Posterior reversible encephalopathy syndrome in malignancy: Hypercalcemic storm?

Mehndi Dandwani Danbury Hospital, Yale Affiliated Hospitals Program, Danbury, CT info_outline Mehndi Dandwani, Suma Sri Chennapragada, Shivani Sharma, Kamleshun Ramphul, Petras Lohana

Authors Mehndi Dandwani Danbury Hospital, Yale Affiliated Hospitals Program, Danbury, CT info_outline Mehndi Dandwani, Suma Sri Chennapragada, Shivani Sharma, Kamleshun Ramphul, Petras Lohana Organizations Danbury Hospital, Yale Affiliated Hospitals Program, Danbury, CT, LSU Health Shreveport, Shreveport, LA, Louisiana State University Shreveport, Shreveport, LA, Independent Researcher, Triolet, Mauritius, Jacobi Medical Centre, Bronx, NY Abstract Disclosures Research Funding No funding received None. Background: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological entity characterized by seizures, headaches, altered mental status and visual anomalies associated with vasogenic edema affecting the parietal-occipital lobes on brain magnetic resonance imaging. PRES is rarely described in hypercalcemia of malignancy although multiple mechanisms have been postulated in various case reports. Hence, we conducted this study to evaluate whether there is an increased risk of PRES with hypercalcemia of malignancy. Methods: We analyzed the 2016-2020 National Inpatient Sample (NIS) and extracted patient data with a diagnosis of ovarian cancer, lung cancer, multiple myeloma (MM), breast cancer, diffuse large B-cell lymphoma (DLBCL), and secondary bone cancer. Cases with a history of primary hyperparathyroidism, vitamin D intoxication and familial hypocalciuric hypercalcemia were excluded. The presence of hypercalcemia and PRES were estimated (per 10,000 cases), and their respective adjusted odds ratios (aOR) were calculated via multivariate regression analysis. Results: We identified 1,775 PRES cases in 3,781,899 cancer patients studied. Patients with breast cancers (26 per 10,000 hypercalcemia cases vs. 4 per 10,000 cases with no hypercalcemia, aOR 4.523, 95% CI 3.418-5.984, p < 0.01), ovarian cancers (41 per 10,000 hypercalcemia cases vs. 8 per 10,000 cases with no hypercalcemia, aOR 5.224, 95% CI 3.075-8.875, p < 0.010), and secondary bone neoplasms (14 per 10,000 hypercalcemia cases vs. 5 per 10,000 cases with no hypercalcemia, aOR 2.160, 95% CI 1.671-2.793, p < 0.01) exhibited a statistically significant increased outcome of PRES in association with hypercalcemia. The presence of hypercalcemia among lung cancer patients (aOR 0.755, 95% CI 0.451-1.263, p = 0.284), MM (aOR 1.005, 95% CI 0.751-1.346, p = 0.973), and DLBCL (aOR 1.393, 95% CI 0.806-2.408, p = 0.236) did not show a valid odds ratio for PRES. Conclusions: Our study found a higher association of PRES among hypercalcemia patients with ovarian cancer, breast cancer and secondary bone neoplasms. Prompt recognition of PRES and hypercalcemia-directed treatment can allay the morbidity related to PRES. While our study was limited in quantifying the cut-off values of hypercalcemia causing PRES, designated protocols entitled solely to determining serum calcium thresholds in these cancers warranting rigorous treatments are needed. PRES’s association with hypercalcemia in female-dominant cancers also paves way for further studies looking into the influences of sex hormones and hormonal therapies on the development of PRES with hypercalcemia.