Concept description and accuracy evaluation of a moldable surgical targeting system.

Purpose: We explain our concept for customization of a guidance instrument, present a prototype, and describe a set of experiments to evaluate its positioning and drilling accuracy. Methods: Our concept is characterized by the use of bone cement, which enables fixation of a specific configuration for each individual surgical template. This well-established medical product was selected to ensure future intraoperative fabrication of the template under sterile conditions. For customization, a manually operated alignment device is proposed that temporary defines the planned trajectory until the bone cement is hardened. Experiments ( n = 10 ) with half-skull phantoms were performed. Analysis of accuracy comprises targeting validations and experiments including drilling in bone substitutes. Results: The resulting mean positioning error was found to be 0.41 ± 0.30 mm at the level of the target point whereas drilling was possible with a mean accuracy of 0.35 ± 0.30 mm . Conclusion: We proposed a cost-effective, easy-to-use approach for accurate instrument guidance that enables template fabrication under sterile conditions. The utilization of bone cement was proven to fulfill the demands of an easy, quick, and prospectively intraoperatively doable customization. We could demonstrate sufficient accuracy for many surgical applications, e.g., in neurosurgery. The system in this early development stage already outperforms conventional stereotactic frames and image-guided surgery systems in terms of targeting accuracy.

In vitro evaluation of physiologically relevant concentrations of teriflunomide on activation and proliferation of primary rodent microglia.

BACKGROUND: Teriflunomide, an inhibitor of dihydroorotate dehydrogenase, is thought to ameliorate multiple sclerosis by reducing activation-induced proliferation of lymphocytes, which is highly dependent on de novo pyrimidine synthesis. Nevertheless, its immunomodulatory effects on resident glial cells in the central nervous system are only poorly understood. METHODS: In this study, we employed physiologically relevant concentrations of teriflunomide and investigated its effects on survival, proliferation, activation, and function of primary rat microglia in vitro. RESULTS: We demonstrate that teriflunomide had no cytotoxic effect on microglia and had only a minor impact on microglial activation. In a concentration- and time-dependent manner, teriflunomide significantly downregulated surface expression of the co-stimulatory molecule CD86. Furthermore, in the highest concentration applied (5 µM), it slightly increased the expression of interleukin-10 in microglia in response to lipopolysaccharide. Treatment with low concentrations of teriflunomide (0.25-1 µM) did not have any impact on the activation or proliferation of microglia. At 5 µM concentration of teriflunomide, we observed a reduction of approximately 30 % in proliferation of microglia in mixed glial cell cultures. CONCLUSIONS: Taken together, our in vitro findings suggest that at higher concentrations, teriflunomide potentially exerts its effects by reducing microglial proliferation and not by modulating the M1-/M2-like cell differentiation of primary rat microglia. Thus, teriflunomide has no major impact on the plasticity of microglia; however, the anti-proliferative and minimal anti-inflammatory effects might be clinically relevant for immune modulation in the treatment of neuroinflammatory CNS diseases such as multiple sclerosis.