A follow-up study of cognitive function in young adults who had resective epilepsy surgery in childhood.

This study examined cognitive function in young adults who had epilepsy surgery in childhood. Thirty-seven individuals with medically intractable epilepsy with onset at 16 years or younger who had resective epilepsy surgery at least two years in the past (mean follow-up duration of 8.5 years) were assessed; of these, 13 had seizures within the year prior to the study, and the remainder had none. A comparison group of 16 individuals with childhood-onset intractable epilepsy who had not had surgery, all of whom had experienced at least one seizure in the past 12 months, was also included. The cognitive tests included measures of vocabulary, visuoconstructive ability, memory, and concept formation. Group differences were found only for the vocabulary and verbal memory tests, with the surgical group with seizures having the lowest performance. A subset of the surgical patients had preoperative data available on comparable tests, allowing for an examination of performance over time. Vocabulary scores were higher at follow-up, a finding which was present irrespective of seizure status. The results suggest that after epilepsy surgery in childhood or adolescence, few improvements in cognitive skills related to surgery or seizure outcome are to be expected.

Determinants of quality of life in children with chronic somatic disease: pilot data from the GapS Questionnaire.

PURPOSE: Quality of life (QoL) is a ubiquitous yet poorly defined concept; the precise determinants of QoL are rarely identified. We used pilot data from the GapS Questionnaire to investigate the most important determinants of QoL in children with chronic somatic illness. METHODS: We enrolled 92 participants including 60 parents and 32 of their children. The sample comprised rheumatology, diabetes, epilepsy, gastroenterology, cystic fibrosis, and day unit patients. Trained interviewers administered the GapS Questionnaire to parents, and to children if ≥ 10 years. We determined the relative importance of different items for QoL. RESULTS: Child participants had a mean age of 14.7 years. Children identified "having good friendships", "being happy most days", and "getting along with parents" as most important. Parents ranked most highly "being allowed to do all the things you like doing", "getting told you have done a good job at something", and "being physically able to do everything you enjoy doing". CONCLUSIONS: Physical health items were not as important as social and psychological determinants of QoL in our pilot sample.

Quality of life in young adults who underwent resective surgery for epilepsy in childhood.

PURPOSE: This study investigated quality of life (QOL) in young adults who had undergone epilepsy surgery before the age of 16 years. The contribution to QOL of seizure status in the prior year, sex, number of antiepileptic drugs, and mood were evaluated. METHODS: Sixty-nine young adults who had undergone surgery were subdivided into those who were seizure-free in the past year (n = 38) and those who had seizures (n = 31) in that time. A nonsurgical comparison group of young adults (n = 29) with childhood-onset medically intractable epilepsy was also studied. All groups completed measures of QOL and mood. KEY FINDINGS: After accounting for mood, sex, and number of antiepileptic drugs, the seizure-free group reported better cognitive and physical function and overall QOL, experienced less seizure worry, and had better self-perception. Mood was the most consistently predictive covariate, and was independently predictive of many aspects of QOL. SIGNIFICANCE: Seizure freedom associated with surgery in childhood is associated with improved QOL in certain domains. Findings highlight the importance of mood in determining self-perception of QOL.

Self-reported symptoms of psychological well-being in young adults who underwent resective epilepsy surgery in childhood.

PURPOSE: This study investigated the relationship of childhood resective surgery for lesional epilepsy and recent seizure history on self-reported symptoms of mood and psychological distress in young adults (aged 18-30). METHODS: Ninety-eight individuals with epilepsy of childhood onset were divided into three groups: a seizure-free surgical group (n = 39), a surgical group still experiencing seizures (n = 31), and a nonsurgical epilepsy comparison group (n = 28). Participants completed two standardized questionnaires about current mood state and psychological and psychiatric symptoms: the Profile of Mood States (POMS) and the Symptom Checklist-90 Revised (SCL-90R). KEY FINDINGS: Forty-eight percent of all participants reported a history of psychological problems. The percentage of the seizure-free surgical group who met the SCL-90R criteria for current clinically significant distress was statistically less than in the other groups. Those who were seizure free also reported significantly fewer total symptoms on the SCL-90R. The current number of antiepileptic medications was related to scores on a number of the scales. SIGNIFICANCE: These results provide modest support for the contention that seizure freedom after pediatric epilepsy surgery is associated with reduced risk for psychological distress during early adulthood.

Topographic movie of intracranial ictal high-frequency oscillations with seizure semiology: epileptic network in Jacksonian seizures.

PURPOSE: We developed a technique to produce images of dynamic changes in ictal high-frequency oscillations (HFOs) >40 Hz recorded on subdural electroencephalography (EEG) that are time-locked to the ictal EEG and ictal semiology video. We applied this technique to Jacksonian seizures to demonstrate ictal HFO propagation along the homunculus in the primary sensory-motor cortex to visualize the underlying epileptic network. METHODS: We analyzed intracranial ictal EEGs from two patients with intractable Jacksonian seizures who underwent epilepsy surgery. We calculated the degrees of increase in amplitude within 40-80, 80-200, and 200-300 Hz frequency bands compared to the interictal period and converted them into topographic movies projected onto the brain surface picture. We combined these data with the ictal EEGs and video of the patient demonstrating ictal semiology. KEY FINDINGS: The ictal HFOs began in the sensory cortex and appeared concomitantly with the sensory aura. They then propagated to the motor cortex at the same time that focal motor symptoms evolved. As the seizure progressed, the ictal HFOs spread or reverberated in the rolandic region. However, even when the seizure became secondarily generalized, the ictal HFOs were confined to the rolandic region. In both cases, there was increased amplitude of higher frequency bands during seizure initiation compared to seizure progression. SIGNIFICANCE: This combined movie showed the ictal HFO propagation corresponding to the ictal semiology in Jacksonian seizures and revealed the epileptic network involved in seizure initiation and progression. This method may advance understanding of neural network activities relating to clinical seizure generation and propagation.

Focal resection of fast ripples on extraoperative intracranial EEG improves seizure outcome in pediatric epilepsy.

PURPOSE: High-frequency oscillations (HFOs), termed ripples at 80-200 Hz and fast ripples (FRs) at >200/250 Hz, recorded by intracranial electroencephalography (EEG), may be a valuable surrogate marker for the localization of the epileptogenic zone. We evaluated the relationship of the resection of focal brain regions containing high-rate interictal HFOs and the seizure-onset zone (SOZ) determined by visual EEG analysis with the postsurgical seizure outcome, using extraoperative intracranial EEG monitoring in pediatric patients and automated HFO detection. METHODS: We retrospectively analyzed 28 pediatric epilepsy patients who underwent extraoperative intracranial video-EEG monitoring prior to focal resection. Utilizing the automated analysis, we identified interictal HFOs during 20 min of sleep EEG and determined the brain regions containing high-rate HFOs. We investigated spatial relationships between regions with high-rate HFOs and SOZs. We compared the size of these regions, the surgical resection, and the amount of the regions with high-rate HFOs/SOZs within the resection area with seizure outcome. KEY FINDINGS: Ten patients were completely seizure-free and 18 were not at 2 years after surgery. The brain regions with high-rate ripples were larger than those with high-rate FRs (p = 0.0011) with partial overlap. More complete resection of the regions with high-rate FRs significantly correlated with a better seizure outcome (p = 0.046). More complete resection of the regions with high-rate ripples tended to improve seizure outcome (p = 0.091); however, the resection of SOZ did not influence seizure outcome (p = 0.18). The size of surgical resection was not associated with seizure outcome (p = 0.22-0.39). SIGNIFICANCE: The interictal high-rate FRs are a possible surrogate marker of the epileptogenic zone. Interictal ripples are not as specific a marker of the epileptogenic zone as interictal FRs. Resection of the brain regions with high-rate interictal FRs in addition to the SOZ may achieve a better seizure outcome.

Ethical issues in surgical decision making concerning children with medically intractable epilepsy.

The widespread inclusion of surgical strategies in the treatment of medically intractable epilepsy is largely justified by the medical and psychosocial burden of the illness. Performing these procedures in pediatric populations is associated with distinct challenges ranging from unique seizure etiologies to issues surrounding brain development and functional plasticity. As the trend toward more aggressive surgical intervention continues, the ethical foundation of current and emerging practices must be increasingly scrutinized. Here, we present the first article discussing ethical issues in the surgical management of medically intractable epilepsies in children. We discuss principles of informed consent, harm reduction, and justice in this vulnerable patient population. We also highlight the unique ethical challenge of surgical decision making concerning developmentally delayed children. The recognition of these issues is essential to providing patient-centered, responsible, and ethical care.

Patient-reported outcome of pediatric epilepsy surgery: social inclusion or exclusion as young adults?

PURPOSE: The purpose of this study was to examine the social relationships and participation in educational, vocational, and community life in young adults who had undergone epilepsy surgery during childhood or adolescence. METHODS: This was a retrospective, cross-sectional, case-controlled, and multisite design study. Findings were compared between young adults who had undergone epilepsy surgery and were seizure-free in the previous 12 months (n = 38), those who had undergone epilepsy surgery and were not seizure-free (n = 33), and a group of individuals with epilepsy who had not undergone surgery (n = 31). RESULTS: The surgical seizure-free group had significantly better general social well-being than the other two groups. Specifically, these participants were employed for more months over the past year, were less likely to report that epilepsy had affected their employment, and were more likely to belong to at least one community organization. However, these participants were not any more likely to be involved in a relationship than those in the other two groups. In addition, there were no group differences in the reported number of friends or the frequency of visits with friends, or in what participants described as their principal activity (i.e., student, employed or unemployed). DISCUSSION: There are a number of benefits to social functioning associated with having had epilepsy surgery and being seizure-free in the past year. Further research is recommended to increase our understanding of the mechanisms involved in the social and personal challenges that these individuals face.

Self-perceptions of social function 2 years after pediatric epilepsy surgery.

The present qualitative study explored how participants perceive their quality of life within the social domain 2 years following epilepsy surgery. Semistructured, open-ended interviews were conducted with 27 participants (11-21 years old), 2 years following epilepsy surgery. Thirteen of the 27 participants were seizure free. Data were transcribed and coded inductively to allow for the identification of salient themes. Many of the seizure-free participants reported greater independence following surgery. However, most participants, irrespective of seizure status, continued to report some problems with peer relations and isolation. These findings suggest that self-perceived improvements in social function among seizure-free participants may require longer than 2 years to develop.

Sex differences in episodic memory among children with intractable epilepsy.

This study investigated whether children with epilepsy exhibit sex differences in episodic memory. Fifty-one children and adolescents (26 boys and 25 girls) with intractable epilepsy were administered two verbal-auditory tasks (learning and recall of a word list and story recall) and two visual tasks (design recall and face recognition). Girls exhibited an advantage on the delayed recall of stories and on the learning phase of the word list task. No significant differences were observed on the delayed recall of words or the visual tasks. These results identify a particular risk for cognitive impairment in boys that could have an important impact on their academic performance.

Memory outcome after pediatric epilepsy surgery: objective and subjective perspectives.

Memory was investigated in 27 children and adolescents in a longitudinal study before and at one and two years after epilepsy surgery. A comparison group with intractable epilepsy (n = 15), matched in age, sex, age of seizure onset, and IQ, was studied at comparable points in time. Methods included administration of standardized measures of story recall and face recognition, and qualitative interviews to probe the participants' perceptions of their memory function over time. There was no significant change over time in either group on the standardized measures. Site and laterality of excision, age at surgery, and seizure outcome were not predictive of change within the surgical group. The narratives revealed facets of memory that were problematic in daily life. The objective and subjective results showed low concordance regarding change, possibly due to limitations in the objective measures for capturing semantic and autobiographical memory.

Characterizing magnetic spike sources by using magnetoencephalography-guided neuronavigation in epilepsy surgery in pediatric patients.

OBJECT: The authors sought to validate magnetoencephalography spike sources (MEGSSs) in neuronavigation during epilepsy surgery in pediatric patients. METHODS: The distributions of MEGSSs in 16 children were defined and classified as clusters (Class I), greater than or equal to 20 MEGSSs with 1 cm or less between MEGSSs; small clusters (Class II), 6 to 19 with 1 cm or less between; and scatters (Class III), less than 6 or greater than 1 cm between spike sources. Using neuronavigation, the MEGSSs were correlated to epileptic zones from intra- and extraoperative electrocorticography (ECoG), surgical procedures, disease entities, and seizure outcomes. Thirteen patients underwent MEGSSs: nine had clusters; two had small clusters, one with and one without clusters; and three had scatters alone. All 13 had scatters. Clusters localized within and extended from areas of cortical dysplasia and at margins of tumors or cystic lesions. All clusters were colocalized to ECoG-defined epileptic zones. Four of 10 patients with clusters and/or small clusters underwent complete excisions, and six underwent partial excision with or without multiple subpial transections. In the three patients with scatters alone, ECoG revealed epileptic zones buried within MEGSS areas; these regions of scatters were completely excised and treated with multiple subpial transections. Coexisting scatters were left untreated in nine of 10 patients. Postoperatively, nine of 13 patients were seizure free; the four patients with residual seizures had clusters in unresected eloquent cortex. Three patients in whom no MEGSSs were demonstrated underwent lesionectomies and were seizure free. CONCLUSIONS: Magnetoencephalography spike source clusters indicate an epileptic zone requiring complete excision. Coexisting scatters remote from clusters are nonepileptogenic and do not require excision. Scatters alone, however, should be examined by ECoG; an epileptic zone may exist within these distributions.

Identifying the primary epileptogenic hemisphere from electroencephalographic (EEG) and magnetoencephalographic dipole lateralizations in children with intractable epilepsy.

We used electroencephalographic (EEG) and magnetoencephalographic dipole lateralizations to identify the primary epileptogenic hemisphere in 41 children with intractable localization-related epilepsy. We compared EEG and magnetoencephalographic dipole lateralizations, EEG ictal onsets, and magnetic resonance images (MRIs). Concordant lateralization of EEG and magnetoencephalographic dipoles (> 50% of each lateralizing to the same hemisphere) occurred in 34 patients, with EEG ictal onsets in the same hemisphere in 23 (68%) and concordant MRI lesions in 23 (68%). Focal resection in 16 of 20 patients resulted in a good surgical outcome. Of the seven children with nonconcordant magnetoencephalographic and EEG lateralizations, one (14%) had EEG ictal onset and one (14%) had MRI lesions that lateralized; none had surgery. The relationship between lateralized EEG and magnetoencephalographic dipoles forecasts surgical candidacy. Concordant lateralizations predict good seizure control after surgery by identifying the primary epileptogenic hemisphere. Discordant lateralizations signify an undetermined epileptogenic hemisphere and contraindicate surgery without further testing.

Complications of invasive subdural grid monitoring in children with epilepsy.

OBJECT: This study was performed to evaluate the complications of invasive subdural grid monitoring during epilepsy surgery in children. METHODS: The authors retrospectively reviewed the records of 35 consecutive children with intractable localization-related epilepsy who underwent invasive video electroencephalography (EEG) with subdural grid electrodes at The Hospital for Sick Children between 1996 and 2001. After subdural grid monitoring and identification of the epileptic regions, cortical excisions and/or multiple subpial transections (MSTs) were performed. Complications after these procedures were then categorized as either surgical or neurological. There were 17 male and 18 female patients whose mean age was 11.7 years. The duration of epilepsy before surgery ranged from 2 to 17 years (mean 8.3 years). Fifteen children (43%) had previously undergone surgical procedures for epilepsy. The number of electrodes on the grids ranged from 40 to 117 (mean 95). During invasive video EEG, cerebrospinal fluid leaks occurred in seven patients. Also, cerebral edema (five patients), subdural hematoma (five patients), and intracerebral hematoma (three patients) were observed on postprocedural imaging studies but did not require surgical intervention. Hypertrophic scars on the scalp were observed in nine patients. There were three infections, including one case of osteomyelitis and two superficial wound infections. Blood loss and the amounts of subsequent transfusions correlated directly with the size and number of electrodes on the grids (p < 0.001). Twenty-eight children derived significant benefit from cortical resections and MSTs, with a more than 50% reduction of seizures and a mean follow-up period of 30 months. CONCLUSIONS: The results of this study indicate that carefully selected pediatric patients with intractable epilepsy can benefit from subdural invasive monitoring procedures that entail definite but acceptable risks.

Adolescent and Maternal Perspectives of Quality of Life and Neuropsychological Status Following Epilepsy Surgery.

A convenience sample of 13 adolescents who had undergone epilepsy surgery and their mothers reported their perceptions of change in areas affecting quality of life (physical, affect/behavior, social, cognition/academics, and family). A mixed method approach was used, with self-report and maternal-report narratives (qualitative measures), as well as neuropsychological profiles (quantitative measures). The results demonstrate that change after epilepsy surgery is multifaceted, and that adolescent and maternal perceptions are notably different. Whereas most adolescents experienced positive changes, mothers simultaneously reported many more negative changes along with positive changes. Furthermore, mothers frequently described aspects of their adolescent's life that continued to be of concern, whereas adolescents did not. The findings strongly suggest that the processes involved in postsurgical adjustment are complex. The development of a theoretical model is essential to help build an understanding of factors that contribute to positive and negative outcomes.

Characteristics of prolonged afterdischarges in children with malformations of cortical development.

We investigated aberrant cortical excitability in malformations of cortical development From subdural electrodes, we recorded afterdischarges lasting > or = 6 seconds in 12 of 13 patients with malformations of cortical development and 6 of 10 pediatric patients with nonmalformations of cortical development and reviewed amperage thresholds, distribution of afterdischarges, and motor responses. In patients with malformation of cortical development, motor response thresholds were high; afterdischarge and motor response thresholds, which essentially overlapped, inversely correlated with age (P < .01); afterdischarge thresholds declined with age; and 8 patients showed afterdischarges in remote sites. In nonmalformation of cortical development, afterdischarge thresholds did not significantly correlate with age; motor response thresholds tended to decline with age; and 2 patients had remote afterdischarges. Adolescent patients with malformations of cortical development had lower afterdischarge thresholds than adolescents with nonmalformation of cortical development (P < .05). From their high afterdischarge (and motor response) thresholds, we concluded that preadolescent patients with malformation of cortical development have less excitable, immature cortices, whereas adolescent patients with malformation of cortical development with low afterdischarge thresholds have hyperexcitable cortices. Remote afterdischarges over focal dysplastic cortex suggest aberrant cortical excitability and neural circuits.

Electroencephalographic dipoles of spikes with and without myoclonic jerks caused by epilepsia partialis continua.

We used electroencephalographic (EEG) dipole analysis to investigate the generators of spikes with and without myoclonic jerks in a 12-year-old patient with epilepsia partialis continua secondary to left parietal cortical dysplasia. We recorded EEG and right wrist extensor electromyography (EMG) and collected 42 spikes with jerks (jerking spikes) and 42 spikes without jerks (nonjerking spikes). We applied a single moving dipole model to the individual and averaged spikes. Dipoles at the negative peak of individual jerking and nonjerking spikes were localized in the dysplastic area. At the onset of the averaged jerking spike that preceded the EMG discharges by 20 ms, the dipole was in the motor cortex, whereas for the averaged nonjerking spike, the dipole was in the sensory cortex. The dipole moment at averaged jerking spike onset was twice that of the averaged nonjerking spike. Electroencephalographic dipole analysis of averaged spikes differentiated the generator of jerking and nonjerking spikes in epilepsia partialis continua. Individual dipoles demonstrated the area of epileptogenic cortical dysplasia.

Source localization of interictal spike-locked neuromagnetic oscillations in pediatric neocortical epilepsy.

OBJECTIVE: To evaluate the utility of an event-related beamforming (ERB) algorithm in source localization of interictal discharges. METHODS: We analyzed interictal magnetoencephalography data in 35 children with intractable neocortical epilepsy. We used a spatiotemporal beamforming method to estimate the spatial distribution of source power in individual interictal spikes. We compared ERB results to source localization using the equivalent current dipole model and to the seizure onset zones on intracranial EEG. RESULTS: Focal beamformer localization was observed in 66% of patients and multifocal in the remaining 34%. ERB localized within 2 cm of the equivalent current dipole cluster centroid in 77% of the patients. ERB localization was concordant with the seizure onset zone on intracranial EEG at the gyral level in 69% of patients. Focal ERB localization area was included in the resection margin in 22/23 patients. However, focal ERB localization was not statistically associated with better surgical outcome. CONCLUSIONS: ERB can be used for source localization of interictal spikes and can be predictive of the ictal onset zone in a subset of patients with neocortical epilepsy. SIGNIFICANCE: These results support the utility of beamformer source localization as a fast semi-automated method for source localization of interictal spikes and planning the surgical strategy.

Epilepsy and cysticercosis in Northwest Cameroon: a serological study.

PURPOSE: The prevalence of epilepsy in Cameroon is higher than that of the industrialized world and other developing countries. Neurocysticercosis due to Taenia solium infestation has been reported as a major cause of epilepsy in some parts of Cameroon although there are some conflicting data. The prevalence of epilepsy is especially high in the Momo division of the North-West Province of Cameroon. We hypothesized that individuals with epilepsy in this region have a higher percentage of seropositivity to T. solium than matched controls. METHODS: We conducted a case-control study in the Momo subdivision of Ngie. Individuals with epilepsy were recruited from the health centers in Ngie. Control subjects were selected from 19 Ngie villages. Potential cases of people with epilepsy (PWE) were identified through a questionnaire applied by trained field workers, using history of epileptic seizures as a key indicator. Blood samples were taken from all consenting individuals by finger prick, stored in StabilZyme Select, and assayed for antibodies to T. solium in an Atlanta based reference laboratory. RESULTS: We accrued 249 patients with epilepsy, of whom 237 met the inclusion criteria, and 245 age-matched controls. There was no significant difference in seropositivity to T. solium between those individuals with epilepsy (5%) and controls (4.9%). CONCLUSIONS: Our data do not support the hypothesis that epilepsy is associated with seropositivity to T. solium. It is highly unlikely that cysticercosis plays a causative role in the high prevalence of epilepsy in this region of Cameroon.

Access to surgery for paediatric patients with medically refractory epilepsy: a systems analysis.

PURPOSE: A systems analysis perspective was undertaken to evaluate access to surgery for children with medically refractory epilepsy (MRE) in Ontario, the largest province in Canada. The analysis focused on the assessment of referral patterns, healthcare utilization, time intervals and patient flow to determine surgical candidacy in children with MRE. The purpose of this systems analysis study was to identify rate limiting steps that may lead to delayed surgical candidacy decision and surgery. METHODS: Prolonged video electroencephalography (vEEG) is the common entry point into the process for all potential epilepsy surgery candidates. Therefore, a single centre retrospective chart review of children and adolescents referred to the epilepsy monitoring unit (EMU) for vEEG monitoring at the primary referral centre for paediatric epilepsy surgery in the province. Basic demographic and referral data were abstracted for all screened cases. Included cases were: (1) age <19 years old at time of first EMU admission, (2) date of EMU admission between April 1, 2004 and March 31, 2006 and (3) referral for elective vEEG and/or overnight with vEEG greater than 8h duration. Data were collected on number of seizure conferences, surgical candidacy, surgical outcomes (seizure free and seizure reduction), resource utilization, and recorded time stamps for each event to estimate system delays. RESULTS: During the two-year period, 463 patients were referred to the EMU of whom 349 received prolonged vEEG (>8h). Forty five percent (n=160) of patients came to seizure conference for discussion of their data, of whom 40% (64/160) were considered surgical candidates. Time from first seizure to EMU referral was approximately 4.6 years. Time from referral to admission and admission to first seizure conference were approximately 103 days and 71 days, respectively. From initial EMU referral to surgery ranged from 1.6 to 1.1 years depending on whether the patient required invasive monitoring with intracranial EEG. Overall, 95% of surgical patients had a reduction in seizure frequency, 74% were seizure free after one year post-surgery. SIGNIFICANCE: Referral rates for surgical assessment are low relative to the estimated number of children living with MRE in Ontario, less than 2%. Hence, only a limited number of children with this disorder in the province of Ontario who could benefit from epilepsy surgery are being assessed for surgical candidacy. The majority of Ontario children with MRE are not being provided the potential opportunity to be seizure free and live without functional limitations following surgical intervention. These data document the critical need for health system redesign in Ontario, the goal of which should be to provide more consistent and just access to evidence-based medical and surgical care for those citizens of the province who suffer from epilepsy.