Altered mental status in a case of multiple myeloma not related to a metabolic cause.

Sir,

Altered mental status (AMS) in a patient with multiple myeloma (MM) is generally attributed to uremia, hypercalcemia, hyperviscosity and/or increased serum ammonia. We present an unusual case of altered mental status that could not be attributed to metabolic encephalopathy.

Our patient was a 68-year-old African American male who was admitted for AMS. The patient was asymptomatic 1 week prior to admission. On examination, no focal neurologic deficit other than altered sensorium was found. The rest of his physical examination was normal. Routine laboratory analysis revealed elevated BUN of 58 mg/dl (7–25 mg/dl), creatinine of 4.9 mg/dl (0.7–1.4 mg/dl), calcium of 12.1 mg/dl (8.5–10.3 mg/dl), total protein of 9.6 g/ dl (5.5–9 g/dl) and serum ammonia of 65 mcg/dl (35–65 mcg/dl) with normal liver function tests. A toxicology screen was negative. Intravenous hydration with normal saline was initiated. Magnetic resonance imaging (MRI) of brain showed chronic microvascular ischaemic changes with no acute infarct. On cerebrospinal fluid (CSF) analysis, he was found to have elevated protein of 172 g/dl (15–45 g/dl), no pleocytosis and a negative gram stain. Polymerase chain reaction on CSF for herpes simplex was negative. Electroencephalogram (EEG) showed no seizure activity. Though all metabolic parameters normalized by the third day (creatinine of 1.3 mg/dl and calcium of 9.3 mg/dl), there was no improvement in his sensorium. To rule out paraneoplastic syndrome of unknown aetiology, a whole body CT scan was done. It showed a soft tissue mass in the pre-sacral area with multiple diffuse lytic bone lesions. The bone marrow was diagnostic for plasma cell myeloma. Serum immunofixation revealed 5050 mg/dl (700–1600 mg/dl) of monoclonal IgG. The serum viscosity was normal. A repeat lumbar puncture revealed a CSF with negative cytology, but abnormal bands of high intensity in the immunoglobulin region identical to the serum electrophoresis pattern. Four days after the normalization of all his metabolic parameters, there was still no improvement in his sensorium. The patient was started on intravenous dexamethasone for MM. After the first cycle, his sensorium returned to normal.

The most common cause of AMS in a patient with MM and acute renal failure (ARF) is metabolic encephalopathy. Though rare, direct invasion of CNS by the myeloma cells has been reported. Currently, 70 cases of leptomeningeal myelomatosis (LMM) and intraparenchymal plasmacytoma have been published [1,2]. Schluterman et.al. published a case series of 23 patients. They were diagnosed up to 29 months (median, 13 months) after the initial diagnosis of MM. The presenting symptom in 65% of the patients was AMS. The CSF analysis revealed pleocytosis and/or increased protein (generally >100 g/dl) similar to our case. CSF cytology showed myeloma cells; however, it was negative in 4 out of the 23 patients at initial presentation. Unlike our patient, cranial leptomeningeal contrast enhancement was seen on MRI in as many as 70% of the cases. Our patient did not fulfil all the diagnostic criteria of LMM but did have a dramatic recovery of his sensorium after the first cycle of dexamethasone therapy. His altered mental sensorium may represent a paraneoplastic manifestation of MM or alternatively, the patient falls into the spectrum of disease activity before fully evolved LMM. He was discharged from the hospital and was referred to an oncologist for further management of MM.

In conclusion, altered mental status in a patient with multiple myeloma may be due to a paraneoplastic manifestation of MM or due to direct invasion of the CNS by myeloma cells. Intrathecal chemotherapy should be used for patients that meet the diagnostic criteria of LMM. However, even those who do not may still show a significant improvement in their neurologic status after treatment with intravenous dexamethasone.

Conflict of interest statement. None declared.