Cognitive impairment and markers of optical neurodegeneration in early multiple sclerosis.

INTRODUCTION: Cognitive impairment and retinal atrophy have been proposed as two potential markers of neurodegeneration in multiple sclerosis (MS). We aimed at assessing the relation between peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) atrophy and cognitive performance in early MS. METHODS: This is a multicenter cross-sectional study on patients with early MS (clinically isolated syndrome and relapsing-remitting MS), with an EDSS score ≤ 3.0. Patients with previous optic neuritis, other ocular diseases, psychiatric illness, or recent relapse were excluded. All patients underwent standardized optical coherence tomography (OCT) and neuropsychological evaluation with validated tests for MS patients. Cognitive impairment was defined as having two cognitive tasks below age- and education-adjusted norms. RESULTS: We recruited 52 patients with early MS, with an average age of 37 years (SD = 10.5), an average disease duration of 3.69 years (SD = 2.3), and a median EDSS of 1.0 (IQR = 0.5). In this sample, 15/52 patients presented cognitive impairment. Regarding OCT measurements, 7/52 patients had an average pRNFL below the 5th percentile and 2/52 had an average mGCL below the 5th percentile. The average pRNFL thickness was comparable in cognitively impaired and cognitively preserved patients (100.3 µm vs 103.1 µm, p = 0.52); the average mGCL thickness had also similar values between groups (50.5 µm vs 53 µm, p = 0.38). CONCLUSIONS: Cognitive impairment was frequent in our sample of early MS. However, no association with reduced pRNFL or mGCL thickness was found. When compared to OCT, cognitive assessment could provide an earlier marker of neurodegeneration in MS.

Acute reversible toxic encephalopathy during capecitabine and oxaliplatin treatment.

INTRODUCTION: Capecitabine is a fluoropyrimidine commonly used in the treatment of colorectal cancer which may cause central nervous system toxicity, namely cerebellar dysfunction. CASE REPORT: We describe a 77-year-old man undergoing adjuvant treatment of colon cancer with capecitabine and oxaliplatin who presented with acute cerebellar ataxia and encephalopathy that progressed to coma. Diagnosis of toxic encephalopathy was made after the exclusion of alternative causes of neurological dysfunction and complete resolution of clinical findings with permanent discontinuation of chemotherapy. DISCUSSION: When patients with cancer develop symptoms and signs of central nervous dysfunction, metabolic and infectious causes plus tumor involvement of central nervous system must be sought. However, chemotherapy may also cause toxicity to the central nervous system. Capecitabine is no exception, although cerebellar dysfunction is rarely reported. CONCLUSION: Although rare, capecitabine-induced encephalopathy may be severe and physicians should be aware of this possible side effect.

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

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.

The electroclinical spectrum, etiologies, treatment and outcome of nonconvulsive status epilepticus in the elderly.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) in the elderly is particularly difficult to diagnose, mainly due to subtle clinical manifestations and associated comorbidities. The recently validated electroencephalography (EEG) diagnostic criteria for NCSE and the proposed operational classification of status epilepticus provide tools that can allow an earlier diagnosis and better management of NCSE in this age group, possibly contributing to reduce its high mortality. MATERIAL AND METHODS: we used these tools to identify and characterize a cohort of elderly (>60year-old) patients admitted at our institution in a 3-year period; the video-EEG and clinical files of the patients fulfilling EEG diagnostic criteria for NCSE were reviewed, being in this study described their electroclinical spectrum, etiologies, treatment, inhospital mortality, and status epilepticus severity score (STESS). RESULTS: Fourty patients (23 women; mean age 76.6years) were identified. Although dyscognitive NCSE associated with >2.5Hz of epileptiform discharges (ED) was the most frequent electroclinical phenotype, this was quite heterogeneous, ranging from patients with aura continua to patients in coma, associated with frequent ED or rhythmic slow activities. Acute symptomatic (45%) and multifactorial (27.5%) etiologies were the most common, and associated with the worst prognosis. There was a trend to use newer antiepileptic drugs in the early steps of NCSE treatment. The inhospital mortality was high (22.5%) and predicted by STESS scores ≥3. CONCLUSION: In the elderly, NCSE has heterogeneous electroclinical phenotypes and etiologies. In spite of the treatment limitations conditioned by the comorbidities, more aggressive treatments could be justified to reduce mortality in patients with high STESS scores.

Soil charcoal as long-term pyrogenic carbon storage in Amazonian seasonal forests.

Forest fires (paleo + modern) have caused charcoal particles to accumulate in the soil vertical profile in Amazonia. This forest compartment is a long-term carbon reservoir with an important role in global carbon balance. Estimates of stocks remain uncertain in forests that have not been altered by deforestation but that have been impacted by understory fires and selective logging. We estimated the stock of pyrogenic carbon derived from charcoal accumulated in the soil profile of seasonal forest fragments impacted by fire and selective logging in the northern portion of Brazilian Amazonia. Sixty-nine soil cores to 1-m depth were collected in 12 forest fragments of different sizes. Charcoal stocks averaged 3.45 ± 2.17 Mg ha(-1) (2.24 ± 1.41 Mg C ha(-1) ). Pyrogenic carbon was not directly related to the size of the forest fragments. This carbon is equivalent to 1.40% (0.25% to 4.04%) of the carbon stocked in aboveground live tree biomass in these fragments. The vertical distribution of pyrogenic carbon indicates an exponential model, where the 0-30 cm depth range has 60% of the total stored. The total area of Brazil's Amazonian seasonal forests and ecotones not altered by deforestation implies 65-286 Tg of pyrogenic carbon accumulated along the soil vertical profile. This is 1.2-2.3 times the total amount of residual pyrogenic carbon formed by biomass burning worldwide in 1 year. Our analysis suggests that the accumulated charcoal in the soil vertical profile in Amazonian forests is a substantial pyrogenic carbon pool that needs to be considered in global carbon models.

Blood neutrophils, oligoclonal bands and bridging corticosteroids as predictive factors for MOGAD course: Insights from a multicentric Portuguese cohort.

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.

Validation of the Portuguese MDS-UPDRS: Challenges to Obtain a Scale Applicable to Different Linguistic Cultures.

BACKGROUND: The MDS-UPDRS has been available in English since 2008, showing satisfactory clinimetric results and being proposed as the new official benchmark scale for Parkinson's disease (PD), being cited as a core instrument for PD in the National Institutes of Neurological Disorders and Stroke Common Data Elements program. For this reason, the MDS created guidelines for development of MDS-UPDRS official, clinimetrically validated translations. OBJECTIVE: This study presents the formal process used to obtain the officially approved Portuguese version of the MDS-UPDRS. METHODS: The study consisted of three phases: (1) Independent translation by Portuguese and Brazilian teams followed by a challenging consensus process that this article particularly emphasizes; (2) Cognitive pretest involving raters and patients from both Portugal and Brazil; (3) Validation test with a sample of 367 native Portuguese-speaking PD patients. RESULTS: The overall factor structure of the Portuguese version was consistent with the English version based on a comparative fit index ≥0.96 for all four parts of the MDS-UPDRS. CONCLUSION: This version can be designated as the official Portuguese version of the MDS-UPDRS.

Consensus for the Early Identification of Secondary Progressive Multiple Sclerosis in Portugal: a Delphi Panel.

INTRODUCTION: Multiple sclerosis is a disease with a heterogeneous evolution. The early identification of secondary progressive multiple sclerosis is a clinical challenge, which would benefit from the definition of biomarkers and diagnostic tools applicable in the transition phase from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis. We aimed to reach a Portuguese national consensus on the monitoring of patients with multiple sclerosis and on the more relevant clinical variables for the early identification of its progression. MATERIAL AND METHODS: A Delphi panel which included eleven Portuguese Neurologists participated in two rounds of questions between July and August of 2021. In the first round, 39 questions which belonged to the functional, cognitive, imaging, biomarkers and additional evaluations were included. Questions for which no consensus was obtained in the first round (less than 80% of agreement), were appraised by the panel during the second round. RESULTS: The response rate was 100% in both rounds and consensus was reached for a total of 33 questions (84.6%). Consensus was reached for monitoring time, evaluation scales and clinical variables such as the degree of brain atrophy and mobility reduction, changes suggestive of secondary progressive multiple sclerosis. Additionally, digital devices were considered tools with potential to identify disease progression. Most questions for which no consensus was obtained referred to the cognitive assessment and the remaining referred to both functional and imaging domains. CONCLUSION: Consensus was obtained for the determination of the monitorization interval and for most of the clinical variables. Most questions that did not reach consensus were related with the confirmation of progression taking into account only one test/domain, reinforcing the multifactorial nature of multiple sclerosis.

FXTAS is rare among Portuguese patients with movement disorders: FMR1 premutations may be associated with a wider spectrum of phenotypes.

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by expansions of 55-200 CGG repeats in the 5'UTR of the FMR1 gene. These FMR1 premutation expansions have relatively high frequency in the general population. To estimate the frequency of FMR1 premutations among Portuguese males with non-familial, late-onset movement disorders of unknown etiology, we assessed CGG repeat size in males with disease onset after the age of 50 and negative or unknown family history for late-onset movement disorders, who were sent for SCA, HD, or PD genetic testing at a reference laboratory. The selected patients had a primary clinical diagnosis based on one of the following cardinal features of FXTAS: ataxia, tremor, or cognitive decline. A total of 86 subjects were genotyped for the CGG repeat in the FMR1 gene. We detected one patient with an expansion in the premutation range. The frequency of FMR1 premutations was 1.9% (1/54) in our group of patients with ataxia as the primary clinical feature, and 1.2% (1/86) in the larger movement disorders group. In the family of the FXTAS case, premutation-transmitting females presented a history of psychiatric symptoms, suggesting that, given the wide phenotypical expression of the premutation in females, neuropsychiatric surveillance is necessary. In conclusion, genetic testing for FXTAS should be made available to patients with adult-onset movement disorders to enable adequate genetic counseling to family members.

Brief cognitive assessment in the early stages of Parkinson disease.

INTRODUCTION: Cognitive dysfunction is an integral part of the Parkinson disease (PD) symptom spectrum. Early detection of cognitive dysfunction could help to delineate prevention strategies. Our main objective was to study the validity of brief cognitive tests, the Frontal Assessment Battery (FAB) and Mini-Mental State Examination (MMSE), as cognitive screening tools for detecting global and executive cognitive deficits in early stages of PD, as compared to a healthy control population. METHODS: We evaluated 75 early-stage PD patients and 45 healthy age-matched and education-matched controls with the MMSE (global test) and FAB (frontal test), and compared total and subtest scores. We evaluated PD motor function with the Unified Parkinson Disease Rating Scale Part III. We assessed the relationship between cognitive and motor variables. RESULTS: Frontal and global cognitive dysfunction was significantly more frequent in PD patients. PD patients scored significantly lower on FAB total and similarities, motor series, and conflicting instructions scores, and on the MMSE total, visuoconstructive, and memory scores. MMSE scores correlated significantly with Unified Parkinson Disease Rating Scale part III total score, speech, and bradykinesia scores. CONCLUSIONS: Early-stage PD patients present with frontal, memory, and visuoconstructive deficits in brief cognitive tests. Our results suggest that these brief bedside tests are useful for cognitive deficit screening in the early stages of PD. Our study did not account for the influence of depression in cognition. This constitutes a limitation, because many PD patients have depressive symptoms, which some studies have shown can be related to cognitive dysfunction.

Multiple Sclerosis Patient Management During the COVID-19 Pandemic: Practical Recommendations From the Portuguese Multiple Sclerosis Study Group (GEEM).

The spread of the COVID-19 pandemic has imposed significant challenges on healthcare provision, requiring changes in the conventional patient management, particularly in chronic diseases like multiple sclerosis (MS). To increase patient safety and reduce the risk of infection, while ensuring an appropriate and regular follow-up, tele-medicine gained prominence as a valid alternative to face-to-face appointments. However, the urgency of the implementation and the lack of experience in most MS centers led to "ad hoc" and extremely diverse approaches, which now merit to be standardized and refined. Indeed, while tele-consultation cannot fully replace face-to-face visits, it certainly can, and will, be incorporated as part of the routine care of MS patients in the near future. Bearing this in mind, the Portuguese Multiple Sclerosis Study Group (GEEM) has developed a set of recommendations for the usage of tele-medicine in the management of MS patients, both during the pandemic and in the future. The consensus was obtained through a two-step modified Delphi methodology, resulting in 15 recommendations, which are detailed in the manuscript.

Opinions, beliefs and knowledge of people with multiple sclerosis on COVID-19 pandemic and vaccine.

BACKGROUND: Considering the potential COVID-19 impact on pwMS health and the importance of vaccination for this population, we decided to assess: (a) pwMS' beliefs and knowledge on COVID-19 pandemic; (b) their acceptance towards COVID-19 vaccination and (c) pwMS' opinions on general vaccination. METHODS: Observational study, based on a cross-sectional (10-20th September 2020) online survey, conducted in a cohort of pwMS' followed at two Portuguese hospitals. The survey included measures to characterize the sample and a questionnaire designed to assess the topics defined for this study. RESULTS: 270 respondents completed the full survey (response rate 58.2%). pwMS greatest concern during the pandemic was an aggravation of MS, especially by patients older than 50 years old. Almost 40% of the patients older than 50 felt that the pandemic negatively affected their MS related medical assistance. Most patients believed they would recover from COVID-19 infection. More than half of the responders feared a MS aggravation if they got COVID-19; this was more pronounced in patients with progressive MS. About 12% of the participants did not want to be vaccinated and almost 40% was unsure. Regarding vaccines in general, almost a third of the participants feared their side effects or MS related complications. CONCLUSION: Having knowledge of pwMS' opinions on COVID-19 pandemic impact and vaccination is useful to better address these issues. Fears and expectations towards vaccination must be discussed with pwMS.

Therapeutic inertia in relapsing-remitting multiple sclerosis.

BACKGROUND: Therapeutic inertia (TI) is defined as a failure to initiate or intensify treatments despite evidence of disease activity. Its prevalence and determining factors in Relapsing-Remitting Multiple Sclerosis (RRMS) patients in Portugal are not known. The main objective of this work was to ascertain the prevalence of TI in RRMS and its determining factors. METHODS: We conducted a multicentre retrospective observational study of RRMS patients followed in MS Clinics of six Portuguese hospitals with at least one medical appointment in 2018. TI was defined as the absence of treatment initiation or intensification when therapeutic goals were unmet, that is when there was evidence of disease activity based on the definition of "no evidence of disease activity" (NEDA) which refers to absence of clinical relapses, absence of disease progression measured by expanded disability status scale (EDSS) and absence of new disease activity (new T2 lesions/enhancing lesion) on magnetic resonance imaging (MRI) over the period of observation. RESULTS: We included 427 patients with RRMS meeting inclusion criteria, 69.6% females, with a mean age of 41.66 years old. The mean age at diagnosis was 33.17 years old and the average number of years since diagnosis was 8.72. MS relapses were reported on 54 patients. Moderate to severe relapses were reported in 59.3%. Median EDSS score was 1.5. Intention to get pregnant was explicit in 39 patients, representing 18.8% of the women at childbearing age. Among the 365 patients who had an MRI, 23.8% had new T2 lesions and 7.4% had enhancing lesions. Regarding DMT, 72.8% were treated with interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate, 20.6% were under fingolimod, natalizumab, rituximab, and cladribine, and the remaining 6.6% were without treatment. Adverse events were reported in 12.9% of patients, and 10.1% mentioned preferences regarding the treatment. TI was present in 80 (18.7%) patients, representing 54.8% of those with potential to inertia. Patients with a radiologically less active disease, who were already on a DMT and who had no adverse events from their current treatment were more likely to have TI (p<0,05). Also, patients followed in centers classified as higher level of care (level 1) had more TI compared with patients followed in centers of levels 2 and 3. CONCLUSION: TI was present in 1 in 5 patients, exceeding half of the sample with the potential to inertia, corroborating the high prevalence of TI in other studies. The determining factors of TI were the absence of relapses or the occurrence of mild relapses, being already on DMT, absence of adverse events, and follow-up in higher care level centers. TI is a topic rarely addressed in MS and this work highlights the importance of therapeutic optimization in these patients. Further studies should be held to explore the factors that influence TI once they have a great impact on therapeutic decisions.

Defining the prodromal phase of multiple sclerosis based on healthcare access in a Portuguese population - ProdMS study.

BACKGROUND: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system. Prodromal symptoms and higher healthcare use have been suggested in patients who later develop MS. OBJECTIVES: Assess the healthcare utilization pattern of relapsing-remitting MS (RRMS) patients in the five years prior to MS diagnosis. METHODS: Retrospective, multicentric study. Demographic and clinical data, drug prescriptions and diagnostic tests were collected from electronic health records five-years previous to MS diagnosis and compared with national data. RESULTS: Included 168 patients, 112 (66.7%) female, median age 34±11 years. The mean number of healthcare use per patient per year was 3.14±2,69, most of them in primary healthcare (47%). Most frequent symptoms were musculoskeletal (22%), gastrointestinal (17%), sensitive (14%) and sensory organs (14%). Median number of diagnostic tests per patient was 6 (IQR 7), and drug prescriptions per patient was 6 (IQR 9). Most frequently prescribed drugs were analgesic/anti-inflammatories, antibiotics and anxiolytics and there was a high request rate of MRIs. CONCLUSION: RRMS patients had a high frequency of healthcare utilization when compared to national data. This supports the current evidence showing a prodromal phase in MS.

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

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.

Risk of Developing Parkinson Disease in Bipolar Disorder: A Systematic Review and Meta-analysis.

Importance: Parkinson disease (PD) manifests by motor and nonmotor symptoms, which may be preceded by mood disorders by more than a decade. Bipolar disorder (BD) is characterized by cyclic episodes of depression and mania. It is also suggested that dopamine might be relevant in the pathophysiology of BD. Objective: To assess the association of BD with a later diagnosis of idiopathic PD. Data Sources: An electronic literature search was performed of Cochrane Controlled Register of Trials, MEDLINE, Embase, and PsycINFO from database inception to May 2019 using the terms Parkinson disease, bipolar disorder, and mania, with no constraints applied. Study Selection: Studies that reported data on the likelihood of developing PD in BD vs non-BD populations were included. Two review authors independently conducted the study selection. Data Extraction and Synthesis: Two review authors independently extracted study data. Data were pooled using a random-effects model, results were abstracted as odds ratios and 95% CIs, and heterogeneity was reported as I2. Main Outcome and Measures: Odds ratios of PD. Results: Seven studies were eligible for inclusion and included 4 374 211 participants overall. A previous diagnosis of BD increased the likelihood of a subsequent diagnosis of idiopathic PD (odds ratio, 3.35; 95% CI, 2.00-5.60; I2 = 92%). A sensitivity analysis was performed by removing the studies that had a high risk of bias and also showed an increased risk of PD in people with BD (odds ratio, 3.21; 95% CI, 1.89-5.45; I2 = 94%). Preplanned subgroup analyses according to study design and diagnostic certainty failed to show a significant effect. Conclusions and Relevance: This review suggests that patients with BD have a significantly increased risk of developing PD compared with the general population. Subgroup analyses suggested a possible overestimation in the magnitude of the associations. These findings highlight the probability that BD may be associated with a later development of PD and the importance of the differential diagnosis of parkinsonism features in people with BD.

[Recommendations about Multiple Sclerosis Management during Pregnancy, Partum and Post-Partum: Consensus Position of the Portuguese Multiple Sclerosis Study Group]. / Recomendações sobre a Abordagem da Esclerose Múltipla na Gravidez, Parto e Pós-Parto: Posição de Consenso do Grupo de Estudos de Esclerose Múltipla.

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.

A esclerose múltipla afecta tipicamente mulheres jovens em idade reprodutiva. Desta forma, todo os profissionais de saúde envolvidos no seguimento destes doentes deverão estar preparados para abordar as questões relacionadas com a gravidez e amamentação e fornecer o melhor aconselhamento possível. No entanto, existem ainda muitas dúvidas e abordagens clínicas heterogéneas em parte devido à ausência de consensos e normas orientadoras. No que concerne ao manuseamento das terapêuticas modificadoras de doença durante os períodos de gravidez e pós-parto, as incertezas têm sido agravadas devido ao aumento do número de fármacos disponíveis nos últimos anos. Este artigo visa apresentar a informação mais atual e fornecer orientações baseadas no melhor nível de evidência disponível e na opinião de peritos relativamente ao seguimento das doentes com esclerose múltipla em diferentes etapas: planificação da gravidez, gravidez, parto e período pós-parto.

Consensus Recommendations of the Multiple Sclerosis Study Group and the Portuguese Neuroradiological Society for the Use of Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 2.

INTRODUCTION: Magnetic resonance imaging is recognized as the most important diagnostic test in the diagnosis of multiple sclerosis, differential diagnosis and evaluation of progression/therapeutic response. However, to make optimal use of magnetic resonance imaging in multiple sclerosis, the use of a standard, reproducible and comparable imaging protocol is of uttermost importance. In this context, the Portuguese Society of Neuroradiology and the Group of Studies of Multiple Sclerosis, 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. This document represents the second part of the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. MATERIAL AND METHODS: The Portuguese Society of Neuroradiology and the Group of Studies of Multiple Sclerosis, after discussing the topic in national meetings and after a working group meeting held in Figueira da Foz, May 2017, appointed a committee of experts that have developed several standard protocols on the use of magnetic resonance imaging on multiple sclerosis by consensus. The document obtained was based on the best scientific evidence and expert opinion. Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Standardized strategies of magnetic resonance imaging referral in clinical practice for diagnosis and follow-up of multiple sclerosis were published in the first part of this paper. RESULTS: We provide magnetic resonance imaging acquisition protocols regarding multiple sclerosis diagnostic and monitoring and the information to be included in the report for application across Portuguese healthcare institutions. CONCLUSION: We hope that these first Portuguese magnetic resonance imaging guidelines will contribute to optimize multiple sclerosis management and improve patient care in Portugal.

Introdução: A ressonância magnética é considerada o exame complementar mais importante para o diagnóstico de esclerose múltipla, seus diagnósticos diferenciais e avaliação da sua progressão/resposta terapêutica. No entanto, para um uso ótimo desta ferramenta na esclerose múltipla, é essencial a aplicação de um protocolo de imagem padronizado, reprodutível e comparável. Neste contexto, o Grupo de Estudos de Esclerose Múltipla e a Sociedade Portuguesa de Neurorradiologia, após discussão conjunta, designaram um comité de peritos para a criação de recomendações adaptadas à realidade nacional sobre a utilização da ressonância magnética na esclerose múltipla. Este documento corresponde à segunda parte das primeiras recomendações de consenso portuguesas sobre a utilização da ressonância magnética na esclerose múltipla na prática clínica. Material e Métodos: O Grupo de Estudos de Esclerose Múltipla e a Sociedade Portuguesa de Neurorradiologia após discussão do tema em reuniões de âmbito nacional e de uma reunião do grupo de trabalho que teve lugar na Figueira da Foz em maio de 2017, designaram um comité de peritos que elaboraram por método de consenso protocolos padronizados sobre o uso da ressonância magnética na esclerose múltipla. O documento teve como base a melhor evidência científica e a opinião dos peritos. Posteriormente, o documento foi enviado para escrutínio à maioria dos responsáveis de consulta de esclerose múltipla e dos departamentos de neurorradiologia; tendo sido considerados os seus comentários e sugestões. As estratégias padronizadas de referenciação imagiológica na prática clínica para o diagnóstico e seguimento da esclerose múltipla foram publicadas na primeira parte deste artigo. Resultados: Neste artigo são propostos os protocolos de aquisição de ressonância magnética adequados para o diagnóstico e monitorização da esclerose múltipla, bem como a informação a constar do relatório imagiológico, tendo em vista a sua aplicação nas várias instituições de saúde portuguesas. Conclusão: Os autores esperam que estas primeiras orientações portuguesas sobre a utilização da ressonância magnética na esclerose múltipla na prática clínica contribuam para otimizar a gestão desta patologia e melhorar o tratamento destes doentes em Portugal.

Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration.

Hereditary spastic paraplegias (HSP) are neurodegenerative diseases mainly characterized by lower limb spasticity associated, in complicated forms, with additional neurological signs. We have analysed a large series of index patients (n = 76) with this condition, either from families with an autosomal recessive inheritance (n = 43) or isolated patients (n = 33), for mutations in the recently identified SPG11 gene. We found 22 truncating mutations, including the first four splice-site mutations, segregating in seven isolated cases and 13 families. Nineteen mutations were novel. Two recurrent mutations were found in Portuguese and North-African patients indicating founder effects in these populations. The mutation frequency varied according to the phenotype, from 41%, in HSP patients presenting with a thin corpus callosum (TCC) visualized by MRI, to 4.5%, in patients with mental impairment without a TCC. Disease onset occurred during the first to the third decade mainly by problems with gait and/or mental retardation. After a mean disease duration of 14.9 +/- 6.6 years, the phenotype of 38 SPG11 patients was severe with 53% of patients wheelchair bound or bedridden. In addition to mental retardation, 80% of the patients showed cognitive decline with executive dysfunction. Interestingly, the phenotype also frequently included lower motor neuron degeneration (81%) with wasting (53%). Slight ocular cerebellar signs were also noted in patients with long disease durations. In addition to a TCC (95%), brain MRI revealed white matter alterations (69%) and cortical atrophy (81%), which worsened with disease duration. In conclusion, our study reveals the high frequency of SPG11 mutations in patients with HSP, a TCC and cognitive impairment, including in isolated patients, and extends the associated phenotype.