van Bruggen H Willemijn, Wijngaarde Camiel A, Asselman Faylynn, Stam Marloes, Creugers Nico H J, Wadman Renske I, van der Pol W Ludo, Kalaykova Stanimira I
Department of Dentistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Department of Neurology and Neurosurgery and Spieren voor Spieren Kindercentrum, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
J Neuromuscul Dis. 2024;11(3):655-664. doi: 10.3233/JND-240007.
Hereditary proximal spinal muscular atrophy (SMA) is characterized by abnormal alpha motor neuron function in brainstem and spinal cord. Bulbar dysfunction, including limited mouth opening, is present in the majority of patients with SMA but it is unknown if and how these problems change during disease course.
In this prospective, observational, longitudinal natural history study we aimed to study bulbar dysfunction in patients with SMA types 2 and 3.
We included 44 patients with SMA types 2 and 3 (mean age was 33.6 (95% CI 28.4;38.9) and re-examined them after on average 4 years. None were treated with SMN-modulating treatments before or during the course of this study. Longitudinal assessments included a questionnaire on mandibular and bulbar function, the Mandibular Function Impairment Questionnaire (MFIQ), and a clinical examination of masticatory performance, maximum voluntary bite force, and mandibular movements including the active maximal mouth opening.
We found significant higher MFIQ scores and a significant decrease of all mandibular movements in patients with SMA type 2 (p < 0.001), but not in SMA type 3. Masticatory performance and maximum voluntary bite force did not change significantly. Mean reduction of active maximal mouth opening at follow-up was 3.5 mm in SMA type 2 (95% CI: 2.3; 4.7, p < 0.001). SMA type 2 was an independent predictor for a more severe reduction of the mouth opening (β= -2.0 mm (95% CI: -3.8; -0.1, p = 0.043)).
Bulbar functions such as mandibular mobility and active maximum mouth opening decrease significantly over the course of four years in patients with SMA type 2.
遗传性近端脊髓性肌萎缩症(SMA)的特征是脑干和脊髓中的α运动神经元功能异常。大多数SMA患者存在球部功能障碍,包括张口受限,但尚不清楚这些问题在疾病过程中是否以及如何变化。
在这项前瞻性、观察性、纵向自然史研究中,我们旨在研究2型和3型SMA患者的球部功能障碍。
我们纳入了44例2型和3型SMA患者(平均年龄为33.6岁(95%置信区间28.4;38.9)),并在平均4年后对他们进行了重新检查。在本研究过程之前或期间,没有患者接受过SMN调节治疗。纵向评估包括一份关于下颌和球部功能的问卷、下颌功能损害问卷(MFIQ),以及对咀嚼性能、最大自主咬合力和下颌运动(包括主动最大张口)的临床检查。
我们发现2型SMA患者的MFIQ评分显著更高,所有下颌运动均显著减少(p<0.001),但3型SMA患者没有。咀嚼性能和最大自主咬合力没有显著变化。2型SMA患者随访时主动最大张口的平均减少量为3.5毫米(95%置信区间:2.3;4.7,p<0.001)。2型SMA是张口减少更严重的独立预测因素(β=-2.0毫米(95%置信区间:-3.8;-0.1,p=0.043))。
在4年的病程中,2型SMA患者的球部功能,如下颌活动度和主动最大张口度显著下降。