Seizure-onset patterns in focal cortical dysplasia and neurodevelopmental tumors: Relationship with surgical prognosis and neuropathologic subtypes.

OBJECTIVES: The study of intracerebral electroencephalography (EEG) seizure-onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure-onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions. METHODS: We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malformation of cortical development (MCD; including focal cortical dysplasia [FCD] and neurodevelopmental tumors [NDTs]). RESULTS: We identified six seizure-onset patterns using visual and time-frequency analysis: low-voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure-onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure-onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable. SIGNIFICANCE: Six different seizure-onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA.

Occipital and occipital "plus" epilepsies: A study of involved epileptogenic networks through SEEG quantification.

Compared with temporal or frontal lobe epilepsies, the occipital lobe epilepsies (OLE) remain poorly characterized. In this study, we aimed at classifying the ictal networks involving OLE and investigated clinical features of the OLE network subtypes. We studied 194 seizures from 29 consecutive patients presenting with OLE and investigated by stereoelectroencephalography (SEEG). Epileptogenicity of occipital and extraoccipital regions was quantified according to the 'epileptogenicity index' (EI) method. We found that 79% of patients showed widespread epileptogenic zone organization, involving parietal or temporal regions in addition to the occipital lobe. Two main groups of epileptogenic zone organization within occipital lobe seizures were identified: a pure occipital group and an occipital "plus" group, the latter including two further subgroups, occipitotemporal and occipitoparietal. In 29% of patients, the epileptogenic zone was found to have a bilateral organization. The most epileptogenic structure was the fusiform gyrus (mean EI: 0.53). Surgery was proposed in 18/29 patients, leading to seizure freedom in 55% (Engel Class I). Results suggest that, in patient candidates for surgery, the majority of cases are characterized by complex organization of the EZ, corresponding to the occipital plus group.

18FDG-PET in different subtypes of temporal lobe epilepsy: SEEG validation and predictive value.

OBJECTIVE: The objective of the study was to characterize interictal 18-fluorodeoxyglucose-positron emission tomography ((18) FDG-PET) whole-brain voxel-based metabolic patterns among distinct subtypes of temporal lobe epilepsy (TLE), as defined by stereo-electroencephalography (SEEG) and to determine predictive value of PET result on postoperative outcome. METHODS: Fifty-four consecutive patients with pharmacoresistant TLE were enrolled retrospectively after a comprehensive presurgical evaluation. This evaluation defined: 7 lateral TLE, 17 mesial TLE, 14 "plus" TLE, and 16 bilateral TLE. Whole-brain voxel-based brain metabolism was studied in each group of patients, in comparison to 23 healthy subjects, and individual classification was evaluated by cross-validation using the found clusters. An (18) FDG-PET index was moreover calculated for each patient, based on the individual Z-score of the most significant cluster extracted on the comparison between patients' subgroup and healthy subjects. Logistic regression analysis was used to estimate factors associated with postoperative outcome (Engel's classes III-IV vs. I-II), including age, gender, disease duration, seizure frequency, as well as magnetic resonance imaging (MRI) and PET findings. RESULTS: Different patterns of hypometabolism were found inside and outside the epileptogenic zone, among patients with distinct subgroups of TLE, in comparison to healthy subjects (p < 0.001, corrected for the cluster). At individual level, cross-validation showed satisfactory discrimination between the four groups with 71.4-88.2% overall accuracy. Multivariate analysis shows that (18) FDG-PET index was the only significant predictor of postoperative outcome to distinguish between Engel's classes I-II and III-IV (p = 0.037). SIGNIFICANCE: Overall, this whole-brain voxel-based analysis validates specific patterns of hypometabolism, inside and outside the EZ, in distinct subgroups of patients with TLE, as defined by SEEG gold standard, and in relation with postoperative outcome.

Clinical, neuropsychological, and metabolic characteristics of transient epileptic amnesia syndrome.

OBJECTIVE: Transient epileptic amnesia (TEA) is a recently individualized syndrome occurring in adult patients that includes epileptic seizures with amnestic features and interictal memory disturbances. METHODS: We investigated the clinical, neuropsychological, and 18F-FDG positron emission tomography (18F-FDG-PET) features of 30 consecutive cases of TEA in our center. RESULTS: The mean age of onset of amnestic seizures was 59 years. Pure acute amnesia was the only epileptic manifestation in 17% of cases. Interictal electroencephalography (EEG) abnormalities were present in 57% on awake recording and in most patients in whom sleep EEG was performed (96%). Nine of 30 patients showed anterograde memory deficit and six of 30 exhibited mild executive functioning impairment. On the autobiographical memory interview (AMI), patients showed a significant deficit for the recent period of the episodic subscale. Outcome under treatment was favorable in the majority of cases. A significant improvement was noted on recollection of autobiographical memory. 18F-FDG-PET (22 cases) showed positive correlations between left mesial temporal metabolism levels and anterograde and retrograde memory scores. SIGNIFICANCE: TEA is an emerging epileptic syndrome that likely remains misidentified and misdiagnosed. Neurometabolic data support a dysfunction of a hippocampal-neocortical network sustaining episodic memory.

Reading epilepsy from the dominant temporo-occipital region.

BACKGROUND: Reading epilepsy is a rare form of epilepsy, classified among idiopathic, age- and localisation-related (partial) epilepsies as a reflex epilepsy syndrome. Seizures usually consist of myoclonic jerks restricted to the jaw. However, distinct ictal features including visual symptoms and paroxysmal a- or dyslexia are described in some patients. The anatomical substrate of ictogenesis in reading epilepsy remains poorly understood. METHODS: The authors report here the case of a primary reading epilepsy for which ictal semiology was characterised by visual symptoms and dyslexia, investigated by MRI, interictal high-resolution EEG and PET, ictal video-EEG and SPECT. Brain MRI was normal. Interictal high-resolution EEG was performed with 64 scalp channels, a realistic head model and different algorithms to solve the inverse problem. RESULTS: Interictal source localisations highlighted the left occipito-temporal junction. Interictal PET demonstrated bilateral occipito-temporal hypometabolism with left-sided predominance. Ictal EEG showed a rhythmic discharge in left temporo-parieto-occipital junction channels, with left occipito-temporal predominance. MRI fusion of the coregistered subtraction between ictal and interictal SPECT individualised relative hyperperfusion affecting (a) the left occipito-parietal junction area, (b) the left lateral middle and inferior temporal gyri and (c) the left inferior frontal area. CONCLUSION: Besides reading-induced myoclonic jerks of the jaw, a second variant of reading epilepsy exists with clearly partial seizures manifested by visual symptoms and a- or dyslexia. These seizures originate from the occipito-temporal region of the dominant hemisphere, corresponding to the posterior part of the neural network that underlies the function of reading.

From mesial temporal lobe to temporoperisylvian seizures: a quantified study of temporal lobe seizure networks.

PURPOSE: The determination of epileptogenic structures in partial epilepsy is crucial in the context of epilepsy surgery. In this study we have quantified the "epileptogenicity" of mesial temporal lobe structures (M), lateral neocortical regions (L), and extratemporal perisylvian structures (ET) in patients with temporal lobe epilepsy (TLE), in order to classify the brain networks involved in seizure generation. METHODS: Thirty-four patients having TLE investigated by intracerebral recordings using stereotactic electroencephalography (EEG) (SEEG) were selected. Epileptogenicity of M, L, and ET structures was quantified according to the "epileptogenicity index" (EI), a new way to quantify rapid discharges at seizure onset, ranging from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). RESULTS: Automatic clustering using EI values from M, L, and ET separated patients into four classes: mesial group (max EI in M), lateral group (max EI in L), mesiolateral group (high EI in both M and L) and temporoperisylvian group (TPS) (high values in ET). The median number of highly epileptogenic structures (defined by EI >0.3) was four, a result confirming that most TLE is organized as "epileptogenic networks." We found that the duration of epilepsy was correlated with the number of epileptogenic structures and that surgical prognosis was also related to the extent of the epileptogenicity in the brain. CONCLUSIONS: Several distinct epileptogenic networks are involved in seizure generation in TLE. Findings advocate for a progressive recruitment of epileptogenic structures in human brain with time.

Local and remote epileptogenicity in focal cortical dysplasias and neurodevelopmental tumours.

During the pre-surgical evaluation of drug-resistant epilepsy, the assessment of the extent of the epileptogenic zone and its organization is a crucial objective. Indeed, the epileptogenic zone may be organized as a simple focal lesional site or as a more complex network (often referred to as the 'epileptogenic network') extending beyond the lesion. This distinction is particularly relevant in developmental lesions such as focal cortical dysplasias or dysembryoplastic neuroepithelial tumours and may determine both the surgical strategy and the prognosis. In this study, we have quantified the epileptogenic characteristic of brain structures explored by depth electrodes in 36 patients investigated by stereoelectroencephalography and suffering from focal drug-resistant epilepsy associated with focal cortical dysplasias or dysembryoplastic neuroepithelial tumours. This quantification was performed using the 'Epileptogenicity Index' method that accounts for both the propensity of a brain area to generate rapid discharges and the time for this area to get involved in the seizure. Epileptogenicity Index values range from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). We determined Epileptogenicity Index from signals recorded in distinct brain structures including the lesional site. We studied the type of epileptogenic zone organization (focal versus network) and looked for a correlation with clinical data and post-surgical outcome. Mean Epileptogenicity Index in lesional regions was 0.87 (+/-0.25), and 0.29 (+/-0.30) in 'non-lesional' structures. The number of highly epileptogenic structures (defined by Epileptogenicity Index value >or=0.4) was 3.14 (+/-1.87) in the whole population. We found that 31% of patients had only one epileptogenic structure (N(EI>or=0.4) = 1), therefore disclosing a strictly focal epileptogenic zone organization while 25 patients had more than one epileptogenic region, disclosing a network (61%) or bilateral (8%) epileptogenic zone organization. We observed a trend for a difference in seizure outcome according to the type of epileptogenic zone organization. Indeed, 57% of patients with network organization and 87% with focal organization were seizure-free while none of those with bilateral organization became seizure-free. The determination of Epileptogenicity Index computed from electrophysiological signals recorded according to the stereoelectroencephalography technique is a novel tool. Results suggest that it can help in the delineation of the epileptogenic zone associated with brain lesions and that it could be used in the definition of the subsequent surgical resection.

Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia.

Diagonistic dyspraxia (DD) is by far the most spectacular manifestation reported by sufferers of acute corpus callosum (CC) injury (so-called "split-brain"). In this form of alien hand syndrome, one hand acts at cross purposes with the other "against the patient's will". Although recent models view DD as a disorder of motor control, there is still little information regarding its neural underpinnings, due to widespread connectivity changes produced by CC insult, and the obstacle that non-volitional movements represent for task-based functional neuroimaging studies. Here, we studied patient AM, the first report of DD in patient with complete developmental CC agenesis. This unique case also offers the opportunity to study the resting-state connectomics of DD in the absence of diffuse changes subsequent to CC injury or surgery. AM developed DD following status epilepticus (SE) which resolved over a 2-year period. Whole brain functional connectivity (FC) was compared (Crawford-Howell [CH]) to 16 controls during the period of acute DD symptoms (Time 1) and after remission (Time 2). Whole brain graph theoretical models were also constructed and topological efficiency examined. At Time 1, disrupted FC was observed in inter-hemispheric and intra-hemispheric right edges, involving frontal superior and midline structures. Graph analysis indicated disruption of the efficiency of salience and right frontoparietal (FP) networks. At Time 2, after remission of diagnostic dyspraxia symptoms, FC and salience network changes had resolved. In sum, longitudinal analysis of connectivity in AM indicates that DD behaviors could result from disruption of systems that support the experience and control of volitional movements and the ability to generate appropriate behavioral responses to salient stimuli. This also raises the possibility that changes to large-scale functional architecture revealed by resting-state functional magnetic resonance imaging (fMRI) (rs-fMRI) may provide relevant information on the evolution of behavioral syndromes in addition to that provided by structural and task-based functional imaging.

The role of sub-hippocampal versus hippocampal regions in bitemporal lobe epilepsies.

OBJECTIVE: We aimed at better delineating the functional anatomical organization of bitemporal lobe epilepsy. METHODS: We studied the epileptogenic zone (EZ) by quantifying the epileptogenicity of brain structures explored by depth electrodes in patients investigated by stereoelectroencephalography (SEEG). We compared 15 patients with bilateral mesial temporal lobe epilepsy (BTLE) and 15 patients with unilateral mesial temporal lobe epilepsy (UTLE). This quantification was performed using the 'Epileptogenicity Index' (EI). RESULTS: Age at epilepsy onset, and epilepsy duration, were not statistically different in both groups. UTLE patients more frequently displayed maximal epileptogenicity in hippocampal structures, whereas BTLE patients had maximal values in subhippocampal areas (entorhinal cortex, temporal pole, parahippocampal cortex). CONCLUSIONS: Our results suggest different organization of the EZ in the two groups. SIGNIFICANCE: BTLE was associated with more involvement of subhippocampal regions, a result in agreement with known anatomical connections between the two temporal lobes.

Responders to vagus nerve stimulation (VNS) in refractory epilepsy have reduced interictal cortical synchronicity on scalp EEG.

EEG desynchronization has been proposed to be an important mechanism for antiepileptic effect of vagus nerve stimulation (VNS) but has never been clearly documented in human. The aim of this study was to evaluate impact of VNS on the synchronicity of interictal EEG rhythms. We estimated synchronization between scalp EEG signals using phase lag index (PLI) in 19 patients with chronic VNS therapy. We estimated changes in synchronization between ON and OFF phases and between responder (R) and non-responder (NR) patients. We found that R have a lower global level of synchronization (EEG broadband) than NR (p<0.0001) In addition, ON periods were characterized by lower values in comparison with OFF periods (p<0.001). R had significantly lower global synchronization levels in delta and alpha frequency bands (p<0.0001). Patients responding to VNS have thus a lower level of broadband EEG synchronization than non-responders. Estimating changes of synchronization level is thus a promising tool for predicting response to VNS.

[Lateglacial and Holocene vegetation history in the mountain range of central Pyrenees]. / Dynamique tardiglaciaire et holocène de la végétation a l'etage montagnard dans les Pyrénées centrales.

We present the pollen analysis of a new sedimentary sequence taken at La Pouretère ( 1720 m), in the mountain vegetation zone of the Marcadau valley (central Pyrenees). The Lateglacial and Holocene chronology is supported by six 14C-dating results. The complementary analysis of some vegetal macroremains, stomata, pollen-clusters and the use of pollen influx allows us to elucidate the dynamic of mountain species such as Pinus and specially Abies but also to infer the unusual part played by Betula at the beginning of the Postglacial period.

Intraoperative monitoring in pediatric orthopedic spinal surgery: three hundred consecutive monitoring cases of which 10% of patients were younger than 4 years of age.

STUDY DESIGN: Analysis of a prospective series of 300 consecutive cases undergoing intraoperative monitoring in pediatric orthopedic spinal surgery, of which 10% were children younger than 4 years. OBJECTIVE: Determine feasibility and performance of intraoperative monitoring in children younger than 4 years. Analyze distinct physiopathologic mechanisms of relevant alerts. SUMMARY OF BACKGROUND DATA: There are few studies in the literature concerning the intraoperative monitoring of children younger than 4 years. During childhood, the development of sensori-motor pathways is dominated by two coexisting phenomena, which have opposite effects: maturation decreasing latencies and height increasing them. METHODS: We used intraoperative somatosensory-evoked potentials and neurogenic mixed evoked potentials with a flexible bipolar epidural electrode. Uniform total intravenous anesthesia was used. RESULTS: Values of sensitivity and specificity of the monitoring showed slight differences between patients younger than 4 years versus older patients. There was no false-negative outcome. Various tendencies were highlighted. There were more true positive alerts for secondary etiologies than for idiopathic ones, for revision spinal surgeries than for index ones, and for boys than for girls. There were no more true positive alerts for children younger than 4 years than for older patients whereas the proportion of hemivertebrae was obviously greater for the younger group. Relevant monitoring alerts were more frequent in case of kyphoscoliosis. This is highlighted in case reports. CONCLUSION: In some cases of kyphoscoliosis, during a posterior-based vertebral column resection, monitoring changes were corrected by positioning a rod that allowed correction of the position of the spine in the sagittal plane. Intraoperative spinal cord monitoring can be performed in children younger than 4 years and allows real-time assessment of spinal functional integrity.

Neural networks underlying parietal lobe seizures: a quantified study from intracerebral recordings.

In this study we have quantified the "epileptogenicity" of several brain regions in seizures originating in the posterior parietal cortex in 17 patients investigated by intracerebral recordings using stereotactic EEG (SEEG). Epileptogenicity of brain structures was quantified according to the "epileptogenicity index" (EI), a way to quantify rapid discharges at seizure onset. Seven patients had maximal epileptogenicity in the superior parietal lobule-BA area 7 (Gr1), 2 patients in the superior parietal lobule-area 5 (Gr2), 4 patients in inferior parietal lobule (Gr3) and 4 in the opercular region (Gr4). A large majority of patients (15/17 (88%)) reported to have at least one aura during the course of their disease. Somato-sensory manifestations were reported in the four groups. Vestibular disturbance was observed mainly in seizures from the superior parietal lobule (Gr1 and 2). Ipsilateral version was the most frequent objective manifestation (64%). Hyperkinetic behaviour (motor agitation) was found to be frequent, observed in 4/17 cases (23%) and observed in seizures from inferior parietal regions. In conclusion, the electrophysiological organization and the clinical manifestations of PLS are various and complex. The subjective manifestations are frequent and often suggestive, therefore must be actively sought.

Déjà-vu in temporal lobe epilepsy: metabolic pattern of cortical involvement in patients with normal brain MRI.

To contribute to the identification of brain regions involved in déjà-vu, we studied the metabolic pattern of cortical involvement in patients with seizures of temporal lobe origin presenting with or without déjà-vu. Using voxel-based analysis of 18FDG-PET brain scans, we compared glucose metabolic rate of 8 patients with déjà-vu, 8 patients without déjà-vu, and 20 age-matched healthy subjects. Patients were selected after comprehensive non-invasive presurgical evaluation, including normal brain MRI and surface electroclinical features compatible with unilateral temporal lobe epilepsy (TLE). Patients with and without déjà-vu did not differ in terms of age, gender, epilepsy lateralization, epilepsy onset, epilepsy duration, and other subjective ictal manifestations. TLE patients with déjà-vu exhibited ipsilateral hypometabolism of superior temporal gyrus and of parahippocampal region, in the vicinity of perirhinal/entorhinal cortex, in comparison either to healthy subjects or to TLE patients without déjà-vu (p<0.05 FDR-corrected). By contrast, no difference was found between patient subgroups for hypometabolism of hippocampus and amygdala. At an individual-level, in comparison to healthy subjects, hypometabolism of both parahippocampal region and superior temporal gyrus was present in 7/8 patients with déjà-vu. Hippocampal metabolism was spared in 3 of these 7 patients. These findings argue for metabolic dysfunction of a medial-lateral temporal network in patients with déjà-vu and normal brain MRI. Within the medial temporal lobe, specific involvement of the parahippocampal region, often in the absence of hippocampal impairment, suggests that the feeling of familiarity during seizures greatly depends on alteration of the recognition memory system.

Acute motor and sensory axonal neuropathy and concomitant encephalopathy during tumor necrosis factor-alpha antagonist therapy.

A woman with Crohn's disease developed acute neuropathy and concomitant encephalopathy while being treated with infliximab. The etiological investigations were negative. Infliximab was stopped and she was given four series of polyvalent immunoglobulin injections. Eighteen months later, the encephalitic symptoms had disappeared and the neuropathic symptoms were less severe. TNF-alpha antagonists have been previously blamed for triggering neurological disorders, but no cases of acute neuropathy concomitant with encephalopathy have been reported so far.