'MRI-negative PET-positive' temporal lobe epilepsy (TLE) and mesial TLE differ with quantitative MRI and PET: a case control study

Background: \u27MRI negative PET positive temporal lobe epilepsy\u27 represents a substantial minority of temporal lobe epilepsy (TLE). Clinicopathological and qualitative imaging differences from mesial temporal lobe epilepsy are reported. We aimed to compare TLE with hippocampal sclerosis (HS+ve) and non lesional TLE without HS (HS-ve) on MRI, with respect to quantitative FDG-PET and MRI measures.Methods: 30 consecutive HS-ve patients with well-lateralised EEG were compared with 30 age- and sex-matched HS+ve patients with well-lateralised EEG. Cerebral, cortical lobar and hippocampal volumetric and co-registered FDG-PET metabolic analyses were performed.Results: There was no difference in whole brain, cerebral or cerebral cortical volumes. Both groups showed marginally smaller cerebral volumes ipsilateral to epileptogenic side (HS-ve 0.99, p = 0.02, HS+ve 0.98, p &lt; 0.001). In HS+ve, the ratio of epileptogenic cerebrum to whole brain volume was less (p = 0.02); the ratio of epileptogenic cerebral cortex to whole brain in the HS+ve group approached significance (p = 0.06). Relative volume deficits were seen in HS+ve in insular and temporal lobes. Both groups showed marked ipsilateral hypometabolism (p &lt; 0.001), most marked in temporal cortex. Mean hypointensity was more marked in epileptogenic-to-contralateral hippocampus in HS+ve (ratio: 0.86 vs 0.95, p &lt; 0.001). The mean FDG-PET ratio of ipsilateral to contralateral cerebral cortex however was low in both groups (ratio: HS-ve 0.97, p &lt; 0.0001; HS+ve 0.98, p = 0.003), and more marked in HS-ve across all lobes except insula.Conclusion: Overall, HS+ve patients showed more hippocampal, but also marginally more ipsilateral cerebral and cerebrocortical atrophy, greater ipsilateral hippocampal hypometabolism but similar ipsilateral cerebral cortical hypometabolism, confirming structural and functional differences between these groups.<br /

Classification and Lateralization of Temporal Lobe Epilepsies with and without Hippocampal Atrophy Based on Whole-Brain Automatic MRI Segmentation

Brain images contain information suitable for automatically sorting subjects into categories such as healthy controls and patients. We sought to identify morphometric criteria for distinguishing controls (n = 28) from patients with unilateral temporal lobe epilepsy (TLE), 60 with and 20 without hippocampal atrophy (TLE-HA and TLE-N, respectively), and for determining the presumed side of seizure onset. The framework employs multi-atlas segmentation to estimate the volumes of 83 brain structures. A kernel-based separability criterion was then used to identify structures whose volumes discriminate between the groups. Next, we applied support vector machines (SVM) to the selected set for classification on the basis of volumes. We also computed pairwise similarities between all subjects and used spectral analysis to convert these into per-subject features. SVM was again applied to these feature data. After training on a subgroup, all TLE-HA patients were correctly distinguished from controls, achieving an accuracy of 96 ± 2% in both classification schemes. For TLE-N patients, the accuracy was 86 ± 2% based on structural volumes and 91 ± 3% using spectral analysis. Structures discriminating between patients and controls were mainly localized ipsilaterally to the presumed seizure focus. For the TLE-HA group, they were mainly in the temporal lobe; for the TLE-N group they included orbitofrontal regions, as well as the ipsilateral substantia nigra. Correct lateralization of the presumed seizure onset zone was achieved using hippocampi and parahippocampal gyri in all TLE-HA patients using either classification scheme; in the TLE-N patients, lateralization was accurate based on structural volumes in 86 ± 4%, and in 94 ± 4% with the spectral analysis approach. Unilateral TLE has imaging features that can be identified automatically, even when they are invisible to human experts. Such morphometric image features may serve as classification and lateralization criteria. The technique also detects unsuspected distinguishing features like the substantia nigra, warranting further study

Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls-A Voxel Based Morphometry Study.

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender

Zebrafish brd2a and brd2b are paralogous members of the bromodomain-ET (BET) family of transcriptional coregulators that show structural and expression divergence

<p>Abstract</p> <p>Background</p> <p>Brd2 belongs to the bromodomain-extraterminal domain (BET) family of transcriptional co-regulators, and functions as a pivotal histone-directed recruitment scaffold in chromatin modification complexes affecting signal-dependent transcription. Brd2 facilitates expression of genes promoting proliferation and is implicated in apoptosis and in egg maturation and meiotic competence in mammals; it is also a susceptibility gene for juvenile myoclonic epilepsy (JME) in humans. The <it>brd2 </it>ortholog in <it>Drosophila </it>is a maternal effect, embryonic lethal gene that regulates several homeotic loci, including Ultrabithorax. Despite its importance, there are few systematic studies of <it>Brd2 </it>developmental expression in any organism. To help elucidate both conserved and novel gene functions, we cloned and characterized expression of <it>brd2 </it>cDNAs in zebrafish, a vertebrate system useful for genetic analysis of development and disease, and for study of the evolution of gene families and functional diversity in chordates.</p> <p>Results</p> <p>We identify cDNAs representing two paralogous <it>brd2 </it>loci in zebrafish, <it>brd2a </it>on chromosome 19 and <it>brd2b </it>on chromosome 16. By sequence similarity, syntenic and phylogenetic analyses, we present evidence for structural divergence of <it>brd2 </it>after gene duplication in fishes. <it>brd2 </it>paralogs show potential for modular domain combinations, and exhibit distinct RNA expression patterns throughout development. RNA <it>in situ </it>hybridizations in oocytes and embryos implicate <it>brd2a </it>and <it>brd2b </it>as maternal effect genes involved in egg polarity and egg to embryo transition, and as zygotic genes important for development of the vertebrate nervous system and for morphogenesis and differentiation of the digestive tract. Patterns of <it>brd2 </it>developmental expression in zebrafish are consistent with its proposed role in <it>Homeobox </it>gene regulation.</p> <p>Conclusion</p> <p>Expression profiles of zebrafish <it>brd2 </it>paralogs support a role in vertebrate developmental patterning and morphogenesis. Our study uncovers both maternal and zygotic contributions of <it>brd2</it>, the analysis of which may provide insight into the earliest events in vertebrate development, and the etiology of some forms of epilepsy, for which zebrafish is an important model. Knockdowns of <it>brd2 </it>paralogs in zebrafish may now test proposed function and interaction with homeotic loci in vertebrates, and help reveal the extent to which functional novelty or partitioning has occurred after gene duplication.</p

GABAergic Neuron Deficit As An Idiopathic Generalized Epilepsy Mechanism: The Role Of BRD2 Haploinsufficiency In Juvenile Myoclonic Epilepsy

Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/− mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/− males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/− female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/− vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/− mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/− mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE

Bi-hemispheric engagement in the retrieval of autobiographical episodes

Vandekerckhove MMP, Markowitsch HJ, Mertens M, Woermann FG. Bi-hemispheric engagement in the retrieval of autobiographical episodes. BEHAVIOURAL NEUROLOGY. 2005;16(4):203-210.Functional magnetic resonance imaging (fMRI) was used to study the neural correlates of neutral, stressful, negative and positive autobiographical memories. The brain activity produced by these different kinds of episodic memory did not differ significantly, but a common pattern of activation for different kinds of autobiographical memory was revealed that included (1) largely bilateral portions of the medial and superior temporal lobes, hippocampus and parahippocampus, (2) portions of the ventral, medial, superior and dorsolateral prefrontal cortex, (3) the anterior and posterior cingulate, including the retrosplenial, cortex, (4) the parietal cortex, and (5) portions of the cerebellum. The brain regions that were mainly activated constituted an interactive network of temporal and prefrontal areas associated with structures of the extended limbic system. The main bilateral activations with left-sided preponderance probably reflected reactivation of complex semantic and episodic self-related information representations that included previously experienced contexts. In conclusion, the earlier view of a strict left versus right prefrontal laterality in the retrieval of semantic as opposed to episodic autobiographical memory, may have to be modified by considering contextual variables such as task demands and subject variables. Consequently, autobiographical memory integration should be viewed as based on distributed bi-hemispheric neural networks supporting multi-modal, emotionally coloured components of personal episodes

In vivo short echo time H-1-magnetic resonance spectroscopic imaging (MRSI) of the temporal lobes

Two different methodologies for obtaining PRESS-localized magnetic resonance spectroscopic imaging (MRSI) data from the mesial and lateral temporal lobes were investigated. The study used short echo times (30 ms) and long repetition times (3000 ms) to minimize relaxation effects. Inhomogeneity and spectral distortions from the proximity of the temporal bones precluded the attainment of consistently good-quality data from both temporal lobes at once. Even when the right and left temporal lobes were studied separately, distortions often disturbed spectra from the anterior lateral temporal lobe. Quantitative analysis using LCModel was therefore performed only on the posterior lateral temporal lobe, and the posterior, middle, and anterior mesial temporal lobe. No significant left-right differences in metabolite content were found in a series of 10 controls. Significantly higher concentrations of myoinositol and choline were found in the anterior mesial temporal lobe, even when grey matter content was included as a covariate. The concentration of N-acetyl aspartate plus N-acetyl aspartyl glutamate (NAc) was not found to vary significantly along the length of the hippocampus. The previously observed lower anterior ratios of NAA to creatine plus choline (NAA/(Cr + Cho) may instead have been due to higher anterior choline. Large differences in metabolite concentrations were seen between posterior lateral temporal lobe (predominantly subcortical white matter) and the posterior mesial temporal lobe, most notably lower creatine, glutamate/glutamine, and myo-inositol, and higher NAA/(Cr + Cho) in the lateral than mesial temporal lobe. This pattern was similar to that previously seen for grey/white matter differences in the frontal, parietal and occipital regions. (C) 2001 Academic Press

Affective aggression in patients with temporal lobe epilepsy - A quantitative MRI study of the amygdala

Recurrent episodes with interictal affective aggression are a rare but well-recognized problem in patients with temporal lobe epilepsy. They are referred to as episodic dyscontrol or, more precisely, as intermittent explosive disorder (IED), The amygdala play a crucial role in the affective evaluation of multimodal sensory input and the neurobiological mediation of aggressive behaviour. With hippocampal sclerosis, in the context of mesial temporal lobe sclerosis, being the most common cause of temporal lobe epilepsy, me hypothesized that the amygdala might be affected by the same pathogenic process in aggressive patients. We investigated 50 patients with temporal lobe epilepsy: 25 with and 25 without a history of IED, Data from clinical, electrophysiological, neuropsychological and psychometric investigations were obtained, as well as MRI scans for the quantitative assessment of possible amygdala pathology. We found no evidence of a higher prevalence of amygdala sclerosis In the aggressive patients, Hippocampal sclerosis was significantly less common in patients with temporal lobe epilepsy and IED, However, a significant subgroup of patients (20%) with temporal lobe epilepsy and aggressive behaviour had severe amygdala atrophy in the context of a history of encephalitis, Another subgroup of aggressive patients (28%) had different left temporal lesions affecting either the amygdala or periamygdaloid structures, IED was associated with left-sided or bilateral EEG and MRI abnormalities, low IQ and high scores in depression and anxiety