title: Myasthenic symptoms in anti-low-density lipoprotein receptor-related protein 4 antibody-seropositive amyotrophic lateral sclerosis: two case reports.
abstract: BACKGROUND
  Myasthenic symptoms can be present in patients with amyotrophic lateral sclerosis (ALS). These symptoms have been considered to be caused by the degeneration of distal motor neurons and the neuromuscular junction (NMJ). Recent studies suggested that antibody to low-density lipoprotein receptor-related protein 4 (LRP4) was a pathogenic agent of myasthenia gravis (MG), and it was also detected in ALS patients.
  
  
  METHODS
  Patient 1: A 58-year-old Japanese man developed progressive weakness and subsequent myasthenic symptoms including oculomotor disturbance. Clinical examination and electrophysiological studies confirmed upper and lower motor neuron involvement and NMJ dysfunction, and anti-LRP4 antibody was detected in his serum. A series of immunotherapies, including steroid pulse therapy, intravenous immunoglobulin, and plasmapheresis, was performed, and the myasthenic symptoms partially improved. The titer of anti-LRP4 antibody subsequently decreased. However, the therapeutic effect was transient, and ALS symptoms progressed. His clinical findings fulfilled the criteria of probable ALS using the Awaji criteria. Patient 2: A 74-year-old Japanese man suffered from progressive weakness of all limbs and dropped head in the evening. He complained of diplopia with a lateral horizontal gaze. Probable ALS was diagnosed because of the upper and lower motor neuron signs, whereas anti-LRP4 antibody was detected. Several immunotherapies were administered, and the myasthenic symptoms partially responded to each therapy. However, the truncal muscle weakness progressed, and he died of respiratory failure.
  
  
  CONCLUSIONS
  We report two anti-LRP4 antibody-seropositive ALS patients with myasthenia who were not typical of ALS patients, and showed partial responses to immunotherapies. The anti-LRP4 antibody-seropositive status may influence developing ALS and cause additional ALS symptoms.
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-0841, Japan.|Department of Neurology, National Hospital Organization Maizuru Medical Center, Maizuru, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-0841, Japan. y-noto@koto.kpu-m.ac.jp.
authors.forename: Yu-Ichi
authors.initials: YI
authors.lastname: Noto
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-0841, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Makita
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-0841, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Kushimura-Okada
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-0841, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Ishii
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-0841, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-0841, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohara
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Nakane
authors.affiliation: Department of Clinical Research, Nagasaki Kawatana Medical Center, Kawatana, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Higuchi
authors.affiliation: Director of North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-0841, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications* / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human
keywords: Amyotrophic lateral sclerosis; Anti-LRP4 antibody; Case report; Immunotherapy; Luciferase immunoprecipitation systems; Myasthenia gravis; Myasthenic symptom