The localizing value of auras in partial seizures: a prospective and retrospective study.

Doubts concerning the localizing significance of auras in partial seizures have recently been expressed. Prompted by this, we studied this issue by re-examining two groups of patients; the first, studied retrospectively, consisted of patients in whom the site of origin of the seizures was known beyond a reasonable doubt; the second, studied prospectively, comprised patients in whom specific auras were correlated with the localization of interictal epileptiform EEG abnormalities and the final diagnostic impression. The data from the retrospective series were suitable for rigorous statistical analysis. The two groups yielded similar results: the frequency of auras in partial seizures and the localizing significance of those for which large enough numbers could be collected was high. We conclude that the type of aura, when elicited by careful history-taking, provides as useful localizing, but often not lateralizing, information as the EEG and modern high-technology procedures such as CT, MRI, and PET.

The EEG in deep midline lesions.

We studied the electroencephalograms (EEGs) of 154 patients with well-defined diencephalic, mesencephalic, or posterior fossa lesions. Electrographic and clinical parameters were statistically evaluated. The results indicated considerable overlap of EEG abnormalities from different subcortical sites. Focal or lateralized abnormalities were relatively specific, suggesting a diencephalic lesion, whereas bilateral paroxysmal slow-wave disturbances were unspecific and not of precise diagnostic significance. There was no specific feature in this series to clearly distinguish the EEG pattern in deep midline lesions from that seen with diffuse cortical and subcortical encephalopathies.

Brain lesions that produce delta waves in the EEG.

Localized delta activity appears in cortex overlying a circumscribed white matter lesion. Less commonly, localized delta activity may result from a localized thalamic lesion. Unilateral diffuse delta activity appears on the side of thalamic or hypothalamic lesions. Bilateral delta activity results from bilateral lesions of the midbrain tegmentum. Localized lesions of the cerebral cortex, unilateral mesencephalic tegmental lesions, and vasogenic edema of the cerebral white matter do not produce delta activity. Marked edema of a cerebral hemisphere when no surgical decompression is provided may produce unilateral delta activity by pressure on or displacement of the brain stem or diencephalon.

Response of generalized penicillin epilepsy in the cat to ethosuximide and diphenylhydantoin.

The effects of ethosuximide and diphenylhydantoin sodium on feline generalized penicillin epilepsy, a model of human generalized corticoreticular (centreccephalic) epilepsy, were significantly reduced following administration of ethosuximide with plasma levels of 60 mug per milliliter, and there was a linear correlation between the plasma level and antiephilepileptic effect (p less than 0.01). Diphenylhydantoin produced a lesser reduction in epileptic activity, and there was no correlation between the plasma level and effect. Four cats that received both drugs successively responded well to ethosuximide, while only two responded to diphenylhdantoin. The good response to ethosuximide is in accord with clinical experience in human generalized corticoreticular epilepsy.

Dopaminergic mechanism in generalized photosensitive epilepsy.

Apomorphine, a dopamine receptor agonist, blocked epileptic photosensitivity in patients with primary corticoreticular epilepsy. This effect was not modified by naloxone, a narcotic antagonist, suggesting that apomorphine acts on cerebral dopaminergic receptors. Apomorphine did not block spontaneous spike-and-wave discharges in patients with nonphotosensitive primary corticoreticular epilepsy. The different actions of apomorphine on spontaneous and photically induced spike-and-wave activity suggest that there is a selective dopaminergic mechanism in human epileptic photosensitivity.

Concepts of absence epilepsies: discrete syndromes or biological continuum?

There are two current approaches to the clinical conceptualization of the generalized epilepsies. The syndromic approach attempts to subdivide the patient population into relatively homogeneous groups, largely on the basis of clinical and EEG criteria. In contrast, the neurobiological approach aims to formulate a unique profile for each patient by incorporating particulars of the patient onto the background of knowledge regarding the etiologic factors important in generalized epilepsy. The value of these two approaches is discussed with regard to the dual aims of, first, improving the understanding of generalized epilepsy, and second, providing a precise diagnosis, an accurate prognosis, and optimal treatment for the patient.

Does head-turning during a seizure have lateralizing or localizing significance?

Forced lateralized head-turning, occurring as the first clinical sign in 106 epileptic seizures in 43 patients, was recorded on videotape simultaneously with the EEG. Forty-five ictal EEGs were obtained with stereotaxically implanted intracerebral electrodes. Forced head-turning was seen with seizures that had a frontal, temporal, unilateral diffuse, or a generalized onset in the EEG. Ipsilateral was as common as contralateral head-turning in all groups, including the seizures with frontal lobe onset. Initial head-turning in a seizure has no localizing or lateralizing significance.

Water-drinking as ictal behavior in complex partial seizures.

The urge to demand, pour, and drink water at the time of an attack was encountered in 20 patients who had seizures with complex partial symptomatology. Two patients were studied with bitemporal stereotaxically implanted depth electrodes. Drinking was associated with electrographic and clinical seizures starting in the amygdala, hippocampus, and parahippocampal gyrus. Sometimes, this was the only clinical manifestation of an attack, and its significance would not have been recognized without depth recording. Ictal drinking was never encountered in patients without electroencephalographic evidence of temporal epileptic abnormality, and therefore seems to have localizing significance.

Late-onset drop attacks in temporal lobe epilepsy: a reevaluation of the concept of temporal lobe syncope.

We report the clinical, radiologic, and EEG features of six patients with temporal lobe drop attacks (TLDA), all of whom underwent temporal resection. Postoperative follow-up of at least 1 year was available in all. TLDA were never the first manifestation but followed the onset of epilepsy after a long delay ranging from 7 to 43 years (mean, 24.4 years). Seizures were of unilateral temporal origin. In one patient, stereo EEG recording of TLDA showed rapid spread of the ictal discharge away from the temporal lobe in less than 1 second. Postoperatively, three patients were seizure free; one has had no TLDA but experiences sporadic auras; another, despite a reduction of more than 50%, continues to have complex partial seizures and TLDA; and the sixth has had sporadic secondarily generalized seizures upon reduction of antiepileptic medication. In conclusion, drop attacks may occur in temporal lobe epilepsy, usually long after the onset of epilepsy. They lead to increased disability and suggest a rapid spread of the ictal discharge and possible involvement of the pontine reticular formation rather than the presence of bitemporal foci or an extratemporal origin.

MRI volumetric measurement of amygdala and hippocampus in temporal lobe epilepsy.

We performed MRI volumetric measurements of the amygdala (AM), the hippocampal formation (HF), and the anterior temporal lobe in a group of 30 patients with intractable temporal lobe epilepsy (TLE) and in seven patients with extratemporal lobe foci. Measurements were analyzed with a semiautomated software program and the results compared with those of normal controls and correlated with the findings of all other investigations. In particular, we compared the results with the lateralization of epileptic abnormalities in the EEG. Volumetric studies of AM and HF showed lateralization of measurable atrophy consistent with that derived from extracranial and intracranial EEG examinations. The HF volumes were more sensitive and provided a lateralization in 87%. Combined measurements of AM and HF showed lateralization in 93%, always congruent with the results of EEG lateralization. This slight but important additional improvement in discrimination justifies using AM measurements in MRI volumetric studies of mesial temporal structures. Volumetric studies combined with other currently employed noninvasive techniques may diminish the need for invasive methods of investigation in patients with TLE.

Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: an MRI volumetric study.

We performed MRI volumetric measurements of the amygdala (AM) and hippocampal formation (HF) in a group of 43 patients with temporal lobe epilepsy not controlled by optimal drug treatment. Fifteen patients (35%) had a history of prolonged febrile convulsions (PFC) in early childhood; 30 patients underwent surgery, and histopathology was available in twenty-four. The mean values of AM and HF volumes ipsilateral to the EEG focus were significantly smaller than those of normal controls. The volumetric measurements showed a more pronounced atrophy of the AM in patients with a history of PFC, although the HF volumes were also smaller in this group. Patients with a history of PFC had a higher proportion of more severe mesial temporal sclerosis (MTS) compared with those with no PFC. These findings confirm a correlation between early childhood PFC, the severity of atrophy of mesial structures, and MTS.

Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging.

Both the amygdala and the hippocampus are involved in the pathogenesis of a number of neurologic conditions, including temporal lobe epilepsy, postanoxic amnesia, and Alzheimer's disease. To enhance the investigation and management of patients with these disorders, we developed a protocol to measure the volumes of the amygdala and as much of the hippocampus as possible (approximately 90 to 95%) using high-resolution MRI. We present the anatomic basis of these two protocols and our results in normal control subjects. These volumetric studies of the amygdala may clarify the role of this structure in the pathogenesis of temporal lobe epilepsy.

Early history of IBRO: the birth of organized neuroscience.

To celebrate the thirtieth anniversary of the founding of the International Brain Research Organization (IBRO), a symposium was organized for the III Congress of the World Federation of Neuroscientists in Montreal to present, on 7 August 1991, the recollections of some of the early participants in IBRO's history and to place it in the context of other significant world organizations. Edited and slightly condensed transcripts of the talks together with the discussions are presented. L. Marshall reviewed the antecedent conferences that led to the Moscow Colloquium in 1958 and the subsequent formation of IBRO with UNESCO support. The ambience of that period for scientific organization on an international level was discussed by W. A. Rosenblith who emphasized how IBRO goals fitted into the rising interest in brain and behavior research. The scientific careers of six past executive secretaries were briefly reviewed by P. Gloor, with special tribute to the first, Herbert Jasper. One of IBRO's major achievements, the world survey of resources and needs in brain research, was described first-hand by G. Krauthamer. To discuss IBRO's image, C. Blakemore invoked the travails of reorganization and recovery from a period of inactivity. Finally, placing IBRO in a national and international context, S. Cozzens presented the perspective of the historian of sociology on an upbeat note.

Intracellular recordings in pericruciate neurons during spike and wave discharges of feline generalized penicillin epilepsy.

Concurrent EEG and intracellular recordings from pericruciate neurons of cats obtained before and after i.m. injection of penicillin inducing the syndrome of feline generalized penicillin epilepsy (FGPE) characterized by spike and wave (SW) discharge in the EEG, display large excitatory postsynaptic potentials (EPSPs) at the time of the EEG 'spike' which alternate with hyperpolarizing potentials occurring in coincidence with the EEG 'wave' component of the SW complex. The large EPSPs trigger discharges of single or multiple high-frequency action potentials which do not show a progressive decrement in amplitude nor an appreciable increase in duration. These bursts thus differ in some respects from typical paroxysmal depolarization shifts. The hyperpolarizing potentials show an early phase which is reversed by intracellular Cl- injection or diffusion and thus behaves like a classical inhibitory postsynaptic potential (IPSP). The late phase is unaffected by Cl-. Hyperpolarizing potentials of pericruciate neurons induced by antidromic activation of the cerebral peduncle (CP) or by direct cortical stimulation are not altered after i.m. injections of penicillin at doses sufficient to induce generalized SW discharge. The early phase of hyperpolarization both before and after i.m. penicillin is reversed by intracellular Cl- injection or diffusion, the late phase remains unchanged. The early phase thus represents a classical IPSP, which does not appear to be affected by the low brain penicillin concentrations sufficient to induce generalized SW discharge. It is concluded that this form of epileptic discharge cannot be attributed to blockage of phasic (presumably somatic) postsynaptic inhibition by penicillin. These results indicate that to regard all forms of epileptic discharge as the consequence of a blockage of gamma-aminobutyric acid-mediated phasic postsynaptic inhibition acting on the soma represents an unduly restrictive view of epileptogenesis.

Participation of cortical recurrent inhibition in the genesis of spike and wave discharges in feline generalized penicillin epilepsy.

Cortical recurrent inhibition (RI) evoked in pericruciate cortex by antidromic stimulation of the cerebral peduncle (CP) was studied in normal cats and in cats exhibiting the signs of feline generalized penicillin epilepsy (FGPE) following the i.m. injection of penicillin. Two measures of RI evoked by antidromic CP stimulation were used: (i) the averaged focal potential in the pericruciate gyrus; and (ii) the duration of the suppression or diminution of extracellularly recorded action potential (ap) discharge of antidromically activated pericruciate neurons measured in peristimulus time histograms (PSTHs). After i.m. injection of 350,000 IU/kg of penicillin RI remained preserved as long as only generalized spike and wave (SW) discharges appeared in the EEG, although in 5/17 neurons a modest to moderate reduction in the duration of RI occurred once SW discharges had appeared in the EEG. This inconstant reduction was probably not caused by a direct anti-inhibitory action of penicillin, but is a consequence of the increased number of ap discharges curtailing RI. At the small concentrations of penicillin existing in brain in FGPE its anti-inhibitory action evident with larger concentrations cannot be demonstrated. When focal or generalized tonic-clonic (T-C) seizures occurred, RI was reduced in slightly more than half of the instances for a few minutes before the onset of these seizures. This suggests that the transition from SW discharge to T-C seizure may be caused by a breakdown of RI.

The electromicrophysiology of delta waves induced by systemic atropine.

Delta waves in the EEG can be induced by the intravenous administration of atropine. In cats we have investigated with several computer averaging programs the relationship of extracellular unit discharge to the EEG on the surface and within the cortex. We have also studied the laminar profiles and the vertical current density profiles of these slow waves. Our results indicate that surface-positive delta waves are related to events associated with excitation of cortical neurons, while surface-negative delta waves are related to a decreased probability of unit firing suggesting the possibility of inhibition. Laminar analysis of atropine-induced slow waves indicated that these were probably generated by pyramidal cells in a similar way to delta waves induced by brain lesions. These results suggest that a disturbance in cholinergic input to the cortex might be responsible for delta waves in the EEG.

Differential participation of some 'specific' and 'non-specific' thalamic nuclei in generalized spike and wave discharges of feline generalized penicillin epilepsy.

Extracellular single unit and electroencephalographic (EEG) activity during generalized spike and wave discharges (SW) induced by i.m. penicillin was recorded simultaneously in the cortex, in a 'specific' thalamic nucleus (n. lateralis posterior, LP) and in some 'non-specific' thalamic nuclei (n. centralis medialis, NCM; n. centrum medianum, CM; n. centralis lateralis, CL) Computer-generated EEG averages and histograms of single unit activity were triggered by either peaks of EEG transients or action potentials. The time at which cortical neurons (66/66) were most likely to fire was during the 'spike' of the SW complex while absence of firing was the rule during the 'wave'. Most LP neurons (23/26) showed a similar pattern, 3 cells firing preferentially during the 'wave'. In NCM only 17 of 39 neurons fired during the 'spike', 8 of 39 neurons during the 'wave' while the others showed no change in their firing pattern during SWs. Twenty-six of 30 CM and 20 of 24 CL neurons fired during the 'spike' of SW; the other cells in these nuclei did not change their firing pattern during SWs. When present, rhythmic fluctuations in firing linked to SW discharge were less prominent in these 'non-specific' thalamic nuclei than in cortex and LP. Furthermore, participation of NCM, CM and CL neurons in the SW rhythm occurred only after neurons in cortex and LP had become involved in it. Thus, as is the case for cortical neurons, the main firing pattern of thalamic cells during SWs consists of an oscillation between 'excitation' during the 'spike' and 'inhibition' during the 'wave' of the SW complex. However, the coupling between cortical and thalamic neuronal firing is less intimate for cells of the 'non-specific' thalamic nuclei than for a 'specific' nucleus such as LP. Thus, at least some 'specific' thalamic nuclei are more intimately involved in the mechanism of SW discharge than the midline intralaminar nuclei.

A microelectrode study of amygdaloid afferents: temporal neocortical inputs.

Acute experiments were performed on anesthetized cats using standard techniques of electrical stimulation and single unit recording in order to study the responses of amygdaloid neurons to neocortical inputs. Satisfactory records were obtained from 272 amygdaloid neurons. The majority of those fired spontaneously, at low rates, with single, randomly occurring spikes. The lateral neocortex, particularly the portion which is homologous to temporo-insular cortex in man, is capable of influencing the discharges of many amygdaloid neurons. The typical response pattern consisted of an excitatory-inhibitory sequence with the median onset latency of 12.0 msec, which is consistent with monosynaptic excitation of the output-type nerve cells in the affected regions of the amygdala (Al, Ac, Ab). There was an absence of clear topographical arrangement: all of the effective neocortical areas influenced the neuronal discharges in Al, Ac and Ab fairly equally. These results correlate well with neuroanatomical studies of amygdaloid structure and connectivity. Our finding of diffuse non-topographic excitatory influence upon the lateral, central and basal amygdaloid nuclei exerted by insular-temporal regions known to be involved with higher order sensory analysis and pattern recognition is quite consistent with a view of this system serving as a link between neocortical information stores and the fundamental motivational drive mechanisms of the hypothalamus.

Interictal discharges in the hippocampus of rats with long-term pilocarpine seizures.

Systemic administration of pilocarpine to adult rats induces an acute status epilepticus followed by spontaneous recurrent seizures after a 1-2-week silent period. We recorded field potentials in hippocampal slices obtained from rats with spontaneous recurrent seizures after pilocarpine-induced status. The frequency of the interictal discharges induced in these slices by 4-aminopyridine (4AP) was reduced and their duration was increased. Cutting the Schaffer collaterals caused interictal discharges in CA1 to disappear in normal rats and in rats 3 weeks after pilocarpine-induced status. However, 12 weeks after pilocarpine, these discharges remained in CA1 after such a cut but occurred at a lower frequency. These findings show that in rat hippocampi with a lesion similar to that of human Ammon's horn sclerosis some electrophysiological features of 4AP-induced interictal discharges are altered in comparison to those induced in normal hippocampi.

Simultaneous recording of cortical and thalamic EEG and single neuron activity in the cat association system during spindles.

Simultaneous recording of the EEG and single unit activity in cortex and thalamus shows that during spindles the cortical and thalamic EEGs within a given thalamocortical sector are highly correlated, but that the firing of only a fraction of cortical and thalamic neurons shows a close mutual correlation or exhibits a close relationship to the cortical and thalamic EEGs. Thus, only a fraction of thalamic and cortical neurons is involved in generating spindles. The synchronized activity of these neurons, even if some of it is subliminal for action potential discharge, suffices to produce a recordable EEG signal.