Trastuzumab-Associated Posterior Reversible Encephalopathy Syndrome in a Patient With Metastatic Gastric Cancer

Abstract

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome of seizures, headache, altered mental status and posterior cerebral white matter edema on neuroimaging. The exact pathophysiology of PRES is unclear. However, blood brain barrier vascular endothelial dysfunction has been proposed. Trastuzumab is rarely reported as a cause of PRES. To our knowledge, this is second reported case of trastuzumab-associated PRES, and the first case in a gastric cancer patient. Case summary: A 51-year-old female with a history of hypertension and stage 4, HER-2 positive, gastric adenocarcinoma with peritoneal, bone and lymph nodes metastasis. She presented with an episode of tonic clonic seizure. She did not have any previous history of seizures. The patient was diagnosed with stage 4 cancer two years ago. She was started on trastuzumab, cisplatin and capecitabine for 3 cycles and continued trastuzumab till her presentation (last cycle was 4 weeks prior to presentation). Her vital signs and labs are shown in table 1. A Brain MRI w/wo contrast (figure 1) showed bilateral, symmetric areas of T2 FLAIR hyperintensity involving the occipital and posterior parietal lobes. There was no evidence of acute stroke, intracranial hemorrhage or intracranial metastasis. This was suggestive of PRES. A multi-disciplinary discussion involved medicine, neurology and oncology teams decided that PRES could be due to the toxic effect of trastuzumab or hypertension. They decided to discharge patient on levetiracetam, continue trastuzumab, strictly control the BP and repeat the MRI in 3 months. During that period, the patient's BP was controlled on multiple encounters with all readings < 140/90. A repeated brain MRI w/wo contrast showed persistent T2 FLAIR hyperintensity in the occipital and posterior parietal lobes suggestive of PRES. Trastuzumab was held for 1 month. The patient was admitted shortly with worsening epigastric pain and concern of disease progression. An EGD (figure 2) showed a large, malignant looking, partially obstructing mass in the gastric body with no active bleeding. She died after 2 days of cardiac arrest. Conclusion: PRES has been reported with some chemotherapeutic protocols. Whether the toxic effect of the chemotherapy alone or history of metastatic cancer is responsible is not fully understood. It is extremely important to rule out other common causes of PRES, especially poorly controlled hypertension.Figure: Brain MRI w/wo contrast. A) T2-TSE, B) T2- FLAIR sequence. Showing a bilateral, symmetric areas of T2 FLAIR hyperintensity involving the posterior parietal and occipital lobes. There was no evidence of acute stroke, intracranial hemorrhage, hydrocephalus, dural venous sinuses thrombosis or intracranial metastatic disease.Figure: EGD showing a large malignant looking, friable, fungating, ulcerated mass in the gastric body.Table: Table. Patient's vital signs and laboratory workup