Case Presentation: A 67 year-old woman presented with six weeks of worsening disorientation. Her husband reported severe insomnia, abnormal behaviors, decreased short-term memory, and very labile mood. She had a history of well-controlled bipolar disorder on chronic lithium therapy. She had a forty pack-year smoking history. She was diagnosed with a urinary tract infection and delirium eight weeks prior, was treated with 5 days of nitrofurantoin, and her symptoms and delirium resolved. She had no fevers, headaches, abnormal urinary symptoms, alcohol use, drug use, or changes in medications. She had normal vital signs with no fevers. She was disoriented and did not follow commands. She had a normal cardiopulmonary exam, no neck stiffness, normal cranial nerve and strength exam, no suprapubic pain or costovertebral angle tenderness, no skin rashes, ataxia, or asterixis. She had speech with labile prosody, shifting between calm and yelling, with markedly labile affect. Her white blood cell count was eighteen. Platelets were normal. Lithium level was normal. Blood cultures and a urine culture had no growth. Vitamin B twelve and thyroid stimulating hormone levels were normal. HIV antibody and syphilis treponemal antibody were negative. Cerebrospinal fluid testing had no white blood cells, normal glucose and protein, negative bacterial cultures, paraneoplastic antibody, and herpes simplex virus testing. Electroencephalogram had no epileptiform activity.Her hospital course was prolonged by severe persistent delirium despite trials of quetiapine fifty milligrams nighty, high dose intravenous thiamine, and ramelteon eight milligrams nightly. She scratched and pinched nursing staff and removed several intravenous lines. A magnetic resonance imaging brain scan was negative for stroke, brain mass, or subdural hematoma. A positron-emission computed tomography scan had no hypermetabolic uptake. Repeated lithium levels were normal. Psychiatric evaluation was not consistent with mania.Lithium was empirically discontinued with psychiatry consultation. After two days, she had a rapid, marked, durable improvement in her delirium. She was continued on nightly quetiapine. Another three days later she was discharged to home. Months later her bipolar disorder remained well controlled, and delirium remained resolved.

Discussion: Delirium is common in hospitalized patients. The differential diagnosis for delirium is often broad. This patient’s differential diagnosis included recurrent urinary tract infection, mania, central nervous system bacterial or viral infections, abscess, bacteremia, paraneoplastic encephalitis, autoimmune encephalitis, hypothyroidism, vitamin B twelve deficiency, Wernicke encephalopathy, steroid responsive encephalopathy associated with autoimmune thyroiditis, hepatic encephalopathy, human immunodeficiency virus infection, neurosyphilis, seizure disorder, and medication adverse effects. She had taken lithium for many years. Consistent with prior case reports, lithium is a rare cause of a prolonged severe delirium. The pathophysiology is unknown. Serum lithium levels are often normal.

Conclusions: Lithium is a rare cause of prolonged severe delirium and should be suspected when an extensive workup of a broad differential diagnosis is unrevealing. Marked improvement of delirium following lithium discontinuation is consistent with lithium-related delirium. Close monitoring after discontinuation of lithium is required to monitor for depression or mania.