1.Expert consensus on pediatric orthodontic therapies of malocclusions in children
Zhou CHENCHEN ; Duan PEIPEI ; He HONG ; Song JINLIN ; Hu MIN ; Liu YUEHUA ; Liu YAN ; Guo JIE ; Jin FANG ; Cao YANG ; Jiang LINGYONG ; Ye QINGSONG ; Zhu MIN ; Jiang BEIZHAN ; Ruan WENHUA ; Yuan XIAO ; Li HUANG ; Zou RUI ; Tian YULOU ; Gao LI ; Shu RUI ; Chen JIANWEI ; Liu RENKAI ; Zou SHUJUAN ; Li XIAOBING
International Journal of Oral Science 2024;16(2):186-196
Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.
2.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
3.Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study
Xiaoyan LI ; Shanghao LIU ; Chuan LIU ; Hongmei ZU ; Xiaoqing GUO ; Huiling XIANG ; Yan HUANG ; Zhaolan YAN ; Yajing LI ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Fei LIU ; Lei HUANG ; Fanping MENG ; Xiaoning ZHANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Zhangshu QU ; Min YUAN ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yongzhong LI ; Qiaohua YANG ; Huai LI ; Xuelan ZHAO ; Zemin TIAN ; Hongji YU ; Xiaojuan ZHANG ; Chenxi WU ; Zhijian WU ; Shengqiang LI ; Qian SHEN ; Xuemei LIU ; Jianping HU ; Manqun WU ; Tong DANG ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Dongmei YAN ; Jun LIU ; Wei FU ; Jie YU ; Fusheng WANG ; Xiaolong QI ; Junliang FU
Chinese Journal of Hepatology 2023;31(9):961-968
Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.
4.Risk factors for recurrence after intravitreal anti-vascular endothelial growth factor injection for retinopathy of prematurity.
Qing-Fei HAO ; Jing CHEN ; Peng RUAN ; Gao-Pan LI ; Jing ZHANG ; Hao-Ming CHEN ; Hong-Xiang GUO ; Xiao-Juan SUN ; Xiu-Yong CHENG
Chinese Journal of Contemporary Pediatrics 2022;24(11):1207-1212
OBJECTIVES:
To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence.
METHODS:
A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment.
RESULTS:
After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05).
CONCLUSIONS
Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.
Female
;
Humans
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Infant
;
Infant, Newborn
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Pregnancy
;
Angiogenesis Inhibitors/therapeutic use*
;
Endothelial Growth Factors/therapeutic use*
;
Hemorrhage
;
Hypertension, Pregnancy-Induced
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Oxygen/therapeutic use*
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Retinopathy of Prematurity/drug therapy*
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Retrospective Studies
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Risk Factors
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Vascular Endothelial Growth Factor A
5.Clinical characteristics of 18 children with chronic nonbacterial osteomyelitis.
Hai Mei LIU ; Ying Yan SHI ; Xie Mei RUAN ; Yi Ru GONG ; Tao ZHANG ; Yi Fan LI ; Qiao Qian ZENG ; Qian Ying LYU ; Guo Min LI ; Zhong Wei QIAO ; Ha WU ; Da Hui WANG ; Lian CHEN ; Hui YU ; Hong XU ; Li SUN
Chinese Journal of Pediatrics 2022;60(12):1271-1275
Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.
Female
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Male
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Humans
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Child
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Retrospective Studies
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Osteomyelitis/drug therapy*
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Arthralgia
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Diphosphonates
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Fever
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Graft vs Host Disease
6. Morphological analysis of thoracic pedicle of 12-15-year-old idiopathic scoliosis and normal spine in northern Shaanxi province
Cai-Lian RUAN ; Xue-Feng HUI ; Lu WANG ; Hui ZHU ; Lin ZHAO ; Bo-Feng LIU ; Xiao-Ji LI ; Hong-Tao GUO
Acta Anatomica Sinica 2022;53(2):225-237
Objective To study the anatomical structure of normal and scoliotic thoracic vertebrae in adolescents aged 12-15 years in Northern Shanxi Province, to provide detailed information for pedicle screw placement, and to provide data references for screw size design. Methods Totally 120 cases of normal thoracolumbar CT of 120 adolescents aged 12 to 15 years and 30 cases of adolescent idiopathic scoliosis were collected in Northern Shaanxi Province. The raw data of thoracolumbar tomographic images scanned continuously were imported into Mimics16. 0 software for analysis and measurement in DICOM format. Measurement indicators: pedicle width, pedicle height, pedicle length, transverse diameter of spinal canal, longitudinal diameter of spinal canal, transverse pedicle angle,maximum transverse pedicle angle, sagittal pedicle angle and pedicle area. Results Pedicle width:12-13 years old, T
7.Deep learning applied to two-dimensional color Doppler flow imaging ultrasound images significantly improves diagnostic performance in the classification of breast masses: a multicenter study.
Teng-Fei YU ; Wen HE ; Cong-Gui GAN ; Ming-Chang ZHAO ; Qiang ZHU ; Wei ZHANG ; Hui WANG ; Yu-Kun LUO ; Fang NIE ; Li-Jun YUAN ; Yong WANG ; Yan-Li GUO ; Jian-Jun YUAN ; Li-Tao RUAN ; Yi-Cheng WANG ; Rui-Fang ZHANG ; Hong-Xia ZHANG ; Bin NING ; Hai-Man SONG ; Shuai ZHENG ; Yi LI ; Yang GUANG
Chinese Medical Journal 2021;134(4):415-424
BACKGROUND:
The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images.
METHODS:
Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists.
RESULTS:
The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%).
CONCLUSIONS:
The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists.
TRIAL REGISTRATION
Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
Area Under Curve
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Breast/diagnostic imaging*
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Breast Neoplasms/diagnostic imaging*
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China
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Deep Learning
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Humans
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ROC Curve
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Sensitivity and Specificity
8.Forensic Identification of Diving Deaths.
Wei WU ; Bing-Bing GUO ; Jing-Guo ZHANG ; Rong-Shuai WANG ; Hong-Bin RUAN ; Liang LIU
Journal of Forensic Medicine 2021;37(5):683-686
Investigation of the cause of death during diving is one of the contents of forensic pathology. In this article, relevant foreign literature is reviewed to summarize the techniques and methods used in the identification of diving deaths, such as accident reconstruction, diving monitoring data, postmortem CT examination and gas analysis (location and quantity) in the body of the corpse, in order to provide a reference for forensic identification of such cases.
Autopsy/methods*
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Diving
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Forensic Medicine
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Forensic Pathology
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Humans
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Postmortem Changes
9.Efficiency comparison of Kwak and ACR ( 2017 ) Thyroid Imaging Reporting and Data System ( TI‐RADS) classification :a polycentric retrospective study
Yu LIANG ; Linxian YUE ; Qin CHEN ; Jie LIN ; Daoning GUO ; Peng HE ; Fang YANG ; Wensheng YUE ; Hong ZHENG ; Jiaquan RUAN ; Haijun LIU ; Jianqiong SONG ; Lingying YANG ; Juan WANG ; Chengting ZHOU ; Yutian WU ; Siyi WANG ; Yanqiong TANG ; Mengxia YUAN ; Yan ZHAO
Chinese Journal of Ultrasonography 2019;28(5):419-424
Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P<0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P < 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .
10.Oculoleptomeningeal amyloidosis associated with transthyretin Leu12Pro mutation in a Chinese family
Rongjing GUO ; Ting CHANG ; Shaobo ZHANG ; Yu LIU ; Zhe RUAN ; Hong LIN
Chinese Journal of Neurology 2019;52(5):394-398
Objective To discuss the characteristics of clinical presentation,neuroimaging and genetics in a Chinese family of oculeptomeningeal amyloidosis (OLMA) associated with the transthyretin (TTR) Leul2Pro mutation.Methods Clinical characteristics of the pedigree and peripheral blood samples of an OLMA patient with TTR Leu12Pro mutation were collected from Tangdu Hospital on September 25,2015.Firstly,exon detection was performed on the proband and the family validation of her father and sister was carried out.The clinical,neuroimaging and genetic characteristics of the disease were analyzed.Results A 36-year-old right-handed woman was suffered recurrent episodes of slurred speech with right-sided weakness.She presented initi.ally with headache,autonomic dysfunction,visual and hearing loss.Magnetic resonance imaging showed extensive leptomeningeal enhancement,and cerebrospinal fluid analysis showed a raised protein of 1566.54 mg/L.The examination of the both eyes showed dry eye,vitreous opacity,and mild cataract.The proband and her sister,the sister's eldest daughter,the proband's son showed c.95T>C mutation in exon2 of TTR gene and Leu12Pro mutation in TTR protein.Conclusions OLMA should be suspected if central nervous system symptoms are observed in combination with one or more of the following:family history of a neuropathy,autonomic dysfunction,cardiac hypertrophy,hear or ocular involvement,gadolinium-enhanced magnetic resonance imaging of the brain and spine revealing diffuse leptomeningeal enhancement,lumbar puncture demonstrating elevated protein without evidence of malignant cells on cytology.Genetic testing for pathogenic mutation in TTR gene is helpful for diagnosis of OLMA.

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