Non-invasive localization of the epileptogenic focus by EEG dipole modeling.

Localization of epileptogenic foci by traditional visual inspection of EEG traces is simplistic. Voltage topography and subsequent spatio-temporal multiple dipole modeling are new techniques to assess the character of cerebral generators of EEG spikes and seizure rhythms. These predictions have been validated by intracranial monitoring. Patients with mesial temporal seizures have ipsilateral spikes and early ictal rhythms with a strong tangential (vertical) dipole component that often leads any radial source activity. This suggests propagation from baso-mesial to lateral cortex. Those with infero-lateral temporal cortical seizures have similar findings, but tangential sources are synchronous with or lag radial sources. Patients with lateral temporal cortical seizures have spikes and ictal activity that are modeled principally by radial dipoles.

Estimating the importance of epileptiform abnormalities discovered on cassette electroencephalographic monitoring.

Assessment of the importance of interictal epileptiform abnormalities discovered with cassette electroencephalographic (EEG) monitoring requires some appreciation of the frequency with which such abnormalities may be encountered in individuals without epilepsy. From a clinical experience involving more than 2500 patients, we have defined a group of 184 patients referred because of headache, with no additional referral information to suggest seizures. Only one (0.5%) of these patients had epileptiform abnormalities on cassette EEG, yielding 95% and 99% confidence limits for the incidence of epileptiform abnormalities in the unselected nonepileptic headache population of 1.5% and 1.8%. Presuming that the incidence of cassette EEG epileptiform abnormalities in the healthy population would be no higher than in this patient group, we suggest that epileptiform abnormalities are no more likely to be incidental findings on cassette EEG monitoring than on routine EEG. Consequently, the detection of such abnormalities seems a worthwhile aspect of cassette EEG interpretation when the goal of monitoring is the detection of evidence to support a diagnosis of epilepsy.

Cassette electroencephalography in the evaluation of neonatal seizures.

Three-channel cassette electroencephalographic (EEG) recording for up to 24 hours was obtained from 37 neonates with clinically diagnosed or suspected seizures but no seizure activity on routine EEG. EEG seizures were recorded in seven patients, five of whom had experienced clinical seizures in the 24 hours prior to cassette EEG recording. EEG seizures were detected in only one of nine neonates with recurring clinical episodes believed unlikely to be seizures and in only one of 18 without recent clinical events. Cassette EEG can enhance the detection and differentiation of seizures in neonates with persistent clinical episodes but is of low yield otherwise.

EEG outside the hairline: detection of epileptiform abnormalities.

We have assessed the reliability in 25 epileptic patients of EEG recording using disposable self-adhesive electrodes and a seven-channel extra-hairline montage, through comparison to simultaneous standard cable telemetry. Epileptiform abnormalities were detected in all patients on blind interpretation of data acquired using the novel technique. On comparison of specific epileptiform abnormalities identified blindly, a false positive rate of 10% and a false negative rate of 8% were encountered. Posterior temporal complexes accounted for most false negatives, and most false positives did not represent failings of the recording technique. We conclude that EEG recording outside the hairline with disposable electrodes represents a reliable means to acquire, quickly and simply, EEG evidence of epilepsy. As such, it may prove useful in the acute evaluation of patients presenting with apparent seizures.

Evaluation of ambulatory cassette EEG monitoring: III. Diagnostic accuracy compared to intensive inpatient EEG monitoring.

We assessed the ability to recognize epileptiform abnormalities on a video review of ambulatory cassette EEGs (A/EEG) by comparing two independent interpretations of an A/EEG to those derived from a routine recording and intensive monitoring by cable telemetry (C/EEG) of the same 40 patients. Both A/EEG readings concurred with the C/EEG interpretation as to normality or epileptiform abnormality in 77% of cases. Seventy-nine percent of focal and 100% of generalized interictal abnormalities, as well as all seizures, noted on C/EEG were detected by both A/EEG reviewers. Of patients with normal baseline EEGs, 37% showed epileptiform features on A/EEG versus 44% with C/EEG. Limits to the characterization of abnormalities by A/EEG and a protocol for the video review of A/EEG tapes are discussed. In those specific areas for which intensive surface EEG monitoring is most useful, ambulatory cassette EEG appears to be an acceptable intermediate-level alternative.

Spike voltage topography identifies two types of frontotemporal epileptic foci.

We characterized voltage topography of frontotemporal EEG spikes in 24 patients with complex partial seizures and identified two distinct patterns. "Type 1" spikes possessed a "dipolar" field with a negative region over the inferolateral temporal scalp and a positive region over the contralateral, centroparietal scalp. "Type 2" spikes showed only a broad, frontotemporal negative field. One or the other spike type predominated in all but two patients. Correlations with clinical data and intracranial EEG suggest that type 2 spikes arise from temporal or frontal neocortex, while type 1 spikes involve mesial temporal structures as well as lateral cortex.

The clinical utility of ambulatory cassette EEG.

We obtained ambulatory EEG monitoring (A/EEG) before intensive monitoring in 33 patients newly referred to an epilepsy center. The A/EEG yield of evidence to support a diagnosis of epilepsy was 83% of that of intensive monitoring and 2.5 times that of routine EEG. Accuracy of A/EEG analysis was confirmed by two blind reviews for each tape, with only three misreadings among 99 interpretations rendered. Among 25 patients with specifically diagnostic referrals, A/EEG served the purpose of admission as well as intensive monitoring in 60%. Episodes not accompanied by A/EEG change required behavioral observation for correct identification.

Ambulatory cassette EEG in clinical practice.

We reviewed ambulatory cassette EEG (A/EEG) records of 500 patients. Epileptiform abnormalities, seizures, or both were detected in 87 patients (17.4%), including 22 who were not taking anticonvulsant drugs. Epileptiform abnormalities were found in 1.5% of patients with syncope and in none without a clear history of episodic complaints. Abnormalities were found in 5.1% of patients referred by nonneurologic physicians. Some clinical seizures were not accompanied by A/EEG change and some episodes were not seizures, despite detection of epileptiform abnormalities.

Direct comparison of 3- and 8-channel ambulatory cassette EEG with intensive inpatient monitoring.

During the intensive monitoring of 30 patients by means of cable telemetry EEG, simultaneous 3- and 8-channel ambulatory EEG recordings were also obtained. Blinded interpretations of the cassette tapes were compared with those of the cable telemetry records. Both 3- and 8-channel ambulatory EEG reviews correctly identified 93% of the records as either normal or epileptiform. Lateralization of abnormalities was equally good with either cassette system, but more detailed characterization was achieved with 8-channel ambulatory EEG. Although 100% of seizures were detected on both systems, there were more false-positive errors when only three data channels were available. Better ability to differentiate renal abnormalities from artifacts was the most significant advantage of 8-channel over 3- to 4-channel ambulatory EEG.

An evaluation of ambulatory, cassette EEG monitoring: I. Montage design.

Ambulatory EEGs using cassette tape recorders have only four channels. Questions have been raised about the limitations this imposes on detection of focal interictal epileptiform events. A review of EEGs from inpatients undergoing prolonged monitoring demonstrated an overwhelming representation of these abnormalities in the frontal and anterior temporal scalp regions. Three-channel montages were designed to sample these regions and were tested by simultaneously recording them with multichannel montages. Successful montages combining a frontal transverse and two longitudinal channels adequately detected 74 to 100% of interictal epileptic events.

An evaluation of ambulatory, cassette EEG monitoring: II. Detection of interictal abnormalities.

Although they are clearly useful for generalized ictal events, the ability of ambulatory, cassette EEG systems to detect interictal abnormalities routinely remains in question. The EEGs of 25 patients have been simultaneously monitored by cable telemetry and Oxford Medilog recorder, using a three-channel montage. Output from the cassette recorder amplifiers was of high fidelity compared to cable telemetry, and EEG reproduction from tape suffered only minimal signal degradation. Ambulatory EEG detection rate for interictal abnormalities averaged 85% and was commensurate with the montage design study. Perceptual demand during video scanning, including the recognition of normal transients and artifacts, was addressed as an important limiting factor. Ambulatory EEG monitoring by cassette recorder appears to be a useful intermediate-level screening technique for epileptiform abnormalities, both ictal and interictal.

Identification of penicillin diffusion at the onset of epileptogenesis in the cat striate cortex following differential laminar microinjection.

Diffusion patterns of 14C-labeled penicillin, resulting from microinjections into different neocortical laminae, were compared with simultaneous electrophysiologic monitoring of epileptogenesis across these laminae. Injections into layer IV produced response alterations quickly in all recorded layers even with penicillin confined to this granular cell layer. Supra- and infragranular layer injections also initiated epileptic response abnormalities, though much more slowly and only after penicillin had diffused into layer IV. Injections where penicillin diffusion was shown to be limited to either of the non-granular layers did not induce epileptogenesis. These results indicate not only that layer IV is the most penicillin-sensitive neocortical layer, but that (1) it is sufficient for epileptogenesis when initially injected and, that due to this heightened sensitivity, (2) it serves as a natural trigger for epileptiform response development in other layers when they are injected first. Neurochemical and neuromorphologic correlates within striate cortex are discussed in an attempt to identify the reason for this granule cell layer sensitivity to penicillin-induced epileptogenesis.

Phenytoin preferentially suppresses epileptiform activity in the superficial cortical layers of the cat.

Clinically, phenytoin is thought to be useful in controlling seizure activity by preventing it's spread from the focus to neighboring tissue. Experimentally, it has been suggested that phenytoin's principal action is no longer polysynaptic pathways with primary foci affected less than surrounding tissue. In this study, we present data confirming these basic experimental conclusions in foci induced in striate neocortical layer 4 of the cat. By using discrete penicillin microinjections strategically placed into this most penicillin-sensitive neocortical layer and recording simultaneously from several layers, we have been able to expand upon these conclusions by identifying this differential action at the interlaminar level. Epileptiform activity recorded from superficial laminae bordering layer 4, and into which layer 4's primary projections terminate, is suppressed preferentially by phenytoin. These superficial layers are also those that project into neighboring areas of the cat visual cortex. It would appear, then, that phenytoin begins protecting the cortex from seizure spread at the first synaptic termination into which this layer 4 primary focus projects. A discussion of the basic mechanisms of action that may be responsible for these results is also presented.

Intracortical evoked potentials of cats elicited by punctate visual stimuli in receptive field peripheries.

Intracortical visual evoked potentials, related to stimulus eccentricity from receptive field center, were investigated as a possible measure of interaction among adjacent populations of cortical neurons. Displacement of the stimuli from field center resulted in (1) a progressive decline in amplitude of the primary potential and (2) an enhancement or development of longer latency (60-100 ms) 'secondary' potentials often not apparent with field center stimulation.

The laminar sensitivity of cat striate cortex to penicillin induced epileptogenesis.

By utilizing the microinjection of low nanoliter volumes of convulsant drug and recording from the injection site, we have been able to electrophysiologically identify a layer of cat striate cortex that is most sensitive to the epileptogenic effects of penicillin. This band encompasses cortical depths of approximately 1000-1250 micrometers when the smallest volumes of penicillin are injected. Comparable penicillin injections made either superficial to or deeper than this were not as effective in producing epileptiform alterations in normal activity. Histochemical marks made at the site of these injections have identified cortical cytoarchitectonic layer IV as the site of maximal neocortical penicillin sensitivity. The vulnerability of layer IV to penicillin epileptogenesis may be related to certain distinctive anatomic features of this layer.

Laminar interactions during neocortical epileptogenesis.

Interactions among laminar subpopulations of cat striate cortical neurons were assessed during the evolution of discrete and temporary epileptic foci, which were induced by selective microinjection of penicillin into different cortical layers. Field potentials and multiunit cellular discharges, evoked by selective visual field stimulation, were recorded simultaneously from 3 layers by multibarreled glass microelectrodes. Laminar response profiles at distinct stages of epileptogenesis were characterized for foci induced in superficial pyramidal, middle stellate, and deep pyramidal layers. Layer 4 was verified to be the most susceptible to epileptogenesis. Penicillin's action within this stellate layer appeared to be sufficient for epileptogenesis and was supportative of, if not necessary for, the development of foci originating in pyramidal cell layers. These findings could not be fully appreciated by monitoring only spontaneous interictal spike potentials. Of the two types of neuronal discharge routinely observed, early latency bursting was principally a characteristic of layer 4 stellate populations, whereas longer-latency bursts comparable to paroxysmal depolarization shifts were recorded equally well from both stellate and pyramidal layers. Epileptiform alterations in both field potential and unit responses were quickly evident in cortical laminae having known anatomic connections with the layer where the focus was induced: e.g. in layers 2-3 with layer 4 foci, in layers 5-6 with layers 2-3 foci, and in layer 4 with layers 5-6 foci. The spread of epileptogenesis was slower between laminae where pathways are purported to be less well developed, and appeared to be principally dependent upon the diffusion of penicillin.

Differences between strychnine and penicillin epileptogenesis suggest a laminar organization of neocortical inhibition.

Transient foci of epileptiform alteration in neuronal population activity were induced by microinjection of strychnine sulfate into different layers of cat striate cortex. Potentials evoked by visual field-specific photic stimulation were recorded from microelectrodes at the injection site and in adjacent laminae. Epileptogenesis, characterized by an enhancement of the normal primary response followed by the development of a large late potential, occurred only with strychnine injections into superficial pyramidal layers 2 and 3. By contrast, stellate layer 4 has been shown to be most susceptible to epileptogenic effects of penicillin and bicuculline. Since disinhibitory convulsants should be most effective where their actions antagonize the prevalent type of inhibition, these findings suggest that there may be a laminar segregation of neocortical inhibition, possibly glycine-mediated in layers 2-3 and probably gamma aminobutyric acid (GABA)-mediated in layer 4.

Defining epileptogenic foci: past, present, future.

There is a direct relationship between the geometry (location, area, and orientation) of cortex-generating epileptiform discharges and resultant spike or seizure voltage fields at the scalp. Epileptogenic foci have been localized traditionally with EEG by identifying the negative field maximum (e.g., a phase reversal between adjacent bipolar channels). However, it is the shape of the entire voltage field over the head, including both negative and positive maxima, which provides information necessary to characterize the focus properly. Source location and orientation can be inferred from spike or seizure voltage topography, however, three-dimensional visualization can be obtained from mathematical source models, such as an equivalent dipole. Recent investigations have shown that dipole models can identify the location of epileptogenic foci with sub-lobar precision. Accuracy is enhanced by using additional electrodes, particularly on the lower half of the head, and by measuring their location. Realistic head models obtained from three-dimensional reconstructions of MR images can overcome errors introduced by simple spherical models of the cranium. Co-registering EEG voltage topography and source models with a patient's own cerebral anatomy will make EEG an unparalleled functional imaging technique for defining epileptogenic foci.

Ambulatory cassette EEG.

The neurophysiologic evaluation of patients with possible or proven paroxysmal disorders is no longer limited to routine laboratory EEGs or intensive inpatient monitoring. Expanded temporal sampling of the EEG, which increases the probability of documenting, characterizing, and quantitating the electrographic manifestations of these illnesses, is now available on a portable, outpatient, and less cumbersome inpatient basis by means of ambulatory cassette recordings. Ambulatory EEG has evolved from clinical need and from new technology that has provided small multichannel tape recorders, miniature preamplifiers, and rapid video/audio playback units. Clinical series and controlled trials have confirmed the usefulness of cassette EEG monitoring in a wide range of neurologic disorders, particularly epilepsy. Ambulatory EEG diagnostic yields have been shown to be superior to routine laboratory studies and nearly as good as inpatient telemetry evaluations. The role of cassette recordings in clinical EEG is being redefined as new applications are established.

Long-term inpatient audiovisual scalp EEG monitoring.

Long-term audiovisual scalp EEG monitoring is an essential diagnostic tool for the evaluation of paroxysmal disorders. The definitive classification of both nonepileptic and epileptic events is often possible only with the use of this technique. Assessment of response to treatment and the noninvasive presurgical localization of seizure foci are other important uses. The optimization of both clinical semiology and electrophysiologic data obtained from such studies is the subject of significant research efforts. Outcomes studies and advanced EEG analysis research should ultimately serve to minimize the cost of this valuable technique as well as maximizing its utility.