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Rapid stereological quantitation of temporal neocortex in TLE.

To determine the extent of neocortical atrophy in the temporal lobe using rapid stereological analysis of magnetic resonance slices in patients with temporal lobe epilepsy and to compare the findings to those obtained by visual analysis of high-resolution magnetic resonance images. 25 patients with temporal lobe epilepsy, along with 25 age-matched controls were scanned using a 1.5 Tesla magnetic resonance imaging machine (GE signa systems Paris). Visual analysis was performed on standard high-resolution images. Volumetric analysis of hippocampus and temporal neocortex was performed using computer-aided stereology (MEASURE program, Patrick Barta, Johns Hopkins, Baltimore, USA). Stereological volumetric analysis demonstrated isolated hippocampal atrophy in only nine (36%) cases including three (12%) with bilateral disease. However, eight (32%) cases had combined hippocampal and neocortical atrophy and three (12%) had isolated neocortical atrophy. All volumetric measurements took less than 10 min. On the other hand, visual analysis suggested that 17 (68%) had hippocampal atrophy alone with only two (8%) having combined neocortical atrophy and a further two (8%) having isolated neocortical atrophy. Nearly half of the patients had temporal neocortical atrophy with or without hippocampal atrophy. This rapid, accurate and non-biased quantitative technique has wide clinical utility and is significantly more valuable in detecting neocortical atrophy than visual analysis alone. The results support the notion that abnormalities may be overlooked by current standards of routine magnetic resonance imaging.

Adult↗

Chronic low-dose corticosterone supplementation enhances acquired epileptogenesis in the rat amygdala kindling model of TLE.

Mesial temporal lobe epilepsy (MTLE) is associated with high rates of depression and anxiety. A bidirectional causal relationship has been suggested, with these psychiatric comorbidities themselves enhancing epileptogenesis, possibly via hypercortisolemia. We examined the effects on epileptogenesis of chronic supplementation with low-dose corticosterone (CS) in the electrical amygdala kindling rat model. Adult Wistar rats were ovariectomized and implanted with bipolar electrodes into the left amygdala. After 1 week recovery, one group (n=7) had CS (3 mg/100 ml--approx. 4.5 mg/kg/day) and a control group saline (n=7) added to their drinking water, and both groups underwent twice daily electrical stimulations. Rats were culled 2 weeks after reaching the fully kindled state. A stereological optical fractionator technique was used to estimate the number of CA1 pyramidal cells in the hippocampus ipsilateral to the stimulations. Fewer stimulations were required in the CS-supplemented rats than in controls to reach the fully kindled state (32 vs 81, p<0.03, Student's t-test) and the first Class V seizure (14 vs 57, p<0.05). The mean after-discharge length was greater in the CS group (p=0.03, repeated measures analysis of variance). There was no difference in the mean number of CA1 neurons (1.05 x 10(5) vs 1.04 x 10(5), p=0.98). These data demonstrate that low-dose CS enhances epileptogenesis in this model of MTLE. This provides support for the hypothesis that chronic hypercortisolemia, as a result of stress, anxiety, and/or depression, may facilitate the development and progression of epilepsy in patients with MTLE. The lack of difference in hippocampal CA1 neurons indicates that the mechanism does not primarily involve pyramidal cell loss.

Amygdala↗

The lateralizing and surgical prognostic value of a single 2-hour EEG in mesial TLE.

We investigated 109 patients who received anterior temporal lobectomy for intractable mTLE by post-operative follow-up for at least 11/2 years. We reviewed pre-operative 2-hour interictal EEGs, counted interictal epileptiform discharges (IEDs), and compared the lateralization of IEDs with the side of surgery and surgical outcome. Twenty of 22 patients who had no spikes and 44 of 51 who had unitemporal spikes became seizure free after surgical resection. The correct lateralization of the epileptogenic side was possible in 90. 9% of the patients with unitemporal IEDs. In 12 seizure-free patients of 15 patients with less than 70% predominance of IED in one temporal lobe, the positive predictive value of the lateralization was 41.7%. In 16 seizure-free patients of 21 with more than 70% preponderance of IED in one lobe, the positive predictive value was 81.3%. Surgical outcome of patients with unitemporal and bitemporal IEDs were not significantly different. Interictal scalp EEG can be used as a lateralizing tool in mTLE when the temporal IEDs appear with more than 70% preponderance in one side. Although the presence of bitemporal IEDs often causes confusion in terms of the correct lateralization, it does not affect the surgical outcome.

Adult↗

Asymmetric ending of secondarily generalized seizures: a lateralizing sign in TLE.

The authors investigated whether asymmetric ending of the clonic phase of secondarily generalized tonic clonic seizures (SGTCS) has lateralizing value concerning the hemisphere of seizure onset. They studied 70 patients with mesial temporal lobe epilepsy who underwent epilepsy surgery. Asymmetric ending of the clonic phase occurred in 43% of patients. The last clonic movement appeared on the upper extremity ipsilateral to the hemisphere of seizure onset in 83%.

Chi-Square Distribution↗

TLE patients with postictal psychosis: mesial dysplasia and anterior hippocampal preservation.

The authors studied six patients with refractory temporal lobe epilepsy and postictal psychosis using quantitative MRI and histopathology, and compared the results with 45 patients with temporal lobe epilepsy without postictal psychosis. Total hippocampal volumes were not different between the two groups. However, patients with postictal psychosis had a relatively preserved anterior hippocampus, and temporal lobe dysplasia was more frequent (p = 0.006, chi-square test). These findings may be associated with the clinical symptoms.

Adult↗

[Infectious conjunctivitis. The tear leukocyte esterase reaction (TLE) as a diagnostic aid].

Lacrimal fluid is absorbed on a cottonwool swab. This swab is pressed on the test field for leukocyte esterase on the stix. The colour change is read after exactly one minute. The sensitivity of the test is 90% and the specificity is 98% as assessed on 94 cases of infectious conjunctivitis and 439 normal individuals. The test is suitable for assessing cases of conjunctivitis in view of antibiotic therapy, control of contact lenses etc.

Conjunctivitis, Bacterial↗

Differential features of metabolic abnormalities between medial and lateral temporal lobe epilepsy: quantitative analysis of (18)F-FDG PET using SPM.

UNLABELLED: Because limited resection could yield an equally good surgical outcome as standard anterior resection in temporal lobe epilepsy (TLE), the differentiation of medial from lateral TLE is important. We tried to find the differential features in metabolic abnormalities between medial and lateral TLE groups using quantitative analysis including statistical parametric mapping (SPM). METHODS: We examined 113 (18)F-FDG PET scans of TLE patients who had surgically and pathologically proven lesions and a good surgical outcome (78 medial TLE, 35 lateral TLE). Each scan was compared with those of 22 healthy control subjects to detect hypometabolic regions using a t test of the SPM method and interhemispheric asymmetry using 2-group, 2-condition analysis on SPM. Group analysis was performed between medial and lateral TLE using mirrored PET images. The sensitivity was defined as the detection rate of hypometabolism in the ipsilateral temporal lobes, and the specificity was defined as the nondetection rate in the contralateral lobes. The extent of the hypometabolism was calculated as the number of significant voxels, and the severity was calculated by the asymmetry index (ASI), in the medial or lateral temporal lobes on Statistical Probabilistic Anatomical Map template images. RESULTS: The hypometabolism in the temporal lobes was detected ipsilateral to the seizure focus in 76% of the TLE patients (76% in medial TLE, 77% in lateral TLE) but on the contralateral temporal lobes in 32% of the patients. After considering interhemispheric temporal asymmetry, the sensitivity was found to be 89%, and the specificity was 91% without differences between the medial and lateral TLE groups. In both medial and the lateral TLE, the hypometabolism was more prominent in the lateral cortical structures than in the medial structures. The hypometabolism in the medial temporal structures was found less frequently in the lateral TLE group, and the extent of the hypometabolism was significantly larger in the medial TLE group. ASIs of the medial temporal structure and superior temporal gyrus of lateral temporal structure were significantly higher in the medial TLE. CONCLUSION: SPM analysis of (18)F-FDG PET in TLE patients could localize accurately the seizure focus and helped in the discrimination of the medial TLE from the lateral TLE. We suggest the lateral TLE, rather than the medial TLE, should be considered when glucose metabolism is relatively preserved in the medial temporal structures.

Adult↗

Hippocampal alterations in children with temporal lobe epilepsy with or without a history of febrile convulsions: evaluations with MR volumetry and proton MR spectroscopy.

BACKGROUND AND PURPOSE: The causal effect of early febrile convulsions (FC) on later-onset temporal lobe epilepsy (TLE) remains unclear. In this study, we sought to examine the hippocampal alterations in epileptic children with or without FC history by using MR spectroscopy and volumetry. METHODS: Fifty-five children ranging in age from 18 months to 15 years were enrolled in this study. Subjects were divided into three groups: the control group without either TLE or history of FC (n = 16), the TLE group with early history of FC (TLE + FC; n = 22), and the TLE group without FC history (n = 17). Measurement of hippocampal volume (HV) was performed on thin section T1-weighted images acquired with a 3D gradient echo MR image and normalized by the intracranial volume. Each individual subject had two measures of lateralization; one gives the smaller side of HV and the other the contralateral larger side of HV, assuming that the side with smaller HV is the possible primary site of seizure focus and the contralateral larger HV the secondary or normal site. Single-voxel proton MR spectroscopy of the hippocampi was performed, with metabolic ratio n-acetylaspartate (NAA)/choline (Cho) + creatine plus phosphocreatine (Cr) calculated and grouped separately as were with volumetry. RESULTS: The overall mean HV for the control group was 2.61 +/- 0.21 cm(3) at an average intracranial volume of 965 +/- 241 cm(3), and the asymmetry index for hippocampal volume was (2.32 +/- 1.58)%. The overall mean HV was 2.30 +/- 0.33 cm(3) for TLE + FC group and 2.34 +/- 0.33 cm(3) for TLE group. Mean HV differed significantly for the three groups (P < .01). When the small and large sides were analyzed separately, significant differences were found between control and TLE as well as between control and TLE + FC for the smaller side (P < .05), whereas for the larger side significant differences were found only between control and TLE + FC. In MR spectroscopic measurements, the mean NAA/(Cr + Cho) of bilateral hippocampi was 0.77 +/- 0.06 for control group, 0.62 +/- 0.12 for TLE + FC group, and 0.66 +/- 0.11 for TLE group. In terms of statistically significant difference between groups, spectroscopic results were similar to volumetric measurements, except that there was no significant interaction effect between groups and measures of asymmetrical indices (P = .272). CONCLUSION: Children with TLE and early history of FC tend to have lower hippocampal volumes and NAA/(Cr + Cho) ratios than do TLE children without FC history. The TLE + FC group seems to have increased vulnerability of the contralateral hippocampus as compared with TLE group. MR volumetry and spectroscopy are equally capable of showing the trends of hippocampal alternations in children with TLE with or without FC history.

Adolescent↗

Hippocampal formation involvement in a language-activation task in patients with mesial temporal lobe epilepsy.

PURPOSE: The study aims to explore the contribution of the hippocampal formation to the retained language-comprehension network in patients with unilateral mesial temporal lobe epilepsy (TLE). METHODS: We performed a functional magnetic resonance (MRI) study based on a language comprehension paradigm in 45 right-handed patients with unilateral mesial TLE and 35 healthy control subjects. Activations in the hippocampal formations in both hemispheres were analyzed for each subject as well as for groups of left TLE, right TLE, and controls. RESULTS: In sum, 82% of TLE patients displayed hippocampal activations. A significant difference in hippocampal activation between left and right TLE was found: Right TLE patients showed increased activity in the left hippocampal formation compared with left TLE patients. In contrast, patients with left TLE did not show increased activity in the right hippocampal formation compared with right TLE patients. In comparison with a healthy control group, right TLE patients activated the left hippocampal formation to a greater extent, whereas patients with left TLE did not activate the right hippocampal formation to a greater degree. These findings point to an increased involvement of the left hippocampal formation during a language-comprehension task in right TLE patients. In contrast, left TLE in right-handed patients seems not associated with an enhanced involvement of the right hippocampal formation in retained language comprehension. CONCLUSIONS: These findings suggest that effective language comprehension in right-handed subjects with TLE depends on the involvement of the left hippocampal formation and underline the risks of postoperative language decline in patients with left TLE.

Adolescent↗

Neuronal dysfunction in children with newly diagnosed temporal lobe epilepsy.

We sought to determine whether neuronal dysfunction throughout the temporal lobes of children with temporal lobe epilepsy (TLE) is already as severe at the time of diagnosis as it is in patients with long-standing intractable TLE (INT-TLE). Proton magnetic resonance spectroscopic imaging was used to measure N-acetylaspartate/creatine (NAA/Cr) ratios in the temporal lobes of five consecutive children with newly diagnosed TLE (ND-TLE), five with INT-TLE, and 30 normal control subjects. The median age of those with ND-TLE and those with INT-TLE did not significantly differ (P = 0.92). All five patients with ND-TLE had bilateral reductions in the NAA/Cr ratio. Two of the five patients with INT-TLE had bilateral reductions in the NAA/Cr ratio; three had unilateral reductions in the NAA/Cr ratio. In the three patients with lesions the NAA/Cr ratio decrease extended outside these lesions. No significant differences were detected in any temporal lobe region between the ND-TLE and INT-TLE groups. The severity of the neuronal dysfunction in the children with ND-TLE was at least as severe as in those with INT-TLE and was not restricted to one temporal lobe, implying that the neuronal abnormalities observed in patients with TLE occur before the clinical manifestations.

Adolescent↗

Traffic law enforcement in Hyderabad, India.

The aim of the study was to understand traffic law enforcement (TLE) carried out by the police to reduce non-compliance with traffic laws on the roads of Hyderabad city in India for 2001-2003. The Traffic Police database of citations issued to drivers who violated traffic laws in Hyderabad was analysed for the years 2001-2003 to describe the TLE activities of the police, to describe and compare the TLE activities for the different types of vehicles and to compare the TLE activities for the 3 years. The violations were classified in five categories - those related to driving, parking, vehicle, document and others; and TLE into safety and other TLE. A total of 646 161 traffic-law violations were registered in 2001, 904 447 in 2002 and 964 275 in 2003 for Hyderabad. Driving and parking violations were the most common violations registered in all 3 years, with parking violations slightly higher in 2001 (43.5%) and driving violations slightly higher in 2002 (35%) and 2003 (36.4%). Auto-rickshaws (three-wheel commercial passenger vehicles) accounted for the highest violations registered in 2001 (41.4%) whereas motorized two-wheelers had the highest registered violations in 2002 (35.5%) and 2003 (33.2%). Safety TLE activity (detecting and registering driving violations) was only one-third of all the TLE activity performed by the police in the 3 years, and disobeying traffic signals was the most common violation registered under safety TLE. Indian rupees 50 (US$1.1) were collected by way of a fine in 87% of the cases registered. Age and gender of the violators were not recorded in the database. These data can be used for planning, monitoring and evaluating TLE in Hyderabad. These can help identify traffic control and human factors that could lead to traffic noncompliance, and help identify priorities for improving road safety. These data indicate a need to enhance the safety TLE activity of the police, to make TLE more visible in Hyderabad, and to assess the effectiveness of the current legal action as deterrence to improve road safety. Recommendations to enhance TLE within the given resources of the police are made. More effort is needed towards systematic collection and analysis of data on TLE in India to facilitate long-term improvements in TLE for safer roads.

Automobile Driving↗

Bilateral hippocampal atrophy: consequences to verbal memory following temporal lobectomy.

BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL. RESULTS: Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups. CONCLUSION: Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss.

Adolescent↗

Mild non-lesional temporal lobe epilepsy. A common, unrecognized disorder with onset in adulthood.

OBJECTIVE: To compare mild vs. severe non-lesional temporal lobe epilepsy (TLE). METHODS: Data from 104 consecutive patients with non-lesional TLE were reviewed. Seventy-three of the 104 fulfilled the criteria for inclusion in this study of a follow-up period longer than three years at our Institute. Patients were considered to have a mild TLE if they were seizure free for at least three years after appropriate antiepileptic medication, or had rare (< or = 2/year) complex partial or secondarily generalized seizures for at least three years with or without appropriate antiepileptic therapy. Clinical, EEG and MRI data of mild vs. severe non-lesional TLE patients were compared on the basis of a cross-sectional study design. RESULTS: Of the 73 patients with non-lesional TLE included in the study, 43 (59%) had mild TLE, and 30 (41%) had severe TLE. Duration of epilepsy was significantly shorter (mean 15.2 +/- 10.5 years vs. 26.4 +/- 13.2 years) and age at onset was significantly higher (mean 34.3 +/- 15.3 years vs. 7.8 +/- 6.8 years) in mild than in severe TLE group. Patients with mild TLE had also a significantly higher prevalence of positive family history of epilepsy (37.2% vs. 10%), and a significantly lower occurrence rate of febrile convulsions (FC) (4.7% vs. 33.3%), mesial temporal sclerosis (MTS) (6.9% vs. 36.7%), and intelligence deficiency (0% vs. 20%). In mild TLE there was also a significantly high rate (58.1 vs. 0%) of delayed diagnosis (from 1 to 28 years), because of misdiagnosis (39.5%) or no medical counseling (18.6%). CONCLUSIONS: Mild non-lesional TLE is a common, unrecognized disorder mainly characterized by both onset in adulthood and high prevalence of familial history of epilepsy. The present findings suggest that mild non-lesional TLE may represent a clinical entity different from severe non-lesional TLE.

Adolescent↗

Nocturnal temporal lobe epilepsy.

OBJECTIVE: To analyze clinical, electrophysiologic, and neuroradiologic characteristics and prognostic factors in a group of patients with temporal lobe epilepsy (TLE) and complex partial seizures (CPS) occurring exclusively or predominantly after they fall asleep or before they awaken. BACKGROUND: CPS arising during sleep are classically identified with frontal lobe epilepsy. TLE associated with seizures occurring only or predominantly during sleep (nocturnal TLE) is less common. METHODS: From a series of patients with refractory TLE studied between 1980 and 1996, the authors identified 26 patients (15 men) with nonlesional nocturnal TLE (mean age, 40 years). Clinical and laboratory characteristics of these individuals were studied and compared with a group of 72 age-matched, randomly selected patients with nonlesional TLE and predominantly diurnal seizures (diurnal TLE). RESULTS: Mean age at seizure onset was similar for both groups (16.3 versus 18.7 years). In the nocturnal TLE group, 2 of 26 patients had a positive family history of epilepsy, 18 reported an aura, 4 presented with CPS in clusters, 11 had unilateral and 15 bilateral temporal EEG abnormalities, and 14 of 21 studied had unilateral mesial temporal atrophy. None of these factors differed significantly in the two groups except for higher frequency of the following in the diurnal TLE group compared with the nocturnal TLE group: positive family history for epilepsy (33% versus 8%, p=0.01), estimated frequency of seizures (median, 14 versus 2 per month; p < 0.01), and presence of antecedent febrile convulsions (33% versus 11%, p=0.04). In the nocturnal TLE group, eight patients underwent surgical therapy and became seizure free (follow-up, > 12 months). Only two were seizure free on medication. CONCLUSIONS: Infrequent and nonclustered seizures, rare family history of epilepsy, and low prevalence of childhood febrile convulsions characterize nocturnal TLE. Within the TLEs, the nocturnal TLE form seems to have a better surgical prognosis.

Adult↗

Do recurrent seizures cause neuronal damage? A series of studies with MRI volumetry in adults with partial epilepsy.

Despite optimal treatment, 30% of epilepsy patients develop intractable epilepsy and continue to have recurrent seizures or other symptoms of epileptic syndrome restricting their ability to lead a full life. Hippocampal sclerosis is found in 60-70% of patients with intractable temporal lobe epilepsy (TLE). However, it is not known whether the damage in the hippocampus is the cause or the consequence of TLE. The purpose of the present series of studies was to investigate with magnetic resonance imaging (MRI) the appearance of medial temporal lobe damage during the course of partial epilepsy, and, particularly, to determine whether recurrent or prolonged seizures contribute to the damage. Altogether 259 partial epilepsy patients were investigated with quantitative MRI. High lifetime seizure number, complex febrile convulsions in the medical history, and early age at the onset of spontaneous seizures contributed to hippocampal damage in patients with TLE. The risk factors that predicted amygdaloid volume reduction were intracranial infection and complex febrile convulsions. Damage in the hippocampus or in the amygdala was rare at the time of first spontaneous seizures in TLE. In contrast, hippocampal damage was apparent in chronic TLE patients with years of frequent seizures. Chronic cryptogenic drug-resistant TLE patients had smaller mean hippocampal volumes ipsilateral to the seizure focus than controls. In all TLE patients, ipsilateral hippocampal volume correlated negatively with the lifetime seizure number. The mean amygdaloid volumes in chronic TLE patients did not differ from those in controls. However, about 20% of chronic patients had > or = 20% volume reduction in the amygdala. The mean volumes of the entorhinal cortex ipsilateral to the epileptic focus in cryptogenic TLE patients did not differ from those in controls. However, the entorhinal cortex was damaged in a subpopulation of TLE patients with associated hippocampal damage TLE. The findings of the present series of studies support the hypothesis that damage in the medial temporal lobe structures may be both the cause and consequence of TLE. The data provide evidence that in some patients hippocampal damage may progress as a function of repeated seizures, and argue for efficient drug therapy or early surgery to reach complete seizure control. Future research should address strategies for disease-modifying therapies and ultimately remission of the epileptic process.

Adolescent↗

Temporal hypometabolism at the onset of cryptogenic temporal lobe epilepsy.

Most patients with intractable temporal lobe epilepsy (TLE) exhibit temporal glucose hypometabolism. The reasons for the development of this abnormality are as yet unclear. The current notion is that an initial injury causes seizures, which in turn give rise to hypometabolism. The aim of this study was to assess whether temporal reductions in glucose metabolism in non-lesional TLE are the result of repeated seizures or whether hypometabolism represents an initial disturbance at the onset of disease. Glucose consumption was assessed with fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in 62 patients with cryptogenic non-refractory TLE in different stages of disease. Twelve subjects without neurological illness served as controls. Patients with onset of epilepsy at least 3 years prior to the PET scan were defined as having chronic TLE. Using this criterion, the whole patient cohort included 27 patients with de novo TLE and 35 patients with chronic TLE. The groups were matched for age and sex. The appearance of high-resolution magnetic resonance images of the brain was unremarkable in all patients. In the total cohort, number, duration and frequency of seizures had a significant relation to the magnitude of hypometabolism. Temporal hypometabolism was exhibited by 26 of the 62 patients (42%), including 8 out of 27 (30%) with newly diagnosed TLE and 18 out of 35 (51%) with chronic TLE. The disturbances were more extensive and more severe in patients with chronic TLE. It is concluded that temporal hypometabolism may already be present at the onset of TLE, but is less frequent and less severe in newly diagnosed than in chronic TLE. The metabolic disturbance correlates with the number of seizures. These findings suggest that an initial dysfunction is present in a considerable number of patients and that hypometabolism is worsened by continuing epileptic activity.

Adolescent↗