Rationale: Septo-optic dysplasia (SOD) is a neurodevelopmental disorder marked by significant phenotypic variability. Diagnosed by the presence of at least two key findings—optic nerve hypoplasia, pituitary hypoplasia, absence of the septum pellucidum and/or dysgenesis of the corpus callosum —SOD often presents with seizures. However, the relationship between specific brain abnormalities and seizure presentation in SOD remains underexplored. This study aims to elucidate the associations between neuroimaging findings and clinical characteristics and development of epilepsy in children with SOD.
Methods: We conducted a chart review to identify children (< 19 years) diagnosed with SOD between 2013 and 2018. Statistical associations between seizure development and demographic factors, brain abnormalities, and clinical characteristics were assessed using the Kruskal-Wallis rank sum test and Fisher’s exact test. Multivariate binomial regression was utilized to predict seizure development based on SOD diagnostic criteria.
Results: Our cohort consisted of 46 children with SOD, 22 (48%) of whom experienced seizures. The median age of seizure onset was 1 year (IQR=0 to 4.75 years). Of the 33 patients with abnormal neurological examinations, 18 (55%) developed seizures. Developmental delay was noted in 19 (41%) patients, 13 of whom also had seizures. SOD patients with seizures had a significantly higher median number of emergency department visits (8.5, IQR=4.25 to 14.75) compared to those without seizures (1, IQR=0 to 2.5) (p< 0.001). Similarly, hospitalizations were more frequent in patients with seizures (6, IQR=3 to 11) than in those without (3, IQR=1 to 6) (p< 0.001). None of the individual SOD diagnostic criteria were significant predictors of seizures. However, patients with seizures were more likely to exhibit developmental delays (p=0.041). Additional MRI findings included ventriculomegaly (n=17, 37%), schizencephaly (n=10, 22%), cerebellar abnormalities (n=9, 26%), intracranial hemorrhage (n=5, 11%), heterotopia (n=3, 6.5%), and polymicrogyria (n=12, 26.1%). Although none of the
aforementioned MRI findings were significantly associated with seizures, the presence of schizencephaly was marginally associated with seizures (p = 0.052).
Conclusions: Our findings indicate that neither diagnostic criteria for SOD nor the presence of other additional brain abnormalities are predictive of seizure occurrence. Therefore, comprehensive screening for seizures is recommended for all SOD patients, irrespective of specific phenotypic presentations. Moreover, given the significant association between seizures and developmental delays, it is crucial to evaluate developmental progress in SOD patients with seizures. The higher healthcare utilization observed in seizure-affected patients underscores the need for regular and proactive outpatient follow-ups. These results emphasize the importance of vigilant seizure screening and management to mitigate the healthcare burden and improve outcomes for SOD patients.
Funding: n/a