Therapeutic Problems in Patients Suffering from Aluminum Encephalopathy

Abstract

Aluminium encephalopathy is a neurological syndrome occurring almost exlusively among patients under regular dialysis treatment (1). Leading symptoms are dementia (98%), speech disturbances (95%), myoclonus (81%), epileptic seizures (57%), and psychotic episodes (52%) (3). The cause of the disease is thought to be a chronic intoxication by aluminium leading to an increase of the metal in the brain tissue. Aluminium can cause intoxication in four ways. First, end-stage renal failure results in a reduced renal aluminium clearance. Second, treatment with phosphate binders is given in order to prevent a secondary hyperparathyroidism. Third, there may be increased aluminium in the dialysis bath, which crosses the dialysis membrane. Forth, mobilization of aluminium deposits — in various organs, accumulated over years — may occur during immobilization of the patient, for example after kidney transplantation or another illness. The course of the disease is rapidly progressive, and if untreated it is almost always fatal. Since characteristic alterations in the EEG, like paroxysmal dysrhythmic discharges with spikes and sharp waves, occur early in the disease almost before clinical signs become apparent, treatment of the patient using chelating agents like desferrioxamine can start early (2). During this phase the patient runs a high risk of having a seizure which can result in a bone fracture, even of the vertebral column. Thus, attempts have been made to prevent epileptic events by giving diazepam. This drug, however, provokes seizures when adequate compliance is missing. Therefore, based on the finding that the half-life of phenytoin was not affected by hemodialysis, this anticonvulsant was used as a prophylactic treatment (4). Serum anticonvulsant levels before and after dialysis showed, however, significant reductions of plasma levels. A systematic change was not detected. In all patients under investigation the measurements showed individual profiles of drug concentration, sometimes even changing from week to week. On the whole, anticonvulsant treatment using phenytoin for patients suffering from dialysis encephalopathy is difficult. The dosage has to be adjusted according to the patient’s individual plasma level, which has to be monitored closely. The cause might be altered protein binding of phenytoin due to alteration of pH in patients with end-stage renal failure resulting in variability of the phenytoin clearance by dialysis.