TY - JOUR
T1 - Development of measures of polyneuropathy impairment in hATTR amyloidosis
T2 - From NIS to mNIS + 7
AU - Dyck, P. James B.
AU - González-Duarte, A.
AU - Obici, L.
AU - Polydefkis, M.
AU - Wiesman, J. F.
AU - Antonino, I.
AU - Litchy, W. J.
AU - Dyck, Peter J.
N1 - Funding Information:
This manuscript was funded by Alnylam Pharmaceuticals, Cambridge, MA, USA.Editorial support for the preparation of the manuscript was provided by Adelphi Communications and funded by Alnylam Pharmaceuticals, Cambridge, MA, USA.
Publisher Copyright:
© 2019 The Authors
PY - 2019/10/15
Y1 - 2019/10/15
N2 - Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a rare, life-threatening disease, caused by point mutations in the transthyretin gene. It is a heterogeneous, multisystem disease with rapidly progressing polyneuropathy (including sensory, motor, and autonomic impairments) and cardiac dysfunction. Measures used to assess polyneuropathy in other diseases have been tested as endpoints in hATTR amyloidosis clinical trials (i.e. Neuropathy Impairment Score [NIS], NIS-lower limb, and NIS + 7), yet the unique nature of the polyneuropathy in this disease has necessitated modifications to these scales. In particular, the heterogeneous impairment and the aggressive disease course have been key drivers in developing scales that better capture the disease burden and progression of polyneuropathy in hATTR amyloidosis. The modified NIS + 7 (mNIS + 7) scale was specifically designed to assess polyneuropathy impairment in patients with hATTR amyloidosis, and has been the primary endpoint in two recent, phase III studies in this disease. The mNIS + 7 uses highly standardized, quantitative, and referenced assessments to quantify decreased muscle weakness, muscle stretch reflexes, sensory loss, and autonomic impairment. Physicians using this scale in clinical trials should be specifically trained and monitored to minimize variability. This article discusses the different scales that have been/are being used to assess polyneuropathy in patients with hATTR amyloidosis, their correlation with other disease assessments, and reflects on how and why scales have evolved to the latest iteration of mNIS + 7.
AB - Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a rare, life-threatening disease, caused by point mutations in the transthyretin gene. It is a heterogeneous, multisystem disease with rapidly progressing polyneuropathy (including sensory, motor, and autonomic impairments) and cardiac dysfunction. Measures used to assess polyneuropathy in other diseases have been tested as endpoints in hATTR amyloidosis clinical trials (i.e. Neuropathy Impairment Score [NIS], NIS-lower limb, and NIS + 7), yet the unique nature of the polyneuropathy in this disease has necessitated modifications to these scales. In particular, the heterogeneous impairment and the aggressive disease course have been key drivers in developing scales that better capture the disease burden and progression of polyneuropathy in hATTR amyloidosis. The modified NIS + 7 (mNIS + 7) scale was specifically designed to assess polyneuropathy impairment in patients with hATTR amyloidosis, and has been the primary endpoint in two recent, phase III studies in this disease. The mNIS + 7 uses highly standardized, quantitative, and referenced assessments to quantify decreased muscle weakness, muscle stretch reflexes, sensory loss, and autonomic impairment. Physicians using this scale in clinical trials should be specifically trained and monitored to minimize variability. This article discusses the different scales that have been/are being used to assess polyneuropathy in patients with hATTR amyloidosis, their correlation with other disease assessments, and reflects on how and why scales have evolved to the latest iteration of mNIS + 7.
KW - Hereditary transthyretin-mediated amyloidosis
KW - Modified neuropathy impairment score+7
KW - Neuropathy impairment score
KW - Polyneuropathy
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U2 - 10.1016/j.jns.2019.116424
DO - 10.1016/j.jns.2019.116424
M3 - Review article
C2 - 31445300
AN - SCOPUS:85070893314
SN - 0022-510X
VL - 405
JO - Journal of the neurological sciences
JF - Journal of the neurological sciences
M1 - 116424
ER -