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Psychosis of epilepsy (POE) can be a devastating condition, and its neurobiological basis remains unclear. In a previous study, we identified reduced posterior hippocampal volumes in patients with POE. The hippocampus can be further subdivided into anatomically and functionally distinct subfields that, along with the hippocampal fissure, have been shown to be selectively affected in other psychotic disorders and are not captured by gross measures of hippocampal volume. Therefore, in this study, we compared the volume of selected hippocampal subfields and the hippocampal fissure in 31 patients with POE with 31 patients with epilepsy without psychosis. Cortical reconstruction, volumetric segmentation, and calculation of hippocampal subfields and the hippocampal fissure were performed using FreeSurfer. The group with POE had larger hippocampal fissures bilaterally compared with controls with epilepsy, which was significant on the right. There were no significant differences in the volumes of the hippocampal subfields between the two groups. Our findings suggest abnormal development of the hippocampus in POE. They support and expand the neurodevelopmental model of psychosis, which holds that early life stressors lead to abnormal neurodevelopmental processes, which underpin the onset of psychosis in later life. In line with this model, the findings of the present study suggest that enlarged hippocampal fissures may be a biomarker of abnormal neurodevelopment and risk for psychosis in patients with epilepsy., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging., Methods: Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships., Results: First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology., Conclusions: Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To investigate whether genetics, underlying pathology, or repeated seizures contribute to atrophy in specific white matter tracts., Methods: Medically refractory unilateral temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS-TLE, n = 26) was studied as an archetype of focal epilepsy, using fixel-based analysis of diffusion-weighted imaging. A genetic effect was assessed in first-degree relatives of HS-TLE subjects who did not have epilepsy themselves (HS-1°Rel; n = 26). The role of disease process was uncovered by comparing HS-TLE to unilateral TLE with normal clinical magnetic resonance imaging (MRI-neg TLE; n = 26, matched for seizure severity). The effect of focal seizures was inferred from lateralized atrophy common to both HS-TLE and MRI-neg TLE, in comparison to healthy controls (n = 76)., Results: HS-1 °Rel had bilaterally small hippocampi, but no focal white matter atrophy was detected, indicating a limited effect of genetics. HS-TLE subjects had lateralized atrophy of most temporal lobe tracts, and hippocampal volumes in HS-TLE correlated with parahippocampal cingulum and anterior commissure atrophy, indicating an effect of the underlying pathology. Ipsilateral atrophy of the tapetum, uncinate, and inferior fronto-occipital fasciculus was found in both HS-TLE and MRI-neg TLE, suggesting a common lateralized effect of focal seizures. Both epilepsy groups had bilateral atrophy of the dorsal cingulum and corpus callosum fibers, which we interpret as a consequence of bilateral insults (potentially generalized seizures and/or medications)., Interpretation: Underlying pathology, repeated focal seizures, and global insults each contribute to atrophy in specific tracts. Genetic factors make less of a contribution in this cohort. A multifactorial model of white matter atrophy in focal epilepsy is proposed. Ann Neurol 2017;81:240-250., (© 2016 American Neurological Association.)

Objective: To define the functional network changes that characterize MRI-negative temporal lobe epilepsy (TLE) and TLE with hippocampal sclerosis (HS-TLE)., Methods: We studied 36 patients with medically refractory unilateral TLE, having either a normal clinical MRI (n = 18) or unilateral hippocampal sclerosis (n = 18). Patients were compared to healthy controls of equivalent age and sex (n = 27). Functional connectivity in 10 minutes of task-free functional MRI was assessed using a voxel-resolution graph theoretic analysis, using the metrics of degree, clustering coefficient, eigenvector, and betweenness centrality. Significant clusters were further explored with a seed-based analysis., Results: MRI-negative TLE showed decreased connectivity at the ipsilateral superior and middle temporal gyri compared to controls (decreased eigenvector centrality). No functional abnormality was detected within mesial temporal structures. In contrast, HS-TLE showed increased connectivity within the affected hippocampus and anterior thalamus (increased clustering coefficient) and decreased connectivity of the ventromesial prefrontal cortex (decreased betweenness centrality). Using the detected clusters as seed regions revealed decreased connectivity from the sclerotic hippocampus to both the contralateral temporal lobe and regions of the default mode network., Conclusion: MRI-negative TLE is associated with impaired interictal connectivity of the temporal neocortex, lateralized to the epileptic side. HS-TLE shows a different pattern, with functional segregation of the sclerotic hippocampus and impairment of its long-range connectivity. This suggests that MRI-negative TLE is not merely a subtle version of hippocampal sclerosis, but is rather a separate condition that involves distinct brain networks., (© 2016 American Academy of Neurology.)

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., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Changes in hardware or image-processing settings are a common issue for large multicenter studies. To pool MRI data acquired under these changed conditions, it is necessary to demonstrate that the changes do not affect MRI-based measurements. In these circumstances, classical inference testing is inappropriate because it is designed to detect differences, not prove similarity. We used a method known as statistical equivalence testing to address this limitation. Equivalence testing was carried out on 3 datasets: (1) cortical thickness and automated hippocampal volume estimates obtained from healthy individuals imaged using different multichannel head coils; (2) manual hippocampal volumetry obtained using two readers; and (3) corpus callosum area estimates obtained using an automated method with manual cleanup carried out by two readers. Equivalence testing was carried out using the "two one-sided tests" (TOST) approach. Power analyses of the TOST were used to estimate sample sizes required for well-powered equivalence testing analyses. Mean and standard deviation estimates from the automated hippocampal volume dataset were used to carry out an example power analysis. Cortical thickness values were found to be equivalent over 61% of the cortex when different head coils were used (q < .05, false discovery rate correction). Automated hippocampal volume estimates obtained using the same two coils were statistically equivalent (TOST P = 4.28 × 10(-15) ). Manual hippocampal volume estimates obtained using two readers were not statistically equivalent (TOST P = .97). The use of different readers to carry out limited correction of automated corpus callosum segmentations yielded equivalent area estimates (TOST P = 1.28 × 10(-14) ). Power analysis of simulated and automated hippocampal volume data demonstrated that the equivalence margin affects the number of subjects required for well-powered equivalence tests. We have presented a statistical method for determining if morphometric measures obtained under variable conditions can be pooled. The equivalence testing technique is applicable for analyses in which experimental conditions vary over the course of the study., (Copyright © 2015 by the American Society of Neuroimaging.)

Objective: We sought evidence of a hereditary component for hippocampal sclerosis (HS) by determining whether close relatives of probands with temporal lobe epilepsy (TLE) with HS also had asymptomatic HS or subtle variation in hippocampal morphology., Methods: First-degree relatives from 15 families in which probands had TLE with HS and 32 age- and sex-matched controls were included in the study. Left and right hippocampal volumes and T2 relaxometry were measured using 3-tesla MRI., Results: Thirty-two asymptomatic first-degree relatives and 3 relatives with a history of seizures or epilepsy were studied. None of the first-degree relatives had HS on visual analysis and T2 relaxation times were normal, excluding the presence of HS. Mean hippocampal volume was smaller (6.4%) in asymptomatic relatives (2.94 ± 0.27 cm(3), 95% confidence interval = 2.87-3.01) than in controls (3.14 ± 0.22 cm(3), 95% confidence interval = 3.09-3.19, p < 0.005); the effect was greater in relatives of probands with a positive family history of epilepsy. The relatives also had more asymmetric hippocampi (asymmetric index 0.92 ± 0.05) than controls (0.96 ± 0.03, p = 0.001)., Conclusions: Small asymmetric hippocampi in healthy relatives are likely to represent a familial developmental variant that may predispose to the formation of TLE with HS. The underlying histopathology of these small hippocampi is unknown. This observation may provide an imaging marker for future studies seeking susceptibility genes for HS.

Purpose: 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., Methods: 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., Key Findings: 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., Significance: 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., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

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.

Although the hippocampus is a key brain region in the pathophysiology of schizophrenia, it is unclear whether structural or biochemical abnormalities predate illness onset. In this study, we used magnetic resonance imaging and spectroscopy data acquired prior to both the onset of psychosis and treatment with antipsychotics to determine this. Sixty-six young people clinically at ultra high-risk of development of psychosis were recruited, 59 of whom did not later develop a psychotic disorder and 7 who had done so after at least 24 months follow-up. These participants were compared with 29 healthy comparison subjects on multiple independent magnetic resonance measures: hippocampal volume, hippocampal T2 relaxation time, and medial temporal lobe metabolite concentrations (including N-acetylaspartate). We found similar reductions in left hippocampal volume in the at-risk group compared to comparison subjects regardless of later transition status; on the right this only reached significance for the at-risk group who did not transition to psychosis. T2 relaxation time in the left hippocampal head was significantly elevated in the later-psychotic group, and this elevation positively correlated with total positive symptoms in the UHR group as a whole. Medial temporal lobe metabolite concentrations did not differ. These findings suggest that there are subtle pathological changes in the hippocampus prior to the development of psychosis, but that they are limited to the left hippocampal head. However, standard measures of neuroanatomical disturbance do not appear to be predictive of later transition, and instead are likely to be non-specific and common in cases that later develop a non-psychotic disorder., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: 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., Methods: 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., Results: 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., Discussion: 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.

Abnormalities in the brain generally manifest on MRI as changes in shape (morphometry) or changes in the nature of the tissue (signal intensity). Voxel Based Morphometry (VBM) is a whole brain quantitative way of assessing morphometric changes. Voxel Based Relaxometry (VBR) directly assesses signal intensity changes in quantitative maps of T2 relaxation time, but this requires specialised multiple-echo acquisition sequences that are not usually available at clinical sites. This paper introduces and assesses an objective voxel-based statistical method for evaluation of signal intensity in groups of routinely acquired qualitative images. We call the method Voxel-Based Iterative Sensitivity (VBIS) analysis. It adaptively optimises the relative global scaling of images to maximise sensitivity to regional effects. We apply and validate the method of analysis for T2-weighted images of the human brain. To validate the method, it was directly compared with VBR by extracting T2-weighted images of a single echo from multi-echo T2 relaxometry acquisitions from a group of 24 patients with left hemisphere hippocampal sclerosis and 97 healthy controls. Expected signal abnormalities in the patients were detectable with VBIS-T2, confirming the feasibility of the technique. This opens the door to the use of a voxel-based analysis approach on the vast amount of T2-weighted image data that has been and is being acquired on MRI scanners. When a quantitative modality is not available, VBIS can be an effective way to quantify differences between groups. We expect the method could also assist quantitative analysis of other qualitative modalities such as T1-weighted MRI, SPECT and CT.

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 TLE 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.

The present study explored the left mesial temporal lobe correlates of verbal memory in patients with temporal lobe epilepsy (TLE). An index of structural integrity, T2 relaxation time, was measured bilaterally in three mesial temporal regions of interest, and correlated with measures of verbal memory. The acquisition of verbal arbitrary relational material was most strongly associated with left perirhinal T2 signal. In contrast, verbal memory consolidation was related to T2 signal in the left hippocampus. Our findings suggest a key role for the left perirhinal region in the uptake of arbitrary linkages that underlie new learning. The hippocampus, on the other hand, is important for protecting newly learned information from the effects of interference. This double dissociation provides a neurocognitive account of the left mesial temporal memory syndrome.

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, T(2) 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 < or = 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.

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.

Background and Purpose: Increased T2 relaxation times in the ipsilateral hippocampus are present in patients with hippocampal sclerosis. Visual assessment of T2-weighted images of these patients suggests increased signal intensity in the anterior temporal lobe as well. Our aim was to assess hippocampal and anterior temporal T2 relaxation times in patients with partial epilepsy by using a new T2-relaxometry sequence implemented by using a 3-T General Electric imaging unit., Methods: Coronal view T2 maps were generated by using an eight-echo Carr-Purcell-Meiboom-Gill sequence (TE, 28-231) with an acquisition time of 7 min on a 3-T General Electric Signa Horizon LX imaging unit. T2 relaxation times were measured in the hippocampus and anterior temporal lobe of 30 healthy control volunteers and 20 patients with partial epilepsy., Results: For the 30 control volunteers, the mean hippocampal T2 relaxation time was 98 +/- 2.8 ms. In all measured areas, the asymmetry index was small (<0.01). For the 15 patients with independent evidence of hippocampal sclerosis established by visual, volumetric, and, when available, pathologic criteria, mean hippocampal T2 relaxation times were 118 +/- 7 ms (P <.0001) on the ipsilateral side and 101 +/- 4 ms (P =.005) on the contralateral side. The T2 values were also increased in the anterior temporal lobe (ipsilateral: 82 +/- 6 ms, P <.0001; contralateral: 79 +/- 6 ms, P =.01) as compared with the values for the control volunteers (75 +/- 3 ms). The five patients with focal cortical dysplasia had hippocampal T2 relaxation times that were not different from control values., Conclusion: T2 relaxometry at 3 T is feasible and useful and confirmed marked ipsilateral hippocampal signal intensity increase in patients with hippocampal sclerosis. Importantly, definite signal intensity change was also present in the anterior temporal lobe. T2 relaxometry is a sensitive means of identifying abnormalities in the hippocampus and other brain structures.

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.

The aim of this study was to determine whether partial epilepsy is associated with abnormalities in hippocampi that are not the primary seizure focus. As hippocampal T2 relaxometry is useful for identifying abnormalities that are not obvious on visual assessment of MRI, this was the method employed. Of 457 consecutive children and young adults from whom T2 relaxometry data were obtained, 96 had well characterized partial epilepsy and were enrolled, along with 27 control subjects. The patients were divided on the basis of clinical, video-EEG and visual MRI assessment into three groups: (i) those with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS) (MTS-TLE); (ii) lesional TLE (l-TLE); or (iii) extratemporal epilepsy (ETE). There was a significant and similar prolongation of T2 relaxation time identified in hippocampi remote from the seizure focus in all patient groups when compared with control subjects. In the non-sclerotic hippocampus of patients with MTS, T2 relaxation time was prolonged by a mean of 3.3 ms [95% confidence interval (CI), 0.8-5.9 ms; P = 0.01], patients with l-TLE had prolongation of T2 relaxation time by a mean of 4.3 ms (95% CI, 1.8-7.1 ms; P = 0.001) and those with ETE had prolongation of T2 relaxation time by a mean of 3.7 ms (95% CI, 1.6-6.6 ms; P = 0.006) compared with control subjects after adjustment for age. Unsurprisingly, in patients with MTS-TLE, T2 relaxation time in the sclerotic hippocampus was prolonged by a mean of 19 ms (95% CI = 14.6-22.4 ms; P < 0.001). The similarity in the extent of prolongation of T2 relaxation time in hippocampi that are not the primary epileptogenic focus, the wide variety of structural associations and the varied sites of epileptogenic foci, considered together, suggest that the abnormalities are likely to be caused by ongoing seizure activity rather than by underlying aetiology or site of epileptogenic focus.

Background and Purpose: Ipsilateral loss of anterior temporal gray-white matter definition, due mainly to white matter signal intensity abnormality, is frequently seen on MR images of patients with hippocampal sclerosis. Our aim was to determine the prevalence and clinical correlations of these anterior temporal changes in pediatric cases of hippocampal sclerosis and to determine whether cumulative damage from seizures is important for their development., Methods: We reviewed the MR images and clinical details of 54 children (age range, 1.5-19 years) with typical hippocampal sclerosis. Specific imaging features noted included hippocampal sclerosis, anterior temporal changes, anterior temporal atrophy, and extra-hippocampal abnormality., Results: Thirty-one (57%) of 54 children with hippocampal sclerosis had associated ipsilateral anterior temporal changes. Ipsilateral anterior temporal atrophy was associated with anterior temporal changes (P <.03). Children whose images showed anterior temporal changes were younger at onset of epilepsy (P <.01) and younger at antecedent cerebral insult (P <.03) than those with normal anterior temporal lobes. Most (84%) children whose images showed anterior temporal changes had experienced the onset of epilepsy or antecedent cerebral insult before the age of 2 years (P <.0009). Eighty-one percent of children with anterior temporal changes shown on their images experienced seizures at the time of antecedent insult., Conclusion: Ipsilateral anterior temporal changes identical to those observed in adult cases are seen on the MR images of young children with hippocampal sclerosis, with a similar prevalence, and are associated with either epilepsy onset or seizure-related cerebral insult before the age of 2 years. We suggest that the loss of gray-white matter definition may represent a persistent immature appearance, including an abnormality of myelin or myelination, possibly a result of seizures occurring during maturation of the temporal pole.

This longitudinal quantitative magnetic resonance imaging study of 24 patients with mild temporal lobe epilepsy shows an ipsilateral hippocampal volume decrease of 9% (range, -30 to +0.5%; p = 0.002, paired t test) over a period of 3.5 +/- 0.7 years. The hippocampal volume loss was correlated to the number of generalized seizures between the scans (p = 0.0007, r = 0.6), suggesting seizure-associated hippocampal damage.

Background: The MR and pathologic features of hippocampal sclerosis (HS) are well described and include volume decrease and T2-weighted signal increase for MRI, and neuron cell loss and gliosis for pathology., Objective: To confirm the established correlation between hippocampal volumes and neuron cell counts, and to study the still controversial association between signal change and gliosis., Methods: The authors studied 44 patients (22 men and 22 women; mean age at surgery, 37 years) with refractory temporal lobe epilepsy. Quantitative assessment of hippocampal volumes and T2 relaxometry, and neuron and glial cell count in the region CA1 and molecular layer of the dentate gyrus was performed. The proportion of glial fibrillary acidic protein (GFAP)-positive glial cells (reactive astrocytes) was indicated., Results: In a stepwise regression, the ipsilateral hippocampal volume was predicted best by the neuron cell count in the dentate gyrus (p = 0.005, r = 0.4). Hippocampal T2 time, however, was predicted best by the glial cell count in the dentate gyrus (p = 0.01, r = 0.4). None of the other cell counts contributed to either model. In the dentate, 31% of the glial cells were reactive astrocytes, whereas in CA1, 5% were reactive., Conclusion: The results confirmed the correlation between hippocampal volumes and neuron cell counts. T2-weighted signal increase in the hippocampus was mainly influenced by gliosis in the dentate gyrus, where a high proportion of glial cells show abnormal activity. This activity may reflect changes important in the development of hippocampal epileptogenicity.

ObjectiveRecent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features.MethodsWe extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1-weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers. Features with a moderate case-control effect size (Cohen d ≥ .5) were used to train an event-based model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance.ResultsIn MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10-16 ), age at onset (ρ = -.18, p = 9.82 × 10-7 ), and ASM resistance (area under the curve = .59, p = .043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE-HS with mild or nondetectable abnormality on T1W MRI.SignificanceFrom cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features.

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.

Rationale Globally, stroke and dementia are leading causes of disability and mortality. More than one third of stroke patients will develop dementia, but mechanisms are unclear. Aims The study aims to establish whether brain volume change is associated with poststroke dementia, and to elucidate potential causal mechanisms, including genetic markers, amyloid deposition and vascular risk factors. An understanding of whether - and in whom - stroke is neurodegenerative is critical for the strategic use of potential disease-modifying therapies. Hypotheses That stroke patients will exhibit greater brain volume loss than comparable cohorts of stroke-free controls; and that those who develop dementia will exhibit greater brain volume loss than those who do not. Design Advanced brain imaging techniques are used to longitudinally measure brain volume and cortical thickness in 135 stroke patients. Concurrent neuropsychological testing will correlate clinical profile with these measures. Primary outcomes Primary imaging end-point is brain volume change between three-months and three-years poststroke; primary clinical outcome is the presence of dementia at three-years. Secondary outcomes We will examine the correlations with the following variables: dementia subtype; physical activity levels; behavioral dysfunction as measured by patient and caregiver-reported scales; structural and functional brain connectivity disruption; apolipoprotein E; and specific neuropsychological test scores. Discussion Magnetic resonance imaging markers of structural brain aging and performance on neuropsychological tests are powerful predictors of dementia. We need to understand the trajectory of regional brain volume change and cognitive decline in patients after stroke. This will allow future risk stratification for prognostic counseling, service planning, and early therapeutic intervention. [ABSTRACT FROM AUTHOR]

Acute seizure-associated changes have been described in the animal and human literature. Controversy exists over whether seizures cause permanent damage to the brain, and whether a (prolonged) seizure can induce changes that lead to an epileptic lesion, resulting in habitual seizures and epilepsy. Current magnetic resonance imaging (MRI) offers a variety of imaging tools and is capable of detecting acute seizure-associated changes. In contrast to the histologic examination, serial MRI studies are possible and allow longitudinal observation of the fate of these changes. This report reviews the literature on acute seizure-associated effects emphasizing the MRI evidence. [ABSTRACT FROM AUTHOR]

Abstract: We used magnetic resonance imaging to examine the effect of ethyl-eicosapentaenoic acid (E-EPA) on hippocampal T2 relaxation time in first episode psychosis patients at baseline and after 12weeks of follow-up. There was an increase in T2 in the placebo group but not in the E-EPA group, suggesting a neuroprotective effect of E-EPA treatment. In addition, the smaller the increase in T2, the greater the improvement in negative symptoms. [Copyright &y& Elsevier]