title: Amyotrophic lateral sclerosis with neuronal intranuclear protein inclusions.
abstract: A 46-year-old patient developed amyotrophic lateral sclerosis (ALS) characterized by rapid progression. She needed respiratory assistance after a course of 9 months. She died 4.5 years after onset. Autopsy showed dramatic atrophy of the spinal cord, sparing only the posterior tracts, associated with neuronal loss and astrogliosis in various areas including the anterior horns, motor cortex, striatum, thalamus, and substantia nigra. Ubiquitin immunohistochemistry showed rare skein-like inclusions in the surviving spinal and medullary motor neurons. Eosinophilic inclusions were found in the nuclei of pyramidal neurons in the hippocampus. These inclusions were immunoreactive to antibodies against ubiquitin, promyelocytic leukemia gene product, proteasome, and ataxin-3. They were not immunoreactive to antibodies against tau, cystatin C, neurofilament, alpha-synuclein, SOD-1, and polyglutamine (1C2), and were not stained by ethidium bromide. Similar inclusions were found in the motor cortex. The immunoreactivity of the inclusions was similar to that encountered in diseases associated with CAG repeats, except for the negativity of the immunolabelling with 1C2. At the ultrastructural level, the nuclear inclusions were made of straight filaments (10-12 nm in diameter) arranged at random, reminiscent of the polyglutamine intranuclear hyaline inclusions.
authors.affiliation: Laboratoire de Neuropathologie Raymond Escourolle, INSERM U360, Association Claude Bernard, Hôpital de La Salpêtrière, 47 boulevard de l'Hôpital, 75651, Paris cedex 13, France. danielle.seilhean@psl.ap-hop-paris.fr
authors.forename: Danielle
authors.initials: D
authors.lastname: Seilhean
authors.forename: Junko
authors.initials: J
authors.lastname: Takahashi
authors.forename: Khalid Hamid
authors.initials: KH
authors.lastname: El Hachimi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Fujigasaki
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lebre
authors.forename: Valérie
authors.initials: V
authors.lastname: Biancalana
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.forename: François
authors.initials: F
authors.lastname: Salachas
authors.forename: Jean
authors.initials: J
authors.lastname: Hogenhuis
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Hauw
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000067699:Ataxin-3; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron / Q000379:methods; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism; D011180:Postmortem Changes; D000071156:Promyelocytic Leukemia Protein; D046988:Proteasome Endopeptidase Complex; D012097:Repressor Proteins; D013194:Staining and Labeling; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; C070576:PML protein, human; C092341:ATXN3 protein, human; D000067699:Ataxin-3; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex