TY - JOUR
T1 - Transthyretin amyloid neuropathy has earlier neural involvement but better prognosis than primary amyloid counterpart
T2 - an answer to the paradox?
AU - Loavenbruck, Adam J.
AU - Singer, Wolfgang
AU - Mauermann, Michelle L.
AU - Sandroni, Paola
AU - B. Dyck, P. James
AU - Gertz, Morie
AU - Klein, Christopher J.
AU - Low, Phillip A.
N1 - Publisher Copyright:
© 2016 American Neurological Association
PY - 2016/9/1
Y1 - 2016/9/1
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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U2 - 10.1002/ana.24725
DO - 10.1002/ana.24725
M3 - Article
C2 - 27422051
AN - SCOPUS:84985986844
SN - 0364-5134
VL - 80
SP - 401
EP - 411
JO - Annals of Neurology
JF - Annals of Neurology
IS - 3
ER -