A 24-year-old woman with newly diagnosed APL received ATRA/ATO induction therapy. This was complicated by acute kidney injury, pneumonia, diffuse alveolar hemorrhage, and a pericardial effusion. She additionally developed a progressive encephalopathy, seizures, and subsequently ophthalmoplegia and quadriparesis. Electrodiagnostics demonstrated a severe axonal sensorimotor polyneuropathy. Serial MR brain imaging studies demonstrated stigmata of intracranial hypertension and leukoencephalopathy, bilateral medial thalamic injury, and a transient cytotoxic lesion of the corpus callosum. The intrathecal opening pressure measured 50 cm H2O; cerebrospinal fluid studies revealed 7 WBC/mm³, protein 152 mg/dL, 2000 RBC/mm³, and glucose 152 mg/dL. A comprehensive infectious and inflammatory evaluation was unrevealing.

Therapeutic lumbar punctures and acetazolamide decreased intracranial pressure. In the setting of ATO, which carries a warning for functional thiamine deficiency, Wernicke encephalopathy was suspected. High-dose intravenous thiamine was initiated, resulting in gradual improvement in mental status and ocular motility. Arsenic chelation was not administered based on decreasing urine arsenic levels. After stabilization, ATRA was cautiously reintroduced with close neurologic and ophthalmologic monitoring.

This case highlights several neurotoxic complications during APL therapy with ATRA and ATO: (1) intracranial hypertension; (2) multiple cranial neuropathies; (3) functional thiamine deficiency resulting in Wernicke encephalopathy; (4) severe axonal polyneuropathy; (5) seizures; and (6) a transient cytotoxic splenial lesion. Practical implications include early neuro-ophthalmic surveillance and intrathecal pressure monitoring, and the recognition of Wernicke encephalopathy associated with ATO exposure.