title: Efficacy of diflunisal on autonomic dysfunction of late-onset familial amyloid polyneuropathy (TTR Val30Met) in a Japanese endemic area.
abstract: OBJECTIVE
  To evaluate the long-term efficacy and safety of diflunisal in late-onset familial amyloid polyneuropathy (FAP) in a Japanese endemic area.
  
  
  METHODS
  Consecutive six FAP patients (mean age: 65.8 ± 7.3 years) with a transthyretin (TTR) Val30Met mutation from an endemic area of late-onset FAP were prospectively recruited to an open label study with oral diflunisal (250 mg twice a day). We evaluated clinical symptoms, Kumamoto FAP score, modified body mass index (mBMI), Medical Research Council sum score, nerve conduction studies (NCS), electrocardiogram (ECG), ECG Holter monitor test, echocardiography, and (123)iodine-metaiodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy.
  
  
  RESULTS
  One patient ceased to take diflunisal because of hematuria which was reversible. The other five patients were treated with diflunisal for 3-5 (4.4 ± 0.9 years) years. Autonomic symptoms (orthostatic hypotension and gastrointestinal symptoms) disappeared after treatment in two of the four patients with the symptoms. Delayed heart to mediastinum ratio on (123)I-MIBG imaging, a marker of cardiac postganglionic sympathetic nerve function, increased during the three-year treatment. mBMI was maintained through observation period. While, motor and sensory symptoms, Kumamoto FAP scores, and data on NCS gradually deteriorated.
  
  
  CONCLUSIONS
  Diflunisal might be effective especially for autonomic dysfunction in late-onset FAP with a TTR Val30Met mutation.
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: ryo-tk@med.kanazawa-u.ac.jp.
authors: Ryoichi
authors: R
authors: Takahashi
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: onoken@med.kanazawa-u.ac.jp.
authors: Kenjiro
authors: K
authors: Ono
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: s-sbt@med.kanazawa-u.ac.jp.
authors: Shutaro
authors: S
authors: Shibata
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: k-nkmr@med.kanazawa-u.ac.jp.
authors: Keiko
authors: K
authors: Nakamura
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: kjunji@med.kanazawa-u.ac.jp.
authors: Junji
authors: J
authors: Komatsu
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: yoshi-i@med.kanazawa-u.ac.jp.
authors: Yoshihisa
authors: Y
authors: Ikeda
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: tokuhei@med.kanazawa-u.ac.jp.
authors: Tokuhei
authors: T
authors: Ikeda
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: kimiharu@med.kanazawa-u.ac.jp.
authors: Miharu
authors: M
authors: Samuraki
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: ksakai@med.kanazawa-u.ac.jp.
authors: Kenji
authors: K
authors: Sakai
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: neuiwasa@med.kanazawa-u.ac.jp.
authors: Kazuo
authors: K
authors: Iwasa
authors: Department of Nuclear Medicine/Biotracer Medicine, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: kayano@nmd.m.kanazawa-u.ac.jp.
authors: Daiki
authors: D
authors: Kayano
authors: Department of Neurology and Neurobiology of Aging, Kanazawa University, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: m-yamada@med.kanazawa-u.ac.jp.
authors: Masahito
authors: M
authors: Yamada
mesh_terms: D019797:3-Iodobenzylguanidine; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000150:complications / Q000235:genetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001342:Autonomic Nervous System Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D004061:Diflunisal / Q000627:therapeutic use*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010597:Pharmacogenetics; D011228:Prealbumin / Q000235:genetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D014633:Valine / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011228:Prealbumin; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D004061:Diflunisal; D008715:Methionine; D014633:Valine
keywords: (123)Iodine-metaiodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy; Amyloidosis; Diflunisal; Echocardiogram; Familial amyloid polyneuropathy (FAP); Transthyretin