A 57-year-old woman with history of bipolar I disorder treated with risperidone and lithium for over 10 years was sent to the ED for stroke evaluation by her primary care physician due to significant confusion and slurred speech. The patient’s family reported a 3-day history of tremulousness, a week of ataxia with a wide-based gait, and worsening bouts of confusion and slurred speech since undergoing knee arthroplasty 2 months prior. Stroke was ruled out by imaging, and labs revealed an elevated lithium level of 2.3 mmol/L. Lithium was discontinued, risperidone was continued at a higher dose to manage her bipolar disorder, and she was given IV fluids. Though her lithium levels normalized by day 3 of hospitalization, she continued to demonstrate ataxia, tremors, dysarthria, dysmetria, and delirium, leading us to a diagnosis of irreversible lithium-effectuated neurotoxicity. While her delirium improved by day 10, other neurologic symptoms persisted, and she was discharged to a subacute rehabilitation center for further therapy.
Discussion:
This case exemplifies a less common presentation of persistent lithium toxicity, the syndrome of irreversible lithium-effectuated neurotoxicity (SILENT), and illustrates the need for a broader recognition of this condition for both diagnostic and preventative purposes. Patients with chronic lithium poisoning are especially at risk for developing SILENT, where neurologic and psychiatric symptoms of toxicity persist long after removal of lithium from the patient’s system. In this case, ataxia, dysarthria, tremors, and dementia persisted despite removal of the drug, which are among the numerous manifestations of SILENT reported in the 90 published cases found in a 2005 review of the literature. The pathophysiology is not well-established, but the predominant theory is that extensive demyelination at multiple CNS sites underlies the sustained symptoms, and this may be reflected in a patient’s MRI. Clinical presentations include cerebellar dysfunction, extrapyramidal symptoms, and central pontine myelinosis among others, and diagnosis is often not made until subtle changes give way to late overt symptoms. Sequelae commonly persist for months and resolve or may persist for years and be for all practical purposes regarded as irreversible.
Conclusions:
Despite a narrow therapeutic index and significant toxicity, lithium has maintained its status as a first-line treatment for bipolar disorder for decades. In contrast to acute toxicity which may be easier to identify based on patient history and typical gastrointestinal and cardiac derangements, chronic toxicity can occur gradually even at therapeutic doses. Worsening renal impairment, medication changes, dehydration, or prolonged immobility as in our patient can lead to chronic toxicity. As SILENT can present insidiously and mimic depression or stroke especially in the elderly, there is a need for higher awareness of this condition among hospitalists.