BACKGROUND & AIMS:
PURPOSE:Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS.
METHODS:Twenty-four epilepsy PM cases (age range 25-87 years) and eight controls (age range 38-85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases.
KEY FINDINGS:The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in HS.
SIGNIFICANCE:Our study demonstrates that stereotypical pathologic changes, as seen in HS, are not clearly defined in the thalamus. This may be partly explained by the heterogeneity of our PM study group. With quantitation, there is some evidence for preferential involvement of the MD, suggesting a potential role in TLE, which requires further investigation.
背景与目标:
目的:临床,实验和神经影像数据均表明,丘脑参与与颞叶癫痫(TLE)有关的变化网络,特别是与海马硬化(HS)有关,并可能在癫痫发作的起始和传播中起作用。丘脑的病理变化可能是由于最初的侮辱,持续的癫痫发作或丘脑和边缘区域之间的相互联系导致的逆行变性所致。我们的目的是对死后(PM)癫痫发作系列中的丘脑进行神经病理学分析,以评估病理变化的分布,严重程度和性质及其与HS的关系。
方法:研究了24例癫痫患者(25-87岁)和8例对照(38-85岁)。 HS分为单侧(UHS,11例),双侧(BHS,4例)或不存在(无HS,9例)。用甲酚紫(CV)对丘脑左右两侧的样品进行染色,并用胶质原纤维酸性蛋白(GFAP)和突触素进行染色。使用图像分析,在四个丘脑核中测量神经元密度(NDs)或视野分数染色值(GFAP,突触素):前腹核(AV),背背核(LD),中腹核(MD)和腹外侧核(VL) )。在案例内和案例之间对结果进行了比较。
主要发现:病例之间丘脑病理的严重程度,性质和分布各不相同。一种出现的模式是在UHS病例中MD优先参与,HS侧同侧平均ND减少(p = 0.05)。在UHS病例中,与其他丘脑核相比,在大多数情况下,在硬化侧MD患侧,GFAP的视野分数更高,而突触素和ND的视野更低。此外,在同侧MD中发现经典HS,非典型HS和No-HS病例之间的平均ND差异(p <0.05),在HS中观察到的值较低。
意义:我们的研究表明,丘脑中没有明确定义成见的典型病理变化,如在HS中所见。我们PM研究小组的异质性可能部分解释了这一点。通过定量分析,有一些证据表明MD优先参与,提示在TLE中可能发挥作用,这需要进一步研究。