Background: Infantile Epileptic Spasms Syndrome (IESS) is an epileptic syndrome characterized by the onset of epileptic spasms, typically appearing within the first two years of life, which may be associated with characteristic electroencephalographic abnormalities and a slowing, arrest, or regression of neurodevelopment. IESS exhibits marked etiological heterogeneity, encompassing genetic, structural, metabolic, and infectious causes, as well as cases in which no underlying cause can be identified. The underlying etiology and the persistence of epileptic activity can significantly influence clinical and neurodevelopmental trajectories, with potential impacts on cognitive, motor, and behavioral development. In this context, early diagnosis and the prompt initiation of effective therapy represent pivotal aspects in the management of IESS, making the identification of factors associated with treatment response and long-term outcomes of paramount clinical interest. Objectives: To evaluate the efficacy of first-line treatments in the acute phase of spasms and to analyze the association between treatment timeliness and therapeutic response. Furthermore, to evaluate the relationship between etiology and long-term outcomes, considering freedom from spasms and from other seizure types, as well as neurodevelopmental, neurological, and cognitive parameters at follow-up. Study Design: A retrospective observational study was conducted on a cohort of 38 patients with IESS, with a mean age of spasm onset of approximately 6 months. Patients were categorized into three groups based on etiology: known or presumed genetic, structural, and structural-genetic. The electroclinical response to initial treatment, treatment timeliness, the potential need for subsequent lines of treatment, and clinical and neurodevelopmental outcomes at follow-up were analyzed. Results: Spasm onset age showed no statistically significant differences across the different etiological groups. In the acute phase, electroclinical response was significantly associated with first-line treatment, demonstrating a higher remission rate in patients treated with ACTH compared to those treated with vigabatrin. At follow-up, freedom from spasms was achieved in the majority of patients (94.7%), with no evidence of a significant association with either the initial drug or treatment timeliness. Conversely, freedom from other seizure types was significantly associated with etiology, showing a higher frequency of remission in patients with genetic etiology. Neurodevelopmentally, slightly more than half of the patients demonstrated normal psychomotor development. Frequent cognitive impairment was observed, in contrast to substantial preservation of motor functions in the majority of patients. Conclusions: These results highlight the importance of accurate etiological classification in the management of IESS. In the acute phase, first-line treatment was significantly associated with electroclinical response, whereas treatment timeliness showed no significant association with spasm freedom at follow-up. In the long term, underlying etiology was associated with the control of non-spasm seizures, whereas neurodevelopmental outcomes exhibited greater variability. These findings underscore the necessity of an early, personalized diagnostic and therapeutic approach coupled with prolonged clinical, neurological, and neurodevelopmental follow-up.
Background: La Sindrome degli Spasmi Epilettici Infantili (Infantile Epileptic Spasms Syndrome, IESS) è una sindrome epilettica caratterizzata dalla comparsa di spasmi epilettici, generalmente ad esordio nel primo biennio di vita, che possono associarsi a caratteristiche alterazioni elettroencefalografiche e a un rallentamento, arresto o regressione dello sviluppo. La IESS presenta un’elevata eterogeneità eziologica, comprendendo forme di origine genetica, strutturale, metabolica e infettiva, oltre a casi nei quali non è possibile identificare una causa. L’eziologia sottostante e la persistenza dell’attività epilettica possono influenzare significativamente l’evoluzione clinica e neuroevolutiva, con possibili ripercussioni sullo sviluppo cognitivo, motorio e comportamentale. In questo contesto, la diagnosi precoce e l’avvio tempestivo di una terapia efficace rappresentano aspetti centrali nella gestione della IESS e rendono di particolare interesse l’identificazione dei fattori associati alla risposta al trattamento e agli outcome a lungo termine. Obiettivi: Valutare l’efficacia dei trattamenti di prima linea nella fase acuta degli spasmi e analizzare l’associazione tra tempestività dell’intervento e risposta terapeutica. Valutare, inoltre, la relazione tra eziologia e outcome a lungo termine, considerando la libertà dagli spasmi e dalle altre crisi epilettiche, nonché gli aspetti neuroevolutivi, neurologici e cognitivi al follow-up. Studio: È stato condotto uno studio osservazionale retrospettivo su una coorte di 38 pazienti con IESS, con un’età media di esordio degli spasmi di circa 6 mesi. I pazienti sono stati suddivisi in tre gruppi in base all’eziologia: genetica nota o presunta, strutturale e strutturale-genetica. Sono state analizzate la risposta elettroclinica al primo trattamento, la tempestività dell’intervento terapeutico, l’eventuale necessità di successive linee di trattamento e gli outcome clinici e neuroevolutivi al follow-up. Risultati: L’età di esordio degli spasmi, non ha mostrato differenze statisticamente significative tra i diversi gruppi eziologici. Nella fase acuta, la risposta elettroclinica è risultata significativamente associata al trattamento di prima linea, con una maggiore frequenza di remissione nei pazienti trattati con ACTH rispetto a quelli trattati con vigabatrin. Al follow-up, la libertà dagli spasmi è stata raggiunta nella maggior parte dei pazienti (94,7%), senza evidenza di una significativa associazione né con il primo farmaco utilizzato né con la tempestività del trattamento. Al contrario, la libertà dalle altre crisi epilettiche è risultata significativamente associata all’eziologia, con una maggiore frequenza di remissione nei pazienti con eziologia genetica. Sul piano neuroevolutivo, poco più della metà dei pazienti ha presentato uno sviluppo psicomotorio nella norma. È stata inoltre riscontrata una frequente compromissione cognitiva, a fronte di una sostanziale conservazione delle funzioni motorie nella maggior parte dei pazienti. Conclusioni: I risultati evidenziano l’importanza di un accurato inquadramento eziologico nella gestione della IESS. Nella fase acuta, il trattamento di prima linea è risultato significativamente associato alla risposta elettroclinica, mentre la tempestività dell’intervento, non ha mostrato una significativa associazione con la libertà dagli spasmi al follow-up. Nel lungo termine, l’eziologia è risultata associata al controllo delle crisi epilettiche diverse dagli spasmi, mentre gli outcome neuroevolutivi hanno mostrato una maggiore variabilità. Questi dati sottolineano la necessità di un approccio diagnostico e terapeutico precoce e personalizzato, associato ad un follow-up clinico, neurologico e neuroevolutivo prolungato.
Sindrome degli Spasmi Epilettici Infantili: studio retrospettivo delle correlazioni tra eziologia, strategie terapeutiche e outcome clinico.
SARCHIE', LAURA
2025/2026
Abstract
Background: Infantile Epileptic Spasms Syndrome (IESS) is an epileptic syndrome characterized by the onset of epileptic spasms, typically appearing within the first two years of life, which may be associated with characteristic electroencephalographic abnormalities and a slowing, arrest, or regression of neurodevelopment. IESS exhibits marked etiological heterogeneity, encompassing genetic, structural, metabolic, and infectious causes, as well as cases in which no underlying cause can be identified. The underlying etiology and the persistence of epileptic activity can significantly influence clinical and neurodevelopmental trajectories, with potential impacts on cognitive, motor, and behavioral development. In this context, early diagnosis and the prompt initiation of effective therapy represent pivotal aspects in the management of IESS, making the identification of factors associated with treatment response and long-term outcomes of paramount clinical interest. Objectives: To evaluate the efficacy of first-line treatments in the acute phase of spasms and to analyze the association between treatment timeliness and therapeutic response. Furthermore, to evaluate the relationship between etiology and long-term outcomes, considering freedom from spasms and from other seizure types, as well as neurodevelopmental, neurological, and cognitive parameters at follow-up. Study Design: A retrospective observational study was conducted on a cohort of 38 patients with IESS, with a mean age of spasm onset of approximately 6 months. Patients were categorized into three groups based on etiology: known or presumed genetic, structural, and structural-genetic. The electroclinical response to initial treatment, treatment timeliness, the potential need for subsequent lines of treatment, and clinical and neurodevelopmental outcomes at follow-up were analyzed. Results: Spasm onset age showed no statistically significant differences across the different etiological groups. In the acute phase, electroclinical response was significantly associated with first-line treatment, demonstrating a higher remission rate in patients treated with ACTH compared to those treated with vigabatrin. At follow-up, freedom from spasms was achieved in the majority of patients (94.7%), with no evidence of a significant association with either the initial drug or treatment timeliness. Conversely, freedom from other seizure types was significantly associated with etiology, showing a higher frequency of remission in patients with genetic etiology. Neurodevelopmentally, slightly more than half of the patients demonstrated normal psychomotor development. Frequent cognitive impairment was observed, in contrast to substantial preservation of motor functions in the majority of patients. Conclusions: These results highlight the importance of accurate etiological classification in the management of IESS. In the acute phase, first-line treatment was significantly associated with electroclinical response, whereas treatment timeliness showed no significant association with spasm freedom at follow-up. In the long term, underlying etiology was associated with the control of non-spasm seizures, whereas neurodevelopmental outcomes exhibited greater variability. These findings underscore the necessity of an early, personalized diagnostic and therapeutic approach coupled with prolonged clinical, neurological, and neurodevelopmental follow-up.| File | Dimensione | Formato | |
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Descrizione: La tesi analizza la Sindrome degli Spasmi Epilettici Infantili (IESS), con particolare attenzione all'eziologia, alla risposta ai trattamenti di prima linea e all'outcome clinico e neuroevolutivo al follow-up.
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https://hdl.handle.net/20.500.12075/28507