Sophie Dupont

Pure alexia as a disconnection syndrome: New diffusion imaging evidence for an old concept

Functional neuroimaging and studies of brain-damaged patients made it possible to delineate the main components of the cerebral system for word reading. However, the anatomical connections subtending the flow of information within this network are still poorly defined. Here we study the connectivity of the Visual Word Form Area (VWFA), a pivotal component of the reading network achieving the invariant identification of letter strings, and reproducibly located in the left lateral occipitotemporal sulcus. Diffusion images and functional imaging data were gathered in a patient who developed pure alexia following a small surgical lesion in the vicinity of his VWFA. We had a unique opportunity to compare images obtained before, early after, and late after surgery. Analysis of diffusion images with white matter tractography and voxel-based morphometry showed that the VWFA was mainly linked to the occipital cortex through the inferior longitudinal fasciculus (ILF), and to perisylvian language areas (supramarginal gyrus) through the arcuate fasciculus. After surgery, we observed the progressive and selective degeneration of the ILF, while the VWFA was anatomically intact. This allowed us to establish the critical causal role of this fiber tract in normal reading, and to show that its disruption is one pathophysiological mechanism of pure alexia, thus clarifying a long-standing debate on the role of disconnection in neurocognitive disorders.

Diffusion tensor imaging in medial temporal lobe epilepsy with hippocampal sclerosis

Interictal diffusion imaging studies in patients with medial temporal lobe epilepsy (MTLE) accompanied by hippocampal sclerosis (HS) have shown an increased diffusivity in the epileptogenic hippocampus. In this study, we wanted to explore the whole brain in order to determine if MTLE could have an impact on the organization and the architecture of a large cerebral network and to identify clinical factors that could mediate diffusion abnormalities. Diffusion tensor imaging (DTI) and statistical parametric mapping of the entire brain were performed in 35 well-defined MTLE patients and in 36 healthy volunteers. SPM analyses identified three abnormal areas: an increased diffusivity was detected in the epileptic hippocampus and the ipsilateral temporal structures associated with a decreased anisotropy along the temporal lobe, a decreased diffusivity was found in the contralateral non-sclerotic hippocampus, the amygdala, and the temporal pole, and finally, a decreased anisotropy was noted ipsilaterally in posterior extratemporal regions. Duration of epilepsy, age at onset, and the frequency of generalized tonic-clonic seizures or partial complex seizures did not correlate with the presence of diffusion abnormalities. Region of interest analysis in the hippocampus/parahippocampus demonstrated a correlation between lower ipsilateral diffusivity values and occurrence of epigastric aura and between higher anisotropy values in both hemispheres and history of febrile seizures. In conclusion, this study showed that diffusion abnormalities are not restricted to the pathologic hippocampus and involve a larger network. This pattern may indirectly reflect the epileptogenic network and may be interpreted as a cause or a consequence of epilepsy.

Productive and perceptive language reorganization in temporal lobe epilepsy.

The aim of this work was to determine whether productive and perceptive language functions are differentially affected in homogeneous groups of epilepsy patients with right and left temporal lobe epilepsy (TLE). Eighteen patients with left TLE, 18 with right TLE, and 17 healthy volunteers were studied using fMRI during performance of three tasks assessing the productive and perceptive aspects of language (covert semantic verbal fluency, covert sentence repetition, and story listening). Hemispheric dominance for language was calculated in the frontal and temporal regions using laterality indices (LI). Atypical lateralization was defined as a right-sided LI (LI<-0.20) in the frontal lobes during the verbal fluency task or in the temporal lobes during the story listening task. Control subjects and right TLE patients demonstrated a strong left lateralization for language in the frontal lobes during the fluency task, whereas activation was less lateralized to the left hemisphere in left TLE patients, although the difference did not reach significance. In the story listening and the repetition tasks, activation was significantly more right sided in the temporal lobes of patients with left TLE. Atypical language representation was found in 19% of TLE patients (five left and two right TLE). The shift toward the right hemisphere was significantly larger in the temporal than the frontal lobes in patients with atypical language lateralization compared to TLE patients with a typical language lateralization. Neuropsychological performances of patients with atypical language patterns were better than those of patients with typical patterns, suggesting that this reorganization may represent a compensatory mechanism.

Long-term Prognosis and Psychosocial Outcomes after Surgery for MTLE

Summary:  Purpose: To assess the seizure‐freedom rates and self‐perceived psychosocial changes associated with the long‐term outcome of epilepsy surgery in patients with refractory medial temporal lobe epilepsy associated with hippocampal sclerosis.

Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study

Somesthetic and emotional symptoms that are common in patients with mesial temporal lobe epilepsy are usually related to hippocampo‐amygdalar complex involvement. Recent stereo‐electroencephalographic studies have shown a relationship between such symptoms and epileptic insular discharges. To further investigate this problem, we carried out a positron emission tomography study using fluorodeoxyglucose (18F‐FDG) and flumazenil (11C‐FMZ) in mesial temporal lobe epilepsy patients. The aim of our study was to assess the existence of a cortical insular involvement in order to examine its clinical correlates and the relationship between the postoperative outcome and the insular involvement. Fluorodeoxyglucose and flumazenil‐positron emission tomography studies were carried out in 18 patients with mesial temporal lobe epilepsy patients. A statistical parametric mapping (SPM96) was performed to analyze the data in comparison to 18 healthy volunteers. For each set of fluorodeoxyglucose and flumazenil images a group and an individual analysis were performed. In addition, a region of interest analysis was performed to validate the results. Focusing on the metabolic abnormalities, we also investigated the role of insular cortex in the symptoms experienced by the patients and the prognostic value of insular metabolic abnormalities. Highly significant hypometabolism and BZR binding decreases were detected in the insular cortex. Results were similar using the region of interest approach. Insular involvement (mainly ipsilateral to the seizure focus) was present in 60% of the patients. Emotional symptoms correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, whereas somesthetic symptoms correlated with hypometabolism in the posterior part. No relationship between postoperative outcome and ipsilateral insular hypometabolism was found. Unilateral mesial temporal lobe epilepsy is associated with insular hypometabolism and benzodiazepine receptor loss. Our results also suggest that the anterior part of the insular cortex is involved in the emotional symptoms and the posterior insular cortex is involved in the somesthetic symptoms. Hypometabolism located in the insula did not influence postoperative outcome after anterior lobectomy.

The underlying pathophysiology of ictal dystonia in temporal lobe epilepsy An FDG-PET study

Background: Unilateral dystonic posturing of limbs occurs frequently in medial temporal lobe epilepsy (MTLE) but its underlying anatomic basis is still unknown. Objective: To investigate the pathophysiology of dystonic posturing, we examined the relation between the occurrence of dystonia and interictal cerebral metabolic abnormalities using fluorodeoxyglucose (FDG)-PET in MTLE patients. Methods: Video recordings of 30 patients with documented MTLE were reviewed to assess the presence of ictal dystonic posturing. Interictal FDG-PET was performed in all patients. Results: Eighteen patients exhibited dystonic posturing-contralateral to the seizure focus in 16 cases, bilateral in one, and ipsilateral in one. Dystonia was statistically associated with more severe hypometabolism in the striatal and in the orbitofrontal regions ipsilateral to the seizure focus. Conclusion: Hypometabolism observed in the striatal region of patients with ictal dystonic posturing suggests that the basal ganglia are involved in the generation of ictal dystonic posturing in MTLE.

Structural connectivity differences in left and right temporal lobe epilepsy.

Our knowledge on temporal lobe epilepsy (TLE) with hippocampal sclerosis has evolved towards the view that this syndrome affects widespread brain networks. Diffusion weighted imaging studies have shown alterations of large white matter tracts, most notably in left temporal lobe epilepsy, but the degree of altered connections between cortical and subcortical structures remains to be clarified. We performed a whole brain connectome analysis in 39 patients with refractory temporal lobe epilepsy and unilateral hippocampal sclerosis (20 right and 19 left) and 28 healthy subjects. We performed whole-brain probabilistic fiber tracking using MRtrix and segmented 164 cortical and subcortical structures with Freesurfer. Individual structural connectivity graphs based on these 164 nodes were computed by mapping the mean fractional anisotropy (FA) onto each tract. Connectomes were then compared using two complementary methods: permutation tests for pair-wise connections and Network Based Statistics to probe for differences in large network components. Comparison of pair-wise connections revealed a marked reduction of connectivity between left TLE patients and controls, which was strongly lateralized to the ipsilateral temporal lobe. Specifically, infero-lateral cortex and temporal pole were strongly affected, and so was the perisylvian cortex. In contrast, for right TLE, focal connectivity loss was much less pronounced and restricted to bilateral limbic structures and right temporal cortex. Analysis of large network components revealed furthermore that both left and right hippocampal sclerosis affected diffuse global and interhemispheric connectivity. Thus, left temporal lobe epilepsy was associated with a much more pronounced pattern of reduced FA, that included major landmarks of perisylvian language circuitry. These distinct patterns of connectivity associated with unilateral hippocampal sclerosis show how a focal pathology influences global network architecture, and how left or right-sided lesions may have differential and specific impacts on cerebral connectivity.

Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome

Background Mutations in SCN1A can cause genetic epilepsy with febrile seizures plus (GEFS+, inherited missense mutations) or Dravet syndrome (DS, de novo mutations of all types). Although the mutational spectra are distinct, these disorders share major features and 10% of DS patients have an inherited SCN1A mutation. Objectives and patients 19 selected families with at least one DS patient were studied to describe the mechanisms accounting for inherited SCN1A mutations in DS. The mutation identified in the DS probands was searched in available parents and relatives and quantified in the blood cells of the transmitting parent using quantitative allele specific assays. Results Mosaicism in the blood cells of the transmitting parent was demonstrated in 12 cases and suspected in another case. The proportion of mutated allele in the blood varied from 0.04–85%. In the six remaining families, six novel missense mutations were associated with autosomal dominant variable GEFS+ phenotypes including DS as the more severe clinical picture. Conclusion The results indicate that mosaicism is found in at least 7% of families with DS. In the remaining cases (6/19, 32%), the patients were part of multiplex GEFS+ families and seemed to represent the extreme end of the GEFS+ clinical spectrum. In this latter case, additional genetic or environmental factors likely modulate the severity of the expression of the mutation.

Levetiracetam in progressive myoclonic epilepsy An exploratory study in 9 patients

The authors conducted an open study of levetiracetam as add-on therapy in nine patients with well-defined progressive myoclonic epilepsies and refractory myoclonus. Myoclonus was evaluated semiquantitatively (territory, intensity, daily living activities). Five patients had improvement of their myoclonus score. Levetiracetam may benefit myoclonus in progressive myoclonic epilepsy.

Bilateral hemispheric alteration of memory processes in right medial temporal lobe epilepsy

Objective: Functional MRI (fMRI ) was used to investigate right medial temporal lobe epilepsy (RTLE) effects on verbal memory. Methods: BOLD fMRI data were collected from seven right sided MTLE patients (RTLE) and compared with the data previously acquired from seven left sided MTLE patients (LTLE) and 10 control subjects. Twenty two contiguous images covering the whole brain were acquired using an EPI echoplanar sequence. Subjects were instructed to learn a list of 17 words, and to recall it immediately and at 24 hours interval. Group analyses were performed using SPM96. Results: RTLE patients retrieval performances were significantly impaired as compared with the performance of control subjects. As compared with control subjects and LTLE patients, RTLE patients exhibited a different pattern of hemispheric activations and a global decrease in left hemisphere functional activity. Conclusion: MTLE cannot be considered as a model of pure well lateralised hippocampal dysfunction. The verbal memory impairment depicted in RTLE patients may be considered as the witness of a bilateral impairment of the neuroanatomical circuits subserving memory.