Central nervous system involvement of previously undiagnosed chronic lymphocytic leukemia in a patient with neuroborreliosis.

Leukemic involvement of the central nervous system (CNS) in previously undiagnosed chronic lymphocytic leukemia (CLL) is very rare. We report the case of a 62-year-old man with neuroborreliosis in which cytologic, immunocytochemical, and flow cytometry analyses revealed the presence of clonal B-lymphocytes in the cerebrospinal fluid (CSF). After the patient received antimicrobial therapy, his meningeal symptoms cleared up, and the number of cells in the CSF decreased. Monoclonal lymphocytes were still detectable at the same percentage, however, despite systemic chlorambucil therapy. The application of intrathecal dexamethasone therapy led to the disappearance of B-cell CLL (B-CLL) cells in the CSF. We presumed that the neuroborreliosis enabled the transmigration of leukocytes, including B-CLL cells, across the blood-brain barrier via activation of matrix metalloproteinase 9, an enzyme known to open the blood-brain barrier.

Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk1, Erk2, and p38 in the response of astrocytes to Borrelia burgdorferi lipoproteins.

Lyme borreliosis, which is prevalent both in the US and in Europe, is an infectious disease that may cause local inflammation in numerous organs. We have hypothesized that, as with some neurodegenerative diseases, the pathogenesis of the neurocognitive deficiencies associated with Lyme neuroborreliosis of the central nervous system also has an inflammatory component. Dysregulated production of pro-inflammatory cytokines such as IL-6 and TNF-alpha can lead to neuronal damage. Mitogen-activated protein kinases (MAPK) play a key role in the regulation of neuronal development, growth, and survival, as well as that of pro-inflammatory cytokine production. As a model, we explored the possibility that MAPK-mediated lipoprotein-induced apoptosis and gliosis of rhesus monkey astrocytes stimulated in vitro. Lipoproteins are the key inflammatory molecule type of Borrelia burgdorferi, the spirochete that causes Lyme disease, and we had previously shown that lipoprotein-induced TNF-alpha production in astrocytes caused astrocyte apoptosis, and IL-6 enhanced proliferation of these cells. Lipoproteins readily activated p38 and Erk1/2 MAPK, thus enlisting these pathways among the kinase pathways that spirochetes may address as they invade the central nervous system. We also investigated whether specific inhibition of p38 and Erk1/2 MAPK would inhibit TNF-alpha and IL-6 production and thus astrocyte apoptosis, and proliferation, respectively. Lipoprotein-stimulated IL-6 production was unaffected by the MAPK inhibitors. In contrast, inhibition of both p38 and Erk1/2 significantly diminished TNF-alpha production, and totally abrogated production of this cytokine when both MAPK pathways were inhibited simultaneously. MAPK inhibition thus may be considered as a strategy to control inflammation and apoptosis in Lyme neuroborreliosis.

[Evaluation of oxidoreductive potential of patients with neuroborreliosis]. / Ocena potencjalu oksydoredukcyjnego u chorych z neuroborelioza.

AIM: The purpose of the study was to evaluate parameters of oxidoreductive system in serum and cerebrospinal fluid (CSF) of patients with neuroborreliosis. MATERIAL AND METHODS: The cases were 25 patients aged 21 to 64 (x = 42.3) hospitalized with diagnosis of neuroborreliosis. Activity of superoxide dismutase (Cu, Zn-SOD), glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px) and concentration of sulphydryl groups (-SH) and malondialdehyde (MDA) in serum and CSF were tested. The control group consisted of 10 patients with diagnosis of discopathy. An examination was performed twice: before and after treatment. RESULTS: Results of the study showed lack of stability in an oxidoreductive system during neuroborreliosis both in serum and in CSF. In CSF activity of SOD was increased while activity of GSH-Px and GSSG-R were decreased. Also concentration of -SH and lipid peroxidation products measured as MDA were increased. The increase of SOD, GSH-Px, GSSG-R activity and concentration of -SH and MDA in serum were detected. CONCLUSIONS: Disorders of an oxidoreductive system in CSF and serum during neuroborreliosis were observed. These changes persisted despite treatment and normalization of inflammatory CSF markers.