对小脑型多系统萎缩(MSA-C)的明确诊断具有挑战性。我们假设MRI上脑桥和小脑中梗直径的变化率将是MSA-C独有的,并可作为诊断生物标志物。我们在健康对照组的脑MRI上定义了前后脑桥和小脑中部横梗直径的规范数据,进行直径-体积相关性,并测量评估者内和评估者间的可靠性。我们研究了88名MSA-C和78名其他小脑共济失调患者的探索性队列(2002-2014),和49MSA-C的验证队列(2015-2021),13帕金森病型多系统萎缩(MSA-P),其他99例小脑共济失调患者和314例非共济失调患者。我们在基线和随后的MRI上测量了前后脑桥和小脑中梗直径,并将结果与简要共济失调量表评分相关。我们评估了中脑:脑桥和中脑花梗:脑桥的比率。标准前后桥直径为23.6±1.6mm,小脑中部花梗直径16.4±1.4mm。桥孔直径与体积相关,r=0.94,P<0.0001。与所有其他共济失调相比,MSA-C首次扫描时的前后脑桥和小脑中梗测量值较小;前后脑桥直径:探究性,19.3±2.6mm对20.7±2.6mm,验证,19.9±2.1mm与21.1±2.1mm;小脑中柄横径,探索性的,12.0±2.6mm对14.3±2.1mm,验证,13.6±2.1mm对15.1±1.8mm,所有P<0.001。MSA-C的前后脑桥和中小脑花梗变化率比所有其他共济失调快;前后脑桥直径变化率:探索性,-0.87±0.04毫米/年与-0.09±0.02毫米/年,验证,-0.89±0.48毫米/年与-0.10±0.21毫米/年;小脑中梗横径变化率:探索性,-0.84±0.05毫米/年与-0.08±0.02毫米/年,验证,-0.94±0.64毫米/年与-0.11±0.27毫米/年,所有值P<0.0001。前后脑桥和小脑中梗直径在可能之间无法区分,可能的和确定的MSA-C前后脑桥萎缩率呈线性,与共济失调严重程度相关。使用较低的阈值前后桥直径减少-0.4毫米/年,以平衡灵敏度和特异性,将MSA-C与其他共济失调区分开的曲线下面积为0.94,敏感性为0.92,特异性为0.87.对于小脑中部花梗,阈值下降-0.5毫米/年,曲线下面积为0.90,敏感性为0.85,特异性为0.79.MSA-C中脑:脑桥比率逐渐增加,而小脑中部花梗:脑桥的比例几乎没有变化。MSA-C的前后脑桥和小脑中梗直径小于MSA-P,P<0.001。我们从这项为期20年的纵向临床和影像学研究中得出结论,前后脑桥和小脑中梗直径是MSA-C的表型影像学生物标志物。在正确的临床背景下,前后脑桥和横向小脑中部花梗直径下降约0.8毫米/年就足以诊断MSA-C。
Definitive diagnosis of multiple system atrophy of the cerebellar type (MSA-C) is challenging. We hypothesized that rates of change of pons and middle cerebellar peduncle diameters on MRI would be unique to MSA-C and serve as diagnostic biomarkers. We defined the normative data for anterior-posterior pons and transverse middle cerebellar peduncle diameters on brain MRI in healthy controls, performed diameter-volume correlations and measured intra- and inter-rater reliability. We studied an Exploratory cohort (2002-2014) of 88 MSA-C and 78 other cerebellar ataxia patients, and a Validation cohort (2015-2021) of 49 MSA-C, 13 multiple system atrophy of the parkinsonian type (MSA-P), 99 other cerebellar ataxia patients and 314 non-ataxia patients. We measured anterior-posterior pons and middle cerebellar peduncle diameters on baseline and subsequent MRIs, and correlated results with Brief Ataxia Rating Scale scores. We assessed midbrain:pons and middle cerebellar peduncle:pons ratios over time. The normative anterior-posterior pons diameter was 23.6 ± 1.6 mm, and middle cerebellar peduncle diameter 16.4 ± 1.4 mm. Pons diameter correlated with volume, r = 0.94, P < 0.0001. The anterior-posterior pons and middle cerebellar peduncle measures were smaller at first scan in MSA-C compared to all other ataxias; anterior-posterior pons diameter: Exploratory, 19.3 ± 2.6 mm versus 20.7 ± 2.6 mm, Validation, 19.9 ± 2.1 mm versus 21.1 ± 2.1 mm; middle cerebellar peduncle transverse diameter, Exploratory, 12.0 ± 2.6 mm versus 14.3 ±2.1 mm, Validation, 13.6 ± 2.1 mm versus 15.1 ± 1.8 mm, all P < 0.001. The anterior-posterior pons and middle cerebellar peduncle rates of change were faster in MSA-C than in all other ataxias; anterior-posterior pons diameter rates of change: Exploratory, -0.87 ± 0.04 mm/year versus -0.09 ± 0.02 mm/year, Validation, -0.89 ± 0.48 mm/year versus -0.10 ± 0.21 mm/year; middle cerebellar peduncle transverse diameter rates of change: Exploratory, -0.84 ± 0.05 mm/year versus -0.08 ± 0.02 mm/year, Validation, -0.94 ± 0.64 mm/year versus -0.11 ± 0.27 mm/year, all values P < 0.0001. Anterior-posterior pons and middle cerebellar peduncle diameters were indistinguishable between Possible, Probable and Definite MSA-C. The rate of anterior-posterior pons atrophy was linear, correlating with ataxia severity. Using a lower threshold anterior-posterior pons diameter decrease of -0.4 mm/year to balance sensitivity and specificity, area under the curve analysis discriminating MSA-C from other ataxias was 0.94, yielding sensitivity 0.92 and specificity 0.87. For the middle cerebellar peduncle, with threshold decline -0.5 mm/year, area under the curve was 0.90 yielding sensitivity 0.85 and specificity 0.79. The midbrain:pons ratio increased progressively in MSA-C, whereas the middle cerebellar peduncle:pons ratio was almost unchanged. Anterior-posterior pons and middle cerebellar peduncle diameters were smaller in MSA-C than in MSA-P, P < 0.001. We conclude from this 20-year longitudinal clinical and imaging study that anterior-posterior pons and middle cerebellar peduncle diameters are phenotypic imaging biomarkers of MSA-C. In the correct clinical context, an anterior-posterior pons and transverse middle cerebellar peduncle diameter decline of ∼0.8 mm/year is sufficient for and diagnostic of MSA-C.