Portal de Periódicos da CAPES

MULTIPLE MYELOMA PRESENTING AS HYPERAMMONEMIC ENCEPHALOPATHY

2010; Wiley; Volume: 58; Issue: 8 Linguagem: Inglês

10.1111/j.1532-5415.2010.02994.x

1532-5415

Blandine Bénet, Jean‐François Alexandra, Valérie Andrieu‐Ponel, Frédéric Sedel, Nadine Ajzenberg, T. Papo,

Multiple Myeloma Research and Treatments

To the Editor: We report on an unusual cause of confusion in an old woman. An 89-year-old woman of Italian origin presented to the emergency department with confusion, asthenia, and weight loss (−5 kg) over the previous 2 months. She had neither fever nor sweats. She had no relevant medical history. No medications and no alcohol or drug intake were reported. Neurological examination revealed confusion with marked spatial disorientation without focal abnormality or meningitis. Cardiopulmonary, rheumatological, and abdominal examinations were normal without stigmata of portal hypertension. Neurological status worsened shortly, and she fell into a coma. Laboratory findings on admission revealed an aregenerative anemia (7.8 g/dL). White blood cell and platelet counts were in the normal range, and no abnormal cells were seen on blood smear. Total serum protein was 90 g/L (normal range 65–80 g/L), serum albumin was 32 g/L (normal range 35–45 g/L), and C-reactive protein was 24 mg/L. Serum protein electrophoresis and immunofixation showed a monoclonal immunoglobulin (Ig) G lambda at 31 g/L with a low serum IgA level (0.52 g/L; normal range 0.7–4.5 g/L) and a serum IgM level of 0.64 g/L (normal range 0.6–2.5 g/L). Blood sodium, calcium, urea, creatinine, and glucose levels were normal, as were liver function tests and prothrombin time. No toxins (salicylates, paracetamol, phenobarbital, benzodiazepines) were detected in the blood. Blood ammonia level was high at 211 μmol/L (normal value <47 μmol/L). Plasma amino acid levels (high-performance liquid chromatography) and urine organic acid levels (gas chromatography) were normal. Serum lactate dehydrogenase and b2-microglobulin levels were 474 UI/L (normal value <470 UI/L) and 6.8 mg/L (normal range 1.6–2.7 mg/L), respectively. Cerebrospinal fluid was normal. Bone marrow examination showed a 79% malignant plasma cell infiltrate with myelofibrosis. No cytogenetic study could be performed. No osteolytic lesion was seen on conventional radiography. Cranial computed tomography without injection was normal. Triphasic waves on electroencephalogram revealed a diffuse metabolic encephalopathy. Abdominal echography showed no hepatic disorder. Hyperammonemic encephalopathy related to stage IIIA multiple myeloma (MM) was suspected. Chemotherapy consisted of cyclophosphamide infusion at 500 mg/m2 with methylprednisolone hemisuccinate bolus at 100 mg per day for 4 days. Further treatment included 4-days courses of melphalan (6 mg/m2) and prednisone (80 mg) every 6 weeks for 18 months, associated with thalidomide at 50 mg per day. The patient's mental status improved dramatically within a few days. Blood ammonia level decreased abruptly and normalized 6 days after treatment initiation (Figure 1). At 6 months, the patient had fully recovered. Serum ammonia level (μmol/L) in a patient with multiple myeloma treated with chemotherapy. We report on hyperammonemia revealing MM in a 89-year-old woman. Hyperammonemia in adults is usually found in the context of terminal liver failure or portosystemic shunt. Drugs such as valproate1 and asparaginase2 and high-dose chemotherapy3 can also cause hyperammonemia. Rarely, hyperammonemia can reveal an inborn error of metabolism, including urea cycle defects, organic acidurias, or fatty acid β-oxidation.4 In MM, hyperammonemia has seldom been reported, with only 27 cases found in the literature (mean age 64).5 The main manifestations were confusion, lethargy, hallucinations, seizures, coma, and death. The mechanism for hyperammonemia in MM has not been elucidated. It usually occurs in advanced forms of MM (stage III) and after several lines of chemotherapy. The rapid decrease in blood ammonia level after MM chemotherapy (Figure 1) suggests a direct link between malignant plasma cells and blood ammonia level. High amounts of ammonia have been measured in the culture supernatant of MM cell lines,6, 7 suggesting that plasma cells might synthesize high levels of ammonia or might interfere with the urea metabolism. The liver might detoxify ammonia until the tumour burden exceeds its clearance ability. A retrospective study screening 279 MM patients found only eight patients (3.8%) with encephalopathy and hyperammonemia (data on age unavailable).8 Hence, not only plasma cell proliferation might cause hyperammonemia in MM, but hepatic dysfunction (older age, prior chemotherapy) might also contribute to it, even if usual liver tests fail to detect hepatic failure. In elderly patients, confusion, drowsiness, and loss of consciousness are frequent reasons for hospitalization. Delirium without dementia has been shown to be an independent prognostic marker for mortality in such patients.9 In elderly patients with unexplained confusion, blood ammonia level should be measured. Serum protein electrophoresis is warranted to detect underlying MM because hyperammonemia is a rare complication of MM that improves dramatically with targeted chemotherapy. 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: Blandine Bénet: manuscript preparation. Jean-François Alexandra: physician in charge of the patient and helped write the manuscript. Valérie Andrieu: performed bone marrow aspiration and took part in the last reading of the manuscript. Frederic Sedel: helped in the diagnosis and manuscript preparation. Nadine Ajzenberg: manuscript preparation. Thomas Papo: took part in the last reading of the manuscript. Sponsor's Role: None.