Millward Jason Michael, Pilgrim Elias, Baumann Matthias, Wendel Eva-Maria, El Naggar Ines, Bertolini Annikki, Bartels Frederik, Finke Carsten, Paul Friedemann, Niendorf Thoralf, Rostásy Kevin, Waiczies Sonia
From the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Ultrahigh Field Facility (B.U.F.F.); Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany; Division of Paediatric Neurology, Department of Paediatrics I, Medical University of Innsbruck, Austria; Department of Pediatric Neurology, Olgahospital/Klinikum Stuttgart; Department of Paediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University and Department of Neurology, Charité - Universitätsmedizin Berlin, Germany.
Neurol Neuroimmunol Neuroinflamm. 2025 Jan;12(1):e200337. doi: 10.1212/NXI.0000000000200337. Epub 2024 Dec 23.
Pediatric patients with acute disseminated encephalomyelitis (ADEM) are at risk of impaired brain growth, with long-term neuropsychiatric consequences. We previously reported transient expansions of cerebral ventricle volume (VV) in experimental autoimmune encephalomyelitis, which subsequently normalized. In this study, we investigated changes in VV in ADEM in relation to other brain structures and clinical outcomes.
We investigated brain MRI scans acquired in routine clinical practice from a multicenter cohort of 61 pediatric patients with ADEM, of whom 39 were myelin oligodendrocyte glycoprotein (MOG) antibody-positive. Patients were compared with 1,219 pediatric healthy controls (HCs). Volumes of multiple brain structures were computed using a contrast-agnostic machine learning-based tool and analyzed with mixed-effect models regarding other clinical parameters.
Patients with ADEM had larger VV than HCs at initial clinical presentation, before immune therapy. Most of the patients showed further VV increases within 2 months after disease onset. Patients had smaller brain volumes than HCs, with specific reductions in deep gray matter structures. These changes were more pronounced in MOG antibody-negative patients.Of the patients with more than 2 MRI scans, 12 of 22 resolved their VV expansion back to within 15% of baseline values while 10 of 22 had persistently increased VV at the last available MRI within 1 year from onset. Patients with persistent VV expansion had greater reductions in volumes of other brain structures at the than patients whose VV resolved and were more likely to have residual neurologic signs. The VV and patients did not differ regarding age, sex, elevated CSF cell counts at baseline, or occurrence of relapses. However, patients with a larger magnitude of VV expansion-≥90% of baseline volume-were more likely to be in the group.
We could distinguish between 2 outcomes of VV changes in ADEM: one in which the VV expanded but ultimately returned to normal and one in which the expansions continued after disease onset and treatment but failed to resolve. The latter was associated with reduced brain volume, particularly in deep gray matter structures. This highlights the necessity for patients with ADEM to undergo regular MRI scans to assess whether developing VV expansions indicate a greater risk of permanent brain atrophy.
急性播散性脑脊髓炎（ADEM）患儿存在脑生长受损风险，并伴有长期神经精神方面的后果。我们之前报道过实验性自身免疫性脑脊髓炎中脑室容积（VV）的短暂扩大，随后又恢复正常。在本研究中，我们调查了ADEM患者中VV的变化与其他脑结构及临床结局的关系。
我们研究了在常规临床实践中从61例患ADEM的儿科患者多中心队列获取的脑部MRI扫描结果，其中39例为髓鞘少突胶质细胞糖蛋白（MOG）抗体阳性。将患者与1219名儿科健康对照者（HCs）进行比较。使用基于对比无关机器学习的工具计算多个脑结构的容积，并结合其他临床参数用混合效应模型进行分析。
在初始临床表现时，即在免疫治疗前，ADEM患者的VV比HCs大。大多数患者在疾病发作后2个月内VV进一步增加。患者的脑容积比HCs小，深部灰质结构有特定程度的减少。这些变化在MOG抗体阴性患者中更为明显。在进行了超过2次MRI扫描的患者中，22例中有12例的VV扩大恢复到基线值的15%以内，而22例中有10例在发病后1年内最后一次可用MRI检查时VV持续增加。与VV恢复的患者相比，VV持续扩大的患者在最后一次MRI检查时其他脑结构的容积减少更明显，且更有可能有残留神经体征。VV持续扩大和恢复的患者在年龄、性别、基线时脑脊液细胞计数升高或复发情况方面没有差异。然而，VV扩大幅度较大（≥基线容积的90%）的患者更有可能属于持续扩大组。
我们可以区分ADEM中VV变化的两种结局：一种是VV扩大但最终恢复正常，另一种是疾病发作和治疗后扩大持续但未缓解。后者与脑容积减少有关，尤其是深部灰质结构。这凸显了ADEM患者定期进行MRI扫描以评估不断发展的VV扩大是否表明永久性脑萎缩风险更高的必要性。
