Fröhlich Kilian, Macha Kosmas, Siedler Gabriela, Sekita Alexander, Haupenthal David, Mrochen Anne, Wang Ruihao, Schembs Leah, Dörfler Arnd, Seifert Frank, Schwab Stefan, Winder Klemens
Departments of Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany.
Departments of Neuroradiology, University Hospital Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany.
Sci Rep. 2025 Mar 23;15(1):10020. doi: 10.1038/s41598-025-93869-7.
Headache is very frequent in multiple sclerosis. However, the question whether headache is just coincidental or may be secondary due to inflammatory cerebral multiple sclerosis lesions is yet to be clarified. This study intended to evaluate the distribution of cerebral lesion sites and the potential presence of specific lesion clusters in patients with multiple sclerosis and comorbid headache using voxel-based lesion symptom mapping (VLSM). Patients with multiple sclerosis and headache were prospectively identified and included in a university neurological center between 2017 and 2023. Only patients with headache onset after first manifestation of multiple sclerosis were included. Demographic and clinical data were assessed, and lesion volumes calculated. Cerebral lesion sites were correlated voxel-wise with presence and absence of headache using non-parametric permutation testing. A cohort of multiple sclerosis patients served as controls for the VLSM-analysis. 48 multiple sclerosis patients with headache were included, as well as 92 controls without headache. Of the 48 patients with headache, 39 (81%) were female and nine (19%) were male. Mean age was significantly higher in headache patients than in controls (51 + / - 11 vs. 42 + / - 11 years, p < 0.05). EDSS, disease duration and lesion volumes did not significantly differ between both groups. Lesion overlap of all patients demonstrated a distribution of white matter lesions consistently in all subcortical brain areas. The VLSM-analysis showed associations between headache and lesion clusters in the left insula, left hippocampus and right thalamus. In our study, multiple sclerosis lesions in the left insula, left hippocampus and right thalamus were associated with headache in multiple sclerosis patients. The data therefore indicates that headache in multiple sclerosis may, in a proportion of patients, result from lesions in the central nervous systems' pain processing network.Trial registration: No. 93_17 B, Ethics committee of the University Hospital Erlangen-Nürnberg.
头痛在多发性硬化症中非常常见。然而，头痛是仅仅巧合，还是可能继发于炎症性脑多发性硬化病变，这一问题尚待阐明。本研究旨在使用基于体素的病变症状映射（VLSM）评估多发性硬化症合并头痛患者的脑病变部位分布以及特定病变簇的潜在存在情况。2017年至2023年期间，在一所大学神经中心前瞻性地识别并纳入了患有多发性硬化症和头痛的患者。仅纳入在多发性硬化症首次出现后出现头痛的患者。评估了人口统计学和临床数据，并计算了病变体积。使用非参数置换检验，对脑病变部位与头痛的有无进行了逐体素相关性分析。一组多发性硬化症患者作为VLSM分析的对照。纳入了48例患有头痛的多发性硬化症患者，以及92例无头痛的对照。在48例头痛患者中，39例（81%）为女性，9例（19%）为男性。头痛患者的平均年龄显著高于对照组（51±11岁 vs. 42±11岁，p<0.05）。两组之间的扩展残疾状态量表（EDSS）、病程和病变体积无显著差异。所有患者的病变重叠显示，所有皮质下脑区均一致存在白质病变分布。VLSM分析显示，头痛与左侧岛叶、左侧海马体和右侧丘脑的病变簇之间存在关联。在我们的研究中，左侧岛叶、左侧海马体和右侧丘脑的多发性硬化症病变与多发性硬化症患者的头痛有关。因此，数据表明，在一部分患者中，多发性硬化症中的头痛可能源于中枢神经系统疼痛处理网络中的病变。试验注册号：93_17 B，埃尔朗根 - 纽伦堡大学医院伦理委员会。
