Udo Wieshmann

Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy.

We used voxel-based morphometry (VBM), an automatic whole-brain MR image analysis technique, to investigate gray matter abnormalities in patients with temporal lobe epilepsy (TLE), in whom hippocampal atrophy (HA) was demonstrated by application of the Cavalieri method of modern design stereology. VBM results (P < 0.05, corrected) indicated preferential gray matter concentration (GMC) reduction in anterior hippocampus in patients with left HA and posterior hippocampus in patients with right HA. GMC reduction was also found in right dorsal prefrontal cortex in left and right HA patients. Prefrontal atrophy may be due to epileptiform excitotoxic discharges from the reciprocally connected pathological hippocampus, and may be the underlying biological cause for executive dysfunction in patients with TLE. GMC excess in ipsilateral parahippocampal, cerebellar, and pericallosal regions was common to both left and right HA groups relative to controls, and is hypothesized to reflect diminished gray-white matter demarcation, underlying white matter atrophy, or structural displacement due to cerebrospinal fluid expansion. However, bilateral temporal lobe GMC excess was observed in left HA patients, while ipsilateral temporal lobe GMC excess was observed in right HA patients. This work demonstrates methodological consistency between automated VBM and manual stereological analysis of the hippocampus in group comparisons, indicates widespread extrahippocampal gray matter abnormalities in unilateral HA, and suggests that there may be inherent differences in the effect of TLE on temporal lobe structures depending on the side of HA.

Voxel based morphometry of grey matter abnormalities in patients with medically intractable temporal lobe epilepsy: effects of side of seizure onset and epilepsy duration

Objectives: To investigate the use of whole brain voxel based morphometry (VBM) and stereological analysis to study brain morphology in patients with medically intractable temporal lobe epilepsy; and to determine the relation between side, duration, and age of onset of temporal lobe epilepsy, history of childhood febrile convulsions, and grey matter structure. Methods: Three dimensional magnetic resonance images were obtained from 58 patients with left sided seizure onset (LSSO) and 58 patients with right sided seizure onset (RSSO), defined using EEG and foramen ovale recordings in the course of presurgical evaluation for temporal lobectomy. Fifty eight normal controls formed a comparison group. VBM was used to characterise whole brain grey matter concentration, while the Cavalieri method of modern design stereology in conjunction with point counting was used to estimate hippocampal and amygdala volume. Age and sex were used as confounding covariates in analyses. Results: LSSO and RSSO patients showed significant reductions in volume (using stereology) and grey matter concentration (using VBM) of the hippocampus, but not of the amygdala, in the presumed epileptogenic zone when compared with controls, but hippocampal (and amygdala) volume and grey matter concentration were not related to duration or age of onset of epilepsy. LSSO and RSSO patients with a history of childhood febrile convulsions had reduced hippocampal volumes in the presumed epileptogenic zone compared with patients without such a history. Left amygdala volume was also reduced in LSSO patients with a history of childhood convulsions. VBM results indicated bilateral thalamic, prefrontal, and cerebellar GMC reduction in patients, which correlated with duration and age of onset of epilepsy. Conclusions: Hippocampal sclerosis is not necessarily the consequence of recurrent temporal lobe seizures. A major cause of hippocampal sclerosis appears to be an early aberrant neurological insult, such as childhood febrile seizures. Secondary brain abnormalities exist in regions outside the presumed epileptogenic zone and may result from recurrent seizures.

Reduced anisotropy of water diffusion in structural cerebral abnormalities demonstrated with diffusion tensor imaging

We used diffusion tensor imaging (DTI) to investigate the behavior of water diffusion in cerebral structural abnormalities. The fractional anisotropy, a measure of directionality of the molecular motion of water, and the mean diffusivity, a measure of the magnitude of the molecular motion of water, were measured in 18 patients with longstanding partial epilepsy and structural abnormalities on standard magnetic resonance imaging and the results compared with measurements in the white matter of 10 control subjects. Structural abnormalities were brain damage (postsurgical brain damage, nonspecific brain damage, perinatal brain damage, perinatal infarct, ischemic infarct, perinatal hypoxia, traumatic brain damage (n = 3), mitochondrial cytopathy and mesiotemporal sclerosis), dysgenesis (cortical dysplasia (n = 2) and heterotopia) and tumors (meningioma (n = 2), hypothalamic hamartoma and glioma). Anisotropy was reduced in all structural abnormalities. In the majority of abnormalities this was associated with an increased mean diffusivity; however, 30% of all structural abnormalities (some patients with brain damage and dysgenesis) had a normal mean diffusivity in combination with a reduced anisotropy. There was no correlation between fractional anisotropy and mean diffusivity measurements in structural abnormalities (r = -0.1). Our findings suggest that DTI is sensitive for the detection of a variety of structural abnormalities, that a reduced anisotropy is the common denominator in structural cerebral abnormalities of different etiologies and that mean diffusivity and fractional anisotropy may be, in part, independent. Combined measurements of mean diffusivity and fractional anisotropy are likely to increase the specificity of DTI.

The detection and significance of subtle changes in mixed-signal brain lesions by serial MRI scan matching and spatial normalization

The purpose of this work is to detect and assess the significance of subtle signal changes in mixed-signal lesions based on serial MRI scan matching. Pairs of serially acquired T1-weighted volume MR images from 20 normal controls and seven patients with epilepsy were matched and difference images obtained. The precision and consistency of the registration were evaluated. The Gaussian noise level in the difference images was determined automatically. A structured difference filter was then used to segment structured (changed) voxels from the Gaussian noise. In the controls, the structured difference images were normalized into Talairach space, resulting in a structured noise map. The significance of changes in patients was assessed by spatial normalization and comparison with the structured noise map. The precision and consistency of the co-registration were < or = 0.06 mm with a registration success rate of 100%. The Gaussian noise level in the difference images was in the range 3.0-6.9. In the controls, an average of 1.6% of the brain voxels were classified as structured. Sine-based registration resulted in a reduction of < 1% in the amount of structure compared to linear interpolation. The structured noise map in controls showed high noise density in areas affected by image artefacts. We show examples of significant changes found in lesions which had been reported as unchanged on visual inspection. A novel quantitative approach has been presented for the detection and quantification of subtle signal changes in lesions. This method is of potential clinical value in the non-invasive characterization of signal change and biological behaviour of neoplastic lesions.

Comparison of standard and optimized voxel-based morphometry for analysis of brain changes associated with temporal lobe epilepsy

We compared statistical parametric maps (SPMs) of group-wise regional gray matter differences between temporal lobe epilepsy (TLE) patients with unilateral hippocampal atrophy (HA) determined by manual volumetric analysis relative to a healthy control population using standard and optimized voxel-based morphometry (VBM). We also investigated the impact of customized neuroanatomical templates on SPMs. Standard and optimized VBM analyses of gray matter concentration (GMC) and gray matter volume (GMV) correctly identified HA, regardless of the template used for normalization. The distribution of hippocampal and extrahippocampal abnormalities differed according to the technique (standard v optimized; GMC v GMV), but was not dependent on template type (default v customized) within each technique. In particular, hippocampal GMC reduction was confined to subregions of hippocampus, whereas GMV reduction was observed in the hippocampal head, body, and tail. Unlike standard and optimized GMC reduction, symmetrical GMV reduction was observed in bilateral thalamus, lenticular nuclei, cerebellum, and ipsilateral entorhinal cortex, perirhinal cortex, and fusiform gyrus in both left and right HA patients. These results show that group-wise SPMs of GMC (i.e., regional distribution of gray matter) and GMV (i.e., volume per se) reduction can identify focal atrophy that has been quantified with manual region of interest techniques, although effects are attenuated in analyses of GMC. Unlike SPMs of GMC, analyses of GMV revealed similar extrahippocampal abnormalities as previous region-of-interest volumetric and histopathological studies of intractable TLE. We suggest that in studies of neurological disorders, optimized VBM analyses of GMV may reveal subtle neuroanatomical changes that are not identified in analyses of GMC.

Diffusion tensor imaging demonstrates deviation of fibres in normal appearing white matter adjacent to a brain tumour

the objective was to study fibre orientation in the cerebral white matter of a patient with a brain tumour using diffusion tensor imaging (DTI).  A patient with a mild left hemiparesis and a tumour in the right frontal lobe and 20 healthy volunteers were scanned with a DTI sequence. The scans were spatially normalised and the fibre orientation in the patient compared with the fibre orientation in normal controls.  DTI disclosed a change of the orientation of fibres in the patient compared with normal controls. In the normal appearing white matter adjacent to the tumour fibres deviated from the normal superior inferior orientation in the corona radiata by about 30o. This finding was consistent with a displacement by distant mass effect rather than a destruction of fibres, in agreement with the neurological examination.  In conclusion, DTI demonstrated a deviation of fibres in normal appearing white matter adjacent to a tumour. The technique will improve understanding of the effects of structural abnormalities on fibres. This will assist the interpretation of clinical findings and functional imaging studies and guide neurosurgical interventions.

Development of hippocampal atrophy: A serial magnetic resonance imaging study in a patient who developed epilepsy after generalized status epilepticus

Summary: Purpose: To investigate changes in hippocampal volume.

Water diffusion in the human hippocampus in epilepsy

The hippocampus plays a central role in the generation and propagation of seizures in patients with complex partial seizures. Hippocampal sclerosis (HS) is a common structural abnormality in patients with refractory epilepsy. The aim of this study was to quantify diffusion in the hippocampus in patients with epilepsy to evaluate the diffusion changes associated with HS. We scanned 20 subjects (14 patients and 6 controls) with a 1.5T magnetic resonance (MR) system using a cardiac-gated, navigated spin-echo diffusion-weighted sequence. Hippocampal ADC measurements were performed on maps of the ADC measured in three orthogonal directions labeled x, y, and z. The mean ADC (ADCav) and an anisotropy index (AI) were calculated. Hippocampi which fulfilled the MR criteria for HS had a higher ADCav (p < 0.001) and a lower AI (p=0.04) than normal appearing hippocampi in patients and hippocampi in controls. These results imply a loss of structural organization in sclerotic hippocampi and an expansion of the extracellular space. Quantitative measurements of diffusion can be used as an independent parameter for the identification and characterization of abnormal hippocampi in epilepsy.

Multimodal MR Imaging: Functional, Diffusion Tensor, and Chemical Shift Imaging in a Patient with Localization‐Related Epilepsy

Summary: Purpose: To demonstrate the integration of complementary functional and structural data acquired with magnetic resonance imaging (MRI) in a patient with localization‐related epilepsy.

The seizure outcome after amygdalohippocampectomy and temporal lobectomy.

The aim of this study was to compare the seizure outcome of two different types of epilepsy surgery, selective amydalohippocampectomy (AHE) and anterior temporal lobectomy (ATLE) in patients with temporal lobe epilepsy. We included 114 patients who had mesio‐temporal lobe epilepsy and hippocampal sclerosis or gliosis on histology. Patients had ATLE if the non‐dominant hemisphere was affected or if the whole temporal lobe was atrophic. Patients had AHE if the dominant hemisphere was affected. Standardized seizure outcome at 1 year following surgery was used. Overall 40% of the 114 patients who had temporal lobe epilepsy surgery were seizure‐free at 1‐year (Engels class Ia). A good outcome (Engels classes I and II) was significantly more frequent in ATLE than in AHE. (66% and 44%, respectively, P = 0.03). ATLE had a better seizure outcome than AHE.