Multiple sclerosis under the age of ten: the challenge of a rare diagnosis in a special population – a case series

IntroductionMultiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system which, when it begins before the age of 18, is defined as paediatric MS. Most common clinical presentations include long tract involvement, brainstem/cerebellum syndromes, optic neuritis and acute disseminated encephalomyelitis. Paediatric-onset MS typically has a more inflammatory-active course and a higher lesion burden in imaging studies, but an extensive post-relapse recovery, with a slower long-term disability progression. The first demyelinating clinical attack occurs before 10 years old in less than 1% of patients, and, in this special population, the condition has particularities in clinical presentation, differential diagnosis, diagnostic assessment, current treatment options and outcome.Clinical casesWe present the cases of four Caucasian children (2 girls) diagnosed with relapsing–remitting MS before the age of ten, with a mean age at the time of the first relapse of 7.4 ± 2.4 years. Clinical presentation included optic neuritis, myelitis, brainstem syndrome, and acute disseminated encephalomyelitis. Baseline MRI identified several lesions, frequently large and ill-defined. Two patients were included in clinical trials and two patients remain in clinical and imaging surveillance.ConclusionDiagnosis of MS before the age of 10 years is rare, but it has significant long-term physical and cognitive consequences, as well as a substantial impact on the current and future quality of life of the child and family. Early and correct diagnosis is essential. Prospective, randomized, large cohort studies are needed to assess the efficacy and safety of disease-modifying treatments in children under the age of ten

Clinical predictors of NEDA-3 one year after diagnosis of pediatric multiple sclerosis: an exploratory single-center study

IntroductionMultiple sclerosis (MS) is an inflammatory and demyelinating disorder of central nervous system that can be diagnosed in pediatric age (<18 years) in 3–5% of the cases. This early onset is associated with higher relapse rates and earlier progression to neurological disability. By using NEDA-3 (No Evidence of Disease Activity-3) criteria, we aimed to identify clinical predictors associated with absence of disease activity and control of disease progression 12 months after the diagnosis, in a cohort of pediatric-onset MS (POMS) patients regularly followed-up in our center.MethodsWe analyzed demographic, clinical, laboratorial and imaging variables of patients with POMS identified in our center, between 2010 and 2021, in two moments: at the diagnosis and 12 months after it. Statistical tests were applied to compare the distribution of those variables between groups defined by NEDA-3 status and by each one of its three variable components.ResultsWe included 27 patients in the study (18 female), with a mean age of 14.8 years (± 2.8), being all diagnosed with relapsing–remitting MS and with a median score of 1.5 at the Expanded Disability Status Scale (EDSS). The use of natalizumab (p = 0.017) and the negativity for anti-EBV IgG antibodies (p = 0.018) at diagnosis were associated with a higher achievement of NEDA-3 status 12 months after, in our cohort. Prescribed treatment was also associated with statistically significant differences in the “absence of MRI activity” component of NEDA-3 (p = 0.006): patients under treatment with natalizumab had a higher probability of achieving this status, and the opposite was observed in glatiramer acetate-treated children.Discussion and conclusionOur exploratory results underline the pivotal importance that an early and more effective therapeutical approach may have in the control of disease activity, in POMS. Additionally, they also seem to suggest that the presence of anti-EBV antibodies is not innocent, as it can be related to a less favorable evolution of the disease, even at a very early stage. Further studies are needed to confirm the applicability of these variables as prognostic and personalized tools in this clinical setting

Headache Health Services in Portugal – 2022: a survey by the Portuguese Headache Society

Introdução: Com o objectivo de otimizar os cuidados médicos prestados aos doentes com cefaleias em Portugal, a Sociedade Portuguesa de Cefaleias (SPC) transpôs para a realidade portuguesa as recomendações europeias para organização dos serviços de saúde neste contexto. Nesse documento são calculadas as necessidades de recursos, em termos de serviços de saúde, para garantir um apoio efetivo e de qualidade a estes doentes quer a nível de cuidados de saúde primários, quer de cuidados diferenciados, estes atribuídos à especialidade de neurologia. Neste sentido, considerou-se necessário efetuar um levantamento relativo à oferta de serviços de saúde diferenciados em cefaleias existente em Portugal e à sua perspetiva de evolução, nos próximos anos, de forma a perceber se corresponde às necessidades estimadas. Métodos: Foi disponibilizado um inquérito online aos sócios da SPC e da Sociedade Portuguesa de Neurologia que caracteriza a oferta de serviços de saúde diferenciados em cefaleias. Resultados: Foram obtidas respostas de 52 médicos, pertencentes a 40 instituições, 24(59%) do sistema nacional de saúde, cobrindo adequadamente o território nacional exceto nas regiões do Alentejo e Algarve. A maioria dos centros tem consulta de cefaleias, 88% com médicos dedicados e 91% dispondo de técnicas avançadas de tratamento (bloqueios, toxina e anticorpos monoclonais). Na maioria destes centros há 1 ou 2 médicos atribuídos a esta função, oferecendo em média 169 consultas por dia útil – cada instituição oferece, em média, 20 consultas por semana. O tempo de espera para a consulta é superior a 3 meses em 65% dos centros do SNS, mas as consultas e tratamentos tem a duração e dispõem de recursos técnicos adequados. A maioria dos centros tem expectativa de aumentar a oferta nos próximos 2 anos. Conclusão: Muito embora com limitações condicionadas pelo método, podemos afirmar que existem um número de centros adequado para apoio diferenciado aos doentes com cefaleias em Portugal, no entanto com uma oferta inferior à necessária (cerca de 13%), condicionada sobretudo por escassez de tempo médico atribuído a esta função.Introduction: Aiming to improve the medical care provided to patients with headaches in Portugal, the Portuguese Headache Society (SPC) transposed the Eu-ropean recommendations for the organization of health services for headache to the Portuguese context. This document calculates the need for resources, in terms of health services, to ensure effective and quality support for headache patients, both in terms of primary and specialized care, the latter being attributed to neurology. In this sense, it was considered necessary to survey he offer of differentiated health services for headaches in Portugal and its’ perspective of evolution, in the coming years, in order to understand if it corresponds to the estimated needs. Methods: An online survey was made available to members of the SPC and the Portuguese Society of Neurology, which characterizes the provision of differentiated health services in headache. Results: Responses were obtained from 52 doctors, of 40 health care facilities, 24 (59%) belonging to the national health system. The national territory was covered adequately, except in the regions of Alentejo and Algarve. Most centers have headache clinics, 88% with dedicated doctors and 91% with advanced treatment tech-niques (nerve blocks, botulinum toxin and monoclonal antibodies). Most of these centers have only 1 or 2 physicians assigned to this function, providing an average of 169 consultations per working day – each institution offers an average of 20 consultations per week. The waiting time for the consultation is over 3 months in 65% of the centers of the SNS, but the consultations and treatments allocated time is adequate and most have adequate technical resources. Most centers expect to in-crease their offer in the next 2 years. Conclusion: Although with limitations conditioned by the method, we can state that there are an adequate number of centers for differentiated support of headaches patients in Portugal, although the services offer in lower than necessary (about 13%), conditioned mainly by scarcity of medical time assigned to this role.info:eu-repo/semantics/publishedVersio

Implication of Low HDL-c Levels in Patients with Average LDL-c Levels: A Focus on Oxidized LDL, Large HDL Subpopulation, and Adiponectin

To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF-α, adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients' subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin

Emergent Biomarkers of Residual Cardiovascular Risk in Patients with Low HDL-c and/or High Triglycerides and Average LDL-c Concentrations: Focus on HDL Subpopulations, Oxidized LDL, Adiponectin, and Uric Acid

This study intended to determine the impact of HDL-c and/or TGs levels on patients with average LDL-c concentration, focusing on lipidic, oxidative, inflammatory, and angiogenic profiles. Patients with cardiovascular risk factors (n = 169) were divided into 4 subgroups, combining normal and low HDL-c with normal and high TGs patients. The following data was analyzed: BP, BMI, waist circumference and serum glucose, Total-c, TGs, LDL-c, oxidized-LDL, total HDL-c and HDL subpopulations, paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. The two populations with increased TGs levels, regardless of the normal or low HDL-c, presented obesity and higher waist circumference, Total-c, LDL-c, Ox-LDL, and uric acid. Adiponectin concentration was significantly lower and VEGF was higher in the population with cumulative low values of HDL-c and high values of TGs, while HDL quality was reduced in the populations with impaired values of HDL-c and/or TGs, viewed by reduced large and increased small HDL subfractions. In conclusion, in a population with cardiovascular risk factors, low HDL-c and/or high TGs concentrations seem to be associated with a poor cardiometabolic profile, despite average LDL-c levels. This condition, often called residual risk, is better evidenced by using both traditional and nontraditional CV biomarkers, including large and small HDL subfractions, Ox-LDL, adiponectin, VEGF, and uric acid.info:eu-repo/semantics/publishedVersio

Natalizumab for the treatment of pediatric-onset multiple sclerosis in Portugal

Background: A significant proportion of pediatric-onset multiple sclerosis (POMS) patients do not respond to first-line disease-modifying therapies. Clinical trials showed that natalizumab is effective and safe in adults, but there are limited clinical trial data for children. Natalizumab is currently prescribed off-label for POMS. We aimed to characterize the effectiveness, safety and tolerability of natalizumab in all POMS cases treated in Portugal (from 2007 to 2018). Methods: Data from clinical records were retrospectively collected for all POMS cases treated with natalizumab in Portugal. Results: Twenty-one patients were included, 14 (67%) of which were female. The median age at POMS diagnosis was 13 years old. The median duration of treatment with natalizumab was 2 years and 3 months. Median Expanded Disability Status Scale score decreased from 1.5 to 1.0 after 24 months. The Annualized Relapse Rate decreased from 1.31 events/patient/year before treatment with natalizumab to 0 after 12 months of treatment and to 0.04 after 24 months. No gadolinium-enhancing lesions or new or enlarged T2 hyperintense lesions were observed in 8/8 patients (100%) after 12 months, and 4/5 (80%) after 24 months. There was one possible serious adverse event, which did not require dose adjustment. Five patients discontinued treatment due to positive anti-JCV (JC virus) antibody JC serostatus. Conclusion: Natalizumab may be an effective and safe disease-modifying therapy for POMS. Our results are in line with data published for the adult population, as well as with similar observational studies in pediatric populations in other regions.publishersversionpublishe

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Anticorpos Monoclonais para Tratamento da Esclerose Múltipla

Since their introduction in medical therapy, in the last quarter of the 20th century, monoclonal antibodies have gained an increasing importance in the treatment of various diseases. Neurology has been one of the medical specialties benefiting of the therapeutic potential of these monoclonal antibodies and certain neurological conditions may now contain such drugs in their therapeutic algorithms. Multiple sclerosis is one of these diseases and, in addition to the monoclonal antibodies already licensed for clinical use, several others are in development for future utilization in this specific area. The future will certainly pass through this kind of drugs and, in this article, a review of the most relevant data related to monoclonal antibodies already in use and also in clinical development for multiple sclerosis treatment will be performed.Desde a sua introdução na terapêutica médica, no último quarto do século XX, os anticorpos monoclonais têm ganho cada vez mais importância no tratamento de várias doenças. A Neurologia tem sido uma das especialidades médicas a beneficiar do potencial terapêutico destes anticorpos monoclonais e algumas doenças neurológicas podem já contar com fármacos deste tipo nos seus algoritmos terapêuticos. A esclerose múltipla é uma dessas doenças e, para além dos já licenciados para utilização clínica, são vários os anticorpos monoclonais que se encontram em desenvolvimento para futura utilização nesta área específica. O futuro passará certamente por fármacos deste tipo e, neste artigo, far-se-á uma revisão dos dados mais relevantes relacionados com os anticorpos monoclonais já em uso e também em desenvolvimento clínico para tratamento da esclerose múltipla