Benign reversible encephalopathy syndrome after bevacizumab therapy for metastatic ovarian cancer

Abstract

Posterior reversible encephalopathy syndrome (PRES) is now a well-described entity in neurology, diagnosed by the clinical picture of altered mental status, headache, visual disturbances, hypertension and seizures, associated with the classical MRI findings of cortical and subcortical abnormalities in multiple brain areas, predominantly in the posterior lobes. This entity has been associated with eclampsia, hypertensive encephalopathy, neurotoxic drugs, immunosuppressants and electrolyte disturbances [1]. We describe a case of PRES, following bevacizumab therapy in a patient with metastatic ovarian carcinoma. We are presenting this case to highlight the benign nature of the seizure component of this syndrome and to suggest modifying its nomenclature to benign reversible encephalopathy syndrome (BRES) because most of the reported cases in the literature describe lesion in the frontal and temporal lobes and not only the posterior lobes and the prognosis for recovery from this condition is very good. A 31-year-old female with metastatic high-grade endometrioid ovarian squamous cell carcinoma on multiple chemotherapy regimens presented with a focal tonic–clonic seizure activity with secondary generalization 16 h after receiving intravenous bevacizumab for the first time. The seizures were controlled by intravenous benzodiazepines, phenytoin and valproic acid. The patient was not known to have any previous neurological disorder or metastatic cerebral disease. Neurological examination was consistent with a postictal state, following benzodiazepine treatment. Cerebrospinal fluid analysis was normal with no malignant cells. MRI of the brain showed abnormal high signal intensity on T2 and FLAIR sequences in the cortical and subcortical matter of the parietal and occipital lobes, posterior fossa, as well as the left pons, left cerebral peduncle and both frontal lobes (Fig. 1). EEG revealed severe generalized cortical slowing with no ongoing epileptiform activity. The patient recovered slowly over a fortnight and was discharged home seizure free to continue treatment for her ovarian cancer. PRES is an acute encephalopathy with diverse neurologic symptoms including headache, visual disturbance, altered mental status, hypertension and seizures [1]. It is diagnosed by the clinical setting associated with typical MRI changes in hyperintense lesion on T2 and FLAIR sequences in multiple regions of the brain, predominantly in the posterior lobes and posterior fossa [1, 2]. It has been associated with eclampsia, hypertensive crisis, chemotherapeutic agents, and immunosuppressant therapy and electrolyte disturbances [1, 2]. The pathophysiology of this syndrome is not clearly defined. One theory attributes hypertension and hyperperfusion to endothelial damage, while a second theory suggests vasoconstriction and hypoperfusion as the trigger to generalized vasogenic edema of the cortex and subcortical white matter, leading to the described MR image [2–4]. Bevacizumab is a recombinant humanized monoclonal IgG antibody, which binds and inhibits vascular endothelial growth factors (VEGF) reducing angiogenesis and regressing tumor growth [3–5]. PRES has been associated with bevacizumab in multiple reported cases since 2006 [2–6]. The common features in these reports and other papers describing this syndrome are R. Sawaya (&) W. Radwan S. Hammoud American University Medical Center, POB 113-6044/C-27, Beirut, Lebanon e-mail: rs01@aub.edu.lb