Identification of blood metabolic biomarkers associated with diabetic distal symmetric sensorimotor polyneuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Distal symmetric sensorimotor polyneuropathy (DSPN) is a common neurologic complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms and changes in serum metabolites remain largely undefined. This study aimed to characterize the plasma metabolite profiles of participants with T2DM using targeted metabolomics analysis and identify potential biomarkers for DSPN. METHODS: A combined liquid chromatography MS/MS and direct flow injection were used to quantify plasma metabolite obtained from 63 participants with T2DM, 81 with DSPN, and 33 nondiabetic control participants. A total of 130 metabolites, including amino acids, biogenic amines, sphingomyelins (SM), phosphatidylcholines, carnitines, and hexose, were analyzed. RESULTS: A total of 16 plasma metabolites and 3 cholesterol-related laboratory parameters were found to have variable importance in the projection score >1.0 and false discovery rate <5.0% between control, T2DM, and DSPN. Among these variables, five serum metabolites, including phenylalanine (AUC = 0.653), alanine (AUC = 0.630), lysine (AUC = 0.622) tryptophan (AUC = 0.620), and SM C16:0 (AUC = 0.630), are potential biomarkers (all p < .05) in distinguishing T2DM with DSPN from those without (AUC = 0.720). CONCLUSIONS: In this cross-sectional study, derangement of several metabolites in the plasma was observed in T2DM with and without DSPN, and these metabolites may be potential biomarkers for predicting DSPN. Longitudinal studies are warranted.

Threshold growth has a limited role in differentiating hepatocellular carcinoma from other focal hepatic lesions.

BACKGROUND AND OBJECTIVE: The role of threshold growth, as one of the major features (MFs) of hepatocellular carcinoma (HCC) in the Liver Imaging Reporting and Data System (LI-RADS) is inconsistent. This study evaluated the LI-RADS diagnostic performance for HCC when threshold growth was removed or replaced by independently significant ancillary features (AFs). MATERIALS AND METHODS: This retrospective institutional review board-approved study included patients with a high HCC risk who underwent gadoxetic acid-enhanced MRIs. The MRI findings were consistent with pathologically proven focal hepatic observations. The pathological results were used as the gold standard reference. The sizes of the lesions with and without threshold growth were compared. Univariate and multivariate logistic regression analyses were used to confirm the independently significant AFs of HCC. In addition to the classification criteria of LI-RADS version 2018 (LI-RADS v2018), the lesions were also reclassified according to the following two schemes: scheme A, using all MFs except threshold growth, with threshold growth feature treated as an AF favouring malignancy; and scheme B, replacing the threshold growth feature with independently significant AFs and treated them as new MFs. The diagnostic performance of the above two LI-RADS schemes for HCC was calculated and compared with that of LI-RADS v2018. RESULTS: A total of 379 patients and 426 observations were included. Threshold growth was not an independent significant MF for HCC diagnosis [odds ratio (OR), 1.0; 95% confidence interval (CI), 0.6-1.8; p = 0.927]. For all three groups of observations (HCCs, non-HCC malignancies, and benign lesions), the mean size with threshold growth was smaller than that without threshold growth (all p < 0.05). The nodule-in-nodule feature was an independent significant AF (OR, 9.8; 95% CI, 1.2-79.3; p = 0.032) and was used to replace threshold growth as a new MF in scheme B. The sensitivities of schemes A and B were 74.0% and 75.6%, respectively. The specificities of schemes A and B were the same (88.6%). None of the diagnostic performance metrics for HCC (sensitivity, specificity, accuracy) of either scheme A or B was significantly different from those of LI-RADS v2018 (all p > 0.05). CONCLUSION: Threshold growth is not an independently significant MF for HCC diagnosis. The diagnostic performance of LI-RADS for HCC is not affected regardless of whether threshold growth is removed from the list of MFs or replaced with an independently significant and more HCC-specific AF, which is the nodule-in-nodule feature.

Establishment of a new classification system for chronic inflammatory demyelinating polyneuropathy based on unsupervised machine learning.

INTRODUCTION/AIMS: A model for predicting responsiveness to immunotherapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) has not been well established. We aimed to establish a new classifier for CIDP patients based on clinical characteristics, laboratory findings, and electrophysiological features. METHODS: The clinical, laboratory, and electrophysiological features of 172 treatment-naïve patients with CIDP between 2003 and 2019 were analyzed using an unsupervised hierarchical clustering. The identified pivotal features were used to establish simple classifications using a tree-based model. RESULTS: Three clusters were identified: 1, n = 65; 2, n = 70; and 3, n = 37. Patients in Cluster 1 scored lower on the disability assessment score before treatment. More patients in Clusters 2 (90.0%) fulfilled demyelinating criteria than patients in Cluster 1 (30.8%, p < .001). Cluster 3 had more patients with chronic kidney disease (CKD) (27.0%) and hypoalbuminemia (3.40 g/dL) than did Cluster 2 (CKD: 0%, p < .001; hypoalbuminemia: 4.09 g/dL, p < .001). The responsiveness to pulse steroid therapy was higher in Cluster 2 (70.0%) than in Clusters 1 (31.8%; p = .043) and 3 (25.0%; p = .014). A tree-based model with four pivotal features classified patients in our cohort into new clusters with high accuracy (89.5%). DISCUSSION: The established hierarchical clustering with the tree-based model identified key features contributing to differences in disease severity and response to pulse steroid therapy. This classification system could assist clinicians in the selection of treatments and could also help researchers by clustering patients for clinical treatment trials.

Isaacs' syndrome as the initial presentation of malignant thymoma and associated with double-positive voltage-gated potassium channel complex antibodies, a case report.

BACKGROUND: Isaacs' syndrome is a peripheral nerve hyperexcitability (PNH) syndrome due to peripheral motor nerve instability. Acquired Isaacs' syndrome is recognized as a paraneoplastic autoimmune disease with possible pathogenic voltage-gated potassium channel (VGKC) complex antibodies. However, the longitudinal correlation between clinical symptoms, VGKC antibodies level, and drug response is still unclear. CASE PRESENTATION: A 45-year-old man had progressive four limbs soreness, muscle twitching, cramps, and pain 4 months before admission. Electromyography (EMG) studies showed myokymic discharges, neuromyotonia, and an incremental response in the high-rate (50 Hz) repetitive nerve stimulation (RNS) test. Isaacs' syndrome was diagnosed based on clinical presentations and EMG reports. Serum studies showed positive VGKC complex antibodies, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. The acetylcholine receptor antibody was negative. Whole-body computed tomography (CT) and positron emission tomography revealed a mediastinal tumor with the great vessels encasement, right pleura, and diaphragm seeding. Biopsy confirmed a World Health Organization type B2 thymoma, with Masaoka stage IVa. His symptoms gradually improved and both LGI1 and CASPR2 antibodies titer became undetectable after concurrent chemoradiotherapy (CCRT) and high dose steroid treatment. However, his Isaacs' syndrome recurred after the steroid was reduced 5 months later. Follow-up chest CT showed probable thymoma progression. LGI1 antibody turned positive again while CASPR2 antibody remained undetectable. CONCLUSIONS: Our patient demonstrates that Isaacs' syndrome could be the initial and only neuromuscular manifestation of malignant thymoma. His Isaacs' syndrome is correlated well with the LGI1 antibody level. With an unresectable thymoma, long-term immunosuppressant therapy may be necessary for the management of Isaacs' syndrome in addition to CCRT for thymoma.

The First Guillain-Barr? Syndrome After SARS-CoV-2 Vaccination in Taiwan.

PURPOSE: Guillain-Barre syndrome (GBS) is an immune-mediated disease of the peripheral nerves and could be fatal and has severe neurologic complications. This study herein reports the clinical course of the first patient of GBS after SARS-CoV-2 Oxford/AstraZeneca vaccination in Taiwan. CASE REPORT: A 38-year-old woman who presented with progressive numbness and weakness of both upper and lower limbs over 1 week. Ascending patterns was noted, and bilateral leg were more severe with diffused absence of deep tendon reflex. Clinical examination and investigation findings confirmed with the diagnosis of GBS. Deterioration of muscle power and respiratory failure had developed during the hospitalization. She had no common GBS predisposing history, but she had received her first SARS-CoV-2 Oxford/AstraZeneca vaccination intramuscularly 10 days prior to her symptoms. Clinical symptoms had much improved after double filtration plasmapheresis. CONCLUSION: Our case is the first case of GBS developed after AstraZeneca vaccine injection in Taiwan, presenting with atypical manifestation of early facial and bulbar involvement. The vaccination associated GBS should be closely monitored as other safety profile, since it may result in respiratory failure and severe neurologic complications. Keyword: Guillain-Barre Syndrome, SARS-CoV-2 Vaccination.

Real-world evidence on the safety and effectiveness of fingolimod in patients with multiple sclerosis from Taiwan.

BACKGROUND/PURPOSE: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. METHODS: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). RESULTS: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 103/uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353. CONCLUSION: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan.

[Remote sensing extraction method of Codonopsis pilosula planting area in Weiyuan county].

Due to the large amount of Codonopsis pilosula planted in Weiyuan county,and the arable land area,the local medicinal materials office uses a large amount of manpower,financial resources and material resources to estimate its area every year. In order to extract the information of local Chinese medicinal materials more quickly and simply,we try to apply remote sensing technology to the extraction of Chinese medicinal materials. This paper will use Weiyuan county of Gansu province as the research area,and use the domestic ZY-3 Satellite multi-spectral remote sensing image as the data source to find out the spectral characteristics of the party's participation in other remote sensing images. The visual interpretation method was used to extract the planting area of the C. pilosula in Weiyuan county. The estimated value of the planting area of C. pilosula using satellite remote sensing technology was 75 965 mu( 1 mu≈667 m2),which was basically consistent with the field survey data of the local medicinal materials office. After the accuracy verification,it was found that the precision of C. pilosula planted by visual interpretation was more than 70%. It is concluded that the satellite remote sensing technology can be used to extract the information of C. pilosula and it can provide the relevant information of the planting area of Chinese medicinal materials quickly and accurately.

[Extraction of distribution information of Angelicae sinensis plants in Weiyuan county based on remote sensing technology].

Due to the large amount of nutrients required during the cultivation of Angelica sinensis and in order to prevent the occurrence of pests and diseases,and the annual reduction of the planting area of Angelica and the balance of supply and demand of A. sinensis,the A. sinensis plantation adopts the rotation mode. This paper takes Wuyuan county of Gansu province as the research scope and use GF-1 Satellite data as the data source,using remote sensing technology combined with field survey results,to explore the effective method of visual interpretation for the extraction of A. sinensis planting area. A sample was selected to generate a spectrum according to different feature types. The different characteristics of A. sinensis and other features were analyzed and distinguished in remote sensing images,so that the A. sinensis planting plots were extracted and verified in remote sensing images. The results showed that the accuracy verification value of the visual interpretation method was 95. 85%. It is determined that the visual interpretation method can effectively extract the A. sinensis planting plots within the research scope and realize the comprehensive grasp of the spatial distribution information of A. sinensis.

Phoenixin: a novel brain-gut-skin peptide with multiple bioactivity.

In this brief review we summarize the current fndings relative to the discovery of a small peptide ligand, phoenixin (PNX). Using a bioinformatic approach, two novel peptides PNX-14 and PNX-20 containing 14 and 20 amino acids, respectively, were isolated from diverse tissues including the brain, heart, lung and stomach. Mass spectrometry analysis identified a major and minor peak corresponding to PNX-14 and PNX-20, in rat or mouse spinal cord extracts. With the use of a rabbit polyclonal antiserum, phoenixin immunoreactivity (irPNX) was detected in discrete areas of the rodent brain including several hypothalamic subnuclei and dorsal motor nucleus of the vagus. In addition, irPNX was detected in a population of sensory ganglion cells including dorsal root ganglion, nodose ganglion and trigeminal ganglion, and in cell processes densely distributed to the superficial layers of the dorsal horn, nucleus of the solitary tract and spinal trigeminal tract. irPNX cell processes were also detected in the skin and myenteric plexus, suggesting a brain-gut and/or brain-skin connection. Pharmacological studies show that PNX-14 injected subcutaneously to the nape of the neck of mice provoked dose-dependent repetitive scratching bouts directed to the back of the neck with the hindpaws. Our result suggests that the peptide PNX-14 and/or PNX-20, may serve as one of the endogenous signal molecules transducing itch sensation. Additionally, results from other laboratories show that exogenous PNX may affect a number of diverse behaviors such as memory formation, depression, reproduction, food-intake and anxiolytic-like behaviors.

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese.

BACKGROUND: The disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the early diagnosis of this heterogeneous and fatal disease becomes critical. METHODS: We retrospectively reviewed the characteristics of genetically confirmed ATTR Ala97Ser patients at a tertiary referral medical center. RESULTS: Eight patients from 7 different families were enrolled (61.7 ± 5.5 years). Gastrointestinal symptoms, dyspnea or chest tightness, rather than sensory symptoms, were the initial symptoms in two patients (2/7 = 29%). Body weight loss (3/7 = 43%), muscle wasting (4/7 = 57%), or dysphagia (3/7 = 43%) were the consecutive symptoms. Orthostatic symptoms including orthostatic hypotension (7/7 = 100%), dizziness (6/7 = 86%) and syncope (5/7 = 71%) tended to develop in the late phase of the disease. Autonomic dysfunction was conspicuous. Cardiographic findings included a combination of ventricular wall thickening and pericardial effusion (7/7 = 100%), a granular sparkling appearance of the ventricular myocardium (4/7 = 57%), or conduction abnormalities (5/7 = 71%). CONCLUSIONS: This study broadens the recognition of the initial signs and symptoms, including cardiographic findings and longitudinal manifestations in Taiwanese individuals with ATTR Ala97Ser mutation. These manifestations should prompt doctors to perform further studies and make an early diagnosis.

[Detection of gene mutation in glucose-6-phosphate dehydrogenase deficiency by RT-PCR sequencing].

OBJECTIVE: Since glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary hemolytic erythrocyte enzyme deficiency, most cases have single nucleotide mutations in the coding region, and current test methods for gene mutation have some missed detections, this study aimed to investigate the feasibility of RT-PCR sequencing in the detection of gene mutation in G6PD deficiency. METHODS: According to the G6PD/6GPD ratio, 195 children with anemia of unknown cause or who underwent physical examination between August 2013 and July 2014 were classified into G6PD-deficiency group with 130 children (G6PD/6GPD ratio <1.00) and control group with 65 children (G6PD/6GPD ratio≥1.00). The primer design and PCR amplification conditions were optimized, and RT-PCR sequencing was used to analyze the complete coding sequence and verify the genomic DNA sequence in the two groups. RESULTS: In the G6PD-deficiency group, the detection rate of gene mutation was 100% and 13 missense mutations were detected, including one new mutation. In the control group, no missense mutation was detected in 28 boys; 13 heterozygous missense mutations, 1 homozygous same-sense mutation (C1191T) which had not been reported in China and abroad, and 14 single nucleotide polymorphisms of C1311T were detected in 37 girls. The control group showed a high rate of missed detection of G6PD deficiency (carriers) in the specimens from girls (35%, 13/37). CONCLUSIONS: RT-PCR sequencing has a high detection rate of G6PD gene mutation and a certain value in clinical diagnosis of G6PD deficiency.

Clinical presentation and electrophysiological findings of porphyric neuropathies: a follow-up study.

INTRODUCTION: A case series of acute intermittent porphyria (AIP) is described that focuses on the clinical course of the disease with regard to neurological manifestations of the peripheral nervous system. METHODS: Eight patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogendeaminase activity, neuropathic patterns, serial changes in nerve conduction studies (NCS), and temporal relationship of central nervous system involvement. RESULTS: Six patients diagnosed with AIP<2 months after symptom onset had neuropathy that was predominantly upper extremity, motor, and proximal. NCS recovery rates were slower in the lower than the upper limbs. Two patients diagnosed >2 months after symptom onset had distal sensorimotor polyneuropathy. CONCLUSIONS: The findings from this case series suggest that the peripheral nerves may be differentially and selectively involved in different diagnostic stages of porphyric neuropathy.

Clinical and radiological findings suggesting disorders other than tolosa-hunt syndrome among ophthalmoplegic patients: a retrospective analysis.

OBJECTIVE: To investigate clinical and radiological features of Tolosa-Hunt syndrome (THS) and examine their diagnostic value, and to propose clinical and radiological features that indicate other symptomatic painful ophthalmoplegias (SPOs) in order to distinguish them from THS. BACKGROUND: Clinical presentations of THS are nonspecific and may overlap with many etiologies. Therefore, excluding other SPOs is essential for correct diagnosis. At the present time, the predictive value of the current International Classification of Headache Disorders (ICHD) criteria is not well established, and specific imaging markers that can discriminate SPOs from THS are lacking. METHODS: Patients referred with painful ophthalmoplegia over 12 years were recruited retrospectively and allocated into THS or SPO groups. Typical symptoms (episodic unilateral orbital pain preceding or developing with diplopia) and imaging of THS (inflammatory lesions in the cavernous sinus/orbit by magnetic resonance imaging) were proposed based on ICHD-3 beta criteria and previous literature. Atypical clinical and radiological features suggesting alternative diagnoses were also proposed to predict SPO. Initial presentations and imaging findings were registered and correlated with diagnostic outcomes. The predictive value of clinical and imaging findings was then evaluated. RESULTS: Of the 61 referred cases, 25 were classified as THS and 36 as SPO. Of the SPO cases, 52.8% manifested typical THS symptoms at onset. Patients with SPOs were prone to have atypical symptoms (47.2%) and radiographical findings (82.1%) in comparison to those with THS (4.0% and 4.2%, respectively; both P < .001). Both typical symptoms and imaging findings predicted a diagnosis of THS with high sensitivity (95.8% and 100%, respectively) but low specificity (47.2% and 28.6%, respectively). High sensitivity (82.1%) and specificity (95.8%) were achieved using atypical imaging features to predict SPO. CONCLUSION: A diagnosis of THS based strictly on clinical presentations or imaging results is not completely reliable. Identification of atypical imaging features may have a useful role in discriminating SPOs and thus avoid erroneous diagnoses of THS. Future studies with larger sample sizes are warranted to evaluate their validity in general population.

Wegener's granulomatosis with nervous system involvement: a hospital-based study.

BACKGROUND: The aim of this study was to ascertain the clinical manifestations of granulomatosis with polyangiitis (Wegener's) (GPA) with the involvement of the peripheral nervous system (PNS) and central nervous system (CNS). SUMMARY: All neurologic inpatients in a hospital over a 12-year period were reviewed. Nine patients met both the ACR 1990 traditional format criteria for the classification of GPA and the Chapel Hill nomenclature mandatory criteria for GPA. We focused on the clinical presentation, serological data, biopsy reports, disease activities [as assessed by the Birmingham Vasculitis Activity Score (BVAS)], electrophysiology, and brain images. Nine patients met the diagnostic criteria for GPA. The neurological signs of the initial manifestation of GPA were found in 6/9 (67%) patients. Eight patients had GPA-related CNS involvement, including four patients with chronic hypertrophic pachymeningitis, with either diffuse or focal thickening; three had intracranial hemorrhages and two had orbital mass lesions with optic nerve compression. In addition, six patients showed PNS involvement, including three with asymmetric sensorimotor polyneuropathy, two with symmetric sensorimotor polyneuropathy, and one with bilateral mononeuropathy. Key Messages: Neurological manifestation is not uncommon and can be the first clinical sign of GPA. The involvement of both CNS and PNS raises the possibility of GPA in hospitalized neurologic patients.

[Recovery and relapse of left ventricular systolic dysfunction in hospitalized patients with dilated cardiomyopathy: frequency and related factors].

OBJECTIVE: To investigate the frequency and predictors of recovery and relapse of left ventricular systolic dysfunction (LVSD) in hospitalized patients with dilated cardiomyopathy (DCM). METHODS: Patients with DCM hospitalized in Fuwai Hospital from October 2008 to December 2013 with repeat echocardiography results after discharge were reviewed and followed to December 2014 or until all-cause death or cardiac transplantation. Rate of recovery of LVSD, defined as an absolute increase in left ventricular ejection fraction (LVEF) of >10% to a level of >50% on follow-up, and those with relapse of LVSD, defined as a decrease in LVEF to a level of <45% after initial recovery was obtained and related factors affecting LVSD recovery and relapse were analyzed. RESULTS: After a mean follow-up of (28 ± 17) months, recovery of LVSD was evidenced in 114 of 382 patients (29.8%), LVEF increased from (31.6 ± 6.0) % to (55.8 ± 3.7) % (P<0.01) and left ventricular end-diastolic diameter (LVEDD) decreased from (65.1 ± 6.7) mm to (53.5 ± 4.9) mm (P<0.01) in these patients. Multiple logistic regression analysis showed that symptom duration of heart failure (OR=0.986, P<0.01), systolic blood pressure (SBP) (OR=1.026, P<0.01), LVEDD (OR=0.938, P<0.01) and LVEF (OR=1.038, P<0.05) at admission were independent predictors of LVSD recovery. During the subsequent follow-up of (24 ±1 3) months after initial recovery, 17 of 88 patients (19.3%) suffered a relapse of LVSD, LVEF decreased from (54.3 ± 2.6) % to (36.6 ± 5.1) % (P<0.01), LVEDD increased from (57.5 ± 4 .2) mm to (62.8 ± 6.8) mm (P<0.01) in these patients. Multiple logistic regression analysis showed that less decrease in LVEDD at initial recovery of LVSD was independent predictor of LVSD relapse. CONCLUSIONS: About 30% hospitalized patients with DCM experienced LVSD recovery in this patient cohort. Symptom duration of heart failure, SBP, LVEDD and LVEF on admission were predictors of LVSD recovery. Moreover, LVSD relapse was observed in around 20% patients after initial LVSD recovery and less decrease in LVEDD at initial recovery serves as an independent risk factor for LVSD relapse.

[Plasma amino-terminal pro-brain natriuretic peptide level and affecting factors in a community-based healthy Chinese population].

OBJECTIVE: To investigate the plasma level of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and related influencing factors in a community-based healthy population in Beijing area. METHODS: We measured plasma NT-proBNP level by fluoroimmunoassay between March 2012 and July 2012 from 1 034 healthy subjects (including 486 men and 548 women). Empiric method was used to determine the reference value and influencing factors were analyzed. RESULTS: Age and gender are important factors affecting the level of NT-proBNP in healthy subjects. NT-proBNP plasma level is significantly higher in women than in men within each age strata below 75 years old, i.e. < 45, 45-54, 55-64 and 65-74 years old (P = 0.005, 0.001, 0.001, 0.011 respectively), but NT-proBNP plasma level is similar between male and female older than 75 years (P = 0.504). NT-proBNP level also increases with age irrespective of gender. Body mass index (BMI) is another independent influencing factor of NT-proBNP (P < 0.001), while estimated glomerular filtration rate is not influencing factor. The reference range of NT-proBNP is < 133 ng/L for men and < 289 ng/L for women aged < 55 years old, < 185 ng/L for men and < 333 ng/L for women aged between 55 and 64 years old, and < 465 ng/L for men and < 378 ng/L for women aged ≥ 75 years old. CONCLUSION: The major influencing factors of NT-proBNP level in the healthy population are age, gender and BMI. It essential to establish normal reference range of NT-proBNP according to these factors for Chinese population.

High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs. METHODS: A total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed. RESULTS: Mutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20 ± 18 years) compared with those with preservation of partial or total AAA cassette (32 ± 19 years, p = 0.041). For those with SPG4 mutations, disease severity was related to the patients' current age, and the progression rate of disease was positively correlated with age at onset. CONCLUSIONS: SPG4 accounts for most of the AD-HSP cases in Taiwanese, with a frequency significantly higher than in other populations. SPAST mutations which predict complete loss of the spastin AAA cassette were associated with an earlier onset of disease.

Comparison between the cranial magnetic resonance imaging features of neuromyelitis optica spectrum disorder versus multiple sclerosis in Taiwanese patients.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the central nervous system with different pathogenesis, brain lesion patterns, and treatment strategies. However, it is still difficult to distinguish these two disease entities by neuroimaging studies. Herein, we attempt to differentiate NMOSD from MS by comparing brain lesion patterns on magnetic resonance imaging (MRI). METHODS: The medical records and cranial MRI studies of patients with NMOSD diagnosed according to the 2006 Wingerchuk criteria and the presence of anti-aquaporin 4 (anti-AQP4) antibodies, and patients with MS diagnosed according to the Poser criteria, were retrospectively reviewed. RESULTS: Twenty-five NMOSD and 29 MS patients were recruited. The NMOSD patients became wheelchair dependent earlier than MS patients (log rank test; P = 0.036). Linear ependymal (28% vs. 0%, P = 0.003) and punctate lesions (64% vs. 28%, P = 0.013) were more frequently seen in NMOSD patients. Ten NMOSD patients (40%) had brain lesions that did not meet the Matthews criteria (MS were separated from NMOSD by the presence of at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion or a Dawson finger-type lesion). The different image patterns of NMOSD didn't correlate with the clinical prognosis. However, NMOSD patients with more (≧10) brain lesions at onset became wheelchair dependence earlier than those with fewer (<10) brain lesions (log rank test; P < 0.001). CONCLUSIONS: The diagnostic sensitivity of NMOSD criteria can be increased to 56% by combining the presence of linear ependymal lesions with unmet the Matthews criteria. The prognoses of NMOSD and MS are different. A specific imaging marker, the linear ependymal lesion, was present in some NMOSD patients. The diagnosis of NMOSD can be improved by following the evolution of this imaging feature when anti-AQP4 antibody test results are not available.

Painful ophthalmoplegia with normal cranial imaging.

BACKGROUND: Painful ophthalmoplegia with normal cranial imaging is rare and confined to limited etiologies. In this study, we aimed to elucidate these causes by evaluating clinical presentations and treatment responses. METHODS: Cases of painful ophthalmoplegia with normal cranial MRI at a single center between January 2001 and June 2011 were retrospectively reviewed. Diagnoses of painful ophthalmoplegia were made according to the recommendations of the International Headache Society. RESULTS: Of the 58 painful ophthalmoplegia cases (53 patients), 26 (44.8%) were diagnosed as ocular diabetic neuropathy, 27 (46.6%) as benign Tolosa-Hunt syndrome (THS), and 5 (8.6%) as ophthalmoplegic migraine (OM). Patients with ocular diabetic neuropathy were significantly older (62.8 ± 7.8 years) than those with benign THS (56.3 ± 12.0 years) or OM (45.8 ± 23.0 years) (p < 0.05). Cranial nerve involvement was similar among groups. Pupil sparing was dominant in each group. Patients with benign THS and OM responded exquisitely to glucocorticoid treatment with resolved diplopia, whereas patients with ocular diabetic neuropathy didn't (p < 0.05). Patients with OM recovered more rapidly than the other groups did (p < 0.05). Overall, most patients (94.8%) recovered completely during the follow-up period. CONCLUSIONS: Ocular diabetic neuropathy and benign THS accounted for most of the painful ophthalmoplegias in patients with normal cranial imaging. Patient outcomes were generally good.

[Frequency and predictors of recovery of normal left ventricular ejection fraction and end-diastolic diameter in patients with dilated cardiomyopathy].

OBJECTIVE: To observe the frequency and predictors of recovery of normal left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD) in patients with dilated cardiomyopathy (DCM). METHODS: A consecutive cohort of 296 patients with DCM were reviewed and followed up for at least 12 months or to death or cardiac transplantation, to identify those with recovery of normal LVEF, defined as LVEF ≥ 50%, or recovery of normal LVEDD, defined as LVEDD ≤ 55/50 mm for male/female, or both by follow up echocardiography.Variables regarded as potentially relevant to left ventricular function and dimension recovery were evaluated to identify predictors using multivariable logistic regression analysis. RESULTS: After a median follow-up of 28 months, normal LVEF was evidenced in 81 patients (27.4%), normal LVEDD was found in 63 patients (21.3%) and both parameters were recovered in 52 patients (17.6%), LVEF was increased from (31.7 ± 6.3)% to ( 57.5 ± 5.2)% (P < 0.01) and LVEDD decreased from (62.7 ± 4.3) mm to (50.2 ± 3.7) mm (P < 0.01) in these 52 patients. Multivariable logistic regression analysis showed that shorter symptom duration, higher systolic blood pressure at admission, smaller LVEDD and lower LVEF by echocardiography at baseline were independent predictors of subsequent recovery of normal LVEF and LVEDD. CONCLUSION: Current therapy for heart failure could lead to recovery of normal LVEF and LVEDD in part of DCM patients, especially for DCM patients with short symptom duration, higher systolic blood pressure at admission, less enlarged LVEDD and less reduced LVEF at baseline echocardiography.