found that Cronbachs alpha was 0.769 and the test-retest reliability was 0.916. RBDSQ scores in iRBD and sRBD patients were similar and higher than those in controls. A total of five points represented the best cut-off value for detecting all RBD patients. In Parkinsons disease, a total score of six points represented the best cut-off value for detecting sRBD. There was no statistically significant difference in total RBDSQ score between iRBD and sRBD, or male and female patients. There was no significant correlation between the RBDSQ score and duration or severity of RBD symptoms. The Chinese version of the RBDSQ had high sensitivity, specificity and reliability and could be used as a tool for screening RBD patients in China.

Elevation of serum TNF-α levels in mild and moderate Alzheimer patients with daytime sleepiness

OBJECTIVES Sleep disturbance has been noted to accompany Alzheimer disease and is more pronounced as dementia severity increases. The aim of this study was to examine whether sleep disturbance in a cohort of patients with mild/moderate AD was associated with serum levels of IL-1β and TNF-α. METHODS Forty three drug-free AD patients and twenty two healthy controls were evaluated. All subjects underwent two consecutive full-night polysomnography. Their daytime sleepiness was assessed by Epworth Sleepiness Scale (ESS). Serum levels of IL-1β and TNF-α were measured by enzyme linked immunoassays. RESULTS AD patients showed lower sleep efficiency, more awakenings and less slow wave sleep (SWS). IL-1β was detectable only in two AD patients. Serum TNF-α concentrations did not differ significantly between AD patients and controls. When AD patients were classified as AD patients with daytime sleepiness (n=20, ESS>10) or AD patients without daytime sleepiness (n=23, ESS<10) according to their ESS scores, serum levels of TNF-α was significantly higher in AD patients with daytime sleepiness than that in those without daytime sleepiness or controls (32.7±17.9 vs 5.2±2.4, p<0.05; 40.9±22.3 vs 5.7±2.2, p<0.05). Serum level of TNF-α was significantly correlated with ESS score. DISCUSSION These data indicate that daytime sleepiness in mild and moderate AD patients is associated with elevation of serum TNF-α concentrations.

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.