Neuropathologic findings and neurologic symptoms in twenty-three children with hemophagocytic lymphohistiocytosis
Neuropathologic findings and neurologic symptoms in twenty-three children with hemophagocytic lymphohistiocytosis
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DOI：
10.1016/s0022-3476(97)70196-3
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发表时间：
1997-03-01
影响因子：
5.1
通讯作者：
Nennesmo, I
中科院分区：
文献类型：
--
作者：
Henter, JI;Nennesmo, I
背景：原发性噬血细胞淋巴组织细胞增多症是一种常染色体隐性遗传性疾病，病死率很高，主要累及婴幼儿，以发热、肝脾肿大和细胞减少为特征。临床上非常重要的是神经系统症状，这种症状很常见，甚至可能主导临床图景，出现在全身症状之前。这些症状多种多样，从易怒、颧骨肿胀、颈部僵硬，到抽搐、脑神经瘫痪、共济失调、偏瘫/四肢瘫痪和意识不清。方法：为了进一步阐明这种神经损害，我们回顾了23例儿童的神经病理尸检结果和他们的神经系统症状。结果：从宏观上看，许多病例都存在水肿，在一些晚期疾病中，组织软化和破坏明显，显微图像变化极大，从几乎正常到非常严重的变化。在最轻的HLH型中，只有脑膜有淋巴细胞和巨噬细胞的浸润(I期)，而更晚期的病例也有血管周围的浸润(II期)。在更严重的疾病中，组织中也有弥漫性渗透(III期)，以及多灶性坏死。在这些病例中出现了明显的星形胶质细胞增生症。结论：影响中枢神经系统的人促黄体生成素类似于几种神经系统疾病，可能被误诊。提出了神经病理发现的分期系统。对于有中枢神经系统症状和进行性脑病的儿童，可以考虑诊断为HLH，特别是因为有治疗方法可用。
Background: Primary hemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disorder with very high mortality rates, mainly affecting infants and young children, which is characterized by fever, hepatosplenomegaly, and cytopenias. Of great clinical importance are the neurologic symptoms, which are common and may even dominate the clinical picture and precede the systemic presentation. These symptoms are extremely variable, ranging from irritability, bulging fontanelle, and neck stiffness, to convulsions, cranial nerve palsies, ataxia, hemiplegia/tetraplegia, and unconsciousness.Methods: To elucidate this neurologic involvement further, we reviewed the neuropathologic postmortem findings from 23 children and their neurologic symptoms.Results: Macroscopically, edema was present in many cases, and in some with advanced disease, softening and destruction of the tissue were conspicuous, The microscopic picture was exceedingly variable, ranging from almost normal to very advanced changes. In the mildest form of HLH, only the meninges were involved with infiltration of lymphocytes and macrophages (stage I), whereas more advanced cases in addition also showed perivascular infiltrates (stage II). In even more advanced disease there was also a diffuse infiltration in the tissue (stage III), as well as a multifocal necrosis. A prominent astrogliosis was present in such cases. Hemophagocytosis was seen in most patients, most commonly in the leptomeninges.Conclusions: HLH affecting the central nervous system imitates several neurologic disorders and may be misdiagnosed. A staging system for the neuropathologic findings is presented. In children with obscure central nervous systems symptoms and a progressive encephalopathy, the diagnosis of HLH may be considered, in particular because treatments are available.