僵直性脊椎炎病患之薦腸關節與腰椎周圍軟組織的超音波特徵

Abstract

研究背景：僵直性脊椎炎 (Ankylosing spondylitis, AS) 為自體免疫之慢性發炎性疾病，在肌肉骨骼系統上，主要侵犯人體的中軸骨骼，包含骨盆、薦腸關節與脊椎關節，其中薦腸關節炎 (sacroiliitis) 為較早的中軸骨骼侵犯的表現型，再逐漸進展到脊椎關節。接骨點炎是僵直性脊椎炎的主要病灶之一，Masi等人 (2011) 提出之免疫生物學和力學生物學機轉，並用於解釋僵直性脊椎炎接骨點和關節病變的發生。Masi等人認為：機械應力可導致僵直性脊椎炎軟組織張力過高或接骨點微損傷，並過度活化先天性免疫反應，導致慢性發炎和新骨生成。此免疫生物學和力學生物學機轉亦指出，中軸脊椎周圍的軟組織，尤其是薦腸關節與腰椎區域，也可能表現出對僵直性脊椎炎的適應不良。總結以上，僵直性脊椎炎中的接骨點炎不僅顯示接骨點有微損傷，還暗示著韌帶或肌肉在接近接骨點時出現發炎反應和對機械應力的適應不良，這些適應不良可能反應在其形態與機械特性的改變。然而，未有研究分析僵直性脊椎炎患者薦腸關節與腰椎區域的韌帶或肌肉的形態力學特徵，且無相關研究分析以上特徵與病史的相關性。 研究目的：本實驗目的為比較已確診之僵直性脊椎炎男性患者與健康控制組受試者薦腸關節與腰椎韌帶與肌肉的超音波巨觀形態、機械特性、血管化與微觀形態的差異，以及探討梨狀肌近端肌肉之超音波量測參數與患病時間之相關性。 研究設計：本研究為觀察型橫斷實驗。 研究對象：徵招20至45歲男性之僵直性脊椎炎患者，以及與病患組年齡、身高和體重相仿的健康對照組受試者。 研究方法：本研究徵招男性僵直性脊椎炎患者20位，健康對照組受試者19位。利用B模式超音波掃描兩組受試者的背側短薦腸韌帶、骨間薦腸韌帶、背側長薦腸韌帶、腸腰韌帶、梨狀肌近端肌肉與薦骨坐骨粗隆韌帶，並量測其厚度 (thickness) 代表巨觀形態，以超音波剪力波彈性影像量測其彈性模數 (elastic modulus) 以代表機械特性，並且使用方向性能量都卜勒超音波檢測其能量都卜勒血流訊號差異，最後利用空間頻率分析針對該軟組織之B模式影像進行分析，以峰值空間頻率半徑 (peak spatial frequency radius, PSFR) 代表軟組織微觀形態；並探討梨狀肌近端肌肉之超音波參數與患病時間之相關性。 統計分析：本實驗收取之人口統計學資料與超音波參數使用Shapiro-Wilk test進進行常態分布檢定，部分參數未呈現常態分布，因此連續變項 (continuous variables) 使用曼惠特尼U檢定 (Mann-Whitney U Test)，類別變項 (categorical variables) 則使用卡方檢定 (Chi-square test) 檢測兩組之間的差異；以及使用斯皮爾曼等級相關係數 (Spearman's rank correlation coefficient) 分析僵直性脊椎炎患者梨狀肌近端肌肉之超音波參數與患病時間之相關性。 結果：僵直性脊椎炎患者的背側短薦腸韌帶、骨間薦腸韌帶、背側長薦腸韌帶、腸腰韌帶、梨狀肌近端肌肉與薦骨坐骨粗隆韌帶，相較於健康受試者皆具有增厚現象 (all p values <0.05)；病患組的軟組織彈性模數亦大於控制組 (all p values <0.05)；病患組之腸腰韌帶、梨狀肌近端肌肉、薦骨坐骨粗隆韌帶相較於控制組，亦具有較多之方向性能量都卜勒訊號 (p<0.001)；兩組之間的峰值空間頻率半徑無統計顯著差異；梨狀肌近端肌肉之彈性模數與患病時間 (disease duration) 呈現中等程度之正相關性 (r=0.640, p=0.003)。 結論：僵直性脊椎炎病患的薦腸關節與腰椎的韌帶與肌肉之超音波特徵具有厚度增加、剛性上升、血管化顯著的情況。僵直性脊椎炎不僅會對骨骼造成重塑效應，也會對於中軸骨骼周圍的韌帶與肌肉造成影響，而使得可藉由超音波偵測其改變，這或許提供了另外可以監測疾病的途徑之一，未來研究可針對僵直性脊椎炎患者薦腸關節與腰椎的韌帶或肌肉進行組織學或免疫生物化學相關分析方法做進一步探討。

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease. In the musculoskeletal system, patients with ankylosing spondylitis mainly suffer from inflammation of the axial bone, including sacroiliac joints and the spine. Sacroiliitis is one of the earlier manifestations of axial bone involvement, which then progresses to the spinal joints. Masi et al. (2011) proposed immunobiological and mechanobiological mechanisms to explain the occurrence of enthesitis and osteopathy in ankylosing spondylitis. Mechanical stress can cause soft tissue hypertonicity or enthesis microinjury in ankylosing spondylitis and overactive the innate immune response, resulting in chronic inflammation and new bone formation. This mechanism also suggested that the soft tissues surrounding the axial bone, particularly the sacroiliac joint and lumbar region, may exhibit maladaptation of ankylosing spondylitis. To summarize, enthesitis not only means micro-injury in the site of the enthesis but also implies the inflammation and maladaptation to mechanical stress in ligaments or muscles approaching the enthesis. These maladaptations may reflect changes in their morphological and mechanical properties. However, no studies have analyzed the morpho-mechanical characteristics of ligaments or muscles surrounding sacroiliac joints and lumbar regions in patients with ankylosing spondylitis. No studies have explored the correlation between these characteristics and medical history. Purpose: The aim of the study was to compare the macro-morphology, mechanical properties, vascularization, and micro-morphology of ultrasound characteristics of ligaments and muscle surrounding sacroiliac joints and lumbar region in patients with ankylosing spondylitis and the healthy controls. In addition, we investigated the correlation between the elastic modulus of piriformis and disease duration. Study design: This study was an observational cross-sectional study Participants: The study recruited 20 to 45-year-old male patients with ankylosing spondylitis as a patient group (under-diagnosed by Modified New York criteria and ASAS criteria), healthy participants with matched age, heights, and weights as the healthy control group. Methods: We recruited twenty male patients with ankylosing spondylitis and 19 healthy control subjects. We scanned the short posterior sacroiliac ligament (SPSL), interosseous sacroiliac ligament (ISL), long posterior sacroiliac ligament (LPSL), and iliolumbar ligament (ILL), proximal piriformis muscle (PM) and sacrotuberous ligament with B-mode ultrasound. We measured the thickness to represent the macro-morphology, elastic modulus by shear wave elastography to represent mechanical properties, vascularization by directional power Doppler ultrasound, and micro-morphology by peak spatial frequency radius of spatial frequency analysis. We explored the correlation between the elastic modulus of piriformis and disease duration. Statistical analysis: We examined the normal distribution of the demographic data and ultrasonic parameters by Shapiro-Wilk test, and some parameters did not show a normal distribution. As a result, we used the Mann-Whitney U test to determine statistical significance in continuous variables and the Chi-square test to determine statistical significance in categorical variables between two groups. In addition, Spearman's rank correlation coefficient was used to examine the correlation between the elastic modulus of piriformis and disease duration. Results: The thickness of short posterior sacroiliac ligament, interosseous sacroiliac ligament, long posterior sacroiliac ligament, iliolumbar ligament, proximal piriformis muscle, and sacrotuberous ligament in the patient group were thicker than in healthy groups (all p<0.01). The elastic modulus of the soft tissues in the patient group was also greater than that in the control group (all p<0.01). The iliolumbar ligament, proximal piriformis muscle, and sacrotuberous ligament in the patient group also had more directional power Doppler signals than the control group (all p<0.001), but there was no significance of directional power Doppler signals in the short posterior sacroiliac ligament, interosseous sacroiliac ligament, long posterior sacroiliac ligament between groups. There were no statistically significant differences in peak spatial frequency radius between the two groups (p>0.05). There was a moderate correlation between the elastic modulus of the proximal piriformis muscle and disease duration (r=0.640, p=0.003). Conclusion: In patients with ankylosing spondylitis, the ultrasound characteristics of the ligaments and muscle around the sacroiliac joints and lumbar region are marked by increased thickness, stiffness, and vascularization. Ankylosing spondylitis affects not only the bone but also the ligaments and muscles that surround the axial skeleton. Future studies could look into the histological or immunobiochemical analysis of the ligaments or muscles surrounding the sacroiliac joints and lumbar spine in patients with ankylosing spondylitis.