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Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a heterogeneous entity with either a monophasic or relapsing course. Well-established predictors of relapsing disease are lacking., Objective: Identifying predictors of relapsing MOGAD, particularly at disease onset., Methods: A multicentre observational retrospective study was conducted to characterise a cohort of Portuguese adult MOGAD patients. Patients were identified from participating centre databases. Clinical and demographic data were collected from medical records. Bivariate analysis was conducted to compare patients with relapsing and monophasic MOGAD. Significant variables were included in a stepwise multiple regression analysis to identify independent predictors of relapse., Results: Eighty-seven MOGAD patients from 8 public hospitals were included. Relapsing MOGAD was found in 35.6% (n = 31). Mean diagnostic delay was 3.2 (±6.2) years and time to relapse was 4.4 (±6.4) years. Multiple logistic regression showed that higher neutrophil count (p < 0.01), presence of oligoclonal bands (p = 0.025) and no bridging corticosteroids (p = 0.038) at first attack were predictive of relapsing MOGAD., Conclusion: Neutrophil count and oligoclonal bands at first attack may facilitate early decision-making regarding maintenance immunotherapy. Bridging corticosteroids may also influence the course of MOGAD. Further studies with prospective design are warranted., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have influenced the results reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status., Objective: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort., Results: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6., Conclusion: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability., Competing Interests: Declaration of competing interest Authors declare no conflict of interest regarding this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits., Objective: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics., Methods: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included., Results: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome., Conclusion: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries., (Copyright © 2021. Published by Elsevier B.V.)

Acute optic neuritis is the most common neuro-opthalmologic manifestation of multiple sclerosis (MS). Treatment with high-dose intravenous corticosteroids accelerates visual recovery, although it has no long-term visual benefit. MS has several others, less common, neuro-ophthalmological manifestations, where corticotherapy may not be the best treatment option. Neuro-ophthalmologic manifestations of MS other than optic neuritis can be divided in afferent and efferent visual pathways, acute and chronic and may be associated with drugs that are employed in MS. The authors propose is to review the neuro-ophthalmologic manifestations of multiple sclerosis other than optic neuritis. Recognition of these leads to a more targeted treatment and may prevent visual deterioration., (Copyright © 2020. Published by Elsevier B.V.)

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.)

Objective: Patients with amnestic Mild Cognitive Impairment (aMCI), usually considered an early stage of Alzheimer's disease, have deficits not only in retrospective memory (RM), that is, recalling of past events, words or people, but also on prospective memory (PM), the cognitive ability of remembering to execute delayed intentions in the future. This study investigated whether patients with aMCI refer more PM complaints as compared with RM complaints, and whether this might depend upon short-term vs long-term items or time-based vs event-based tasks., Methods: Patients with aMCI (n = 178) and healthy controls (n = 160) underwent the Prospective and Retrospective Memory Questionnaire (PRMQ), a 16-item instrument to appraise differences between PM and RM complaints, as well as a general mental state examination, a subjective memory complaints questionnaire, objective memory tests, and assessment of depressive symptoms and activities of daily living., Results: Patients with aMCI reported more memory complaints evaluated with the PRMQ (total score = 44.3 ± 10.8) as compared with controls (36.7 ± 9.8, P < 0.001). Using a mixed effect repeated-measures analysis of covariance (ANCOVA) showed that participants generally referred more retrospective than prospective memory complaints. Patients with aMCI had significantly more complaints on short-term memory as compared with long-term memory, and more complaints in time-based (auto-initiated) as compared with event-based tasks, than healthy controls., Conclusion: Patients with aMCI reported significantly more difficulties on short-term memory, presumably reflecting internal temporal lobe pathology typical of Alzheimer's disease, and more complaints on time-based tasks, which are cognitively very demanding, but did not seem particularly troubled regarding prospective memory., (Copyright © 2018 John Wiley & Sons, Ltd.)

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.

Background: Nowadays, the number of patients undergoing carotid artery stenting (CAS) is increasing rapidly, and these patients require follow-up to monitor the patency of the device and the potential development of an in-stent restenosis (ISR)., Methods: Patients undergoing CAS at our institution underwent duplex ultrasound (DUS) at 6 months, 12 months, and yearly thereafter, using a prespecified protocol. Restenosis was defined as a more than 50% diameter-reducing stenosis. Patients with DUS-diagnosed restenosis underwent carotid computerized tomography angiography (CTA) to confirm the presence of ISR. The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. Interactions between restenosis and baseline variables were assessed using odds ratio., Results: Between August 2007 and March 2012 were performed 100 procedures in 96 patients, with a median age of 72.9 years. The mean duration of follow-up was 29.2 months (±8.4). Restenosis occurred in 6 carotid arteries. The Kaplan-Meier estimate for the frequency of restenosis in 2 years was 6.0% and for severe restenosis was 3.0%. There were no occlusions. Diabetic patients seem to have a higher risk of ISR (OR=3.23, 95% CI .55-18.9). Carotid CTA was in agreement with the degree of stenosis estimated by DUS in all cases., Conclusions: Our results, using a DUS protocol and a specific peak systolic velocity threshold, showed that the frequency of restenosis at 2 years after CAS is 6.0% and so that CAS is probably a durable revascularization procedure. We emphasize the diagnostic agreement achieved between DUS and carotid CTA., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

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.)

Osseointegration of metallic implants used in orthopedic surgery requires that osteoprogenitor cells attach and adhere to the surface, then proliferate, differentiate into osteoblasts, and finally produce mineralized matrix. Because the ability of progenitor cells to attach to a scaffold surface during early stages is important in the development of new tissue structures, we developed in our laboratory, a strategy involving grafting of implants with a polymer of sodium styrene sulfonate (polyNaSS) used as a scaffold which enables human mesenchymal stem cells (hMSCs) interactions. In the present study, we investigated the cellular response of hMSCs to polyNaSS surfaces of titanium (Ti). In particular, cell proliferation, cell viability, cell differentiation, and cell spreading were evaluated. Results showed that cell proliferation and cell viability did not differ with any statistical significance between modified and unmodified Ti surfaces. Interestingly, culture of MSCs on polyNaSS surfaces resulted in a significant increase of cell spreading and cell differentiation compared with the other tested surfaces. These results suggest that titanium surface grafted with polyNaSS is a suitable scaffold for bone tissue engineering., (Copyright © 2012 Wiley Periodicals, Inc.)