Jacquie A. Wrennall

Transcallosal resection of hypothalamic hamartomas, with control of seizures, in children with gelastic epilepsy.

OBJECTIVE Hypothalamic hamartomas (HHs) are associated with precocious puberty and gelastic epilepsy; the seizures are often refractory to antiepileptic medications and associated with delayed development and disturbed behavior. The current opinion is that surgery to treat intrahypothalamic lesions is formidable and that complete excision is not technically achievable. We report our experience with a transcallosal approach to the resection of HHs. METHODS Five children (age, 4–13 yr) with intractable epilepsy and HHs underwent preoperative clinical, electroencephalographic, and imaging evaluations. Two patients experienced only gelastic seizures, and three patients experienced mixed seizure disorders with drop attacks; all experienced multiple daily seizures. Patients were evaluated with respect to seizures, cognition, behavior, and endocrine status 9 to 37 months (mean, 24 mo) after surgery. The HHs were approached via a transcallosal-interforniceal route to the third ventricle and were resected using a microsurgical technique and frameless stereotaxy. RESULTS Complete or nearly complete (>95%) excision of the HHs was achieved for all patients, with no adverse neurological, psychological, or visual sequelae. Two patients experienced mild transient diabetes insipidus after surgery. Two patients developed appetite stimulation, but no other significant endocrinological sequelae were observed. Three patients are seizure-free and two patients have experienced only occasional, brief, mild gelastic seizures after surgery, all with reduced antiepileptic medications. On the basis of parental reports and our own subjective observations, the children also exhibited marked improvements in behavior, school performance, and quality of life. CONCLUSION Complete or nearly complete resection of HHs can be safely achieved via a transcallosal approach, with the possibility of seizure freedom and neurobehavioral improvements.

Temporal lobe epilepsy in childhood: Clinical, EEG, and neuroimaging findings and syndrome classification in a cohort with new-onset seizures

Sixty-three children with new-onset temporal lobe epilepsy (TLE) underwent extensive clinical, EEG, and neuroimaging investigation as part of a prospective, community-based cohort study of the natural history of TLE in childhood. Complex partial seizures occurred in 94% of the children, and tonic-clonic seizures occurred in 14%. Developmental, behavioral, or learning problems were present in 38%. Eighteen children (29%) had a significant illness/event prior to the onset of TLE, including febrile status epilepticus in seven, meningitis in four, respiratory arrest in two, and head injury in one. Magnetic resonance imaging or computed tomography revealed structural abnormalities of the temporal lobe in 24 children (38%), including hippocampal sclerosis (HS) in 13 and tumor in eight. There was a strong association between HS and a history of significant illness/event prior to the onset of TLE (p < 0.001). Analysis of past history and neuroimaging findings led us to propose three etiologically defined subgroups of TLE; developmental TLE (10 children with long-standing, nonprogressive temporal lobe tumors and malformations), TLE with HS/significant antecedents (18 children with HS or a history of a significant illness/event), and cryptogenic TLE (34 children with normal neuroimaging findings and no significant past history). Etiologic differences between children with new-onset TLE may confer prognostic information that will be useful for counselling families and planning treatment.

New-onset temporal lobe epilepsy in children: Lesion on MRI predicts poor seizure outcome

Objective: To determine factors predictive of long-term seizure outcome in children with new-onset temporal lobe epilepsy (TLE). Methods: A community-based cohort of 77 children with new-onset TLE, including 14 with possible TLE, were followed prospectively with formal review 7 and 14 years following seizure onset. Diagnoses were re-evaluated at each review, and changed when new clinical, EEG, or imaging data were compelling. Results: Sixty-four patients sustained the diagnosis of TLE over time; two were lost to follow-up. Age at follow-up was 12 to 29 years (median 20 years). Median follow-up was 13.7 years, 95% being followed for greater than 10 years. Nineteen patients were seizure free (SF) and off treatment, having not had seizures for 5 to 15 years. Duration of active TLE in the SF group was 1 to 8 years, the children being treated with 0 to 3 antiepileptic drugs (AEDs). Forty-three patients were not seizure free (NSF) and had ongoing seizures or had undergone epilepsy surgery. These children were treated with 1 to 10 AEDs. Fifteen NSF patients experienced 22 nonterminal seizure remissions of 1 to 7 years duration. Seventeen children had a significant antecedent to TLE. Lesions were identified on neuroimaging in 28 and included hippocampal sclerosis (HS) in 10, tumor in 8, and dysplasia in 7. All children with lesions on MRI were NSF (p < 0.001). Focal slowing on EEG was also associated with persistent seizures (p = 0.05), although this was correlated with a lesion on MRI. Infantile onset of epilepsy, family history of seizures, initial seizure frequency, antecedents, and early seizure remissions were not predictive of seizure outcome. Conclusion: Seizures spontaneously remit in approximately one third of children with new-onset TLE. A lesion on MRI predicts intractable seizures in TLE and the potential need for epilepsy surgery.

Generalized epilepsy in hypothalamic hamartoma: evolution and postoperative resolution.

Objective: To better understand the epileptogenesis of symptomatic generalized epilepsy in patients with hypothalamic hamartoma and intractable epilepsy, many of whom experience remission of generalized seizures and slow spike-wave discharges following surgery. Methods: The authors documented the evolution of symptomatic generalized epilepsy in 12 of 20 children who underwent transcallosal microsurgical hypothalamic hamartoma resection. In seven patients they recorded intraoperative EEG from the hamartoma and simultaneously from the scalp and frontal cortex before, during, and after resection. Results: Gelastic seizures began on average at 6 months of age (range birth to 3 years); tonic seizures began at 6 years (range 2 months to 9 years). Normal EEG were reported in early childhood; thereafter, abnormalities were progressive. Interictal spike-wave was recorded intraoperatively over the scalp and cortex in six patients, but not from the hypothalamic hamartoma. Hamartoma resection had no immediate effect on cortical spike-wave, but waking spike-wave was absent in seven patients on subsequent postoperative EEG. Tonic seizures ceased in 11 of 12 patients, but 6 of these had postoperative generalized seizures that resolved over 1 to 6 months. Conclusion: Gelastic seizures in hypothalamic hamartoma arise from the hamartoma itself; the interictal spike-wave does not. The evolution of EEG abnormalities, the development of generalized seizures years after onset of gelastic seizures, and the postoperative running down of interictal spike-wave and generalized seizures in these patients may reflect secondary epileptogenesis.

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.

Language lateralization correlates with verbal memory performance in children with focal epilepsy

Purpose:  Assessment of language dominance with functional magnetic resonance imaging (fMRI) and neuropsychological evaluation is often used prior to epilepsy surgery. This study explores whether language lateralization and cognitive performance are systematically related in young patients with focal epilepsy.

Measuring intellectual ability in children with cerebral palsy: Can we do better?

Standard intelligence tests such as the WPPSI-III have limitations when testing children with motor impairment. This study aimed to determine the proportion of children with cerebral palsy with sufficient verbal and motor skills to complete the WPPSI-III, to determine their comparative ability to complete tasks with and without a significant motor component, and to investigate short forms of the WPPSI-III as alternatives. Participants were 78 of 235 eligible 4-5 year old children with cerebral palsy resident in the Australian state of Victoria. Verbal IQ (VIQ), Performance IQ (PIQ), and Full-scale IQ (FSIQ) were determined using the WPPSI-III. Initial screening for pointing and verbal abilities determined which tests were attempted. The impact of speed was investigated by comparing scores on the Block Design subtest with and without an imposed time limit. FSIQ scores were calculated from two short forms of the WPPSI-III and compared to the full form. On screening, 16 children had inadequate pointing (14) and verbal abilities (2). FSIQ was obtained in 62 (82%) children. Strong associations were seen between completion of the entire test battery and topographical pattern, level of manual ability and level of gross motor function. Scores on subtests requiring manual ability were depressed relative to other scores. Children performed better using short forms of the WPPSI-III and, for a minority, when time limits were disregarded. In summary, children with cerebral palsy often lack the fine and gross motor skills necessary to complete the WPPSI-III, scoring relatively poorly on tasks requiring a fine motor response. Using short-form estimations of FSIQ comprised of subtests without a significant fine motor component has the potential to increase a childs FSIQ by approximately 5 points. These findings have important clinical implications when assessing a child with both motor and cognitive limitations.

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.

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.

The implications of childhood bacterial meningitis for language development.

Bacterial meningitis is a life threatening infection of the central nervous system. This illness is most prevalent early in life when the healthy child is rapidly acquiring language. This study investigated whether children with a history of bacterial meningitis were at risk for language difficulties post illness. Thirty post-meningitic children, aged between 9 years 0 months and 11 years 0 months, participated in this study. Each subject was administered a measure of non-verbal cognitive ability and a range of language tasks. These children performed poorly on applied language tasks, which tap skills used in effective discourse. These deficits occurred despite age appropriate performances on measures of linguistic/grammatical knowledge. These findings clearly illustrate that bacterial meningitis has implications for ongoing language development, which emphasises the importance of long term follow up. In developmental terms, this discrepancy between verbal knowledge and problem solving represents a dissociation between language skills which develop early in life and those which emerge later. This pattern of results suggests that bacterial meningitis may result in a delay in language development. A young age at illness was identified as an additional risk factor for adverse outcome. This study highlights the need to inform parents/guardians that post-meningitic children are at risk for experiencing language difficulties throughout childhood.