[Animal models in neurology: prospects and limitations]. / Tiermodelle in der Neurologie: Möglichkeiten und Grenzen.

Animal models play an important role for exploration of the aetiology, pathogenesis and therapy of various neurological diseases. Their benefit and limitations are being discussed mainly focussed at experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). To answer specific questions concerning the genetics, pathogenesis, diagnostics and treatment of inflammatory, degenerative, ischemic, traumatic und neoplastic diseases of the nervous system different animal models are needed. So far, these are only partially available. Rarely there are alternative methods such as cell, tissue and organ cultures and computer simulations. New phase-specific biomarkers are needed in order to improve the potency of experimental results to be translated into clinical practice.

Laboratory diagnosis of radicular and pseudoradicular syndromes in cerebrospinal fluid (CSF): reliability of methods in consideration of pathogenetic aspects. Report on section "CSF diagnosis" of 4th Klagenfurter Neurology Workshop Conference on radicular and pseudoradicular syndromes, Klagenfurt, Austria, August 28-29, 1992.

Laboratory tests may be used to confirm the clinical differentiation of pseudoradicular syndromes and radicular syndromes. In the presence of pseudoradicular syndromes, CSF and blood samples yield no positive results with either non-specific or specific methods. Radicular syndromes give rise to positive findings; using non-specific methods they can be subdivided into inflammatory and non-inflammatory forms, with and without blood-nerve barrier impairment. Non-specific quantities of CSF routine diagnosis are total protein, albumin, leukocyte counts and differential cell count, L-lactate, intrathecal -IgG, -IgA, -IgM and immunoglobulin-class oligoclonal bands. Oligoclonal bands enable the highly sensitive differentiation of non-inflammatory from subacute-chronically inflammatory forms of radicular syndromes. Most of the specific quantities are the subject of current research, e.g. bacterial antigens, D-lactate, cultivation tests, polymerase chain reaction tests and pathogen-specific oligoclonal bands. Pathomechanisms affecting the permeability of the blood-nerve barrier to increasing concentrations of protein and to leukocyte subsets possibly explain the CSF findings in radicular and pseudoradicular syndromes.

Classical and modern methods of cerebrospinal fluid analysis. Report on the First All-German Symposium of the Society for Laboratory Medicine (FRG) and the Study Group for CSF Analysis and Clinical Neurochemistry of the Society for Psychiatry and Neurology (formerly GDR) in Marburg a. d. Lahn, October 5-6, 1990.

The aim of the symposium was to prepare an inventory of cerebrospinal fluid (CSF) analysis used in Germany, and to evaluate them in comparison with modern methods. From the large field of CSF analysis, four main topics were selected, all related to the practical application of the methods. The following conclusions were drawn: Classical techniques of cytodiagnosis are clinically important. Therefore, manual and mechanized techniques must be further improved with respect to counting, collection, and differentiating of CSF cells. As cytokines and complement factors are early mediators of diverse processes in CNS, highly sensitive techniques must be developed for their routine analysis e.g. in CNS inflammation. Recent efforts to detect specifically viral and bacterial agents (e.g. by polymerase chain reaction, Particle Counting Immuno-Assay, Enzyme Immuno-Assay) or antibodies (e.g. affinity-mediated immunoblot, specific antibody index) in CSF must be continued in order to develop definite and practicable assays for daily routine. For the detection of intrathecally produced antibodies, qualitative procedures appear to be more reliable then quantitative ones, provided that the former are highly sensitive and specific.

Immunoadsorption and plasma exchange in multiple sclerosis: complement and plasma protein behaviour.

Three groups of patients suffering from acute attacks or progressive multiple sclerosis (MS) are under investigation. First results revealed remarkable clinical improvements of patients with acute attacks in the groups treated by therapeutic plasma exchange (TPE) and immunoadsorption (IA). Only slight or no improvements were seen in the patients of the control group treated only with steroids. Plasma protein levels (IgG, IgM, IgA, fibrinogen) were considerably reduced in patients of the TPE group after each treatment procedure as expected. The same holds true concerning the total hemolytic capacities (THC) of the complement of the classic (CP) and the alternative (AP) pathway. On the other hand in the IA group only slight decreases of plasma proteins (about 20%) were observed, but the behaviour of THC's were quite similar than those seen in the patients of the TPE group. The THC decreases in both groups can be explained by removal of all complement factors (TPE group) or by the adsorption of single factors (IA group) of both complement pathways according to earlier in vitro investigations. The THC decreases in patients of both groups suffering from acute MS attacks could mean an "antiinflammatory" effect and could--at least partially--contribute to the clinical improvements of these patients.

[Etiology and pathogenesis of multiple sclerosis: current aspects of causative factors in the disease course]. / Atiologie und Pathogenese der Multiplen Sklerose: derzeitige Aspekte zu den Ursachefaktoren des Erkrankungsablaufs.

The components of pathogenesis of multiple sclerosis are presented. (I.) Genetic and metabolic factors were found to be fundamental for cellular immune reaction; the association with class 2 MHC (HLA-DR; IR) antigens is more relevant than that of class 1 MHC (HLA-ABC) antigens. (II.) A reaction to several viruses may be significant for the induction and the heterogenous course of disease; some mechanisms of an immune-dysbalance--induced by viruses--are exposed. (III.) Disturbances of cellular immunoregulation, a reduced activity of T-suppressor-lymphocytes, a break of immune tolerance and cytotoxic effector mechanisms are decisive for the autoimmune processes. In all, on the basis of multi-genetic anomalies a multi-phase pathogenesis may be assumed, developing in manner of a cascade in several steps and phases.

[Forms of disease progression and prognostic factors in multiple sclerosis]. / Verlaufsformen und Prognosefaktoren der Multiplen Sklerose.

Basing on the diagnostic criteria, an analysis of 687 cases of multiple sclerosis (MS) is represented according to the different forms of course, their frequency and the degree of severity. For the progressive course--either secondary after attacks or primary--a higher proportion of disease with severe disturbances resp. comparatively malignant forms have been found; furthermore, a critical time of progression could be ascertained. The determination of the disability status (using the EDSS) during a longer space of time showed a more unfavourable prognosis for the males. The development of disability was more distinct at onset of disease in the elder-aged groups. The problems of uncertain factors influencing the course and prognosis of disease are pointed out in connection with the heterogeneity of MS, basing on the pathogenetic components.

[The problem and value of therapy in multiple sclerosis]. / Zur Problematik und Wertigkeit der Therapie bei Multipler Sklerose.

Some fundamental problems of therapy in multiple sclerosis (MS) and the difficulties in assessing the results of treatment are represented. Basing on a survey of several principles of therapy, the findings of own therapeutic trials using corticosteroids, immunosuppressive agents (azathioprine, cyclophosphamide, antihumanlymphocyte globulin) are pointed out; in particular, the analysis of a longer period of the course of disease produced few favourable effects. In further therapeutic studies, i.e. plasmapheresis and immunoadsorption, a long lasting observation of the course is lacking; this likewise concerns the study on ultraviolet irradiation of blood. As to the aspects of a multi-stage pathogenesis of MS an appraisal of therapeutic conceptions and procedures is given; in critical evaluation their efficacy is little convincing.

Incidence of multiple sclerosis: a periodic or stable phenomenon.

For diseases of unknown aetiology, the question as to whether the incidence is constant or variable is very important. A study on multiple sclerosis in a defined northern area of the German Democratic Republic showed a prevalence of 68.6 and an incidence rate of 3.0. Retrospective and prospective investigations concerning an observation period of 22 years revealed cyclic periods (6-7 years) of high incidence rates (up to 4.5) interrupted by shorter intervals (4-5 years) with low rates (about 1.8). The differences (1963-1968 vs. 1969-1973, 1974-1978 vs. 1979-1983) are significant. In accordance with the findings of Kurtzke et al. on a cyclic outbreak of multiple sclerosis in the Faroes and Iceland, our results are considered to be a consequence of environmental factors, such as epidemic viral infections.