Quantitative Assessment of Acute Intracranial Clot and Collaterals on High Resolution Magnetic Resonance Imaging.

INTRODUCTION: There has been an increasing demand for imaging methods that provide a comprehensive evaluation of intracranial clot and collateral circulation, which are helpful for clinical decision-making and predicting functional outcomes. We aimed to quantitatively evaluate acute intracranial clot burden and collaterals on high-resolution magnetic resonance imaging (HR-MRI). METHODS: We analyzed acute ischemic stroke patients with internal carotid artery or middle cerebral artery occlusion in a prospective multicenter study. The clot burden was scored on a scale of 0-10 based on the clot location on HR-MRI. The collateral score was assigned on a scale of 0-3 using the minimum intensity projection from HR-MRI. Uni- and multivariable logistic regression analyses were performed to assess their correlation with clinical outcome (modified Rankin Scale >2 at 90 days). Thresholds were defined to dichotomize into low and high score groups and predictive performances were assessed for clinical and radiologic outcomes. RESULTS: Ninety-nine patients (mean age of 60.77 ± 11.54 years) were included in the analysis. The interobserver correlation was 0.89 (95% CI: 0.77-0.95) for the clot burden score and 0.78 (95% CI: 0.53-0.90) for the collateral score. Multivariable logistic regression analysis demonstrated that the collateral score (odds ratio: 0.41, 95% CI: 0.19-0.90) was significantly associated with clinical outcomes. A better functional outcome was observed in the group with clot burden scores greater than 7 (p=0.011). A smaller final infarct size and a higher diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score were observed in the group with collateral scores greater than 1 (all p<0.05). CONCLUSIONS: HR-MRI offers a new tool for quantitative assessment of clot burden and collaterals simultaneously in future clinical practices and research endeavors.

Pharmacological treatment of neuropsychiatric symptoms of dementia: a network meta-analysis.

BACKGROUND: Pharmacological treatments are very common to be used for alleviating neuropsychiatric symptoms (NPS) in dementia. However, decision on drug selection is still a matter of controversy. AIMS: To summarise the comparative efficacy and acceptability of currently available monotherapy drug regimens for reducing NPS in dementia. METHOD: We searched PubMed, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials between inception and 26 December 2022 without language restrictions; and reference lists scanned from selected studies and systematic reviews. Double-blind randomised controlled trials were identified from electronic databases for reporting NPS outcomes in people with dementia. Primary outcomes were efficacy and acceptability. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). RESULTS: We included 59 trials (15,781 participants; mean age, 76.6 years) and 15 different drugs in quantitative syntheses. Risperidone (standardised mean difference [SMD] -0.20, 95% credible interval [CrI] -0.40 to -0.10) and galantamine (-0.20, -0.39 to -0.02) were more effective than placebo in short-term treatment (median duration: 12 weeks). Galantamine (odds ratio [OR] 1.95, 95% CrI 1.38-2.94) and rivastigmine (1.87, 1.24-2.99) were associated with more dropouts than placebo, and some active drugs. Most of the results were rated as low or very low according to CINeMA. CONCLUSIONS: Despite the scarcity of high-quality evidence, risperidone is probably the best pharmacological option to consider for alleviating NPS in people with dementia in short-term treatment when considering the risk-benefit profile of drugs.

Effect and mechanism of "Danggui-kushen" herb pair on ischemic heart disease.

AIMS: The purpose of this study was to investigate the mechanism and effects of "Danggui-kushen" herb pair (DKHP) better than single drug in ischemic heart disease (IHD). METHODS: IHD model was established by left anterior descending branch of coronary artery in rats. Rats were randomized into six groups and oral administration for 7 days: control, model, Danshen dripping pills (DS) (5.103 g/kg), Danggui (DG) (2.7 g/kg), Kushen (KS) (2.7 g/kg) and DKHP (2.7 g/kg). Electrocardiogram (ECG), myocardial infarction and damage assessment, histological inspection analysis, and various biochemical indexes of myocardial tissue were measured to evaluate the myocardial damage and the protective effects of drugs. The inflammatory levels were identified by HE staining and serum cytokine, and the expression of hypoxia-inducible factor 1α (HIF-1α), inhibitor kappa B kinaseß (IKKß) and nuclear transcription factor kappa B (NF-κB) were measured by immunohistochemistry. KEY FINDINGS: The results suggested that: compared with the control group, model group showed significantly myocardial tissue abnormalities, and increased levels of inflammatory cytokine. Treatment with drugs inhibited the increase of α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), creatinekinase isoenzyme (CK-MB), interleukin 1 (IL-1) and interleukin 6 (IL-6). The results of immunohistochemical showed that drugs-treatment inhibited the expression of IKKß and the P-p65, increased the expression of HIF-1α, which demonstrated that the anti-inflammatory effects of DKHP was achieved by suppressing of NF-κB signaling. CONCLUSION: These observations indicated that DKHP can ameliorate myocardial injury better than single. And these are related to the inhibition of NF-κB and actives HIF-1α signaling.

[Potential suitable area and niche shift of different ploidy kiwifruit]. / 不同倍性猕猴桃的适生区预测及生态位分化.

Niche shift between polyploid and diploid plants is an important requirement for the success of polyploid. Diploid, tetraploid, and hexaploid of kiwifruit distribute in different areas. Whether there is obvious niche differentiation and the major environmental factors which could influence the ecological niche of different ploidy kiwifruits are still unknown. Based on the natural distribution information collected from literature and by field works, the maximum entropy model (MaxEnt) was used to predict the potentially suitable ranges and the major climatic factors affecting distribution of different ploidy kiwifruits. Niche divergence between different ploidy kiwifruits was quantified by niche identity test. The results showed that there were obvious differences in the potential suitable areas of different ploidy kiwifruits. Diploid occurred in lower altitude Hunan foothills. Tetraploid nearly overlapped with diploid but tended to northern Guizhou and eastern Chongqing. Hexaploid were centered in Guizhou Plateau, northwestern Hunan, southwestern Hubei and southern Shanxi. Hexaploid kiwifruits preferred higher altitudes and latitudes. In addition, the hexaploid had wider highly suitable areas. Results of niche identity test showed overlapped niches between diploid and tetraploid, and different niches between diploid/tetraploid and hexaploid kiwifruits. Minimum temperature of the coldest month (Bio6) and precipitation of the driest month (Bio14) were key environmental factors driving the niche shift of ploidy kiwifruits. Polyploid kiwifruits could maintain a higher probability of existence under lower Bio6 and Bio14, which indicated more extreme niche in cold and arid mountains for polyploids.

Linguistic Characteristics of Mandarin-Speaking Huntington's Disease Patients.

Objective Linguistic problem is common in Huntington's disease (HD) patients. It has been studied before in native speakers of alphabetic languages, such as English. As a hieroglyphic language, Chinese differs from alphabetic languages in terms of phonology, morphology, semantics and syntax. We aimed to investigate the linguistic characteristics of manifest HD in native speakers of Mandarin. Meanwhile, we expected to explore the linguistic differences associated with cortical or subcortical pathology.Methods Five HD patients and five Alzheimer's disease (AD) patients matched in age, gender, disease course and educational level were enrolled. All the participants were Mandarin native speakers. All finished history inquiry, physical examination, basic test, genetic test and neuropsychological assessment. Language evaluation was performed by Aphasia Battery of Chinese.Results HD patients had a mean disease course of 5.4±2.97 (range, 2-10) years. They showed a linguistic disorder close to transcortical motor aphasia. They exhibited prominent phonological impairment, as well as slight semantic and syntactic abnormality. Tonic errors were found in speech. Character structural errors and substitutions were detected in writing. In comparison, AD patients showed a more severe linguistic impairment, characterized by global aphasia with more semantic errors. Conclusion Mandarin-speaking HD patients have a transcortical motor aphasia-like disturbance with prominent phonological impairment, whereas AD patients have a more severe global aphasia with salient semantic impairment.

A proposed synergistic effect of CSF1R and NMUR2 variants contributes to binge eating in hereditary diffuse leukoencephalopathy with spheroids.

BACKGROUND: The genetic mechanisms of binge eating (BE) as a disease identity remain obscure. BE is usually viewed as a part of the behavioral variant of frontotemporal dementia (bvFTD) features. We encountered a family with hereditary diffuse leukoencephalopathy with spheroids (HDLS) that manifested uniformly with binge-eating-onset dementia. The genetic factors associated with the rare phenotype were investigated. METHODS: The detailed phenotypes of the patients were described. We performed whole-exome sequencing (WES) of family members and repeat-primed PCR to analyze the patients' expansion size of C9orf72, a well-established gene causing FTD. The WES results of additional HDLS patients without BE manifestations were also investigated. RESULTS: All affected individuals had a BE-dementia-epilepsy pattern of disease progression. A recurrent disease-causing mutation in CSF1R established the diagnosis of HDLS in the family. No abnormalities in the expansion size of C9orf72 were detected. The concurrence of a recurrent CSF1R mutation and a rare variant in NMUR2, a gene functionally related to BE, was revealed in the affected family members. No potentially pathogenic variants in other known BE-associated genes were identified. Both the NMUR2 variant and the CSF1R mutation cosegregated with the BE-dementia-epilepsy phenotype in the family. In three additional HDLS patients without BE, no pathogenic variants in NMUR2 were detected. CONCLUSIONS: We propose that synergistic genetic effects of NMUR2 and CSF1R variants may exist and contribute to the development of the BE phenotype in HDLS. NMUR2 is one of the potential susceptible genes in BE and may contribute in a background of a disrupted structural neuronetwork. Further studies in other BE-related disorders are required.

Clinical experience of uterine tumors resembling ovarian sex cord tumors: a clinicopathological analysis of 6 cases.

OBJECTIVE: To compare the clinicopathological features, diagnosis, treatment, and prognosis of two types of uterine sex cord-like tumors. METHODS: The clinicopathological features of four uterine tumors resembling ovarian sex cord tumors (UTROSCTs) and two endometrial stromal tumors with sex cord-like elements (ESTSCLEs) were analyzed retrospectively. RESULTS: All patients were premenopausal women. The most common clinical presentation was vaginal bleeding (four cases). Total hysterectomy with or without bilateral adnexectomy was the most common treatment pattern (five cases). A patient with UTROSCTs, presenting with recurrence 10 months after transvaginal submucous myomectomy, underwent a total hysterectomy (case 2). All tumors were polypoid or intramural masses, usually located in the uterine fundus or submucosa. The majority of UTROSCTs were positive for cytokeratin (4/4 cases), one was positive for Wilms tumor protein, and of two cases with smooth muscle actin immunoreactivity, two were positive for desmin. UTROSCTs were positive for two or more sex cord markers, whereas sex cord markers were less frequently detected in ESTSCLEs. CD10 was variably positive in two UTROSCT patients and strongly positive in all ESTSCLE patients. Three UTROSCTs and one ESTSCLE were positive for both estrogen and progesterone receptors. All patients with UTROSCTs were alive without evidence of recurrence. One patient with ESTSCLEs underwent postoperative chemotherapy after total vaginal hysterectomy but developed recurrence at the vaginal stump (case 5). The other patient with ESTSCLEs was lost to follow-up. CONCLUSION: These UTROSCTs are polymorphic neoplasms with true sex cord differentiation and uncertain malignant potential, which possess a distinct biology from ESTSCLEs.

Serum antibodies to 25 myelin oligodendrocyte glycoprotein epitopes in multiple sclerosis and neuromyelitis optica: clinical value for diagnosis and disease activity.

BACKGROUND: Whether antibody to myelin oligodendrocyte glycoprotein (MOG) can be a diagnostic marker for multiple sclerosis (MS) is still controversial. Recent studies suggested that serum specific anti-MOG epitope antibody might be an MS specific marker. However, these studies did not include neuromyelitis optica (NMO) which might be proven to also have anti-MOG antibody. Hence, the present study was undertaken to investigate the clinical value of serum antibodies to 25 MOG epitopes in conventional MS (CMS) and NMO. METHODS: Serum anti-MOG epitope IgG was detected in 61 CMS patients, 54 NMO patients, and 77 healthy controls, using enzyme-linked immunosorbent assay (ELISA). RESULTS: Anti-MOG(27-38) IgG levels in both CMS and NMO patients were significantly higher than that in healthy controls (optical density (OD): 0.64 ± 0.38, 0.48 ± 0.23 vs. 0.19 ± 0.09; P = 0.000). CMS and NMO patients in relapse stage had significantly higher anti-MOG(27-38) IgG level than patients in remission stage (OD: 0.55 ± 0.14 vs. 0.24 ± 0.09, P = 0.027). CONCLUSION: Although serum anti-MOG epitope IgG could not differentiate MS from NMO, it may be a useful marker for monitoring disease activity.

Correlations between serum uric acid level and disease activity, intrathecal inflammation reactivity in patients with multiple sclerosis.

OBJECTIVE: To explore the correlations between serum uric acid (UA) levels and the clinical and cerebrospinal fluid (CSF) parameters of multiple sclerosis (MS). METHODS: The medical reports of 47 MS patients admitted to Peking Union Medical College Hospital during 2008 and 2010 were reviewed. And 49 age- and gender-matched cerebral infarction patients were enrolled as control. The mean serum UA level of the MS patients was compared with that of the control group. The correlations between the UA levels and the clinical parameters including gender, disease duration, relapse rate, and disease disabilities as assessed by the Expanded Disability Status Scale score, were explored. Forty-one patients had CSF examinations. The correlations between the UA levels and the CSF parameters reflecting inflammation and tissue damage, including CSF protein, white blood cell count, oligoclonal band, 24-hour IgG index, and myelin basic protein, were also investigated. RESULTS: The mean serum UA level in the MS patients was lower than that in the control group (247.75±52.59 µmol/L vs. 277.94±74.33 µmol/L, P=0.025) and inversely correlated with the relapse rate (P=0.049). MS patients with lower serum UA levels tended to have higher white blood cell counts and myelin basic protein level. But there was no correlation between CSF protein levels (r=0.165, P=0.273), white blood cell counts (r=-0.051, P=0.732), IgG index (r=0. 045, P=0.802), or myelin basic protein level (r=-0.248, P=0.145) and the serum UA level, respectively. CONCLUSION: In MS patients, UA levels might partly reflect the extent of disability and inflammation.

[Characteristics of cerebral artery lesions in patients with limb-shaking transient ischemic attacks and its treatment].

OBJECTIVE: To investigate the characteristics of cerebral artery lesions in patients with limb-shaking transient ischemic attacks (LS-TIA) and its treatment. METHODS: We retrospectively analyzed the clinical data of 20 patients with LS-TIA who received treatment in Peking Union Medical College Hospital from 2005 to 2008. RESULTS: Critical stenosis or occlusion of contralateral arteries were found in the siphonic part of internal carotid artery (ICA) in 6 patients, terminal ICA or proximal middle cerebral artery (MCA) in 6 patients, and distal MCA in 1 patient. Seven patients had proximal ICA occlusion. The brain MRI showed typical watershed cerebral infarctions in 8 patients. EEG studies failed to show epileptiform activity associated with LS-TIA, but found focal frontotemporal lobe slow activity in 6 patients, which was consistent with hypoperfusion area in CT perfusion. Six patients received surgical revascularization and no one recurred. CONCLUSION: Intracranial artery including the siphonic part of ICA, terminal ICA and proximal MCA stenosis is the main underlying cause of LS-TIA in Chinese, and surgical revascularization may be effective in abolishing the attacks.