Altered structural connectivity in patients with medial temporal lobe epilepsy: A Diffusion Spectrum Imaging and Graph Analysis study

In this study we investigated the effect of medial temporal lobe epilepsy (MTLE) on the global characteristics of brain connectivity estimated by topological measures. We used DSI (Diffusion Spectrum Imaging) to construct a connectivity matrix where the nodes represents the anatomical ROIs and the edges are the connections between any pair of ROIs weighted by the mean GFA/FA values. A significant difference was found between the patient group vs control group in characteristic path length, clustering coefficient and small-worldness. This suggests that the MTLE network is less efficient compared to the network of the control group.

Lateralization of olfactory processing: Differential impact of right and left temporal lobe epilepsies.

Olfactory processes were reported to be lateralized. The purpose of this study was to further explore this phenomenon and investigate the effect of the hemispheric localization of epileptogenic foci on olfactory deficits in patients with temporal lobe epilepsy (TLE). Olfactory functioning was assessed in 61 patients and 60 healthy control (HC) subjects. The patients and HC subjects were asked to rate the intensity, pleasantness, familiarity, and edibility of 12 common odorants and then identify them. Stimulations were delivered monorhinally in the nostril ipsilateral to the epileptogenic focus in TLE and arbitrarily in either the left or the right nostril in the HC subjects. The results demonstrated that regardless of the side of stimulation, patients with TLE had reduced performance in all olfactory tasks compared with the HC subjects. With regard to the side of the epileptogenic focus, patients with left TLE judged odors as less pleasant and had more difficulty with identification than patients with right TLE, underlining a privileged role of the left hemisphere in the emotional and semantic processing of odors. Finally, irrespective of group, a tendency towards a right-nostril advantage for judging odor familiarity was found in agreement with a prominent role of the right hemisphere in odor memory processing.

Emotionally negative stimuli can overcome attentional deficits in patients with visuo-spatial hemineglect.

Left unilateral spatial neglect resulting from right brain damage is characterized by loss of awareness for stimuli in the contralesional side of space, despite intact visual pathways. We examined using fMRI whether patients with neglect are more likely to consciously detect in the neglected hemifield, emotionally negative complex scenes rather than visually similar neutral pictures and if so, what neural mechanisms mediate this effect. Photographs of emotional and neutral scenes taken from the IAPS were presented in a divided visual field paradigm. As expected, the detection rate for emotional stimuli presented in the neglected field was higher than for neutral ones. Successful detection of emotional scenes as opposed to neutral stimuli in the left visual field (LVF) produced activations in the parahippocampal and anterior cingulate areas in the right hemisphere. Detection of emotional stimuli presented in the intact right visual field (RVF) activated a distributed network of structures in the left hemisphere, including anterior and posterior cingulate cortex, insula, as well as visual striate and extrastriate areas. LVF-RVF contrasts for emotional stimuli revealed activations in right and left attention related prefrontal areas whereas RVF-LVF comparison showed activations in the posterior cingulate and extrastriate visual cortex in the left hemisphere. An additional analysis contrasting detected vs. undetected emotional LVF stimuli showed involvement of left anterior cingulate, right frontal and extrastriate areas. We hypothesize that beneficial role of emotion in overcoming neglect is achieved by activation of frontal and limbic lobe networks, which provide a privileged access of emotional stimuli to attention by top-down modulation of processing in the higher-order extrastriate visual areas. Our results point to the importance of top-down regulatory role of the frontal attentional systems, which might enhance visual activations and lead to greater salience of emotional stimuli for perceptual awareness.

Chronic deep brain stimulation in mesial temporal lobe epilepsy.

The objective of this study was to evaluate the efficiency and the effects of changes in parameters of chronic amygdala-hippocampal deep brain stimulation (AH-DBS) in mesial temporal lobe epilepsy (TLE). Eight pharmacoresistant patients, not candidates for ablative surgery, received chronic AH-DBS (130 Hz, follow-up 12-24 months): two patients with hippocampal sclerosis (HS) and six patients with non-lesional mesial TLE (NLES). The effects of stepwise increases in intensity (0-Off to 2 V) and stimulation configuration (quadripolar and bipolar), on seizure frequency and neuropsychological performance were studied. The two HS patients obtained a significant decrease (65-75%) in seizure frequency with high voltage bipolar DBS (≥1 V) or with quadripolar stimulation. Two out of six NLES patients became seizure-free, one of them without stimulation, suggesting a microlesional effect. Two NLES patients experienced reductions of seizure frequency (65-70%), whereas the remaining two showed no significant seizure reduction. Neuropsychological evaluations showed reversible memory impairments in two patients under strong stimulation only. AH-DBS showed long-term efficiency in most of the TLE patients. It is a valuable treatment option for patients who suffer from drug resistant epilepsy and who are not candidates for resective surgery. The effects of changes in the stimulation parameters suggest that a large zone of stimulation would be required in HS patients, while a limited zone of stimulation or even a microlesional effect could be sufficient in NLES patients, for whom the importance of the proximity of the electrode to the epileptogenic zone remains to be studied. Further studies are required to ascertain these latter observations.

Psychogenic seizures and frontal disconnection: EEG synchronisation study.

Objective Psychogenic non-epileptic seizures (PNES) are paroxysmal events that, in contrast to epileptic seizures, are related to psychological causes without the presence of epileptiform EEG changes. Recent models suggest a multifactorial basis for PNES. A potentially paramount, but currently poorly understood factor is the interplay between psychiatric features and a specific vulnerability of the brain leading to a clinical picture that resembles epilepsy. Hypothesising that functional cerebral network abnormalities may predispose to the clinical phenotype, the authors undertook a characterisation of the functional connectivity in PNES patients. Methods The authors analysed the whole-head surface topography of multivariate phase synchronisation (MPS) in interictal high-density EEG of 13 PNES patients as compared with 13 age- and sex-matched controls. MPS mapping reduces the wealth of dynamic data obtained from high-density EEG to easily readable synchronisation maps, which provide an unbiased overview of any changes in functional connectivity associated with distributed cortical abnormalities. The authors computed MPS maps for both Laplacian and common-average-reference EEGs. Results In a between-group comparison, only patchy, non-uniform changes in MPS survived conservative statistical testing. However, against the background of these unimpressive group results, the authors found widespread inverse correlations between individual PNES frequency and MPS within the prefrontal and parietal cortices. Interpretation PNES appears to be associated with decreased prefrontal and parietal synchronisation, possibly reflecting dysfunction of networks within these regions.

Complete loss of vision caused by a giant mucocele of the frontal sinus.

The authors report the case of a 75-year-old man presenting with an exceptionally large giant posttraumatic mucocele of the frontal sinus years after a gunshot blast to the head. The lesion had grown so extensively that the right eye had shrunk and calcified, resulting in total monocular blindness, a complication that has been reported only once. To the best of our knowledge, it is the first time that a giant mucocele of such a large size is reported. We describe how the patient underwent surgical removal of this massive lesion, cranial base reconstruction, and a cosmetic oculoplastic procedure. The etiology, clinical presentation, and possible complications are reviewed, as well as the importance of a regular clinical follow-up and early surgical cure. Although the diagnosis and management of mucoceles are nowadays considered quite standard, the exceptional size of the lesion illustrated here emphasizes the destructive potential of such seemingly indolent lesions. Despite the benign histology of mucoceles, one should never underestimate their morbid potential or be lulled in delaying surgical cure. Large mucoceles should be removed as quickly as possible to prevent such unacceptable complications as permanent visual loss.

Prediction of functional outcome 18 months after a first psychotic episode: a proton magnetic resonance spectroscopy study.

CONTEXT: Recent magnetic resonance imaging studies have attempted to relate volumetric brain measurements in early schizophrenia to clinical and functional outcome some years later. These studies have generally been negative, perhaps because gray and white matter volumes inaccurately assess the underlying dysfunction that might be predictive of outcome. OBJECTIVE: To investigate the predictive value of frontal and temporal spectroscopy measures for outcome in patients with first-episode psychoses. DESIGN: Left prefrontal cortex and left mediotemporal lobe voxels were assessed using proton magnetic resonance spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline-containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio). These data were used to predict outcome at 18 months after admission, as assessed by a systematic medical record audit. SETTING: Early psychosis clinic. PARTICIPANTS: Forty-six patients with first-episode psychosis. MAIN OUTCOME MEASURES: We used regression models that included age at imaging and duration of untreated psychosis to predict outcome scores on the Global Assessment of Functioning Scale, Clinical Global Impression scales, and Social and Occupational Functional Assessment Scale, as well as the number of admissions during the treatment period. We then further considered the contributions of premorbid function and baseline level of negative symptoms. RESULTS: The only spectroscopic predictor of outcome was the NAA/Cr ratio in the prefrontal cortex. Low scores on this variable were related to poorer outcome on all measures. In addition, the frontal NAA/Cr ratio explained 17% to 30% of the variance in outcome. CONCLUSIONS: Prefrontal neuronal dysfunction is an inconsistent feature of early psychosis; rather, it is an early marker of poor prognosis across the first years of illness. The extent to which this can be used to guide treatment and whether it predicts outcome some years after first presentation are questions for further research.

Differences in Frontal Activation in Adult Patients with Schizophrenia and in Psychotic Adolescents with Schizophrenic Symptoms in Two Fmri Tasks

Background: Language processing abnormalities and inhibition difficulties are hallmark features of schizophrenia. The objective of this study is to asses the blood oxygenation level-dependent (BOLD) response at two different stages of the illness and compare the frontal activity between adolescents and adults with schizophrenia. Methods: 10 adults with schizophrenia (mean age 31,5 years) and 6 psychotic adolescents with schizophrenic symptoms (mean age 16,2 years) underwent functional magnetic resonance imaging while performing two frontal tasks. Regional activation is compared in the bilateral frontal areas during a covert verbal fluency task (letter version) and a Stroop task (inhibition task). Results: Preliminary results show poorer task performance and less frontal cortex activation during both tasks in the adult group of patients with schizophrenia. In the adolescent patients group, fMRI analysis show significant and larger activity in the left frontal operculum (Broca's area) in the verbal fluency task and greater activity in the medium cingulate during the inhibition phase of the Stroop task. Conclusions: These preliminary findings suggest a decrease of frontal activity in the course of the illness. We assume that schizophrenia contributes to frontal brain activity reduction.

Neuropsychological outcome after extra-temporal epilepsy surgery.

BACKGROUND: The neuropsychological results of temporal lobe epilepsy surgery are well reported in the literature. The aim of this study was to analyse the neuropsychological outcome in a consecutive series of patients with extra-temporal epilepsy. METHODS: We retrospectively analysed the data of patients operated between 1996 and 2008 for extra-temporal epilepsy. Standard neuropsychological tests were applied. We assessed the neuropsychological outcome after surgery and the correlation of the neuropsychological outcome with (1) side and localisation of surgery, (2) Engel scale for seizure outcome and (3) timing of surgery. FINDINGS: Patients had a better neuropsychological outcome when undergoing non-frontal resection [χ2 (2) =6.66, p = 0.036]. Subjects who had undergone left or right resection showed no difference in outcome [χ2 (2) =0.533, p = 0.766]. The correlation between the Engel scale for seizure re-occurence and the neuropsychological scores showed only a tendency for better outcome (Spearman ρ = -0.437; p = 0.069). The global measure of change did not correlate significantly with delay of surgery (Spearman ρ = -0.163; p = 0.518). CONCLUSIONS: Resective epilepsy surgery improves neuropsychological status outcome in patients with extra-temporal epilepsy even if the patient did not become seizure free. The outcome is better for non-frontal localisation.

Can postictal memory predict postoperative memory in patients with temporal lobe epilepsy?

We investigated the contribution of postictal memory testing for lateralizing the epileptic focus and predicting memory outcome after surgery for temporal lobe epilepsy (TLE). Forty-five patients with TLE underwent interictal, postictal, and postoperative assessment of verbal and nonverbal memory. Surgery consisted of anterior temporal lobectomy (36), selective isolated amygdalohippocampectomy (6), or amygdalohippocampectomy coupled to lesionectomy (3). Postictal and postoperative but not interictal memory were significantly lower in left TLE than in right TLE. Nonverbal memory showed no significant difference in left TLE versus right TLE in all conditions. Postictal memory was significantly correlated with postoperative memory, but the effect disappeared when the lateralization of the focus was considered. Postictal verbal memory is a useful bedside tool that can help lateralize the epileptic focus. Larger studies are needed to further estimate its predictive value of the postoperative outcome.

Cellular perspectives on the glutamate-monoamine interactions in limbic lobe structures and their relevance for some psychiatric disorders.

Dopaminergic, serotonergic and noradrenergic nuclei form the trimonoamine modulating system (TMMS). This system modulates emotional/motivational activities mediated by the limbic circuitry, where glutamate is the major excitatory neurotransmitter. Two main concepts are the basis of this review. First, since 1950 and the discovery of the antipsychotic activity of the dopamine D2 receptor antagonist chlorpromazine, it appears that drugs that can modulate the TMMS possess therapeutic psychiatric properties. Second, the concept of glutamate/trimonoamine imbalance in the cortico-striato-thalamo-cortical loop that has been so successful in explaining the pathophysiology of Parkinson disease has been applied in the pathophysiology of schizophrenia. This review will focus on the complex interactions between the fast synaptic glutamatergic transmission and the TMMS in specific parts of the limbic lobe and we will try to link these interactions to some psychiatric disorders, mainly depression, schizophrenia and drug addiction.

Brain Connectivity Analysis in Children. Effects of Prematurity. and Prenatal Growth Restriction

Introduction: Survival of children born prematurely or with very low birth weight has increased dramatically, but the long term developmental outcome remains unknown. Many children have deficits in cognitive capacities, in particular involving executive domains and those disabilities are likely to involve a central nervous system deficit. To understand their neurostructural origin, we use DTI. Structurally segregated and functionally regions of the cerebral cortex are interconnected by a dense network of axonal pathways. We noninvasively map these pathways across cortical hemispheres and construct normalized structural connection matrices derived from DTI MR tractography. Group comparisons of brain connectivity reveal significant changes in fiber density in case of children with poor intrauterine grown and extremely premature children (gestational age<28 weeks at birth) compared to control subjects. This changes suggest a link between cortico-axonal pathways and the central nervous system deficit. Methods: Sixty premature born infants (5-6 years old) were scanned on clinical 3T scanner (Magnetom Trio, Siemens Medical Solutions, Erlangen, Germany) at two hospitals (HUG, Geneva and CHUV, Lausanne). For each subject, T1-weighted MPRAGE images (TR/TE=2500/2.91,TI=1100, resolution=1x1x1mm, matrix=256x154) and DTI images (30 directions, TR/TE=10200/107, in-plane resolution=1.8x1.8x2mm, 64 axial, matrix=112x112) were acquired. Parent(s) provided written consent on prior ethical board approval. The extraction of the Whole Brain Structural Connectivity Matrix was performed following (Cammoun, 2009 and Hagmann, 2008). The MPARGE images were registered using an affine registration to the non-weighted-DTI and WM-GM segmentation performed on it. In order to have equal anatomical localization among subjects, 66 cortical regions with anatomical landmarks were created using the curvature information, i.e. sulcus and gyrus (Cammoun et al, 2007; Fischl et al, 2004; Desikan et al, 2006) with freesurfer software (http://surfer.nmr.mgh.harvard.edu/). Tractography was performed in WM using an algorithm especially designed for DTI/DSI data (Hagmann et al., 2007) and both information were then combined in a matrix. Each row and column of the matrix corresponds to a particular ROI. Each cell of index (i,j) represents the fiber density of the bundle connecting the ROIs i and j. Subdividing each cortical region, we obtained 4 Connectivity Matrices of different resolution (33, 66, 125 and 250 ROI/hemisphere) for each subject . Subjects were sorted in 3 different groups, namely (1) control, (2) Intrauterine Growth Restriction (IUGR), (3) Extreme Prematurity (EP), depending on their gestational age, weight and percentile-weight score at birth. Group-to-group comparisons were performed between groups (1)-(2) and (1)-(3). The mean age at examination of the three groups were similar. Results: Quantitative analysis were performed between groups to determine fibers density differences. For each group, a mean connectivity matrix with 33ROI/hemisphere resolution was computed. On the other hand, for all matrix resolutions (33,66,125,250 ROI/hemisphere), the number of bundles were computed and averaged. As seen in figure 1, EP and IUGR subjects present an overall reduction of fibers density in both interhemispherical and intrahemispherical connections. This is given quantitatively in table 1. IUGR subjects presents a higher percentage of missing fiber bundles than EP when compared to control subjects (~16% against 11%). When comparing both groups to control subjects, for the EP subjects, the occipito-parietal regions seem less interhemispherically connected whilst the intrahemispherical networks present lack of fiber density in the lymbic system. Children born with IUGR, have similar reductions in interhemispherical connections than the EP. However, the cuneus and precuneus connections with the precentral and paracentral lobe are even lower than in the case of the EP. For the intrahemispherical connections the IUGR group preset a loss of fiber density between the deep gray matter structures (striatum) and the frontal and middlefrontal poles, connections typically involved in the control of executive functions. For the qualitative analysis, a t-test comparing number of bundles (p-value<0.05) gave some preliminary significant results (figure 2). Again, even if both IUGR and EP appear to have significantly less connections comparing to the control subjects, the IUGR cohort seems to present a higher lack of fiber density specially relying the cuneus, precuneus and parietal areas. In terms of fiber density, preliminary Wilcoxon tests seem to validate the hypothesis set by the previous analysis. Conclusions: The goal of this study was to determine the effect of extreme prematurity and poor intrauterine growth on neurostructural development at the age of 6 years-old. This data indicates that differences in connectivity may well be the basis for the neurostructural and neuropsychological deficit described in these populations in the absence of overt brain lesions (Inder TE, 2005; Borradori-Tolsa, 2004; Dubois, 2008). Indeed, we suggest that IUGR and prematurity leads to alteration of connectivity between brain structures, especially in occipito-parietal and frontal lobes for EP and frontal and middletemporal poles for IUGR. Overall, IUGR children have a higher loss of connectivity in the overall connectivity matrix than EP children. In both cases, the localized alteration of connectivity suggests a direct link between cortico-axonal pathways and the central nervous system deficit. Our next step is to link these connectivity alterations to the performance in executive function tests.

Deficit in memory consolidation (abnormal forgetting rate) in childhood temporal lobe epilepsy. Pre and postoperative long-term observation.

Deficits in memory consolidation have been reported in adult patients with epilepsy but, not to our knowledge, in children. We report the long-term follow-up (9 y. o. to 18 y. o.) of a boy who suffered from temporal lobe epilepsy and underwent a left temporal lobectomy with amygdalo-hippocampal resection at the age of 10. He showed an abnormal forgetting rate when trying to encode new information and a significant deficit for retrieving remote episodic memories (when compared with his twin brother), both consistent with a consolidation disorder. His memory condition slightly improved after cessation of the epilepsy, nevertheless did not normalize. No standard memory assessment could pinpoint his memory problem, hence an adapted methodology was needed. We discuss the nature of the memory deficit, its possible causes and its clinical implications.

Flujos de detritos recientes en la cordillera frontal de Mendoza: Un ejemplo de riesgo natural en la ruta 7 = Recent debris flows in the Frontal Cordillera of Mendoza: An example of natural risk on the Road 7

In this paper is presented a study dealing with the debris flows that reached the national road 7 in January 2005, in the km 1,118.5, Mendoza province. The area is located in the Frontal Cordillera near the limit of the Precordillera. A detailed geomorphologic map has been realized for this study using a Quickbird satellite imagery of the year 2006. Various calculations of volumes, velocities and peak discharges have been performed with the field data and using a geographic information system (GIS). The geomorphologic survey has permitted to propose three propagation scenarios in case of a new event. These allowed creating a map of debris flows susceptibility for the stretch of the road that has been studied. Finally, it has been proposed protection and mitigation measures, based on the results of the study, to protect the road from a new event.