Der klinische Phänotyp bei familiärer Multipler Sklerose

Die Multiple Sklerose ist eine Erkrankung des Zentralen Nervensystems, die klinisch als auch pathologisch eine große Heterogenität aufweist. Deutschland gehört mit einer Prävalenz von 60/100.000 Einwohnern zu den Hochrisikoländern. Bei 15 % der Betroffenen liegt eine familiäre Form der Erkrankung vo...

Full description

Saved in:
Bibliographic Details
Main Author: Korsukewitz, Catharina Renate
Contributors: Sommer, Norbert (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2007
Online Access:PDF Full Text
Tags: Add Tag
No Tags, Be the first to tag this record!

Multiple sclerosis is a demyelinating disease of the central nervous system with profound heterogeneity of the clinical and pathological phenotype. Germany is a high risk area with a prevalence of 60/100.000. The rate of familial disease amounts to 15%. Three courses of disease can be differentiated (relapsing-remitting, secondary progressive, primary progressive). Initial presentation varies with the disease course and the study population. According to different disease courses, age of onset changes and the progression of disease evolve heterogeneously. Pathological analysis revealed different patterns of myelin destruction and inflammation defined by the contribution of cell and humoral mediated immunity. The aetiology of multiple sclerosis is unknown. Familial clustering and the geographic prevalence pattern have yielded acceptance of a genetic susceptibility. The environmental factors triggering the autoimmune reaction have not been found yet. Genome screens failed to show any susceptibility genes beside the locus of the HLA system. Based on this, the study should characterize the clinical phenotype of patients with familial multiple sclerosis in Germany and provide the opportunity of clinical differentiation. 156 patients (98 sib pairs) with familial multiple sclerosis were recruited by the department of neurology of the University Hospital of Marburg, rehabilitation clinics and neurological practices. The control group was matched with sib pairs in age, disease course, sex and duration of disease. A second control group including 284 patients with sporadic multiple sclerosis was used for all patients with familial multiple sclerosis. The first end point of the study was the progression of disability measured by the telephone EDSS by Lechner-Scott and the progression index (PI = EDSS/duration of disease). Secondary, age at onset and first symptom according to anamnestic data and patient records were examined. Previously, we evaluated the validity of the telephone EDSS in a double blind study with 52 patients of the MS clinic. In patients with familial multiple scleroses PI declined more in the course of disease than in sporadic patients. Patients with familial MS reported significantly more often brain stem symptoms at the beginning of disease than patients with sporadic MS. The PI, the EDSS and the age at onset did not differ between the two groups. Sib pairs were concordant in the age at onset, the first symptom and the PI. The results show that the clinical phenotype in familial and sporadic multiple sclerosis differ in some aspects. The results should appeal for a prospective study on clinical data that gives the opportunity to form subgroups for further genetic analysis.