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Journal of Biosciences and Medicines 2020年第5期8卷 84-95页

作者： Silin Du Chun Zeng Zhiwei Zhang The First Affiliated Hospital of Chongqing Medical University Chongqing China

Objective: To longitudinally assess dynamic changes of iron deposition and volume of the precentral gyrus and its correlation with clinical manifestations of Relapse-Remitting Multiple sclerosis(RRMS) by using 3D enhanced T2* weighted angiography(ESWAN). Methods: Thirty RRMS patients and thirty age- and sex-matched healthy controls were recruited and underwent ESWAN and 3D T1WI twice interval of one year with the same parameters. The mean phase values (MPVs) and volumes in precentral gyrus gray matter (PGM) were measured, and change of iron content and its correlation with volume, clinical manifestations were analyzed. Results: Compared with controls, the RRMS had higher iron deposition in both single-time measurements, but the volume decreased. Comparing to the first scan, we found significant difference in MPVs between the two times (P rs = 0.764, P rs = 0.592, P rs = 0.582, P rs = -0.399, P rs = -0.745, P rs = -0.367, P Conclusions: With the disease progression, the content of iron in PGM in RRMS patients is increasing, while the volume has no obvious change, suggesting that the iron deposition may precede or develop faster than cerebral atrophy.

关键词： Relapse-Remitting Multiple sclerosis Precentral Gyrus Iron Brain Atrophy

Lesion contrast differences in MRI sequences in multiple sclerosis: Correlation to clinical disability

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Journal of Biomedical Science and Engineering 2013年第3期6卷 319-326页

作者： Maija Rossi Minna Raunio Pertti Ryymin Irina Elovaara Prasun Dastidar Department of Neurology and Rehabilitation Tampere University Hospital Tampere Finland Medical Imaging Centre Department of Radiology Tampere University Hospital Tampere Finland Tampere Medical School Tampere Finland

The purpose of this study was to analyze the lesion brightness (image contrast) in multiple MRI sequences in patients with relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and clinically isolated syndrome (CIS);and to correlate the lesion contrast with lesion volumes and neurological disability. MRI ex- amination at 1.5 T was performed on 80 patients with RRMS, SPMS, PPMS, or CIS. The protocol included T1- and T2-weighted spin echo (SE), fluid attenuated inversion recovery (FLAIR), T1-weighted SE with magnetization transfer preparation, and diffusion weighted imaging (DWI). Contrast was measured between MS lesions and normal appearing white matter. Lesion volume was calculated in T1-weighted- and FLAIR-images. All patients were examined neurologically including evaluation of expanded disability status scale (EDSS) score. Lesion contrast correlated with total brain lesion volume (p = 0.000 - 0.040). In patients with low EDSS, three sequences were able to differentiate between CIS and RRMS. SPMS and PPMS were separated by DWI. Lesion contrast correlated with EDSS score on T1-weighted imaging, with or without magnetization transfer preparation. Patient age correlated with lesion contrasts. Contrast measurements seem limited in radiological and clinical diagnosis of MS in reference to disease course, its activity and progression. The differentiation between MS subgroups might improve at 3 T and could help in leading to earlier treatment of the disease.

关键词： Magnetic Resonance Imaging Multiple sclerosis Imaging Sequences

Associations with Organ Involvement and Autoantibodies in Systemic sclerosis: Results from the Canadian Scleroderma Research Group (CSRG)

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Open Journal of Rheumatology and Autoimmune Diseases 2013年第2期3卷 113-118页

作者： Vikram Tangri Carly Hewson Murray Baron A. Bonner Marvin Fritzler Janet E. Pope McGill University Montreal Canada McMaster University Hamilton Canada University of Calgary Calgary Canada University of Western Ontario London Canada

Objective: Serum from SSc patients was analyzed centrally to determine ANA patterns and extractable nuclear antigens (ENAs) between lcSSc and dcSSc and associations with organ involvement. Methods: 1145 SSc patients had ANA and ENA analyzed by indirect immunofluorescence on HEp-2 substrate at a screening serum dilution of 1/160. Most ENA antibodies [Sm. U1-RNP, Ro52, SS-A/Ro60, topoisomeraseI (Topo1), SS-B/La, chromatin, ribosomal P and Jo1] were measured by laser bead immunoassay;and RNA polymerase III (RNAP) by ELISA. Results: ANA was positive in 95% (same in lcSSc, and dcSSc). Centromere pattern was present in 34%, speckled 22%, nucleolar 18%, homogeneous and speckled (H&S) 16%, multiple nuclear dots 6%. Anti-centromere Ab (ACA) occurred in 46% of lcSSc and 11% of dcSSc (P = 0.0001). ENAs that differed between lcSSc and dcSSc subsets were Topo1 (OR 2.4, P = 0.0001) and RNAP (OR 5.6, P 0.0001) more common in dcSSc. Overall, 15% had positive Topo1;usually with a H&S pattern (67%);Topo1 was associated with ILD on CXR (OR 2.3;95% CI 1.5 - 3.5) and HRCT (OR 3.8;95% CI 1.8 - 8.2). RNAP occurred in 18.5% (35.4% in dcSSc vs. 8.9% in lcSSc). Scleroderma renal crisis (SRC) was 13 times more likely if RNAP positive;P = 0.0001. ACA was only weakly associated with sPAP > 50 mmHg (OR 1.8;95%CI 1.1 - 3.0). Conclusion: ANA homogeneous pattern alone is rare in SSc;ACA was significantly more common in lcSSc. Many ENAs are equal in lcSSc and dcSSc except RNAP and Topo1. RNAP has the highest OR of SRC. Topo1 is less strongly associated with ILD. Abstract word count: 249, Body word count 1246, Figures 2, Tables 2. Key Messages: 1) 95% of SSc has a positive ANA and ANA patterns in SSc include centromere, nucleolar, and homogeneous and speckled together;2) Most ENAs are equal in both dcSSc and lcSSc except anti RNA polymerase III and topoisomerase I;3) RNA polymerase III has the highest association (odds ratio) with scleroderma renal crisis, topoisomerase I is associated with interstitial lung disease;whereas anticentromere was not

关键词： Scleroderma SSc Systemic sclerosis Antibodies Anticentromere Topoisomerase I RNA Polymerase III Organ Involvement Scleroderma Renal Crisis Pulmonary Fibrosis ILD ANA Pulmonary Hypertension

Urodynamic Abnormalities in Patients with Relapsing Remitting Multiple sclerosis

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World Journal of Neuroscience 2018年第4期8卷 423-431页

作者： Alaaeldin Sedky Bekhit Mohammed Saber-Khalaf Department of Neuropsychiatry Sohag University Sohag Egypt Department of Urology Sohag University Sohag Egypt

Background: Multiple sclerosis (MS) is a disease with wide variability in clinical presentation. Bladder dysfunctions are very common in MS patients. Early detection of bladder abnormalities is important to improve the outcome in MS patients. Objectives: The aim of this study is to evaluate the urodynamic detected bladder dysfunctions in relapsing remitting MS patients with mild or without lower urinary tract symptoms. Methods: This is a prospective study for 32 patients with relapsing remitting Multiple sclerosis from January 2017 to June 2018. We included patients with mild or without lower urinary tract symptoms (LUTS) who had mild to moderate disability. Urodynamic studies were performed for all patients. Results: Urodynamic abnormalities were detected in 22 patients (68.75%). Detrusor overactivity (DO) was present alone in 8 patients (25%);DO combined with detrusor external sphincter dyssynergia in 8 patients (25%);DO with low compliant bladder and impaired contractility in another 4 patients (13%) while DO with low complaint bladder in 2 patients (6%). Bladder dysfunction was correlated to high disability score;longer duration of illness;frequent relapses and the presence of LUTS. Conclusion: Urodynamic abnormalities were found in 68.75% of our patients. This highlights the importance of urodynamic studies in the early evaluation of relapsing remitting Multiple sclerosis.

关键词： Urodynamic Bladder Dysfunction Multiple sclerosis

Transient Receptor Potential Melastatin 3 and Intracellular Calcium in Natural Killer Cells in Multiple sclerosis

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International Journal of Clinical Medicine 2018年第7期9卷 541-565页

作者： Laura Clarke Simon L. Broadley Thao Nguyen Samantha Johnston Natalie Eaton Donald Staines Sonya Marshall-Gradisnik School of Medicine Griffith University Gold Coast Australia Department of Neurology Gold Coast University Hospital Gold Coast Australia The National Centre for Neuroimmunology and Emerging Diseases Menzies Health Institute Griffith University Gold Coast Australia School of Medical Science Griffith University Brisbane Australia

Background: Natural killer (NK) cell phenotypes have reported to be implicated in the pathomechanism of Multiple sclerosis (MS). Several investigators have observed reduced peripheral numbers, reduced cytotoxic activity, and altered CD56Dim and CD56Bright NK cell phenotypes. This current project, for the first time, investigates the NK cell cytotoxicity, calcium mobilisation and transient receptor potential melastatin 3 (TRPM3) surface expression. Methods: NK cell cytotoxic activity and calcium signaling were examined in CD56Dim and CD56Bright NK cells before and after stimulation using Ionomycin, Pregnenolone sulphate, 2-Aminoethoxydiphenyl borate and Thapsigargin. Purified NK cells were labelled with antibodies to determine TRPM3, CD69 and CD107a surface expression using flow cytometry. Results: Twenty-two MS patients and 22 healthy controls were recruited for this project. Twelve of the 22 previously received Alemtuzumab (Lemtrada®) and the remaining ten reported nil medication. We report TRPM3 was significantly increased in untreated MS patients compared with healthy controls and treated MS patients (p-value 0.034). There was a significant decrease in CD69 surface expression on CD56Dim NK cell phenotype for untreated MS patients (p-value 0.031) and treated MS patients (p-value 0.036). We report altered calcium mobilisation in CD56Bright NK cells and to a lesser extent CD56Dim NK cells between healthy controls, treated and untreated MS patients. Conclusion: This investigation suggests variations in TRPM3 expression and calcium mobilisation of NK cells may be implicated in the pathogenesis of MS. Further investigation is required to determine the mechanism by which alemtuzumab alters calcium signaling in NK cells.

关键词： Natural Killer Cells Multiple sclerosis Calcium Signalling Transient Receptor Potential Melastatin 3 Ion Channels

Detection of Mycoplasmas in Patients with Amyotrophic Lateral sclerosis

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Advances in Microbiology 2014年第11期4卷 712-719页

作者： Constantino Gil Alma Aurora Sánchez González Isidro Lecona León Antonio Rivera Rayo Santellán Olea Lilia Cedillo Centro de Investigaciones en Ciencias Microbiológicas Instituto de Ciencias Benemérita Universidad Autónoma de Puebla Edificio 103J Ciudad Universitaria Col. San Manuel Puebla Pue México Escuela de Biología Benemérita Universidad Autónoma de Puebla Edificio 112A Ciudad Universitaria Col. San Manuel Puebla Pue México Servicio de Neurología Centro Médico Nacional Manuel ávila Camacho IMSS Puebla México

Amyotrophic Lateral sclerosis (ALS) is a progressive degenerative disease of the motor neurons and the cause is unknown. Diverse factors such as genetic defects, nutritional deficiencies, head trauma, environmental toxin, autoimmune responses and viral and bacterial infections are involved. Mycoplasmas have been implicated as causal agents of different illnesses in human. The purpose of this study was to investigate the presence of mycoplasmas in the bloodstream of patients with ALS. Patients with ALS and healthy individuals were included in the study. A blood sample was taken in tubes with or without anticoagulant. Mycoplasmas were detected by culture or direct PCR, and the presence of antibodies IgM and IgG against LAMPs of these microorganisms by Western blot. Cultures for aerobic facultative bacteria were also done. Blood samples from 13 patients and 44 healthy individuals were screened. All blood cultures for non-fermentative mycoplasmas and aerobic facultative bacteria were negative. Cultures for fermentative mycoplasmas were considered positive after identification of mycoplasmal DNA by PCR. Mycoplasma sp. was detected by culture or direct PCR in 6/13 (46%) patients and in 4/44 (9%) of healthy individuals. M. fermentans was detected by PCR using specific primers in six patients and in two healthy individuals. IgM against LAMPs of M. fermentans were detected in 6/13 (46%) blood samples from patients and in 13/44 (30%) from healthy individuals, while. IgG was detected in 4/13 (31%) patients and in 3/44 (7%) healthy individuals. The results of this study show that mycoplasmas cause a systemic infection and could play a role in the origin or progression of the ALS.

关键词： Amyotrophic Lateral sclerosis Mycoplasmas Immune Response

Stroke Due to Hypercoagulable State Can Mimic Multiple sclerosis: A Case Report

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World Journal of Neuroscience 2017年第3期7卷 267-274页

作者： Niknam Zahra Saadat Alireza Nabavi Seyed-Massood Morsali Damineh Hatami-Sadabadi Farhad Kheirkhahan Meghdad Mehdipour Baharak Neurologist Neurology Department University of Baghiatalahaazam Tehran Iran University of Baghiatalahaazam Tehran Iran Department of Regenerative Biomedicine Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran Senior postdoctoral fellow Neurology department Texas University Huston Texas USA General physician Kheradmand Clinical Research Center Medical Affairs Division Actoverco Pharmaceutical Company Tehran Iran

Introduction: Stroke is the second major cause of mortality worldwide and in several cases, and it may lead to disability. Factor V Leiden is a common genetic thrombophilia, which causes activated protein C (APC) resistance. Hyperhomocysteinemia and factor V Leiden deficiency, two independent coagulopathy factors, can lead to venous and arterial infarctions in multiple small and large arteries and veins anywhere in the body. Case Report: Here, we report a unique case in which both hyperhomocysteinemia and factor V Leiden deficiency are documented together with MTHFR (C677T) (Methylene Tetra Hydro Folate Reductase) gene polymorphism and activated protein C resistance respectively. Conclusion: More interestingly, the mode of presentation in this case highly resembled that of progressive multiple sclerosis;all signs and symptoms slowly progressed without any systemic signs at first few years. Further studies needed to assess current outcomes.

关键词： Hyperhomocysteinemia Thrombophilia V MTHFR (C677T) Gene Polymorphism Activated Protein C Resistance Multiple sclerosis

Association Study of Two Polymorphisms in Vitamin D Pathway with Multiple sclerosis in the Moroccan Population

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World Journal of Neuroscience 2017年第4期7卷 363-375页

作者： Asmae Skalli El Hachmia Ait Ben Haddou Rachid Tazi-Ahnini Ghislain Armel Mpandzou Houyam Tibar Naima Bouslam Ali Benomar Khadija Hajjout Mohamed Yahyaoui Elmostafa El Fahime Ahmed Bouhouche Research Team in Neurology and Neurogenetics Medical School and Pharmacy Mohammed V University Rabat Morocco Department of Neurology and Neurogenetics Specialties Hospital Rabat Morocco Laboratory of Biotechnology Medical School and Pharmacy Mohammed V University Rabat Morocco National Blood Transfusion Center Rabat Morocco Assistance Units for Scientific and Technical Research Rabat Morocco

Background: Hypovitaminosis D is reported through the literature to be involved in autoimmune diseases such as multiple sclerosis (MS). In the last decade, numerous studies have investigated the association of single nucleotide polymorphisms (SNPs) with MS, including rs2248359 (CYP24A1) and rs703842 (CYP27B1) that are involved in vitamin D metabolic pathway. However, results were conflicting, probably due to ethnic differences between the studied populations. In this context, the present study aimed to analyze the association between these two SNPs and MS within the Moroccan population. Methods: rs2248359 and rs703842 were genotyped in 113 patients and 146 healthy controls. To assess their association with the disease risk, we compared the genotypic and allelic frequencies between the study groups. We also explored their possible influence on certain clinical features (age at onset, type, disability status and severity score) and with vitamin D3 serum level (DSL) by comparing mean values of these variables between the different genotypes. Results: No statistically significant differences in the distribution of both SNPs were found between patients and controls. A trend has emerged concerning the minor G allele of rs703842 which appears to have a protective effect on developing MS, but this result remained slightly below significance. Also, the two polymorphisms had no impact on the clinical features tested and the DSL. Conclusion: There is no convincing evidence that rs2248359 and rs703842 are associated with MS risk, its clinical features or vitamin D level in Moroccans. Further larger investigations are needed to confirm these findings.

关键词： Multiple sclerosis Risk rs2248359 rs703842 Clinical Features Serum 25(OH)D3 Level

Serum Level of Vitamin C in a Sample of Egyptian Patients with Multiple sclerosis

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Neuroscience & Medicine 2019年第4期10卷 398-406页

作者： Asmaa Ibrahim Taha K. Alloush Yousry Abo Elnaga Mohamed Hamdy Mohamed M. Fouad Department of Neurology Faculty of Medicine Ain Shams University Cairo Egypt

Background: Antioxidants such as vitamin C can eliminate free radicles responsible for oxidative stress. Objective: To assess the serum level of vitamin C in a sample of multiple sclerosis (MS) patients to investigate a possible role of vitamin C in the pathogenesis of MS. Subjects and Methods: Forty patients with MS and twenty healthy controls were included in this study. Vitamin C level was estimated for each participant. Results: Serum vitamin C levels were significantly lower among the patients (ranging from 0.28 mg/dL to 0.75 mg/dL with mean 0.47 ± 0.14 mg/dL and median of 0.46 mg/dL) compared to controls (ranging from 0.60 mg/dL to 2.90 mg/dL with mean 1.87 ± 0.61 mg/dL and median of 1.90 mg/dL) (P Conclusion: Patients with MS tended to have low serum vitamin C levels, and younger patients had lower serum levels.

关键词： Vitamin C Multiple sclerosis

Pulmonary arterial hypertension associated with systemic sclerosis: Current diagnostic approach and therapeutic strategies

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World Journal of Rheumatology 2012年第2期2卷 12-20页

作者： Olga Vera-Lastra Mateo Porres-Aguilar Department of Internal Medicine Hospital de Especialidades Centro Médico Nacional la Raza IMSS Universidad Nacional Autónoma de México02990 Mexico City México Division of Hospital Medicine Department of Internal Medicine Texas Tech University Health Sciences Center/Paul L.Foster School of MedicineEl Paso TX 79905 United States

Pulmonary arterial hypertension(PAH) represents a devastating vascular complication of systemic sclerosis(SSc) and is found in 10%-15% of cases carrying a severe prognosis. PAH has a dramatic impact on the clinical course and overall survival, being the single most common cause of death in patients with this entity. The clinical course and aggressive progression of PAH has led clinicians to perform annual screening for it, since early detection and diagnosis are the cornerstone of a prompt therapeutic intervention. The diagnosis of PAH can be challenging to clinicians, particularly in its early stages, since in the context of SSc, the multiple causes of dyspnea need to be assessed. Doppler echocardiography represents the best initial screening tool, however, right heart catheterization remains the gold standard and definitive diagnostic means. Remarkable advances have been achieved in elucidating the pathogenesis of PAH in the past two decades, leading to the development of disease-specific targeted therapies: prostacyclin analogues, endothelin receptor antagonists and inhibitors of five phosphodiesterase pathways. However, the clinical response to these therapies in SSc-associated PAH has not been as great as the one seen with idiopathic PAH. This review also focuses on the diagnosis and novel therapies that are currently available for PAH, as well as potential future therapeutic developments based on newly acquired knowledge of diverse pathogenic mechanisms.

关键词： Pulmonary arterial hypertension Systemic sclerosis Diagnosis Therapy Prognosis