White matter microvascular alterations in temporal lobe epilepsy (TLE) may be relevant to acquired neurodegenerative processes and cognitive impairments associated with this condition. We quantified microvascular changes, myelin, axonal, glial and extracellular-matrix labelling in the gyral core and deep temporal lobe white matter regions in surgical resections from 44 TLE patients with or without hippocampal sclerosis. We compared this pathology data with in vivo pre-operative MRI diffusion measurements in co-registered regions and neuropsychological measures of cognitive impairment and decline. In resections, increased arteriolosclerosis was observed in TLE compared to non-epilepsy controls (greater sclerotic index, p < 0.001), independent of age. Microvascular changes included increased vascular densities in some regions but uniformly reduced mean vascular size (quantified with collagen-4, p < 0.05–0.0001), and increased pericyte coverage of small vessels and capillaries particularly in deep white matter (quantified with platelet-derived growth factor receptorβ and smooth muscle actin, p < 0.01) which was more marked the longer the duration of epilepsy (p < 0.05). We noted increased glial numbers (Olig2, Iba1) but reduced myelin (MAG, PLP) in TLE compared to controls, particularly prominent in deep white matter. Gene expression analysis showed a greater reduction of myelination genes in HS than non-HS cases and with age and correlation with diffusion MRI alterations. Glial densities and vascular size were increased with increased MRI diffusivity and vascular density with white matter abnormality quantified using fixel-based analysis. Increased perivascular space was associated with reduced fractional anisotropy as well as age-accelerated cognitive decline prior to surgery (p < 0.05). In summary, likely acquired microangiopathic changes in TLE, including vascular sclerosis, increased pericyte coverage and reduced small vessel size, may indicate a functional alteration in contractility of small vessels and haemodynamics that could impact on tissue perfusion. These morphological features correlate with white matter diffusion MRI alterations and might explain cognitive decline in TLE.

颞叶癫痫 （TLE） 中的白质微血管改变可能与获得性神经退行性过程和与该病相关的认知障碍有关。我们量化了 44 例伴有或不伴有海马硬化的 TLE 患者手术切除的脑回核心和深颞叶白质区域的微血管变化、髓鞘、轴突、神经胶质和细胞外基质标记。我们将这些病理数据与共同注册区域的体内术前 MRI 弥散测量以及认知障碍和衰退的神经心理学测量进行了比较。在切除中，与非癫痫对照相比，在 TLE 中观察到小动脉硬化增加 （硬化指数更高，p < 0.001），与年龄无关。微血管变化包括某些区域的血管密度增加，但平均血管大小均匀减小（用胶原蛋白-4 量化，p < 0.05–0.0001），以及小血管和毛细血管的周细胞覆盖率增加，特别是在深白质中（用血小板衍生生长因子受体 β 和平滑肌肌动蛋白量化，p < 0.01），癫痫持续时间越长越明显 （p< 0.05）。我们注意到与对照组相比，TLE 中的神经胶质细胞数量 （Olig2 、 Iba1） 增加但髓鞘 （MAG 、 PLP） 减少，在深白质中尤为突出。基因表达分析显示，HS 中髓鞘形成基因的减少幅度大于非 HS 病例，并且随着年龄的增长以及与弥散 MRI 改变的相关性。神经胶质密度和血管大小随着 MRI 弥散率和血管密度的增加而增加，并使用基于 fixel 的分析量化白质异常。 血管周围间隙增加与手术前各向异性分数减少以及年龄加速认知能力下降有关 （p < 0.05）。总之，TLE 中可能的获得性微血管病变化，包括血管硬化、周细胞覆盖率增加和小血管尺寸减小，可能表明小血管收缩力和血流动力学的功能改变可能影响组织灌注。这些形态学特征与白质弥散 MRI 改变相关，可能解释 TLE 的认知能力下降。