Chinese Medical Journal

Status of Noninvasive Brain Stimulation in the Therapy of Alzheimer's Disease Yi-Cong Lin, Yu-Ping Wang Chinese Medical Journal 2018 131(24):2899-2903

Monitoring Value of Multimodal Magnetic Resonance Imaging in Disease Progression of Amyotrophic Lateral Sclerosis: A Prospective Observational Study Dong-Chao Shen, Yin-Yan Xu, Bo Hou, Hong-Fei Tai, Kang Zhang, Shuang-Wu Liu, Zhi-Li Wang, Feng Feng, Ming-Sheng Liu, Li-Ying Cui Chinese Medical Journal 2018 131(24):2904-2909 Background: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. Methods: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry; cerebral blood flow (CBF) evaluated by arterial spin labeling; functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI; and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. Results: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. Conclusion: Multimodal MRI could be used to monitor short-term brain changes in ALS patients.

An Investigation and Suggestions for the Improvement of Brain Death Determination in China Ying-Ying Su, Wei-Bi Chen, Gang Liu, Lin-Lin Fan, Yan Zhang, Hong Ye, Dai-Quan Gao, Yi-Fei Liu, Meng-Di Jiang Chinese Medical Journal 2018 131(24):2910-2914 Background: Brain death is the irreversible cessation of the function of the brain including the brainstem. In 2013, the Brain Injury Evaluation Quality Control Centre (BQCC) of the National Health and Family Planning Commission issued criteria and practical guidelines for the determination of brain death. This study aimed to evaluate whether the institutions have adopted these guidelines and to make suggestions for the improvement of the current criteria and practical guidelines for brain death determination in China. Methods: Consecutive brain death cases from 44 hospitals were evaluated for summary statistics for the following data: the performance of BQCC criteria and practical guidelines, clinical examination, apnea testing, ancillary testing, and the number of examinations as well as the waiting periods between examinations and details of who determined brain death. Data analysis was conducted from January 2013 to December 2017. Results: A total of 550 cases were obtained. All patients were determined to have deep coma and met the prerequisites for clinical testing. The performance rates of four brainstem reflex examinations (except cough reflex) ranged from 97.5% to 98.0%, and the completion rate as well as the coincidence rate were both 100.0%. The 238 cases (50.7%) completed apnea testing, and 231 cases (42.0%) had to stop apnea testing during the examination because of instability. The performance rates of the three ancillary tests, including electroencephalogram, short-latency somatosensory evoked potential, and transcranial Doppler, were 89.5%, 67.5%, and 79.5%, respectively; furthermore, the coincidence rates were 98.6%, 96.5%, and 99.5%, respectively. The combination of two ancillary tests was more accurate than one single ancillary test. A total of 401 (72.9%) cases successfully underwent two separate examinations to determine brain death with at least a 12-h waiting period. All brain death cases were determined by at least two qualified physicians. Conclusion: This study might provide suggestions for brain death determination in China.

New-Onset Geriatric Epilepsy in China: A Single-Center Study Jian-Hua Chen, Xiang-Qin Zhou, Qiang Lu, Li-Ri Jin, Yan Huang Chinese Medical Journal 2018 131(24):2915-2920 Background: Few studies have been published on new-onset geriatric epilepsy especially in older Chinese people. This study was to have a comprehensive understanding of new-onset geriatric epilepsy and find a more reasonable diagnosis and management of epilepsy in older people. Methods: One hundred and three patients with onset age 60 years and older were admitted between January 2008 and December 2016. Electronic medical records were reviewed to collect information. Results: There were 103 older patients with new-onset epilepsy. The mean age of the patients was 68.5 ± 6.4 years (range: 60–89 years), and there were 67 (65%) men and 36 (35%) women. The mean onset age was 67.9 ± 6.2 years (range: 60–89 years). The most common identifiable etiology of symptomatic seizures was autoimmune epilepsy in 43 (41.7%) patients. The second most common etiology was stroke in 15 (14.6%) patients. Seven (6.8%) older patients with acute seizures present with status epilepticus and 26 (25.2%) patients experienced clustered seizures (more than three events in 24 h) at seizure onset. Focal seizures (96.1%) were more common than generalized seizures (3.9%). Fifty-three (51.5%) patients had an abnormal brain magnetic resonance imaging (MRI) scan. Among them, video-electroencephalogram findings in 31 (30.1%) patients correlated with MRI abnormalities. Levetiracetam was the most used drugs before admission, in hospital, and during follow-up. Conclusions: Autoimmune encephalitis is becoming an increasing risk factor of subsequent epilepsy in older people. Older patients with new epilepsy are more likely to respond to antiepileptic drugs, and drug-resistant epilepsy is uncommon.

Diagnosis of Spinal Muscular Atrophy: A Simple Method for Quantifying the Relative Amount of Survival Motor Neuron Gene 1/2 Using Sanger DNA Sequencing Yan-Yan Cao, Wen-Hui Zhang, Yu-Jin Qu, Jin-Li Bai, Yu-Wei Jin, Hong Wang, Fang Song Chinese Medical Journal 2018 131(24):2921-2929 Background: Spinal muscular atrophy (SMA) is caused by homozygous deletion or compound heterozygous mutation of survival motor neuron gene 1 (SMN1), which is the key to diagnose SMA. The study was to establish and evaluate a new diagnostic method for SMA. Methods: A total of 1494 children suspected with SMA were enrolled in this study. Traditional strategy, including multiplexed ligation-dependent probe amplification (MLPA) and TA cloning, was used in 1364 suspected SMA children from 2003 to 2014, and the 130 suspected SMA children were tested by a new strategy from 2015 to 2016, who were also verified by MLPA combined with TA cloning. The SMN1 and SMN2 were simultaneously amplified by polymerase chain reaction using the same primers. Mutation Surveyor software was used to detect and quantify the SMN1 variants by calculating allelic proportions in Sanger sequencing. Finally, turnaround time and cost of these two strategies were compared. Results: Among 1364 suspected SMA children, 576 children had SMN1 homozygous deletion and 27 children had SMN1 compound heterozygous mutation. Among the 130 cases, 59 had SMN1 homozygous deletion and 8 had heterozygous deletion: the SMN1-specific peak proportion on exon 7 was 34.6 ± 1.0% and 25.5 ± 0.5%, representing SMN1:SMN2 to be 1:2 and 1:3, respectively. Moreover, five variations, including p.Ser8Lysfs *23 (in two cases), p.Leu228*, p.Pro218Hisfs *26, p.Ser143Phefs*5, and p.Tyr276His, were detected in 6/8 cases with heterozygous deletion, the mutant allele proportion was 31.9%, 23.9%, 37.6%, 32.8%, 24.5%, and 23.6%, which was similar to that of the SMN1-specific site on exon 7, suggesting that those subtle mutations were located in SMN1. All these results were consistent with MLPA and TA cloning. The turnaround times of two strategies were 7.5 h and 266.5 h, respectively. Cost of a new strategy was only 28.5% of the traditional strategy. Conclusion: Sanger sequencing combined with Mutation Surveyor analysis has potential application in SMA diagnosis.

Comparison and Correlation of Magnetic Resonance Imaging and Clinical Severity in Nonhuman Immunodeficiency Virus Patients with Cryptococcal Infection of Central Nervous System Xue-Qin Li, Shuang Xia, Jian-Song Ji, Yong-Hua Tang, Mei-Zhu Zheng, Yong-Mei Li, Fei Shan, Zhi-Yan Lu, Jian Wang, Jin-Kang Liu, Hui-Juan Zhang, Yu-Xin Shi, Hong-Jun Li Chinese Medical Journal 2018 131(24):2930-2937 Background: The incidence of cryptococcal meningitis among immunocompetent patients increases, especially in China and imaging plays an important role. The current study was to find the correlation between magnetic resonance imaging (MRI) manifestation and clinical severity in nonhuman immunodeficiency virus patients with cryptococcal infection of central nervous system (CNS). Methods: A total of 65 patients with CNS cryptococcal infection from August 2014 to October 2016 were retrospectively included in this study. All the patients had MRI data and clinical data. The patients were divided into two groups according to whether the patients were confirmed with identifiable underlying disease. Comparison and correlation of MRI and clinical data in both groups were investigated using independent sample t- test, Chi-square test, Mann-Whitney test and Spearman rank correlation analysis. Results: In all 65 patients, 41 cases (41/65, 63.1%; Group 1) had normal immunity and 24 cases (24/65, 36.9%; Group 2) had at least one identifiable underlying disease. Fever, higher percentage of neutrophil (NEUT) in white blood cell (WBC), and increased cell number of cerebral spinal fluid (CSF) were much common in patients with underlying disease (Group 1 vs. Group 2: Fever: 21/41 vs. 21/24, χ2 = 8.715, P = 0.003; NEUT in WBC: 73.15% vs. 79.60%, Z = −2.370, P = 0.018; cell number of CSF: 19 vs. 200, Z = −4.298, P < 0.001; respectively). Compared to the patients with normal immunity, the lesions are more common in the basal ganglia among patients with identifiable underlying disease (Group 1 vs. Group 2: 20/41 vs. 20/24, χ2 = 7.636, P = 0.006). The number of the involved brain areas in patients with identifiable underlying disease were well correlated with the number of cells and pressure of CSF (r = −0.472, P = 0.031; r = 0.779, P = 0.039; respectively). Conclusions: With the increased number of the involved brain areas in patients with identifiable underlying disease, the body has lower immunity against the organism which might result in higher intracranial pressure and more severe clinical status.

Clinical Features and Prognostic Risk Factors of Choroid Plexus Tumors in Children Wen-Jian-Long Zhou, Xi Wang, Jia-Yi Peng, Shun-Chang Ma, Dai-Nan Zhang, Xiu-Dong Guan, Jin-Fu Diao, Jian-Xing Niu, Chun-De Li, Wang Jia Chinese Medical Journal 2018 131(24):2938-2946 Background: Decision-making concerning the treatment of choroid plexus tumor (CPT) in pediatric patients remains a topic of considerable debate. The aim of this work was to describe clinical features and prognostic risk factors of CPT in the pediatric population and to provide theoretical opinions regarding clinical decisions for CPT. Methods: The data of 96 patients with CPT and younger than 14 years were retrospectively analyzed. Clinical characteristics such as pathological type of CPTs, rate and severity of hydrocephalus, treatment and outcome, and recurrence were investigated. For categorical variables, the Pearson's Chi-square test was performed. The Mann–Whitney U-test was used for comparisons between nonnormally distributed parameters. Log-rank test was used for progression-free survival (PFS). Results: The study included 70 choroid plexus papilloma (CPP) cases, 17 atypical choroid plexus papilloma (aCPP) cases, and 9 choroid plexus carcinoma (CPC) cases. Compared with patients with CPP or aCPP, patients with CPC had a shorter disease course (median: CPP, 4 months; aCPP, 2 months; CPC, 1 month; H: 23.5, P < 0.001), higher rate of acute hydrocephalus (CPP, 27.1%; aCPP, 52.9%; CPC, 77.8%; χ2 = 10.9, P < 0.05), and lower incidence of cure rate (CPP, 85.7%; aCPP, 70.5%; CPC, 33.3%; χ2 = 13.5, P < 0.05). The severity of hydrocephalus with tumor in the lateral or third ventricle was significantly higher than that with tumors in the fourth ventricle (severe hydrocephalus: lateral ventricle, 51.7%; third ventricle, 47.0%; fourth ventricle, 11.1%; χ2 = 26.0, P < 0.001). Patients with gross total surgical resection had no better PFS than those with partial resection because of the use of adjuvant therapy in the latter (χ2 = 4.0, P > 0.05). Patients with CPC experienced shorter time for recurrence than those with CPP or aCPP (χ2 = 40.1, P < 0.0001). Conclusions: Our results indicated that CPP in the fourth ventricle could trigger serious clinical symptoms at an early stage, requiring early intervention. Adjuvant treatment might be necessary for patients with partially resected CPP, aCPP, and CPC to achieve a favorable outcome.

Plasminogen Activator Inhibitor 1 as a Poor Prognostic Indicator in Resectable Pancreatic Ductal Adenocarcinoma Wen-Jing Liu, Li Zhou, Zhi-Yong Liang, Wei-Xun Zhou, Lei You, Tai-Ping Zhang, Yu-Pei Zhao Chinese Medical Journal 2018 131(24):2947-2952 Background: Plasminogen activator inhibitor 1 (PAI-1) was previously established to impact several phenotypes in many kinds of cancer, including pancreatic cancer. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) needs support of further evidence. This study was designed to address the issue. Methods: PAI-1 expression was detected by tissue microarray-based immunohistochemical staining in formalin-fixed paraffin-embedded specimens from 93 PDAC patients with surgical resection from September 2004 to December 2008. Its relationships with clinicopathologic variables and tumor-specific survival (TSS) were further evaluated using Chi-square, Kaplan-Meier, log-rank, as well as Cox regression analyses. Results: Expression of PAI-1 was much higher in tumor than that in nontumor tissues, based on comparison of all samples and 74 matched ones (95 [47.5, 180] vs. 80 [45, 95], Z = −2.439, P = 0.015 and 100 [46.9, 182.5] vs. 80 [45, 95], Z = −2.594, P = 0.009, respectively). In addition, tumoral PAI-1 expression was positively associated with N stage (22/35 for N1 vs. 21/51 for N0, χ2 = 3.903, P = 0.048). Univariate analyses showed that TSS of patients with high PAI-1 tumors was significantly poorer than that of those with low PAI-1 tumors (log rank value = 19.00, P < 0.0001). In multivariate Cox regression test, PAI-1 expression was identified as an independent predictor for long-term prognosis of resectable PDAC (hazard ratio = 2.559, 95% confidence interval = 1.499–4.367, P = 0.001). Conclusion: These results suggest that expression of PAI-1 is upregulated in PDAC and might serve as a poor prognostic indicator.

Clinicopathological Features of Nondiabetic Renal Diseases from Different Age Groups: An Observational Cross-sectional Study Xiao-Min Liu, Qian Wang, Zhe-Yi Dong, Wei-Guang Zhang, Guang-Yan Cai, Li Zhang, Yong Wang, Han-Yu Zhu, Li Tang, Wan-Jun Shen, Xiang-Mei Chen Chinese Medical Journal 2018 131(24):2953-2959 Background: Diabetes mellitus (DM) has become the leading cause of chronic kidney disease (CKD). Nondiabetic renal diseases (NDRDs) have different clinicopathological features and prognosis from those of diabetic nephropathy. Our study sought to analyze the clinical and pathological features of NDRDs, in different age groups through a cross-sectional study. Methods: All patients with type 2 DM at our center who underwent renal biopsy between March 1997 and March 2017 were screened and divided into three groups by age: Group 1 (youth group), 18–44 years old; Group 2 (middle-aged group), 45–59 years old; and Group 3 (elderly group), ≥60 years old. We analyzed the clinicopathological data and risk factors by univariate and multivariate logistic regression for NDRD of the patients to identify the features of NDRD in different age groups. Results: We included 982 patients in the final analysis. Patients with NDRD accounted for 64.4% of all patients. IgA nephropathy (IgAN) was the most common pathological pattern in young patients with NDRD, accounting for 26.3%. In the middle-aged group, the two most common pathological patterns were IgAN and membranous nephropathy. Membranous nephropathy was the most common pathological pattern in elderly patients with NDRD, accounting for 29.3%. Consistent with pathological features, glomerular hematuria is a risk factor for NDRD in Group 1 (odds ratio [OR], 26.514; 95% confidence interval [CI], 2.503–280.910; P = 0.006). On the other hand, rapidly increasing proteinuria or nephrotic syndrome is a risk factor for NDRD in Group 2 (OR, 5.921; 95% CI, 2.061–17.013; P = 0.001) and Group 3 (OR, 90.409; 95% CI, 6.198–1318.826; P = 0.001). Conclusions: This single-center study showed that the proportion and composition of NDRD differ among different age groups. Consistent with pathological features, some clinical indices such as hematuria and proteinuria showed different features among different age groups.

Anatomical Risk Factors of Anterior Cruciate Ligament Injury Lei Shen, Zhi-Gao Jin, Qi-Rong Dong, Liu-Bing Li Chinese Medical Journal 2018 131(24):2960-2967 Background: Nowadays, the anterior cruciate ligament (ACL) injury has been one of the most common diseases of the knee joint. The relationships between the ACL injury and the anatomical structures are still controversial. This study aimed to identify the anatomical risk factors of ACL injury by magnetic resonance imaging (MRI) of the knee. Methods: This was a retrospective study of 125 patients undergoing primary ACL reconstruction between July 2013 and May 2017. Another 125 patients without any organic knee joint injury were served as controls. The shape of intercondylar notch, the intercondylar notch width index, the intercondylar notch height index, the α angle, the β angle, and the medial and lateral tibial plateau slope were measured with MRI and compared. The data were compared by binary logistic regression to find the risk factors. Results: The two groups differed in the proportion of male patients (70.4% vs. 52.0%, χ2 = 8.911, P = 0.003), but gender was excluded as a risk factor for ACL injury with regression analysis (odds ratio = 1.476, 95% confidence interval [CI]: 0.689–3.160, P = 0.317). The injured group was found to have a smaller notch width index (95% CI = 7.960E-23–2.154E-9, P < 0.001), a larger β angle (95% CI = 1.311–1.785, P < 0.001), and a larger lateral tibial plateau slope (95% CI = 1.201–1.683, P < 0.001). The cutoff values of notch width index, β angle, and the lateral tibial plateau slope were 0.252, 38.5°, and 7.5°, respectively. Conclusions: In this study, a narrow intercondylar notch (intercondylar notch width index <0.252), a larger lateral tibial slope (>7.5°), and larger β angle (>38.5°) might be the factors associated with ACL injury. Trial Registration: ChiCTR-RRC-17014116; http://www.chictr.org.cn/showproj.aspx?proj=24119.