Daichi Sone

Effect of electroconvulsive therapy on gray matter volume in major depressive disorder

BACKGROUND Although the clinical efficacy of electroconvulsive therapy (ECT) is well established, the underlying mechanisms of action remain elusive. The aim of this study was to elucidate structural changes of the brain following ECT in patients with major depressive disorder (MDD). METHOD Fifteen patients with MDD underwent magnetic resonance imaging scanning before and after ECT. Their gray matter volumes were compared between pre- and post-ECT. RESULTS There were significant volume increases after ECT in the bilateral medial temporal cortices, inferior temporal cortices, and right anterior cingulate. Further, the increase ratio was correlated with the clinical improvement measured by the Hamilton Depression Rating scale. LIMITATION All subjects were treated with antidepressants that could have a neurotoxic or neuroprotective effect on the brain. CONCLUSIONS We found that there were significant increases of gray matter volume in medial temporal lobes following ECT, suggesting that a neurotrophic effect of ECT could play a role in its therapeutic effect.

Automated subfield volumetric analysis of hippocampus in temporal lobe epilepsy using high-resolution T2-weighed MR imaging.

Background and purpose Automated subfield volumetry of hippocampus is desirable for use in temporal lobe epilepsy (TLE), but its utility has not been established. Automatic segmentation of hippocampal subfields (ASHS) and the new version of FreeSurfer software (ver.6.0) using high-resolution T2-weighted MR imaging are candidates for this volumetry. The aim of this study was to evaluate hippocampal subfields in TLE patients using ASHS as well as the old and new versions of FreeSurfer. Materials and methods We recruited 50 consecutive unilateral TLE patients including 25 with hippocampal sclerosis (TLE-HS) and 25 without obvious etiology (TLE-nonHS). All patients and 45 healthy controls underwent high-resolution T2-weighted and 3D-volume T1-weighted MRI scanning. We analyzed all of their MR images by FreeSurfer ver.5.3, ver.6.0 and ASHS. For each subfield, normalized z-scores were calculated and compared among groups. Results In TLE-HS groups, ASHS and FreeSurfer ver.6.0 revealed maximal z-scores in ipsilateral cornu ammonis (CA) 1, CA4 and dentate gyrus (DG), whereas in FreeSurfer ver.5.3 ipsilateral subiculum showed maximal z-scores. In TLE-nonHS group, there was no significant volume reduction by either ASHS or FreeSurfer. Conclusions ASHS and the new version of FreeSurfer may have an advantage in compatibility with existing histopathological knowledge in TLE patients with HS compared to the old version of FreeSurfer (ver.5.3), although further investigations with pathological findings and/or surgical outcomes are desirable.

Evaluation of amygdala pathology using 11C-methionine positron emission tomography/computed tomography in patients with temporal lobe epilepsy and amygdala enlargement

OBJECTIVE The association between amygdala enlargement (AE) and temporal lobe epilepsy (TLE) has increasingly been reported. However, the pathology of AE remains poorly understood. The purpose of this study was to explore AE pathology using (11)C-methionine (Met) positron emission tomography (PET)/computed tomography (CT) in patients who have TLE with AE. MATERIALS AND METHODS Twenty-six TLE patients with AE and 18 TLE patients without AE underwent (11)C-Met PET/CT and magnetic resonance imaging (MRI). (11)C-Met uptake in amygdala was evaluated by both visual inspection and semi-quantitative measurement. MRI was assessed visually and semi-quantitatively for AE. Laterality index (LI) was obtained by comparing the amygdala volumes of ipsilateral and contralateral sides. The clinical course and histopathological findings of all patients were also analyzed. RESULTS On (11)C-Met PET/CT images, visual examination detected increased uptake in the enlarged amygdala in 7 of 26 (27%) TLE patients with AE, and the results were confirmed by semi-quantitative analysis. Among six TLE patients with AE who underwent surgery, histopathology revealed neoplasms (low grade astrocytoma and gangliocytoma) in two patients and focal cortical dysplasia in one patient with increased (11)C-Met uptake, but non-neoplastic lesions (focal cortical dysplasia, vacuolar degeneration, and hamartoma) in all three patients with no increased (11)C-Met uptake. On MRI, volume of the affected amygdala was significantly larger compared to the contralateral amygdala. LI was significantly higher in the group with AE than in the group without AE. CONCLUSIONS This study revealed that some TLE patients with AE showed increased (11)C-Met uptake in the enlarged amygdala. (11)C-Met PET/CT is potentially useful for the evaluation of AE pathology, and may provide beneficial information for appropriate decision-making.

Comparing CAT12 and VBM8 for Detecting Brain Morphological Abnormalities in Temporal Lobe Epilepsy

The identification of the brain morphological alterations that play important roles in neurodegenerative/neurological diseases will contribute to our understanding of the causes of these diseases. Various automated software programs are designed to provide an automatic framework to detect brain morphological changes in structural magnetic resonance imaging (MRI) data. A voxel-based morphometry (VBM) analysis can also be used for the detection of brain volumetric abnormalities. Here, we compared gray matter (GM) and white matter (WM) abnormality results obtained by a VBM analysis using the Computational Anatomy Toolbox (CAT12) via the current version of Statistical Parametric Mapping software (SPM12) with the results obtained by a VBM analysis using the VBM8 toolbox implemented in the older software SPM8, in adult temporal lobe epilepsy (TLE) patients with (n = 51) and without (n = 57) hippocampus sclerosis (HS), compared to healthy adult controls (n = 28). The VBM analysis using CAT12 showed that compared to the healthy controls, significant GM and WM reductions were located in ipsilateral mesial temporal lobes in the TLE-HS patients, and slight GM amygdala swelling was present in the right TLE-no patients (n = 27). In contrast, the VBM analysis via the VBM8 toolbox showed significant GM and WM reductions only in the left TLE-HS patients (n = 25) compared to the healthy controls. Our findings thus demonstrate that compared to VBM8, a VBM analysis using CAT12 provides a more accurate volumetric analysis of the brain regions in TLE. Our results further indicate that a VBM analysis using CAT12 is more robust and accurate against volumetric alterations than the VBM8 toolbox.

Computed-tomography-guided anatomic standardization for quantitative assessment of dopamine transporter SPECT

PurposeFor the quantitative assessment of dopamine transporter (DAT) using [123I]FP-CIT single-photon emission computed tomography (SPECT) (DaTscan), anatomic standardization is preferable for achieving objective and user-independent quantification of striatal binding using a volume-of-interest (VOI) template. However, low accumulation of DAT in Parkinson’s disease (PD) would lead to a deformation error when using a DaTscan-specific template without any structural information. To avoid this deformation error, we applied computed tomography (CT) data obtained using SPECT/CT equipment to anatomic standardization.MethodsWe retrospectively analyzed DaTscan images of 130 patients with parkinsonian syndromes (PS), including 80 PD and 50 non-PD patients. First we segmented gray matter from CT images using statistical parametric mapping 12 (SPM12). These gray-matter images were then anatomically standardized using the diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) algorithm. Next, DaTscan images were warped with the same parameters used in the CT anatomic standardization. The target striatal VOIs for decreased DAT in PD were generated from the SPM12 group comparison of 20 DaTscan images from each group. We applied these VOIs to DaTscan images of the remaining patients in both groups and calculated the specific binding ratios (SBRs) using nonspecific counts in a reference area. In terms of the differential diagnosis of PD and non-PD groups using SBR, we compared the present method with two other methods, DaTQUANT and DaTView, which have already been released as software programs for the quantitative assessment of DaTscan images.ResultsThe SPM12 group comparison showed a significant DAT decrease in PD patients in the bilateral whole striatum. Of the three methods assessed, the present CT-guided method showed the greatest power for discriminating PD and non-PD groups, as it completely separated the two groups.ConclusionCT-guided anatomic standardization using the DARTEL algorithm is promising for the quantitative assessment of DaTscan images.

Graph Theoretical Analysis of Structural Neuroimaging in Temporal Lobe Epilepsy with and without Psychosis

Purpose Psychosis is one of the most important psychiatric comorbidities in temporal lobe epilepsy (TLE), and its pathophysiology still remains unsolved. We aimed to explore the connectivity differences of structural neuroimaging between TLE with and without psychosis using a graph theoretical analysis, which is an emerging mathematical method to investigate network connections in the brain as a small-world system. Materials and Methods We recruited 11 TLE patients with unilateral hippocampal sclerosis (HS) presenting psychosis or having a history of psychosis (TLE-P group). As controls, 15 TLE patients with unilateral HS without any history of psychotic episodes were also recruited (TLE-N group). For graph theoretical analysis, the normalized gray matter images of both groups were subjected to Graph Analysis Toolbox (GAT). As secondary analyses, each group was compared to 14 age- and gender-matched healthy subjects. Results The hub node locations were found predominantly in the ipsilateral hemisphere in the TLE-N group, and mainly on the contralateral side in the TLE-P group. The TLE-P group showed significantly higher characteristic path length, transitivity, lower global efficiency, and resilience to random or targeted attack than those of the TLE-N group. The regional comparison in betweenness centrality revealed significantly decreased connectivity in the contralateral temporal lobe, ipsilateral middle frontal gyrus, and bilateral postcentral gyri in the TLE-P group. The healthy subjects showed well-balanced nodes/edges distributions, similar metrics to TLE-N group except for higher small-worldness/modularity/assortativity, and various differences of regional betweenness/clustering. Conclusion In TLE with psychosis, graph theoretical analysis of structural imaging revealed disrupted connectivity in the contralateral hemisphere. The network metrics suggested that the existence of psychosis can bring vulnerability and decreased efficiency of the whole-brain network. The sharp differences in structural networks between morphologically homogeneous groups are remarkable and may contribute to a better understanding of psychosis in TLE.

White matter abnormalities in patients with temporal lobe epilepsy and amygdala enlargement: Comparison with hippocampal sclerosis and healthy subjects

PURPOSE Cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have increasingly been reported. However, the white matter (WM) abnormalities of TLE patients with AE remain poorly investigated. Here we explored macrostructural and microstructural WM abnormalities in TLE patients with AE compared to normal controls and TLE patients with hippocampal sclerosis (HS). MATERIAL AND METHODS We selected 17 patients with unilateral TLE with AE (TLE-AE) based on automated amygdala volumetry using FreeSurfer software, and 34 healthy controls and 35 patients with unilateral TLE with HS (TLE-HS) were also recruited. Subsequently, differences in gray matter (GM) and WM volumes and fractional anisotropy (FA) among the three groups were analyzed using SPM8 software. RESULTS The volume analysis of GM obtained results that are consistent with the structural characteristics of TLE with AE and with HS (i.e. amygdala increase in the TLE-AE, and mesial temporal atrophy in the TLE-HS). In the volume of WM, only the TLE-HS patients had WM reductions mainly in the ipsilateral temporal lobe. Compared to the controls, the TLE-AE group showed a significant FA decrease in the ipsilateral anterior cingulum and the corpus callosum, whereas an extended FA decrease in the whole cerebrum was observed in the TLE-HS group. CONCLUSION Our findings regarding the WM of TLE patients with AE may reflect characteristic pathophysiology such as the anatomical and functional connection between the amygdala and medial prefrontal cortex, and our results may thus provide insights into TLE with AE.

Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases☆☆☆★

Classic antidepressants have been known to induce convulsive seizures and nonconvulsive status epilepticus (NCSE). On the other hand, many reports have emphasized the safety of novel antidepressants. However, we encountered three cases of NCSE in the elderly associated with the use of newer antidepressants at therapeutic doses. All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each), impaired consciousness appeared. Electroencephalography (EEG) showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

Intraventricular cerebrospinal fluid temperature analysis using MR diffusion-weighted imaging thermometry in Parkinson's disease patients, multiple system atrophy patients, and healthy subjects

We examined the temperature of the intraventricular cerebrospinal fluid (Tv) in patients with Parkinsons disease (PD) and those with multiple system atrophy (MSA) in comparison with healthy subjects, and we examined normal changes in this temperature with aging.

Validation of the cingulate island sign with optimized ratios for discriminating dementia with Lewy bodies from Alzheimer’s disease using brain perfusion SPECT

ObjectiveDementia with Lewy bodies (DLB) is often cited as the second most common dementia after Alzheimer’s disease (AD). It is clinically important to distinguish DLB from AD because specific side effects of antipsychotic drugs are limited to DLB. The relative preservation of cingulate glucose metabolism in the posterior cingulate gyri versus that in the precuni, known as the cingulate island sign (CIS), in patients with DLB compared with AD is supposed to be highly specific for diagnosing DLB. In a previous study, using brain perfusion SPECT, the largest value (0.873) for the area under the receiver operating characteristic (ROC) curve (AUC) for differentiating DLB from AD was obtained with the ratio of the posterior cingulate gyri from an early Alzheimer’s disease-specific hypoperfusion volume of interest (VOI) versus the medial occipital lobe. Two purposes of this study are as follows: one is optimization of VOI setting for calculating CIS values and the other is to evaluate their accuracy and simultaneously to retest the method described in our previous paper.MethodsWe conducted a retest of this SPECT method with another cohort of 13 patients with DLB and 13 patients with AD. Furthermore, we optimized VOIs using contrast images obtained from group comparisons of DLB and normal controls; the same 18 patients with DLB and 18 normal controls examined in our previous study. We obtained DLB-specific VOIs from areas where brain perfusion was significantly decreased in DLB. As the numerators of these ratios, early Alzheimer’s disease-specific VOIs were used after subtracting DLB-specific VOIs. The DLB-specific VOIs were used as the denominator.ResultsIn retest, the obtained AUC was 0.858 and the accuracy, sensitivity, and specificity were 84.6, 84.6, and 84.6%, respectively. The ROC curve analysis with these optimized VOIs yielded a higher AUC of 0.882; and the accuracy, sensitivity, and specificity of these new CIS ratios were 84.6, 92.3, and 76.9%, respectively, with a threshold value of 0.281.ConclusionOptimized CISs using brain perfusion SPECT are clinically useful for differentiating DLB from AD.