Brain dysfunction in uremia: a question of cortical hyperexcitability?

OBJECTIVE: To investigate whether patients with end-stage renal disease (ESRD) in different stages of the disease and undergoing different treatments display alterations in cortical excitability. METHOD: A total of 36 patients with ESRD were evaluated at different stages of the disease and under different treatment by using standard transcranial magnetic stimulation (TMS) parameters. Moreover patients under haemodialysis underwent a double-blind crossover study (mannitol vs placebo) in order to better elucidate the pathophysiology of the acute effects of haemodialysis on cortical excitability. RESULTS: Patients with ESRD in conservative therapy showed a significant reduction of short-interval intra-cortical inhibition (SICI). This alteration could be reversed by haemodialysis, peritoneal dialysis and by renal transplantation. After haemodialysis there was a significant increase of intra-cortical facilitation (ICF) inversely correlated with the drop in plasma osmolarity induced by the dialytic procedure. Mannitol infusion prevented the drop in plasma osmolarity and the haemodialysis-related changes in ICF. CONCLUSIONS: ESRD patients showed alterations in cortical excitability that can be reversed by replacement therapies. We propose that the drop in plasma osmolarity is a key to the mechanism underlying post-haemodialysis cortical hyperexcitability. SIGNIFICANCE: The results of this study give further insight to the pathophysiology of brain abnormalities in patients with chronic renal failure.