Retrospective study of a TTR FAP cohort to modify NIS + 7 for therapeutic trials

Suanprasert, Narupat; Berk, John L.; Benson, Merrill D.; Dyck, Peter J.; Klein, Christopher J.; Gollob, Jared; Bettencourt, Brian R.; Karsten, Verena

doi:10.1016/j.jns.2014.06.041

Cited by 61 publications

(76 citation statements)

References 40 publications

(57 reference statements)

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“…The improved approaches to assess neuropathic impairments represented by mNIS17 have been previously studied. 18,22 While the NIS17 has a maximum of 270, the FAP-specific mNIS17 used in the present study has 304 points maximum. 27 The NIS progression rate of 14.3 points/year as observed in this study corresponds to an mNIS17 progression rate of 17.8 points/year.…”

Section: Resultsmentioning

confidence: 89%

“…Recently, the modified NIS17 (mNIS17) was developed specifically to improve quantification and monitoring of neuropathy in patients with FAP. 18 The objective of the present study was to use NIS to determine the association between the severity of neuropathy and disease stage as well as estimate the rate of neuropathy progression from cross-sectional analysis of a large multinational population of patients with FAP.…”

mentioning

confidence: 99%

“…16 The lower limb NIS17, or NIS17, was modified for use in generalized length-dependent sensorimotor polyneuropathy (e.g., TTR FAP) to more comprehensively assess sensation topographically. 20 The scores include different attributes of nerve conduction from those used in earlier studies, 18 in addition to more and different autonomic endpoints. The mNIS17 score for evaluation of patients with FAP used in the present study is shown in figure e-1.…”

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confidence: 99%

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Rapid progression of familial amyloidotic polyneuropathy

et al. 2015

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Objectives: To assess the association between severity of neuropathy and disease stage, and estimate the rate of neuropathy progression in a retrospective cross-sectional analysis of a multinational population of patients with familial amyloidotic polyneuropathy (FAP). Methods:We characterize neuropathy severity and rate of progression in available patients with FAP in France, the United States, Portugal, and Italy. Neuropathy Impairment Scores (NIS), time from symptom onset to NIS measurement, polyneuropathy disability (PND) scores, FAP disease stage, and manual grip strength data were collected. We estimated neuropathy progression using Loess Fit and Gompertz Fit models.Results: For the 283 patients studied (mean age, 56.4 years), intercountry genotypic variation in the transthyretin (TTR) mutation was observed, with the majority of patients in Portugal (92%) having early-onset Val30Met-FAP. There was also marked intercountry variation in PND score, FAP stage, and TTR stabilizer use. NIS was associated with PND score (NIS 10 and 99 for scores I and IV, respectively; p , 0.0001) and FAP stage (NIS 14 and 99 for stages 1 and 3, respectively; p , 0.0001). In addition, there was an association between NIS and TTR genotype. The estimated rate of NIS progression for a population with a median NIS of 32 was 14.3 points/year; the corresponding estimated rate for the modified NIS17 is 17.8 points/year. Conclusions:In a multinational population of patients with FAP, rapid neuropathic progression is observed and the severity of neuropathy is associated with functional scales of locomotion. Familial amyloidotic polyneuropathy (FAP) is a progressive, fatal condition, with survival after diagnosis of 5 to 15 years.1 This rare, hereditary, autosomal dominant form of amyloidosis is caused by transthyretin (TTR) gene mutations, 2-4 which can result in misfolding and aggregation of the TTR protein and formation of insoluble amyloid fibrils.5 Tissue deposition of mutant and wild-type TTR fibrils results in intractable peripheral sensorimotor neuropathy, autonomic neuropathy, and/or cardiomyopathy. [6][7][8][9] Clinical manifestations of FAP are influenced by a patient's TTR genotype and geographic location.10 Val30Met (V30M) is the most common gene mutation in FAP, with the largest patient cluster reported in Portugal.10,11 Symptoms at presentation and clinical progression in patients with V30M-FAP differ among countries. Early-onset FAP is common in Portugal, 12 while late-onset cases of FAP are predominant in the United States and in France, with variation reported in the clinical presentation of neurologic phenotypes. 13In FAP clinical trials, change in neurologic function over time has been assessed using the Neuropathy Impairment Score (NIS), the NIS-lower limb, and the NIS plus 7 (NIS17) [14][15][16][17] From the National

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Section: Resultsmentioning

confidence: 89%

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confidence: 99%

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confidence: 99%

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Rapid progression of familial amyloidotic polyneuropathy

et al. 2015

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“…Scales for assessment of progression of the neuropathy in TTR-FAP Neuropathic scores have been used to monitor progression of the neuropathy in TTR FAP, moving from NIS score, to NIS+7 [52] and more recently to modified NIS+7 [53], taking into account quantitative sensory testing for a length dependent polyneuropathy, autonomic dysfunction, and neurophysiological sensory and motor markers of axonal loss (TABLE 4).…”

Section: Ttr Gene Silencingmentioning

confidence: 99%

“…It affects 5-27% of the patients and remains asymptomatic in the first stages of the disease [58]. It should be closely monitored and treated aggressively (53). Vitreous deposits causing visual impairment should be managed surgically.…”

Section: Ocular Managementmentioning

confidence: 99%

Current and future treatment of amyloid neuropathies

Adams¹,

Cauquil²,

Théaudin³

et al. 2014

Expert Review of Neurotherapeutics

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Amyloid neuropathies of acquired or genetic origin are disabling and life-threatening, until recently there were few treatment options available. Poor prognosis is related to progressive neuropathy and associated, although often underdiagnosed, cardiac involvement in specific transthyretin (TTR) gene mutations. Recent progress has modified prognosis and management of amyloid neuropathies. In TTR-familial amyloidosis with polyneuropathy, major changes have occurred over the last 30 years: better knowledge concerning genetics, phenotypes and epidemiology, and the advent of possible treatments. Liver transplantation, first performed in 1990, stopped disease progression, thus doubling survival in early onset V30M patients. More recently tetramer stabilizers (Tafamidis and Diflunisal) showed a significant reduction of progression of neuropathic scores; Tafamidis is now recommended in Stage I patients. Two multicentric clinical trials are now ongoing to evaluate TTR gene silencing by antisense Oligonucleotides (ASO) or siRNA. In the near future we should have new therapeutical options for patients with amyloid neuropathy.

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