Search

IntroductionPolyneuropathy 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.MethodsWe 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.ResultsThe 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.ConclusionsSpecially 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.

Introduction: Inotersen, an antisense oligonucleotide inhibitor of transthyretin (TTR) protein production, demonstrated significant benefit versus placebo in the modified Neuropathy Impairment Score (NIS) +7 neurophysiologic tests (mNIS+7) in patients with hereditary TTR-mediated amyloidosis (hATTR) with polyneuropathy. This analysis assessed the mNIS+7 components by anatomic location and the lower limb function (LLF) test.Methods: Adults with hATTR in the NEURO-TTR trial (NCT01737398) were randomly assigned to receive weekly doses of subcutaneous inotersen 300 mg or placebo for 65 weeks. The mNIS+7 and LLF were assessed at 35 and 66 weeks.Results: All major mNIS+7 components (muscle weakness, muscle stretch reflexes, sensation) and the LLF showed significant efficacy in patients receiving inotersen versus placebo; however, NIS-reflexes (upper limb), touch pressure (upper and lower limbs), and heart rate during deep breathing did not show significant effects.Discussion: The results of this analysis reinforce the beneficial effect of inotersen on slowing neuropathy progression in patients with hATTR polyneuropathy. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary transthyretin (hATTR) amyloidosis is a progressive, degenerative disease, with peripheral neuropathy, cardiomyopathy, and other clinical manifestations. In this study we examine the impact of hATTR amyloidosis on quality of life (QOL).Methods: Neuropathy-specific QOL, measured with the Norfolk QOL-Diabetic Neuropathy questionnaire, was compared between patients with hATTR amyloidosis and patients with type 2 diabetes, whereas generic QOL, measured with the 36-item Short Form Health Survey version 2 (SF-36v2), was compared between patients with hATTR amyloidosis, the general population, and patients with chronic diseases.Results: Neuropathy-specific QOL for patients with hATTR amyloidosis was nearly equivalent to that of patients with type 2 diabetes with diabetic neuropathy accompanied by a history of ulceration, gangrene, or amputation. Generic QOL was worse than that seen in the general population, with physical functioning worse than that for patients with multiple sclerosis and congestive heart failure.Discussion: Patients with hATTR amyloidosis show significant burden on QOL, particularly in physical functioning. Muscle Nerve 60: 169-175, 2019. [ABSTRACT FROM AUTHOR]

Abstract Objective Report on the kind and distribution of somatotopic sensation loss and its utility in assessing severity of sensation loss in study of a large international cohort of patients with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN). Methods Smart Somatotopic Quantitative Sensation Testing (S ST QSTing) using Computer Assisted Sensation Evaluator IVc (CASE IVc) was used to assess the somatotopic distribution of touch pressure (TP) and heat pain (HP) sensation loss twice of untreated hATTR-PN patients in the Ionis NEURO-TTR trial (www.clinicaltrials.gov , NCT01737398). Results Of the studied cohort of 169 patients, 163 (97%) had sensation loss, both TP and HP in 121/169 (75%), TP only in 39/169 (23%), and HP only in 3/169 (2%). Sensation loss typically affected both lower (152/169–90%) and upper limb (135/169–82%), and overall TP sensation loss was greater than HP loss, except for early-onset Val30Met patients in which HP exceeded TP loss. Conclusion Using S ST QSTing, a highly quantitated, standardized, referenced, and automated QSTing approach of the body's surface distribution of sensation loss we have shown that: 1) reliable and useful measurement of the body surface distribution of sensation loss is possible; 2) this measure is abnormal in most patients with hATTR-PN and is an indication of polyneuropathy severity; and 3) cutaneous sensation loss involves both large and small sensory fibers in this disease but slightly more small fibers in early onset Val30Met patients. Highlights • S ST QSTing provides a reliable and useful measurement of body's sensation loss. • S ST QSTing is abnormal in virtually all patients with hATTR-PN. • S ST QSTing correlates strongly with quantitative measures of hATTR-PN. • Cutaneous sensation loss involves both large and small sensory fibers in hATTR-PN. • Small sensory fibers are slightly more affected in early onset Val30Met patients. [ABSTRACT FROM AUTHOR]