The lateralizing value of ictal clinical symptoms in uniregional temporal lobe epilepsy

Since 1984, the Cancer and Leukemia Group B (CALGB) has focused its clinical research in stage IV non-small cell lung cancer (NSCLC) on investigations of new agents and combinations. Currently, efforts are aimed at identifying non-cisplatin-based combinations with an increased therapeutic index. In stage III disease multimodality therapies have been pursued. Dillman et al. reported a study comparing standard radiotherapy versus induction chemotherapy followed by radiotherapy in patients with unresectable stage III NSCLC. The chemotherapy-treated patients were found to benefit with a 4-month increase in median survival time compared with patients receiving radiotherapy alone (13.8 vs. 9.7 months) and an increased 3-year survival rate of 23% versus 11%. This was the first randomized cooperative group study demonstrating a survival advantage resulting from the use of induction chemotherapy in locoregionally advanced NSCLC. In a subsequent study, the administration of additional "posterior" chemotherapy was not found to be feasible because of early disease progression and toxicity, while the administration of induction chemotherapy followed by concomitant chemoradiotherapy was feasible; therefore, the latter approach was studied further in a randomized phase III setting. This study compared a standard of two cycles of cisplatin and vinblastine followed by radiotherapy with an experimental arm of cisplatin and vinblastine followed by radiotherapy and concomitant carboplatin. Accrual to this study has been completed and results are expected in the near future. In resectable stage III disease, studies have focused on the optimal sequencing of multimodality therapy. A randomized study comparing standard regional therapy with radiotherapy and surgery versus a previously piloted approach combining chemotherapy, surgery, and radiotherapy was closed prematurely due to poor accrual. The next generation of studies in stage III NSCLC will focus on the integration of new chemotherapy agents into the treatment armamentarium for NSCLC. A randomized phase II study investigating paclitaxel, gemcitabine, and vinorelbine in combination with cisplatin in the induction setting and as concomitant chemoradiotherapy has recently been activated.     

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.     

Frontopolar ictal epileptiform discharges on scalp electroencephalogram in temporal lobe epilepsy

OBJECTIVE: To determine the prevalence of the smoking habit among Mexican physicians as well as some of their attitudes and information on specific issues concerning smoking. MATERIAL AND METHODS: In 1993, a survey was carried out among 3,568 physicians of the three major official health care institutions in Mexico City. A questionnaire designed for The Mexican National Survey of Addictions (ENA 1993) was used. Prevalence of cigarette smoking, age of onset, number of cigarettes per day; also information and attitudes concerning smoking were assessed. RESULTS: The mean age was 37, 66% were males. Of the 3,488 (98%) surveyed, 26.9% were smokers (62% daily), 20.6% were ex-smokers and 52.5% non-smokers. There were differences related to age and sex (p < 0.05). Of daily smokers, 36% smoked between 1 and 5 cigarettes. There was a significant trend among ex-smokers that linked the time they had ceased smoking with the fear to start smoking again. Physicians were well informed of the relationship between cigarette smoking and lung cancer. Over 80% considered tobacco an addictive drug but only 65% were in favor of banning smoking from their workplaces and over 10% were not aware that it is forbidden to smoke inside health care facilities. CONCLUSIONS: These results differ from other studies that find the prevalence of smoking among physicians lower than in the general population. Our study revealed a greater prevalence of the smoking habit among female physicians and the number of cigarettes smoked per day was greater than in the general population regardless of sex.     

Intracranial ictal recordings in Mesial frontal lobe epilepsy

Localization of ictal onset in patients with medically refractory frontal lobe epilepsy is challenging even with intracranial monitoring. We present a series of nine patients with presumed mesial frontal lobe epilepsy in whom successful localization of ictal onset was achieved in most cases. Intracranial electrodes were placed over cingulate and supplementary motor cortex bilaterally, with additional electrodes placed over lateral and inferior frontal lobes as part of an evaluation for epilepsy surgery. Localization of the ictal onset was clearly defined in seven of nine patients and was characterized by a pattern of lower amplitude beta/gamma range frequencies noted in one to four adjacent electrodes arising from cingulate cortex or supplementary motor cortex in six patients. In the remaining patient, ictal onset was characterized by periodic high amplitude spike and slow-wave discharges evolving into a higher voltage faster rhythm. Electrographic onset occurred coincident with or preceded clinical findings. Ictal pattern also did not demonstrate a widespread propagation pattern in most of the recordings in which ictal onset was well localized. Precise localization of ictal onset within the mesial frontal lobe is possible. Rapid propagation to regions within and outside the frontal lobe does not always occur.     

Microdysgenesis in mesial temporal lobe epilepsy: a clinicopathological study

The interrelationship of mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis, and febrile convulsions still remains an enigma. Additional microscopical cortical dysplasia or microdysgenesis has been suggested as pre-existent susceptibility factor rendering the affected brain vulnerable to the development of MTLE after initial precipitating injuries such as febrile convulsions. Twenty-four MTLE cases with histopathologically definite hippocampal sclerosis were examined for clearly defined features of microdysgenesis and further signs of neocortical dysplasia. Although unequivocal signs of dysplasia were absent, 29.2% of cases showed cortical neuronal clustering, 25.0% showed perivascular clustering, and 20.8% showed increased white matter neurons. The features of microdysgenesis studied here were not linked with each other and were not related to initial precipitating injuries, positive family history, or any other clinical parameter. Their suggested fundamental role as dysplastic factor within development of hippocampal sclerosis and MTLE is not confirmed.     

Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study

OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT) abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We reviewed the MR scans and clinical histories of 50 consecutive patients with intractable TLE. Histopathology was available in 42 surgically treated cases. RESULTS: MRI demonstrated loss of the gray-white matter differentiation and decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58% of the 50 patients. This appearance was observed in 64% of the 36 patients with hippocampal sclerosis (HS) but was also seen in patients without HS. These changes were associated with temporal lobe atrophy, a higher hippocampal T2 relaxation time, and a history of febrile convulsions. Pathologic examination showed that the MRI appearances were not caused by dysplasia, degenerative abnormalities, or inflammatory change. Histologic quantitation showed increased glial cell nuclei counts in the intractable TLE cases compared with controls. There was no difference in glial cell numbers between cases with AT abnormality and those without this appearance. Presence or absence of changes was not predictive of preoperative neuropsychology, postoperative change in neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific increase in water content in the temporal lobe. This may be due to myelin abnormalities or some other as yet unidentified pathologic factor.     

Outcome after temporal lobectomy in bilateral temporal lobe epilepsy

We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.     

Stereotaxic surgery of temporal lobe epilepsy

Forty patients with temporal epilepsy were operated on with a stereotaxic technique. Eleven patients had a unilateral localization of the epileptic focus, and in 29 bitemporal foci were diagnosed. In evaluating the results of the treatment the dynamics of the epileptic fits, the peculiarities of changes in the mental status, and the degree of social adaptation were taken into consideration. A postoperative improvement was achieved in 73% of the patients with monotemporal lesions, while in those with bitemporal epilepsy and distinct persistent mental disorders the state was improved in 44% of the cases. Indications for the choice of the zone of destruction depending on the clinical peculiarities of the lesion are presented.     

Relationship between anatomic lesions of the temporal lobe and temporal lobe epilepsy

A structural lesion of the brain is a frequent finding in intractable partial epileptic patients. We analyse anatomo-electro-clinical characteristics of 58 patients in which MR showed a lesion inside the temporal lobe. They are 29 males and 29 females with a mean age at surgery of 23.5 +/- 10.7 years (2.6-45.9). The mean epilepsy duration is of 13.4 +/- 8 years (1.3-35.5), with a mean seizure frequency of 28.7 +/- 43.6 per month, with a great inter-individual variability (from 3 per month to 15 a day). The minimum follow-up is 3.5 years. A video-EEG monitoring was performed in 21 cases, while a stereo-EEG investigation was judged mandatory in 26. On the basis of anatomo-electro-clinical correlations and of the results of presurgical investigations, the epileptogenic area was proved to be temporal in 49 cases, temporal but controlateral to the lesion in 1, and at least bilobar in 8 patients.     

Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor outcome after temporal lobe resection

We describe 5 women and 5 men with periventricular nodular heterotopia and electroclinical features suggestive of temporal lobe epilepsy, who were surgically treated for control of medically refractory seizures. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of the 10 patients. Because of the lack of clear localization, 6 patients were studied with intracranial depth electrode recordings. Seizures were of hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients followed for more than 12 months postoperatively were seizure free. Two patients were initially seizure free for approximately 18 months, but then seizures recurred. One patient had a major reduction in seizure frequency at a 39-month follow-up after most of the unilateral heterotopic tissue was included in the temporal resection. Temporal resection did not lead to a long-term favorable outcome in this group of patients with periventricular nodular heterotopia and epileptogenic discharges involving the temporal lobe. This suggests a more widespread disorder with epileptogenic activity possibly originating in or near the heterotopic tissue. The clinical and electrographic features of periventricular nodular heterotopia pointing to temporal lobe origin are misleading and temporal resection does not result in long-term cessation of seizures.     

Familial temporal lobe epilepsy: a clinically heterogeneous syndrome

We describe the clinical characteristics of a group of patients with familial temporal lobe epilepsy (TLE) in 11 kindreds with 36 affected individuals identified and investigated at the Montreal Neurological Hospital. Seizure types were simple partial (n = 20), complex partial (n = 29), and rare generalized tonic-clonic. Simple and complex partial seizures were infrequent or well controlled by anticonvulsant medication in 17 of 29 patients (59%) and without optimal response to medical therapy in 12 of 29 patients (41%). Pedigree analysis suggested autosomal dominant inheritance with incomplete penetrance. The syndrome of familial TLE has heterogeneous clinical manifestations and is not always benign.     

Dynamics of the paroxysmal syndrome in temporal lobe epilepsy

Results of studying the time course of the paroxysmal syndrome based on long-term follow-up of 151 patients with temporal epilepsy are presented. Some regularities of the syndrome course are determined, a rather high degree of the variability of its manifestations over the period of the disease is established, a relative constancy of the aura, transformations of which were noted only in half of the observations, is shown. It is noted that the paroxysmal syndrome is the most developed within a period of 5 to 15 years after the disease onset. Results of conservative therapy are evaluated.     

Quantitative analysis of interictal behavior in temporal lobe epilepsy

Patients with unilateral temporal epileptic foci were contrasted with normal subjects and patients with neuromuscular disorders in the evaluation of specific psychosocial aspects of behavior. Eighteen traits were assessed in equivalent questionnaires completed by both subjects and observers. The epileptic patients self-reported a distinctive profile of humorless sobriety, dependence, and obsessionalism; raters discriminated temporal lobe epileptics on the basis of circumstantiality, philosophical interests, and anger. The right temporal epileptic displayed emotional tendencies in contrast to ideational traits of left temporal epileptic. Right temporal epileptics exhibited "denial," while left temporal epileptics demonstrated a "catastrophic" overemphasis of dissocial behavior. The results support the hypotheses that sensory-affective associations are established within the temporal lobes, and that, in man, there exists a hemispheric asymmetry in the expression of affect.     

Functional MRI lateralization of memory in temporal lobe epilepsy

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.     

Up-regulation of neuropeptide Y-Y2 receptors in an animal model of temporal lobe epilepsy

OBJECTIVE: To clarify the incidence and background of clinical relapse (escape phenomenon) during low-dose methotrexate therapy for rheumatoid arthritis. METHODS: Seventy one patients with rheumatoid arthritis (RA) were analyzed. They were started on therapy with methotrexate (MTX) between April 1, 1991 and May 30, 1995. Among them, 60 patients showed clinical improvement within 6 months after the start of the therapy and were subjected to the analysis for clinical relapse (escape phenomenon). RESULTS: Twelve patients showed an initial improvement followed by a relapse with increased serum CRP and number of painful joints despite the MTX therapy was continued. Two types of the relapses were seen; (1) early, escape (relapse after an initial brief improvement) in 7 patients, and (2) late escape (relapse after a long-term improvement with MTX therapy) in 5 patients. The early escape was seen at 9.0 +/- 0.7 months after the start of therapy while the late escape was seen at 23.3 +/- 4.8 months. Patients with both types of escape phenomenon had the longer duration of the disease and more advanced stage. There was no relationship between clinical relapse and age, baseline RA activity, MTX dose, or concurrent use of corticosteroids and other disease modifying anti-rheumatic drugs. The efficacy of MTX for RA was restored by increasing dose of MTX in 11 patients. CONCLUSION: These results suggest that clinical relapse is not rare in RA patients during low-dose methotrexate therapy, but could be improved by increasing dose.     

Amygdala damage in experimental and human temporal lobe epilepsy

The amygdala complex is one component of the temporal lobe that may be damaged unilaterally or bilaterally in children and adults with temporal lobe epilepsy (TLE) or following status epilepticus. Most MR (magnetic resonance) imaging studies of epileptic patients have shown that volume reduction of the amygdala ranges from 10-30%. In the human amygdala, neuronal loss and gliosis have been reported in the lateral and basal nuclei. Studies in rats have more specifically identified the amygdaloid regions that are sensitive to status epilepticus-induced neuronal damage. These areas include the medial division of the lateral nucleus, the parvicellular division of the basal nucleus, the accessory basal nucleus, the posterior cortical nucleus, and portions of the anterior cortical and medial nuclei. Otherwise, other amygdala nuclei, such as the magnocellular and intermediate divisions of the basal nucleus and the central nucleus, remain relatively well preserved. Amygdala kindling studies in rats have shown that the density of a subpopulation of GABAergic inhibitory neurons that also contain somatostatin may be reduced even after a low number of generalized seizures. While analyses of histological sections and MR images indicate that in approximately 10% of TLE patients, seizure-induced damage is isolated to the amygdala, more often amygdala damage is combined with damage to the hippocampus and/or other brain areas. Moreover, recent data from rodents and nonhuman primates suggest that structural and functional alterations caused by seizure activity originating in the amygdala are not limited to the amygdala itself, but may also affect other temporal lobe structures. The information gathered so far on damage to the amygdala in epilepsy or after status epilepticus suggests that local alterations in inhibitory circuitries may contribute to a lowered seizure threshold and greater excitability within the amygdala. Furthermore, damage to select nuclei in the amygdala may predict impairment of performance in behavioral tasks that depend on the integrity of the amygdaloid circuits.     

Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Sex differences in patients with mesial temporal lobe epilepsy

Possible sex differences in the pattern of interictal hypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobe hypometabolism ipsilateral to the seizure onset (p<0.0001) and a spread of epileptiform activity to this region (p=0.001). By contrast, female patients more often exhibited hypometabolism (p=0.0052) and an ictal spread to the contralateral temporal lobe (p=0.0097). These findings suggest sex differences in spatial distribution of brain dysfunction in MTLE, perhaps reflecting sexual dimorphism in regional cerebral connectivity.