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  • Efficacy and Safety of IncobotulinumtoxinA in Older Patients with Upper Limb Spasticity: a Pooled Analysis.
    Publication . Munin, Michael C; Camões-Barbosa, Alexandre; Cordero-García, Carlos; Baricich, Alessio; Carda, Stefano; Althaus, Michael; Comes, Georg; Vacchelli, Matteo; Wissel, Jörg
    : The aim of this study was to compare the efficacy and safety of a single cycle of incobotulinumtoxinA versus placebo in pooled data from older patients (aged ≥65 years) with upper limb spasticity (ULS). : This study was a post hoc analysis of pooled data from seven prospective, multicenter, phase II or III trials of incobotulinumtoxinA in adult patients aged ≥65 years from across the world with post-stroke ULS or upper and lower limb spasticity, including a subgroup with moderate-to-severe ULS. Changes from baseline in ULS severity were evaluated using the (modified) Ashworth Scale across different spasticity patterns at 4 and 12 weeks after incobotulinumtoxinA injection. : In 267 older patients with ULS, including a subgroup of 207 with moderate-to-severe ULS, all ULS patterns statistically analyzed (elbow flexion, thumb-in-palm, clenched fist, wrist flexion, and pronated forearm) were improved more by incobotulinumtoxinA than placebo at week 4 ( < 0.05). For most of these patterns, the difference remained significant at week 12 ( < 0.05). IncobotulinumtoxinA was generally well tolerated. : This study, which analyzed data from the largest cohort of older patients in the literature, provides information regarding the use of incobotulinumtoxinA in ULS, the efficacy and favorable safety profile of incobotulinumtoxinA for the treatment of ULS in older patients, particularly in those with moderate-to-severe spasticity, was confirmed.
  • Acute Onset of Adult Alexander Disease and the Concept of GFAP Toxicity.
    Publication . Godinho, Filipe; Guerreiro, Carolina; Parente Freixo, João; Oliveira, Jorge; Lourenço Rosa, José
  • Seizure Prediction in Cerebral Venous Thrombosis - a Retrospective Single-Centre Observational Study.
    Publication . Faustino, Patrícia; Melancia, Diana
    Cerebral venous thrombosis (CVT) accounts for 0.5-1% of all strokes and 24-50% of these patients develop acute symptomatic seizures (AS). Clinical and radiological characteristics have been associated with an increased risk of AS in CVT. We aimed to identify clinical and imaging predictors associated with a higher risk of AS in CVT patients.We conducted a single-centre, retrospective cohort study and included all patients with CVT admitted to our stroke unit between January/2011-December/2022. Our primary outcome was AS occurence. Clinical and radiological characteristics were compared through a logistic binary regression, followed by a multivariable analysis.We included 156 patients, 80.8% female and a mean age of 41.5 ± 15.2 years. Fifty-two patients (33.3%) had a seizure during follow-up, the majority as AS (30.1%). We found an increased risk of AS in patients with focal signs at presentation (OR 5.35), superior longitudinal sinus (SLS) or cortical vein involvement (OR 5.03; OR 3.94), hemorrhagic lesions or oedema (OR 3.88; OR 4.17) and lesions located in the frontal or the parietal lobe (OR 4.61; OR 4.61). A multivariable analysis was also conducted and only SLS involvement (OR 6.06), cortical vein involvement (OR 2.76) and hemorrhagic lesion (OR 3.47) remained statistically significant.Seizures occurred in about a third of our CVT patients, the majority as AS. Haemorrhagic lesions, SLS and cortical vein involvement had a stronger association with AS that may raise our awareness for the risk of seizures in this population during the acute phase.
  • Multiple Sclerosis Relapse Incomplete Recovery and Associated Factors - a Systematic Review and Meta-Analysis.
    Publication . Ladeira, Filipa; Soares, Mafalda; Faustino, Patrícia; Leal Rato, Miguel; Gomes, Inês; Caetano, André; Taipa, Ricardo; Sá, Maria José
    Objectives: We conducted a meta-analysis to assess the frequency of incomplete recovery from multiple sclerosis (MS) relapses and a systematic review to evaluate the influence of six factors on incomplete recovery: relapse severity, age, sex, disease duration, disease-modifying treatment use, and the presence of contrast-enhancing lesions at relapse. Methods: We searched Scientific databases to identify suitable publications. Our outcome was MS relapse incomplete recovery, defined as a post-relapse EDSS measured at least 6 months after the event higher than the pre-relapse EDSS. We synthesized the rate of incomplete recovery using meta-analysis (random effect model). and summarized the effect estimates (or HR) for demographic and clinical factors. Results: We included 13 studies (with a total of 19,920 patients and 27672 relapses having at least six month of follow up) . The pooled rate of incomplete recovery was 0.42 (95 % confidence interval 0.31 to 0.54). The subgroup systematic review identified that relapse severity was the most consistent and strongest predictor of incomplete recovery, with odds ratios ranging from 2.4 to 17.2. Other factors were less consistently associated with relapse recovery. Conclusion: This systematic review indicates that relapse recovery is often incomplete, with relapse severity being the strongest and most consistent predictor of incomplete recovery.
  • Validation of a Portuguese Version of the Four-Item Migraine Interictal Burden Scale.
    Publication . Ferrão Malheiro, Sofia; Dourado Sotero, Filipa; Pereira, Manuel Bragança; Nunes Vicente, Beatriz; Franco, Roberto Luís Mendes; Duardte Rodrigues Casanosa, Sofia; Ramos Ferreira, Jorge Miguel; Santos Gil Gouveia, Raquel; Andrade, Carlos; Pavão Martins, Isabel
    Background: Migraine is the most common neurological disorder and the second leading cause of disability. While the impact of migraine on daily life is often assessed by the frequency and intensity of attacks, the impairment between episodes is frequently overlooked. The four-item Migraine Interictal Burden Scale (MIBS-4) is a tool that can provide information and help in the evaluation of interictal disability. Objective: To adapt and validate a translated version of the MIBS-4 for the Portuguese population. Methods: A prospective, multicentric observational study was conducted between July 2023 and February 2024 in six tertiary headache centers across Portugal. The MIBS-4 was translated and back-translated to obtain a consensus version. The scale was administered to 459 patients with migraine, and its psychometric properties were assessed through correlations with established measures, including the Migraine Disability Assessment Scale (MIDAS), 12-item Short Form Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS). Results: A total of 459 patients were evaluated, including 430 women (93.7%), with an average age of 45.06 years. The MIBS-4 demonstrated good internal consistency with a Cronbach's alpha of 0.84 (95% confidence interval 0.81-0.86) and significant correlations with the MIDAS (r = 0.304, p < 0.001), SF-12 (r = 0.483, p < 0.001), and HADS (r = 0.211, p < 0.001), confirming its reliability and construct validity. Conclusion: This analysis showed that the Portuguese version of the MIBS-4 showed identical psychometric properties to the original scale and can effectively assess interictal disability in patients with migraine in Portuguese speaking populations. Its validation provides a valuable tool for clinical practice and research, enabling improved assessment of migraine burden and contributing to better patient care in lusophone countries.
  • Evaluation of the Efficacy of the SARS-CoV-2 Vaccine Additional and Booster Doses in Immunocompromised Patients With Multiple Sclerosis: the COVACiMS Study.
    Publication . Ladeira, Filipa; Nobrega, Claudia; Cerqueira, João
    Studies evaluating COVID-19 primary vaccination with two vaccines reported a blunt response in Multiple Sclerosis (MS) patients under anti-CD20 and sphingosine-1-phosphate (S1P) modulators. An extended primary vaccination (EPV) was recommended in immunosuppressed MS patients. Data on the effectiveness of the EPV and subsequent booster dose are limited. A prospective cohort study (n = 270) was conducted to evaluate the humoral and cellular immunogenicity of the EPV scheme in immunocompromised MS patients (i.e., treated with anti-CD20, S1P modulators, natalizumab, teriflunomide, or dimethyl fumarate) vs. regular primary vaccination in non-treated patients - primary course (PC) cohort. The effect of a subsequent booster dose was also assessed - first booster (FB) cohort . The seroconversion rates were 55% and 56% in anti-CD20 and 75% and 67% in S1P modulators group in PC and FB cohort, respectively, and 100% in the remaining groups. A positive SARS-CoV-2 Spike T-spot was observed in 22% of patients under S1P modulators in PC cohort and 67% in FB cohort; the remaining groups had 75% or more. Similar rates of breakthrough infection were observed in both groups vs. controls. Compared to non-treated MS patients, immunosuppressed patients under anti-CD20 and S1P modulators drugs receiving EPV scheme or booster dose still present lower protection rates to SARS-CoV-2.
  • Multiple Sclerosis Disease-Modifying Treatment Algorithms: 2025 Positioning of the Portuguese Multiple Sclerosis Study Group.
    Publication . Capela, Carlos; Santos, Ernestina; Palavra, Filipe; Guimarães, Joana; Cerqueira, João; Vale, José; Sousa, Lívia; Batista, Sónia; Sá, Maria José
    Multiple sclerosis (MS) is a chronic autoimmune-mediated neurodegenerative disease characterized by inflammation, demyelination, and axonal/neuronal damage in the central nervous system. In Portugal, the prevalence of MS is approximately 64.4 per 100 000 individuals. It is typically diagnosed in young adults aged 30 to 40, with a higher incidence in women, although it can also affect children/adolescents and the elderly. Recent advances in MS treatment include the development and approval of several new disease-modifying therapies (DMTs) such as ocrelizumab, cladribine, siponimod, and others, thus expanding options for relapsing-remitting MS (RRMS). However, the options for progressive forms of MS remain limited. In Portugal, MS management strategies, guided by the 2015 recommendations of the Directorate-General of Health and the Portuguese medicines agency, need updating to incorporate recent scientific evidence and clinical expertise. The aim of this manuscript is to highlight gaps in current Portuguese MS treatment algorithms and propose enhancements aligned with global standards, thus improving treatment selection and patient outcomes in the Portuguese healthcare system. Developed by nine Portuguese neurology experts from the Portuguese Multiple Sclerosis Study Group, this document not only provides evidence and clinical practice-based recommendations but also includes DMT algorithms tailored for various MS subtypes, including radiologically and clinically isolated syndromes, RRMS, progressive MS, and specific situations in MS treatment such as pediatric-onset MS, late-onset MS, pregnancy and breastfeeding. This document provides evidence- and clinical practice-based recommendations to optimize decision-making during MS management in Portuguese centers. The experts aim to prompt the urgent revision of national MS treatment frameworks, incorporating the latest advancements in MS research and international guidelines, to reduce the socio-economic burden on the national healthcare system and improve the long-term health outcomes of MS patients.
  • Predictors of Functional Outcome After Symptomatic Intracranial Hemorrhage Complicating Intravenous Thrombolysis: Results From the SITS-ISTR.
    Publication . Tsivgoulis, Georgios; Palaiodimou, Lina; Stefanou, Maria-Ioanna; Theodorou, Aikaterini; Kõrv, Janika; Paiva Nunes, Ana; Candelaresi, Paolo; Dall'Ora, Elisa; Sariaslani, Payam; Provinciali, Leandro; Conforto, Adriana B; Cidrao, Alan Alves de Lima; Karapanayiotides, Theodore; Ahmed, Niaz
    Background and purpose: Several risk factors of symptomatic intracerebral hemorrhage (SICH) following intravenous thrombolysis for acute ischaemic stroke have been established. However, potential predictors of good functional outcome post-SICH have been less studied. Methods: Patient data registered in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) from 2005 to 2021 were used. Acute ischaemic stroke patients who developed post intravenous thrombolysis SICH according to the SITS Monitoring Study definition were analyzed to identify predictors of functional outcomes. Results: A total of 1679 patients with reported SICH were included, out of which only 2.8% achieved good functional outcome (modified Rankin Scale scores of 0-2), whilst 80.9% died at 3 months. Higher baseline National Institutes of Health Stroke Scale (NIHSS) score and 24-h ΔNIHSS score were independently associated with a lower likelihood of achieving both good and excellent functional outcomes at 3 months. Baseline NIHSS and hematoma location (presence of both SICHs, defined as remote and local SICH concurrently; n = 478) were predictors of early mortality within 24 h. Independent predictors of 3-month mortality were age, baseline NIHSS, 24-h ΔNIHSS, admission serum glucose values and hematoma location (both SICHs). Age, baseline NIHSS score, 24-h ΔNIHSS, hyperlipidemia, prior stroke/transient ischaemic attack, antiplatelet treatment, diastolic blood pressure at admission, glucose values on admission and SICH location (both SICHs) were associated with reduced disability at 3 months (≥1-point reduction across all modified Rankin Scale scores). Patients with remote SICH (n = 219) and local SICH (n = 964) had comparable clinical outcomes, both before and after propensity score matching. Conclusions: Symptomatic intracerebral hemorrhage presents an alarmingly high prevalence of adverse clinical outcomes, with no difference in clinical outcomes between remote and local SICH.
  • Gender Disparities in the Academic Performance of Neurology Residents in Portugal.
    Publication . Ladeira, Filipa; Faustino, Patrícia; Soares, Mafalda; Carvalho, Vanessa
    Implicit bias has been linked to gender disparities in medical careers, impacting not only access to leadership positions but also early career opportunities. We aimed to evaluate if there were differences in the assessment of Neurology residents according to gender. We collected publicly available grades and rankings of two major evaluations that residents are submitted to, one at the beginning and another at the end of the neurology residency program, the National Board Exam and neurology examination, respectively. The National Board Examination is a multiple-choice gender-blinded evaluation, while the neurology examination is an oral gender-unblinded evaluation. We found that 36.5% of women and 21.6% of men were in the first quartile of the National Board Examination ranking, which reflects a similar representation among top classifications when assessed through a gender-blinded examination. On the other hand, the percentage of men who were in the top classification of NE, a gender-unblinded evaluation, was more than twice as high compared to women (37.8% vs 18.3%, p < 0.05). The findings of the present study may imply that there could be a disparity in women's career progression among neurology residents in Portugal, although the recruitment seems balanced between genders.
  • Early Prediction of Delayed Ischemia and Functional Outcome in Acute Subarachnoid Hemorrhage: Role of Diffusion Tensor Imaging.
    Publication . Fragata, Isabel; Alves, Marta; Papoila, Ana Luísa; Nunes, Ana Paiva; Ferreira, Patrícia; Canto-Moreira, Nuno; Canhão, Patrícia
    Background and purpose: Diffusion tensor imaging (DTI) parameters are markers of cerebral lesion in some diseases. In patients with acute subarachnoid hemorrhage (SAH), we investigated whether DTI parameters measured at <72 hours might be associated with delayed cerebral ischemia (DCI) and with poor functional outcome at 3 months (modified Rankin Scale score ≥3). Methods: DTI was performed in a prospective cohort of 60 patients with nontraumatic SAH at <72 hours. Association of fractional anisotropy and apparent diffusion coefficient values at <72 hours with the occurrence of DCI and outcome at 3 months was evaluated with logistic regression models, adjusting for known predictors of prognosis. Results: At <72 hours after SAH, fractional anisotropy values at the cerebellum were associated with DCI occurrence (78% less odds of DCI for each 0.1 increase in fractional anisotropy; P=0.019). Early apparent diffusion coefficient values were not associated with DCI. After adjusting for confounding variables, an increase of 10 U in apparent diffusion coefficient at the frontal centrum semiovale corresponded to 15% increased odds of poor outcome (P=0.061). Conclusions: DTI parameters at <72 hours post-SAH are independently associated with the occurrence of DCI and functional outcome. These preliminary results suggest the role of DTI parameters as surrogate markers of prognosis in nontraumatic SAH.