Routine EEG and Temporal Lobe Epilepsy: Relation to Long-Term EEG Monitoring, Quantitative MRI, and Operative Outcome

Summary: Purpose: To investigate the relation among routine EEG, long-term EEG monitoring (LTM), quantitative magnetic resonance imaging (MRI), and surgical outcome in temporal lobe epilepsy (TLE).
Methods: We evaluated 159 patients with intractable TLE who underwent an anterior temporal lobectomy between 1988 and 1993. The epileptogenic temporal lobe was determined by ictal LTM. A single awake-sleep outpatient EEG with standard activating procedures was performed before LTM. EEGs were analyzed by a blinded investigator.
Results: MRI scans showed unilateral medial temporal atrophy (109 patients) or symmetrical hippocampal volumes (50 patients). The surgically excised epileptogenic brain tissue revealed mesial temporal sclerosis, gliosis, or no histopathologic alteration. Routine EEG revealed temporal lobe epileptiform discharges in 123 patients. Routine EEG findings correlated with the temporal lobe of seizure origin (p < 0.0001) and the results of MRI volumetric studies (p < 0.0001). Interictal epileptiform discharges were seen only during LTM in 24 patients. Routine EEG was disconcordant with interictal LTM in another 20 patients. MRI-identifed unilateral medial temporal lobe atrophy was a strong predictor of operative success (p < 0.0001). There was no significant relation between the routine EEG findings and operative outcome (p > 0.20).
Conclusions: Results of this study modified our approach in patients with TLE. Interictal epileptiform discharges localized to one temporal lobe on serial routine EEGs or during LTM may be adequate to identify the epileptogenic zone in patients with MRI-identified unilateral medial temporal lobe atrophy.     

Neuronal loss and gliosis of the amygdaloid nucleus in temporal lobe epilepsy

Although clinical and electrophysiological evidence indicates that the amygdaloid body plays an important role in the pathogenesis of temporal lobe epilepsy, there are very few detailed data on histopathological changes in this nucleus in epilepsy patients. In the present study we have examined the lateral nucleus of the amygdaloid body in 70 surgical specimens from patients with temporal lobe epilepsy and in 10 control specimens with respect to neuronal density and gliosis. The results were compared to the neuronal loss in the hippocampal formation. Our goal was to examine the pathological alterations of the amygdaloid body and their correlation with other morphological changes in temporal lobe epilepsy. In epilepsy patients with Ammon’s horn sclerosis or focal lesions of the temporal lobe, the neuronal density of the lateral amygdaloid nucleus was significantly decreased as compared to normal controls (P < 0.001). Overall, the mean volumetric density in epilepsy patients was reduced to 59% of that in normal individuals. There was no correlation between the neuronal density in the lateral amygdaloid nucleus and that in the different segments of the hippocampal formation or to the age at onset or the duration of epilepsy. The neuronal loss of the amygdaloid nucleus correlated well with the presence of fibrillary gliosis. Our findings demonstrate that the amygdaloid body is severely altered in most patients with temporal lobe epilepsy and that these changes are independent of those in the hippocampus. The presence of neuronal loss and gliosis in the amygdaloid nucleus of patients with focal lesions but no Ammon’s horn sclerosis is compatible with an involvement of the amygdala in secondary epileptogenesis. Received: 28 September 1996 / Revised, accepted: 7 January 1997     

Role of cortical dysplasia in epileptogenesis following prolonged febrile seizure

Purpose: Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model. Methods: Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM‐treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long‐term video‐EEG (electroencephalography). Results: The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC‐only and MAM‐only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group. Discussion: Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE.     

Generation of scalp discharges in temporal lobe epilepsy as suggested by intraoperative electrocorticographic recordings

OBJECTIVES: To study the variability, topography, polarity, duration, and incidence of interictal epileptiform discharges (EDs) in the scalp EEG and electrocorticogram (ECoG) from 16 patients with temporal lobe epilepsy who underwent surgical treatment. METHODS: Preoperative scalp EEGs during quinalbarbitone induced sleep were compared with preresection ECoGs obtained under general anaesthesia. The analysis was based on the initial ECoG record obtained before activation by intravenous thiopentone, and the EEG during stages I and II of sleep. RESULTS: On the scalp, 15 patients had a single discharge pattern, spikes were predominantly negative, EDs were of largest amplitude at the anterior temporal electrode in 13 patients and mean discharge incidence was 4.0 (SD 4.2) discharges/min. In ECoG recordings, nine patients had two independent ECoG patterns, the polarity of spikes was negative, positive-negative, or positive, the site of maximal amplitude varied greatly between subjects, discharge incidence was 7.3 (SD 3.9) discharges/min. There was no relation between the topography of the largest spikes on the scalp and in the ECoG. In 14 patients, scalp spikes showed statistically significant longer duration on the scalp than in the ECoG. In seven patients who had frequent widespread ECoG discharges, averaging spikes across ECoG channels generated spiky patterns of duration similar to that of scalp spikes. CONCLUSION: It seems that, in temporal lobe epilepsy, scalp discharges originate from widespread ECoG discharges and tend to produce a stereotyped pattern on the scalp with largest amplitudes at the anterior temporal electrodes. This is probably due to local anatomical peculiarities in the brain coverings, such as skull discontinuities, rather than to the location of neuronal generators within the temporal lobe. Due to spatiotemporal averaging, widespread cortical discharges which become asynchronous during propagation appear with increased duration and blunted waveform in the EEG, whereas sharply localised phenomena such as positive focal spikes are not recorded from the scalp.     

Frequency of bitemporal independent interictal epileptiform discharges in temporal lobe epilepsy

PURPOSE: Bitemporal interictal epileptiform discharges (IEDs) occur in < or =42% of scalp EEGs in patients with temporal lobe epilepsy (TLE) studied with routine EEGs or partial analysis of long-term recordings. METHODS: Twenty-eight patients with TLE demonstrating exclusively unilateral temporal IEDs on routine EEGs underwent 24-h continuous recording. The entire record was visually inspected for epileptiform discharges. We used continuous EEG to assess the significance of long-term recording in detecting bilateral IEDs. RESULTS: Twenty-two patients had left temporal IEDs; 21 had right temporal IEDs. Seventeen (61%) patients had IEDs originating from both the right and left temporal lobes. The probability of detecting bilateral independent IEDs was correlated with the duration of continuous EEG recording. There was no correlation between the number of IEDs originating from one side and the probability of detecting independent IEDs on the other side. The frequencies of IEDs were not correlated with the length of time since onset of epilepsy. CONCLUSIONS: The findings suggest that when long-term recordings are performed, the incidence of bilateral discharges in TLE is higher than previously reported in the literature and supports the view that TLE is commonly a bilateral disease.     

cDNA profiling of epileptogenesis in the rat brain

Symptomatic temporal lobe epilepsy typically develops in three phases: brain insult --> latency period (epileptogenesis) --> recurrent seizures (epilepsy). We hypothesized that remodeling of neuronal circuits underlying epilepsy is associated with altered gene expression during epileptogenesis. Epileptogenesis was induced by electrically triggered status epilepticus (SE) in rats. Animals were continuously monitored with video-EEG, and the hippocampus and temporal lobe were collected either during epileptogenesis (1, 4 and 14 days) or after the first spontaneous seizures (14 days) for cDNA array analysis. Altogether, 282 genes had altered expression, from which 87 were in the hippocampus and 208 in the temporal lobe (overlap in 13). Assessment of hippocampal gene expression during epileptogenesis indicated that 37 genes were altered in the 1-day group, 12 in the 4-day group and 14 in the 14-day epileptogenesis group. There were 42 genes with altered expression in the 14-day epilepsy group. In the temporal lobe, the number of genes with altered expression was 29 in the 1-day group, 155 in the 4-day group, 32 in the 14-day epileptogenesis group and 62 in the 14-day epilepsy group. Products of the altered genes are involved in neuronal plasticity, gliosis, organization of the cytoskeleton or extracellular matrix, cell adhesion, signal transduction, regulation of cell cycle, and metabolism. As most of these genes have not previously been implicated in epileptogenesis or epilepsy, these data open new avenues for understanding the molecular basis of epileptogenesis and provide new targets for rational development of anti-epileptogenic treatments for patients with an elevated risk of epileptogenesis after brain injury.     

Interictal EEG in temporal lobe epilepsy in childhood.

The authors clarified the value of interictal discharges and verified which extratemporal regions may also show epileptiform activity in temporal lobe epilepsy (TLE) in childhood. Thirty consecutive patients aged 3 to 18 years (mean age = 12.16 years; 16 male) with TLE associated with hippocampal atrophy were studied. Each patient had 1 to 15 interictal EEG recordings (mean: 5.6; total = 192 EEGs). Video-EEG monitoring was performed in 20 patients. All patients had MRI. The findings were compared with a control group of 53 consecutive TLE adult outpatients with hippocampal atrophy. Each adult patient underwent 3 to 21 routine EEGs (mean: 10.67; total = 566). Interictal EEGs of children with TLE showed extratemporal epileptiform discharges more frequently than EEGs of adults with TLE. Frontal, parietal, and occipital discharges were more frequently seen in children (P < 0.05). These results suggest a close interaction between temporal and other cerebral regions in children with epilepsy and provide further evidence of the existence of neural networks.     

Alterations of the microvascular network in the sclerotic hippocampus of patients with temporal lobe epilepsy

Hippocampal sclerosis is the most frequent pathology encountered in resected tissue obtained from patients with temporal lobe epilepsy. The main hallmarks of hippocampal sclerosis are neuronal loss and gliosis. Several authors have proposed that an increase in blood vessel density is a further indicator, based on interpretations from staining of markers related to both blood–brain barrier disruption and the formation of new blood vessels. However, previous studies performed in our laboratory using correlative light and electron microscopy revealed that many of these “blood vessels” are in fact atrophic vascular structures with a reduced or virtually absent lumen and are often filled with processes of reactive astrocytes. Thus, “normal” vasculature within the sclerotic CA1 field is drastically reduced. Since this decrease is consistently observed in the human sclerotic CA1, this feature can be considered another key pathological indicator of hippocampal sclerosis associated with temporal lobe epilepsy.This article is part of a Special Issue entitled “NEWroscience 2013”.     

Lateralizing value of interictal spikes on overnight sleep-EEG studies in temporal lobe epilepsy

PURPOSE: To determine the lateralizing value of interictal epileptiform discharges (IEDs) recorded during overnight sleep-EEG studies in temporal lobe epilepsy. Because IEDs are more prevalent in non-rapid eye movement (NREM) sleep than in wakefulness, overnight sleep-EEG recordings may contribute additional lateralizing information to the epilepsy surgery evaluation beyond daytime EEGs. METHODS: Twenty-four subjects with medically refractory temporal lobe epilepsy underwent continuous overnight sleep-EEG recordings. Subjects were seizure free > or =24 h before study and receiving stable doses of medication. The IED foci recorded on overnight studies were compared with daytime EEGs, interictal samples, and ictal recordings during long-term monitoring, brain magnetic resonance images (MRIs), and surgical outcome. RESULTS: (a) In all 24 subjects, including 13 without IEDs on daytime EEGs, temporal IEDs were present during NREM sleep and were exclusively or predominantly (>95%) unilateral in 15 and bitemporal in nine. (b) Unilateral NREM IEDs were concordant with surface or depth ictal-onset regions in 14 subjects, even if MRIs were normal (three subjects) or surface ictal-onset regions were bilateral (five subjects). Eleven of 12 subjects with unilateral concordant NREM IEDs who have undergone surgery are seizure free. (c) Bitemporal IEDs were associated with postoperative seizures in all subjects with normal MRIs or widespread MRI abnormalities. However, all subjects with bitemporal IEDs and MRI hippocampal abnormalities concordant with ictal-onset regions had good to excellent surgical outcomes. CONCLUSIONS: When combined with other investigations, IEDs recorded on overnight studies add prognostic data to the epilepsy surgery evaluation not provided by daytime EEGs.     

Anticonvulsant and neuroprotective effects of the novel calcium antagonist NP04634 on kainic acid‐induced seizures in rats

Kainic acid (KA)‐induced status epilepticus (SE) is a well‐characterized model of excitotoxic neuronal injury. Excitotoxicity results from activation of specific glutamate receptors, with resultant elevation of intracellular Ca²⁺. The CA1 and CA3 subregions of the hippocampus are especially vulnerable to KA, and this pattern of neuronal injury resembles that occurring in patients with temporal lobe epilepsy. Calcium plays an essential role in excitotoxicity, and accordingly calcium channel inhibitors have been shown to have protective effects in various experimental models of epilepsy and brain injury. Moreover, they also potentiate the antiseizure efficacy of conventional antiepileptic drugs. This study was undertaken to determine whether NP04634, a novel compound, reported as a non‐L‐type voltage‐sensitive calcium channel (VSCC) inhibitor, could prevent the entrance in SE and the neuronal loss evoked by intraperitoneal injection of KA. Our results show that intragastrical administration of NP04634 reduced the percentage of rats that entered SE after KA injection, increased the latency of SE entry, and significantly reduced the mortality of rats that entered SE. Also, NP04634 prevented the loss of hippocampal CA1 and CA3 pyramidal neurons and reduced the gliosis induced by KA. These results point to a potential anticonvulsant and neuroprotective role for NP04634. © 2009 Wiley‐Liss, Inc.     

Temporal Lobe Epileptogenesis and Epilepsy in the Developing Brain: Bridging the Gap Between the Laboratory and the Clinic. Progression, But in What Direction?

Summary:  The origins of human mesial temporal lobe epilepsy and hippocampal sclerosis are still not well understood. Hippocampal sclerosis and temporal lobe epileptogenesis involve a series of pathologies including hippocampal neuronal loss and gliosis, axonal reorganization, and maybe hippocampal neoneurogenesis. However, the causality of these events is unclear as well as their relation to the factors that may precipitate epileptogenesis. Significant differences between temporal lobe epileptogenesis in the adult and immature brain may require differential approaches. Hereditary factors also may participate in some cases of hippocampal sclerosis. The key point is to identify the significance of these age-dependent changes and to design preventive treatments. Novel strategies for the prevention and treatment of mesial temporal lobe epilepsy and hippocampal sclerosis may include rational use of neuroprotective agents, hormonotherapy, immunizations, and immunotherapy.     

Nasopharyngeal EEG recording in psychiatric patients

Because psychiatric patients with underlying CNS pathology in the temporal lobe areas may not respond well to traditional medications, the detection of electroencephalogram (EEG) abnormalities in patients with behavior dysfunction can be valuable to the evaluation process. As EEGs recorded with nasopharyngeal electrodes can monitor dysrhythmic discharges in the basomedial aspects of the temporal lobe that are not visible with the routine wake scalp EEG, the authors tried to determine whether the nasopharyngeal lead EEGs are more effective than the scalp EEGs in detecting spike and spike-and-wave discharges. The EEGs of 648 psychiatric inpatients and outpatients, which were recorded over an 18-month period from January 1985 to June 1986, were retrospectively studied, and the results showed that the nasopharyngeal lead recordings revealed a greater percentage of epileptiform abnormalities.     

Parenchymal lesions in pharmacoresistant temporal lobe epilepsy: dual and multiple pathology

OBJECTIVES: Dual pathology is reported in 5-30% of temporal lobe resections performed in pharmacoresistant epilepsy. Dual pathology may be of importance for surgical planning and also for the understanding of the pathogenesis of epilepsy. We describe the frequency of dual or multiple pathology, i.e. more than one histopathological diagnosis, in adults with temporal lobe resections. MATERIAL AND METHODS: Surgical specimens from 33 consecutive patients with resections including mesial as well as neocortical temporal structures were reviewed. All histopathological findings were recorded. Post-mortem specimens from 11 control subjects were also reviewed. RESULTS: Dual or multiple pathology was found in almost half of the epilepsy patients (48%). Hippocampal sclerosis was found in 25 patients (76%), malformations of cortical development in 15 (46%), of which 12 (36%) were microdysgenesis, and low-grade tumours in seven (21%). Apart from mild gliosis, there were no histopathological changes in the control specimens. CONCLUSION: Dual or multiple pathology was a common finding in this group of adults with temporal lobe resections. In order to increase our understanding of how aetiological factors may combine in the development of seizures, we consider it relevant and important to report all histopathological findings in epilepsy surgery series.     

Clinical and EEG analysis of initial status epilepticus during infancy in patients with mesial temporal lobe epilepsy

This study investigated the clinical and EEG characteristics of initial status epilepticus (SE) during infancy in patients with mesial temporal lobe epilepsy (MTLE). The subjects were six patients who had been brought to our emergency clinic and treated for their initial SE between 1977 and 1988, and later developed MTLE. We reviewed the medical records and laboratory findings at the time of the initial SE, and the clinical evolution up to the development of MTLE. The six patients included four females and two males. The initial SE developed at ages ranging from 7 months to 2 years and 9 months with a mean of 1 year and 2 months. These episodes were characterized by an elevated temperature of more than 38 degrees C (4/6 cases), clusters of prolonged seizures during one episode of SE (4/6 cases), long-lasting SE (120-380 min, mean 227 min, 6/6 cases), postictal prolonged loss of consciousness (median 5 h, 6/6 cases), and the presence of Todd's paralysis (3/6 cases). The lateralization of the ictal or postictal EEGs of the SE in five of the six cases was identical to that of the hippocampal atrophy later confirmed by MRI. Follow-up EEG examinations at a 6 month interval demonstrated temporal spike discharges appearing only after the onset of complex partial seizures. Two patients, who had no fever at the initial SE, were characterized by a very early appearance of epileptic EEG abnormality and a short interval between the initial SE and the development of complex partial seizures, suggesting that the SE was the first epileptic manifestation. The result of this study showed that SE progressing to MTLE tends to have complicated clinical manifestations characterized by clusters of unilateral or generalized SE followed by prolonged postictal unconsciousness, generalized clinical manifestations despite lateralized ictal EEG discharges, and the Todd's paresis in addition to the prolonged seizure duration.     

Temporal lobe epilepsy: analysis of patients with dual pathology

OBJECTIVES: To determine the frequency and types of dual pathology in patients with temporal lobe epilepsy (TLE) and to analyze the clinical manifestations and surgical outcome. MATERIAL AND METHODS: A total of 240 patients with TLE underwent temporal resections following a comprehensive pre-surgical evaluation. Thirty-seven (15.4%) of these had hippocampal sclerosis (HS) or temporal lobe gliosis in association with another lesion (dual pathology). RESULTS: Eighteen of 37 patients with dual pathology had heterotopia of the temporal lobe, nine had cortical dysplasia, four had cavernous angiomas or arteriovenous malformations, one had a dysembryoplastic neuroepithelial tumor, one had a contusion and four patients had cerebral infarctions in childhood. 68.5% had abnormal head magnetic resonance imagings, 91.3% had abnormal positron emission tomography scans, and 96% had abnormal ictal SPECT. The intracarotid amobarbital procedure (IAP) showed impaired memory of the epileptogenic side in 72% of the patients. Twenty patients had left and 17 had right-sided en bloc temporal resections, including the lesion and mesial temporal structures. Twenty-six (70.2%) became seizure-free, eight (21.6%) had rare seizures, two (5.4%) had worthwhile seizure reduction and one (2.7%) had no improvement (range of follow-up 1-16 years, mean = 7.4 years). CONCLUSIONS: 15.4% had dual pathology. The dual pathology was almost exclusively seen in patients whose lesions were congenital, or occurred early in life, suggesting that the hippocampus is more vulnerable and more readily develops HS in early childhood. Resections, including the lateral and mesial temporal structures led to a favorable outcome with no mortality and little morbidity.     

Magnetic resonance imaging in the study of the lithium-pilocarpine model of temporal lobe epilepsy in adult rats

PURPOSE: In temporal lobe epilepsy, it remains to be clarified whether hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the temporal evolution of the lesions in the lithium-pilocarpine model of epilepsy in the rat with magnetic resonance imaging (MRI) to determine the progressive morphologic changes occurring before the appearance of chronic epilepsy. METHODS: MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution of lesions using T(2)- and T(1)-weighted sequences before and after the injection of gadolinium from 2 h to 9 weeks. RESULTS: At 2 h after status epilepticus (SE), a blood-brain barrier breakdown could be observed only in the thalamus; it had disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the piriform and entorhinal cortices together with extensive neuronal loss; it disappeared progressively over a 5-day period. During the chronic phase, a cortical signal reappeared in all animals; this signal corresponded to gliosis, which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically stained sections as hypertrophic astrocytes with thickened processes. In the hippocampus, the correlation between histopathology and T(2)-weighted signal underscored the progressive constitution of atrophy and sclerosis, starting 2 days after SE. CONCLUSIONS: These data show the reactivity of the cortex that characterizes the initial step leading to the development of epilepsy and the late gliosis that could result from the spontaneous seizures. Moreover, it appears that hippocampal sclerosis progressively worsened and could be both the cause and the consequence of epileptic activity.     

Progressive, potassium-sensitive epileptiform activity in hippocampal area CA3 of pilocarpine-treated rats with recurrent seizures

Rat hippocampal area CA3 pyramidal cells synchronously discharge in rhythmic bursts of action potentials after acute disinhibition or convulsant treatment in vitro. These burst discharges resemble epileptiform activity, and are of interest because they may shed light on mechanisms underlying limbic seizures. However, few studies have examined CA3 burst discharges in an animal model of epilepsy, because a period of prolonged, severe seizures (status epilepticus) is often used to induce the epileptic state, which can lead to extensive neuronal loss in CA3. Therefore, the severity of pilocarpine-induced status epilepticus was decreased with anticonvulsant treatment to reduce damage. Rhythmic burst discharges were recorded in the majority of slices from these animals, between two weeks and nine months after status epilepticus. The incidence and amplitude of bursts progressively increased with time after status, even after spontaneous behavioral seizures had begun. The results suggest that modifying the pilocarpine models of temporal lobe epilepsy to reduce neuronal loss leads to robust network synchronization in area CA3. The finding that these bursts increase long after spontaneous behavioral seizures begin supports previous arguments that temporal lobe epilepsy exhibits progressive pathophysiology.     

Synaptophysin immunoreactivity in temporal lobe epilepsy-associated hippocampal sclerosis

We have previously devised a semiquantitative grading system for hippocampal sclerosis (HS) in specimens resected for intractable temporal lobe epilepsy. The grades range from zero to four based on the amount and distribution of neuronal loss and gliosis. In the present study hippocampal sections from 25 patients who had temporal lobe epilepsy and had previously been assigned a grade were examined with synaptophysin immunohistochemistry, and the synaptic content in specific hippocampal fields was correlated with the results of the HS grading system. There was evidence of both significant synaptic loss and increased synaptic density in different fields of the hippocampus with increasing HS. A marked decrement of synaptic immunostaining was present in fields CA1 and CA4 that were highly correlated with HS grade. Sector CA4 seemed to respond in a more graded or continuous way to the pathological insults occurring in temporal lobe epilepsy than did CA1, which appeared to exhibit an all or nothing response. Also, while the width of the outer part of the molecular layer of the dentate (mld) gyrus decreased with increasing HS grade, the inner part of the mld became wider and showed an increased synaptic density so that the overall width of the mld was increased in the high-grade group. We conclude that quantitative measurement of synaptic loss in CA1 and CA4 using synaptophysin immunohistochemistry is a sensitive method for detecting HS and correlates well with the empirically derived HS grading scale, with CA4 exhibiting a more graded response than CA1. In addition, a plasticity response in the inner part of the mld in patients with high-grade HS has been confirmed and quantitated. Received: 8 September 1998 / Revised, accepted: 21 October 1998     

A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: evidence for distinctive patient subcategories

PURPOSE: This study is a retrospective analysis of the pathology of the hippocampus from patients with medically intractable temporal lobe epilepsy. We attempted to relate neuronal density, immunohistochemistry, electrophysiologic data, and surgical outcome. METHODS: Immunostaining patterns for neuropeptide Y, somatostatin, substance P, and dynorphin defined the immunohistochemical characteristics of the hippocampi. Neuronal densities were determined by microscopic cell counts. Sharp electrode recordings from dentate granule cells determined measures of inhibition and excitation. RESULTS: Patient hippocampi without evidence of sclerosis generally resembled autopsy controls on the basis of neuronal densities of hippocampal subfields and patterns of immunostaining. The nonsclerotic hippocampi were divisible into two subgroups on the basis of neuronal density correlations between hippocampal subfields, the excitability of dentate granule cells, etiology, and surgical outcome. Hippocampi with sclerosis were divisible into those with significant neuronal loss confined to area CA1 and those with neuronal loss throughout the hippocampus and dentate gyrus. In the former, the dentate gyrus resembled in morphology the nonsclerotic hippocampi but with slightly increased excitability of the dentate granule cells. The hippocampi with more extensive neuronal loss had changes in immunostaining patterns associated with the dentate gyrus, correlated with significant hyperexcitability of dentate granule cells. The surgical outcome, with the exception of one group, was good in approximately 70-90%. CONCLUSIONS: Hippocampi from patients with intractable temporal lobe epilepsy can be assigned to several groups on the basis of pathophysiology. Different pathologies may represent differing causative mechanisms of intractable temporal lobe epilepsy and be predictive of surgical outcome.     

Quantitative neuropathology of the entorhinal cortex region in patients with hippocampal sclerosis and temporal lobe epilepsy

PURPOSE: Clinical, radiologic, and experimental evidence indicates that the entorhinal cortex (EC) region may be linked to the pathophysiology of hippocampal sclerosis (HS) in patients with temporal lobe epilepsy. Few neuropathologic studies of this region have been undertaken in patients with HS undergoing surgery, some suggesting preferential loss of layer III neurones. METHODS: We carried out a quantitative analysis in 26 patients with HS, nine patients with lesional temporal lobe epilepsy (LTLE), and eight postmortem controls. We measured neuronal densities in EC by using a three-dimensional cell-counting technique on NeuN immunostained and Nissl-stained sections. We also quantified the density of calretinin-positive interneurones in this region and the density of neurones in adjacent subiculum and CA1 subfields. We also assessed the patterns of gliosis in the EC in the patient groups and the presence of any neocortical neurone loss. RESULTS: No significant difference was found in the mean neuronal densities in the EC region between HS and LTLE groups or postmortem controls. Laminar gliosis in midcortical layers was seen in a proportion of HS cases but also in the LTLE group. No significant difference was seen in the density of calretinin interneurones and no correlation between the presence of neocortical neuronal loss and EC neuronal densities. CONCLUSIONS: A stereotypical pattern of neuronal loss and gliosis in the EC region in patients with HS is not confirmed that distinguishes this pathologic process from that in patients with lesional TLE.