Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders
The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (S...
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| description | The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions. |
| doi_str_mv | 10.1371/journal.pone.0151376 |
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We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0151376</identifier><identifier>PMID: 26999347</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age of Onset ; Amyotrophic lateral sclerosis ; Antibodies ; Atrophy ; Biology and Life Sciences ; Biopsy ; Dementia ; Diagnosis ; Diagnostic systems ; Disease ; Disorders ; Enzymes ; Fetuses ; Fibers ; Genetic aspects ; Hospitals ; Humans ; Immunohistochemistry ; Lesions ; Medical diagnosis ; Medicine and Health Sciences ; Microscopy ; Middle Aged ; Mitochondria - metabolism ; Motor neuron disease ; Motor Neuron Disease - genetics ; Motor Neuron Disease - pathology ; Motor neuron diseases ; Muscle proteins ; Muscle Proteins - metabolism ; Muscle, Skeletal - pathology ; Muscle, Skeletal - ultrastructure ; Muscles ; Mutation ; Myosin ; Neurology ; Pathology ; Patients ; Physiological aspects ; Risk factors ; Skeletal muscle ; Spinal and bulbar muscular atrophy ; Vacuoles</subject><ispartof>PloS one, 2016-03, Vol.11 (3), p.e0151376-e0151376</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Jokela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions.</description><subject>Age of Onset</subject><subject>Amyotrophic lateral sclerosis</subject><subject>Antibodies</subject><subject>Atrophy</subject><subject>Biology and Life Sciences</subject><subject>Biopsy</subject><subject>Dementia</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Disease</subject><subject>Disorders</subject><subject>Enzymes</subject><subject>Fetuses</subject><subject>Fibers</subject><subject>Genetic aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Lesions</subject><subject>Medical diagnosis</subject><subject>Medicine and Health Sciences</subject><subject>Microscopy</subject><subject>Middle Aged</subject><subject>Mitochondria - metabolism</subject><subject>Motor neuron disease</subject><subject>Motor Neuron Disease - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jokela, Manu</au><au>Huovinen, Sanna</au><au>Raheem, Olayinka</au><au>Lindfors, Mikaela</au><au>Palmio, Johanna</au><au>Penttilä, Sini</au><au>Udd, Bjarne</au><au>Wishart, Thomas M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-03-21</date><risdate>2016</risdate><volume>11</volume><issue>3</issue><spage>e0151376</spage><epage>e0151376</epage><pages>e0151376-e0151376</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26999347</pmid><doi>10.1371/journal.pone.0151376</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Age of Onset Amyotrophic lateral sclerosis Antibodies Atrophy Biology and Life Sciences Biopsy Dementia Diagnosis Diagnostic systems Disease Disorders Enzymes Fetuses Fibers Genetic aspects Hospitals Humans Immunohistochemistry Lesions Medical diagnosis Medicine and Health Sciences Microscopy Middle Aged Mitochondria - metabolism Motor neuron disease Motor Neuron Disease - genetics Motor Neuron Disease - pathology Motor neuron diseases Muscle proteins Muscle Proteins - metabolism Muscle, Skeletal - pathology Muscle, Skeletal - ultrastructure Muscles Mutation Myosin Neurology Pathology Patients Physiological aspects Risk factors Skeletal muscle Spinal and bulbar muscular atrophy Vacuoles |
| title | Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders |
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