Developmental stage affects cognition in children with recently-diagnosed symptomatic focal epilepsy.

This study explored the impact of developmental stage on cognitive function in children with recently-diagnosed epilepsy. In keeping with a neurodevelopmental framework, skills in a critical developmental period were expected to be more vulnerable than those stable at the time of seizure onset. We studied children with early-onset (EO) symptomatic focal epilepsy (onset: 3-5 years; n=18) and compared their performance with that of the group with late-onset (LO) epilepsy (onset: 6-8 years performance of; n=8) on a range of cognitive tasks. Performance of both groups was compared with normative standards. 'Critical' and 'stable' classifications were based on developmental research. Nonparametric analyses revealed that skills in a critical developmental period for the group with EO epilepsy fell below normative standards (Phonological Processing: p=.007, Design Copying: p=.01, Visuomotor Precision:, p=.02) and fell below the performance of the group with LO epilepsy (Design Copying: p=.03, Visuomotor Precision: p=.03). There were no differences between the group with EO epilepsy and the group with LO epilepsy on measures of receptive vocabulary and memory, which were proposed to be in a stable developmental period across both groups. Auditory span, as measured by Word Order, was reduced for both the group with EO epilepsy (p=.02) and the group with LO epilepsy (p=.02) relative to normative standards, but the groups did not differ from each other. These results are consistent with a prolonged period of critical development for this skill. These findings support the notion that skills in a critical phase of development are particularly vulnerable following the onset of symptomatic focal epilepsy in childhood.

Developmental outcomes of childhood-onset temporal lobe epilepsy: a community-based study.

PURPOSE: To assess the impact of childhood-onset temporal lobe epilepsy (TLE) on the attainment of normative developmental tasks and identify predictors of long-term developmental outcomes. METHODS: In 1992-1993, a prospective longitudinal cohort study of childhood-onset TLE was commenced in the State of Victoria, Australia. At review in 2004-2006, we assessed developmental tasks, which are age-specific individual psychosocial achievements tied to particular phases of the lifespan. The cohort comprised 54 individuals (33 female) with a mean age of 20 years (range 12-29), and mean age at TLE onset of 6 years (range 0.2-15). KEY FINDINGS: Individuals were clustered into three groups representing distinct developmental trajectories: (1) a Normal group (52%) who achieved most of their developmental tasks, (2) an Altered group (37%) who achieved some, and (3) a Delayed group (11%) who achieved few. The groups showed significant cognitive differences, with the Normal group outperforming the Altered and Delayed groups on a range of measures (p < 0.05). Multiple discriminant function analysis indicated that membership of the groups was independently predicted by the chronicity of seizures, cognitive functioning, having surgically remediable epilepsy, and gender (p < 0.001). Seizure chronicity and cognition discriminated between all three trajectories, while surgical intervention and gender primarily discriminated between the Altered and Delayed trajectories. SIGNIFICANCE: Childhood-onset TLE can disrupt achievement of normative developmental tasks that is independently predicted by medical, biologic, and cognitive factors. Assessment of developmental tasks across the lifespan provides a practical framework for guiding prognostic counseling of patients and families.

Neurodevelopmental functioning of infants with untreated single-suture craniosynostosis during early infancy.

PURPOSE: Single-suture craniosynostosis (SSC) is a congenital craniofacial disorder, in which premature fusion of one of the skull sutures restricts and distorts growth of the cranium and underlying brain. This disorder of prenatal onset occurs during a critical phase of rapid growth and development of the immature brain. Craniosynostosis carries a known risk of developmental impairment. The neurodevelopmental sequelae of SSC prior to treatment remains however incompletely understood. This study sought to determine the neurodevelopmental sequelae of untreated single-suture craniosynostosis during early infancy. METHODS: Fifty-six consecutive patients with unoperated SSC (sagittal, metopic and unicoronal) comprised the sample cohort. Patients were aged between 4 and 16 months (M = 8.9 months, SD = 2.9 months). Neurodevelopmental functioning was assessed with the mental (Mental Development Index) and motor (Psychomotor Development Index) scales of the Bayley Scales of Infant Development, second edition. RESULTS: Children with SSC displayed significantly lower mean mental (M = 97.7, SD = 6.7, p < 0.05) and motor (M = 87.7, SD = 13.0, p < 0.001) scores than normative population averages. The distribution of these scores also differed significantly from the normative distribution; an increased rate of significant motor developmental delay was found, and none of the children displayed accelerated development. Subgroup comparisons between the primary diagnostic subtypes in this sample revealed no significant differences in mental or motor skill functioning. CONCLUSIONS: Untreated SSC is associated with an increased incidence of developmental delay during early infancy, with motor skills appearing the most vulnerable to impairment during this developmental phase.

One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia.

OBJECTIVE: To determine whether 1-stage, limited corticectomy controls seizures in patients with MRI-positive, bottom-of-sulcus dysplasia (BOSD). METHODS: We reviewed clinical, neuroimaging, electrocorticography (ECoG), operative, and histopathology findings in consecutively operated patients with drug-resistant focal epilepsy and MRI-positive BOSD, all of whom underwent corticectomy guided by MRI and ECoG. RESULTS: Thirty-eight patients with a median age at surgery of 10.2 (interquartile range [IQR] 6.0-14.1) years were included. BOSDs involved eloquent cortex in 15 patients. Eighty-seven percent of patients had rhythmic spiking on preresection ECoG. Rhythmic spiking was present in 22 of 24 patients studied with combined depth and surface electrodes, being limited to the dysplastic sulcus in 7 and involving the dysplastic sulcus and gyral crown in 15. Sixty-eight percent of resections were limited to the dysplastic sulcus, leaving the gyral crown. Histopathology was focal cortical dysplasia (FCD) type IIb in 29 patients and FCDIIa in 9. Dysmorphic neurons were present in the bottom of the sulcus but not the top or the gyral crown in 17 of 22 patients. Six (16%) patients required reoperation for postoperative seizures and residual dysplasia; reoperation was not correlated with ECoG, neuroimaging, or histologic abnormalities in the gyral crown. At a median 6.3 (IQR 4.8-9.9) years of follow-up, 33 (87%) patients are seizure-free, 31 off antiseizure medication. CONCLUSION: BOSD can be safely and effectively resected with MRI and ECoG guidance, corticectomy potentially being limited to the dysplastic sulcus, without need for intracranial EEG monitoring and functional mapping. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that 1-stage, limited corticectomy for BOSD is safe and effective for control of seizures.

Psychological outcome profiles in childhood-onset temporal lobe epilepsy.

PURPOSE: To examine the effect of childhood-onset temporal lobe epilepsy (TLE) on long-term psychological function and to identify outcome profiles related to the natural course and treatment of TLE. METHODS: Psychological function was studied in a prospective, community-based cohort of childhood-onset TLE, approximately 13 years following seizure onset. Fifty-three patients were assessed using a semi-structured psychosocial interview, supplemented by self-report questionnaires measuring quality-of-life, depression, self-esteem, and anxiety. RESULTS: Common patterns were observed, giving rise to four distinct patient groups and psychological outcomes: (1) patients who experienced spontaneous remission of their seizures fared best; their psychological profile was characterized by heightened worry about the possibility of seizure recurrence; (2) patients who progressed to surgery and were seizure free reported adjustment difficulties associated with learning to become "well"; (3) patients who progressed to surgery and were not seizure free had the poorest psychological outcomes, with depression featuring prominently; and (4) patients with ongoing intractable epilepsy reported psychological and social features consistent with the effects of their chronic illness. DISCUSSION: Patients with childhood-onset TLE face distinctive long-term psychological challenges. The specific nature of these challenges can be understood in terms of the natural evolution and treatment of their epilepsy.

A neuropsychological model for the pre-surgical evaluation of children with focal-onset epilepsy: An integrated approach.

This review explores the complexities of pre-surgical neuropsychological assessment for children with focal-onset epilepsy. A model is proposed outlining a range of factors that potentially influence the neuropsychological formulation. These factors include a developmental, epilepsy, psychological and cognitive dimension, together with family and social context and intrinsic factors. This model is child-centered and recognizes that these factors will be weighted differently for each individual. In some instances the neuropsychological profile might suggest localized and lateralized function, but there are significant limitations to this approach in the context of the contemporary view of epilepsy as a network disorder. This review recognizes that a range of issues impact on neuropsychological function in children with focal-onset epilepsy, including the connectivity between neural systems and the dynamic nature of development. The aim of this review is to provide a neuropsychological framework to enhance and support clinical decision-making in the pre-surgical evaluation of children with focal-onset epilepsy.

Temporoparietooccipital disconnection in children with intractable epilepsy.

OBJECT: Temporoparietooccipital (TPO) disconnection is described mainly in children with diffuse posterior quadrant lesions and concordant electroencephalography (EEG) findings. The authors report on 16 children who underwent TPO surgery, including 4 with no definite epileptogenic lesion and 8 with generalized electroclinical manifestations. METHODS: The authors conducted a retrospective review of clinical, neuropsychological, EEG, imaging, and histopathological data in 16 children with intractable epilepsy who underwent TPO disconnection and/or resection at their center between December 1998 and March 2010. RESULTS: Seizure onset occurred between the ages of 1 and 24 months, and TPO surgery was performed between the ages of 0.2 and 17 years. All children had refractory seizures, including epileptic spasms in 10 and tonic seizures in 7, and all had developmental delay. Twelve children had epileptogenic lesions on MR imaging, including 6 with posterior quadrant dysplasia. Four children had only subtle white matter signal change or unusual sulcation on MR imaging, associated with subtle but concordant EEG and functional imaging abnormalities. After a mean follow-up of 52 months (range 12-114 months), 9 children (56%) are seizure-free and 5 (31%) experienced seizure reduction of greater than 50%. Focal or regional background slowing on EEG was correlated with favorable seizure outcome. Five children showed developmental progress and 3 had acceleration in development following surgery. None of the children developed new motor deficits postoperatively. CONCLUSIONS: Temporoparietooccipital disconnection is an effective, motor-sparing epilepsy surgery procedure for selected children with refractory focal or generalized seizures with localization to the posterior quadrant on 1 side, with or without a discrete lesion on MR imaging.

Intellectual outcomes in children and adolescents with syndromic and nonsyndromic craniosynostosis.

BACKGROUND: Craniosynostosis, the premature fusion of the skull bones, is a congenital deformity that has functional and morphologic implications. Cranial vault reconstructive surgery is required to improve skull shape and increase intracranial volume. Craniosynostosis disorders carry a risk of brain insult and associated neurologic and cognitive dysfunction. This study investigated the long-term effects of craniosynostosis on intelligence in children and adolescents with syndromic and nonsyndromic disorders who had undergone cranial expansion surgery during infancy. METHODS: Global intellectual evaluations were obtained on 31 children aged 7 to 16 years with mixed syndromic (n = 13) and nonsyndromic (n = 18) craniosynostoses. Results of intellectual assessment were compared with norm-referenced data. Age at surgery and gender comparisons were also made. RESULTS: Mean +/- SD general intelligence quotient of the total sample was within the average range (intelligence quotient, 95.6 +/- 21.2). Intellectual functioning was significantly lower in children with syndromic craniosynostosis (mean intelligence quotient, 83.1 +/- 21.9) than nonsyndromic craniosynostosis (mean intelligence quotient, 104.7 +/- 15.8). The majority of children with syndromic craniosynostosis (77 percent) were of normal intelligence. Children with nonsyndromic craniosynostosis did not display obvious evidence of intellectual dysfunction. There were no age or gender differences in intellectual outcomes in this sample. CONCLUSIONS: Findings are contrary to the historical impression that has regarded syndromic craniosynostosis as synonymous with intellectual disability. Children with nonsyndromic craniosynostosis are of normal intelligence during their school-age years.

Neuropsychological diversity in Apert syndrome: a comparison of cognitive profiles.

Apert syndrome is characterized by craniosynostosis, central nervous system anomalies, midface hypoplasia, and syndactyly. Current research has focused on genetic and neurologic correlates. Cognitive assessment has been primarily limited to global intellectual evaluations, which can fail to detect the diverse cognitive attributes of these children at an individual level. This report describes in detail the neuropsychological profiles of 2 children with Apert syndrome, incorporating clinical, radiographic, molecular and surgical data. One child showed intellectual deficits consistent with a moderate intellectual disability. The second child, while of normal intelligence, displayed neuropsychological deficits associated with anterior-brain-region cognitive functions. These data highlight the diversity of neuropsychological outcomes in Apert syndrome in the same genetic mutation and underline the importance of detailed neuropsychological evaluations as integral to the management protocols of affected individuals.