Philippa A. Bartlett

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.

Progressive neocortical damage in epilepsy

Our objective was to determine the pattern and extent of generalized and focal neocortical atrophy that develops in patients with epilepsy and the factors associated with such changes. As part of a prospective, longitudinal follow‐up study of 122 patients with chronic epilepsy, 68 newly diagnosed patients, and 90 controls, serial magnetic resonance imaging scans were obtained 3.5 years apart. Image subtraction was used to identify diffuse and focal neocortical change that was quantified with a regional brain atlas and a fully automated segmentation algorithm. New focal or generalized neocortical volume losses were identified in 54% of patients with chronic epilepsy, 39% of newly diagnosed patients and 24% of controls. Patients with chronic epilepsy were significantly more likely to develop neocortical atrophy than control subjects. The increased risk of cerebral atrophy in epilepsy was not related to a history of documented seizures. Risk factors for neocortical atrophy were age and multiple antiepileptic drug exposure. Focal and generalized neocortical atrophy commonly develops in chronic epilepsy. Neocortical changes seen in a quarter of our control group over 3.5 years were likely to reflect physiological changes. Our results show that ongoing cerebral atrophy may be widespread and remote from the putative epileptic focus, possibly reflecting extensive networks and interconnections between cortical regions. Ann Neurol 2003

Short echo time single-voxel 1H magnetic resonance spectroscopy in magnetic resonance imaging-negative temporal lobe epilepsy : Different biochemical profile compared with hippocampal sclerosis

Single‐voxel proton magnetic resonance spectroscopy (1H MRS) has shown abnormalities in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). Many TLE patients, however, do not have HS or other lesions on quantitative magnetic resonance imaging (MRI) (MRI‐negative). Fifteen control subjects, 15 patients with unilateral HS, and 15 MRI‐negative TLE patients underwent 1H MRS at an echo time of 30 msec on a 1.5‐T GE Signa scanner. Voxels were tailored to the individual hippocampi. N‐Acetylaspartate (NAA), creatine, choline, total glutamate plus glutamine (Glx), and myo‐inositol (Ins) were quantitated by using an external standard and LCModel, a user‐independent quantitation method. Normal ranges were defined as the control mean ± 2.5 SD. In HS patients, 12 of 15 had abnormally low NAA in sclerotic hippocampi; 3 of these 12 also had abnormally low NAA contralaterally. Abnormally low NAA/Ins ratios lateralized the side affected by HS in 7 of 15 patients, without any bilateral abnormalities. In 15 MRI‐negative TLE patients, 4 had abnormally low hippocampal NAA ipsilateral to seizure onset, 1 of whom had abnormally low NAA bilaterally. Analysis of groups of subjects showed a bilateral decrease in NAA, most marked in patients with HS and on the side of seizure onset. The mean NAA/Ins ratio was lower in patients with HS than in control subjects and in MRI‐negative patients. The concentration of Glx was higher ipsilateral to seizure onset in MRI‐negative patients than in HS patients. Quantitative short echo time 1H MRS identified abnormalities in 87% of patients with HS and 27% of MRI‐negative TLE patients in concordance with other lateralizing data. In individual and group comparisons, 1H MRS described a metabolite profile in the hippocampi of MRI‐negative TLE patients that was different from patients with HS, with an increase in Glx and a less marked decrease in NAA than was seen in HS. Ann Neurol 1999;45:369–376

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.

Cerebral Damage in Epilepsy: A Population‐based Longitudinal Quantitative MRI Study

Summary:  Purpose: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community‐based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex.

High-resolution diffusion tensor imaging of the hippocampus in temporal lobe epilepsy

PURPOSE To assess the quantitative diffusion characteristics of the hippocampus with high-resolution diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE). METHODS Thirteen controls and seven unilateral TLE patients (six with hippocampal sclerosis, one with normal magnetic resonance imaging (MRI)) were scanned with DTI using a zonally magnified oblique multislice echo planar imaging (ZOOM-EPI) acquisition. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampi. RESULTS The mean hippocampal MD ipsilateral to the seizure focus was higher than the contralateral MD in patients (p<0.05) and the mean MD in controls (p<0.001). Hippocampal FA ipsilateral to the seizure focus was lower than the mean FA in controls (p<0.05). MD asymmetry indexes were significantly different between the patient and control groups (p<0.01). All six individual HS patients had ipsilateral hippocampal MD >or=2 standard deviations (S.D.) above the control mean. The patient with normal structural MRI had bilaterally low hippocampal FA and high MD. DISCUSSION High-resolution DTI identifies lateralizing abnormalities of MD and FA in TLE patients. This quantitative data on hippocampal integrity may assist in evaluating TLE patients with normal MRI, and in longitudinal studies.

A Short‐echo‐time Proton Magnetic Resonance Spectroscopic Imaging Study of Temporal Lobe Epilepsy

Summary:  Purpose: We used short‐echo‐time proton magnetic resonance spectroscopy imaging (MRSI) to study metabolite concentration variation through the temporal lobe in patients with temporal lobe epilepsy (TLE) with and without abnormal MRI.

The structural consequences of newly diagnosed seizures

Intractable epilepsy may be associated with widespread structural cerebral damage. We determined whether structural damage occurs to the hippocampus, cerebellum and neocortex in the first few years following a diagnosis of seizures. Sixty‐eight patients over the age of 14 years with newly diagnosed seizures and 90 matched controls underwent serial magnetic resonance imaging (MRI) brain scans 3.5 years apart. Using quantitative analysis of serial scans, we determined changes in hippocampal volume, hippocampal T2 relaxometry and total and regional brain volumes. Thirty‐four (50%) patients had recurrent unprovoked seizures between baseline and follow‐up scans. One patient with pre‐existing hippocampal sclerosis (HS) did not develop progressive hippocampal damage. Group analyses found no difference in change in cerebral measures between patients and controls or between patients with and without recurrent seizures. Significant quantitative changes in individuals were largely attributable to pre‐existing cerebral lesions or alcohol abuse. Subtle changes detected in individuals over 3.5 years but were not related to a history of overt seizures. Our results show patients with newly diagnosed seizures are not generally at increased risk of seizure‐induced structural cerebral damage as detected with MRI. Cerebral damage may occur before the onset of seizures or develop insidiously over a more prolonged period.

A Longitudinal Quantitative MRI Study of Community-Based Patients with Chronic Epilepsy and Newly Diagnosed Seizures: Methodology and Preliminary Findings

Experimental and human data suggest that progressive cerebral damage may result from the cumulative effect of brief recurrent seizures. Longitudinal studies addressing this fundamental question, however, are lacking. We have addressed this need with a large prospective community-based observational study, which aims to rescan 154 patients with chronic active epilepsy and 90 patients with newly diagnosed seizures, after an interval of 3.5 years. Here, we describe the quantitative magnetic resonance methods used to identify subtle volume changes in hippocampal, cerebellar, and neocortical structures over time and report preliminary findings. Using this methodology, we have previously shown that we can reliably detect individual hippocampal volume (HV) and cerebellar volume (CBV) changes greater than 3.1 and 3.0%, respectively (Lemieux et al, 2000). Analysis of the first 53 subjects (24 patients with chronic active epilepsy, 9 patients with newly diagnosed seizures, and 20 controls) has demonstrated significant HV losses in 4 individuals. Automated and semiautomated calculation has detected significant reductions in CBV, total brain volume, and gray matter volume in 2, 3, and 1 subject, respectively. There were no significant white matter volume losses detected. Data collected from rescanning the entire cohorts will help to provide further information on the relationship between recurrent seizures and secondary brain damage.

Magnetic resonance imaging in epilepsy with a fast FLAIR sequence.

OBJECTIVE: To assess the diagnostic value of the fast FLAIR sequence in patients with epilepsy. METHODS: One hundred and twenty eight patients with epilepsy and 10 control subjects were scanned with the fast FLAIR sequence with 5 mm slices, a coronal gradient echo (GRE) T1 weighted sequence with 1.5 mm slices and spin echo (SE) or fast spin echo (FSE) proton density and T2 weighted sequences with 5 mm slices. All images were compared by an unblinded neuroradiologist and neurologist. Fast FLAIR images of patients with hippocampal sclerosis (HS) and normal control subjects were also evaluated by two blinded independent raters. RESULTS: Fast FLAIR provided a high conspicuity of neocortical damage, hamartomas, dysembryoplastic neuroepithelial tumours, and clear cut hippocampal sclerosis. However, the same information could be obtained from the coronal T1 and T2 weighted images. In three patients fast FLAIR showed a clearly abnormal signal when SE T2 weighted images had not been definitely abnormal. Heterotopia was less conspicuous on fast FLAIR than GRE T1 weighted images. The two blinded raters detected all but one of the patients with clear cut hippocampal sclerosis on fast FLAIR images but missed all borderline cases of hippocampal atrophy and there were two false positives. Clear cut hippocampal sclerosis was more conspicuous on fast FLAIR images than on SE T2 weighted images in most patients, but additional patients were not identified. CONCLUSION: Fast FLAIR has the advantage of identifying neocortical lesions and definite hippocampal sclerosis with a short scanning time and may also demonstrate lesions when other sequences are normal in a limited number of cases. The technique was not useful, however, for identifying mild hippocampal sclerosis or heterotopia.