Status Epilepticus and Blindness in a Patient with Carfilzomib-Associated Posterior Reversible Encephalopathy Syndrome

Abstract

Posterior reversible encephalopathy syndrome (PRES) is a neurological condition characterized by headaches, visual disturbances, and seizures. A magnetic resonance imaging (MRI) scan of an affected brain typically shows symmetrical white matter edema in the posterior cerebral hemispheres. The onset of PRES can constitute a medical emergency, especially when accompanied by status epilepticus. If promptly recognized and treated, the clinical syndrome and associated radiological findings are usually resolved in a matter of weeks or months. Carfilzomib is a proteasome inhibitor that is newly approved for relapsing myeloma in a patient who has received one or more lines of therapy. In this paper, we report on a 52-year-old female on carfilzomib for multiple myeloma who developed PRES following her second dose of treatment. She was admitted for chronic obstructive pulmonary disease (COPD) exacerbation, and while she was in the hospital, she developed a severe headache, blindness, and status epilepticus. A brain MRI showed signs consistent with PRES. After carfilzomib was discontinued, her symptoms resolved within three days. Unfortunately, the patient passed away shortly after being discharged, so there was no opportunity to perform a repeat MRI.

Carfilzomib Induced Tumor Lysis Syndrome and Other Adverse Events

“…11 However, there have been a small number of cases of CFZ-induced posterior reversible encephalopathy syndrome (PRES) in postmarket reporting. [25][26][27] Posterior reversible encephalopathy syndrome, evidenced by white matter edema on magnetic resonance imaging has been linked to multiple diseases and drug exposure. Pathogenesis of CFZ-induced PRES remains unknown.…”

Posterior reversible encephalopathy syndrome (PRES) and myeloma

“…In multiple myeloma, PRES has only been described in a few cases. It has been reported with Thalidomide [ 2 , 3 ] but mainly with proteasome inhibitors such as Bortezomib [4] , [5] , [6] , [7] , [8] , [9] or Carfilzomib [10] , [11] , [12] , and with autologous stem cell transplantation [13] .…”

“…Regarding chemotherapy, the reported cases of PRES seem to be mainly associated with proteasome inhibitors, bortezomib [4] , [5] , [6] , [7] , [8] , [9] or carfilzomib [10] , [11] , [12] . The mechanism is not yet fully understood, but it has been hypothesized that proteasome inhibitors may be responsible for a decreased transcription of certain growth factors including vascular endothelial growth factor (VEGF), which may lead to endothelial dysfunction, vasospasm, and blood-brain barrier disruption, promoting the development of PRES [ 10 , 11 ].…”