[Analysis of misdiagnosed cases with benign paroxysmal positional vertigo].

OBJECTIVE: To analyze the misdiagnosed cases with benign paroxysmal positional vertigo (BPPV). METHODS: During October 2010 to January 2011, a total of 287 patients with dizziness visited the Dizziness Clinic at Changzheng Hospital, Second Military Medical University. Forty-eight misdiagnosed cases with BPPV were collected and their clinical data were analyzed. All 48 cases were diagnosed by the Dix-Hallpike or Roll test maneuver. RESULTS: (1) CLINICAL FEATURES: there were 38 females and 10 males with an average age of 54 ± 12 years old (range: 31 - 87). Posterior semicircular canal was involved in 75.0% (36/48) whereas the horizontal semicircular and multiple canals in 20.8% (10/48) and 4.2% (2/48) respectively. All patients were treated successfully. And 41 cases (85.4%) were cured on the first visiting day. Recurrences of BPPV occurred in 6 cases during the follow-up. (2) The initial visiting departments consisted of the department of general internal medicine 43.8% (21/48), department of neurology 27.1% (13/48), department of osteology 18.7% (9/48), ear, nose & throat (ENT) department 2.1% (1/48) and other departments 8.3% (4/48). In addition, 68.7% (33/48) of them frequented the general out-patient clinics during their initial visits and the other 31.3% (15/48) used the emergency services. (3) The initial diagnoses included vertebrobasilar insufficiency/cerebral circulation insufficiency 27.1% (13/48), cervical spondylosis 27.1% (13/48), cerebral infarction 4.2% (2/48), Meniere's disease 2.1% (1/48) and others 10.4% (5/48); Besides, 29.1% (14/48) of them had no diagnosis. (4) The average clinic visits per patient were 3.4 times (164 visits/48 cases). (5) The most commonly performed tests included brain computed tomography (CT) (28 person-times), cervical magnetic resonance imaging (MRI) (19 person-times), brain MRI (18 person-times), cervical radiography (18 person-times) and cervical CT (8 person-times). CONCLUSION: In these misdiagnosed cases of BPPV, most of them were middle-aged women. They were most likely to have their first consultations in the departments of general internal medicine and neurology. Therefore these two departments should pay more attention to applying the maneuver of Dix-Hallpike or Roll test so as to reduce the misdiagnosis of BPPV and the waste of healthcare resources.

WNK3-PER1 interactions regulate the circadian rhythm in the suprachiasmatic nucleus in rats.

PER1 is a core component of the internal time-keeping system. In the suprachiasmatic nucleus, it serves as the primary circadian pacemaker in mammalian brains. PER1 functions with other clock components to generate a feedback loop involving the transcriptional repression of gene expression to produce a circadian rhythm with an approximately 24-hour cycle. Post-transcriptional modifications (PTMs) are a basic regulatory mechanism that both perpetuate self-sustained oscillations and interpret metabolic input into circadian physiology by affecting factors such as protein stability, interactions, localization, and activity. Here we examined whether the serine/threonine protein kinase WNK3, which is expressed in a circadian rhythm, can interact and colocalize with PER1 in the SCN. In rats, WNK3 knockdown in the SCN is associated with altered sleep patterns. Moreover, WNK3 can phosphorylate PER1 to promote its degradation and is associated with circadian oscillations when PER1 is expressed in vitro.

Nanoparticles-based anti-aging treatment of Alzheimer's disease.

Age is the strongest risk factor for Alzheimer's disease (AD). In recent years, the relationship between aging and AD has been widely studied, with anti-aging therapeutics as the treatment for AD being one of the mainstream research directions. Therapeutics targeting senescent cells have shown improvement in AD symptoms and cerebral pathological changes, suggesting that anti-aging strategies may be a promising alternative for AD treatment. Nanoparticles represent an excellent approach for efficiently crossing the blood-brain barrier (BBB) to achieve better curative function and fewer side effects. Thereby, nanoparticles-based anti-aging treatment may exert potent anti-AD therapeutic efficacy. This review discusses the relationship between aging and AD and the application and prospect of anti-aging strategies and nanoparticle-based therapeutics in treating AD.

Molecular Mediators of Estrogen Reduction-induced Otolith Shedding.

OBJECTIVE: Previous study suggested that estradiol (E2) plays an important role in otolith shedding by regulating the expression of otoconin 90 (OC90). The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith. METHODS: The rats receiving bilateral ovariectomy (OVX) were used as animal models. Co-immunoprecipitation was used to observe the relationship between estrogen receptor (ER) and estrogen-related receptor α (ERRα). The morphology of otolith was observed under the scanning electron microscopy. Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRα in regulating OC90 expression. RESULTS: The looser otoliths were observed in rats receiving bilateral OVX, which could be reversed by supplementation with E2. The level of ERRα was decreased in bilateral OVX rats. ER and ERRα interacted with each other on the regulation of the expression of OC90. CONCLUSION: Our results suggest ER and ERRα are both important downstream receptors involved in regulating OC90 expression in utricles of rats, and ERRα probably functions by interacting with ER. This provides evidence for the mechanism of otolith shedding. And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.

Evaluation on Effectiveness of a New System as well as Analysis on Optimal Horizontal Eye Position for Vertical Video Head Impulse Test.

OBJECTIVE: To compare the performances among three different systems for video head impulse test (vHIT), and to identify an optimal target angle for precisely evaluating the function of vertical semicircular canals in vHIT. METHODS: A two-center prospective study was done. Participants were sit 1.2 m away from the wall in a noise-proved room that dedicated for vHIT experiments. During the comparison experiments, similar settings were ensured in both hospitals, with the same distance to wall and angle of staring. For each equipment, the procedures followed the developers' recommendations. The same examiner performed the comparison between two systems in one location. For the eye-position projects, targets were placed on the wall sequentially at the pre-marked lines for different angles. For the comparison projects, 9 and 13 participants were recruited, respectively. Any participant with otologic or vestibular disorders was excluded. A total of 26 healthy participants were recruited in the eye-position experiments, 16 of which were further involved in inter-examiner tests. RESULTS: Our evaluations of three different systems showed that a new vHIT system, VertiGoggles® ZT-VNG-I (VG) performed as good as the long-tested Otometrics® ICS impulse (Oto) and EyeSeeCam® (ESC). During the comparison, we validated 25-degree, instead of right ahead at 0 degree, is a better place to set the targets when torsion was applied at vertical semicircular canal planes. CONCLUSION: The new VG system is good for clinical practices. Furthermore, we proposed a new protocol to set the targets 25 degrees from right ahead after tilting head 45 degrees to evaluate vertical canals during vHIT.

The Value of Subjective Visual Vertical in Diagnosis of Vestibular Migraine.

OBJECTIVE: To study the value of the subjective visual vertical (SVV) in the diagnosis of vestibular migraine (VM). METHODS: This study recruited 128 VM patients and 64 age-matched normal subjects. We detected the SVV during the interval between attacks in both groups, in sitting upright, and the head tilted at 45° to the left or right. We then examined the correlation between the SVV results with the vestibular evoked myogenic potential (VEMP) and canal paresis (CP). RESULTS: It was found there was a significant difference in SVV at the upright position between VM patients and normal controls (P=0.006) and no significant difference was found at the tilts of 45° to the left or right between the two groups. The SVV results at the upright position were significantly correlated with cervical VEMP (P=0.042) whereas not significantly correlated with CP and VEMP. There existed no significant difference in the conformity to the Müller effect (M effect) between the two groups. ROC analysis exhibited that the sensitivity, specificity of SVVs at the upright were 67.200% and 62.500% respectively. The diagnostic value of SVV at the upright position was significantly higher than that at tilts of 45° to the left and right (P=0.006). Nonetheless the diagnostic accuracy was relatively low. CONCLUSION: Abnormality in SVV possibly stems from the lasting functional disorder of cerebellar or high-level cortical centers in VM patients or is linked to the vestibular compensation. The SVV is of low diagnostic value for VM and the value of SVV in VM warrants further study.

Relationship between ß-amyloid protein 1-42, thyroid hormone levels and the risk of cognitive impairment after ischemic stroke.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is not only a common consequence of stroke but also an important factor for adverse prognosis of patients. Biochemical indicators such as blood lipids and blood pressure are affected by many factors, and the ability of evaluating the progress of patients with PSCI is insufficient. Therefore, it is necessary to find sensitive markers for predicting the progress of patients and avoiding PSCI. Recent studies have shown that ß-amyloid protein 1-42 (Aß1-42) and thyroid hormone levels are closely related to PSCI, which may be the influencing factors of PSCI, but there are few related studies. AIM: To investigate the relationship between serum levels of Aß and thyroid hormones in acute stage and PSCI and its predicted value. METHODS: A total of 195 patients with acute cerebral infarction confirmed from June 2016 to January 2018 were enrolled in this study. Baseline data and serological indicators were recorded to assess cognitive function of patients. All patients were followed up for 1 year. Their cognitive functions were evaluated within 1 wk, 3 mo, 6 mo and 1 yr after stroke. At the end of follow-up, the patients were divided into PSCI and non-PSCI according to Montreal cognitive assessment score, and the relationship between biochemical indexes and the progression of PSCI was explored. RESULTS: Compared with patients with non-PSCI, the levels of Aß1-42, triiodothyronine (T3) and free thyroxin were lower in the patients with PSCI. Repeated measures analysis of variance showed that the overall content of Aß1-42 and T3 in PSCI was also lower than that of the non-PSCI patients. Further analysis revealed that Aß1-42 (r = 0.348), T3 (r = 0.273) and free thyroxin (r = 0.214) were positively correlated with disease progression (P < 0.05), suggesting that these indicators have the potential to predict disease progression and outcome. Cox regression analysis showed that Aß1-42 and T3 were important factors of PSCI. Then stratified analysis showed that the lower the Aß1-42 and T3, the higher risk of PSCI in patients who were aged over 70, female and illiterate. CONCLUSION: Aß1-42 and T3 have the ability to predict the progression of PSCI, which is expected to be applied clinically to reduce the incidence of PSCI and improve the quality of life of patients.

The effects of different meditation exercises on sleep quality in older people: a network meta-analysis.

BACKGROUND: Chronic sleep loss or sleep disorders is a public health problem affecting older people and cause many health problems. We aim to estimate the effects of different meditation exercises on relieving and improvement of sleep disorders in older people using the pairwise and network meta-analyses. METHODS: Randomized controlled trials, which were published in English and reported on meditation exercises for sleep disorders in the older people, were retrieved from PubMed and EMBASE up to May 2018. Publication bias of the included studies were assessed by the Cochrane Collaboration recommendations. Network meta-analysis was performed by ADDIS, and all test models used random-effects model. Pooled effect sizes were presented with weighted mean differences (WMDs) and 95% confidence interval (CI). RESULTS: A total of ten studies were included in our research. Pairwise comparisons indicated that Qigong could significantly improve the quality of sleep in older people with sleep disorders compared with Activities (WMD = - 4.28, 95% CI - 5.75 to - 2.81). In addition, there were significant differences in Education vs. Usual care (WMD = 2.60, 95% CI 1.03-4.17) and Tai Chi vs. Activities (WMD = - 1.05, 95% CI - 1.73 to - 0.38). With great consistence and convergence, network meta-analysis showed that there was a significant difference in Qigong vs. Activities (WMD = - 4.23, 95% CI - 8.31 to - 0.21). Moreover, Qigong showed a best outcome in relieving sleep disorders, followed by Yoga. CONCLUSIONS: Qigong, Yoga, and Tai Chi improved sleep disorders in the older people, and Qigong intervention had the best effect followed by Yoga. A long-term clinical verification should be needed in the future.

Roles of neuroimage in toxic encephalopathy induced by 1, 2-Dichloroethane.

OBJECTIVES: Toxic encephalopathy induced by exposure to 1,2-dichloroethane(1,2-DCE) may result in central nervous system (CNS) abnormalities. The study was to describe the clinical and neuroimaging features in toxic encephalopathy induced by 1, 2-DCE. PATIENTS AND METHODS: The study evaluates six patients with clinical symptoms and neuroimaging who are exposed to 1, 2-DCE, including medical and neurologic examination, CT imaging, proton MR spectroscopy (MRS), Diffusion weighted MR (DW MR) and T1-and T2-weighted MR imaging. RESULTS: All patients who had been exposed to DCE subsequently had seizures or symptoms of intracranial hypertension,including headache, nausea, and vomiting. CT findings: All lesions appeared as low density and bilateral symmetry. The lesions appeared in white matter of cerebral hemisphere diffusely, bilateral cerebellar dentate nuclei, thalamus and globus pallidus. MRI features: All lesions showed high signal intensity on T2WI. Cerebral sulci swelling and compressed or occluded ventricles were seen on CT and MRI. DW MR images obtained at b = 1000s/mm2 revealed symmetrical high signal intensity changes. The apparent diffusion coefficient (ADC) values of lesions were decreased. MR spectroscopic findings established the spectral patterns: increased choline-containing compounds and decreased N-acetylaspartate. CONCLUSION: The clinical symptoms of intracranial hypertension and the features of CT and MR imagings are useful for early diagnosis and prompt treatment in toxic encephalopathy.

Nanomedicine Strategies for Sustained, Controlled and Targeted Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most devastating diseases worldwide. The current drugs for AD can only ameliorate the symptoms rather than reverse or prevent the progress of AD. On the other hand, blood-brain barrier (BBB), as a natural barrier, significantly impedes drug delivery from the blood circulation into the brain. Nanomedicine can be a safe, effective and promising approach to treat AD. OBJECTIVE: This review summarizes the recent nanomedicine research in this area, including the use of liposomes and nanoparticles (NPs), to provide new approach for targeted treatment of AD. METHOD: Collecting and referring to the related literature in recent 10 years, via searching MeSH Terms "Alzheimer's disease; nanomedicine; nanoparticle; amyloid ß peptide; tau protein; autophagy". RESULTS: Nanomedicines show superiority over conventional anti-AD drugs as a potential weapon against AD by the five proposed mechanisms: many unfavorable pharmaceutical properties of conventional anti-AD drugs maybe greatly overcome by nanomedicine; nanomedicines trigger efficient production of high-titer anti-Aß antibodies following controlled release of antigens by them; some apolipoprotein- based nanomedicines could preferably bind to Aß and increase the elimination of Aß nanomedicine-induced autophagy could be facilitated to increase the elimination of Aß nanomedicineinduced inhibition of tau aggregation. CONCLUSION: Therefore, nanomedicine-mediated drug therapy is promising in the treatment of AD.

Chronic Sleep Restriction Induces Cognitive Deficits and Cortical Beta-Amyloid Deposition in Mice via BACE1-Antisense Activation.

AIMS: To clarify the correlation between chronic sleep restriction (CSR) and sporadic Alzheimer disease (AD), we determined in wild-type mice the impact of CSR, on cognitive performance, beta-amyloid (Aß) peptides, and its feed-forward regulators regarding AD pathogenesis. METHODS: Sixteen nine-month-old C57BL/6 male mice were equally divided into the CSR and control groups. CSR was achieved by application of a slowly rotating drum for 2 months. The Morris water maze test was used to assess cognitive impairment. The concentrations of Aß peptides, amyloid precursor protein (APP) and ß-secretase 1 (BACE1), and the mRNA levels of BACE1 and BACE1-antisense (BACE1-AS) were measured. RESULTS: Following CSR, impairments of spatial learning and memory consolidation were observed in the mice, accompanied by Aß plaque deposition and an increased Aß concentration in the prefrontal and temporal lobe cortex. CSR also upregulated the ß-secretase-induced cleavage of APP by increasing the protein and mRNA levels of BACE1, particularly the BACE1-AS. CONCLUSIONS: This study shows that a CSR accelerates AD pathogenesis in wild-type mice. An upregulation of the BACE1 pathway appears to participate in both cortical Aß plaque deposition and memory impairment caused by CSR. BACE1-AS is likely activated to initiate a cascade of events that lead to AD pathogenesis. Our study provides, therefore, a molecular mechanism that links CSR to sporadic AD.

Interleukin-1ß Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

Sleep alleviates Alzheimer's disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1ß and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1ß and APOEε4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015). Compared to the IL-1ß CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13-2.61, p = 0.010). AD patients carrying the APOEε4 allele and the IL-1ß TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1ß levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1ß-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1ß-31TT genotype and homozygous APOEε4 combined are associated with increased risk of developing AD with sleep disturbance.

[Clinical features of horizontal semicircular canal benign paroxysmal positional vertigo].

OBJECTIVE: To explore the clinical features of horizontal semicircular canal benign paroxysmal positional vertigo. METHODS: The clinical manifestations of 239 patients with horizontal semicircular canal benign paroxysmal positional vertigo from August 2003 to December 2010 were retrospectively analyzed. RESULTS: 25.7% (239/931) of all the benign paroxysmal positional vertigo patients were the horizontal semicircular canal benign paroxysmal positional vertigo was involved. One hundred and ninety-seven patients showed geotropic nystagmus in head rolling test with a mean latency period of (0.88 ± 0.72) s and a mean duration period of (26.36 ± 19.71) s. Forty-two patients showed apogeotropic nystagmus in head rolling test with a mean latency period of (2.69 ± 1.83) s and a mean duration period of (53.48 ± 43.12) s. Among all the horizontal semicircular canal benign paroxysmal positional vertigo patients, 39 (16.3%) presented horizontal nystagmus with slight upbeating component. The nystagmus latency in apogeotropic nystagmus group was longer than that in geotropic nystagmus group (t = -6.33, P < 0.001), and nystagmus duration period was also longer (t = -3.99, P < 0.001). Applied Barbecue maneuver to the patients with geotropic nystagmus, 192 patients were cured after (1.6 ± 0.8) rotations; After applied head shaking maneuver to the patients with apogeotropic nystagmus, 40 patients changed to geotropic nystagmus and cured after (1.9 ± 0.8) rotations. CONCLUSIONS: Incidence rate of horizontal semicircular canal benign paroxysmal positional vertigo was higher than expectation. Barbecue maneuver was applied to patients with geotropic nystagmus. While to the patients with apogeotropic nystagmus, head shaking maneuver should be performed firstly and then followed by Barbecue maneuver.