Krett Jonathan D, Wang Yujie, Miles Ashley, Chen Herbert R, Afshar Hanyeh, Elfasi Aisha, Lin Doris D, Newsome Scott D
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Neurology, University of Washington Medical Center - Northwest, Seattle, Washington, USA.
Eur J Neurol. 2025 May;32(5):e70166. doi: 10.1111/ene.70166.
Cerebellar ataxia is associated with greater disability in glutamic acid decarboxylase-65 (GAD65) antibody-associated neurological disorders and can occur in isolation or as part of stiff person syndrome (SPS) spectrum disorders (SPSD). We sought to phenotypically characterize this subpopulation with cerebellar dysfunction.
Observational study of GAD65 antibody-seropositive individuals with cerebellar involvement seen at Johns Hopkins (1997-2024). Subjects were divided into two groups based on cerebellar dysfunction in the presence (SPSD; SPS-plus and progressive encephalomyelitis with rigidity and myoclonus [PERM]) or absence (pure cerebellar ataxia [pCA]) of classic SPS features. Clinical and paraclinical findings were analyzed descriptively.
Seventy-two patients were selected among 356 (62 SPSD, 10 pCA). Mean age for patients with pCA was 58 ± 16 years versus 46 ± 15 years for SPSD (p = 0.012). Males comprised 50% of the pCA group versus 19% SPSD (p = 0.049). High GAD65 antibody serum titers occurred in 76% without group differences, while cerebrospinal fluid antibody positivity occurred in 35/37 (95%) of SPSD versus 5/8 (62%) pCA (p = 0.033). Although the modified Rankin scale was similar (median 3, interquartile range 2-4) in both groups, the brief ataxia rating scale indicated a higher burden of cerebellar abnormalities in pCA versus SPSD, and there was a trend toward greater cerebellar atrophy by MRI in pCA (p = 0.44). Rituximab and benzodiazepine use was more frequent in SPSD versus pCA.
GAD65 antibody-associated ataxia is disabling irrespective of accompanying SPS features. Patients with pCA were older, more commonly male, and may have more frequent cerebellar atrophy than those with SPSD. Prospective validation of cerebellar outcomes and neuroimaging findings is needed.
在谷氨酸脱羧酶65（GAD65）抗体相关的神经系统疾病中，小脑共济失调与更严重的残疾相关，可单独出现或作为僵人综合征（SPS）谱系障碍（SPSD）的一部分出现。我们试图对这一小部分伴有小脑功能障碍的患者进行表型特征分析。
对约翰·霍普金斯医院（1997 - 2024年）收治的有小脑受累的GAD65抗体血清学阳性个体进行观察性研究。根据是否存在经典SPS特征（SPSD；SPS加型和伴有僵硬和肌阵挛的进行性脑脊髓炎[PERM]）或不存在（单纯小脑共济失调[pCA]）将受试者分为两组。对临床和辅助检查结果进行描述性分析。
在356例患者中选取了72例（62例SPSD，10例pCA）。pCA患者的平均年龄为58±16岁，而SPSD患者为46±15岁（p = 0.012）。pCA组男性占50%，而SPSD组为19%（p = 0.049）。76%的患者GAD65抗体血清滴度高，无组间差异，而脑脊液抗体阳性率在SPSD组为35/37（95%），pCA组为5/8（62%）（p = 0.033）。尽管两组的改良Rankin量表评分相似（中位数为3，四分位间距为2 - 4），但简短共济失调评定量表显示pCA组的小脑异常负担高于SPSD组，且pCA组MRI显示小脑萎缩更明显的趋势（p = 0.44）。SPSD组使用利妥昔单抗和苯二氮䓬类药物的频率高于pCA组。
无论是否伴有SPS特征，GAD65抗体相关的共济失调都会导致残疾。pCA患者年龄更大，男性更常见，且可能比SPSD患者有更频繁的小脑萎缩。需要对小脑结局和神经影像学结果进行前瞻性验证。
