Cystic fibrosis patients with and without central nervous system complications following lung transplantation

Abstract

Central nervous system (CNS) complications occur more frequently in cystic fibrosis (CF) patients than other lung transplant recipients. The purpose of this study was to compare CF patients with and without CNS complications following lung transplantation, to identify risk factors for CNS events. Records of 21 patients with CF who underwent lung transplant between 1991-1996 were reviewed. Data were collected on multiple variables, including: age at transplant; gender; cytomegalovirus (CMV) status; cholesterol and triglyceride levels; sinusitis; percent ideal body weight (IBW); body mass index (BMI); augmented immunosuppression, acute lung rejection episodes (ALR); cyclosporine doses; electrolytes; magnesium, blood urea nitrogen (BUN), and creatinine levels; and 6-month survival. CNS complications identified were seizures, severe headaches (HA), strokes, or confusional episodes.Eleven of 21 patients (52%) with CF had CNS events: eight had seizures, five HA, three strokes, and one confusional episode. There was no difference in age at transplant, pretransplant percent IBW or BMI, cholesterol and triglyceride levels, or number of ALR. CMV mismatch and clinical sinusitis had no effect. Cyclosporine doses did not differ between groups at 30 days, or 3 or 6 months posttransplant. Both BUN and creatinine concentrations showed a rise over time that did not differ between groups. Potassium levels were within normal limits for both groups. While sodium levels did not differ between groups pretransplant, or at 30 days or 6 months posttransplant, a decrease in sodium values was seen at the time of CNS events. There was no difference in 6-month survival.We could not identify any pre-or posttransplant risk factors that predicted CNS events. It is likely that cyclosporine toxicity is the major cause of CNS complications. Despite the high rate of CNS events, the overall prognosis was good, and 6-month survival was not affected.

Expression and Distribution of Cystic Fibrosis Transmembrane Conductance Regulator in Neurons of the Human Brain

“…This further supports the concept that mutation of CFTR affects neuronal function, and seizures in this context may be related to electrolyte disturbances caused by mutant CFTR (Castilla-Guerra et al 2006). Although cyclosporine toxicity was hypothesized to be the cause of CNS complications in CF, changes in CFTR protein could not be ruled out (Goldstein et al 2000). Facial nerve paralysis is an uncommon occurrence in the neonatal period.…”

“…This result suggests that CF can cause molecular accumulation in the brain and lends support to the mutant CFTR-blocking hypothesis. It is also of interest that subclinical extrapyramidal hemosiderosis has also been reported in CF (Wongmongkolrit et al 1985), and seizures occur more frequently in lung transplant recipients with CF (Goldstein et al 2000). This further supports the concept that mutation of CFTR affects neuronal function, and seizures in this context may be related to electrolyte disturbances caused by mutant CFTR (Castilla-Guerra et al 2006).…”

“…CF is characterized by abnormally thick mucus, with symptoms such as meconium ileus, pancreatic insufficiency, and progressive pulmonary failure. Abnormalities have been reported in the central nervous system (CNS) of patients with CF (Goldstein et al 2000), including axonal dystrophy and detectable amyloid precursor protein. CNS complications occur in more than 50% of lung transplant recipients with CF, which is significantly higher than in other groups of lung transplant recipients (Goldstein et al 2000).…”