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Axonal sprouting and synaptogenesis in temporal lobe epilepsy: possible pathogenetic and therapeutic roles of neurite growth inhibitory factors.

Axonal sprouting and synaptic reorganization within the temporal lobe following neuronal injury have been implicated in the pathogenesis of temporal lobe epilepsy (TLE). The molecular species responsible for these structural changes have yet to be fully defined. The recent characterization of molecules whose normal function within the nervous system is to inhibit neurite outgrowth and synaptogenesis prompts the suggestion that a diminution or loss of such molecules might be of relevance to the pathogenesis of TLE. If so, the possibility of developing a novel therapeutic approach to TLE, distinct from currently available symptomatic therapies, to arrest the pathogenetic processes is also raised.

Alzheimer Disease↗

Clinical characteristics of complex partial seizures: a temporal versus a frontal lobe onset.

The site of origin of complex partial seizures (CPS) is predominantly in the temporal lobe, but frontal, parietal, and occipital lobes may also be involved. In order to correlate clinical behaviours with either a temporal or frontal site of origin, we analysed 211 seizures occurring during invasive monitoring in 26 patients with temporal lobe epilepsy (TLE) and in eight patients with frontal lobe epilepsy (FLE). Although leg movements, defined as thrashing, pedalling and kicking, hand posturing, facial twitching, sitting up, and tonic-clonic movements occurred more frequently in FLE, and hand automatisms were more frequent in TLE, no statistically significant difference was found between the two groups. When analysing only electrographic seizures that did not spread or propagated only to homologous controlateral lobes, leg movements and hand posturing were seen only with FLE, and oral automatisms only in TLE. Seizures of temporal lobe origin were longer in duration and had a higher frequency of auras. We therefore conclude that the reliability of clinical behaviour alone to predict the site of origin of an epileptic discharge is limited when the surface EEG is equivocal or the neuroradiologic evidence of a focus is not clear.

Adolescent↗

Emotional facial paresis in temporal lobe epilepsy: its prevalence and lateralizing value.

The selection of patients with medically refractory temporal lobe epilepsy (TLE) for surgery depends on the concordance of data from clinical, imaging and electroencephalographic evaluation. Though clinical examination is often normal, emotional facial paresis has been described in patients with TLE. Utilizing a well-characterized group of mesial TLE (MTLE) patients, who have achieved excellent seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL), we investigated the prevalence, predictive value and associations of emotional facial paresis. When compared to 8 out of 50 control subjects (16%), 36 out of 50 MTLE patients (72%) exhibited unilateral emotional facial paresis; the difference was highly significant (P<0.0001). The presence of contralateral emotional facial paresis correctly predicted the side of ATL in 86.1% patients. The occurrence of emotional facial paresis was significantly associated with longer duration of epilepsy prior to ATL and left ATL. Our observations confirm that emotional facial parersis contralateral to the side of mesial temporal sclerosis (MTS) is a valuable localizing sign in correctly predicting the epileptogenic temporal lobe. We hypothesize that the presence of an intact right hemisphere and pathological changes more extensive than MTS may be required for emotional facial paresis to readily manifest.

Adolescent↗

Relationship of sexual dysfunction to epilepsy laterality and reproductive hormone levels in women.

Sexual dysfunction has been reported to be common among women with epilepsy. Controlled studies, quantitative data, and investigations of potentially contributory factors, however, have been few. The purpose of this investigation was to determine if (1) sexual dysfunction is unusually common among women with partial seizures of temporal lobe origin (TLE), and (2) sexual dysfunction varies in relation to the laterality of EEG epileptiform discharges, antiepileptic drug use, and serum gonadal steroid levels. This controlled prospective investigation used a quantitative sexual rating scale and reproductive hormone measures to compare sexual dysfunction in women with left and right unilateral temporolimbic epilepsy and controls. Sexual dysfunction scores were significantly higher in women with TLE, and sexual dysfunction affected substantially more women with epilepsy than controls. Women with right-sided foci were affected more than women with left-sided foci. There was a significant inverse correlation between sexual dysfunction and bioactive testosterone levels in women with epilepsy as well as in controls. Serum estradiol was lower in women with TLE but did not correlate significantly with overall sexual dysfunction. The findings suggest that sexual dysfunction is significantly more common in women with right-sided epileptiform discharges than in controls and is inversely correlated with bioactive testosterone levels. The value of hormonal replacement or supplementation remains to be explored.

Adolescent↗

Specific memory impairment in a multiple disabled male with fragile X syndrome and temporal lobe epilepsy.

Evaluation of the cognitive repercussions of an epileptic disorder and its treatment are important issues in clinical follow-up. This especially holds true for temporal lobe epilepsy (TLE) where resective surgery can be a valid treatment option. However, in patients where TLE coexists with another neurocognitive disorder, questions can arise about the precise nature of the neuropsychological deficits. The aim of the present study was to evaluate memory impairments, found in a male aged 12 years who had the dual pathology of fragile X syndrome and refractory TLE. Memory functions of this child were compared with those of a male aged 11 years 7 months with fragile X syndrome matched for intellectual functioning as indicated by highly comparable verbal (5 y 5 mo vs 5 y 9 mo) and non-verbal (7 y 2 mo vs 6 y 1 mo) cognitive age equivalents. Performance on each neuropsychological measure was evaluated twice, separately with normative data based on chronological age and on verbal or non-verbal cognitive level. A specific, distinguishable profile of task performance could be found only when controlling for general level of cognitive functioning. This made it possible to accurately evaluate neuropsychological abilities before and 6 months after anterior temporal lobe resection even in this male with a complex neurological pathology.

Abnormalities, Multiple↗

Schizophrenia, temporal lobe epilepsy and psychosis: an in vivo magnetic resonance spectroscopy and imaging study of the hippocampus/amygdala complex.

BACKGROUND: We have used proton magnetic resonance imaging and spectroscopy to measure hippocampus/amygdala volumes and anterior hippocampal metabolite concentrations (N-acetyl aspartate (NAA), creatine/phosphocreatine and choline) in subjects with temporal lobe epilepsy (TLE), schizophrenia and in normal controls. METHOD: Four groups of right-handed patients were selected: 12 with TLE and psychosis (EP), 12 with TLE and no psychosis (ENP), 26 with schizophrenia, and 38 normal controls. Imaging and spectroscopy were performed with a 1.5T Signa GE scanner. RESULTS: The schizophrenia group showed a significant left-sided reduction in all metabolites. In the epilepsy groups NAA was reduced bilaterally. The NAA reduction in the EP group was greater than in the ENP group, especially on the left, although the result did not reach significance. Total hippocampus/amygdala volumes showed no significant differences in any of the groups when compared with normal controls. When compared with controls significant, specific regional volume reductions were present bilaterally in the EP group and in the left hippocampus/amygdala in schizophrenia. The regional volume reduction found in schizophrenia was also present in EP but not in ENP. CONCLUSION: Spectroscopic abnormalities were more pronounced in the epilepsy groups and were bilateral, and abnormalities in schizophrenia were left sided. Specific regional hippocampus/amygdala volume reductions were more marked in the EP group and were bilateral. Left-sided regional volume reduction identified in the dominant hemisphere of schizophrenics was also present in EP patients, but not in ENP, suggesting that this region in the left temporal lobe may be significant in the aetiology of psychosis. This is further supported by the predominantly left-sided NAA reduction in schizophrenia. High resolution morphometric studies may identify specific regions of the brain associated with the development of psychosis.

Adult↗

Temporal lobe epilepsy as a unique manifestation of multiple sclerosis.

OBJECTIVE: To report on five patients with temporal lobe epilepsy (TLE) as the unique manifestation of multiple sclerosis (MS). METHODS: Among 350 consecutive MS patients, we identified 16/350 (4.6%) who also had epileptic seizures. Here, we review their electrophysiological and clinical features. RESULTS: Five of these 16 patients (four female, one male; mean age 34.2 years; range 31 to 38) with MS and epileptic seizures had an extremely homogeneous clinical picture characterized by TLE as the unique manifestation of MS, even at long follow-up (mean: five years; range 4 to 10). In all patients, seizures started in the second or third decade. Brain MRI revealed at least one juxta-cortical lesion within the temporal region. Antiepileptic medication was always effective. CONCLUSIONS: The present study provides the first evidence of a peculiar form of MS characterized by TLE as the unique manifestation of the disease with no disability or MS relapses at long-term follow-up.

Adult↗

Executive functions in children with frontal and temporal lobe epilepsy.

Even though frontal lobe epilepsy (FLE) is a relatively common seizure type, no formal psychometric studies of children with FLE have been reported. We compared 12 children with FLE and 15 children with temporal lobe epilepsy (TLE) on neuropsychological tests of attention, memory, executive functioning, and adaptive functioning. The results of these tests indicated that the children with FLE had deficits in planning and executive functions, whereas their verbal and nonverbal memory was intact. The opposite pattern was observed in children with TLE. Measures of executive functioning and impulse control were the best predictors of adaptive functioning. The findings suggest that children with FLE have a pattern of cognitive deficits that differs markedly from the pattern seen in children with TLE. Children with FLE have prominent deficits in executive functioning that appear to be related to poor behavioral adaptation.

Activities of Daily Living↗

Increased expression of "peripheral-type" benzodiazepine receptors in human temporal lobe epilepsy: implications for PET imaging of hippocampal sclerosis.

Increased binding sites for "peripheral-type" benzodiazepine receptor (PTBR) ligands have been described in a wide range of neurological disorders including both human and experimental epilepsy. This study was undertaken to assess PTBR expression in relation to the presence of hippocampal sclerosis in human temporal lobe epilepsy (TLE). For this purpose, hippocampal CA1 subfields were dissected from surgical samples from patients with therapy-refractive TLE with (n = 5) or without (n = 2) hippocampal sclerosis and from age-matched nonepileptic postmortem controls (n = 5). PTBR expression was assessed by immunohistochemistry and reverse-transcription polymerase chain reaction. Receptor sites were evaluated using an in vitro binding assay and the selective PTBR ligand [3H]PK11195. Epileptic patients with hippocampal sclerosis showed increases in PTBR binding sites, immunoreactivity, and mRNA expression compared to both nonsclerotic TLE patients and postmortem nonepileptic controls. Induction of PTBR expression and binding sites were directly correlated with the presence of hippocampal sclerosis and the accompanying reactive gliosis.

Epilepsy, Temporal Lobe↗

Clinical factors associated with post-ictal headache in patients with epilepsy.

OBJECTIVES: To determine the incidence of post-ictal headaches (PIH) and clinical risk factors associated with the occurrence of PIH in patients with localization-related epilepsy. MATERIALS AND METHODS: The subjects were 77 patients with temporal lobe epilepsy (TLE), 34 patients with occipital lobe epilepsy (OLE), and 50 patients with frontal lobe epilepsy (FLE). The subjects were directly asked whether headaches occurred just after seizures. Medical charts were reviewed to ascertain the clinical characteristics of epilepsy in these patients. RESULTS: The incidence of PIH was 23% for TLE, 62% for OLE, and 42%, for FLE. The risk of PIH was significantly higher for OLE than for TLE or FLE, and for patients with generalized tonic-clonic seizures. Younger age at onset of epilepsy was also a risk factor for PIH. CONCLUSION: The occurrence of PIH may be related to the region of epileptic focus and the region of spread of epileptic discharges.

Adolescent↗

Quality of life and memory performance in patients with temporal lobe epilepsy.

OBJECTIVE: To explore the contribution of memory performance to quality of life (QOL) in patients with left or right temporal lobe epilepsy (TLE). SUBJECTS AND METHODS: Sixty-five patients with left or right TLE compiled the QOL in Epilepsy-89 Inventory (QOLIE-89), the State-Trait Anxiety Inventory (STAI) and the Hopelessness Scale (BDI) for self-evaluation of QOL and mood. Memory was assessed by tests of verbal and non-verbal memory and the Questionnaire of Memory Efficiency (QME). A neuropsychological battery was also administered to assess general intelligence, attention, visual perception, language, set shifting, word fluency and conceptual-motor tracking. RESULTS: On factor analysis, the neuropsychological battery and mood scales consisted of six factors (Memory, Mental Speed, Mood, Praxis, Sorting and Perception), while the QOLIE-89 consisted of five factors (Psychosocial Satisfaction, Epilepsy-Related Effects, Role, Physical Performance, Cognition). On regression analysis, overall QOLIE-89 score was predicted by the factor Mood and QME score. The QOLIE-89 factor Cognition was predicted by QME score and the Memory, Mental Speed, Perception and Praxis factors of the neuropsychological battery. CONCLUSION: In TLE patients self-reported memory, as assessed by QME, is an important predictor of QOL, and also correlates with performance on memory tests. This suggests that memory improvement by specific training may help to improve QOL in these patients.

Adolescent↗

Short-term and long-term memory in early temporal lobe dysfunction.

Following medial temporal damage, mature humans are impaired in retaining new information over long delays but not short delays. The question of whether a similar dissociation occurs in children was addressed by testing children (ages 7-16) with unilateral temporal lobe epilepsy (TLE) and controls on short- and long-term memory tasks, including a spatial delayed response task (SDR). Early-onset TLE did not affect performance on short delays on SDR, but it did impair performance at the longest delay (60 s), similar to adults with unilateral medial temporal damage. In addition, early-onset TLE affected performance on pattern recall, spatial span, and verbal span with rehearsal interference. No differences were found on story recall or on a response inhibition task.

Age of Onset↗

Evidence for the pathological right-handedness hypothesis.

The present study investigated handedness of 109 Korean patients with temporal lobe epilepsy (TLE) and 120 normal control participants. Left TLE was associated with a significantly raised incidence of left-handers relative to normal controls. More important for the present purpose, right TLE was associated with a significantly raised incidence of strong right-handers relative to normal controls. This finding indicates that certain early damage to the right brain causes a mild hypofunction of the left hand in natural weak right-handers, which in turn causes the patient to switch to strong right-handedness. To the authors' knowledge, this finding provides the 1st empirical evidence supporting the pathological right-handedness hypothesis. Prior failure to find evidence of pathological right-handedness may reflect the low base rate of natural left-handers rather than true absence of pathological right-handers.

Adult↗

Intact perceptual and conceptual priming in temporal lobe epilepsy: neuroanatomical and methodological implications.

Explicit memory appears to be supported by medical temporal lobe structures, whereas separate neocortical regions may mediate perceptual and conceptual implicit memory. Children and adults with temporal lobe epilepsy (TLE) and matched controls were administered experimental verbal memory tests. Performance on implicit tests--word identification and word generation--was contrasted with explicit recognition and recall. Encoding conditions emphasized either conceptual or perceptual aspects of study words and were crossed with presentation modality. The priming performance of participants with TLE did not differ from controls, but participants with TLE did show deficits on recognition and recall measures. Thus, intact left temporal cortex does not appear to be necessary for normal implicit memory performance, even when conceptual processing is emphasized at study or test.

Adolescent↗

Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins.

Notch and the m9/10 gene (groucho) of the Enhancer of split (E(spI)) complex are members of the "Notch group" of genes, which is required for a variety of cell fate choices in Drosophila. We have characterized human cDNA clones encoding a family of proteins, designated TLE, that are homologous to the E(spI) m9/10 gene product, as well as a novel Notch-related protein. The TLE genes are differentially expressed and encode nuclear proteins, consistent with the presence of sequence motifs associated with nuclear functions. The structural redundancy implied by the existence of more than one TLE and Notch-homologous gene may be a feature of the human counterparts of the developmentally important Drosophila Notch group genes.

Amino Acid Sequence↗

Enhancement of central dopaminergic activity in the kainate model of temporal lobe epilepsy: implication for the mechanism of epileptic psychosis.

There is an increased incidence of schizophrenia-like psychosis in temporal lobe epilepsy (TLE), and several risk factors have been implicated, including the duration of epilepsy and temporal lobe neuropathology. To investigate the biological mechanism of epileptic psychosis, we examined alterations of central dopaminergic systems in the kainate model of TLE. In adult rats, kainate was microinjected into the left amygdala to induce status epilepticus. An indirect dopamine agonist methamphetamine (MAP, 2 mg/kg, i.p.) was administered before and 1 month after the kainate treatment. MAP-induced locomotor activity was significantly enhanced in the kainate group compared with the baseline (pre-kainate) level, which was antagonized by pretreatment with haloperidol. The enhancement of locomotor activity in the kainate group was significantly correlated with the density of hippocampal CA1 neurons. Although the basal extracellular dopamine concentration was significantly lower in the striatum in the kainate group than in the control group (5.5 vs 39.2 fmol/20-min sample), the maximal concentration following MAP administration did not differ between the two groups. These results clearly demonstrate that hypersensitivity of the dopamine systems develops in the chronic phase of the kainate-induced TLE model, which may be responsible for the mechanism of epileptic psychosis.

Analysis of Variance↗

Multi-center study on post-ictal headache in patients with localization-related epilepsy.

The nature of post-ictal headache (PIH) remains unclear. A multicenter study was conducted in order to evaluate frequency and risk factors for PIH. The subjects consisted of 97 patients with temporal lobe epilepsy (TLE), 65 patients with frontal lobe epilepsy (FLE) and 37 patients with occipital lobe epilepsy (OLE). The subjects were asked about PIH at each institute. Clinical factors of epilepsy were reviewed for each patient and correlated with PIH. Post-ictal headache occurred in 41% of TLE patients, 40% of FLE patients and 59% of OLE patients. Logistic regression analysis revealed that the risk of PIH was significantly higher in OLE than in FLE. In contrast, there were no significant differences in the incidence of PIH between TLE and either OLE or FLE patients. Post-ictal headache occurred significantly more frequently in subjects with generalized tonic-clonic seizure (GTCS) than in those without GTCS. Other clinical factors, such as sex, age, age at onset, duration of illness, seizure frequency, family history of headache and interictal headache were found to have no associations with PIH. A difference was found in the incidence of PIH depending on classification of epilepsy, but only to a relatively slight extent. It was also found that GTCS was significantly related to PIH. These results suggest that both the location of epileptogenic focus and the involvement of certain cerebral areas in the spread of seizure discharges may be closely related to PIH.

Adult↗

Limbic P300s in temporal lobe epilepsy with and without Ammon's horn sclerosis.

Limbic P300 potentials can be recorded within the mesial temporal lobes of patients with temporal lobe epilepsy (TLE). To delineate possible mechanisms of their generation and pathological alteration, we analysed limbic P300s in 55 TLE patients with and 29 without Ammon's horn sclerosis (AHS) and correlated their amplitudes with neuronal cell counts in 30 histopathological specimens. Limbic P300 amplitudes were reduced on the side of the epileptogenic focus only in patients with AHS. Moreover, in AHS patients, limbic P300 latencies were prolonged bilaterally; and in patients with left-sided AHS, amplitudes were reduced bilaterally. Both findings suggest bilateral functional deficits in TLE with unilateral AHS. Limbic P300 areas correlated significantly with neuronal densities of dentate gyrus granule cells but not hippocampal pyramidal cells in the CA1-4 (cornu ammonis) subfields. This finding points to a potential mechanism for the bilateral effects of unilateral AHS as both dentate gyri exhibit strong reciprocal contralateral connectivity.

Adolescent↗