[Adverse effects of cyclosporin A with special reference to the peripheral nervous system]

Since the introduction of Cyclosporine A (CsA) in 1972, several studies have focused on its effects on experimental autologous peripheral nerve transplants. Although several studies have reported neurotoxicity of CsA in the central nervous system, no such data exist regarding the peripheral nervous system. The present study focuses on the effects of CsA in the therapeutic and toxic doses on axon regeneration, particularly the rate and quality of axon regeneration. Autologous nerve transplantation was performed in Lewis rats and axon regeneration evaluated clinically (motor function, body weight), electroneurographically and histologically. In transplanted nerves, even high doses of CsA (30 mg/kg bodyweight) did not lead to delayed or impaired axon regeneration. Long-term application in normal peripheral nerves did however cause axon degeneration with edema and vacuolisation of myelin sheaths, retraction of myelin sheaths from the node of Ranvier, and marked enhancement of the Schmidt-Lantermann incisures. As neurological side effects such as tremor and paresthesia have been reported under application of CsA in man, the above data might be of clinical relevance.