Sporadic Inclusion Body Myositis: MRI Findings and Correlation With Clinical and Functional Parameters

Sporadic Inclusion Body Myositis: MRI Findings and Correlation With Clinical and Functional Parameters1340 AJR:209, December 2017
many similarities between the degenerative changes that occur in sporadic IBM and in Alzheimer and Parkinson diseases [6].
MRI is the pivotal imaging modality to as- sess for sporadic IBM, revealing precise ana- tomic details and changes in the signal inten- sity within the muscles [7, 8]. The reference standard for diagnosis is biopsy, and the typi- cal histologic findings include a combination of muscle degeneration and inflammation mediated by T cells [4]. However, in some cases, the muscle biopsy is nondiagnostic or nonspecific for sporadic IBM, and MRI can support the clinical diagnosis by showing the selective pattern of muscle involvement in the upper and lower limbs [4]. In addition, MRI is the imaging tool of choice to monitor the progression of disease [9–11].
Currently, little is known about specif- ic MRI findings and their correlation with clinical, functional, and laboratory tests, and we hypothesized that MRI findings corre-
Sporadic Inclusion Body Myositis: MRI Findings and Correlation With Clinical and Functional Parameters
Julio Brandao Guimaraes1,2,3
Guimaraes JB, Zanoteli E, Link TM, et al.
1Department of Radiology, Federal University of Sao Paulo, Sao Paulo, Brazil.
2Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Ste 350, San Francisco, CA 94158. Address correspondence to J. B. Guimaraes ([email protected]).
3Department of Radiology, DASA Laboratory, Sao Paulo, Brazil.
4Department of Neurology, Medical School of the University of Sao Paulo, Sao Paulo, Brazil.
5Department of Radiology, University of Brescia, Brescia, Italy.
Musculoskeleta l Imaging • Or ig ina l Research
Supplemental Data Available online at www.ajronline.org.
AJR 2017; 209:1340–1347
© American Roentgen Ray Society
S poradic inclusion body myositis (IBM) is an idiopathic myopathy that typically begins in patients older than 50 years, with an esti-
mated prevalence of 5–10 cases per 1 mil- lion population [1]. Patients show a charac- teristic pattern of muscular involvement with both proximal and distal muscle weak- ness. In particular, the knee extensors and the wrist and finger flexors muscles are the most affected [2]. The rarity of this disease, lack of patient and clinical awareness, and diagnostic difficulties contribute to a sub- stantial delay between the onset of symp- toms and the diagnosis [3–5].
Although this disease was traditionally in- cluded in the group of immune-mediated in- flammatory myopathies, recent studies have shown a peculiar process of muscle degen- eration characterized by abnormal deposi- tion of protein aggregates, sometimes called “inclusion bodies.” Interestingly, there are
Keywords: atrophy, fat infiltration, idiopathic myopathy, inflammatory myopathies, MRI, sporadic body inclusion myositis
DOI:10.2214/AJR.17.17849
Received December 18, 2016; accepted after revision May 7, 2017.
OBJECTIVE. The purpose of this prospective study is to assess MRI findings in pa- tients with sporadic inclusion body myositis (IBM) and correlate them with clinical and functional parameters.
SUBJECTS AND METHODS. This study included 12 patients with biopsy-proven sporadic IBM. All patients underwent MRI of the bilateral upper and lower extremities. The images were scored for muscle atrophy, fatty infiltration, and edema pattern. Clinical data in- cluded onset and duration of disease. Muscle strength was measured using the Medical Re- search Council (MRC) scale, and functional status was assessed using the Modified Rankin Scale. Correlation between MRI and different clinical and functional parameters was calcu- lated using the Spearman rank test and Pearson correlation.
RESULTS. All patients showed MRI abnormalities, which were more severe within the lower limbs and the distal segments. The most prevalent MRI finding was fat infiltration. There was a statistically significant correlation between disease duration and number of mus- cles infiltrated by fat (r = 0.65; p = 0.04). The number of muscles with fat infiltration corre- lated with the sum of the scores of MRC (r = −0.60; p = 0.04) and with the Modified Rankin Scale (r = 0.48; p = 0.03).
CONCLUSION. Our findings suggest that most patients with biopsy-proven sporadic IBM present with a typical pattern of muscle involvement at MRI, more extensively in the low- er extremities. Moreover, MRI findings strongly correlated with clinical and functional param- eters, because both the extent and severity of muscle involvement assessed by MRI and clinical and functional parameters are associated with the early onset of the disease and its duration.
Guimaraes et al. MRI Findings of Sporadic IBM
Musculoskeletal Imaging Original Research
MRI Findings of Sporadic IBM
late with clinical and functional parameters in patients with sporadic IBM. Therefore, the purpose of this prospective study was to characterize the MRI findings in patients with biopsy-proven sporadic IBM and to cor- relate those imaging findings with clinical and functional parameters.
Subjects and Methods Patients and Control Subjects
We assessed 12 patients (six women; mean [± SD] age, 67.3 ± 8.5 years) fulfilling the inclu- sion and exclusion criteria. Inclusion criteria were a biopsy-proven diagnosis of sporadic IBM (Fig. 1), the willingness and capability to undergo an MRI scan, and an available clinical record, includ- ing physical examinations and laboratory tests (as detailed later). The exclusion criterion was the in- ability to undergo an MRI scan (e.g., claustropho- bia or metal devices).
All patients selected gave written informed consent. The institutional review board of Federal University of Sao Paulo approved the study.
Because the patients are older and some amount of atrophy may be expected, a control cohort of 12 healthy sex- and age-matched individuals was se- lected as a reference for normal age- and sex-re- lated muscle MRI anatomy. The mean age of the individuals in this group was 64.9 ± 4.3 years, and five (41%) were female.
Clinical Analyses The clinical data were collected by one neu-
rologist specialized in the diagnosis and treat- ment of neuromuscular disease who performed a complete clinical evaluation of each patient 1 week before the MRI study. The assessment in- cluded age at the onset of symptoms and duration of clinical symptoms. The physical examination included the assessment of muscle strength of the main muscle groups in the superior and inferior extremities, using the Medical Research Council (MRC) scale [12, 13]. The MRC grading system includes the following grades: 0, paralysis; 1, only a trace or flicker of muscle contraction is seen or felt; 2, muscle movement is possible with grav- ity eliminated; 3, muscle movement is possible against gravity; 4, muscle strength is reduced, but movement against resistance is possible; and 5, normal strength.
Functional status was obtained using the Mod- ified Rankin Scale [14]. The Modified Rankin Scale provides the following grades: 0, no symp- toms; 1, no significant disability; 2, light disabil- ity; 3, moderate disability; 4, moderately severe disability; 5, severe disability; and 6, dead [14, 15].
In addition, serum creatinine kinase activity was measured 1 week before the MRI study [16].
MRI and Image Interpretation All patients underwent 1.5-T MRI studies of the
bilateral upper and lower extremities (Magnetom Symphony, version VA 12 A, Siemens Healthcare) with a phased-array torso coil. The FOV was 20 cm2, the matrix was 205 × 256, slice thickness was 7 mm, and slice gap was 0.5 mm. All images were acquired in the axial plane, with fast spin-echo T1-weighted (TR/TE, 600/20; number of signal averages, 2) and STIR (TR/TE, 1400/15; inversion time, 150 ms; number of signal averages, 4) sequences and with patients in the supine position. The coverage of the scan was from the shoulders to the wrists and from the hips to the ankles. Both thighs and legs were scanned together as a single acquisition, and the arms and forearms were scanned individually. Simi- lar axial sequences were obtained for all control sub- jects in the upper or lower extremities at 1.5 T.
Two radiologists specialized in musculoskele- tal disease (with 6 and 9 years of experience) in- dependently evaluated all MRI studies. They were blinded to all clinical and functional parameters, and the cases of disagreement were reconciled by consensus. The readers were asked to consider the entire muscle volume for grading.
Sixty-four muscles per patients (Table 1) were assessed for the presence of atrophy, fatty infiltra-
tion, and edema pattern. Muscle atrophy and fat- ty infiltration were assessed using the fast spin- echo T1-weighted sequence. Muscle atrophy was defined as a visual loss of muscle volume. Mus- cle atrophy was classified as present or absent. Subsequently, it was also graded according to a 4-point visual scale (Fig. 2): grade 0, no atrophy; grade 1, minimal (atrophy < 30% of the muscle total volume); grade 2, moderate (atrophy > 30% and < 60% of the muscle total volume); and grade 3, severe (atrophy > 60% of the muscle total vol- ume). To quantify and score the degree of muscle atrophy, we used an anatomically referenced im- age from the age- and sex-matched group of indi- viduals, using female control subjects for evaluat- ing female patients and male control subjects for evaluating male patients.
Fatty infiltration was classified as present or absent. It was also graded according to a 5-point semiquantitative scale described by Goutallier et al. [17], as follows: grade 0, normal; grade 1, some fatty streaks; grade 2, less than 50% fatty muscle; grade 3, as much fat as muscle; and grade 4, more fat than muscle.
Previous studies considered an abnormal ede- ma pattern to be any level of increased signal in- tensity on STIR sequences in the muscles [18, 19].
TABLE 1: Studied Muscles
Semimembranosus
Semitendinosus
Soleus
Brachioradialis
Extensor digitorum communis
Supinator and pronator teres
Note—Thirty-two muscles were studied on each side, for a total of 64 muscles per patient.
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Guimaraes et al.
Edema patterns in our study were assessed on STIR sequences and were graded on a previous- ly described 3-point scale [20], as follows: 0, nor- mal (muscle with normal intensity); 1, mild (hy- perintensity in less than or equal to one-third of the muscle); or 2, marked hyperintensity (hyper- intensity in more than one-third of the muscle). If the muscle was graded as 1 or 2, the edema pattern was scored as present.
The presence or absence of symmetric involve- ment was scored only in the lower extremities. Both the lower limbs were visualized at the same time, comparing the muscle involvement and the severity between the left and right side.
The undulating fascia sign (Fig. 3) is a common imaging pattern found in patients with sporadic IBM. It is defined by the presence of a wavy fas- cia between the severe atrophic and fat-infiltrat- ed vastus intermedius and vastus lateralis muscles [18, 19]. This sign was scored as present or absent.
Reproducibility To quantify inter- and intraobserver reliability
for edema pattern, fat infiltration, and atrophy, be-
tween the two radiologists in all 12 cases, we cal- culated Cohen kappa coefficients with 95% CIs. The interobserver reliability was a weighted kap- pa of 0.85 (95% CI, 0.79–0.93) for edema pattern, 0.76 (95% CI, 0.71–0.80) for fat infiltration, and 0.65 (95% CI, 0.55–0.74) for atrophy. For intra- reader reproducibility analysis for the evaluation of edema pattern, fat infiltration, and atrophy, one reader repeated the readings in 10 randomly select- ed patients 2 months after the first readings were done. The intraobserver agreement was a weighted kappa of 0.87 (95% CI, 0.81–0.94) for edema pat- tern, 0.80 (95% CI, 0.72–0.89) for fat infiltration, and 0.75 (95% CI, 0.62–0.89) for atrophy.
Statistical Analysis Statistical analysis was performed with SPSS
(version 22.0, IBM) using a two-sided 0.05 level of significance. Descriptive statistical evaluation was performed initially. Correlation between MRI and different clinical parameters was calculated using the Spearman rank test and Pearson correlation. The Mann-Whitney U test was performed to compare patients with and without the undulating fascia sign
and also to compare patients with sporadic IBM and the sex- and age-matched group of individuals.
Results Clinical and MRI Findings
The mean age of disease onset was 58.8 years (59.0 ± 9.1 years) and the mean disease duration was 76 months (73.0 ± 27.7 months). All clini- cal data, functional grading scales, physical ex- amination records, and serum creatinine kinase values are shown in Tables 2 and 3.
MRI studies revealed abnormalities in all patients. The disease was more significant in the lower limbs, in particular in the dis- tal segments (Figs. 3 and 4; see also Tables S1–S7, which can be viewed in the AJR elec- tronic supplement to this article, available at www.ajronline.org).
Fat infiltration was the most common abnor- mality and was present in all patients. Most of the lower leg muscles were affected by fat infil- tration, in particular the medial gastrocnemius (100%; 12/12 patients). The most affected mus- cle with fat infiltration in the forearm was the
TABLE 2: Medical Research Council (MRC) Scores for the Muscle Groups Analyzed
Muscle
MRC Score
1 2 3 4 5 6 7 8 9 10 11 12
Right biceps 4 5 4 4 5 4 2 5 5 4 4 4
Left biceps 4 5 4 4 5 4 3 4 5 4 4 4
Right triceps 4 5 3 5 5 4 3 4 5 5 5 4
Left triceps 4 5 3 5 5 4 3 4 5 5 5 4
Right wrist flexors 3 4 4 4 4 3 4 4 4 4 4 5
Left wrist flexors 3 4 4 4 4 3 4 4 4 4 4 5
Right wrist extensors 4 5 5 5 5 4 3 5 5 5 5 5
Left wrist extensors 4 5 5 5 5 4 3 5 5 5 5 5
Right finger flexors 4 5 3 4 4 3 3 4 4 4 4 4
Left finger flexors 4 4 3 4 4 3 3 4 4 4 4 4
Right finger extensors 4 4 5 5 5 4 3 4 5 5 5 4
Left finger extensors 4 5 5 5 5 4 3 4 5 5 5 4
Right leg flexors 4 5 3 5 4 2 3 5 4 4 3 3
Left leg flexors 4 5 3 5 4 2 3 5 4 4 3 3
Right leg extensors 4 5 3 5 5 3 3 4 4 4 4 4
Left leg extensors 4 5 3 5 5 3 3 4 4 4 4 4
Right knee flexors 4 5 3 4 3 3 4 4 5 4 5 4
Left knee flexors 4 5 3 4 3 3 4 4 5 4 5 4
Right knee extensors 4 4 3 4 3 2 3 4 4 4 4 4
Left knee extensors 4 4 3 4 4 2 3 4 4 4 4 4
Right foot dorsiflexors 3 5 4 5 5 4 4 4 5 5 4 5
Left foot dorsiflexors 3 5 5 5 5 4 4 4 5 5 5 5
Note—Data are number of muscles assigned each MRC score. The MRC scoring system has been described elsewhere [12].
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MRI Findings of Sporadic IBM
flexor digitorum profundus (FDP) (83%; 10/12 patients) (Fig. 5). The mean number of muscles infiltrated by fat per patient was 42 of 64 (range, 8–60). In the thigh, the anterior muscular com- partment was the most frequently and severely affected by fat infiltration, especially the vastus lateralis (83%; 10/12 patients). The rectus fem- oris was least frequently severely compromised by fat infiltration when compared with the oth- ers quadriceps muscles (this particular pattern was found in 75% [9/12] of patients) (Fig. 6). The other thigh muscular compartments were less frequently and severely affected when compared with the muscles of the anterior compartment. Among these muscles, the sar- torius muscle was the most frequently affected by fat infiltration (50%; 6/12 patients) (Fig. 7). Among all fat-infiltrated muscles in all subjects (n = 504), 31% were grade 1, 26% were grade 2, 24% were grade 3, and 19% were grade 4. The muscles most frequently characterized by severe fat infiltration were the medial gastroc- nemius (83%; 10/12 subjects), the vastus late- ralis (75%; 9/12 subjects), and the FDP (66%; 8/12 subjects).
Eleven patients (92%) had muscular atro- phy, and the mean number of muscles with at- rophy per patient was 38 of 64 (range, 0–58). Among all muscles with atrophy in all sub- jects (n = 456), 39% were grade 1, 37% were grade 2, and 24% were grade 3. The muscles most frequently affected by atrophy were the medial gastrocnemius (92%; 11/12 subjects), the vastus lateralis (83%; 10/12 subjects), and the FDP (75%; 9/12 subjects).
Ten patients (83%) had at least one mus- cle with edema pattern, and the mean number
of muscles with edema pattern per patient was three (range, 0–16). The muscles most frequent- ly characterized by edema pattern were the me- dial gastrocnemius (41%; 5/12 subjects) and the FDP (33%; 4/12 subjects). The undulating fascia sign was found in 75% (9/12) of patients.
Asymmetries of MRI findings in the lower limb were present in 50% (6/12) of patients. From all analyzed muscles from the lower extremity (40 muscles in 12 subjects, for a to- tal of 480 muscles), the asymmetry was 35% (n = 168) for fat infiltration, 15% (n = 72) for atrophy, and 11% (n = 52) for edema pattern.
MRI Findings in the Sex- and Age-Matched Control Subjects
None of the sex- and age-matched control subjects (12 subjects) presented any muscle with edema pattern (grades 1 and 2), severe at- rophy (grade 3), or moderate-to-severe fat in- filtration (grades 3 and 4) in the upper or lower extremities. Findings in patients with sporadic IBM were significantly more pronounced. Sta- tistically significantly more muscles had severe fat infiltration (p < 0.001), severe atrophy (p < 0.001), and edema pattern (p = 0.003) in the pa- tient cohort, when compared with the sex- and age-matched group of control subjects.
Correlation of MRI Findings With Clinical and Functional Data
Fat infiltration—There was a statistically significant correlation between disease dura- tion and number of muscles infiltrated by fat (r = 0.65; p = 0.04); long duration of the dis- ease was correlated with a high number of muscles infiltrated by fat. Furthermore, there
was a significant correlation between the age at the onset of the disease and the total num- ber of muscles with severe fat infiltration (r = −0.66; p = 0.02); late disease onset correlated with less-severe fat infiltration.
Muscle weakness was also associated with fat infiltration. The sum of the scores of all tested muscles with MRC had a negative cor- relation with the number of muscles infiltrated by fat (r = −0.60; p = 0.04). Moreover, there was a statistically significant correlation be- tween Modified Rankin Scale and the number of muscles with fat infiltration (r = 0.48; p = 0.03), meaning that the higher the number of muscles with fat infiltration, the worse was the clinical and functional outcome.
Atrophy—Muscle weakness was also as- sociated with atrophy. The sum of the scores of all muscles tested with MRC had a nega- tive correlation with the number of muscles with atrophy (r = −0.58; p = 0.04).
Edema pattern—No significant correla- tion…