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Muscle Nerve ; 61(4): 515-520, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32012291


INTRODUCTION: We compared histological and clinical profiles of primary Sjögren syndrome (pSS) small fiber neuropathy (SFN; pSS-SFN) with idiopathic SFN (i-SFN) and hereditary transthyretin amyloidosis SFN (hATTR-SFN) and described the evolution of pSS-SFN. METHODS: All patients with pSS-SFN, i-SFN, and hATTR-SFN confirmed by reduced intraepidermal nerve fiber density on skin biopsy were retrospectively included, and their characteristics were compared. To analyze prognosis of pSS-SFN, patients prospectively underwent a second evaluation. RESULTS: Fifteen pSS-SFN, 17 hATTR-SFN, and 11 i-SFN were included. Time to diagnosis SFN was longer in pSS-SFN and i-SFN than in hATTR-SFN. Painful and non-length-dependent patterns were more frequent in pSS-SFN than in hATTR-SFN. Twelve (80%) patients with pSS-SFN had a non-length-dependent pattern. Ten patients with pSS were reassessed after 3.1 years (1.7-4.7); none developed large fiber neuropathy linked to pSS. DISCUSSION: Primary Sjögren syndrome SFN is characterized by a more frequent non-length-dependent pattern compared with i-SFN and hATTR-SFN. Primary Sjögren syndrome SFN did not evolve through large fiber neuropathy.

Fibras Nervosas/patologia , Síndrome de Sjogren/complicações , Pele/patologia , Neuropatia de Pequenas Fibras/complicações , Adulto , Idoso , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/patologia , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Sjogren/diagnóstico por imagem , Síndrome de Sjogren/patologia , Neuropatia de Pequenas Fibras/diagnóstico por imagem , Neuropatia de Pequenas Fibras/patologia , Ultrassonografia
Muscle Nerve ; 61(1): 95-100, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31587306


INTRODUCTION: Although peripheral neuropathy and cardiomyopathy are well-recognized manifestations of transthyretin (ATTR) amyloidosis, myopathy has been rarely reported. METHODS: In this study we reviewed our muscle biopsy database (January 1998 to June 2018) to identify patients with ATTR amyloid myopathy confirmed by molecular or proteomic analysis. Clinical and laboratory findings were reviewed. RESULTS: We identified eight ATTR amyloid myopathy patients (5 hereditary ATTR [ATTRv] and 3 wild-type ATTR [ATTRwt]). Myopathy was the initial manifestation in all ATTRwt patients and followed peripheral neuropathy (4 patients) or cardiomyopathy (1 patient) in ATTRv patients. One ATTRv patient developed myopathy after liver transplant. Peripheral neuropathy and cardiac amyloidosis occurred in seven and six patients, respectively. Muscle biopsy showed interstitial amyloid deposition in all patients, rare necrotic/regenerating fibers in six, and vacuoles in four. DISCUSSION: Myopathy can be the initial manifestation of ATTRwt amyloidosis and can precede the peripheral neuropathy or occur after liver transplant in ATTRv amyloidosis.

Neuropatias Amiloides Familiares/patologia , Doenças Musculares/patologia , Pré-Albumina , Adulto , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/complicações , Biópsia , Cardiomiopatias/patologia , Bases de Dados Factuais , Eletromiografia , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Doenças Musculares/etiologia , Necrose , Condução Nervosa , Doenças do Sistema Nervoso Periférico/patologia , Proteômica
Hum Genet ; 138(11-12): 1331-1340, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31659433


Transthyretin (TTR) gene has a causal role in a hereditary form of amyloidosis (ATTRm) and is potentially involved in the risk of wild-type transthyretin amyloidosis (ATTRwt). To understand the genetics of ATTRm and ATTRwt, we conducted a phenome-wide association study of TTR gene in 361,194 participants of European descent testing coding and non-coding variants. Among the 382 clinically relevant phenotypes tested, TTR non-coding variants were associated with 26 phenotypic traits after multiple testing correction. These included signs related to both ATTRm and ATTRwt such as chronic ischaemic heart disease (rs140226130, p = 2.00 × 10-6), heart failure (rs73956431, p = 2.74 × 10-6), atrial fibrillation (rs10163755, p = 4.63 × 10-6), dysphagia (rs2949506, p = 3.95 × 10-6), intestine diseases (rs970866, p = 7.14 × 10-6) and anxiety (rs554521234, p = 8.85 × 10-6). Consistent results were observed for TTR disease-causing mutation Val122Ile (rs76992529) with respect to carpal tunnel syndrome (p = 6.41 × 10-6) and mononeuropathies of upper limbs (p = 1.22 × 10-5). Sex differences were also observed in line with ATTRm and ATTRwt epidemiology. Additionally, we explored possible modifier genes related to TTR function, observing convergent associations of RBP4 variants with the clinical phenotypes associated with TTR locus. In conclusion, we provide novel insights regarding the molecular basis of ATTRm and ATTRwt based on large-scale cohort, expanding our understanding of the phenotypic spectrum associated with TTR gene variation.

Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/metabolismo , Fenótipo , Pré-Albumina/genética , Pré-Albumina/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/genética , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Neuropatias Amiloides Familiares/patologia , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Prognóstico
World Neurosurg ; 131: 104-107, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31369882


BACKGROUND: Transthyretin wild-type (ATTRwt) amyloidosis is a systemic process resulting in deposition of misfolded transthyretin protein in several different tissues throughout the body. It is known to be a cause of progressive, life-threatening cardiomyopathy and lumbar spinal stenosis and carpal tunnel syndrome. CASE DESCRIPTION: Here we present the case of a 71-year-old man who has clinical manifestations of all 3 entities over several years, providing a picture of the natural history of ATTRwt amyloidosis. This patient eventually underwent a heart transplant because of progressive cardiac amyloidosis (CA) resulting in end-stage heart failure. However, symptoms in carpal tunnel and lumbar spine manifested years before the symptoms of heart failure. ATTRwt amyloidosis may present as a clinical triad of lumbar stenosis, carpal tunnel syndrome, and heart failure. Recently developed medications have shown efficacy in slowing the progress of systemic and cardiac amyloidosis. CONCLUSIONS: Knowing that extracardiac symptoms may occur first, we propose that sending ligamentum flavum and flexor tenosynovium for pathologic evaluation may be a unique opportunity to screen and treat a population of patients at risk for developing CA and heart failure.

Neuropatias Amiloides Familiares/patologia , Ligamento Amarelo/diagnóstico por imagem , Vértebras Lombares , Estenose Espinal/diagnóstico por imagem , Idoso , Neuropatias Amiloides Familiares/complicações , Cardiomiopatias/etiologia , Cardiomiopatias/cirurgia , Síndrome do Túnel Carpal/etiologia , Síndrome do Túnel Carpal/cirurgia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Humanos , Ligamento Amarelo/patologia , Ligamento Amarelo/cirurgia , Masculino , Estenose Espinal/etiologia , Estenose Espinal/cirurgia