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Background Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is an uncommon ocular motor disorder which is featured by binocular exotropia and bilateral internuclear ophthalmoplegia.Methods A 71-year-old man with hypertension presented to the emergency department with sudden-onset diplopia. Neurological examination, neuroimaging, blood and cerebrospinal fluid (CSF) testing were performed.Results We presented a typical WEBINO syndrome case with a clear dorsal pontine infarction involving bilateral medial longitudinal fasciculi (MLF) on brain MR scan. The patient’s eye movement abnormalities improved and MR lesions disappeared at 60-day follow-up after treatment of clopidogrel and atorvastatin. Furthermore, we summarised the aetiology and pathophysiology of WEBINO by retrospectively analysing all published WEBINO cases. We found that WEBINO can result from various underlying pathologies, with inflammation most common in the young, and stroke most common in the elderly. Simultaneous lesions of bilateral MLF definitely contribute to the pathophysiology of WEBINO.Conclusions This case underscores the importance of early recognising WEBINO in the emergency department. A timely diagnosis of stroke-induced WEBINO is important so that acute treatment can be considered and for initiating secondary stroke preventive measures to potentially improve the prognosis.

IntroductionKawasaki disease (KD) may increase the risk of myocardial infarction or sudden death. In children, delayed KD diagnosis and treatment can increase coronary lesions (CLs) incidence by 25% and mortality by approximately 1%. This study focuses on the use of deep learning algorithm-based KD detection from cardiac ultrasound images.MethodsSpecifically, object detection for the identification of coronary artery dilatation and brightness of left and right coronary artery is proposed and different AI algorithms were compared. In infants and young children, a dilated coronary artery is only 1-2 mm in diameter than a normal one, and its ultrasound images demonstrate a large amount of noise background-this can be a considerable challenge for image recognition. This study proposes a framework, named Scaled-YOLOv4-HarDNet, integrating the recent Scaled-YOLOv4 but with the CSPDarkNet backbone replaced by the CSPHarDNet framework.ResultsThe experimental result demonstrated that the mean average precision (mAP) of Scaled-YOLOv4-HarDNet was 72.63%, higher than that of Scaled YOLOv4 and YOLOv5 (70.05% and 69.79% respectively). In addition, it could detect small objects significantly better than Scaled-YOLOv4 and YOLOv5.ConclusionsScaled-YOLOv4-HarDNet may aid physicians in detecting KD and determining the treatment approach. Because relatively few artificial intelligence solutions about images for KD detection have been reported thus far, this paper is expected to make a substantial academic and clinical contribution.

Abstract Background With the growing awareness of restless legs syndrome (RLS), sensory disorders similar to RLS but initially confined to the arms, abdomen, and perineum have been reported. One of them is restless abdomen, which refers to a restless sensation in abdomen. Our study is designed to evaluate the clinical phenotype of restless abdomen and investigate its relationship with RLS. Methods We enrolled 10 patients with restless abdomen according to RLS diagnostic criteria, excluding the requiring of leg involvement. Laboratory examinations were performed to exclude mimics and notable comorbidities. Results All 10 patients had RLS like symptoms in the abdomen and otherwise satisfied all other RLS diagnostic criteria, and responded to dopaminergic therapy. Conclusions Neurologists and gastroenterologists should be aware that RLS-related restlessness can occur in extra-leg anatomy in the absence of episodes of worsening or augmentation of restlessness.

Abstract Background Neurological disorders are an economic and public health burden which requires efficient and adequate medical resources. Currently, little is known about the status of the quality of neurological care services available in China. As neurological primary care is mostly provided at the county hospital level, investigation of this geographical level is required. The aim of this study is to evaluate currently available neurology care services in Yangtze River Delta Urban Agglomerations in east China. Methods A multi-site, county-level hospital-based observational survey was conducted in east China from January 2017 to December 2017. A questionnaire was made to assess hospital and the departmental patient care capabilities, human resources and technical capacity in neurology departments. Results Of 228 hospitals across the Yangtze River Delta Urban Agglomerations, 217 documents were returned. Of these, 22 were excluded due to invalid hospital information or duplicate submission. Overall, most hospitals have neurology departments (162, 83.1%) while less than half of the hospitals have a stroke center (80, 41.0%) and neurology emergency department (46, 23.6%). Among 162 hospitals with neurology department, 5 were excluded due to inadequate sharing, leaving 157 hospitals for analysis. About 84.1% of these neurology departments can administer intravenous thrombolysis while about one third of them has the ability to perform arterial thrombectomy (36.9%). In addition, 46.2% of hospitals can carry out computed tomography angiography (CTA) in emergency room. Tertiary care hospitals are much more equipped with modern medical resources compared to the secondary hospitals. In four administrative regions, the neurology services are better in more economically advanced regions. Conclusions Neurological care services need to be enhanced at the county-level hospitals to improve health care delivery.

Abstract Background The prevalence of Restless legs syndrome (RLS) in End Stage Renal Disease (ESRD) patients is higher than that in the general population. However, the associations of RLS within the ESRD population are inconsistent and RLS is usually neglected in dialysis centers, although it impairs the life quality among ESRD patients. We aim to investigate the prevalence of RLS in patients with ESRD undergoing maintenance hemodialysis and evaluate the risk factors of developing RLS and the effect of RLS on quality of life among ESRD patients. Methods ESRD patients undergoing maintenance hemodialysis in Shanghai General Hospital dialysis unit from July 2016 to October 2016 were enrolled in the study. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG). IRLSSG Severity Scale was used to evaluate the severity of RLS. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and Hospital Anxiety and Depression Scale (HADS) was used to estimate anxiety and depression. Serologic and historic variables were analyzed to determine predictors of RLS in the ESRD population. Results A total of 137 ESRD patients were enrolled. The prevalence of RLS among the ESRD patients was 20.44%. The risk of RLS was increased significantly in females (OR = 2.729, p = 0.032) and daily alcohol drinkers (OR = 4.716, p = 0.022). RLS increased the risks of sleep disorders (25/28, 89.3% vs 73/109, 67.0%, p = 0.02) and sedative hypnotics intake (7/28, 25.0% vs 10/109, 9.2%, p = 0.047) and impaired the sleep quality (7/109 vs 11/28, p = 0.001) according to PSQI sum scores. Conclusion A high RLS prevalence among the ESRD patients undergoing hemodialysis was confirmed. ESRD patients who are women and drinking alcohol have a higher risk of RLS. The sleep quality was significantly impaired and sleeping medication use was more common among the ESRD patients with RLS.

The epigenetic modifications, such as DNA methylation and histone acetylation, play a critical role in the pathogenesis of Parkinson's disease (PD). However, the relationship between DNA methylation and histone acetylation in PD is not fully understood. Previous studies have shown that patients with PD exhibit an epigenetic and transcriptional upregulation of Ten-Eleven Translocation 2 (TET2), a member of the DNA hydroxylases family. Silence information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, also plays a critical role in PD development and might be a potential target for PD therapy. Our previous data indicated that demethylation in the Cyclin-dependent kinase inhibitor 2A (CDKN2A) promoter by the TET2 directly activated its expression, then promoted the cell cycle arrest and cell death induced by 1-methyl-4-phenyl-pyridinium ion (MPP+). In this study, we found that the enzyme activity of SIRT1 is negatively correlated with the protein level of TET2. In addition, the deacetylation of TET2 induced by SIRT1 promotes TET2 degradation via the ubiquitin–proteasome pathway. Furthermore, the activation of endogenous SIRT1 by resveratrol (RV) leads to CDKN2A DNA hypermethylation due to the decreased TET2 protein levels, which relieves the inhibitory effect on CDK4 and upregulation of pRb, allowing cell proliferation and growth. Similar effects are observed for the inhibition of endogenous TET2 enzyme activity with TET2 inhibitor. Together, we discover a new mechanism by which the SIRT1-TET2-CDKN2A pathway is involved in the pathogenesis of PD, which may provide a potential target for PD treatment.

Objective: To determine the association between serum phosphate level and 1-year clinical outcomes in patients with acute ischemic stroke and transient ischemic attack.Methods: We included 7,353 patients with acute ischemic stroke and transient ischemic attack from the China National Stroke Registry III for analysis. Participants were divided into 4 groups according to serum phosphate quartiles. Composite end point included recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Poor functional outcome is defined as modified Rankin Scale score of 3 to 6. Multivariable Cox regression or logistic regression was used to evaluate the independent association of serum phosphate with 1-year all-cause mortality, recurrent stroke, composite end point and poor functional outcome.Results: The mean age of the included 7,353 patients was 62.5 years, and 68.6% of them were men. Plotting hazard ratios over phosphate levels suggested a U-shaped association especially for recurrent stroke and composite end point, and therefore the third quartile group was set as reference group. Compared with the third quartile of phosphate (1.06–1.20 mmol/L), the adjusted hazard ratios/odds ratios (95% CI) of the lowest quartile (

Impulse control disorders (ICDs) in Parkinson's disease (PD) are aberrant behavior such as pathological gambling, hypersexuality, binge eating, and compulsive buying, which typically occur as a result of dopaminergic therapy. Numerous studies have focused on the broad spectrum of ICDs-related behaviors and their tremendous impact on patients and their family members. Recent advances have improved our understanding of ICDs. In this review, we discuss the epidemiology, pathogenesis and treatment of ICDs in the setting of PD.

Previous studies have reported the anti-oxidant, anti-inflammatory, and anti-cancer effects of fisetin. However, the therapeutic efficacy of fisetin in Parkinson’s disease (PD) is unclear. In this study, we demonstrated that fisetin could markedly alleviate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in mice. To confirm the reported correlation between gut microbiota and PD, the bacterial DNA in the fresh feces of mice from each group was subjected to 16S rRNA (V3 and V4 regions) sequencing. The results revealed that fisetin changed the number, diversity, and distribution of gut microbiota in MPTP-induced mice model of PD. The alpha and beta diversity analyses showed that the fisetin intervented MPTP group gut microbiota exhibited a significantly higher abundance of Lachnospiraceae and a significantly lower abundance of uncultured_bacterium_g_Escherichia-Shigella and uncultured_bacterium_g_Bacillus than the MPTP group gut microbiota. These findings indicated that fisetin exerts a neuroprotective effect on neurodegeneration by altering the composition and diversity of gut microbiota. Thus, fisetin could be a potential novel therapeutic for PD.

Objective: To investigate the application of optical coherence tomography angiography (OCTA) in cerebral small vessel disease (SVD), ischemic stroke and dementia.Methods: We conducted a systematic search in MEDLINE (from inception) and EMBASE (from 1980) to end 2019 for human studies that measured retinal parameters in cerebral SVD, ischemic stroke, and dementia using OCTA.Results: Fourteen articles (n = 989) provided relevant data. Ten studies included patients with Alzheimer disease (AD) and mild cognitive impairment (n = 679), two investigated pre-symptomatic AD participants (n = 154), and two investigated monogenic SVD patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (n = 32) and Fabry disease (n = 124). Methods to reduce bias and risk factor adjustment were poorly reported. Substantial methodological variations between studies precluded a formal meta-analysis. Quantitative measurements revealed significant yet inconclusive changes in foveal avascular zone, perfusion density, and vessel density (VD) in AD, presymptomatic AD, and SVD patients. Two (n = 160) of three studies (n = 192) showed association between decreased VD and increased white matter hyperintensities. In three (n = 297) of seven studies (n = 563), better cognitive function was associated with increased VD. One study (n = 52) suggested increased VD was associated with increased ganglion cell–inner plexiform layer thickness in AD yet with no covariate adjustment.Conclusions: Changes in retinal microvasculature identified using OCTA are associated with monogenic SVD and different stages of AD, but data are limited and partly confounded by methodological differences. Larger studies with risk factors adjustment and more consistent OCTA methods are needed to fully exploit this technology.PROSPERO registration number: CRD42020166929.

Background: Essential tremor (ET) is manifested as an isolated syndrome of bilateral upper limb action tremor. Parkinson's disease (PD) is the second most common neurodegenerative disease, with typical motor symptoms of bradykinesia, rigidity, and resting tremor. ET-PD describes the new-onset of PD in ET patients. Recently, numerous studies on epidemiology, genetics, pathology, clinical features, and neuroimaging studies are challenging the idea that ET is an isolated disease, suggesting that patients with ET have the tendency to develop PD.Methods: In this review article, we collected recent findings that reveal prodromal markers of PD in patients with ET.Results: Substantia nigra hyperechogenicity serves as a prodromal marker for predicting the development of PD in patients with ET and provides a reference for therapeutic strategies. Additional potential markers include other neuroimaging, clinical features, heart rate, and genetics, whereas others lack sufficient evidence.Conclusion: In consideration of the limited research of PD in patients with ET, we are still far from revealing the prodromal markers. However, from the existing follow-up studies on ET patients, Substantia nigra hyperechogenicity may enable further exploration of the relationship between ET and PD and the search for pathogenesis-based therapies.

BackgroundSelective loss of dopaminergic neurons and diminished putamen gray matter volume (GMV) represents a central feature of Parkinson’s disease (PD). Recent studies have reported specific effects of kinectin 1 gene (KTN1) variants on the putamen GMV.ObjectiveTo examine the relationship of KTN1 variants, KTN1 mRNA expression in the putamen and substantia nigra pars compacta (SNc), putamen GMV, and PD.MethodsWe examined the associations between PD and a total of 1847 imputed KTN1 single nucleotide polymorphisms (SNPs) in one discovery sample [2,000 subjects with PD vs. 1,986 healthy controls (HC)], and confirmed the nominally significant associations (p < 0.05) in two replication samples (900 PD vs. 867 HC, and 940 PD vs. 801 HC, respectively). The regulatory effects of risk variants on the KTN1 mRNA expression in putamen and SNc and the putamen GMV were tested. We also quantified the expression levels of KTN1 mRNA in the putamen and/or SNc for comparison between PD and HC in five independent cohorts.ResultsSix replicable and two non-replicable KTN1-PD associations were identified (0.009 ≤ p ≤ 0.049). The major alleles of five SNPs, including rs12880292, rs8017172, rs17253792, rs945270, and rs4144657, significantly increased risk for PD (0.020 ≤ p ≤ 0.049) and putamen GMVs (19.08 ≤ β ≤ 60.38; 2.82 ≤ Z ≤ 15.03; 5.0 × 10–51 ≤ p ≤ 0.018). The risk alleles of five SNPs, including rs8017172, rs17253792, rs945270, rs4144657, and rs1188184 also significantly increased the KTN1 mRNA expression in the putamen or SNc (0.021 ≤ p ≤ 0.046). The KTN1 mRNA was abundant in the putamen and/or SNc across five independent cohorts and differentially expressed in the SNc between PD and HC in one cohort (p = 0.047).ConclusionThere was a consistent, significant, replicable, and robust positive relationship among the KTN1 variants, PD risk, KTN1 mRNA expression in putamen, and putamen volumes, and a modest relation between PD risk and KTN1 mRNA expression in SNc, suggesting that KTN1 may play a functional role in the development of PD.

Objective: Iron deficiency anemia (IDA) is a well-known cause of secondary restless legs syndrome (RLS). Iron deficiency without anemia (IDNA) is insidious, and its association with RLS is less evaluated. We investigate prevalence and features of IDNA in a consecutive cohort of patients with RLS.Methods: We included sequential primary RLS patients and RLS patients with IDA. We also recruited age- and gender-matched healthy controls. RLS mimics and other comorbidities were carefully excluded.Results: One-hundred and ninety-six RLS patients without anemia, 26 RLS patients with IDA, and 63 controls were included. 42.3% of RLS patients without anemia had iron deficiency. Women were much more susceptible for IDNA with a relative risk of 5.51 (p < 0.0001). Women with IDNA and RLS had younger age both at interview and at RLS onset compared to women with RLS without iron deficiency (NID) (P < 0.01). IDNA RLS patients showed a tendency to higher risk of severe/very severe tiredness or sleepiness during the day as compared to NID RLS patients. Furthermore, IDNA RLS patients had longer duration of RLS (P < 0.01 in men, P < 0.05 in women) and younger age at onset (only in men, P < 0.05) compared to IDA RLS patients.Conclusion: IDNA is frequent in RLS and iron deficiency may be severe despite a normal hemoglobin level. Women are at much higher risk for IDNA, and IDNA in women presents some specific clinical features. Features of IDNA RLS are different from IDA RLS. Regular screening of peripheral iron parameters even in patients with normal blood counts is recommended for timely optimal management.

Abstract Background Rapid eye movement sleep behavior disorder (RBD) and Parkinson’s disease (PD) are two distinct clinical diseases but they share some common pathological and anatomical characteristics. This study aims to confirm the clinical features of RBD in Chinese PD patients. Methods One hundred fifty PD patients were enrolled from the Parkinson`s disease and Movement Disorders Center in Department of Neurology, Shanghai General Hospital from January 2013 to August 2014. This study examined PD patients with or without RBD as determined by the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), assessed motor subtype by Unified PD Rating Scale (UPDRS) III at “on” state, and compared the sub-scale scores representing tremor, rigidity, appendicular and axial. Investigators also assessed the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Parkinson’s disease Sleep Scale (PDSS). Results One hundred fourty one PD patients entered the final study. 30 (21.28%) PD patients had probable RBD (pRBD) diagnosed with a RBDSQ score of 6 or above. There were no significant differences for age, including age of PD onset and PD duration, gender, smoking status, alcohol or coffee use, presence of anosmia or freezing, UPDRS III, and H-Y stages between the pRBD+ and pRBD− groups. pRBD+ group had lower MMSE scores, higher PDSS scores, and pRBD+ PD patients had more prominent proportion in anxiety, depression, constipation, hallucination and a greater prevalence of orthostatic hypotension. Conclusion pRBD+ PD patients exhibited greater changes in non-motor symptoms. However, there was no increase in motor deficits.

Parkinson's disease (PD) is a common neurodegenerative disease, characterized by typical motor symptoms and various non-motor symptoms (NMS). Parkinson's disease dementia (PDD) is one common NMS, with high prevalence, disability rate, and poor response to treatment. Recently there have been increasingly new findings in clinical and experimental studies on PDD. This review focuses on its epidemiology, neuropsychological characteristics, predictive factors, diagnosis and pharmacotherapy from clinical perspective so as to promote its research in China. DOI: 10.3969/j.issn.1672-6731.2017.02.003

Microglia-mediated neuroinflammation contributes to multiple neurodegenerative disorders, including PD. Therefore, the regulation of microglial activation probably has the therapeutic potential. This study is aimed to determine whether NBP could suppress microglial activation and protect dopaminergic neurons from excessive neuroinflammation. In the present study, MPTP-induced PD model was established to explore the neuroprotective and anti-inflammatory effect of NBP. We assessed motor deficits, dopaminergic neurodegeneration and microglial activation in PD mice. In vitro, the anti-inflammatory activity of NBP was confirmed by cell viability assay of SH-SY5Y cells after being treated with conditioned medium from LPS-stimulated BV-2 cells and from 1-Methyl-4-phenylpyridinium iodide (MPP+)-stimulated BV-2 cells. The expression of pro-inflammatory molecules was determined by RT-PCR, Western Blot and ELISA assay. The generation of NO and ROS were also assessed. The involvement of signaling pathways such as MAPK, NF-κB, and PI3k/Akt were further investigated by Western Blot and immunofluorescence assay. The neuroprotective effect of NBP was demonstrated in vivo as shown by the improvement of dopaminergic neurodegeneration, motor deficits and microglial activation in MPTP-induced mouse model of PD. The expression of pro-inflammatory mediators was also reduced by NBP administration. In vitro, NBP also protected dopaminergic neurons from neurotoxicity induced by activated microglia. NBP pretreatment not only reduced pro-inflammatory molecules, but also suppressed NO release and ROS generation in BV-2 cells. Further mechanism research suggested that the inactivation of MAPK, NF-κB and PI3K/Akt may involve in anti-neuroinflammation role of NBP. In conclusion, our results revealed that NBP exerted dopaminergic neuroprotection through inhibition of microglia-mediated neuroinflammation, suggesting the promising therapeutic effect of NBP for PD.

Silent mating type information regulation 2 homolog 1 (Sirt1), a nicotine adenine dinucleotide (NAD+)-dependent enzyme, is well-known in playing a part in longevity. Ischemic stroke is a major neurological disorder and is a leading cause of death and adult disability worldwide. Recently, many studies have focused on the role of Sirt1 in ischemic stroke. Numerous studies consider Sirt1 as a protective factor and investigate the signaling pathways involved in the process under ischemic stress. However, the answer to whether upregulation of Sirt1 improves the outcome of stroke is still a controversy. In this review, we discuss the role and mechanisms of Sirt1 in the setting of ischemic stroke.

Background: This study aimed to examine the effect of disease management program (DMP) on the patients with first-time ischemic stroke (IS). Methods: A DMP with 4 parts of performance indicators (PIs, including outpatient, emergency department, inpatient and follow-up treatment) was implemented in patients with stroke in 2 hospitals (Hospital T and R) in Shanghai China from 2007-2010. The effect of DMP on the outcome of IS patients was analyzed according to the criteria of the National Institute of Health Stroke Scale (NIHSS). Furthermore, the total effective rate of DMP, average length of stay, hospitalization cost, and cost-effectiveness ratio (CER) between DMP and non-DMP patients were calculated, followed by the cost-effectiveness analysis. Results: The total effective rate of DMP (T: 69.9%; R: 76.6%) was significantly (P

As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α) plays an important role in the pathogenesis of Parkinson’s disease (PD). HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD). Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI) may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms. In this study, we examined the therapeutic benefit of a new HIF-PHI, FG-4592, which is currently in phase 3 clinical trials to treat anemia in patients with chronic kidney diseases (CKD) in PD models. FG-4592 attenuates MPP+ -induced apoptosis and loss of tyrosine hydroxylase (TH) in SH-SY5Y cells. Pretreatment with FG-4592 mitigates MPP+-induced loss of mitochondrial membrane potential (MMP), mitochondrial oxygen consumption rate (OCR), production of reactive oxygen species (ROS) and ATP. Furthermore, FG-4592 counterbalances the oxidative stress through up-regulating nuclear factor erythroid 2 p45-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and superoxide dismutase 2 (SOD2). FG-4592 treatment also induces the expression of Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) through increasing the phosphorylation of AMP-activated protein kinase (AMPK). In MPTP-treated mice, FG-4592 protects against MPTP-induced loss of TH-positive neurons of substantia nigra and attenuates behavioral impairments. Collectively, our study demonstrates that FG-4592 is a promising therapeutic strategy for PD through improving the mitochondrial function under oxidative stress.