title: Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders.
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.
authors.affiliation: Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.|Neuromuscular Research Center, Department of Neurology, University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Manu
authors.initials: M
authors.lastname: Jokela
authors.affiliation: Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Huovinen
authors.affiliation: Neuromuscular Research Center, Department of Neurology, University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Olayinka
authors.initials: O
authors.lastname: Raheem
authors.affiliation: Neuromuscular Research Center, Department of Neurology, University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Lindfors
authors.affiliation: Neuromuscular Research Center, Department of Neurology, University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Palmio
authors.affiliation: Neuromuscular Research Center, Department of Neurology, University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Sini
authors.initials: S
authors.lastname: Penttilä
authors.affiliation: Neuromuscular Research Center, Department of Neurology, University Hospital and University of Tampere, Tampere, Finland.|Department of Neurology, Vasa Central Hospital, Vasa, Finland.|Folkhälsan Genetic Institute, Department of Medical Genetics, Helsinki University, Helsinki, Finland.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
mesh_terms: D017668:Age of Onset; D001706:Biopsy; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D016472:Motor Neuron Disease / Q000235:genetics* / Q000473:pathology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D009124:Muscle Proteins