[Core data set for real world data in multiple sclerosis: customization for latin america from a global task force recommendation]. / Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.

INTRODUCTION: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. MATERIAL AND METHODS: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. RESULTS: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. CONCLUSION: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.

TITLE: Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.Introducción. Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados. Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión. El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.

Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Neuromyelitis optica and multiple sclerosis: Seeing differences through optical coherence tomography.

Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies.

Myasthenia gravis and neuromyelitis optica spectrum disorder: a multicenter study of 16 patients.

OBJECTIVE: To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)-mediated myasthenia gravis (AChR-MG). METHODS: The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively. RESULTS: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG. CONCLUSIONS: Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed.

The Brazilian database on pregnancy in multiple sclerosis.

OBJECTIVES: To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy. METHODS: Retrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose. RESULTS: Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients' average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5±1.4; and the relapse rate in the year preceding pregnancy was 1.2±1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes. CONCLUSIONS: Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.

Profile of the Brazilian scientific production in multiple sclerosis.

This paper analyzes the profile of the Brazilian output in the field of multiple sclerosis from 1981 to 2004. The search was conducted through the MEDLINE and LILACS databases, selecting papers in which the term "multiple sclerosis" was defined as the main topic and "Brazil" or "Brasil" as others. The data were analyzed regarding the themes, the state in Brazil and institution where the papers were produced, the journals where the papers were published, journal's impact factor, and language. The search disclosed 141 documents (91 from MEDLINE and LILACS, and 50 from LILACS only) published in 44 different journals (23 of them MEDLINE-indexed). A total of 111 documents were produced by 17 public universities, 29 by 3 private medical schools and 1 by a non-governmental organization. There were 65 original contributions, 37 case reports, 20 reviews, 6 PhD dissertations, 5 guidelines, 2 validation studies, 2 clinical trials, 2 chapters in textbooks, 1 Master of Science thesis, and 1 patient education handout. The journal impact factor ranged from 0.0217 to 6.039 (median 3.03). Of 91 papers from MEDLINE, 65 were published by Arquivos de Neuro-Psiquiatria. More than 90% of the papers were written in Portuguese. São Paulo was the most productive state in the country, followed by Rio de Janeiro, Minas Gerais and Paraná. Eighty-two percent of the Brazilian output came from the Southeastern region.

Profile of the Brazilian scientific production in multiple sclerosis

This paper analyzes the profile of the Brazilian output in the field of multiple sclerosis from 1981 to 2004. The search was conducted through the MEDLINE and LILACS databases, selecting papers in which the term "multiple sclerosis" was defined as the main topic and "Brazil" or "Brasil" as others. The data were analyzed regarding the themes, the state in Brazil and institution where the papers were produced, the journals where the papers were published, journal's impact factor, and language. The search disclosed 141 documents (91 from MEDLINE and LILACS, and 50 from LILACS only) published in 44 different journals (23 of them MEDLINE-indexed). A total of 111 documents were produced by 17 public universities, 29 by 3 private medical schools and 1 by a non-governmental organization. There were 65 original contributions, 37 case reports, 20 reviews, 6 PhD dissertations, 5 guidelines, 2 validation studies, 2 clinical trials, 2 chapters in textbooks, 1 Master of Science thesis, and 1 patient education handout. The journal impact factor ranged from 0.0217 to 6.039 (median 3.03). Of 91 papers from MEDLINE, 65 were published by Arquivos de Neuro-Psiquiatria. More than 90 percent of the papers were written in Portuguese. São Paulo was the most productive state in the country, followed by Rio de Janeiro, Minas Gerais and Paraná. Eighty-two percent of the Brazilian output came from the Southeastern region.

Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ss-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean +/- SEM, 369.5 +/- 69.3 pg/mL) when compared with controls (178.5 +/- 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 +/- 14.4 pg/mL) than in controls (237.1 +/- 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ß-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL) when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL) than in controls (237.1 ± 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

Simple phonic tic in multiple sclerosis.

Movement disorders occurring in association with multiple sclerosis (MS) are rare. Among them paroxysmal dystonia is the most common, although chorea, ballism, palatal myoclonia, spasmodic torticollis, writer's cramp and generalized dystonia have been reported. We describe a 34-year old woman with MS who developed simple phonic tic characterized by throat-clearing sounds. Magnetic resonance imaging showed demyelinating lesions involving the thalamus and basal ganglia. This is the first report of tic disorder occurring as a manifestation of MS.

[Historical aspects of multiple sclerosis]. / Aspectos históricos de la esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is one of the most common diseases of the central nervous system (CNS) in young adults. MS is the most common disorder of the central nervous system in young people living in temperate climate regions. Although a few references to possible cases of the disease come from the xiii century, its scientific observation and systematic study only started in the late xix century. DEVELOPMENT: Robert Carswell e Jean Cruveilhier were the first investigators to document the pathological lesions while the clinical picture was first studied by Charcot. In spite of a huge number of infectious agents has been proposed for the etiology of MS and a genetic susceptibility trait recently defined, the ultimate cause of the disease remains to be determined. The development of diagnostic criteria sets, clinical disability scales and image methods in the latter half of the last century has provided investigators with useful research tools allowing unprecedented advances. In the last 30 years ACTH and corticosteroids have been employed as treatment for MS relapses. Starting in 1993 a new class of drugs called disease modifying agents, such as interferon beta and more recently glatiramer acetate, was introduced with encouraging results. CONCLUSIONS: MS is postulated to be a cell mediated autoimmune disease directed against CNS myelin components and characterized by inflammation and chronic demyelination. This paper is a review of the principal most significant events in the search for knowledge of the disease in the world.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: report on 23 cases.

Schistosoma mansoni infection is likely to be responsible for a significant proportion of cases of myelopathy occurring in areas where schistosomiasis is endemic. The aim of this study is to describe the clinical, laboratory and therapeutic data of 23 patients with schistosomal myeloradiculopathy. The medical records of 23 patients with schistosomal myelopathy admitted to two general hospitals of Belo Horizonte (MG), in Brazil, from 1995 to 1999, were reviewed retrospectively. Seventeen patients were male (74%). The mean age for the whole group was 27 years. Lower limb weakness and associated lumbar and/or lower limb pain were reported by 20 patients (87%), and 16 (70%) were unable to walk. All individuals presented urinary retention and 19 (83%) complained of intestinal dysfunction. The treatment was based on the association of antischistosomal drugs and corticosteroids. Five patients (22%) presented a full response to treatment, 13 (57%) partial response without functional limitations and 4 (17%) partial improvement with limitations or no response. Three out of the 4 patients who stopped steroids before 45 days of treatment developed recurrence of the symptoms and signs of myelopathy. Our cases demonstrate the severe presentation of the disease and the data disclosed here suggest that treatment with steroids should be kept for months after clinical improvement.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: report on 23 cases

Schistosoma mansoni infection is likely to be responsible for a significant proportion of cases of myelopathy occurring in areas where schistosomiasis is endemic. The aim of this study is to describe the clinical, laboratory and therapeutic data of 23 patients with schistosomal myeloradiculopathy. The medical records of 23 patients with schistosomal myelopathy admitted to two general hospitals of Belo Horizonte (MG), in Brazil, from 1995 to 1999, were reviewed retrospectively. Seventeen patients were male (74 percent). The mean age for the whole group was 27 years. Lower limb weakness and associated lumbar and/or lower limb pain were reported by 20 patients (87 percent), and 16 (70 percent) were unable to walk. All individuals presented urinary retention and 19 (83 percent) complained of intestinal dysfunction. The treatment was based on the association of antischistosomal drugs and corticosteroids. Five patients (22 percent) presented a full response to treatment, 13 (57 percent) partial response without functional limitations and 4 (17 percent) partial improvement with limitations or no response. Three out of the 4 patients who stopped steroids before 45 days of treatment developed recurrence of the symptoms and signs of myelopathy. Our cases demonstrate the severe presentation of the disease and the data disclosed here suggest that treatment with steroids should be kept for months after clinical improvement

The clinical profile of childhood optic neuritis.

PURPOSE: To report the clinical features and outcome of a series of children with optic neuritis. METHODS: We reviewed the medical records of patients up to 16 years old with optic neuritis. Group 1 comprised children seen up to two weeks after the onset of visual loss; Group 2 comprised patients already harboring optic atrophy. RESULTS: There were 15 boys and 12 girls. The mean age was 10.9 years. Bilateral optic neuritis occurred in 10. Optic disc pallor was found in 35%, edema in 46%, and 19% had normal fundus. During follow-up visual acuity improved in all but one eye in Group 1, and in six of seven eyes in children in Group 2. Just one child converted to multiple sclerosis. CONCLUSIONS: This study shows that the clinical features of childhood optic neuritis differ from those observed in adults. In children it has a better visual outcome and a lower conversion rate to multiple sclerosis than in adults.

[Recommendations for the use of immunomodulatory drugs in multiple sclerosis: the BCTRIMS consensus] [Brazilian Committee for Treatment and Research in Multiple Sclerosis]. / Recomendações quanto ao uso de drogas imunomoduladoras na esclerose múltipla: o consenso do BCTRIMS.

After brief considerations about clinical course and diagnosis in multiple sclerosis, the members of the BCTRIMS present some recommendations for the use of the immunomodulatory drugs in the treatment of this disease.

[Etiological and clinical characteristics of infectious optic neuritis]. / Caracterização etiológica e clínica das neurites ópticas infecciosas.

Fifty-one patients with infectious optic neuritis (ION) with no associated choroidal or retinal involvement were studied in relation to the etiologic agents, and to the epidemiological and clinical features to look up features which could be used to distinct them from the demyelinating optic neuritis (DON) which have a well-known tendency to convert to multiple sclerosis. Bilateral involvement was found in 23 patients (45.1%), simultaneously in 18 cases. Sex distribution was 2M:1F. The ages ranged from 1 to 82 years (median 34.8); 1/3 of the patients were younger than 20 and 1/3 were 50 years of age or older. Syphilis was found in 19 patients being the single most common etiology, whereas viral infections were found in 41.2% of the cases. Visual acuity was severely damaged in most patients and was worse than 20/200 in 57.3% of the involved eyes. Color vision was affected in 91.8%. Visual field defects were found in 92.2%, with predominance of the central defects (40.7%). The optic disc was abnormal in 90.5% of the eyes. This study clearly demonstrates that ION and DON have distinct epidemiological and clinical features. The awareness of these differences may help clinicians to follow different paths for the correct diagnosis and appropriate treatment and prognostic orientation of their patients.