The mismatch negativity (MMN) potential as a tool for the functional mapping of temporal lobe epilepsies.

Temporal lobe epilepsies are associated with cognitive dysfunctions in memory which are important clues currently used clinically for the lateralization of the epileptic focus in evaluations for epilepsy surgery. Because these lobes also contain the primary auditory cortex, the study of auditory evoked potentials (AEPs) is a candidate, not yet established, complementary method to characterize epilepsy-induced dysfunction. We aimed to establish the clinical usefulness of auditory evoked potentials for the study of pediatric symptomatic temporal lobe epilepsies. A group of 17 patients (ages 4-16) with symptomatic epilepsies undergoing evaluation for epilepsy surgery epilepsy was submitted to auditory evoked potentials using 35-channel scalp EEG recordings. A control group of 10 healthy volunteers was studied with the same protocol. The P100 and mismatch negativity (MMN) potential latencies and normalized amplitudes were studied. We also performed a voxel-based lesion-symptom mapping (VLSM) to determine the anatomical areas associated with changes in the AEPs. Eleven patients had temporal lobe epilepsy, three had frontal lobe epilepsy, and three had occipital lobe epilepsy. Latencies for the P100 were normal in 15/17 and in 11/17 for the MMN, with no consistent correlation with the epilepsy type. The MMN amplitude was abnormal in 7/17 patients, all with temporal lobe epilepsies (sensitivity of 64%). Of these patients, four had a decreased MMN associated with a Heschl's gyrus lesion in the VLSM, and three had an increased MMN associated with hippocampal lesion. No extratemporal epilepsy showed MMN amplitude abnormalities (specificity of 100%). The P100 amplitude was abnormal in 3/17, two with temporal and one with frontal lobe epilepsies. The auditory MMN has a high specificity but a low sensitivity for temporal lobe epilepsy in symptomatic pediatric epilepsies. Amplitude decreases of the MMN are associated with homolateral Heschl's gyrus lesions, and MMN increases with hippocampal lesions.

Neuropsychological abnormalities in children with the Panayiotopoulos syndrome point to parietal lobe dysfunction.

Panayiotopoulos syndrome (PS) is a common epilepsy syndrome associated with rare clinical seizures and unknown localization of the epileptogenic area. Despite findings of normal development in patients with PS, recent neuropsychological studies point to subtle and diverse cognitive impairments. No well-outlined hypothesis about the localization of the brain dysfunction responsible for these impairments has been proposed. We further explored the cognitive dysfunctions in PS and made inferences on the most likely anatomical localization of brain impairment. A group of 19 patients (aged 6-12) with PS was rated according to spike activity and lateralization. The patients were submitted to a neuropsychological evaluation to assess general intelligence, memory, language, visual-perceptual abilities, attention, and executive functions. Using 35-channel scalp EEG recordings, the N170 face-evoked event-related potential (ERP) was obtained to assess the functional integrity of the ventral pathway. All patients with PS showed normal IQ but subtle and consistent neurocognitive impairments. Namely, we found abnormalities in the copy task of the Rey-Osterrieth Complex Figure and in the Narrative Memory Test. There was no correlation between neuropsychological impairments with spike activity and hemispheric spike lateralization. The N170 ERP was normal in all patients except for one. Our neuropsychological findings demonstrate impairments in visual-perceptual abilities and in semantic processing. These findings, paired with the absence of occipital lobe dysfunction in all neuropsychological studies of PS performed to this date, support the existence of parietal lobe dysfunction.

Origin and dynamics of epileptic activity in a symptomatic case of Panayiotopoulos syndrome: correlation with clinical manifestations.

OBJECTIVE: The aim of the study was to demonstrate the dynamics and structure of the epileptic network and provide a tentative correlation with the clinical manifestations, in a symptomatic case of Panayiotopoulos syndrome (PS). METHODS: JP, 5-year-old girl. Gestational period and developmental milestones were normal. At age 4 years, two episodes of recurrent vomiting, tonic eye deviation and consciousness impairment lasting for about 30 min occurred. Multifocal spikes were apparent over frontal areas in the EEG and MRI demonstrated an inferior parietal lobe (IPL) lesion. RESULTS: A long-term 35-channel scalp EEG was obtained, which was processed with a Blind Source Separation algorithm. The most significant components with a dipolar field were submitted to source analysis and the recovered generators used to build the nodes of a brain network associated with each spike type. Analysis of information flow supported epileptic propagation from the left parietal lobe to both frontal and temporal lobes around spike peak. The good spatial overlap with physiological networks controlling eye movements, autonomic functions and consciousness, provides a tentative explanation to the diverse clinical manifestations of PS. CONCLUSIONS: Spreading patterns of epileptic activity form an extended network in PS. SIGNIFICANCE: An epileptic focus in an IPL can reproduce both neurophysiological and clinical features of PS.

Functional brain mapping of ictal activity in gelastic epilepsy associated with hypothalamic hamartoma: a case report.

Hypothalamic hamartomas (HHs) have been demonstrated as the cause of gelastic epilepsy, both by intracranial electrodes and functional imaging. The neocortex becomes secondarily involved, through poorly characterized propagation pathways. The detailed dynamics of seizure spread have not yet been demonstrated, owing to the limited spatial-temporal resolution of available functional mapping. We studied a patient with epilepsy associated with HH and gelastic epilepsy. Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) of several seizure events were obtained, with blood oxygen level dependent (BOLD) activation of the hamartoma, and left hemisphere hypothalamus, hippocampus, parietal-occipital area, cingulate gyrus, and dorsal-lateral frontal area. Integration of regional BOLD kinetics and EEG power dynamics strongly suggests propagation of the epileptic activity from the HH through the left fornix to the temporal lobe, and later through the cingulate fasciculus to the left frontal lobe. The EEG/fMRI method has the spatial-temporal resolution to study the dynamics of seizure activity, with detailed demonstration of origin and propagation pathways.

Origin of frontal lobe spikes in the early onset benign occipital lobe epilepsy (Panayiotopoulos syndrome).

OBJECTIVE: Early onset benign occipital lobe epilepsy (Panayiotopoulos syndrome [PS]) is a common and easily recognizable epilepsy. Interictal EEG spike activity is often multifocal but most frequently localized in the occipital lobes. The origin and clinical significance of the extra-occipital spikes remain poorly understood. METHODS: Three patients with the PS and interictal EEG spikes with frontal lobe topography were studied using high-resolution EEG. Independent component analysis (ICA) was used to decompose the spikes in components with distinct temporal dynamics. The components were mapped in the scalp with a spline-laplacian algorithm. RESULTS: The change in scalp potential topography from spike onset to peak, suggests the contribution of several intracranial generators, with different kinetics of activation and significant overlap. ICA was able to separate the major contributors to frontal spikes and consistently revealed an early activating group of components over the occipital areas in all the patients. The local origin of these early potentials was established by the spline-laplacian montage. CONCLUSIONS: Frontal spikes in PS are consistently associated with early and unilateral occipital lobe activation, suggesting a postero-anterior spike propagation. SIGNIFICANCE: Frontal spikes in the PS represent a secondary activation triggered by occipital interictal discharges and do not represent an independent focus.

Analysis of the dynamics and origin of epileptic activity in patients with tuberous sclerosis evaluated for surgery of epilepsy.

OBJECTIVE: The epilepsies associated with the tuberous sclerosis complex (TSC) are very often refractory to medical therapy. Surgery for epilepsy is an effective alternative when the critical link between the localization of seizure onset in the scalp and a particular cortical tuber can be established. In this study we perform analysis of ictal and interictal EEG to improve such link. METHODS: The ictal and interictal recordings of four patients with TSC undergoing surgery for epilepsy were submitted to independent component analysis (ICA), followed by source analysis, using the sLORETA algorithm. The localizations obtained for the ictal EEG and for the average interictal spikes were compared. RESULTS: The ICA of ictal EEG produced consistent results in different events, and there was good agreement with the tubers that were successfully removed in three of the four patients (one patient refused surgery). In some patients there was a large discrepancy between the localization of ictal and interictal sources. The interictal activity produced more widespread source localizations. CONCLUSIONS: The use of ICA of ictal EEG followed by the use of source analysis methods in four cases of epilepsy and TSC was able to localize the epileptic generators very near the lesions successfully removed in surgery for epilepsy. SIGNIFICANCE: The ICA of ictal EEG events may be a useful add-on to the tools used to establish the connection between epileptic scalp activity and the cortical tubers originating it, in patients with TSC considered for surgery of epilepsy.

Brain mapping of epileptic activity in a case of idiopathic occipital lobe epilepsy (Panayiotopoulos syndrome).

The Panayiotopoulos type of occipital lobe epilepsy has generated great interest, but the particular brain areas involved in the peculiar seizure manifestations have not been established. We studied a patient with the syndrome, using high-resolution EEG and simultaneous EEG and functional magnetic resonance imaging (fMRI). Resolution of the scalp EEG was improved using a realistic spline Laplacian algorithm, and produced a complex distribution of current sinks and sources over the occipital lobe. The spike-related blood oxygen level dependent (BOLD) effect was multifocal, with clusters in lateral and inferior occipital lobe and lateral and anterior temporal lobe. We also performed regional dipole seeding in BOLD clusters to determine their relative contribution to generation of scalp spikes. The integrated model of the neurophysiologic and vascular data strongly suggests that the epileptic activity originates in the lateral occipital area, spreading to the occipital pole and lateral temporal lobe.

Analysis of the generators of epileptic activity in early-onset childhood benign occipital lobe epilepsy.

OBJECTIVE: The Panayiotopoulos type of idiopathic occipital epilepsy has peculiar and easily recognizable ictal symptoms, which are associated with complex and variable spike activity over the posterior scalp areas. These characteristics of spikes have prevented localization of the particular brain regions originating clinical manifestations. We studied spike activity in this epilepsy to determine their brain generators. METHODS: The EEG of 5 patients (ages 7-9) was recorded, spikes were submitted to blind decomposition in independent components (ICs) and those to source analysis (sLORETA), revealing the spike generators. Coherence analysis evaluated the dynamics of the components. RESULTS: Several ICs were recovered for posterior spikes in contrast to central spikes which originated a single one. Coherence analysis supports a model with epileptic activity originating near lateral occipital area and spreading to cortical temporal or parietal areas. CONCLUSIONS: Posterior spikes demonstrate rapid spread of epileptic activity to nearby lobes, starting in the lateral occipital area. In contrast, central spikes remain localized in the rolandic fissure. SIGNIFICANCE: Rapid spread of posterior epileptic activity in the Panayitopoulos type of occipital lobe epilepsy is responsible for the variable and poorly localized spike EEG. The lateral occipital cortex is the primary generator of the epileptic activity.

Analysis of the EEG dynamics of epileptic activity in gelastic seizures using decomposition in independent components.

OBJECTIVE: Gelastic seizures are a frequent and well established manifestation of the epilepsy associated with hypothalamic hamartomas. The scalp EEG recordings very seldom demonstrate clear spike activity and the information about the ictal epilepsy dynamics is limited. In this work, we try to isolate epileptic rhythms in gelastic seizures and study their generators. METHODS: We extracted rhythmic activity from EEG scalp recordings of gelastic seizures using decomposition in independent components (ICA) in three patients, two with hypothalamic hamartomas and one with no hypothalamic lesion. Time analysis of these rhythms and inverse source analysis was done to recover their foci of origin and temporal dynamics. RESULTS: In the two patients with hypothalamic hamartomas consistent ictal delta (2-3 Hz) rhythms were present, with subcortical generators in both and a superficial one in a single patient. The latter pattern was observed in the patient with no hypothalamic hamartoma visible in MRI. The deep generators activated earlier than the superficial ones, suggesting a consistent sub-cortical origin of the rhythmical activity. CONCLUSIONS: Our data is compatible with early and brief epileptic generators in deep sub-cortical regions and more superficial ones activating later. SIGNIFICANCE: Gelastic seizures express rhythms on scalp EEG compatible with epileptic activity originating in sub-cortical generators and secondarily involving cortical ones.

Different electroclinical manifestations of the epilepsy associated with hamartomas connecting to the middle or posterior hypothalamus.

PURPOSE: The epilepsy associated with hypothalamic hamartomas (HHs) has typical clinical, electrophysiologic, and behavioral manifestations refractory to drug therapy and with unfavorable evolution. It is well known that only sessile lesions produce epilepsy, but no correlation has been established between the different types of sessile hamartomas and the diverse manifestations of the epilepsy. We correlate anatomic details of the hamartoma and the clinical and neurophysiologic manifestations of the associated epilepsy. METHODS: HHs of seven patients with epilepsy (ages 2- 25 years) were classified as to lateralization and connection to the anteroposterior axis of the hypothalamus by using high-resolution brain magnetic resonance imaging. We correlated the anatomic classification with the clinical and neurophysiologic manifestations of the epilepsy as evaluated in long-term (24 h) video-EEG recordings. RESULTS: HHs ranged in size from 0.4 to 2.6 cc, with complete lateralization in six of seven patients. Ictal manifestations showed good correlation with the lobar involvement of ictal/interictal EEGs. These manifestations suggest the existence of two types of cortical involvement, one associated with the temporal lobe, produced by hamartomas connected to the posterior hypothalamus (mamillary bodies), and the other associated with the frontal lobe, seen in lesions connecting to the middle hypothalamus. CONCLUSIONS: A consistent clinical and neurophysiologic pattern of either temporal or frontal lobe cortical secondary involvement was found in the patients of our series. It depends on whether the hamartoma connects to the mamillary bodies (temporal lobe cases) or whether it connects to the medial hypothalamus (frontal lobe cases).

Interictal spike EEG source analysis in hypothalamic hamartoma epilepsy.

OBJECTIVE: The epilepsy associated with the hypothalamic hamartomas constitutes a syndrome with peculiar seizures, usually refractory to medical therapy, mild cognitive delay, behavioural problems and multifocal spike activity in the scalp electroencephalogram (EEG). The cortical origin of spikes has been widely assumed but not specifically demonstrated. METHODS: We present results of a source analysis of interictal spikes from 4 patients (age 2-25 years) with epilepsy and hypothalamic hamartoma, using EEG scalp recordings (32 electrodes) and realistic boundary element models constructed from volumetric magnetic resonance imaging (MRIs). Multifocal spike activity was the most common finding, distributed mainly over the frontal and temporal lobes. A spike classification based on scalp topography was done and averaging within each class performed to improve the signal to noise ratio. Single moving dipole models were used, as well as the Rap-MUSIC algorithm. RESULTS: All spikes with good signal to noise ratio were best explained by initial deep sources in the neighbourhood of the hamartoma, with late sources located in the cortex. Not a single patient could have his spike activity explained by a combination of cortical sources. CONCLUSIONS: Overall, the results demonstrate a consistent origin of spike activity in the subcortical region in the neighbourhood of the hamartoma, with late spread to cortical areas.