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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (2): 283-291. doi: 10.19723/j.issn.1671-167X.2023.02.012

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Pathologic features of paraspinal muscle biopsies in patients with adolescent idiopathic scoliosis

Dan-feng ZHENG1,Jun-yu LI2,3,Jia-xi LI4,Ying-shuang ZHANG5,Yan-feng ZHONG1,Miao YU2,3,*()   

  1. 1. Department of Pathology, School of Basic Medical Sciences Peking University/Peking University Third Hospital, Beijing 100191, China
    2. Departmant of Orthopaedics, Peking University Third Hospital, Beijing 100191, China
    3. Beijing Key Laboratory of Spinal Disease Research, Peking University Third Hospital, Beijing 100191, China
    4. School of Basic Medical Sciences, Peking University, Beijing 100191, China
    5. Departmant of Neurology, Peking University Third Hospital, Beijing 100191, China
  • Received:2022-10-17 Online:2023-04-18 Published:2023-04-12
  • Contact: Miao YU E-mail:miltonyu@126.com

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Abstract:

Objective: To characterize the paraspinal muscles of adolescent idiopathic scoliosis (AIS) patients, and to further explore its etiology. Methods: Clinical records and paraspinal muscle biopsies at the apex vertebra region during posterior scoliosis correction surgery of 18 AIS were collected from November 2018 to August 2019. Following standardized processing of fresh muscle tissue biopsy, serial sections with conventional hematoxylin-eosin (HE) and histochemical and immunohistochemical (IHC) with antibody Dystrophin-1 (R-domain), Dystrophin-2 (C-terminal), Dystrophin-3 (N-terminal), Dystrophin-total, Myosin (fast), major histocompatibility complex 1 (MHC-1), CD4, CD8, CD20, and CD68 staining were obtained. Biopsy samples were grouped according to the subjects' median Cobb angle (Cobb angle ≥ 55° as severe AIS group and Cobb angle < 55° as mild AIS group) and Nash-Moe's classification respectively, and the corresponding pathological changes were compared between the groups statistically. Results: Among the 18 AIS patients, 8 were in the severe AIS group (Cobb angle ≥55°) and 10 in the mild AIS group (Cobb angle < 55°). Both severe and mild AIS groups presented various of atrophy and degeneration of paraspinal muscles, varying degrees and staining patterns of immune-expression of Dystrophin-3 loss, especially Dystrophin-2 loss in severe AIS group with significant differences, as well as among the Nash-Moe classification subgroups. Besides, infiltration of CD4+ and CD8+ cells in the paraspinal muscles and tendons was observed in all the patients while CD20+ cells were null. The expression of MHC-1 on myolemma was present in some muscle fibers. Conclusion: The histologic of paraspinal muscle biopsy in AIS had similar characteristic changes, the expression of Dystrophin protein was significantly reduced and correlated with the severity of scoliosis, suggesting that Dystrophin protein dysfunctions might contribute to the development of scoliosis. Meanwhile, the inflammatory changes of AIS were mainly manifested by T cell infiltration, and there seemed to be a certain correlation between inflammatory cell infiltration, MHC-1 expression and abnormal expression of Dystrophin. Further research along the lines of this result may open up new ideas for the diagnosis of scoliosis and the treatment of paraspinal myopathy.

Key words: Scoliosis, Paraspinal muscles, Biopsy, Adolescent, Dystrophin protein

CLC Number: 

  • R682.3

Table 1

Clinical features of the AIS patients"

Patient no. Age/years Age of onset/years Nash-Moe classification Cobb curve angle of thoracic vertebra/(°)
1 12 12 Ⅰ 51.4
2 16 16 Ⅱ 58.5
3 18 18 Ⅲ 73.6
4 22 22 Ⅰ 25.8
5 15 15 Ⅰ 28.3
6 16 16 Ⅰ 29.9
7 20 20 Ⅱ 76.5
8 27 27 Ⅱ 62.5
9 16 16 Ⅰ 33.3
10 16 16 Ⅱ 55.1
11 15 15 Ⅰ 56.8
12 13 13 Ⅱ 57.5
13 15 15 Ⅲ 65.6
14 12 12 Ⅰ 58.1
15 15 15 Ⅰ 44.8
16 14 14 Ⅱ 24.7
17 16 16 Ⅱ 45.4
18 12 12 Ⅲ 70.9

Figure 1

Serial sections of paraspinal muscle biopsy in AIS patients A, various degrees of muscle fiber atrophy could be observed in the paraspinal muscle biopsies of the enrolled patients, as indicated by the small bundles (black arrow) (HE ×10); B, moth-eaten fibers were present in both atrophic and non-atrophic muscle fibers (red arrow) (NADH-TR ×20); C, myosin immunohistochemical staining showed positive results, with uneven presence of type 2 muscle fibers, and type 2 fibers were slightly dominant in the biopsies (Myosin immunohistochemical ×20). AIS, adolescent idiopathic scoliosis."

Table 2

Pathological features of muscle biopsy in AIS patients in the severe and mild AIS groups (n=18)"

Pathological feature or staining pattern Severe scoliosis (Cobb≥55°, n=10) Mild scoliosis (Cobb < 55°, n=8) P
Atrophy degree 0.706
    Mild-moderate 0 1 (12.5)
    Moderate-severe 9 (90) 7 (87.5)
    Severe 1 (10) 0
Atrophy pattern 0.275
    Big group 1 (10) 3 (37.5)
    Small group 9 (90) 5 (62.5)
Degeneration of myofibers >0.999
    None 7 (70) 6 (75.0)
    Present 3 (30) 2 (25.0)
Edema 0.846
    None 4 (40) 4 (50.0)
    Few 4 (40) 2 (25.0)
    Most 2 (20) 2 (25.0)
Whorled fibers 0.321
    None 8 (80) 4 (50.0)
    Present 2 (20) 4 (50.0)
Hypertrophic fibers 0.183
    None 0 2 (25.0)
    Present 10 (100) 6 (75.0)
Internal nuclei >0.999
    None 1 (10) 1 (12.5)
    Present 9 (90) 7 (87.5)
Moth-eaten in NADH-TR 0.153
    None 3 (30) 6 (75.0)
    Present 7 (70) 2 (25.0)
Myosin staining pattern 0.427
    None 0 1 (12.5)
    Several 2 (20) 3 (37.5)
    Small part 8 (80) 4 (50.0)
Dystrophin-1 staining pattern 0.151
    Dizzy lineation 3 (30) 5 (62.5)
    Light-colored lineation 4 (40) 0
    Discontinuous lineation 3 (30) 3 (37.5)
Dystrophin-2 staining pattern 0.047
    Dizzy lineation 3 (30) 7 (87.5)
    Light-colored lineation 3 (30) 0
    Discontinuous lineation 4 (40) 1 (12.5)
Dystrophin-3 staining pattern 0.798
    Dizzy lineation 0 1 (12.5)
    Light-colored lineation 5 (50) 3 (37.5)
    Discontinuous lineation 5 (50) 4 (50.0)
Dystrophin-total staining pattern 0.069
    Dizzy lineation 3 (30) 7 (87.5)
    Light-colored lineation 4 (40) 0
    Discontinuous lineation 3 (30) 1 (12.5)

Figure 2

Dystrophin-2 and Dystrophin-total immunohistochemical staining of paraspinal muscle biopsy in AIS patients A, B, severe AIS group. C, D, mild AIS group. A, Dystrophin-2 was absent in most atrophic muscle fibers and some non-atrophic muscle fibers (Dystrophin-2 ×40); B, Dystrophin-total was absent in most atrophic muscle fibers and some non-atrophic muscle fibers (Dystrophin-total ×40); C, Dystrophin-2 was absent in partial atrophic and non-atrophic muscle fibers (Dystrophin-2 ×40); D, Dystrophin-total was absent in partial atrophic muscle fibers and non-atrophic muscle fibers (Dystrophin-total ×40). AIS, adolescent idiopathic scoliosis."

Figure 3

Immunohistochemical staining of Dystrophin-1 (rod-like domain) and Dystrophin-3 (N-terminal) in AIS paraspinal muscle biopsy Dystrophin-1 immunostaining showed dizzy or light-colored lineation in atrophic muscle fibers, with linear discontinuity in a few cases. Dystrophin-3 immunostaining showed that the myolemma of both atrophic and non-atrophic muscle fibers were weakened or even disappeared in all cases. However, there was no statistically significant difference between the mild and severe AIS groups. A, severe AIS group, Dystrophin-1 showed dizzy or light-colored lineation pattern on atrophic myofibers (Dystrophin-1 ×40); B, severe AIS group, Dystrophin-3 immunostaining showed sarcolemma of atrophic and non-atrophic myofibers faded or even disappeared (Dystrophin-3 ×40); C, mild AIS group, Dystrophin-1 showed dizzy or light-colored lineation pattern on atrophic myofibers (Dystrophin-1 ×40); D, mild AIS group, Dystrophin-3 immunostaining showed sarcolemma of atrophic and non-atrophic myofibers faded or even disappeared (Dystrophin-3 ×40). AIS, adolescent idiopathic scoliosis."

Table 3

Pathological features of muscle biopsy in AIS patients in different Nash-Moe subgroups (n=18)"

Pathological features or staining pattern Nash-Moe type Ⅰ (n=8) Nash-Moe type Ⅱ (n=7) Nash-Moe type Ⅲ (n=3) P
Atrophy degree 0.314
    Mild-moderate 1 (12.5) 0 0
    Moderate-severe 7 (87.5) 7 (100.00) 2 (66.67)
    Severe 0 0 1(33.33)
Atrophy pattern >0.999
    Big group 2 (25.0) 2 (28.57) 0
    Small group 6 (75.0) 5 (71.43) 3 (100.00)
Degeneration of myofibers >0.999
    None 6 (75.0) 5 (71.43) 2 (66.67)
    Present 2 (25.0) 2 (28.57) 1 (33.33)
Edema 0.580
    None 2 (25.0) 4 (57.14) 2 (66.67)
    Few 4 (50.0) 2 (28.57) 0
    Most 2 (25.0) 1 (14.29) 1 (33.33)
Whorled fibers 0.451
    None 4 (50.0) 5 (71.43) 3 (100.00)
    Present 4 (50.0) 2 (28.57) 0
Hypertrophic fibers >0.999
    None 1 (12.5) 1 (14.29) 0
    Present 7 (87.5) 6 (85.71) 3 (100.00)
Internal nuclei 0.451
    None 1 (12.5) 0 1 (33.33)
    Present 7 (87.5) 7 (100.00) 2 (66.67)
Moth-eaten in NADH-TR 0.698
    None 5 (62.5) 3 (42.86) 1 (33.33)
    Present 3 (37.5) 4 (57.14) 2 (66.67)
Myosin staining pattern 0.762
    None 1 (12.5) 0 0
    Several 1 (12.5) 3 (42.86) 1 (33.33)
    Small part 6 (75.0) 4 (57.14) 2 (66.67)
Dystrophin-1 staining pattern 0.075
    Dizzy lineation 5 (62.5) 1 (14.29) 2 (66.67)
    Light-colored lineation 0 4 (57.14) 0
    Discontinuous lineation 3 (37.5) 2 (28.57) 1 (33.33)
Dystrophin-2 staining pattern 0.043
    Dizzy lineation 7 (87.5) 3 (42.86) 0
    Light-colored lineation 0 2 (28.57) 1 (33.33)
    Discontinuous lineation 1 (12.5) 2 (28.57) 2 (66.67)
Dystrophin-3 staining pattern >0.999
    Dizzy lineation 1 (12.5) 0 0
    Light-colored lineation 3 (37.5) 4 (57.14) 1 (33.33)
    Discontinuous lineation 4 (50.0) 3 (42.86) 2 (66.67)
Dystrophin-total staining pattern 0.441
    Dizzy lineation 5 (62.5) 2 (28.57) 3 (100.00)
    Light-colored lineation 1 (12.5) 3 (42.86) 0
    Discontinuous lineation 2 (25.0) 2 (28.57) 0

Figure 4

Inflammatory cells in paraspinal muscle biopsies of AIS patients A, the infiltrating inflammatory cells were mainly CD4+T cells (CD4 ×40); B, CD8+T cells could be seen distributing around small vessels or scattered in fasciculus interstitium (CD8 ×20); C, MHC-1 immunohistochemical staining showed weakly positive results of the myofilm of muscle fibers in almost all cases of AIS (MHC-1 ×40); D, no CD20+B cell infiltration was observed in the fascicles and tendons (CD20 ×20). AIS, adolescent idiopathic scoliosis."

Figure 5

CD68+cells infiltrated in tendons and around small blood vessels in the stroma of muscle bundle (CD68 ×40)"

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