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Amyotrophic lateral sclerosis with neuronal intranuclear protein inclusions

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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.

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Acknowledgements

J. Takahashi was supported by a fellowship from association Claude Bernard. Special thanks to M. Candau, F. Fierville, O. Freytag, A. Matos, C. N’Ze, C. Py, O. Russaouen, and B. Verneau (Laboratoire de Neuropathologie Raymond Escourolle), and to A. Camuzat (INSERM U289) for technical assistance.

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Authors and Affiliations

  1. 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, Junko Takahashi, Jean Hogenhuis, Jean-Jacques Hauw & Charles Duyckaerts

  2. INSERM U106, Hôpital de La Salpêtrière, Paris cedex 13, France

    Khalid Hamid El Hachimi & Charles Duyckaerts

  3. INSERM U289, Hôpital de La Salpêtrière, Paris cedex 13, France

    Hiroto Fujigasaki, Anne-Sophie Lebre, Alexandra Dürr & Alexis Brice

  4. Fédération de Neurologie, Division Mazarin, Hôpital de La Salpêtrière, Paris cedex 13, France

    François Salachas & Vincent Meininger

  5. Faculté de Médecine, Laboratoire de Diagnostic Génétique, 11 rue Humann, Strasbourg cedex, France

    Valérie Biancalana

  6. CNRS UPR 9051, Laboratoire de Biochimie B, Hôpital Saint-Louis, Paris cedex 10, France

    Hugues de Thé

  7. Division of Neuropathology, The Jikei University School of Medicine, Tokyo, Japan

    Junko Takahashi

Authors
  1. Danielle Seilhean
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  2. Junko Takahashi
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  3. Khalid Hamid El Hachimi
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  5. Anne-Sophie Lebre
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  6. Valérie Biancalana
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  9. Jean Hogenhuis
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  10. Hugues de Thé
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  14. Charles Duyckaerts
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Correspondence to Danielle Seilhean.

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Seilhean, D., Takahashi, J., El Hachimi, K.H. et al. Amyotrophic lateral sclerosis with neuronal intranuclear protein inclusions. Acta Neuropathol 108, 81–87 (2004). https://doi.org/10.1007/s00401-004-0855-x

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  • DOI: https://doi.org/10.1007/s00401-004-0855-x

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