The Challenge of Determining the Etiology of Encephalopathy in an Elderly Patient

ABSTRACT Encephalopathy is a heterogeneous clinical syndrome with numerous neurological and systemic etiologies. We report the case of a 67‐year‐old man, a chronic ethanol consumer, admitted with a one‐week history of confusional syndrome. Initial laboratory tests revealed severe hypercalcemia, acute kidney injury, mild anemia, and hyperproteinemia. Serum ammonia levels were within normal limits, reducing the likelihood of hepatic encephalopathy despite the patient's chronic ethanol use. Cerebral imaging excluded acute cerebrovascular events, while abdominal ultrasound demonstrated splenomegaly and normal‐sized kidneys. Serum protein electrophoresis and immunofixation identified a monoclonal IgG‐kappa component, strongly suggestive of multiple myeloma. The patient's neurocognitive symptoms improved rapidly following systemic corticosteroid therapy and fluid–electrolyte rebalancing, confirming hypercalcemia as the primary mechanism of encephalopathy. Hypercalcemic encephalopathy as an initial manifestation of multiple myeloma is exceedingly rare. This case highlights the diagnostic complexity in elderly patients with multiple potential contributors to altered mental status, including chronic ethanol exposure and renal dysfunction. The presence of normal renal dimensions, unexplained hypercalcemia, and a monoclonal component should prompt evaluation for plasma cell malignancy. Early recognition of hypercalcemia‐induced encephalopathy and prompt investigation for underlying hematologic malignancy are essential to prevent irreversible organ damage and to ensure timely initiation of specific therapy.