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Focal onset epilepsy carries a higher risk of intractability than generalized onset epilepsy. Knowledge of the risk factors of intractability will help guide the treatment of children with focal epilepsy. In addition to risk factors present at initial diagnosis, the evolution of clinical and electroencephalographic features may also play a role in predicting intractability.A prospective cohort study was done on children aged one month to three years with newly diagnosed focal epilepsy. Initial treatment of carbamazepine was given according to a standard protocol after assessment of clinical manifestations, neurologic and developmental status, EEG, and brain MRI. Depending on response to therapy, subjects may also receive valproic acid or phenobarbitone following the protocol. Follow-up was done in the second week and every month thereafter. At the end of the study period, seizure type was re-assessed and a repeat neurological and developmental examination and EEG was obtained to evaluate the role of clinical and EEG evolution in predicting intractability.Out of 71 subjects, 21 (29.6%) had intractable epilepsy at the end of the study period. Age of onset (p = 0.216) and neurological status (p = 0.052) were not associated with intractable epilepsy. On logistic regression analysis, evolution of seizure type (p 0.001; RR 56.45; 95%CI 6.56 to 485.85) and evolution of background EEG rhythm (p 0.001; RR 56.51; 95%CI 2.77 to 1152.16) were significantly associated with intractable epilepsy.Changes in seizure type and baseline EEG rhythm may predict intractability in children one month to three years of age with focal epilepsy.

To investigate whether theory of mind (ToM), an important requirement for adaptive social functioning, is different between children with pharmacologically refractory epilepsy who undergo epilepsy surgery and healthy control children, whether ToM is affected by epilepsy surgery in these children, and whether ToM is associated with demographic or epilepsy variables. The "ToM storybooks", a psychometrically sound ToM instrument designed for children, was administered shortly before and 0.5, one and two years after surgery as part of a neuropsychological assessment. Fifteen patients (mean age: 7.1 years) completed the ToM storybooks before and at least twice after surgery. Two sex- and age-matched healthy control children were included per patient. Linear mixed models were used to analyse differences between patients and controls. The association between ToM and demographic, epilepsy and surgical variables was explored. Patients had lower ToM scores than healthy control children, even when corrected for verbal intelligence quotient (VIQ). Epilepsy surgery had neither a harmful nor a favourable effect on ToM. Later epilepsy onset and temporal origin of epilepsy were associated with higher (better) ToM scores relative to earlier epilepsy onset and extra-temporal epilepsy (including hemispherotomy in one case). Children in whom the amygdala was resected had worse ToM scores. Children with refractory epilepsy have a ToM deficit that may not be accounted for by lower VIQ. Epilepsy surgery does not affect ToM functioning. Younger age at epilepsy onset is associated with poorer ToM, and temporal epilepsy with better ToM. Finally, the amygdala is implicated in ToM deficit. Patients and their parents should be educated about the possible consequences of epilepsy with regards to the development of social cognition and should be guided in order to help improve ToM.

The purpose of this study was to determine whether children with epilepsy surgery in their history are able to recognize emotions expressed by faces and whether this recognition is associated with demographic variables [age, sex, and verbal intelligence (VIQ)] and/or epilepsy variables (epilepsy duration, side of the surgery, surgery area, resection of the amygdala, etiology, antiepileptic drug use, and seizure freedom).Two years after epilepsy surgery, the Facial Expression of Emotion: Stimuli and Tests (FEEST) was administered to 41 patients (age: 4-20years, mean: 13.5years, 24 girls) and 82 age- and sex-matched healthy controls. Data obtained longitudinally (before surgery and 6, 12, and 24months after surgery) in a small subset (11 patients and 22 matched controls) were explored to obtain clues about the course of REEF from before surgery.Corrected for VIQ, REEF scored significantly lower in the 41 surgically treated patients than in matched control children. No significant relationship was found between REEF and any epilepsy variable. Only age at assessment predicted REEF score in both patients and controls. The longitudinal data revealed a 'dip' in emotion recognition at the first postsurgical assessment in the six younger patients (age:12.1years). The older patients (age: 13-17years) showed a continuous increase in REEF scores that was similar to that in controls. Two years after surgery, REEF of the younger patients recovered to, but did not exceed, the presurgical level.Neither poor REEF present two years after childhood epilepsy surgery, nor the aberrant course of REEF in younger patients (age:12.1years) was explained by epilepsy variables or poor verbal intelligence. Disentangling the mechanism of the abnormality is urgently needed, as recognizing emotional expressions is a key component in the development of more complex social perception skills.

Item does not contain fulltext Objective: To know whether change in the intelligence quotient (IQ) of children who undergo epilepsy surgery is associated with the educational level of their parents. Methods: Retrospective analysis of data obtained from a cohort of children who underwent epilepsy surgery between January 1996 and September 2010. We performed simple and multiple regression analyses to identify predictors associated with IQ change after surgery. In addition to parental education, six variables previously demonstrated to be associated with IQ change after surgery were included as predictors: age at surgery, duration of epilepsy, etiology, presurgical IQ, reduction of antiepileptic drugs, and seizure freedom. We used delta IQ (IQ 2 years after surgery minus IQ shortly before surgery) as the primary outcome variable, but also performed analyses with pre- and postsurgical IQ as outcome variables to support our findings. To validate the results we performed simple regression analysis with parental education as the predictor in specific subgroups. Results: The sample for regression analysis included 118 children (60 male; median age at surgery 9.73 years). Parental education was significantly associated with delta IQ in simple regression analysis (p = 0.004), and also contributed significantly to postsurgical IQ in multiple regression analysis (p = 0.008). Additional analyses demonstrated that parental education made a unique contribution to prediction of delta IQ, that is, it could not be replaced by the illness-related variables. Subgroup analyses confirmed the association of parental education with IQ change after surgery for most groups. Significance: Children whose parents had higher education demonstrate on average a greater increase in IQ after surgery and a higher postsurgical - but not presurgical - IQ than children whose parents completed at most lower secondary education. Parental education - and perhaps other environmental variables - should be considered in the prognosis of cognitive function after childhood epilepsy surgery. 9 p.

article i nfo Purpose: This study aimed to investigate parenting stress expressed by parents before and two years after their children's epilepsy surgery. Methods: Subjects: Parents of 31 consecutively included surgery patients with epilepsy and parents of 31 healthy sex- and age-matched control children were the subjects of this study. Materials and procedure: The question- naire 'Parenting Stress Index', which distinguishes a Parent domain (stress leading parents to feel themselves inadequate) from a Child domain (child features felt by parent to cause stress) was completed before surgery of the patients and two years thereafter. At both time points, intelligence examination of the child was part of a comprehensive neuropsychological assessment, as were evaluations of recent stress-enhancing life events and epilepsy severity. Results: Prior to surgery, total parenting stress was significantly higher in parents of patients than in parents of con- trols. Two years after surgery, total parenting stress had decreased significantly in parents of patients. The scores on parent-related subscales Role Restriction and Spouse and on the child-related subscale Distractibility/Hyperactivity, all relatively high before surgery, decreased significantly. Still, parents of patients experienced significantly more stress compared with parents of controls mainly because of persistently higher stress scores in par- ents of patients on the subscale Role Restriction (Parent domain) and on five of six subscales in the Child domain. Intelligence of the child was associated with parenting stress: the lower the child's intelligence, the higher the stress score on the subscale Distractibility/Hyperactivity and the lower the stress score on the subscale Mood. Stress decreased more in parents of patients who became seizure-free after surgery than in parents of patients with recurrent seizures. Conclusions: Parenting stress decreases but does not normalize in the first two years after epilepsy surgery. Parents should be offered counseling on epilepsy-related intricacies contributing to parenting stress, immediately after diagnosis as well as after epilepsy surgery, notwithstanding the resulting seizure status of the child.

This literature review on social functioning of children after epilepsy surgery is based on 24 papers addressing two categories of social functioning: social cognition (n = 4) and general social functioning (n = 20). Overall, studies that compared with healthy peers revealed children who had undergone epilepsy surgery to have more problems in both social cognition and general social functioning. Half of the studies found some improvement in social functioning in the first year(s) after epilepsy surgery, but this pertained to general social functioning, not to social cognition. The persistence of the problems in social cognition after surgery may be related to the critical period of brain maturation, lacking improvement of impairments in related cognitive domains or to a defective underlying brain condition — rather than to the epilepsy. Problems in general social functioning may be explained by the adjustments the children and their families had to make because of the child's drug-resistant epilepsy and difficulties to adjust to the new situation after surgery. The neurological and behavioral explanations are likely to be interrelated in light of the multifaceted and complex nature of social functioning. Epilepsy surgery does not appear to solve the problems in social functioning associated with having had drug-resistant epilepsy. As social functioning is an important aspect of healthy development, it should be assessed comprehensively in order to obtain a knowledge base that allows 1) proper treatment of children with epilepsy (CwE) and 2) counseling patients and families prior to and after epilepsy surgery.

AIM: The aim of the study was to assess cognitive outcome in children with periventricular haemorrhagic infarction (PVHI) or perinatal arterial ischaemic stroke (PAIS) and relate these findings to early developmental outcome and neonatal magnetic resonance imaging findings. METHOD: A neuropsychological assessment was performed in 50 children (26 males, 24 females) with unilateral PVHI (n=21) or PAIS (n=29) at a median age of 11 years 9 months (range 6-20y). This included tests for intelligence, verbal memory, visual-motor integration, word comprehension, attention, reaction times, and executive function. The Griffiths Mental Development Scale was used for early developmental assessment at 24 months (range 18-32mo). RESULTS: In children with PVHI, both the early Griffiths scores (mean 87; 95% CI 83-92) and the Full-scale IQ (FSIQ) scores at school age (mean 86; 95% CI 78-94) were below the test mean of 100. In the PAIS group, early Griffiths scores were within the normal range (mean 98; 95% CI 93-104), but at school age FSIQ scores were below average (mean 87; 95% CI 80-94). In children with PVHI, FSIQ scores correlated with the level of maternal education and were lower after ventricular dilatation, whereas both involvement of the basal ganglia and thalami and development of postneonatal epilepsy were associated with lower cognitive outcome in children who had experienced PAIS. INTERPRETATION: Cognitive outcome after PVHI or PAIS is below average, but still within 1SD for most children. Prediction of cognitive outcome remains challenging, but some early predictors can be recognized. Language: en

Item does not contain fulltext Prediction of functional motor outcome after hemispherectomy is difficult due to the heterogeneity of motor outcomes observed. We hypothesize that this might be related to differences in plasticity during the onset of the underlying epileptogenic disorder or lesion and try to identify predictors of motor outcome after hemispherectomy. Thirty-five children with different etiologies (developmental, stable acquired or progressive) underwent functional hemispherectomy and motor function assessment before hemispherectomy and 24 months after hemispherectomy. Preoperatively, children with developmental etiologies performed better in terms of distal arm strength and hand function, but not on gross motor function tests. Postoperatively, the three etiology groups performed equally poor in muscle strength and hand function, but gross motor function improved in those with acquired and progressive etiologies. Loss of voluntary hand function and distal arm strength after surgery was associated with etiology, intact insular cortex and intact structural integrity of the ipsilesional corticospinal tract on presurgical MRI scans. In conclusion, postoperative motor function can be predicted more precisely based on etiology and on preoperative MRI. Children with developmental etiology more often lose distal arm strength and hand function and show less improvement in gross motor function, compared to those with acquired pathology.

Objectives The objective of this study was to explore whether parents experience problems in their own psychological wellbeing and their family functioning two to four years after their child's epilepsy surgery and whether these problems are associated with epilepsy variables, demographic and cognitive variables, and parent-observed behavior problems of the child. Methods Of the 65 approached families, parents of 31 children participated by completing the Brief Symptom Inventory (BSI), the Family Questionnaire, and the Child Behavior Checklist (CBCL). High scores indicating clinically relevant problems were reported and called ‘problem scores’. Correlations between results of questionnaires and demographic and illness variables (abstracted from medical files) were computed for fathers and mothers separately. By comparing the group with at least one problem score with the group without problem scores, risk factors for parent-perceived problems in their own psychological functioning and in family functioning were explored. Results Thirty percent of the mothers had problem scores on hostility and on communication within their family. Only a few fathers obtained problem scores, most of these pertaining to their family's organization. Not one parent had a problem score regarding their partner relationship. Many parents had problem scores on behavior problems in their child. Brain area of surgery was the only epilepsy variable related to parents' wellbeing and family functioning, with lowest problem scores for the hemispherotomy group. Scores on behavior problems in the child were also lowest for children after hemispherotomy and for those who had achieved freedom of seizures and antiepileptic drugs (AEDs). Fathers of older children experienced more problems than those of young children. Conclusions Parent's wellbeing and family functioning cannot be understood from epilepsy or epilepsy surgery variables only but are related to the child's age and behavior. Having epilepsy is associated with emotional and behavior problems and limits children in developing age-appropriate self-dependence. These problems are not resolved after achieving seizure freedom and have great influence on the family. Professionals should set realistic expectations of epilepsy surgery and should assess, acknowledge, and follow up problems of parental psychological wellbeing and family functioning, regardless of the outcome.

The postsurgical medication policy was reviewed for 109 children (age at surgery, 0-16 years) who had epilepsy surgery between 1991 and 2005. Intervals between surgery and both start (n = 84) and completion (n = 68) of withdrawal of antiepileptic drugs (AEDs) were calculated and analyzed in relation to demographic and epilepsy variables and to recurrent seizures. Postoperative seizure freedom was associated with completeness of surgical resection, defined as complete removal of the cortical region exhibiting ictal or interictal abnormalities on intracranial electroencephalography and lesion on magnetic resonance imaging (P = 0.008). Etiology seemed to be related, but numbers were too small for statistical analysis. In 24 children (22%), seizures recurred postoperatively, and in 19 of these 24 children the AEDs were never withdrawn. Two of the five children in whom seizures recurred after medication withdrawal regained seizure freedom. Mean interval from surgery to start of drug withdrawal was 1.71 years (n = 84), and 2.86 years (n = 68) from surgery to complete withdrawal. Seizure recurrence seemed not associated with withdrawal decisions. Timing of seizure relapse was identical in children still on AEDs and in those who stopped. Eight children with early discontinuation (0.6 years from surgery to start of withdrawal and 0.8 years to complete withdrawal) had no seizure recurrence. Long-term continuation of AEDs is probably not indicated in children with complete resection of the epileptogenic zone. The optimal timing needs to be further explored.

This study reports on the findings of longitudinal follow-up of visual function in a 12-year-old girl affected by congenital right hemihydranencephaly. This extremely rare unilateral brain malformation allowed the authors to gather new information on neuronal plasticity and functional compensations of the visual system across a period of 10 years. An extension of the preserved right visual hemifields above the middle line and strategical eye or head positions developed to increase visual functions are discussed. In addition, ophthalmological and orthoptical findings, as well as the development of monocular grating and linear acuity, are described.

Item does not contain fulltext Objective: Poor performance on confrontation naming tasks by children and adolescents with pharmacologically intractable epilepsy has been interpreted as indicating impairments of lexicon, that is, the store of words in long-term memory. However, confrontation naming performance crucially depends not only on word knowledge but also on other functions such as fluency. We applied an alternative method to assess lexicon with the aim of tracing deficits in lexicon before and after surgery in adolescents with pharmacologically intractable epilepsy. Method: Sixteen patients and 32 age- and sex-matched controls completed the Dutch version of the controlled oral word production task. Responses were used to calculate indices of lexical fluency (retrieval efficiency), lexical breadth (vocabulary size), and lexical depth (knowledge of word properties), as well as use of search strategies. Results: Adolescents with pharmacologically intractable epilepsy had lower lexical fluency scores than healthy peers, but did not differ from them on the dimensions of lexical breadth and lexical depth. Patients demonstrated reduced use of search strategies. In fact, the difference in lexical fluency between patients and controls disappeared after controlling for Full Scale IQ (obtained using the Dutch version of the 3rd edition of the Wechsler Intelligence Scale for Children (WISC–IIINL; Kort et al., 2005; Wechsler, 2002) or—for older children—the Dutch version of the first edition of the Kaufman Adult and Adolescent Intelligence Test (KAIT; Kaufman & Kaufman, 1993; Mulder, Dekker, & Dekker, 2004) and use of search strategies. In patients, changes in the use of the antiepileptic drug carbamazepine were associated with lexical fluency. Conclusion: Adolescents with pharmacologically intractable epilepsy differ from their healthy peers mainly in lexical fluency, rather than word knowledge per se. 9 p.

The authors undertook this study to identify predictors of persistent postoperative seizures in their group of 28 Dutch pediatric and adolescent patients with medically intractable epilepsy who underwent functional hemispherectomy.The records of 28 pediatric and adolescent patients who underwent a functional hemispherectomy in the University Medical Center Utrecht were retrospectively analyzed. The authors performed a Cox regression analysis, using the first postoperative seizure as the event. Pathology, age at surgery, age at seizure onset, duration of epilepsy, type of surgery, surgeon, possible incomplete disconnection on MR images, and presence of residual insular cortex were analyzed as potential associated variables during the follow-up period.The patients' mean age at surgery was 69.9 months (range 3.0-294.2 months) and mean duration of follow-up was 39.0 months (range 6.0-132.0 months). Six patients had postoperative seizures (21%). One patient had persistent bilateral status epilepticus and died 4 months after surgery. The Cox regression analysis showed presence of insular cortex to be the only variable statistically associated with postoperative seizures (p = 0.021) in this group of 28 patients.In this group of Dutch pediatric and adolescent patients, residual insular cortex was positively correlated with persistent postoperative seizures. Given the small sample size in this study, however, caution should be used in drawing conclusions about the role of the insular cortex.

Summary: Purpose: We compared epileptiform activity recorded with EEG and magnetoencephalography (MEG) in 19 patients with tuberous sclerosis complex (TSC) and epilepsy. Methods: High-resolution (HR) EEG, HR-MEG, and 1.5-T MRI scans were performed. Epileptiform spikes were identified in EEG and MEG recordings offline by three observers. Spikes for which the interobserver agreement (spike consensus) was >0.40 were used for source localization with CURRYV 3.0 software. MUSIC analysis was performed. The distance between the source determined from EEG and MEG recordings and the border of the closest tuber was calculated and compared. Results: Consensus spikes (kappa >0.4) were identified in 12 patients in the EEG recording and in 14 patients in the MEG recording. MEG sources were closer to tubers in all but one patient. Three patients underwent epilepsy surgery, two of whom are seizure free after complete resection of the tuber. Conclusions: In patients with TSC, epileptogenic sources identified on MEG are closer to the presumed epileptogenic tuber than are similar sources identified on EEG. Moreover, spike consensus is greater with MEG. Clear identification of the epileptogenic zone may offer opportunities for surgery in patients with TSC with intractable epilepsy.

Purpose To evaluate cerebral abnormalities in childhood idiopathic anatomic megalencephaly (MC) by means of different magnetic resonance (MR) modalities. Materials and Methods MRI, volumetry, spectroscopy, and cerebropetal blood flowmetry were performed in six children with idiopathic anatomic MC, and seven volunteers. Results MRI revealed an increased ventricular system in five of six patients. A thalamic hamartoma was found in one patient and a Chiari I malformation was found in two. Volumetric analysis showed a disproportional increase of ventricular volume but normal subarachnoid cerebrospinal fluid (CSF) volume. Supratentorial volume was disproportionally increased compared to cerebellar volume. Intracranial volume correlated significantly with skull circumference. MR spectroscopy (MRS) N-acetyl aspartate/choline (NAA/Cho) peak ratios in WM were significantly higher in patients than in controls. Choline/creatine (Cho/Cr) peak ratios in WM were significantly lower in patients. Cortical gray matter (GM) MRS ratios were unaltered. Cerebropetal flow was increased in MC, possibly related to increased brain volume. Conclusion This study reveals associated developmental anomalies for idiopathic anatomic MC. A relative ventriculomegaly was found, which should not be misinterpreted as true hydrocephalus. In contrast to metabolic MC, MRS showed no severe disturbances. Total intracranial volume is correlated to skull circumference and cerebropetal blood flow. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Summary: Purpose: To measure outcome of epilepsy surgery in terms of health-related quality of life (HrQoL) and self-perceived competence of children and adolescents. Methods: Prospective longitudinal follow-up study of 21 patients (aged 6.2 to 16.8 years). Frequency and severity of seizures and epilepsy-related restrictions, HrQoL, and self-perceived competence were rated before and 6, 12, and 24 months after epilepsy surgery. Data were analysed nonparametrically and using analysis of variance for repeated measures. Results: Group-wise, seizure parameters had almost normalized 6 months after surgery (p < 0.001) and remained so. Two years after surgery, 15 (72%) patients were free of seizures. At the first postsurgical assessment, parents and children evaluated the frequency of activities as improved and that of seizures as diminished (p < 0.05). Parents evaluated their children as having positive emotions more frequently (p < 0.05). Children started to feel better about seizure variables in the second year after surgery. Two years after surgery, children perceived themselves as being socially more competent and having greater self-worth (p = 0.05). In the adolescent group, several aspects of self-perceived competence improved shortly after surgery (p < 0.05), whereas 2 years after surgery, athletic competence and romance had improved (p < 0.05). Conclusions: In children and adolescents, epilepsy surgery sets the stage for improvement in HrQoL and in competence to participate in social and societal domains. Most improvement occurs in the first 6 months after surgery.

Using high resolution EEG and MEG and a realistic volume conductor model, the authors investigated spatio-temporal aspects of the sources of spikes in children with benign rolandic epilepsy. A 64-channel EEG and simultaneous 151-channel MEG of interictal spike activity in five children all having general and/or focal seizures were recorded. A spatio-temporal multiple signal classification (MUSIC) analysis was performed on the spike data. Sources having a complex spatio-temporal configuration as well as single stationary sources were found. Results for the EEG and MEG were different. In this group of five patients, both high resolution EEG and MEG revealed that in some cases sources well separated in space and time exist, whereas in other cases only single source activity can be resolved. For multiple sources, differences for EEG and MEG in timing and localization of activity suggest that sources are spatio-temporally distributed. Sources can propagate from initial activity in the finger/hand area around the central sulcus down to the mouth/tongue area.

The purpose of this study was to identify early predictors of seizure remission in occipital lobe epilepsy irrespective of syndrome classification i.e. idiopathic or symptomatic occipital lobe epilepsy. Forty-three children with occipital lobe epilepsy had taken part in an earlier study of seizure semiology, neurological deficits, psychomotor/cognitive status, electroencephalography (EEG) and neuroimaging. On the basis of the results of a questionnaire on the state of their epilepsy in 2000, two groups were composed. One group (n=17) consisted of the children with a complete seizure remission of 5 years or more, and the other (n=26) comprised children whose last seizure occurred less than 5 years ago. Our findings indicate that neurological deficit and EEG characteristics can predict 5 year outcome of occipital lobe epilepsy. Neuroradiological abnormality, psychomotor/cognitive status and seizure semiology appear to be of more limited value.

We studied how children with epilepsy (CWE) who are candidates for epilepsy surgery, perceive themselves with respect to overarching personality traits and whether the traits change after surgery. We explored influences of demographic and illness variables. A total of 23 CWE [mean age at inclusion 12.8 (sd 2.3); 12 girls] participated. Using the Dutch Personality Questionnaire Juniors (DPQ-J), we assessed 20 of the CWE shortly before epilepsy surgery and compared the results to those of 39 age- and gender-matched healthy controls. Furthermore, we obtained follow-up scores 6, 12 and 24 months after epilepsy surgery from the clinical group. CWE who were candidates for epilepsy surgery scored above average in inadequacy, perseverance, social inadequacy and recalcitrance, whereas healthy peers scored average. Over the two years' period after epilepsy surgery we found no changes, apart from a decrease of social inadequacy. Sporadic illness and demographic variables were related to some personality traits. However, neither post-surgical seizure freedom nor cessation of AEDs did noticeably change the self-evaluations of CWE. Asking CWE to evaluate their personality themselves may offer a shared basis for individually tailored behavior intervention in order to help them adapting to their ameliorated circumstances after surgery.

Visual memory is vulnerable to epilepsy surgery in adults, but studies in children suggest no change or small improvements. We investigated visual memory after epilepsy surgery, both group-wise and in individual children, using two techniques to assess change: 1) repeated measures analysis of variance (ANOVA) and 2) an empirically based technique for detecting cognitive change [standardized regression-based (SRB) analysis]. A prospective cohort consisting of 21 children completed comprehensive assessments of memory both before surgery (T0) and 6 (T1), 12 (T2), and 24 months (T3) after surgery. For each patient, two age- and gender-matched controls were assessed with the same tests at the same intervals. Repeated measures ANOVA replicated the results of previous studies reporting no change or minor improvements after surgery. However, group analysis of SRB results eliminated virtually all improvements, indicating that the ANOVA results were confounded by practice effects. Standardized regression-based group results showed that in fact patients scored lower after surgery than would be predicted based on their presurgical performance. Analysis of individual SRB results showed that per visual memory measure, an average of 18% of patients obtained a significantly negative SRB score, whereas, on average, only 2% obtained a significantly positive SRB score. At T3, the number of significantly negative SRB scores outweighed the number of significantly positive SRB scores in 62% of patients. There were no clear associations of clinical variables (including side and site of surgery and postsurgical seizure freedom) with memory outcome. The present analysis revealed that given their individual presurgical functioning, many children obtained disappointing results on some visual memory tests after epilepsy surgery. Comparison of the SRB analysis with ANOVA results emphasizes the importance of empirically based techniques for detecting cognitive effects of epilepsy surgery in childhood.

Aim Unilateral perinatal brain injury may result in recruitment of ipsilateral projections originating in the unaffected hemisphere and development of unilateral spastic cerebral palsy (USCP). The aim of this study was to assess the predictive value of neonatal neuroimaging following perinatal brain injury for recruitment of ipsilateral corticospinal tracts. Method Neonatal magnetic resonance imaging (MRI) and cranial ultrasound scans of 37 children (20 males, 17 females; median [range] gestational age 36 wks+4 [26+6–42wks+5] and birthweight 2312 g ([770–5230g]) with unilateral perinatal arterial ischaemic stroke (n=23) or periventricular haemorrhagic infarction (n=14) were reviewed and scored for involvement of the corticospinal trajectory. Hand function was assessed using the Assisting Hand Assessment (AHA) and transcranial magnetic stimulation (TMS) was performed (age range 7y 4mo–18y and 7mo) to determine the type of cortical motor organization (normal, mixed or ipsilateral). Neuroimaging scores were used to predict TMS patterns. Results Eighteen children developed USCP with ipsilateral corticospinal tract projections in 13 children (eight mixed, five ipsilateral). AHA scores decreased with increased ipsilateral projections. Asymmetry of the corticospinal tracts seen on neonatal MRI was predictive of development of USCP and recruitment of ipsilateral tracts (positive and negative predictive value of 73% and 91%). Interpretation Neonatal neuroimaging can predict recruitment of ipsilateral corticospinal tracts. Early knowledge of the expected pattern of cortical motor organization will allow early identification of children eligible for early therapy.

Summary Purpose To investigate verbal memory after epilepsy surgery both group-wise and at the level of individual children, and to assess associations with side of surgery and removal of the temporal lobe. Methods A prospective controlled study in a consecutive sample of 21 children undergoing epilepsy surgery, with comprehensive assessments of verbal memory before surgery and six, 12 and 24 months after surgery. For each patient, two age- and gender-matched controls were tested at similar intervals. Standardized regression-based (SRB) analysis was applied to compare post-surgical change in individual patients with change in controls. Results Group-wise, average normed scores on verbal memory tests were higher after epilepsy surgery than before, corroborating earlier reports. By dint of empirically based SRB analysis, however, considerable individual differences in post-surgical change were revealed. Children with resections that included the left temporal lobe functioned significantly poorer than predicted on the basis of their pre-surgical performance. In contrast, verbal memory performance after surgery was consistent with pre-surgical baseline in the majority of children with resections that spared the left temporal lobe. Conclusions Despite cessation of epileptic seizures, verbal memory remains vulnerable in children who required surgery including the left temporal lobe. In most – but not all – children with other types of surgery, post-surgical verbal memory is consistent with their individual pre-surgical base level.

Purpose To evaluate cognition, behavior, daily functioning and health-related quality of life (HrQoL) five years to more than a decade after hemispherectomy (HE) in childhood. Methods This countrywide Dutch cohort study of 31 patients, who underwent HE between 1994 and 2009, included a semi-structured interview with parents, an assessment of cognition, and screening of behavioral problems and HrQoL. Results Twenty-two school-age children and young adults [median age 13.8 years (0.5 at epilepsy onset, 5.3 at HE)] were assessed with age-appropriate cognitive tests. IQ ranged from 45 to 82 (median 61). Despite performing below mean norm scores, these participants could learn and remember, sustain attention, inhibit irrelevant responses, read and write. Nine more children [median age 9.7 years (0.25 at epilepsy onset, 1.4 at HE)] were so mentally retarded that age-appropriate testing was impossible. This group was almost totally dependent on others in daily activities, had the highest proportion of pre-existing contralateral MRI-abnormalities and after HE the highest rates of seizure recurrence and behavioral problems. Parents in both groups rated HrQoL surprisingly positively (mean VAS-score 72.5), with a scarce low rating (40). All parents reported problems with respect to their children's self-care, daily activities and mobility. Conclusion At least five years after HE, cognitive, behavioral and daily functioning encompasses a broad spectrum that varies from profound retardation and almost total dependence to low normal cognition and a reasonably independent existence. Pre-existing contralateral MRI abnormalities reflect a more generally affected brain with a limited ability to mediate development after HE.

Background How adolescents and their caregivers look back on epilepsy surgery performed in early life, and whether epilepsy-related restrictions are still in force years after the operation, are insufficiently known. Aims To obtain retrospective evaluations of the decision for epilepsy surgery at an early age, and to inventory current epilepsy-related restrictions. Methods Of 177 children who underwent epilepsy surgery between 1992 and 2009, 129 could be approached. They and their parents received a rating list inventorying whether, in retrospect, they would opt again for epilepsy surgery, which were motives for their answer, how successful they felt surgery had been and which, if any, epilepsy-related restrictions were still in force. Results Forty-one of 44 seizure-free adolescents and 9 of 10 adolescents with current seizures were inclined to (re-)opt for surgery. Parents also would in majority re-opt for surgery. Age at surgery, post-surgical interval, nor type of surgery was statistically significantly related with re-opting for surgery. Seizure-freedom was the paramount motive of seizure-free respondents; respondents with current seizures in majority mentioned amelioration of seizures and/or medication. For parents of children with current seizures, a better developmental perspective was another important motive. Rare hesitation/refusal was related to uncertainties in weighing advantages and disadvantages. Current seizures were no reason to consider surgery as a failure. Among children who were free of both seizures and anti-epileptic drugs, 42% lived with restrictions. Conclusions Epilepsy surgery that does not result in seizure freedom is nevertheless felt to be beneficial. Proper advice should prevent meaningless continuation of restrictions.

Relatively few SCN1A mutations associated with genetic epilepsy with febrile seizures-plus (GEFS+) and Dravet syndrome (DS) have been functionally characterized. In contrast to GEFS+, many mutations detected in DS patients are predicted to have complete loss of function. However, functional consequences are not immediately apparent for DS missense mutations. Therefore, we performed a biophysical analysis of three SCN1A missense mutations (R865G, R946C and R946H) we detected in six patients with DS. Furthermore, we compared the functionality of the R865G DS mutation with that of a R859H mutation detected in a GEFS+ patient; the two mutations reside in the same voltage sensor domain of Na(v) 1.1. The four mutations were co-expressed with β1 and β2 subunits in tsA201 cells, and characterized using the whole-cell patch clamp technique. The two DS mutations, R946C and R946H, were nonfunctional. However, the novel voltage sensor mutants R859H (GEFS+) and R865G (DS) produced sodium current densities similar to those in wild-type channels. Both mutants had negative shifts in the voltage dependence of activation, slower recovery from inactivation, and increased persistent current. Only the GEFS+ mutant exhibited a loss of function in voltage-dependent channel availability. Our results suggest that the R859H mutation causes GEFS+ by a mixture of biophysical defects in Na(v) 1.1 gating. Interestingly, while loss of Na(v) 1.1 function is common in DS, the R865G mutation may cause DS by overall gain-of-function defects.

Purpose: To obtain systematic knowledge oflanguage development before and after epilepsysurgery in regions that, if damaged, are known toentaillanguageimpairmentinadults.Methods: Twenty-four children (mean age11 years; range 5.8–15.7 years) with pharmacolog-ically intractable epilepsy participated prior to(the majority) anterior temporal lobectomy and6, 12, and 24 months thereafter. Reception andproduction of lexicon (vocabulary) and syntax(sentence structure including grammar) wereexamined using developmental language teststhatprovidenormativedata.Results: Prior to surgery the mean language delayvaried from 1.7 years (productive syntax) to3.5 years (productive lexicon). For lexicon, lan-guage delay was larger, the older the children; forsyntaxitwassmallerinchildrenwithmotherswithhigher education. Over the 2 years following sur-gery, the children developed in all four languagecomponents. Development was, however, slowerthan normal, that is, language delay increased, inthree of the four components: in productive lexi-con it continued to increase, and in receptive lexi-con and productive syntax it appeared to stabilizeduring the second year. Receptive syntax devel-oped at a normal pace. The development of pro-ductivelexiconwasremarkablyslowwhensurgeryand language mediation were both in the lefthemisphere.Discussion:Pharmacologicallyintractableepilepsyof the temporal lobe, or the underlying condition,is a significant risk factor for delayed languagedevelopment. Temporal epilepsy surgery does notresult in acceleration of language development. Iflanguage is still mediated in the operated lefthemisphere, development of particular languagecomponentsmayslowdownaftersurgery.KEY WORDS: Pediatric, Syntax, Lexicon, Assess-ment,Delay.Resective surgery in children with pharmacologicallyintractable temporal lobe epilepsy reduces seizures orevenleadstotheircessation. Theriskofinflictingdamageto developing cognitive functions such as language,although of major concern in the decision process for oragainst epilepsy surgery in a child, is not yet clear. If theepileptogenic zone necessitates resection of cerebral lefttemporal areas, tissue may be sacrificed that, at least inadults, is essential for language mediation. After pediatricepilepsy surgery, both decline and improvement of lan-guage have been observed during 1 year after surgery(Williams et al., 1998; Dlugos et al., 1999; Lendt et al.,1999; Bell et al., 2002; Sinclair et al., 2003; Gleissneret al., 2005). These previous studies addressed wider cog-nitive functioning and were linguistically limited to spe-cific components such as productive lexicon (naming) orreceptive syntax (understanding of sentences). An impor-tantquestioncancurrentlynotbeanswered,viz.,howdoestheepilepsysurgeryaffectthedevelopmentoflanguageinthese children? To address this question, we examined a

Objective In the majority of patients with tuberous sclerosis complex (TSC) multifocal epileptiform activity is present interictally. Therefore, its value in identifying epilepsy surgery candidates has been doubted. We hypothesize that dominant interictal epileptiform foci are concordant with the ictal onset zone in TSC patients. Methods Consistency and dominance of focal interictal epileptiform activity was assessed in 19 patients with a clinical definite diagnosis of TSC. The ictal onset zone was identified. Concordance between interictal en ictal findings was analyzed. If concordance was found epilepsy surgery was proposed. Results We found dominant, consistently present, focal interictal epileptiform activity in 14 of the 19 patients. Concordance between the dominant interictal focus and the ictal onset zone was found in 11 of the 14 patients (79%). In one patient the ictal onset zone could not be identified and discordance was present in two patients. Epilepsy surgery was performed in six patients rendering three of them seizure free, and one had a seizure reduction >90%. In these patients local concordance was found whereas regional concordance was found in the two patients who did not benefit from epilepsy surgery. Conclusions A dominant as well as a consistent interictal focus is concordant with the ictal onset zone in the majority of TSC patients. Significance Future studies of TSC patients addressing the value of interictal foci in the consideration of epilepsy surgery, in absence of clear ictal onset zone, are necessary.

Objective To determine the prevalence of motor impairments and activity limitations and their inter-relationships in Dutch children with spastic cerebral palsy. Patients and methods In a population-based survey 119 children, age range 6-19 years, with spastic cerebral palsy were examined. Anthropometry, muscle tone, abnormal posture, joint range of motion, major orthopaedic impairments and gross motor functioning and manual ability were assessed or classified, in addition to limitations in mobility and self-care activities. Spearman's correlation coefficients, bivariate post hoc analyses and univariate and multivariate logistic regression analyses were used. Results Children with spastic cerebral palsy had a lower body height and weight compared with typically developing peers. Forty percent had no range of motion deficits. Hip dislocations were rarely encountered. Motor impairments were associated with gross motor functioning and manual ability levels. Close to sixty-five percent walked independently. Children with diplegia and tetraplegia differed in activity limitations. Motor impairments and limitations in mobility and self-care activities were only modestly related in multivariate analyses. Conclusion Distribution of cerebral palsy-related characteristics is consistent with that found in representative studies of other countries. The distinction between diplegia and tetraplegia is relevant from an activity point of view. The child's activity limitations are not a mirror of the motor impairments, which suggests multifactorial influences. An activity-oriented rehabilitation approach goes beyond treating specific impairments.

Purpose: To explore psychosocial effects of rectiole emergency treatment. Methods: Children who had at some time been treated with Stesolid rectiole for seizure relief were questioned about feelings of shame in relation to this treatment and their expectation of bullying by peers who might be aware of it. In addition to parental shame, parental worries concerning their children's epilepsy were explored. Data from 39 patients (18 girls) aged 5-19 years were analysed. Results: Of the children aged over seven, most girls (9/12), but not boys (1/6) reported to feeling a sense of shame. Children's shame was not related to parental shame, parental worries or seizure severity. A higher frequency of rectiole applications was related to a stronger expectation of being bullied. Discussion and conclusion: Rectal emergency medication may elicit social fear, particularly in girls and if recurring it may (not solely in girls) elicit increased expectations of bullying. (c) 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved

Tuberous sclerosis complex (TSC) is often associated with intractable epilepsy. Although epilepsy surgery has gained interest in recent years uncertainties exist about which patients are good surgical candidates. A systematic review of the available literature has been undertaken to assess the overall outcome of epilepsy surgery and identify risk factors of seizure recurrence.We searched MEDLINE, Embase, and bibliographies of reviews and book chapters to identify articles published in English since 1960. Twenty-five articles, describing postoperative seizure outcome and type of surgery in 177 TSC patients, were included in this study. Seizure outcome was analyzed both as seizure freedom and good outcome, including patients with90% seizure reduction.Seizure freedom was achieved in 101 patients (57%). Seizure frequency was improved by90% in 32 patients (18%). Moderate or severe intellectual disability (IQ70) (RR 1.8; 95% CI 1.2-2.8) and the presence of tonic seizures (RR 1.7; 95 % CI 1.2-2.4) were related to seizure recurrence.A relation between multiple seizures types with early onset, multiple cortical tubers and multifocal epileptogenicity, and poor outcome is not supported by this systematic analysis. Although there is considerable variation among studies reviewed here, the literature suggests that resective surgery may offer benefit in a selected population of TSC patients with drug-resistant epilepsy.

The aim of this study was to examine whether severity of epilepsy, motor functioning, and epilepsy-related restrictions change in children with medically intractable epilepsy who are ineligible for epilepsy surgery. The study was a prospective, longitudinal, 2-year follow-up of 28 children (14 females, 14 males). Their median age was 6 years 1 month (range 7mo-15y 4mo). Seizure types were: complex partial seizures (n=16), secondary generalized seizures (n=7), simple partial seizures (n=2), and mixed seizures (n=3). Severity of seizures, motor impairments, motor development, activities of daily life, and epilepsy-related restrictions were rated at baseline and 6, 12, and 24 months thereafter. Seizure severity did not change significantly, nor did muscle strength, range of motion, or muscle tone. Motor retardation was ubiquitous but did not increase in 20 children without spasticity. Motor function of eight children with spasticity improved (Gross Motor Function Measure: baseline 70.5 [SD 35.5]; 24 months later 81.6 [SD 29.6], p < 0.05) but remained below reference values in four children. In the entire group, functional skills increased and caregiver assistance lessened. Restrictions did not change significantly. We conclude that during a 2-year follow-up period, in children with medically intractable epilepsy who do not have surgical intervention, seizure severity does not deteriorate, motor impairments do not increase, motor development does not deflect negatively, and activities of daily living and restrictions do not worsen.

Joubert syndrome (JBS) is a clinically variable and genetically heterogeneous developmental brain disorder with autosomal recessive inheritance. Five genes, AHI1, NPHP1, CEP290, MKS3, and RPGRIPIL, and two additional loci on chromosome 9 and I I have been identified so far. The relative contributions of AHI1 mutations and NPHP1 deletions have not yet been determined in a population-based JBS patient cohort. We therefore undertook a nationwide survey of JBS in the Netherlands and performed DNA analysis of the AHI1 and NPHP1 genes, as well as a new candidate gene CYCLIN D1. We obtained clinical data and DNA samples of 25 Dutch JBS patients. DNA analysis of AHI1 revealed pathogenic homozygous or compound heterozygous AHI1 mutations in four patients (16%). Based on the birth prevalence of about I in 100,000 for JBS in the Netherlands, we estimated a carrier frequency of AHI1 mutations of approximately 1 in 400. In another two patients, the AHI1 mutation Arg830Trp was identified (homozygously and heterozygously), a possible low penetrance allele. No deletions of NPHP1 or CYCLIN D1 mutations were detected in these 25 patients. In the four patients with AHI1 mutations, retinal disease (Leber congenital amaurosis or retinal dystrophy) was present in two, whereas none had renal disease. Pooling our data and data from the literature, retinal disease seems to occur in 75% of AHI1-associated JBS patients. Renal disease is present in 10% at most. We conclude that AHI1 mutations are an important cause of JBS in Dutch patients, and should always be looked for in patients suspected of JBS, especially when retinal dystrophy is present. Patients with AHI1 mutations should be regularly checked for retinal and renal disease up until adolescence. (c) 2007 Published by Elsevier Masson SAS.

Purpose We present the outcome of resective epilepsy surgery in 69 pediatric patients who participated in the Dutch Collaborative Epilepsy Surgery Program (DCESP) between 1992 and 2002 with special emphasis on long-term follow-up. Methods Sixty-nine children (aged 3 months to 17 years) operated on before 2003 were included in this study (34 temporal resections (49%), 17 extra-temporal resections (24%) and 19 hemispherectomies (27%)). Engel classification was used to assess seizure outcome annually. Cognitive outcome was assessed if possible. Two telephone surveys were carried out with an interval of 2½ years to obtain data on seizure frequency, use of AEDs and on aspects op psychosocial development. Kaplan–Meier survival curves were constructed to assess recurrence of seizures after initial postsurgical seizure freedom, based on both telephone surveys. Results Seventy percent scored Engel 1, 18% Engel 2, 6% Engel 3 and 6% Engel 4 at the time of the first telephone survey (2½ years later: 77% Engel 1, 8% Engel 2, 12% Engel 3 and 3% Engel 4). Temporal resections were associated with the best seizure outcome (Engel 1 74% and 82%). AEDs could be withdrawn successfully in 53% of patients at time of the last follow-up. No negative impact on cognition was found. The first long-term follow-up (mean 4.5 years after surgery) measurement showed recurrence of seizures after initial seizure freedom in 17%. At time of the second long-term follow-up measurement (mean 7.5 years after surgery) this percentage had increased to 21%. Conclusions Our results support previous reports that surgery for intractable epilepsy in pediatric patients can be safely performed with satisfactory long-term results. Best results are attained in temporal resections.

Summary: Purpose: We addressed consistent localization of focal interictal epileptiform activity on EEGs of patients with tuberous sclerosis complex (TSC) and epilepsy. Methods: Twenty-one patients with TSC with a 10-year history of epilepsy and interictal epileptiform activity in three or more EEG recordings were included. None of the patients had undergone epilepsy surgery. Local maxima of interictal epileptiform activity were measured from 76 EEG traces and 33 EEG reports. Information about the patients' clinical course was extracted from their medical records. Magnetic resonance imaging (MRI) and neuropsychological examinations were performed. Statistical analysis was performed with the Mann–Whitney U test. Results: In eight patients, interictal epileptiform activity was consistently detected in one or two regions (group 1), and in 13 patients, epileptiform activity was detected in three or more regions (group 2). The number of foci increased throughout the disease course in both groups. Age at seizure onset and IQ were significantly higher in group 1. Complex partial seizures occurred more often in the patients of group 1. In 19 of the 21 patients, the most consistent epileptiform activity was localized in the frontotemporal region. Conclusions: Ninety percent of patients with TSC showed at least one region of consistent interictal epileptiform activity. Patients with one or two regions of epileptiform activity were older at seizure onset, often experienced complex partial seizures, and had mild or no mental deficits. These patients may be candidates for epilepsy surgery.

Localization of vital components of neurological functioning has to be performed before epilepsy surgery can be considered in children with intractable epilepsy. This study reports the experience with the Wada procedure in very young children and/or developmentally delayed children with an a priori considerable chance of failing the procedure. The aim of this study was to indicate the applicability of this procedure in this patient group. The Wada procedure is described in 16 children under 10 years of age and/or have intelligence quotient scores below 50 and/or are critically ill and/or are behaviourally disturbed. Information on motor, language and memory functioning is obtained in respectively 13/15, 9/13, and 5/11 children. Nine children underwent epilepsy surgery without postoperative impairment of neurological functioning. In five children epilepsy surgery was not performed because of the results of the Wada procedure or the lack of information during the Wada procedure. One child became seizure-free before surgery. Even in very young, developmentally delayed or behaviourally disturbed children, the Wada test can provide important information with respect to the decision pro or contra epilepsy surgery.

Children with perinatally acquired parenchymal haemorrhage are thought to have better visual perceptual skills than those with leukomalacia. We examined seven prematurely born children with parenchymal haemorrhage and 14 with grades 2-4 leukomalacia, at the age of 5 years. Clinical and magnetic resonance imaging parameters were related to visual perceptual performance assessed with the L94, using performance age. Belonging to the leukomalacia group, the inability to walk, a diminished peritrigonal white matter, a high degree of gliosis and cortical damage were associated with poorer visuo-perceptual skills. Enlarged lateral ventricles, confirming the findings of Melhelm (Radiology 214 (2000) 199), were associated with both cognitive, perceptual and motor problems and probably reflect the considerable extent of the brain damage. Specific factors protecting against visual perceptual impairment were a preserved volume of the right optical radiation and of the splenium of the corpus callosum. Children with leukomalacia are at considerable risk of visual perceptual impairment. Children with right-sided parenchymal haemorrhages also appear to be at risk although they function much better due to better motor and cognitive skills.

To study the selectivity of visual perceptual impairment in children with early brain injury, eight visual perceptual tasks (L94), were administered to congenitally disabled children both with and without risk for cerebral visual impairment (CVI). The battery comprised six object-recognition and two visuoconstructive tasks. Seven tasks were newly designed. For these normative data are presented (age 2.75-6.50 years). Because the recognition tasks required object naming, each item included a canonical control drawing and visual perceptual ability was evaluated relative to the non-verbal intelligence level, instead of chronological age. In 22 multiple disabled children with no indications of CVI, the frequency of impairment did not exceed that in the reference sample for any L94 task. In contrast, in 57 5-year-old children who were at risk for CVI due to pre-maturity or birth asphyxia, a significant increase in the frequency of impairment was seen on six L94 tasks (range 12-38%). However, only five children had more than two impairments, indicating that the deficits were selective, not pervasive. We conclude that early brain lesions interfere with the functioning of particular visual subsystems, yet leave other subsystems intact and functioning within the normal range.

Summary: Background and Purpose: Inducing sleep deprivation is supposed to increase interictal epileptic discharges on EEGs from children suspected of having epilepsy. Although it is supposed that depriving a child from sleep is a burden for both child and parent, this assumption has not been investigated in any study so far. Methods: To analyze the perception of the sleep deprivation procedure, we developed two questionnaires, one for the parent and one for the child over ten years of age at the time of the SDEEG. These questionnaires were sent to parents of all 179 patients and 47 children (older than ten) from which a SDEEG was obtained because of suspected epilepsy. A total of 103 questionnaires were returned by the parents and 18 by the children. The extent to which the SDEEG turned out to be inconvenient was assessed with regard to issues that covered the psychological and physical impact of the SDEEG. Results: Our results showed that the whole procedure of the SDEEG proved to be a burden for 18.6% of the parents and 23.5% of the children. 49.6% of the parents reported complaints including their child- like fatigue, illness and in 2 cases even an increase in seizure frequency. Overall, 47.1% of the children described having symptoms the next day. These consisted mainly of fatigue. Conclusion: Our survey shows that the SDEEG places a notable burden on both parent and child. This should be taken into consideration before requesting an SDEEG.