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.


METHODS
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.


CONCLUSIONS
The results of this study give further insight to the pathophysiology of brain abnormalities in patients with chronic renal failure.
Battaglia
Fortunato
F
Department of Physiology and Pharmacology, City University of New York Medical School, New York, NY, USA. fb@med.cuny.edu
Quartarone
Angelo
A
Bagnato
Sergio
S
Rizzo
Vincenzo
V
Morgante
Francesca
F
Floccari
Francesco
F
Romeo
Adolfo
A
Sant'Angelo
Antonio
A
Grasso
Giovanni
G
Girlanda
Paolo
P
Buemi
Michele
M
D001928:Brain Diseases, Metabolic / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D018592:Cross-Over Studies; D004234:Diuretics, Osmotic / Q000494:pharmacology / Q000627:therapeutic use; D004558:Electric Stimulation; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D016030:Kidney Transplantation; D008280:Magnetics; D008297:Male; D008353:Mannitol / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D009994:Osmolar Concentration; D011712:Pyramidal Tracts / Q000503:physiopathology; D006435:Renal Dialysis / Q000009:adverse effects*; D014511:Uremia / Q000150:complications / Q000628:therapy*; D014882:Water-Electrolyte Balance / Q000502:physiology; D014883:Water-Electrolyte Imbalance / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology
D004234:Diuretics, Osmotic; D008353:Mannitol