Seifert Rebecca M, Klingebiel Randolf, Schäbitz Wolf-Rüdiger
Universitätsklinik für Neurologie, Evangelisches Klinikum Bethel, Bielefeld, Germany.
Institut für diagnostische und interventionelle Neuroradiologie, Evangelisches Klinikum Bethel, Bielefeld, Germany.
Neurol Res Pract. 2025 Apr 26;7(1):26. doi: 10.1186/s42466-025-00382-3.
Research of the past years has refined our perception of cerebral amyloid angiopathy-related inflammation (CAA-ri) as a subacute autoimmune encephalopathy, which is presumably caused by elevated CSF concentrations of anti-amyloid β (Aβ) autoantibodies. A broad understanding of the pathophysiological mechanisms and diagnostic criteria of CAA-ri may lay the foundation for improved immunosuppressive treatment of the disease.
Spontaneous CAA-ri mainly occurs in elderly patients but might also be evoked iatrogenically by modern treatment with amyloid-modifying therapies in Alzheimer's disease (AD). On a histopathological level, CAA-ri is characterized by microglial activation and the formation of vasogenic edemas. Clinically, the disease frequently presents with progressive cognitive decline, focal neurological deficits, headache and epileptic seizures. While brain biopsy has formerly represented the gold standard in the diagnosis of CAA-ri, its importance has been increasingly replaced by clinical as well as radiological diagnostic criteria and the relevance of anti-Aβ autoantibodies in the CSF of affected patients. Though relevant progress has been achieved in immunosuppressive treatment of CAA-ri, the protocols lack standardization as well as decision criteria for the choice of the respective immunosuppressive agent.
CAA-ri gains increasing interest as a spontaneous human model of iatrogenic edematous amyloid-related imaging abnormalities (ARIA-E) in the context of amyloid-modifying therapies. In near future, screening of AD patients for the presence of CAA-ri using CSF anti-Aβ autoantibodies might play a decisive role in the risk stratification as well as dosage finding of amyloid-modifying therapies, as they show high specificity for CAA-ri. The clinical and radiological diagnostic criteria by Auriel et al. allow diagnosis of probable resp. possible CAA-ri with high accuracy. Though only tested in small, specialized patient cohorts to date, additional imaging modalities (C-PK11195 PET) might play a future role in the clinical monitoring of CAA-ri. Therapy of CAA-ri frequently encompasses initial steroid treatment, whereby different schemes, dosages as well as substances are used. Choice of immunosuppressive agents with higher potency still requires objective decision criteria, which should be established in future studies involving larger CAA-ri patient cohorts.
过去几年的研究使我们对脑淀粉样血管病相关炎症（CAA-ri）有了更清晰的认识，它是一种亚急性自身免疫性脑病，可能由脑脊液中抗淀粉样β（Aβ）自身抗体浓度升高引起。对CAA-ri病理生理机制和诊断标准的广泛了解可能为改善该疾病的免疫抑制治疗奠定基础。
自发性CAA-ri主要发生在老年患者中，但也可能由阿尔茨海默病（AD）的淀粉样蛋白修饰疗法的现代治疗医源性诱发。在组织病理学水平上，CAA-ri的特征是小胶质细胞活化和血管源性水肿的形成。临床上，该疾病常表现为进行性认知下降、局灶性神经功能缺损、头痛和癫痫发作。虽然脑活检曾是CAA-ri诊断的金标准，但其重要性已越来越多地被临床及放射学诊断标准以及受影响患者脑脊液中抗Aβ自身抗体的相关性所取代。尽管在CAA-ri的免疫抑制治疗方面取得了相关进展，但方案缺乏标准化以及选择各自免疫抑制剂的决策标准。
在淀粉样蛋白修饰疗法的背景下，CAA-ri作为医源性水肿性淀粉样蛋白相关成像异常（ARIA-E）的自发人体模型越来越受到关注。在不久的将来，使用脑脊液抗Aβ自身抗体筛查AD患者是否存在CAA-ri可能在淀粉样蛋白修饰疗法的风险分层以及剂量确定中起决定性作用，因为它们对CAA-ri具有高特异性。Auriel等人的临床和放射学诊断标准允许准确诊断可能的或疑似的CAA-ri。尽管迄今为止仅在小型、特定患者队列中进行了测试，但其他成像方式（C-PK11195 PET）可能在CAA-ri的临床监测中发挥未来作用。CAA-ri的治疗通常包括初始类固醇治疗，使用不同的方案、剂量和药物。选择效力更高的免疫抑制剂仍需要客观的决策标准，这应在未来涉及更大CAA-ri患者队列的研究中确定。
