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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mapping the distribution of GABAA receptor subtypes represents a promising approach to characterize alterations in cortical circuitry associated with neurological disorders. We previously reported subtype-selective changes in GABAA receptor expression in the grey matter of patients with focal epilepsy. In the present follow-up study, we focused on the subcortical white matter in the same tissue specimens obtained at surgery from 9 patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis, 12 patients with TLE associated with neocortical lesions and 5 patients with frontal lobe epilepsy; post-mortem tissue from 4 subjects served as controls. The subunit composition and distribution of three major GABAA receptor subtypes were determined immunohistochemically with subunit-specific antibodies. In all cases, a majority of neurons in the white matter was distinctly labelled, allowing detailed visualization of their dendritic arborization and revealing a differential, cell type-specific expression pattern of alpha-subunit variants. In controls, alpha1-subunit staining was most prominent, displaying a gradient that decreased with depth, in parallel with the density of NeuN-positive cells. Subsets of pyramidal cells were alpha3-subunit-positive, and alpha2-subunit-labelled neurons were rare. In 19 of the 26 patients with focal epilepsy, no changes were detected as compared with controls. In five patients with TLE, striking changes in the dendritic arborization of a subset of white matter neurons were seen with the alpha1-subunit antibody. In two further patients with TLE, we observed a disorganized dendritic network immuno-positive for the alpha1-subunit, cell clusters selectively expressing the alpha2-subunit and small neuronal aggregates that expressed all subunits and appeared to connect to neighbouring white matter neurons. All seven patients with anomalies in the white matter had a selective reduction in alpha3-containing GABAA receptors in the superficial layers of the grey matter. These results demonstrate a distinct organization of GABAA receptors in human white matter neurons, consistent with an inhibitory network that is likely to be integrated functionally with the overlying grey matter. The altered dendritic morphology and changes in GABAA receptor expression in the white matter of a subset of patients with focal epilepsy are suggestive for a rewiring of neuronal circuits.
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PMID:Selective changes in GABAA receptor subtypes in white matter neurons of patients with focal epilepsy. 1957 38

The pathogenesis of mesial temporal lobe epilepsy (MTLE), the most prevalent form of refractory focal epilepsy in adults, is thought to begin in early life, even though seizures may not commence until adolescence or adulthood. Amongst the range of early life factors implicated in MTLE causation (febrile seizures, traumatic brain injury, etc.), stress may be one important contributor. Early life stress is an a priori agent deserving study because of the large amount of neuroscientific data showing enduring effects on structure and function in hippocampus and amygdala, the key structures involved in MTLE. An emerging body of evidence directly tests hypotheses concerning early life stress and limbic epilepsy: early life stressors, such as maternal separation, have been shown to aggravate epileptogenesis in both status epilepticus and kindling models of limbic epilepsy. In addition to elucidating its influence on limbic epileptogenesis itself, the study of early life stress has the potential to shed light on the psychiatric disorder that accompanies MTLE. For many years, psychiatric comorbidity was viewed as an effect of epilepsy, mediated psychologically and/or neurobiologically. An alternative - or complementary - perspective is that of shared causation. Early life stress, implicated in the pathogenesis of several psychiatric disorders, may be one such causal factor. This paper aims to critically review the body of experimental evidence linking early life stress and epilepsy; to discuss the direct studies examining early life stress effects in current models of limbic seizures/epilepsy; and to suggest priorities for future research.
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PMID:Early life stress as an influence on limbic epilepsy: an hypothesis whose time has come? 1983 25

The aim of this study is to characterize and compare dipole and distributed EEG source localization (ESL) of interictal epileptiform discharges (IEDs) in focal epilepsy. Single and averaged scalp IEDs from eight patients-four with benign focal epilepsy of childhood with centrotemporal spikes (BFEC) and four with mesial temporal lobe epilepsy (MTLE)-underwent independent component analysis (ICA) from IED onset to peak. The boundary element method forward model was applied to one of four inverse models: two dipolar-moving regularized, rotating nonregularized and two distributed-standardized low-resolution electromagnetic tomography with rotating cortical sources or with fixed extended sources. Solutions were studied at IED onset, midupswing, peak; ESL strength maxima; ESL residual deviation minima (best fit). From 11,040 ESL parameter points and 960 ESL maps, best-fit dipole and distributed solutions fell at the IED midupswing in BFEC and MTLE when the dominant ICA component typically peaked, localizing to the lower Rolandic sulcus in BFEC and to basolateral or anterior temporal cortex in MTLE. Single-to-averaged ESL variability was high in MTLE. Dipole and distributed ESL are complementary; best-fit solutions for both occupy the IED midupswing and not the IED peak. ICA, a "blind" statistical operation, aids clinical interpretation of ESL fit quality. Single-to-averaged IED localization discordance can be high, a problem warranting further scrutiny if ESL is to earn a place in routine epilepsy care.
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PMID:Dipole versus distributed EEG source localization for single versus averaged spikes in focal epilepsy. 2046 Oct 16

Temporal lobe epilepsy (TLE) characterized by an epileptogenic focus in the medial temporal lobe is the most common form of focal epilepsy. However, the seizures are not confined to the temporal lobe but can spread to other, anatomically connected brain regions where they can cause similar structural abnormalities as observed in the focus. The aim of this study was to derive whole-brain networks from volumetric data and obtain network-centric measures, which can capture cortical thinning characteristic of TLE and can be used for classifying a given MRI into TLE or normal, and to obtain additional summary statistics that relate to the extent and spread of the disease. T1-weighted whole-brain images were acquired on a 4-T magnet in 13 patients with TLE with mesial temporal lobe sclerosis (TLE-MTS), 14 patients with TLE with normal MRI (TLE-no), and 30 controls. Mean cortical thickness and curvature measurements were obtained using the FreeSurfer software. These values were used to derive a graph, or network, for each subject. The nodes of the graph are brain regions, and edges represent disease progression paths. We show how to obtain summary statistics like mean, median, and variance defined for these networks and to perform exploratory analyses like correlation and classification. Our results indicate that the proposed network approach can improve accuracy of classifying subjects into two groups (control and TLE) from 78% for non-network classifiers to 93% using the proposed approach. We also obtain network "peakiness" values using statistical measures like entropy and complexity-this appears to be a good characterizer of the disease and may have utility in surgical planning.
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PMID:Network-level analysis of cortical thickness of the epileptic brain. 2055 93

Mutations of the LGI1 (leucine-rich, glioma-inactivated 1) gene underlie autosomal dominant lateral temporal lobe epilepsy, a focal idiopathic inherited epilepsy syndrome. The LGI1 gene encodes a protein secreted by neurons, one of the only non-ion channel genes implicated in idiopathic familial epilepsy. While mutations probably result in a loss of function, the role of LGI1 in the pathophysiology of epilepsy remains unclear. Here we generated a germline knockout mouse for LGI1 and examined spontaneous seizure characteristics, changes in threshold for induced seizures and hippocampal pathology. Frequent spontaneous seizures emerged in homozygous LGI1(-/-) mice during the second postnatal week. Properties of these spontaneous events were examined in a simultaneous video and intracranial electroencephalographic recording. Their mean duration was 120 +/- 12 s, and behavioural correlates consisted of an initial immobility, automatisms, sometimes followed by wild running and tonic and/or clonic movements. Electroencephalographic monitoring indicated that seizures originated earlier in the hippocampus than in the cortex. LGI1(-/-) mice did not survive beyond postnatal day 20, probably due to seizures and failure to feed. While no major developmental abnormalities were observed, after recurrent seizures we detected neuronal loss, mossy fibre sprouting, astrocyte reactivity and granule cell dispersion in the hippocampus of LGI1(-/-) mice. In contrast, heterozygous LGI1(+/-) littermates displayed no spontaneous behavioural epileptic seizures, but auditory stimuli induced seizures at a lower threshold, reflecting the human pathology of sound-triggered seizures in some patients. We conclude that LGI1(+/-) and LGI1(-/-) mice may provide useful models for lateral temporal lobe epilepsy, and more generally idiopathic focal epilepsy.
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PMID:Electroclinical characterization of epileptic seizures in leucine-rich, glioma-inactivated 1-deficient mice. 2065 58

We describe a 17-year-old boy with a left extraventricular temporo-mesial neurocytoma associated with cortical dysplasia causing focal pharmacoresistant temporal lobe epilepsy. He presented with a long history of medically refractory, temporal complex partial seizures. MRI showed a left temporo-mesial lesion suspect to be a low-grade tumor. Based on the pre-operative non-invasive neurophysiological studies, the patient underwent a left tailored temporal antero-mesial resection. Histopathological examination showed an extraventricular neurocytoma associated with architectural dysplasia (Type 1a) of the temporal pole. The patient was seizure-free at 2 years follow-up. Extraventricular neurocytomas must be considered in the differential diagnosis of the plethora of low-grade tumors associated with focal epilepsy that typically involve the temporal lobe, and are frequently associated with focal cortical dysplasia.
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PMID:Temporo-mesial extraventricular neurocytoma and cortical dysplasia in focal temporal lobe epilepsy. 2085 5

The symptomatology of auras and seizures is a reflection of activation of specific parts of the brain by the ictal discharge, the location and extent of which represent the symptomatogenic zone. The symptomatogenic zone is presumably, though not necessarily, in close proximity to the epileptogenic zone, the area responsible for seizure generation, the complete removal or disconnection of which is necessary for seizure freedom. Knowledge about the symptomatogenic zone in focal epilepsy is acquired through careful video/EEG monitoring and behavioral correlation of seizures and electrical stimulation studies. Ictal symptomatogy provides important lateralizing and/or localizing information in the presurgical assessment of epilepsy surgery candidates. As the initial symptoms of epileptic seizures, many types of auras have highly significant localizing or lateralizing value. Similarly, motor signs during focal and secondary generalized seizures, language manifestations, and autonomic features offer reliable clues to the delineation of the epileptogenic zone. Some focal epilepsies (e.g., neocortical temporal lobe epilepsy, insular lobe epilepsy, temporal-plus epilepsies, and parieto-occipital lobe epilepsy) generate seizure manifestations that mimic temporal lobe epilepsy, potentially contributing to surgical failure. To optimize surgical outcome, careful interpretation of ictal symptomatology in conjunction with other components of the presurgical evaluation is required.
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PMID:Localizing and lateralizing features of auras and seizures. 2092 50

Although the hippocampus is not considered a key structure in semantic memory, patients with medial-temporal lobe epilepsy (mTLE) have deficits in semantic access on some word retrieval tasks. We hypothesized that these deficits reflect the negative impact of focal epilepsy on remote cerebral structures. Thus, we expected that the networks that support word retrieval tasks would be altered in left mTLE patients. We measured brain activity with fMRI while participants (13 controls, 13 left mTLE, and 13 right mTLE) performed a verb generation task. We examined functional connectivity during this task in relation to language performance on an off-line clinical test of lexical access (Boston Naming Test, BNT). Using task-seed-behavior partial least squares, we identified a canonical language network that was more active during verb generation than the baseline condition, but this network did not correlate with variability in BNT performance in either controls or patients. Instead, additional networks were identified for each group, with more anterior temporal and prefrontal regions recruited for controls and more posterior temporal regions for both left and right mTLE patients. Our findings go beyond the literature emphasizing differences in laterality of language processes in mTLE patients and, critically, highlight how network changes can be used to account for performance variation among patients on clinically relevant measures. This strategy of correlating network changes and off-line behavior may provide a powerful tool for predicting a postoperative decline in language performance.
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PMID:Network alterations supporting word retrieval in patients with medial temporal lobe epilepsy. 2096 92

The consideration of the patient's gender has become an established practice in the choice of antiepileptic drugs (AEDs) for the treatment of epilepsy. This study was undertaken to confirm that temporal lobe epilepsy and the use of hepatic enzyme-inducing AEDs, have a negative effect on sex hormones in men. We calculated the testosterone (T)/luteinizing hormone (LH) ratio to reflect the effects of epilepsy or its treatment on the most important androgen and its pituitary control hormone. Of 324 men with focal epilepsy identified (untreated or on AED monotherapy), 201 were eligible for inclusion (mean age 37.5 years, mean duration of epilepsy 14.7 years). A total of 105 men served as healthy controls (mean age 33.9 years). Patients with temporal lobe epilepsy were more likely to show abnormal T/LH ratios than patients with extratemporal epilepsy (p < 0.01). Patients receiving AEDs with marked hepatic enzyme-inducing effects were more likely to have low T/LH ratios than patients taking nonenzyme-inducing AEDs or healthy controls (p < 0.01). Focus localization and AED choice affect male sex hormones. Findings raise some concerns about the effect of enzyme-inducing AEDs on sexual endocrine functions.
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PMID:Disease- and treatment-related effects on the pituitary-gonadal functional axis: a study in men with epilepsy. 2119 39

Temporal lobe epilepsy is the most common type of focal epilepsy diagnosed in adult patients. According to the location of seizure generation it is classified as mesial temporal lobe epilepsy and neocortical lateral lobe epilepsy. Diagnosis of temporal lobe epilepsy can be proved by the combination of the clinical manifestation of partial complex seizures, scalp-video EEG monitoring, results of magnetic resonance imaging (MRI) and imaging of interictal fluoro-deoxy-glucose positron emission tomography. Mesial temporal sclerosis is the most common finding on MRI. Temporal lobe epilepsy is the most surgically amenable diagnosis and results of surgery treatments are clearly superior to the prolonged medical therapy; surgical treatment of the mesial temporal epilepsy with mesial temporal sclerosis has the best clinical results. Except for standard microsurgical approaches such as anterior temporal resection and selective amygdalo-hippocampectomy, stereotactic thermocoagulation amygdalo-hippocampectomy is provided in our epilepsy centre. This alternative approach has comparable clinical outcome to the standard surgery approaches in 2 years clinical follow-ups. MRI is important not only in diagnostic procedures, but also in neuronavigation of surgery approaches, per operation control of the extent of resections and postoperative follow-ups, especially in failed epilepsy surgery.
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PMID:[Temporal lobe epilepsy in adults and possibilities of neurosurgical treatment: the role of magnetic resonance]. 2163 5


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