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Objective: To strengthen the clinicians' understanding of the clinical characteristics of patients with negative MOGADD antibody. Methods: The clinical data of 23 MOGADD patients with antibody negative conversion who were hospitalized in the Department of Neurology, the First Affiliated Hospital of China Medical University in Shenyang, Liaoning Province from March 2020 to August 2022 were retrospectively analyzed. The general situation, clinical characteristics, laboratory tests, imaging data, antibodies, treatment and follow-up of the patients were analyzed and summarized. Results: The clinical data of 23 patients with MOGADD were retrospectively analyzed. Most of the patients were adult women, and the onset was vision loss. For the 9 MOGAD patients who turned negative after MOGAD treatment (98.9±26.2 days), the treatment time for the antibody turned negative in the earliest one month and the most recent four months was much shorter than that for the 14 persistent MOGAD positive patients (146.7±27.8 days) (p＜ 0.001, statistically significant difference) suggested that the MOGAD therapy-negative group recovered faster than the MOGAD persistently positive group. The treatment time of MOGADD patients with different titers was inconsistent (p＜0.001, the difference was statistically significant) suggested that the higher the titer in the MOGAD treatment negative group, the later the antibody turned negative, and the higher the titer in the persistent MOGAD positive group, the longer the treatment duration. MOGADD patients had increased cerebrospinal fluid chloride (p＜0.05, the difference was statistically significant)suggested that compared with the MOGAD persistent positive group, the increase of cerebrospinal fluid protein was more common in the MOGAD who turned negative after MOGAD treatment, and the MOGAD persistent positive group had more increased cerebrospinal fluid chloride. In the MOGAD treatment negative group, there were multiple long T2 signal shadows in the head (6/9 cases) and multiple short-segment lesions in the spinal cord MRI, while in the MOGAD continuous positive group, there were multiple patchy long T2 signal shadows and more common in the pons (3/14 cases), and most of the spinal cord MRI of the patients were diffuse long segment and single lesion (p＜0.05, the difference was statistically significant). Therefore, it is concluded that, different from the long segment and single lesion in the spinal cord MRI of the MOGAD continuous positive group, the head MRI lesions of the MOGAD treatment negative group are mostly in the pons and the spinal cord lesions are mostly short segment and multiple lesions. Among the 23 MOGAD patients in this study, 14 (14/23 cases) recurs after MOGAD treatment. The number of MOGAD negative group (1/9 cases) was much less than that of MOGAD persistent positive group (13/14 cases) (p＜0.001, the difference was statistically significant), which suggested that the recurrence rate in the MOGAD who turned negative after MOGAD treatment (11.1%) was much lower than that in the MOGAD who remained positive (92.9%). Conclusion: Compared with antibody-positive patients, antibody-negative MOGADD patients have their own clinical and imaging characteristics, low recurrence rate and good prognosis.

Background. We aimed to examine the differences of clinical characteristics between patients with ischemic stroke with active cancer and those without cancer to develop a clinical score for predicting the presence of occult cancer in patients with ischemic stroke. Methods. This retrospective study enrolled consecutive adult patients with acute ischemic stroke who were admitted to our department between December 2017 and January 2019. The demographic, clinical, laboratory, and neuroimaging characteristics were compared between patients with ischemic stroke with active cancer and those without cancer. Multivariate analysis was performed to identify independent factors associated with active cancer. Subsequently, a predictive score was developed using the areas under the receiver operating characteristic curves based on these independent factors. Finally, Bayesian decision theory was applied to calculate the posterior probability of active cancer for finding the best scoring system. Results. Fifty-three (6.63%) of 799 patients with ischemic stroke had active cancer. The absence of a history of hyperlipidemia (odds ratio OR = 0.17 , 95% confidence interval (CI): 0.06–0.48, P < 0.01 ), elevated serum fibrinogen ( OR = 1.72 , 95% CI: 1.33–2.22, P < 0.01 ) and D-dimer levels ( OR = 1.43 , 95% CI: 1.24–1.64, P OR = 22.87 , 95% CI: 9.91–52.78, P < 0.01 ) were independently associated with active cancer. A clinical score based on the absence of hyperlipidemia, serum fibrinogen level of ≥4.00 g/L, and D-dimer level of ≥2.00 μg/mL predicted active cancer with an area under the curve of 0.83 (95% CI: 0.77–0.89, P < 0.01 ). The probability of active cancer was 59% at a supposed prevalence of 6.63%, if all three independent factors were present in a patient with ischemic stroke. Conclusions. We devised a clinical score to predict active cancer in patients with ischemic stroke based on the absence of a history of hyperlipidemia and elevated serum D-dimer and fibrinogen levels. The use of this score may allow for early intervention. Further research is needed to confirm the implementation of this score in clinical settings.

The purpose of our study was to investigate the correlation between neural-derived plasma exosomal amyloid-β (Aβ)42, total tau (T-tau) and tau phosphorylated at threonine 181 (P-T181-tau) protein levels and cognitive impairment in patients with obstructive sleep apnea (OSA).There were 122 subjects without dementia included in the study: 27 patients with OSA and mild cognitive impairment (MCI), 52 OSA patients without MCI, and 43 subjects diagnosed with simple snoring but not MCI as the control group. Neuronal-derived exosomal proteins were measured by ELISA kits for Aβ42, T-tau and P-T181-tau. The cognitive function was evaluated by a Chinese version of the Montreal Cognitive Assessment (MoCA) questionnaire, and a normal cognitive score was ≥26.The exosomal Aβ42, T-tau and P-T181-tau levels in the OSA with MCI group were higher than those in the OSA group. The Aβ42, T-tau, and P-T181-tau levels in the plasma neuronal-derived exosomes were associated with an increased risk of cognitive impairment in OSA patients after additional adjustment for age, gender, education, vascular risk factors, apnea-hypopnea index (AHI) or oxygen reduction index (ODI). Furthermore, there were also significant associations between Aβ42, T-tau, and P-T181-tau in neural-derived plasma exosomes and Epworth Sleepiness Scale, AHI, and ODI in OSA patients. After 1 year of continuous positive airway pressure (CPAP) intervention, the neuronal-derived exosome levels of Aβ42, T-tau, and P-T181-tau were significantly lower than those at baseline (P = 0.001, P = 0.012, and P = 0.034).These findings indicate that peripheral blood levels of neuronal-derived exosomal Aβ and tau proteins were increased in OSA patients with cognitive impairment. CPAP interventions could possibly improve cognitive function and be associated with decreased levels of exosomal Aβ and tau proteins.

Post-stroke cognitive impairment (PSCI) is a common symptom of stroke and affects the quality of life and prognosis of stroke survivors. In our study, we evaluated the efficacy of Human urinary kallidinogenase (HUK) on cognitive function in acute ischemic stroke (AIS) patients, and discussed the role of cystatin C (CysC) in improving PSCI.We enrolled a retrospective cohort with prospective follow-up. From August 2020 to May 2021, 130 patients completed the final follow-up. Among them, 61 patients received HUK combined with basic treatment, which we defined as the HUK group, and 69 patients received basic treatment, which we defined as the control group. We compared the changes of CysC, urea nitrogen and creatinine levels after one week of treatment between the two groups. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at 3-month after AIS.No significant differences in demographic data and Laboratory tests between two groups before treatment. A total of 67 patients (51.5%) were diagnosed as PSCI at 3-month follow-up, among which, 25 patients were in the HUK group and 42 patients were in the control group. Compared with the control group (60.9%), the incidence of PSCI was significantly lower in the HUK group (41.0%). In addition, the serum CysC level after a week of treatment significantly decreased from baseline in HUK group (HUK can reduce the risk of PSCI at 3-month in AIS patients. The decrease of serum CysC level may be one of the mechanisms by which HUK reduces the incidence of PSCI.

Background Recreational N2O abuse is an important etiology of neurological impairment in young patients, which may easily be ignored clinically. Few current studies have investigated the characteristics or the effects experienced by its users. We aimed to explore any correlation between the clinical severity and biomarkers and spinal magnetic resonance imaging (MRI) abnormalities, identify independent factors associated with spinal MRI abnormalities, and ascertain factors affecting depression/anxiety in patients with N2O‐related neurological disorders. Methods Patients with N2O‐related neurological disorders were enrolled retrospectively between February 2017 and July 2020. Their demographic, clinical, laboratory, neuroimaging, electrophysiological, and neuropsychological findings were analyzed. Correlation analyses were conducted using Spearman's or Pearson's correlation and linear regression analysis. Independent factors associated with spinal MRI abnormalities were identified using univariate and multivariate analyses. Results The principal clinical manifestations of N2O‐related neurological disorders (n = 63; 38 men, 25 women; mean age ± SD: 22.60 ± 4.46 years) were sensory disturbance, followed by gait disturbance and pyramidal tract damage. A significant negative correlation existed between serum vitamin B12 levels and clinical severity (r = −0.309, p = .014), which disappeared after linear regression. An interval of less than 6 months between initial N2O abuse and hospitalization was independently associated with spinal MRI abnormalities (39.47% vs. 72.00%, respectively; χ 2 = 6.40, p = .01). Thirty‐eight (60.32%) and 40 (63.49%) patients experienced anxiety and depression, respectively. Moreover, the higher the clinical scores/serum homocysteine levels, the greater the severity of anxiety/depression (r = 0.442, p, We develop a research to explore any correlation between clinical severity and biomarkers and spinal magnetic resonance imaging (MRI) abnormalities, identify independent factors associated with spinal‐MRI abnormalities, and ascertain factors affecting depression/anxiety in patients with N2O‐related neurological disorders.

Background: Apathy is a multidimensional syndrome referring to a primary lack of motivation, frequent in survivors of stroke. And prior studies have demonstrated the negative effect of apathy on recovery from stroke. Methods: A randomized controlled study of acute stroke patients. Four hundred and eighty-eight patients without evidence of apathy or depression at the initial visit were consecutively recruited, 258 males and 230 female. Patients were block randomized into 2 groups. Group A (n = 245) and Group B (n = 243) had physiotherapy according to Motor Relearning Program and Bobath in the first 4 weeks, respectively. The supplemental treatment did not differ in the 2 groups. Patients were assessed with Apathy Evaluation Scale-Clinical, National Institutes of Health Stroke Scale scores, Barthel Index scores, Mini-Mental State Examination scores, Hamilton Depression Scale scores, and Hamilton Anxiety Scale scores upon admission. At 1-, 3-, 6-, 9-, and 12-month follow-up after stroke, patients were assessed for diagnosis and severity of apathy using the Apathy Evaluation Scale-Clinical. Results: Baseline characteristics of the subjects are age mean 65.1 (standard deviations, SD 10.9); 47.1% female; Apathy Evaluation Scale-Clinical mean 24.9 (SD 4.7); National Institutes of Health Stroke Scale mean 3.9 (SD 3.8); Barthel Index mean 87.9 (SD 8.7); Mini-Mental State Examination mean 23.3 (SD 4.5); Hamilton Depression Scale mean 17.5 (SD 6.6); and Hamilton Anxiety Scale mean 14.4 (SD 6.2). Participants in both groups had similar levels of apathy symptoms at study admission (Motor Relearning Program, mean = 24.78, SD = 4.62; Bobath, mean = 25.07, SD = 4.75). The Apathy Evaluation Scale scores of participants in both groups demonstrated to decline gradually from month 1 to month 12. Motor Learning Program participants had significantly less apathy severity compared with Bobath participants with respect to each time point. Participants given Bobath approach were 1.629 times more likely to develop poststroke apathy than patients given Motor Relearning Program over 12 months. Conclusions: Physiotherapy treatment in acute stroke rehabilitation using Motor Relearning program was significantly more effective in preventing of new onset of apathy following stroke compared with Bobath approach.

The existence of the blood–tumor barrier (BTB) severely hinders the transport of anti-tumor drugs to brain tumor tissues. Selectively opening BTB is of great significance to improve the chemotherapy effect of glioma. Pseudogenes have been recognized as important regulators in various biologic processes. In this study, we identified that ribosomal protein L32 pseudogene 3 (RPL32P3) was highly expressed in glioma-exposed endothelial cells (GECs). Knockdown of RPL32P3 decreased the expression of tight junction-related proteins (TJPs) and increased BTB permeability. Subsequent analysis of the underlying mechanism indicated that RPL32P3 recruited lysine methyltransferase 2 A (KMT2A) to the Y-box binding protein 2 (YBX2) promoter region and mediated H3K4me3 to promote YBX2 transcription. Highly expressed YBX2 bound and stabilized hepatocyte nuclear factor 4 gamma (HNF4G) mRNA. Highly expressed HNF4G directly bound to the promoters of TJPs ZO-1, occludin and claudin-5 to promote their transcriptional activities and regulated BTB permeability. The simultaneous knockdown of RPL32P3, YBX2, and HNF4G combined with doxorubicin (DOX) increased the apoptosis of glioma cells. In conclusion, the current study indicated that RPL32P3 knockdown increased BTB permeability through the YBX2/HNF4G pathway. These findings may provide new targets for the comprehensive treatment of glioma.

Jie Gao, Wei Xu, Kun Han, Lu Zhu, Lili Gao, Xiuli Shang Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, China Background: This was a longitudinal study which investigated the relationship between serum uric acid (SUA) and total bilirubin (Tbil) upon admission in elderly stroke patients and the occurrence of postischemic stroke depression (IPSD) at 3, 6, and 9 months of post-stroke follow-up. Subjects and methods: Data were analyzed for 525 acute ischemic stroke patients. Beck Depression Inventory (BDI) scores >17 and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were used separately to screen and diagnose IPSD at 3, 6, and 9 months post-stroke. Once IPSD was diagnosed, follow-up activities were terminated. Results: High levels of SUA (odds ratio [OR]=2.08, P

Previous studies have identified Atherogenic index of plasma (AIP) as a simple measure of atherosclerosis. Because atherosclerosis plays a role in the development of renal damage, our study aims to evaluate the effect of AIP on the risk of reduced eGFR and assess its usefulness to refine the risk stratification of reduced estimated glomerular filtration rate (eGFR).Our study included 15,836 participants from the National Health and Nutritional Survey (NHANES) 2009-2016. Association was investigated by logistic regression. AIP was calculated as log (triglycerides/high-density lipoprotein cholesterol). Reduced eGFR was determined as eGFR60 ml/min per 1.73 m*2.The prevalence of reduced eGFR was 8.01%. In the full model, each SD increase of AIP leaded to 27.4% additional risk for reduced eGFR. After dividing AIP into quartiles, the fourth quartile had a 1.649 times risk than the first quartile. Moreover, smooth curve fitting suggested that the risk of reduced eGFR elevated linearly with the increase of AIP. Subgroup analysis demonstrated that the association between AIP and reduced eGFR was robust in sex, body mass index, hypertension, and diabetes subpopulation, but the association was significantly stronger in black race and people aged less than 50 years old. Additionally, AUC displayed an advancement when introducing AIP into established risk factors (0.875 cs. 0.897, P 0.001), category-free net reclassification index (0.249, 95% CI: 0.192-0.306, P 0.001) and integrated discrimination index (0.007, 95% CI: 0.004-0.009, P 0.001) also suggested the improvement from AIP.The present work suggested a linear association between AIP and reduced eGFR. Furthermore, the results showed that the association was stronger in black race and people aged less than 50 years old. Most importantly, our work implicated the usefulness of AIP to refine the risk stratification of reduced eGFR.

Background: We aimed to examine the differences between the clinical characteristics of patients with ischemic stroke and active cancer and those without cancer and develop a clinical score for predicting occult cancer in patients with ischemic stroke.Methods: This retrospective study enrolled consecutive adult patients with acute ischemic stroke, who were admitted to our department between December 2017 and January 2019. The demographic, clinical, laboratory, and neuroimaging characteristics of patients with ischemic stroke with active cancer and those without cancer were compared. Multivariate analysis was performed to identify independent factors associated with active cancer. Subsequently, a predictive cancer-risk score was developed using the area under the receiver operating characteristic curve.Results: Fifty-three (6.63%) of 799 patients with ischemic stroke had active cancer. The absence of a history of hyperlipidemia [odds ratio (OR)=0.17, 95% confidence interval (CI): 0.06–0.48, PPPPPConclusions: We devised a score to predict active cancer in patients with ischemic stroke based on the absence of a history of hyperlipidemia and elevated serum D-dimer and fibrinogen that highlights the importance of hypercoagulability in these patients and may help determine early intervention and management.

The dysfunction of the blood‐brain barrier (BBB) is one of the main pathological features of Alzheimer's disease (AD). Memantine (MEM), an N‐methyl‐d‐aspartate (NMDA) receptor antagonist, has been reported that been used widely for AD therapy. This study was performed to demonstrate the role of the MEM in regulating BBB permeability in AD microenvironment as well as its possible mechanisms. The present study showed that LINC00094 was dramatically increased in Abeta1‐42‐incubated microvascular endothelial cells (ECs) of BBB model in vitro. Besides, it was decreased in MEM‐incubated ECs. Silencing LINC00094 significantly decreased BBB permeability, meanwhile up‐regulating the expression of ZO‐1, occludin and claudin‐5. Furthermore, silencing LINC00094 enhance the effect of MEM on decreasing BBB permeability in AD microenvironment. The analysis of the mechanism demonstrated that reduction of LINC00094 inhibited Endophilin‐1 expression by up‐regulating miR‐224‐4p/miR‐497‐5p, promoted the expression of ZO‐1, occludin and claudin‐5, and ultimately alleviated BBB permeability in AD microenvironment. Taken together, the present study suggests that the MEM/LINC00094/miR‐224‐5p (miR‐497‐5p)/Endophilin‐1 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment. Silencing LINC00094 combined with MEM provides a novel target for the therapy of AD.

Background Several recent studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, the association between the evolution of dynamic neuroimaging and clinical manifestations has not been reported in patients with N2O-induced SCD. Case presentation We described the case of a 24-year-old man who developed SCD with inverted V-sign hyperintensities over the posterior aspect of the spinal cord caused by frequent, excessive N2O inhalation. One month after treatment, his weakness and paresthesia resolved and serum vitamin B12 levels exceeded the normal levels. However, the hyperintensities had extended horizontally and longitudinally on T2-weighted magnetic resonance imaging (MRI), compared to those on the initial scan. Two months after treatment, the patient experienced some residual numbness in the distal limbs, and his serum homocysteine levels were normal, but the abnormal signals seen on cervical T2-weighted MRI had decreased only slightly compared to those seen on the one-month follow-up MRI. The evolution of conventional MRI findings lagged compared to the clinical manifestation, which was suggestive of a clinical-radiological dissociation. Conclusions Clinical-radiological dissociation might have occurred in this case because T2-weighted imaging was not sensitive enough to reveal cytotoxic edema. Moreover, the serum vitamin B12 level is not a good indicator of cellular vitamin B12. Thus, clinicians should recognize this phenomenon, comprehensively assess the condition of patients with N2O-induced SCD, and avoid terminating treatment based on the resolution of clinical symptoms and serological results.

Apathy is a multidimensional syndrome referring to a primary lack of motivation that occurs frequently in survivors of stroke. Higher C-reactive protein (CRP) level was associated with higher apathy scores among Alzheimer disease cases. However, data on the relationship between CRP levels and apathy in patients with stroke are lacking. So, we hypothesized an association between CRP and poststroke apathy (PSA).Two hundred ninety-two consecutive patients with stroke were recruited within 7 days after stroke. Apathy symptoms were assessed at baseline and at 1, 3, and 6 months after stoke using the Apathy Evaluation Scale-Clinical (AES-C). Demographic and clinical information were obtained using the National Institutes of Health Stroke Scale (NIHSS) scores, Barthel Index (BI) scores, Mini-Mental State Examination (MMSE) scores, Hamilton Depression Scale (HAMD) scores, and Hamilton Anxiety Scale (HAMA) scores. CRP was measured at baseline. The presence and the location of infarcts were evaluated using magnetic resonance imaging.Apathy at baseline was significantly associated with body mass index (BMI), NIHSS, BI, MMSE, HAMD, and CRP (P .05) upon admission. PSA at 6 months was significantly associated with elevated CRP concentrations, high AES-C score, and low BI score (P .05) upon admission. The AES-C scores peaked 3 months after stroke, but then abated over 6 months.CRP, BMI, MMSE, depression, and disability are closely related to apathy during the acute stage of ischemic stroke. Lower BI scores, higher CRP concentrations, and apathy in acute stroke phase increased the risk of PSA at 6 months.

The purpose of the study was to investigate the changes of Ca2+/calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-d-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by Aβ plaque deposition in the brain, which is related to the disorder of autophagosome maturation, transport, and formation of autolysosome. Notably, abnormal insulin signaling is connected with cognitive dysfunction in AD. In this study, using APP/PS1 transgenic mice as AD model, we investigated the mechanism by which S14G-humanin (HNG) improved autophagy and insulin signaling in AD brain. Immunohistochemistry was used to determine the levels of mTOR and Aβ deposition, and Western blot analysis was used to determine IRS-1, IRS-1 pSEr636, ULK1, p62, LC3 I/LC3 II protein levels. Our results demonstrated that HNG could improve the learning ability and memory in APP/PS1 transgenic mice, possibly through decreasing IRS-1 Ser636 phosphorylation and mTOR protein expression in the hippocampus, thus improving insulin resistance in the brain. In addition, HNG increased ULK1 expression, decreased p62 and LC3 I/LC3 II protein levels, thus enhancing autophagy and decreasing Aβ deposition in the brain. Taken together, our results suggest that through the regulation of IRS-1/mTOR insulin signaling in the hippocampus, HNG increases the activity of autophagy and decreases Aβ deposition in the brain, and improves learning ability and memory of AD mice.

Background/Aims: Parkinson’s disease (PD) is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB), an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. Methods: PD was introduced in rats via injection of lipopolysaccharide (LPS) into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), CD11b and ionized calcium binding adaptor molecule (IBA)-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. Results: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. Conclusion: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.

Background and purpose Cognitive impairment is a common non-motor complication of Parkinson’s disease (PD). To investigate cognitive-related changes of gray matter (GM) structure and function in PD using voxel-based morphometry (VBM) and resting state functional connectivity (RSFC). Materials and methods Resting state functional magnetic resonance imaging (rs-fMRI) and 3D-T1-weighted MRI scans were obtained from 21 PD patients with mild cognitive impairment (PD-MCI), 11 PD patients with normal cognitive function (PD-NC), and 21 healthy controls (HC). Functional connectivity (FC) was analyzed by defining the posterior cingulated cortex (PCC) as the seed region. VBM was performed to assess patterns of GM atrophy. Results In PD-NC versus HC, results indicated decreased PCC-FC in the right temporal gyrus(TG) and increased PCC-FC in the left medial temporal lobe(MTL), bilateral precuneus(Pcu), and parieto-occipital junction(POJ), as well as GM atrophy in the bilateral prefrontal-striatal circuit(pFTSC), TG and Pcu. In PD-MCI versus PD-NC, decreased PCC-FC was found in the bilateral prefrontal cortex(PFC), left POJ, and right TG. In addition, PCC-FC of the bilateral Pcu and GM volume of the left MTL, bilateral TG, and PFC were positively associated with cognitive score. Conclusions Structural and functional damage of the PFC and temporal lobe are associated with subtle cognitive decline in PD, while functional enhancement of the MTL and POJ is involved in normal cognitive function of PD. In addition, the combined application of rs-fMRI and VBM analysis might become an effective means to investigate cognitive impairment-related GM abnormalities in PD-MCI patients prior to development of dementia.

Background: A number of recent studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, none have reported the association between the dynamic neuroimaging evolution and clinical manifestations of a patient with N2O-induced SCD. Case presentation: We describe a 24-year-old man who developed SCD with inverted V-sign hyperintensities over the posterior aspect of the spinal cord caused by frequent, excessive N2O inhalation. One month after treatment, his weakness and paresthesia resolved and his serum vitamin B12 level had improved above normal, but the hyperintensities on T2-weighted images had extended horizontally and longitudinally, compared to the initial magnetic resonance images (MRI). Two months after treatment, the patient had some remaining distal limb numbness and normal serum homocysteine level; however, the abnormal signals seen on cervical T2-weighted images had only slightly decreased compared to those seen on the one-month follow-up MRI. The evolution of conventional MRI findings lagged behind the clinical manifestation, suggesting a clinical-radiological dissociation. Conclusions: The clinical-radiological dissociation may have occurred in this case because the T2-weighted imaging did not have sufficient sensitivity to reveal cytotoxic edema. Additionally, the serum vitamin B12 level was not a good indicator of cellular vitamin B12. Clinicians should, therefore, recognize this phenomenon, comprehensively assess the condition of patients with N2O-induced SCD, and avoid terminating treatment based on the resolution of clinical symptoms and serological results.

The blood-brain barrier (BBB) in AD patients and in animal models is changed. However, the mechanisms are still unclear. Here, we found that miR-424–5p was upregulated in Abeta-incubated microvascular endothelial cells. TEER and HRP exudation tests showed that miR-424–5p silencing significantly decreased BBB permeability in vitro BBB model with Abeta-incubated. MiR-424–5p silencing upregulated expression of the tight junction proteins, ZO-1 and occludin in Abeta-incubated microvascular endothelial cells. Furthermore, dual luciferase reporter gene assay results confirmed the presence of a potential binding site for miR-424–5p on the 3′UTR of Endophilin-1. Endophilin-1 was down-regulated in Abeta-incubated endothelial cells in which miR-424–5p was silenced. In conclusion, the present study demonstrates that miR-424–5p could affect the expression of tight junction proteins (ZO-1 and occludin) via Endophilin-1 and thereby maybe regulate BBB permeability in an BBB model in vitro with Abeta incubated endothelial cells. MiR-424–5p may thus serve as a protective target for AD and provide a new strategy for the prevention and treatment of AD.

Background Isolated peripheral facial palsy (P-FP) can lead to lesions involving the inferomedial tegmentum of the pons. However, cases with P-FP in result of a medullary lesion have rarely been reported and result from a paraventricular lesion have never been reported before. Cases presentation We described a 63-year-old man presenting with isolated P-FP due to ipsilateral pontomedullary infarction. Brain diffusion MRI revealed a hyper-intense signal on the left dorsolateral portion of the upper medulla and pontomedullary junction. And then we experienced a 77-year-old man presenting with lateral paraventricular infarction who showed contralateral peripheral type facial palsy. Brain diffusion-weighted image(DWI) showed a high-signal intensity lesion in the right lateral paraventricule and part of the posterior limb of the right internal capsule. Conclusions These two cases caution that a central nervous etiology should be considered in patients with P-FP, especially if they have high risk factors of cerebral infarction.

// Heng Cai 1 , Yixue Xue 2,3 , Ping Wang 2,3 , Zhenhua Wang 4 , Zhen Li 1 , Yi Hu 1 , Zhiqing Li 2,3 , Xiuli Shang 5 and Yunhui Liu 1 1 Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China 2 Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People’s Republic of China 3 Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People’s Republic of China 4 Department of Physiology, College of Basic Medicine, China Medical University, Shenyang, People’s Republic of China 5 Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Correspondence to: Yunhui Liu, email: // Keywords : glioma, TUG1, microRNA-144, blood-tumor barrier, HSF2 Received : February 02, 2015 Accepted : May 25, 2015 Published : June 02, 2015 Abstract Blood-tumor barrier (BTB) limits the delivery of chemotherapeutic agent to brain tumor tissues. Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine upregulated gene 1) was highly expressed in glioma vascular endothelial cells from glioma tissues. It also upregulated in glioma co-cultured endothelial cells (GEC) from BTB model in vitro. Knockdown of TUG1 increased BTB permeability, and meanwhile down-regulated the expression of the tight junction proteins ZO-1, occludin, and claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that TUG1 influenced BTB permeability via binding to miR-144. Furthermore, Knockdown of TUG1 also down-regulated Heat shock transcription factor 2 (HSF2), a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of miR-144. HSF2 up-regulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. In conclusion, our results indicate that knockdown of TUG1 increased BTB permeability via binding to miR-144 and then reducing EC tight junction protein expression by targeting HSF2. Thus, TUG1 may represent a useful future therapeutic target for enhancing BTB permeability.

Objective: To determine the appropriate treatments for post-ischaemic stroke depression at different times after stroke. Design: A single-blind, randomized, controlled trial that compared three intervention groups, with subgroups stratified by time after stroke. Setting: Outpatient clinic. Subjects: Eligible patients were recruited at discharge ( n = 73) and three ( n = 67), six ( n = 65), and nine months ( n = 69) after discharge, and patients completed mood questionnaires. Interventions: Patients were randomly distributed into three groups: Group A received placebos and participated in general discussions; Group B, received citalopram and participated in general discussions; and Group C, received placebos and underwent cognitive behavioural therapy. All three groups participated in rehabilitation during three months of follow-up. Main measures: Outcome was assessed three months after baseline using the 17-item Hamilton Depression Scale (HAMD17) and the Bech–Rafaelsen Melancholia Scale (MES). During treatment, the Udvalg for Kliniske Undersogelser side-effect scale was also administered. Results: When stratification was not considered, the scores of Group B on the Melancholia Scale were lower than those of Group A ( P = 0.02); when the four time-based subgroups were analysed, significant differences were observed between Groups A and B (PMES = 0.02, PHAMD17 = 0.02) in the group recruited six months after discharge and between Groups A and C (PMES = 0.01) in the last time period nine months after discharge. Conclusions: The effects of citalopram or cognitive behavioural therapy is similar to the effect of rehabilitation alone for early-onset post-ischaemic depression; rehabilitation and citalopram for delayed-onset post-ischaemic depression; and rehabilitation and cognitive behavioural therapy for late-onset post-ischaemic depression are more effective than rehabilitation alone.

Introduction Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disease characterized by recurrent dyskinesia or choreoathetosis triggered by sudden movements. Pathogenic variants in PRRT2 are the main cause of PKD. However, only about half of clinically diagnosed PKD patients have PRRT2 mutations, indicating that additional undiscovered causative genes could be implicated. PKD associated with POLG variant has not been reported. Patient concerns A 14-year-old boy presented with a 2-month history of involuntary dystonic movements triggered by sudden activities. He was conscious during the attacks. Neurological examination, laboratory tests, brain magnetic resonance imaging (MRI), electroencephalogram (EEG) were all normal. Genetic analysis showed a novel variant of POLG (c.440G>T, p.Ser147Ile), which was considered to be a likely pathogenic variant in this case. Diagnoses The patient was diagnosed with PKD. Interventions Low dose carbamazepine was used orally for treatment. Outcomes The patient achieved complete resolution of symptoms without any dyskinesia during the 6-month follow up. Conclusion Our study identified the novel POLG variant (c.440G>T, p.Ser147Ile) to be a likely pathogenic variant in PKD.

Bin Zhao,1,2 Hu Liu,3 Huanhuan Li,3 Xiuli Shang1 1Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; 2Department of Neurology, Shenyang Fifth People Hospital, Shenyang 110023, China; 3Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China Purpose: Depressive symptoms are frequent nonmotor symptoms that occur in multiple system atrophy (MSA) patients. However, possible changes that can present in the amygdala (AMY) functional connectivity (FC) of the brain in MSA patients with depressive symptoms (DMSA patients) remain largely unknown. Materials and methods: Resting-state functional magnetic resonance imaging scans were obtained from 29 DMSA patients, 28 MSA patients without depression symptoms (NDMSA patients), and 34 healthy controls (HCs). FC was analyzed by defining the bilateral AMY as the seed region. Correlation analysis was performed between the FC and clinical scores. Results: When compared with NDMSA patients, DMSA patients showed increased bilateral AMY FC in the left middle frontal gyrus (MFG) and decreased right AMY FC in the left middle occipital gyrus. Moreover, the AMY FC values in the left middle frontal cortex were positively correlated with the Hamilton Depression Rating Scale-17 item scores. Furthermore, relative to the HCs, DMSA patients presented decreased bilateral AMY FC values in the visuospatial cortex, sensorimotor networks, and limbic areas. Conclusion: Depressive symptoms are associated with AMY–MFG FC anomalies in MSA patients. We propose that the middle frontal cortex may play an important role in the neuropathophysiology of depression in MSA patients. Keywords: multiple system atrophy, depression, functional magnetic resonance imaging, functional connectivity, amygdala

Platinum nanoparticles anchored N-doped graphene (Pt/NG) catalysts are synthesized using a thermal annealing–potentiodynamic electrodeposition approach with melamine, graphene oxide, and PtCl62− as precursors. SEM, TEM, XRD, and XPS measurements indicate the relatively uniform and good dispersal of Pt nanoparticles on NG nanosheets. Compared to control catalysts of Pt nanoparticles loaded onto glassy carbon, undoped graphene and g-C3N4, the Pt/NG(1-1) catalyst (with a nominal mass ratio of melamine/graphene oxide of 1:1) shows the highest electrocatalytic activity towards the oxidation of ammonia among a series of Pt/NG catalysts. The mass activity of Pt/NG(1-1) catalyst is nearly 5.1 times as high as that of Pt/glassy carbon. The excellent electrochemical performance of Pt/NG catalysts is attributed mainly to the considerable extent of pyridinic N and graphitic N-doping in the graphene network, which improves the dispersion state of Pt nanoparticles on the NG support, resulting in an apparent enhancement in mass activity.