Determinants of Functional Outcome after Pediatric Hemispherotomy.

OBJECTIVE: We aimed to evaluate determinants of functional outcome after pediatric hemispherotomy in a large and recent multicenter cohort. METHODS: We retrospectively investigated the functional outcomes of 455 children who underwent hemispherotomy at 5 epilepsy centers in 2000-2016. We identified determinants of unaided walking, voluntary grasping with the hemiplegic hand, and speaking through Bayesian multivariable regression modeling using missing data imputation. RESULTS: Seventy-five percent of children were seizure-free, and 44% stopped antiseizure medication at a 5.1-year mean follow-up (range = 1-17.1). Seventy-seven percent of children could walk unaided, 8% could grasp voluntarily, and 68% could speak at the last follow-up. Children were unlikely to walk when they had contralateral magnetic resonance imaging (MRI) abnormalities (40/73, p = 0.04), recurrent seizures following hemispherotomy (62/109, p = 0.04), and moderately (50/61, p = 0.03) or severely impaired (127/199, p = 0.001) postsurgical intellectual functioning, but were likely to walk when they were older at outcome determination (p = 0.01). Children were unlikely to grasp voluntarily with the hand contralateral to surgery when they had Rasmussen encephalitis (0/61, p = 0.001) or Sturge-Weber syndrome (0/32, p = 0.007). Children were unlikely to speak when they had contralateral MRI abnormalities (30/69, p = 0.002) and longer epilepsy duration (p = 0.01), but likely to speak when they had Sturge-Weber syndrome (29/35, p = 0.01), were older at surgery (p = 0.04), and were older at outcome determination (p < 0.001). INTERPRETATION: Etiology and bilaterality of structural brain abnormalities were key determinants of functional outcome after hemispherotomy. Longer epilepsy duration affected language outcomes. Not surprisingly, walking and talking ability increased with older age at outcome evaluation. ANN NEUROL 2024;95:377-387.

Perioperative Brain Injury in Relation to Early Neurodevelopment Among Children with Severe Congenital Heart Disease: Results from a European Collaboration.

OBJECTIVE: To examine the relationship between perioperative brain injury and neurodevelopment during early childhood in patients with severe congenital heart disease (CHD). STUDY DESIGN: One hundred and seventy children with CHD and born at term who required cardiopulmonary bypass surgery in the first 6 weeks after birth were recruited from 3 European centers and underwent preoperative and postoperative brain MRIs. Uniform description of imaging findings was performed and an overall brain injury score was created, based on the sum of the worst preoperative or postoperative brain injury subscores. Motor and cognitive outcomes were assessed with the Bayley Scales of Infant and Toddler Development Third Edition at 12 to 30 months of age. The relationship between brain injury score and clinical outcome was assessed using multiple linear regression analysis, adjusting for CHD severity, length of hospital stay (LOS), socioeconomic status (SES), and age at follow-up. RESULTS: Neither the overall brain injury score nor any of the brain injury subscores correlated with motor or cognitive outcome. The number of preoperative white matter lesions was significantly associated with gross motor outcome after correction for multiple testing (P = .013, ß = -0.50). SES was independently associated with cognitive outcome (P < .001, ß = 0.26), and LOS with motor outcome (P < .001, ß = -0.35). CONCLUSION: Preoperative white matter lesions appear to be the most predictive MRI marker for adverse early childhood gross motor outcome in this large European cohort of infants with severe CHD. LOS as a marker of disease severity, and SES influence outcome and future intervention trials need to address these risk factors.

Efficient organisation of the contralateral hemisphere connectome is associated with improvement in intelligence quotient after paediatric epilepsy surgery.

OBJECTIVE: Aims of epilepsy surgery in childhood include optimising seizure control and facilitating cognitive development. Predicting which children will improve cognitively is challenging. We investigated the association of the pre-operative structural connectome of the contralateral non-operated hemisphere with improvement in intelligence quotient (IQ) post-operatively. METHODS: Consecutive children who had undergone unilateral resective procedures for epilepsy at a single centre were retrospectively identified. We included those with pre-operative volume T1-weighted non-contrast brain magnetic resonance imaging (MRI), no visible contralateral MRI abnormalities, and both pre-operative and two years post-operative IQ assessment. The MRI of the hemisphere contralateral to the side of resection was anatomically parcellated into 34 cortical regions and the covariance of cortical thickness between regions was used to create binary and weighted group connectomes. RESULTS: Eleven patients with a post-operative IQ increase of at least 10 points at two years were compared with twenty-four patients with no change in IQ score. Children who gained at least 10 IQ points post-operatively had a more efficiently structured contralateral hemisphere connectome with higher global efficiency (0.74) compared to those whose IQ did not change at two years (0.58, p = 0.014). This was consistent across thresholds and both binary and weighted networks. There were no statistically significant group differences in age, sex, age at onset of epilepsy, pre-operative IQ, mean cortical thickness, side or site of procedure, two year post-operative Engel scores or use of anti-seizure medications between the two groups. CONCLUSIONS: Surgical procedures to reduce or stop seizures may allow children with an efficiently structured contralateral hemisphere to achieve their cognitive potential.

Clinical Outcome, Cognition, and Cerebrovascular Reactivity after Surgical Treatment for Moyamoya Vasculopathy: A Dutch Prospective, Single-Center Cohort Study.

Background: It remains unclear whether revascularization of moyamoya vasculopathy (MMV) has a positive effect on cognitive function. In this prospective, single-center study, we investigated the effect of revascularization on cognitive function in patients with MMV. We report clinical and radiological outcome parameters and the associations between clinical determinants and change in neurocognitive functioning. Methods: We consecutively included all MMV patients at a Dutch tertiary referral hospital who underwent pre- and postoperative standardized neuropsychological evaluation, [15O]H2O-PET (including cerebrovascular reactivity (CVR)), MRI, cerebral angiography, and completed standardized questionnaires on clinical outcome and quality of life (QOL). To explore the association between patient characteristics, imaging findings, and change in the z-scores of the cognitive domains, we used multivariable linear- and Bayesian regression analysis. Results: We included 40 patients of whom 35 (27 females, 21 children) were treated surgically. One patient died after surgery, and two withdrew from the study. TIA- and headache frequency and modified Rankin scale (mRS) improved (resp. p = 0.001, 0.019, 0.039). Eleven patients (seven children) developed a new infarct during follow-up (31%), five of which were symptomatic. CVR-scores improved significantly (p < 0.0005). The language domain improved (p = 0.029); other domains remained stable. In adults, there was an improvement in QOL. We could not find an association between change in imaging and cognitive scores. Conclusion: In this cohort of Western MMV patients, TIA frequency, headache, CVR, and mRS improved significantly after revascularization. The language domain significantly improved, while others remained stable. We could not find an association between changes in CVR and cognitive scores.

Intraoperative electrocorticography using high-frequency oscillations or spikes to tailor epilepsy surgery in the Netherlands (the HFO trial): a randomised, single-blind, adaptive non-inferiority trial.

BACKGROUND: Intraoperative electrocorticography is used to tailor epilepsy surgery by analysing interictal spikes or spike patterns that can delineate epileptogenic tissue. High-frequency oscillations (HFOs) on intraoperative electrocorticography have been proposed as a new biomarker of epileptogenic tissue, with higher specificity than spikes. We prospectively tested the non-inferiority of HFO-guided tailoring of epilepsy surgery to spike-guided tailoring on seizure freedom at 1 year. METHODS: The HFO trial was a randomised, single-blind, adaptive non-inferiority trial at an epilepsy surgery centre (UMC Utrecht) in the Netherlands. We recruited children and adults (no age limits) who had been referred for intraoperative electrocorticography-tailored epilepsy surgery. Participants were randomly allocated (1:1) to either HFO-guided or spike-guided tailoring, using an online randomisation scheme with permuted blocks generated by an independent data manager, stratified by epilepsy type. Treatment allocation was masked to participants and clinicians who documented seizure outcome, but not to the study team or neurosurgeon. Ictiform spike patterns were always considered in surgical decision making. The primary endpoint was seizure outcome after 1 year (dichotomised as seizure freedom [defined as Engel 1A-B] vs seizure recurrence [Engel 1C-4]). We predefined a non-inferiority margin of 10% risk difference. Analysis was by intention to treat, with prespecified subgroup analyses by epilepsy type and for confounders. This completed trial is registered with the Dutch Trial Register, Toetsingonline ABR.NL44527.041.13, and ClinicalTrials.gov, NCT02207673. FINDINGS: Between Oct 10, 2014, and Jan 31, 2020, 78 individuals were enrolled to the study and randomly assigned (39 to HFO-guided tailoring and 39 to spike-guided tailoring). There was no loss to follow-up. Seizure freedom at 1 year occurred in 26 (67%) of 39 participants in the HFO-guided group and 35 (90%) of 39 in the spike-guided group (risk difference -23·5%, 90% CI -39·1 to -7·9; for the 48 patients with temporal lobe epilepsy, the risk difference was -25·5%, -45·1 to -6·0, and for the 30 patients with extratemporal lobe epilepsy it was -20·3%, -46·0 to 5·4). Pathology associated with poor prognosis was identified as a confounding factor, with an adjusted risk difference of -7·9% (90% CI -20·7 to 4·9; adjusted risk difference -12·5%, -31·0 to 5·9, for temporal lobe epilepsy and 5·8%, -7·7 to 19·5, for extratemporal lobe epilepsy). We recorded eight serious adverse events (five in the HFO-guided group and three in the spike-guided group) requiring hospitalisation. No patients died. INTERPRETATION: HFO-guided tailoring of epilepsy surgery was not non-inferior to spike-guided tailoring on intraoperative electrocorticography. After adjustment for confounders, HFOs show non-inferiority in extratemporal lobe epilepsy. This trial challenges the clinical value of HFOs as an epilepsy biomarker, especially in temporal lobe epilepsy. Further research is needed to establish whether HFO-guided intraoperative electrocorticography holds promise in extratemporal lobe epilepsy. FUNDING: UMCU Alexandre Suerman, EpilepsieNL, RMI Talent Fellowship, European Research Council, and MING Fund.

Development and Validation of Prediction Models for Developmental and Intellectual Outcome Following Pediatric Epilepsy Surgery.

BACKGROUND AND OBJECTIVES: To identify predictors of postoperative intelligence and developmental quotients (IQ/DQ) and develop and validate clinically applicable IQ/DQ prediction models. METHODS: We retrospectively analyzed neuropsychological outcomes and their possible determinants for children treated in Bethel and Utrecht since 1990. We performed separate analyses for patients with IQ and those with only DQ available. We developed prediction models based on presurgical determinants to predict dichotomized levels of performance (IQ ≥85, IQ ≥70, DQ ≥50). RESULTS: IQ/DQ data before and 2 years after surgery were available for 492 patients (IQ n = 365, DQ n = 127). At a cutoff level ±10 points, the chance of improvement was considerably higher than the chance of deterioration (IQ 37.3% vs 6.6% and DQ 31.5% vs 15.0%, respectively). Presurgical IQ/DQ was the strongest predictor of postoperative cognition (IQ r = 0.85, p <0.001; DQ r = 0.57, p <0.001). Two IQ models were developed in the Bethel cohort (n = 258) and externally validated in the Utrecht cohort (n = 102). For DQ, we developed the model in the Bethel cohort and used 10-fold cross-validation. Models allowed good prediction at all 3 cutoff levels (correct classification for IQ ≥85 = 86%, IQ ≥70 = 91%, DQ ≥50 = 76%). External validation of the IQ models showed high accuracy (IQ ≥85: 0.82, confidence interval [CI] 0.75-0.91; IQ ≥70: 0.84, CI 0.77-0.92) and excellent discrimination (receiver operating characteristic curves: IQ ≥85: area under the curve [AUC] 0.90, CI 0.84-0.96; IQ ≥70: AUC 0.92, CI 0.87-0.97). DISCUSSION: After epilepsy surgery in children, the risk of cognitive deterioration is very low. Presurgical development has a strong effect on the postoperative trajectory. The presented models can improve presurgical counseling of patients and parents by reliably predicting cognitive outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for children undergoing epilepsy surgery presurgical IQ/DQ was the strongest predictor of postoperative cognition.

Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

OBJECTIVE: To evaluate the relationship between age at seizure onset and neurodevelopmental outcome at age 24 months in infants with TSC, as well as the effect on neurodevelopmental outcome of early versus conventional treatment of epileptic seizures with vigabatrin (80-150 mg/kg/day). METHODS: Infants with TSC, aged ≤4 months and without previous seizures were enrolled in a prospective study and closely followed with monthly video EEG and serial standardized neurodevelopmental testing (Bayley Scales of Infant Development and Autism Diagnostic Observation Schedule). RESULTS: Eighty infants were enrolled. At the age of 24 months testing identified risk of Autism Spectrum Disorder (ASD) in 24/80 children (30.0%), and developmental delay (DD) in 26/80 (32.5%). Children with epilepsy (51/80; 63.8%) had a higher risk of ASD (P = 0.02) and DD (P = 0.001). Overall, no child presented with moderate or severe DD at 24 months (developmental quotient < 55). In 20% of children abnormal developmental trajectories were detected before the onset of seizures. Furthermore, 21% of all children with risk of ASD at 24 months had not developed seizures at that timepoint. There was no significant difference between early and conventional treatment with respect to rate of risk of ASD (P = 0.8) or DD (P = 0.9) at 24 months. INTERPRETATION: This study confirms a relationship between epilepsy and risk of ASD/DD. However, in this combined randomized/open label study, early treatment with vigabatrin did not alter the risk of ASD or DD at age 2 years.

High frequency oscillations relate to cognitive improvement after epilepsy surgery in children.

OBJECTIVE: To investigate how high frequency oscillations (HFOs; ripples 80-250 Hz, fast ripples (FRs) 250-500 Hz) and spikes in intra-operative electrocorticography (ioECoG) relate to cognitive outcome after epilepsy surgery in children. METHODS: We retrospectively included 20 children who were seizure free after epilepsy surgery using ioECoG and determined their intelligence quotients (IQ) pre- and two years postoperatively. We analyzed whether the number of HFOs and spikes in pre- and postresection ioECoGs, and their change in the non-resected areas relate to cognitive improvement (with ≥ 5 IQ points increase considered to be clinically relevant (=IQ+ group) and < 5 IQ points as irrelevant (=IQ- group)). RESULTS: The IQ+ group showed significantly more FRs in the resected tissue (p = 0.01) and less FRs in the postresection ioECoG (p = 0.045) compared to the IQ- group. Postresection decrease of ripples on spikes was correlated with postoperative cognitive improvement (correlation coefficient = -0.62 with p = 0.01). CONCLUSIONS: Postoperative cognitive improvement was related to reduction of pathological HFOs signified by removing FR generating areas with subsequently less residual FRs, and decrease of ripples on spikes in the resection edge of the non-resected area. SIGNIFICANCE: HFOs recorded in ioECoG could play a role as biomarkers in the prediction and understanding of cognitive outcome after epilepsy surgery.

Social functioning of children after epilepsy surgery: A literature review.

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.

Cognitive functioning after epilepsy surgery in children with mild malformation of cortical development and focal cortical dysplasia.

Mild malformation of cortical development (mMCD) and focal cortical dysplasia (FCD) subtypes combined are by far the most common histological diagnoses in children who undergo surgery as treatment for refractory epilepsy. In patients with refractory epilepsy, a substantial burden of disease is due to cognitive impairment. We studied intelligence quotient (IQ) or developmental quotient (DQ) values and their change after epilepsy surgery in a consecutive series of 42 children (median age at surgery: 4.5, range: 0-17.0 years) with refractory epilepsy due to mMCD/FCD. Cognitive impairment, defined as IQ/DQ below 70, was present in 51% prior to surgery. Cognitive impairment was associated with earlier onset of epilepsy, longer epilepsy duration, and FCD type I histology. Clinically relevant improvement of ≥10 IQ/DQ points was found in 24% of children and was related to the presence of presurgical epileptic encephalopathy (EE). At time of postsurgical cognitive testing, 59% of children were completely seizure-free (Engel 1A). We found no association between cognitive outcome and seizure or medication status at two years of follow-up. Epilepsy surgery in children with mMCD or FCD not only is likely to result in complete and continuous seizure freedom, but also improves cognitive function in many.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Cognitive consequences of early versus late antiepileptic drug withdrawal after pediatric epilepsy surgery, the TimeToStop (TTS) trial: study protocol for a randomized controlled trial.

BACKGROUND: The goals of intentional curative pediatric epilepsy surgery are to achieve seizure-freedom and antiepileptic drug (AED) freedom. Retrospective cohort studies have indicated that early postoperative AED withdrawal unmasks incomplete surgical success and AED dependency sooner, but not at the cost of long-term seizure outcome. Moreover, AED withdrawal seemed to improve cognitive outcome. A randomized trial is needed to confirm these findings. We hypothesized that early AED withdrawal in children is not only safe, but also beneficial with respect to cognitive functioning. DESIGN: This is a multi-center pragmatic randomized clinical trial to investigate whether early AED withdrawal improves cognitive function, in terms of attention, executive function and intelligence, quality of life and behavior, and to confirm safety in terms of eventual seizure freedom, seizure recurrences and "seizure and AED freedom." Patients will be randomly allocated in parallel groups (1:1) to either early or late AED withdrawal. Randomization will be concealed and stratified for preoperative IQ and medical center. In the early withdrawal arm reduction of AEDs will start 4 months after surgery, while in the late withdrawal arm reduction starts 12 months after surgery, with intended complete cessation of drugs after 12 and 20 months respectively. Cognitive outcome measurements will be performed preoperatively, and at 1 and 2 years following surgery, and consist of assessment of attention and executive functioning using the EpiTrack Junior test and intelligence expressed as IQ (Wechsler Intelligence Scales). Seizure outcomes will be assessed at 24 months after surgery, and at 20 months following start of AED reduction. We aim to randomize 180 patients who underwent anticipated curative epilepsy surgery below 16 years of age, were able to perform the EpiTrack Junior test preoperatively, and have no predictors of poor postoperative seizure prognosis (multifocal magnetic resonance imaging (MRI) abnormalities, incomplete resection of the lesion, epileptic postoperative electroencephalogram (EEG) abnormalities, or more than three AEDs at the time of surgery). DISCUSSION: Growing experience with epilepsy surgery has changed the view towards postoperative medication policy. In a European collaboration, we designed a multi-center pragmatic randomized clinical trial comparing early with late AED withdrawal to investigate benefits and safety of early AED withdrawal. The TTS trial is supported by the Dutch Epilepsy Fund (NL 08-10) ISRCTN88423240/ 08/05/2013.

Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery.

OBJECTIVE: Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop (TTS) study, we showed that timing of AED withdrawal does not majorly influence long-term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative intelligence quotient (IQ), and change in IQ (delta IQ) following pediatric epilepsy surgery. METHODS: We collected IQ scores of children from the TTS cohort with both pre- and postoperative neuropsychological assessments (NPAs; n = 301) and analyzed whether reduction of AEDs prior to the latest NPA was related to postoperative IQ and delta IQ, using linear regression analyses. Factors previously identified as independently relating to (delta) IQ, and currently identified predictors of (delta) IQ, were considered possible confounders and used for adjustment. Additionally, we adjusted for a compound propensity score that contained previously identified determinants of timing of AED withdrawal. RESULTS: Mean interval to the latest NPA was 19.8 ± 18.9 months. Reduction of AEDs at the latest NPA significantly improved postoperative IQ and delta IQ (adjusted regression coefficient [RC] = 3.4, 95% confidence interval [CI] = 0.6-6.2, p = 0.018 and RC = 4.5, 95% CI = 1.7-7.4, p = 0.002), as did complete withdrawal (RC = 4.8, 95% CI = 1.4-8.3, p = 0.006 and RC = 5.1, 95% CI = 1.5-8.7, p = 0.006). AED reduction also predicted ≥ 10-point IQ increase (p = 0.019). The higher the number of AEDs reduced, the higher was the IQ (gain) after surgery (RC = 2.2, 95% CI = 0.6-3.7, p = 0.007 and RC = 2.6, 95% CI = 1.0-4.2, p = 0.001, IQ points per AED reduced). INTERPRETATION: Start of AED withdrawal, number of AEDs reduced, and complete AED withdrawal were associated with improved postoperative IQ scores and gain in IQ, independent of other determinants of cognitive outcome.

Parental education predicts change in intelligence quotient after childhood epilepsy surgery.

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.

Visual function and compensatory mechanisms for hemianopia after hemispherectomy in children.

OBJECTIVE: Little is known about the functional visual outcome of children after hemispherectomy. Several case reports have described an anomalous head posture (AHP) and exotropia (XT) contralateral to the side of early brain damage, as possible compensatory mechanisms (CMs) for homonymous hemianopia (HH). The aim of this study was to determine visual outcome and the prevalence of such CMs in hemispherectomized children. METHODS: Patient files from all children who underwent hemispherectomy and had a postoperative ophthalmologic examination in the University Medical Center (UMC) Utrecht up to October 2012 were retrospectively reviewed. Preoperative and postoperative clinical information on visual fixation, visual acuity, visual fields, optic discs, head posturing, ocular alignment, and cognitive development was collected. Clinical characteristics were compared between children who developed CMs and those who did not. RESULTS: Forty-five children (21 male) underwent a hemispherectomy (22 right) at a median age of 2.1 years. Median ophthalmologic follow-up was 2.3 years. After hemispherectomy, visual fixation was present in all children, and 87% of the examined children had a normal visual acuity or a mild visual impairment. All children who underwent a visual field measurement had an HH. Anomalous head posturing and continuous or intermittent XT contralateral to the side of hemispherectomy were found in 53% and 38% of children, respectively. Children with CMs had more frequently right-sided surgery and earlier onset of epilepsy, and they tended to be younger when they underwent hemispherectomy than children without. SIGNIFICANCE: Despite HH, the majority of children who undergo hemispherectomy have a good visual outcome. Furthermore, they frequently develop AHP and continuous or intermittent XT contralateral to the hemispherectomy as part of a coping strategy to optimize the functional visual field. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Withdrawal of antiepileptic drugs improves psychomotor speed after childhood epilepsy surgery.

This retrospective study evaluates the impact of postoperative antiepileptic drug (AED) withdrawal on psychomotor speed in seizure-free children, operated for medically refractory epilepsy. Post-surgical medication policy and neuropsychological assessments (performed shortly before and 6, 12 and 24 months after surgery), were evaluated in 57 children (32 female, median age at surgery 13 years). Patients were divided into a withdrawal (n=29) and a no-withdrawal group (n=28). Scores of four psychomotor tests performed at 12 and 24 months after surgery were compared with those of postoperative baseline measurements, performed 6 months after surgery. At 24 months, the withdrawal group had improved significantly more than the no-withdrawal group on three of four tests; reaction time to light (p=0.031), reaction time to sound (p=0.045) and tapping (p=0.003). At 12 months, a non-significant tendency in the same direction was found for both reaction time tests. Drug withdrawal after surgery improves psychomotor speed and may unleash the potential for cognitive improvement.

'With the benefit of hindsight': would you opt again for epilepsy surgery performed in childhood?

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.

Cognitive outcome after epilepsy surgery in children.

The ultimate goal of epilepsy surgery in young children is to stop seizures, interrupt the downhill course of the epileptic encephalopathy, and improve developmental capacities. Postoperative outcome after childhood epilepsy surgery should therefore not only be expressed in terms of seizure freedom, cognitive outcome is an equally important outcome measure. Insight in the mutually dependent variables that can determine pre and postoperative cognitive developmental abilities will improve prediction of outcome and presurgical counseling of parents. The purpose of this review is to discuss the literature regarding cognitive outcome and the predictors of postoperative cognitive functioning after epilepsy surgery in children, particularly those with "catastrophic" epilepsy. There are only few studies in which the relation between possible determinants and cognitive outcome or change was statistically tested in a multivariable manner. Duration of epilepsy, presurgical Developmental Quotient (DQ) or Intelligence Quotient (IQ), and postoperative seizure freedom were the only factors reported in different studies to be independently related to eventual cognitive outcome after epilepsy surgery. Underlying etiology, gender, age at surgery, presurgical DQ/IQ, postoperative seizure freedom, cessation of antiepileptic medication, and follow-up interval have all been described in different surgical cohorts to be independently related to a postoperative change of IQ or DQ scores. To appreciate how each of the pre-epileptic, presurgical, and postoperative variables may independently influence eventual cognitive outcome and postoperative cognitive improvement, we need multicenter studies with large homogenous surgical populations, using standardized tests and multivariable analyses.

Language development before and after temporal surgery in children with intractable epilepsy.

PURPOSE: To obtain systematic knowledge of language development before and after epilepsy surgery in regions that, if damaged, are known to entail language impairment in adults. METHODS: Twenty-four children (mean age 11 years; range 5.8-15.7 years) with pharmacologically intractable epilepsy participated prior to (the majority) anterior temporal lobectomy and 6, 12, and 24 months thereafter. Reception and production of lexicon (vocabulary) and syntax (sentence structure including grammar) were examined using developmental language tests that provide normative data. RESULTS: Prior to surgery the mean language delay varied from 1.7 years (productive syntax) to 3.5 years (productive lexicon). For lexicon, language delay was larger, the older the children; for syntax it was smaller in children with mothers with higher education. Over the 2 years following surgery, the children developed in all four language components. Development was, however, slower than normal, that is, language delay increased, in three of the four components: in productive lexicon it continued to increase, and in receptive lexicon and productive syntax it appeared to stabilize during the second year. Receptive syntax developed at a normal pace. The development of productive lexicon was remarkably slow when surgery and language mediation were both in the left hemisphere. DISCUSSION: Pharmacologically intractable epilepsy of the temporal lobe, or the underlying condition, is a significant risk factor for delayed language development. Temporal epilepsy surgery does not result in acceleration of language development. If language is still mediated in the operated left hemisphere, development of particular language components may slow down after surgery.