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Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.

Objective: Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research.Methods: In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP).Results: Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups.Conclusion: Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy. [ABSTRACT FROM AUTHOR]

Summary: Epilepsy is among the most common chronic neurologic disorders, with 30%‐40% of patients having seizures despite antiepileptic drug treatment. The advent of brain imaging and network analyses has greatly improved the understanding of this condition. In particular, developments in magnetic resonance imaging (MRI) have provided measures for the noninvasive characterization and detection of lesions causing epilepsy. MRI techniques can probe structural and functional connectivity, and network analyses have shaped our understanding of whole‐brain anomalies associated with focal epilepsies. This review considers the progress made by neuroimaging and connectomics in the study of drug‐resistant epilepsies due to focal substrates, particularly temporal lobe epilepsy related to mesiotemporal sclerosis and extratemporal lobe epilepsies associated with malformations of cortical development. In these disorders, there is evidence of widespread disturbances of structural and functional connectivity that may contribute to the clinical and cognitive prognosis of individual patients. It is hoped that studying the interplay between macroscale network anomalies and lesional profiles will improve our understanding of focal epilepsies and assist treatment choices. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The dominant model of cognitive impairment in focal epilepsy has emphasised structural bases for cognitive deficits. Current theories of cognition in the healthy brain emphasise the importance of the reweighting of brain network interactions in support of task performance. Here, we explore the hypothesis that cognitive deficits in epilepsy arise through abnormalities of dynamic functional network interactions. Method: We studied 19 healthy controls and 37 temporal lobe epilepsy (TLE) patients, using a behavioural measure of verbal fluency (the Controlled Oral Word Association Test) and an fMRI verbal fluency paradigm (Orthographic Lexical Retrieval). Results: Behaviourally, verbal fluency was significantly impaired in TLE. Psychophysiological interaction analyses of the fMRI data, which capture state‐dependent changes in network connectivity, revealed reduced task‐dependent modulations of connectivity from left superior medial frontal cortex to left middle frontal gyrus in TLE patients. Individual differences in verbal fluency among TLE cases was correlated with task‐dependent changes in connectivity from left posterior cingulate to left superior medial frontal cortex, and from left superior medial frontal cortex to a range of right predominant brain areas. Interpretation: These data reveal that the typical pattern of task‐driven shifts in network connectivity is not observed in TLE. Our observations go beyond simple structure‐function associations and suggest that failure of network flexibility can be an important contributor to cognitive impairment in epilepsy. [ABSTRACT FROM AUTHOR]

Objective There is considerable difficulty in diagnosing hippocampal malrotation ( HIMAL), with different criteria of variable reliability. Here we assess qualitative and quantitative criteria in HIMAL diagnosis and explore the role of HIMAL in magnetic resonance imaging ( MRI)-negative temporal lobe epilepsy ( TLE). Methods We studied the MRI of 155 adult patients with MRI-negative TLE and 103 healthy volunteers, and we asked (1) what are the qualitative and quantitative features that allow a reliable diagnosis of HIMAL, (2) how common is HIMAL in a normal control population, and (3) is HIMAL congruent with the epileptogenic side in MRI-negative TLE. Results We found that the features that are most correlated with the expert diagnosis of HIMAL are hippocampal shape change with hippocampal diameter ratio > 0.8, lack of normal lateral convex margin, and a deep dominant inferior temporal sulcus ( DITS) with DITS height ratio > 0.6. In a blinded analysis, a consensus diagnosis of unilateral or bilateral HIMAL was made in 25 of 103 controls (24.3% of people, 14.6% of hippocampi-14 left, six right, 10 bilateral) that did not differ from 155 lesion-negative TLE patients where 25 had HIMAL (16.1% of patients, 11.6% of hippocampi-12 left, two right, 11 bilateral). Of the 12 with left HIMAL only, 9 had seizures arising from the left temporal lobe, whereas 3 had right-sided seizures. Of the two with right HIMAL only, both had seizures arising from the left temporal lobe. Significance HIMAL is an anatomic variant commonly found in controls. HIMAL is also an incidental nonpathologic finding in adult MRI-negative TLE and should not influence surgical decision making. [ABSTRACT FROM AUTHOR]

It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic - being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability. [ABSTRACT FROM AUTHOR]

Objective Studies of focal epilepsy have revealed abnormalities of language organization; however, little attention has been paid to disorders of reading in this group. We hypothesized that language functional magnetic resonance imaging ( fMRI) would reveal differences in language organization between focal epilepsy patients with and without reading difficulties. Methods We conducted language fMRI studies of 10 focal epilepsy patients with reading difficulties, 34 focal epilepsy patients without reading difficulties, and 42 healthy controls. Results We defined regions of interests on the basis of activation patterns on an orthographic lexical retrieval task. Comparison of activations within these ROIs on a second Noun-Verb task revealed epilepsy-related effects (relative to healthy controls: reduced activation in left inferior frontal cortex), as well as greater activation in the right temporooccipital cortex specific to the reading difficulty group. Significance These findings identify a focal epilepsy effect in the left frontal region (present in patients with and without reading difficulties), and a functional abnormality specific to the reading difficulty group localized to right temporooccipital cortex-a region implicated in lexicosemantic processing. Our observations suggest a failure of left hemisphere specialization among focal epilepsy patients with reading difficulties. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . [ABSTRACT FROM AUTHOR]

Hippocampal sclerosis (HS) is the most common pathologic finding in intractable temporal lobe epilepsy (TLE). In many patients, HS is accompanied by an extrahippocampal lesion (EHL). We sought to assess the lobar distribution and side of EHLs in relation to HS in a large consecutive series of patients presenting to our epilepsy surgery program. The inclusion criterion was the presence of both definite HS and an unequivocal EHL on magnetic resonance imaging (MRI) studies in patients evaluated for potential epilepsy surgery at our tertiary epilepsy center. Fifty-eight patients were identified over a 7-year period. This represented about one-third of all patients with HS. The mean age was 32 years (SD 18.4), and the mean age of seizure onset 13 years (SD 16.4). Fifty-four percent of the EHLs could be classified as acquired and 36% as developmental. In 98% of patients HS was found on the same side as EHL. Our findings support the hypothesis that HS may be a secondary event from seizures generated initially by another focal lesion. However, HS and EHL may also originate from the same insult to the brain. [ABSTRACT FROM AUTHOR]

Epilepsy due to encephaloceles of the temporal pole may be an under recognized, treatable cause of refractory temporal lobe epilepsy (TLE). We describe three adult patients initially labeled 'lesion negative' TLE. In all, video-electroencephalography (EEG) revealed ictal theta in the left temporal region and positron emission tomography (PET) showed temporal lobe hypometabolism, but neuropsychology revealed preserved verbal memory. Close inspection of structural magnetic resonance imaging (MRI) suggested subtle abnormalities at the tip of the left temporal lobe. High resolution computed tomography (CT) confirmed bony defects in the inner table of the skull. 3T MRI with fine coronal and sagittal slices indicated cerebrospinal fluid (CSF) and brain tissue protruding into the defects. All proceeded to resection of the temporal tip and became seizure free. Patients with 'lesion negative' TLE should have careful review of images covering the temporal pole. If encephalocele is suspected, further imaging with high-resolution CT and MRI can be helpful. Temporal polar resection, sparing mesial structures, appears to be curative. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is not a unitary electroclinical imaging syndrome. We asked if seizures arising from the parahippocampal-inferior temporal (PIT) region differ from those associated with hippocampal sclerosis (HS). The electroclinical features of 22 patients with HS and 14 patients with lesions in the PIT region who underwent epilepsy surgery and were seizure free for at least 2 years postoperatively were analyzed retrospectively. Patients with PIT lesions had a higher frequency of hypermotor and bilateral features and a lower frequency of behavioral arrest at the onset of seizure compared to cases with HS, suggesting that TLE originating in the PIT area can mimic frontal lobe epilepsy or contralateral mesial TLE. [ABSTRACT FROM AUTHOR]

Lesion-negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging-negative frontal or temporal lobe epilepsy. We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T1- and T2-weighted images with relative preservation of the gray–white matter boundary on T1-weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure-free (one has occasional auras only, follow-up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. In patients with lesion-negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features. [ABSTRACT FROM AUTHOR]

Quantitative measurement of hippocampal volume using structural magnetic resonance imaging (MRI) is a valuable tool for detection and lateralization of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE). We compare two automated hippocampal volume methodologies and manual hippocampal volumetry to determine which technique is most sensitive for the detection of hippocampal atrophy in mTLE. We acquired a three-dimensional (3D) volumetric sequence in 10 patients with left-lateralized mTLE and 10 age-matched controls. Hippocampal volumes were measured manually, and using the software packages Freesurfer and FSL-FIRST. The sensitivities of the techniques were compared by determining the effect size for average volume reduction in patients with mTLE compared to controls. The volumes and spatial overlap of the automated and manual segmentations were also compared. Significant volume reduction in affected hippocampi in mTLE compared to controls was detected by manual hippocampal volume measurement (p < 0.01, effect size 33.2%), Freesurfer (p < 0.01, effect size 20.8%), and FSL-FIRST (p < 0.01, effect size 13.6%) after correction for brain volume. Freesurfer correlated reasonably (r = 0.74, p << 0.01) with this manual segmentation and FSL-FIRST relatively poorly (r = 0.47, p << 0.01). The spatial overlap between manual and automated segmentation was reduced in affected hippocampi, suggesting the accuracy of automated segmentation is reduced in pathologic brains. Expert manual hippocampal volumetry is more sensitive than both automated methods for the detection of hippocampal atrophy associated with mTLE. In our study Freesurfer was the most sensitive to hippocampal atrophy in mTLE and could be used if expert manual segmentation is not available. [ABSTRACT FROM AUTHOR]

Purpose: Refractory temporal lobe epilepsy (TLE) is often associated with hippocampal sclerosis (HS). Patients with major depression (MD) may also show structural abnormalities in the limbic system. Co-occurrence of TLE with HS and MD is not uncommon. We have investigated the clinical and morphological characteristics of TLE patients in relation to MD. Methods: 34 TLE patients with HS were assessed at a Comprehensive Epilepsy Programme. All relevant clinical data were obtained, including the history of antecedent events to epilepsy. MD was diagnosed based on detailed psychiatric investigation. MRI was used to measure the volume and tissue signal (T2 relaxometry) of the hippocampus and amygdala. The imaging data were expressed as a percentage of the values obtained in a series of 55 controls. Results: A history of MD was present in 15 (44%) of 34 patients. Patients with MD had a longer duration of their epilepsy (p<0.05) and a lower frequency of antecedent events (13% with MD, 58% without MD, p<0.05). Both groups had a similar degree of ipsilateral HS (small hippocampal volume, increased hippocampal T2 relaxation time) and demonstrated bilateral amygdaloid atrophy. However, the contralateral amygdala showed lower signal in the presence of MD (97 (9) ms; no MD 103 (8) ms; ANCOVA, p = 0.02). Conclusion: The integrity of the amygdala may influence mood disturbances in ILE patients with HS, as depression was associated with a relative preservation of the contralateral amygdala. In contrast, hippocampal abnormalities were not related to the presence of depression. [ABSTRACT FROM AUTHOR]

Purpose: Patients with refractory temporal lobe epilepsy (refractory TLE) often have hippocampal sclerosis (HS). However, some HS patients have less-severe, drug-responsive epilepsy (mild TLE). We investigated the pattern of MR changes in these two HS groups. Methods: We acquired a 3D volumetric sequence, T2 relaxation times (T2) and proton MR spectroscopy (MRS) in 41 HS patients (24 refractory TLE, 17 mild TLE) and 60 controls. Hippocampal volumes were measured bilaterally. T2 was measured in the hippocampus, amygdala, thalamus, in the white matter of the anterior temporal lobe (ATL), and in the frontal lobe. The temporal lobe MRS established concentrations of N-acetylaspartate (NAA), choline, creatine, myoinositol and glutamine/glutamate. Results: The degree of hippocampal volume loss and hippocampal T2 increase was not different between the two HS groups. However, in refractory TLE, the T2 signal in the ipsilateral ATL was increased, and the ipsilateral NAA concentration was reduced (p ≤ 0.05). Conclusions: In this group of HS patients, the degree of HS was not related to the clinical course, possibly reflecting the common cause of epilepsy. In contrast, refractory TLE patients had pronounced white matter changes and metabolite disturbance in the ipsilateral temporal lobe. These abnormalities may indicate the refractory nature of the epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: Early acquired lesions are considered to be a risk factor for atypical language lateralization in epilepsy, whereas developmental lesions are not. Hippocampal sclerosis (HS) can be understood as an early, acquired lesion, whereas developmental tumors (DT) are thought to originate in utero. We assessed whether language lateralization differs between these groups of temporal lobe epilepsy patients. Methods: We used 3-Tesla functional MRI ( fMRI) to assess 41 patients (16 DT, 25 HS) and 50 controls, performing a noun–verb-generation task. fMRI data were processed by using SPM2. A laterality index (LI) was calculated based on the number of activated voxels in left- and right-sided frontal lobe language areas. Atypical lateralization was considered if the index was ≤0.2. Results: Patients had a lower LI (0.42 ± 0.5) than controls (0.6 ± 0.3; p ≤ 0.05), but the LI was not different between DT (0.44 ± 0.5) and HS patients (0.43 ± 0.4; p = 0.9). The frequency of atypical lateralization was increased in patients (27%) compared with controls (8%) but was similar in both patient groups (DT, 31%; HS, 24%). HS patients had an earlier onset and longer duration of epilepsy and a higher frequency of significant antecedent events (p ≤ 0.05). Conclusions: Patients with TLE demonstrate a deviation toward atypical language lateralization. However, language lateralization was not different between patients with presumably acquired lesions compared with patients with developmental pathology. This suggests that the nature of the temporal lobe lesion does not influence overall language lateralization. [ABSTRACT FROM AUTHOR]

Purpose: Subtle microdysplastic features are found in some patients with hippocampal sclerosis (HS) and refractory temporal lobe epilepsy. The significance of these findings is unknown. We investigated their frequency, relation to the pattern of HS, and clinical associations. Methods: One-hundred forty patients with histologically confirmed HS (mean age at operation, 35 years; 85 women) were analyzed. The presence of HS and subtle structural abnormalities (SSAs) in the mesial temporal lobe and in the lateral neocortical tissue was assessed in detail. Antecedents, seizure characteristics, two verbal memory tests, and outcome in HS patients with and without SSAs were determined. Results: SSAs were found in 60 (43%) of the 140 HS patients, being mesial only in 32 of the 60 cases, and lateral only in nine cases; the remaining 19 cases had both mesial and lateral abnormalities. The frequency of SSA was not related to the pattern of HS or other tested variables. Prolonged febrile convulsions were present in 26 (44%) patients with SSAs, and in 26 (34%) patients (not significant) without SSAs. The outcome after surgery did not differ between patients with SSAs (incidence rate ratio for seizure recurrence, 0.9; 95% confidence interval, 0.5–1.6) compared with patients without SSAs (reference ratio, 1). Conclusions: Forty-three percent of HS patients have SSAs in their lobectomy specimens. The presence of SSAs does not predict clinical characteristics, such as presence of prolonged febrile convulsions, postsurgical outcome, or neuropsychological performance, nor does it correlate with the histologic pattern of HS. [ABSTRACT FROM AUTHOR]

Purpose: This study used magnetic resonance spectroscopy (MRS) to examine metabolite abnormalities in the temporal and frontal lobe of patients with temporal lobe epilepsy (TLE) of differing severity. Methods: We investigated myoinositol in TLE by using short-echo MRS in 34 TLE patients [26 late onset (LO-TLE), eight hippocampal sclerosis (HS-TLE)], and 16 controls. Single-voxel short-echo (35 ms) MR spectra of temporal and frontal lobes were acquired at 1.5 T and analyzed by using LCModel. Results: The temporal lobe ipsilateral to seizure origin in HS-TLE, but not LO-TLE, had reduced N-acetylaspartate (NA) and elevated myoinositol (MI; HS-TLE NA, 7.8 ± 1.9 mM, control NA, 9.2 ± 1.3 mM; p < 0.05; HS-TLE MI, 6.1 ± 1.6 mM, control mI 4.9 ± 0.8 mM, p < 0.05). Frontal lobe MI was low in both patient groups (LO-TLE, 4.3 ± 0.8 mM; p < 0.05; HS-TLE, 3.6 ±.05 mM; p < 0.001; controls, 4.8 ± 0.5 mM). Ipsilateral frontal lobes had lower MI (3.8 ± 0.7 mM; p < 0.01) than contralateral frontal lobes (4.3 ± 0.8 mM; p < 0.05). Conclusions: MI changes may distinguish between the seizure focus, where MI is increased, and areas of seizure spread where MI is decreased. [ABSTRACT FROM AUTHOR]

The article focuses on a consensus classification system devised by the Task Force for Neuropathology of the International League Against Epilepsy (ILAE) Commission on Diagnostic Methods for classifying different types of hippocampal sclerosis (HS). The Task Force is said to have used a variety of techniques to classify the HS, which is a common injury in temporal lobe epilepsy (TLE), into three main types. The importance and limitations of the new classification scheme are also discussed.

Objective Amygdala enlargement (AE) is observed in patients with temporal lobe epilepsy (TLE), which has led to the suggestion that it represents a distinct TLE subtype; however, it is unclear whether AE is found at similar rates in other epilepsy syndromes or in healthy controls, which would limit its value as a marker for focal epileptogenicity. Methods We compared rates of AE, defined quantitatively from high-resolution T1-weighted MRI, in a large multi-site sample of 136 patients with nonlesional localization related epilepsy (LRE), including TLE and extratemporal (exTLE) focal epilepsy, 34 patients with idiopathic generalized epilepsy (IGE), and 233 healthy controls (HCs). Results AE was found in all groups including HCs; however, the rate of AE was higher in LRE (18.4%) than in IGE (5.9%) and HCs (6.4%). Patients with unilateral LRE were further evaluated to compare rates of concordant ipsilateral AE in TLE and exTLE, with the hypothesis that rates of ipsilateral AE would be higher in TLE. Although ipsilateral AE was higher in TLE (19.4%) than exTLE (10.5%), this difference was not significant. Furthermore, among the 25 patients with unilateral LRE and AE, 13 (52%) had either bilateral AE or AE contralateral to seizure onset. Conclusion Results suggest that AE, as defined with MRI volumetry, may represent an associated feature of nonlesional localization related epilepsy with limited seizure onset localization value. [ABSTRACT FROM AUTHOR]

The measurement of the T2 relaxation time (T2 relaxometry) had been established as a reliable tool for the assessment of certain conditions such as temporal lobe epilepsy. The standard procedure for analysis of T2 data uses manually drawn regions of interest (ROIs). This approach is limited by its subjective nature and its restricted scope of investigation within selected regions of the brain. In this study, we introduce a voxel-based analysis approach termed voxel-based relaxometry (VBR). Tissue signal changes were assessed in 19 patients with hippocampal sclerosis (HS) and in 38 healthy controls using (i) conventional ROI-based analysis with several bilateral ROIs and also (ii) the VBR method in which the T2 maps are warped to a stereotactic space, smoothed and statistically compared. Conventional ROI analysis identified the expected T2 increase in the sclerotic hippocampus in all HS patients. Furthermore, 13 of the 19 patients displayed a T2 increase in at least one of the other ROIs. The VBR analysis showed a similar pattern of statistically significant areas of increased T2 within the sclerotic hippocampus. In addition, extrahippocampal areas of increased T2 were apparent including the anterior temporal lobe white matter and the parahippocampal gyrus. The results of the VBR analysis are in agreement with the conventional ROI analysis. The VBR analysis has the advantage of providing an even-handed assessment of T2 differences through the brain. We recommend VBR as an alternative means of relaxometry data analysis that provides an objective assessment of differences between subjects. [Copyright &y& Elsevier]