Biomedical subjects

Matthias J Koepp

Publications and source records attributed to Matthias J Koepp.

10 recordsLinked to original sources

PubMed2005

Reading skills after left anterior temporal lobe resection: an fMRI study.

Maintaining language functions after left hemisphere lesions has been associated with compensatory right hemisphere activation. It remains unclear whether recruitment of right hemisphere regions necessarily provides an effective mechanism to compensate for language deficits. To investigate the compensatory mechanisms that mediate good reading skills in patients after left anterior temporal lobe resection for mesial temporal lobe epilepsy (mTLE), we tested for the effect of their reading ability on the regional fMRI (functional MRI) signal elicited by sentence reading. Sixteen control subjects and 16 patients participated in the study. In the activation condition, they silently read nine-word sentences, and in the baseline condition they viewed nine-word sentences after all the letters were transformed into false fonts. Reading ability in controls and patients significantly (P < 0.05, corrected) predicted activations in a left hemisphere middle temporal region that was part of the normal sentence reading system. In addition, reading ability in patients, but not controls, significantly predicted activation in the right inferior frontal sulcus, right hippocampus and right inferior temporal sulcus. Right inferior frontal activation was only observed in the patients. In contrast, right hippocampal and inferior temporal activation was observed in all controls and in patients whose reading ability was within the normal range, indicating the importance of these regions for efficient encoding during normal sentence reading. We conclude that proficient reading skills following left anterior temporal lobe resection for mTLE rely on two mechanisms: (i) integrating regions from the normal system (i.e. the left middle temporal, right hippocampus and anterior superior temporal sulcus); and (ii) recruiting right hemisphere regions (i.e. the right inferior frontal sulcus) that are not activated in control subjects.

Adult↗

PubMed2005

Omega-3 fatty acid supplementation in patients with chronic epilepsy: a randomized trial.

Animal studies and a preliminary clinical observation suggest that nutritional supplementation with long chain omega-3 fatty acids (omega-3 FAs) may be useful in the nonpharmacological treatment of patients with epilepsy. Omega-3 FAs increase seizure thresholds, and lower inflammatory mediators, which are increased in patients with epilepsy. In this first randomized, placebo-controlled parallel group trial of omega-3 FA supplementation with 1 g eicosapentaenoic acid (EPA) and 0.7 g docosahexaenoic acid (DHA) daily, 57 patients completed a 12-week double-blind phase. Seizure frequency was reduced over the first 6 weeks of treatment in the supplement group, but this effect was not sustained. The supplementation produced a significant increase in EPA and DHA concentrations and a reciprocal fall in arachidonic and linoleic acid concentrations. No change in serum AED concentrations was detected. Further studies are required to examine different omega-3 FA preparations, different doses, longer treatment duration, and larger sample sizes.

Adult↗

PubMed2005

Imaging structure and function in refractory focal epilepsy.

Over the past decade there have been many advances in data acquisition and analysis for structural and functional neuroimaging of people with epilepsy. New imaging sequences and analysis techniques have increased the resolution of images such that underlying structural pathology can be seen in many patients with "cryptogenic" epilepsy. When an epileptogenic lesion is present, antiepileptic drugs alone rarely prevent seizures. However, the success of surgical treatment is improved when a structural lesion has been identified. Lesions might not overlap with the area of the cortex generating seizures and may continue into areas sustaining normal functions. To prevent postsurgical morbidity, the spatial relation between functionally important areas and the epileptogenic lesion must be assessed before surgery. In this review we describe the potential of different neuroimaging techniques to show lesions, assess neuronal function, and assist with the prognosis of postsurgical outcome in patients with refractory focal epilepsy.

Brain Neoplasms↗

PubMed2005

Periventricular white matter flumazenil binding and postoperative outcome in hippocampal sclerosis.

PURPOSE: In patients with hippocampal sclerosis (HS), anterior temporal lobe resection offers the possibility of a long-lasting suppression of seizures in two thirds of patients. White matter (WM) [11C]flumazenil volume of distribution (FMZ-Vd) reflects the number of neuronal cell bodies in WM. Our objective was to correlate WM FMZ-Vd in patients with unilateral HS and postsurgical outcome. METHODS: We performed [11C]FMZ-PET in 15 patients with refractory mesial temporal lobe epilepsy (mTLE) and a quantitative MRI diagnosis of unilateral HS subsequently histologically verified in all cases. Median follow-up was 7 years (range, 6-9 years). Metabolite-corrected arterial plasma input functions and spectral analysis were used to generate parametric images of [11C]FMZ-Vd. Statistical parametric mapping (SPM99) with explicit masking was used to investigate the entire brain volume including WM. RESULTS: Eight patients had Engel class IA outcome (completely seizure free since surgery), and seven were not seizure free. Comparison of seizure-free patients with those who continued to have seizures after surgery revealed areas of increased FMZ binding around the posterior horns of the ipsilateral (z=3.7) and contralateral (z=2.7) ventricles in those with suboptimal outcomes. CONCLUSIONS: Preoperative [11C]FMZ-PET can detect periventricular increases of WM FMZ binding, implying heterotopic neurons in WM, in patients with mTLE. The presence of such increases correlates with a poorer outcome.

Adult↗

PubMed2004

Epilepsy.

PURPOSE OF REVIEW: The purpose of this review is to consider the current and potential role of neuroimaging from an epilepsy perspective, and to illustrate that by combining appropriate imaging techniques, neuroimaging can contribute greatly to elucidating the basic mechanisms of the various forms of epileptic disorders. RECENT FINDINGS: New magnetic resonance imaging sequences (magnetization transfer imaging) and positron emission tomography ligands (serotonergic system) were biologically validated in large groups of patients with localization-related epilepsies. Investigations in genetically determined homogenous patient populations (PAX6, juvenile myoclonic epilepsy) have strengthened the link between genetic defects and neuropathological targets (anterior commissure, thalamus). Magnetic resonance spectroscopy and electroencephalogram-triggered functional magnetic resonance imaging provided converging evidence for a key role of the thalamus in the generation of generalized seizures. The role of functional magnetic resonance imaging in identifying eloquent areas of cortex and its relationship to structural lesions, in particular malformations of cortical development, has been further elucidated. Longitudinal magnetic resonance imaging studies reported progressive volume loss after febrile convulsions and in active epilepsy. SUMMARY: Neuroimaging is essential for improving the efficacy and safety of therapeutic, in particular, surgical procedures. Investigations of larger, more homogenous genetic disorders and longitudinal rather than cross-sectional neuroimaging studies have advanced our knowledge about the cause and effect of epileptic disorders, and will ultimately link defects in molecular genetics with specific neuropathological targets.

Brain↗

PubMed2004

The application of functional MRI of memory in temporal lobe epilepsy: a clinical review.

Functional MRI (fMRI) is a useful tool for noninvasively localizing areas in the brain involved in specific cognitive functions. Since its introduction, there has been considerable speculation regarding the role it may play in the presurgical assessment of temporal lobe epilepsy (TLE). This review considers the progress made to date in using fMRI to investigate memory processing in the medial temporal lobe in normal subjects and in those with TLE. Results so far suggest that fMRI will be incorporated into the presurgical assessment of TLE in the coming years to improve definition of eloquent cerebral areas, with the objective of minimizing the adverse cognitive sequelae of anterior temporal lobe resection.

Brain Mapping↗

PubMed2003

Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe.

Probabilistic atlases of neuroanatomy are more representative of population anatomy than single brain atlases. They allow anatomical labeling of the results of group studies in stereotaxic space, automated anatomical labeling of individual brain imaging datasets, and the statistical assessment of normal ranges for structure volumes and extents. No such manually constructed atlas is currently available for the frequently studied group of young adults. We studied 20 normal subjects (10 women, median age 31 years) with high-resolution magnetic resonance imaging (MRI) scanning. Images were nonuniformity corrected and reoriented along both the anterior-posterior commissure (AC-PC) line horizontally and the midsagittal plane sagittally. Building on our previous work, we have expanded and refined existing algorithms for the subdivision of MRI datasets into anatomical structures. The resulting algorithm is presented in the Appendix. Forty-nine structures were interactively defined as three-dimensional volumes-of-interest (VOIs). The resulting 20 individual atlases were spatially transformed (normalized) into standard stereotaxic space, using SPM99 software and the MNI/ICBM 152 template. We evaluated volume data for all structures both in native space and after spatial normalization, and used the normalized superimposed atlases to create a maximum probability map in stereotaxic space, which retains quantitative information regarding inter-subject variability. Its potential applications range from the automatic labeling of new scans to the detection of anatomical abnormalities in patients. Further data can be extracted from the atlas for the detailed analysis of individual structures.

Adult↗

PubMed2003

Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients.

In 20-30% of potential surgical candidates with refractory focal epilepsy, standard MRI does not identify the cause. gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. [(11)C]Flumazenil (FMZ) PET images most subtypes of GABA(A) receptors, present on most neurons. We investigated [(11)C]FMZ binding in grey and white matter in 16 normal controls and in 44 patients with refractory neocortical focal epilepsy and normal optimal MRI. Fourteen patients had unilateral frontal lobe epilepsy, five occipital lobe epilepsy (OLE), six parietal lobe epilepsy (PLE) and 19 neocortical epilepsy that was not clearly lobar. Parametric images of FMZ volume of distribution (FMZ-V(d)) were computed. Statistical parametric mapping (SPM99) with explicit masking, including the white matter, was used to analyse individual patients and groups. Thirty-three of the 44 patients showed focal abnormal FMZ-V(d); increases in 16, decreases in eight, and both increases and decreases in nine. In seven patients, the increases in FMZ binding were periventricular, in locations normally seen in periventricular nodular heterotopia on MRI. There were frontal and parietal increases in FMZ binding in grey and white matter in the PLE group and decreases in the cingulate gyrus in the OLE group. FMZ binding increases, particularly periventricular increases, were a prominent feature of MRI-negative focal epilepsies and may represent neuronal migration disturbances.

Adolescent↗

PubMed2002

Implementation and application of a brain template for multiple volumes of interest.

We present a region template and a protocol for transforming that template to define anatomical volumes of interest (VOIs) in the human brain without operator intervention, based on software contained in the SPM99 package (Statistical Parametric Mapping, Wellcome Department of Cognitive Neurology, London, UK). We used an MRI of a reference brain to create an anatomical template of 41 VOIs, covering the entire brain, that can be spatially transformed to fit individual brain scans. Modified software allows for the reslicing and adaptation of the transformed template to any type of coregistered functional data. Individually defined VOIs can be added. We present an assessment of the necessary spatial transformations and compare results obtained for scans acquired in two different orientations. To evaluate the spatial transformations, 11 landmarks distributed throughout the brain were chosen. Euclidean distances between repeat samples at each landmark were averaged across all landmarks to give a mean difference of 1.3 plus minus 1.0 mm. Average Euclidean distances between landmarks (MRI:transformed template) were 8.1 plus minus 3.7 mm in anterior-posterior commissure (ACPC) and 7.6 plus minus 3.7 mm in temporal lobe (TL) orientation. In this study, we use [(11)C]-flumazenil-(FMZ-)PET as an example for the application of the region template. Thirty-four healthy volunteers were scanned, 21 in standard ACPC orientation, 13 in TL orientation. All had high resolution MRI and FMZ-PET. The average coefficient of variation (CV) of FMZ binding for cortical regions was 0.15, comparable with CVs from manually defined VOIs. FMZ binding was significantly different in 6/19 anatomical areas in the control groups obtained in the different orientations, probably due to anisotropic voxel dimensions. This new template allows for the reliable and fast definition of multiple VOIs. It can be used for different imaging modalities and in different orientations. It is necessary that imaging data for groups compared are acquired in the same orientation.

Adult↗

PubMed2002

Sulthiame in adults with refractory epilepsy and learning disability: an open trial.

This prospective uncontrolled open study explored the efficacy and long-term tolerability of sulthiame (STM) in 52 patients with refractory epilepsy and learning disability. Thirty-six patients completed a 14-weeks trial period with STM and 22 patients achieved a seizure reduction>50% of which three became seizure-free. Twenty-six patients continued taking STM for now up to 120 weeks, one continued to be seizure-free, whilst five patients stopped STM during this period. These promising observations require further evaluation in a controlled trial.

Adult↗