PMID- 37875336
OWN - NLM
STAT- MEDLINE
DCOM- 20240514
LR  - 20240521
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Print)
IS  - 0022-3050 (Linking)
VI  - 95
IP  - 6
DP  - 2024 May 14
TI  - Detailed clinical, physiological and pathological phenotyping can impact access 
      to disease-modifying treatments in ATTR carriers.
PG  - 489-499
LID - 10.1136/jnnp-2023-332180 [doi]
AB  - BACKGROUND: Hereditary transthyretin amyloidosis is a life-threatening autosomal 
      dominant systemic disease due to pathogenic TTR variants (ATTRv), mostly 
      affecting the peripheral nerves and heart. The disease is characterised by a 
      combination of symptoms, organ involvement and histological amyloid deposition. 
      The available disease-modifying ATTRv treatments (DMTs) are more effective if 
      initiated early. Pathological nerve conduction studies (NCS) results are the 
      cornerstone of large-fibre polyneuropathy diagnosis, but this anomaly occurs late 
      in the disease. We investigated the utility of a multimodal neurological and 
      cardiac evaluation for detecting early disease onset in ATTRv carriers. METHODS: 
      We retrospectively analysed a cohort of ATTRv carriers with normal NCS results 
      regardless of symptoms. Multimodal denervation and infiltration evaluations 
      included a clinical questionnaire (Lauria and New York Heart Association (NYHA)) 
      and examination, intra-epidermal nerve fibre density assessment, autonomic 
      assessment based on heart rate variability, Sudoscan, meta-iodo-benzyl-guanidine 
      scintigraphy, cardiac biomarkers, echocardiography, MRI and searches for 
      amyloidosis on skin biopsy and bone scintigraphy. RESULTS: We included 130 ATTRv 
      carriers (40.8% men, age: 43.6+/-13.5 years), with 18 amyloidogenic TTR gene 
      mutations, the majority of which was the late-onset Val30Met variant (42.3%). 
      Amyloidosis was detected in 16.9% of mutation carriers, including 9 (6.9%) with 
      overt disease (Lauria>2 or NYHA>1) and 13 asymptomatic carriers (10%) with organ 
      involvement (small-fibre neuropathy or cardiomyopathy). Most of these patients 
      received DMT. Abnormal test results of unknown significance were obtained for 105 
      carriers (80.8%). Investigations were normal in only three carriers (2.3%). 
      CONCLUSIONS: Multimodal neurological and cardiac investigation of TTRv carriers 
      is crucial for the early detection of ATTRv amyloidosis and initiation of DMT.
CI  - (c) Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Beauvais, Diane
AU  - Beauvais D
AUID- ORCID: 0009-0000-8323-8767
AD  - AP-HP, Service de neurologie, CHU Bicetre, Centre de reference national des 
      neuropathies amyloides familiales et autres neuropathies peripheriques rares, 
      CERAMIC, FILNEMUS Network, Le Kremlin-Bicetre, France diabeauvais@gmail.com.
AD  - Department of Neurology (Nerve-Muscle Unit), AOC National Reference Center for 
      Neuromuscular Disorders, University Hospital of Bordeaux (CHU Pellegrin), 
      Bordeaux, France.
FAU - Labeyrie, Celine
AU  - Labeyrie C
AD  - AP-HP, Service de neurologie, CHU Bicetre, Centre de reference national des 
      neuropathies amyloides familiales et autres neuropathies peripheriques rares, 
      CERAMIC, FILNEMUS Network, Le Kremlin-Bicetre, France.
FAU - Cauquil, Cecile
AU  - Cauquil C
AD  - AP-HP, Service de neurologie, CHU Bicetre, Centre de reference national des 
      neuropathies amyloides familiales et autres neuropathies peripheriques rares, 
      CERAMIC, FILNEMUS Network, Le Kremlin-Bicetre, France.
FAU - Francou, Bruno
AU  - Francou B
AD  - AP-HP, Laboratoire de Genetique Moleculaire, Pharmacogenetique et Hormonologie, 
      CHU Bicetre, Le Kremlin-Bicetre, France.
FAU - Eliahou, Ludivine
AU  - Eliahou L
AD  - AP-HP, Departement de Cardiologie, CHU Bichat, Paris, France.
FAU - Not, Adeline
AU  - Not A
AD  - AP-HP, Service de neurologie, CHU Bicetre, Centre de reference national des 
      neuropathies amyloides familiales et autres neuropathies peripheriques rares, 
      CERAMIC, FILNEMUS Network, Le Kremlin-Bicetre, France.
FAU - Echaniz-Laguna, Andoni
AU  - Echaniz-Laguna A
AD  - AP-HP, Service de neurologie, CHU Bicetre, Centre de reference national des 
      neuropathies amyloides familiales et autres neuropathies peripheriques rares, 
      CERAMIC, FILNEMUS Network, Le Kremlin-Bicetre, France.
AD  - Universite de Paris-Saclay, INSERM U1195, Le Kremlin-Bicetre, France.
FAU - Adam, Clovis
AU  - Adam C
AD  - AP-HP, Service d'Anatomopathologie Clinique, CHU Bicetre, Le Kremlin-Bicetre, 
      France.
FAU - Slama, Michel S
AU  - Slama MS
AD  - AP-HP, Departement de Cardiologie, CHU Bichat, Paris, France.
FAU - Benmalek, Anouar
AU  - Benmalek A
AD  - Faculte de Pharmacie, Universite Paris-Saclay, Gif-sur-Yvette, France.
FAU - Leonardi, Luca
AU  - Leonardi L
AD  - Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), 
      Sant'Andrea Hospital, Sapienza University of Rome, Roma, Italy.
FAU - Rouzet, Francois
AU  - Rouzet F
AD  - AP-HP, Service de Medecine nucleaire, CHU Bichat, Paris, France.
FAU - Adams, David
AU  - Adams D
AD  - AP-HP, Service de neurologie, CHU Bicetre, Centre de reference national des 
      neuropathies amyloides familiales et autres neuropathies peripheriques rares, 
      CERAMIC, FILNEMUS Network, Le Kremlin-Bicetre, France.
AD  - Universite de Paris-Saclay, INSERM U1195, Le Kremlin-Bicetre, France.
FAU - Algalarrondo, Vincent
AU  - Algalarrondo V
AD  - AP-HP, Departement de Cardiologie, CHU Bichat, Paris, France.
AD  - Universite Paris Cite, Paris, France.
FAU - Beaudonnet, Guillemette
AU  - Beaudonnet G
AD  - AP-HP, Service de neurologie, CHU Bicetre, Centre de reference national des 
      neuropathies amyloides familiales et autres neuropathies peripheriques rares, 
      CERAMIC, FILNEMUS Network, Le Kremlin-Bicetre, France.
AD  - AP-HP, Unite de Neurophysiologie Clinique et Epileptologie (UNCE), CHU Bicetre, 
      Le Kremlin-Bicetre, France.
LA  - eng
PT  - Journal Article
DEP - 20240514
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
SB  - IM
CIN - doi: 10.1136/jnnp-2023-332841
CIN - doi: 10.1136/jnnp-2023-332842
MH  - Humans
MH  - Male
MH  - *Amyloid Neuropathies, Familial/genetics/pathology
MH  - Female
MH  - Adult
MH  - Middle Aged
MH  - Retrospective Studies
MH  - *Prealbumin/genetics
MH  - *Phenotype
MH  - Heterozygote
MH  - Neural Conduction/physiology
MH  - Mutation
MH  - Echocardiography
PMC - PMC11103288
OTO - NOTNLM
OT  - AMYLOID
OT  - EMG
OT  - NEUROPATHOLOGY
OT  - NEUROPATHY
OT  - NEUROPHYSIOLOGY
COIS- Competing interests: None declared.
EDAT- 2023/10/25 00:42
MHDA- 2024/05/15 05:44
PMCR- 2024/05/20
CRDT- 2023/10/24 21:13
PHST- 2023/07/14 00:00 [received]
PHST- 2023/09/27 00:00 [accepted]
PHST- 2024/05/15 05:44 [medline]
PHST- 2023/10/25 00:42 [pubmed]
PHST- 2023/10/24 21:13 [entrez]
PHST- 2024/05/20 00:00 [pmc-release]
AID - jnnp-2023-332180 [pii]
AID - 10.1136/jnnp-2023-332180 [doi]
PST - epublish
SO  - J Neurol Neurosurg Psychiatry. 2024 May 14;95(6):489-499. doi: 
      10.1136/jnnp-2023-332180.