[Magnetic resonance tomography. A valuable method in the diagnosis of central nervous system diseases in children].
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Cerebrospinal fluids (CSF) (N = 365) from patients with non-inflammatory diseases of the central nervous system were analyzed for protein distribution by agar gel microelectrophoresis. After subdivision into diagnostically well defined groups, these patients were compared with 79 normal controls. Most of the diseases investigated were found to follow the "plasma-type" pattern. In some of them the deviations from normal were so extensive that a CSF-protein pattern similar to the "acute-phase reaction" in the serum occurred. Moreover, the following characteristics were found: a considerable increase in total protein and the gamma-globulin fractions in neurinomas; a reproducible increase in the alpha1-globulins in metastases of the central nervous system; and a statistically significant difference of CSF protein findings between male and female patients with protrusion of lumbar intervertebral discs.
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Almost a decade ago, it was discovered that the human deficiency virus (HIV) makes use of chemokine receptors to infect blood cells. This appreciation of the clinical relevance of specific chemokine receptors has initiated a considerable boost in the field of chemokine research. It is clear today that chemokine signaling orchestrates the immune system and is widely involved in both physiological and pathophysiological processes. Since the chemokine system offers various targets through which pathology could be influenced, most pharmaceutical companies have chosen this system as a therapeutic target for a variety of diseases. Here recent developments concerning the role of chemokines in diseases of the central nervous system (CNS) as well as their possible therapeutic relevance are discussed.
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Three patients with a central and peripheral nervous system disease complicating a Mycoplasma pneumoniae (M. pn.) infection are presented. Patient 1 suffered from bilateral optic neuritis as well as acute Guillain-Barré syndrome recovering after plasmapheresis. The two other patients suffered from severe haemorrhagic leukoencephalitis (Hurst) which only could be contained by aggressive decompressive craniectomy with duraplasty. All three illnesses were clearly shown to be associated with M. pn. infection. Our three patients represent the full scale of central nervous (CNS) (cerebral and myelitic) as well as peripheral nervous system (PNS) (GBS, optic neuritis) manifestation of a disease caused by the same pathogenetic - post-infectious - mechanism; pathogenic CNS and PNS epitopes might be shared in post-infectious neurological disease following M. pn. infection.
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The presence of increased IgG in the brains of humans with infectious and inflammatory CNS diseases of unknown etiology such as multiple sclerosis may be a clue to the cause of disease. For example, the intrathecally synthesized oligoclonal bands in diseases such as subacute sclerosing panencephalitis (SSPE) or cryptococcal meningitis have been shown to represent Ab directed against the causative agents, measles virus (MV), or Cryptococcus neoformans, respectively. Using SSPE as a model system, we developed a strategy to identify the antigenic targets of the intrathecal disease-relevant IgG in chronic human inflammatory and demyelinating diseases of the CNS. Libraries of cDNA Ags were displayed on the surface of T7Select bacteriophage and biopanned on IgG extracted from the brain of an SSPE patient, or on a monospecific recombinant Fab identified from SSPE brain. After three or six rounds of biopanning on either Ab, positive phage-displayed Ags reacting with IgG were enriched to 35-77% of all panned clones. Sequence analysis of the positive clones identified fragments of the nucleocapsid protein of MV, the cause of SSPE. The sensitivity of the system was determined by diluting the positive clones from this SSPE phage-displayed library at a ratio of 10(-6) into another phage-displayed library that did not contain any detectable MV Ags; after six rounds of panning, the positive clones comprised 34% of all phage and were also shown to be MV nucleocapsid specific. This strategy will be useful to identify potentially rare Ags in diseases of unknown cause.
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