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Open Access 23-10-2023 | Amyloidosis | Original Article

Heterogenous electrophysiological features in early stage of hereditary transthyretin amyloidosis neuropathy

Authors: Stefano Tozza, Giovanni Palumbo, Daniele Severi, Aniello Iovino, Emanuele Spina, Francesco Aruta, Emanuele Cassano, Rosa Iodice, Raffaele Dubbioso, Lucia Ruggiero, Maria Nolano, Lucio Santoro, Fiore Manganelli

Published in: Neurological Sciences | Issue 4/2024

Abstract

Introduction

Hereditary transthyretin-mediated amyloidosis (ATTRv, v for variant) is a progressive disease caused by mutations in the TTR gene, leading to sensory-motor, axonal and length-dependent neuropathy. However, some patients may show variable electrophysiological pattern. The aim of this study was to evaluate the electrophysiological features of TTR amyloid neuropathy at the time of the first nerve conduction study (NCS) to assess whether there were distinguishing features useful for early diagnosis.

Methods

We retrospectively revised the first electrophysiological findings of ATTRv patients, and we categorized the neuropathy based on nerve conduction slowing, type of involved fibres and distribution pattern of PNS involvement. Cluster analysis was performed to evaluate the prevalence of neuropathy features between the early and late stage of disease, based on disease duration and disability burden assessed by NIS.

Results

We recruited 33 patients (27 males) with mean age 63.9 ± 10.8 years, mean disease duration 2.8 ± 2.4 years and mean NIS 47.6 ± 41.8. Overall, the frequency analysis showed that the most common features of ATTRv neuropathy included the categories of axonal, sensory-motor and neuronopathic-like pattern. This electrophysiological pattern of PNS involvement was constant in patients in late stage of disease, whereas ATTRv patients in early stage of disease displayed variable electrophysiological pattern of PNS involvement.

Discussion

Our findings demonstrated that ATTRv neuropathy may present at first NCS in a variable way, and it changes over the course of disease. Such heterogeneity makes the suspicion of ATTRv even more challenging at the time of first electrophysiological examination.

Manganelli F, Fabrizi GM, Luigetti M, Mandich P, Mazzeo A, Pareyson D (2022) Hereditary transthyretin amyloidosis overview. Neurol Sci 43(Suppl 2):595–604. https://doi.org/10.1007/s10072-020-04889-2CrossRefPubMed

Tozza S, Severi D, Spina E, Iovino A, Aruta F, Ruggiero L, Dubbioso R, Iodice R, Nolano M, Manganelli F (2021) The neuropathy in hereditary transthyretin amyloidosis: a narrative review. J Peripher Nerv Syst 26(2):155–159. https://doi.org/10.1111/jns.12451CrossRefPubMedPubMedCentral

Gertz M, Adams D, Ando Y, Beirão JM, Bokhari S, Coelho T, Comenzo RL, Damy T, Dorbala S, Drachman BM, Fontana M, Gillmore JD, Grogan M, Hawkins PN, Lousada I, Kristen AV, Ruberg FL, Suhr OB, Maurer MS, Nativi-Nicolau J, Quarta CC, Rapezzi C, Witteles R, Merlini G (2020) Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner. BMC Fam Pract 21(1):198. https://doi.org/10.1186/s12875-020-01252-4CrossRefPubMedPubMedCentral

Carroll A, Dyck PJ, de Carvalho M, Kennerson M, Reilly MM, Kiernan MC, Vucic S (2022) Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis. J Neurol Neurosurg Psychiatry 93(6):668–678. https://doi.org/10.1136/jnnp-2021-327909CrossRefPubMed

Van den Bergh PYK, van Doorn PA, Hadden RDM, Avau B, Vankrunkelsven P, Allen JA, Attarian S, Blomkwist-Markens PH, Cornblath DR, Eftimov F, Goedee HS, Harbo T, Kuwabara S, Lewis RA, Lunn MP, Nobile-Orazio E, Querol L, Rajabally YA, Sommer C, Topaloglu HA (2021) European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force-second revision. J Peripher Nerv Syst 26(3):242–268. https://doi.org/10.1111/jns.12455. Erratum in: J Peripher Nerv Syst. 2022;27(1):94. Erratum in: Eur J Neurol. 2022;29(4):1288

Selim SZ, Ismail MA (1984) K-means-type algorithms: a generalized convergence theorem and characterization of local optimality. IEEE Trans Pattern Anal Mach Intell 6(1):81–87. https://doi.org/10.1109/tpami.1984.4767478CrossRefPubMed

Coelho T, Maia LF, da Silva AM, Cruz MW, Planté-Bordeneuve V, Suhr OB, Conceiçao I, Schmidt HH, Trigo P, Kelly JW, Labaudinière R, Chan J, Packman J, Grogan DR (2013) Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J Neurol 260(11):2802–2814. https://doi.org/10.1007/s00415-013-7051-7CrossRefPubMedPubMedCentral

Di Stefano V, Fava A, Gentile L, Guaraldi P, Leonardi L, Poli L, Tagliapietra M, Vastola M, Fanara S, Ferrero B, Giorgi M, Perfetto F, Russo M, Russo D (2022) Italian real-life experience of patients with hereditary transthyretin amyloidosis treated with patisiran. Pharmgenomics Pers Med 12(15):499–514. https://doi.org/10.2147/PGPM.S359851CrossRef

Luigetti M, Antonini G, Di Paolantonio A, Gentile L, Grandis M, Leonardi L, Lozza A, Manganelli F, Mazzeo A, Mussinelli R, My F, Obici L, Maria Pennisi E, Romozzi M, Russo M, Sabatelli M, Salvalaggio A, Tagliapietra M, Tozza S (2022) Real-life experience with inotersen in hereditary transthyretin amyloidosis with late-onset phenotype: data from an early-access program in Italy. Eur J Neurol 29(7):2148–2155. https://doi.org/10.1111/ene.15325CrossRefPubMedPubMedCentral

10.

Cortese A, Vegezzi E, Lozza A, Alfonsi E, Montini A, Moglia A, Merlini G, Obici L (2017) Diagnostic challenges in hereditary transthyretin amyloidosis with polyneuropathy: avoiding misdiagnosis of a treatable hereditary neuropathy. J Neurol Neurosurg Psychiatry 88(5):457–458. https://doi.org/10.1136/jnnp-2016-315262CrossRefPubMed

11.

Ohashi N, Kodaira M, Morita H, Sekijima Y (2019) Electrophysiological demyelinating features in hereditary ATTR amyloidosis. Amyloid 26(1):15–23. https://doi.org/10.1080/13506129.2018.1564903CrossRefPubMed

12.

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 (2020) ATTRv pathology: nerve biopsy results from Italian referral centers. Brain Sci 10(11):780. https://doi.org/10.3390/brainsci10110780CrossRefPubMedPubMedCentral

13.

Hou X, Parkington HC, Coleman HA, Mechler A, Martin LL, Aguilar MI, Small DH (2007) Transthyretin oligomers induce calcium influx via voltage-gated calcium channels. J Neurochem 100(2):446–457. https://doi.org/10.1111/j.1471-4159.2006.04210.xCrossRefPubMed

14.

Gasperini RJ, Hou X, Parkington H, Coleman H, Klaver DW, Vincent AJ, Foa LC, Small DH (2011) TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons. Mol Neurodegener 6(1):19. https://doi.org/10.1186/1750-1326-6-19

15.

Salvi F, Pastorelli F, Plasmati R, Bartolomei I, Dall’Osso D, Rapezzi C (2012) Genotypic and phenotypic correlation in an Italian population of hereditary amyloidosis TTR-related (HA-TTR): clinical and neurophysiological aids to diagnosis and some reflections on misdiagnosis. Amyloid 19(Suppl 1):58–60. https://doi.org/10.3109/13506129.2012.682187CrossRefPubMed

16.

Tozza S, Severi D, Spina E, Di Paolantonio A, Iovino A, Guglielmino V, Aruta F, Nolano M, Sabatelli M, Santoro L, Luigetti M, Manganelli F (2022) A compound score to screen patients with hereditary transthyretin amyloidosis. J Neurol 269(8):4281–4287. https://doi.org/10.1007/s00415-022-11056-4CrossRefPubMedPubMedCentral

17.

Leonardi L, Galosi E, Vanoli F, Fasolino A, Di Pietro G, Luigetti M, Sabatelli M, Fionda L, Garibaldi M, Alfieri G, Lauletta A, Morino S, Salvetti M, Truini A, Antonini G (2022) Skin biopsy and quantitative sensory assessment in an Italian cohort of ATTRv patients with polyneuropathy and asymptomatic carriers: possible evidence of early non-length dependent denervation. Neurol Sci 43(2):1359–1364. https://doi.org/10.1007/s10072-021-05434-5CrossRefPubMed

18.

Leonardi L, Costanzo R, Forcina F, Morino S, Antonini G, Salvetti M, Luigetti M, Romano A, Primiano G, Guglielmino V, Fionda L, Garibaldi M, Lauletta A, Rossini E, Tufano L, Ceccanti M, Esposito N, Falco P, di Pietro G, Truini A, Galosi E (2023) Quantitative sensory testing and skin biopsy findings in late-onset ATTRv presymptomatic carriers: relationships with predicted time of disease onset (PADO). J Peripher Nerv Syst 28(3):390–397. https://doi.org/10.1111/jns.12586CrossRefPubMed

19.

Théaudin M, Lozeron P, Algalarrondo V, Lacroix C, Cauquil C, Labeyrie C, Slama MS, Adam C, Guiochon-Mantel A, Adams D; French FAP Network (CORNAMYL) Study Group (2019) Upper limb onset of hereditary transthyretin amyloidosis is common in non-endemic areas. Eur J Neurol 26(3):497–e36. https://doi.org/10.1111/ene.13845

20.

Guy CD, Jones CK (2001) Abdominal fat pad aspiration biopsy for tissue confirmation of systemic amyloidosis: specificity, positive predictive value, and diagnostic pitfalls. Diagn Cytopathol 24(3):181–185. https://doi.org/10.1002/1097-0339(200103)24:3%3c181::aid-dc1037%3e3.0.co;2-dCrossRefPubMed

Title: Heterogenous electrophysiological features in early stage of hereditary transthyretin amyloidosis neuropathy
Authors: Stefano Tozza
Giovanni Palumbo
Daniele Severi
Aniello Iovino
Emanuele Spina
Francesco Aruta
Emanuele Cassano
Rosa Iodice
Raffaele Dubbioso
Lucia Ruggiero
Maria Nolano
Lucio Santoro
Fiore Manganelli
Publication date: 23-10-2023
Publisher: Springer International Publishing
Keyword: Amyloidosis
Published in: Neurological Sciences / Issue 4/2024
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-023-07140-w

At a glance: The STEP trials

Springer Medicine

Heterogenous electrophysiological features in early stage of hereditary transthyretin amyloidosis neuropathy

Abstract

Introduction

Methods

Results

Discussion

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Results

Discussion

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