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. 2022 Aug;269(8):4281-4287.
doi: 10.1007/s00415-022-11056-4. Epub 2022 Mar 13.

A compound score to screen patients with hereditary transthyretin amyloidosis

Stefano Tozza  1 , Daniele Severi  2 , Emanuele Spina  2 , Andrea Di Paolantonio  3   4 , Aniello Iovino  2 , Valeria Guglielmino  3   4 , Francesco Aruta  2 , Maria Nolano  2 , Mario Sabatelli  3   5 , Lucio Santoro  2 , Marco Luigetti  3   4 , Fiore Manganelli  2
Affiliations

A compound score to screen patients with hereditary transthyretin amyloidosis

Stefano Tozza et al. J Neurol. 2022 Aug.

Abstract

Background: Hereditary transthyretin amyloidosis (ATTRv) is a rare, debilitating and fatal disease, mostly characterized by progressive axonal peripheral neuropathy. Diagnosis is still challenging and diagnostic delay in non-endemic area is about 3-4 years. The aim of this study was to arrange a clinical and electrophysiological score to select patients with axonal neuropathy that deserve screening for TTR mutation.

Methods: Thirty-five ATTRv patients and 55 patients with chronic idiopathic axonal polyneuropathy (CIAP) were retrospectively analyzed. Clinical and electrophysiological findings at first evaluation were collected. Based on significant results between the two groups, a compound (clinical and electrophysiological) score was arranged, and ROC analysis was performed to identify the ideal cut-off able to discriminate between the two groups.

Results: ATTRv patients presented a later age at onset, more frequent muscle weakness and carpal tunnel syndrome history. On the other hand, electrophysiological analysis showed that ATTRv patients had lower CMAP and SAP amplitude in all examined nerves. We arranged a compound score constituted by 7 total items, ranging from 0 to 12. ROC analysis showed an Area Under the Curve = 0.8655 and we set the cut-off ≥ 5 points to discriminate ATTRv patients with a sensitivity of 96.6% and a specificity of 63.6%.

Conclusion: Our study demonstrated that our compound score with cut-off ≥ 5 allows to discriminate ATTRv patients among subject affected by axonal polyneuropathy with a sensitivity > 95%. Thus, our compound score is a quick, easy and effective screening tool.

Keywords: Carpal tunnel syndrome; Neuropathy; Neurophysiology; Screening tool; TTR amyloidosis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Composite clinical and electrophysiological score. CTS carpal tunnel syndrome, SAP sensory action potential, CMAP compound motor action potential
Fig. 2
Fig. 2
ROC analysis of composite score. ROC analysis of composite score in patients with ATTRv and CIAP patients showing an area under the curve (AUC) of 0.8655
See this image and copyright information in PMC

References

    1. Manganelli F, Fabrizi GM, Luigetti M, Mandich P, Mazzeo A, Pareyson D. Hereditary transthyretin amyloidosis overview. Neurol Sci. 2020 doi: 10.1007/s10072-020-04889-2. - DOI - PMC - PubMed
    1. Adams D, Koike H, Slama M, Coelho T. Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol. 2019;15(7):387–404. doi: 10.1038/s41582-019-0210-4. - DOI - PubMed
    1. Luigetti M, Romozzi M, Bisogni G, Cardellini D, Cavallaro T, Di Paolantonio A, Fabrizi GM, Fenu S, Gentile L, Grandis M, Marucci G, Massucco S, Mazzeo A, Pareyson D, Romano A, Russo M, Schenone A, Tagliapietra M, Tozza S, Vita G, Sabatelli M. hATTR pathology: nerve biopsy results from italian referral centers. Brain Sci. 2020;10(11):780. doi: 10.3390/brainsci10110780. - DOI - PMC - PubMed
    1. Coelho T, Maia LF, Martins da Silva A, Waddington Cruz M, Planté-Bordeneuve V, Lozeron P, Suhr OB, Campistol JM, Conceição IM, Schmidt HH, Trigo P, Kelly JW, Labaudinière R, Chan J, Packman J, Wilson A, Grogan DR. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology. 2012;79(8):785–792. doi: 10.1212/WNL.0b013e3182661eb1. - DOI - PMC - PubMed
    1. Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Planté-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH, 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):11–21. doi: 10.1056/NEJMoa1716153. - DOI - PubMed

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