Plasma Cell Myeloma Causing Hyperammonemia Associated with High Inpatient Mortality

Hyperammonemia is commonly associated with severe liver cirrhosis. However, reports have described plasma cell myeloma (PCM)-induced hyperammonic encephalopathy. We present a retrospective case series of patients with PCM who present with altered mental status and hyperammonemia without signs of hepatic dysfunction over a twelve-year period. Additionally, we performed a systematic review of the literature looking for additional cases.

A retrospective chart review was performed of patients >18 years diagnosed with PCM between January 2000 and January 2012. A diagnosis of PCM-induced hyperammonemia was made in PCM patients with altered mental status, elevated serum ammonia levels (>50 umol/L) and no other cause of altered mental status including hepatic dysfunction, electrolyte and metabolic abnormalities or intracranial processes. The primary outcome was to examine factors predisposing these patients to hyperammonemia. Additionally, we performed a systematic MEDLINE search using multiple myeloma, ammonia and hyperammonemia looking for case reports and series on patients with PCM-induced hyperammonic encephalopathy meeting the above criteria. Available clinical characteristics were gathered from these reports. Characteristics are presented descriptively.

Our retrospective study included 27 individual patients diagnosed with PCM with elevated ammonia levels in the context of presenting with altered mental status. Six out of the 27 patients had hyperammonemic encephalopathy without other known etiology. The mean age was 76 years with a 5:1 male-to-female ratio. All had stage III based on the International Staging Scale (ISS). Bone marrow biopsies demonstrated 54–98% (mean 69%) plasma cell infiltration. IgA subtype was seen in 50% (n=3), IgG in 33% (n=2) and biclonal IgG/IgA in 17% (n=1). The mean ammonia level was 113 umol/L (range: 50–171 umol/L). Each of these patients had stable hemoglobin, normal electrolytes, liver and kidney function tests, and INR. No intracranial processes were detected on imaging. Three patients had improvement in mental status and decreased ammonia levels after chemotherapy; the other three patients declined further interventions. Inpatient mortality was over 66%. Our MEDLINE search revealed 20 articles originating from the United States and Japan detailing a total of 32 patients who were diagnosed with PCM-induced hyperammonemic encephalopathy. The mean age was 52 years (range 23–89 years) with an equal distribution between men and women. The average ammonia level amongst these patients was 121 umol/L (range: 50–299 umol/L). All of these patients had stage III disease by the ISS or the Durie-Salmon system. IgG was the most common subtype at 44% (n=12), followed by IgA with 37% (n=10), light chain multiple myeloma with 11% (n=3), and IgD with 7% (n=2). Of the 25 patients that received chemotherapy, 15 (60%) survived until discharge. The inpatient mortality was 40% (n=10). Those patients who did not receive chemotherapy had a lower rate of survival at 25%.

Multiple myeloma hyperammonemic encephalopathy is a rare disease process that typically occurs in patients with stage III disease. Hospitalization mortality is high for these patients despite chemotherapy and even higher without chemotherapy administration.

No relevant conflicts of interest to declare.