Evidence for three-dimensional cortical control of gaze from epileptic patients.

Electrophysiological studies in primates indicate that the eye fields of the cerebral hemispheres control gaze in three-dimensional space, and contain neurons that encode both conjugate (versive) and vergence eye movements. Two patients with epilepsy who exhibited disconjugate contraversive horizontal eye movements are described, one during electrical stimulation of the frontal eye fields and the other during focal seizures. We postulate that these eye movements resulted from combined contralateral version and vergence, and suggest that human cortical eye fields also govern visual search in a three-dimensional world, shifting the point of fixation between targets lying in different directions and at different depths.

Focal akinetic seizures as documented by electroencephalography and video recordings.

In three patients with focal epilepsies, focal akinetic seizures that were characterized by ictal paresis of the contralateral arm during preserved consciousness were recorded with EEG and video. MRI and ictal/interictal EEG revealed a frontal or central focus in all patients. Focal akinetic seizures are probably due to epileptic activation of negative motor areas.

Epileptic negative myoclonus. Subdural EEG recordings indicate a postcentral generator.

We report a patient with epileptic negative myoclonus (ENM) presenting as status epilepticus of the right arm. The etiology was a cortical malformation in the contralateral postcentral gyrus. Electrical stimulation of the right median nerve revealed giant surface somatosensory evoked potentials. Subdural recordings, performed to plan epilepsy surgery, demonstrated that the epileptogenic zone was in the left postcentral gyrus. Repetitive left postcentral spikes were consistently followed by an EMG silent period in the right arm with a latency of about 20 to 30 msec. The silent period in the EMG reflected the negative myoclonus and lasted 30 to 340 msec, mostly between 100 and 200 msec. Spikes in other regions of the cortex did not elicit ENM. The amplitude and duration of the spikes correlated with the EMG silent period: the more cortex involved in the spike generation, the longer the duration of the silent period. This suggests that epileptic activation of postcentral cortex leads to an inhibition of tonic activity of motor neurons. Focal ENM may be related to a hyperexcitability of the postcentral cortex.

Ictal scalp EEG in temporal lobe epilepsy with unitemporal versus bitemporal interictal epileptiform discharges.

We investigated the ictal scalp EEG in 228 seizures of 36 patients with unitemporal (n = 25) or bitemporal independent (n = 11) interictal epileptiform discharges (IED). All patients had proven temporal lobe epilepsy since they became seizure-free or only had auras after temporal lobectomy with a minimum follow-up of 1 year. Ictal patterns at seizure onset or later in the course of the seizure were lateralized significantly more often in patients with unitemporal IED (90%, at seizure onset and 96%, later) compared with those with bitemporal independent IED (75%, at seizure onset and 78%, later). Furthermore, scalp ictal EEGs, when lateralized at seizure onset or later in the course of the seizure, were significantly more likely to predict the correct side for surgery in patients with unitemporal (98%, at seizure onset and 100%, later) than bitemporal (64%, at seizure onset and 77%, later) IED. Bilateral independent seizure onsets, asynchrony of ictal activity over the two temporal lobes, and switch of ictal activity from one to the other hemisphere are ictal patterns that are strongly correlated with bitemporal excitability.

Lateralizing signs in intractable partial epilepsy: blinded multiple-observer analysis.

We evaluated the accuracy and interobserver variability of selected ictal and postictal behavioral changes. Three observers, blinded to clinical history, EEG, and side of surgical resection, analyzed videotapes of 166 seizures in 38 patients, looking for lateralizing signs. Twenty-seven patients with temporal lobe resections were seizure-free for > or = 1 year postoperatively, and 11 with extratemporal resections had at least 90% reduction in seizures > or = 1 year postsurgery. The epileptogenic region (ER) was lateralized by analyzing lateralizing signs in 78% of patients; positive predictive value (PPV) was 94% (90% CI = 87% to 100%). Overall kappa was 0.68. Signs were considered present if seen by two or more observers. Forty-five percent had version, ie, forced and sustained head deviation (kappa = 0.76, PPV = 94%); 37% had dystonic posturing of the upper extremity (kappa = 0.47, PPV = 93%); and 34% had unilateral mouth deviation (kappa = 0.83, PPV = 92%). These signs indicated a contralateral ER. Twenty-one percent had unilateral upper extremity automatisms, all ipsilateral to the ER (kappa = 0.65, PPV = 100%); 21% had postictal dysnomia, indicating a dominant-hemisphere ER (kappa = 0.89, PPV = 100%); and 16% had ictal speech, usually indicating a nondominant-hemisphere ER (kappa = 0.75, PPV = 83%). Dystonic posturing, postictal dysnomia, ictal speech, and unilateral upper extremity automatisms may indicate a higher probability of temporal lobe epilepsy. Analysis of lateralizing signs shows good interobserver agreement and provides useful clinical information.

Amnesia of the epileptic aura.

In a prospective study lasting 6 months, we recorded on video 108 seizures with aura of 23 patients in an attempt to evaluate the mechanisms involved in the encoding of memories. In 88 of those seizures, we also recorded an EEG. The percentage of auras remembered decreased significantly with increasing severity of the seizures. The recollection of auras was also significantly dependent on the ictal EEG changes during the aura. Ninety-seven percent of the auras without EEG changes, 94% of the auras with unilateral EEG changes, and 73% of the auras with bilateral EEG changes during the aura were remembered. The spread of the ictal EEG pattern during the aura also showed a significant correlation with the severity of the ensuing seizure. Three patients with bitemporal epilepsy made up a considerable proportion of those who never remembered their aura before secondary generalized tonic-clonic seizures (2 of 3) and of those who had a transient postictal amnesia of their aura (2 of 3). The only patient who failed to remember a previously documented isolated aura also suffered from bitemporal epilepsy. During the second part of the study, we questioned whether information provided during the history could be helpful in defining the type of epilepsy syndrome or localizing the EEG seizure pattern of the 80 patients who had been admitted for presurgical epilepsy diagnosis. Localized (regional, unilateral, and independent left and right lateral) EEG seizure patterns occurred in 82% of the 51 patients with auras in their history as compared with 24% of the 17 patients who did not have auras in their history (p < 0.01).

Photosensitive temporal lobe epilepsy.

Photic-induced seizures are usually generalized. There are several cases of focal seizures reported, and all have been shown to arise from the visual cortex. We report an unusual case of temporal lobe epilepsy, supported by electroclinical data and confirmed by a successful temporal lobectomy, with seizures induced by photic stimulation.

Seizure symptomatology in infants with localization-related epilepsy.

The clinical characteristics of seizures in adults and children with localization-related epilepsy have been clearly described and classified, but few data are available based on video EEG studies of postneonatal infants under 2 years of age. We analyzed 125 videotaped seizures from 23 infants aged 2 to 24 months with localization-related epilepsy defined by localized ictal EEG or localized lesion on neuroimaging with seizure-free surgical outcome. Seizure symptomatology was classified based on observable behavioral and motor manifestations and then correlated with location of the epileptogenic zone. Seizures characterized by decrease in behavioral motor activity with indeterminate level of consciousness and minimal or no automatisms ("hypomotor" seizures) arose from temporal, temporoparietal, or parieto-occipital regions (7 patients). Seizures with localized or bilateral clonic, tonic, or atonic motor phenomena arose predominantly from frontal, frontocentral, central, or frontoparietal areas (12 patients). One patient had versive seizures arising from the contralateral occipital lobe, 2 patients had infantile spasms (one with a frontal tumor, one with temporo-parieto-occipital dysplasia), and one patient had unclassifiable seizures. Disruption of temporal or temporoparietal function resulted primarily in diminution of behavioral activity, whereas ictal activation of motor areas during frontal or central onset seizures resulted mainly in localized or generalized motor phenomena. Infantile spasms occurred because of lesions in either location. Using an approach based on easily observable behavioral and motor phenomena, it was possible to classify the seizures in all but one infant.

Interobserver variability in EEG interpretation.

A random sample of 100 active electroencephalographers in the United States evaluated 10-second samples of 12 selected EEGs. The evaluations consisted of multiple-choice questions related to the age of the patient, EEG finding, artifact, and consciousness of the patient. The rate of reporting the "correct" response was examined in terms of various respondent characteristics such as EEG board certification, age, percent of time in clinical EEG work, and number of recordings interpreted annually. This study indicates that, even today, there is considerable variability in EEG interpretation, and that this variability is influenced by specific reader characteristics.

Postictal in situ MRS brain lactate in the rat kindling model.

OBJECTIVE: To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model. BACKGROUND: Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy. METHODS: We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: <2 hours (n = 8 and 5, stage 0 and stage 5), 2 to 3 hours (n = 5 and 6), and >3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group. RESULTS: In the <2-hour group, Lact/Cr increase was higher in stage-5 rats as compared with stage-0 rats (p = 0.001, unpaired t-test) and sham control rats when all the voxels were considered. Lact/Cr ratios were higher in the stimulated area as compared with all other brain areas in stage-0 rats (p = 0.05, paired t-test) but not in the stage-5 rats. Similar results with more inter-animal variability were measured in the 2- to 3-hour group. NAA/Cr ratios increased significantly after stage-0 kindling in the stimulated hippocampus but not after stage-5 kindling. CONCLUSIONS: Postictal Lact increase as assayed by MRS correlates with EEG and behavioral seizures and suggests that it would be an additional noninvasive technique for seizure localization during the presurgical evaluation of patients with intractable focal epilepsy.

Supplementary motor area seizures: propagation pathways as studied with invasive recordings.

We studied propagation of epileptic discharges in five patients with supplementary motor area (SMA) seizures with subdural grid electrodes implanted over the dorsolateral frontal neocortex and in the interhemispheric fissure. We found that both interictal and ictal epileptic discharges occurred synchronously in the SMA and the primary cortex. The actively involved electrodes were separated by silent electrodes. The time lag between the SMA and the primary motor cortex averaged 25 msec for interictal and 100 msec for ictal discharges. Cortical stimulations of the affected electrodes showed motor effects in corresponding body parts. All patients underwent resections of the EEG onset zone within the SMA while sparing the primary motor cortex and experienced a significant (>90%) reduction of seizure frequency. We conclude that epileptic activity is propagated between the SMA and the primary motor cortex by a somatotopically organized monosynaptic pathway.

Fluid-attenuated inversion recovery: correlations of hippocampal cell densities with signal abnormalities.

BACKGROUND: Hippocampal sclerosis (HS) is characterized by hippocampal atrophy and increased signal on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. OBJECTIVE: To quantitate cell loss and compare it with signal abnormalities on FLAIR images. METHODS: Thirty-one patients with temporal lobe resection, pathologically proven HS, and Engel class I and II outcome were included: 20 with HS only and 11 with HS associated with pathologically proven cortical dysplasia (dual pathology). The signal intensity on FLAIR was rated as present or absent in the hippocampus and correlated with the neuronal losses in the hippocampus. RESULTS: FLAIR signal increases were present in 77% (24/31) of all patients studied. In patients with isolated HS, 90% (18/20) had ipsilateral signal increases, but in patients with dual pathology, only 55% (6/11; p < 0.02) showed FLAIR signal increase. Hippocampal cell losses were significantly higher in the isolated HS group. The average cell loss in patients with FLAIR signal abnormalities was 64.8 +/- 8.0% as compared with only 32.7 +/- 5.1% in patients with no FLAIR signal abnormalities. There was a significant positive correlation between the presence of signal abnormality and average hippocampal cell loss in both pathologic groups. CONCLUSIONS: Ipsilateral FLAIR signal abnormalities occur in the majority of patients with isolated HS but are less frequent in those with dual pathology. The presence of increased FLAIR signal is correlated with higher hippocampal cell loss.

Evidence of cingulate motor representation in humans.

A 44-year-old man with a right frontal lobe tumor and intractable seizures underwent subdural grid evaluation before resection. The electrode locations were identified on a three-dimensional surface-reconstructed image of the brain after subdural grid placement. Electrical stimulation of electrodes placed over the right cingulate gyrus revealed evidence of tonic posturing of the left forearm and wrist and tonic extension of the left leg. This finding provides further evidence of a motor area in the cingulate gyrus in humans.

Complications of invasive video-EEG monitoring with subdural grid electrodes.

OBJECTIVE: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes. METHODS: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997. RESULTS: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization. CONCLUSIONS: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate.

Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging.

UNLABELLED: PET is useful in the presurgical evaluation of temporal lobe epilepsy. The purpose of this retrospective study is to assess the clinical use of statistical parametric imaging in predicting surgical outcome. METHODS: Interictal 18FDG-PET scans in 17 patients with surgically-treated temporal lobe epilepsy (Group A-13 seizure-free, group B = 4 not seizure-free at 6 mo) were transformed into statistical parametric imaging, with each pixel representing a z-score value by using the mean and s.d. of count distribution in each individual patient, for both visual and quantitative analysis. RESULTS: Mean z-scores were significantly more negative in anterolateral (AL) and mesial (M) regions on the operated side than the nonoperated side in group A (AL: p < 0.00005, M: p = 0.0097), but not in group B (AL: p = 0.46, M: p = 0.08). Statistical parametric imaging correctly lateralized 16 out of 17 patients. Only the AL region, however, was significant in predicting surgical outcome (F = 29.03, p < 0.00005). Using a cut-off z-score value of -1.5, statistical parametric imaging correctly classified 92% of temporal lobes from group A and 88% of those from Group B. CONCLUSION: The preliminary results indicate that statistical parametric imaging provides both clinically useful information for lateralization in temporal lobe epilepsy and a reliable predictive indicator of clinical outcome following surgical treatment.

Decreased calmodulin-NR1 co-assembly as a mechanism for focal epilepsy in cortical dysplasia.

The NMDA receptor is one of the ionotropic glutamate receptors essential for excitatory neurotransmission. The NMDAR1 subunit is inactivated by direct interaction with calmodulin. The protein levels of calmodulin, NMDAR1 and their complex were quantified in tissue resected from epileptogenic and non-epileptogenic cortical areas as determined by chronic subdural electrode recordings from three patients (aged 6, 14 and 18 years) with focal epilepsy associated with cortical dysplasia. In all patients, the co-assembly of calmodulin and NMDAR1 was decreased in epileptogenic dysplastic cortex compared with normal appearing non-epileptogenic cortex, while there was no significant difference in the total protein levels of calmodulin or NMDAR1 between the two EEG groups. These results suggest that decreased calmodulin-NMDAR1 co-assembly is a cellular mechanism that contributes to hyperexcitability in dysplastic cortical neurons and in focal seizure onsets.

A short episode of seizure activity protects from status epilepticus-induced neuronal damage in rat brain.

Kainic acid (KA)-induced status epilepticus (SE) in adult rats results in extensive neuronal damage throughout the limbic system and the loss of selectively vulnerable neuronal populations, particularly CA3 neurons. We investigated the effects of a short episode of seizure activity on neuronal death elicited by a subsequent prolonged SE episode. A short episode of seizure activity was produced by sub-cutaneous (s.c.) injection of KA followed after 1 h by pentobarbital administration. Twenty-four hours later, KA was administered again, and animals were sacrificed 3 days later. Neuronal damage was estimated by visual analysis of neuronal density. Our results show that a short episode of seizure activity did not produce neuronal damage but almost completely protected vulnerable neurons from KA-induced neuronal damage. These results extend to epileptic tolerance the notion of tolerance previously described in the case of ischemia.

Somatosensory evoked high-frequency oscillations recorded directly from the human cerebral cortex.

OBJECTIVE: To elucidate the generator sources of high-frequency oscillations of somatosensory evoked potentials (SEPs), we recorded somatosensory evoked high-frequency oscillations directly from the human cerebral cortex. SUBJECTS AND METHODS: Seven patients, 6 with intractable partial epilepsy and one with a brain tumor, were studied. With chronically implanted subdural electrodes, we recorded SEPs to median nerve stimulation in all patients, and also recorded SEPs to lip and posterior tibial nerve stimulation in one. High-frequency oscillations were recorded using a restricted bandpass filter (500-2000 Hz). RESULTS: For the median nerve oscillations, all oscillation potentials were maximum at the electrodes closest to the primary hand sensorimotor area. Most oscillations were distributed similar to or more diffusely than P20/N20. Some later oscillations after the peak of P20 or N20 were present in a very restricted cortical area similar to P25. We investigated the phase change of each oscillation potential around the central sulcus. One-third of the oscillations showed phase reversal around the central sulcus, while later oscillations elicited in a restricted cortical area did not. High-frequency oscillations to posterior tibial nerve and lip stimulation were also maximum in the sensorimotor areas. Most of the lip oscillations showed phase reversal around the central sulcus, but most of the posterior tibial nerve oscillations did not. CONCLUSION: High-frequency oscillations are generated near the primary sensorimotor area. There are at least two different generator mechanisms for the median nerve high-frequency oscillations. We suspect that most oscillations are derived from the terminal segments of thalamocortical radiations or from the primary sensorimotor cortex close to the generator of P20/N20, and some later oscillations from the superficial cortex close to the generator of P25.

Usefulness of prolonged video-EEG monitoring in the elderly.

The diagnosis of epilepsy in the elderly can be difficult. We sought to determine whether video-EEG monitoring (VEEG) is useful in the diagnosis and management of elderly patients with epilepsy. We reviewed the medical records of 20 consecutive patients, over 60 years of age, selected from a total of 1423 patients referred over a five year period for VEEG evaluation for epilepsy. The usefulness of VEEG was assessed by comparing changes in (a) the diagnosis and treatment of these patients before and after VEEG, and (b) the assessments made by an epileptologist who reviewed medical records before and after receiving results of VEEG. Compared to the initial diagnosis by the referring physician, VEEG resulted in changes in either the diagnosis or treatment in 11/20 patients based on the results of VEEG. The epileptologist was able to correctly assess the diagnosis and treatment of 16/20 patients without knowledge of the VEEG results. In 4/20 cases, the VEEG provided additional information to the epileptologist. In selected elderly patients, VEEG is useful in establishing the diagnosis of epilepsy, and may change the management of these patients.

Time-related configuration change in benign focal epileptiform discharges of childhood: from a dipole to a negative monopole in a patient with generalized epilepsy.

The case of a 6-year-old child with generalized epilepsy and benign focal epileptiform discharges (BFEDs) of childhood is presented. During his first EEG, performed when he was 6 years old, the patient had three staring episodes accompanied by bursts of 3-Hz spike-and-wave complexes. Interictally, frequent BFEDs were seen, configured as dipoles with a right temporal negativity and a right frontal positivity. The patient was administered ethosuximide and the staring spells disappeared. On follow-up EEG performed 2 years later, no generalized discharges were seen. However, the EEG again showed frequent spikes with a characteristic morphology of BFEDs. This time they were not configured as dipoles, but as monopoles with a maximum negativity over the right frontal region. The change in the generator's orientation over time (from a horizontal to a vertical dipole) is discussed, as well as the prognostic implications of the morphology and configuration of focal spikes. In addition, the authors review the coexistence of BFEDs and 3-Hz spike-and-wave complexes in their patient database.