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双边额叶皮层脑炎和下肢轻瘫患者anti-MOG抗体
  1. Juichi藤森1,
  2. Yoshiki Takai2,
  3. 中岛美嘉一郎2,
  4. 道格拉斯Kazutoshi佐藤2,
  5. Toshiyuki高桥2,3,
  6. Kimihiko金子2,
  7. 血缘他2,
  8. 米卡渡边4,
  9. 痰迹总裁中西宏明1,
  10. 美智子小林1,
  11. Tatsuro甜点5,
  12. Masashi青木2,
  13. Kazuo藤5
  1. 1神经学部门首页,东北医药大学,仙台,日本
  2. 2神经学部门首页,东北大学研究生院医学,仙台,日本
  3. 3神经学部门首页,Yonezawa国立医院,Yonezawa,日本
  4. 4病理学系,东北大学医院,仙台,日本
  5. 5多发性硬化治疗,东北大学研究生院医学,仙台,日本
  1. 对应到藤森Juichi博士,东北医药大学神经学系1-12-1 Fukumu首页ro, Miyagino-ku,仙台983 - 8512,日本;j-fujimori在{}hosp.tohoku-mpu.ac.jp

http://dx.doi.org/10.1136/jnnp - 2016 - 315094

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    脑炎很少引起下肢轻瘫作为初始症状。在这里,我们报告一例steroid-responsive双边额叶皮质脑炎涉及腿运动区在入学一个病人出现下肢轻瘫。有趣的是,最初的下肢轻瘫演变成一种急性播散性脑脊髓炎(ADEM)例如疾病和视神经炎,病人被发现阳性anti-myelin少突细胞糖蛋白(MOG)抗体。

    病例报告

    一名46岁男子在2008年9月初经历了短暂的眩晕。大脑MRI回顾性略有液体衰减反转恢复(天赋)高强度损伤涉及左额叶皮质(图1)。一周后,病人经历了焦马达发作的右腿随后普遍。此后,他逐步发展头痛和下肢轻瘫在过去的一个星期。在承认,他没有其他神经赤字出现下肢轻瘫,但脊髓MRI是正常的。脑电图显示,没有癫痫放电。脑脊液(CSF)检查发现白细胞升高(56 /µL;多形核白细胞93%的单核细胞,3%)和正常蛋白(36 mg / dL)和葡萄糖(59 mg / dL)的水平。髓磷脂碱性蛋白(MBP)和脑脊液神经胶质原纤维酸性蛋白水平没有升高。细胞化验anti-N-methyl-D-aspartate受体(NMDAR)抗体,anti-voltage-gated钾通道(VGKC)抗体,anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸受体(AMPAR)抗体和anti-γ-aminobutyric acid-B受体(GABA (B) R)抗体的CSF是负的。血液和脑脊液检查对中枢神经系统感染中枢神经系统(CNS)疾病、胶原疾病、血管炎,遗传病疾病、结节病、淋巴瘤、副肿瘤综合征,缺乏维生素B和桥本脑病稀松平常的。

    Upper panel: axial fluid attenuation inversion recovery (FLAIR) images (1.5 T; TR 6000 ms, TE 105 ms). (A) Brain MRI at the onset revealed a faint high-intensity lesion involving the left frontal cortex, and the lesion appeared normal on diffusion-weighted imaging (DWI). Sagittal T2-weighted images (1.5 T; TR 3210 ms, TE 105 ms) (B) and axial and coronal FLAIR images (C–E). Brain MRI taken 12 days after admission revealed a high-intensity lesion involving the corpus callosum, bilateral cingulate gyrus and medial side of the bilateral frontal lobes, and this lesion appeared as a faint high-intensity area on DWI. Coronal T1-weighted images (1.5 T; TR 470 ms, TE 15 ms) after gadolinium enhancement (F). Brain MRI revealed contrast enhancement in these lesions that diminished after steroid pulse therapy. Axial T2-weighted images (1.5 T; TR 3200 ms, TE 544 ms) (G) just before the brain biopsy showed high-intensity signals involving both cingulate gyri, the corpus callosum and the medial aspect of the bilateral frontal lobes. Axial FLAIR images from November 2008 (H–J) revealed new high-intensity lesions surrounding the third ventricle and aqueduct of the midbrain and in the bilateral thalamus, although the high-intensity lesions involving the corpus callosum, bilateral cingulate gyrus and medial side of the bilateral frontal lobes had been resolved. Axial FLAIR images from January 2009 (K) revealed a new high-intensity lesion in the right basal ganglia. Coronal T1-weighted image (1.5 T; TR 615 ms, TE 15 ms) with gadolinium enhancement from August 2010 (L) revealed the enhancement of the right optic nerve. Middle panel: Paraffin-embedded biopsied brain slices. (M) The tissues were extensively spongy, reflecting brain oedema. Some cerebral vessels (rectangle) were cuffed with inflammatory cells. (H&E stain; 200x.) (N) Myelin sheaths throughout the biopsy samples were densely stained with luxol fast blue, thus indicating no evidence of demyelination (Kluver-Barrera stain; 200x). (O–Q) Perivascular cuffing shown in M. T and B lymphocytes infiltrated around the vessels, whereas macrophages were more diffusely scattered in the brain parenchyma (O, CD3; P, CD20; Q, CD68; 400x). (R) The immunostaining of myelin oligodendrocyte glycoprotein (MOG) also revealed intact myelin sheaths (MOG; 400x). (S) Axons stained for neurofilaments were quite well preserved. Only a few axonal alterations were observed in the sample. Lower panel: Indirect immunofluorescence assay of live human-MOG-transfected cells stained with the serum of the patient. MOG cDNA is expressed on the cell surface. (T) HEK293 cells transfected with MOG were stained with the serum of the patient and fluorescein-conjugated goat anti-human IgG antibody. (U) Bright-field micrograph of the cells. (V) Merge of T and U. The cell surface was stained positive.
    " data-icon-position="" data-hide-link-title="0">图1
    图1

    上面板:轴向液体衰减反转恢复(天赋)图像(1.5 T;TR 6000 ms, TE 105 ms)。(A)出现大脑核磁共振显示微弱的高强度损伤涉及左额叶皮质,正常和病变出现在diffusion-weighted成像(驾车)。在t2加权像矢状(1.5 T;TR 3210 ms, TE 105 ms) (B)和轴向和日冕天赋图像(汉英)。大脑MRI 12天入院后显示一个高强度损伤涉及胼胝体、双边扣带回和双边内侧额叶,和这个病变出现微弱的高强度区酒后驾驶。冠状t1影像(1.5 T;TR 470 ms, TE后15 ms)钆增强(F)。脑MRI显示对比度增强后,这些病变,减少类固醇脉冲疗法。在t2加权像轴(1.5 T;TR 3200 ms, TE 544 ms) (G)在脑活检显示高强度信号涉及两个扣带脑回,胼胝体和双边额叶内侧的方面。 Axial FLAIR images from November 2008 (H–J) revealed new high-intensity lesions surrounding the third ventricle and aqueduct of the midbrain and in the bilateral thalamus, although the high-intensity lesions involving the corpus callosum, bilateral cingulate gyrus and medial side of the bilateral frontal lobes had been resolved. Axial FLAIR images from January 2009 (K) revealed a new high-intensity lesion in the right basal ganglia. Coronal T1-weighted image (1.5 T; TR 615 ms, TE 15 ms) with gadolinium enhancement from August 2010 (L) revealed the enhancement of the right optic nerve. Middle panel: Paraffin-embedded biopsied brain slices. (M) The tissues were extensively spongy, reflecting brain oedema. Some cerebral vessels (rectangle) were cuffed with inflammatory cells. (H&E stain; 200x.) (N) Myelin sheaths throughout the biopsy samples were densely stained with luxol fast blue, thus indicating no evidence of demyelination (Kluver-Barrera stain; 200x). (O–Q) Perivascular cuffing shown in M. T and B lymphocytes infiltrated around the vessels, whereas macrophages were more diffusely scattered in the brain parenchyma (O, CD3; P, CD20; Q, CD68; 400x). (R) The immunostaining of myelin oligodendrocyte glycoprotein (MOG) also revealed intact myelin sheaths (MOG; 400x). (S) Axons stained for neurofilaments were quite well preserved. Only a few axonal alterations were observed in the sample. Lower panel: Indirect immunofluorescence assay of live human-MOG-transfected cells stained with the serum of the patient. MOG cDNA is expressed on the cell surface. (T) HEK293 cells transfected with MOG were stained with the serum of the patient and fluorescein-conjugated goat anti-human IgG antibody. (U) Bright-field micrograph of the cells. (V) Merge of T and U. The cell surface was stained positive.

    入学后,下肢轻瘫逐渐进展,和病人成为完全截瘫的痉挛状态在入院12天。此外,发烧、记忆衰退和昏睡。iT2-weighted和天赋的大脑核磁共振显示hyperintensities涉及胼胝体,双边的扣带脑回和内侧方面与对比度增强双边额叶(图1B-F)。因此,我们怀疑某种类型的脑炎,大剂量静脉注射甲基强的松龙(3天1 g)和阿昔洛韦(1500毫克/天)开始。他的症状改善,口服强的松(PSL)(60毫克/天)是管理2008年10月初开始。当时,脑脊液检查显示积极寡克隆免疫球蛋白乐队,后来在2008年10月中旬变得消极。CSF-MBP不高在2008年10月初重新评估。

    由于诊断的不确定性,脑活检进行2008年11月初在正确的扣带回。病理检查发现没有脱髓鞘斑块相对温和的组织损伤,神经轴突丧失或星形破坏尽管炎症和水肿的变化与t细胞和b细胞的渗透。没有观察到肿瘤细胞(图1m)。症状改善明显,所以PSL是锥形20毫克/天。

    在2008年11月下旬,虽然最初的天赋hyperintense面积变得越来越小,新的无症状的天赋hyperintense病变出现在第三脑室和脑导水管,以及双边丘脑和下橄榄核的权利。然而,这些病变后自发退化(图1H-K)。PSL是锥形7毫克/天。2009年3月,病人可能没有援助和出院就走。这时,最初的天赋高强度区也明显变得小了。

    在2010年7月下旬,PSL是进一步的锥形5毫克/天4毫克/天。1个月后,病人复发与正确的视神经炎(图1L)。他在他的右眼20/200视力。他负anti-serum水通道蛋白4抗体。脑脊液检查显示正常的白细胞值(1 /µl;单核细胞100%),蛋白质(29.6 mg / dL)和葡萄糖(55 mg / dL)。病人接受类固醇治疗,导致完全康复。此后,PSL管理局(5毫克/天)仍在继续。他最终扩大残疾状态Kurtzke规模为2.0。

    2014年2月,我们自身的细胞试验1显示病人阳性血清anti-MOG抗体(图1过程)。他在初始集脑炎抗体滴定度在2008年10月中旬,在他在2010年8月下旬与视神经炎复发,在缓解4096 x 2014年2月下旬,分别为4096 x 512 x。

    讨论

    我们的独特之处在于,涉及双边的脑炎患者额叶皮质出现下肢轻瘫在入学。常见的原因急性和亚急性非创伤性截瘫是炎症,血管和肿瘤疾病的胸线,但有一些罕见的non-myelopathic截瘫的原因,如polyradiculitis hyperkalemic或hypokalemic瘫痪,心因性截瘫和旁矢状面的皮质综合症。2尽管双边旁矢状面的皮质综合征可以观察到两国在大脑前动脉的局部贫血病例领土和快速增长的肿瘤旁矢状面的地区,脑炎通常不包括在截瘫的鉴别诊断。2

    目前的情况当时anti-MOG抗体阳性的诊断脑炎、ADEM-like病变和单侧视神经炎。我们认为anti-MOG抗体参与ADEM-like病变、视神经炎在我们的例子中,由于临床过程和MRI发现类似的报道anti-MOG-antibody-positive病例。然而,致病的anti-MOG抗体参与独特的脑炎是不清楚脑部脱髓鞘病变活检和脑脊液MBP水平升高之前所示anti-MOG-antibody-positive病人3 4在目前情况下被证实。最近,情况下,anti-NMDAR脑炎和anti-MOG-antibody-associated脱髓鞘综合症共存已报告。5VGKC,在我们的案例中,尽管没有NMDAR AMPAR或GABA (B) R抗体检测自身免疫性脑炎除了autoantibody-mediated脑炎涉及这些抗体可能与anti-MOG-antibody-associated共存脱髓鞘综合症。进一步的研究需要阐明的扩展频谱anti-MOG-antibody-associated疾病。

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