Treating neuromyelitis optica with azathioprine: 20-year clinical practice.

BACKGROUND: Neuromyelitis optica leads to severe disability. Preventive treatment includes steroids and immunosuppressants, and indications are based on retrospective and observational studies. METHODS: We analyzed 158 patients with neuromyelitis optica regarding disease course, prognostic factors, and treatment response to azathioprine, a widely available low-cost drug. Disability accumulation was used as an endpoint to treatment response. RESULTS: Eight patients with monophasic and 150 with relapsing disease with a median 7 years of disease duration and 4.6 years of follow-up were evaluated. All relapsing patients received preventive treatment, 100 with azathioprine. Only 30% reached Expanded Disability Status Scale (EDSS) 6, and 69% of patients presented no disability accumulation along follow-up. The time under azathioprine and prednisone use were inversely correlated to the hazard of disability accumulation (hazard ratio (HR) = 0.981 and 0.986, respectively; p < 0.01). Each month under azathioprine use reduced disability accumulation by 2.6% (HR = 0.974, p < 0.01), corresponding to an 80% decrease in EDSS progression over 5 years. INTERPRETATION: We report less disability accumulation than previous series on patients with neuromyelitis optica, two-thirds presenting no disability accumulation along follow-up. Continued azathioprine used from early disease onset was strongly associated to maintenance of neurological function and should be offered as a viable option for low-income scenarios.

Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration.

AIM: Experimental autoimmune encephalomyelitis (EAE) is a CD4(+)-mediated autoimmune pathology of the central nervous system (CNS) that is used as a model for the study of the human neuroinflammatory disease, multiple sclerosis. During the development of EAE, auto-reactive Th1 and Th17 CD4(+) T cells infiltrate the CNS promoting inflammatory cells recruitment, focal inflammation and tissue destruction. In this sense, statins, agents used to lower lipid levels, have recently shown to exert interesting immunomodulatory function. In fact, statins promote a bias towards a Th2 response, which ameliorates the clinical outcome of EAE. Additionally, simvastatin can inhibit Th17 differentiation. However, many other effects exerted on the immune system by statins have yet to be clarified, in particular during neuroinflammation. Thus, the aim of this study was to investigate the effects of simvastatin on the development of experimental autoimmune encephalomyelitis. METHODS: Mice were immunized with MOG(35-55) and EAE severity was assessed daily and scored using a clinical scale. Cytokine secretion by mononuclear cells infiltrating the CNS was evaluated by flow cytometry. RESULTS: Simvastatin (5 mg/kg/day) improved clinical outcome, induced an increase in TGF-ß mRNA expression and inhibited IL-6, IL-12p40, IL-12p70, RANTES and MIP-1ß secretion (p < 0.05). This was accompanied by a significant decrease in CNS inflammatory mononuclear cell infiltration, with reduced frequencies of both Th1 and Th17 cells. Simvastatin inhibited the proliferation of T lymphocytes co-cultured with primary microglial cells. CONCLUSIONS: Simvastatin treatment promotes EAE clinical amelioration by inhibiting T cell proliferation and CNS infiltration by pathogenic Th1 and Th17 cells.

A mixture model for differentiating longitudinal courses of multiple sclerosis.

BACKGROUND: Multiple sclerosis has a broad spectrum of clinical courses. Early identification of patients at greater risk of accumulating disability is essential. OBJECTIVES: Identify groups of patients with similar presentation through a mixture model and predict their trajectories over the years. METHODS: Retrospective study of patients from 1994 to 2019. We performed a latent profile analysis followed by a latent transition analysis based on eight parameters: age, disease duration, EDSS, number of relapses, multi-topographic symptoms, motor impairment, sphincter impairment, and infratentorial lesions. RESULTS: We included 629 patients, regardless of the phenotypical classification. We identified three distinct groups at the beginning and end of the follow-up. The three-classes model disclosed the "No disability regardless disease duration" (NDRDD) class with low EDSS and younger patients, the "Disability within a short disease duration" (DSDD) class with the worse disability besides short illness, and the "Disability within a long disease duration" (DLDD) class that achieved high EDSS over a long disease duration. EDSS, disease duration, and no sphincter impairment had the best entropy to distinguish classes at the initial presentation. Over time, the patients from NDRDD had a 52.1 % probability of changing to DLDD and 7.7 % of changing to DSDD. CONCLUSIONS: We identified three groups of clinical presentations and their evolution over time based on considered prognostic factors. The most likely transition is from NDRDD to DLDD.

Spontaneous intracranial hypotension: from cerebral venous thrombosis to neurosurgical treatment: a case series experience from a Brazilian tertiary health care center.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a secondary cause of headache and an underdiagnosed disease. The clinical presentation can be highly variable. It typically presents with isolated classic orthostatic headache complaints, but patients can develop significant complications such as cerebral venous thrombosis (CVT). OBJECTIVE: To report 3 cases of SIH diagnosis admitted and treated in a tertiary-level neurology ward. METHODS: Review of the medical files of three patients and description of clinical and surgical outcomes. RESULTS: Three female patients with SIH with a mean age of 25.6 ± 10.0 years old. The patients had orthostatic headache, and one of them presented with somnolence and diplopia because of a CVT. Brain magnetic resonance imaging (MRI) ranges from normal findings to classic findings of SIH as pachymeningeal enhancement and downward displacement of the cerebellar tonsils. Spine MRI showed abnormal epidural fluid collections in all cases, and computed tomography (CT) myelography could determine an identifiable cerebrospinal fluid (CSF) leak in only one patient. One patient received a conservative approach, and the other two were submitted to open surgery with laminoplasty. Both of them had uneventful recovery and remission in surgery follow-up. CONCLUSION: The diagnosis and management of SIH are still a challenge in neurology practice. We highlight in the present study severe cases of incapacitating SIH, complication with CVT, and good outcomes with neurosurgical treatment.

ANTECEDENTES: Hipotensão intracraniana espontânea (HIE) é uma causa secundária de cefaleia e uma doença subdiagnosticada. A apresentação clínica pode ser muito variável. Tipicamente, se apresenta com queixas isoladas de cefaleia ortostática clássica, porém pode evoluir com complicações significativas como trombose venosa cerebral (TVC). OBJETIVO: Relatar 3 casos de diagnóstico de hipotensão intracraniana espontânea manejados em uma enfermaria de neurologia de nível terciário. MéTODOS: Revisão dos prontuários de três pacientes e descrição dos resultados clínicos e cirúrgicos. RESULTADOS: Três pacientes do sexo feminino com média de idade de 25.6 ± 10.0 anos. As pacientes apresentavam cefaleia ortostática e uma delas apresentou sonolência e diplopia devido a TVC. A ressonância magnética (RM) do encéfalo varia de achados normais até achados clássicos de HIE como realce paquimeníngeo e deslocamento inferior das tonsilas cerebelares. A RM da coluna mostrou coleções anormais de líquido epidural em todos os casos e a mielografia por tomografia computadorizada (TC) foi capaz de determinar fístula liquórica identificável em apenas uma paciente. Uma paciente recebeu abordagem conservadora e as outras duas foram submetidas a cirurgia aberta com laminoplastia. Ambas tiveram recuperação e remissão sem intercorrências no seguimento cirúrgico. CONCLUSãO: O diagnóstico e manejo da hipotensão intracraniana ainda são desafios na prática neurológica. Destacamos no presente estudo casos graves, complicação com TVC e bons resultados com tratamento neurocirúrgico.

Sleep disorders in multiple sclerosis: a case-control study using the São Paulo Epidemiologic sleep study (Episono) database.

BACKGROUND: Sleep disorders such as obstructive sleep apnea and restless legs syndrome are prevalent in the general population and patients with chronic diseases such as multiple sclerosis (MS). OBJECTIVES: This study compared the prevalence of sleep disorders complaints, fatigue, depression, and chronotype of adult patients with multiple sclerosis (PwMS) to a representative sample of São Paulo city residents. METHODS: A comparative study was made between PwMS and volunteers from the São Paulo Epidemiologic Sleep Study (Episono) study. We compared the scores of sleep questionnaires using the multivariate analysis of variance (MANOVA) test to evaluate the effects and analysis of variance (ANOVA) as a follow-up test. Covariates were age, sex, and physical activity. The Pearson correlation test was performed to measure the correlation between Expanded Disability Status Scale (EDSS) and the scores of the sleep questionnaires. Finally, we applied propensity score matching to reduce bias in estimating differences between the two groups. Analyses were performed using Stata 14 (StataCorp, College Station, TX, USA) and IBM SPSS Statistics for Windows version 22.0 (IBM Corp., Armonk, NY, USA). RESULTS: The Episono group had worse sleep quality, and more excessive daytime sleepiness than PwMS. Obstructive sleep apnea and restless legs syndrome were more frequent in the Episono group. There was no difference in chronotype between the two groups, with morning and intermediate preference. There was no correlation between EDSS and sleep complaints. Fatigue was intensively present among PwMS. CONCLUSIONS: Disease Modifying Drug (DMD)-treated PwMS had a lower frequency of sleep complaints, no difference in chronotype, and a higher prevalence of fatigue than a sample of São Paulo city residents. The immunomodulatory drugs commonly used to treat MS may have contributed to these findings.

ANTECEDENTES: Os distúrbios do sono são prevalentes na população em geral e em pacientes com doenças crônicas, como a esclerose múltipla (EM). OBJETIVOS: No presente estudo, comparamos a prevalência de queixas de distúrbios do sono, fadiga, depressão e cronotipo de pacientes adultos com EM com uma amostra representativa dos moradores da cidade de São Paulo. MéTODOS: Estudo comparativo entre pacientes com EM e voluntários saudáveis do estudo São Paulo Epidemiologic Sleep Study Episono. Comparamos as pontuações dos questionários de sono usando o teste de análise de variância multivariada (MANOVA, na sigla em inglês) para avaliar os efeitos e o teste de análise de variância (ANOVA, na sigla em inglês) como um teste de acompanhamento. As covariáveis usadas foram idade, gênero e atividade física. O teste de correlação de Pearson foi aplicado para medir a correlação entre o Expanded Disability Status Scale (EDSS) e os escores dos questionários de sono. Por fim, aplicamos o Propensity Score Matching para reduzir o viés na estimativa das diferenças entre os dois grupos. RESULTADOS: O grupo Episono apresentou pior qualidade do sono e mais sonolência excessiva diurna do que os pacientes com EM. A apneia obstrutiva do sono e a síndrome das pernas inquietas foram mais frequentes no grupo Episono. Não houve diferença no cronotipo entre os dois grupos, com predomínio matutino e intermediário. Os pacientes com EM apresentaram mais fadiga do que o grupo controle. CONCLUSõES: Pacientes com EM tratados apresentaram menor frequência de queixas de sono, sem diferença no cronotipo, com maior prevalência de fadiga do que uma amostra de moradores da cidade de São Paulo. Os medicamentos imunomoduladores comumente usados para tratar EM podem ter contribuído para estes achados.

Translation and cultural validation of the Revised Illness Perception Questionnaire for Healthcare Professionals for Brazilian Portuguese.

BACKGROUND: Multiple sclerosis progression and disability can be rated differently by healthcare professionals. Therefore, how physicians perceive the disease can impact treatment decisions. There are no previous studies on this matter. OBJECTIVE: To translate and transculturally validate the Revised Illness Perception Questionnaire for Healthcare Professionals (IPQ-R HP), for use in Brazilian Portuguese. METHODS: The process used to validate the IPQ-R HP was based on the steps presented in the guide proposed by Dorcas Beaton. The final version of the IPQ-R HP had 38 questions, divided into seven different dimensions to assess the patient's disease. Also, two clinical cases that were representative of real-life patients with multiple sclerosis (MS) were assembled to consider the two main profiles of the disease. We applied the questionnaire to neurologists at the Federal University of São Paulo (UNIFESP) to assess their perception of MS. These doctors also answered a brief survey to establish the profile of the interviewees. For statistical analysis, we used Bayesian CFA models and kappa statistics. CONCLUSIONS: The kappa statistics showed a general agreement of 0.4. For the Bayesian CFAs with seven-factor correlation solution, we had a poor fit for case 1 with a 95% confidence interval ranging from -52.893 to 273.797 and a PPP of 0.107. Regarding case 2, the model did not converge even after 50,000 iterations, which indicated that the specified model (i.e. seven-factor correlation solution) for case 2 was inadmissible. Thus, the IPQ-R HP questionnaire in Brazilian Portuguese has not been validated.

INFß treatment affects global DNA methylation in monocytes of patients with multiple sclerosis.

The combination of genetic and epigenetic influences alters the development of complex diseases. Aberrant patterns of DNA methylation are associated with inflammation and clinical activity in MS. We evaluated the differences between global DNA methylation in lymphocytes and monocytes of patients with MS compared to healthy controls. Thirty-three patients with RRMS (PwRMS) and five healthy individuals were included. DNA was isolated from PBMCs by a phenol-chloroform method, and global methylation was analyzed by Imprint® Methylated DNA Quantification Kit. We observed a cell-type-specific DNA methylation pattern and showed that monocyte global DNA methylation was significantly affected by IFNß treatment.

Myelopathies in patients older than 50: not to miss inflammatory etiologies.

BACKGROUND: Inflammatory myelopathies are primarily associated with younger age, and there are few studies in the elderly. Longitudinally extensive spinal cord lesions (LECL) are common in inflammatory myelopathies, but when the first event occurs in older age may have a broader differential diagnosis. OBJECTIVES: To identify all non-traumatic myelopathies' etiologies in patients older than 50 years in a tertiary care hospital and to evaluate characteristics that differentiate inflammatory from non-inflammatory etiologies, focusing on the late-onset (≥50 years old) longitudinally extensive spinal cord lesions (LO-LECL) group. METHODS: Retrospective study of patients admitted between 2008 to 2019. Demographic, clinical, laboratory, and magnetic resonance imaging (MRI) data of all patients were analyzed to identify predictors that could more easily identify inflammatory from non-inflammatory etiologies and further identify the etiologies of LO-LECL. RESULTS: One hundred and three patients 50 years or older diagnosed with non-traumatic myelopathy were included, despite the lesion extension. Five were vascular (5%), 10 spondylotic (10%), 16 other etiologies (16%), 22 inflammatory (21%) and 50 neoplastic myelopathies (49%). Among 23 LO-LECL, 3 were vascular (13%), 4 neoplastic (17%), 7 other etiologies (30%) and 9 inflammatory (39%). The inflammatory LO-LECL had the median time to nadir significantly different from the neoplastic and the other etiologies groups and had the median EDSS at last visit (3.5) significantly lower than the non-inflammatory LO-LECL (7.0-7.5). CONCLUSIONS: Inflammatory etiologies are not to be disregarded in older adults with non-traumatic myelopathies. The symptoms' temporal profile is critical to differentiate inflammatory LO-LECL from other etiologies and it has better functional recovery after adequate treatment.

What can be expected to be seen in a Neurology ward? Eleven-year experience in a Brazilian university hospital.

BACKGROUND: Neurological disorders are significant causes of morbidity and mortality worldwide. However, data about general neurological inpatient admissions in Brazil is limited. Objective: To investigate the prevalence of neurological disorders according to disease group and lesion site among patients admitted to a general Neurology ward. METHODS: This was an observational and descriptive study. The hospital discharge database for the Neurology ward was surveyed in accordance with the International Classification of Diseases, 10th edition (ICD-10), from September 2008 to October 2019. The final diagnosis was classified into neurological disorder groups and site. RESULTS: Overall, 2,606 clinical neurological patient files were included, with mean length of hospitalization of 16.7 days and a total of 325 readmissions (12.5%). The overall mortality rate in the ward was 3.8% (100 patients). Among all the diagnoses, cerebrovascular disease was the most prevalent (45.8%), followed by inflammatory disorders (22.2%). The brain was the most common lesion site (66.0%), followed by peripheral nerves (10.0%) and meninges and cerebrospinal fluid (7.7%). CONCLUSIONS: The disease pattern upon admission showed that a majority of the cases consisted of cerebrovascular disorders and that the brain was the most frequently affected structure, although we observed that a wide variety of cases were admitted, encompassing all neurological disorders.

Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy.

For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.

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.

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.

Employment status of people diagnosed with multiple sclerosis in Brazil.

OBJECTIVE: To describe the employment status of Brazilians with multiple sclerosis (MS). METHODS: Analysis of a cross-sectional online survey including questions on demographic and occupational status at the time of diagnosis and survey completion, and time from the first symptom to diagnosis. RESULTS: Of those who answered the survey, 804 Brazilians with MS were included. Median age of onset and current age were 28.3 and 36.2 years; median time to diagnosis and disease duration were 2.7 and 7.9 years; 67% held a university degree and 29% finished high school; 94% had a paid occupation contributing to the family income at least once in their lives, 77% were employed at the time of diagnosis but only 59% were employed at the time of survey. Longer disease duration, longer time to diagnosis and younger age at the first symptom, were identified as factors correlated with being unemployed. CONCLUSIONS: The rate of unemployment doubled after the first symptoms of MS, and only 59% of highly-educated people with MS in their productive years were employed. The longer time to diagnosis may imply treatment delay, and strategies focusing on early diagnosis and adequate treatment may favor employment retention and reduce disability related costs, such as social benefits and pension fund use.

Multiple sclerosis has a distinct lipid signature in plasma and cerebrospinal fluid.

OBJECTIVE: The diagnosis of multiple sclerosis (MS) has changed over the last decade, but remains a composite of clinical assessment and magnetic resonance imaging to prove dissemination of lesions in time and space. The intrathecal synthesis of immunoglobulin may be a nonspecific marker and there are no plasma biomarkers that are useful in the diagnosis of MS, presenting additional challenges to their early detection. METHODS: We performed a preliminary untargeted qualitative lipidomics mass spectrometry analysis, comparing cerebrospinal fluid (CSF) and plasma samples from patients with MS, other inflammatory neurological diseases and idiopathic intracranial hypertension. RESULTS: Lipid identification revealed that fatty acids and sphingolipids were the most abundant classes of lipids in the CSF and that glycerolipids and fatty acids were the main class of lipids in the plasma of patients with MS. The area under the curve was 0.995 (0.912-1) and 0.78 (0.583-0.917), respectively. The permutation test indicated that this ion combination was useful for distinguishing MS from other inflammatory diseases (p < 0.001 and 0.055, respectively). CONCLUSION: This study concluded that the CSF and plasma from patients with MS bear a unique lipid signature that can be useful as a diagnostic biomarker.

Demyelinating disease in patients with myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness, caused by impaired neuromuscular transmission. Patients with MG can present other autoimmune diseases in association, commonly hypo or hyperthyroidism. The association of MG to demyelinating disease is rare and has been described before. We report on three Brazilian patients with MG that presented distinct demyelinating diseases, two monophasic and one recurrent neuromyelitis optica, several years after the diagnosis of MG, and discuss their clinical courses.

Neuromyelitis optica: brain abnormalities in a Brazilian cohort.

Neuromyelitis optica (NMO) is a demyelinating disease consisting of relapsing-remitting optic neuritis and myelitis with a more severe course than Multiple Sclerosis. Recently, it has been shown that almost 50% of patients with NMO can have brain magnetic resonance imaging (MRI) abnormalities. We report on six Brazilian patients with NMO, fulfilling the 1999 Wingerchuck criteria for this disease, with abnormal brain MRI and discuss their clinical and radiological features.

Pediatric-onset multiple sclerosis in Brazilian patients: Clinical features, treatment response and comparison to pediatric neuromyelitis optica spectrum disorders.

BACKGROUND: Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are acquired demyelinating syndromes of the central nervous system more frequently in young adults and their beginning before 18 years of age is rare. They are autoimmune diseases with distinct pathophysiology, clinical presentation, treatment and prognoses. During childhood these conditions often present similar clinical features and differential diagnosis among pNMOSD, pMS and acute disseminated encephalomyelitis (ADEM) is still difficult at disease onset. The aim of this article is to describe the epidemiologic and clinical features, to evaluate the response to treatment and to compare the mains characteristics between the patients with MS and NMOSD who had the first event prior to 18 years of age followed at the Universidade Federal de São Paulo (UNIFESP). METHODS: Retrospective analysis of patients with MS and NMOSD who started the disease before 18 years of age followed for at UNIFESP. All patients fulfilled the McDonald 2010 criteria for MS and the IPND 2015 criteria or 2006 diagnostic criteria for NMOSD. For treatment analysis, we select patients with a follow-up of more than 6 months. RESULTS: Sixty-eight patients fulfilled the inclusion criteria for MS and were selected for analysis. Mean age of onset was 15 years, 73.5% were female and the mean follow-up was 6.7 years. Mean annualized relapse rate (aRR) observed was 0,82 relapse/year and mean progression index (PI) was 0.31 EDSS points/year. The multivariate analysis showed a significant association between the EDSS on first appointment and total number of relapses with neurological disabilities in long term in patients with MS. The treatment with interferon-beta (IFN-ß) and glatiramer acetate (GA) was safe and patients treated with high dose IFN-ß and GA had a statistically significant reduction in disability progression. Eleven patients fulfilled the inclusion criteria for NMOSD: mean age of onset was 14 years, 72.7% were female and the mean follow-up was 6.3 years. Mean aRR observed was 1.5 relapse/year and mean PI was 2.2 EDSS points/year. The treatment with azathioprine was safe and significant halts disability progression. Patients with NMOSD reached EDSS 6 prior than those with MS. CONCLUSIONS: Pediatric demyelinating diseases in Brazil are similar to the diseases described abroad. In patients with pMS, the EDSS score at the first appointment and the total number of relapses were associated with poor prognosis. NMOSD is more severe than MS in pediatric patients. Treatment with DMD and azathioprine was well tolerated and effective in reducing relapse rate and disability.

Recurrent Optic Neuritis as the Initial Symptom in Demyelinating Diseases.

BACKGROUND AND PURPOSE: Optic neuritis (ON) is an inflammation of the optic nerve that can be recurrent, with unilateral or bilateral presentation. Diagnosing recurrent cases may be challenging. We aimed to compare patients with recurrent ON as their initial symptom according to their following final diagnoses: multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), or chronic relapsing inflammatory optic neuropathy (CRION). METHODS: The medical records of patients with initial recurrent ON who were followed at the Neuroimmunology Clinic of the Federal University of São Paulo between 2004 and 2016 were analyzed retrospectively. Patients were classified according to their final diagnosis into MS, NMOSD, or CRION, and the characteristics of these groups were compared to identify predictive factors. RESULTS: Thirty-three patients with recurrent ON were included, and 6, 14, and 13 had final diagnoses of MS, NMOSD, and CRION, respectively. Most of the patients were female with unilateral and severe ON in their first episode, and the initial Visual Functional System Score (VFSS) was ≥5 in 63.6%, 85.7%, and 16.7% of the patients with CRION, NMOSD, and MS, respectively. Anti-aquaporin-4 antibodies were detected in 9 of 21 (42.8%) tested patients. Seven of nine (77.8%) seropositive NMOSD patients experienced transverse myelitis episodes during the follow-up period. A multivariate regression analysis showed that the VFSS at the last medical appointment predicted the final diagnosis. CONCLUSIONS: A lower VFSS at the last medical appointment was predictive of MS. Patients with NMOSD and CRION have similar clinical characteristics, whereas NMOSD patients tend to have worse visual acuity.

CCR5Δ32 - A piece of protection in the inflammatory puzzle of multiple sclerosis susceptibility.

BACKGROUND: Leucocyte infiltration and activation in the central nervous system (CNS) is an important step in the pathogenesis of multiple sclerosis (MS). The Chemokine receptor 5 (CCR5) is implicated in immune cell migration and cytokine release in the CNS, and it was demonstrated to strongly contribute to CNS inflammation and damage in several models of sterile and pathogen-mediated CNS diseases. Although the inhibition of CCR5 results in a beneficial effect in experimental models of MS, conflicting results have been found about the loss-of-function variant CCR5Δ32 (rs333) in MS patients. The aim of this study was to evaluate the association of CCR5Δ32 and MS in a Brazilian case/control cohort. PATIENTS AND METHODS: 261 MS patients and 435 healthy controls were genotyped for CCR5Δ32. Allelic and genotypic frequencies were compared between patients and controls (case/control analysis), and among patients classified according to the MS clinical form (relapsing remitting versus progressive) and severity (EDSS, MSSS and progression index). RESULTS AND DISCUSSION: The CCR5Δ32 variant frequency was statistically higher in controls as compared to patients presenting European-derived ethnic background. The variant was more frequent in progressive MS as compared to RR-MS patients, and, although not statistically significant, a higher frequency of the truncated allele was observed among patients with less severe forms of MS. These findings emphasize the potential involvement of CCR5 signaling in CNS inflammation and damage in MS. CONCLUSION: The CCR5Δ32 deletion is a protective factor against the development and progression of MS in European-derived Brazilian patients.