Delphine Taussig

Insular and insulo-opercular epilepsy in childhood: An SEEG study

PURPOSE In recent years, there have been series analysing the electro-clinical correlations of insular epilepsy in adult populations. In contrast, the ictal semiology in children with insular epilepsy is poorly described. Considering that early and successful surgery may greatly improve the cognitive outcome and quality of life, it is worthwhile to deepen our knowledge of insular epilepsy in children. METHODS We retrospectively evaluated ten children with drug-resistant focal insular epilepsy who had been consecutively explored with stereoelectroencephalography (SEEG), followed by individually tailored resective surgery that included part of the insula in all cases. A detailed anatomo-electro-clinical analysis of non-invasive EEG and SEEG data was performed. At least one of the electrodes explored the insular cortex. SEEG analysis confirmed that the insular cortex was included in the ictal onset zone. RESULTS Epilepsy onset was mostly during the first year of life, characterized by subtle seizures as well as spasms and myoclonic seizures. Later on, neurovegetative signs and asymmetric tonic and hypermotor seizures (HMS) dominated the ictal semiology. The epileptogenic zone was frequently wider than insular with frontal and central predominance. In eight patients, the tailored resection included a lesion. In seven patients, an Engel class 1 outcome as well as neuropsychological and behavioural improvement was obtained. CONCLUSIONS SEEG is feasible and useful in children with drug-resistant insular epilepsy which is often characterized by autonomic symptoms as the initial symptoms and should be suspected in cases with HMS, asymmetric tonic seizures and even asymmetric spasms. Early propagation is mostly frontal and central. Analysis of a larger population is required to refine these findings.

Stereo-electroencephalography (SEEG) in 65 children: an effective and safe diagnostic method for pre-surgical diagnosis, independent of age

AIM We report our experience of stereoelectroencephalography (SEEG) in 65 children with drug-resistant seizures, with a particular emphasis on young children. METHODS We retrospectively studied all SEEG performed between 2009 and 2011 in our centre. As SEEG can have several indications, the patients were classified into three categories, according to the probability of surgery. The contribution of SEEG to the final decision regarding surgery was evaluated for each category separately. We also compared the main demographic and surgical data of children younger than 5 years of age (Group 1; 21 children) with those older than five years of age at the time of investigation (Group 2; 44 patients). RESULTS MRI was not contributory in 20% of patients (9.5% in group 1; 25% in group 2). Electrical stimulations localised the motor area in all patients when performed (49% of patients), even in group 1 (62% of patients). SEEG led to surgery in 78% of patients (90.5% in group 1; 73% in group 2), after a second invasive investigation in 9.2 % of patients. The resection involved more than one lobe in 25% of patients (37% in group 1; 19% in group 2). Ultimately, 78% of patients with a low probability of having surgery before SEEG received surgery (88% in group 1). The surgical outcome of Engel class 1 was reported for 67% of patients (79% of patients in group 1 and 59% in group 2). No complications occurred. CONCLUSION SEEG in children is safe and useful, and the surgical outcome in younger children is as good as, or sometimes even better than, that in older children. As a result of lower rates of complication and morbidity, SEEG appears to be more appropriate, in comparison to subdural grids, in situations where it is unclear if patients will have surgery after an invasive investigation.

Invasive EEG explorations

The Wada test was adapted from the procedure described by Wada in 1964. It still has a role in the prognostic evaluation of memory disorders after mesial temporal lobectomy. The test consists of injecting a short-acting anesthetic into one hemisphere, under continuous EEG monitoring and during carotid catheterization, to verify the function of contralateral structures. Intracranial EEG recordings deliver signals with few artifacts, and which are quite specific of the zone explored. Three types of electrodes are in common use: (a) foramen ovale (FO) electrodes: electrodes can be inserted directly, without any stereotactic procedure, to provide easy and comparative EEG recordings of the lower and middle portions of the temporal lobe close to the hippocampus. These allow validation of the temporal lobe origin of seizures using FO electrodes recording coupled with scalp EEG; (b): subdural strip or grip electrodes. This relatively aggressive technique carries infectious and hemorrhagic risks and does not allow the exploration of deep cortical structures. However, it permits precise functional cortical mapping via electrical stimulation because of dense and regular positioning of electrodes over the cortical convexity; (c) stereotactically implanted depth electrodes (stereo-electroencephalography [SEEG]). Electrodes are individually planned and inserted within the brain parenchyma through small burr holes. This technique is less aggressive than subdural grid exploration. However it offers relatively limited spatial sampling that may be less well adapted to precise functional evaluation. It allows recording from deep cortical structures and can be argued to be the gold standard of presurgical EEG exploration.

Stereo-electroencephalography (SEEG) in children surgically cured of their epilepsy

PURPOSE SEEG in children has a low morbidity and leads to a good surgical outcome, in particular in younger patients. We analysed, in detail, the SEEG data of patients that were subsequently cured by surgery. METHODS We selected the 48 children explored between 2009 and 2013 in our centre and surgically cured after SEEG-based resections with at least one-year follow-up. We retrospectively studied demographic and surgical data and paid particular attention to the data acquired during the invasive recording. Moreover, we compared the children younger than 5 years of age (group 1: 17 children) to those older than 5 years of age at the time of exploration (group 2: 31 patients). RESULTS SEEG was well tolerated. Only one patient had slight intracerebral bleeding seen on the post-operative CT-scan without any clinical consequence and which did not prevent the recording. SEEG explored at least four lobes in 59% of patients, either because of a suspected very widespread epileptogenic zone or because of the lack of a precise hypothesis. Auras were recorded only in group 2 (32% of patients, P=0.0009). Despite these difficulties, SEEG led to tailored resections including multilobar resections in 14% and infralobar resections in 69% of patients. The electrical pattern of seizures had no particularities as compared with adults. Interictal spikes and slow waves outside the resection zone were significantly less frequent in group 1 (P=0.02). In symptomatic epilepsies, the lesion matched the irritative zone in only 11% of patients and the ictal onset zone in 32% respectively. CONCLUSION Our study confirms the low morbidity of SEEG in children. SEEG can disclose a limited epileptogenic zone. Our data suggest that the epileptic network is less complex in younger patients, which has to be confirmed by a quantitative analysis of SEEG signals.

Magnetoencephalographic studies of two cases of diffuse subcortical laminar heterotopia or so-called double cortex.

Two cases (a young male and a girl, suffering intractable epilepsy) of diffuse subcortical laminar heterotopia, or so-called double cortex (DC) have been investigated using magnetoencephalography (MEG). MEG confirmed involvement of both cortices (hetero- and normocortex) in the genesis of interictal spikes, and, according to the heterogeneity of DC syndrome, some differences were observed: spike initiation in the normocortex and latter involvement of the heterotopic cortex in the man, and rather a cancellation in both cortices in the girl. In addition, participation of heterotopic cortex in physiological activities could be demonstrated in the man.

Indications and limits of stereoelectroencephalography (SEEG)

Epilepsy surgery is now an accepted treatment to achieve seizure control in carefully selected patients, both children and adults, suffering from drug-resistant focal epilepsy. Although surgical strategies can often be defined on the basis of non-invasive diagnostic procedures, and despite the recent advances in this field, an increasing number of more complex cases requires invasive EEG (iEEG) to provide precise information on the localization of the epileptogenic zone (EZ), its relationships with eloquent cortex (EC), and the feasibility of a tailored surgical resection. Stereoelectroencephalography (SEEG) is one of the iEEG techniques currently used in the presurgical work-up, and it is well-distinguished from other invasive techniques, such as subdural grids and strips. SEEG depth electrodes enable exploration of deeply located structures and lesions, and of buried cortex, which are not easily assessable by subdural or other iEEG methods. Simultaneous recording of SEEG signals from deep and superficial brain structures allows, when the position of each electrode is precisely determined, delineation of a three-dimensional, spatial and temporal organization of epileptic activities. In the following chapter we discuss some specific indications (temporal or extra-temporal, lesional or non-lesional epilepsies) as well as the limits of the SEEG technique, with respect to some epileptological issues during presurgical evaluation.

Refractory spasms of focal onset—A potentially curable disease that should lead to rapid surgical evaluation

PURPOSE Infantile spasms (IS) can occur as the only seizure type in children with surgically amenable epilepsies. Although early surgery has shown positive effects, little is known regarding outcomes. METHODS We retrospectively reviewed all children with IS referred to our tertiary center between 2002 and 2014 and try to define factors of outcome. RESULTS Sixty-eight children with focal onset seizures were referred: twenty children with a hemispheric implication and 48 with one or more lobes involved. The age of onset was significantly earlier in the hemispheric population (8.0 versus 16.7 months in the focal population). There was no difference in the age of onset between anterior and posterior onset zones, as we could expect regarding the maturation gradient. The epilepsy began earlier in life in tuberous sclerosis than in DNET. Only three children of the 48 non-hemispheric patients had a normal MRI at the time of the surgery. Temporal lobe was involved only in a third of the population. More than 86% of the patients were operated on. Patients with hemispheric lesions were operated on younger (2.6 years+/- 2.1 years) compared to 4.6+/- 3.5 years in the whole population. The most frequent etiologies were in descending order: dysplasia, ganglioglioma or dysembryoplastic tumours and tuberous sclerosis. The global seizure outcome was favorable (Engel 1a) in 74.6% of the patients, and 87.9% if the delay between the first seizure and the surgery was less than 36 months. It fell to 64.7% if the delay exceeded 50 months. CONCLUSION Spasms of focal onset have a similar postsurgical outcome as other seizure types so surgery may be an excellent option for treating selected patients with focal infantile spasms. Volume and type but not topography of the lesion influence the age of onset. MRI is very helpful to locate the pathology in the pediatric population, since only a small portion had a normal MRI.

Hemispherotomy for isolated infantile spasms following perinatal ischemic stroke

BACKGROUND Infantile spasms (IS) are a severe epileptic encephalopathy. In patients with early focal ischemia and refractory IS, a preoperative evaluation is required even if IS are the only ictal manifestation. METHODS We report three such patients who presented with IS between 5 and 7 months of age without any other focal seizure types. Imaging exhibited a perinatal middle cerebral artery (MCA) stroke. RESULTS All patients had hemiparesis and experienced psychomotor regression after the onset of IS. Scalp video-electroencephalogram (EEG) monitoring for presurgical assessment showed interictal and ictal EEG characteristics between the pathological and the healthy hemisphere and surgery was proposed despite the lack of any focal seizures. The three patients underwent hemispherotomy at a mean age of 27 months and became seizure-free without medication (follow-up 49-144 months). The two patients who underwent early hemispherotomy acquired normal verbal intelligence, whereas the third, operated on at 38 months of age, remained with severe mental retardation. CONCLUSION Early hemispherotomy in drug-resistant epilepsy related to a perinatal MCA may cure the seizures even if the patient has IS as sole type and prevent mental retardation in some children.

Refractory epilepsy in preschool children with tuberous sclerosis complex: Early surgical treatment and outcome

PURPOSE Epilepsy surgery has been shown to be effective in treating focal epilepsy related to tuberous sclerosis complex (TSC). We analyzed the advantage of early surgical management in terms of seizure frequency and development. METHOD We retrospectively studied the 15 patients younger than 6 years who underwent resective surgery between 2006 and 2016. Fourteen of them had invasive monitoring while the 15th was operated on under corticography. RESULTS Epilepsy began before 5 months of age in all patients. Overall 13 patients (86%) had a dramatic improvement of epilepsy after surgery (Engel 1 and 2) including 9 patients (60%) seizure free (Engel 1 A). In the group of 9 patients younger than 20 months at the time of surgery who presented with catastrophic epilepsies, 77% are Engel 1 A and the other 23% Engel 2. In this subpopulation, no one developed autism and four (44%) regained normal development. CONCLUSIONS In early onset epilepsies associated with TSC, surgical treatment is highly effective, in particular when performed early. Invasive monitoring contributes to the successful outcome. Those data have to be confirmed by multicentric studies including quantitative analyses of the recordings.

Reciprocal interactions between epileptogenic zone and maturating cortex in children

Objectives Epilepsy in children can be devastating as it interferes with cortical maturation. Consequences could both disturb cognitive functions and create antiepileptic drugs resistance. Reciprocal interactions between epileptogenic zone and maturating cortex in children were analyzed through stereo EEG data. Methods Characteristics of neurophysiological and clinical data in focal drug-resistant epilepsy in children were analyzed both in Rothschild Foundation series and in the literature and were compared to adult data to highlight differences. We also try to find out reciprocal interactions between epileptogenic zone and maturating cortex. Results Younger children have often huge cortical lesions containing more than one epileptic zone. These regional multifocal foci could cause multiple types of seizures. The diffusion of abnormalities from the epileptogenic zone is wider than in the adult population and causes disruptions in the adjacent and also remote functional cortex. Focal pediatric epilepsy can evolve in acute worsening as prolonged status epilepticus with permanent activation of the focus, which is quite rare in adult population. Moreover, the extension of the epileptogenic zone can vary with age in the same patient and lead to appearance of new types of seizures, event after cortical resection. Surprisingly, we show that the posterior-anterior maturational gradient has no impact on the activation of epileptogenic zone. And finally, as the child is getting older, he can explain his subjective symptoms and electro-clinical correlations allow to better delineate the epileptogenic zone. Conclusion Epileptogenic zone can be multiple in children, even in surgical candidates, but electro-clinical correlations are still possible, even in younger children. Reciprocal interactions between epileptogenic zone and maturating cortex in children lead to worsen both epilepsy and cognitive development. When possible, cortical resection or disconnection should then be discussed as soon as possible in pediatric population.