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Ammon's horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy.

Ammon's horn sclerosis (AHS) is the major neuropathological substrate in patients with temporal lobe epilepsy (TLE). Histopathological hallmarks include segmental loss of pyramidal neurons, granule cell dispersion and reactive gliosis. Pathogenetic mechanisms underlying this distinct hippocampal pathology have not yet been identified and it remains to be resolved whether AHS represents the cause or the consequence of chronic seizure activity and pharmacoresistant TLE. Whereas the clinical history indicates an early onset in most patients, ie, occurrence of febrile seizures at a young age, surgical treatment is usually carried out at an end stage of the disease. It has, therefore, been difficult to analyse the sequential development of hippocampal pathology in TLE patients. Recent molecular neuropathological studies focusing on developmental aspects of hippocampal organization revealed 2 intriguing findings in AHS specimens: i) The persistence of Cajal-Retzius cells in AHS patients points towards an early insult and an altered Reelin signaling pathway and ii) increased neurogenesis in and abnormal architectural organization of the dentate granule cell layer can be observed in young patients with early hippocampal seizure onset. These findings would be compatible with a model that involves a neurodevelopmental component in the formation of AHS. Its association with a lowered seizure threshold and an increased susceptibility for segmental cell loss in the hippocampus during the long course of the disease may constitute additional elements in a pathogenic cascade.

Amygdala↗

Material-specific memory in temporal lobe epilepsy: effects of seizure laterality and language dominance.

This study investigated the effects of seizure laterality and language dominance on material-specific memory in temporal lobe epilepsy (TLE). Left TLE (LTLE) patients with left-hemisphere language dominance (LHLD) showed significantly higher nonverbal than verbal memory capacity, whereas right TLE patients with LHLD showed significantly better verbal than nonverbal memory capacity. LTLE patients with non-left-hemisphere language dominance (NLHLD) showed significantly better verbal memory capacity compared with LTLE patients with LHLD. Thus, selective verbal or nonverbal memory deficits that are dependent on side of seizure onset were apparent in patients with LHLD but not in patients with NLHLD. Relative sparing of verbal memory capacity in LTLE patients with NLHLD may reflect interhemispheric reorganization of verbal memory function.

Adult↗

Neurotransmitters and their receptors in human temporal lobe epilepsy.

Patients with medically intractable temporal lobe epilepsy (TLE) undergo medial temporal lobectomy with hippocampectomy for one of two reasons. (1) A lesion (tumor or arteriovenous malformation) adjacent to, but not invasive of, the hippocampus, results in the removal of the lesion and adjacent hippocampus in order to ensure a tumor-free margin. This group will be referred to as tumor-related TLE (TTLE) patients. (2) The operation is performed when depth electrode recordings and other evaluative techniques point to the hippocampus as the focus of seizure initiation. This group will be referred to as cryptogenic TLE (CTLE) patients. Analysis of the hippocampi of these two groups of patients reveals that the TTLE hippocampus is quite similar to that of autopsy subjects in its chemical neuroanatomy. However, the dentate gyrus of the CTLE patients shows considerable morphological and cytochemical reorganization. This reorganization is characterized by a number of features. (1) There is a loss of granule cells which occurs either as a patchy loss and/or a thinning of the granule cell layer. (2) Remaining granule cells which contain dynorphin appear to produce recurrent collaterals into the inner molecular layer of the dentate gyrus. (3) In the subgranular region of the hilus (the polymorphic layer) there is a selective loss of interneurons immunoreactive for somatostatin, neuropeptide Y and substance P. (4) There appears to be an increase in fibers immunoreactive for somatostatin and neuropeptide Y which extend throughout the dentate molecular layer. Somatostatin fibers being less numerous than neuropeptide Y fibers (5). The distributions of a number of neurotransmitter receptors also show striking reorganization in the dentate gyrus of the CTLE hippocampus. (6) Second messenger systems protein kinase C and adenylate cyclase, and Na+, K(+)-ATPase activity, as determined by ouabain binding, is increased in the molecular layer of CTLE. This remodeling of the CTLE hippocampus may hold the key to the mechanisms of hyperexcitability of the granule cells in the hippocampus of this group, and consequently the generation of seizures. The removal of the hippocampus in CTLE patients results in good control of seizures, whereas removal of hippocampi that do not show such reorganization, in a group of patients classified as atypical CTLE patients, results in inadequate seizure control. These findings suggest a complex series of processes in converting the properly regulated granule cells into hyperexcitable ones.

Afferent Pathways↗

Diffusion tensor imaging of the hippocampal formation in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is a noninvasive technique that can be used to assess the integrity of cerebral tissue. The purpose of this study was to assess DTI measurements in the hippocampal formation (HF) and to investigate the role of DTI in lateralizing the seizure focus in temporal lobe epilepsy (TLE). METHODS: We evaluated 12 patients with unilateral TLE and 14 healthy subjects. We collected diffusion-weighted images along six different directions with a b value of 1000 s/mm(2), as well as an image acquired without diffusion weighting (b = 0 s/mm(2)). A 1.5-T imager was used to acquire 17 (3-mm) coronal sections covering the temporal lobes. We compared the mean diffusivity (trace D) and fractional anisotropy (FA) from symmetrical voxels by sampling the anterior HF bilaterally. We compared measurements with the EEG, high-resolution MR imaging, and clinical information. RESULTS: The patient group had significantly increased diffusivity and decreased FA in the HF ipsilateral to the seizure focus, as compared with values in the contralateral HF. When compared with healthy subjects, patients had significantly higher mean diffusivity in the ipsilateral HF; ipsilateral FA values were lower and did not reach statistical significance. Measurements in the contralateral HF did not show differences. Left-right and absolute diffusivity indices lateralized the abnormal HF in eight and five of 12 patients, respectively. CONCLUSION: Abnormal DTI measurements and the epileptogenic HF are associated in unilateral TLE. This finding may reflect hippocampal sclerosis and may aid in presurgical evaluation.

Adult↗

A reevaluation of sustained attention performance in temporal lobe epilepsy.

Reports of normal Continuous Performance Test (CPT) accuracy in patients with temporal lobe epilepsy (TLE) stand in contrast to a demonstration of nonspecific absolute reaction time (RT) deficits in this population. In this study, we examined CPT data from a TLE sample for potential RT deficits across three consecutive blocks of time during the vigil. Seventeen patients with medically intractable epilepsy of temporal lobe origin and 17 healthy volunteers participated. The Conners CPT was used to assess sustained attention over a 14-min vigil. There were no significant group differences in accuracy. There was, however, a significant interaction between groups and time intervals, with disproportionate RT increases for patients at the end of the vigil. These findings are consistent with a report of nonspecific RT deficits in TLE despite normal accuracy scores, and further indicate impaired RT performance over time.

Journal Article↗

Differential forgetting in patients with temporal lobe dysfunction.

Delayed recall performance was investigated in 13 patients with temporal lobe epilepsy (TLE) and 13 healthy age-matched controls who were matched on a pairwise basis for initial learning on the Selective Reminding test. TLE patients performed significantly worse on the 30-minute delayed recall condition despite equivalent initial continuous long-term retrieval scores. These data suggest that TLE patients forget at disproportionately rapid rates as compared to healthy controls despite equivalent initial learning. Consequently, delayed recall may increase group discrimination when initial learning levels are similar.

Journal Article↗

[Prognostic value of MRI and 1H MRS in patients with temporal lobe epilepsy].

OBJECTIVE: To evaluate the prognostic value of hippocampal MRI scan, MRI volumetry and 1H MRS in patients with temporal lobe epilepsy (TLE). METHODS: 50 intractable TLE patients operated in Huashan hospital were studied. Before surgery, traditional MRI scans were used to exclude tumor and vascular malformation of the brain. All patients were examined by tilted coronal images which were perpendicular to the long axis of the hippocampus, using T1-weighted, T2-weighted and FLAIR sequence. MRI volumetric measurement of both hippocampal formation were performed. 38 patients also took 1H MRS scan. Unilateral anterior temporal lobectomy was performed in all patients and pathology showed different degrees of hippocampal sclerosis. The prognosis was categorized into three grades with grade I being assigned to the group of good outcome, and grade II and III being assigned to the bad outcome group. Correlative analysis between the results of several examinations and the prognosis were performed respectively. RESULTS: MRI-positive cases with hippocampal scans were about 84% of the 50 cases. Hippocampal atrophy, increase of signal intensity or the loss of internal morphological structure were detected. 98% of the MRI-positive patients had good outcome, and 38% of the MRI-negative patients had good outcome. The prognosis between MRI-positive group and MRI-negative group had significant difference (chi(2) = 23.00, P = 0.000). Among the right-side operated cases, the average hippocampal volume on the operated side of the bad outcome group was larger than that of the good outcome group. While among the left-side operated cases, the hippocampal volume on the non-operated side of the bad outcome group was smaller than that of the good outcome group. Significant differences were found in statistics respectively. In both groups, prognosis was found to be statistically related to the DHF value (difference of bilateral hippocampal volume). The DHF value of the good outcome group was larger than that of the bad outcome group. 38 patients took 1H MRS examination. The average NAA/(Cr + Cho) ratio on the operated side of the patients in the bad outcome group was greater than that of the good outcome group. The average NAA/(Cr + Cho) ratio on the contralateral side of the patients in the bad outcome group was lower than that of the good outcome group. But no significant differences were found in statistics respectively. 90% cases of MRS unilateral abnormalities had good outcome, while 77% cases of MRS bilateral abnormalities had good outcome. But no statistically significant difference was found among different groups (chi(2) = 0.493, P = 0.781). CONCLUSION: Hippocampal MRI scan, MRI volumetry and 1H MRS may be used as prognostic tools in TLE patients before surgery. The combination of several noninvasive methods before surgery can help choose suitable patients for surgery, and, as a result, improve surgical outcome.

Adolescent↗

[A family with autosomal dominant temporal lobe epilepsy accompanied by motor and sensory neuropathy].

We report a 20-year-old man with temporal lobe epilepsy (TLE) accompanied by hereditary motor and sensory neuropathy (HMSN). He had experienced complex partial seizures (CPS), which started with a nausea-like feeling, followed by loss of consciousness and automatism, since he was 6 years old. The frequency of attacks was at first decreased by phenytoin. However, attacks increased again when he was 18 years old. On admission, neurological examination showed mild weakness of the toes, pes cavus, hammer toe and mildly impaired vibratory sensation in his legs. Ten people in four generations of his family showed a history of epilepsy in the autosomal dominant inheritance form. His younger sister and mother had a history of epilepsy accompanied with pes cavus, hammer toe, weakness of toe and finger extension and mildly impaired vibratory sensation as well. Direct sequencing of the glioma-inactivated leucine-rich gene (LGI1), in which several mutations were reported in patients with familial lateral temporal lobe epilepsy, showed no specific mutation in this family. On consecutive video-EEG monitoring, paroxysmal rhythmic activity was confirmed in his left fronto-temporal region when he showed automatism, and then a generalized slow burst activity was detected when he lost consciousness. For his seizures, TLE with secondary generalization was diagnosed. In the nerve conduction study, delayed nerve conduction, distal motor latency and decreased amplitudes of the compound muscle action potentials (CMAP) of bilateral peroneal nerves were observed, indicating the existence of mild axonal degeneration. Based on these data, we consider that this family to be a new phenotype of autosomal dominant TLE accompanied by motor and sensory neuropathy.

Adult↗

Clinical utility of 11C-flumazenil positron emission tomography in intractable temporal lobe epilepsy.

BACKGROUND: 11C-flumazenil (FMZ) positron emission tomography (PET) is a new entrant into the armamentarium for pre-surgical evaluation of patients with intractable temporal lobe epilepsy (TLE). AIMS: To analyze the clinical utility of FMZ PET to detect lesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to magnetic resonance imaging (MRI), 2-Deoxy-2 [18F] fluoro-D-glucose, (18F FDG) PET, electrophysiological findings and semiology of epilepsy in patients with intractable TLE. MATERIALS AND METHODS: Patients underwent a high resolution MRI, prolonged Video-EEG monitoring before 18F FDG and 11C FMZ PET studies. Regional cortical FMZ PET abnormalities were defined on co-registered PET images using an objective method based on definition of areas of abnormal asymmetry (asymmetry index {AI}>10%). SETTINGS AND DESIGN: Prospective. STATISTICAL ANALYSIS: Student's "t" test. RESULTS: Twenty patients (Mean age: 35.2 years [20-51]; M:F=12:8) completed the study. Mean age at seizure onset was 10.3 years (birth-38 years); mean duration, 23.9 years (6-50 years). Concordance with the MRI lesion was seen in 10 patients (nine with hippocampal sclerosis and one with tuberous sclerosis). In the other 10, with either normal or ambiguous MRI findings, FMZ and FDG uptake were abnormal in all, concordant with the electrophysiological localization of the epileptic foci. Remote FMZ PET abnormalities (n=18) were associated with early age of seizure onset (P=0.005) and long duration of epilepsy (P=0.01). CONCLUSIONS: FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.

Adult↗

Is impairment in set-shifting specific to frontal-lobe dysfunction? Evidence from patients with frontal-lobe or temporal-lobe epilepsy.

Frontal-lobe epilepsy (FLE), temporal-lobe epilepsy (TLE), and matched-control subjects were administered the Trail Making Test (TMT) of the Delis-Kaplan Executive Function System (D-KEFS; Delis et al., 2001), which assesses set-shifting on a visuomotor sequencing task. Results indicated that patients with FLE were impaired in both speed and accuracy on the switching condition relative to patients with TLE and controls. The two patient groups did not differ from controls on the four baseline conditions of the test, which assess visual scanning, motor speed, number sequencing, and letter sequencing. In addition, seizure-related variables (i.e., age of seizure onset, duration of epilepsy, and seizure frequency) failed to correlate with set-shifting performance in patients with FLE. These results suggest that patients with FLE can be reliably distinguished from those with TLE and control subjects on set-shifting as measured by the DKEFS TMT.

Adult↗

[Video-electroencephalography prolonged monitoring in patients with ambulatory diagnosis of medically refractory temporal lobe epilepsy: application of fuzzy logic's model].

INTRODUCTION: The video-electroencephalography (video-EEG) prolonged monitoring is an important auxiliary diagnostic instrument in epilepsy, and provides valuable information to classify the type of crisis and epileptic syndromes and to localize the epileptogenic zone. The fuzzy logic gives an efficient and intelligent analysis method, able to make inferences over ambiguous systems, and has been increasing used in several areas. AIMS: To correlate clinical and electroencephalographic data obtained with video-EEG of patients with clinical and interictal electroencephalography criteria of medically refractory temporal lobe epilepsy (TLE) and to make inferences of diagnosis precision with the application of the Fuzzy Hierarchy COPPE/Cosenza Model; to investigate the frequency in which the clinical, syndromic and topographic diagnosis can be modified in these patients; to evaluate the usefulness and applicability of fuzzy logic on the analysis of this type of study. PATIENTS AND METHODS: Transversal, prospective study, that included 22 adult outpatients with ambulatory diagnosis of medically refractory TLE, submitted to video-EEG monitoring that varied from 48 hours to 10 days. The grade of diagnosis precision was infered by fuzzy logic. RESULTS: The clinical diagnosis of epilepsy was modified in two (9%) patients, the syndromic in six (27.2%) and the topographic in 16 (72.7%). The fuzzy indicators of ambulatory diagnostic precision were: 0.91 to clinical diagnosis; 0.74 to syndromic diagnosis and 0.36 to topographic diagnosis, considering 1 the maximal precision diagnostic value (attributed to the video-EEG results). CONCLUSIONS: The video-EEG prolonged monitoring established the clinical, syndromic and topographic correct diagnosis in these patients; the fuzzy logic best defined a mathematical value of the correspondence between ambulatorial diagnosis of TLE and the video-EEG prolonged monitoring.

Adult↗

[Predictive factors for the results of surgical treatment in temporal lobe epilepsy].

The most effective type of epilepsy surgery in adults is temporal lobe epilepsy (TLE) surgery. Three quarter of the patients become seizure free, however the remaining patients experience seizures after resection. In our study we analyzed retrospectively the possible electro-clinical, neuroimaging and surgery-related outcome predictors in 94 adult patients who had anterior temporal lobectomy (ATL) from the material of Epilepsy Centre of the National Institute of Psychiatry and Neurology, Budapest since the beginning of the surgery program in 1989 until 2001. Three outcome endpoints were chosen: the seizure status at the last visit, the longest seizure free period and the time to the first non-acute postoperative seizure. The predictors were assessed by multivariate and Cox regression methods. After one year of surgery 72% of the patients were seizure free, after two years 67% and after five years 59%. Factors predicting favorable outcome in TLE surgery were: typical temporomesial aura, strictly unilateral interictal anterotemporal spikes, unilateral ictal onset, slow contralateral propagation, hippocampal sclerosis (HS) as etiology. Factors predicting poor outcome in TLE surgery were: increase in seizure frequency in the last two preoperative years, presence of preoperative psychiatric disturbances, ictal contralateral propagation, MRI lesion distant from the surgery site, incongruency of data of preoperative investigations, postoperative sequels and non-HS type MR residuum.

Adolescent↗

[Enterotoxigenicity of Salmonella strains of various origins].

The study of the enterotoxigenicity of S. typhimurium with the use of the skin test on rabbits (to detect the delayed permeability factor) has revealed that these strains produce an enterotoxin similar to Escherichia coli thermolabile enterotoxin (TLE). Study of the enterotoxic activity of lysates obtained from 39 S. typhimurium strains and 5 S. dublin strains by sonication has revealed that 87% of S. typhimurium strains and all S. dublin strains produce an enterotoxin similar to E. coli TLE, as demonstrated by all tests used in this investigation, while 59% of S. typhimurium cultures and all S. dublin strains have been positive when tested for the capacity of producing the rapid permeability factor. "Hospital" strains and polyresistant cultures isolated from the environment (phagovar 20) are characterized by a higher rate of producing an enterotoxin similar to E. coli TLE, detected by the tests used in this investigation (90%), than antibiotic-sensitive strains of different origin (78%).

Animals↗

[Analysis of postoperative seizure recurrence after 65 temporal lobe partial resections].

Sixty-five patients (aged between 3 years 5 months and 60 years) suffering from medically resistant temporal lobe epilepsy (TLE) were operated on over a period of 33 months in Bethel Epilepsy Center. Thirty-three patients had mesial TLE and 32 patients had TLE of different etiology. The postoperative follow-up lasted 2 years in 30 patients and was on average 13.2 months or at least 8 months in the 35 patients who did not have their last examination 2 years after surgery. Many of the patients (70.9%) were seizure-free; 92.3% achieved a rewarding improvement in seizure frequency and quality of life. Reduction of medication was the cause for relapse in 10 patients, in 6 patients incomplete resection, and in 5 patients the prognosis was not good even before surgery. The cause remained unclear in 4 patients. Freedom from seizures was achieved again by renewed medication or by repeated operation in 10 of 25 patients.

Adolescent↗

[Efficacy of the fluid attenuated inversion recovery (FLAIR) sequence of MRI as a preoperative diagnosis of hippocampal sclerosis].

A newly advanced MRI pulse sequence, the FLAIR (fluid attenuated inversion recovery) imaging, in which a long TE spin echo sequence is used with suppression of the CSF with an inversion pulse, displays the CSF space as a no-signal intensity area. There have been only a few reports on the FLAIR pulse sequence of temporal lobe epilepsy (TLE) as yet. We examined 9 cases of intractable TLE by FLAIR images and analyzed the advantages and disadvantages of the FLAIR pulse sequence for decision making on temporal lobectomy. All patients underwent anterior temporal lobectomy with hippocampectomy, and the diagnoses were confirmed histologically after surgery. Abnormally high T2 signals (HT2S) were more conspicuous with the FLAIR sequence than with any of the conventional sequences. Tilted axial plane, orientated along to the long axis of the hippocampal body, clearly demonstrated hippocampal atrophy (HA). Selection of a FLAIR sequence into the routine MR examination of patients with TLE is recommended.

Adolescent↗

[Relationship between imaging and pathological features and clinical factors in surgical cases of temporal lobe epilepsy].

The relationships between imaging, pathology and presumed causes in surgical cases of temporal lobe epilepsy (TLE) was studied. The subject was 62 patients (33 males and 29 females) who had had no attacks for more than one year after surgery. Average age at surgery was 28.2 +/- 9.9 years. Obvious neurological abnormalities were not found in these cases. MRI, PET and SPECT were performed. Hematoxylin and eosin was used for pathological judgement. Their medical charts were used to investigate their clinical factors. Although patients suspected of having encephalitis/meningitis had been hospitalized for 2 days to three months during childhood due to disturbance of consciousness with high fever and convulsion for several days; they were not diagnosed with encephalitis/meningitis at that time, and they suffered almost no handicaps other than epilepsy for several years following their comatose episodes. [Result] (1) On MRI, mesial temporal sclerosis (MTS) was detected in 48 of 52 patients (92%); 32 (62%) had high-signal intensity on T 2-weighted images; 31 (60%) had atrophy ¿23 (44%) had high-signal intensity on T 2 + atrophy¿; 5 (10%) had calcified lesions; and 2 (4%) had cystic lesions. On PET and SPECT, abnormal cerebral blood flow was noted in 33 of 36 (92%). (2) On pathological findings (61 cases), Ammon's horn sclerosis (AHS), tumors, gliosis in lateral temporal and meningeal inflammatory finding were detected in 42 (69%), 10 (23%) and 8 (13%) cases, respectively, whereas 2 showed no abnormalities. The 2 patients with normal pathology showed both high-signal intensity and atrophy on MRI. (3) The presumed causes of TLE were encephalitis/meningitis and/or suspected of these diseases in 15 patients (24%), injuries at birth in 5 (8%), and none in 42 (68%). The presumed causes in the 43 patients with AHS were encephalitis/meningitis in 11, injuries at birth in 3, and none in 29. Of the 15 patients in whom encephalitis/meningitis was estimated as the causes of TLE, only 6 (40%) had pathological evidence of meningeal inflammatory finding. Of the 42 patients in whom cause could not be determined, 2 had pathological evidence of meningeal inflammatory finding.

Adolescent↗

Comparative effects of schizophrenia and temporal lobe epilepsy on memory.

The goal of this study was to further characterize episodic memory functioning in schizophrenia. This study compared verbal and visual learning and memory performance in (1) patients with schizophrenia (N = 35), (2) patients with temporal lobe epilepsy (TLE; N = 30), and (3) normal controls (N = 25). Results indicated significant memory impairments in patients with schizophrenia and TLE. "Savings" score measures of memory decay showed that the loss of information in schizophrenia and TLE was approximately equal, and quantitatively mild compared to that found in most neurologic groups with memory disorders. The severe difficulty shown by the schizophrenia group on a task of incidental recall suggested that the absence of instructional set added to a vulnerability to memory deficit. In contrast, relatively mildly impaired performance on paired associate learning suggested that patients with schizophrenia benefited from retrieval cues, multiple trials, and short (nonsupraspan) informational loads. Because patients with schizophrenia consisted of a relatively nonchronic sample with a mean IQ of 99.7, their memory disorder could not be attributed to schizophrenic dementia, nor was it accounted for by other potential confounds. Patients with schizophrenia, even those relatively early in the course of illness, have a mild episodic memory disorder.

Adolescent↗

Synergism of procoagulation effect of thrombin-like enzymes from Dienagkistrodon acutus and Agkistrodon halys snake venoms.

AIM: To study the synergistic effect of thrombin-like enzymes (TLE) of Dienagkistrodon acutus (DA) and Agkistrodon halys (AH) venoms. METHODS: TLE were isolated from venoms of DA and AH by successive column chromatography. Effects of combination of DATLE and AHTLE and related factors on the clotting time and clot quality were tested in vitro. RESULTS: One coagulation unit was 2.7 micrograms for DATLE and 304.4 micrograms, for AHTLE with reference standard of thrombin (42.2 micrograms). TLE-induced clot was a fibrin monomer which was fragile and did not retract. Combination of AHTLE and DATLE shortened the clotting time and decreased the solubility of the clot in urea 5 mol.L-1. When subthreshold concentration of thrombin or physiological concentration of Ca2+ was added, the clotting time was further shortened, the clot was no longer soluble in urea and retracted well, and the resistance of the clot to plasmin degradation was increased. CONCLUSION: A synergistic effect of DATLE and AHTLE accelerated hemocoagulation and improve clot quality.

Agkistrodon↗