Digestive Diseases and Sciences, Vol. 38, No. 9 (September 1993), pp. 1746-1750 CASE REPORT Intractable Neurological Wilson's Disease Treated with Orthotopic Liver Transplantation A. L. MASON, MMBS, W. MARSH, MD, and D. H. ALPERS, MD KEY WORDS: orthotopic liver transplantation; Wilson's disease; neurologic dysfunction; splenic artery aneurysm. Orthotopic liver transplantation has been success- fully employed to correct isolated metabolic lesions for patients with normal liver function (1) but severe neurological Wilson's disease has not been consid- ered an indication for transplantation when liver function is stable (2-4), despite several encouraging case reports highlighting marked neurologic im- provement following liver transplantation for liver failure (5-9). We report our experience with our patient who underwent orthotopic liver transplan- tation, despite stable liver function, to reverse his severe neurologic deficit, which was unresponsive to medical therapy. CASE REPORT The patient was born in 1964 with spina bifida and developed recurrent urinary tract infections in childhood due to his neurogenic bladder, requiring self-catheteriza- tion. He was an extremely promising 20-year-old college student when he presented to an outside hospital com- plaining of tiredness, weight loss, and hypersplenism. There were no other signs of chronic liver or neurological disease and his liver function tests were normal. He was neutropenic and thrombocytopenic and had a normal bone marrow biopsy. During splenectomy, the liver ap- peared nodular, and a liver biopsy revealed cirrhosis. The patient was then transferred to Barnes Hospital, St. Louis, for further management. The diagnosis of Wilson's disease was made following the exclusion of other chronic liver diseases and the discovery of Kayser- Fleisher rings by slit lamp examination, low serum ceru- Manuscript received December 17, 1992; revised manuscript received March 22, 1993; accepted April 5, 1993. From the Gastroenterology Division, and Department of Sur- gery, Washington University School of Medicine, St. Louis, Missouri. Address for reprint requests: Dr. D.H. Alpers, Gastroenterol- ogy Division, Washington University School of Medicine, 660 South Euclid, Box 8124, St. Louis, Missouri 63110. loplasmin (3 mg/dl, normal range 23-58 mg/dl), low plasma copper (2 mg/dl, normal range 70-140 mg/dl), and a high urinary copper (459 mg/dl, normal range 15-50 mg/dl). There was no family history of hepatic or neuro- logical disorders and the rest of the family had normal copper studies. In June 1984 the patient was started on a low copper diet (10) and D-penicillamine, 250 mg four times a day, resulting in a rapid deterioration in his psychological and neurolog- ical condition. Within a month, he became depressed, he developed a masklike face with slow and awkward move- ments. He then started to slur his speech and had difficulty swallowing. His disabilities became so distressing that penicillamine was discontinued and zinc therapy, 200 mg/ day, was instituted within two months of starting his che- lation therapy. However, his ataxia and dystonia wors- ened, he started to drool, and became severely dysarthric. After four months of therapy, he required Elavil therapy and hospitalization for extreme depression, violent mode swings, and auditory hallucinations telling him to kill him- self. He was now unable to talk and communicated only by writing. He had difficulty swallowing, a recurrent cough, and later developed aspiration pneumonia. He could not move his bowels and required manual disimpaction. His ataxia had resulted in repeated falls, which precipitated injury to his back and a decubitus ulcer. During this inpa- tient stay in October 1984, he was treated with BAL, 30 ml intramuscularly, with pyridoxine, 50 mg daily, in an at- tempt to curb the severity of his symptoms. This therapy reduced his urinary coppers from 1050 rag/24 hr to 262 rag/24 hr over the month he was in hospital and, although his behavior improved, there was little improvement in his physical state. Over the next five years there was little neurological improvement. Following release from hospital, D-penicil- lamine was reinstituted and increased to 1500 mg/day in May 1985. At that point his family reported that he was compliant with his medication, could now say "Hi" and could eat some nonliquidized food. In January 1987 he had another course of intramuscular BAL. Because of decreased appetite, his D-penicillamine was changed to Trientene, 250 mg four times a day, in January 1989, which was then increased to 1500 mg/day in August 1989. 1746 Digestive Diseases and Sciences, VoL 38, No. 9 (September 1993) 0163-2116/93/0900-1746507.00/0 9 1993 Plenum Publishing Corporation