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.

The unfolding spectrum of inherited distal myopathies

“…Although muscle MRI diagnostic sensitivity and specificity is low, it can be useful in some instances in guiding genetic analysis. A recent study showed that MRI analysis led to the correct diagnosis of myotilin‐distal myopathy and titin‐distal myopathy with early respiratory failure …”

Novel Desmin Mutation Causing Myofibrillar Myopathy in a Hmong Family

“…It should be noted however that selective involvement of the semitendinosus has also been reported in hereditary myopathy with early respiratory failure caused by titin mutations and is therefore not pathognomonic of desminopathy (14). While muscle MRI was successful in distinguishing myotilinopathy from other distal myopathies (5), its sensitivity and specificity for desminopathy in this context remains to be established. In inherited myopathies, MRI should therefore be interpreted in the context of the clinical picture and results of molecular genetic testing.…”

“…In light of the paucity of functional assays available for most forms of MFM, it is often challenging to determine the pathogenicity of these variants. Muscle MRI however has shown promise in distinguishing certain forms of MFM from other distal myopathies based on patterns of muscle involvement and may similarly be of assistance in the interpretation of VUS (5). We report here a family with an adult-onset distal myopathy caused by a novel heterozygous missense variant in the desmin gene and highlight the role of muscle MRI in interpreting genetic testing results in this family.…”

Distale Myopathien

“…In einer Reihe von Arbeiten wurden entsprechende Pattern für die einzelnen Krankheitsentitäten beschrieben, zusammenfassen- de Übersichtsarbeiten wurden unter anderem von Leung sowie Bugiardini et al publiziert [47,48]. Einschränkend muss angemerkt werden, dass die entsprechenden muskulären Veränderungen meist nicht-systematisch bzw.…”

“…Einschränkend muss angemerkt werden, dass die entsprechenden muskulären Veränderungen meist nicht-systematisch bzw. unter Verwendung differenter Bewertungssyteme erfasst wurden und teils kleine Fallzahlen vorliegen [47]. Gegenwärtig hat sich an den universitären neuromuskulären Zentren die Durchführung einer Ganzkörper-MRT der Muskulatur als Goldstandart etabliert, durch die zukünftig wertvolle Zusatzinformationen und eine bessere Abgrenzung der einzelnen distalen Myopathien gegeneinander zu erwarten ist.…”