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小脑性共济失调可以是遗传性，也可以是非遗传性的。早发型和进展性共济失调常与常染色体隐性遗传相关。然而，部分非遗传性共济失调也可发生于儿童期或青年期1,2。 组织细胞增多症是一种可以累及中枢神经系统的全身性疾病。累及小脑的组织细胞增多症可类似常染色体隐性遗传性共济失调，表现出缓慢进展的共济失调特点3。本文的研究目的在于描述一例表现为缓慢进展共济失调的朗格汉斯细胞增多症，其首发和主要神经系统体征与遗传性共济失调相似（小脑组织细胞增多症）。 一项大样本试验对2008年至2016年间970例不同类型的进展性共济失调患者进行了评价。其中4例朗格汉斯细胞增多症患者以进展性共济失调为主要临床表现，最初是按遗传性共济失调进行检查的：脊髓小脑性共济失调（SCA1,2,3,6,7,10,12,17）和弗里德希氏共济失调（FRDA）。基因检查结果阴性。血清甲胎蛋白和白蛋白正常，排除了继发性共济失调。 12岁男孩，表现为进展性步态不稳。查体：共济失调，腱反射亢进伴痉挛步态。6岁时患有尿崩症。颅脑MRI示：小脑中脚、齿状核，小脑白质高信号（图A）。小脑活检未定性。在疾病进程中，骨扫描显示胫骨和上颌骨溶骨性损伤，提示朗格汉斯细胞增多症。给予化疗未见明显改善。 13岁女孩，表现为进展性共济失调2年。查体：共济失调，腱反射活跃，巴氏征（+）。颅脑MRI：齿状核，脑干背侧，小脑白质高信号（图B）。骨扫描显示：枕骨和下颌骨溶骨性损伤。颊粘膜活检证实为朗格汉斯细胞增多症。化疗治疗后无明显改善。 41岁男性，表现为进展性共济失调4年。查体：共济失调，构音障碍。颅脑MRI：脑干及小脑中脚高信号（图C）。小脑活检未定性。在病程中出现皮肤病变，活检证实为朗格汉斯细胞增多症。未予特殊治疗。 12岁男孩，表现为进展性共济失调5年。查体：共济失调，轻度痉挛步态。全身成像显示溶骨性损伤，提示朗格汉斯细胞增多症。颅脑MRI：脑干及小脑上脚高信号（图D）。化疗后步态部分改善。 图：4例累及小脑的朗格汉斯细胞增多症影像学特征 （A）患者1（FLAIR及T2）：小脑中脚，齿状核，小脑白质高信号；（B）患者2（FLAIR及T2）：齿状核、脑干背侧及小脑白质高信号；（C）患者3（FLAIR及T2）：脑干及桥小脑中脚高信号；（D）患者4（T2和T1）：脑干及小脑上脚结节样高信号，伴有结节和强化。同时可见偏侧蛛网膜囊肿。 在上述4例朗格汉斯细胞增多症患者中，进展性共济失调是其主要神经系统表现。除病例3外，余患者均为年轻起病，遂怀疑遗传性疾病可能，如FRDA，并进行了检查。其他常染色体隐性遗传性共济失调，包括共济失调伴动眼失用，维生素E缺乏，SYNE1共济失调等也应被考虑。有趣的是，3例患者表现为进展性痉挛性共济失调，此症状可引导医生对遗传性痉挛性共济失调做进一步检查，例如痉挛性截瘫7型，常染色体隐性遗传的Charlevoix-Saguenay痉挛性共济失调和迟发型FRDA4。 组织细胞增多症是一种表现为各种组织及器官内树突细胞、巨噬细胞或单核细胞异常增殖的系统性疾病。神经系统受累表现多种多样，可见于20%-50%的朗格汉斯细胞增多症患者。主要两种中枢神经系统受损表现:肿瘤和变性。变性性损伤主要表现为缓慢进展的共济失调和痉挛；肿瘤性病变常因细胞增殖引起局灶性神经病损。值得注意的是，尽管朗格汉斯细胞增多症主要为炎性病变，近期有研究显示某些致病基因与细胞增多症相关，如BRAF基因突变5。目前朗格汉斯细胞增多症的诊断仍然通过病理证实，而非基因学，所以无法确定上述4例患者的遗传学情况。另外，本研究的局限性在于并未对患者行外显子测序检查。 其他临床表现（尿崩症，骨和皮肤病变）合并影像结果提示朗格汉斯细胞增多症，指导了进一步行病理检查。典型的“小脑组织细胞增多症”脑影像学包括：双侧齿状核，小脑脚和小脑白质高信号及桥脑后部的不规则信号异常6。强化更常见，我们3例患者均可见。怀疑朗格汉斯细胞增多症时推荐行脑活检检查，但病理结果存在不能定性可能。也可通过淋巴结或皮肤活检诊断7。 小脑性组织细胞增多症的其中一种临床类型即表现为进展性小脑症状，与遗传性共济失调很相似，通常早发，常伴锥体束征。其他临床特点及神经影像学表现可提示应行朗格汉斯细胞增多症的检查。由于小脑细胞增多症与遗传性共济失调治疗及遗传咨询存在不同，故必须正确诊断。 Cerebellar ataxias may have genetic and nongenetic causes. Early onset and progressive ataxias are frequently related to an autosomal recessive inheritance. However, some nongenetic ataxias may occur in childhood or young adulthood.1,2 小脑性共济失调可以是遗传性，也可以是非遗传性的。早发型和进展性共济失调常与常染色体隐性遗传相关。然而，部分非遗传性共济失调也可发生于儿童期或青年期1,2。 Histiocytosis is a systemic disease that may affect the CNS. Cerebellar involvement in histiocytosis may cause a slow progressive ataxia mimicking an autosomal recessive ataxia.3 The aim of this study is to describe the Langerhans cell histiocytosis (LCH) that manifests with slow progressive ataxia as the initial and main neurologic sign resembling a hereditary ataxia (cerebellar histiocytosis). 组织细胞增多症是一种可以累及中枢神经系统的全身性疾病。累及小脑的组织细胞增多症可类似常染色体隐性遗传性共济失调，表现出缓慢进展的共济失调特点3。本文的研究目的在于描述一例表现为缓慢进展共济失调的朗格汉斯细胞增多症，其首发和主要神经系统体征与遗传性共济失调相似（小脑组织细胞增多症）。 A large sample comprising 970 patients with different forms of progressive cerebellar ataxias were evaluated from 2008 to 2016. Four patients with LCH had progressive ataxia as the main neurologic manifestation and were first evaluated for hereditary ataxias: spinocerebellar ataxia spanel (SCA1,2,3,6,7,10,12,17) and Friedreich ataxia (FRDA). The genetic results were negative. Serum α-fetoprotein and albumin were normal. Secondary ataxias were also ruled out. 一项大样本试验对2008年至2016年间970例不同类型的进展性共济失调患者进行了评价。其中4例朗格汉斯细胞增多症患者以进展性共济失调为主要临床表现，最初是按遗传性共济失调进行检查的：脊髓小脑性共济失调（SCA1,2,3,6,7,10,12,17）和弗里德希氏共济失调（FRDA）。基因检查结果阴性。血清甲胎蛋白和白蛋白正常，排除了继发性共济失调。 In a 12-year-old boy with progressive gait instability, examination showed ataxia and increased deep tendon reflexes with spasticity. He developed diabetes insipidus at 6 years of age. Brain MRI disclosed hyperintense signal in middle cerebellar peduncles, dentate nucleus, and cerebellar white matter (figure, A). Cerebellar biopsy was inconclusive. During the disease course, bone scintigraphy disclosed osteolytic lesions in tibia and maxilla suggesting LCH. He underwent chemotherapy with no improvement. 12岁男孩，表现为进展性步态不稳。查体：共济失调，腱反射亢进伴痉挛步态。6岁时患有尿崩症。颅脑MRI示：小脑中脚、齿状核，小脑白质高信号（图A）。小脑活检未定性。在疾病进程中，骨扫描显示胫骨和上颌骨溶骨性损伤，提示朗格汉斯细胞增多症。给予化疗未见明显改善。 A 13-year-old girl presented with progressive ataxia that started 2 years ago. Examination showed ataxia, brisk deep tendon reflexes, and Babinski sign. Brain MRI showed hyperintense signal in dentate nucleus, dorsal brainstem, and cerebellar white matter (figure, B). Bone scintigraphy。demonstrated occipital and mandibular osteolytic lesions. Jugal mucosa biopsy confirmed LCH and chemotherapy was started with no improvement. 13岁女孩，表现为进展性共济失调2年。查体：共济失调，腱反射活跃，巴氏征（+）。颅脑MRI：齿状核，脑干背侧，小脑白质高信号（图B）。骨扫描显示：枕骨和下颌骨溶骨性损伤。颊粘膜活检证实为朗格汉斯细胞增多症。化疗治疗后无明显改善。 A 41-year-old man presented with a 4-year history of progressive ataxia. Examination showed global ataxia and dysarthria. Brain MRI depicted hyperintense signal in brainstem and middle cerebellar peduncles (figure, C). Cerebellar biopsy was inconclusive. Skin lesions appeared during the course of the disease, and biopsy confirmed LCH. No specific treatment was started. 41岁男性，表现为进展性共济失调4年。查体：共济失调，构音障碍。颅脑MRI：脑干及小脑中脚高信号（图C）。小脑活检未定性。在病程中出现皮肤病变，活检证实为朗格汉斯细胞增多症。未予特殊治疗。 A 12-year-old boy presented with progressive ataxia that started 5 years ago. Examination disclosed ataxia and mild spasticity. Whole body imaging showed bone osteolytic lesions suggesting LCH. Brain MRI showed hyperintense signal in brainstem and superior cerebellar peduncles (figure, D). He received chemotherapy with partial improvement in gait. 12岁男孩，表现为进展性共济失调5年。查体：共济失调，轻度痉挛步态。全身成像显示溶骨性损伤，提示朗格汉斯细胞增多症。颅脑MRI：脑干及小脑上脚高信号（图D）。化疗后步态部分改善。 图：4例累及小脑的朗格汉斯细胞增多症影像学特征 （A）患者1（FLAIR及T2）：小脑中脚，齿状核，小脑白质高信号；（B）患者2（FLAIR及T2）：齿状核、脑干背侧及小脑白质高信号；（C）患者3（FLAIR及T2）：脑干及桥小脑中脚高信号；（D）患者4（T2和T1）：脑干及小脑上脚结节样高信号，伴有结节和强化。同时可见偏侧蛛网膜囊肿。 Progressive ataxia was the main neurologic manifestation in all 4 patients with LCH. Considering that most of them had an early onset (except for patient 3), a genetic condition- such as FRDA was suspected and investigated. Other autosomal recessive ataxias that should be considered include ataxia with oculomotor apraxia, vitamin E deficiency, and SYNE1 ataxia. Interestingly, 3 patients had progressive spastic ataxia, which could guide the investigation for hereditary spastic ataxias, such as spastic paraplegia type 7, autosomal recessive spastic ataxia of Charlevoix-Saguenay, and late-onset FRDA.4 在上述4例朗格汉斯细胞增多症患者中，进展性共济失调是其主要神经系统表现。除病例3外，余患者均为年轻起病，遂怀疑遗传性疾病可能，如FRDA，并进行了检查。其他常染色体隐性遗传性共济失调，包括共济失调伴动眼失用，维生素E缺乏，SYNE1共济失调等也应被考虑。有趣的是，3例患者表现为进展性痉挛性共济失调，此症状可引导医生对遗传性痉挛性共济失调做进一步检查，例如痉挛性截瘫7型，常染色体隐性遗传的Charlevoix-Saguenay痉挛性共济失调和迟发型FRDA4。 Histiocytosis is a systemic disease characterized by uncontrolled proliferation of dendritic cells, macrophages, or monocyte derived cells in various tissues and organs. Neurologic involvement is variable and occurs in 20%–50% of patients with LCH. Two major types of CNS lesions are described: tumor and degenerative lesions. Degenerative lesions usually present with slowly progressive ataxia and spasticity, while tumor lesions due to cell proliferation cause focal neurologic deficits.5 Of note, although usually characterized by inflammation, recent studies have linked some causative genes to LCH, such as BRAF mutations.5 Considering that the diagnosis criteria for LCH are still through pathology, and not genetics, it is not possible to state that our 4 patients have a genetic condition. Furthermore, a limitation of our study is that patients did not undergo exome sequencing. 组织细胞增多症是一种表现为各种组织及器官内树突细胞、巨噬细胞或单核细胞异常增殖的系统性疾病。神经系统受累表现多种多样，可见于20%-50%的朗格汉斯细胞增多症患者。主要两种中枢神经系统受损表现:肿瘤和变性。变性性损伤主要表现为缓慢进展的共济失调和痉挛；肿瘤性病变常因细胞增殖引起局灶性神经病损。值得注意的是，尽管朗格汉斯细胞增多症主要为炎性病变，近期有研究显示某些致病基因与细胞增多症相关，如BRAF基因突变5。目前朗格汉斯细胞增多症的诊断仍然通过病理证实，而非基因学，所以无法确定上述4例患者的遗传学情况。另外，本研究的局限性在于并未对患者行外显子测序检查。 Additional clinical features (diabetes insipidus, bone and skin lesions) associated with imaging findings suggesting LCH guided investigation for pathologic studies. The typical brain imaging of “cerebellar histiocytosis” includes bilateral hyperintense signal in dentate nucleus, cerebellar peduncles, and cerebellar white matter and irregular signal abnormalities in the posterior pons.6 Contrast enhancement is common and was present in 3 patients from our sample. Brain biopsy is recommended when LCH is suspected, but pathologic studies may be inconclusive. The pathologic diagnosis is also possible with lymph node or skin biopsy.7 其他临床表现（尿崩症，骨和皮肤病变）合并影像结果提示朗格汉斯细胞增多症，指导了进一步行病理检查。典型的“小脑组织细胞增多症”脑影像学包括：双侧齿状核，小脑脚和小脑白质高信号及桥脑后部的不规则信号异常6。强化更常见，我们3例患者均可见。怀疑朗格汉斯细胞增多症时推荐行脑活检检查，但病理结果存在不能定性可能。也可通过淋巴结或皮肤活检诊断7。 This is a clinical categorization of cerebellar histiocytosis that manifests with progressive cerebellar symptoms mimicking a hereditary ataxia, usually with early onset and associated with pyramidal signs. Additional clinical features and neuroimaging findings may guide the investigation for LCH. Since treatment and genetic counseling for cerebellar histiocytosis and hereditary ataxia are different, a correct diagnosis is mandatory. 小脑性组织细胞增多症的其中一种临床类型即表现为进展性小脑症状，与遗传性共济失调很相似，通常早发，常伴锥体束征。其他临床特点及神经影像学表现可提示应行朗格汉斯细胞增多症的检查。由于小脑细胞增多症与遗传性共济失调治疗及遗传咨询存在不同，故必须正确诊断。 （全文终） |
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来自： zskyteacher > 《中枢神经系统》
