The association of magnetoencephalography high-frequency oscillations with epilepsy types and a ripple-based method with source-level connectivity for mapping epilepsy sources

Objective

To explore the association between high-frequency oscillations (HFOs) and epilepsy types and to improve the accuracy of source localization.

Methods

Magnetoencephalography (MEG) ripples of 63 drug-resistant epilepsy patients were detected. Ripple rates, distribution, spatial complexity, and the clustering coefficient of ripple channels were used for the preliminary classification of lateral temporal lobe epilepsy (LTLE), mesial temporal lobe epilepsy (MTLE), and nontemporal lobe epilepsy (NTLE), mainly frontal lobe epilepsy (FLE). Furthermore, the seizure site identification was improved using the Tucker LCMV method and source-level betweenness centrality.

Results

Ripple rates were significantly higher in MTLE than in LTLE and NTLE (p < 0.05). The LTLE and MTLE were mainly distributed in the temporal lobe, followed by the parietal lobe, occipital lobe, and frontal lobe, whereas MTLE ripples were mainly distributed in the frontal lobe, then parietal lobe and occipital lobe. Nevertheless, the NTLE ripples were primarily in the frontal lobe and partially in the occipital lobe (p < 0.05). Meanwhile, the spatial complexity of NTLE was significantly higher than that of LTLE and MTLE and was lowest in MTLE (p < 0.01). However, an opposite trend was observed for the standardized clustering coefficient compared with spatial complexity (p < 0.01). Finally, the tucker algorithm showed a higher percentage of ripples at the surgical site when the betweenness centrality was added (p < 0.01).

Conclusion

This study demonstrated that HFO rates, distribution, spatial complexity, and clustering coefficient of ripple channels varied considerably among the three epilepsy types. Additionally, tucker MEG estimation combined with ripple rates based on the source-level functional connectivity is a promising approach for presurgical epilepsy evaluation.     

Association of ipsilateral motor automatisms and contralateral dystonic posturing: a clinical feature differentiating medial from neocortical temporal lobe epilepsy.

BACKGROUND: Clinical features that may help to differentiate medial temporal lobe epilepsy (MTLE) from neocortical temporal lobe epilepsy (NTLE) are lacking. OBJECTIVE: To investigate the localizing and lateralizing value of the association of ipsilateral motor automatisms and contralateral dystonic posturing in patients with medically refractory temporal lobe epilepsy. PATIENTS AND METHODS: Videotapes of 60 patients with well-defined MTLE, NTLE, or both were reviewed to assess the presence and the localizing value of unilateral dystonic posturing associated with motor automatisms. RESULTS: Twenty-eight of the 60 patients exhibited unilateral dystonic posturing. This sign was observed in patients with MTLE and NTLE. It was mostly contralateral to the seizure focus in patients with MTLE and exclusively ipsilateral in patients with NTLE. Unilateral motor automatisms occurred in 26 of the 60 patients with MTLE or NTLE. It was predominantly ipsilateral to the seizure focus in patients with MTLE and exclusively contralateral in patients with NTLE. The association of ipsilateral motor automatisms and contralateral dystonic posturing was found in 14 patients with MTLE but in none of the patients with NTLE. Two patients who had medial and neocortical seizure onset also exhibited this clinical feature. This association was not significantly correlated with the postoperative outcome in patients with MTLE. CONCLUSIONS: The association of ipsilateral motor automatisms and contralateral dystonic posturing may help to differentiate MTLE from NTLE with a reliable lateralizing value. This clinical association may reflect a specific pattern in the spread of the ictal discharge.     

Clinical,semiological, electroencephalographic,and neuropsychological features of “pure” neocortical temporal lobe epilepsy

Aims: We examined the clinical, semiological, scalp EEG, and neuropsychological features of patients with “pure” neocortical temporal lobe epilepsy (NTLE) who were successfully treated by neocortical temporal resection sparing the mesial temporal structures. Methods: This retrospective study included 17 patients with lesional NTLE who satisfied the following criteria: presence of a discrete structural lesion in the lateral temporal lobe on preoperative MRI; lateral temporal resection sparing the mesial temporal structures; follow‐up for at least two years after surgery; and favourable postoperative seizure outcome (Engel Class I). The study included 10 females and seven males, and the age at surgery ranged from 15 to 48 years (mean: 30.7 years). Auras, video‐recorded seizure semiology, interictal and ictal EEG, and pre‐ and post‐operative neuropsychological data were reviewed. Twenty patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, who had a favourable postoperative seizure outcome (Engel Class I), were selected as a control group. Results: Age at seizure onset was significantly greater in patients with NTLE than in controls. A history of febrile convulsion was significantly less frequent in NTLE patients. Epigastric ascending sensation (6% versus 40%; p=0.017), oral automatisms (29% versus 80%; p=0.003), gestural automatisms (47% versus 80%; p=0.047), and dystonic posturing (0% versus 40%; p=0.003) were significantly less frequent in NTLE than controls. Ictal unitemporal rhythmic theta activity was also significantly less frequent in NTLE than controls (35.3% versus 75%; p=0.015). Preoperative IQ score (range: 68 to 114; mean: 88.9) and preoperative memory quotient score (range: 56–122; mean: 98.1) were significantly higher in NTLE (p=0.003 and p=0.048, respectively). Conclusion: There were notable differences in clinical, semiological, EEG, and neuropsychological features between “pure” NTLE and MTLE. These findings may be useful to identify the epileptogenic zone.     

How common is brain atrophy in patients with medial temporal lobe epilepsy?

Purpose: It is unclear whether extrahippocampal brain damage in patients with medial temporal lobe epilepsy (MTLE) is a homogeneous phenomenon, as most data relates to the average volume reduction in groups of patients. This study aimed to evaluate where and how much atrophy is to be expected in an individual patient with MTLE. Methods: High‐resolution T₁ magnetic resonance imaging (MRI) was obtained from 23 consecutive patients with unilateral MTLE and from a matched control group. Parametric tests of voxel‐based gray matter volume evaluated mean regional atrophy in MTLE compared with controls. Gray matter images were then submitted to a voxel by voxel calculation of the fitted receiver operating characteristic (ROC) curve area, plotting the sensitivity versus 1–specificity for a binary classifier (MTLE vs. controls). The area under the curve (AUC) was calculated for each voxel and a resulting three‐dimensional map of gray matter voxel‐wise AUCs was obtained. Results: On average, patients with MTLE showed atrophy in the ipsilateral hippocampus and on a limbic network. Elevated AUC was demonstrated in the ipsilateral hippocampus and medial temporal lobe, the ipsilateral thalamus and occipitotemporal cortex, the ipsilateral cerebellum, the cingulate, the contralateral insula, and the occipitoparietal and dorsolateral prefrontal cortex. Conclusion: This study suggests that the medial temporal lobe, occipitotemporal areas, the cerebellum, the cingulate cortex, the ipsilateral insula, and thalamus are more likely to be atrophied in randomly selected patients with MTLE. Structures such as the orbitofrontal cortex, the contralateral medial temporal areas and insula, the putamen, and the caudate may be atrophied, but not as consistently.     

Memory characteristics in mesial temporal lobe epilepsy: Insights from an eye tracking memory game and neuropsychological assessments

Aims

To compare different patterns of memory impairment in patients with two subtypes of mesial temporal lobe epilepsy (MTLE) and healthy controls.

Methods

Thirty-five healthy controls and 41 patients with MTLE were recruited, of which 25 patients were diagnosed as hippocampal sclerosis (HS-MTLE), and the rest 16 patients were lesion-negative (MRI-neg MTLE). Participants completed the Wechsler memory assessment and a short-term memory game on an automated computer-based memory assessment platform with an eye tracker.

Results

Both the MRI-neg MTLE and HS-MTLE groups took longer time to complete the short-term memory game than healthy controls (p < 0.001, Cohen's d = 1.087; p = 0.047, Cohen's d = 0.787). During the memory encoding phase, the MRI-neg MTLE group spent significantly shorter time than healthy controls on the difficult levels with three (p = 0.004, Cohen's d = 0.993) and four targets (p = 0.016, Cohen's d = 0.858). During the memory decoding phase, the HS-MTLE group spent less time looking on the targets compared to controls when recalling and finding four targets (p = 0.004, Cohen's d = −0.793), while the MRI-neg MTLE group spent significantly longer time on the distractors and shorter time on the region of interests (ROIs) for all difficulty levels (all p < 0.05) than controls. Furthermore, the eye tracking data were correlated with the scores of the Wechsler Memory Scale after Bonferroni correction (p < 0.05).

Conclusion

Patients with MRI-neg MTLE demonstrate impaired memory mostly due to attention deficits, while those with HS-MTLE show memory impairment with relative sparing of attention. Eye tracking technology has the potential of facilitating the investigation of the mechanism of memory defect in MTLE and can serve as a supplementary neuropsychological tool for clinical diagnosis and long-term monitoring.     

Sex differences in patients with mesial temporal lobe epilepsy

Possible sex differences in the pattern of interictalhypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobehypometabolism ipsilateral to the seizure onset (p<0.0001) and aspread of epileptiform activity to this region (p=0.001). By contrast,female patients more often exhibited hypometabolism (p=0.0052) and anictal spread to the contralateral temporal lobe (p=0.0097). Thesefindings suggest sex differences in spatial distribution of braindysfunction in MTLE, perhaps reflecting sexual dimorphism in regionalcerebral connectivity.

     

Shared functional network abnormality in patients with temporal lobe epilepsy and their siblings

Aim

Temporal lobe epilepsy is a neurological network disease in which genetics played a greater role than previously appreciated. This study aimed to explore shared functional network abnormalities in patients with sporadic temporal lobe epilepsy and their unaffected siblings.

Methods

Fifty-eight patients with sporadic temporal lobe epilepsy, 13 unaffected siblings, and 30 healthy controls participated in this cross-sectional study. We examined the task-based whole-brain functional network topology and the effective functional connectivity between networks identified by group-independent component analysis.

Results

We observed increased global efficiency, decreased clustering coefficiency, and decreased small-worldness in patients and siblings (p < 0.05, false discovery rate-corrected). The effective network connectivity from the ventral attention network to the limbic system was impaired (p < 0.001, false discovery rate-corrected). These features had higher prevalence in unaffected siblings than in normal population and was not correlated with disease burden. In addition, topological abnormalities had a high intraclass correlation between patients and their siblings.

Conclusion

Patients with temporal lobe epilepsy and their unaffected siblings showed shared topological functional disturbance and the effective functional network connectivity impairment. These abnormalities may contribute to the pathogenesis that promotes the susceptibility of seizures and language decline in temporal lobe epilepsy.     

Phosphorus magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy

Phosphorus magnetic resonance spectroscopic imaging has previously demonstrated localized metabolic abnormalities within the epileptogenic region in patients with temporal lobe epilepsy, including alkalosis, increased inorganic phosphate level, and decreased phosphomonoester levels. We studied 8 patients with frontal lobe epilepsy, finding interictal alkalosis in the epileptogenic region compared to the contralateral frontal lobe in all patients (7.10 ± 0.05 vs 7.00 ± 0.06, p < 0.001). Seven patients exhibited decreased phosphomonoester levels in the epileptogenic frontal lobe compared to the contralateral frontal lobe (16.0 ± 6.0 vs 23.0 ± 4.0, p < 0.01). In contrast to findings in temporal lobe epilepsy, inorganic phosphate level was not increased in the epileptogenic region. Based on values derived from normal control subjects, 5 patients had elevated pH in the seizure focus and 2 patients had decreased phosphomonoesters while none had abnormalities in the contralateral frontal lobe. These data suggest that magnetic resonance spectroscopy will be useful in the presurgical evaluation of patients with frontal lobe epilepsy.     

Postoperative changes in cerebral metabolism in temporal lobe epilepsy

BACKGROUND: Fludeoxyglucose F 18 positron emission tomography ((18)F-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. DESIGN: Interictal preoperative and postoperative (18)F-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. SETTING: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. PATIENTS: Twenty-two patients with refractory TLE. RESULTS: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. CONCLUSION: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. Arch Neurol. 2000;57:1447-1452     

Monoamine neurotransmitters in resected hippocampal subparcellations from neocortical and mesial temporal lobe epilepsy patients: in situ microvoltammetric studies

It is known that epilepsy patients diagnosed with neocortical temporal lobe epilepsy (NTLE), differ from those diagnosed with mesial temporal lobe epilepsy (MTLE), e.g., in hippocampal (HPC) pathology. In the present studies, we tested the hypothesis that NTLE and MTLE subtypes of human epilepsy might differ in regards to their HPC monoamine neurochemistry. Monoamine neurotransmitters were studied in separate signals and within s with semiderivative microvoltammetry, used in combination with stearate indicator, Ag-AgCl reference and stainless steel auxiliary microelectrodes. Anterior HPC specimens from the patients' epileptogenic zone, defined by electrocorticography, were resected neurosurgically from 13 consecutive patients with intractable temporal lobe epilepsy. Four patients were diagnosed with NTLE and nine with MTLE. The criteria for the diagnosis of NTLE versus MTLE was absence versus presence of HPC sclerosis, respectively, based on MRI examination of resected tissue. In addition, NTLE patients demonstrated seizure onset in anterolateral temporal neocortex on electroencephalography (EEG). HPC subparcellations studied were: (a) Granular Cells of the Dentate Gyrus (DG), (b) Polymorphic Layer of DG and (c) Pyramidal Layer: subfields, CA1 and CA2. Dopamine (DA), serotonin (5-HT), norepinephrine (NE) and ascorbic acid (AA) (co-factor in DA to NE synthesis), exhibited separate and characteristic half-wave potentials in millivolts. Each half-wave potential, i.e., the potential at which maximum current was generated, was experimentally established in vitro. Concentrations of neurotransmitters found in HPC subparcellations were interpolated from calibration curves derived in vitro from electrochemical detection of monoamines and AA in saline phosphate buffer. Significant differences between subtypes in concentration of monoamines were analyzed by the Mann Whitney rank sum test and those differences in probability distribution of monoamines were analyzed by the Fisher Exact test; in each case, P<0.01 was the criteria selected for determining statistical significance. DA concentrations were higher in NTLE compared with MTLE in each HPC subparcellation [P=0.037, 0.024 and 0.007, respectively (P<0.01)] and DA occurred more frequently in NTLE in the Pyramidal Layer [P=0.077 (P<0.01)]. AA was present in one NTLE patient. NE concentrations were higher in MTLE vs. NTLE in each subparcellation [P=0.012, 0.067 and 0.07, respectively (P<0.01)] and NE occurred more frequently in MTLE in Granular Cells of DG and Pyramidal Layer [P=0.052 and 0.014, respectively (P<0.01)]. In MTLE, NE concentrations in the CA1 subfield of the Pyramidal Layer were decreased vs. the CA2 subfield [P=0.063 (P<0.01)]. Serotonin was found in every HPC subparcellation of each subtype but 5-HT concentrations were higher in NTLE vs. MTLE in the Granular Cells of DG and the Pyramidal Layer (CA1 subfield) [P=0.076 and 0.095, respectively (P<0.01)]. Thus, this preliminary study showed that marked differences in HPC monoamine neurochemistry occurred in NTLE patients as compared with MTLE patients.     

Biogenic amines in the human neocortex in patients with neocortical and mesial temporal lobe epilepsy: identification with in situ microvoltammetry

Biogenic amines in well defined subtypes of human temporal lobe epilepsy (TLE) have not been well characterized. Specimens from five patients with neocortical TLE (NTLE) and nine with mesial TLE (MTLE) were immediately placed in Ringer's lactate; stearate indicator microelectrodes were placed in temporal gray matter, Ag/AgCl reference microelectrodes and auxiliary microelectrodes were placed 3-7 mm contralaterally to the indicator microelectrode. Dopamine (DA), ascorbic acid (AA), norepinephrine (NE) and serotonin (5-HT) were identified by their characteristic oxidative potentials in vitro. Four of five patients with NTLE had NE depletion in temporal neocortex while eight of nine patients with MTLE had high concentrations of NE (chi-square P<0.01). Significant concentrations of DA were present in the temporal lobes of three of five NTLE patients but in only one of the nine MTLE patients (chi-square P<0.05). 5-HT was present in the neocortex of both NTLE and MTLE patients in similar concentrations. AA was found in the neocortex of one NTLE patient. These data support an association between NE depletion and NTLE. The relative NE deficiency along with the consistent presence of DA in NTLE patients suggest an impairment in the catecholamine pathway. The presence of AA, a co-factor in NE synthesis, in the neocortex of one NTLE patient may also be related since AA is a cofactor in NE synthesis.     

Clinical features of neocoritcal temporal lobe epilepsy

Few Studies have examined the clinical features of neocortical temporal lobe epilepsy (NTLE) in carefully selected patients. We reviewed records from 21 patients wtih NTLE, defined by intracranial electroencephal9ogram (EEG), who have been seizure free for 1 year or more following temporal lobectomy. The mean age of onset at the time of first seizure was 14 years (range, 1–41 years). Febrile seizures were reported in only 2 patients (9.5%). In contrast to prior mesial temporal lobe epilepsy (MTLE) studies, seizure-free intervals between the initial cerebral insult or first seizure and habitual seizures were uncommon. Possible or known risk factors for epilepsy were reported in 13 of 21 patients (62%). Fifteen (71%) patients reproted auras, with experiential phenomena being the most common type. Magnetic resonance imaging was normal or nospecific in 15 patients, revealed mild hippocampal atrophy in 2, tumors in 2, and resonance imaging was normal or nospecifc in 15 patients, revealed mild hippocampal atrophy in 2, tumors in 2, and heterotopic gray matter and hippocampal atrophy in 1, and cortical dysgensis in 1. Neuropsychological testing showed deficits consistent with the seizure focus in 13 patients (62%), and Wada test showed ipsilateral memory deficits in 10 (48%). The most common behavioral manifestatin was a motionless stare at ictal onset (48%). In contrast to prior studies of MTLE, only 1 NTLE patient had frequent independent, contralateral temporal lobe epileptiform spikes on scalp EEG.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

OBJECTIVE: The goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE. METHODS: Children with symptomatic TLE (n=14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n=14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery. RESULTS: Children with MTLE with unilateral hippocampal atrophy (n=9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n=14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex. CONCLUSIONS: Similar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy

OBJECTIVE: The objective of this study was to assess the volumes of medial temporal lobe structures using high resolution magnetic resonance images from patients with chronic refractory medial temporal lobe epilepsy (MTLE). METHODS: We studied 30 healthy subjects, and 25 patients with drug refractory MTLE and unilateral hippocampal atrophy (HA). We used T1 magnetic resonance images with 1 mm isotropic voxels, and applied a field non-homogeneity correction and a linear stereotaxic transformation into a standard space. The structures of interest are the entorhinal cortex, perirhinal cortex, parahippocampal cortex, temporopolar cortex, hippocampus, and amygdala. Structures were identified by visual examination of the coronal, sagittal, and axial planes. The threshold of statistical significance was set to p<0.05. RESULTS: Patients with right and left MTLE showed a reduction in volume of the entorhinal (p<0.001) and perirhinal (p<0.01) cortices ipsilateral to the HA, compared with normal controls. Patients with right MTLE exhibited a significant asymmetry of all studied structures; the right hemisphere structures had smaller volume than their left side counterparts. We did not observe linear correlations between the volumes of different structures of the medial temporal lobe in patients with MTLE. CONCLUSION: Patients with refractory MTLE have damage in the temporal lobe that extends beyond the hippocampus, and affects the regions with close anatomical and functional connections to the hippocampus.     

Interictal regional delta slowing is an EEG marker of epileptic network in temporal lobe epilepsy

Purpose: Several studies have suggested that interictal regional delta slowing (IRDS) carries a lateralizing and localizing value similar to interictal spikes and is associated with favorable surgical outcomes in patients with temporal lobe epilepsy (TLE). However, whether IRDS reflects structural dysfunction or underlying epileptic activity remains controversial. The objective of this study is to determine the cortical electroencephalography (EEG) correlates of scalp‐recorded IRDS, in so doing, to further understand its clinical and biologic significances. Methods: We examined the cortical EEG substrates of IRDS with electrocorticography (ECoG‐IRDS) and delineated the spatiotemporal relationship between ECoG‐IRDS and both interictal and ictal discharges by recording simultaneously scalp and intracranial EEG in 18 presurgical candidates with TLE. Key Findings: Our results demonstrated that ECoG‐IRDS is typically a mixture of delta/theta slowing and spike‐wave potentials. ECoG‐IRDS was predominantly recorded from basal and anterolateral temporal cortex, occasionally in mesial, posterior temporal, and extratemporal regions. Abundant IRDS was most commonly observed in patients with neocortical temporal lobe epilepsy (NTLE), whereas infrequent to moderate IRDS was usually observed in patients with mesial temporal lobe epilepsy (MTLE). The anatomic distribution of ECoG‐IRDS was highly correlated with the irritative and seizure‐onset zones in 10 patients with NTLE. However, it was poorly correlated with the irritative and seizure‐onset zones in the 8 patients with MTLE. Significance: These findings demonstrate that IRDS is an EEG marker of epileptic network in patients with TLE. Although IRDS and interictal/ictal discharges likely arise from the same neocortical generator in patients with NTLE, IRDS in patients with MTLE may reflect a network disease that involves temporal neocortex.     

Quantitative MRI in temporal lobe epilepsy: evidence for fornix atrophy.

OBJECTIVE: To investigate whether the fornix and mamillary bodies, being part of the limbic system, are abnormal in patients with mesial temporal lobe epilepsy (MTLE). BACKGROUND: The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. This system is implicated in complex functions, including memory and emotion, and in diseases such as MTLE. METHODS: The authors performed volumetric measurements of hippocampus, amygdala, fornix, and mamillary bodies in 50 patients with MTLE and compared the results with normal controls and patients with extratemporal lobe epilepsy. RESULTS: Control (n = 17) measurements of the amygdala, hippocampus, and fornix revealed larger volumes of the right hemisphere structures (p < 0.001). Normalized fornix volumes revealed atrophy in 86% of studies concordant with hippocampal atrophy in all cases but one. Similarly, the mean hippocampal and fornix volumes for the group discriminated the epileptogenic temporal lobe (p < 0.001). Limbic volumes were normal in all patients with extratemporal lobe epilepsy. CONCLUSIONS: Quantitative MRI findings support the concept that MTLE is not a process limited to the hippocampus but also involves other interrelated limbic system structures, in particular, the fornix.     

Widespread cortical and subcortical brain atrophy in Parkinson’s disease with excessive daytime sleepiness

Our aim was to determine regional brain atrophy in Parkinson’s disease (PD) patients with excessive daytime sleepiness (EDS) using voxel-based morphometry (VBM). From 71 consecutive probable PD patients, nine non-demented and non-hallucinating patients with an Epworth Sleepiness Scale (ESS) ≥ 10 and 13 PD patients with an ESS ≤ 3 were selected as having EDS and as not having EDS, respectively. We also enrolled 22 healthy age- and sex-matched controls. Regional brain atrophy was assessed using VBM with 3-T magnetic resonance imaging. There was no difference in the dosage of dopaminergic drugs between PD patients with EDS and PD patients without EDS. PD patients with EDS showed marked atrophy in the gray matter of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to controls (false discovery rate corrected p < 0.05). In contrast, PD patients without EDS did not show any significant difference in gray matter atrophy compared to controls (false discovery rate corrected p < 0.05). PD patients with EDS showed significant atrophy of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to PD patients without EDS (uncorrected p < 0.001). PD patients with EDS, even without dementia and hallucination, showed significant gray matter atrophy compared to PD patients without EDS and controls.     

Voxel-based morphometry reveals gray matter network atrophy in refractory medial temporal lobe epilepsy

BACKGROUND: Conventional volumetric studies have shown that brain structures functionally and anatomically related to the hippocampus are smaller in patients with drug-refractory medial temporal lobe epilepsy (MTLE). OBJECTIVES: To determine the extent of gray matter atrophy in the brains of patients with MTLE and to examine the pattern of atrophy. DESIGN: We performed a voxel-based morphometric study of 43 consecutive patients with unilateral drug-refractory MTLE (21 patients with right-sided MTLE and 22 patients with left-sided MTLE) whose magnetic resonance images showed signs of unilateral hippocampal atrophy. The data from the patients with MTLE were compared with the data from 49 healthy control subjects to identify differences between groups in gray matter concentration (GMC). SETTING: Academic hospital's epilepsy clinic. RESULTS: We observed that patients with left- and right-sided MTLE exhibited GMC reduction in the hippocampus ipsilateral to the seizure origin. In addition, we found GMC reduction in the ipsilateral parahippocampal and isocortical temporal regions. Patients with MTLE also showed GMC reduction in subcortical nuclei such as the thalamus and caudate, in the cerebellum, in the midbrain, and in parieto-occipital regions. CONCLUSIONS: Patients with MTLE exhibit a reduction in GMC in regions outside the temporal lobe, specifically in areas that are connected to the hippocampus and parahippocampal region, suggesting an anatomical route for atrophy.     

Asymmetric Gray Matter Volume Changes Associated with Epilepsy Duration and Seizure Frequency in Temporal-Lobe-Epilepsy Patients with Favorable Surgical Outcome

MethodsVBM analysis of brain MRI using statistical parametric mapping 8 (SPM8) was performed for 30 left MTLE (LMTLE) and 30 right MTLE (RMTLE) patients and 30 age- and sex-matched healthy controls. We also analyzed the correlations between GMV changes and clinical features of MTLE patients.ResultsIn SPM8-based analyses, MTLE patients showed significant GMV reductions in the hippocampus ipsilateral to the epileptic focus, bilateral thalamus, and contralateral putamen in LMTLE patients. The GMV reductions were more extensive in the ipsilateral hippocampus, thalamus, caudate, putamen, uncus, insula, inferior temporal gyrus, middle occipital gyrus, cerebellum, and paracentral lobule in RMTLE patients. These patients also exhibited notable reductions of GMV in the contralateral hippocampus, thalamus, caudate, putamen, and inferior frontal gyrus. We observed that GMV reduction was positively correlated with several clinical features (epilepsy duration and seizure frequency in RMTLE, and history of febrile seizure in LMTLE) and negatively correlated with seizure onset age in both the RMTLE and LMTLE groups.ConclusionsOur study revealed GMV decreases in the hippocampus and extrahippocampal regions. Furthermore, the GMV reduction was more extensive in the RMTLE group than in the LMTLE group, since it included the contralateral hemisphere in the former. This difference in the GMV reduction patterns between LMTLE and RMTLE may be related to a longer epilepsy duration and higher seizure frequency in the latter.