Summary:Purpose: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLEno.Methods: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 ± 9.7 years), 17 TLE-no (mean age, 35.6 ± 11.1 years), and 30 healthy controls (mean age, 30.3 ± 11.1 years).Results: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi-and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS.Conclusions: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi-and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself. Key Words: TLE-Extratemporal-Voxel-based morphometryMesiotemporal sclerosis-Normal MRI.Mesial temporal lobe epilepsy (mTLE) is one of most frequent forms of partial epilepsy in adults. Based on neuroimaging and histologic characteristics, two main subtypes of mTLE can be distinguished: (a) TLE with hippocampal sclerosis (TLE-MTS), found in ∼60-70% of mTLE patients, which is characterized by an increased hippocampal T 2 signal and/or atrophied hippocampal formation on the MRI and significant neuronal loss in one or more hippocampal subfields in the histologic examination (1); and (b) MTLE without structural abnormalities on MRI (TLE-no) and only very mild or no neuronal loss in the hippocampus, which is found in ∼20-30% of mTLE patients. In both types of mTLE, seizures are not restricted to the medial temporal lobe but involve

Summary:Purpose: The aim of this study was to identify metabolically abnormal extrahippocampal brain regions in patients with temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) magnetic resonance imaging (MRI) evidence for mesial-temporal sclerosis (MTS) and to assess their value for focus lateralization by using multislice 1 H magnetic resonance spectroscopic imaging (MRSI).Methods: MRSI in combination with tissue segmentation was performed on 14 TLE-MTS and seven TLE-no and 12 age-matched controls. In controls, N-acetylaspartate/(creatine + choline) [NAA/(Cr+Cho)] of all voxels of a given lobe was expressed as a function of white matter content to determine the 95% prediction interval for any additional voxel of a given tissue composition. Voxels with NAA/(Cr+Cho) below the lower limit of the 95% prediction interval were defined as "pathological" in patients and controls. Z-scores were used to identify regions with a higher percentage of pathological voxels than those in controls.Results: Reduced NAA/(Cr+Cho) was found in ipsilateral temporal and parietal lobes and bilaterally in insula and frontal lobes. Temporal abnormalities identified the epileptogenic focus in 70% in TLE-MTS and 83% of TLE-no. Extratemporal abnormalities identified the epileptogenic focus in 78% of TLE-MTS but in only 17% of TLE-no.Conclusions: TLE is associated with extrahippocampal reductions of NAA/(Cr+Cho) in several lobes consistent with those brain areas involved in seizure spread. Temporal and extratemporal NAA/(Cr+Cho) reductions might be helpful for focus lateralization. Key Words: TLE-Extratemporal-Normal MRIMesial-temporal sclerosis.In medial temporal lobe epilepsy (mTLE), seizures originate in the hippocampal formation. About 60% of mTLE patients have magnetic resonance imaging (MRI) evidence of ipsilateral mesial temporal lobe sclerosis (MTS; i.e., hippocampal atrophy and/or increased T 2 signal), 20-30% have normal MRI (1), and the remainder has structural lesions (e.g., tumors or vascular malformations). However, the epileptogenic activity is usually not restricted to the hippocampus but spreads to other brain regions as well, particularly to the temporal lobes, insula, and frontal lobes (2-5). Consequently, many previous studies have shown abnormalities beyond the hippocampus including abnormalities of brain structure (6,7), cognitive function (8), cerebral glucose metabolism, and benzodiazepine (BZD) receptor binding (9-13).1 H magnetic resonance spectroscopy (MRS) identifies the epileptogenic hippocampus by a reduction of the neu- ronal marker N-acetylaspartate (NAA) in mTLE with evidence for MTS (TLE-MTS) (14N18). In mTLE without MR evidence for MTS (TLE-no), reduced NAA may predict surgical outcome, but the lateralization of the epileptogenic hippocampus is less accurate than that in . Although NAA reductions in brain regions beyond the hippocampus could give additional information for the identification of the primary epileptogenic region, especially in TLE-no, only a few MRS studies have investigated extrahip...

Differences in intestinal MDR1 and MRP2 expression may influence carbamazepine and phenytoin disposition and may account for interindividual pharmacokinetic variability.

BACKGROUND AND PURPOSE VBM, DBM, and cortical thickness measurement techniques are commonly used automated methods to detect structural brain changes based on MR imaging. The goal of this study was to demonstrate the pathology detected by the 3 methods and to provide guidance as to which method to choose for specific research questions. This goal was accomplished by 1) identifying structural abnormalities associated with TLE with (TLE-mts) and without (TLE-no) hippocampal sclerosis, which are known to be associated with different types of brain atrophy, by using these 3 methods; and 2) determining the aspect of the disease pathology identified by each method. MATERIALS AND METHODS T1-weighted MR images were acquired for 15 TLE-mts patients, 14 TLE-no patients, and 33 controls on a high-field 4T scanner. Optimized VBM was carried out by using SPM software, DBM was performed by using a fluid-flow registration algorithm, and cortical thickness was analyzed by using FS-CT. RESULTS In TLE-mts, the most pronounced volume losses were identified in the ipsilateral hippocampus and mesial temporal region, bilateral thalamus, and cerebellum, by using SPM-VBM and DBM. In TLE-no, the most widespread changes were cortical and identified by using FS-CT, affecting the bilateral temporal lobes, insula, and frontal and occipital lobes. DBM revealed 2 clusters of reduced volume complementing FS-CT analysis. SPM-VBM did not show any significant volume losses in TLE-no. CONCLUSIONS These results demonstrate that the 3 methods detect different aspects of brain atrophy and that the choice of the method should be guided by the suspected pathology of the disease.

Summary:Purpose: Vigabatrin (VGB) is a new antiepileptic drug that increases the human brain ␥-aminobutyric acid (GABA) level by irreversibly inhibiting GABA transaminase. Although some patients respond to VGB with a significant seizure reduction, others do not. The aim of this study was to identify possible responders before or in an early phase of VGB treatment by measuring the GABA and homocarnosine contaminated with macromolecules/creatine and phosphocreatine ratio (GABA+/Cr) signal by means of proton-nuclear magnetic resonance ( 1 H NMR) spectroscopy. Methods: Measurements were performed immediately before and after a titration period of 1 month (2 g/day during the past 2 weeks). A third measurement followed a maintenance period of 3 months (2 or 3 g/day). In 14 patients with drugresistant temporal lobe epilepsy and 3 patients with occipital lobe epilepsy, GABA+/Cr was measured in the ipsilateral (i.e., epileptogenic) hemisphere and contralateral (i.e., nonepileptogenic) hemisphere in a volume of 8 cm 3 .Results: Depending on the therapeutic efficacy of VGB, we defined three groups: (a) full responders (n ‫ס‬ 7), (b) nonresponders (n ‫ס‬ 7), and (c) partial responders (n ‫ס‬ 3). The nonresponders had no significant change in the GABA+/Cr signal during the treatment compared with baseline. The full responders had a significant increase of the GABA+/Cr signal during the whole treatment phase and a lower ipsilateral level at baseline. The partial responders had also a lowered ipsilateral GABA+/Cr signal at baseline and an increase during treatment but a decrease when the seizures started again.Conclusions: Responders to VGB could be identified by a lower ipsilateral baseline GABA+/Cr signal and a steeper increase during VGB treatment. However, it was not possible to predict the duration of the response (full versus partial responder) with these criteria.