HYPERAMMONEMIC ENCEPHALOPATHY DUE TO A URINARY DIVERSION: AN UNCOMMON CAUSE OF REVERSIBLE DEMENTIA

Abstract

To the Editor: Patients with cognitive impairment may have potentially reversible conditions. Metabolic diseases constitute an important group of these nondegenerative etiologies. Urinary diversion has been reported to cause hyperammonemic encephalopathy (HE), even without liver disease. This letter presents the case of a patient with hyperammonemia and history of a Bricker diversion after radical cystectomy for bladder cancer previously misdiagnosed with early-onset dementia. After specific treatment for hyperammonemia, the patient's cognition improved greatly. A 74-year-old man was admitted to the acute geriatric unit of our hospital because of a 3-week history of drowsiness and general stiffness. He had a prior medical history of a Bricker uretero-ileostomy after radical cystectomy for bladder cancer performed 1 year before admission and cognitive impairment, labelled as Alzheimer's disease, detected 3 months before by his general physician, although no specific tests had been performed to evaluate it. Omeprazole and lorazepam were his regular medications. On examination, he was unaware of time and place, and he presented with signs of dehydration. Neurological findings included slurred speech, drowsiness, clumsiness, stiffness, postural instability, and bradykinesia. Symptoms were present and stable all day. Blood tests showed mildly high C-reactive protein (3.5 mg/dL), hypernatremia (156 mEq/L), and leucocytosis (18 × 109/L). Glucose, calcium, magnesium, Vitamin B12, thyroid hormone, and renal and liver function tests were normal. Urine sediment evidenced mild leukocyturia with bacteriuria. Chest radiography was normal. Initial diagnosis was hypernatremia secondary to dehydration and urinary infection, and fluid therapy and antibiotic with ceftriaxone were started. Urinary culture was negative. Natremia normalized progressively, but the patient's symptoms did not improve at all. A cranial computed tomography (CT) scan showed mild diffuse cerebral atrophy, and an electroencephalogram revealed diffuse nonspecific encephalopathy. Despite normal liver function, given the urinary diversion, blood ammonia levels were tested revealing marked hyperammonemia (122 μmol/L). An abdominal–pelvic CT scan did not evidence signs of obstruction or dilatation of the uretero-ileal anastomosis. Specific treatment with dietary protein restriction and lactulose therapy was initiated. In a few days, ammonemia became normal, and the patient quickly showed great improvement in his mental state (Mini-Mental State Examination score 29/30 at 1 month after discharge). The global prevalence of dementia in the elderly population is approximately 5%.1 Alzheimer's disease is the most common disorder, accounting for 60% to 80% of cases, followed by vascular dementia (10–20%).2 The prevalence of a potentially reversible cause (Table 1) ranges from less than 1% to 9%, being higher in younger (<60) than older adults and significantly more common in patients with only subjective symptoms than in patients with established dementia.2–4 The most common reversible causes are depression, drugs, hydrocephalus, and metabolic diseases; thyroid disease and vitamin B12 deficiency are the most frequently detected causes from metabolic diseases.2,3 HE is an uncommon reversible etiology of cognitive impairment. Liver diseases, some drugs, portosystemic shunting, congenital defects of enzymes of the urea cycle, parenteral nutrition, hematological dyscrasia, and urinary diversion have been reported as causes of hyperammonemia.5–7 Nonhepatic hyperammonemia in patients undergoing urinary diversion is due to the prolonged contact of urine and the intestinal epithelium that results in high intestinal uptake of urine-excreted products, which can overload the detoxifying capacity of the liver, leading to the download of ammonia into the blood flow.8 Furthermore, urinary tract infections with urease-producing bacteria may cause urine ammonia concentration to rise. Proteus mirabilis and Pseudomonas aeruginosa are the best-known urea-splitting bacteria.9 There are no standardized guidelines for treating acute nonhepatic hyperammonemia. The reduction of intestinal ammonia levels by limiting protein ingestion to 20 g/d and using nonabsorbable disaccharides such as lactulose and lactitol to increase intestinal ammonia elimination is encouraged. If urinary tract infection is suspected, an antibiotic should also be started.10 In conclusion, unexplained neurological or neuropsychiatric symptoms in a patient with a urinary diversion should include hyperammonemia in the differential diagnosis. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors: diagnosis and care of patients and preparation of manuscript. Sponsor's Role: None.