title: Association of a paraneoplastic motor neuron disease with anti-Ri antibodies and a novel SOD1 I18del mutation.
abstract: BACKGROUND
  Whether motor neuron diseases (MNDs) can be considered in some cases of paraneoplastic syndromes is controversial. We report a case of rapidly progressive motor neuronopathy following a diagnosis of breast carcinoma, with a presence of anti-Ri antibodies, and a novel SOD1 gene mutation.
  
  
  METHODS
  An 80-year-old woman with mucinous adenocarcinoma of the left breast for 4 years developed sub-acute quadriparesis. Myography revealed chronic denervation signs. The patient had serum anti-Ri onconeural antibodies. The diagnosis of paraneoplastic MND was established. Because of a familial history of ALS, a genetic analysis for familial ALS was performed. We identified a novel heterozygous mutation in SOD1 gene, SOD I18del. This mutation may reflect a genetic predisposition to develop a MND, inducing fragility of motor neurons. Neurological improvement was observed after three months of both intravenous gamma globulin and corticosteroids.
  
  
  CONCLUSIONS
  The present observation supports the idea that MND can be considered as a paraneoplastic syndrome. A combination of anti-Ri onconeural antibodies and a particular SOD1 gene mutation, consisting in risk factor, might be in cause in the process of motor neuron death. When in doubt, paraneoplastic cause should be suspected in the differential diagnosis of MND. Immunotherapy treatment may lead to a favorable outcome.
authors.affiliation: Service de Neurologie et Neurophysiologie Clinique, CHRU Tours, France. Electronic address: capucine.diarddetoeuf@gmail.com.
authors.forename: Capucine
authors.initials: C
authors.lastname: Diard-Detoeuf
authors.affiliation: Laboratoire de Biochimie et Biologie moléculaire, CHRU Tours, France; UMR INSERM U930, Université François-Rabelais, Tours, PRES Centre, Val de Loire Université, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Dangoumau
authors.affiliation: Service de Neurologie et Neurophysiologie Clinique, CHRU Tours, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Limousin
authors.affiliation: Service de Neurologie et Neurophysiologie Clinique, CHRU Tours, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Biberon
authors.affiliation: Laboratoire de Biochimie et Biologie moléculaire, CHRU Tours, France; UMR INSERM U930, Université François-Rabelais, Tours, PRES Centre, Val de Loire Université, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.affiliation: Laboratoire de Biochimie et Biologie moléculaire, CHRU Tours, France; UMR INSERM U930, Université François-Rabelais, Tours, PRES Centre, Val de Loire Université, France.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.affiliation: Service de Neurologie et Neurophysiologie Clinique, CHRU Tours, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: de Toffol
authors.affiliation: Service de Neurologie et Neurophysiologie Clinique, CHRU Tours, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Praline
mesh_terms: D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D006801:Humans; D008958:Models, Molecular; D016472:Motor Neuron Disease / Q000150:complications / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D000090682:Neuro-Oncological Ventral Antigen; D010257:Paraneoplastic Syndromes / Q000150:complications / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000276:immunology*; D017384:Sequence Deletion / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D009419:Nerve Tissue Proteins; D000090682:Neuro-Oncological Ventral Antigen; D016601:RNA-Binding Proteins; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Genetic predisposition; Motor neuron disease; Nova antigen; Onconeuronal antibodies; Paraneoplastic syndrome; SOD1 mutations