Progressive brachial plexus enlargement in hereditary transthyretin amyloidosis

Alessandro Salvalaggio^{1

2}, Daniele Coraci³, Laura Obici⁴, Mario Cacciavillani⁵, Marco Luigetti^{6

7}, Anna Mazzeo⁸, Francesca Pastorelli⁹, Marina Grandis^{10

11}, Tiziana Cavallaro¹², Giulia Bisogni¹³, Alessandro Lozza⁴, Chiara Gemelli¹⁰, Luca Gentile⁸, Massimo Russo⁸, Mario Ermani¹, Gian Maria Fabrizi¹², Rosaria Plasmati⁹, Federica De Napoli¹, Marta Campagnolo¹, Francesca Castellani¹, Fabrizio Salvi⁹, Silvia Fenu¹⁴, Grazia Devigili¹⁵, Davide Pareyson¹⁴, Roberto Gasparotti¹⁶, Claudio Rapezzi^{17

18}, Carlo Martinoli^{11

19}, Luca Padua^{3

7}, Chiara Briani²⁰

Affiliations

¹ Department of Neurosciences, University of Padova, Via Giustiniani 5, 35128, Padova, Italy.
² Padova Neuroscience Center (PNC), University of Padova, Padova, Italy.
³ Neuroriabilitazione Ad Alta Intensità, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁴ Amyloidosis Research and Treatment Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
⁵ CEMES-EMG Lab, Synlab Group, Padova, Italy.
⁶ Neurology Unit, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
⁷ Department of Geriatrics, Neurosciences and Orthopaedics, Catholic University of the Sacred Heart, Rome, Italy.
⁸ Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁹ Division of Neurology, IRCCS Institute of Neurological Sciences, Bellaria Hospital, Bologna, Italy.
¹⁰ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Genova, Italy.
¹¹ Ospedale Policlinico San Martino IRCCS, Genova, Italy.
¹² Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
¹³ Centro Clinico NEMO Adulti, Rome, Italy.
¹⁴ Rare Neurodegenerative and Neurometabolic Diseases Unit, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
¹⁵ Neurological Unit I, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
¹⁶ Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
¹⁷ Cardiological Center, University of Ferrara, Ferrara, Italy.
¹⁸ Maria Cecilia Hospital, GVM Care & Research, Cotignola, RA, Italy.
¹⁹ Department of Scienze Della Salute, University of Genova, Genova, Italy.
²⁰ Department of Neurosciences, University of Padova, Via Giustiniani 5, 35128, Padova, Italy. chiara.briani@unipd.it.

PMID: 34410494
PMCID: PMC8940842
DOI: 10.1007/s00415-021-10754-9

Progressive brachial plexus enlargement in hereditary transthyretin amyloidosis

Alessandro Salvalaggio et al. J Neurol. 2022 Apr.

. 2022 Apr;269(4):1905-1912.

doi: 10.1007/s00415-021-10754-9. Epub 2021 Aug 19.

Authors

Affiliations

¹ Department of Neurosciences, University of Padova, Via Giustiniani 5, 35128, Padova, Italy.
² Padova Neuroscience Center (PNC), University of Padova, Padova, Italy.
³ Neuroriabilitazione Ad Alta Intensità, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁴ Amyloidosis Research and Treatment Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
⁵ CEMES-EMG Lab, Synlab Group, Padova, Italy.
⁶ Neurology Unit, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
⁷ Department of Geriatrics, Neurosciences and Orthopaedics, Catholic University of the Sacred Heart, Rome, Italy.
⁸ Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁹ Division of Neurology, IRCCS Institute of Neurological Sciences, Bellaria Hospital, Bologna, Italy.
¹⁰ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Genova, Italy.
¹¹ Ospedale Policlinico San Martino IRCCS, Genova, Italy.
¹² Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
¹³ Centro Clinico NEMO Adulti, Rome, Italy.
¹⁴ Rare Neurodegenerative and Neurometabolic Diseases Unit, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
¹⁵ Neurological Unit I, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
¹⁶ Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
¹⁷ Cardiological Center, University of Ferrara, Ferrara, Italy.
¹⁸ Maria Cecilia Hospital, GVM Care & Research, Cotignola, RA, Italy.
¹⁹ Department of Scienze Della Salute, University of Genova, Genova, Italy.
²⁰ Department of Neurosciences, University of Padova, Via Giustiniani 5, 35128, Padova, Italy. chiara.briani@unipd.it.

PMID: 34410494
PMCID: PMC8940842
DOI: 10.1007/s00415-021-10754-9

Abstract

Axonal polyneuropathy is the main feature of hereditary transthyretin amyloidosis (ATTRv). Nerve morphological abnormalities have been reported, but longitudinal changes have never been assessed. We performed a prospective widespread nerve ultrasound evaluation and nerve cross-sectional area (CSA) was compared with baseline data in both ATTRv patients and pre-symptomatic carriers. Thirty-eight subjects were evaluated (mean follow-up 17.1 months), among them 21 had polyneuropathy while 17 were pre-symptomatic carriers. CSA significantly increased at brachial plexus in both groups (p = 0.008 and p = 0.012) pointing to progressive brachial plexus enlargement as a longitudinal biomarker of both disease progression and disease occurrence in pre-symptomatic carriers.

Keywords: Amyloidosis; Brachial plexus; Peripheral nerves; Transthyretin; Ultrasound.

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Conflict of interest statement

Alessandro Salvalaggio reports travel grants from Akcea, Alnylam and Pfizer and consulting honoraria from Alnylam. Laura Obici reports speaker and consulting honoraria from Akcea, Alnylam and Pfizer. Marco Luigetti reports financial grants (honoraria and speaking) from Akcea, Alnylam and Pfizer, and travel grants from Pfizer, Kedrion and Grifols. Gulia Bisogni reports financial grants (honoraria and speaking) from Alnylam and travel grants from Pfizer and Grifols. Gian Maria Fabrizi reports consulting honoraria from Akcea and Alnylam, and travel grants from Kedrion and Alnylam. Chiara Gemelli reports travel grants from Akcea and Pfizer. Carlo Martinoli reports financial relationships (consultant, speaker fees, adv board) with Pfizer, Novartis, Sobi, Takeda and Novonordisk. Chiara Briani reports speaker and consulting honoraria from Akcea, Alnylam and Pfizer, and travel grants from Kedrion, Alnylam and CSL Behring. Davide Pareyson reports financial grants (honoraria and speaking) from Alnylam, Akcea, Pfizer, and Inflectis, and travel grants from Kedrion and Pfizer. Silvia Fenu received financial grants (honoraria and speaking) from Alnylam, Akcea, and Pfizer and travel grants from Alnylam and Akcea. Luca Gentile is sub-investigator in clinical trials of Alnylam, Ionis, Takeda and reports travel grants from Kedrion and CSL Behring financial grants (consulting and speaking) from Pfizer.

Figures

**Fig. 1**
Schematic representation of the site of ultrasound evaluation along the course of nerves

**Fig. 2**
a Position of the probe in the US evaluation of right brachial plexus. b Right brachial plexus (contoured by dot line) in a healthy control, subclavian artery is visualized in color mode. Arrow points out the first rib, * is positioned on the lung

**Fig. 3**
C5, C6 and C7 US appearance in a healthy control. Nerve roots are contoured by a circle, arrows point out the transvers processes (posterior tubercle)

**Fig. 4**
Brachial plexus CSA values at baseline and follow-up. Dotted lines represent ATTRv-PN patients and solid lines represent pre-symptomatic carriers. *CSA* cross-sectional area

**Fig. 5**
Right brachial plexus (contoured by dot lines) at supraclavicular space of a 57-year-old TTR-PN female patient. At first evaluation (a), brachial plexus CSA was 66 mm², at second evaluation (b) 20 months later, CSA measured 108 mm². The normal CSA value is < 82mm². *ATTRv-PN* hereditary transthyretin amyloidotic polyneuropathy, *CSA* cross-sectional area

See this image and copyright information in PMC

References

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Progressive brachial plexus enlargement in hereditary transthyretin amyloidosis

Affiliations

Progressive brachial plexus enlargement in hereditary transthyretin amyloidosis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Research Materials