A case of NMDAR Encephalitis with muscular pain as the main presentation.

BACKGROUND: Persistent somatoform pain disorder (PSPD) is often the initial diagnosis in patients seeking treatment in psychiatric departments, making it challenging to consider organic nervous system diseases. However, autoimmune encephalitis can present with atypical initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture, with antibody support, plays a crucial role in diagnosing autoimmune encephalitis. CASE PRESENTATION: This report describes a 40-year-old male adult patient who was initially diagnosed with persistent somatoform pain disorder in 2022. The patient reported a reduction in pain while resting on his back. There were no fever or relevant medical history. Despite 8 months of symptomatic treatment, the symptoms did not improve. Moreover, the patient developed confusion, gibberish speech, non-cooperation during questioning, and increased frequency and amplitude of upper limb convulsions. Lumbar puncture revealed elevated protein levels and protein-cell dissociation. The autoimmune encephalitis antibody NMDAR (+) was detected, leading to a diagnosis of autoimmune encephalitis (NMDAR). CONCLUSION: Autoimmune encephalitis (NMDAR), starting with persistent somatoform pain (PSPD), often presents with atypical symptoms and can be easily misdiagnosed. Therefore, it is important to consider the possibility of organic nervous system disease in time, and to test serum or cerebrospinal fluid antibodies to rule out organic nervous system disease after symptomatic treatment of mental disorders is ineffective. This approach facilitates the early diagnosis of autoimmune encephalitis and other underlying organic neurological disorders.

RBM3 enhances the stability of MEF2C mRNA and modulates blood-brain barrier permeability in AD microenvironment.

Blood-brain barrier (BBB) changes are acknowledged as early indicators of Alzheimer's disease (AD). The permeability and integrity of the BBB rely significantly on the essential role played by the tight junction proteins (TJPs) connecting endothelial cells. This study found the reduced RNA binding motif protein 3 (RBM3) expression in brain microvascular endothelial cells (BMECs) incubated with Aß1-42. This downregulation of RBM3 caused a decrease in the levels of ZO-1 and occludin and increased the permeability of BBB cell model in AD microenvironment. Myocyte enhancer factor 2C (MEF2C) expression was also inhibited in BMECs incubated with Aß1-42. A decrease in MEF2C expression led to increased permeability of BBB cell model in AD microenvironment and reductions in the levels of ZO-1 and occludin. Further analysis of the underlying mechanism revealed that RBM3 binds to and stabilizes MEF2C mRNA. MEF2C binds to the promoters of ZO-1 and occludin, enhancing their transcriptional activities and modulating BBB permeability. RBM3 increases the stability of MEF2C mRNA and subsequently modulates BBB permeability through the paracellular pathway of TJPs. This may provide new insights for AD research.

Lower glomerular filtration rate after mild stroke induces cognitive impairment by causing endothelial dysfunction.

The incidence of post stroke cognitive impairment (PSCI) is high in patients with mild stroke (MIS), and the risk factors and mechanism are uncertain. Increased cystatin C (CysC) levels after stroke may reflect lower glomerular filtration rate (GFR) and renal impairment. Previous studies have suggested endothelial dysfunction (ED) is closely related to renal impairment and cognitive impairment, respectively. We aimed to observe whether lower GFR estimated by CysC after MIS leaded to a high incidence of PSCI, and the role of ED in this process. 256 patients were enrolled in this prospective observational study. Renal function was assessed using GFR estimated by serum CysC. Endothelial function was evaluated by reactive hyperemia index (RHI) which calculated automatically by peripheral arterial tonometry (PAT). The cognitive function at baseline and 3 months was evaluated by MoCA score, and MoCA score ≤ 26 indicates the presence of PSCI. Spearman correlation analysis and linear regression were conducted to explore the factors affecting ED. Univariate and multivariate analysis was used to identify the independent risk factors of PSCI. The receiver operating characteristic (ROC) curve was applied to explore the optimal cutoff value of the independent risk factors levels for predicting PSCI. A total of 141 patients (55.1%) suffered from ED. Multiple linear regression analysis showed that there was a strong linear correlation between eGFRcys and RHI (p < 0.001). At the three-month follow-up, a total of 150 (58.6%) patients had been diagnosed with PSCI. Multivariate logistic regression analysis showed that RHI was an independent factor affecting the occurrence of PSCI (p < 0.05). ROC curve showed that the area under the curve was 0.724, and the optimal cut-off value of RHI was 1.655, with the sensitivity and specificity for PSCI were 72.7% and 73.6%, respectively. The lower eGFRcys level after MIS was significantly associated with ED, and ED may mediate the higher incidence of PSCI at 3 months after MIS.

Cpeb4-mediated Dclk2 promotes neuronal pyroptosis induced by chronic cerebral ischemia through phosphorylation of Ehf.

Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. Cpeb4 upregulated Dclk2 expression by increasing Dclk2 mRNA stability. Knockdown of Cpeb4 or Dclk2 inhibited neuronal pyroptosis in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. By binding to the promoter regions of Caspase1 and Caspase3, the transcription factor Ehf reduced their promoter activities and inhibited the transcription. Dclk2 phosphorylated Ehf and changed its nucleoplasmic distribution, resulting in the exit of p-Ehf from the nucleus and decreased Ehf levels. It promoted the expression of Caspase1 and Caspase3 and stimulated neuronal pyroptosis of HT22 cells induced by OGD. Cpeb4/Dclk2/Ehf pathway plays an important role in the regulation of cerebral ischemia-induced neuronal pyroptosis.

Association between dietary potassium intake and severe headache or migraine in US adults: a population-based analysis.

Background: Migraine is a prevalent neurovascular headache disorder. The link between dietary potassium and blood pressure has been established. We sought to delineate the relationship between dietary potassium intake and the prevalence of migraines. Methods: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2004, comprising 10,254 participants aged ≥20 years. Participants who reported severe headaches or migraine in the self-report questionnaire were identified as migraineurs. A 24-h dietary recall methodology was used to assess dietary potassium intake. Multivariate regression analysis and restricted cubic spline (RCS) modeling were utilized to elucidate the relationship between dietary potassium and migraines. Results: Among the 10,254 participants, 20.1% were identified with migraine or severe headaches. The adjusted odds ratio (OR) for migraine occurrence in the Q2 dietary potassium intake (1771-2,476 mg/d) was 0.84 (95% CI: 0.73-0.97, p = 0.021) compared to the lowest quartile (Q1, ≤ 1771 mg/d). The relationship between dietary potassium and migraine exhibited an L-shaped pattern (non-linear, p = 0.016) with an inflection at approximately 1439.3 mg/d. In the subgroup analysis, when compared to Q1, who had the lowest dietary potassium intake, the adjusted OR for Q2 in females, those in the medium-high household income group, and with a Body Mass Index (BMI) ≥ 25 kg/m2 were as follows: (OR, 0.82; 95% CI, 0.69-0.98), (OR, 0.79; 95% CI, 0.66-0.95), and (OR, 0.78; 95% CI, 0.66-0.93), respectively. No significant interaction was observed across groups after adjusting for all possible covariates. Conclusion: The relationship between dietary potassium intake and migraine prevalence among US adults appears to follow an L-shaped curve.

Case report: Creutzfeldt-Jakob disease: a case that initiated with the onset of obsessive-compulsive state.

Background: Obsessive-compulsive disorder (OCD) is a common reason for patients to seek symptomatic treatment in psychiatric departments, which makes it challenging to consider underlying organic nervous system diseases. However, Creutzfeldt-Jakob disease (CJD) can present with atypical symptoms, sometimes even as initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture and brain DWI are important diagnostic methods for CJD, and the detection of 1,433 protein can be performed to confirm the diagnosis. Case presentation: We present the case of a 63-year-old woman who was initially diagnosed with obsessive-compulsive disorder in 2022. Despite seven months of symptomatic treatment, her symptoms did not improve. She also developed symptoms of altered consciousness, such as upper limb tremors and mutism. Based on brain DWI and positive results from the detection of 1,433 protein, she was ultimately diagnosed with CJD. Conclusion: Creutzfeldt-Jakob disease (CJD) can manifest initially as obsessive-compulsive disorder (OCD) with atypical symptoms, making it prone to misdiagnosis. Therefore, it is crucial to conduct further investigations, including lumbar puncture and imaging, to exclude organic nervous system diseases before initiating symptomatic treatment for psychiatric disorders. This approach can facilitate early diagnosis of CJD and other potential organic neurological diseases.

Case Report: Paroxysmal weakness of unilateral limb as an initial symptom in anti-LGI1 encephalitis: a report of five cases.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common kind of autoimmune encephalitis following anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Anti-LGI1 encephalitis is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders, epileptic seizures, faciobrachial dystonic seizures (FBDS), and refractory hyponatremia. Recently, we found an atypical manifestation of anti-LGI1 encephalitis, in which paroxysmal limb weakness was the initial symptom. In this report, we describe five cases of anti-LGI1 encephalitis with paroxysmal limb weakness. Patients had similar presentations, where a sudden weakness involving a unilateral limb was observed, which lasted several seconds and occurred dozens of times each day, with the anti-LGI1 antibody being positive in both serum and cerebrospinal fluid (CSF). FBDS occurred after a mean of 12 days following paroxysmal limb weakness in three of five patients (Cases 1, 4, and 5). All patients were given high-dose steroid therapy, which had a good effect on their condition. Based on this report, we suggest that paroxysmal unilateral weakness may be a kind of epilepsy and be connected to FBDS. As an unusual neurological presentation, paroxysmal weakness can be included in the clinical manifestations of anti-LGI1 encephalitis, helping to raise awareness of the recognition of anti-LGI1 encephalitis in patients with this symptom and leading to early diagnosis and early treatment, which would contribute to improved clinical outcomes.

Association between estimated pulse wave velocity and silent lacunar infarct in a Korean population.

Aims: Previous studies have proposed the estimated pulse wave velocity (ePWV) as a simple and cost-effective measure of arterial stiffness. Since arterial stiffness plays a role in the progression of silent lacunar infarct (SLI), our present work aims to evaluate the association between ePWV and the presence of SLI. Methods: The present work was based on a cross-section study. Our study included 1,011 neurologically healthy Korean participants. The SLI was evaluated using brain magnetic resonance images (MRI). The ePWV was derived from a published equation using age and mean blood pressure (MBP). Logistic regression analyses were performed to investigate the association between ePWV and SLI. The linear relationship and robustness were evaluated using smooth curve fitting and subgroup analyses, respectively. Results: The prevalence of SLI was 11.87%. After fully adjusting for covariates, per 1 m/s increase of ePWV casted 31% additional risk for SLI (P = 0.009). When dividing the ePWV into quartiles, the top quartile had 4.01 times risk compared with the bottom quartile. The increasing trend across the quartiles was statistically significant (P for trend < 0.001). Consistently, smooth curve fitting revealed that the risk of SLI elevated linearly with the increase of ePWV. Finally, subgroup analysis suggested that the association was robust in several sub-populations divided by age, sex, smoking, hypertension, diabetes mellitus (DM), coronary artery occlusive disease (CAOD), hyperlipidemia, and statin medication (all P for interaction > 0.05). Conclusion: The current study revealed an independent and positive association between ePWV and the presence of SLI in a neurologically healthy Korean population.

Complement protein levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea.

STUDY OBJECTIVES: An association between neuroinflammation and cognitive decline has been established. The complement system regulates neuroinflammation. Dysregulation, impairment, or inadvertent activation of complement components contribute to preclinical Alzheimer's disease. The astrocyte-derived exosome (ADE) complement proteins, including C3b and C5b-9, may be predictive biomarkers of mild cognitive impairment conversion to Alzheimer's disease dementia. We hypothesized that complement proteins might be involved in cognitive impairment during obstructive sleep apnea (OSA). The aim of our study was to explore the correlation between the complement system and mild cognitive impairment (MCI) in patients with OSA. METHODS: All participants with subjective snoring complaints from the Sleep Medicine Center underwent polysomnography. OSA was defined as apnea-hypopnea index ≥ 5 events/h. MCI was defined as the Montreal Cognitive Assessment < 26 and met the criteria: (1) a subjective cognitive impairment; (2) an objective impairment in 1 or more cognitive domains; (3) complex instrumental daily abilities can be slightly impaired but independent daily living abilities are maintained; and (4) no dementia. The ADEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of complement proteins, including C3b, C5b-9, and CD55. The participants who received continuous positive airway pressure were followed up and their complement protein levels were reassessed after 1 year of treatment. RESULTS: A total of 212 participants (66.98% males; mean age of 56.71 ± 10.10 years) were divided into the OSA+MCI group (n = 90), OSA-MCI group (n = 79), and controls (normal cognitive state without OSA) (n = 43). The ADE levels of C3b and C5b-9 in the OSA+MCI group were higher than those in the OSA-MCI and control groups. The C3b and C5b-9 were independently associated with cognitive impairment in patients with OSA. The relationship between apnea-hypopnea index and Montreal Cognitive Assessment scores was mediated by C3b and C5b-9. We found no linear correlation between the complement proteins and the severity of OSA. The complement proteins were negatively correlated with global cognitive performance and cognitive subdomains. The complement protein levels significantly decreased after continuous positive airway pressure treatment. CONCLUSIONS: Complement proteins were implicated in cognitive impairment in patients with OSA and may be promising biomarkers for predicting cognitive impairment in patients with OSA. CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trial Registry; Name: Study on early diagnostic markers in patients with dementia and mild cognitive impairment; URL: https://www.chictr.org.cn/; Identifier: ChiCTR1900021544. CITATION: Li M, Sun C, Xue S, et al. Complement proteins levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea. J Clin Sleep Med. 2023;19(4):727-739.

Human urinary kallidinogenase decreases the incidence of post-stroke cognitive impairment in acute ischemic stroke patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p = 0.037), in comparison, the serum CysC level in the control group was basically unchanged (p = 0.951). There was a significant negative correlation between MoCA score and the level of CysC after treatment (p = 0.003, r = -0.373). CONCLUSIONS: 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.

Altered amyloid-ß and tau proteins in neural-derived plasma exosomes in obstructive sleep apnea.

OBJECTIVE: The purpose of our study was to investigate the correlation between neural-derived plasma exosomal amyloid-ß (Aß)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). METHODS: 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 Aß42, 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. RESULTS: The exosomal Aß42, T-tau and P-T181-tau levels in the OSA with MCI group were higher than those in the OSA group. The Aß42, 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 Aß42, 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 Aß42, T-tau, and P-T181-tau were significantly lower than those at baseline (P = 0.001, P = 0.012, and P = 0.034). CONCLUSIONS: These findings indicate that peripheral blood levels of neuronal-derived exosomal Aß 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 Aß and tau proteins.

Prognostic value of the systemic inflammation response index in patients with acute ischemic stroke.

OBJECTIVES: Inflammation plays an essential role in acute ischemic stroke (AIS). Recent studies have recognized the systemic inflammation response index (SIRI) as a useful index to indicate inflammation status and predict the prognosis of multiple diseases. However, the relationship between SIRI and AIS prognosis is unclear. Our study is aimed to investigate the association between SIRI and the prognosis of AIS. METHODS: Our study prospectively recruited 287 consecutive patients with first-ever stroke within 72 h after stroke. Demographic and clinical information was collected at baseline. The functional prognosis was assessed 3 months after AIS using the modified Rankin Scale (mRS). A poor outcome was defined as mRS > 2. SIRI was calculated as neutrophil × monocyte/lymphocyte count. Univariate and multivariate analyses were introduced to identify the association between SIRI and AIS prognosis. Receiver operating characteristic curve and reclassification analyses were used to evaluate the predictive value of SIRI for AIS prognosis. RESULTS: The patients with poor prognosis account for 27.5% of all participants. After fully adjusting for all covariates, each standard deviation increment of SIRI caused 58.9% additional risk for poor prognosis after AIS. When dividing SIRI into quartiles, the fourth quartile had a 6.152 times risk than the first quartile. Moreover, after adding SIRI into established clinical risk factors, AUC showed a significant improvement (0.829 vs. 0.790, p for comparison = .016). Consistently, category-free net reclassification index (NRI, 0.761, 95% CI: 0.517-1.004, p < .001) and integrated discrimination index (IDI, 0.093, 95% CI: 0.0512-0.134, p < .001) confirmed the improvement by SIRI to predict poor prognosis of AIS, CONCLUSION: SIRI is an independent prognostic indicator for AIS. Elevated SIRI is associated with poor functional outcome of AIS. Our findings suggest the usefulness of SIRI to refine the risk stratification of unfavorable prognosis of AIS.

Association between serum cystatin C level and post-stroke cognitive impairment in patients with acute mild ischemic stroke.

BACKGROUND: Mild ischemic stroke (MIS) has been proved to be closely related to post-stroke cognitive impairment (PSCI). However, there are relatively few studies on the risk factors of MIS. We aimed to evaluate the relationship between serum cystatin C (CysC) level and cognitive function in patients with acute MIS. METHODS: Four hundred consecutive patients with acute MIS were screened and 281 patients were eligible for this study. The serum CysC levels were detected within 24 h after admission. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at 3 months after acute MIS. Logistic regression was used to identify the predictors of PSCI, and the receiver operating characteristic (ROC) curve was applied to explore the optimal cut-off value. RESULTS: One hundred sixty-four (58.4%) patients were diagnosed with PSCI at 3 months follow-up. The serum CysC levels in patients with PSCI were significantly higher than patients without PSCI (p < .001). The binary logistic regression analysis showed that higher serum CysC level was an independent predictor for PSCI at 3 months (odds ratio [OR], 5.745; 95% confidence interval, [CI], 1.089-30.311; p = 0.039). The ROC curve showed that area under the curve (AUC) was 0.723, and at a 0.945 mg/l CysC cut-off point, the sensitivity and specificity for PSCI at 3 months were 79.9% and 58.1%, respectively. CONCLUSION: Our findings suggested that the serum CysC levels were increased after acute MIS, and higher serum CysC levels at baseline might be an independent risk factor for PSCI in patients with acute MIS, but further research are warranted.

Pseudogene RPL32P3 regulates the blood-tumor barrier permeability via the YBX2/HNF4G axis.

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.

Nitrous oxide-related neurological disorders: Clinical, laboratory, neuroimaging, and electrophysiological findings.

BACKGROUND: Recreational N2 O 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 N2 O-related neurological disorders. METHODS: Patients with N2 O-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 N2 O-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 N2 O abuse and hospitalization was independently associated with spinal MRI abnormalities (39.47% vs. 72.00%, respectively; χ2  = 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 < .01; r = 0.346, p < .01; r = 0.477, p < .01; r = 0.324, p < .01). CONCLUSIONS: The significant inverse correlation between initial vitamin B12 levels and clinical severity could aid prognosis prediction in patients with N2 O-related neurological disorders. Spinal MRI abnormalities were not related to clinical severity but depended on the time interval between initial N2 O abuse and hospitalization. Anxiety and depression were common comorbidity in these patients, and their severity increased with the intensity of clinical impairment and/or serum homocysteine levels.

Post-stroke Anxiety Analysis via Machine Learning Methods.

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.

Score for Predicting Active Cancer in Patients with Ischemic Stroke: A Retrospective Study.

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 <0.01), and stroke of undetermined etiology (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.

Pseudogene ACTBP2 increases blood-brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aß1-42 microenvironment.

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. ß-Amyloid (Aß) 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 Aß1-42 microenvironment. BBB model treated with Aß1-42 for 48 h were used to simulate Aß-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 Aß1-42 microenvironment. In Aß1-42-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 Aß1-42 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 Aß1-42 microenvironment, which may provide a novel target for the therapy of AD.

Paroxysmal kinesigenic dyskinesia associated with a novel POLG variant: A case report.

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.