Clinical Profile of Posterior Reversible Encephalopathy Syndrome(PRES)-Related Epilepsy in Patients Following Haploidentical Hematopoietic Stem Cell Transplantation:a 10-Year Study

Abstract

Introduction

Posterior reversible encephalopathy syndrome (PRES) is a clinical-neuroradiological entity characterized by seizures, headache, altered mental status and visual disturbances associated with typical transient lesions on magnetic resonance imaging (MRI). Haploidentical hematopoietic stem cell transplant (haplo-HSCT) is an upfront and effective therapy for hematological patients, but it has a large spectrum of neurological complications including PRES. Epilepsy is a common manifestation but there is no information on epilepsy following PRES. The aim of the present study was to describe clinical characteristics and potentially unrecognized risk factors for PRES-related epilepsy following haplo-HSCT.

Methods

A nested case-control study was conducted at the Institute of Hematology, Peking University People's Hospital between January 2007 and July 2017.Forty patients with PRES-related epilepsy were identified, and 122 controls were matched for transplantation type, and time of transplantation. The diagnosis of PRES was based on characteristic clinical findings and characteristic findings of subcortical white matter lesions on CT or MRI of the brain. PRES-related epilepsy was defined as at least two unprovoked seizures occurring >24 h apart more than one month after the inciting episode with complete or near complete resolution of imaging abnormalities (Fisher RS, et al. Epilepsia 2014; Sha Z,et al. Epilepsy Behav 2015; Hinduja,et al. Epilepsy Behav 2016).Additionally, patients with prior history of epilepsy were excluded. A provoked seizure was defined as a seizure that occurred in the context of a precipitating cause that could lower the seizure threshold.

Results

Forty patients were defined as PRES-related epilepsy. The cumulative incidences of the disease at 100 days, 1 year and 2 years post-transplantation were 0.4%, 1.7%, 2.2%, respectively.Magnetic resonance imaging (MRI) or computed tomography(CT) was collected during 4 days of the onset of epilepsy seizures. CT was performed in 3 patients. The median time of appearance for PRES-related epilepsy was 107.1 days(rang:15-839). The mean age at the time of presentation was 18 years(range:5-47). Eleven patients had acute myeloid leukemia,12 patients had acute lymphoblastic leukemia,4 patients had chronic myelogenous leukemia,6 patients had aplastic anemia,7 patients had myelodysplastic syndrome.Thirty-two patients (80%) were diagnosed with GVHD, and 8 patients (20%) had grade Ⅲ to IV GVHD before day 100.Five patients died from disease relapse,6 patients from infection.In univariate analysis, an increased risk of PRES-related epilepsy was associated with age (<10years/³10years), mean arterial pressure (MAP), hyponatremia, hypochloremia, serum lactate dehydrogenase (LDH) and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) (³1) were related to the occurrence of PRES-related epilepsy. Multivariate analysis showed that MAP (OR= 1.053,95% CI 1.031 to 1.075,P=0.000), hyponatremia (OR=1.27,95% CI 1.139 to 1.417,P=0.000), hypochloremia (OR=0.77,95% CI 0.692 to 0.856,P=0.000) and HCT-CI (³1) (OR=9.505, 95% CI 1.262 to 71.574,P=0.027) were risk factors for PRES-related epilepsy.The median follow-up for the survivors was 1423 days (rang:95-3018).The 10-year overall survival did not significantly differ between the two groups (PRES-related epilepsy 73.2% and control 82.8%,P = 0.184).

Conclusion

MAP, hyponatremia, hypochloremia and HCT-CI(³1) are related with the occurrence of PRES-related epilepsy after haplo-HSCT. PRES-related epilepsy had no influence on long-term survival.