title: Transthyretin amyloid neuropathy has earlier neural involvement but better prognosis than primary amyloid counterpart: an answer to the paradox?
abstract: OBJECTIVE
  To systematically compare transthyretin with primary amyloid neuropathy to define their natural history and the underlying mechanisms for differences in phenotype and natural history.
  
  
  METHODS
  All patients with defined amyloid subtype and peripheral neuropathy who completed autonomic testing and electromyography at Mayo Clinic Rochester between 1993 and 2013 were included. Medical records were reviewed for time of onset of defined clinical features. The degree of autonomic impairment was quantified using the composite autonomic severity scale. Comparisons were made between acquired and inherited forms of amyloidosis.
  
  
  RESULTS
  One hundred one cases of amyloidosis with peripheral neuropathy were identified, 60 primary and 41 transthyretin. Twenty transthyretin cases were found to have Val30Met mutations; 21 had other mutations. Compared to primary cases, transthyretin cases had longer survival, longer time to diagnosis, higher composite autonomic severity scale scores, greater reduction of upper limb nerve conduction study amplitudes, more frequent occurrence of weakness, and later non-neuronal systemic involvement. Four systemic markers (cardiac involvement by echocardiogram, weight loss > 10 pounds, orthostatic intolerance, fatigue) in combination were highly predictive of poor survival in both groups.
  
  
  CONCLUSIONS
  These findings suggest that transthyretin has earlier and greater predilection for neural involvement and more delayed systemic involvement. The degree and rate of systemic involvement is most closely related to prognosis. Ann Neurol 2016;80:401-411.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Loavenbruck
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Singer
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Mauermann
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Paola
authors.initials: P
authors.lastname: Sandroni
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: P James
authors.initials: PJ
authors.lastname: B Dyck
authors.affiliation: Department of Hematology, Mayo Clinic, Rochester, MN.
authors.forename: Morie
authors.initials: M
authors.lastname: Gertz
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Klein
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN. low@mayo.edu.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Low
mesh_terms: D000368:Aged; D000682:Amyloid / Q000378:metabolism*; D017772:Amyloid Neuropathies / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D000682:Amyloid; D011228:Prealbumin; C041120:amyloid prealbumin