Gert Wiegand

Long‐term seizure outcome in 211 patients with focal cortical dysplasia

Focal cortical dysplasia (FCD) is currently recognized as the most common cause of neocortical pharmacoresistant epilepsy. Epilepsy surgery has become an increasingly successful treatment option. Herein, the largest patient cohort reported to date is analyzed regarding long‐term outcome and factors relevant for long‐term seizure control.

Combination of EEG-fMRI and EEG source analysis improves interpretation of spike-associated activation networks in paediatric pharmacoresistant focal epilepsies.

Simultaneous recording of EEG and functional MRI (EEG-fMRI) is a promising tool that may be applied in patients with epilepsy to investigate haemodynamic changes associated with interictal epileptiform discharges (IED). As the yield of the EEG-fMRI technique in children with epilepsy is still unclear, the aim of this study was to evaluate whether the combination of EEG-fMRI and EEG source analysis could improve localization of epileptogenic foci in children. Six children with an unambiguous focus localization were selected based on the criterion of the consistency of ictal EEG, PET and ictal SPECT. IEDs were taken as time series for fMRI analysis and as averaged sweeps for the EEG source analysis based on the distributed linear local autoregressive average (LAURA) solution. In four patients, the brain area with haemodymanic changes corresponded to the epileptogenic zone. However, additional distant regions with haemodynamic response were observed. Source analysis located the source of the initial epileptic activity in all cases in the presumed epileptogenic zone and revealed propagation in five cases. In three cases there was a good correspondence between haemodynamic changes and source localization at both the beginning and the propagation of IED. In the remaining three cases, at least one area of haemodynamic changes corresponded to either the beginning or the propagation. In most children analysed, EEG-fMRI revealed extended haemodynamic response, which were difficult to interpret without an appropriate reference, i.e. a priori hypothesis about epileptogenic zone. EEG source analysis may help to differentiate brain areas with haemodynamic response.

Everolimus in tuberous sclerosis patients with intractable epilepsy: A treatment option?

BACKGROUND Tuberous Sclerosis Complex (TSC) is an often severe neurodevelopmental disorder caused by overactivation of the mTOR pathway due to mutations in either the TSC1 or TSC2 genes. Seizures are the primary cause of neurologic morbidity and often refractory. The mTOR inhibitor everolimus was recently approved for the treatment of giant cell astrocytomas and renal angiomyolipomas in TSC. Whether everolimus has any direct effect on epilepsy in TSC is not known. METHODS Within the framework of a compassionate use trial, we evaluated the safety and efficacy of everolimus in seven patients with TSC and intractable epilepsy. We evaluated seizure frequency, seizure-free days and adverse effects including standard laboratory parameters. Seizure frequency was analysed in each patient using a non-parametric test for trend and using a Generalized Estimating Equations Model in the total patient group. The observation period was continued for nine months. RESULTS One patient discontinued the medication at the beginning of the observation period due to side effects (flushing). In the remaining 6 patients, we observed a reduction of seizures in 4/6 patients with a reduction of 25-100%. In addition, the percentage of seizure-free days increased in 3/4 of these patients. In 2/6 patients, no alteration of seizure frequency was noted. We observed an increase of mild infections and an increase of triglycerides and various liver function tests. We did not encounter life-threatening infections or other side effects of everolimus. INTERPRETATION In some patients with TSC, everolimus may have an anticonvulsant effect with a reduction in seizure frequency and increase of seizure-free days. Everolimus was well tolerated, with adverse effects similar to those reported in previous studies.

Seizure and cognitive outcomes of epilepsy surgery in infancy and early childhood

AIMS To investigate seizure and developmental outcomes following epilepsy surgery in very young children and determine their predictive factors. METHODS We retrospectively reviewed the clinical data, surgical variables, and outcomes of 30 children under 3 years of age that underwent resection for refractory focal epilepsy in our institution in 2001-2011. RESULTS Seizure onset was in the first year of life in 27 (90%) cases and mean age at surgery was 20 months (range 5-33.6). Pathology consisted of cortical malformations in 24 (80%) cases, glioneuronal tumour and infarction with or without cortical dysplasia in three (10%) cases each. Morbidity was comparable with older paediatric cohorts. At 1-11.6 year follow-up (mean 4.1) 21 of 30 (70%) children achieved seizure freedom (Engel I), six (20%) demonstrated worthwhile improvement (Engel II/III) and three (10%) did not benefit from surgery (Engel IV). Intralobar lesionectomy more often resulted in seizure freedom than multilobar or hemispheric surgery. The abundance of non-regional interictal and ictal EEG findings did not preclude seizure freedom. Presurgical developmental impairment was established in 25 of 28 (89%) children; its severity correlated with longer epilepsy duration and determined postoperative developmental outcome. Developmental progress was established in 26 out of 28 (93%) children following surgery, showing stabilized trajectories rather than catch-up. CONCLUSIONS Resective surgery in very young children is safe and effective in terms of seizure control and developmental progress. Our findings underline the importance of early intervention in order to timely stop seizures and their deleterious effects on the developing brain.

Seizure control and developmental trajectories after hemispherotomy for refractory epilepsy in childhood and adolescence

To evaluate the seizure control and developmental outcomes after hemispherotomy for refractory epilepsy in childhood and to identify their predictive factors.

EEG-fMRI study of generalized spike and wave discharges without transitory cognitive impairment

Generalized spike and wave discharges (GSW) are often accompanied by transitory cognitive impairment (TCI). As a possible neurophysiological correlate of TCI, activation in the thalamus and deactivation in the frontoparietal brain regions associated with GSW were discussed in previous studies which used simultaneous recordings of EEG and functional MRI (EEG-fMRI) in patients with absence epilepsy. We report on a girl having GSW up to 10seconds without any clinical concomitants. The girl underwent an EEG-fMRI investigation with simultaneous behavioral testing (continuous performance task). Although GSW repeatedly occurred during the task, no TCI was observed. EEG-fMRI revealed bilateral deactivation in frontoparietal brain areas and activation in the thalamus in association with GSWs. This study challenges the relation between cognitive impairment during absences and the characteristic pattern of thalamic activation and deactivation in frontoparietal areas associated with GSW.

The value of EEG‐fMRI and EEG source analysis in the presurgical setup of children with refractory focal epilepsy

Purpose:  In the presurgical evaluation of children and juvenile patients with refractory focal epilepsy, the main challenge is to localize the point of seizure onset as precisely as possible. We compared results of the conventional electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) analysis with those obtained with a newly developed method using voltage maps of average interictal epileptiform discharges (IEDs) recorded during clinical long‐term monitoring and with the results of the electric source imaging (ESI).

Reoperation for refractory epilepsy in childhood: a second chance for selected patients.

BACKGROUND Reoperations account for >10% in pediatric epilepsy surgery cohorts, and they are especially relevant in young children with catastrophic epilepsy. OBJECTIVE To determine surgical outcomes and their predictive factors in reoperations for refractory epilepsy in childhood. METHODS We retrospectively analyzed presurgical findings, resections, and outcomes of 23 consecutive children who underwent reoperations from 2000 to 2011. RESULTS Etiology included cortical dysplasia with/without glioneuronal tumor in 19 patients (83%), sole glioneuronal tumor in 2, and tuberous sclerosis and Rasmussen encephalitis in 1 each. The reasons for the failure of the initial surgery were functional considerations in 8 (35%), incorrect delineation of the epileptogenic zone in 8 (35%), and resection not performed as initially planned in 7 (30%) cases. Final procedures included 8 (35%) intralobar, 8 (35%) multilobar resections, and 7 (30%) hemispherotomies. Following reoperations, 14 (61%) patients were seizure free, 6 (26%) showed significant or worthwhile improvement, and 3 (13%) did not respond to surgery. Six of 8 patients who underwent the first resection before the age of 3 years, 6 of 8 whose first resection was limited by functional considerations, and all 7 with hemispherotomy as the final resection achieved seizure freedom after reoperation. CONCLUSION Reoperation is particularly beneficial for selected children with refractory epilepsy associated with cortical dysplasia that did not respond to an initial limited and/or early resection but achieved seizure freedom after extensive procedures. When indicated, reoperation should be performed at the youngest possible age to profit from higher functional plasticity in compensating for neurological deficit.

Posterior cortex epilepsy surgery in childhood and adolescence: Predictors of long‐term seizure outcome

We aimed to investigate the long‐term seizure outcome of children and adolescents who were undergoing epilepsy surgery in the parietooccipital cortex and determine their predictive factors.

Frontal Lobe Epilepsy Surgery in Childhood and Adolescence: Predictors of Long-Term Seizure Freedom, Overall Cognitive and Adaptive Functioning

BACKGROUND Although frontal lobe resections account for one-third of intralobar resections in pediatric epilepsy surgery, there is a dearth of information regarding long-term seizure freedom, overall cognitive and adaptive functioning. OBJECTIVE To identify outcome predictors and define the appropriate timing for surgery. METHODS We retrospectively analyzed the data of 75 consecutive patients aged 10.0 ± 4.9 yr at surgery that had an 8.1 yr mean follow-up. RESULTS Etiology comprised focal cortical dysplasia (FCD) in 71% and benign tumors in 16% cases. All patients but one had a magnetic resonance imaging-visible lesion. At last follow-up, 63% patients remained seizure-free and 37% had discontinued antiepileptic drugs. Presurgical predictors of seizure freedom were a shorter epilepsy duration, strictly regional epileptic discharges in electroencephalography (EEG), and an epileptogenic zone and/or lesion distant from eloquent cortex. Postsurgical predictors were the completeness of resection and the lack of early postoperative seizures or epileptic discharges in EEG. Higher presurgical overall cognitive and adaptive functioning was related to later epilepsy onset and to a sublobar epileptogenic zone and/or lesion. Following surgery, scores remained stable in the majority of patients. Postsurgical gains were determined by higher presurgical performance and tumors vs FCD. CONCLUSION Our findings highlight the favorable long-term outcomes following frontal lobe epilepsy surgery in childhood and adolescence and underline the importance of early surgical intervention in selected candidates. Early postsurgical relapses and epileptic discharges in EEG constitute key markers of treatment failure and should prompt timely reevaluation. Postsurgical overall cognitive and adaptive functioning is stable in most patients, whereas those with benign tumors have higher chances of improvement.