9-HODE associates with thalamic atrophy and predicts white matter damage in multiple sclerosis

IF 2.9 3区医学 Q2 CLINICAL NEUROLOGY Multiple sclerosis and related disorders Pub Date : 2024-10-16 DOI:10.1016/j.msard.2024.105946

Wing Hee Fung , Marike R. van Lingen , Jelle Y. Broos , Ka-Hoo Lam , Maureen van Dam , Wing Ka Fung , Samantha Noteboom , Ismail Koubiyr , Helga E. de Vries , Bas Jasperse , Charlotte E. Teunissen , Martin Giera , Joep Killestein , Hanneke E. Hulst , Eva M.M. Strijbis , Menno M. Schoonheim , Gijs Kooij

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Abstract

Background

Multiple sclerosis (MS) is characterized by extensive tissue damage leading to a range of complex symptoms, including physical disability and cognitive dysfunction. Recent work has indicated the clinical relevance of bioactive lipid mediators (LMs), which are known to orchestrate inflammation and its resolution and are deregulated in MS. However, it is unknown whether LM profiles relate to white matter (WM) damage.

Objectives

To investigate the potential association between plasma-derived LMs and MRI-quantified WM damage using fractional anisotropy (FA) and grey matter (GM) atrophy in dimethyl fumarate-treated relapsing remitting MS (RRMS) patients.

Methods

Severity of FA-based WM damage and GM atrophy was determined in RRMS patients (n = 28) compared to age- and sex-matched controls (n = 31) at treatment initiation (baseline) and after 6 months. Plasma LMs were assessed using HPLC-MS/MS and baseline LMs were correlated to changes in FA and brain volumes.

Results

We observed significant WM damage in RRMS patients (mean age 41.4 [SD 9.1]) at baseline and follow-up (z-score=-0.33 and 0.31, respectively) compared to controls (mean age 41.9 [SD 9.5]; p < 0.001 for both comparisons). Patients with severe WM damage showed a decline of thalamic volume (p = 0.02), and this decline correlated (r = 0.51, p < 0.001) with lower baseline levels of 9-HODE. This LM also predicted FA worsening (beta = 0.14, p < 0.001) over time at 6 months.

Conclusion

Despite the relatively small sample size, lower baseline levels of the LM 9-HODE correlated with more thalamic atrophy and predicted subsequent worsening of WM damage in RRMS patients.

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9-HODE 与丘脑萎缩有关，可预测多发性硬化症的白质损伤。

背景：多发性硬化症（MS）的特点是广泛的组织损伤导致一系列复杂的症状，包括身体残疾和认知功能障碍。最近的研究表明，生物活性脂质介质（LMs）具有临床意义，众所周知，脂质介质可协调炎症及其缓解，但在多发性硬化症中却出现了失调。然而，目前尚不清楚脂质介质的特征是否与白质（WM）损伤有关：目的：在接受富马酸二甲酯治疗的复发性缓解型多发性硬化症（RRMS）患者中，研究血浆衍生的LMs与使用分数各向异性（FA）和灰质（GM）萎缩进行MRI量化的WM损伤之间的潜在关联：与年龄和性别匹配的对照组（31例）相比，RRMS患者（28例）在开始治疗时（基线）和治疗6个月后，基于FA的WM损伤和GM萎缩的严重程度得到确定。使用 HPLC-MS/MS 评估血浆 LMs，并将基线 LMs 与 FA 和脑容量的变化相关联：与对照组（平均年龄 41.9 [SD 9.5]；两组比较均 p < 0.001）相比，我们观察到 RRMS 患者（平均年龄 41.4 [SD 9.1]）在基线和随访期间的 WM 明显受损（z-score=-0.33 和 0.31）。严重WM损伤的患者丘脑体积下降（p = 0.02），这种下降与较低的9-HODE基线水平相关（r = 0.51，p < 0.001）。这一丘脑体积也预示着6个月后FA的恶化（β=0.14，p<0.001）：尽管样本量相对较小，但低密度脂蛋白9-HODE的基线水平较低与丘脑萎缩程度较高相关，并可预测RRMS患者WM损伤的后续恶化。

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来源期刊

Multiple sclerosis and related disorders CLINICAL NEUROLOGY-

CiteScore

5.80

自引率

20.00%

发文量

814

审稿时长

66 days

期刊介绍： Multiple Sclerosis is an area of ever expanding research and escalating publications. Multiple Sclerosis and Related Disorders is a wide ranging international journal supported by key researchers from all neuroscience domains that focus on MS and associated disease of the central nervous system. The primary aim of this new journal is the rapid publication of high quality original research in the field. Important secondary aims will be timely updates and editorials on important scientific and clinical care advances, controversies in the field, and invited opinion articles from current thought leaders on topical issues. One section of the journal will focus on teaching, written to enhance the practice of community and academic neurologists involved in the care of MS patients. Summaries of key articles written for a lay audience will be provided as an on-line resource. A team of four chief editors is supported by leading section editors who will commission and appraise original and review articles concerning: clinical neurology, neuroimaging, neuropathology, neuroepidemiology, therapeutics, genetics / transcriptomics, experimental models, neuroimmunology, biomarkers, neuropsychology, neurorehabilitation, measurement scales, teaching, neuroethics and lay communication.