Publications by authors named "Maria Jose Sá"

54 Publications

RISCOP-Cognitive profile in a Portuguese cohort of radiological isolated syndrome patients: A case-control study.

Mult Scler Relat Disord 2021 Feb 10;50:102832. Epub 2021 Feb 10.

Department of Neurology, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte, Lisboa, Portugal.

Introduction: Radiologically isolated syndrome (RIS) refers to the incidental discovery of white matter lesions suggestive of MS, on brain MRI, in asymptomatic patients. Recent studies suggest similar features of cognitive impairment between RIS and MS patients. Also, lower levels of health-related quality of life (QOL) and fatigue are reported in such patients.

Aims: characterize and compare the cognitive profile of a multicentric Portuguese cohort of RIS patients with a control group.

Methods: multicentric comparative study of a cohort of adult patients with RIS, and age and gender-matched controls followed in the headache outpatient clinic with prior MRI not fulfilling criteria for RIS diagnosis. We conducted interviews with participants, collected clinical data and applied the BICAMS battery and self-reported questionnaires (HADS, MFIS, MSQOL-54).

Results: we evaluated 31 patients with RIS (median age 46 years, IQR [(Dusankova et al., 2012-52], 72% women) and 19 control individuals (median age 32 years, IQR [(O'Jile et al., 2005-48], 71% women). Prevalence of cognitive impairment did not differ between groups (16% of the RIS and 10% of the controls, p=0.579). We found no differences between groups on the BICAMS tests, although the results of the California Verbal Learning Test (CVLT-II) score presented a trend to significance, with a lower value on the RIS group (53.9 vs. 59.3, p=0.066). There were no significant differences regarding fatigue, QOL, anxiety/depression scores.

Conclusion: this is the first study on a Portuguese cohort of RIS patients assessing cognitive profile with BICAMS. A non-neglectable part of our cohort presented cognitive impairment. Our findings add to previous studies in suggesting that a more pronounced impairment of verbal memory and learning, evaluated by CVLT-II, may be present in RIS patients compared to controls. BICAMS should be assessed on future studies with larger cohorts.
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http://dx.doi.org/10.1016/j.msard.2021.102832DOI Listing
February 2021

Determinants of therapeutic lag in multiple sclerosis.

Mult Scler 2021 Jan 11:1352458520981300. Epub 2021 Jan 11.

CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia/Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.

Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.

Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants.

Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5).

Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.
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http://dx.doi.org/10.1177/1352458520981300DOI Listing
January 2021

Delay from treatment start to full effect of immunotherapies for multiple sclerosis.

Brain 2020 09;143(9):2742-2756

CORe, Department of Medicine, University of Melbourne, Melbourne, 3050, Australia.

In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag.
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http://dx.doi.org/10.1093/brain/awaa231DOI Listing
September 2020

[Recommendations about Multiple Sclerosis Management during Pregnancy, Partum and Post-Partum: Consensus Position of the Portuguese Multiple Sclerosis Study Group].

Acta Med Port 2020 Sep 1;33(9):611-621. Epub 2020 Sep 1.

Serviço de Neurologia. Hospital Beatriz Ângelo. Loures. Portugal.

Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare professionals involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and postpartum, existing uncertainties have been complicated by the increase in the number of treatments available in recent years. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period.
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http://dx.doi.org/10.20344/amp.12777DOI Listing
September 2020

Trends in hospital readmissions in Multiple Sclerosis patients between 2009 and 2015.

Mult Scler Relat Disord 2020 Oct 12;45:102396. Epub 2020 Jul 12.

Neurology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal.

Background: Readmission rate is an important healthcare quality metric and remains a problem in Multiple Sclerosis (MS) patients, nonetheless information about this issue is scarce. We present the first study to estimate hospital readmissions in a MS hospital-based European cohort.

Methods: Retrospective cohort study of patients with at least one hospitalization with a primary discharge of MS from August 1, 2009 and July 31, 2015. The primary outcome was hospitalization within 30 days post-discharge (30-DR). The secondary outcomes included length of stay during index and readmission, total hospital readmissions during the study period, predictors and causes of readmission.

Results: Forty-four (41.5%) patients had a hospital readmission during the six years of this study, 11.3% of them 30-DR, mainly due to infections (58.5%). The two most common comorbidities in these patients were neurogenic bladder (47.7%) and ischemic heart disease (18.1%). Progressive MS subtype was the main predictor of 30-DR, even after adjustment for therapy (OR: 6.29; p = 0.016), with an area under the curve of 0.73.

Conclusion: Progressive MS subtypes and "second-line drugs" carry a higher risk of hospital readmission soon after discharge. The impact and cost-effectiveness of strategies to lower readmission rates in MS should be the focus of upcoming studies.
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http://dx.doi.org/10.1016/j.msard.2020.102396DOI Listing
October 2020

State of the Art and Future Challenges in Multiple Sclerosis Research and Medical Management: An Insight into the 5th International Porto Congress of Multiple Sclerosis.

Neurol Ther 2020 Dec 14;9(2):281-300. Epub 2020 Jul 14.

Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

The 5th International Porto Congress of Multiple Sclerosis took place between the 14th and 16th of February 2019 in Porto, Portugal. Its intensive programme covered a wide-range of themes-including many of the hot topics, challenges, pitfalls and yet unmet needs in the field of multiple sclerosis (MS)-led by a number of well-acknowledged world experts. This meeting review summarizes the talks that took place during the congress, which focussed on issues in MS as diverse as the development and challenges of progressive MS, epidemiology, differential diagnosis, medical management, molecular research and imaging tools.
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http://dx.doi.org/10.1007/s40120-020-00202-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606370PMC
December 2020

The epidemiology of multiple sclerosis in the entre Douro e Vouga region of northern Portugal: a multisource population-based study.

BMC Neurol 2020 May 19;20(1):195. Epub 2020 May 19.

Serviço de Neurologia, Centro Hospitalar de Entre Douro e Vouga, Santa Maria da Feira, Portugal.

Background: The prevalence of Multiple Sclerosis (MS) has been increasing worldwide and the north-south gradient of prevalence may be disappearing in the Northern hemisphere. The few previous prevalence studies performed in Portugal have reported a lower prevalence than the average for Western Europe. The aim of this study is to estimate the prevalence of MS in the Entre Douro e Vouga region, in Northern Portugal.

Methods: Multiple overlapping sources were used to ascertain all cases from the reference population: records from hospitals in the region and neighbouring regions; diagnostic databases of primary care physicians; and applications for disability benefits. The prevalence date was set at 1 January 2014. The reference population was 274,859 inhabitants. Patients' neurologists were contacted to retrieve clinical information and confirm the diagnosis based.

Results: A total of 177 patients were identified after eliminating duplicates from different sources. The female to male ratio was 1.9 and the mean age at disease onset was 33.5 (standard deviation: 10.3). Clinically isolated syndrome accounted for 9.0% of patients, relapsing remitting for 58.8%, secondary progressive for 20.3% and primary progressive for 11.8%. The prevalence was estimated in 64.4 patients per 100,000 (95% confidence interval: 54.9;73.9).

Conclusions: In this study we report a higher point prevalence of MS than had been previously described in Portugal, but still far from the higher values recently reported in other Southern European countries.
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http://dx.doi.org/10.1186/s12883-020-01755-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236954PMC
May 2020

Correction to: Abstracts from the 5th International Porto Congress of Multiple Sclerosis.

Authors:
Maria José Sá

Neurol Ther 2019 Dec;8(2):511

Department of Neurology, Hospital de S. Joáo Al. Hernáni Monteiro, Porto, Portugal.

The given name of one of the authors was incorrectly published as Vera in abstract EPIII028 "Anti-MOG Antibody-Positive Isolated Longitudinally Extensive Transverse Myelitis". The correct name should read as follows.
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http://dx.doi.org/10.1007/s40120-019-00161-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858888PMC
December 2019

JC virus antibodies in Portuguese multiple sclerosis patients: JUSTIFY study results.

J Neurol Sci 2019 Nov 13;406:116426. Epub 2019 Aug 13.

Centro Hospitalar de Setúbal, Hospital de São Bernardo, Department of Neurology, Setubal, Portugal.

Objective: To confirm anti-JC virus (JCV) antibody seroprevalence in Portuguese patients with relapsing-remitting multiple sclerosis (RRMS) and to determine their anti-JCV antibody index.

Methods: JUSTIFY was a retrospective, multicentre study that included 655 RRMS patients tested at least once with the anti-JCV antibody assay STRATIFY JCV DxSelect. Demographic data, multiple sclerosis history and results of the anti-JCV antibody test were collected, along with physicians' reasons for requesting the test and the impact of the results.

Results: Overall anti-JCV antibody seroprevalence was 60.8% (95% confidence interval, 56.9-64.5). Seroprevalence was associated with higher age (P = .030) and was lower in natalizumab-treated patients (P < .001). The mean anti-JCV antibody index of immunosuppressant-naive patients was 1.5 ± 1.3 (n = 378). The main reasons for performing the test were clinical characterization (35.5%) and medication change (26.2%). In patients who switched treatments (n = 109), fingolimod (47.7%) and natalizumab (26.6%) were the most commonly chosen new treatments.

Conclusions: The study confirmed the high anti-JCV antibody prevalence in Portuguese RRMS patients and its association with age. These data can be used to better understand the benefit-risk profile of natalizumab treatment in Portuguese patients and to support progressive multifocal leukoencephalopathy risk management strategies.
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http://dx.doi.org/10.1016/j.jns.2019.116426DOI Listing
November 2019

Recognizing migraine in patients with multiple sclerosis improves the quality of health care.

Authors:
Maria José Sá

Arq Neuropsiquiatr 2019 23;77(9):599-600. Epub 2019 Sep 23.

Centro Hospitalar Universitário de São João, Departamento de Neurologia, Porto, Portugal.

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http://dx.doi.org/10.1590/0004-282X20190101DOI Listing
March 2020

A multicenter, non-interventional study to evaluate the disease activity in Multiple Sclerosis after withdrawal of Natalizumab in Portugal.

Clin Neurol Neurosurg 2019 Sep 16;184:105390. Epub 2019 Jun 16.

Neurology Department, Hospital Santo António dos Capuchos, Centro Hospitalar de Lisboa Central, Alameda Santo António dos Capuchos, 1169-050, Lisbon, Portugal.

Objectives: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study.

Patients And Methods: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model.

Results: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ± 8.3 years at diagnosis, and a mean age of 37.2 ± 10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ± 1.2, 0.2 ± 0.5 and 0.6 ± 1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks.

Conclusion: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal.
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http://dx.doi.org/10.1016/j.clineuro.2019.105390DOI Listing
September 2019

Abstracts from the 5th International Porto Congress of Multiple Sclerosis.

Authors:
Maria José Sá

Neurol Ther 2019 Jun;8(Suppl 1):1-31

Department of Neurology, Hospital de S. Joáo Al. Hernáni Monteiro, Porto, Portugal.

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http://dx.doi.org/10.1007/s40120-019-0135-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542906PMC
June 2019

Diagnostic Delay of Multiple Sclerosis in a Portuguese Population.

Acta Med Port 2019 Apr 30;32(4):289-294. Epub 2019 Apr 30.

Neurology Department. Centro Hospitalar do Porto. Porto. Portugal.

Introduction: Multiple sclerosis is a chronic inflammatory disease, in which a diagnostic delay could reduce the available therapeutic options. Therefore, it is important to monitor the time to diagnosis and understand factors that may potentially reduce it. The objective of this study was to determine the time between the first symptoms and the diagnosis of multiple sclerosis and which factors may contribute to a diagnostic delay.

Material And Methods: Cross-sectional multicenter study, with retrospective data analysis, conducted in five tertiary Portuguese hospitals. Patients were consecutively selected from each local multiple sclerosis patients´ database. Sociodemographic and initial clinical data were collected through a questionnaire. Date of final diagnosis and multiple sclerosis classification was obtained from clinical files.

Results: A total of 285 patients were included with mean age at diagnosis of 36 years. The median time between first clinical manifestation and multiple sclerosis diagnosis was nine months (IQR 2 - 38). Diagnostic delay was associated with an older age (p < 0.001; r = 0.35), motor deficit at onset [26.5 months (IQR 4.5 - 56.5); p = 0.0005], higher number of relapses before diagnosis (p < 0.001; r = 0,626), first observation by other medical specialty [11 months (IQR 2 - 48); p < 0.001], prior alternative diagnosis [20 months (IQR 4 - 67.5); p < 0.001] and primary progressive subtype [37 months (IQR 25 - 64.5); p < 0.001]. The most significant delay occurred between the initial symptom and neurological observation.

Discussion: A significant delay occurred between initial symptoms and the diagnosis of multiple sclerosis, reflecting the need toincrease awareness of this entity and its diverse symptom presentation.
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http://dx.doi.org/10.20344/amp.11187DOI Listing
April 2019

Electrochemical Immunosensor for TNFα-Mediated Inflammatory Disease Screening.

ACS Chem Neurosci 2019 06 18;10(6):2676-2682. Epub 2019 Apr 18.

International Iberian Nanotechnology Laboratory , Braga 4715-330 , Portugal.

Inflammation associated with cancer, neurodegenerative, ocular, and autoimmune diseases has a considerable impact on public health. Tumor necrosis factor alpha (TNFα) is a key mediator of inflammatory responses, responsible for many of the systemic manifestations during the inflammatory process. Thus, inhibition of TNFα is a commonplace practice in the treatment of these disorders. Successful therapy requires the ability to determine the appropriate dose of anti-TNFα drugs to be administered in a timely manner, based on circulating TNFα levels. In this Letter, we report the development of an immunosensor technology able to quantify TNFα at the picogram level in relevant human body fluids, holding the potential to early detect inflammation  and monitor TNFα levels during treatment, enabling TNFα-targeted treatments to be tailored according to the immune status of an individual patient. This immunosensor technology is significantly more rapid and sensitive than conventional enzyme linked immunosorbent assays, maintaining high specificity and requiring small sample volumes. These features might also be advantageous in the context of personalized medicine, as this analytical platform can deliver advanced diagnostics and reduce clinical burden.
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http://dx.doi.org/10.1021/acschemneuro.9b00036DOI Listing
June 2019

[Recommendations About Multiple Sclerosis Management During Pregnancy, Partum and Post-Partum: Consensus Position of The Portuguese Multiple Sclerosis Study Group and The Portuguese Society of Obstetrics and Maternal-Fetal Medicine].

Acta Med Port 2018 Dec 28;31(12):785-795. Epub 2018 Dec 28.

Serviço de Neurologia. Hospital Beatriz Ângelo. Loures. Portugal.

Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare providers involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues, and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and the postpartum period, uncertainties have been complicated by the increase in recent years of the number of available treatments. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period.
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http://dx.doi.org/10.20344/amp.10752DOI Listing
December 2018

Pregnancy outcomes in Portuguese women with multiple sclerosis: The PREGNIMS study.

Mult Scler Relat Disord 2019 Feb 26;28:172-176. Epub 2018 Dec 26.

Centre for Child Development, Neuropediatrics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Avenida Afonso Romão, 3000-602 Coimbra, Coimbra, Portugal; Laboratory of Pharmacology & Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Electronic address:

Introduction: Several questions about pregnancy in women with multiple sclerosis (MS) have been discussed, but clarification is still needed in some very practical issues. Portuguese data on this subject remain scattered and need to be analyzed in order to standardize clinical practice.

Objective: This study aimed to describe and analyze the impact of MS on pregnancy and perinatal health of children born to Portuguese mothers with the disease.

Material And Methods: This is a multicenter, retrospective study of a cohort of Portuguese women with MS who were pregnant and who gave birth between 01/01/2011 and 31/12/2015. Demographic and clinical data related to maternal disease, pregnancy progression and events, childbirth and newborn health were collected.

Results: Ninety-seven women were recruited and 90 live births were evaluated. The mean maternal age at conception was 32.5 years, and 63.9% had no relapses in the previous year (98.0% had a relapsing-remitting MS and the EDSS score was ≤ 3 in 92.8% of the cases). Only 50.5% of the women had a preconception specific evaluation and 60 children were exposed to immunomodulatory therapies during pregnancy. Nineteen women had relapses during pregnancy. Childbirth was induced in 22.7% of the cases, and the caesarean section rate was 34%. Children exposed to immunomodulatory drugs during pregnancy had a lower birth length (p = 0.014), and there was also a trend toward lower birth weight (p = 0.054) in these newborns. Pre-conception EDSS score negatively correlated with the duration of pregnancy (r = -0.22; p = 0.029), weight (r = -0.23; p = 0.031) and cephalic perimeter at birth (r = -0.24; p = 0.033). There was no relationship between the occurrence of relapses or progression in EDSS score during pregnancy with any variables related to the newborn.

Conclusions: In our cohort, it has been confirmed that MS has no negative effect on pregnancy or on children's perinatal health. However, the use of immunomodulatory drugs may have some impact on newborns' somatometric features.
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http://dx.doi.org/10.1016/j.msard.2018.12.033DOI Listing
February 2019

International consensus on quality standards for brain health-focused care in multiple sclerosis.

Mult Scler 2019 11 1;25(13):1809-1818. Epub 2018 Nov 1.

Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK.

Background: Time matters in multiple sclerosis (MS). Irreversible neural damage and cell loss occur from disease onset. The MS community has endorsed a management strategy of prompt diagnosis, timely intervention and regular proactive monitoring of treatment effectiveness and disease activity to improve outcomes in people with MS.

Objectives: We sought to develop internationally applicable quality standards for timely, brain health-focused MS care.

Methods: A panel of MS specialist neurologists participated in an iterative, online, modified Delphi process to define 'core', 'achievable' and 'aspirational' time frames reflecting minimum, good and high care standards, respectively. A multidisciplinary Reviewing Group (MS nurses, people with MS, allied healthcare professionals) provided insights ensuring recommendations reflected perspectives from multiple stakeholders.

Results: Twenty-one MS neurologists from 19 countries reached consensus on most core (25/27), achievable (25/27) and aspirational (22/27) time frames at the end of five rounds. Agreed standards cover six aspects of the care pathway: symptom onset, referral and diagnosis, treatment decisions, lifestyle, disease monitoring and managing new symptoms.

Conclusion: These quality standards for core, achievable and aspirational care provide MS teams with a three-level framework for service evaluation, benchmarking and improvement. They have the potential to produce a profound change in the care of people with MS.
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http://dx.doi.org/10.1177/1352458518809326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826858PMC
November 2019

Validation of the brief international cognitive assessment for multiple sclerosis (BICAMS) in the Portuguese population with multiple sclerosis.

BMC Neurol 2018 Oct 17;18(1):172. Epub 2018 Oct 17.

MS Clinic, Department of Neurology, Centro Hospitalar São João Porto, Alameda Prof. Hernâni Monteiro, 4200 - 319, Porto, Portugal.

Background: The validation of international cognitive batteries in different multiple sclerosis (MS) populations is essential. Our objective was to obtain normative data for the Portuguese population of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and assess its reliability.

Methods: The BICAMS was applied to 105 MS patients and 60 age, gender and education matched healthy controls (HC). In order to test its reliability, BICAMS was re-administered in a subset of 25 patients after a 7-month interval.

Results: Most participants were women, with a mean age of 37, 21 years and a mean of 14,08 years of education. The vast majority of the MS patients (92.4%) had the relapsing remitting type, 58.1% were professionally active, mean disease duration was 6.52 years, median EDSS score was 1.5 (range: 0-6.0) and the median MSSS score was 2.01 (IQR range: 3.83). The MS group presented significantly higher scores of anxiety and depression than HC and 47,4% had fatigue. The MS group performed significantly worse than the control group across the three neuropsychological tests, yielding the following values: SDMT: t(165) = 3.77, p = .000; CVLT-II: t(165) = 2.98, p = .003; and BVMT-R: t(165) = 2.94, p = .004. The mean raw scores for Portuguese normative data were as follows: SDMT: 58.68 ± 10.02; CVLT-II: 60.47 ± 10.12; and BVMT-R: 24.68 ± 5.52. Finally, test-retest reliability coefficients for each test were as follows: SDMT: r = .90; CVLT-II: r = .71; and BVMT-R: r = .84.

Conclusions: The Portuguese version of BICAMS here in described is a reliable monitoring instrument for identifying MS patients with cognitive impairment.
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http://dx.doi.org/10.1186/s12883-018-1175-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192303PMC
October 2018

Consensus Recommendations of the Multiple Sclerosis Study Group and Portuguese Neuroradiological Society for the Use of the Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 1.

Acta Med Port 2018 May 30;31(5):281-289. Epub 2018 May 30.

Serviço de Neurologia. Hospital Beatriz Ângelo. Loures. Portugal.

Introduction: Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice.

Material And Methods: The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper.

Results: We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis.

Conclusion: We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.
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http://dx.doi.org/10.20344/amp.10503DOI Listing
May 2018

Emerging Biosensing Technologies for Neuroinflammatory and Neurodegenerative Disease Diagnostics.

Front Mol Neurosci 2018 16;11:164. Epub 2018 May 16.

International Iberian Nanotechnology Laboratory, Braga, Portugal.

Neuroinflammation plays a critical role in the onset and progression of many neurological disorders, including Multiple Sclerosis, Alzheimer's and Parkinson's diseases. In these clinical conditions the underlying neuroinflammatory processes are significantly heterogeneous. Nevertheless, a common link is the chronic activation of innate immune responses and imbalanced secretion of pro and anti-inflammatory mediators. In light of this, the discovery of robust biomarkers is crucial for screening, early diagnosis, and monitoring of neurological diseases. However, the difficulty to investigate biochemical processes directly in the central nervous system (CNS) is challenging. In recent years, biomarkers of CNS inflammatory responses have been identified in different body fluids, such as blood, cerebrospinal fluid, and tears. In addition, progress in micro and nanotechnology has enabled the development of biosensing platforms capable of detecting in real-time, multiple biomarkers in clinically relevant samples. Biosensing technologies are approaching maturity where they will become deployed in community settings, at which point screening programs and personalized medicine will become a reality. In this multidisciplinary review, our goal is to highlight both clinical and recent technological advances toward the development of multiplex-based solutions for effective neuroinflammatory and neurodegenerative disease diagnostics and monitoring.
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http://dx.doi.org/10.3389/fnmol.2018.00164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964192PMC
May 2018

Depressive Symptomatology, Presenteeism Productivity, and Quality of Life: A Moderated Mediation Model.

J Occup Environ Med 2018 04;60(4):301-308

ISCTE-IUL, Lisboa, Portugal (Lopes, Drs Ferreira, Passos, Neves); Hospital S. João, Porto, Portugal (Sousa, Dr Sá); and Health Sciences, University Fernando Pessoa, Porto, Portugal (Dr Sá).

: In this study, we intend to test if presenteeism productivity influences the relationship between depressive symptoms and quality of life and also if this relation is conditional upon levels of information processing speed. Data were collected from 231 participants who completed a neuropsychological test and self-reported measures. Results revealed a significant indirect effect and a significant moderation effect. The association between depressive symptoms and presenteeism productivity was moderated by information processing speed only in their medium and high levels. Our findings suggest that individuals with higher levels of processing speed may have more difficulty in focusing on work without being distracted by health problems. The present investigation has made a significant contribution to the existing literature about cognitive function and productivity in workers with depressive symptomatology and its effects on their quality of life.
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http://dx.doi.org/10.1097/JOM.0000000000001253DOI Listing
April 2018

Cerebral autoregulation is preserved in multiple sclerosis patients.

J Neurol Sci 2017 Oct 8;381:298-304. Epub 2017 Sep 8.

Department of Clinical Neurosciences and Mental Health, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal; Department of Neurology, São João Hospital Center, 4200-319 Porto, Portugal.

Multiple sclerosis (MS) is an inflammatory disease that may also be associated with vascular dysfunction. One master component of vascular regulation is cerebral autoregulation (CA). We aimed to investigate the integrity of CA in MS patients and study its relationship with autonomic dysfunction (AD), magnetic-resonance-imaging (MRI) lesion load and hemodynamic parameters. We enrolled 20 relapsing-remitting MS and 20 healthy subjects. CA was assessed by transfer function analysis parameters (coherence, gain and phase), as obtained in the very low, low and high-frequency domains (VLF, LF, HF, respectively). We evaluated the autonomic parameters heart rate variability and spontaneous baroreflex sensitivity (BRS). There were no significant differences in CA parameters between MS and controls (p>0.05). Lesion load was not correlated with any CA parameter. LF gain was positively correlated with BRS in both groups (MS: p=0.017; controls: p=0.025). Brainstem lesion load in MS was associated with higher systolic blood pressure (SBP; p=0.009). Our findings suggest that CA is preserved in our MS cohort. On the other hand, AD in MS patients with brainstem lesions could contribute to the increase of supine SBP. Whether this systemic deregulation could contribute to disease burden remains to be investigated.
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http://dx.doi.org/10.1016/j.jns.2017.09.009DOI Listing
October 2017

Verbal Selective Reminding Test (six-trial administration): Regression-based norms for a portuguese version.

Appl Neuropsychol Adult 2018 Nov-Dec;25(6):523-531. Epub 2017 Jun 30.

a BRU-IUL, Instituto Universitário de Lisboa (ISCTE-IUL) , Lisboa , Portugal.

The Verbal Selective Reminding Test (VSRT) is a widely used measure to evaluate verbal learning and memory associated with different neurological conditions. The goal of this study was to extend the use of the six-version trial of this test to the Portuguese population, through the production of adjusted normative data. The normative sample consists of 309 healthy participants aged between 20 and 70, with an educational level ranging from 4 to 23 years of formal. Gender, education, and age effects were explored. In addition, the reliability of the test was also analyzed and normative data produced. Gender, age, and education were significantly associated with VSRT performance. The test revealed excellent inter-rater reliability and good test-retest reliability. The normative data is presented as a regression-based formula to adjust test scores for gender, education and age. The correspondence between adjusted scores and percentile distribution was calculated. Since a test with appropriate norms is fundamental to an appropriate assessment of memory functioning, the normative data produced in this study improves the applicability of VRST for both clinical and research proposes in the Portuguese population. Further studies might also explore the adequacy of these norms for other Portuguese-speaking countries.
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http://dx.doi.org/10.1080/23279095.2017.1336712DOI Listing
October 2018

New insights into the burden and costs of multiple sclerosis in Europe: Results for Portugal.

Mult Scler 2017 Aug;23(2_suppl):143-154

Mapi Group, Stockholm, Sweden.

Background: In order to assess the value of management strategies in multiple sclerosis (MS), outcome data have to be combined with cost data. This, in turn, requires that cost data be regularly updated.

Objective And Methods: This study is part of a cross-sectional retrospective study in 16 countries collecting current data on resource consumption, work capacity and health-related quality of life (HRQoL). Descriptive analyses are presented by level of severity; costs are estimated in the societal perspective, in EUR 2015.

Results: A total of 535 patients (mean age 48.5 years) participated; 92% were below retirement age and of these, 43% were employed. Employment was related to disease severity, and MS was felt to affect productivity at work by 72% of patients, most often through fatigue. Overall, 98% and 74% of patients felt that fatigue and cognition were a problem. Mean utility and costs were 0.756 and €16,500 at the Expanded Disability Status Scale (EDSS) 0-3, 0.572 and €28,700 at EDSS 4-6.5 and 0.206 and €34,400 at EDSS 7-9. The average cost of a relapse was estimated at €2930.

Conclusion: This study illustrates the burden of MS on Portuguese patients and provides current data that are important for the development of health policies.
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http://dx.doi.org/10.1177/1352458517708667DOI Listing
August 2017

Social support network and quality of life in multiple sclerosis patients.

Arq Neuropsiquiatr 2017 May;75(5):267-271

Universidade Beira Interior, Faculdade de Ciências da Saúde, Covilhã, Portugal.

Objective: To analyse the relationship between the social support network (SSN) and health related quality of life (HRQOL) in multiple sclerosis (MS) patients.

Methods: The sample comprised 150 consecutive MS patients attending our MS clinic. To assess the socio-demographic data, a specifically designed questionnaire was applied. The HRQOL dimensions were measured with the Short-Form Health Survey Questionnaire-SF36 and the SSN with the Medical Outcomes Study Social Support Survey. Spearman's correlation was used to compare the magnitude of the relationship between the SSN and HRQOL.

Results: The mean patient age was 41.7 years (± 10.4; range: 18-70 yr); the mean Expanded Disability Status Score was 2.5 (±2.4; range: 0-9). There was a statistically significant correlation between the structure of the SSN and the HRQOL.

Conclusion: The composition of the SSN, social group membership and participation in voluntary work have an important role in the HRQOL of patients with MS.
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http://dx.doi.org/10.1590/0004-282X20170036DOI Listing
May 2017

Paced Auditory Serial Addition Test (PASAT 3.0 s): Demographically corrected norms for the Portuguese population.

Appl Neuropsychol Adult 2018 Sep-Oct;25(5):417-423. Epub 2017 May 23.

c Serviço de Neurologia , Centro Hospitalar São João , Porto , Portugal.

The main goal of this study was to produce adjusted normative data for the Portuguese population on the Paced Auditory Serial Addition Test (PASAT 3.0 s), the version used in the Brief Repeatable Battery of Neuropsychological Tests developed by the National Multiple Sclerosis Society. The study included 326 community-dwelling individuals (199 women and 127 men) aged between 20 and 70 (mean = 40.33, SD = 14.40), who had educational backgrounds ranging from 4 to 23 years of schooling (mean = 12.28, SD = 4.39). Age, gender and qualifications revealed differences in explaining their performance on the PASAT 3.0 s. Men had significantly better performance on the PASAT 3.0 s than women, even though this represents a small effect size r = 0.18. Demographically corrected normative data was developed and important information regarding performance on the PASAT 3.0 s test is provided. Results are discussed and presented in tables and a formula is presented for computing age, gender and education adjusted T-scores for performance on the PASAT 3.0 s. These results should be considered as useful reference values for clinicians and investigators when applying the PASAT 3.0 s to assess cognitive function like information processing speed in different pathologies.
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http://dx.doi.org/10.1080/23279095.2017.1323752DOI Listing
October 2018

Autonomic dysfunction in multiple sclerosis is better detected by heart rate variability and is not correlated with central autonomic network damage.

J Neurol Sci 2016 Aug 25;367:133-7. Epub 2016 May 25.

Dept. Neurology, Centro Hospitalar de São João, Faculty of Medicine of University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address:

Background: MS-associated autonomic dysfunction (AD) in multiple sclerosis (MS) is poorly understood and the best method for its detection unestablished. We compared classical Ewing battery and newer methods as heart rate variability (HRV) and spontaneous baroreflex sensibility (BRS) to detect AD in MS and related them to central autonomic network (CAN) lesions.

Methods: We enrolled 20 relapsing-remitting MS patients, median age of 36 (interquartile range 32-46) years, disease duration of 5.5 (2.2-6.8) years, Expanded Disability Status Scale (EDSS) score of 1.0 (1.0-1.5) and 20 age- and gender-matched healthy controls. We assessed Ewing battery and spontaneous HRV and BRS. CAN involvement was evaluated by magnetic resonance imaging.

Results: HRV showed both parasympathetic and sympathetic significant impairment in MS (p<0.05). From Ewing battery only isometric test was significantly decreased in MS (p=0.006). Disease duration and severity, lesion burden and CAN involvement were not correlated with laboratorial parameters.

Conclusions: Our MS cohort had both sympathetic and parasympathetic dysfunction independently from disease duration, neurological deficits and lesion burden or CAN involvement. HRV analysis maybe more useful than classical Ewing battery to screen AD.
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http://dx.doi.org/10.1016/j.jns.2016.05.049DOI Listing
August 2016

BRBN-T validation: adaptation of the Selective Reminding Test and Word List Generation.

Arq Neuropsiquiatr 2015 Oct;73(10):867-72

Hospital S. João, Porto, PT.

Objective This study aims to present the Selective Reminding Test(SRT) and Word List Generation (WLG) adaptation to the Portuguese population, within the validation of the Brief Repeatable Battery of Neuropsychological Tests (BRBN-T)for multiple sclerosis (MS) patients.Method 66 healthy participants (54.5% female) recruited from the community volunteered to participate in this study.Results A combination of procedures from Classical Test Theory (CTT) and Item Response Theory (ITR) were applied to item analysis and selection. For each SRT list, 12 words were selected and 3 letters were chosen for WLG to constitute the final versions of these tests for the Portuguese population.Conclusion The combination of CTT and ITR maximized the decision making process in the adaptation of the SRT and WLG to a different culture and language (Portuguese). The relevance of this study lies on the production of reliable standardized neuropsychological tests, so that they can be used to facilitate a more rigorous monitoring of the evolution of MS, as well as any therapeutic effects and cognitive rehabilitation.
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http://dx.doi.org/10.1590/0004-282X20150134DOI Listing
October 2015

Gluten chorea.

Clin Neurol Neurosurg 2015 Nov 17;138:8-9. Epub 2015 Jul 17.

Department of Neurology, Centro Hospitalar de São João, Alameda Professor Hernâni Monteiro, 4202-451 Porto, Portugal; Faculty of Health Sciences, Universidade Fernando Pessoa, Praça 9 de Abril 349, 4249-004 Porto, Portugal.

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http://dx.doi.org/10.1016/j.clineuro.2015.07.009DOI Listing
November 2015

Relapsing-remitting multiple sclerosis: patterns of response to disease-modifying therapies and associated factors: a national survey.

Neurol Ther 2014 Dec 3;3(2):89-99. Epub 2014 Sep 3.

Centro Hospitalar e Universitário de Coimbra, Hospitais da Universidade de Coimbra, Coimbra, Portugal.

Introduction: Current treatments for relapsing-remitting multiple sclerosis (RRMS) are only partially effective. The objective of this study was to characterize treatment response in RRMS patients in Portugal to 12-month therapy with first-line disease-modifying therapies.

Methods: In this retrospective study, neurologists at participating centers completed survey questionnaires using records of patients with RRMS who had received first-line treatment with one of five European Medicine Agency-approved agents in the 12 months prior to inclusion in the survey. Sub-optimal responders included patients treated for at least 1 year, and who had ≥1 relapse(s) or an increase of 1.5 points on the Expanded Disability Status Scale (EDSS; if baseline EDSS was 0) or an increase of ≥0.5 points (baseline EDSS ≥1). Optimal responders included patients treated for at least 1 year without relapse and who had an increase of <1.5 points on EDSS (if baseline EDSS was 0) or no increase in EDSS (baseline EDSS ≥1).

Results: Data for 1,131 patients from 15 centers were analyzed. Twenty-six percent (95% confidence interval 23-28%) of patients had sub-optimal treatment response. Duration of therapy (P < 0.001), age at the start of therapy (P = 0.03), and baseline EDSS score (P < 0.001), were significantly different among treatments. Sub-optimal treatment response appeared to be related only to a more severe EDSS score at baseline and did not differ among therapies.

Conclusion: Neurologists should closely monitor patients to optimize treatment strategies and better control disease, improving prognosis.
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http://dx.doi.org/10.1007/s40120-014-0019-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386429PMC
December 2014