Mix Lucas, Schreiber-Katz Olivia, Wurster Claudia D, Uzelac Zeljko, Platen Sophia, Gipperich Christina, Ranxha Gresa, Wieselmann Gary, Osmanovic Alma, Ludolph Albert C, Petri Susanne, Lulé Dorothée
Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.
Department of Neurology, Hannover Medical School, Hannover, Germany.
Orphanet J Rare Dis. 2021 Jan 6;16(1):10. doi: 10.1186/s13023-020-01661-9.
Spinal muscular atrophy (SMA) issues from mutations in the survival of motor neuron (SMN) 1 gene. Loss or reduction of the SMN protein results in progressive muscle weakness. Whether this protein deficiency also affects cortical function remains unclear. While no data on adult patients exists so far, prior studies in children with SMA indicate cognitive abilities equal or even superior to healthy controls. This may suggest a possible compensatory-neuropsychological and interactional-process. The goal of this study was to assess the cognitive profile of adult patients with SMA, with a special focus on social cognition as a potential candidate for enhanced cognitive function through compensatory processes.
In a cross-sectional design, N = 31 adult SMA patients (types II and III) were assessed for language, verbal fluency, memory, visuospatial abilities and executive function with the Edinburgh Cognitive and Behavioural ALS Screen and for social cognition with the Reading the Mind in the Eyes Test. Physical function was evaluated using the Hammersmith Functional Motor Scale Expanded. N = 19 neurologically healthy controls were matched with patients for age, sex and years of education.
In none of the abovementioned cognitive domains significant differences between SMA patients and controls were found. Among patients, no differences between type II SMA and type III SMA were detected for any domain. However, a trend towards better social cognition in patients with type II SMA, compared to those with type III SMA was observed. Furthermore, a significant inverse correlation of physical function and executive function was detected: lower motor function was associated with a better executive function.
This study shows cognitive abilities in adult SMA in the normal range for all assessed domains. Thus, reduction of SMN protein has no obvious negative impact on cognitive function. Executive functions are identified as the only cognitive domain correlated with disease severity. Therefore, executive functions may play a role in the adaptation to physical restrictions in SMA, making them a promising target for future research.
脊髓性肌萎缩症（SMA）由运动神经元存活（SMN）1基因的突变引起。SMN蛋白的缺失或减少会导致进行性肌肉无力。这种蛋白质缺乏是否也会影响皮质功能仍不清楚。虽然目前尚无关于成年患者的数据，但先前对SMA儿童的研究表明，其认知能力与健康对照组相当甚至更优。这可能提示存在一种可能的代偿性神经心理和交互过程。本研究的目的是评估成年SMA患者的认知特征，特别关注社会认知，因为它可能是通过代偿过程增强认知功能的潜在候选因素。
采用横断面设计，对N = 31名成年SMA患者（II型和III型）使用爱丁堡认知与行为性肌萎缩侧索硬化症筛查量表评估语言、言语流畅性、记忆、视觉空间能力和执行功能，并使用“读心术”测试评估社会认知。使用扩展的哈默史密斯功能运动量表评估身体功能。N = 19名神经功能正常的对照者在年龄、性别和受教育年限方面与患者进行匹配。
在上述任何认知领域中，均未发现SMA患者与对照组之间存在显著差异。在患者中，未检测到II型SMA和III型SMA在任何领域存在差异。然而，观察到II型SMA患者与III型SMA患者相比，存在社会认知更好的趋势。此外，检测到身体功能与执行功能之间存在显著的负相关：运动功能越低，执行功能越好。
本研究表明，成年SMA患者在所有评估领域的认知能力均在正常范围内。因此，SMN蛋白的减少对认知功能没有明显的负面影响。执行功能被确定为唯一与疾病严重程度相关的认知领域。因此，执行功能可能在SMA患者适应身体限制方面发挥作用，使其成为未来研究的一个有前景的靶点。
