UCSD, University of California San Diego School of Medicine, San Diego, CA, USA.
UCSF, University of California San Francisco School of Medicine, San Francisco, CA, USA.
J Neurovirol. 2022 Dec;28(4-6):505-513. doi: 10.1007/s13365-022-01051-w. Epub 2022 Oct 7.
Human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) affects up to 50% of people with HIV and is associated with depression, unemployment, and generally worsened quality of life. Previous work on the cortical mechanism of HIV neuropathy found decreased gray matter volume in the bilateral midbrain, thalamus, and posterior cingulate cortex, but structural connectivity in this context remains under-studied. Here we examine alterations in white matter microstructure using diffusion imaging, hypothesizing that cortical white matter degeneration would be observed in continuation of the peripheral white matter atrophy previously observed in HIV-DSP. Male HIV seropositive patients (n = 57) experiencing varying degrees of HIV neuropathy underwent single-shell diffusion tensor imaging with 51 sampling directions. The scans were pooled using tractography and connectometry to create a quantitative map of white matter tract integrity, measured in generalized fractional anisotropy (GFA). The relationship between GFA and neuropathy severity was evaluated with linear regression. Correction for multiple comparisons was done using false discovery rate (FDR), a statistical method commonly used in genomics and imaging to minimize false positives when thousands of individual comparisons are made. Neuropathy severity was associated with decreased GFA along thalamocortical radiations leading along the lateral thalamus to sensorimotor cortex, with r = -0.405 (p < 0.001; FDR), as well as with the superior bilateral cingulum (r = -0.346 (p < 0.05; FDR)). Among a population of HIV neuropathy patients, greater neuropathy severity was correlated with lower white matter integrity running from midbrain to somatosensory cortex. This suggests ascending deafferentation extending from damaged peripheral nerves further downstream than seen previously, into the axons of third-order neurons. There is also evidence of cingulum degeneration, implying some more complex mechanism beyond the ascending atrophy observed here.
人类免疫缺陷病毒相关性远端感觉性多发性神经病（HIV-DSP）影响多达 50%的 HIV 感染者，与抑郁、失业和生活质量普遍下降有关。先前关于 HIV 神经病皮质机制的研究发现，双侧中脑、丘脑和后扣带回的灰质体积减少，但这方面的结构连通性仍研究不足。在这里，我们使用扩散成像研究白质微观结构的变化，假设在 HIV-DSP 先前观察到的周围白质萎缩的延续中，会观察到皮质白质退化。经历不同程度 HIV 神经病变的男性 HIV 血清阳性患者（n=57）接受了 51 个采样方向的单壳扩散张量成像。使用轨迹追踪和连接计数对扫描进行汇总，以创建白质束完整性的定量图谱，用广义各向异性分数（GFA）来衡量。使用线性回归评估 GFA 与神经病变严重程度之间的关系。使用假发现率（FDR）进行多重比较校正，这是一种在基因组学和影像学中常用的统计方法，用于在进行数千个个体比较时最大限度地减少假阳性。神经病变严重程度与沿外侧丘脑向感觉运动皮层延伸的丘脑皮质辐射的 GFA 降低相关，r=-0.405（p<0.001；FDR），以及双侧上扣带束（r=-0.346（p<0.05；FDR））。在一组 HIV 神经病变患者中，神经病变严重程度与从中脑到体感皮层的白质完整性降低呈正相关。这表明，脱传入延伸超出了先前观察到的受损周围神经，延伸到第三级神经元的轴突。扣带束退化的证据也表明，除了这里观察到的上行萎缩之外，还有一些更复杂的机制。
