Ictal and interictal MEG in pediatric patients with tuberous sclerosis and drug resistant epilepsy.

PURPOSE: Drug resistant epilepsy (DRE) is common in patients with tuberous sclerosis (TS). Interictal MEG has been shown as a valuable instrument in the presurgical workup. The goal of our study was to evaluate the role of ictal MEG in epileptogenic tuber selection, especially in patients with multiple irritative zones. METHODS: The clinical and MEG data of 23 patients with TS and DRE from two medical/research centers were reviewed. Seven pediatric patients, who had seizures during MEG recording and underwent resection or disconnection surgery, were included into the study. Cortical sources of ictal and interictal epileptiform MEG discharges were compared with epileptogenic zone location in six patients with favorable surgery outcome. RESULTS: In patients who improved substantially after surgery all resected and several other tubers demonstrated epileptiform activity on interictal MEG. Ictal MEG provided crucial information about lobar location of the seizure onset zone (SOZ) in two cases, and in the other four it confirmed the SOZ location derived from the interictal data. In one case, ictal MEG findings were unreliable. In one patient, who did not benefit from surgical treatment, the resected tubers did not overlap with interictal and ictal MEG sources. CONCLUSION: The combination of interictal and ictal MEG is a valuable tool for identification of the epileptogenic tuber/tubers in presurgical work-up in patients with TS.

Combined use of non-invasive techniques for improved functional localization for a selected group of epilepsy surgery candidates.

Invasive cortical mapping is conventionally required for preoperative identification of epileptogenic and eloquent cortical regions before epilepsy surgery. The decision on the extent and exact location of the resection is always demanding and multimodal approach is desired for added certainty. The present study describes two non-invasive preoperative protocols, used in addition to the normal preoperative work-up for localization of the epileptogenic and sensorimotor cortical regions, in two young patients with epilepsy. Magnetoencephalography (MEG) was used to determine the primary somatosensory cortex (S1) and the ictal onset zones. Navigated transcranial magnetic stimulation (nTMS) was used to determine the location and the extent of the primary motor representation areas. The localization results from these non-invasive methods were used for guiding the subdural grid deployment and later compared with the results from electrical cortical stimulation (ECS) via subdural grids, and validated by surgery outcome. The results from MEG and nTMS localizations were consistent with the ECS results and provided improved spatial precision. Consistent results of our study suggest that these non-invasive methods can be added to the standard preoperative work-up and may even hold a potential to replace the ECS in a subgroup of patients with epilepsy who have the suspected epileptogenic zone near the sensorimotor cortex and seizures frequent enough for ictal MEG.

Artifact and head movement compensation in MEG.

PURPOSE: Magnetoencephalography (MEG) is traditionally considered impractical if the subject's head moves during measurements. A novel approach to correct the head position and the associated movement-related artifacts does, however, exist: continuous head position monitoring and movement compensation (MC) realized by the signal space separation (SSS) or its temporal extension (tSSS). The latter is especially important for rejection of close-to-sensor artifacts. The goal of the present work was to study how MC-SSS and its temporal extension MC-tSSS would influence MEG results. METHODS: Somatosensory evoked MEG responses to electrical median nerve stimulation were recorded with 204 planar gradiometers and 102 magnetometers. We compared the localization error of the N20m source, the averaged baseline noise, goodness of fit and confidence volume on data processed by MC-SSS vs. MC-tSSS on a subject moving in a controlled manner. RESULTS: We defined two patterns of disturbances with MC-SSS: stimulus artifact increase and random noise increase mainly on the lowermost sensors in very low head positions (5-6 cm shift). Up to 5-cm head shift, MC-SSS decreased mean localization error from 3.91 to 2.13 cm, but at the same time increased noise on gradiometers from 3.4 to 5.3 fT/cm. The noise increment occurred simultaneously with signal enhancement as MC transformed the head position closer to the sensors. Replacement of SSS by tSSS reduced the noise on gradiometers from 5.3 to 2.8 fT/cm and on magnetometers from 1.4 to 0.8 fT, reduced the mean localization error from 2.13 to 0.89 cm and increased the goodness of fit from 61.5% to 76.5%. Thus, tSSS specifically suppressed the random noise and nearby artifacts without suppressing the signal and thereby improved the signal to noise ratio. CONCLUSIONS: Head position recalculation should be combined with a powerful artifact rejection method. We recommend limiting MC use up to 3 cm head shift and using tSSS-based MC.

Electromagnetic function of polymicrogyric cortex in congenital bilateral perisylvian syndrome.

BACKGROUND: Congenital bilateral perisylvian syndrome (CBPS) is characterised by bilateral perisylvian polymicrogyria and suprabulbar paresis. Mild tetraparesis, cognitive impairment, and epilepsy are frequently associated. Sensory deficits are surprisingly rare, even though polymicrogyria often extends to auditory and sensorimotor cortex. OBJECTIVES: To study the sensorimotor and auditory cortex function and location in CBPS patients. METHODS: We mapped the sensory and motor cortex function onto brain magnetic resonance images in six CBPS patients and seven control subjects using sources of somatosensory and auditory evoked magnetic fields, and of rhythmic magnetoencephalographic (MEG) activity phase-locked to surface electromyogram (EMG) during voluntary hand muscle contraction. RESULTS: MEG-EMG coherence in CBPS patients varied from normal (if normal central sulcus anatomy) to absent, and could occur at abnormally low frequency. Coherent MEG activity was generated at the central sulcus or in the polymicrogyric frontoparietal cortex. Somatosensory and auditory evoked responses were preserved and also originated within the polymicrogyric cortex, but the locations of some source components could be grossly shifted. CONCLUSION: Plastic changes of sensory and motor cortex location suggest disturbed cortex organisation in CBPS patients. Because the polymicrogyric cortex of CBPS patients may embed normal functions in unexpected locations, functional mapping should be considered before brain surgery.

Infantile spasms: diagnosis and assessment of treatment response by video-EEG.

The purpose of this study was to investigate early electroclinical manifestations and evaluate treatment responses by video-EEG in infants with newly diagnosed spasms. Spasms were recorded in 44 infants (27 males, 17 females) before adequate treatment. Mean ages at onset of spasms and at first video-EEG were 5.3 months (range 0.9 to 9 months) and 5.9 months (range 2.4 to 11.5 months) respectively. Thirteen infants had cryptogenic and 31 had symptomatic aetiology. First treatment was vigabatrin in 36 infants. All infants were followed until 12 months of age or death. Treatment response in the first months of therapy was assessed by repeated video-EEG studies in 23 infants. On the first video-EEG, 34 infants had typical symmetric motor spasms, three infants showed asymmetric or asynchronous behaviour, and seven infants had only subtle spasms. Interictal EEG showed hypsarrhythmia in 27 infants and multifocal spikes with normal or nearly normal background in 17 infants. Subtle spasms, asymmetric or asynchronous spasms, and asymmetric ictal or interictal EEG abnormalities were associated with symptomatic aetiology and poor cognitive and seizure outcome at 12 months. Serial video-EEG recordings showed a transition from motor to subtle spasms during the first 2 weeks of vigabatrin therapy in four infants and only subtle spasms in two therapy-resistant infants at 12 months. Cessation of spasms usually preceded disappearance of hypsarrhythmia or multifocal spikes, but persistence of multifocal spikes over several weeks was always associated with existing spasms. Transition of hypsarrhythmia into multifocal spikes was observed during vigabatrin therapy even in infants with intractable spasms. Initial diagnosis of infantile spasms requires video-EEG studies especially in infants with symptomatic aetiology who may show only subtle spasms. Video-EEG is the only reliable method for assessing treatment response as spasms and interictal EEG abnormalities are modified by treatment and may become subtle.

Proton spectroscopic imaging shows abnormalities in glial and neuronal cell pools in frontal lobe epilepsy.

PURPOSE: Proton magnetic resonance spectroscopic imaging (1H MRSI) can lateralize the epileptogenic frontal lobe by detecting metabolic ratio abnormalities in frontal lobe epilepsy (FLE). We used 1H MRS to lateralize and localize the epileptogenic focus, and we also sought to characterize further the metabolic abnormality in FLE. METHODS: We measured signals from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and creatine + phosphocreatine (Cr) in the supraventricular brain of 14 patients with frontal or frontoparietal epilepsy and their matched controls. The supratentorial brain also was segmented into gray matter, white matter, and cerebrospinal fluid classes. Regional metabolite alterations were compared with localizing and lateralizing results from other examination modalities and with histology from three patients. RESULTS: Spectroscopy lateralized the epileptogenic focus in 10 patients in agreement with video-EEG and functional imaging. In four patients, spectroscopy showed bilateral, focal metabolic abnormality, whereas video-EEG suggested unilateral or midline abnormality. In the epileptogenic focus, Cho and Cr were increased by 23% and 14%, respectively, and NAA was decreased by 11%, suggesting metabolic disturbances both in the glial and in the neuronal cell pools. Two Taylor dysplasia lesions confirmed by histology and one with radiologic diagnosis showed high Cho and low or normal NAA, whereas two dysembryoplastic neurogenic tumors had normal Cho and low NAA. Contralateral hemisphere NAA/(Cho + Cr) was decreased in FLE, indicating diffusely altered brain metabolism. Segmentation of brain tissue did not reveal atrophic changes in FLE. CONCLUSIONS: Spectroscopy is useful in lateralizing frontoparietal epilepsy and shows promise as a "noninvasive biopsy" in epileptogenic lesions.

Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment.

Two familial X-linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X-linked transmission. On the other hand, the pedigrees of 2 families ruled out X-linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X-linked syndrome of cortical maldevelopment.

Magnetoencephalography in presurgical evaluation of children with the Landau-Kleffner syndrome.

PURPOSE: Our aim was (a) to localize the primary epileptogenic cortex for possible multiple subpial transsection in four children with the Landau-Kleffner syndrome (LKS), and (b) to evaluate the impact of magnetoencephalography (MEG) in the localizing process. METHODS: We used EEG to detect the overall epileptiform activity and MEG for selective recording of fissural spikes. The cortical generators of MEG spikes were modeled with dipoles, and their activation order was determined. The voltage distribution, consistent with the earliest MEG sources, was then identified during the course of the patient's EEG spikes to determine the relative timing between stereotypic EEG and MEG spikes and to distinguish the earliest (primary) source area among the secondary ones. RESULTS: In all patients, the earliest spike activity originated in the intrasylvian cortex, spreading in one subject to the contralateral sylvian cortex within 20 ms. Secondary spikes occurred within 10-60 ms in ipsilateral perisylvian, temporooccipital, and parietooccipital areas. A single intrasylvian pacemaker initiated all epileptic activity in two patients, whereas the other two had independent left- and right-hemisphere circuits or focal spikes. MEG source dynamics predicted the results of the methohexital suppression test in two patients and was confirmed by surgery outcome in one patient, in whom all epileptic activity ceased after a small transsection of the sylvian pacemaker. CONCLUSIONS: (a) The intrasylvian cortex is a likely pacemaker of epileptic discharges in LKS, and (b) MEG provides useful presurgical information of the cortical spike dynamics in LKS patients.

Apparent asynchrony between interictal electric and magnetic spikes.

We recorded simultaneous multichannel electroencephalogram (EEG) and magnetoencephalogram (MEG) in four children with partial epilepsy. Sources of averaged spikes were modelled with current dipoles. Of 10 spike averages obtained, three peaked simultaneously in MEG and EEG, and in seven averages, the MEG peak preceded the main EEG peak by 9-40 ms. A small positive early EEG signal coincided with the MEG peak in six asynchronous spikes. The simultaneous MEG and EEG spikes originated within 5-23 mm, while sources of asynchronous peaks were 12-67 mm apart. We conclude that non-identical neurone currents underlie the MEG and EEG signals, and emphasize the importance of modelling early phases of EEG spikes when localizing interictal epileptic zones.

Auditory evoked magnetic fields to tones and pseudowords in healthy children and adults.

Neuromagnetic responses to tones and pseudowords were measured with a 24-channel magnetometer in nine adults and in 23 children, the latter aged 0.3-15 years. Both stimulus types elicited substantially similar responses in all subjects. At 0.9-s interstimulus interval (ISI), the adult response was a stable P1m-N1m-P2m-N2m sequence peaking at 50, 100, 200, and 250 ms, respectively. A biphasic P1m-N1,2m response with peaks at 100 and 260 ms occurred in children up to 12 years of age. At longer ISIs (1.2-2.4 s), an adult-type N1m response appeared in most children. N1m amplitude suppression at short ISIs was stronger in children than in adults and may reflect a longer refractory period of the N1 generator neurons during early childhood than later in life. Peak latencies of P1m, N1m, and N2m decreased with age, most rapidly < 7 years of age. All deflections originated in nearby cortical areas within the posterior sylvian fissure, and may serve as functional landmarks for that anatomic area.

Sounds triggers spikes in the Landau-Kleffner syndrome.

Auditory evoked magnetic fields and spontaneous epileptic activity were recorded with a 24-channel planar gradiometer in 7 children with acquired epileptic speech disorders. Six children had a marked loss of speech comprehension (the Landau-Kleffner syndrome--LKS); in one child, only the speech fluency was affected. Auditory evoked fields were abnormal in five patients studied during active disease. Sounds triggered signals identical to the spontaneous spikes in three LKS patients. In two patients, the triggered spikes lagged the tone onset by 100 ms, whereas the interstimulus interval affected the lag in the third. The neural generator sites of spontaneous and triggered spikes did not differ: both were within a 2-6-cm2 patch of cortex aligning the sylvian fissure in one or both hemispheres. The epileptiform activity of LKS patients may be produced by sound-responsive neurons in the nonprimary auditory cortex within the middle and posterior sylvian fissures. The generators of the auditory 100-ms response probably contribute to the spikes in a group of LKS patients, but other pathogenetic mechanisms may coexist.

Magnetoencephalographic evaluation of children and adolescents with intractable epilepsy.

Magnetoencephalographic (MEG) discharges were recorded with multichannel superconducting quantum interference device (SQUID) gradiometers in 13 young candidates for epilepsy surgery. The sources of epileptic activity were related to generators of somatosensory and auditory evoked cortical responses and projected on magnetic resonance imaging (MRI) scans. Seven subjects had restricted or regional MEG foci, located in the frontoopercular (1), sensorimotor (3), perisylvian (1), mesiotemporal (1), or temporooccipital cortex (1). The MEG foci in the 3 patients who underwent operation agreed with the intracranial findings. Findings in the other patients emphasize the need to collect further data to define the ultimate role of MEG in preoperative evaluation of epilepsy.

Cortical reactivity in progressive myoclonus epilepsy.

We studied 4 patients with progressive myoclonus epilepsy (Unverricht-Lundborg disease; ULD). Somatosensory evoked fields (SEFs), auditory evoked fields (AEFs), and spontaneous activity over the somatomotor cortex were recorded with a 24-channel SQUID gradiometer. All patients had "giant" 20-45 msec median nerve SEFs at the first somatomotor cortex, with 2-6 times larger amplitudes than the healthy control subjects. Later deflections were not similarly enhanced. The dependence of SEF amplitudes on interstimulus interval (0.2-4 sec) and on successive ulnar-median nerve stimulation (stimulus interval 40 msec) was comparable to that in controls. Cortical AEFs were attenuated and delayed. In 3 patients, the spontaneous activity consisted of 6-8 Hz mu rhythm, which originated within 2 cm from the sources of SEFs and was abolished by clenching of the contralateral fist. Control subjects had major spectral peaks around 10 and 20 Hz. The SEF amplitudes and the strength of the 6-10 Hz mu correlated strongly, suggesting that some components of evoked and spontaneous activity obtain contributions from overlapping neuronal populations. The results imply that ULD is associated with thalamo-cortical hyperreactivity in the sensorimotor but not in the auditory system.

Parietal epileptic mirror focus detected with a whole-head neuromagnetometer.

Whole-head magnetoencephalographic recordings revealed two parietal epileptic foci in homotopic areas of the hemispheres. The discharges occurred 17-20 ms later on the left than on the right hemisphere, implying the existence of a left-sided mirror focus. The foci were about 1 cm posterior to the hand primary somatosensory area, identified by evoked response measurements, and thus suggested epileptic activity at the parietal association cortex, in agreement with the observed callosal conduction time.

Magnetoencephalographic localization of epileptic cortex--impact on surgical treatment.

A 24-channel, planar, superconducting quantum interference device gradiometer, sampling a fourth of the head surface over brain tissue, was used to determine the site of an epileptic focus in a 36-year-old woman with intractable complex partial epilepsy. The other presurgical findings appeared divergent: a large arachnoid cyst over the right parietal convexity, dissimilar interictal electroencephalographic patterns, and several neuropsychological dysfunctions. The equivalent current sources of magnetoencephalographic spikes were in the right posterior temporal region of the cortex, 4 cm apart from the cyst. Surgical exploration of the area pinpointed by magnetoencephalography revealed a pachygyric patch of cortex displaying focal discharges on the electrocorticogram. After resection, a dramatic reduction of seizures occurred. The good agreement between electrocorticography and magnetoencephalography warrants future investigation of multichannel magnetoencephalography as a potential alternative to invasive presurgical recordings.

Cerebral magnetic fields to lingual stimulation.

We recorded cerebral magnetic fields to electric stimulation of the tongue in 7 healthy adults. The two main deflections of the response peaked around 55 msec (P55m) and 140 msec (N140m). During both of them the magnetic field pattern, determined with a 7- or 24-channel SQUID magnetometer, suggested a dipolar current source. The topography of P55m can be explained by a tangential dipole at the first somatosensory cortex (SI) in the posterior wall of the central sulcus. The equivalent source of N140m is, on average, about 1 cm lateral to the source of P55m. The reported method allows non-invasive determination of the cortical tongue representation area.

Landau-Kleffner syndrome: epileptic activity in the auditory cortex.

The Landau-Kleffner syndrome (LKS) is characterized by electroencephalographic spike discharges and verbal auditory agnosia in previously healthy children. We recorded magnetoencephalographic (MEG) spikes in a patient with LKS, and compared their sources with anatomical information from magnetic resonance imaging. All spikes originated close to the left auditory cortex. The evoked responses were contaminated by spikes in the left auditory area and suppressed in the right--the latter responses recovered when the spikes disappeared. We suggest that unilateral discharges at or near the auditory cortex disrupt auditory discrimination in the affected hemisphere, and lead to suppression of auditory information from the opposite hemisphere, thereby accounting for the two main criteria of LKS.

Magnetoencephalography in the study of epilepsy.

A brief review is given about the basic principles of magnetoencephalography (MEG), a noninvasive brain research method in which weak magnetic fields are detected outside the human head with SQUID (Superconducting Quantum Interference Device) magnetometers. The active brain areas, producing the signal, are modelled by current dipoles, which are assumed to be situated in a spherically symmetric volume conductor. The locations of these "equivalent dipoles" can be found, in the optimal case, with a precision of a few millimeters. The new multichannel magnetometers allow measurements of spontaneous brain activity without EEG-triggered averaging. The 3-dimensional locations of superficial epileptogenic foci can be determined with respect to external landmarks on the skull and to known generator areas of evoked responses in the brain. Examples are given about MEG recordings of epileptic patients.