Association between hippocampal structure and serum Brain-Derived Neurotrophic Factor (BDNF) in healthy adults: A registered report.

The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). However, evidence on the relationship between hippocampal volume (HCV) and peripheral BDNF levels is scarce and limited to elderly and patient populations. Further, despite evidence that BDNF expression differs throughout the hippocampus and is implicated in adult neurogenesis specifically in the dentate gyrus, no study has so far related peripheral BDNF levels to the volumes of individual hippocampal subfields. Besides its clinical implications, BDNF-facilitated hippocampal plasticity plays an important role in regulating cognitive and affective processes. In the current registered report, we investigated how serum BDNF (sBDNF) levels relate to volumes of the hippocampal formation and its subfields in a large sample of healthy adults (N = 279, 160 f) with a broad age range (20-55 years, mean 40.5) recruited in the context of the ReSource Project. We related HCV to basal sBDNF and, in a subsample (n = 103, 57 f), to acute stress-reactive change in sBDNF. We further tested the role of age as a moderator of both associations. Contrary to our hypotheses, neither basal sBDNF levels nor stress-reactive sBDNF change were associated with total HCV or volume of the dentate gyrus/cornu ammonis 4 (DG/CA4) subfield. We also found no evidence for a moderating effect of age on any of these associations. Our null results provide a first point of reference on the relationship between sBDNF and HCV in healthy mid-age, in contrast to patient or aging populations. We suggest that sBDNF levels have limited predictive value for morphological differences of the hippocampal structure when notable challenge to its neuronal integrity or to neurotrophic capacity is absent.

Review: Neurodegenerative processes in temporal lobe epilepsy with hippocampal sclerosis: Clinical, pathological and neuroimaging evidence.

Cognitive decline is increasingly described as a co-morbidity of temporal lobe epilepsy (TLE). Mechanisms underlying cognitive impairment are not fully understood despite examining clinical factors, such as seizure frequency, and cellular mechanisms of excitotoxicity. We review the neuropsychometry evidence for progressive cognitive decline and examine the pathology and neuroimaging evidence supporting a neurodegenerative process in hippocampal sclerosis (HS)-related TLE. Accelerated cognitive decline is described in groups of adult HS-related TLE patients. Large childhood studies show early onset of seizures result in poor development of verbal memory and a hindrance in achieving cognitive potential. We discuss HS classification according to different patterns of neuronal loss and correlation to post-temporal lobectomy cognitive outcomes in refractory TLE patients. Factors such as lateralization of HS pathology, neuronal density and subtype have correlated to cognitive outcomes with varying significance between different studies. Furthermore, alterations in neuronal maturity, regenerative capacity and aberrant connectivity appear to affect cognitive performance post-operatively suggesting a complex multifactorial process. More recent studies have identified tau pathology being present in HS-related TLE and correlated to post-operative cognitive decline in some patients. A traumatic head injury-related or novel tauopathy has been hypothesized as an underlying process. We discuss the value of prospective and cross-sectional imaging in assessing cognition and review volumetric magnetic resonance studies with progressive ipsilateral hippocampal atrophy identified to correlate with seizure frequency. Finally, we consider the use of positron emission tomography biomarkers, such as tau tracers, and connectivity studies that may examine in vivo pathways and further explore cognitive decline in TLE.

Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens.

Pregnancy-associated Plasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSAPAM) can be used in vitro to select parasites from nonpregnant donors to express VSAPAM and that this selection for VSAPAM expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA.

Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures.

OBJECTIVES: To assess hippocampal volumes (HV) and signal changes on diffusion-weighted imaging (DWI) within 5 days of prolonged febrile seizures (PFS) and compare them with the PFS duration and EEG. METHODS: We studied 12 children (mean age: 32 +/- 21 months, range 10 months-5 years) within 5 days of a first episode of PFS (a seizure or series of seizures lasting for 30 min or longer, without return of consciousness between the seizures). The HV measurements were carried out using high-resolution magnetic resonance imaging and signal intensity abnormalities were evaluated visually on DWI. HV in patients were compared with those of 13 neurologically normal controls (mean age 31 +/- 16 months, range 15 months-5 years). HV abnormalities correlated with PFS duration. HV and DWI abnormalities were compared with EEG abnormalities. RESULTS: Seizure duration ranged from 40 to 95 min. In seven out of twelve patients, seizures were refractory and lasted for 60 min or longer despite intravenous infusion of diazepam. In the patients with PFS for 60 min or longer, HV were significantly larger than that of controls. In all patients, there was a positive correlation between HV and seizure duration. DWI showed hyperintensity in unilateral hippocampus in three patients with intractable seizures, ipsilateral thalamus in two, and cingulate in one. EEG showed abnormalities in temporal areas ipsilateral to the DWI abnormalities in these patients. CONCLUSIONS: Large HV and hippocampal hyperintensity on DWI were seen in patients with refractory PFS. Our results suggest that medically refractory PFS lasting for 60 min or longer may cause structural changes in limbic structures that could promote later epileptogenesis.

Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures.

OBJECTIVES: To assess hippocampal volumes (HV) and signal changes on diffusion-weighted imaging (DWI) within 5 days of prolonged febrile seizures (PFS) and compare them with the PFS duration and EEG. METHODS: We studied 12 children (mean age: 32 +/- 21 months, range 10 months-5 years) within 5 days of a first episode of PFS (a seizure or series of seizures lasting for 30 min or longer, without return of consciousness between the seizures). The HV measurements were carried out using high-resolution magnetic resonance imaging and signal intensity abnormalities were evaluated visually on DWI. HV in patients were compared with those of 13 neurologically normal controls (mean age 31 +/- 16 months, range 15 months-5 years). HV abnormalities correlated with PFS duration. HV and DWI abnormalities were compared with EEG abnormalities. RESULTS: Seizure duration ranged from 40 to 95 min. In seven out of twelve patients, seizures were refractory and lasted for 60 min or longer despite intravenous infusion of diazepam. In the patients with PFS for 60 min or longer, HV were significantly larger than that of controls. In all patients, there was a positive correlation between HV and seizure duration. DWI showed hyperintensity in unilateral hippocampus in three patients with intractable seizures, ipsilateral thalamus in two, and cingulate in one. EEG showed abnormalities in temporal areas ipsilateral to the DWI abnormalities in these patients. CONCLUSIONS: Large HV and hippocampal hyperintensity on DWI were seen in patients with refractory PFS. Our results suggest that medically refractory PFS lasting for 60 min or longer may cause structural changes in limbic structures that could promote later epileptogenesis.

Analysis of shape and positioning of the hippocampal formation: an MRI study in patients with partial epilepsy and healthy controls.

The purpose of this study was to evaluate systematically shape and positioning of the hippocampal formation (HF) in patients with partial epilepsy related to malformations of cortical development (MCD) and those with temporal lobe epilepsy (TLE). We studied 76 patients with MCD, including focal cortical dysplasia (n = 29; lesions located outside the temporal lobe in all), heterotopia (lesions outside of the temporal lobe, n = 14; lesions extending into the temporal lobe, n = 16), polymicrogyria (bilateral perisylvian, n = 14; unilateral perisylvian, n = 3) and 30 patients with TLE (hippocampal atrophy, n = 15; normal hippocampal volumes, n = 15). Shape and positioning of the HF were evaluated using a set of eight predefined morphological characteristics. In addition, the degree of hippocampal vertical orientation and medial positioning were assessed quantitatively. Patients were compared with 50 healthy controls. At least three criteria describing abnormal HF shape and positioning were found in 5/50 (10%) healthy controls, 37/76 (49%) MCD and 13/30 (43%) TLE patients. An association with all criteria was found in MCD and TLE, but not in healthy controls. In MCD there was no association between the side of HF shape abnormalities and the side of the cortical malformation or the EEG focus. Likewise, in TLE, HF abnormalities were not related to the side of the EEG focus. In both MCD and TLE patients who had hippocampal atrophy, no association was found between the side of HF shape abnormalities and the side of atrophy. Abnormal HF shape and positioning are found in a similar proportion in MCD and TLE. In TLE, they may be a marker of a more extensive disorder of brain development and may participate in the development of this condition.

Lateralizing value of peri-ictal headache: A study of 100 patients with partial epilepsy.

To determine the lateralizing value of peri-ictal headache, the authors conducted a standardized interview of 100 patients with partial epilepsy, 60 with temporal lobe epilepsy (TLE) and 40 with extratemporal epilepsy (ETE). Peri-ictal headache occurred in 47 of 100 (47%) patients. Peri-ictal headache was more likely to be ipsilateral to the seizure onset in TLE (27 of 30 = 90%) than in ETE (two of 17 = 12%; p< 0.001). For both groups, peri-ictal headache usually conformed to the diagnostic criteria for common migraine (18 of 30 = 60% in TLE; 7 of 17 = 41% in ETE).

Entorhinal cortex in temporal lobe epilepsy: a quantitative MRI study.

BACKGROUND: The entorhinal cortex (EC) is a distinct anatomic and functional region of the anterior parahippocampal gyrus, which plays a role in seizure generation and propagation in temporal lobe epilepsy (TLE). In tissue resected from TLE patients, cell loss in the EC has been described. OBJECTIVES: To develop a standardized protocol for identifying the anatomic boundaries of the EC using high-resolution MRI and to examine morphologic changes of the EC in TLE. METHODS: We performed T1-weighted MRIs in 20 patients (7 males) with TLE (mean age 34 years) and 18 normal controls (mean age 26 years). Eleven patients had a left and 9 a right epileptic focus as defined by history, video-EEG, and surgical outcome. The volumes of the EC, the hippocampus, and the amygdala were measured using a standardized MRI protocol. Analysis of variance (ANOVA) was used to examine the effect of seizure focus lateralization and hemisphere on these volumes. An asymmetry ratio [A (%) = 100 x (R-L)/(R+L)/2] was also compared between groups using ANOVA. RESULTS: In normal controls the volume of the right EC was 1,247 +/- 127 mm3 (mean +/- standard deviation), and that of the left EC was 1,215 +/- 135 mm3 (p > 0.05). We found a bilateral reduction in the volume of the EC in TLE patients compared with controls (p < 0.05). Examination of the asymmetry ratios showed that the reduction in volume of the EC was greater ipsilateral to the epileptic focus (p < 0.05). The volumes of the hippocampus and the amygdala were smaller on the side of the focus in TLE patients compared with controls (p < 0.05). CONCLUSIONS: With a standardized protocol for the quantitative assessment of the EC, patients with unilateral TLE show bilateral reduction in the volume of the EC. However, this reduction is more severe ipsilateral to the epileptic focus.

Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes.

OBJECTIVE: To determine whether MRI volumetric measurement of the entorhinal cortex could detect structural damage and lateralize the seizure focus in patients with temporal lobe epilepsy in whom no measurable hippocampal abnormalities were found. BACKGROUND: A reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy and hippocampal atrophy was recently shown. METHODS: MRI volumetric analysis of the entorhinal cortex was performed using a T1-weighted three-dimensional gradient echo sequence in 24 control subjects and 22 patients with temporal lobe epilepsy and normal hippocampal volumes. Thirteen patients underwent surgery, with a mean postoperative follow-up of 36 months. RESULTS: Group analysis (multivariate analysis of variance) showed a reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with left (p < 0.0001) and right temporal lobe epilepsy (p < 0.0001). Lateralization of the seizure focus could be done in 14 of 22 patients (64%) based on entorhinal cortex volumetry. CONCLUSION: Entorhinal cortex atrophy ipsilateral to the seizure focus supports the presence of structural damage in the mesial temporal lobe in patients with temporal lobe epilepsy and normal hippocampal volumes and emphasizes the participation of the entorhinal cortex in the pathogenesis of this disorder.

Morphometric MRI analysis of the parahippocampal region in temporal lobe epilepsy.

Despite neuropathological and electrophysiological evidence for the involvement of parahippocampal structures in temporal lobe epilepsy (TLE), little attention has been paid to morphometric changes in these structures, and the relation of these changes to TLE. We performed high-resolution MRI volumetric analysis to examine in vivo the morphology of the parahippocampal region in 20 healthy subjects and 6 TLE patients with MRI evidence of unilateral hippocampal atrophy. In normal controls the standardized volume of the left entorhinal cortex (EC) was 1305 +/- 138 mm3 and that of the right EC was 1376 +/- 170 mm3; the left perirhinal cortex (PC) was 2900 +/- 554 mm3 and the right PC was 2771 +/- 486 mm3; the left posterior parahippocampal cortex (PPC) was 2499 +/- 583 mm3 and the right PPC was 2234 +/- 404 mm3. Using a 2 standard deviation cutoff from the mean of normal controls, we found ipsilateral to the seizure focus: (i) a reduction in the volume of the EC in all patients; (ii) a reduction of the PC in 2/6 (33%) patients; (iii) no reduction in the volume of the PPC in any patient. In 3/6 (50%) of patients, the EC was also abnormally small contralateral to the seizure focus. In patients with unilateral TLE, the EC is the most affected structure within the parahippocampal region. Whether this is due to a primary role of the EC in the genesis of TLE or is the consequence of its pivotal position in the reciprocal flow of information between the hippocampus and the neo- and limbic cortices remains to be explored.

Sensorimotor organization in patients who have undergone hemispherectomy: a study with (15)O-water PET and somatosensory evoked potentials.

To identify cortical structures that subserve residual motor and sensory function in patients with congenital hemiparesis due to a porencephalic cyst, we examined, using [(15)O]H2O, PET and somatosensory evoked potentials (SEPs) in three patients with left-sided hemiparesis who had undergone hemispherectomy. Motor stimulation of the affected hand produced ipsilateral activation in the premotor area in all patients, the SMA in two patients, and SII in two patients. Vibrotactile stimulation resulted in activation of the ipsilateral SII in all subjects. Median nerve stimulation of the affected hand produced ipsilateral long-latency SEPs in fronto-centro-parietal areas, whereas stimulation of the non-affected hand produced normal early cortical potentials in the contralateral hemisphere. Our results suggest that residual function in the paretic hand is warranted through non-primary motor and sensory areas, and higher order associative areas in the intact hemisphere.

Increased temporolimbic cortical folding complexity in temporal lobe epilepsy.

OBJECTIVE: Converging evidence suggests that abnormalities of brain development may play a role in the pathogenesis of temporal lobe epilepsy (TLE). As sulco-gyral patterns are thought to be a footprint of cortical development, we set out to quantitatively map folding complexity across the neocortex in TLE. Additionally, we tested whether there was a relationship between cortical complexity and features of hippocampal maldevelopment, commonly referred to as malrotation. METHODS: To quantify folding complexity, we obtained whole-brain surface-based measures of absolute mean cortical curvature from MRI scans acquired in 43 drug-resistant patients with TLE with unilateral hippocampal atrophy, and 40 age- and sex-matched healthy controls. In patients, we correlated changes in cortical curvature with 3-dimensional measures of hippocampal positioning. RESULTS: We found increased folding complexity in the temporolimbic cortices encompassing parahippocampal, temporopolar, insular, and fronto-opercular regions. Increased complexity was observed ipsilateral to the seizure focus in patients with left TLE (LTLE), whereas these changes were bilateral in patients with right TLE (RTLE). In both TLE groups, increased temporolimbic complexity was associated with increased hippocampal malrotation. We found tendencies for increased complexity in bilateral posterior temporal cortices in LTLE and contralateral parahippocampal cortices in RTLE to be predictive of unfavorable seizure outcome after surgery. CONCLUSION: The anatomic distribution of increased cortical complexity overlapping with limbic seizure networks in TLE and its association with hippocampal maldevelopment further imply that neurodevelopmental factors may play a role in the epileptogenic process of TLE.

Longitudinal and cross-sectional analysis of atrophy in pharmacoresistant temporal lobe epilepsy.

BACKGROUND: Whether recurrent epileptic seizures induce brain damage is debated. Disease progression in epilepsy has been evaluated only in a few community-based studies involving patients with seizures well controlled by medication. These studies concluded that epilepsy does not inevitably lead to global cerebral damage. OBJECTIVE: To track the progression of neocortical atrophy in pharmacoresistant temporal lobe epilepsy (TLE) using longitudinal and cross-sectional designs. METHODS: Using a fully automated measure of cortical thickness on MRI, we studied a homogeneous sample of patients with pharmacoresistant TLE. In the longitudinal analysis (n = 18), fixed-effect models were used to quantify cortical atrophy over a mean interscan interval of 2.5 years (range = 7 to 90 months). In the cross-sectional analysis (n = 121), we correlated epilepsy duration and thickness. To dissociate normal aging from pathologic progression, we compared aging effects in TLE to healthy controls. RESULTS: The longitudinal analysis mapped progression in ipsilateral temporopolar and central and contralateral orbitofrontal, insular, and angular regions. In patients with more than 14 years of disease, atrophy progressed more rapidly in frontocentral and parietal regions that in those with shorter duration. The cross-sectional study showed progressive atrophy in the mesial and superolateral frontal, and parietal cortices. CONCLUSIONS: Our combined cross-sectional and longitudinal analysis in patients with pharmacoresistant temporal lobe epilepsy demonstrated progressive neocortical atrophy over a mean interval of 2.5 years that is distinct from normal aging, likely representing seizure-induced damage. The cumulative character of atrophy underlies the importance of early surgical treatment in this group of patients.

Basal temporal sulcal morphology in healthy controls and patients with temporal lobe epilepsy.

BACKGROUND: We previously demonstrated that shape variants of the hippocampal formation are more prevalent in patients with temporal lobe epilepsy (TLE) than in healthy individuals. OBJECTIVE: To categorize sulcal patterns of the basal temporal lobe in TLE compared to healthy controls. METHODS: We studied 51 healthy controls and 69 patients with TLE (37 left, 32 right TLE). Brain sulci were identified and labeled automatically on MRI using an algorithm based on a congregation of neural networks that allows mapping three-dimensional sulcal models on the cortical surface. We used four sulcal patterns classes to categorize the sulcal arrangement in the inferior surface of the temporal lobe in each subject: Type 1, i.e., single-branch, unbroken collateral sulcus (CS) connected with the rhinal sulcus (RS) anteriorly; Type 2, i.e., CS connected with the occipitotemporal sulcus (OTS), but separated from the RS; Type 3, i.e., CS separated from the OTS and RS, which are connected; and Type 4, i.e., CS, OTS and RS separated. RESULTS: In healthy controls, Type 1 and Type 2 were the patterns seen most frequently. Overall, 82% (42/51) of subjects had the same sulcal pattern in both temporal lobes. Inter-rater reliability for 35 randomly selected subjects indicated excellent agreement (Cohen's Kappa: 0.84). Compared to controls, we found an increased frequency of Type 1 CS in patients with TLE, both in the left (77% vs 47%, p = 0.004) and the right hemispheres (72% vs 41%, p = 0.002). On the other hand, we found a decreased frequency of Type 2 CS in patients with TLE, both in the left (4% vs 31%, p = 0.00002) and the right hemisphere (4% vs 35%, p < 0.00001). CONCLUSIONS: A single-branch, unbroken collateral sulcus is the predominant sulcal pattern found in temporal lobe epilepsy. This "simplified" arrangement may be an indicator of neurodevelopmental deviance associated with this condition.

MR-based neurological disease classification methodology: application to lateralization of seizure focus in temporal lobe epilepsy.

Classification approaches for neurological diseases tend to concentrate on specific structures such as the hippocampus (HC). The hypothesis for the novel methodology presented in this work is that pathologies will impact large tissue areas with detectable variations of T1-weighted MR signal intensity and registration metrics. The technique is applied to lateralization of seizure focus in 127 patients with intractable temporal lobe epilepsy (TLE), in which the site of seizure onset was determined by comprehensive evaluation (69 with left MTL seizure focus (SF) (group "L") and 58 with right SF (group "R")). The method analyses large, non-specific Volumes of Interest (VOI) centered on the left and right medial temporal lobes (MTL) (55 x 82 x 80 voxels) in pre-processed scans aligned in stereotaxic space. Extracted VOIs are linearly and nonlinearly registered to a reference target image. Principal Components Analyses of (i) the normalized intensity and (ii) the trace, a measure of local volume change, are used to generate a multidimensional reference space from a set of 152 neurologically healthy subjects. VOIs from TLE patients, processed in a similar fashion, are projected in this space, and leave-one-out, forward stepwise linear discriminant analysis of the eigencoordinate distributions is used for classification. Following manual MRI volumetric analysis, 80 patients had HC atrophy (group "HA") ipsilateral to the SF (42 with left SF or "LHA", and 38 with right or "RHA"), and the remaining 47 had normal HC volumes (group "HNV") (27 with left SF or "LNV", and 20 with right SF or "RNV"). The automated method was 100% accurate at separating "HA" vs. "HNV", "LHA" vs. "RHA", and "LNV" vs "RNV". It was also 96% accurate at separating "L" vs. "R". Our results indicate that MR data projected in multidimensional feature domains can lateralize SF in epilepsy patients with a high accuracy, irrespective of HC volumes. This single-scan, practical and objective method holds promise for the pre-surgical evaluation of TLE patients.

Individual voxel-based analysis of gray matter in focal cortical dysplasia.

High-resolution MRI of the brain has made it possible to identify focal cortical dysplasia (FCD) in an increasing number of patients. There is evidence for structural abnormalities extending beyond the visually identified FCD lesion. Voxel-based morphometry (VBM) has the potential of detecting both lesions and extra-lesional abnormalities because it performs a whole brain voxel-wise comparison. However, on T1-weighted MRI, FCD lesions are characterized by a wide spectrum of signal hyperintensity that may compromise the results of the segmentation step in VBM. Our purpose was to investigate gray matter (GM) changes in individual FCD patients using voxel-based morphometry (VBM). In addition, we sought to assess the performance of this technique for FCD detection with respect to lesion intensity using an operator designed to emphasize areas of hyperintense T1 signal. We studied 27 patients with known FCD and focal epilepsy and 39 healthy controls. We compared the GM map of each subject (controls and patients) with the average GM map of all controls and obtained a GM z-score map for each individual. The protocol being designed to achieve a maximal specificity, no differences in GM concentration were found in the control group. The z-score maps showed an increase in GM that coincided with the lesion in 21/27 (78%) patients. Five of the six remaining patients whose lesions were not detected by VBM presented with a strong lesion hyperintensity, and a significant part of their lesion was misclassified as white matter. In 16/27 (59%) patients, there were additional areas of GM increase distant from the primary lesion. Areas of GM decrease were found in 8/27 (30%) patients. In conclusion, individual voxel-based analysis was able to detect FCD in a majority of patients. Moreover, FCD was often associated with widespread GM changes extending beyond the visible lesion. In its current form, however, individual VBM may be unable to detect lesions characterized by strong signal intensity abnormalities.

Segmentation of focal cortical dysplasia lesions on MRI using level set evolution.

Focal cortical dysplasia (FCD) is the most frequent malformation of cortical development in patients with medically intractable epilepsy. On MRI, FCD lesions are not easily differentiable from the normal cortex and defining their spatial extent is challenging. In this paper, we introduce a method to segment FCD lesions on T1-weighted MRI. It relies on two successive three-dimensional deformable models, whose evolutions are based on the level set framework. The first deformable model is driven by probability maps obtained from three MRI features: cortical thickness, relative intensity and gradient. These features correspond to the visual characteristics of FCD and allow discriminating lesions and normal tissues. In a second stage, the previous result is expanded towards the underlying and overlying cortical boundaries, throughout the whole cortical section. The method was quantitatively evaluated by comparison with manually traced labels in 18 patients with FCD. The automated segmentations achieved a strong agreement with the manuals labels, demonstrating the applicability of the method to assist the delineation of FCD lesions on MRI. This new approach may become a useful tool for the presurgical evaluation of patients with intractable epilepsy related to cortical dysplasia.

Patterns of hippocampal abnormalities in malformations of cortical development.

OBJECTIVE: To assess whether different types of malformation of cortical development (MCD) are associated with specific patterns of hippocampal abnormalities. METHODS: A total of 122 consecutive patients with MRI diagnosis of MCD (53 males, age range 1-58 years) were included in the study. Hippocampal measurements were made on 1-3 mm coronal T1-weighted MRIs and compared with MRIs of normal controls. RESULTS: A total of 39 patients had focal cortical dysplasia, 5 had hemimegalencephaly, 5 had lissencephaly-agyria-pachygyria, 11 had SLH, 11 had PNH, 12 had bilateral contiguous PNH, 5 had schizencephaly, and 34 had polymicrogyria. The frequency of hippocampal abnormalities in these patients with MCD was 29.5%. A small hippocampus was present in all types of MCD. Only patients with lissencephaly and SLH had an enlarged hippocampus. Abnormalities in hippocampal rotation and shape were present in all types of MCD; however, these predominated in PNH. None of the patients with lissencephaly-agyria-pachygyria or SLH had hyperintense signal on T2 or FLAIR images or abnormal hippocampal internal architecture. CONCLUSION: A small hippocampus was present in all types of MCD; however, the classic MRI characteristics of hippocampal sclerosis were often lacking. Abnormal enlargement of the hippocampus was associated with only diffuse MCD due to abnormal neuronal migration (lissencephaly-agyria-pachygyria and SLH).

Segmentation of focal cortical dysplasia lesions using a feature-based level set.

Focal cortical dysplasia (FCD), a malformation of cortical development, is an important cause of medically intractable epilepsy. FCD lesions are difficult to distinguish from non-lesional cortex and their delineation on MRI is a challenging task. This paper presents a method to segment FCD lesions on T1-weighted MRI, based on a 3D deformable model, implemented using the level set framework. The deformable model is driven by three MRI features: cortical thickness, relative intensity and gradient. These features correspond to the visual characteristics of FCD and allow to differentiate lesions from normal tissues. The proposed method was tested on 18 patients with FCD and its performance was quantitatively evaluated by comparison with the manual tracings of two trained raters. The validation showed that the similarity between the level set segmentation and the manual labels is similar to the agreement between the two human raters. This new approach may become a useful tool for the presurgical evaluation of patients with intractable epilepsy.

Gustatory agnosia.

OBJECTIVE: To report the assessment of a patient exhibiting gustatory agnosia. METHODS: Preoperative and postoperative neuropsychological, neuroimaging, and chemosensory evaluations were performed in a 39-year-old woman undergoing surgical treatment for intractable epilepsy. RESULTS: Preoperative MRIs showed bilateral (right > left) atrophy in the medial temporal lobes and complete atrophy of the left insula. Evaluation of gustatory function revealed normal suprathreshold intensity estimation, affective evaluation, and detection thresholds but elevated recognition thresholds. A functional neuroimaging study showed activation to stimulation of aversive taste in the left amygdala. Surgical treatment entailed resection from the left medial temporal lobe that included the region of amygdala that had responded to taste. Postoperatively, detection, naming, and intensity estimation for taste remained normal, but the patient was unable to recognize different tastes (sweet, sour, salty, and bitter). A second evaluation 2.5 years after her surgery revealed no change in taste ability. CONCLUSION: The anteromedial temporal lobe has an important role in recognizing taste quality.