Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy.
Unità Operativa Complessa di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Acta Neuropathol Commun. 2023 Oct 17;11(1):165. doi: 10.1186/s40478-023-01660-4.
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant epigenetic disorder with highly variable muscle involvement and disease progression. Ongoing clinical trials, aimed at counteracting muscle degeneration and disease progression in FSHD patients, increase the need for reliable biomarkers. Muscle magnetic resonance imaging (MRI) studies showed that the appearance of STIR-positive (STIR+) lesions in FSHD muscles represents an initial stage of muscle damage, preceding irreversible adipose changes. Our study aimed to investigate fibrosis, a parameter of muscle degeneration undetectable by MRI, in relation to disease activity and progression of FSHD muscles. We histologically evaluated collagen in FSHD1 patients' (STIR+ n = 27, STIR- n = 28) and healthy volunteers' (n = 12) muscles by picrosirius red staining. All patients (n = 55) performed muscle MRI before biopsy, 45 patients also after 1 year and 36 patients also after 2 years. Fat content (T1 signal) and oedema/inflammation (STIR signal) were evaluated at baseline and at 1- and 2-year MRI follow-up. STIR+ muscles showed significantly higher collagen compared to both STIR- (p = 0.001) and healthy muscles (p < 0.0001). STIR- muscles showed a higher collagen content compared to healthy muscles (p = 0.0194). FSHD muscles with a worsening in fatty infiltration during 1- (P = 0.007) and 2-year (P < 0.0001) MRI follow-up showed a collagen content of 3.6- and 3.7-fold higher compared to FSHD muscles with no sign of progression. Moreover, the fibrosis was significantly higher in STIR+ muscles who showed a worsening in fatty infiltration in a timeframe of 2 years compared to both STIR- (P = 0.0006) and STIR+ muscles with no sign of progression (P = 0.02). Fibrosis is a sign of muscle degeneration undetectable at MRI never deeply investigated in FSHD patients. Our data show that 23/27 of STIR+ and 12/28 STIR- muscles have a higher amount of collagen deposition compared to healthy muscles. Fibrosis is higher in FSHD muscles with a worsening in fatty infiltration thus suggesting that its evaluation with innovative non-invasive techniques could be a candidate prognostic biomarker for FSHD, to be used to stratify patients and to evaluate the efficacy of therapeutic treatments.
面肩肱型肌营养不良症（FSHD）是一种常染色体显性遗传的表观遗传疾病，肌肉受累和疾病进展具有高度可变性。目前正在进行的临床试验旨在对抗 FSHD 患者的肌肉退化和疾病进展，这增加了对可靠生物标志物的需求。肌肉磁共振成像（MRI）研究表明，FSHD 肌肉中出现短 T1 反转恢复（STIR）阳性（STIR+）病变代表肌肉损伤的初始阶段，先于不可逆的脂肪变化。我们的研究旨在研究纤维化，这是一种 MRI 无法检测到的肌肉退化参数，与 FSHD 肌肉的疾病活动和进展有关。我们通过苦味酸红染色对 FSHD1 患者（STIR+ n=27，STIR- n=28）和健康志愿者（n=12）的肌肉进行了组织学评估胶原。所有患者（n=55）在活检前进行了肌肉 MRI，45 名患者在 1 年后和 36 名患者在 2 年后也进行了 MRI。在基线和 1 年和 2 年的 MRI 随访时评估脂肪含量（T1 信号）和水肿/炎症（STIR 信号）。STIR+肌肉与 STIR-（p=0.001）和健康肌肉（p<0.0001）相比，胶原含量显著更高。STIR-肌肉与健康肌肉相比，胶原含量更高（p=0.0194）。在 1 年（P=0.007）和 2 年（P<0.0001）MRI 随访中脂肪浸润恶化的 FSHD 肌肉与无进展迹象的 FSHD 肌肉相比，胶原含量高 3.6-和 3.7 倍。此外，与无进展迹象的 STIR-（P=0.0006）和 STIR+肌肉（P=0.02）相比，在 2 年内脂肪浸润恶化的 STIR+肌肉中的纤维化显著更高。纤维化是一种 MRI 无法检测到的肌肉退化的迹象，在 FSHD 患者中从未进行过深入研究。我们的数据显示，27 例 STIR+和 28 例 STIR-肌肉中有 23/27 和 12/28 例与健康肌肉相比，胶原沉积量更高。在脂肪浸润恶化的 FSHD 肌肉中，纤维化程度更高，这表明使用创新的非侵入性技术评估纤维化可能成为 FSHD 的候选预后生物标志物，用于对患者进行分层，并评估治疗效果。
