From the Sorbonne Universite (S.T.d.M., E.P., P.L.-D., A.D.), Paris Brain Institute, Inserm, INRIA, CNRS, APHP, France; The Houston Methodist Research Institute (T.O., T.A.), TX; Department of Neurology (J.F., T.K.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (J.F., T.K.), Bonn, Germany; Department of Neurology (K.B.), University of Minnesota, Minneapolis; University of California, Los Angeles (S.P.); Norman Fixel Center for Neurological Disorders (S.H.S.), College of Medicine, University of Florida, Gainesville; Department of Translational Neuroscience (D.M., B.J.), Michigan State University, Grand Rapids; Department of Neurology (K.P.F., S.M.P.), University of Utah, Salt Lake City; Functional Unit of Cellular and Molecular Neurogenetics (A.-L.F.-A.), Genetic Department, AP-HP Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France; Institute of Medical Genetics and Applied Genomics (C.D.), University of Tubingen, Tübingen, Germany; Department of Neurology (H.L.P.), University of Michigan, Ann Arbor; and Center for Magnetic Resonance Research (G.O.), Department of Radiology, University of Minnesota, Minneapolis.
Neurology. 2023 Apr 25;100(17):e1836-e1848. doi: 10.1212/WNL.0000000000207088. Epub 2023 Feb 16.
In spinocerebellar ataxia, ataxia onset can be preceded by mild clinical manifestation, cerebellar and/or brainstem alterations, or biomarker modifications. READISCA is a prospective, longitudinal observational study of patients with spinocerebellar ataxia type 1 (SCA1) and 3 (SCA3) to provide essential markers for therapeutic interventions. We looked for clinical, imaging, or biological markers that are present at an early stage of the disease.
We enrolled carriers of a pathologic or expansion and controls from 18 US and 2 European ataxia referral centers. Clinical, cognitive, quantitative motor, neuropsychological measures and plasma neurofilament light chain (NfL) measurements were compared between expansion carriers with and without ataxia and controls.
We enrolled 200 participants: 45 carriers of a pathologic expansion (31 patients with ataxia [median Scale for the Assessment and Rating of Ataxia: 9; 7-10] and 14 expansion carriers without ataxia [1; 0-2]) and 116 carriers of a pathologic expansion (80 patients with ataxia [7; 6-9] and 36 expansion carriers without ataxia [1; 0-2]). In addition, we enrolled 39 controls who did not carry a pathologic expansion in or . Plasma NfL levels were significantly higher in expansion carriers without ataxia than controls, despite similar mean age (controls: 5.7 pg/mL, SCA1: 18.0 pg/mL [ < 0.0001], SCA3: 19.8 pg/mL [ < 0.0001]). Expansion carriers without ataxia differed from controls by significantly more upper motor signs (SCA1 = 0.0003, SCA3 = 0.003) and by the presence of sensor impairment and diplopia in SCA3 ( = 0.0448 and 0.0445, respectively). Functional scales, fatigue and depression scores, swallowing difficulties, and cognitive impairment were worse in expansion carriers with ataxia than those without ataxia. Ataxic SCA3 participants showed extrapyramidal signs, urinary dysfunction, and lower motor neuron signs significantly more often than expansion carriers without ataxia.
READISCA showed the feasibility of harmonized data acquisition in a multinational network. NfL alterations, early sensory ataxia, and corticospinal signs were quantifiable between preataxic participants and controls. Patients with ataxia differed in many parameters from controls and expansion carriers without ataxia, with a graded increase of abnormal measures from control to preataxic to ataxic cohorts.
ClinicalTrials.gov NCT03487367.
在脊髓小脑性共济失调中，共济失调的发作可能先于轻度的临床表现、小脑和/或脑干改变或生物标志物改变。READISCA 是一项针对脊髓小脑性共济失调 1 型（SCA1）和 3 型（SCA3）患者的前瞻性、纵向观察性研究，旨在为治疗干预提供必要的标志物。我们寻找在疾病早期存在的临床、影像学或生物学标志物。
我们招募了来自 18 个美国和 2 个欧洲共济失调转诊中心的致病性 或 扩展携带者和对照组。比较了扩展携带者（伴或不伴共济失调）和对照组之间的临床、认知、定量运动、神经心理学测量和血浆神经丝轻链（NfL）测量值。
我们共纳入 200 名参与者：45 名致病性 扩展携带者（31 名有共济失调患者[中位数评分量表评估和评级共济失调：9；7-10]和 14 名无共济失调的扩展携带者[1；0-2]）和 116 名致病性 扩展携带者（80 名有共济失调的患者[7；6-9]和 36 名无共济失调的扩展携带者[1；0-2]）。此外，我们还招募了 39 名未携带 或 病理性扩展的对照组。尽管年龄相似（对照组：5.7 pg/mL，SCA1：18.0 pg/mL [ < 0.0001]，SCA3：19.8 pg/mL [ < 0.0001]），但无共济失调的扩展携带者的血浆 NfL 水平明显高于对照组。无共济失调的扩展携带者与对照组相比，上运动体征差异显著（SCA1 = 0.0003，SCA3 = 0.003），SCA3 中存在传感器损伤和复视（ = 0.0448 和 0.0445）。有共济失调的扩展携带者的功能量表、疲劳和抑郁评分、吞咽困难和认知障碍比无共济失调的扩展携带者更差。与无共济失调的扩展携带者相比，有共济失调的 SCA3 参与者明显更常出现锥体外系体征、尿功能障碍和下运动神经元体征。
READISCA 展示了在跨国网络中进行协调数据采集的可行性。在预共济失调参与者和对照组之间，可以定量检测 NfL 改变、早期感觉性共济失调和皮质脊髓体征。有共济失调的患者在许多参数上与对照组和无共济失调的扩展携带者不同，从对照组到预共济失调组再到共济失调组，异常指标呈梯度增加。
ClinicalTrials.gov NCT03487367。
