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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.

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.

Post-stroke anxiety (PSA) has caused wide public concern in recent years, and the study on risk factors analysis and prediction is still an open issue. With the deepening of the research, machine learning has been widely applied to various scenarios and make great achievements increasingly, which brings new approaches to this field. In this paper, 395 patients with acute ischemic stroke are collected and evaluated by anxiety scales (i.e., HADS-A, HAMA, and SAS), hence the patients are divided into anxiety group and non-anxiety group. Afterward, the results of demographic data and general laboratory examination between the two groups are compared to identify the risk factors with statistical differences accordingly. Then the factors with statistical differences are incorporated into a multivariate logistic regression to obtain risk factors and protective factors of PSA. Statistical analysis shows great differences in gender, age, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level between PSA group and non-anxiety group with HADS-A and HAMA evaluation. Meanwhile, as evaluated by SAS scale, gender, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level differ in the PSA group and the non-anxiety group. Multivariate logistic regression analysis of HADS-A, HAMA, and SAS scales suggest that hypertension, diabetes mellitus, drinking, high NIHSS score, and low serum HDL-C level are related to PSA. In other words, gender, age, disability, hypertension, diabetes mellitus, HDL-C, and drinking are closely related to anxiety during the acute stage of ischemic stroke. Hypertension, diabetes mellitus, drinking, and disability increased the risk of PSA, and higher serum HDL-C level decreased the risk of PSA. Several machine learning methods are employed to predict PSA according to HADS-A, HAMA, and SAS scores, respectively. The experimental results indicate that random forest outperforms the competitive methods in PSA prediction, which contributes to early intervention for clinical treatment.

The blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.

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.

Objectives Lesions limited to the bilateral middle cerebellar peduncles (MCPs) are uncommon. This retrospective study investigated diseases with a proclivity for the bilateral MCPs and explored the associations between their neuroimaging features and clinical findings for the differential diagnosis of such lesions. Methods We enrolled 26 patients who were admitted to our department between January 2016 and March 2019 with bilateral MCP abnormalities on magnetic resonance imaging (MRI). The demographic, clinical, and neuroimaging characteristics, and the biomarkers and diagnoses were evaluated. Results Although all patients exhibited symmetrical bilateral MCP hypointensities on T1‐weighted imaging and hyperintensities on T2‐weighted and fluid‐attenuated inversion recovery imaging, they were diagnosed with different conditions. Diagnoses included acute cerebral infarction (ACI) (n = 9, 34.62%), Wallerian degeneration (WD) (n = 8, 30.77%), multiple system atrophy (MSA) (n = 6, 23.08%), neuromyelitis optica (NMO) (n = 1, 3.85%), heroin‐induced leukoencephalopathy (n = 1, 3.85%), and primary central nervous system lymphoma (PCNSL) (n = 1, 3.85%). Patients with ACI exhibited bilateral MCP‐restricted diffusion hyperintensities on diffusion‐weighted imaging and corresponding stenosis or occlusion of the vertebrobasilar system. The initial MRI of patients with WD depicted pontine infarctions, while symmetrical MCP lesions were observed on follow‐up MRI. Symmetrical MCP lesions, cruciform hyperintensity, and marked atrophy in the posterior fossa were characteristic manifestations of MSA. Longitudinally extensive myelitis affecting more than three vertebral segments on cervical MRI and positive serum AQP4‐IgG may be indicative of NMO. Heroin‐induced leukoencephalopathy was characterized by extra‐symmetrical lesions in the posterior limbs of the internal capsules, while the anterior limbs were spared. PCNSL was indicated by a significant and characteristic “fist” sign on contrast‐enhanced MRI. Conclusions Bilateral MCP lesions were most frequently observed in cerebrovascular diseases, followed by neurodegenerative diseases, inflammatory diseases, toxic encephalopathies, and lymphomas. Our findings demonstrate that bilateral MCP signal abnormalities are more common in patients with ACI and WD, with fewer degenerative processes than previously believed. The high frequency of WD may be attributed to the specific awareness of this pathology. WD can also present with stage‐related restricted diffusion and should not be mistaken for a new infarction. The symmetrical bilateral MCP hypointensities on T1‐weighted imaging and hyperintensities on T2‐weighted imaging often raise concern regarding a demyelinating process. Our findings emphasize that neurologists should consider the aforementioned conditions and correlate the specific neuroimaging characteristics and medical history before arriving at the final diagnosis., We report a retrospective case series of 26 patients with bilateral middle cerebellar peduncle (MCP) lesions and compared the differences in clinical presentations and neuroimaging features of their associated diseases. Our findings showed that symmetrical bilateral MCP lesions occurred in various pathologic conditions, which were most frequent in cerebrovascular diseases, followed by neurodegenerative diseases, inflammatory diseases, toxic encephalopathies, and lymphoma, and the features differed in manners that could aid in distinguishing among the diseases.

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.

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.

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.

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

Late-Onset Epilepsy (LOE), with onset in adult life, is often attributed to cerebrovascular disease and intracranial tumor. Herein we present a LOE patient with history of Linear Scleroderma en Coup de Sabre (LScs) and abnormal cranial MRI signs. Curiously, his band-like skin lesion, presenting on the forehead, was in line with the surface projection of the intracranial focus shown in MRI. This gave a clue of the link between the skin lesion and the intracranial focus and the epilepsy. To sum up, it exposed a rare cause of LOE. Moreover, it underlined the significance of recognizing the cause to be associated with a substantially increased risk of developing epilepsy.

Summary Aim The nontoxic mutant of diphtheria toxin (DT) has been demonstrated to act as a receptor-specific carrier protein to delivery drug into brain. Recent research showed that the truncated “receptorless” DT was still capable of being internalized into cells. This study investigated the effects and potential mechanisms of DT270-326, a truncated “receptorless” DT, on the permeability of the blood–tumor barrier (BTB). Methods BTB and GECs were subjected to DT270-326 treatment. HRP flux assays, immunofluorescent, co-immunoprecipitation, Western blot, CCK-8, and Flow cytometry analysis were used to evaluate the effects of DT270-326 administration. Results Our results revealed that 5 μM of DT270-326 significantly increased the permeability of BTBin vitro, which reached its peak at 6 h. The permeability was reduced by pretreatment with filipinIII. DT270-326 co-localized and interacted with caveolin-1 via its caveolin-binding motif. The mRNA and protein expression levels of caveolin-1 were identical with the changes of BTB permeability. The upregulated expression of caveolin-1 was associated with Src kinase-dependent tyrosine phosphorylation of caveolin-1, which subsequently induced phosphorylation and inactivation of the transcription factor Egr-1. The combination of DT270-326 with doxorubicin significantly enhanced the loss of cell viability and apoptosis of U87 glioma cells in contrast to doxorubicin alone. Conclusions: DT270-326 might provide a novel strategy to increase the delivery of macromolecular therapeutic agents across the BTB.