"Locked-in syndrome" after intrathecal cytosine arabinoside therapy for malignant immunoblastic lymphoma

A 22-year-old man with malignant immunoblastic lymphoma had "locked-in" syndrome within 48 hours of receiving a single (100 mg) dose of intrathecal cytosine arabinoside (ara-C) in conjunction with intravenous ara-C, cisplatin, and doxorubicin. Eight hours after therapy, the patient had central hypoventilation and blurred vision that progressed to blindness within 3 hours. During the next 10 hours, he became completely quadriplegic but remained intermittently alert and was able to respond to commands by eye or head movements. Radiographic studies showed necrosis of the medulla and swelling of the entire spinal cord. The patient persisted in a locked-in state until his death 3 weeks later, after removal of life support systems. Autopsy confirmed extensive necrosis of the lower medulla, optic chiasm, cranial nerves I and IV, and spinal cord. This case was unusual for its severity. The temporal relationship to ara-C instillation favors a toxic idiosyncratic response to chemotherapy. The authors advocate caution when bolus intrathecal and intravenous ara-C are administered to a patient within a short time of each other.