Little research exists characterizing the neuropsychological profile of pediatric insular epilepsy. Accurate diagnosis of insular epilepsy is challenging due to difficulties localizing deep brain structures with current non-invasive neurodiagnostic tools, as well as seizure semiology that may mimic temporal, frontal, and parietal seizures for this patient population [1]. Therefore, we investigated trends across neuropsychological data to help characterize the cognitive profile of pediatric insular epilepsy. This is important because studies that could accurately characterize insular epilepsy into cognitive phenotypes could potentially provide supporting evidence for insular localization during epilepsy surgery work-up. The insula is situated underneath the temporal, parietal, and frontal opercula, and has a number of diffuse projections to key brain structures involved in language, executive functioning, motor coordination, and sensory function [2]. Therefore, we hypothesized that children with insular epilepsy will demonstrate particular weaknesses in language and executive functioning skills.

Retrospective medical records review identified 19 children with insular epilepsy who completed neuropsychological assessment (Age: M=8.2 years, SD=3.4) at Boston Children’s Hospital. Insular epilepsy was defined by ictal insular localization on long-term monitoring EEG. The current sample includes 59% males and 41% females. The majority of participants (69%) had left sided lateralization and more than one seizure type (63%). MRI findings were widely distributed across frontal, temporal, and multiple lobes as well as insular and perisylvian brain regions. A lesion was identified on MRI findings for most participants (63%).

Descriptive analyses showed that overall IQ (FSIQ: M=84, SD=12, range=68-102) fell in the Low Average range. Verbal and visual reasoning skills were equally developed in the Low Average range (VIQ: M=88, SD=12, range=70-104; PIQ: M=88, SD=16, range=53-117). Participants exhibited lower performance on speeded expressive language measures, including measures of phonemic fluency (M=5.5, SD=1.5, range=2-8) and semantic fluency (M=6.7, SD=2.5, range=3-11). With regard to executive functioning, reduced cognitive flexibility was observed on D-KEFS Trail Making Test (Trial 4, Number-Letter Switching: M=5.9, SD=4.9, range=1-12). Additionally, working memory skills fell in the Below Average range (WMIQ: M=77, SD=8.5, range=67-88).

Our results indicate that pediatric patients with insular epilepsy present with reduced scores across aspects of speeded expressive language and executive functioning, including working memory and cognitive flexibility. Additional research is needed to replicate these preliminary findings with a larger sample size and determine whether these trends in cognitive profile would help with seizure localization. Future research should investigate whether insular epilepsy has a clearly identifiable and distinct cognitive phenotype that could be helpful in differential diagnostic workup.

Succinic semialdehyde dehydrogenase (SSADH) deficiency (γ-hydroxybutyric aciduria) is a rare neurometabolic disorder of γ-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology.

We overview the phenotype of 33 adolescents and adults (10.1–39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data.

Sixty-six percent of patients (n=21) presented by 6 months of age, 14% from 6–12 months of age, 5% from 1–2 years of age, and 14% from 2–4 years of age, mean age at first symptoms was 11±12 months. However, mean age at diagnosis was 6.6±6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had ≥3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized.

The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood.