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Purpose: We performed this study to determine whether significant head trauma in human adults can result in hippocampal cell loss, particularly in hilar (polymorph) and CA3 neurons, similar to that observed in animal models of traumatic brain injury. We examined the incidence of hippocampal pathology and its relation to temporal neocortical pathology, neuronal reorganization, and other variables., Methods: Twenty-one of 200 sequential temporal lobectomies had only trauma as a risk factor for epilepsy. Tissue specimens from temporal neocortex and hippocampus were stained with glial fibrillary acidic protein (GFAP) and hematoxylin and eosin (H&E). Eleven hippocampal specimens had additional analysis of neuronal distributions by using cresyl violet and immunolabeling of a neuron-specific nuclear protein., Results: The median age at onset of trauma was 19 years, the median time between trauma and onset of seizures was 2 years, and the median epilepsy duration was 16 years. The length of the latent period was inversely related to the age at the time of trauma (r=0.75; Spearman). The neocortex showed gliosis in all specimens, with hemosiderosis (n=8) or heterotopias (n=6) in some, a distribution differing from chance (p=0.02; Fisher). Hippocampal neuronal loss was found in 94% of specimens, and all of these had cell loss in the polymorph (hilar) region of the dentate gyrus. Hilar cell loss ranged from mild, when cell loss was confined to the hilus, to severe, when cell loss extended into CA3 and CA1. Some degree of mossy fiber sprouting was found in the dentate gyrus of all 10 specimens in which it was evaluated. Granule cell dispersion (n=4) was seen only in specimens with moderate to severe neuronal loss., Conclusions: Neocortical pathology was universally present after trauma. Neuronal loss in the hilar region was the most consistent finding in the hippocampal formation, similar to that found in the fluid-percussion model of traumatic head injury. These findings support the idea that head trauma can induce hippocampal epilepsy in humans in the absence of other known risk factors.

Clinically differentiating between localisation related and generalised epilepsy is important because it carries significant implications for planning diagnostic management strategy. Asymmetry of body parts such as toes, popliteal crease levels, thumbs, cubital crease levels, and forehead and facial structures, are common in patients with localisation related epilepsy syndromes. We retrospectively studied 337 patients with seizure disorders. Body part asymmetry was routinely documented. Fifty-six were excluded because of non-epileptic seizures, pure psychiatric disorders, non-epileptic neurological disorders, brain tumours and strokes. The relationship between clinically detectable body asymmetry (BA) and the electro-anatomic characteristics of their epilepsy was explored. Body asymmetry was found in 88 out of 282 cases, in which 64 (73.5%) suffered from localisation related epilepsy. Among localisation related epilepsy, BA were found in 41.5% (n=64/154) of patients. In contrast, only 18.75% (n=24/128) of patients with generalised seizure disorders showed similar findings (P<0.0001). Among patients with partial onset seizures, lateralisation of BA was concordant with their seizure origin in 75.9% (n=41/54) and discordant in 24.1% (n=13/54). Investigation results of 10 partial epilepsy cases were non-lateralising at the time of study. Peak age of onset of concordant case was 0-5 years old while discordant group was 6-15 years old. We conclude that BA in patients with seizure disorder is a useful clue to diagnosis of localisation related seizure and may provide clues for lateralising seizure origin in partial onset seizures.

Purpose: Positron emission tomography with 2-deoxy fluoroglucose positron emission tomography (18-FDG-PET) is widely used in the pre-surgical evaluation of subjects with epilepsy, but little is known of its usefulness in a non-surgical population., Procedures: We analyzed the sensitivity of PET as a diagnostic tool in a large unselected population of epilepsy subjects. Pre-surgical and non-surgical portions of this population were individually assessed as well. The relationship of PET abnormalities to other neurodiagnostic tests was examined. Statistical assessment relied primarily on contingency tables (chi-square tests), with ANOVA or non-parametric assessment used as necessary., Results: While PET was more likely to identify areas of decreased metabolism in the surgical population than in the non-surgical populations, it nevertheless found a significant number of abnormalities in the total population and in the non-surgical group alone. Even in groups in which the clinical diagnosis was unknown, abnormalities were found 40% of the time. PET was useful as an exclusionary diagnostic tool for non-epileptic seizures (NES) and primary generalized epilepsies (PGE) with sensitivity, specificity, and accuracy > 90%. The PET was somewhat more sensitive than magnetic resonance imaging (MRI) in finding abnormalities in the total population, but was less sensitive than electroencephalography (EEG)., Conclusion: PET may be a useful diagnostic tool in the general epilepsy population even when a definitive clinical diagnosis is not suggested by other modalities.

In this study we examined 37 subjects with a diagnosis of intractable frontal lobe epilepsy (FLE) based on non-invasive pre-surgical evaluation. Twenty-six underwent chronic intracranial ictal recordings (CIR) with video monitoring; 20 of these went on to surgical resection. Eleven underwent surgery without CIR. Retrospectively, we determined that 19 had pure FLE, 12 had frontal plus extrafrontal epileptogenic zones, and six others did not have FLE. We analysed the whole group and individual categories to evaluate the determinants of surgical outcome. Sixty percent of the pure frontal group is seizure free with all having > or = 75% reduction. The frontal-plus group had only 10% seizure free with 70% having > or = 75% reduction. Being in the pure frontal group was associated with better outcomes than the 'frontal-plus' group (P < 0.05; chi-square). Subjects with FSIQ > or = 85, focal pathologies and 18FDG-PET scans which were normal or had focal abnormalities (P < or = 0.05, all, chi-square) were more likely to have excellent outcomes. MRI abnormalities, surface EEG, and location and size of resection were not predictive of surgical outcomes. Rasmussen's encephalitis, incomplete surgical strategies and bilateral foci were apparent in those with poor outcomes, and surgical size predicted post-operative deficits (chi-square; P < 0.001). We conclude that careful, hypothesis-driven implants and operating procedures can result in good surgical outcomes for frontal lobe epilepsy subjects even when lesions are not apparent on routine neuroimaging.

Objectives: To determine whether herpes simplex virus causes monofocal epilepsy and to assess the presence of herpes simplex virus 1 (HSV-1) and HSV-2 in surgical specimens from patients with epilepsy by using polymerase chain reaction and Southern blot analysis., Background: Herpes simplex virus is a common neurotropic virus capable of latency within the central nervous system; it has a predilection for the temporal lobe. Central nervous system infection with HSV has been associated with seizure activity., Design and Methods: Surgical specimens were removed from 50 patients as part of a treatment protocol for monofocal epilepsy. Neuropathological classification was done, and adjacent sections were screened for HSV by using polymerase chain reaction. Tissues obtained post mortem from the temporal lobe cortex of persons with Alzheimer disease (n=17), Parkinson disease (n=14), or nonneurological disease (n=17) served as controls., Results: Twenty (40%) of the 50 epilepsy cases and 2 (4%) of the 48 control cases had at least one sample that tested positive for HSV (P<.001). Sixty-seven percent (8/12) of the epilepsy cases with heterotopia were positive for HSV., Conclusions: There was a statistically significant difference in the frequency of HSV-positive surgical specimens from monofocal seizure epicenters compared with nonepilepsy control specimens. These data suggest an association of the virus with seizure activity. All specimens positive for HSV (surgical specimens and control specimens) should be examined to determine the activity or latency state of the virus and cellular localization.

Background: The popularity of subdural electrodes for the presurgical evaluation of patients with intractable seizures is increasing. However, few reports have prospectively dealt with their efficacy and safety., Methods: We conducted a 5-year prospective study of patients evaluated by the California Comprehensive Epilepsy Program, who subsequently underwent subdural electrode implantation at one of two institutions. Efficacy was examined by ultimate outcome with regards to postsurgery resection seizure frequency. Fifty-five patients underwent 58 implant procedures and postresection outcomes were available in 47 patients. Safety was defined by the incidence of expected and unexpected complications, and neuropathologic examination of tissue specimens., Results: The most common expected adverse effects during implant were fever < or = 102 degrees (41%), cerebrospinal fluid leakage (19%), headache (15%), and nausea (4%). There were no infections. Unexpected adverse events included fever > 102 degrees F (5%), migraine (5%), iatrogenic electrode dysfunction (5%), and temporalis muscle fibrosis (5%). The incidence of pathologic findings suggestive of foreign body reaction was 10%. There were no permanent sequelae. Surgical outcomes were excellent in all (> or = 75% seizure reduction) with 50% seizure free regardless of the focus., Conclusions: Subdural electrodes are a safe, easy, and efficacious tool for evaluating seizure foci prior to resective surgery. They should no longer be considered investigational devices.

Status epilepticus is defined as having two tonic-clonic convulsive seizures in a row without regaining consciousness or continuous absence, complex partial, or partial seizure activity for 30 minutes or longer. This article discusses classification and prognosis of status epilepticus, principles of management, and drug treatment in adults and adolescents.

The effectiveness of long term EEG monitoring in the localization of the epileptic focus was studied in 37 patients with temporal lobe epilepsy comprising 190 recorded seizures, in 19 frontal lobe epileptic patients with 172 recorded seizures and in 12 additional patients which were classified as fronto-temporal. In the temporal lobe group, 49/190 seizures began focally (26%) and 20/190 seizures exhibited a regional onset (10%). In the frontal lobe group, only 21 out of 172 seizures (12%) had a focal ictal onset. 41/172 seizures began regionally (24%). In the fronto-temporal group, 31/55 seizures disclosed a focal EEG onset (57%). This study demonstrates that there is a two-fold increase in seizures beginning focally in the temporal lobe epilepsy group versus the frontal lobe group.

Patients with CPS often display recent memory deficits. Typically, general intelligence, perceptual skills, language, remote memory, and primary memory are all normal. However, the ability to learn new combinations of cognitively complex material is deficient. This deficit may be specific for verbal material (e.g., as a difficulty with learning to recall a response word given an unrelated cue word), for nonverbal material (e.g., as a difficulty in drawing a complex figure from memory), or for both verbal and nonverbal material. Because these characteristics are typical of memory deficits after MTL damage, it is reasonable to suspect that these deficits in patients with epilepsy also reflect MTL damage. In many cases, MTL damage is apparent from neuroimaging studies, whereas seizure semiology suggests MTL onset. In these patients, the same pathology might be the cause of both the ictus and memory deficits. In other cases, memory impairment appears to be secondary to seizures. This suggestion is supported by cases where prolonged complex partial status resulted in a permanent global amnesia. Cases with shorter-lasting memory deficits were also presented. Neuropsychological testing revealed specific recent-memory deficits that cleared 2 weeks after a flurry of CPS and 24 hr after a single seizure. Depth recordings have demonstrated that MTL electrographic seizures can occur without subjective manifestations. When these are evoked by local electrical stimulation, a profound inability to learn new material may be observed during the afterdischarge. Similarly, artificially induced MTL spike-and-wave complexes interfere with the memory for simultaneously presented complex visual scenes. Recent evidence suggests that all of the above phenomena may reflect the engagement by epileptiform processes of the association-cortex (AC)-MTL circuits used in normal human memory. In recent memory tasks, cognitive evoked-potential components N4 and P3 are generated in the MTL and to a lesser degree in related AC regions. The N4/P3 are strongly modulated by familiarity in recent memory. This modulation is eliminated by anterior temporal lobectomy. The typical slow wave following spontaneous MTL interictal spikes has the same MTL voltage topography, and thus probably similar synaptic generators, as the cognitive P3 potential. Furthermore, MTL spike-and-wave complexes can be evoked in recent memory tasks at a fixed latency equal to that of the N4.(ABSTRACT TRUNCATED AT 400 WORDS)

Eight patients were diagnosed as having extratemporal seizures based on their ictal electroclinical manifestations. The correlation between the focus based on semiology and that based on intracranial electrographic recording and surgical excision was excellent in five, good in three. The electroclinical manifestations of seizures are important data to consider in the diagnosis and treatment of extratemporal seizure foci.

In 15 patients we hypothesized the origin of epilepsies to be 'extratemporal' based on videotaped seizures and surface EEG. Neuropsychological tests and neuroimaging (CAT, MRI, and PET scans) were then compared to the hypothesized ictal sites. Neuropsychological tests were abnormal in 86.6% and FDG-PET scans were abnormal in 73%. The neuropsychological tests and PET localized or lateralized areas of dysfunction to the same sites as electroclinical characteristics did in 85% of patients (P less than 0.01, Fisher exact test). No statistically significant correlation between lesion sites on CT and MRI and the ictal origin was observed due to the high proportion of normal or non-specific scans. These observations should be verified in a larger series of extratemporal seizures.

Seventeen patients had type I complex partial seizures (CPS) with three consecutive phases: initial motionless staring, oral-alimentary automatisms, and reactive quasipurposeful movements during impaired consciousness. Fifteen patients had stereoelectroencephalography. Focal or regional 8- to 20-Hz low-voltage epileptiform paroxysms in either hippocampus (10 patients), amygdala (1 patient), or both (1 patient) preceded initial motionless staring. Focal sphenoidal or nasopharyngeal ictal paroxysms preceded seizures in three other patients who underwent lobectomy. All 15 patients are seizure-free 2 to 11 years after temporal lobectomy. Type I CPS are most commonly of hippocampal origin.

We studied the first clinical manifestations of 72 complex partial seizures (CPS) in 17 drug-resistant patients. CPS were indicated to be of hippocampal-amygdalar origin by scalp and depth EEG. We asked: (a) Do all CPS of hippocampal-amygdalar origin start with an initial motionless stare and/or oroalimentary automatisms? (b) If not, what other clinical manifestations appear at onset of the CPS? Results showed that approximately 39% of CPS begin with motionless staring, 25% with nonfocal discrete movements, 21% with oroalimentary automatisms, 10% with perseverative stereotyped automatisms, and 6% with vocalizations. Nonfocal discrete movements and oroalimentary automatisms were identified as the most common second and third clinical sequential manifestations during a CPS. We conclude that although approximately 60% of CPS of hippocampal-amygdalar origin start with motionless staring or oroalimentary automatisms, 40% do not.

Hemispheric language dominance, as determined by intracarotid amobarbital sodium injections, and handedness, as reflected by writing and drawing preference, were evaluated in a select group of patients with intractable seizures who had documented focal epilepsy originating from one temporal lobe. Of the patients with left temporal lobe seizure focus, an unusually high percentage of right-handed patients (4/26 [15%]) had right hemisphere language dominance. Pathologic findings of the resected temporal lobe in these patients revealed microscopic damage (hippocampal sclerosis) of the hippocampus in three of three cases; one patient also had a small hamartoma in the midtemporal gyrus. We hypothesize that crossed dominance resulted from disruption by epileptiform activity during early development of selective areas of the left hemisphere.

Surface and depth EEG seizure patterns were compared in 34 patients with intractable temporal lobe epilepsy in whom depth EEG electrodes had been chronically implanted in order to localize epileptogenic sites with a view to surgery. EEG records accompanied by clinical seizures, auras, no behavioral changes, as well as records for which no behavioral observations had been made, were judged with respect to the manner in which seizure activity originating unilaterally in the depth of one of the temporal lobes spread to the surface. For each EEG record, the onset of seizure activity in depth was classified as being focal or regional in form, and seizure activity was judged as: (1) not spreading to the surface, (2) spreading bilaterally and synchronously to the surface, (3) spreading initially to the surface ipsilateral to the depth site(s) in which the electrographic seizure first appeared, or (4) spreading initially to the surface contralateral to the depth site(s) in which the seizure activity initially occurred. EEG seizure activity was found to be less likely to propagate to the surface for those records that were either unaccompanied by behavior changes or accompanied only by auras than for those records accompanied by clinical seizures. In records accompanied by clinical seizures, seizure activity commonly propagated to the surface in a bilateral and synchronous fashion and was also found to spread initially to the ipsilateral but not to the contralateral surface. Anatomical and electrophysiological data accounting for the occurrence of ipsilateral spread were discussed. Diagnostic usefulness of surface recordings during clinical seizures in temporal lobe epilepsy was discussed.

We describe a patient who had a violent automatism that occurred during a partial complex seizure. The initial spike wave activity was recorded from nasopharyngeal leads that were lost as the patient began his vigorous, violent activity. This activity included nondirected, automatic, stereotyped behavior with physical assaults on objects in his path.

Reasons why nine patients with Type II complex partial seizures continue to have disabling attacks after anterior temporal lobectomy were sought. Videotaped seizures revealed extratemporal features during onset of ictus, such as postural, contraversive head, eyes, and focal motor movements in four patients, and automatic ambulation, running, and motions similar to bicycling action or "bringing in a catch of fish" in five patients. Depth electrographic patterns also suggested a focus outside the hippocampus or amygdala in seven patients. Two patients had frontal lobe dysfunction on neuropsychological tests. Anterior temporal lobectomy is not indicated in Type II complex partial seizures.