Seizure anticipation in human neocortical partial epilepsy

Brain (2002), 125, 640±655 Seizure anticipation in human neocortical partial epilepsy Vincent Navarro,1,2 Jacques Martinerie,1 Michel Le Van Quyen,1 SteÂphane Clemenceau,1,3 Claude Adam,1,2 Michel Baulac1,2 and ²Francisco Varela1 1Laboratoire de Neurosciences Cognitives et Imagerie CeÂreÂbrale (LENA), CNRS UPR 640, 2Unite d'Epileptologie and 3Service de Neurochirurgie, HoÃpital de la PitieÂSalpeÃtrieÁre, Paris Correspondence to:Professor Michel Baulac, Unite d'Epileptologie, Clinique Paul Castaigne, HoÃpital de la PitieÂ-SalpeÃtrieÁre, 47 boulevard de l'HoÃpital, 75651 Paris cedex 13, France E-mail: ²Deceased Summary The transition of brain activity towards an epileptic seizure is still a poorly understood phenomenon. Dynamic changes in brain activity have been detected several minutes before seizure emergence in populations of patients with mesial temporal lobe epilepsy (MTLE), using non-linear analysis of intracranial EEG recordings. Similar detection of a pre-ictal state has been obtained with standard scalp EEG recordings using a modi®ed non-linear method. Here we applied this strategy to the seizures of patients with neocortical partial epilepsy. Results obtained by non-linear similarity analysis of 41 seizures from 11 patients with refractory partial epilepsy originating from various sites of the neocortex showed that (i) a pre-ictal state was detected in 90% of the patients and in 83% of the seizures whatever their location, with a mean anticipation time of 7.5 min; (ii) similar pre-ictal dynamic changes were May 28, 2001 detected when non-linear analysis methods were applied to either intracranial or scalp EEG recordings; (iii) the recording sites exhibiting these pre-ictal changes were distributed both within the epileptogenic focus and at remote locations; (iv) most pre-ictal dynamic changes were not correlated with linear changes in the frequency spectrum or with changes in the visually inspected EEG and the patients' behaviour. Hypotheses on the neuronal mechanisms underlying the pre-ictal period are discussed. The present results, together with those recently obtained in an MTLE population, suggest that changes in pre-ictal dynamics are a general phenomenon associated with seizure emergence in a wide population of patients with partial epilepsy, wherever the epileptogenic focus is located. The possibility of anticipating the onset of seizures has considerable therapeutic implications. Keywords: neocortical epilepsy; scalp electroencephalogram; intracranial electroencephalogram; non-linear analysis; seizure anticipation Abbreviations: ANOVA = one-way analysis of variance; MTLE = mesial temporal lobe epilepsy Introduction For patients with intractable epilepsy, the unpredictability of seizure occurrence underlies an increased risk of sudden unexpected death (Cockerell et al., 1994) or morbidity (Buck et al., 1997) and is a major factor contributing to a poor quality of life (Devinsky et al., 1995). Anticipation of seizures would permit their consequences to be minimized and also allow therapeutic measures to be taken before seizures occur. Traditional approaches for detecting pre-ictal changes have encountered dif®culties. Clinical distinctions between premonitory sensations and the aura are delicate (Rajna et al., 1997), and if they are prodroma they may imply ã Guarantors of Brain 2002 very subtle and variable feelings even in the same patient. Only a few fortuitous (Baumgartner et al., 1998) or invasive (Weinand et al., 1997) studies using functional cerebral imaging have provided evidence for pre-ictal changes of regional cerebral blood ¯ow in patients with mesial temporal lobe epilepsy (MTLE). Traditional analyses of EEG signals have failed to detect speci®c changes preceding seizures, either by visual inspection of the recordings, even during intracerebral investigation, or using linear methods based on spectral analysis (Rogowski et al., 1981; Katz et al., 1991). Table 1 Summary of clinical and surgical data of the patients Patient Gender Age at onset (years) Age* (years) Epileptic focus Side Brain MRI Neuropathological ®ndings Surgical procedure Outcome (follow-up) Frontal focus 1 (B.I.L.) M 9 23 Pars orbitalis of F3 L Normal Astrocytic gliosis IA (6 m) 2 (D.E.P.) F 18 30 Anterior orbital gyrus R Normal 3 (M.A.Z.) M 16 30 Middle frontal gyrus L Normal Astrocytic gliosis and minor changes in cortical architecture Astrocytic gliosis Basal±frontal external resection and F3 subpial transections Basal±frontal resection 30 45 T2 R 14 31 T1 R External temporal scar Normal Temporal neocortical focus 4 (Q.U.A.) M 5 (C.L.O.) F Temporo-occipital junction focus 6 (P.I.C.) F 2 months Anterior frontal resection IA (3 m) Astrocytic gliosis T2 cortical resection IIB (3 y) Astrocytic gliosis T1 cortical resection IVB (3.5 y) Posterior TO parahippocampal cortical resection and amygdalohippocampectomy Partial TO cortical resection Lesionectomy IIIA (4 y) ID (7 m) Lesionectomy IA (5.5 y) None (implication of multiple foci and functional area) Lesionectomy IIB (1.5 y) 24 R External TO lesion Dysplasia M 12 21 R External TO scar Astrocytic gliosis 8 (F.A.B.) M 17 40 R External TO lesion 9 (T.Y.R.) M 18 23 L Parieto-occipital focus 10 (P.I.N.) M External TO lesion Dysembryoplastic neuroepithelial tumour Meningioangiomatosis 13 18 L Normal 24 26 R Parietooccipital lesion F Meningioma IB (1 y) Surgical outcome was scored according to Engel, 1987. *At the time of the video-EEG recordings. M = male; F = female; y = years; m = months; R = right; L = left; TO = temporooccipital. Anticipation of neocortical seizures 7 (E.L.G.) 11 (C.R.E.) IA (3.5 y) 641 642 V. Navarro et al. Strategies of non-linear analysis have succeeded in demonstrating pre-ictal changes in the intracerebral EEG in patients with MTLE (Lehnertz and Elger, 1998; Martinerie et al., 1998). Changes in EEG dynamics, extracted by different non-linear measures, were detected several minutes before the onset of the seizure, when patients reported no speci®c sensations and visual inspection of the recording showed no clear changes in the EEG signal (Martinerie et al., 1998). Non-linear methods were developed initially to describe the dynamics of complex physical systems with non-linear components, implying that their time course does not follow the linearity of the classical deterministic laws, but may instead exhibit non-proportional responses to speci®c inputs. Self-organizing behaviour and intermittency are other interesting properties of non-linear systems which permit transitions between states in the absence of external triggers. The epileptic process is also chronically intermittent and spontaneous, except for rare re¯ex epilepsies, and mathematical tools for the characterization of non-linear deterministic systems have been used successfully to determine changes in the state of brain activit (...truncated)