Viviane Bouilleret

Can structural or functional changes following traumatic brain injury in the rat predict epileptic outcome

Posttraumatic epilepsy (PTE) occurs in a proportion of traumatic brain injury (TBI) cases, significantly compounding the disability, and risk of injury and death for sufferers. To date, predictive biomarkers for PTE have not been identified. This study used the lateral fluid percussion injury (LFPI) rat model of TBI to investigate whether structural, functional, and behavioral changes post‐TBI relate to the later development of PTE.

Progressive Metabolic and Structural Cerebral Perturbations After Traumatic Brain Injury: An In Vivo Imaging Study in the Rat

Traumatic brain injury (TBI) has a high incidence of long-term neurologic and neuropsychiatric morbidity. Metabolic and structural changes in rat brains were assessed after TBI using serial 18F-FDG PET and 3-dimensional MRI in vivo. Methods: Rats underwent lateral fluid percussion injury (FPI; n = 16) or a sham procedure (n = 11). PET and MR images were acquired at 1 wk and at 1, 3, and 6 mo after injury. Morphologic changes were assessed using MRI-based regions of interest, and hippocampal shape changes were assessed with large-deformation high-dimensional mapping. Metabolic changes were assessed using region-of-interest analysis and statistical parametric mapping with the flexible factorial analysis. Anxiety-like behavior and learning were assessed at 1, 3, and 6 mo after injury. Results: PET analyses showed widespread hypometabolism in injured rats, in particular involving the ipsilateral cortex, hippocampus, and amygdalae, present at 1 wk after FPI, most prominent at 1 mo, and then decreasing. Compared with the sham group, rats in the FPI group had decreased structural volume which progressively increased over 3–6 mo, occurring in the ipsilateral cortex, hippocampus, and ventricles after FPI (P < 0.05). Large-deformation high-dimensional mapping showed evolving hippocampal shape changes across the 6 mo after FPI. Injured rats displayed increased anxiety-like behavior (P < 0.05), but there were no direct correlations between the severity of the behavior abnormalities and functional or structural imaging changes. Conclusion: In selected brain structures, FPI induces early hypometabolism and delayed progressive atrophic changes that are dynamic and continue to evolve for months. These findings have implications for the understanding of the pathophysiology and evolution of long-term neurologic morbidity following TBI, and indicate an extended window for targeted neuroprotective interventions.

Dystonic posturing in seizures of mesial temporal origin: Electroclinical and metabolic patterns

Objective: To test the hypothesis that extratemporal neuronal networks are involved in dystonic posturing (DP) observed in mesial temporal epilepsy (MTLE). Methods: The authors analyzed electroclinical findings in 36 patients with MTLE with or without DP. Three DP types were defined (types I, II, III) corresponding to a gradual increase in duration and complexity. Interictal [18F]fluorodeoxyglucose-PET in different groups and subgroups was compared with control subjects using statistical parametric mapping software (SPM99). Results: DP was found in 20 patients (55%), contralateral to the epileptogenic focus in 95%. Patients with DP had longer seizure duration, higher frequency of head deviation, salivation, motor manifestations, secondary generalization, severe clouding of consciousness, and prolonged postictal confusion when compared with patients without DP. Ictal discharge patterns during DP consisted of fast rhythmic activity spreading to frontal or suprasylvian areas, whereas slow rhythmic activity restricted to the temporal areas occurred in the absence of DP. In patients with DP, widespread temporal and extratemporal hypometabolism including the putamen was found. Hypometabolism was restricted to the anteromesial part of the temporal lobe and anterior insula in patients without DP. Putaminal hypometabolism was found in all DP types, but different extratemporal cortical involvements were found in DP subgroups: insula and inferior frontal gyrus in type I, inferior and superior frontal gyri and anterior cingulate gyrus in type II, and parietal areas in type III. Conclusion: Dystonic posturing may result from involvement of both putaminal and extratemporal cortical areas. Moreover, different frontal or parietal networks may be involved according to the duration or complexity of dystonic posturing.

Morphometric abnormalities and hyperanxiety in genetically epileptic rats: A model of psychiatric comorbidity?

BACKGROUND Imaging studies of epilepsy patients with comorbid affective disturbance demonstrate morphometric changes in limbic brain regions implicated in psychiatric disease. Genetic Absence Epilepsy Rats from Strasbourg (GAERS), specifically bred for their epilepsy phenotype, also exhibit elevated anxiety-like behaviors suggesting a common causality. Here we examined whether relevant cerebral morphological alterations exist in this rat strain using volumetric measurements and large deformation high dimensional mapping (HDM-LD), a tool recently validated to produce accurate three-dimensional surface representations of the hippocampus. METHODS Volumetric MRI and the Open Field test of anxiety were performed in adult female GAERS (n=12) and Non-Epileptic Controls (NEC; n=11). The volumes of selected brain regions, including cortex, hippocampus, amygdala, thalamus, hypothalamus and lateral ventricles, were measured using Region-Of-Interest analysis from the MRI data and total volumes compared between the two strains. RESULTS GAERS had increased amygdala (right: p=0.003; left p<0.001), cortices (right: p=0.006; left p=0.012) and ventricular volumes (p=0.002) when compared with NEC rats. Further, HDM-LD showed GAERS to have hippocampal volume loss in two regions: the medial hippocampal surface immediately caudal to the hippocampal commissure, and the lateral hippocampal surface over the mid-portion of the septotemporal axis. GAERS exhibited increased anxiety in the Open Field compared with NEC rats: reduced distance traveled (p<0.001) and reduced time in the centre area (p=0.042). CONCLUSIONS Morphometric brain changes in GAERS could be relevant to their hyperanxious and epileptic phenotypes. This model may be useful in illuminating the pathogenesis of affective disorders generally, as well as modeling psychiatric comorbidities of epilepsy.

Progressive Brain Changes on Serial Manganese-Enhanced MRI following Traumatic Brain Injury in the Rat

Traumatic brain injury (TBI) has a high incidence of long-term morbidity. Manganese-enhanced MRI (MEMRI) provides high contrast structural and functional detail of the brain in-vivo. The study utilized serial MEMRI scanning in the fluid percussion injury (FPI) rats model to assess long-term changes in the brain following TBI. Rats underwent a left-sided craniotomy and a 3.5 atmosphere FPI pulse (n = 23) or sham procedure (n = 22). MEMRI acquisition was performed at baseline, 1 day, 1 month, and 6 months after FPI. Volume changes and MnCl(2) enhancement were measured blindly using region-of-interest analysis and the results analyzed with repeated measures MANOVA. Compared to the shams, FPI animals showed a progressive decrease in brain volume from 1 (right, p = 0.02; left, p = 0.008) to 6 months (right, p = 0.04; left, p = 0.006), with progression over time (F = 7.16, p = 0.00018). Similar changes were found in the cortex and the hippocampus. Conversely, the ventricular volume was increased at 1 (p = 0.02) and 6 months (p = 0.003), with progression over time (F = 7.27, p = 0.0001). There were no differences in thalamic or amygdalae volumes. The severity of the early neuromotor deficits and the T2 signal intensity of the subacute focal lesion were highly predictive of the severity of the long-term hippocampal decrease, and the former was also associated with the degree of neuronal sprouting. Differential MnCl(2) enhancement occurred only in the dentate gyrus at 1 month on the side of trauma (p = 0.04). Progressive functional and structural changes occur in specific brain regions post-FPI. The severity of the neuromotor deficit and focal signal changes on MRI subacutely post-injury are predictive of severity of these long-term neurodegenerative changes.

Optimizing statistical parametric mapping analysis of 18F-FDG PET in children

BackgroundStatistical parametric mapping (SPM) procedure is an objective tool to analyze 18F-fluoro-2-deoxy-d-glucose-positron-emission tomography (FDG-PET) images and a useful complement to visual analysis. However, SPM requires a comparison to control data set that cannot be obtained in healthy children for ethical reasons. Using adults as controls showed some limitations. The purpose of the present study was to generate and validate a group of pseudo-normal children as a control group for FDG-PET studies in pediatrics.MethodsFDG-PET images of 47 children (mean ± SD age 10.2 ± 3.1 years) with refractory symptomatic (MRI-positive, n = 20) and cryptogenic (MRI-negative, n = 27) focal epilepsy planned for surgery were analyzed using visual and SPM analysis. Performances of SPM analysis were compared using two different control groups: (1) an adult control group consisting of healthy young adults (n = 25, 30.5 ± 5.8 years, adult PET template) and (2) a pediatric pseudo-control group consisting of patients (n = 24, 10.6 ± 3.1 years, children PET template) with refractory focal epilepsy but with negative MRI and with PET considered normal not only on visual analysis but also on SPM.ResultsAmong the 47 children, visual analysis succeeded detecting at least one hypometabolic area in 87% of the cases (interobserver kappa = 0.81). Regarding SPM analysis, the best compromise between sensitivity and specificity was obtained with a threshold of p less than 0.001 as an extent of more than 40 voxels. There was a significant concordance to detect hypometabolic areas between both SPM analyses [kappa (K) = 0.59; p < 0.005] and between both SPM and visual analyses (K = 0.45; p < 0.005), in symptomatic (K = 0.74; p < 0.005) as in cryptogenic patients (K = 0.26; p < 0.01). The pediatric pseudo-control group dramatically improved specificity (97% vs. 89%; p < 0.0001) by increasing the positive predictive value (86% vs. 65%). Sensitivity remained acceptable although it was not better (79% vs. 87%, p = 0.039). The main impact was to reduce by 41% the number of hypometabolic cortical artifacts detected by SPM, especially in the younger epileptic patients, which is a key point in clinical practice.ConclusionsThis age-matched pseudo-control group is a way to optimize SPM analysis of FDG-PET in children with epilepsy. It might also be considered for other brain pathologies in pediatrics in the future.

18F-FDG PET Reveals Frontotemporal Dysfunction in Children with Fever-Induced Refractory Epileptic Encephalopathy

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a recently described epileptic entity whose etiology remains unknown. Brain abnormalities shown by MRI are usually limited to mesial-temporal structures and do not account for the catastrophic neuropsychologic findings. Methods: We conducted FIRES studies in 8 patients, aged 6–13 y, using 18F-FDG PET to disclose eventual neocortical dysfunction. Voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping and an age-matched control group. Results: Group analysis revealed a widespread interictal hypometabolic network including the temporoparietal and orbitofrontal cortices bilaterally. The individual analyses in patients identified hypometabolic areas corresponding to the predominant electroencephalograph foci and neuropsychologic deficits involving language, behavior, and memory. Conclusion: Despite clinical heterogeneity, 18F-FDG PET reveals a common network dysfunction in patients with sequelae due to fever-induced refractory epileptic encephalopathy.

Diffusion tensor imaging tractography parameters of limbic system bundles in temporal lobe epilepsy patients.

To investigate changes in diffusion tensor imaging (DTI) measures in limbic system white matter of patients with temporal lobe epilepsy (TLE) using diffusion tensor tractography.

Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults

To examine the long‐term consequences of manganese exposure due to the use of manganese‐enhanced magnetic resonance imaging (MEMRI) in a model of closed head injury, the fluid‐percussion injury (FPI) model.

Sudden and isolated Broca's aphasia: A new clinical phenotype of anti NMDA receptor antibodies encephalitis in children

BACKGROUND Anti NMDA receptor (anti NMDAR) encephalitis is a well-characterized entity in children associating movement disorders, psychiatric features and speech difficulties. Novel phenotypes have been described in adults. METHODS AND RESULTS A 4-year-old girl presented partial seizures which evolved towards sudden and isolated Brocas aphasia. Anti NMDAR antibodies were positive in CSF and serum confirming anti NMDAR encephalitis. Clinical recovery was observed after a specific treatment. CONCLUSION This case widens the clinical spectrum of anti-NMDAR encephalitis in children and awareness of this newly identified symptom is important as early treatment is a predictor of good outcome.