Postpartum Treatment With Immunoglobulin Does Not Prevent Relapses of Multiple Sclerosis in the Mother.

Multiple sclerosis (MS) is a chronic, neurological, immune-mediated disease that can worsen in the postpartum period. There is no consensus on the use of immunoglobulin for prevention of disease relapses after delivery. We have shown that the controversial beneficial effect of immunoglobulin given immediately after birth could not be observed in patients with MS.

New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19.

We report on nine patients (eight cases of MS and one case of NMOSD) who presented a disease relapse in close temporal association with their first AZD1222 vaccination dose against COVID-19. These patients had been stable for a median period of six years, with no evidence of disease activity and no change in their medication. After a median of 13 days (7 to 25 days) from vaccination, they developed a new relapse with increased disability and new lesions on magnetic resonance imaging. Although this association may be rare, it might be an adverse event of AZD1222.

Coronavirus disease 2019 in Latin American patients with multiple sclerosis.

Patients with multiple sclerosis (MS) who present coronavirus disease 2019 (COVID-19) are of particular interest to neurologists. These patients have a neuroimmune disease and receive immunomodulatory or immunosuppressive therapies in the long-term. We present here data from 73 patients with MS and a confirmed diagnosis of COVID-19 from five Latin American countries. Fifteen patients (20.5%) were hospitalized and two patients died. The use of anti-CD20 therapies was the only risk factor associated to hospitalization and death. Despite the small sample size, this study highlights the awareness regarding therapeutic options for MS during the pandemic.

Severe Exacerbation of Multiple Sclerosis Following Withdrawal of Fingolimod.

BACKGROUND: Fingolimod is an effective therapy for multiple sclerosis (MS). Isolated reports of very aggressive MS rebound after discontinuation of fingolimod are drawing neurologists' attention to this potentially severe complication of the drug. OBJECTIVE: Our objective was to collect literature data on cases of MS rebound following fingolimod withdrawal. In addition, we report six new cases of this adverse event in Brazil. METHODS: We carried out a systematic review of published data on cases of MS rebound after fingolimod was discontinued. In addition, the study reports a retrospective data series of Brazilian patients presenting this rebound reaction. RESULTS: Twenty papers have been published reporting on 52 patients with severe MS rebound after fingolimod withdrawal. Six new patients are included in the present paper, all of them with aggressive rebound and accumulated disability sequelae. CONCLUSION: We recommend gradual discontinuation of fingolimod with replacement by other treatment. The washout period should not exceed 4 weeks.

Seroconversion of JCV antibodies is strongly associated to natalizumab therapy.

Previous infection with John Cunningham virus (JCV) increases the risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS) undergoing treatment with natalizumab. Patients who test negative for JCV antibodies must be assessed every six months due to the risk of seroconversion. Data from the United States of America, Portugal, Holland, France, United Kingdom and Sweden have shown a strong correlation between the use of natalizumab and JCV seroconversion. The authors present now data on patients from Brazil, as there are no data from Latin American countries published on this subject yet. A group of 86 patients with MS with negative results for antibodies against JCV were included in this analyses with at least two JCV antibodies testing. Twenty-five patients (29% of the total group) did not use natalizumab at any time, while the remaining 71% used natalizumab for a median period of 800 days (equivalent to 28 monthly infusions). Seroconversion was observed in 19 patients (22.1%). There was no association of seroconversion with gender, age, previous pulses of corticosteroid or specific MS-modifying drugs. The use of natalizumab was strongly associated to seroconversion (p < 0.0001). The present results confirm the influence of natalizumab therapy on JCV antibodies in several countries and continents.

Late Onset of Neuromyelitis Optica Spectrum Disorders.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. NMOSD starting after the age of 50 years is considered a "late onset" (LO-NMOSD) and seems to be particularly aggressive. The objective of this paper is to present a series of 37 Brazilian patients with LO-NMOSD. METHODS: Retrospective data collection from medical records of patients with LO-NMOSD seen at 14 Brazilian specialized units. RESULTS: The ratio of women to men in the sample was 4.3 to 1. The patients were followed up for a median period of 4 years. Sex, age at disease onset, and ethnic background were not associated with the number of relapses or disability outcomes. Extensive longitudinal myelitis affected 86% of patients, while optic neuritis affected 70%, and brainstem syndromes were present in only 16% of these patients. Six patients are currently using some type of support for walking or are wheelchair-bound. Three have died. Therapeutic options for NMOSD were particularly complicated for these elderly patients, since medications for controlling NMOSD are, in essence, immunosuppressive. Long-term use of corticosteroids can be an issue when the patients have high blood pressure, diabetes mellitus, or dyslipidemia (conditions often seen in elderly individuals). CONCLUSION: This series of LO-NMOSD cases highlights the importance of prompt diagnosis and treatment for these patients.

Clinical Characteristics of Patients With Neuromyelitis Optica Spectrum Disorders With Early Onset.

Neuromyelitis optica spectrum disorder is a severe and disabling disease that manifests with severe relapses of optic neuritis, longitudinally extensive myelitis, and/or brainstem syndromes. The disease is complex and, although onset typically occurs in middle age, children and adolescents may be affected. The present study adds to the literature through detailed clinical data from 36 Brazilian patients with neuromyelitis optica spectrum disorder starting before age 21. This was a retrospective assessment of medical records from 14 specialized units in Brazil. The results showed that the course of neuromyelitis optica spectrum disorder was worse in patients with disease onset before the age of 12 years. Gender and ethnic background did not influence disability accumulation. Over a median period of 8 years, 14% of the patients who presented the initial symptoms of neuromyelitis optica spectrum disorder before the age of 21 years died. In conclusion, the present study adds to the reports from other authors examining the severity of early-onset neuromyelitis optica spectrum disorder.

Clinical characteristics of 153 Brazilian patients with neuromyelitis optica spectrum disorder (NMOSD).

BACKGROUND: The 2015 criteria for diagnosing neuromyelitis optica spectrum disorder (NMOSD) have encouraged several groups across the world to report on their patients using these criteria. The disease typically manifests with severe relapses of optic neuritis, longitudinally extensive myelitis and/or brainstem syndromes, often leading to severe disability. Some patients are seropositive for antibodies against aquaporin-4 (AQP4), others are positive for anti-myelin oligodendrocyte glycoprotein (MOG), while a few are negative for both biomarkers. The disease is complex, and only now are specific therapeutic clinical trials being carried out. The present study adds to the literature through detailed clinical data from 153 medical records of Brazilian patients. METHODS: Retrospective assessment of medical records from nine specialized units in Brazil. RESULTS: NMOSD was more prevalent in females (4.1:1), who had significantly fewer relapses than males (p = 0.007) but presented similar levels of disability over time. African ancestry was associated with higher levels of disability throughout the disease course (p < 0.001), although the number of relapses was similar to that observed in white patients. Concomitant autoimmune diseases were relatively rare in this population (6.5%). Positivity for anti-AQP4 antibodies was identified in 62% of the patients tested, while 3% presented anti-MOG antibodies. Anti-AQP4 antibodies were not associated to worse disease course. The last medical record showed that six patients had died and 13 were wheelchair-bound. Seventy percent of the patients did not respond to first-line therapy (azathioprine and/or corticosteroids), and five patients continued to relapse even after four different courses of treatment. CONCLUSION: The present study adds to the reports from other countries presenting original data on Brazilian patients diagnosed with NMOSD according to the 2015 criteria.

Migraine in 746 patients with multiple sclerosis.

Migraine adds to the burden of patients suffering from multiple sclerosis (MS). The ID-migraine is a useful tool for screening migraine, and the Migraine Disability Assessment questionnaire can evaluate disease burden. The aim of the present study was to assess the presence and burden of migraine in patients with MS. METHODS Patients diagnosed with MS attending specialized MS units were invited to answer an online survey if they also experienced headache. RESULTS The study included 746 complete responses from patients with MS and headache. There were 625 women and 121 men, and 69% of all the patients were aged between 20 and 40 years. Migraine was identified in 404 patients (54.1%) and a moderate-to-high burden of disease was observed in 68.3% of the patients. CONCLUSION Migraine is a frequent and disabling type of primary headache reported by patients with MS.

High levels of alexithymia in patients with multiple sclerosis.

Alexithymia is a personality trait characterized by difficulties identifying and describing feelings. Some researchers describe high levels of alexithymia among patients with multiple sclerosis (MS) but literature data on this subject are scarce. OBJECTIVE: The objective of the present study was to characterize findings of alexithymia in patients with MS. METHODS: This cross-sectional case-control study included 180 patients with MS and a matched control group. Data for patients with MS included disease duration, number of demyelinating relapses and degree of neurological disability, as assessed by the Expanded Disability Scale Score (EDSS). In addition, the Hospital Anxiety and Depression (HAD) scale and the Toronto Alexithymia Scale (TAS) were used. RESULTS: There were 126 women and 54 men in each group, with median age of 37 years and median education of 16 years. Patients with MS had higher degrees of depression (p<0.01), anxiety (p=0.01) and alexithymia (p<0.01) than did control subjects. For individuals with MS, depressive traits (p<0.01), anxious traits (p=0.03), higher age (p=0.02), lower education level (p=0.02), higher degree of disability (p<0.01) and not being actively employed (p=0.03) were associated with higher rates of alexithymia. CONCLUSION: Alexithymia was a relevant finding in patients with MS.

Alexitimia é um traço de personalidade caracterizado pelas dificuldades na identificação e descrição dos sentimentos. Alguns pesquisadores descrevem altos índices de alexitimia em pacientes com esclerose múltipla (EM), porém os dados na literatura são escassos. OBJETIVO: O objetivo do presente estudo foi caracterizar achados de alexitimia em pacientes com EM. MÉTODOS: Este estudo transversal incluiu 180 pacientes com EM e um grupo controle pareado. Dados de pacientes com EM incluíram a duração da doença, número de surtos clínicos de desmielinização e grau de incapacidade neurológica avaliados pela Escala Expandida do Grau de Incapacidade (EDSS). Foram também utilizadas a escala Hospitalar de Ansiedade e Depressão (HAD) e a escala de Alexitimia de Toronto (TAS) foram utilizadas. RESULTADOS: Cada grupo era constituído por 126 mulheres e 54 homens, com mediana de idade de 37 anos e mediana de escolaridade de 16 anos. Pacientes com EM apresentaram maior grau de depressão (p<0.01), ansiedade (p=0.01) e alexitimia (p<0.01) que os controles. Para pessoas com EM, traços depressivos (p<0.01), ansiosos (p=0.03), maior idade (p=0.02), menor nível educacional (p=0.02), maior grau de incapacidade (p<0.01) e o fato de não estar ativamente trabalhando (p=0.03) levaram a maiores níveis de alexitimia. CONCLUSÃO: Alexitimia foi um importante achado em pacientes com EM.

Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis.

Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). OBJECTIVE: To identify the serologic profile of JCV in patients with MS. METHODS: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. RESULTS: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. CONCLUSION: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

Superficial siderosis of the central nervous system is a rare and possibly underdiagnosed disorder.

METHODS: Series of cases collected from Brazilian centers. RESULTS: We studied 13 cases of patients presenting with progressive histories of neurological dysfunction caused by SS-CNS. The most frequent clinical findings in these patients were progressive gait ataxia, hearing loss, hyperreflexia and cognitive dysfunction. The diagnoses of SS-CNS were made seven months to 30 years after the disease onset. CONCLUSION: SS-CNS is a rare disease that may remain undiagnosed for long periods. Awareness of this condition is essential for the clinician.

[Cerebellar infarction: analysis of 151 patients]. / Infarto cerebelar: análise de 151 pacientes.

This report presents the treatment of 151 patients with cerebellar infarction, 98 men (65%) and 53 women (35%), mean age 62.4 years old. Occlusive hydrocephalus was diagnosed in 7.9% of the patients associated with an extensive cerebellar infarction and in all 11 surgical patients (7.2%). Four patients underwent an external ventricular drainage with 3 deaths (75%) and 7 underwent a decompressive suboccipital craniectomy with 2 deaths (28.5%). Mortality of the clinical group was 15 patients (10.7%). Vertigo, vomiting, Romberg sign and dysmetria were the signs and symptoms of cerebellar involvement that were most frequently observed. Cerebellar infarction from embolism after cardiovascular surgery occurred in 57 patients (37.7%). Cerebellar infarction, as an isolated fact, occurred in 59 patients (39%) and cerebellar plus infarction in other regions occurred in 92 patients (61%). Magnetic resonance image was the best diagnostic form for cerebellar lesions, however computerized tomography could show cerebellar infarction in 68 patients (78%).

Dengue fever in patients with multiple sclerosis taking fingolimod or natalizumab.

Dengue fever is the most prevalent mosquito-borne viral illness in humans. There may be different clinical manifestations of the disease, from mild symptoms to hemorrhagic forms of dengue fever and even neurological complications of this viral infection. Blood cells are usually affected, and thrombocytopenia is the hallmark of the disease. This paper presents 15 cases of dengue fever in patients with multiple sclerosis (MS) taking fingolimod or natalizumab. There were no complications of dengue fever or worse outcomes of MS in these patients, and only four of them needed short-term treatment withdrawal due to lymphopenia.

Cerebrum-cervical arterial dissection in adults during sports and recreation.

UNLABELLED: Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities. METHODS: Retrospective data on patients with arterial dissection related to sports and recreation. RESULTS: Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature. CONCLUSION: Arterial dissection may be a complication from practicing sports.

Alternatives for reducing relapse rate when switching from natalizumab to fingolimod in multiple sclerosis.

Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.

Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system / Recomendações do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia (DCNI/ABN) e do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e Doenças Neuroimunológicas (BCTRIMS) sobre vacinação em geral e contra a SARS-CoV-2 para pacientes com doenças desmielinizantes do sistema nervoso central

ABSTRACT The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

RESUMO O DC de Neuroimunologia da ABN e o BCTRIMS trazem, nesse documento, as recomendações sobre vacinação da população com doenças desmielinizantes do sistema nervoso central (SNC) contra infecções em geral e contra o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2), causador da COVID-19. Destaca-se a gravidade do atual momento frente ao avanço da COVID-19 em nosso País, o que torna mais evidente e importante a criação de guia de referência para orientação aos médicos, pacientes e autoridades de saúde pública quanto à vacinação, meio efetivo e seguro no controle de determinadas doenças infecciosa. O DCNI/ABN e o BCTRIMS recomendam que os pacientes com doenças desmielinizantes do SNC (ex., EM e NMOSD) sejam constantemente monitorados, quanto a atualização do seu calendário vacinal, especialmente, no início ou antes da mudança do tratamento com uma droga modificadora de doença (DMD). É importante também salientar que as vacinas são seguras e os médicos devem estimular o seu uso em todos os pacientes. Evidentemente, deve ser dada especial atenção às vacinas com vírus vivos atenuados. Por fim, é importante que os médicos verifiquem qual DMD o paciente está em uso e quando foi feita a sua última dose, pois cada fármaco pode interagir de forma diferente com a indução da resposta imune.

Fingolimod Prescribed for the Treatment of Multiple Sclerosis in Patients Younger Than Age 18 Years.

BACKGROUND: There have been no clinical trials for approval of medications for treating multiple sclerosis in patients younger than age 18 years. All treatments are based on personal experience and data from open observational studies. Fingolimod is an oral drug for multiple sclerosis that has been shown to be efficient and safe in adults. The aim of our study is to describe patients with multiple sclerosis who started treatment with fingolimod before the age of 18 years. PARTICIPANTS AND METHODS: Seventeen patients treated with fingolimod were identified in the Brazilian database of children and adolescents with multiple sclerosis. The average time of use of the drug was 8.6 months. RESULTS: Fingolimod showed a good safety and efficacy profile in these patients, all of whom had very active multiple sclerosis. After starting treatment with fingolimod, only one patient had a relapse and a new lesion on magnetic resonance imaging. The patients' degree of disability did not progress. No major adverse events were reported in relation to the first dose of the drug, nor in the short- and medium-term treatment. No patient has been followed for longer than 18 months, thus limiting long-term conclusions. CONCLUSIONS: Off-label use of fingolimod in patients younger than age 18 years may be a good therapeutic option for multiple sclerosis control.