S Bonelli

Voxel-based diffusion tensor imaging in patients with mesial temporal lobe epilepsy and hippocampal sclerosis

BACKGROUND Mesial temporal lobe epilepsy (mTLE) with hippocampus sclerosis (HS) is an important cause for focal epilepsy. In this study, we explored the integrity of connecting networks using diffusion tensor imaging (DTI) and two whole-brain voxel-based methods: statistical parametric mapping (SPM) and tract-based spatial statistics (TBSS). METHODS Thirty-three consecutive patients with mTLE and HS undergoing presurgical evaluation were scanned at 3 T, a DTI data set was acquired and parametric maps of fractional anisotropy (FA) and mean diffusivity (MD) were calculated. Twenty-one patients had left hippocampal sclerosis (LHS) and 12 patients had right HS (RHS). These groups were compared to 37 normal control subjects using both SPM5 and TBSS. RESULTS The ipsilateral temporal lobe showed widespread FA reduction in both groups. The limbic system was clearly abnormal in the LHS group, also involving the arcuate fasciculus. In RHS, changes were more restricted but also showed involvement of the contralateral temporal and inferior frontal lobe. Increased MD was found in the ipsilateral hippocampus by SPM that was only marginally detected by TBSS. In white matter regions, however, TBSS was more sensitive to changes than SPM. CONCLUSION DTI detects extensive changes in mTLE with HS. The affected networks were principally in the ipsilateral temporal lobe and the limbic system but also the arcuate fasciculus. SPM and TBSS gave complementary information with higher sensitivity to FA changes using TBSS.

Imaging memory in temporal lobe epilepsy: predicting the effects of temporal lobe resection

Functional magnetic resonance imaging can demonstrate the functional anatomy of cognitive processes. In patients with refractory temporal lobe epilepsy, evaluation of preoperative verbal and visual memory function is important as anterior temporal lobe resections may result in material specific memory impairment, typically verbal memory decline following left and visual memory decline after right anterior temporal lobe resection. This study aimed to investigate reorganization of memory functions in temporal lobe epilepsy and to determine whether preoperative memory functional magnetic resonance imaging may predict memory changes following anterior temporal lobe resection. We studied 72 patients with unilateral medial temporal lobe epilepsy (41 left) and 20 healthy controls. A functional magnetic resonance imaging memory encoding paradigm for pictures, words and faces was used testing verbal and visual memory in a single scanning session on a 3T magnetic resonance imaging scanner. Fifty-four patients subsequently underwent left (29) or right (25) anterior temporal lobe resection. Verbal and design learning were assessed before and 4 months after surgery. Event-related functional magnetic resonance imaging analysis revealed that in left temporal lobe epilepsy, greater left hippocampal activation for word encoding correlated with better verbal memory. In right temporal lobe epilepsy, greater right hippocampal activation for face encoding correlated with better visual memory. In left temporal lobe epilepsy, greater left than right anterior hippocampal activation on word encoding correlated with greater verbal memory decline after left anterior temporal lobe resection, while greater left than right posterior hippocampal activation correlated with better postoperative verbal memory outcome. In right temporal lobe epilepsy, greater right than left anterior hippocampal functional magnetic resonance imaging activation on face encoding predicted greater visual memory decline after right anterior temporal lobe resection, while greater right than left posterior hippocampal activation correlated with better visual memory outcome. Stepwise linear regression identified asymmetry of activation for encoding words and faces in the ipsilateral anterior medial temporal lobe as strongest predictors for postoperative verbal and visual memory decline. Activation asymmetry, language lateralization and performance on preoperative neuropsychological tests predicted clinically significant verbal memory decline in all patients who underwent left anterior temporal lobe resection, but were less able to predict visual memory decline after right anterior temporal lobe resection. Preoperative memory functional magnetic resonance imaging was the strongest predictor of verbal and visual memory decline following anterior temporal lobe resection. Preoperatively, verbal and visual memory function utilized the damaged, ipsilateral hippocampus and also the contralateral hippocampus. Memory function in the ipsilateral posterior hippocampus may contribute to better preservation of memory after surgery.

Defining Meyer's loop–temporal lobe resections, visual field deficits and diffusion tensor tractography

Anterior temporal lobe resection is often complicated by superior quadrantic visual field deficits (VFDs). In some cases this can be severe enough to prohibit driving, even if a patient is free of seizures. These deficits are caused by damage to Meyers loop of the optic radiation, which shows considerable heterogeneity in its anterior extent. This structure cannot be distinguished using clinical magnetic resonance imaging sequences. Diffusion tensor tractography is an advanced magnetic resonance imaging technique that enables the parcellation of white matter. Using seed voxels antero-lateral to the lateral geniculate nucleus, we applied this technique to 20 control subjects, and 21 postoperative patients. All patients had visual fields assessed with Goldmann perimetry at least three months after surgery. We measured the distance from the tip of Meyers loop to the temporal pole and horn in all subjects. In addition, we measured the size of temporal lobe resection using postoperative T1-weighted images, and quantified VFDs. Nine patients suffered VFDs ranging from 22% to 87% of the contralateral superior quadrant. In patients, the range of distance from the tip of Meyers loop to the temporal pole was 24–43 mm (mean 34 mm), and the range of distance from the tip of Meyers loop to the temporal horn was −15 to +9 mm (mean 0 mm). In controls the range of distance from the tip of Meyers loop to the temporal pole was 24–47 mm (mean 35 mm), and the range of distance from the tip of Meyers loop to the temporal horn was −11 to +9 mm (mean 0 mm). Both quantitative and qualitative results were in accord with recent dissections of cadaveric brains, and analysis of postoperative VFDs and resection volumes. By applying a linear regression analysis we showed that both distance from the tip of Meyers loop to the temporal pole and the size of resection were significant predictors of the postoperative VFDs. We conclude that there is considerable variation in the anterior extent of Meyers loop. In view of this, diffusion tensor tractography of the optic radiation is a potentially useful method to assess an individual patients risk of postoperative VFDs following anterior temporal lobe resection.

Imaging language networks before and after anterior temporal lobe resection: Results of a longitudinal fMRI study

Purpose:  Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left‐hemisphere–dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks.

The structural plasticity of white matter networks following anterior temporal lobe resection

Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy patients before and a mean of 4.5 months after anterior temporal lobe resection. The whole-brain analysis technique tract-based spatial statistics was used to compare pre- and postoperative data in the left and right temporal lobe epilepsy groups separately. We observed widespread, significant, mean 7%, decreases in fractional anisotropy in white matter networks connected to the area of resection, following both left and right temporal lobe resections. However, we also observed a widespread, mean 8%, increase in fractional anisotropy after left anterior temporal lobe resection in the ipsilateral external capsule and posterior limb of the internal capsule, and corona radiata. These findings were confirmed on analysis of the native clusters and hand drawn regions of interest. Postoperative tractography seeded from this area suggests that this cluster is part of the ventro-medial language network. The mean pre- and postoperative fractional anisotropy and parallel diffusivity in this cluster were significantly correlated with postoperative verbal fluency and naming test scores. In addition, the percentage change in parallel diffusivity in this cluster was correlated with the percentage change in verbal fluency after anterior temporal lobe resection, such that the bigger the increase in parallel diffusivity, the smaller the fall in language proficiency after surgery. We suggest that the findings of increased fractional anisotropy in this ventro-medial language network represent structural reorganization in response to the anterior temporal lobe resection, which may damage the more susceptible dorso-lateral language pathway. These findings have important implications for our understanding of brain injury and rehabilitation, and may also prove useful in the prediction and minimization of postoperative language deficits.

l-Dopa responsiveness in dementia with Lewy bodies, Parkinson disease with and without dementia

The authors analyzed whether nondemented (PD) and demented Parkinson patients (PDD) and patients with dementia with Lewy bodies (DLB) respond similarly in the levodopa test (LDT). Percentage of motor improvement was similar in the three groups; the proportion of patients with 10% and more improvement was greater in PD than in PDD and DLB. Positive LDT was predictive for favorable response in chronic levodopa treatment, but also some nonresponsive demented patients profited from chronic levodopa therapy.

Idiopathic generalized epilepsy phenotypes associated with different EFHC1 mutations

We sequenced 61 patients with various idiopathic generalized epilepsy (IGE) syndromes for mutations in the EFHC1 gene. We detected three novel heterozygous missense mutations (I174V, C259Y, A394S) and one possibly pathogenic variant in the 3′ UTR (2014t>c). The mutation I174V was also detected in 1 of 372 screened patients with temporal lobe epilepsy. We conclude that mutations in the EFHC1 gene may underlie different types of epilepsy syndromes.

A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy

Functional magnetic resonance imaging has demonstrated reorganization of memory encoding networks within the temporal lobe in temporal lobe epilepsy, but little is known of the extra-temporal networks in these patients. We investigated the temporal and extra-temporal reorganization of memory encoding networks in refractory temporal lobe epilepsy and the neural correlates of successful subsequent memory formation. We studied 44 patients with unilateral temporal lobe epilepsy and hippocampal sclerosis (24 left) and 26 healthy control subjects. All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words with subsequent out-of-scanner recognition assessments. A blocked analysis was used to investigate activations during encoding and neural correlates of subsequent memory were investigated using an event-related analysis. Event-related activations were then correlated with out-of-scanner verbal and visual memory scores. During word encoding, control subjects activated the left prefrontal cortex and left hippocampus whereas patients with left hippocampal sclerosis showed significant additional right temporal and extra-temporal activations. Control subjects displayed subsequent verbal memory effects within left parahippocampal gyrus, left orbitofrontal cortex and fusiform gyrus whereas patients with left hippocampal sclerosis activated only right posterior hippocampus, parahippocampus and fusiform gyrus. Correlational analysis showed that patients with left hippocampal sclerosis with better verbal memory additionally activated left orbitofrontal cortex, anterior cingulate cortex and left posterior hippocampus. During face encoding, control subjects showed right lateralized prefrontal cortex and bilateral hippocampal activations. Patients with right hippocampal sclerosis showed increased temporal activations within the superior temporal gyri bilaterally and no increased extra-temporal areas of activation compared with control subjects. Control subjects showed subsequent visual memory effects within right amygdala, hippocampus, fusiform gyrus and orbitofrontal cortex. Patients with right hippocampal sclerosis showed subsequent visual memory effects within right posterior hippocampus, parahippocampal and fusiform gyri, and predominantly left hemisphere extra-temporal activations within the insula and orbitofrontal cortex. Correlational analysis showed that patients with right hippocampal sclerosis with better visual memory activated the amygdala bilaterally, right anterior parahippocampal gyrus and left insula. Right sided extra-temporal areas of reorganization observed in patients with left hippocampal sclerosis during word encoding and bilateral lateral temporal reorganization in patients with right hippocampal sclerosis during face encoding were not associated with subsequent memory formation. Reorganization within the medial temporal lobe, however, is an efficient process. The orbitofrontal cortex is critical to subsequent memory formation in control subjects and patients. Activations within anterior cingulum and insula correlated with better verbal and visual subsequent memory in patients with left and right hippocampal sclerosis, respectively, representing effective extra-temporal recruitment.

Automated normalized FLAIR imaging in MRI-negative patients with refractory focal epilepsy.

Background:  Patients with focal epilepsy that is refractory to medical treatment are often considered candidates for resective surgery. Magnetic resonance imaging (MRI) has a very important role in the presurgical work‐up of these patients, but is unremarkable in about one‐third of cases. These patients are often deferred from surgery or have a less positive outcome if surgery is eventually undertaken. The aim of this study was to evaluate our recently described voxel‐based technique using routine T2‐FLAIR (fluid‐attenuated inversion‐recovery) scans in MRI‐negative patients and to compare the results with video‐EEG (electroencephalography) telemetry (VT) findings.

Hippocampal activation correlates with visual confrontation naming: fMRI findings in controls and patients with temporal lobe epilepsy

Summary Purpose In patients with left temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) decreased naming ability is common, suggesting a critical role for the medial left temporal lobe in this task. We investigated the integrity of language networks with functional MRI (fMRI) in controls and TLE patients. Experimental design We performed an fMRI verbal fluency paradigm in 22 controls and 66 patients with unilateral mesial TLE (37 left HS, 29 right HS). Verbal fluency and naming ability were investigated as part of the standard presurgical neuropsychological assessment. Naming ability was assessed using a visual confrontation naming test. Results Left TLE patients had significantly lower naming scores than controls and those with right TLE. Right TLE patients performed less well than controls, but better than those with left TLE. Left TLE had significantly lower scores for verbal fluency than controls. In controls and right TLE, left hippocampal activation during the verbal fluency task was significantly correlated with naming, characterised by higher scores in subjects with greater hippocampal fMRI activation. In left TLE no correlation with naming scores was seen in the left hippocampus, but there was a significant correlation in the left middle and inferior frontal gyri, not observed in controls and right TLE. In left and right TLE, out of scanner verbal fluency scores significantly correlated with fMRI activation for verbal fluency in the left middle and inferior frontal gyri. Conclusion Good confrontation naming ability depends on the integrity of the hippocampus and the connecting fronto-temporal networks. Functional MRI activation in the left hippocampus during verbal fluency is associated with naming function in healthy controls and patients with right TLE. In left TLE, there was evidence of involvement of the left frontal lobe when naming was more proficient, most likely reflecting a compensatory response due to the ongoing epileptic activity and/or underlying pathology.