ATL1-related spastic paraplegia SPG3A is a pure form of hereditary spastic paraplegia. Rare complex phenotypes have been described, but few data concerning cognitive evaluation or molecular imaging of these patients are available. We relate a retrospective collection of patients with SPG3A from the Neurology Department of Nancy University Hospital, France. For each patient were carried out a ¹⁸F-FDG PET (positron emission tomography), a electromyography (EMG), a sudoscan®, a cerebral and spinal cord MRI (magnetic resonance imaging) with measurement of cervical and thoracic surfaces, a neuropsychological assessment. The present report outlines standardised clinical and paraclinical data of five patients from two east-France families carrying the same missense pathogenic variation, NM_015915.4(ATL1): c.1483C > T p.(Arg495Trp) in ATL1. Mean age at onset was 14 ± 15.01 years. Semi-quantitatively and in comparison to healthy age-matched subjects, PET scans showed a significant cerebellar and upper or mild temporal hypometabolism in all four adult patients and hypometabolism of the prefrontal cortex or precuneus in three of them. Sudoscan® showed signs of small fibre neuropathy in three patients. Cervical and thoracic patients’ spinal cords were significantly thinner than matched-control, respectively 71 ± 6.59mm² (p = 0.01) and 35.64 ± 4.35mm² (p = 0.015). Two patients presented with a dysexecutive syndrome. While adding new clinical and paraclinical signs associated with ATL1 pathogenic variations, we insist here on the variable penetrance and expressivity. We report small fibre neuropathy, cerebellar hypometabolism and dysexecutive syndromes associated with SPG3A. These cognitive impairments and PET findings may be related to a cortico-cerebellar bundle axonopathy described in the cerebellar cognitive affective syndrome (CCAS).

ATL1相关的痉挛性截瘫 SPG3A 是一种纯粹的遗传性痉挛性截瘫。已经描述了罕见的复杂表型，但很少有关于这些患者的认知评估或分子成像的数据可用。我们将来自法国南锡大学医院神经科的 SPG3A 患者的回顾性收集联系起来。对每位患者进行了¹⁸F-FDG PET（正电子发射断层扫描）、肌电图 (EMG)、sudoscan®、脑和脊髓 MRI（磁共振成像）以及颈部和胸部表面测量、神经心理学评估。本报告概述了来自两个法国东部家庭的五名患者的标准化临床和临床旁数据，这些患者携带相同的错义致病变异，NM_015915.4(ATL1)：c.1483C > T p.(Arg495Trp) in ATL1. 平均发病年龄为 14 ± 15.01 岁。半定量和与年龄匹配的健康受试者相比，PET 扫描显示所有四名成年患者的小脑和上颞叶或轻度颞叶代谢减退，其中三名患者的前额叶皮质或楔前叶代谢减退。Sudoscan® 在三名患者中显示出小纤维神经病变的迹象。颈椎和胸椎患者的脊髓明显比匹配对照组细，分别为 71 ± 6.59mm ² ( p  = 0.01) 和 35.64 ± 4.35mm ² ( p  = 0.015)。两名患者出现执行障碍综合征。在添加与 ATL1 相关的新临床和副临床体征时致病性变异，我们在这里坚持可变的外显率和表现力。我们报告了与 SPG3A 相关的小纤维神经病、小脑代谢减退和执行障碍综合征。这些认知障碍和 PET 结果可能与小脑认知情感综合征 (CCAS) 中描述的皮质小脑束轴索病有关。