Background: Haematopoietic stem cell transplantation (HSCT) is an invaluable and useful tool to treat many oncological and non-oncological conditions. It can be associated to different central nervous system complications, of which epileptic seizures are frequent manifestations. Rationale: This study aims at defining both the prevalence of neurological complications in patients undergoing HSCT and the prevalence of epileptic seizures in patients affected by CNS complications. It also tried to identify any possible risk factor for the development of epileptic seizures in this context and to understand if a long-term risk for epilepsy exists. Methods: In this retrospective single-centre study, we analysed medical records of 379 children and adolescents, transplanted between 2011 and 2021 in San Matteo Hospital, and we identified 52 patients who suffered from CNS complications. Then, we performed a statistical analysis comparing patients who suffered from seizures with patients who did not. Results: In our study population, 67,0% were males, the median age at transplantation was 11 years old, and 57,7% had an oncological diagnosis. Moreover, these patients received different types of HSCT: 20 (38,5%) underwent MUD transplant, 19 (36,5%) underwent haploidentical transplant, 10 (19,2%) underwent HLA-matched related donor transplant, and 3 (5,8%) underwent autologous transplant. Mortality remains high (32,7%). Risk factors associated with an increase in mortality were identified: male sex (94,1% vs 54,3% in patients who survived; p = 0,03), oncological diagnosis (83,3% vs 45,7% in patients who survived; p = 0,009) and the type of CNS complications, with cerebro-vascular complications having the greatest impact (35,3% vs 6,1% in patients who survived; p = 0,012). Risk factor for an abnormal neurological outcome were identified as well: male sex (50,0% vs 54,8% in patients with a normal neurological outcome; p = 0,041) and the type of CNS complications, with CNS infections being the most important factor (50,0% vs 3,6% in patients with a normal neurological outcome; p = 0,002). Seizures occurred in 26 patients (50,0%): 69,2% of them were males, the median age at transplantation was 9 years old, and the most frequent aetiologies were found to be posterior reversible encephalopathy syndrome (PRES, 10 patients: 38,5%), and cerebro-vascular complications (4 patients: 15,4%). Seizures were generalized in 50,0% of cases, 21 patients (80,8%) needed administration of acute anti- seizure medication, and 11 (42,3%) received chronic anti-seizure therapy. Moreover, 18 patients (69,2%) had abnormal neuroimaging findings, and 7 patients (26,9%) needed ICU admission. No risk factors for the occurrence of seizures were identified. Finally, four of our patients were diagnosed with epilepsy: in one case epilepsy was considered a post-HSCT complication, while in the other three cases epilepsy developed independently from the transplant. Conclusions: Epileptic seizures are frequent manifestations in the post-HSCT phase, and they may be associated to reversible and irreversible CNS complications; a minority of cases develop epilepsy as a consequence. Even though this study did not yield statistically significant results about the relationship between HSCT and epilepsy, it provides useful information about these patients and, for the first time, it reports cases of epilepsy after HSCT. Nevertheless, it reports significant risk factors regarding mortality and neurological outcome in patients suffering from neurological complications. For this reason, it is of invaluable importance to perform further studies in order to better clarify the possible correlation between seizures and HSCT, as well as epilepsy and HSCT, in light of the dreadful morbidity and mortality correlated with these outcomes.
Background: Il trapianto di cellule staminali ematopoietiche (TCSE) rappresenta uno strumento utile nel trattamento di malattie oncologiche e non-oncologiche; esso può essere associato a diverse complicazioni del sistema nervoso centrale, di cui le crisi epilettiche possono essere una manifestazione frequente. Razionale: Il nostro studio è nato con l’obiettivo di definire la prevalenza delle complicazioni del SNC nei pazienti sottoposti a TCSE e la prevalenza delle crisi epilettiche nei pazienti affetti da complicazioni del SNC; mira, inoltre, a identificare dei possibili fattori di rischio che predispongano alla manifestazione di crisi epilettiche in questo contesto clinico, e ha tentato di stabilire una correlazione tra il suddetto trapianto e lo sviluppo di epilessia nei pazienti pediatrici. Metodi: In questo studio mono-centrico retrospettivo, sono stati analizzati i documenti clinici di 379 bambini e adolescenti, sottoposti a TCSE tra il 2011 e il 2021 presso l’I.R.C.S.S. Policlinico San Matteo di Pavia, e sono stati identificati 52 pazienti, nel cui periodo post-trapianto sono insorte complicazioni del SNC. Inoltre, abbiamo eseguito un’analisi statistica paragonando i pazienti che hanno sofferto di crisi epilettiche e i pazienti che non ne hanno sofferto. Risultati: Nella nostra popolazione di studio, 67,0% erano maschi, l’età mediana al momento del trapianto era 11 anni, e 57,7% dei pazienti avevano una diagnosi oncologica. Inoltre, i pazienti sono stati sottoposti a diversi tipi di trapianto: MUD (38,5%), aploidentico 836,5%), HLA-MR (19,2%), e autologo (5,8%). Il tasso di mortalità rimane molto alto (32,7%). Sono stati identificati alcuni fattori di rischio che predispongono ad un aumento della mortalità nei pazienti con complicazioni del SNC: il sesso maschile (p = 0,03), la diagnosi oncologica (p = 0,09), e il tipo di complicazione neurologica (p = 0,012). Sono stati identificati dei fattori di rischio anche per un outcome neurologico alterato: il sesso maschile (p = 0,041) e il tipo di complicazione neurologica (p = 0,002). Le crisi epilettiche sono state riscontrate in 26 pazienti (50,0%): il 69,2% dei pazienti erano maschi, l’età mediana al trapianto era di 9 anni, e le cause principali delle suddette crisi sono state la Sindrome da leucoencefalopatia posteriore reversibile (PRES, 10 pazienti: 38,5%), e le complicazioni cerebro-vascolari (4 pazienti: 15,4%). Le crisi sono state generalizzate nel 50,0% dei casi. Infine, quattro dei nostri pazienti hanno ricevuto una diagnosi di epilessia: uno di questi casi è stato definito come una complicazione post-TCSE, mentre negli altri tre casi l’epilessia si è sviluppata indipendentemente dal trapianto. Conclusioni: Le crisi epilettiche sono una manifestazione frequente a seguito del TCSE, e possono essere associate sia a cause reversibili che irreversibili; una minoranza di casi, inoltre, evolve in epilessia. Sebbene questo studio non abbia evidenziato risultati statisticamente significativi riguardo la possibile correlazione tra il TCSE e l’epilessia, fornisce informazioni utili riguardo questi pazienti, e, per la prima volta, riporta dei casi di sviluppo di epilessia successivi al TCSE. Questo studio, inoltre, fornisce dei dati interessanti riguardo i fattori di rischio predisponenti alla mortalità e ad un alterato sviluppo neurologico dopo TCSE. È di fondamentale importanza, dunque, approfondire questi studi per poter delineare un’eventuale correlazione tra le crisi epilettiche e il TCSE, e tra l’epilessia e il TCSE, alla luce della morbidità e della mortalità correlate a queste manifestazioni neurologiche.
Seizures in children undergoing HSCT: clinical and radiological features, and long-term risk of epilepsy.
RISO, MARINA
2022/2023
Abstract
Background: Haematopoietic stem cell transplantation (HSCT) is an invaluable and useful tool to treat many oncological and non-oncological conditions. It can be associated to different central nervous system complications, of which epileptic seizures are frequent manifestations. Rationale: This study aims at defining both the prevalence of neurological complications in patients undergoing HSCT and the prevalence of epileptic seizures in patients affected by CNS complications. It also tried to identify any possible risk factor for the development of epileptic seizures in this context and to understand if a long-term risk for epilepsy exists. Methods: In this retrospective single-centre study, we analysed medical records of 379 children and adolescents, transplanted between 2011 and 2021 in San Matteo Hospital, and we identified 52 patients who suffered from CNS complications. Then, we performed a statistical analysis comparing patients who suffered from seizures with patients who did not. Results: In our study population, 67,0% were males, the median age at transplantation was 11 years old, and 57,7% had an oncological diagnosis. Moreover, these patients received different types of HSCT: 20 (38,5%) underwent MUD transplant, 19 (36,5%) underwent haploidentical transplant, 10 (19,2%) underwent HLA-matched related donor transplant, and 3 (5,8%) underwent autologous transplant. Mortality remains high (32,7%). Risk factors associated with an increase in mortality were identified: male sex (94,1% vs 54,3% in patients who survived; p = 0,03), oncological diagnosis (83,3% vs 45,7% in patients who survived; p = 0,009) and the type of CNS complications, with cerebro-vascular complications having the greatest impact (35,3% vs 6,1% in patients who survived; p = 0,012). Risk factor for an abnormal neurological outcome were identified as well: male sex (50,0% vs 54,8% in patients with a normal neurological outcome; p = 0,041) and the type of CNS complications, with CNS infections being the most important factor (50,0% vs 3,6% in patients with a normal neurological outcome; p = 0,002). Seizures occurred in 26 patients (50,0%): 69,2% of them were males, the median age at transplantation was 9 years old, and the most frequent aetiologies were found to be posterior reversible encephalopathy syndrome (PRES, 10 patients: 38,5%), and cerebro-vascular complications (4 patients: 15,4%). Seizures were generalized in 50,0% of cases, 21 patients (80,8%) needed administration of acute anti- seizure medication, and 11 (42,3%) received chronic anti-seizure therapy. Moreover, 18 patients (69,2%) had abnormal neuroimaging findings, and 7 patients (26,9%) needed ICU admission. No risk factors for the occurrence of seizures were identified. Finally, four of our patients were diagnosed with epilepsy: in one case epilepsy was considered a post-HSCT complication, while in the other three cases epilepsy developed independently from the transplant. Conclusions: Epileptic seizures are frequent manifestations in the post-HSCT phase, and they may be associated to reversible and irreversible CNS complications; a minority of cases develop epilepsy as a consequence. Even though this study did not yield statistically significant results about the relationship between HSCT and epilepsy, it provides useful information about these patients and, for the first time, it reports cases of epilepsy after HSCT. Nevertheless, it reports significant risk factors regarding mortality and neurological outcome in patients suffering from neurological complications. For this reason, it is of invaluable importance to perform further studies in order to better clarify the possible correlation between seizures and HSCT, as well as epilepsy and HSCT, in light of the dreadful morbidity and mortality correlated with these outcomes.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/16016