系统性淀粉样变性常累及骨骼肌而被忽视。

Skeletal muscle involvement in systemic amyloidosis is often overlooked.

机构信息

Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

出版信息

Neuropathol Appl Neurobiol. 2024 Aug;50(4):e12996. doi: 10.1111/nan.12996.

DOI:10.1111/nan.12996

PMID:38982616

Abstract

AIM

Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated.

METHODS

We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry.

RESULTS

Twenty-eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light-chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL-λ, one with AL-κ and two with ATTR. Group 2 included 15 patients with AL-λ and two patients with AL-κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies.

CONCLUSIONS

Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis.

摘要

目的

全身性淀粉样变性是一种错误折叠的淀粉样纤维在组织中沉积的疾病。淀粉样肌病是全身性淀粉样变性的一种罕见表现。然而，骨骼肌受累是否被低估，以及这种沉积是否保证了临床和病理肌病特征，仍有待研究。

方法

我们回顾性分析了 2018 年 1 月至 2023 年 6 月期间在我们中心进行全身性淀粉样变性骨骼肌活检的患者。共纳入 28 例疑诊全身性淀粉样变性患者，其中 21 例表现为心肌病但无肌病症状。进一步分析这些患者的临床和病理数据。通过免疫组化证实淀粉样蛋白类型。

结果

28 例疑诊全身性淀粉样变性患者接受了肌肉活检。24 例患者的骨骼肌中证实有淀粉样沉积，其中 22 例为轻链淀粉样变性（AL），2 例为转甲状腺素淀粉样变性（ATTR）。24 例患者中，7 例出现肌肉无力和肌肉力量下降（有症状肌病组，Group 1），而其余 17 例表现为肌肉力量正常（无症状肌病组，Group 2）。Group 1 包括 4 例 AL-λ、1 例 AL-κ 和 2 例 ATTR。Group 2 包括 15 例 AL-λ 和 2 例 AL-κ。Group 1 中有 6 例患者出现神经病变，而 Group 2 中仅有 1 例患者神经传导研究显示亚临床神经病变。间质中淀粉样沉积是最明显的改变，24 例患者均可见。神经病变改变，包括去神经萎缩和肌纤维分组，也很常见。除了 2 型纤维萎缩外，其他肌病改变均较轻且非特异性。未观察到肌膜破坏。免疫组化分析显示，在有淀粉样沉积的区域，MAC 和 MHC1 表达明显阳性。临床病理分析显示，两组间肌肉中淀粉样沉积的程度无显著差异。然而，Group 1 患者的骨骼肌活检显示出更明显的神经源性萎缩。