Transthyretin amyloid neuropathy has earlier neural involvement but better prognosis than primary amyloid counterpart: an answer to the paradox?

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6 Citations (Scopus)

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. Interpretation: 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.

Original languageEnglish (US)
Pages (from-to)401-411
Number of pages11
JournalAnnals of Neurology
Volume80
Issue number3
DOIs
StatePublished - Sep 1 2016

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Amyloid Neuropathies
Prealbumin
Peripheral Nervous System Diseases
Amyloidosis
Natural History
Orthostatic Intolerance
Mutation
Survival
Neural Conduction
Electromyography
Upper Extremity
Medical Records
Fatigue
Weight Loss
Primary amyloidosis
Phenotype

ASJC Scopus subject areas

  • Medicine(all)
  • Neurology
  • Clinical Neurology

Cite this

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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. Interpretation: 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.",
author = "Loavenbruck, {Adam J.} and Wolfgang Singer and Mauermann, {Michelle M} and Paola Sandroni and Dyck, {P. James B} and Morie Gertz and Klein, {Christopher Jon} and Low, {Phillip Anson}",
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T1 - Transthyretin amyloid neuropathy has earlier neural involvement but better prognosis than primary amyloid counterpart

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AU - Loavenbruck, Adam J.

AU - Singer, Wolfgang

AU - Mauermann, Michelle M

AU - Sandroni, Paola

AU - Dyck, P. James B

AU - Gertz, Morie

AU - Klein, Christopher Jon

AU - Low, Phillip Anson

PY - 2016/9/1

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N2 - 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. Interpretation: 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.

AB - 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. Interpretation: 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.

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