| Scientific relevance. In 1999 the Stichting Vrienden MS Research made funds available to start a CSF bank dedicated to multiple sclerosis (MS) research, based on grant number 98-345 that highlighted the relevance of cerebrospinal fluid (CSF) investigation in well documented multiple sclerosis (MS) patients and make the CSF available to researchers all over the world. Obviously, CSF is closely related to the CNS, the site where inflammatory and neurodegenerative processes in MS take place. Therefore CSF can reflect the biochemical changes taking place in MS brain, as has been described before. The way of collecting and storing the fluid can be of influence on some biochemical markers; therefore a standardized method is needed. To get more insight into the disease and various subtypes, it is of utmost importance to collect additional data, such as clinical scales often used in MS (Expanded Disability Status Scale, GUY's Neurologic Disability Scale, Multiple Sclerosis Functional Composite), cognitive (neuropsychological battery of test, described by Rao in 1990) and Magnetic Resonance Imaging (MRI) data. The collection of the data and CSF take place by doctors well informed of MS research, so knowledge, techniques and recent developments in this field can be made available and a continued update of standardized CSF and data collection and protocol of processing CSF and storage is necessary. In order to provide research groups all over the world with this unique material the Netherlands Brain Bank is involved, which has an outstanding reputation and a longstanding experience with postmortem tissue. Another advantage of the involvement of the Netherlands Brain Bank is the availability of tissue and postmortem CSF from patients with brain diseases and normal controls. So far, the number of publications interpreting data derived from postmortem CSF is only limited. A linkage between CSF from living patients, postmortem brain tissue and postmortem CSF will be of great relevance for MS research as can also be shown by a recent publication on the heterogeneity of the disease. These data (Luchinetti et al.) showed that although most MS lesions contained an inflammatory reaction mainly composed of lymphocytes and macrophages, four different patterns of myelin destruction were observed when analysing lesions using a broad spectrum of immunological and neurobiological markers. It is possible that different pathogenic mechanisms of demyelination may operate in different subgroups of MS patients. Though being of great scientific importance, the day-to-day relevance of these patterns is limited by the fact that these data are derived from detailed analysis of brain tissue, which is only available from patients who died or from whom a brain biopsy was obtained (small number of very atypical cases). So far, attempts to correlate these four patterns with clinical or paraclinical characteristics of patients are quite limited. Future studies will need to define specific clinical or paraclinical parameters that allow for differentiating the heterogeneous pathogenetic components in MS lesions by correlating them for example to CSF proteins. Since our previous application, also new techniques, assays, improvements in detection systems and computer technology have become available in the field of basic science, which may be applicable for MS research. One of the new applications in genome-wide genetic mapping, physical mapping and gene expression studies are microarrays. Recent publications have identified by microarray several genes which might be involved in MS. These genes are encoding for inflammatory cytokines, particularly interleukin-6 and -17, interferon-gamma (Lock et al. 2002), 5-lipoxygenase, a key enzyme in the biosynthesis of the proinflammatory leukotrienes (Whitney et al. 2001) and osteopontin (Chabas et al. 2001). Since DNA in these publications was derived from brain plaques or EAE models, it will be worthwhile to look for these markers in DNA derived from CSF in living MS patients. Next to DNA array-based methods, the analysis of proteins in an analogues format is becoming prevalent within proteomics research. Array-based protein technologies are emerging for basic biological research, molecular diagnostics and therapeutic development with the potential of providing parallel functional analysis of hundreds or perhaps hundreds of thousands of proteins simultaneously. Protein microarrays also show applications for enzyme-substrate, DNA-protein and different types of protein-protein interactions. |
