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Clinical Trial
. 2017 Nov;56(5):901-911.
doi: 10.1002/mus.25563. Epub 2017 Apr 7.

Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial

Peter J Dyck  1 , John C Kincaid  2 , P James B Dyck  1 , Vinay Chaudhry  3 , Namita A Goyal  4 , Christina Alves  5 , Hayet Salhi  6 , Janice F Wiesman  7 , Celine Labeyrie  8 , Jessica Robinson-Papp  9 , Márcio Cardoso  5 , Matilde Laura  10 , Katherine Ruzhansky  11 , Andrea Cortese  12 , Thomas H Brannagan 3rd  13 , Julie Khoury  14 , Sami Khella  15 , Márcia Waddington-Cruz  16 , João Ferreira  17 , Annabel K Wang  18 , Marcus V Pinto  16 , Samar S Ayache  6 , Merrill D Benson  19 , John L Berk  20 , Teresa Coelho  5 , Michael Polydefkis  3 , Peter Gorevic  9 , David H Adams  8 , Violaine Plante-Bordeneuve  6 , Carol Whelan  10 , Giampaolo Merlini  21 , Stephen Heitner  14 , Brian M Drachman  15 , Isabel Conceição  17 , Christopher J Klein  1 , Morie A Gertz  1 , Elizabeth J Ackermann  22 , Steven G Hughes  22 , Michelle L Mauermann  1 , Rito Bergemann  23 , Karen A Lodermeier  1 , Jenny L Davies  1 , Rickey E Carter  1 , William J Litchy  1
Affiliations
Clinical Trial

Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial

Peter J Dyck et al. Muscle Nerve. 2017 Nov.

Abstract

Introduction: Polyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis ), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial.

Methods: We assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis ) and its subscores and correlation with disability and health scores.

Results: The mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests.

Conclusions: Specially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis , broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901-911, 2017.

Keywords: disability; familial amyloidotic polyneuropathy (FAP); neurophysiologic tests; oligonucleotide trials; peripheral neuropathy; polyneuropathy signs; proficiency.

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Figures

Figure 1
Figure 1
The distribution of the measured values (mean of the 2 assessments) of the components of mNIS+7Ionis of the first 100 patients entered into IONIS-TTRRX Phase 3 FAP trial. Note that the clinical measures of weakness, muscle stretch reflexes, and clinical sensation scale abnormality with only a small ceiling effect observed for NIS reflexes. Among the clinical neurophysiological tests, scaling is robust for most tests, but approximately one-fourth of patients have no abnormality of Somatotopically assessed heat as pain 5 (HP5). Heart rate decrease with deep breathing was at ceiling in 7 patients. The data in this figure illustrate that mNIS+7Ionis represents the kind and range of severities of functional polyneuropathy abnormalities that occur in FAP. While muscle weakness, muscle stretch reflexes, and sensation loss of both large and small sensory fibers are broadly represented in the score, autonomic dysfunction is inadequately represented, because of frequent cardiac arrhythmias and electronic pacing.
Figure 2
Figure 2
The mNIS+7Ionis score values of patients who have stage 1, 2, and 3 PND abnormalities.
See this image and copyright information in PMC

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