Familial Factors Influence Disability In MS Multiplex Families:
The French Multiple Sclerosis Genetics Group.
Brassat D, Azais-Vuillemin C, Yaouanq J, Semana G, Reboul J, Cournu I, Mertens C, Edan G, Lyon-Caen O, Clanet M, Fontaine B
Neurology 1999 May 12;52(8):1632-6
Federation de Neurologie and INSERM, Groupe Hospitalier Pitie-Salpetriere, Paris, France
PMID# 10331690; UI# 99260533
Both Genetic and Environmental factors play a role in the PathoPhysiology of MS and may influence the clinical expression of the disease.
To determine the contribution of familial factors to the clinical expression of MS.
The French Multiple Sclerosis Genetics Group identified 87 sibling pairs. For each patient, sex, age at onset, duration of the disease, and disease course from onset were recorded.
Disability was determined by the Progression Index (PI), defined as the ratio of the Expanded Disability Status Scale (EDSS) score disease duration when the latter exceeded 5 years.
Statistical analyzes were performed either with a group of patients (clinical features, relation between Human Lymphocyte Antigene and clinical features) or with a group of sibpairs (concordance for clinical features).
The mean age at onset was 29.6 years, the ratio of women to men was 59:28, and the mean PI was 0.27. There was no correlation for disease course and age at onset between sibs with MS. In contrast, we observed a weak but significant correlation of the PI in MS sibpairs (r = 0.234, p = 0.03).
This study revealed a concordance in MS sibling pairs for the disease severity, supporting the hypothesis that the degree of Disability might be partly influenced by Familial Factors (Environmental or Genetic).
Werring DJ, Clark CA, Barker GJ, Thompson AJ, Miller DH
Neurology 1999 May 12;52(8):1626-32
NMR Research Unit, Institute of Neurology, the National Hospital for Neurology and NeuroSurgery, London, UK
PMID# 10331689; UI# 99260532
To determine whether Diffusion Tensor Imaging (DTI) can detect structural changes in Normal-Appearing White Matter, and to distinguish between Plaques of different pathologic severity, in patients with MS.
Conventional MRI detects lesions sensitively in MS but has limited pathologic specificity.
The Diffusion of water molecules in Brain tissue, most fully expressed mathematically by a Tensor quantity, reflects its intrinsic MicroStructure.
It is now possible to estimate the Diffusion Tensor noninvasively in the human Brain using MR DTI.
This method is unique in providing precise and rotationally invariant measurements of the amount and directional bias (Anisotropy) of Diffusion in White Matter Tracts relating to tissue integrity and orientation.
DTI was performed in six patients with MS and in six age-matched control subjects.
Diffusion was characterized in Normal-Appearing White Matter in both groups, and in lesions of different pathologic subtypes (Inflammatory, NonInflammatory, T1 HypoIntense, and T1 IsoIntense).
DTI identified significantly altered water Diffusion properties in the Normal-Appearing White Matter of patients compared with control subjects (p < 0.001), and distinguished between lesion types.
The highest Diffusion was seen in destructive (T1 HypoIntense) lesions, whereas the greatest change in Anisotropy was found in Inflammatory (Gadolinium-Enhancing) lesions.
DTI detects diffuse abnormalities in the Normal-Appearing White Matter of MS patients, and the findings in Lesions appear to relate to pathologic severity.
Its use in serial studies and in larger clinical cohorts may increase our understanding of PathoGenetic mechanisms of reversible and persistent Disability.
Ozenci V, Rinaldi L, Teleshova N, Matusevicius D, Kivisakk P, Kouwenhoven M, Link H
J AutoImmun 1999 Jun;12(4):297-303
Karolinska Institute, Huddinge Univ Hospital, Division of Neurology, Stockholm, Sweden
Matrix MetalloProteinases (MMPs) comprise a family of ProteoLytic Enzymes. MMPs are capable of disrupting the Blood-Brain Barrier (BBB), mediating the destruction of ExtraCellular Matrix and Myelin components.
MMPs are also involved in the processing of a variety of cell surface molecules, including the Pro-Inflammatory Cytokine TNF-. Each of these mechanisms are thought to be important in the PathoGenesis of Multiple Sclerosis (MS).
We investigated mRNA expression of MMP-3, MMP-9 and two Tissue Inhibitors of MetalloProteinases (TIMP-1 and TIMP-2) in parallel in blood MonoNuclear Cells (MNC) from patients with MS and controls, using in situ hybridization.
Numbers of MMP-9 mRNA-expressing cells in blood were higher in patients with MS compared to Other Neurological Diseases (OND), Other Inflammatory Neurological Diseases (OIND) and healthy subjects (P<0.0001 for all comparisons).
Patients with MS had also higher levels of MMP-3 and TIMP-1 mRNA expressing blood MNC compared to patients with OND and healthy subjects. A positive correlation was observed for MMP-9 and TIMP-1 mRNA expression in MS.
These results demonstrate that MMPs and TIMPs are upregulated in MS and may contribute to the PathoGenesis of the disease.
Copyright 1999 Academic Press