An 84 year-old man with a history of diet-controlled diabetes, atrial fibrillation, and MGUS was admitted for back pain and 30 pounds of unintentional weightloss over 3 months. His wife also reported that he had had a mild cognitive decline over this period. On admission, he was noted to have new thrombocytopenia and anemia. He was initially fully alert and oriented, but noted to be tangential. However, over the next few days, his mental status declined such that he was only oriented to self and year and was occasional agitated and requiring soft restraints. During this time, a new diagnosis of multiple myeloma was made and confirmed with bone marrow biopsy. His mental status did not improve and his encephalopathy did not resolve over the next 10 days.
He had an extensive workup for encephalopathy including vitamin B12 and folate levels, thyroid function tests, liver function tests, CT Brain, and MR brain. He had an infectious workup including urinalysis and chest x-ray. None of these tests or studies pointed to a potential cause. He was not on any medications known to cause encephalopathy.
An ammonia level was checked and was found to be 90 (normal 0-53), and on recheck was 125. Liver function tests were normal, except for low albumin and total protein, and a liver ultrasound was normal. He had no history of heavy alcohol use. He was started on oral lactulose and rifaximin and also given 1 gram of methylprednisolone, and his mental status improved, though not back to his former baseline. He was initiated on weekly methylprednisolone and velcade as an outpatient and his ammonia levels did normalize as did his mental status. However, he was readmitted several weeks later with encephalopathy and elevated ammonia levels again.
Discussion:
Encephalopathy is a common problem that hospitalists treat. Hyperammonemia is a rare cause of encephalopathy or cognitive decline in multiple myeloma. At the time of a case series published in 2008, there were twenty-seven reported cases. This complication is most common with IgA myeloma, and all patients in the case series presented with severe or resistant forms of multiple myeloma.1 The mechanism is not well-understood but hypotheses include that plasma cells may secrete large amounts of ammonia or that plasma cells may interfere with urea metabolism.2 The most effective treatment seems to be chemotherapy.1 While cirrhosis is the most common cause of hyperammonemia, it is important to note that there are other rare causes of ammonia-induced encephalopathy including multiple myeloma, stem cell transplant, valproic acid toxicity, chemotherapy, urea cycle inborn error of metabolism, GI bleed with a portosystemic shunt, severe constipation with a ureterosigmoidostomy, and even UTI (by ammonia producing bacteria).3,4 It is important that hospitalists be aware that there are number of potential causes of hyperammonemia besides cirrhosis which can cause encephalopathy.
Conclusions:
Hyperammonemia is a rare, but possibly underreported cause of altered mental status in patients with multiple myeloma. This heralds an especially poor prognosis among patients with multiple myeloma and expedited treatment with chemotherapy should be considered. Clinicians should consider hyperammonemia as a potential cause of unexplained altered mental status even in patients who do not have cirrhosis.