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Familial amyloid polyneuropathy with the substitution of methionine for valine at position 30 in the TTR gene is the most common type of hereditary transthyretin amyloidosis. Although several authors have previously reported a size-dependent fibre loss, predominantly involving unmyelinated and small-diameter myelinated fibres, the mechanisms of nerve fibre loss have not been fully understood. In this study, we establish the morphometric pattern of peripheral neuropathy in patients with familial amyloid polyneuropathy and asymptomatic mutation carriers in the biopsies from our archive and correlated the pathological findings with clinical features. A total of 98 patients with familial amyloid polyneuropathy and 37 asymptomatic mutation carriers ( TTR Val30Met mutation), aged between 17 and 84 years, who underwent sural nerve biopsy between 1981 and 2017 at Centro Hospitalar Universitário do Porto were studied. Thirty-one controls were included for comparison. The median age at nerve biopsy was 26.0 [interquartile range = 23.5-39.5] years for asymptomatic mutation carriers, 45.0 [35.0-60.0] years for patients with familial amyloid polyneuropathy and 44.0 [30.0-63.0] years for controls. The median duration between nerve biopsy and symptoms' onset was 7.0 [3.3-11.8] years (range: 1-27 years) in the asymptomatic carriers. Most patients were in an earlier disease stage (93% with a polyneuropathy disability scale ≤2). Patients had loss of small and myelinated fibres compared with both asymptomatic carriers and controls ( P  <   0.001), whereas asymptomatic carriers showed loss of small myelinated fibres when compared with controls ( P  <   0.05). The loss of myelinated fibres increased with disease progression ( P  <   0.001), and patients in more advanced clinical stage showed more frequent amyloid deposition in the nerve ( P  =   0.001). There was a positive correlation between large myelinated fibre density and time to symptoms' onset in the asymptomatic carriers that developed early-onset form of the disease ( r =  0.52, P  <   0.01). In addition, asymptomatic carriers with amyloid deposition already present in sural nerve biopsies developed symptoms earlier than those with no amyloid ( P  <   0.01). In conclusion, this study confirms that the loss of small fibre size is an initial event in familial amyloid polyneuropathy, already present in asymptomatic gene carriers, starting several years before the onset of symptoms. We show for the first time that large myelinated fibres' loss and amyloid deposition are pathological features that correlate independently with short period to the onset of symptoms for asymptomatic carriers that developed early-onset form of the disease. These findings are therapeutically relevant, as it would allow for a better interpretation of the role of disease-modifying agents in transthyretin familial amyloid polyneuropathy., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: In multiple sclerosis (MS), even in the absence of a clinical episode of optic neuritis (ON), the optic nerve and retinal nerve fiber layer (RNFL) may be damaged leading to dyschromatopsia. Subclinical dyschromatopsia has been described in MS associated with lower motor and cognitive performances., Objectives: To set the prevalence of dyschromatopsia in eyes of MS patients without a history of ON, to compare its prevalence in patients with and without ON history, and to explore the association between dyschromatopsia and disease duration, average peripapillary RNFL thickness, macular volume, and cognitive and motor performances., Methods: An observational cross-sectional study was conducted at multiple medical centers. Data were collected after single neurological and ophthalmological evaluations. Dyschromatopsia was defined by the presence of at least 1 error using Hardy-Rand-Rittler plates., Results: In our population of 125 patients, 79 patients (63.2%) never had ON and 35 (28.8%) had unilateral ON. The prevalence of dyschromatopsia in eyes of patients without ON was 25.7%. Patients with dyschromatopsia had a statistically significant lower RNFL thickness (P = 0.004 and P = 0.040, right and left eyes, respectively) and worse performance in symbol digit modalities test (P = 0.012). No differences were found in macular volume or motor function tasks., Conclusions: Dyschromatopsia occurs frequently in MS patients. It may be associated with a worse disease status and possibly serve as a marker for the detection of subclinical disease progression since it was detected even in the absence of ON. It correlated with thinner peripapillary RNFL thickness and inferior cognitive performance.

Ten years ago, we synthesized "bioactive model polymers" bearing sulfonate groups and proposed a mechanism of their modulation effect at different steps of the cell response. Then, we set up the grafting of polymers bearing sulfonate on Ti6Al4V surfaces by a grafting "from" technique making sure of the creation of covalent bonds between the grafted polymer and the Ti6Al4V surface. We have checked and confirmed the positive effect of grafted sulfonate groups on the osteoblastic cell response in vivo and in vitro but we did not elucidate the mechanism. The aim of this basic work consists first in investigating the role of sulfonate groups in the presence and in the absence of proteins at early stages of the osteointegration process on poly(sodium styrene sulfonate) poly(NaSS) grafted and ungrafted Ti6Al4V surfaces, in vitro. To understand the role of poly(NaSS) grafted chains on osteoblast-like cell response and to confirm/elucidate the importance of fetal bovine serum (FBS) proteins in the culture medium, MC3T3-E1 cells were seeded onto poly(NaSS) grafted and non-grafted Ti6Al4V surfaces. Cultures were carried out in a complete (10% FBS) and in a non-complete medium (without FBS). Cell viability assay, cell attachment number and cell adhesion strength were followed up to 3days of culture. The presence of proteins enhanced cell growth and development whatever the surface and the presence of sulfonate groups enhanced the cell attachment even in the absence of proteins, which suggests and confirms that the sulfonate groups can modify the activity of cells such as the secretion of binding proteins. Statistical differences were found in the attachment strength tests on poly(NaSS) grafted and ungrafted surfaces and showed that the sulfonate groups play an important role in the cell resistance to shear stress., (Copyright © 2014 Elsevier B.V. All rights reserved.)