Recurrent transverse myelitis following neurobrucellosis: immunologic features and beneficial response to immunosuppression.

The authors report the clinical course and immune system response of a patient with disease-associated recurrent transverse myelitis (TM) following cerebral infection with Brucellosis melitensis. The patient suffered four recurrences of his TM (each at a distinct spinal cord level) over the course of 2 years following his initial presentation, which ultimately progressed to quadriplegia. He had progressively declining cerebrospinal fluid (CSF) brucella antibody titers, suggesting a postinfectious, rather than an infectious, etiology. The authors simultaneously examined the expression of multiple cytokines in the CSF of this patient using cytokine antibody arrays and found a marked elevation of interleukin (IL)-6, IL-8, and macrophage chemoattractant protein (MCP)-1 levels relative to controls. Quantitative enzyme-linked immunosorbent assay (ELISA) analysis of the CSF confirmed a 1700-fold elevation of IL-6 and more modest elevations of IL-8 and MCP-1. IL-6 levels returned to baseline following treatment of the patient with intravenous cyclophosphamide and plasma exchange and the patient experienced a significant and sustained recovery of function.

Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats.

We generated spinal motoneurons from embryonic stem (ES) cells to determine the developmental potential of these cells in vitro and their capacity to replace motoneurons in the adult mammalian spinal cord. ES cell-derived motoneurons extended long axons, formed neuromuscular junctions, and induced muscle contraction when cocultured with myoblasts. We transplanted motoneuron-committed ES cells into the spinal cords of adult rats with motoneuron injury and found that approximately 3,000 ES cell-derived motoneurons (25% of input) survived for >1 month in the spinal cord of each animal. ES cell-derived axonal growth was inhibited by myelin, and this inhibition was overcome by administration of dibutyryl cAMP (dbcAMP) or a Rho kinase inhibitor in vitro and in vivo. In transplanted rats infused with dbcAMP, approximately 80 ES cell-derived motor axons were observed within the ventral roots of each animal, whereas none were observed in transplanted rats not treated with dbcAMP. Because these cells replicate many of the developmental and mature features of true motoneurons, they are an important biological tool to understand formation of motor units in vitro and a potential therapeutic tool to reconstitute neural circuits in vivo.