Introduction: Posterior Reversible Encephalopathy syndrome (PRES) is a rare and recently described clinical and neuroradiological condition. In children, it is frequently associated with hypertension and/or calcineurin inhibitors toxicity in the context of hematopoietic stem-cells transplantation, and is clinically characterized by headache, convulsions, vomiting, nausea, visual abnormalities and impaired mental function. Materials and methods: we retrospectively analyzed the clinical records of all the children (<18 years) evaluated in the Pediatric Clinic and Oncohematological Department of the IRCCS Policlinico San Matteo (Pavia – Italy) from January 2010 to December 2019, with a definite diagnosis of PRES. Clinical and radiological characteristics were reviewed by an independent pediatric neurologist to confirm the diagnosis. Demographic data and information on triggers, clinical evolution, neuro-imaging exams, EEG, life-threating complications, therapy and outcome were recorded. Results: 18 patients were included in the study (9 females and 9 males). Average age was 8.8 years. 6/12 (33,3%) patients had oncological diseases (4 with Acute Lymphoblastic Leukamia and 2 with myelodysplastic syndrome) and 12/18 (66,7%) had non-oncological diseases (5 with Thalassemia major, 4 with Sickle Cell Disease, 1 with Congenital Dyserythropoietic Anemia type II, 1 with Blackfan-Diamond anemia and 1 with Hemophagocytic Lymphohistiocytosis). Risk factors for PRES included hypertension 13/18 (72,2%) and / or drug toxicity 14/18 (77,8%), including the use of calcineurin inhibitors. Short-term complications (coma, status epilepticus, hemorrhagic complications and life-threating complications) and long-term complications (epilepsy and recurrent PRES) were found in 7/18 (38,9%) and 3/18(16,7%) subjects, respectively. Seizures were the onset symptom in 16/18 (88,9%) patients, of which 6/16 (37,5%) evolved in status epilepticus (5 Convulsive Status Epilepticus CSE and 1 Non Convulsive Status Epilepticus NCSE) . EEG was performed in 17 (94%) patients, showing alterations in all cases: ictal anomalies 5/17 (41,2%), posterior or generalized slowing 7/17 (41,2%) and periodic lateralized epileptic discharges (PLEDs) 5/17 (41,2%). Brain MRI was performed in 16/18 (88,9%) subjects and alterations were found in all cases, mostly in the parieto-occipital regions (12/16; 75%), while CT showed negative results in 10/18 (55,6%). 1/18 (5,5%) patient had recurrence PRES after 7 months. All patients required antiepileptic therapy and - in the 13/18 (72,2%) cases taking cyclosporine - a therapeutic switch was made in 8/13 (61,5%) patients with tacrolimus and none patient have had relapse after this change. 7/18 (38,9%) patients were transferred to Intensive Care Unit due to the onset of complications (Life threating complications, coma, epilepticus status). Sub-analysis was conducted taking into account two age groups: patients younger than 6 years and ≥6 years. Pre-school children were found to be at higher risk for status epilepticus 2/3 (66,7%) and admission to intensive care unit 3/3 (100%). Prophylactic antiepileptic therapy was prolonged on average for 512 days. Two patients (11,1%) developed epilepsy as a long-term complication. 2/18 (11,1%) patients died from causes not directly correlated to PRES, due to the underlying diseases. Conclusions: Hypertension and neurotoxic drugs such as calcineurin inhibitors are significant risk factors for PRES. Although the diagnosis of PRES still lacks precise criteria and specific biomarkers, seizures (and even status epilepticus) are frequently reported at onset, and the diagnosis relies on the timely performance of brain MRI and EEG. Furthermore, PRES is not always posterior (as it may involve the fronto-temporal areas in more than one third of the cases) and not always reversible (as it may lead to long-term brain damage and epilepsy). Bigger multicenter studies are needed to confirm our results.
Introduzione: la Posterior Reversible Encephalopathy syndrome (PRES) è una condizione clinica e neuroradiologica rara e recentemente descritta. Nei bambini è spesso associata ad ipertensione e/o tossicità dovuta agli inibitori della calcineurina nel contesto del trapianto di cellule staminali ematopoietiche ed è clinicamente caratterizzato da cefalea, convulsioni, vomito, nausea, anomalie visive e compromissione della funzione mentale. Materiali e metodi: abbiamo analizzato retrospettivamente le cartelle cliniche di tutti i bambini (<18 anni) presi in carico nella Clinica Pediatrica e nel Dipartimento di Oncoematologia dell'IRCCS Policlinico San Matteo (Pavia - Italia) da gennaio 2010 a dicembre 2019, con una diagnosi definita di PRES. Le caratteristiche cliniche e radiologiche sono state riviste da un neurologo pediatrico indipendente per confermare la diagnosi. Sono stati registrati dati demografici e informazioni su trigger, evoluzione clinica, esami neuroradiologici, EEG, complicanze life- threating, terapia ed esito. Risultati: 18 pazienti sono stati inclusi nello studio (9 femmine e 9 maschi). L'età media era di 8,8 anni. 6/12 (33,3%) pazienti avevano malattie oncologiche (4 con leucemia linfoblastica acuta e 2 con sindrome mielodisplastica) e 12/18 (66,7%) avevano malattie non oncologiche (5 con Thalassemia major, 4 con drepanocitosi, 1 con anemia congenita diseritropoietica di tipo II, 1 con anemia di Blackfan-Diamond e 1 con linfocitosi emofagocitica). I fattori di rischio per la PRES includevano l'ipertensione 13/18 (72,2%) e / o la tossicità da farmaci 14/18 (77,8%), compreso l'uso di inibitori della calcineurina. Complicanze a breve termine (coma, stato di male epilettico, complicanze emorragiche e complicanze life-threating) e complicanze a lungo termine (epilessia e recidiva PRES) sono stati trovati rispettivamente in 7/18 (38,9%) e 3/18 (16,7%) soggetti. Le crisi epilettiche sono state il sintomo di esordio in 16/18 (88,9%) pazienti, di cui 6/16 (37,5%) evoluti in stato di male epilettico (5 Convulsive Status Epilepticus CSE e 1 Non Convulsive Status Epilepticus NCSE). L'EEG è stato eseguito in 17/18 (94,4%) pazienti, mostrando alterazioni in tutti i casi: rallentamento posteriore o generalizzato 7/17 (41,2%), anomalie Ictal 5/17 (41,2%) e periodic lateralized epileptic discharges (PLEDs) 5/17 (41,2%). La RM cerebrale è stata eseguita in 16/18 (88,9%) soggetti e le alterazioni sono state riscontrate in tutti i casi, principalmente nelle regioni parieto-occipitali (12/16; 75%), mentre la TC ha mostrato risultati negativi in 10/18 (55,6%) pazienti. 1/18 (5,5%) pazienti ha manifestato una recidiva PRES. Tutti i pazienti hanno richiesto una terapia antiepilettica e - in 13/18 (72,2%) casi di assunzione di ciclosporina – è stato effettuato uno switch terapeutico in 8/13 (61,5%) pazienti con il tacrolimus e nessun paziente ha mostrato recidiva dopo tale cambiamento. 7/18 (38,9%) pazienti sono stati trasferiti al reparto di Terapia Intensiva a causa dell'insorgenza di complicanze (life-threating complications, coma, stato di male epilettico). I bambini in età prescolare hanno manifestato un più alto rischio di stato di male epilettico 2/3 (66,7%) e di trasferiemnto all'unità di terapia intensiva 3/3 (100%). La terapia profilattica antiepilettica è stata prolungata in media per 512 giorni. Due pazienti (11,1%) hanno sviluppato l'epilessia come complicanza a lungo termine. 2/18 (11,1%) pazienti sono morti per cause non direttamente correlate a PRES. Conclusioni: l'ipertensione e i farmaci neurotossici come gli inibitori della calcineurina sono fattori di rischio significativi per la PRES. Le crisi epilettiche (e persino lo stato di male epilettico) sono frequentemente segnalate all'esordio e la diagnosi si basa sulle tempestiche di RM e EEG. La PRES non è sempre posteriore e non sempre reversibile. Sono necessari ulteriori studi multicentrici.
Analisi retrospettiva dei pazienti pediatrici affetti da Posterior Reversible Encephalopathy Syndrome (PRES): aspetti clinici e prognostici
PARATI, NICOLE
2019/2020
Abstract
Introduction: Posterior Reversible Encephalopathy syndrome (PRES) is a rare and recently described clinical and neuroradiological condition. In children, it is frequently associated with hypertension and/or calcineurin inhibitors toxicity in the context of hematopoietic stem-cells transplantation, and is clinically characterized by headache, convulsions, vomiting, nausea, visual abnormalities and impaired mental function. Materials and methods: we retrospectively analyzed the clinical records of all the children (<18 years) evaluated in the Pediatric Clinic and Oncohematological Department of the IRCCS Policlinico San Matteo (Pavia – Italy) from January 2010 to December 2019, with a definite diagnosis of PRES. Clinical and radiological characteristics were reviewed by an independent pediatric neurologist to confirm the diagnosis. Demographic data and information on triggers, clinical evolution, neuro-imaging exams, EEG, life-threating complications, therapy and outcome were recorded. Results: 18 patients were included in the study (9 females and 9 males). Average age was 8.8 years. 6/12 (33,3%) patients had oncological diseases (4 with Acute Lymphoblastic Leukamia and 2 with myelodysplastic syndrome) and 12/18 (66,7%) had non-oncological diseases (5 with Thalassemia major, 4 with Sickle Cell Disease, 1 with Congenital Dyserythropoietic Anemia type II, 1 with Blackfan-Diamond anemia and 1 with Hemophagocytic Lymphohistiocytosis). Risk factors for PRES included hypertension 13/18 (72,2%) and / or drug toxicity 14/18 (77,8%), including the use of calcineurin inhibitors. Short-term complications (coma, status epilepticus, hemorrhagic complications and life-threating complications) and long-term complications (epilepsy and recurrent PRES) were found in 7/18 (38,9%) and 3/18(16,7%) subjects, respectively. Seizures were the onset symptom in 16/18 (88,9%) patients, of which 6/16 (37,5%) evolved in status epilepticus (5 Convulsive Status Epilepticus CSE and 1 Non Convulsive Status Epilepticus NCSE) . EEG was performed in 17 (94%) patients, showing alterations in all cases: ictal anomalies 5/17 (41,2%), posterior or generalized slowing 7/17 (41,2%) and periodic lateralized epileptic discharges (PLEDs) 5/17 (41,2%). Brain MRI was performed in 16/18 (88,9%) subjects and alterations were found in all cases, mostly in the parieto-occipital regions (12/16; 75%), while CT showed negative results in 10/18 (55,6%). 1/18 (5,5%) patient had recurrence PRES after 7 months. All patients required antiepileptic therapy and - in the 13/18 (72,2%) cases taking cyclosporine - a therapeutic switch was made in 8/13 (61,5%) patients with tacrolimus and none patient have had relapse after this change. 7/18 (38,9%) patients were transferred to Intensive Care Unit due to the onset of complications (Life threating complications, coma, epilepticus status). Sub-analysis was conducted taking into account two age groups: patients younger than 6 years and ≥6 years. Pre-school children were found to be at higher risk for status epilepticus 2/3 (66,7%) and admission to intensive care unit 3/3 (100%). Prophylactic antiepileptic therapy was prolonged on average for 512 days. Two patients (11,1%) developed epilepsy as a long-term complication. 2/18 (11,1%) patients died from causes not directly correlated to PRES, due to the underlying diseases. Conclusions: Hypertension and neurotoxic drugs such as calcineurin inhibitors are significant risk factors for PRES. Although the diagnosis of PRES still lacks precise criteria and specific biomarkers, seizures (and even status epilepticus) are frequently reported at onset, and the diagnosis relies on the timely performance of brain MRI and EEG. Furthermore, PRES is not always posterior (as it may involve the fronto-temporal areas in more than one third of the cases) and not always reversible (as it may lead to long-term brain damage and epilepsy). Bigger multicenter studies are needed to confirm our results.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/20.500.14239/11690