Cerebellar ataxia associated with antibodies against GAD65: A case report and literature review

doi:10.3969/j.issn.1004-583X.2024.06.010

Abstract

Abstract:

Objective To investigate the clinical characteristics, diagnosis, treatment and prognosis of cerebellar ataxia associated with antibodies against glutamic acid decarboxylase 65 (GAD65). Methods Clinical data of a case of cerebellar ataxia associated with antibodies against GAD65 were analyzed. Clinical characteristics, diagnosis, treatment and prognosis of cerebellar ataxia associated with antibodies against GAD65 were summarized by searching clinical cases at home and abroad reported before December 2023 in online databases of Pubmed, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service platform and Chinese Science and Technology Periodical Database (VIP) using the key words of “GAD65 antibody” and “cerebellar ataxia”. Results A 67-year-old male presented with weakness in both lower limbs slowly and gradually worsened, and finally he was unable to independently walk. Physical examination showed unclear articulation, level 5 muscle strength of both lower limbs, decreased tendon reflexes in lower limbs, bilateral limb ataxia, unable to walk in a straight line, positive Romberg signs, and positive Babiniski signs. Brain magnetic resonance imaging (MRI) suggested brain atrophy. A panel of 14 diagnostic serum markers of autoimmune cerebellar ataxia showed a weak positivity for GAD65 antibody (IgG 1:30). After hormonal shock therapy and oral immunotherapy, the patient presented an improved symptom of limb weakness, increased red cell count and hemoglobin, and decreased thyroid hormone. Thyroid peroxidase antibody was not significantly changed. Through literature review, 15 case reports and 6 articles reported 186 patients with cerebellar ataxia associated with antibodies against GAD65. The disease develops slowly and progressively. Gait ataxia is the typical clinical manifestation. Cerebellar ataxia associated with antibodies against GAD65 involves the brain stem, and may accompany other autoimmune diseases, but occasionally combines with tumors. Immune therapy is able to alleviate symptoms, and an early treatment provides more clinical benefits. Conclusion Cerebellar ataxia associated with antibodies against GAD65 is a rare type of cerebellar ataxia. Positive detection of GAD65 antibodies in cerebrospinal fluid (CSF) or serum is important for the diagnosis. At present, clinical treatment of cerebellar ataxia associated with antibodies against GAD65 has not yet reached a unified understanding, and immunotherapy can improve clinical symptoms.

Key words: cerebellar ataxia, GAD65, antibody

CLC Number:

R742.82

Zhang Li, Fu Qingxi, Su Mingzhao, Su Quanping. Cerebellar ataxia associated with antibodies against GAD65: A case report and literature review[J]. Clinical Focus, 2024, 39(6): 542-547.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2024.06.010

https://huicui.hebmu.edu.cn/EN/Y2024/V39/I6/542

Figures/Tables 5

References 21

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文献	性别	年龄 (岁)	病程 (月)	临床症状	体征	共病
刘峥等^[4]	女	45	42	眩晕,视物成双,右侧肢体活动不协调,行走不稳	右眼睑下垂,双眼上视受限,下视出现垂直眼震(右>左);右下肢肌力5-级,右侧肢体共济失调,不能直线行走	无
刘静等^[5]	女	62	9	头晕,左侧肢体活动不灵,行走不稳	双眼左视水平凝视眼震;左侧肢体共济失调,步基宽,吟诗样语言,闭目难立征阳性,双下肢腱反射减退,双滑征阳性	自身免疫相关性糖尿病并发周围神经损害
朱丽平等^[6]	男	62	6	复视,构音不清,行走不稳	双眼上视受限,各方向复视,构音欠清,双侧肢体共济失调	无
杨桦等^[7]	女	59	3	头晕,视物模糊,行走不稳	双眼水平旋转粗大眼震,小脑步态,双下肢共济失调,闭目难立征阳性,右侧病理征可疑阳性	无
高颖等^[8]	女	61	12	视物重影,行走不稳	左眼睑下垂,双眼水平眼震;步基宽,不能直线行走,左侧肢体共济失调,右侧霍夫曼征阳性,闭目难立征阳性,右侧Chaddock征阳性	无
任若琳等^[9]	女	53	18	双足趾屈曲痉挛疼痛,大汗,气促,行走不稳	步基宽,不能直线行走,闭目难立征阳性	僵人综合征;亚临床甲状腺功能减退,自身免疫性甲状腺炎
刘芳芳等^[10]	女	65	12	头晕,视物晃动,行走不稳	垂直下跳性眼震;不能直线行走,闭目难立征阳性	无
本例	男	67	1.5	言语含糊,双下肢无力,不能独立行走	构音欠清,双下肢肌力5-级,双下肢腱反射减退,双侧肢体共济失调,不能直线行走,闭目难立征阳性,双侧病理征阳性	甲状腺功能减退症

文献	性别	年龄 (岁)	病程 (月)	临床症状	体征	共病
刘峥等^[4]	女	45	42	眩晕,视物成双,右侧肢体活动不协调,行走不稳	右眼睑下垂,双眼上视受限,下视出现垂直眼震(右>左);右下肢肌力5-级,右侧肢体共济失调,不能直线行走	无
刘静等^[5]	女	62	9	头晕,左侧肢体活动不灵,行走不稳	双眼左视水平凝视眼震;左侧肢体共济失调,步基宽,吟诗样语言,闭目难立征阳性,双下肢腱反射减退,双滑征阳性	自身免疫相关性糖尿病并发周围神经损害
朱丽平等^[6]	男	62	6	复视,构音不清,行走不稳	双眼上视受限,各方向复视,构音欠清,双侧肢体共济失调	无
杨桦等^[7]	女	59	3	头晕,视物模糊,行走不稳	双眼水平旋转粗大眼震,小脑步态,双下肢共济失调,闭目难立征阳性,右侧病理征可疑阳性	无
高颖等^[8]	女	61	12	视物重影,行走不稳	左眼睑下垂,双眼水平眼震;步基宽,不能直线行走,左侧肢体共济失调,右侧霍夫曼征阳性,闭目难立征阳性,右侧Chaddock征阳性	无
任若琳等^[9]	女	53	18	双足趾屈曲痉挛疼痛,大汗,气促,行走不稳	步基宽,不能直线行走,闭目难立征阳性	僵人综合征;亚临床甲状腺功能减退,自身免疫性甲状腺炎
刘芳芳等^[10]	女	65	12	头晕,视物晃动,行走不稳	垂直下跳性眼震;不能直线行走,闭目难立征阳性	无
本例	男	67	1.5	言语含糊,双下肢无力,不能独立行走	构音欠清,双下肢肌力5-级,双下肢腱反射减退,双侧肢体共济失调,不能直线行走,闭目难立征阳性,双侧病理征阳性	甲状腺功能减退症

文献	GAD65 抗体	脑脊液 OCB	副肿瘤综合征抗体	颅脑MRI	治疗	预后
刘峥等^[4]	血清1∶100,CSF 1∶100	阳性	血清SOX1弱阳性	右侧小脑蚓部轻度萎缩逐渐加重	甲强龙1 g/d×5 d,之后口服泼尼松60 mg/d	1周后症状均有减轻,但仍有双眼上视受限
刘静等^[5]	血清1∶100,CSF 1:320	阳性	阴性	未见明显异常	口服泼尼松1 mg/kg/d,每周减2.5 mg	病情趋于稳定
朱丽平等^[6]	血清弱阳性,CSF强阳性	阳性	未查	未见明显异常	甲强龙1 g/d,每3天减量一半,之后口服泼尼松1 mg/kg	3 d后症状明显减轻,2周后在搀扶下能行走
杨桦等^[7]	血清1:10,CSF 1:320	未查	阴性	未见明显异常	注人免疫球蛋白25 g,每日1次,持续1周	1周后能独立站立,1个月后无明显变化
高颖等^[8]	血清和CSF强阳性	未查	未查	未见明显异常	甲强龙1 g/d,每3天减量一半,之后口服泼尼松1 mg/kg,口服3周	3个月后症状改善,仍有行走不稳
任若琳等^[9]	血清63AU(阳性),脑脊液6AU(灰区)	阴性	阴性	未见明显异常	甲强龙500 mg×5 d,之后口服泼尼松80 mg,每3天减5 mg,口服45 d	症状改善,日常生活不受影响
刘芳芳等^[10]	血清1∶100,CSF 1∶100	阴性	未查	未见明显异常	静脉滴注丙种球蛋白冲击×5 d,之后口服泼尼松30 mg/d,逐渐减量	1个月后头晕好转,ICARS国际共济失调评定量表评分18分降低为12分
本例	血清1∶30	未查	未查	脑萎缩	甲强龙500 mg/d,每3天减量一半,之后口服泼尼松并口服60 mg每周减量1片,并口服吗替麦考酚酯长期治疗	出院时言语不清好转,出院1个月后症状缓解,但仍走路不稳

文献	GAD65 抗体	脑脊液 OCB	副肿瘤综合征抗体	颅脑MRI	治疗	预后
刘峥等^[4]	血清1∶100,CSF 1∶100	阳性	血清SOX1弱阳性	右侧小脑蚓部轻度萎缩逐渐加重	甲强龙1 g/d×5 d,之后口服泼尼松60 mg/d	1周后症状均有减轻,但仍有双眼上视受限
刘静等^[5]	血清1∶100,CSF 1:320	阳性	阴性	未见明显异常	口服泼尼松1 mg/kg/d,每周减2.5 mg	病情趋于稳定
朱丽平等^[6]	血清弱阳性,CSF强阳性	阳性	未查	未见明显异常	甲强龙1 g/d,每3天减量一半,之后口服泼尼松1 mg/kg	3 d后症状明显减轻,2周后在搀扶下能行走
杨桦等^[7]	血清1:10,CSF 1:320	未查	阴性	未见明显异常	注人免疫球蛋白25 g,每日1次,持续1周	1周后能独立站立,1个月后无明显变化
高颖等^[8]	血清和CSF强阳性	未查	未查	未见明显异常	甲强龙1 g/d,每3天减量一半,之后口服泼尼松1 mg/kg,口服3周	3个月后症状改善,仍有行走不稳
任若琳等^[9]	血清63AU(阳性),脑脊液6AU(灰区)	阴性	阴性	未见明显异常	甲强龙500 mg×5 d,之后口服泼尼松80 mg,每3天减5 mg,口服45 d	症状改善,日常生活不受影响
刘芳芳等^[10]	血清1∶100,CSF 1∶100	阴性	未查	未见明显异常	静脉滴注丙种球蛋白冲击×5 d,之后口服泼尼松30 mg/d,逐渐减量	1个月后头晕好转,ICARS国际共济失调评定量表评分18分降低为12分
本例	血清1∶30	未查	未查	脑萎缩	甲强龙500 mg/d,每3天减量一半,之后口服泼尼松并口服60 mg每周减量1片,并口服吗替麦考酚酯长期治疗	出院时言语不清好转,出院1个月后症状缓解,但仍走路不稳

文献	病例数	平均年龄 (岁)	女性 [例(%)]	神经系统症状	鞘内合成 GAD65抗体	脑脊液 OCB	共病
Honnorat et al^[11]	14	51(20~74)	13(93%)	步态共济失调(100%),肢体共济失调(86%),眼球震颤(86%),构音障碍(57%)	5/6(83%)	10/14(71%)	T1DM(71%),甲状腺炎(57%),恶性贫血(14%),重症肌无力(7%),肿瘤(14%)
Saiz et al^[12]	17	59(39~77)	16(94%)	步态共济失调(100%),肢体共济失调(59%),眼球震颤(65%),构音障碍(65%)	12/12(100%)	9/13(69%)	T1DM(53%),甲状腺炎(41%),恶性贫血(12%),白癜风(6%),肿瘤(12%)
Arino et al^[13]	34	58(33~80)	28/34(82%)	步态共济失调(91%),肢体共济失调(74%),构音障碍(71%),眼球震颤(59%)	13/15(87%)	16/22(73%)	T1DM(38%),甲状腺炎(53%),恶性贫血(21%),白癜风(6%),肿瘤(12%)
Budhram et al^[14]	55	59 (14~83)	42(76%)	未记录	55/55(100%)	13/31(42%)	全身性免疫疾病(65%),T1DM (33%),甲状腺疾病(36%),恶性贫血(20%),其他疾病(13%),肿瘤(13%)
Bai et al^[3]	11	54(43~63)	9(81.8%)	步态共济失调(100%),头晕或复视(63.6%),构音障碍(63.4%)	11/11(100%)	4/6(66.7%)	相关自身免疫性疾病(36%),脑炎/癫痫(36%),僵人综合征(9%),肿瘤(9%)