Quantifying and Treating Myofascial Dysfunction in Post Stroke Shoulder Pain

项目总结 肩痛在中风后非常常见，30%-70%的患者会发生肩痛。慢性卒中后 肩痛(PSSP)会导致抑郁，干扰运动恢复，并降低生活质量。 尽管PSSP被认为是由肩关节周围的肌筋膜组织受损引起的，但 PSSP的肌筋膜功能障碍和疼痛的病理生理学机制尚未阐明，导致漏诊。 早期诊断的机会和疼痛治疗的不同成功。透明质酸蓄积 肌肉及其筋膜中的酸(HA)可导致肌筋膜功能障碍。HA是一种糖胺聚糖(GAG)和一种 肌肉细胞外基质的主要成分。在生理量上，它起到了润滑剂的作用 粘弹性减震器，在肌肉收缩和拉伸过程中实现力传递。减缩关节 活动和痉挛可导致肌肉中HA的局灶性堆积和改变，导致 束带绷紧，深筋膜和肌层滑行功能障碍，活动范围缩小 (Rom)，和痛苦。肌肉HA浓度可以使用T1ρ磁共振成像和肌筋膜成像 功能障碍可以用定量超声的回声纹理分析和剪切应变图来评估。 (美国)，可作为有用的生物标志物，以阐明肌筋膜功能障碍的病理生理学。 PSSP。因此，在R61阶段，我们将：(1)使用T1ρ磁共振成像量化GAG/HA在 偏瘫与非偏瘫肩转肌的对比，并将T1ρ磁共振测量结果与超声回声相关联 质地测量，以开发一种临床友好的工具，以推断HA累积的程度；以及(2) 应用同一肌肉的US剪切应变图区分潜伏期和活动期PSSP 被动肩外旋(ER)时偏瘫侧与非轻瘫侧比较 与PSSP密切相关。为了继续到R33阶段，我们将展示一个具有统计意义的 (1)T1ρ磁共振的GAG/HA积聚与(2)潜伏期和活动期剪切应变图的差异 使用定量超声的PSSP。在R33阶段，我们将使用R61阶段中确定的成像指标来 监测肌肉注射透明质酸酶以增加无痛的临床试验中的治疗反应 被动肩部急诊室。我们将给患者注射重组人透明质酸酶或生理盐水 肩带肌肉功能障碍，并测量无痛肩ER-ROM(主要结果)(1) 注射前，(2)注射后1-2周(主要终点)，(3)注射后6-8周。我们期待着 局部注射透明质酸酶将分解累积的HA，导致无痛肩ER增加， 这种改善将与定量磁共振成像和US成像指标相关联。在其结论中，这是 提案将开发肌筋膜功能障碍的定量成像生物标记物，以监测对 治疗并与NIH Hear Initiative保持一致，以支持加强疼痛管理的研究。

PROJECT SUMMARY Shoulder pain is extremely common after stroke and occurs in 30-70% of patients. Chronic post stroke shoulder pain (PSSP) contributes to depression, interferes with motor recovery, and decreases quality of life. Although PSSP is thought to be caused by damage to the myofascial tissues around the shoulder joint, the pathophysiology of myofascial dysfunction and pain in PSSP has not been elucidated, leading to missed opportunities for early diagnosis and variable success with pain management. The accumulation of hyaluronic acid (HA) in muscle and its fascia can cause myofascial dysfunction. HA is a glycosaminoglycan (GAG) and a chief constituent of the extracellular matrix of muscle. In physiologic quantities, it functions as a lubricant and a viscoelastic shock absorber, enabling force transmission during muscle contraction and stretch. Reduced joint mobility and spasticity can result in focal accumulation and alteration of HA in muscle, leading to the development of taut bands, dysfunctional gliding of deep fascia and muscle layers, reduced range of motion (ROM), and pain. Muscle HA concentrations can be imaged using T1rho (T1ρ) MRI, and myofascial dysfunction can be assessed using echo texture analysis and shear strain mapping on quantitative ultrasound (US), which may serve as useful biomarkers to elucidate the pathophysiology of myofascial dysfunction in PSSP. Hence, in the R61 phase we will: (1) Quantify the extent of GAG/HA accumulation using T1ρ MRI in the paretic versus non-paretic shoulder rotator muscles, and correlate the T1ρ MRI measurements with US echo texture measurements to develop a clinic-friendly tool to infer the extent of HA accumulation; and (2) Distinguish between latent versus active PSSP using US shear strain mapping of the same muscles on the paretic side compared with the non-paretic side during passive shoulder external rotation (ER), which is strongly associated with PSSP. To proceed to the R33 phase, we will demonstrate a statistically significant difference in (1) GAG/HA accumulation using T1ρ MRI, and (2) shear strain mapping for latent and active PSSP using quantitative US. In the R33 phase, we will use the imaging metrics identified in the R61 phase to monitor treatment response in a clinical trial of intramuscular (IM) hyaluronidase injections to increase pain-free passive shoulder ER-ROM. We will administer human recombinant hyaluronidase or normal saline injections in the dysfunctional shoulder girdle muscles, and measure pain-free shoulder ER-ROM (primary outcome) (1) pre-injection, (2) 1–2 weeks post-injection (primary endpoint) and (3) 6-8 weeks post-injection. We expect that local hyaluronidase injections will breakdown the accumulated HA leading to increased pain-free shoulder ER, and that the improvement will correlate with quantitative MRI and US imaging metrics. At its conclusion, this proposal will develop quantitative imaging biomarkers of myofascial dysfunction to monitor response to treatment and aligns with the NIH HEAL Initiative to bolster research to enhance pain management.