Xiaolong Sun

Prediction of functional outcome in patients with convulsive status epilepticus: the END-IT score

BackgroundPrediction of the functional outcome for patients with convulsive status epilepticus (CSE) has been a challenge. The aim of this study was to characterize the prognostic factors and functional outcomes of patients after CSE in order to develop a practicable scoring system for outcome prediction.MethodsWe performed a retrospective explorative analysis on consecutive patients diagnosed with CSE between March, 2008 and November, 2014 in a tertiary academic medical center in northwest China. The modified Rankin Scale (mRS) was used to measure the functional outcome at three months post discharge.ResultsA total of 132 CSE patients was included, with a median age of 25.5 years and 60.6 % were male. Three months post discharge, an unfavorable outcome with mRS of 3–6 was seen in 62 (47.0 %) patients, 25 (18.9 %) of whom died. Logistic regression analysis revealed that encephalitis (p = 0.029), nonconvulsive SE (p = 0.018), diazepam resistance (p = 0.005), image abnormalities (unilateral lesions, p = 0.027; bilateral lesions or diffuse cerebral edema, p < 0.001) and tracheal intubation (p = 0.032) were significant independent predictors for unfavorable outcomes. Based on the coefficients in the model, these predictors were assigned a value of 1 point each, with the exception of the image, creating a 6-point scoring system, which we refer to as END-IT, for the outcome prediction of CSE. The area under the receiver operating characteristic curve for the END-IT score was 0.833 and using a cut-off point of 3 produced the highest sum sensitivity (83.9 %) and specificity (68.6 %). Compared with status epilepticus severity score (STESS) and Epidemiology-based Mortality score in SE (EMSE), END-IT score showed better discriminative power and predictive accuracy for the outcome prediction.ConclusionsWe developed an END-IT score with a strong discriminative power for predicting the functional outcome of CSE patients. External prospective validation in different cohorts is needed for END-IT score.

Oral Anticoagulant Use in Atrial Fibrillation-Associated Ischemic Stroke: A Retrospective, Multicenter Survey in Northwestern China

BACKGROUND Anticoagulation therapy has been recommended by major guidelines to reduce the risk of recurrent stroke in patients with atrial fibrillation-associated ischemic stroke (AFAIS). However, in real-world clinical practice, oral anticoagulants with either vitamin K antagonists or nonvitamin K antagonists are often underused for these patients. Here, we sought to investigate the current status of oral anticoagulant use in patients with AFAIS in northwestern China. METHODS We reviewed medical records of consecutive patients with AFAIS discharged from 14 hospitals in northwestern China between January 2012 and May 2015. RESULTS A total of 1014 cases were included in this study. The mean age of the patients was 70.3 ± 10.8 years. Fifty-four percent were female. Among all participants, only 20.0% received anticoagulants (19.4% warfarin and .6% nonvitamin K antagonist oral anticoagulants), whereas 57.5% took antiplatelet drugs and 22.5% received neither anticoagulant nor antiplatelet treatment. Anticoagulant use decreased with increasing age and CHA2DS2-VASc scores. The proportions of anticoagulant use at discharge in patients younger than 65 years, 65-74 years, and 75 years or older were 28.5%, 20.7%, and 13.9%, respectively. Nonvalvular atrial fibrillation patients with CHA2DS2-VASc scores of 2, 3, 4, 5, 6, and 7 had anticoagulant use rates at discharge of 19.2%, 24.8%, 20.3%, 13.7%, 8.1%, and 8.0%, respectively. CONCLUSIONS In northwestern China, oral anticoagulants are substantially underutilized in patients with AFAIS, especially in patients at higher risk of stroke, suggesting a large treatment gap in the secondary prevention management in patients with AFAIS.

Astrocytic Acid-Sensing Ion Channel 1a Contributes to the Development of Chronic Epileptogenesis.

Unraveling mechanisms underlying epileptogenesis after brain injury is an unmet medical challenge. Although histopathological studies have revealed that reactive astrogliosis and tissue acidosis are prominent features in epileptogenic foci, their roles in epileptogenesis remain unclear. Here, we explored whether astrocytic acid-sensing ion channel-1a (ASIC1a) contributes to the development of chronic epilepsy. High levels of ASIC1a were measured in reactive astrocytes in the hippocampi of patients with temporal lobe epilepsy (TLE) and epileptic mice. Extracellular acidosis caused a significant Ca2+ influx in cultured astrocytes, and this influx was sensitive to inhibition by the ASIC1a-specific blocker psalmotoxin 1 (PcTX1). In addition, recombinant adeno-associated virus (rAAV) vectors carrying a GFAP promoter in conjunction with ASIC1a shRNA or cDNA were generated to suppress or restore, respectively, ASIC1a expression in astrocytes. Injection of rAAV-ASIC1a-shRNA into the dentate gyrus of the wide type TLE mouse model resulted in the inhibition of astrocytic ASIC1a expression and a reduction in spontaneous seizures. By contrast, rAAV-ASIC1a-cDNA restored astrocytic ASIC1a expression in an ASIC1a knock-out TLE mouse model and increased the frequency of spontaneous seizures. Taken together, our results reveal that astrocytic ASIC1a may be an attractive new target for the treatment of epilepsy.

Diagnostic Accuracy of Cerebrospinal Fluid Procalcitonin in Bacterial Meningitis Patients with Empiric Antibiotic Pretreatment

ABSTRACT Accurate diagnosis of bacterial meningitis (BM) relies on cerebrospinal fluid (CSF) Gram staining and bacterial culture, which often present high false-negative rates because of antibiotic abuse. Thus, a novel and reliable diagnostic biomarker is required. Procalcitonin (PCT) has been well demonstrated to be specifically produced from peripheral tissues by bacterial infection, which makes it a potential diagnostic biomarker candidate. Here, we performed a prospective clinical study comprising a total of 143 patients to investigate the diagnostic value of CSF PCT, serum PCT, and other conventional biomarkers for BM. Patients were assigned to the BM (n = 49), tuberculous meningitis (TBM) (n = 25), viral meningitis/encephalitis (VM/E) (n = 34), autoimmune encephalitis (AIE) (n = 15), or noninflammatory nervous system diseases (NINSD) group (n = 20). Empirical antibiotic pretreatment was not an exclusion criterion. Our results show that the CSF PCT level was significantly (P < 0.01) higher in patients with BM (median, 0.22 ng/ml; range, 0.13 to 0.54 ng/ml) than in those with TBM (median, 0.12 ng/ml; range, 0.07 to 0.16 ng/ml), VM/E (median, 0.09 ng/ml; range, 0.07 to 0.11 ng/ml), AIE (median, 0.06 ng/ml; range, 0.05 to 0.10 ng/ml), or NINSD (median, 0.07 ng/ml; range, 0.06 to 0.08 ng/ml). Among the assessed biomarkers, CSF PCT exhibited the largest area under the receiver operating characteristic curve (0.881; 95% confidence interval, 0.810 to 0.932; cutoff value, 0.15 ng/ml; sensitivity, 69.39%; specificity, 91.49%). Our study sheds light upon the diagnostic dilemma of BM due to antibiotic abuse. (This study has been registered at ClinicalTrials.gov under registration no. NCT02278016.)

CHRNA4 variant causes paroxysmal kinesigenic dyskinesia and genetic epilepsy with febrile seizures plus

PURPOSE Paroxysmal kinesigenic dyskinesia (PKD) and epilepsy are thought to have a shared genetic etiology. PRRT2 has been identified as a causative gene of both disorders. In this study, we aim to explore the potential novel causative gene in a PRRT2-negative family with three individuals diagnosed with PKD or genetic epilepsy with febrile seizures plus (GEFS+). METHODS Clinical data were collected from all the affected and unaffected members of a PKD/GEFS+ family. The Brain magnetic resonance imaging and 24 h video-EEG of all three affected members were analyzed. Targeted gene-panel sequencing was used to detect the genetic defect in genomic DNAs of three affected and five normal individuals. Co-segregation analysis of putatively pathogenic mutations with the phenotype was carried out in all the family members alive to examine the inheritance status. RESULTS The inheritance model of this pedigree was autosomal dominant. A novel, fully co-segregated mutation (NM_000744: c.979G > A) in CHRNA4 was identified in the family with three individuals diagnosed with PKD or GEFS+. CONCLUSIONS CHRNA4 may be a novel gene causing of PKD and GEFS+. Our study extends the genotypic-phenotypic spectrum of combined epileptic and dyskinetic syndromes, and provides a genetic linkage between PKD and GEFS+.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) with intracranial Epstein-Barr virus infection: A Case Report.

Background:Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological features. The pathophysiology of CLIPPERS still remains unclear and the reports are quite few. Although the radiological lesions were reported to be located predominantly in the pons, brachium pontis, and cerebellum, other adjacent structures such as the white matter and spinal cord were very recently reported as involved regions in CLIPPERS. In this study, we report a case of CLIPPERS presenting with intracranial Epstein–Barr virus (EBV) infection and diffuse white matter involvement. Case summary:A 37-year-old male was diagnosed with mediastinal Hodgkins lymphoma (lymphocyte predominance type) at the age of 26, and then obtained complete remission after treatment and remained free of relapse for 11 years. He was admitted with 7 months’ history of mental disorder, and 20 days’ history of gait and limb ataxia, dysphagia, and cough. The diagnosis of CLIPPERS was established based on the findings of punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the mid-brain, the pontine brachium, and diffuse white matter in magnetic resonance imaging (MRI), together with CD3+ T-lymphocytic inflammatory infiltration in perivascular and parenchymal area revealed by bilateral parietal lobe brain biopsy. Also, our patient exhibited a good response to steroid therapy and remained free of relapse for 5 months. Importantly, we found intracranial Epstein–Barr virus infection in this patient. Conclusion:CLIPPERS might be an autoimmune disorder, and intracranial EBV-infection raises the possibility that EBV-associated autoimmunity is associated with CLIPPERS pathogenesis.

Development and validation of a risk score to predict 30-day mortality in patients with atrial fibrillation-related stroke: GPS-GF score.

ABSTRACT Objective Stroke due to atrial fibrillation (AF) is common and frequently devastating. However, there is no specific tool to accurately estimate the risk of mortality. This study aims to develop and validate a comprehensive risk score for predicting 30-day mortality in the patients with AF-related stroke. Methods A retrospective multi-center clinical study was performed based on the data from the project of secondary prevention of stroke in patients with nonvalvular AF in Shaanxi province, China. A total of 1077 consecutive patients were randomly classified into derivation (66.7%, n = 718) and internal validation cohort (33.3%, n = 359). Independent predictors of 30-day mortality were obtained using univariate and multivariable analyses. The area under the receiver operating characteristic curve (AUROC) and the Hosmer–Lemeshow test were used to assess model discrimination and calibration, respectively. Results Two hundred patients (18.6%) of 1077 participants died within 30 days. An 8-point score was generated from the five independent predictors for 30-day mortality including Glasgow Coma Scale, pneumonia, midline shift on brain images, blood glucose, and female sex, which was named GPS-GF. The resulting score showed good discrimination (AUROC) and well calibrated (Hosmer–Lemeshow test) in the derivation (0.909; p = 0.102) and internal validation cohort (0.922; p = 0.153). Compared with iScore, the GPS-GF score exhibited remarkably better discriminative power and predictive accuracy regarding the 30-day mortality in patients with AF-related stroke. Conclusion The GPS-GF score is a simple and valid tool for predicting 30-day mortality in patients with AF-related stroke.

Prognostic analysis for short- and long-term outcomes of newly diagnosed epilepsy

PURPOSE To explore predictors for short- and long-term prognosis of newly diagnosed epilepsy. METHODS 549 consecutive patients with newly diagnosed epilepsy were reviewed, 336 were enrolled in the study. Two-year remission in the short term (5 years) and five-year remission in the long term (>5, up to 8 years) were assessed as the outcomes. Logistic regression was used to identify independent predictors for unfavorable outcomes. χ2 test was used to compare the retention rates of old and new antiepileptic drugs (AEDs). RESULTS 185 patients (55%) attained two-year remission in the short term, 163 (48.5%) attained terminal remission in the long term. The time interval between index seizure and AED start >12 months implied an unfavorable outcome in the short term (OR=1.9, p=0.03). Two or more seizures in the first year after AED start showed the strongest negative prognostic impact in the both short- and long-term outcomes (OR=2.3, p=0.02; OR=1.9, p=0.03). As the seizure frequency rose, the possibility for unfavorable outcome increased. The terminal retention rates of traditional and new AEDs were not significantly different (p=0.07). CONCLUSIONS For patients with newly diagnosed epilepsy, the time interval between index seizure and AED start only influences the short-term outcome. Number of seizures in the first year after AED start is associated with both short- and long-term outcomes. Its imperative to initiate adequate, tolerated and appropriately chosen AED schedules after the definitive diagnosis of epilepsy.

Erratum: Corrigendum: Astrocytic Acid-Sensing Ion Channel 1a Contributes to the Development of Chronic Epileptogenesis

Scientific Reports 6: Article number: 31581; published online: 16 August 2016; updated: 06 December 2016