Lesion Mechanism Dependent, Differential Changes In NeuroFilaments And MicroTubules: A Pathological And Experimental Study
Fressinaud C, Jean I, Dubas F
Rev Neurol (Paris) 2005 Jan;161(1):55-60
UPRES EA 3143, CHU, Departement de Neurologie, Angers
The consequences of Axonal or DeMyelinating injuries on the Axonal CytoSkeleton have rarely been described.
In nine patients with Axonal Neuropathies of undetermined Etiology (AUE)
Six with Necrotizing Angeitis with Neuropathy (NAN)
Seven with Chronic Inflammatory DeMyelinating Neuropathy (CIDP)
In five controls, as well as in six patients with chronic Multiple Sclerosis (MS)
We have compared the density of fibers labeled by Anti-NeuroFilaments (NF) and Anti-ß Tubulin (TUB) to the density of total Fibers:
We also studied DeMyelinated rat Corpus Callosum after LysoPhosphatidyl (LPC) microinjection.
In AUE and NAN NF positive fibers decreased together with total Fiber Density, whereas TUB increased.
In DeMyelinating lesions TUB was not altered (CIDP) or strongly decreased (MS, LPC); NF were strongly reduced in MS (where Axon Loss was prominent) and in LPC lesions (despite the lack of fiber degeneration) and for fiber densities< 3900/mm2 in CIDP.
The initial mechanism of a disease, either Axonal Degeneration or DeMyelination, could result into a specific pattern of Axonal CytoSkeleton alterations.
Two Genes Encoding Immune-Regulatory Molecules (LAG3 And IL7R) Confer Susceptibility To Multiple Sclerosis
Zhang Z, Duvefelt K, Svensson F, Masterman T, Jonasdottir G, Salter H, Emahazion T, Hellgren D, Falk G, Olsson T, Hillert J, Anvret M
Genes Immun 2005 Jan 27
AstraZeneca R&D Sodertalje, Department of Molecular Sciences, Section for Genetics and Bioinformatics, Sodertalje, Sweden
Multiple Sclerosis (MS) is a T-Cell-mediated disease of the Central Nervous System, characterized by damage to Myelin and Axons, resulting in progressive Neurological disability.
Genes may influence susceptibility to MS, but results of association studies are inconsistent, aside from the identification of HLA Class II HaploTypes.
Whole-Genome linkage screens in MS have both confirmed the importance of the HLA region and uncovered non-HLA loci that may harbor susceptibility Genes.
In this two-stage analysis, we determined GenoTypes, in up to 672 MS patients and 672 controls, for 123 Single-Nucleotide Polymorphisms (SNPs) in 66 genes. Genes were chosen based on their Chromosomal positions or biological functions.
In stage one, 22 genes contained at least one SNP for which the carriage rate for one allele differed significantly (P < 0.08) between patients and controls.
After additional GenoTyping in stage two, two Genes-each containing at least three significantly (P < 0.05) associated SNPs-conferred susceptibility to MS: LAG3 on Chromosome 12p13, and IL7R on 5p13.
LAG3 inhibits activated T-Cells, while IL7R is necessary for the maturation of T and B-Cells.
These results imply that germline Allelic variation in genes involved in Immune homeostasis-and, by extension, derangement of Immune homeostasis-influence the risk of MS.
Genes and Immunity advance online publication, 27 January 2005; doi:10.1038/sj.gene.6364171.
Short-term Accrual Of Gray Matter Pathology In Patients With Progressive Multiple Sclerosis: An In Vivo Study Using Diffusion Tensor MRI
Rovaris M, Gallo A, Valsasina P, Benedetti B, Caputo D, Ghezzi A, Montanari E, Sormani MP, Bertolotto A, Mancardi G, Bergamaschi R, Martinelli V, Comi G, Filippi M
NeuroImage 2005 Feb 15;24(4):1139-46
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Department of Neurology, Milan, Italy
The mechanisms underlying the Progressive course of Multiple Sclerosis (MS) are not fully understood yet.
The present study investigated the value of DT MRI-derived measures for the assessment of the short-term accumulation of White and Gray Matter (GM) pathology in patients with Primary/Progressive (PP) and Secondary/Progressive (SP) MS.
Since Diffusion Tensor (DT) MRI can provide quantitative estimates of both MRI-visible and MRI-occult Brain damage related to MS.
Fifty-four patients with PPMS and 22 with SPMS were studied at baseline and after a mean follow-up of 15 months.
Dual-echo, T1-weighted, and DT MRI scans of the Brain were acquired on both occasions. Total Lesion Volumes (TLV) and Percentage Brain Volume Changes (PBVC) were computed.
Mean Diffusivity (MD) and Fractional Anisotropy (FA) maps of the Normal-Appearing White (NAWM) and Gray Matter (NAGM) were produced, and Histogram analysis was performed.
In both patient groups, a significant increase of average lesion MD (P = 0.01) and of average NAGM MD (P = 0.007) was found at follow-up.
No significant differences between PPMS and SPMS patient groups were found for the on-study changes of any MRI-derived measure.
No significant correlations were found between the percentage changes of DT MRI-derived measures and those of TLV and PBVC.
No significant changes of DT MRI-derived measures were observed in age-matched healthy controls over the same study period.
Over a 1-year period of follow-up, DT MRI can detect tissue changes beyond the resolution of conventional MRI in the NAGM of patients with Progressive MS.
The accumulation of DT MRI-detectable Gray Matter damage does not seem to merely depend upon the concomitant increase of T2-visible lesion load and the reduction of Brain Volume.
These observations suggest that Progressive NAGM damage might yet be an additional factor leading to the accumulation of disability in Progressive MS.
The Role Of Edema And DeMyelination In Chronic T1 Black Holes: A Quantitative Magnetization Transfer Study
Levesque I, Sled JG, Narayanan S, Santos AC, Brass SD, Francis SJ, Arnold DL, Pike GB
J Magn Reson Imaging 2005 Feb;21(2):103-10
McGill University, Montreal Neurological Institute, McConnell Brain Imaging Centre, Montreal, H3A 2B4 Quebec, Canada
To use quantitative Magnetization Transfer Imaging (qMTI) in an investigation of T1-weighted HypoIntensity observed in clinical Magnetic Resonance Imaging (MRI) scans of Multiple Sclerosis (MS) patients,.
Which has previously been proposed, as a more specific indicator of tissue damage than the more commonly detected T2 HyperIntensity.
Materials And Methods
A cross-sectional study of 10 MS patients was performed using qMTI. A total of 60 MTI measurements were collected in each patient at a resolution of 2 x 2 x 7 mm, over a range of saturation pulses.
The observed T1 and T2 were also measured. qMT model parameters were estimated using a Voxel-by-Voxel fit.
A total of 65 T2-HyperIntense lesions were identified; 53 were also T1 HypoIntense.
In these black holes, the qMTI-derived semisolid pool fraction F correlated negatively with T(1,obs) (r2 = 0.76; P < 0.0001).
The water pool absolute size (PDf) showed a weaker correlation with T(1,obs) (positive, r2 = 0.53; P < 0.0001). The Magnetization Transfer Ratio (MTR) showed a similarly strong correlation with F and a weaker correlation with PDf (r2 = 0.18; P < 0.04).
T1 increases in chronic Black Holes strongly correlated with the decline in semisolid pool size.
And, somewhat less to the confounding effect of Edema. MTR was less sensitive than T(1,obs) to liquid pool changes associated with Edema.
(c) 2005 Wiley-Liss, Inc.
Quantification Of Cervical Cord Pathology In Primary/Progressive MS Using Diffusion Tensor MRI
Agosta F, Benedetti B, Rocca MA, Valsasina P, Rovaris M, Comi G, Filippi M
Neurology 2005 Feb 22;64(4):631-5
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Department of Neurology, Via Olgettina, 60, 20132 Milan, Italy
To investigate the extent and severity of Cervical Cord damage using Diffusion Tensor MRI (DT-MRI) and Histogram analysis in patients with Primary/Progressive MS (PPMS).
Diffusion-weighted Sensitivity-Encoded (SENSE) Echo Planar images of the Cervical Cord and Brain Dual-Echo and Diffusion-weighted scans were acquired from 24 patients with PPMS and 13 healthy controls.
Cord and Brain Mean Diffusivity and Fractional Anisotropy Histograms were produced. An analysis of variance model, adjusting for Cord volume, was used to compare Cord DT-MRI parameters from controls and patients.
Compared to healthy controls, PPMS patients had reduced Cervical Cord Cross-Sectional Area and average Cord Fractional Anisotropy (p = 0.007), and increased Cord Mean Diffusivity (p = 0.024).
No correlations were found between DT-MRI metrics of the Cord and quantities obtained from conventional and DT-MRI of the Brain.
DT-MRI of the Cervical Cord can quantify the extent of diffuse Cord pathology in patients with PPMS.
Such Cord Diffusivity changes in patients with PPMS are likely to reflect irreversible Axonal Injury and reactive Gliosis and seem to be independent of Brain damage.
Intrathecal sICAM-1 Production In Multiple Sclerosis Correlation With Triple Dose Gd-DTPA MRI Enhancement And IgG Index
Acar G, Idiman F, Kirkali G, Ozakbas S, Oktay G, Cakmakci H, Idiman E
J Neurol 2005 Feb;252(2):146-150
Karsiyaka Neurology Outpatient Clinic, Dokuz Eylul University, Izmir, Turkey
In this study the aim was to evaluate the Intrathecal sICAM-1 production in Multiple Sclerosis (MS) patients during relapse and remission.
In addition to this, we assessed whether there is a correlation between Intrathecal sICAM-1 production and other disease activity markers such as IgG index and Gadolinium enhancement in Magnetic Resonance Imaging (MRI).
Twenty four Relapsing/Remitting MS patients were included in the study. Serum and CerebroSpinal Fluid (CSF) samples were obtained both during relapse and remission.
The soluble form of ICAM (sICAM) was measured by the ELISA method in Serum and CSF. Cranial MRI with triple dose Gadolinium injection was performed for each patient both during relapse and remission.
Serum levels of sICAM-1 (245.23+/-92.88 ng/ml) were higher during relapse than those in remission (219.90+/-110.94 ng/ml), but the difference was not statistically significant.
In relapse periods CSF levels of sICAM-1 (1.304+/-0.92 ng/ml) were higher than those in remission (1.06+/-0.86 ng/ml), but this was not significant.
However, during relapse periods patients had significantly higher sICAM-1 index values (1.76+/-0.60) than those found during remission periods (1.01+/-0.44) (p < 0.05). The IgG index values were higher in relapse periods than in remission (0.88+/-0.37 vs. 0.67+/-0.28) (p < 0.005).
On T1 weighted images following triple dose Gd injection, at least two or more enhancing lesions were present in 22/24 of the patients (91 %) in relapse and 4/24 of the patients (19 %) in remission.
There was strong correlation both between the sICAM-1 index and Gd enhancement (r=0.72 p < 0.05) and sICAM-1 index and IgG index in relapse (r=0.69 p < 0.05).
In conclusion, there is association between high sICAM-1 and IgG indices, as well as between high sICAM-1 index and Gd enhancing MRI lesions in Relapsing MS patients.
AntiEpileptic Medications In Multiple Sclerosis: Adverse Effects In A Three-Year Follow-Up Study
Solaro C, Brichetto G, Battaglia MA, Messmer Uccelli M, Mancardi GL
Neurol Sci 2005 Feb;25(6):307-10
P. A. Micone Hospital, Department of Neurology, Via D. Oliva 22, Genoa, Sestri Ponente, Italy
Neuropathic Pain and paroxysmal symptoms are common in Multiple Sclerosis (MS) patients, although no double-blind clinical trial has been conducted to support AntiEpileptic Medications (AED) use in MS.
The aim of the study was to evaluate the frequency of AED utilization and reported adverse events, in a cohort of MS patients.
For a period of 3 years the rationale for prescribing AED, adverse effects, treatment duration and reasons for discontinuation were recorded in a database.
Carbamazepine (CBZ) was prescribed in 36 patients, with adverse effects reported in 20 cases, of which 12 mimicked a relapse.
Gabapentin (GBP) was prescribed in 94 patients, with adverse effects reported in 16 cases and in one case mimicked a relapse. Lamotrigine (LMT) was prescribed in 22 patients, with adverse effects reported in 4 cases, none mimicking a relapse.
The present study found a significantly higher incidence of adverse effects in patients treated with CBZ, with a high rate of discontinuation at low dosages and episodes of evident worsening of Neurological functioning compared to GBP or LMT.