Limited improvement in outcomes of infantile epileptic spasms syndrome despite therapeutic advances
Article information
Key message
· Despite advances in treatment, infantile epileptic spasms syndrome remains associated with poor long-term epilepsy and developmental outcomes.
· Improved seizure control alone may not be sufficient, underscoring the need for early diagnosis and etiology-driven management strategies.
Infantile epileptic spasms syndrome (IESS), among the most severe epilepsy syndromes in early infancy, is characterized by epileptic spasms, developmental regression, and a high risk of long-term neurological impairment. Recent efforts by the International League Against Epilepsy emphasized integrating electroclinical features with etiology, particularly in early-onset epilepsies in which both seizures and the underlying disease contribute to the infant’s developmental outcomes [1].
In this context, a recent multicenter study from Korea provided valuable real-world data on the long-term outcomes of children with IESS [2]. Its findings highlighted that a large proportion of patients develop chronic epilepsy, nearly one-third progress to drug-resistant epilepsy, and most exhibit intellectual disabilities. These results are broadly consistent with those of previous long-term studies of IESS and related conditions [3,4], and reflect the persistent burden of IESS despite treatment advances.
One particularly notable aspect of this study was the potential dissociation between seizure outcomes and neurodevelopmental trajectories. Although seizure control appears to have improved in the more recent treatment eras, developmental outcomes remain largely unchanged [2]. This observation deserves careful interpretation, as early or appropriate treatments should not be considered ineffective. Rather, this highlights the limitations of the current therapeutic approaches and the complexity of the disorder.
The concept of developmental and epileptic encephalopathy provides a useful framework for understanding this gap. In IESS, seizures and their underlying etiology independently contribute to cognitive impairment [1,5]. This implies that even early seizure control does not necessarily lead to improved developmental outcomes, particularly in patients whose diseases have structural or genetic causes. This suggests the need to move beyond focusing solely on seizure control to a more comprehensive etiology-driven approach that incorporates early diagnostic precision and tailored interventions.
Another important consideration is the heterogeneity of patient populations and treatment pathways. Variables such as treatment delay, access to specialized care, and differences in therapeutic strategies may significantly influence patient outcomes [6]. Previous studies reported that a shorter time to treatment is associated with a better developmental prognosis [7]. However, such factors are often difficult to fully capture in retrospective multicenter studies; thus, caution is required when interpreting temporal trends.
Global variability in IESS management provides the context for these findings (Table 1). Differences in access to electroencephalography, first-line therapies such as adrenocorticotropic hormone or vigabatrin, and advanced genetic testing contribute to heterogeneity in both care and outcomes despite international recommendations for managing IESS [8].
Global variations in management of infantile epileptic spasms syndrome
These differences highlight the important implications of the present study. Although the authors suggested the need for consensus guidelines adapted to local clinical practice, their findings also identify a broader issue. Long-term outcomes remain suboptimal, even in settings with relatively advanced healthcare systems. This suggests that the standardization of care, although important, may be unable to substantially alter disease trajectories.
Recent studies, including those from Korean groups, have emphasized early etiological stratification and precise approaches to managing pediatric epilepsy [9,10]. Advances in genetic testing, neuroimaging, and targeted therapies offer promise, particularly for selected etiologies. However, these developments have yet to produce a clear improvement in the overall developmental outcomes across broader patient populations, highlighting the need for further studies to translate these advances into improved clinical outcomes.
This study reflects both its progress and limitations. Although improvements in seizure control are evident, they do not fully address the complexity of IESS. For clinicians, the key message is that current treatments are incomplete rather than ineffective. Therefore, clinicians should cautiously interpret improved seizure control and continue to prioritize early diagnosis, rapid treatment initiation, and etiological evaluation.
Future efforts should focus on achieving early diagnosis, minimizing treatment delays, and developing therapies that target the underlying disease mechanisms rather than seizures alone. Until these advances are realized, IESS remains a significant challenge for clinicians in terms of both seizure control and long-term developmental outcomes.
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.