Evolution of Infantile Spasms to Lennox-Gastaut Syndrome: What Is There to Know?

Abstract

Objective: Children with infantile spasms may develop Lennox-Gastaut syndrome. The diagnostic criteria for Lennox-Gastaut syndrome are vague, and many experts use varying combinations of the following criteria for diagnosis: paroxysmal fast activity on electroencephalography (EEG), slow spike and wave on EEG, developmental delay, multiple seizure types, and nocturnal tonic seizures. Our objective was to determine the prevalence of Lennox-Gastaut syndrome in a high-risk cohort of children with a history of infantile spasms and the characteristics of infantile spasms that were associated with the diagnosis of Lennox-Gastaut syndrome. Methods: Children with infantile spasms who were diagnosed and treated at Children’s Hospital Colorado between 2012 and 2018 were included. Lennox-Gastaut syndrome was defined as having 3 of 5 of the following characteristics: paroxysmal fast activity, slow spike and wave, current developmental delay, multiple seizure types, or tonic seizures. Descriptive statistics were performed using median and interquartile range. Univariable analysis was performed with Pearson chi-square, Fisher exact, or the Kruskal-Wallis test. Results: Ninety-seven children met inclusion criteria, and 36% (35/97) met criteria for Lennox-Gastaut syndrome. Developmental delay and history of seizures prior to the onset of infantile spasms were identified as risk factors for the development of Lennox-Gastaut syndrome ( P = .003) as was poor response to first treatment for spasms ( P = .004). Children with an unknown etiology of infantile spasms were less likely to develop Lennox-Gastaut syndrome ( P = .019). Eighty percent (28/35) of the children who met Lennox-Gastaut syndrome criteria lacked a documented diagnosis. Conclusions: Thirty-six percent of children with infantile spasms met criteria for Lennox-Gastaut syndrome. Risk factors for development of Lennox-Gastaut syndrome were developmental delay and seizures prior to the onset of infantile spasms and poor response to first treatment for infantile spasms. Children with an unknown etiology of infantile spasms were less likely to develop Lennox-Gastaut syndrome. Eighty percent of the children who met our criteria were not given a documented diagnosis of Lennox-Gastaut syndrome, which highlights the fact that many children may not be receiving a diagnosis of Lennox-Gastaut syndrome. We recommend establishing clear guidelines for the diagnosis of Lennox-Gastaut syndrome to ensure that the diagnosis is being made accurately.

Epileptic spasms: A South African overview of aetiologies, interventions, and outcomes

“…This proportion with poorer developmental outcome is higher than expected given that most patients with epileptic encephalopathy/DEE had LTTT of less than 1 month and were treated with corticosteroids. We suspect that the LTTT was longer and many events were not recognized by the caregivers 31 . In the group with developmental encephalopathy, 69 out of 77 (90%) had moderate to profound delay at 1 year of age.…”

“…We suspect that the LTTT was longer and many events were not recognized by the caregivers. 31 In the group with developmental encephalopathy, 69 out of 77 (90%) had moderate to profound delay at year of age. Patients with developmental encephalopathy should not have typical preceding development; however, a limitation of our study was that developmental history was often reliant on parent-reporting.…”

“…This may reflect clinical challenges in South Africa relating to failure to diagnose epileptic spasms (diagnostic gap) and referral to tertiary centres only undertaken in the setting that epileptic spasms are identified or consultation made because of adverse change in the infant's neurobehaviour. Some of the challenges experienced are not unique to low‐ and middle‐income countries 31 . If the clinician or parent does not identify the clinical concern, referral will not occur and care will continue locally.…”

“…Some of the challenges experienced are not unique to low-and middle-income countries. 31 If the clinician or parent does not identify the clinical concern, referral will not occur and care will continue locally. TBH did not have the capacity to perform repeat EEG after treatment and therefore only the clinical resolution of spasms after treatment was undertaken in this group.…”

Interrater and Intrarater Agreement of Epileptic Encephalopathy Among Electroencephalographers for Children with Infantile Spasms Using the Burden of Amplitudes and Epileptiform Discharges (BASED) EEG Grading Scale: Study Design and Statistical Considerations

“…Infantile spasm syndrome is a catastrophic form of childhood epilepsy that often manifests between 3 and 7 months of infancy [1,2] and is characterized by involuntary, massive motor spasms during early infancy that herald a lifelong disorder of severe seizures and intellectual disability [3][4][5][6][7]. Electroencephalography (EEG) can be used to diagnose infantile spasms and to assess the therapeutic effect [8].…”