LAUSR

Posterior reversible encephalopathy syndrome (PRES) is an acute neurological disorder characterized by headache, visual disturbances, seizures and vigilance status alteration. Brain magnetic resonance imaging (MRI) reveals subcortical vasogenic edema usually affecting the posterior circulation territories (e.g., occipito-parietal cortical and subcortical areas or, very rarely, cerebellum or brainstem [1]). PRES is described in patients with acute fluctuating hypertension (HTN), renal failure, eclampsia, sepsis, autoimmune diseases, or undergoing cancer chemotherapy (CT) and immunomodulatory agents [2]. In the last decade, PRES has been reported as a rare and early side effect of anti-vascular endothelial grow factor (VEGF) drugs, both monoclonal antibodies (bevacizumab) and tyrosine kinase inhibitors (sunitinib, sorafenib, regorafenib and pazopanib) [3, 4]. As recently suggested [4], BBB dysfunction and subsequent vasogenic edema could be triggered by anti-VEGF drugs with two different mechanisms. The first one is HTN, which is a common side effect of these drugs and the main supposed etiologic factor of idiopathic PRES. In patients exposed to anti-VEGF drugs, HTN is probably caused by the reduced production of nitric oxide (NO) secondary to VEGF pathway inhibition [5]. The second but not mutually exclusive mechanism is that NO decreased production could directly lead to endothelial dysfunction, perhaps even independently of HTN [4]. So far, eleven cases of PRES secondary to sunitinib, approved for metastatic clear cell type renal carcinoma and gastrointestinal stromal tumor, have been described in the literature. The mean age of onset was 59.4 years and female:male ratio was 6:5. Previous HTN history and evidence of acute HTN at PRES onset were reported in 40 and 91% of the cases, respectively [3, 4]. In all reports, PRES occurrence was usually limited to the first months of drug administration and with the usual dosage regimen. Only in one case, as recently reported by Fukui et al. [3], disease developed more than 2 years after first administration of drug, but it has to be precised that in this patient sunitinib had been interrupted for one year and then restarted just 5 months before PRES onset. In contrast, we describe the unusual case of a patient who developed this clinical condition about 4 years after sunitinib introduction (without any interruption), despite a low-dose drug regimen. A 70-year-old female complained of fluctuating hypertension (blood pressure, BP 180/80 mmHg) associated with nausea and emesis. The following day she was admitted to the Emergency Department (ED) for the acute onset of bilateral painless vision loss and mental confusion, followed by soporous status and then rapidly progressive coma. Vital signs measurement showed severe HTN (BP 220/100 mmHg). Eight years before, in 2008, she underwent left nephrectomy with distal splenopancreatectomy due to a grade III Fuhrman clear renal cell carcinoma (pT1pN0). About 2 years later, in the evidence of oncological disease progression, multiple pulmonary nodule resections and thyroidectomy were performed, in February & Giovanni Meola [email protected]