Distinct white matter abnormalities in different idiopathic generalized epilepsy syndromes

Purpose: By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic–clonic seizures only (IGE‐GTC). Methods: We assessed white matter integrity and gray matter volume using diffusion tensor tractography–based analysis of fractional anisotropy and voxel‐based morphometry, respectively, in 25 patients with IGE, all of whom had experienced generalized tonic–clonic convulsions. Specifically, 15 patients with JME and 10 patients with IGE‐GTC were compared to two groups of similarly matched controls separately. Correlations between total lifetime generalized tonic–clonic seizures and fractional anisotropy were investigated for both groups. Key Findings: Tractography revealed lower fractional anisotropy in specific tracts including the crus of the fornix, body of corpus callosum, uncinate fasciculi, superior longitudinal fasciculi, anterior limb of internal capsule, and corticospinal tracts in JME with respect to controls, whereas there were no fractional anisotropy differences in IGE‐GTC. No correlation was found between fractional anisotropy and total lifetime generalized tonic–clonic seizures for either JME or IGE‐GTC. Although false discovery rate–corrected voxel‐based morphometry (VBM) showed no gray matter volume differences between patient and control groups, spatial extent cluster–corrected VBM analysis suggested a trend of gray matter volume reduction in frontal and central regions in both patient groups, more lateral in JME and more medial in IGE‐GTC. Significance: The findings support the idea that the clinical syndromes of JME and IGE‐GTC have unique anatomic substrates. The fact that the primary clinical difference between JME and IGE‐GTC is the occurrence of myoclonus in the former raises the possibility that disruption of white matter integrity may be the underlying mechanism responsible for myoclonus in JME. The cross‐sectional study design and relatively small number of subjects limits the conclusions that can be drawn here; however, the absence of a correlation between fractional anisotropy and lifetime seizures is suggestive that the white matter abnormalities observed in JME may not be secondary to seizures.     

弥散张量成像在继发全面性发作癫痫患者中的应用研究

目的 评价弥散张量成像(DTI)对于常规MRI未发现病灶的部分性继发全面性发作癫痫患者的病灶检出能力.方法 使用Siemens 3.0T磁共振成像系统对30例成年继发全面性发作癫痫患者和30例正常对照者进行扫描,得到弥散加权成像,采用基于体素的分析方法对癫痫患者和正常对照组的数据进行分析.结果 癫痫组右侧梭状回和楔前叶、右侧额内侧回和钩回、左侧扣带回、左侧颞下回、左侧小脑扁桃体和左侧中央前回的脑区FA值较正常对照组降低,差异有统计学意义(P＜0.001);癫痫组右侧海马旁回、右侧颞下回、右侧胼胝体、右侧额内侧回、右侧额下回、扣带回、右侧前扣带回、右侧舌回、右侧梭状回和枕中回,左侧颞中回、左侧钩回和左侧中央前回的脑区ADC值较正常对照组升高,差异具有统计学意义(P＜0.001);左侧直回的脑区ADC值较正常对照组降低,差异具有统计学意义(P＜0.001).结论 DTI检查可发现常规MRI检查为阴性的部分性继发全面性发作癫痫患者存在的广泛脑白质微结构异常.     

Thalamic white matter in multiple sclerosis: A combined diffusion‐tensor imaging and quantitative susceptibility mapping study

Thalamic white matter (WM) injury in multiple sclerosis (MS) remains relatively poorly understood. Combining multiple imaging modalities, sensitive to different tissue properties, may aid in further characterizing thalamic damage. Forty‐five MS patients and 17 demographically‐matched healthy controls (HC) were scanned with 3T MRI to obtain quantitative measures of diffusivity and magnetic susceptibility. Participants underwent cognitive evaluation with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Tract‐based spatial statistics identified thalamic WM. Non‐parametric combination (NPC) analysis was used to perform joint inference on fractional anisotropy (FA), mean diffusivity (MD) and magnetic susceptibility measures. The association of surrounding WM lesions and thalamic WM pathology was investigated with lesion probability mapping. Compared to HCs, the greatest extent of thalamic WM damage was reflected by the combination of increased MD and decreased magnetic susceptibility (63.0% of thalamic WM, peak p = .001). Controlling for thalamic volume resulted in decreased FA and magnetic susceptibility (34.1%, peak p = .004) as showing the greatest extent. In MS patients, the most widespread association with information processing speed was found with the combination of MD and magnetic susceptibility (67.6%, peak p = .0005), although this was not evident after controlling for thalamic volume. For memory measures, MD alone yielded the most widespread associations (45.9%, peak p = .012 or 76.7%, peak p = .001), even after considering thalamic volume, albeit with smaller percentages. White matter lesions were related to decreased FA (peak p = .0063) and increased MD (peak p = .007), but not magnetic susceptibility, of thalamic WM. Our study highlights the complex nature of thalamic pathology in MS.     

Juvenile myoclonic epilepsy – a generalized epilepsy syndrome?

Juvenile myoclonic epilepsy (JME) has been classified as a syndrome of idiopathic generalized epilepsy and is characterized by specific types of seizures, showing a lack of pathology using magnetic resonance imaging (MRI) and computed tomography scanning. However, JME is associated with a particular personality profile, and behavioral and neuropsychologic studies have suggested the possible involvement of frontal lobe dysfunction. The development of highly sensitive neuroimaging techniques has provided a means of elucidating the underlying mechanisms of JME. For example, positron emission tomography has demonstrated neurotransmitter changes in the cerebral cortex, quantitative MRI has revealed significant abnormalities of cortical gray matter in medial frontal areas, and ¹H-magnetic resonance spectroscopy has shown evidence of thalamic dysfunction, which appears to be progressive. Such techniques provide evidence of multi-focal disease mechanisms, suggesting that JME is a frontal lobe variant of a multi-regional, thalamocortical 'network' epilepsy, rather than a generalized epilepsy syndrome.     

Group‐specific regional white matter abnormality revealed in diffusion tensor imaging of medial temporal lobe epilepsy without hippocampal sclerosis

Purpose: In comparison to temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (TLE‐HS), TLE patients without HS (TLE‐NH) have a similar clinical course but may result in worse surgical outcome. We investigated whether the clinical features related to the lack of HS in TLE patients (TLE‐NH) can be explained by water diffusion abnormalities throughout diffusion tensor imaging (DTI) by voxel‐based analysis. Methods: Nineteen patients with TLE‐HS (left/right TLE 12:7), 18 patients with TLE‐NH (left/right TLE 10:8), and 20 controls were included in the study. By statistical parametric mapping (SPM2), the diffusion properties specific to disease characteristics (TLE‐HS vs. TLE‐NH) were analyzed. Results: In TLE‐HS, we found the areas of increased mean diffusivity (MD) in their ipsilateral temporal and extratemporal areas including the hippocampus, parahippocampal, and frontoparietal regions. Left TLE‐HS showed a characteristic MD increase in the ipsilateral posterior cingulum, isthmus of corpus callosum, and contralateral occipital and temporal regions, which was not observed in right TLE‐HS group. In left TLE‐NH, two regions of increased MD were observed in the ipsilateral posterior fornix (within fusiform gyrus) and posterior cingulum. Right TLE‐NH did not show any increased MD. Discussion: In left TLE‐NH, we could find the water diffusion change along the posterior cingulum, which was quite different from the extensive abnormality from TLE‐HS. In addition, there was a lesion‐side–specific distribution (left predominant) of pathology in mesial TLE. This provides a possibility that TLE‐NH is a heterogenous or entity different from TLE‐HS.     

Identifying juvenile myoclonic epilepsy via diffusion tensor imaging using machine learning analysis

The aim of this study was to evaluate the feasibility of using a machine learning approach based on diffusion tensor imaging (DTI) to identify patients with juvenile myoclonic epilepsy. We analyzed the usefulness of combining conventional DTI measures and structural connectomic profiles. This retrospective study was conducted at a tertiary hospital. We enrolled 55 patients with juvenile myoclonic epilepsy. All of the subjects underwent DTI from January 2017 to March 2020. We also enrolled 58 healthy subjects as a normal control group. We extracted conventional DTI measures and structural connectomic DTI profiles. We employed the support vector machines (SVM) algorithm to classify patients with juvenile myoclonic epilepsy and healthy subjects based on the conventional DTI measures and structural connectomic profiles. The SVM classifier based on conventional DTI measures had an accuracy of 68.1% and an area under the curve (AUC) of 0.682. Another SVM classifier based on the structural connectomic profiles demonstrated an accuracy of 72.7% and an AUC of 0.727. The SVM classifier based on combining the conventional DTI measures and structural connectomic profiles had an accuracy of 81.8% and an AUC of 0.818. DTI using machine learning is useful for classifying patients with juvenile myoclonic epilepsy and healthy subjects. Combining both the conventional DTI measures and structural connectomic profiles results in a better classification performance than using conventional DTI measures or the structural connectomic profiles alone to identify juvenile myoclonic epilepsy.     

Whole brain‐based analysis of regional white matter tract alterations in rare motor neuron diseases by diffusion tensor imaging

Different motor neuron disorders (MND s ) are mainly defined by the clinical presentation based on the predominance of upper or lower motor neuron impairment and the course of the disease. Magnetic resonance imaging (MRI) mostly serves as a tool to exclude other pathologies, but novel approaches such as diffusion tensor imaging (DTI) have begun to add information on the underlying pathophysiological processes of these disorders in vivo. The present study was designed to investigate three different rare MNDs, i.e., primary lateral sclerosis (PLS, N = 25), hereditary spastic paraparesis (HSP, N = 24), and X‐linked spinobulbar muscular atrophy (X‐SBMA, N = 20), by use of whole‐brain‐based DTI analysis in comparison with matched controls. This analysis of white matter (WM) impairment revealed widespread and characteristic patterns of alterations within the motor system with a predominant deterioration of the corticospinal tract (CST) in HSP and PLS patients according to the clinical presentation and also in patients with X‐SBMA to a lesser degree, but also WM changes in projection s to the limbic system and within distinct areas of the corpus callosum (CC), the latter both for HSP and PLS. In summary, DTI was able to define a characteristic WM pathoanatomy in motor and extra‐motor brain areas, such as the CC and the limbic projectional system, for different MNDs via whole brain‐based FA assessment and quantitative fiber tracking. Future advanced MRI‐based investigations might help to provide a fingerprint‐identification of MNDs. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Extratemporal white matter abnormalities in mesial temporal lobe epilepsy demonstrated with diffusion tensor imaging

PURPOSE: Recent studies have demonstrated bilateral white matter abnormalities in temporal lobe epilepsy (TLE) patients with unilateral mesial temporal sclerosis (MTS). The purpose of this project was to determine whether abnormalities of water diffusion are seen in extratemporal white matter of patients with TLE and pathologically confirmed MTS and to determine whether these findings are associated with worse surgical outcome. METHODS: Eleven patients with TLE and unilateral MTS confirmed in surgical specimens and 14 controls were studied by using cerebrospinal fluid-suppressed diffusion tensor imaging (DTI) and T2 relaxometry. RESULTS: Hippocampal T2 signal for patients was significantly elevated both ipsilateral (p<0.001) and contralateral (p=0.006) to MTS. DTI demonstrated reduced fractional anisotropy of the genu of the corpus callosum (p=0.003) and external capsule (p=0.02) and elevated mean diffusivity of the genu (p=0.005), splenium (p=0.03), and external capsule (p<0.001). For both the genu and external capsule, parallel diffusion of patients was not different from that of controls (genu, p=0.81; external capsule, p=0.45), whereas perpendicular diffusion was elevated (genu, p=0.001; external capsule, p<0.001). With mean postsurgical follow-up of 18.5 months, eight of 11 patients were entirely seizure free and the remaining three had all experienced a worthwhile reduction in seizure frequency. CONCLUSIONS: Our findings suggest that although patients with TLE and MTS have extensive bilateral and extratemporal pathology, these findings may not be associated with a worse postsurgical outcome.     

Acute white matter changes following sport‐related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study

Recent neuroimaging studies have suggested that following sport‐related concussion (SRC) physiological brain alterations may persist after an athlete has shown full symptom recovery. Diffusion MRI is a versatile technique to study white matter injury following SRC, yet serial follow‐up studies in the very acute stages following SRC utilizing a comprehensive set of diffusion metrics are lacking. The aim of the current study was to characterize white matter changes within 24 hours of concussion in a group of high school and collegiate athletes, using Diffusion Tensor and Diffusion Kurtosis Tensor metrics. Participants were reassessed a week later. At 24 hours post‐injury, the concussed group reported significantly more concussion symptoms than a well‐matched control group and demonstrated poorer performance on a cognitive screening measure, yet these differences were nonsignificant at the 8‐day follow‐up. Similarly, within 24‐hours after injury, the concussed group exhibited a widespread decrease in mean diffusivity, increased axial kurtosis and, to a lesser extent, decreased axial and radial diffusivities compared with control subjects. At 8 days post injury, the differences in these diffusion metrics were even more widespread in the injured athletes, despite improvement of symptoms and cognitive performance. These MRI findings suggest that the athletes might not have reached full physiological recovery a week after the injury. These findings have significant implications for the management of SRC because allowing an athlete to return to play before the brain has fully recovered from injury may have negative consequences. Hum Brain Mapp 37:3821–3834, 2016. © 2016 Wiley Periodicals, Inc .     

应用弥散张量成像实现神经纤维追踪的方法*☆

背景：目前的神经纤维追踪方法众说纷纭,不同的追踪方法往往对数据的要求比较严格,格式比较单一,并且在特定的条件下,才能进行纤维追踪,但都没有统一可执行标准。因此需要研究一种简便通用的神经纤维追踪处理方法。 目的：提出一种简便通用,并且可以在不同的数据采集方法情况下,转变为固定的数据采集格式的弥散张量神经纤维追踪方法。 方法：首先采用MRIcro软件在原始DTI图像上,找出梯度因子b值,组成梯度方向文件并把DICOM原始文件软件转换成Analyze格式文件,然后利用SPM软件对格式文件标准化,最后采用DTI-track软件进行神经纤维追踪处理。 结果与结论：通过对DTI图像进行处理,证明该方法能有效的得出扩散梯度因子b值文件,并且能把不同的DTI数据转变为统一的格式进行DTI处理,得到预期的DTI纤维追踪图像,为DTI研究提供了一个简便有效的具体实现方法。 关键词：弥散张量成像;纤维追踪;扩散梯度因子;神经纤维;功能磁共振     

A meta-analysis of white matter changes in temporal lobe epilepsy as studied with diffusion tensor imaging

Purpose: Diffusion tensor imaging (DTI) is used increasingly to study white matter integrity in people with temporal lobe epilepsy (TLE). Most studies report fractional anisotropy (FA) decrease and mean diffusivity (MD) increase in multiple white matter regions. The disturbance of white matter integrity varies across studies and between regions. We aimed to obtain a more consistent estimate of white matter diffusion characteristics and relate these to the distance from the seizure focus. Methods: Studies comparing diffusion characteristics of people with epilepsy with those of healthy controls were systematically reviewed and quantified using random and mixed effects meta analysis. In addition to the overall meta‐analysis, pooled FA and MD differences were determined per hemisphere and white matter category separately. Key Findings: We included 13 cross‐sectional studies. The pooled FA difference for all white matter was ?0.026 (95% confidence interval [CI] ?0.033 to ?0.019) and MD difference was 0.028 × 10^?3 mm²/s (95% CI 0.015–0.04). FA was reduced significantly in people with TLE compared with healthy controls in both ipsilateral (mean difference ?0.03) and contralateral white matter (?0.02). MD was significantly increased ipsilaterally and contralaterally. MD differed significantly between white matter connected to the affected temporal lobe and remote white matter. Significance: The meta‐analysis provides a better estimation of the true diffusion characteristics. White matter structural integrity in TLE is disturbed more severely in the ipsilateral than in the contralateral hemisphere, and tracts closely connected with the affected temporal lobe are most disturbed. The exact underlying mechanisms remain to be elucidated.     

Propriospinal myoclonus: utility of magnetic resonance diffusion tensor imaging and fiber tracking.

Propriospinal myoclonus (PSM) is a rare movement disorder characterized by involuntary spinal-generated muscular jerks that spread rostrally and caudally to other spinally innervated muscles. Most patients have no clear etiology, and conventional MRI of the spinal cord is generally normal. Here we report the use of magnetic resonance diffusion tensor imaging (DTI) and fiber tracking to detect tract-specific abnormalities in a patient with propriospinal myoclonus. As the patient had the fragile-X premutation and antithyroid antibodies, spinal cord DTI abnormalities may be related to these conditions. Tract-specific analysis may provide new insights into the pathophysiology of propriospinal myoclonus.     

Microstructural white matter abnormality and frontal cognitive dysfunctions in juvenile myoclonic epilepsy

Purpose: Previous neuroimaging studies provide growing evidence that patients with juvenile myoclonic epilepsy (JME) have both structural and functional abnormalities of the thalamus and frontal lobe gray matter. However, limited data are available regarding the issue of white matter (WM) involvement, making the microstructural WM changes in JME largely unknown. In the present study we investigated changes of WM integrity in patients with JME, and their relationships with cognitive functions and epilepsy-specific clinical factors. Methods: We performed diffusion tensor imaging (DTI) and neuropsychological assessment in 25 patients with JME and 30 control subjects matched for age, gender, and education level. Between-group comparisons of fractional anisotropy (FA) and mean diffusivity (MD) were carried out in a whole-brain voxel-wise manner by using tract-based spatial statistics (TBSS). In addition, both FA and MD were correlated with cognitive performance and epilepsy-specific clinical variables to investigate the influence of these clinical and cognitive factors on WM integrity changes. Key Findings: Neuropsychological evaluation revealed that patients with JME had poorer performance than control subjects on most of the frontal function tests. TBSS demonstrated that, compared to controls, patients with JME had significantly reduced FA and increased MD in bilateral anterior and superior corona radiata, genu and body of corpus callosum, and multiple frontal WM tracts. Disease severity, as assessed by the number of generalized tonic-clonic seizures in given years, was negatively correlated with FA and positively correlated with MD extracted from regions of significant differences between patients and controls in TBSS. Significance: Our findings of widespread disturbance of microstructural WM integrity in the frontal lobe and corpus callosum that interconnects frontal cortices could further support the pathophysiologic hypothesis of thalamofrontal network abnormality in JME. These WM abnormalities may implicate frontal cognitive dysfunctions and disease progression in JME.     

How to diagnose and classify idiopathic (genetic) generalized epilepsies

Idiopathic or genetic generalized epilepsies (IGE) constitute an electroclinically well‐defined group that accounts for almost one third of all people with epilepsy. They consist of four well‐established syndromes and some other rarer phenotypes. The main four IGEs are juvenile myoclonic epilepsy, childhood absence epilepsy, juvenile absence epilepsy and IGE with generalized tonic‐clonic seizures alone. There are three main seizure types in IGE, namely generalized tonic‐clonic seizures, typical absences and myoclonic seizures, occurring either alone or in any combination. Diagnosing IGEs requires a multidimensional approach. The diagnostic process begins with a thorough medical history with a specific focus on seizure types, age at onset, timing and triggers. Comorbidities and family history should be questioned comprehensively. The EEG can provide valuable information for the diagnosis, including specific IGE syndromes, and therefore contribute to their optimal pharmacological treatment and management.