ramucirumab is a recombinant monoclonal antibody that binds to vascular endothelial growth factor receptor-2 ( vegfr-2 ) , and is approved for use in advanced gastric , lung , and colon cancer . pivotal studies in gastric cancer have shown that ramucirumab as a single agent or in combination with paclitaxel prolonged overall survival . in the rainbow trial , patients with advanced gastric cancer ( disease progression after 4 months of first - line therapy with platinum plus fluoropyrimidine ) who received ramucirumab plus paclitaxel ( n = 330 ) demonstrated significantly prolonged median survival compared to the paclitaxel plus placebo group ( n = 335 ; 9.6 vs. 7.4 months , p = 0.017 ) . in the regard trial , ramucirumab single - agent therapy ( n = 238 ) also significantly extended median survival compared to placebo ( n = 117 ) in patients with advanced gastric cancer ( 5.2 vs. 3.8 months , p = 0.047 ) . arterial thromboembolism ( te ) occurred slightly more frequently in the ramucirumab arm , but the difference was not statistically significant ( 2% any grade and 1% grade 3 or higher vs. 0% placebo , p = 0.55 ) . though reported as an adverse event in publications of the clinical trials and the product brochure , to the best of our knowledge , this is the first case report detailing the clinical manifestations and workup of a patient suspected of having a cerebral te event associated with ramucirumab . an 82-year - old male patient with a diagnosis of metastatic gastric cancer presented to the emergency department after an episode of confusion and fall . until 2 weeks prior to this event , the patient was functionally independent with a performance status of ecog 1 , but recently displayed increasing confusion , unsteady balance , numerous falls , and sometimes difficulty with speech . there was no significant tobacco , alcohol , or recreational drug use history . his past medical history was significant for peripheral neuropathy affecting his feet , hypertension , and hypothyroidism . he was diagnosed with gastric cancer 11 months prior by stomach wall biopsy demonstrating poorly differentiated adenocarcinoma with signet ring cells . staging ct scans showed metastases to the omentum , retroperitoneum , diaphragmatic lymph nodes , and malignant ascites . he initially began standard chemotherapy with carboplatin and paclitaxel , with a partial response which lasted for several months . six months later , he was switched to capecitabine due to disease progression , which was poorly tolerated and discontinued after 1 cycle . subsequently he received ramucirumab single - agent therapy at the dose of 8 mg / kg given intravenously . he received four doses , each spaced 2 weeks apart , with the last dose 2 weeks prior to presentation . his physical exam was significant for orientation to person only and ataxia on the finger - nose - finger test . initial laboratory results were within normal limits except for creatinine 1.6 mg / dl , bun 30 mg / dl , and tsh 14.24 ct of the head did not show any acute changes to explain the patient 's symptoms . transthoracic and transesophageal echocardiogram was negative for thrombus or severe atrial dilation ; it did note a patent foramen ovale with a very small amount of right - to - left shunting . mri with gadolinium of the brain revealed multifocal mildly increased diffusion signals with a corresponding increased t2 and flair signal , likely subacute , involving the bilateral cerebellar hemispheres , bilateral occipital lobes , and bilateral parietal cortex ( fig .  1 ) , confirming multifocal ischemic stroke , while in the hospital the patient underwent physical and occupational therapy and did achieve improvement in his symptoms . however , due to his poor prognosis and overall decline in functional status it was decided by the patient and his family to be discharged home with hospice . angiogenesis inhibitors are used in certain types of cancer to block neovascularization for rapid tumor growth . in a systematic review of adverse outcomes associated with vegf inhibitors , faruque et al . report an increase in thrombotic events which is not statistically significant : 227/1,897 experienced any thrombosis versus 144/1,850 controls ( rr 1.53 , 95% ci 1.072.20 , p = 0.07 ) , and 89/3,503 experienced arterial thrombosis compared to 42/2,741 controls ( rr 1.80 , 95% ci 1.242.59 , p = 0.67 ) . two studies in the review testing bevacizumab plus axitinib coadministered with gemcitabine in pancreatic cancer patients reported combined rate of fatal and nonfatal stroke of 7/582 with vegf inhibitor therapy and 6/571 with control therapy ( rr 1.12 , 95% ci 0.383.30 , p = 0.94 ) [ 4 , 5 , 6 ] . despite this lack of statistical significance , there are case reports of stroke thought to be due to bevacizumab . it is difficult to determine the attributable risk of stroke due to the use of vegf inhibitors in these cases as they are rare . in the rainbow trial , ramucirumab plus paclitaxel however , in the regard trial with ramucirumab monotherapy , 4/236 patients randomized to ramucirumab experienced an arterial te event , compared to 0/115 on placebo . this category of adverse event broadly included angina pectoris , cardiac arrest , cerebral ischemia , cerebrovascular accident , myocardial infarction , or myocardial ischemia . ischemic stroke is divided into five categories based on likely etiology : large artery atherosclerosis , cardioembolism , small vessel occlusion , stroke of other determined etiology , and stroke of undetermined etiology . although the spatial distribution and the age of these strokes are consistent with an embolic pattern , no source of embolus could be identified . it appeared likely that the strokes were most likely due to in situ thrombosis , related to the prothrombotic side effects of ramucirumab . in this case , the patient 's risk could have been further increased by his hypercoagulable state due to metastatic disease , advanced age , and history of hypertension . physicians must be appropriately educated regarding the potential morbidity and mortality associated with increased stroke risk , especially in patient groups with other risk factors for arterial te events .