The Diagnostic Value of MRI Pattern Recognition in Distal Myopathies

Abstract

Objective: Distal myopathies are a diagnostically challenging group of diseases. We wanted to understand the value of MRI in the current clinical setting and explore the potential for optimizing its clinical application. Methods: We retrospectively audited the diagnostic workup in a distal myopathy patient cohort, reassessing the diagnosis, whilst documenting the usage of MRI. We established a literature based distal myopathies MRI pattern template and assessed its diagnostic utility in terms of sensitivity, specificity, and potential impact on the diagnostic workup. Results: Fifty-five patients were included; in 38 with a comprehensive set of data the diagnostic work-up was audited. The median time from symptoms onset to diagnosis was 12.1 years. The initial genetic diagnostic rate was 39%; 18% were misdiagnosed as neuropathies and 13% as inclusion body myositis (IBM). Based on 21 publications we established a MRI pattern template. Its overall sensitivity (50%) and specificity (32%) were low. However in some diseases (e.g., MYOT-related myopathy, TTN-HMERF) MRI correctly identified the causative gene. The number of genes suggested by MRI pattern analysis was smaller compared to clinical work up (median 1 vs. 9, p < 0.0001) but fewer genes were correctly predicted (5/10 vs. 7/10). MRI analysis ruled out IBM in all cases. Conclusion: In the diagnostic work-up of distal myopathies, MRI is useful in assisting genetic testing and avoiding misdiagnosis (IBM). The overall low sensitivity and specificity limits its generalized use when traditional single gene test methods are applied. However, in the context of next generation sequencing MRI may represent a valuable tool for interpreting complex genetic results.

Keywords: MRI pattern; distal myopathies; imaging genetics; muscular dystrophies; next generation sequencing.

Figures

Figure 1

Results of the clinical-pathological re-evaluation. The diseases are reported using gene symbols apart for IBM. For TTN and NEB two different phenotypes were considered. FLNC refers to the phenotype described in the distal ABD-filaminopathy. In black the disease scored as typical and in gray as consistent. A cross indicates the gene confirmed as positive. HMERF, hereditary myopathy with early respiratory failure; TMD, tibial muscular dystrophy.

Figure 2

Literature based patterns. For every disease we reported name, gene and number of patients per article. A gray scale matching appearances on T1-weighted images was used to indicate the degree of involvement. Black indicated a muscle generally spared, dark gray a muscle less severely or less frequently involved, light gray a muscle most severely or most frequently involved. If muscles were not reported in the literature, such as the adductor longus, they were omitted from the pattern diagram. From left to right are represented early and late involvements. °Near the disease's name indicates pattern for whom the individual muscle score was not available. *Muscles reported as either almost never or almost always involved. Stripes: discordant or highly variable involvement; indicating limited use for pattern assessment.

Figure 3

Results of the MRI pattern analysis. In black the disease scored as typical and in gray as consistent. A cross indicates the gene identified as pathogenic whereas the star indicated a negative genetic test. For TTN and NEB two different phenotypes were considered. Variants of uncertain significance in DES gene were found in ID 23, 52, 68, 59, 51.

Figure 4

Muscle MRI patterns. Axial T1-weighted images at mid-thigh and mid-calf level in selected subjects. (A–C) Patients with genetically confirmed MYOT mutations all correctly identified. They are all characterized by a relative sparing of the semitendinosus (ST) muscle. The vastus intermedius and sartorius muscles are more affected than the gracilis muscle. All calf muscles can be affected; the gastrocnemius lateralis muscle is usually less affected than the medialis. (D) Patient with TTN (ID18) mutation. He was not correctly identified as the calf was severely involved without the characteristic pattern. However the selective involvement of semitendinosus (ST) within the thigh is characteristic and could represent a key feature of this disease. (E,F) Patients with GNE mutations. One patient (E, ID11) was not correctly identified. The rectus femoris muscles were spared and the vastus lateralis muscles were involved contrary to the reported pattern. However both patients (E,F) revealed severe involvement of short head of biceps femoris (SB) muscles which could represent a key feature of the disease.