Analysis Of Multiple Sclerosis Research Articles

Cervical spinal cord MTR histogram analysis in multiple sclerosis using a 3D acquisition and a B-spline active surface segmentation technique.

The application of a three-dimensional magnetization transfer (MT) sequence and B-spline active surface segmentation method to produce MT histograms of the cervical spinal cord in a pilot study of controls and multiple sclerosis (MS) patients is presented. Subjects' cervical spinal cords were imaged with (a) a volume-acquired inversion-prepared fast spoiled gradient echo sequence and (b) a volume-acquired noninversion-prepared fast spoiled gradient echo MT sequence. The images were segmented using the B spline active surface technique and MT histograms were produced from the MT images. The method was sensitive enough to detect differences between seven MS patients and 10 controls in mean MT ratio (42.4 pu versus 44.0 pu, p = 0.03) and peak location (45.2 versus 46.8, p = 0.03). The spinal cord volumes obtained from the two sequences were associated with each other (parameter estimate 0.972, 95% confidence intervals 0.742, 1.202, p < 0.001).

DISTRIBUTION AND CLUSTERING OF ALS AND MS

ISEE-423 Introduction: Some neurologic diseases such as Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are thought to be caused by a complex interplay of environmental, genetic, and autoimmune determinants. Additionally, the mortality incidence of ALS and MS incidence has risen over time. As such, these conditions are of special interest to the environmental public health tracking network (EPHTN), and the public. As a prelude to environmental exposure and hazard linkage, we studied the space-time distribution and potential clustering of ALS and MS mortality and hospitalization in Wisconsin. Space-time clustering, denoting areas and periods of increased or decreased incidence, could suggest populations, regions, exposure periods, and potential environmental risk factors for enhanced tracking scrutiny as the EPHTN is fully deployed. Methods: ALS and MS deaths were selected (underlying cause) from the 1990-2001 death files; hospitalizations from 1990-2002 (principal diagnosis) using ICD9 and 10 codes. Cases were arrayed by age, gender, and county. Rates were constructed using annual county, age, and gender specific census estimates. SaTScanTM software was used to analyze space-time point data using the scan statistic, testing whether these conditions were randomly distributed over space and time. An age adjusted Poisson-based model was used; separate models were constructed for males, females, and genders combined. Results: There were a total of 1,361 ALS deaths (2.2/100,000), and 2,123 hospitalizations (3.1/100,000), while there were 1,176 MS deaths (1.9/100,000) and 24,015 MS hospitalizations (35.5/100,000). With combined genders, an ALS cluster consisting of a four county mortality deficit was detected, but not significant (p>0.05). A single county cluster excess (RR=1.8, ns, p>0.05) was similarly found. ALS hospitalizations significantly clustered in a four county region (RR=1.8, p=0.001), while another four county area was significantly low (RR=0.4, p<0.01). The MS mortality analysis revealed a non-significant 3 county elevation (RR=1.4, p>0.05) as well as two single counties, one with an elevation, the other with a deficit risk (both not significant). However MS hospitalizations found a total of 19 significant clusters (p<0.05), three clusters with elevations and 16 cluster regions of decreased risk. Discussion: A Poisson space-time scan statistical analysis of ALS and MS revealed a number of regional disease clusters, consisting of both rate elevations and deficits. These findings will be used to inform exposure database modeling and follow back inquiry for the full implementation of Wisconsin’s Environmental Public Health Tracking Network.

Serial Amino-neurochemicals Analysis in Progressive Lesion Analysis of Multiple Sclerosis by Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopic Imaging

Serial Amino-neurochemicals Analysis in Progressive Lesion Analysis of Multiple Sclerosis by Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopic Imaging

Linkage analysis in multiple sclerosis of chromosomal regions syntenic to experimental autoimmune disease loci

Multiple sclerosis is a demyelinating disorder of the central nervous system with a putative autoimmune aetiology in which several genes are thought to be involved. Four published genomic screens have confirmed that a gene influencing MS resides within or close to the HLA class II region in 6p21. Still, this locus is likely to confer only a part of the genetic susceptibility in MS. Further, all four studies identified a number of other regions with possible linkage. We have investigated eight chromosomal intervals syntenic to loci of importance for experimental autoimmune model diseases in the rat in 74 Swedish MS families. Possible linkage (a non-parametric linkage NPL score of 1.16 by GENEHUNTER computer package) was observed with markers in 12p13.3, a region syntenic to the rat Oia2 locus which is importance for oil induced arthritis (OIA). Four markers in the T cell receptor beta chain gene region in 7q35 showed possible linkage (highest NPL score of 1.16). This locus is syntenic to the rat Cia3 locus (collagen induced arthritis). These two loci at least partially overlap with chromosomal regions showing indicative evidence for linkage in the previous MS genomic screens. Indeed, both Oia2 and Cia3 were recently found to be linked also with experimental autoimmune encephalomyelitis, a commonly used model for MS. Markers in 2p12, 3p25, 10q11.23, 17q21-25, 19q13.1, and 22q12-13 failed to provide evidence for linkage. We conclude that evidence is amounting that 12p13-12 and 7q34-36 may harbour genes with an importance for MS. The synteny with experimental loci may eventually facilitate their identification.

Electroencephalographic coherence analysis in multiple sclerosis: correlation with clinical, neuropsychological, and MRI findings

OBJECTIVETo explore functional corticocortical connections in multiple sclerosis by means of coherence of the EEG, and to evaluate their correlations with the degree of cognitive impairment and with brain lesion...

Spinal Cord Analysis in Multiple Sclerosis

Spinal Cord Analysis in Multiple Sclerosis

Linkage analysis of candidate myelin genes in familial multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. A complex genetic etiology is thought to underlie susceptibility to this disease. The present study was designed to analyze whether differences in genes that encode myelin proteins influence susceptibility to MS. We performed linkage analysis of MS to markers in chromosomal regions that include the genes encoding myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMGP), and myelin oligodendrocyte glycoprotein (MOG) in a well-characterized population of 65 multiplex MS families consisting of 399 total individuals, 169 affected with MS and 102 affected sibpairs. Physical mapping data permitted placement of MAG and PLP genes on the Genethon genetic map; all other genes were mapped on the Genethon genetic map by linkage analysis. For each gene, at least one marker within the gene and/or two tightly linked flanking markers were analyzed. Marker data analysis employed a combination of genetic trait model-dependent (parametric) and model-independent linkage methods. Results indicate that MAG, MBP, OMGP, and PLP genes do not have a significant genetic effect on susceptibility to MS in this population. As MOG resides within the MHC, a potential role of the MOG gene could not be excluded.

Cytokine analysis in multiple sclerosis by competitive RT – PCR: A decreased expression of IL-10 and an increased expression of TNF-α in chronic progression

Cytokine analysis in multiple sclerosis by competitive RT – PCR: A decreased expression of IL-10 and an increased expression of TNF-α in chronic progression

Autonomic evaluation by means of standard tests and power spectral analysis in multiple sclerosis (A reply)

Muscle & NerveVolume 21, Issue 5 p. 679-680 Letter to the Editor Autonomic evaluation by means of standard tests and power spectral analysis in multiple sclerosis (A reply) Dieter Linden MD, Corresponding Author Dieter Linden MD Autonomic Laboratory, Department of Neurology and Clinical Neurophysiology, Alfried Krupp-Hospital, Alfried Krupp-Strasse 21, Essen, GermanyAutonomic Laboratory, Department of Neurology and Clinical Neurophysiology, Alfried Krupp-Hospital, Alfried Krupp-Strasse 21, Essen, GermanySearch for more papers by this author Dieter Linden MD, Corresponding Author Dieter Linden MD Autonomic Laboratory, Department of Neurology and Clinical Neurophysiology, Alfried Krupp-Hospital, Alfried Krupp-Strasse 21, Essen, GermanyAutonomic Laboratory, Department of Neurology and Clinical Neurophysiology, Alfried Krupp-Hospital, Alfried Krupp-Strasse 21, Essen, GermanySearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1097-4598(199805)21:5<679::AID-MUS24>3.0.CO;2-PCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume21, Issue5May 1998Pages 679-680 RelatedInformation

Autonomic evaluation by means of standard tests and power spectral analysis in multiple sclerosis

Autonomic evaluation by means of standard tests and power spectral analysis in multiple sclerosis

The Receptor for Complement Anaphylatoxin C3a Is Expressed by Myeloid Cells and Nonmyeloid Cells in Inflamed Human Central Nervous System: Analysis in Multiple Sclerosis and Bacterial Meningitis

The complement anaphylatoxins C5a and C3a are released at the inflammatory site, where they contribute to the recruitment and activation of leukocytes and the activation of resident cells. The distribution of the receptor for C5a (C5aR) has been well studied; however, the receptor for C3a (C3aR) has only recently been cloned, and its distribution is uncharacterized. Using a specific affinity-purified anti-C3aR peptide Ab and oligonucleotides for reverse transcriptase-PCR analysis, C3aR expression was characterized in vitro on myeloid and nonmyeloid cells and in vivo in the brain. C3aR was expressed by adult astrocytes, astrocyte cell lines, monocyte lines THP1 and U937, neutrophils, and monocytes, but not by K562 or Ramos. C3aR staining was confirmed by flow cytometry, confocal imaging, and electron microscopy analysis. A 65-kDa protein was immunoprecipitated by the anti-C3aR from astrocyte and monocyte cell lysates. Our results at the protein level were confirmed at the mRNA level. Using reverse transcriptase-PCR, Southern blot, and sequencing we found that C3aR mRNA was expressed by fetal astrocytes, astrocyte cell lines, and THP1, but not by K562 or Ramos. The astrocyte C3aR cDNA was identical with the reported C3aR cDNA. C3aR expression was not detected in normal brain sections. However, a strong C3aR staining was evident in areas of inflammation in multiple sclerosis and bacterial meningitis. In meningitis, C3aR was abundantly expressed by reactive astrocytes, microglia, and infiltrating cells (macrophages and neutrophils). In multiple sclerosis, infiltrating lymphocytes did not express C3aR, but a strong staining was detected on smooth muscle cells (pericytes) surrounding blood vessels.

Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis.

To assess the correlation between cognitive dysfunction and disease burden in multiple sclerosis (MS) during a 1-year period. The Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis was performed at entrance and 1 year. Patients underwent at least 20 proton density (range, 20-24) and T2-weighted axial magnetic resonance imaging (MRI) brain scans except for stable patients who were scanned monthly. Magnetic resonance imaging was evaluated using computer-automated, 3-dimensional volumetric analysis. A research clinic of a university hospital. Forty-four patients with MS of the following disease categories: relapsing-remitting (14), relapsing-remitting progressive (12), chronic progressive (13), and stable (5). The relationships between scores on the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and brain to intracranial cavity volume ratio) were assessed using linear regression. These MRI measures were also compared with cognitive status at 1 year using analysis of variance. Overall, there was no decline in mean cognitive test performance during 1 year. Significant correlations were found between baseline neuropsychological test scores of nonverbal memory, information-processing speed, and attention and both MRI measures. Patients with chronic progressive MS demonstrated the strongest correlations. At 1 year, change in information-processing speed and attention correlated with change in total lesion volume. The mean increase in total lesion volume was 5.7 mL for 4 patients whose cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable. During a 1-year period mean cognitive performance did not worsen. Automated volumetric MRI measures of total lesion volume and brain to intracranial cavity volume ratio correlated with neuropsychological performance, especially in patients with chronic progressive MS. Worsening MRI lesion burden correlated with cognitive decline.

Autonomic evaluation by means of standard tests and power spectral analysis in multiple sclerosis.

Standard autonomic tests [heart rate response to deep breathing (HRDB), change in systolic blood pressure due to tilt], and spectral analysis of heart rate (HR), arterial blood pressure (ABP), and the associated transfer function analysis (gains and phases) were performed in 20 patients with multiple sclerosis to determine their diagnostic value. Transfer function analysis suggested impairment of baroreflex function in 7 patients and an alteration of cardiorespiratory coupling on a brain stem level in 4 patients. In addition, sympathetic vasomotor outflow was reduced in 2 patients (spectral ABP measures in the mid frequency band) and a decrease of vagal outflow was suggested by abnormal respiratory HR parameters in another 2 patients. An abnormal HRDB was present in 5 patients and was probably due to a central alteration (cardiorespiratory coupling) in 2 patients and due to diminished respiratory effort in 1 patient. Spectral analysis of both HR and ABP oscillations and their transfer function may considerably improve the pathophysiological interpretation of cardiovascular autonomic dysfunction in patients with central nervous system disease.

EEG coherence analysis in multiple sclerosis: Correlation with clinical, neuropsychological and MRI findings

EEG coherence analysis in multiple sclerosis: Correlation with clinical, neuropsychological and MRI findings

New insights into the immunogenetics of multiple sclerosis.

The genetic analysis of multiple sclerosis has been based mainly on candidate gene association studies in selected populations. However, the candidate gene approach, although straightforward, is problematic in diseases of unknown or partially known etiology. With the advent of genomic screening and novel statistical approaches, it is possible now to perform an efficient screen of the entire human genome to identify the genetic components of multiple sclerosis.

P349 EEG coherence analysis in multiple sclerosis: Correlation with clinical, neuropsychological and MRI findings

To confirm previously reported abnormalities in time domain EEG components during a go/no-go task in schizophrenia, and to test the hypothesis that patients exhibit abnormalities in frequency domain components reflecting indices of behavioural impairment.EEG data were recorded from 17 male schizophrenia patients in a stable phase of illness and 17 healthy controls.As compared with controls, patients displayed smaller N200 amplitudes and less evoked theta for correct hit trials; and smaller N200 and P300 amplitudes and less evoked delta and theta for correct reject trials. Effect sizes were largest for evoked delta. Source localisation revealed reduced activation in schizophrenia patients during the N200 and P300 time windows in anterior and posterior cingulate, medial frontal gyrus and precuneus. Evoked delta and theta oscillations were significantly correlated with the variability of reaction times and the performance level statistic d-prime.The results demonstrate impairment of frontal and parietal brain areas involved in response control in schizophrenia. They also suggest that the timing of oscillations in patients is less precise leading to smaller evoked amplitudes and more variable reaction times.These findings add to the evidence that abnormal EEG oscillations contribute to impaired behavioural control in schizophrenia.

Quantitative volumetric magnetization transfer analysis in multiple sclerosis: estimation of macroscopic and microscopic disease burden.

Magnetization transfer imaging (MTI) has been shown to be sensitive to both macroscopic and microscopic disease in multiple sclerosis (MS). In this study three-dimensional MTI was used to estimate the global burden of disease in large volumes of brain tissue. MTI was performed in 15 MS patients and 11 normal controls. In seven MS patients MTI was performed on two different occasions. MTI data were displayed as magnetization transfer ratio (MTR) histograms and analyzed. The peak height of the histograms, presumably reflecting the residual amount of normal brain tissue, was lower in MS patients as compared with normal controls (P < 0.001), and was found to correlate with the duration of disease (P < 0.05). A decrease of the MTR histogram peak height was observed in the course of the disease (P < 0.01). These findings suggest that in MS, volumetric MTI provides quantitative information reflecting the global burden of disease.

Two-locus linkage analysis in multiple sclerosis (MS).

One of the major challenges in genetic linkage analyses is the study of complex diseases. We demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, we have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family members than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested.

Tear analysis in multiple sclerosis.

We examined tears from 12 MS patients and 20 normal controls. In MS tears, the total IgG concentration was increased. Electrophoresis revealed low molecular weight bands (25 to 34k) in tears from patients with demyelinating optic neuritis; similar, less intense bands were seen in some patients with a history of optic neuritis. Production of tears was impaired in almost one-half of MS patients, especially in clinical exacerbations. Analysis of tears may offer new insight into immune function in MS, particularly of the mucosal immune system.

Tumor necrosis factor-alpha polymorphism and susceptibility to multiple sclerosis in the Iranian population.

Background:Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Tumor necrosis factor-α (TNF-α) microsatellite as a proinflammatory cytokine is believed to play an important role in the etiology of this disease.Objectives:The aim of this study was to investigate the association of TNF-α microsatellite sequence variation in patients with MS and its risk factor in the southern Iranian population.Patients and Methods:This polymorphism was investigated in an Iranian population of 163 native southern people [81 patients with MS according to the poser criteria and 82 healthy controls (HC) with the same age, sex, social, ethnical and geographical features (Hormozgan and Fars provinces)]. All the controls were nonimmunological, neurological patients. All the cases and controls were chosen randomly and genotyped for polymorphism of TNF-α microsatellite.Results:The frequencies of TNF-α*11 (0.25, P < 0.005) and TNF-α*10 (P < 0.005) alleles increased in patients with MS compared with controls, showing a significant difference among the studied population.Conclusions:The current study adds evidence to the association of TNF-α gene polymorphism and MS in this southern south Iranian population which is consistent with the genetic analysis of MS in Europeans (GAMES) project reports and these two alleles reported in this study may be one of the genetic risk factor for MS. Furthermore, this data can be used to build the Iranian gene bank for future studies.