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Interictal temporal delta activity in temporal lobe epilepsy: correlations with pathology and outcome.

PURPOSE: To determine the characteristics and the clinical significance of focal slow activity and its association with focal epileptogenesis in patients with temporal lobe epilepsy (TLE). METHODS: We analyzed the interictal EEGs of 141 patients who had temporal lobe resections for intractable focal seizures and correlated the findings with pathologic changes and outcome. The pathologic changes were categorized into medial temporal sclerosis, tumors, and nonspecific changes. RESULTS: Lateralized slow activity was found in 66% of the patients, and it was mainly temporal, of delta frequency and irregular morphology. None of its characteristics, including quantity and reactivity to eye opening, was substrate specific. It was highly concordant with temporal spiking (60%), without any difference across the three groups, but provided additional information in 19 (15%) patients who had no lateralizing spikes. The effect of sleep also was similar in all three groups and included transition of slow waves into spikes. Lateralized slow activity to the side of the operation was significantly associated with favorable outcome only in the group with nonspecific pathology (p = 0.008), regardless of the presence, laterality, or topography of spikes. CONCLUSIONS: Our findings suggest that in patients with TLE whose brain magnetic resonance imaging (MRI) is either normal or suggestive of medial temporal sclerosis, interictal temporal slow activity has a lateralizing value similar to that of temporal spiking. Its association with a favorable outcome in patients with nonspecific pathology also suggests that candidates with lateralizing temporal delta and normal MRI should not be barred from further preoperative assessment.

Adolescent↗

A 5-month period of epilepsy impairs spatial memory, decreases anxiety, but spares object recognition in the lithium-pilocarpine model in adult rats.

PURPOSE: In temporal lobe epilepsy (TLE), interictal behavioral disorders affect patients' quality of life. Therefore we studied long-term behavioral impairments in the lithium-pilocarpine (li-pilo) model of TLE. METHODS: Eleven li-pilo adult rats exhibiting spontaneous recurrent seizures (SRSs) during 5 months were compared with 11 li-saline rats. Spatial working memory was tested in a radial arm maze (RAM), anxiety in an elevated plus-maze (EPM), and nonspatial working memory in an object-recognition paradigm. Neuronal loss was assessed on thionine brain sections after behavioral testing. RESULTS: In the RAM, the time to complete each session and the number of errors per session decreased over a 5-day period in li-saline rats but remained constant and significantly higher in li-pilo rats. In the EPM, the number of entries in and time spent on open arms were significantly higher in li-pilo than li-saline rats. In the object-recognition task, the two groups exhibited a comparable novelty preference for the new object. Neuronal loss reached 47-90% in hilus, CA1, amygdala, and piriform and entorhinal cortex. CONCLUSIONS: In li-pilo rats having experienced SRS for 5 months, performance in the object-recognition task is spared, which suggests that object discrimination remains relatively intact despite extensive damage. Neuronal loss in regions mediating memory and anxiety, such as hippocampus, entorhinal cortex, and amygdala, may relate to impaired spatial orientation and decreased anxiety.

Animals↗

Structure-activity and conformational studies of a series of modified C-terminal hexapeptide neurotensin analogues.

Neurotensin (NT), is a linear tetradecapeptide (pGlu1-Leu2-Tyr3-Glu4-Asn5- Lys6-Pro7-Arg8-Arg9-Pro10-Tyr11-Ile12-Leu13) that has been found in the central nervous system and peripheral tissues and appears to have a variety of physiological properties. A C-terminal hexapeptide analogue [N alpha Me-Arg-Lys-Pro-Trp-Tle-Leu, (1) Tle = tert-leucine] has recently been reported to have high affinity for the NT receptor and appears to possess central activity after systemic administration. In an effort to probe the structure-activity and conformational properties of the dipeptide, Pro-Trp for binding and functional activity, these residues have been substituted with several natural and unnatural amino acids. Some of these analogues have binding affinities similar to compound 1, while in other cases, such as D-amino acid substitutions, the peptides had negligible binding affinity. In general, the Pro10 position seems more tolerant of substitution by amino acids that favor a reverse turn, rather than those that favor an extended conformation. The Trp11 position accepted extra steric bulk more readily than conformational constraints.

Animals↗

Primary generalized epilepsy and temporal lobe epilepsy: a psychological study using Rorschach tests.

Rorschach tests were performed on patients with primary generalized epilepsy (PGE) and on patients with temporal lobe epilepsy (TLE) combined with generalized tonic-clonic convulsions. Each group consisted of 20 cases and the two groups were matched as closely as possible. Patients with PGE were found to be characterized by variable responses, sensitivity, extroversion and undifferentiated tendencies. Patients with TLE are practical but inefficient and constricted in character. Cases not on medication displayed the same character types. On the basis of the above findings, speculation is made concerning the features of neurotic or psychotic PGE patients.

Adult↗

Characteristics of postictal headache in patients with partial epilepsy.

Migraine-like features sometimes characterize the headache that follows epileptic seizure (postictal headache, PIH). We compared patients with different types of epilepsy to investigate the association between migraine-like PIH and seizure type. Subjects comprised 364 patients with partial epilepsy. Epilepsy types were temporal lobe epilepsy (TLE, n = 177), frontal lobe epilepsy (FLE, n = 116), and occipital lobe epilepsy (OLE, n = 71). Patients participated in a structured interview pertaining to PIH as well as interictal headache and family history of migraine. Headaches were classified according to the International Headache Society criteria, which was modified for this study. Forty percent had PIH and 26% of these patients had migraine-like PIH. Migraine-like PIH occurred significantly more often in cases of TLE and OLE than in cases of FLE. In addition, the incidence of interictal migraine headache was significantly higher in patients with migraine-like PIH. These results suggest that migraine-like PIH is related to particular regions of epileptogenic focus and that susceptibility to migraine headache predisposes to migraine-like PIH.

Adolescent↗

Nuclear magnetic resonance imaging, a new approach to the investigation of refractory temporal lobe epilepsy.

Nuclear magnetic resonance is a noninvasive technique of imaging the brain using signals produced by magnetic fields and radiowaves. Sixteen patients with refractory temporal lobe epilepsy (TLE) had magnetic resonance imaging (MRI) during investigation for possible surgical management. These images plus those of 10 normal controls, were interpreted blind and the results from the TLE patients compared to the EEG and computerized tomographic (CT) scan findings. Fourteen patients compared with one normal control had one or more of the following: small temporal lobe, small mesial temporal structures, small hemisphere, and focal mesial temporal prolonged spin-spin relaxation time. These findings correlated with the electrographically determined seizure focus in 11 patients. Enlarged or asymmetrical temporal horns were seen with equal frequency in patients and controls and did not correlate with the seizure focus. CT scans were less likely to show these changes than MRI. Correlation of the MRI changes with histopathology of resected temporal lobes was poor. MRI reveals structural and possibly functional alterations which may aid in the localization of the seizure focus in the temporal lobes of patients with refractory complex partial seizures.

Adolescent↗

Scalp and limbic P3 event-related potentials in the assessment of patients with temporal lobe epilepsy.

Auditory oddball scalp and limbic P3s were recorded from 18 patients with unilateral temporal lobe epilepsy (TLE) prior to seizure surgery. Limbic P3s were unilaterally absent ipsilateral to the seizure focus and were present in the nonepileptogenic temporal lobe in all 18 cases studied. Scalp P3s, recorded from C3 and C4, on the other hand, were elicited bilaterally and there was no significant difference in amplitude or latency between the epileptogenic and nonepileptogenic sides. These data concur with studies of scalp P3 performed following surgery and suggest that the assessment of the contribution of limbic P3 to scalp P3 may be masked by volume conduction effects and other generators of P3. We conclude that the P3 recorded from central scalp sites, unlike its limbic counterpart, offers little clinical information in the presurgical assessment of patients with TLE.

Acoustic Stimulation↗

Ontogeny of feline temporal lobe epilepsy, II: Stability of spontaneous sleep epilepsy in amygdala-kindled kittens.

We previously described a model of spontaneous "sleep epilepsy" in kindled kittens with temporal lobe epilepsy (TLE). We now describe the postkindling course of this model from preadolescence to maturity and suggest pathophysiologic mechanisms. Spontaneous epilepsy, particularly generalized tonic-clonic convulsions (GTCs), developed 1h to 4 months after amygdala kindling and persisted to adulthood. At first, GTCs were detected only in sleep; later, convulsions also occurred during wakefulness. Two factors were consistently associated with the sequential onset of sleep and waking GTCs: seizure clusters and anatomic seizure localization. (1) Seizure clusters. Cats with infrequent or unclustered GTCs continued to exhibit "sleep epilepsy," defined by convulsions occurring exclusively during sleep. In contrast, cats with frequent seizure clusters developed recurrent or terminal convulsive status in conjunction with GTCs during waking and sleep. Severe seizure manifestations therefore appeared to contribute to the dissociation of convulsions from the sleep-wake cycle. (2) Anatomical seizure localization. Focal seizure origin appeared to differentiate sleep from waking GTCs. Onset during sleep was first recorded in the kindled amygdala, whereas onset during waking was initially detected outside the temporal lobe. Findings thus suggest secondary "kindling" of multifocal epilepsy. Secondary epileptogenesis is consistent with "transsynaptic" kindling effects. This phenomenon is defined in mature animals by rapid secondary site kindling (transfer) and subtle morphologic changes distal to the stimulating electrode. Transfer may be accentuated by youth, because kittens developed spontaneous seizure foci in previously unstimulated tissue. Moreover, multifocal interactions and diffuse cell loss were implicated as possible mechanisms. Collectively, the findings indicate complications with early onset TLE in kindled cats. Onset during youth can have an unfavorable prognosis, reflected by recurrent status epilepticus and multifocal epilepsy with convulsions distributed throughout the sleep-wake cycle.

Amygdala↗

Temporal lobe epilepsy in early childhood.

To explore the electroclinical features of temporal lobe epilepsy (TLE) in early childhood, we studied results of video-EEG and other tests of 14 children aged 16 months to 12 years selected by seizure-free outcome after temporal lobectomy. Four children had mesiotemporal sclerosis, 1 had cortical dysplasia, and 9 had low-grade temporal neoplasms. The children had complex partial seizures (CPS) with symptomatology similar to that of adults with TLE, including decreased responsiveness and automatisms. Automatisms tended to be simpler in the younger children, typically limited to lip smacking and fumbling hand gestures. Scalp/sphenoidal EEG showed anterior/inferior temporal interictal sharp waves and unilateral temporal seizure onset in the 4 children with mesiotemporal sclerosis and in the child with cortical dysplasia, but EEG findings in 9 children with low-grade temporal tumors were complex, including multifocal interictal sharp waves or poorly localized or falsely lateralized EEG seizure onset. In children without tumors, video-EEG was critical to localization of the epileptogenic zone for resection, but in patients with tumors video-EEG was less localizing and its main value was to confirm that the reported behaviors were epileptic seizures with semiology typical of temporal lobe onset.

Age Factors↗

Ictal 99mTc-HMPAO single photon emission computed tomography in children with temporal lobe epilepsy.

Seventeen ictal 99mTc-HMPAO single photon emission computed tomography (SPECT) studies were performed in 15 children with temporal lobe epilepsy (TLE) aged 7-14 years (mean 10.3 years). Ictal SPECT was informative in 16 of 17 (94%) studies in 14 of 15 (93%) children, showing unilateral temporal lobe hyperperfusion. In all 16 informative ictal SPECT studies, lateralization was concordant with ictal EEG, magnetic resonance imaging (MRI), and pathology. In 4 children, ictal SPECT provided additional localizing information that was not apparent from concurrent ictal EEG recording. Blinded interpretation of ictal SPECT studies by two independent investigators showed correct lateralization of the epileptic focus in every child. Results of visual analysis of ictal SPECT images were corroborated by quantitative analysis. Although interictal SPECT studies showed a degree of temporal lobe hypoperfusion in all children, in 9 of 15 hypoperfusion was either minimal, bilateral, contralateral, or associated with extratemporal hypoperfusion. In children with TLE, ictal SPECT provides reliable lateralizing information to corroborate or supplement that obtained from surface EEG and MRI.

Adolescent↗

Electrophysiology of bimanual-bipedal automatisms.

To determine the localizing value and electrophysiology of bimanual-bipedal automatisms (BBAs), we studied these behaviors in 54 seizures of 8 patients with temporal or frontal lobe seizure onset. BBAs occurred with a frequency of 27% in frontal lobe epilepsy (FLE) and of 7% in temporal lobe epilepsy (TLE). The distribution of electrode sites showing ictal activity during these automatisms was significantly different in the two patient groups (0.0001 Chi-square). Mesio- and/or laterotemporal plus orbital frontal areas were involved areas when the behaviors appeared in patients with TLE; dorsolateral and mesiofrontal regions were the most commonly involved when the behaviors occurred during the course of frontal lobe seizures. We concluded that BBAs represent activation of frontal lobe circuitry but are not unique to seizures of frontal lobe origin. Eyelid flutter and repetitive body movements in either the axial or sagittal plane were significantly associated with the frontal lobe group whereas oral-alimentary automatisms were associated with the temporal lobe group. Thus, these associated behaviors may help indicate whether a frontal or temporal lobe seizure onset has occurred when BBAs are observed. A new concept of ictal expression is proposed to conform with the results as well as with other apparently disparate ictal behaviors that may have localizing value.

Adult↗

Temporal and spatial characteristics of intracerebral seizure propagation: predictive value in surgery for temporal lobe epilepsy.

We examined the prognostic value of spatial and temporal characteristics of intracerebral propagation of seizures during temporal lobe epilepsy (TLE) surgery. Seven TLE patients resistant to standard anterotemporal lobectomy who had no known causes of resistance [e.g., extratemporal (ET), lesions, multifocal epilepsy] were matched with 7 seizure-free patients and 7 others who were almost seizure-free after operation. Intracerebral ictal propagation pathways were not different in the three groups. Propagation was multidirectional, most frequently to the frontal lobes and sometimes to the contralateral temporal lobe (CTL). ET propagation delays were significantly shorter in resistant patients than in markedly improved patients. The resistant group also had more frequent propagation delays < 1.0 s, but propagation times > 1.0 s were equally likely in all groups. The extent of ET propagation and frequency of focal onsets were not different among the groups. Results suggest that very short propagation times predict reduced efficacy of operation, and that long propagation times are not related to surgical success.

Electroencephalography↗

Focal intermittent delta activity in patients with mesiotemporal atrophy: a reliable marker of the epileptogenic focus.

We attempted to determine the significance of background abnormalities and their relation with spikes and location of atrophy in 56 patients with temporal lobe epilepsy (TLE) and mesiotemporal atrophy (MTA) assessed by volumetric magnetic resonance imaging (MRI): 35 patients had unilateral (group I) and 21 had bilateral atrophy with lateralized predominance (group II). Trains of delta waves over temporal regions were observed in > or = 90% of patients. They lateralized with accuracy equal to that of the spikes to the site of atrophy (delta 92% or 29 of 32 patients in group I and 63% or 12 of 19 of group II; spikes 85% or 28 of 33 of group I and 65% or 13 of 20 of group II). Delta waves and spikes occurred together in > 85% of cases. With respect to their location, a striking concordance was observed: delta activity almost always occurred ipsilateral with unilateral spiking (90% or 19 of 21 of patients with unilateral and 88% or 7 of 8 of patients with bilateral atrophy) and bilaterally independently with bilateral spiking (67% or 6 of 9 of patients in group I and 100% or 10 of 10 in group II). Furthermore, spiking and delta activity were never in disagreement with respect to lateralization. In TLE related to MTA, delta transients are a reliable indicator of the epileptogenic focus and presumably reflect the epileptogenic process rather than the underlying structural pathology.

Adolescent↗

Learned helplessness, attributional style, and depression in epilepsy. Bozeman Epilepsy Surgery Consortium.

PURPOSE: We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy. METHODS: Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale. RESULTS: Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance]. CONCLUSIONS: The results indicate that the concept of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.

Adult↗

Lateralizing value and semiology of ictal limb posturing and version in temporal lobe and extratemporal epilepsy.

PURPOSE: Unilateral dystonic limb posturing in partial seizures has been shown to be an accurate lateralizing sign indicating seizure onset in the contralateral hemisphere. However, its clinical utility may be reduced by confusion with other lateralized ictal motor phenomena. In this study, the ictal phenomena of dystonic limb posturing, tonic limb posturing, unilateral immobile limb, and version were distinguished and examined in patients with temporal and extratemporal seizures. METHODS: Partial seizures in 54 patients, successfully treated by surgery (34 temporal, 20 extratemporal; 14 frontal, 3 parietal, and 3 occipital), were analyzed blindly by 3 reviewers. Interobserver agreement was tested with kappa indexes and positive predictive value (PPV) was determined for each sign. RESULTS: In patients with temporal lobe epilepsy (TLE), dystonic posturing occurred in 35.3% (kappa 0.78, positive predictive value (PPV) for the sign being contralateral to seizure onset 92%); tonic limb posturing occurred in 17.7% (kappa 0.36, PPV 40%); unilateral immobile limb occurred in 11.8% (kappa 0.23, PPV 100%); and version occurred in 35.3% (kappa 0.77, PPV 100%). In patients with extratemporal epilepsy, dystonic posturing occurred in 20.0% (kappa 0.31, PPV 100%); tonic limb posturing occurred in 15.0% (kappa 0.08, PPV 67%); and version occurred in 40.0% (kappa 0.54, PPV 100%). The higher kappa indexes were significant for dystonic posturing (p < 0.001) and tonic limb posturing (p = 0.032) in TLE. Dystonic posturing (p = 0.034), tonic posturing (p = 0.07), and version (p = 0.0038) occurred earlier in extratemporal seizures than in temporal seizures. CONCLUSIONS: Of the limb ictal motor phenomena, only dystonic posturing was accurate and had good interobserver agreement.

Adolescent↗

Continuous source imaging of scalp ictal rhythms in temporal lobe epilepsy.

PURPOSE: We wished to determine whether continuous EEG source imaging can predict the location of seizure onset with sublobar accuracy in temporal lobe epilepsy (TLE). METHODS: We retrospectively analyzed the earliest scalp ictal rhythms, recorded with 23- to 27-channel EEG, in 40 patients with intractable TLE. A continuous source analysis technique with multiple fixed dipoles (Focus 1.1) decomposed the EEG into source components representing the activity of major cortical sublobar surfaces. For the temporal lobe, these were basal, anterior tip, anterolateral, and posterolateral cortex. Ictal EEG onset was categorized according to its most prominent and leading source component. All patients underwent intracranial EEG studies before epilepsy surgery, and all had a successful surgical outcome (follow-up >1 year). RESULTS: Most patients with ictal rhythms having a predominant basal source component had hippocampal-onset seizures, whereas those with seizures with prominent lateral source activity had predominantly temporal neocortical seizure origins. Seizures with a prominent anterior temporal tip source component mostly had onset in entorhinal cortex. Seizures in some patients had several equally large and nearly synchronous source components. These seizures, which could be modeled equally well by a single oblique dipole, had onset predominantly in either entorhinal or lateral temporal cortex. CONCLUSIONS: Multiple fixed dipole analysis of scalp EEG can provide information about the origin of temporal lobe seizures that is useful in presurgical planning. In particular, it can reliably distinguish seizures of mesial temporal origin from those of lateral temporal origin.

Electrodes, Implanted↗

Abnormal cortical activation during planning of voluntary movement in patients with epilepsy with focal motor seizures: event-related desynchronization study of electroencephalographic mu rhythm.

PURPOSE: The spatiotemporal distribution of EEG mu rhythm desynchronization was analyzed in patients with partial epilepsy to determine whether frequent focal motor seizures could induce a change of cortical activation during the planning of a voluntary movement. METHODS: The event-related desynchronization (ERD) of the mu rhythm was quantified during a self-paced voluntary movement of the thumb. The results were compared between two groups of patients with epilepsy: in one group (n = 12), the patients had frontal lobe epilepsy with frequent focal motor seizures (FMS); in the second group (n = 12), they had temporal lobe epilepsy (TLE) with complex partial seizures but no ictal movement disorder. The results were also compared with those of control subjects of same age (n = 10). RESULTS: In the control group, desynchronization of mu rhythm began over the contralateral central region 2,000 ms before the movement onset. In the FMS group, the desynchronization of mu rhythm was delayed, appearing only 500 ms before the movement onset, and the amplitude of ERD was increased over the frontocentral region. In the TLE group, the spatiotemporal pattern of ERD was the same as in normal subjects, but the amplitude of ERD was increased. CONCLUSIONS: These results indicate that there is a change of reactivity of mu rhythm in patients with partial epilepsy. The change in spatiotemporal pattern of ERD in patients with frequent focal motor seizures suggests that there is an abnormal cortical activation during the planning of a voluntary movement.

Adult↗

Antiepileptic effects of tiagabine, a selective GABA uptake inhibitor, in the rat kindling model of temporal lobe epilepsy.

PURPOSE: We determined the antiepileptic profile of tiagabine (TGB), a selective gamma-aminobutyric acid (GABA) uptake inhibitor, in the rat kindling model of temporal lobe epilepsy (TLE). METHODS: The anticonvulsant and adverse effects of TGB were examined in amygdala- or hippocampal-kindled rats and compared with those of other GABA uptake inhibitors (SKF89976A and NNC-711) and conventional antiepileptic drugs [AEDs: valproate (VPA) and carbamazepine (CBZ)]. In addition, the antiepileptogenic effects of TGB on amygdala kindling development were examined. RESULTS: TGB (2.5-40 mg/kg intraperitoneally, i.p.) had potent and dose-dependent anticonvulsant effects on both amygdala- and hippocampal-kindled seizures. The order of anticonvulsant potency of the three GABA uptake inhibitors tested was: NNC-711 > TGB > SKF-89976A and paralleled the in vitro GABA uptake efficacy. In addition, daily treatment with TGB 10 mg/kg for 10 days significantly retarded kindling development. Although adverse effects of TGB on motor systems were significantly less than those of VPA and CBZ, high toxic doses of TGB often caused EEG paroxysm and myoclonus. CONCLUSIONS: Our results indicate the clinical usefulness of TGB for treatment of drug-resistant TLE.

Amygdala↗