Mayo Clinic, College of Medicine, Rochester, MN 55905, USA.
Neurology. 2011 Apr 5;76(14):1229-37. doi: 10.1212/WNL.0b013e318214332c. Epub 2011 Mar 2.
To characterize the neuropathologic features of neuromyelitis optica (NMO) at the medullary floor of the fourth ventricle and area postrema. Aquaporin-4 (AQP4) autoimmunity targets this region, resulting in intractable nausea associated with vomiting or hiccups in NMO.
This neuropathologic study was performed on archival brainstem tissue from 15 patients with NMO, 5 patients with multiple sclerosis (MS), and 8 neurologically normal subjects. Logistic regression was used to evaluate whether the presence of lesions at this level increased the odds of a patient with NMO having an episode of nausea/vomiting.
Six patients with NMO (40%), but no patients with MS or normal controls, exhibited unilateral or bilateral lesions involving the area postrema and the medullary floor of the fourth ventricle. These lesions were characterized by tissue rarefaction, blood vessel thickening, no obvious neuronal or axonal pathology, and preservation of myelin in the subependymal medullary tegmentum. AQP4 immunoreactivity was lost or markedly reduced in all 6 cases, with moderate to marked perivascular and parenchymal lymphocytic inflammatory infiltrates, prominent microglial activation, and in 3 cases, eosinophils. Complement deposition in astrocytes, macrophages, and/or perivascularly, and a prominent astroglial reaction were also present. The odds of nausea/vomiting being documented clinically was 16-fold greater in NMO cases with area postrema lesions (95% confidence interval 1.43-437, p = 0.02).
These neuropathologic findings suggest the area postrema may be a selective target of the disease process in NMO, and are compatible with clinical reports of nausea and vomiting preceding episodes of optic neuritis and transverse myelitis or being the heralding symptom of NMO.
描述第四脑室底和孤束核的视神经脊髓炎（NMO）的神经病理学特征。水通道蛋白 4（AQP4）自身免疫靶向该区域，导致 NMO 患者出现顽固性恶心，伴有呕吐或打嗝。
这项神经病理学研究使用了 15 例 NMO 患者、5 例多发性硬化症（MS）患者和 8 例神经正常对照者的存档脑干组织。采用逻辑回归评估该水平的病变是否增加 NMO 患者出现恶心/呕吐发作的几率。
6 例 NMO 患者（40%）存在单侧或双侧累及孤束核和第四脑室底的病变，但无 MS 患者或正常对照者存在此类病变。这些病变的特征为组织稀疏、血管增厚、无明显神经元或轴突病理学改变，室管膜下延髓被盖的髓鞘保持完好。AQP4 免疫反应性在所有 6 例中均缺失或明显减少，伴有中度至重度血管周围和实质淋巴细胞炎症浸润、明显的小胶质细胞激活，在 3 例中还有嗜酸性粒细胞。补体在星形胶质细胞、巨噬细胞和/或血管周围沉积，以及明显的星形胶质细胞反应也存在。有孤束核病变的 NMO 病例出现恶心/呕吐的临床记录的几率是无病变的 16 倍（95%置信区间 1.43-437，p = 0.02）。
这些神经病理学发现提示孤束核可能是 NMO 疾病过程的选择性靶标，与视神经炎和横贯性脊髓炎发作前出现恶心和呕吐的临床报告或 NMO 的先兆症状相一致。
