Erik Achten

Long-term amygdalohippocampal stimulation for refractory temporal lobe epilepsy.

Short‐term deep brain stimulation (DBS) recently has been shown to be efficacious in refractory temporal lobe epilepsy. We (1) evaluated long‐term DBS in medial temporal lobe structures in patients with normal magnetic resonance imaging (MRI) findings and (2) investigated the use of chronic DBS electrodes for the localization of the ictal onset zone before DBS. In three patients with complex partial seizures (CPSs), DBS electrodes were implanted in the amygdalohippocampal region to identify and subsequently stimulate the ictal onset zone. CPSs were compared before and after chronic DBS. Side effects were carefully monitored. DBS electrodes yielded high‐quality electroencephalogram recordings showing unilateral seizure onset in medial temporal lobe structures. For all patients, unilateral amygdalohippocampal stimulation was performed. After a mean follow‐up of 5 months (range, 3–6 months), all patients had a greater than 50% reduction in seizure frequency. In two patients, antiepileptic drugs could be tapered. None of the patients reported side effects. This open study demonstrates the feasibility of consecutive electroencephalographic recordings and DBS in medial temporal lobe structures using DBS electrodes. These results prompt further studies in a larger patient population to establish the efficacy and safety of chronic DBS as an alternative treatment for refractory temporal lobe epilepsy.

PET visualization of microglia in multiple sclerosis patients using [11C] PK11195

Activated microglia are involved in the immune response of multiple sclerosis (MS). The peripheral benzodiazepine receptor (PBR) is expressed on microglia and up‐regulated after neuronal injury. [11C]PK11195 is a positron emission tomography (PET) radioligand for the PBR. The objective of the present study was to investigate [11C]PK11195 imaging in MS patients and its additional value over magnetic resonance imaging (MRI) concerning the immuno‐pathophysiological process. Seven healthy and 22 MS subjects were included. Semiquantitative [11C]PK11195 uptake values were assessed with normalization on cortical grey matter. Uptake in Gadolinium‐lesions was significantly increased compared with normal white matter. Uptake in T2‐lesions was generally decreased, suggesting a PBR down‐regulation. However, uptake values increased whenever a clinical or MR‐relapse was present, suggestive for a dynamic process with a transient PBR up‐regulation. During disease progression, an increase of normal‐appearing white matter (NAWM) uptake was found, propagating NAWM as the possible real burden of disease. In conclusion, [11C]PK11195 and PET are able to demonstrate inflammatory processes with microglial involvement in MS.

99mTc-ECD brain perfusion SPET: variability, asymmetry and effects of age and gender in healthy adults.

Abstract. Reliable and high-resolution reference data for regional cerebral blood flow measured with single-photon emission tomography (SPET) are necessary for optimal clinical and research use. Therefore, a large dataset of normal technetium-99m labelled ethylene cysteine dimer (ECD) perfusion SPET in carefully screened healthy volunteers with an age range spanning six decades was created, with correction for non-uniform attenuation and scatter and based on an anatomically standardised analysis. Eighty-nine healthy volunteers, stratified for gender (46 females, 43 males; age 20–81 years), were included. Twelve volunteers underwent repeated 99mTc-ECD SPET after 2.5±2.3 weeks. An automated whole-brain volume of interest analysis with MANOVA as well as voxelwise analysis using SPM99 was conducted. Average intersubject variability was 4.8% while intrasubject reproducibility was 3.0%. An age-related decline in tracer uptake was found in the anterior cingulate gyrus, bilateral basal ganglia, left prefrontal, left lateral frontal and left superior temporal and insular cortex (all P=0.001–0.02). There was an overall increase in right/left asymmetry with age, which was most pronounced in the frontal and temporal neocortex. The most significant correlations between AI and age decade were found in the prefrontal (R=0.35, P=0.001) and superior temporal neocortex (R=0.43, P<0.001). Women had significantly higher uptake in the right parietal cortex (P<0.001), while men showed higher uptake in the cerebellum and the left anterior temporal and orbitofrontal cortex (all P<0.01). This normative dataset allows age- and gender-specific patient and group assessment of 99mTc-ECD perfusion SPET under a wide variety of clinical circumstances in relation to normal variations and highlights the importance of both age- and gender-specific normal datasets for optimal analysis sensitivity.

Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis : a correlative study

Objective: The objectives of the present study were to assess brain atrophy in multiple sclerosis (MS) patients during different disease stages and to investigate by PET and [11C]PK11195, a marker of microglial activation, the relationship between inflammation, atrophy and clinically relevant measures. Methods: Eight healthy subjects and 22 MS patients were included. Semiquantitative [11C]PK11195 uptake values, with normalization on cortical grey matter, were measured for magnetic resonance imaging T2- and T1-lesions and normal appearing white matter (NAWM). As atrophy index we used the ratio of the amount of white and grey matter divided by the ventricular size, using an optimized a priori based segmentation algorithm (SPM99). Results: Atrophy was significantly greater in MS patients compared to age-matched controls. A significant correlation was found between brain atrophy and both disease duration and disability, as measured with the Expanded Disability Status Scale. For NAWM, [11C]PK11195 uptake increased with the amount of atrophy, while T2-lesional [11C]PK11195 uptake values decreased according to increasing brain atrophy. Conclusions: The present study suggests that brain atrophy, correlating with disease duration and disability, is directly related to NAWM and T2-lesional inflammation as measured by microglial activation.

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience.

Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0–100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.

A neuroradiologist's guide to arterial spin labeling MRI in clinical practice

Arterial spin labeling (ASL) is a non-invasive MRI technique to measure cerebral blood flow (CBF). This review provides a practical guide and overview of the clinical applications of ASL of the brain, as well its potential pitfalls. The technical and physiological background is also addressed. At present, main areas of interest are cerebrovascular disease, dementia and neuro-oncology. In cerebrovascular disease, ASL is of particular interest owing to its quantitative nature and its capability to determine cerebral arterial territories. In acute stroke, the source of the collateral blood supply in the penumbra may be visualised. In chronic cerebrovascular disease, the extent and severity of compromised cerebral perfusion can be visualised, which may be used to guide therapeutic or preventative intervention. ASL has potential for the detection and follow-up of arteriovenous malformations. In the workup of dementia patients, ASL is proposed as a diagnostic alternative to PET. It can easily be added to the routinely performed structural MRI examination. In patients with established Alzheimer’s disease and frontotemporal dementia, hypoperfusion patterns are seen that are similar to hypometabolism patterns seen with PET. Studies on ASL in brain tumour imaging indicate a high correlation between areas of increased CBF as measured with ASL and increased cerebral blood volume as measured with dynamic susceptibility contrast-enhanced perfusion imaging. Major advantages of ASL for brain tumour imaging are the fact that CBF measurements are not influenced by breakdown of the blood–brain barrier, as well as its quantitative nature, facilitating multicentre and longitudinal studies.

Artefacts in multi-echo T2 imaging for high-precision gel dosimetry: II. Analysis of B1-field inhomogeneity

In BANG gel dosimetry, the spin-spin relaxation rate, R2 = 1/T2, is related to radiation dose that has been delivered to a gel phantom. R2 is calculated by fitting the pixel intensities of a set of differently T2-weighted base images. The accuracy that is aimed for in this quantitative MR application is about 5% relative to the maximum dose. In a conventional imaging MR scanner, however, several imaging artefacts may perturb the final dose map. These deviations manifest themselves as either a deformation of the dose map or an inaccuracy of the dose pixel value. Inaccuracies in the dose maps are caused by both spatial and temporal deviations in signal intensities during scanning. This study deals with B1-field inhomogeneities as a source of dose inaccuracy. First, the influence of B1-field inhomogeneities on slice profiles is investigated using a thin-slice phantom. Secondly, a FLASH sequence is used to map the B1-field by assessing the effective flip angle in each voxel of a homogeneous phantom. In addition, both experiments and computer simulations revealed the effects of B1 field inhomogeneities on the measured R2. This work offers a method to correct R2 maps for B1 -field inhomogeneities.

Changes in Lumbar Muscle Activity Because of Induced Muscle Pain Evaluated by Muscle Functional Magnetic Resonance Imaging

Study Design. Experimental study of changes in muscle recruitment during trunk extension exercise at 40% of the repetition maximum, because of induced muscle pain. Objective. To investigate the effect of lumbar muscle pain on muscle activity of the trunk muscles using muscle functional magnetic resonance imaging. Summary of Background Data. Changed muscle recruitment in patients has an important impact on the etiology and recurrence of low back pain. The mechanisms of these changes in muscle activity are still poorly understood. An experimental study investigating the cause-effect relationship of muscle pain on muscle recruitment patterns can help to clarify these mechanisms. Methods. In 15 healthy subjects, the muscle activity of the lumbar multifidus, lumbar erector spinae, and psoas muscles was investigated with muscle functional magnetic resonance imaging. Measurements at rest and after trunk extension exercise at 40% of repetition maximum were performed without and with induced pain. Results. The lumbar multifidus and lumbar erector spinae were significantly active during the trunk extension exercise, whereas the psoas showed no significant activity. The activity of the lumbar multifidus, lumbar erector spinae, and psoas muscles, was reduced bilaterally and multilevel during the exercise with unilateral low back muscle pain. Conclusion. These data demonstrate that unilateral muscle pain can cause hypoactivity of muscles during trunk extension at 40% of the repetition maximum. The changes were not limited to the side and level of pain. Moreover, the inhibition was not limited to the multifidus muscle; also the lumbar erector spinae and psoas muscles showed decreased activity during the pain condition. Further research has to assess possible compensation mechanisms for this reduced activity in other muscles.

Artefacts in multi-echo T2 imaging for high-precision gel dosimetry: I. Analysis and compensation of eddy currents

In BANG gel dosimetry, the spin-spin relaxation rate, R2 = I/T2, is related to the radiation dose that has been delivered to the gel phantom. R2 is calculated by fitting the pixel intensities of a set of differently T2-weighted base images. In gel dosimetry for radiotherapy, an accuracy of 5% in dose and 3 mm spatially, whichever is lower, is the objective. Therefore, possible sources of artefacts must be considered and dealt with. To obtain a set of base images a multiple spin-echo sequence is used. However, in a conventional MR scanner eddy currents will be provoked by switching the imaging gradients. As the eddy currents change in the course of the sequence, the net magnetization will be affected accordingly. Hence, eddy currents may have a significant influence on the quantitative R2 images themselves as well as on their slice position. In this study, we report an analysis of the eddy currents as they appear in the multiple spin-echo sequence. Eddy currents are measured using a frequency shift method resulting in eddy current field maps. The related geometrical displacements are obtained by use of a pyramidal phantom. The R2 versus dose relation is determined in the three main directions of the magnet, revealing a dependence of the measured R2 on slice orientation. The time course of eddy currents is then used in a computer simulation to estimate the effects they produce in the recorded R2 images. A compensation method for eddy current effects in multi-echo T2 mapping is described.

Altered default-mode network activation in mild cognitive impairment compared with healthy aging

IntroductionRapidly increasing aging of the world’s population is causing a heightened prevalence of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The global burden, caused by this, is tremendous. In order to slow down the progression of the disease and preserve quality of life as much as possible, early identification of subjects at risk is indispensable within this framework.MethodsIn the present study, we combined independent component analysis and statistical parametric analysis to identify and compare the default-mode network (DMN) in healthy elderly and patients with MCI, with a special interest for hippocampal and lateral temporal involvement.ResultsFunctional results indicated reduced cortical activation in the DMN for MCI patients, compared with age- and education-matched healthy elderly controls, mainly in the retrosplenial region/posterior cingulate cortex, left hippocampus, and bilateral inferior and middle frontal areas. Increased activation for patients was observed in the medial prefrontal and bilateral middle temporal/angular cortex. Lateral temporal involvement in the DMN was in both the elderly control samples, and the patient group detected and suggested a slightly increased activation, more right than left, in middle temporal areas in the MCI patients, compared with healthy elderly.ConclusionResults are discussed with reference to the existing literature on early pathological changes in MCI and AD and subsequent compensation mechanisms in resting state and memory circuits.