Epileptic seizures in patients following allogeneic hematopoietic stem cell transplantation: a retrospective analysis of incidence, risk factors, and survival rates

Abstract

The incidence of epileptic seizures among allogeneic hematopoietic stem cell transplant (allo-HSCT) patients has been poorly described. No report has systematically studied epilepsy's possible causes, risk factors, and effect on prognosis among allo-HSCT patients. We retrospectively examined data from 1461 patients who underwent allo-HSCT within the past 6.5 yr at the Institute of Hematology and People's Hospital, Peking University. The cumulative incidence of all epileptic seizure complications was 7.1%. Of the 79 transplant patients who had epileptic seizures, 3 (3.8%) experienced a seizure during the conditioning stage, 52 (65.8%) between day 0 and day 100, 20 (25.3%) from day 100 to the first year, and 4 (5.1%) after the first year. Multivariate regression analysis identified the age of the recipient as (≤ 18 yr) (p < 0.001), donor type (p = 0.004), graft versus host disease (aGVHD) (p = 0.018), and hyponatremia (p = 0.003) as independent risk factors for epileptic seizures among allo-HSCT patients. The median survival time of patients with epileptic seizures was 246 d after transplantation (ranging between 18 and 2170 d). Survival after one yr and 6.5 yr was significantly reduced in patients who developed epileptic seizure complications compared with those who did not (57.2% vs. 75.7% at one yr, p = 0.015, and 31.1% vs. 71.4% at five yr, p < 0.001). Of the 79 patients who experienced epileptic seizure complications, 53.2% died (n = 42). The survival rate of these patients was relatively low, and cerebrovascular disorders or central nervous system infection-related epileptic seizures usually resulted in a high mortality and poor prognosis. A patient transplantation age which is younger than 18 yr, related mismatched transplants, aGVHD, and hyponatremia are risk factors for epileptic seizures in allo-HSCT recipients. Epileptic seizures among allo-HSCT patients are associated with a poor prognosis.

Acute central nervous system complications in pediatric hematopoietic stem cell patients

“…There appears to be no close correlation between pre-transplant disease or symptoms and etiology of CNS complications. One-year survival declined significantly in patients who experienced seizures (57% versus 75%) [69]. Risk factors for seizures included young age, allogeneic transplant, acute GVHD and hyponatremia.…”

Immune-Mediated Complications after Hematopoietic Stem Cell Transplantation

“…All patients who developed IMNs had underlying hematologic malignancies. Other risk factors associated with IMNs include unrelated donor, infection, and GVHD [83,84]. Although dysregulated immune reconstitution has been implicated, early relapse of primary hematologic malignancy was associated with IMN in 1 retrospective analysis, suggesting that paraneoplastic antibody production is implicated [80].…”

“…Peripheral nervous system IMNs include acute and chronic inflammatory demyelinating polyneuropathy, autonomic neuropathies, plexopathies, mononeuropathies, and polyradiculopathies, such as Guillain-Barré syndrome [80][81][82]. IMN after HSCT is uncommon, with incidence ranging from .36% to 3.6% [75,80,83].…”

Seizures after transplantation

“…Drake et al [37] and Wells et al [38] found that seizures may be related to low blood glucose or to a drop in blood osmotic pressure and serum sodium but that hypomagnesemia or hypocalcemia may not increase the risk of developing seizures in renal transplant recipients. In addition, the literature reported that the etiology for most seizures involves hyponatremia combined with hypokalemia in recipients of hematopoietic stem cell transplantation [39].…”

“…Listeria aspergillus, Cryptococcus neoformans and aspergillus fumigatus are the main pathogens causing central nervous system infections [40]. Central nervous system infections, particularly viral or fungal infections, can cause brain damage and induce seizures [39,[41][42][43]. In addition, seizures may also be related to the inflammatory response, and there is literature reported that IL-1beta can break the balance between glutamate and GABA [44].…”