Secondarily generalized seizures in mesial temporal epilepsy: clinical characteristics, lateralizing signs, and association with sleep-wake cycle.

PURPOSE: Secondarily generalized seizures (SGSs) are often considered to be stereotyped, presumably sharing a common electrical pathway. We examined whether SGSs are uniform in a homogeneous group of patients with mesial temporal epilepsy, and whether certain clinical signs associated with generalization are lateralizing with regard to seizure origin. METHODS: A comprehensive, standardized video/EEG analysis was performed of the clinical characteristics of 29 patients (69 SGSs) with mesial temporal seizure onset. RESULTS: The sequence of tonic postures, as well as the sequence of tonic and clonic activity, was variable in SGSs of mesial temporal origin. The sequence of tonic activity, followed by vibratory and then clonic activity alone, was seen only in 51.7% of patients. Tonic and clonic activity could occur simultaneously. The most common clinical signs were forced head deviation (89.7%) and vocalization (75.9%). The most common tonic posture was bilateral arm extension (72.4%). All other clinical signs occurred in <60% of patients. Among these, early forced head deviation, asymmetric tonic facial contraction, tonic arm abduction with elbow flexion, and tonic arm extension combined with opposite arm flexion had lateralizing significance. The preceding partial seizure in SGSs (mean, 43.6 s) was significantly shorter than partial seizures without generalization (mean, 105.2 s; p < 0.001). SGSs occurred more often out of sleep (p < 0.01). CONCLUSION: Secondarily generalized seizures of mesial temporal origin are not uniform in their clinical presentation. The final phases of SGSs are more stereotyped than the initial clinical signs of generalization. This suggests variable electrical spread patterns, which may end in a common pathway. Some asymmetric motor signs have lateralizing significance. SGSs were associated with sleep and abbreviated partial seizures.

Responses of human auditory association cortex to the omission of an expected acoustic event.

Unexpected auditory events initiate a complex set of event-related potentials (ERPs) that vary in their latency and anatomical localization. Such "mismatch" responses include active responses to the omission of an expected event or the omission of elements in expected stimulus composites. Here we describe intracranial recordings of middle-latency ERPs elicited by the omission of an auditory event. We first presented a sequence of tones at regular temporal intervals and the tone was omitted 20% of the time. In a second condition, we presented a sequence of tone pairs and the second tone of the pair was omitted 20% of the time. These two conditions are complementary in that the single tone conformed to the expectancy in one condition, but violated the expectancy in the other. All patients demonstrated localized cortical responses to missing tones that were topographically similar to the responses evoked by actual tones. Responses to both actual and omitted tones were observed bilaterally in the vicinity of the temporal--parietal junction, where we also obtained midlatency ERPs to a variety of other auditory stimuli. Responses that appeared to be selective for the nonoccurrence of expected tones were also observed in a number of subjects. We interpret these effects in terms of processes associated with the comparison of sensory inputs to the contents of a short-term auditory memory. Such a system could automatically detect deviant auditory events, and provide input to higher-level, task-dependent cognitive processes.

Investigation of extra-temporal epilepsy.

Medically intractable epilepsy of extra-temporal origin can represent a difficult therapeutic challenge. Our Epilepsy Service has managed these patients using standard investigative methods as well as ictal SPECT and intracranial electrode recording. In the present series of patients, image-guided surgery was used for all electrode implantation and resective surgery. Seizure localization and successful resection were achieved in 70-80% of 42 patients with follow-up of at least one year. Normal MRI and previous failed intracranial investigation were not associated with poorer outcome.

Does performing image registration and subtraction in ictal brain SPECT help localize neocortical seizures?

UNLABELLED: Ictal brain SPECT (IS) findings in neocortical epilepsy (patients without mesiotemporal sclerosis) can be subtle. This study is aimed at assessing how the seizure focus identification was improved by the inclusion of individual IS and interictal brain SPECT (ITS)-MRI image registration as well as performing IS - ITS image subtraction. METHODS: The study involved the posthoc analysis of 64 IS scans using 99mTc-ethyl cysteinate dimer that were obtained in 38 patients without mesiotemporal sclerosis but with or without other abnormalities on MRI. Radiotracer injection occurred during video-electroencephalographic (EEG) monitoring. Patients were injected 2-80 s (median time, 13 s) after clinical or EEG seizure onset. All patients had sufficient follow-up to correlate findings with the SPECT results. All patients had ITS and MRI, including a coronal volume sequence used for registration. Image registration (IS and ITS to MRI) was performed using automated software. After normalization, IS - ITS subtraction was performed. The IS, ITS, and subtraction studies were read by 2 experienced observers who were unaware of the clinical data and who assessed the presence and localization of an identifiable seizure focus before and after image registration and subtraction. Correlation was made with video-EEG (surface and invasive) and clinical and surgical follow-up. RESULTS: Probable or definite foci were identified in 38 (59%) studies in 33 (87%) patients. In 52% of the studies, the image registration aided localization, and in 58% the subtraction images contributed additional information. In 9%, the subtraction images confused the interpretation. In follow-up after surgery, intracranial EEG or video-EEG monitoring (or both) has confirmed close or reasonable localization in 28 (74%) patients. In 6 (16%) patients, SPECT indicated false seizure localization. CONCLUSION: Image registration and image subtraction improve the localization of neocortical seizure foci using IS, but close correlation with the original images is required. False localizations occur in a minority of patients.

Functional differentiation of medial temporal and frontal regions involved in processing novel and familiar words: an fMRI study.

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, approximately 1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior-posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

Magnetic resonance imaging versus computed tomography for target localization in functional stereotactic neurosurgery.

OBJECTIVE: To determine whether magnetic resonance imaging (MRI), compared with computed tomography (CT), provides consistent and accurate target localization for ventrolateral thalamotomy and posteroventral pallidotomy. METHODS: For 93 procedures (78 pallidotomies and 15 thalamotomies) in 83 patients, coordinates for the anterior commissure, posterior commissure, and stereotactic target were calculated from MRI- and CT-derived images and compared. RESULTS: The mean differences for the target were -0.41 mm on the x axis (P < 0.001), 0.06 mm on the y axis (P = 0.412), and -0.34 mm on the z axis (P < 0.01). The mean absolute differences were 0.53 mm on the x axis (median, 0.50 mm; range, 0.00-2.00 mm), 0.46 mm on the y axis (median, 0.50 mm; range, 0.00-2.00 mm), and 0.78 mm on the z axis (median, 0.50 mm; range, 0.00-6.00 mm). The mean three-dimensional distance between MRI- and CT-derived coordinates for the anterior commissure was 1.65 mm, with a distance of more than 4 mm in two cases (2%). The mean three-dimensional distance for the posterior commissure was 1.65 mm, with a distance of more than 4 mm in two cases (2%). The mean three-dimensional distance for the target was 1.25 mm (median, 1.14 mm; range, 0.00-6.27 mm), with a distance of more than 4 mm in one case (1%). CONCLUSION: Statistically significant but relatively small differences between MRI- and CT-derived target coordinates were found. In some cases (approximately 2% of this series), the differences between MRI- and CT-derived coordinates may be relatively large (greater than 4 mm and up to 8 mm). However, given the superior anatomic resolution of MRI and the nature of the stereotactic procedures under consideration, we conclude that MRI, when validated within an institution, may be used alone for target localization in pallidotomy and thalamotomy.

Localized pain associated with seizures originating in the parietal lobe.

PURPOSE: Ictal pain is a rare symptom of seizures. Epileptic pain may be experienced unilaterally (lateral/ peripheral), cephalically, or in the abdomen. Painful seizures have been associated with seizure origin in both the parietal and the temporal lobes. We report on the different types of epileptic pain and discuss its etiology and possible localizing value. METHODS: We reviewed the records of patients referred to our epilepsy program over the last 6 years. Eight (1.4%) of 573 patients had pain as an early prominent symptom of their seizures. RESULTS: Pain was predominantly unilateral in three patients, cephalic in two, and abdominal in three patients. Seizure onset was in or involving the parietal lobe in all patients, and when the painful symptoms were lateralized, they were contralateral to the side of seizure origin. Parietal lobe seizure origin was determined by both intracranial EEG recording and neuroimaging [magnetic resonance imaging (MRI), ictal single photon emission computed tomography (SPECT)] in five patients, and by both scalp EEG and neuroimaging in three patients. CONCLUSIONS: We conclude that ictal pain is a rare symptom of parietal lobe seizure origin with lateralizing potential.

Utilization of impedance measurements in pallidotomy using a monopolar electrode.

OBJECT: This study was performed to evaluate the reliability and utility of using monopolar impedance monitoring for estimation of the location of the thermocouple electrode during a pallidotomy procedure. METHODS: In 26 patients, impedance profiles were measured at 2-mm intervals and anatomical boundaries were marked on postoperative MRI studies in 19 patients. The pattern of change in impedance as the electrode was towards the target coordinates in the globus pallidus was studied empirically in relation to MRI-defined anatomy and by electrical stimulations. The pattern of impedance change was of greater reliability than absolute impedance values. A drop in impedance was noted in 10 cases where the electrode entered the putamen or globus pallidus upon exiting the internal capsule, and in 9 of these this drop was measured before or at the distal boundary of the internal capsule. A variable pattern in the region of the base of the globus pallidus was observed, with 10 of 19 cases demonstrating a decrease and 8 cases an increase, consistent with the proximity of a CSF cistern in the former and the ansa lenticularis and optic tract in the latter. Simulations showed that the monopolar electrode was more sensitive to the approach of a boundary than the bipolar electrode. CONCLUSION: Our measurements and simulations suggest that a monopolar electrode could predict a nearby region of high or low impedance before penetrating it and a trend of decreasing impedance as the distal edge of the globus pallidus is approached.

Medial temporal lobe epilepsy: videotape analysis of objective clinical seizure characteristics.

PURPOSE: The syndrome of temporal lobe epilepsy has been described in great detail. Here we focus specifically on the clinical manifestations of seizures originating in the hippocampus and surrounding mesial temporal structures. METHODS: Seizure origin was confirmed in 67 cases by depth EEG recording and surgical cure after mesial temporal resection. RESULTS: Among nonlateralized manifestations, we commonly found oral automatisms, pupillary dilatation, impaired consciousness, and generalized rigidity. Appendicular automatisms were often ipsilateral to the seizure focus, whereas dystonia and postictal hemiparesis were usually contralateral. Head deviation, when it occurred early in the seizure, was an ipsilateral finding, but was contralateral to the seizure focus when it occurred late. Clear ictal speech and quick recovery were found when seizures originated in the non-language-dominant hemisphere, but postictal aphasia and prolonged recovery time were characteristic of seizure origin in the language-dominant hemisphere. CONCLUSIONS: These signs help to define the mesial temporal lobe epilepsy (MTLE) syndrome and often provide information as to the side of seizure origin.

The evaluation and image-guided surgical treatment of the patient with a medically intractable seizure disorder.

Over the past decade, there has been a remarkable increase in awareness of the role surgery may play in the management of the patient with medically intractable epilepsy. This article explores the role of emerging interactive image-guided techniques in noninvasive and invasive preoperative seizure evaluation and the planning and execution of surgical treatments.

Direct stereotactic targeting of the globus pallidus: an MRI-based anatomic variability study.

An anatomic variability study of the spatial relationship between the imaged globus pallidus, the optic tract, and the anterior and posterior commissures was performed using T1-weighted gradient echo three-dimensional volume acquisition MRI of 20 patients. Imaging data were resized, reformatted, and manually segmented for the above structures, and mean values and standard deviations for their medial, superior, lateral, and inferior limits determined. Findings demonstrate that the globus pallidus can be consistently and reliably imaged by MRI, that direct stereotactic targeting of this structure can account for normal anatomic variability which may be as much as several millimeters, and that the risk of injury to the optic tract may be reduced with this technique.

SEP topographies elicited by innocuous and noxious sural nerve stimulation. III. Dipole source localization analysis.

The dipole source localization method was used to determine which of the brain areas known to be involved in somatosensation are the best candidate generators of the somatosensory evoked potential evoked by sural nerve stimulation. The ipsilateral central negativity and contralateral frontal positivity which occurred between 58 and 90 msec post stimulus (stable period 1) were best represented by a single source located in the primary somatosensory cortex (SI). The symmetrical central negativity and bilateral frontal positivity which occurred between 92 and 120 msec post stimulus (stable period 2) was best represented by 3 sources. One of these sources was located in SI and the other 2 were located bilaterally in either the frontal operculum or near the second somatosensory cortex (SII). The widespread negativity whose minimum was located in the contralateral fronto-temporal region and which occurred between 135 and 157 msec post stimulus (stable period 3) was also best represented by 3 sources. Two of these sources may be located bilaterally in the hippocampus. We cannot, however, eliminate the possibility that multiple sources in the cortex overlying the hippocampus (e.g., SII and frontal cortex) are responsible for these potentials. At innocuous stimulus levels the third source for stable period 3 was located near the vertex, possibly involving the supplementary motor cortex, whereas at noxious levels this source appears to be located in the cingulate cortex. We were unable to achieve any convincing source localization for the widespread positivity which occurred between 178 and 339 msec post stimulus (stable periods 4-6). Available evidence suggests that more sources were active during this interval than the three we could reliably test under these conditions.

Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination.

In order to more precisely define a syndrome of medial temporal lobe epilepsy, histories and physical findings were evaluated in 67 patients studied with intracranial electrodes who had medial temporal seizure onset and became seizure free following temporal lobectomy. Patients with circumscribed, potentially epileptogenic mass lesions were excluded. Fifty-four patients (81%) had histories of convulsions during early childhood or infancy, 52 of which were associated with fever. Complicated febrile seizures occurred in 33 (94%) of the 35 patients in whom detailed descriptions of the febrile seizures were available. Bacterial (5) or viral (2) central central nervous system infections were present in 7 patients with seizures and fevers. Other less common, but probably significant, risk factors included head trauma (10%) and birth trauma (3%). Only 5 patients had no apparent risk factors. The mean age at habitual seizure onset was 9 years. All patients had complex partial seizures, with half having only complex partial seizures. The other half also had secondarily generalized tonic-clonic seizures, but these were never the predominant seizure type. Only 3 patients had histories of convulsive status epilepticus and no patient had a history of nonconvulsive status epilepticus. All but 3 patients reported auras before some or all of their seizures, with an abdominal visceral sensation being by far the most common type of aura (61%). Of the 60 patients with identified risk factors, all but 2 had an interval between the presumed cerebral insult and the development of habitual seizures, with a mean seizure-free interval of 7.5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic/semichronic limbic epilepsy produced by microinjection of tetanus toxin in cat hippocampus.

We describe an animal preparation in which a semichronic or chronic limbic epileptiform syndrome can be produced reliably by unilateral microinjection of tetanus toxin in cat ventral hippocampus. Injections were given at 1-week intervals until abnormal EEG activity was observed. After two to five injections, the animals abruptly began to exhibit intermittent spikes and subclinical discharges that soon gave way to spontaneous and recurrent behavioral seizures which gradually increased in frequency, duration, and severity in the next 12-48 h. Anticonvulsant therapy (phenobarbital, PB) was required within the first 3 days of the syndrome, since life-threatening generalized tonic-clonic seizures (GTCS) and status epilepticus would develop if the animal were left untreated. If severe seizures were prevented by antiepileptic drugs (AEDs) there was complete remission of the syndrome and repeat injection was necessary to reinitiate seizures. Animals that experienced severe seizures or that were reinjected after remission developed a chronic seizure syndrome and could be maintained with AEDs for long times (greater than 1 year) without significant debilitation. Although early spikes and subclinical discharges were typically focal to ipsilateral limbic sites, initial seizures appeared explosively in the form of a high-amplitude, high-frequency discharge, which often had an apparently bilateral limbic onset. On the other hand, chronic seizures had much more gradual onset and spread, often consisting of periodic sharp waves or low-amplitude sinusoidal discharge that was more clearly focal to ipsilateral limbic sites. Throughout the syndrome, ictal behavioral manifestations were highly stereotyped and very comparable to those described by other investigators in studies of clinical and experimental limbic epilepsy. All animals exhibited signs of independent contralateral involvement during the syndrome, ranging from independent contralateral spikes to subclinical discharges with a clear contralateral onset. None of the animals exhibited structural lesions on histologic examination at the level of light microscopy.

Parietal lobe epilepsy: diagnostic considerations and results of surgery.

Eleven patients, evaluated between 1983 and 1988, with parietal lobe seizure origin as determined by circumscribed lesion detection in all and successful surgery in 10, were retrospectively evaluated in terms of clinical seizure characteristics and electroencephalographic (EEG) findings. Seven of 11 patients reported auras prior to seizures. In 4 patients, auras were lateralized somatosensory sensations, but in 1 they were ipsilateral to the side of seizure origin, and in 2 they had only occurred many years previously when seizures began. Other auras were either nonspecific or suggested seizure origin outside of the parietal lobe. Observed seizures were of two types: asymmetrical tonic seizures with or without clonic activity and complex partial seizures with loss of contact and automatisms. Four patients had only the first type of seizure and an equal number had only the second type. Three patients had both types of seizures during different episodes. Scalp EEGs correctly localized the side and region of seizure onset in only 1 patient. Three additional patients with congruent parietal localization on scalp EEG had additional misleading EEG findings. All patients had lesions detected with neuroimaging, but in 5 this detection occurred after they had been initially evaluated. These 5 patients had intracranial EEG studies designed to localize the region of seizure origin, and correct seizure onset localization was achieved in 2. Of the other 3 patients, false localization occurred in 1, and 2 could not be localized. Four patients with known lesions and 2 of the patients in whom lesions were detected after initial intracranial evaluations were studied with subdural grid electrodes placed over the lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Occipital lobe epilepsy: clinical characteristics, seizure spread patterns, and results of surgery.

Twenty-five patients with occipital lobe seizure origin were retrospectively evaluated to determine clinical seizure characteristics and electroencephalographic manifestations. Certain symptoms and signs served to identify occipital lobe origin in 22 (88%). These included elementary visual hallucinations, ictal amaurosis, eye movement sensations, early forced blinking or eyelid flutter, and visual field deficits. Eye or head deviation, or both, was observed frequently and was contralateral to the side of seizure origin in 13, but 3 patients exhibited ipsilateral deviation in some or all their seizures. After the initial signs and symptoms, clinical seizure characteristics resembled those of seizures originating elsewhere. Seizures typical of temporal lobe origin with loss of contact and various types of automatic, semipurposeful activity occurred in 11 patients. Seizures in 3 patients exhibited asymmetrical tonic or focal clonic motor patterns characteristic of frontal lobe seizures. Eleven of the 25 patients had, on two occasions, two or more distinctly different seizure types. Scalp electroencephalographic findings were seldom helpful for occipital lobe localization and were frequently misleading. Intracranial electroencephalographic recording correctly identified occipital lobe seizure origin in most, but not all, patients who had such studies. Intracranial electroencephalic recording also proved the variability in clinical seizure characteristics was related to different seizure spread patterns, medially or laterally above and below the sylvian fissure, both ipsilateral and contralateral to the occipital lobe of seizure origin. Eighteen patients had occipital lobe lesions detected with computed tomographic or magnetic resonance imaging scans or both. Resection of the lesions in 16 patients produced excellent results in 14 (88%). Five patients had temporal lobectomies, with good results in 3, but poor results in 2. Two patients with unlocalized seizures had complete section of the corpus callosum, 1 with a good result and the other with a poor result.

Two inexpensive electronic circuits for analog display of multichannel EEG signals.

Two electronic circuits useful for high-resolution EEG recording systems are described. The first is an analog display driver that formats large numbers of EEG signals for display in a variety of modes on a standard CRT display. The second is an analog demultiplexer circuit that reconstitutes large numbers of analog EEG signals from multiplexed D/A outputs. Each provides a readily expandable, high-resolution EEG display that can easily provide real-time or faster performance and that is much less expensive than computer-based digital display systems with comparable capabilities.

Chronic focal epilepsy induced by microinjection of tetanus toxin into the cat motor cortex.

The tetanus toxin model of epilepsy, involving direct microinjection of toxin into the mammalian brain, has a number of advantages relative to other chronic models. However, chronic seizure foci have been confined primarily to the hippocampus. In the present study, 5 cats received total doses of 7.5-22.5 ng of tetanus toxin applied to the left primary motor cortex through an epidural cannula. After 2-18 days, all 5 cats exhibited similar persistent epileptiform syndromes. Three distinct types of spontaneous seizures were noted: focal motor seizures of variable complexity, focal motor seizures with secondary generalization, and epilepsia partialis continua. All cats required anticonvulsant therapy. Simple focal motor seizures, which predominated, were electrographically characterized by 3-5 Hz spike-sharp wave activity, originating in the left motor cortex, associated with contralateral shoulder and forepaw clonus and jacksonian spread. Electrographic activity quickly spread to ipsilateral neocortical structures, and in longer episodes to the cingulate gyri. Seizure foci were still active as long as 37 days after toxin injection. Light microscopic damage attributable to the toxin was absent. These experiments further generalized the tetanus toxin model and confirmed its advantages.