1. 	Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO) 
BMJ Open. 2020 Oct 29;10(10):e035397. doi: 10.1136/bmjopen-2019-035397.
Authors 
Svenja Specovius  1   2 , Hanna G Zimmermann  1   2 , Frederike Cosima Oertel  1   2 , Claudia Chien  1   2 , Charlotte Bereuter  1   2 , Lawrence J Cook  3 , Marco Aurélio Lana Peixoto  4 , Mariana Andrade Fontenelle  4 , Ho Jin Kim  5 , Jae-Won Hyun  5 , Su-Kyung Jung  6 , Jacqueline Palace  7 , Adriana Roca-Fernandez  8 , Alejandro Rubio Diaz  7 , Maria Isabel Leite  7 , Srilakshmi M Sharma  9 , Fereshte Ashtari  10 , Rahele Kafieh  11 , Alireza Dehghani  12 , Mohsen Pourazizi  12 , Lekha Pandit  13 , Anitha Dcunha  13 , Orhan Aktas  14 , Marius Ringelstein  14   15 , Philipp Albrecht  14 , Eugene May  16 , Caryl Tongco  16 , Letizia Leocani  17 , Marco Pisa  17 , Marta Radaelli  17 , Elena H Martinez-Lapiscina  18 , Hadas Stiebel-Kalish  19   20 , Mark Hellmann  19 , Itay Lotan  19 , Sasitorn Siritho  21 , Jérôme de Seze  22 , Thomas Senger  22 , Joachim Havla  23 , Romain Marignier  24 , Caroline Tilikete  25 , Alvaro Cobo Calvo  24 , Denis Bernardi Bichuetti  26 , Ivan Maynart Tavares  27 , Nasrin Asgari  28   29 , Kerstin Soelberg  28   29 , Ayse Altintas  30 , Rengin Yildirim  31 , Uygur Tanriverdi  32 , Anu Jacob  33 , Saif Huda  33 , Zoe Rimler  34 , Allyson Reid  34 , Yang Mao-Draayer  35 , Ibis Soto de Castillo  36 , Michael R Yeaman  37   38 , Terry J Smith  39   40 , Alexander U Brandt #  1   2   41 , Friedemann Paul #  42   2   43 , GJCF International Clinical Consortium for NMOSD
Affiliations 
	•	1 Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
	•	2 NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
	•	3 Department of Pediatrics, University of Utah, Salt Lake CIty, Utah, USA.
	•	4 CIEM MS Research Center, University of Minas Gerais, Medical School, Belo Horizonte, Brazil.
	•	5 Department of Neurology, National Cancer Center, Goyang, Republic of Korea.
	•	6 Department of Ophthalmology, National Cancer Center, Goyang, Republic of Korea.
	•	7 Department of Neurology, Oxford University Hospitals, National Health Service Trust, Oxford, UK.
	•	8 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
	•	9 Department of Ophthalmology, Oxford University Hospitals, National Health Service Trust, Oxford, UK.
	•	10 Kashani MS Center, Isfahan University of Medical Sciences, Isfahan, Iran.
	•	11 School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
	•	12 Department of Ophthalmology, Isfahan Eye Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
	•	13 Department of Neurology, KS Hegde Medical Academy, Nitte University, Mangalore, India.
	•	14 Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
	•	15 Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
	•	16 Swedish Neuroscience Institute Neuro-Ophthalmology, Seattle, Washington, USA.
	•	17 Neurological Department and Institute of Experimental Neurology (INSPE) Scientific Institute, Hospital San Raffaele; and University Vita-Salute San Raffaele, Milan, Italy.
	•	18 Hospital Clinic of Barcelona-Institut d'Investigacions, Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain.
	•	19 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
	•	20 Neuro-Ophthalmology Division, Department of Ophthalmology, Rabin Medical Center, Petah Tikva, Israel.
	•	21 Division of Neurology, Department of Medicine, Siriraj Hospital and Bumrungrad International Hospital, Bangkok, Thailand.
	•	22 Neurology Service, University Hospital of Strasbourg, Strasbourg, France.
	•	23 Institute of Clinical Neuroimmunology, University Hospital, Ludwig Maximilians University, Munich, Germany.
	•	24 Neurology, Multiple Sclerosis, Myelin Disorders and Neuroinflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Lyon, France.
	•	25 Department of Neuro-Ophthalmology, Hospices Civils de Lyon, Lyon, France.
	•	26 Departamento de Neurologia e Neurocirurgia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
	•	27 Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
	•	28 Departments of Neurology, Slagelse Hospital, Slagelse, Denmark.
	•	29 Institutes of Regional Health Research and Molecular Medicine, University of Southern Denmark, Odense, Denmark.
	•	30 Neurology Department, School of Medicine, Koc University and Istanbul University - Cerrahpasa School of Medicine, Istanbul, Turkey.
	•	31 Department of Ophthalmology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
	•	32 Neurology Department Istanbul, Istanbul University, Cerrahpasa School of Medicine, Istanbul, Turkey.
	•	33 Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK.
	•	34 Department of Neurology, NYU Multiple Sclerosis Comprehensive Care Center, NYU School of Medicine, New York, New York, USA.
	•	35 Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
	•	36 Department of Neurology, Hospital Clínico de Maracaibo, Maracaibo, Venezuela.
	•	37 Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, USA.
	•	38 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
	•	39 Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, Ann Arbor, Michigan, USA.
	•	40 Division of Metabolism, Endocrine and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
	•	41 Department of Neurology, University of California, Irvine, California, USA.
	•	42 Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany friedemann.paul@charite.de.
	•	43 Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
# Contributed equally.
	•	PMID: 33122310 
	•	PMCID: PMC7597491 
	•	DOI: 10.1136/bmjopen-2019-035397 
Free PMC article
Abstract 
Purpose: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD. 
Participants: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices. 
Findings to date: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline. 
Future plans: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications. 
Keywords: medical retina; neuro-ophthalmology; neurology; radiology & imaging. 
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. 
	•	64 references 
	•	2 figures 
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2. 	Multiple sclerosis has a distinct lipid signature in plasma and cerebrospinal fluid 
Arq Neuropsiquiatr. 2019 Oct 24;77(10):696-704. doi: 10.1590/0004-282X20190122. eCollection 2019.
Authors 
Enedina Maria Lobato de Oliveira  1 , Daniela Antunes Montani  2 , Diogo Oliveira-Silva  3 , André Filipe Rodrigues-Oliveira  3 , Sandro Luiz de Andrade Matas  1 , Gustavo Bruniera Peres Fernandes  4 , Ismael Dale Cotrim Guerreiro da Silva  5 , Edson Guimarães Lo Turco  2 
Affiliations 
	•	1 Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia Disciplina de Neurologia, São Paulo SP, Brasil.
	•	2 Universidade Federal de São Paulo, Centro de Pesquisa em Urologia, Departamento de Cirurgia. Disciplina de Urologia, São Paulo SP, Brasil.
	•	3 Universidade Federal de São Paulo, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Departamento de Química, São Paulo SP, Brasil.
	•	4 Universidade Federal de São Paulo, Departamento de Psicobiologia, Disciplina de Psicobiologia, São Paulo SP, Brasil.
	•	5 Universidade Federal de São Paulo, Laboratório de Ginecologia Molecular, Departamento de Ginecologia e Obstetrícia, São Paulo SP, Brasil.
	•	PMID: 31664345 
	•	DOI: 10.1590/0004-282X20190122 
Free article
Abstract 
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. 
	•	Cited by 2 articles 
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3. 	Employment status of people diagnosed with multiple sclerosis in Brazil 
Arq Neuropsiquiatr. 2019 May 1;77(5):341-345. doi: 10.1590/0004-282X20190051.
Authors 
Carolina Martines Estrutti  1 , Gustavo San Martin Elexpe Cardoso  2 , Maykon Anderson Pires de Novais  3 , Enedina Maria Lobato de Oliveira  4 , Denis Bernardi Bichuetti  4 
Affiliations 
	•	1 Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo SP, Brasil.
	•	2 Amigos Múltiplos pela Esclerose, Guarulhos SP, Brasil.
	•	3 Universidade Federal de São Paulo, Escola Paulista de Medicina, Disciplina de Economia e Gestão em Saúde, São Paulo SP, Brasil.
	•	4 Universidade Federal de São Paulo, Escola Paulista de Medicina, Disciplina de Neurologia, Ambulatório de Neuroimunologia, São Paulo SP, Brasil.
	•	PMID: 31188998 
	•	DOI: 10.1590/0004-282X20190051 
Free article
Abstract 
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. 
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4. 	Retinal nerve fibre layer evaluation in multiple sclerosis patients with and without optic neuritis 
Acta Ophthalmol. 2019 Jun;97(4):e662-e663. doi: 10.1111/aos.13947. Epub 2018 Oct 14.
Authors 
Fabiana F Gonçalves  1 , Luiz F A Lucatto  1 , Andre S de Camargo  1 , Alessandra B Falcão  2 , Luiz Alberto S Melo Jr  1 , Eric P Andrade  1 , Tiago de A Macruz  1 , Denis B Bichuetti  2 , Enedina M L de Oliveira  2 , Ivan M Tavares  1 
Affiliations 
	•	1 Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.
	•	2 Department of Neurology and Neurosurgery, Paulista School of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.
	•	PMID: 30318736 
	•	DOI: 10.1111/aos.13947 
Free article
No abstract available
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5. 	Pediatric-onset multiple sclerosis in Brazilian patients: Clinical features, treatment response and comparison to pediatric neuromyelitis optica spectrum disorders 
Mult Scler Relat Disord. 2018 Oct;25:138-142. doi: 10.1016/j.msard.2018.07.036. Epub 2018 Jul 20.
Authors 
Manuela de Oliveira Fragomeni  1 , Denis Bernardi Bichuetti  2 , Enedina Maria Lobato Oliveira  2 
Affiliations 
	•	1 Department of Neurology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: manuelafragomeni@gmail.com.
	•	2 Department of Neurology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
	•	PMID: 30075406 
	•	DOI: 10.1016/j.msard.2018.07.036 
Abstract 
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-β) and glatiramer acetate (GA) was safe and patients treated with high dose IFN-β 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. 
Keywords: Epidemiology; Multiple sclerosis; Neuromyelitis optica; Pediatrics; Prognosis; Treatment. 
Copyright © 2018 Elsevier B.V. All rights reserved. 
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6. 	Recurrent Optic Neuritis as the Initial Symptom in Demyelinating Diseases 
J Clin Neurol. 2018 Jul;14(3):351-358. doi: 10.3988/jcn.2018.14.3.351. Epub 2018 May 31.
Authors 
Alessandra Billi Falcão-Gonçalves  1 , Denis Bernardi Bichuetti  2 , Enedina Maria Lobato de Oliveira  2 
Affiliations 
	•	1 Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. alebfalcao@gmail.com.
	•	2 Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
	•	PMID: 29856159 
	•	PMCID: PMC6031992 
	•	DOI: 10.3988/jcn.2018.14.3.351 
Free PMC article
Abstract 
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. 
Keywords: aquaporin 4; multiple sclerosis; neuromyelitis optica; optic neuritis; recurrence. 
Copyright © 2018 Korean Neurological Association. 
Conflict of interest statement 
The authors have no financial conflicts of interest.
	•	Cited by 1 article 
	•	21 references 
	•	4 figures 
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7. 	Treating neuromyelitis optica with azathioprine: 20-year clinical practice 
Mult Scler. 2019 Jul;25(8):1150-1161. doi: 10.1177/1352458518776584. Epub 2018 May 15.
Authors 
Denis Bernardi Bichuetti  1 , Marília Mamprim de Moraes Perin  1 , Nilton Amorim de Souza  1 , Enedina Maria Lobato de Oliveira  1 
Affiliation 
	•	1 Neuroimmunology Clinic, Disciplina de Neurologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
	•	PMID: 29761736 
	•	DOI: 10.1177/1352458518776584 
Abstract 
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. 
Keywords: Neuromyelitis optica; azathioprine; epidemiology; prognosis; treatment. 
	•	Cited by 1 article 
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8. 	CCR5Δ32 - A piece of protection in the inflammatory puzzle of multiple sclerosis susceptibility 
Hum Immunol. 2018 Aug;79(8):621-626. doi: 10.1016/j.humimm.2018.04.015. Epub 2018 May 2.
Authors 
Lian Lopes Troncoso  1 , Alessandra Pontillo  2 , Enedina Maria Lobato de Oliveira  3 , Alessandro Finkelszteijn  4 , Silvete Schneider  4 , José Artur Bogo Chies  5 
Affiliations 
	•	1 Laboratório de Imunobiologia e Imunogenética, Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
	•	2 Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Imunologia, São Paulo, SP, Brazil.
	•	3 Ambulatório de Doenças Desmielinizantes da disciplina de Neurologia, Escola, Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
	•	4 Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
	•	5 Laboratório de Imunobiologia e Imunogenética, Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address: jabchies@terra.com.br.
	•	PMID: 29729320 
	•	DOI: 10.1016/j.humimm.2018.04.015 
Abstract 
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. 
Keywords: CCR5Δ32; Central nervous system; Immunogenetics; Multiple sclerosis. 
Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 
	•	Cited by 2 articles 
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9. 	Movement disorders in multiple sclerosis and neuromyelitis optica: A clinical marker of neurological disability 
Parkinsonism Relat Disord. 2018 Jun;51:73-78. doi: 10.1016/j.parkreldis.2018.03.001. Epub 2018 Mar 3.
Authors 
Carolina Candeias da Silva  1 , Denis Bernardi Bichuetti  1 , Sonia Maria Cesar de Azevedo Silva  1 , Henrique Ballalai Ferraz  1 , Enedina Maria Lobato de Oliveira  2 , Vanderci Borges  1 
Affiliations 
	•	1 Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Brazil.
	•	2 Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Brazil. Electronic address: enedinamariaoliveira@gmail.com.
	•	PMID: 29530725 
	•	DOI: 10.1016/j.parkreldis.2018.03.001 
Abstract 
Introduction: Movement disorders are not rare in demyelinating diseases but there are few studies comparing their frequency between multiple sclerosis and neuromyelitis optica spectrum disorder. Our aim was to determine the frequency and the related features of movement disorders in a cohort of patients with multiple sclerosis and neuromyelitis optica spectrum disorder. 
Methods: It is a cross-sectional study of patients with multiple sclerosis and neuromyelitis optica spectrum disorder. Patients were evaluated by a movement disorder specialist. Data from a personal interview and neurological examination were collected. Fahn-Tolosa-Marin tremor rating scale was used for tremor evaluation. Health-related quality of life was assessed using EuroQol instrument. 
Results: Two hundred fifty-three patients were included (mean [SD] age, 40 [12] years; 74.3% female; median [IQR] EDSS score 2.5 [1.0-6.0]); 26% presented with movement disorders. Paroxysmal dystonia (n = 32) and tremor (n = 27) were the most common movement disorders. Patients with multiple sclerosis and low Expanded Disability Status Scale score (below 4.0) have fewer movement disorders than patients with neuromyelitis optica spectrum disorder. The diagnosis of neuromyelitis optica spectrum disorder was strongly associated with paroxysmal dystonia (OR = 22.07, 95% CI = 2.56-189.78; p = 0.005). Patients with multiple sclerosis and patients without movement disorders have a slightly better quality of life. 
Conclusions: Paroxysmal dystonia was the most common movement disorder in demyelinating diseases and strongly associated with neuromyelitis optica spectrum disorder. 
Keywords: Movement disorders; Multiple sclerosis; Neuromyelitis optica; Paroxysmal dystonia; Tremor. 
Copyright © 2018 Elsevier Ltd. All rights reserved. 
	•	Cited by 1 article 
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10. 	Multiple sclerosis risk perception and acceptance for Brazilian patients 
Arq Neuropsiquiatr. 2018 Jan;76(1):6-12. doi: 10.1590/0004-282X20170167.
Authors 
Denis Bernardi Bichuetti  1 , Carolina Azze Franco  1 , Isaac Elias  1 , Andreia C R Mendonça  2 , Lorraine Fiama Diniz Carvalho  2 , Denise Sisterolli Diniz  3 , Carmen Tur  4   5 , Mar Tintoré  4 , Enedina Maria Lobato de Oliveira  1 
Affiliations 
	•	1 Universidade Federal de São Paulo, Disciplina de Neurologia, São Paulo SP, Brasil.
	•	2 Universidade Federal de Goiás, Faculdade Estácio de Sá de Goiás,Centro de Referência e Investigação em Esclerose Múltipla, Goiânia GO, Brasil.
	•	3 Universidade Federal de Goiás,Centro de Referência e Investigação em Esclerose Múltipla, Goiânia GO, Brasil.
	•	4 Universitat Autònoma de Barcelona, Hospital Universitari Valld'Hebron, Centre of Catalonia, Department of Neurology-Neuroimmunology and Multiple Sclerosis, Barcelona Spain.
	•	5 University College London, Institute of Neurology, Department of Neuroinflammation, London, United Kingdom.
	•	PMID: 29364388 
	•	DOI: 10.1590/0004-282X20170167 
Free article
Abstract 
The perception of multiple sclerosis (MS) severity and risk associated with therapies might influence shared decision making in different countries. We investigated the perception of MS severity and factors associated with risk acceptance in Brazil in 96 patients with relapsing-remitting MS using a standardized questionnaire and compared this with two European cohorts. Multiple sclerosis was perceived as a very severe disease and the risk of developing progressive multifocal leukoencephalopathy due to natalizumab was seen as moderate to high. Seventy-six percent considered a risk of 1:1,000, or higher, an impediment for natalizumab use. Older age was the only variable associated with higher risk acceptance and our patients showed a more conservative profile than German and Spanish patients. Our patients perceived MS severity and progressive multifocal leukoencephalopathy risk similarly to elsewhere, but their willingness to take risks was more conservative. This should be considered when discussing therapeutic options and it might have an impact on guideline adaptations. 
	•	Cited by 1 article 
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11. 	Devic's disease in an adolescent girl with juvenile dermatomyositis 
Rev Bras Reumatol Engl Ed. Sep-Oct 2017;57(5):475-478. doi: 10.1016/j.rbre.2014.12.004. Epub 2015 Mar 9.
[Article in En, Portuguese] 
Authors 
Melissa Mariti Fraga  1 , Enedina Maria Lobato de Oliveira  2 , Claudio Arnaldo Len  1 , Maria Fernanda Campos  2 , Maria Teresa Terreri  3 
Affiliations 
	•	1 Universidade Federal de São Paulo, Departamento de Pediatria, Unidade de Reumatologia Pediátrica, São Paulo, SP, Brazil.
	•	2 Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, São Paulo, SP, Brazil.
	•	3 Universidade Federal de São Paulo, Departamento de Pediatria, Unidade de Reumatologia Pediátrica, São Paulo, SP, Brazil. Electronic address: teterreri@terra.com.br.
	•	PMID: 29037319 
	•	DOI: 10.1016/j.rbre.2014.12.004 
Free article
No abstract available
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12. 	Late onset multiple sclerosis: concerns in aging patients 
Arq Neuropsiquiatr. 2017 Jul;75(7):451-456. doi: 10.1590/0004-282X20170070.
Authors 
Claudia Beatriz de Campos Lotti  1 , Acary Souza Bulle Oliveira  1 , Denis Bernardi Bichuetti  1 , Isac de Castro  2 , Enedina Maria Lobato Oliveira  1 
Affiliations 
	•	1 Universidade Federal de São Paulo, Departamento de Neurologia, São Paulo SP, Brasil.
	•	2 Universidade de São Paulo, Faculdade de Medicina, Disciplina de Nefrologia, São Paulo SP, Brasil.
	•	PMID: 28746432 
	•	DOI: 10.1590/0004-282X20170070 
Free article
Abstract 
Late onset multiple sclerosis (LOMS) is when the first symptom starts after 50 years of age, representing 4.5% of multiple sclerosis (MS) patients. This study describes the clinical characteristics of patients with LOMS followed at a specialized MS center in São Paulo. Data was obtained from medical records of 742 patients with MS. The LOMS frequency was 4.18%, median age at onset was 54 years and the predominant disease course was primary progressive (64.3%). The patients reached the disability landmarks of EDSS grades 3.0, 6.0 and 7.0 in the following proportion and time: EDSS 3.0: 77.42% of patients in 3.7 years; EDSS 6.0: 58.06% in 5.1 years and EDSS 7.0: 32.26% in 5.7 years. The comparative analysis with a matched control group of patients with early onset MS showed that late onset, associated with a progressive course, were predictors of reaching EDSS 3.0 and 6.0 in a shorter time. 
	•	Cited by 2 articles 
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13. 	Association between demyelinating disease and autoimmune rheumatic disease in a pediatric population 
Rev Bras Reumatol Engl Ed. May-Jun 2017;57(3):224-228. doi: 10.1016/j.rbre.2016.09.016. Epub 2016 Oct 25.
[Article in En, Portuguese] 
Authors 
Ana Luiza M Amorim  1 , Nadia C Cabral  2 , Fabiane M Osaku  3 , Claudio A Len  3 , Enedina M L Oliveira  4 , Maria Teresa Terreri  5 
Affiliations 
	•	1 Universidade Federal de São Paulo (Unifesp), Departamento de Pediatria, Setor de Reumatologia Pediátrica, São Paulo, SP, Brazil. Electronic address: amorim.analuiza@gmail.com.
	•	2 Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brazil.
	•	3 Universidade Federal de São Paulo (Unifesp), Departamento de Pediatria, Setor de Reumatologia Pediátrica, São Paulo, SP, Brazil.
	•	4 Universidade Federal de São Paulo (Unifesp), Departamento de Neurologia e Neurocirurgia, Setor de Doenças Desmielinizantes, São Paulo, SP, Brazil.
	•	5 Universidade Federal de São Paulo (Unifesp), Departamento de Pediatria, Setor de Reumatologia Pediátrica, São Paulo, SP, Brazil. Electronic address: teterreri@terra.com.br.
	•	PMID: 28535894 
	•	DOI: 10.1016/j.rbre.2016.09.016 
Free article
Abstract 
Introduction: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. 
Objective: To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. 
Method: 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. 
Results: Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. 
Conclusion: Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults. 
Keywords: Autoimmune diseases; Childhood; Demyelinating diseases; Doenças autoimunes; Doenças desmielinizantes; Doenças reumáticas; Infância; Rheumatic diseases. 
Copyright © 2016 Elsevier Editora Ltda. All rights reserved. 
	•	Cited by 1 article 
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14. 	Positive correlation between functional disability, excessive daytime sleepiness, and fatigue in relapsing-remitting multiple sclerosis 
Arq Neuropsiquiatr. 2016 Jun;74(6):433-8. doi: 10.1590/0004-282X20160069.
Authors 
Douglas Martins Braga  1 , Gilmar Fernandes do Prado  1 , Denis Bernardi Bichueti  1 , Enedina Maria Lobato de Oliveira  1 
Affiliation 
	•	1 Universidade Federal de São Paulo, Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, São Paulo SP , Brasil, Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, Setor de Doenças Desmielizantes e Neuro-sono, São Paulo SP, Brasil.
	•	PMID: 27332066 
	•	DOI: 10.1590/0004-282X20160069 
Free article
Abstract 
Method: Retrospective review of medical records from patients with multiple sclerosis to collect data on severity of fatigue, disability, daytime sleepiness, and depression. From 912 medical records reviewed, 122 reported daytime sleepiness: 67% had relapsing remitting, 12% had primary progressive, and 21% had secondary progressive. 
Results: In 95% of the patients with relapsing remitting who complained of daytime sleepiness and fatigue, association was found between these symptoms and neurological disability. Patients with relapsing remitting who complained of daytime sleepiness and fatigue also experienced depression (p = 0.001). No association between fatigue, excessive daytime sleepiness, depression, and disability was found in patients with progressive disease. 
Conclusion: In relapsing remitting, there is correlation between functional disability, excessive daytime sleepiness and fatigue, a finding not confirmed in primary progressive and secondary progressive form. 
	•	Cited by 1 article 
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15. 	Cost analysis of multiple sclerosis in Brazil: a cross-sectional multicenter study 
BMC Health Serv Res. 2016 Mar 24;16:102. doi: 10.1186/s12913-016-1352-3.
Authors 
Nilceia Lopes da Silva  1 , Maira L S Takemoto  2 , Alfredo Damasceno  3 , Yara D Fragoso  4 , Alessandro Finkelsztejn  5 , Jefferson Becker  6 , Marcus V M Gonçalves  7 , Charles Tilbery  8 , Enedina M L de Oliveira  9 , Dagoberto Callegaro  10 , Fernanda C Boulos  11 
Affiliations 
	•	1 Novartis Biociências SA, Av. Professor Vicente Rao, 90. 04636-000, São Paulo, SP, Brazil. nilceia.lopes@novartis.com.
	•	2 ANOVA Tradução do Conhecimento em Saúde, Rio de Janeiro, RJ, Brazil.
	•	3 Medical School, Universidade Estadual de Campinas, Campinas, SP, Brazil.
	•	4 Medical School, Universidade Metropolitana de Santos, Santos, SP, Brazil.
	•	5 Department of Neurology, HC de Porto Alegre, Porto Alegre, RS, Brazil.
	•	6 Hospital São Lucas da PUCRS, Porto Alegre, RS, Brazil.
	•	7 Hospital Regional Hans Dieter Schimidt, Joinville, SC, Brazil.
	•	8 Division of Neurology, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.
	•	9 Universidade Federal de São Paulo, São Paulo, Brazil.
	•	10 Hospital das Clínicas da USP, São Paulo, SP, Brazil.
	•	11 Novartis Biociências SA, Av. Professor Vicente Rao, 90. 04636-000, São Paulo, SP, Brazil.
	•	PMID: 27009599 
	•	PMCID: PMC4806464 
	•	DOI: 10.1186/s12913-016-1352-3 
Free PMC article
Abstract 
Background: Multiple sclerosis (MS) is a central nervous system disease associated with irreversible progression of disability, which imposes a substantial socioeconomic onus. The objective of this study was to determine the economic impact of multiple sclerosis from the Brazilian household and healthcare system perspectives. Secondary objectives were to assess the impact of fatigue on daily living and health-related quality of life (HRQL) of MS patients. 
Methods: This is a cross-sectional study in which Brazilian eligible patients attending eight major MS specialized sites answered an interview capturing data on demographics, disease characteristics and severity, comorbidities, resource utilization, fatigue, utilities and health-related quality of life from November/2011 to May/2012 . Costs were assessed considering a prevalence-based approach within 1 year of resource consumption and were estimated by multiplying the amount used by the corresponding unit cost. Patients were classified as having mild, moderate or severe disability according to the Expanded Disability Status Scale (EDSS). 
Results: In total, 210 patients who met eligibility criteria were included, 40 % had mild, 43 % moderate and 16 % severe disability; disability level was missing for 1 %. The average total direct cost per year was USD 19,012.32 (SD = 10,465.96), and no statistically significant differences were not observed according to MS disability level (p = 0.398). The use of disease modifying therapies (DMTs) corresponded to the majority of direct expenditures, especially among those patients with lower levels of disability, representing around 90 % of total costs for mild and moderate MS patients. It was also observed that expenses with medical (except DMTs) and non-medical resources are higher among patients with more severe disease. Worsening disability also had an important influence on health-related quality of life and self-perceived impact of fatigue on daily living. 
Conclusion: Our data demonstrates the significant economic impact of MS on both Brazilian household and health system, in terms of DMTs and other disease management costs. When patients move upwards on the disease severity scale, costs with health resources other than drugs are significantly increased. 
Keywords: Cost analysis; Cost of illness; Multiple sclerosis; Quality of life. 
	•	Cited by 5 articles 
	•	51 references 
	•	2 figures 
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16. 	Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration 
Inflammopharmacology. 2015 Dec;23(6):343-54. doi: 10.1007/s10787-015-0252-1. Epub 2015 Nov 11.
Authors 
Daniel May de Oliveira  1   2 , Enedina Maria Lobato de Oliveira  3 , Merari de Fátima Ramires Ferrari  4 , Patrícia Semedo  5 , Meire Ioshie Hiyane  6 , Marcos Antônio Cenedeze  7 , Alvaro Pacheco-Silva  7 , Niels Olsen Saraiva Câmara  7   6 , Jean Pierre Schatzmann Peron  8 
Affiliations 
	•	1 Neuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo, SP, 05508-900, Brazil. daniel-larissa@hotmail.com.
	•	2 Laboratory for Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo (USP), São Paulo, SP, 05508-090, Brazil. daniel-larissa@hotmail.com.
	•	3 Discipline of Clinical Neurology, Federal University of São Paulo UNIFESP, São Paulo, SP, 04023-900, Brazil.
	•	4 Department of Genetics and Evolutive Biology, Biosciences Institute, University of São Paulo (USP), São Paulo, SP, 05508-090, Brazil.
	•	5 Biosciences Institute, University of São Paulo, São Paulo, SP, 05508-900, Brazil.
	•	6 Laboratory for Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo (USP), São Paulo, SP, 05508-090, Brazil.
	•	7 Laboratory of Clinical and Experimental Immunology, Nephrology Division, Medicine Department, Federal University of São Paulo UNIFESP, São Paulo, SP, 04023-900, Brazil.
	•	8 Neuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo, SP, 05508-900, Brazil.
	•	PMID: 26559850 
	•	DOI: 10.1007/s10787-015-0252-1 
Abstract 
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-β mRNA expression and inhibited IL-6, IL-12p40, IL-12p70, RANTES and MIP-1β 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. 
Keywords: Chemokine; Experimental autoimmune encephalomyelitis; Proliferation; Simvastatin; Th1; Th17. 
	•	Cited by 9 articles 
	•	61 references 	
17. 	Why this is not multiple sclerosis: a case based approach 
Arq Neuropsiquiatr. 2015 Dec;73(12):985-92. doi: 10.1590/0004-282X20150163. Epub 2015 Oct 13.
Authors 
Zaira Fernanda Martinho Nicolau  1 , Enedina Maria Lobato de Oliveira  1 , Denis Bernardi Bichuetti  1 
Affiliation 
	•	1 Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
	•	PMID: 26465284 
	•	DOI: 10.1590/0004-282X20150163 
Free article
Abstract 
Objective: To present a case series of patients previously diagnosed as multiple sclerosis (MS) which were later confirmed as an alternative diagnosis, and describe the clinical and paraclinical signs that led to this change. 
Method: Nine patients are described. We reviewed the patient's clinical chart, magnetic resonance images (MRI) and cerebrospinal fluid. 
Results: There was a mean of three typical symptoms of MS and four clinical red flags per patient. MRI red flags were found in 88,9% of all referrals, with a mean of 3 encountered per patient. 
Conclusion: We identified that, not only the misdiagnosed patients did not fulfill MS diagnosis criteria, but also how the described red flags are a useful tool in the differentiation of MS from other diseases. This data is important for guiding future diagnosis, especially for general clinicians and neurologists, which directly interfere with the patient's management, treatment, prognosis and quality of life. 
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18. 	Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers 
Arq Neuropsiquiatr. 2015 Sep;73(9):736-40. doi: 10.1590/0004-282X20150098.
Authors 
Enedina Maria Lobato de Oliveira  1 , Renata Faria Simm  2 , Gorana Dasic  3 , Marília Mamprim de Morais  1 , Samira Luiza dos Apostolos Perreira  2 , Dagoberto Callegaro  2 
Affiliations 
	•	1 Departamento de Neurologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, BR.
	•	2 Departamento de Neurologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, BR.
	•	3 Biogen Idec Inc, Sao Paulo, SP, BR.
	•	PMID: 26352489 
	•	DOI: 10.1590/0004-282X20150098 
Free article
Abstract 
Objective Analyze the demographics, clinical characteristics, efficacy and safety of natalizumab treatment in Brazilian patients with multiple sclerosis (MS) followed up for at least 12 months, in two tertiary MS care centers in São Paulo.Method We evaluated the effect of natalizumab treatment on annualized relapse rate and disability progression in 75 patients with MS treated with natalizumab for at least 12 months. A subgroup analysis was performed to evaluate efficacy of natalizumab treatment in patients with Expanded Disability Status Scale (EDSS) ≤ 3.0 vs patients with EDSS > 3.Results Patients treated for at least one year with natalizumab showed a 91% reduction in aRR, as well and an improvement in neurological disability. The impact of natalizumab treatment was greater in patients with EDSS < 3.0. Overall, natalizumab was safe but one patient developed progressive multifocal leukoencephalopathy.Conclusion Natalizumab as a third line therapy is safe and efficacious, especially in patients with mild neurological disability. 
	•	Cited by 1 article 
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19. 	Use of Fingolimod in the Management of Relapsing-Remitting Multiple Sclerosis: Experience from Latin America 
Adv Ther. 2015 Jul;32(7):612-25. doi: 10.1007/s12325-015-0226-0. Epub 2015 Jul 14.
Authors 
Jorge Correale  1 , Jose Flores, Juan Garcia Bonitto, Claudia Cárcamo Rodríguez, Enedina M L Oliveira
Affiliation 
	•	1 Department of Neurology, Institute for Neurological Research Raúl Carrea, FLENI, Buenos Aires, Argentina, jcorreale@fleni.org.ar.
	•	PMID: 26170106 
	•	PMCID: PMC4522024 
	•	DOI: 10.1007/s12325-015-0226-0 
Free PMC article
Abstract 
Once-daily fingolimod 0.5 mg (FTY720; Gilenya(®), Novartis Pharma AG, Basel, Switzerland) is a sphingosine 1-phosphate receptor modulator that is approved for the treatment of relapsing multiple sclerosis (MS); currently, this includes approval in 13 Latin American countries. However, despite a well-characterized efficacy and safety profile in a large clinical development program, thus far there has been limited representation of patients from across the Latin American region. Differences in MS disease characteristics have been reported for the Latin American population compared with Caucasians, which may be additional to recent improvements in MS diagnosis. Furthermore, healthcare provision and regional socioeconomic factors exist that are unique to Latin America compared with other regions. Therefore, to optimize MS treatment pathways and improve patient clinical outcomes, it is important to investigate the efficacy and safety profile of fingolimod using ethnically relevant data. Here, we review key data from Hispanic patients enrolled in the fingolimod clinical trial program, summarize recent findings from the FIRST LATAM study, and appraise fingolimod data from real-world patient populations. 
Funding: Novartis Pharma AG, Basel, Switzerland. 
	•	63 references 
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20. 	Neuromyelitis optica shorter lesion can cause important pyramidal deficits 
J Neurol Sci. 2015 Aug 15;355(1-2):189-92. doi: 10.1016/j.jns.2015.06.017. Epub 2015 Jun 11.
Authors 
Denis Bernardi Bichuetti  1 , Marcelo Delboni Lemos  2 , Isac de Castro  3 , Gustavo Balthazar da Silveira Carvalho  2 , Renato Sartori de Carvalho  2 , Nitamar Abdala  2 , Enedina Maria Lobato de Oliveira  4 
Affiliations 
	•	1 Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Brazil. Electronic address: bichuetti@unifesp.br.
	•	2 Department of Radiology, Universidade Federal de São Paulo, Brazil.
	•	3 Disciplina de Neurologia, Universidade Federal de São Paulo, Brazil.
	•	4 Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Brazil.
	•	PMID: 26076879 
	•	DOI: 10.1016/j.jns.2015.06.017 
Abstract 
Objective: Evaluate the correlation between spinal cord lesion length and pyramidal function system score in a cohort of patients with NMO. 
Methodology: Retrospective retrieval of all exams performed in our center from January 2004 to December 2012 for patients with NMO. The exams were evaluated for lesion length, contrast enhancement and T1 hypointensity; these variables were correlated with the functional system score from the EDSS, performed no more than three months from the scan. 
Results: 41 patients were included. Although patients with lesion extension ≥2 vertebral segments did not present worse pyramidal scores in a direct comparison, the influence of lesion length was not so strong when patients were separated in 3 groups (≥2, ≥3 or ≥4 vertebral segments) and evaluated with a receiving operating characteristics (ROC) curves. Gadolinium enhancement also contributed to more severe pyramidal system scores, but T1 hypointensity did not. 
Conclusion: Although patients with spinal cord lesion extending ≥3 vertebral segments had more pyramidal disability, its difference was not so strong when compared to patients with ≥2 or ≥4 vertebral segments. This suggests that lesion extension might not be the most important factor in favoring a worse prognosis in spinal cord lesions in NMO. 
Keywords: Clinical correlation; Magnetic resonance imaging; Neuromyelitis optica; Prognosis; Pyramidal deficit; Short lesion. 
Copyright © 2015 Elsevier B.V. All rights reserved. 
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21. 	The profile of patients followed at the Neuroimmunology Clinic at UNIFESP: 20 years analysis 
Arq Neuropsiquiatr. 2015 Apr;73(4):304-8. doi: 10.1590/0004-282X20150004. Epub 2015 Apr 1.
Authors 
Denis Bernardi Bichuetti  1 , Alessandra Billi Falcão  1 , Fernanda de Castro Boulos  1 , Marilia Mamprim de Morais  1 , Claudia Beatriz de Campos Lotti  1 , Manuela de Oliveira Fragomeni  1 , Maria Fernanda Campos  1 , Nilton Amorim de Souza  1 , Enedina Maria Lobato Oliveira  1 
Affiliation 
	•	1 Departamento de Neurologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
	•	PMID: 25992520 
	•	DOI: 10.1590/0004-282X20150004 
Free article
Abstract 
Objective: To describe the clinical activities at the Neuroimmunology Clinic of the Universidade Federal de São Paulo (UNIFESP) from 1994 to 2013. 
Method: The final diagnosis of all patients that attended the center was reviewed and established upon specific guidelines for each disease. The number of total appointments and extra clinical activities (reports and prescriptions) were also analyzed, as are part of routine activities. 
Results: 1,599 patients attended the Clinic from 1994 to 2013: 816 with multiple sclerosis (MS), 172 with clinical isolated syndromes, 178 with neuromyelitis optica (NMO), 216 with other demyelinating disease, 20 with metabolic disorder, 42 with a vascular disease and 155 with other or undetermined diagnosis. A mean 219 outpatient visits and 65 extra clinical activities were performed monthly. 
Conclusion: We identified that 15% of patients seen have NMO. As patients with NMO have a more severe disease than MS, this data may be important for planning local health care policies. 
	•	Cited by 1 article 
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22. 	Laparoscopic implantation of neuromodulators for treating urinary dysfunctions and improving locomotion in multiple sclerosis patients 
Int Urogynecol J. 2015 Dec;26(12):1871-3. doi: 10.1007/s00192-015-2702-0. Epub 2015 May 6.
Authors 
Nucelio Lemos  1 , Denis Bernardi Bichuetti  2 , Renato Moretti Marques  3 , Maria S Conde  2 , Acary S B Oliveira  2 , Manoel J B C Girão  3 
Affiliations 
	•	1 Pelvic Neurodysfunction Clinic of the Department of Obstetrics and Gynecology, Federal University of São Paulo, Rua Jose de Magalhaes, 373 ap904, São Paulo, SP, 04026-090, Brazil. nucelio@gmail.com.
	•	2 Neuromuscular Diseases Clinic of the Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, Brazil.
	•	3 Pelvic Neurodysfunction Clinic of the Department of Obstetrics and Gynecology, Federal University of São Paulo, Rua Jose de Magalhaes, 373 ap904, São Paulo, SP, 04026-090, Brazil.
	•	PMID: 25944656 
	•	DOI: 10.1007/s00192-015-2702-0 
Abstract 
Introduction and hypothesis: The laparoscopic implantation of neuromodulation electrodes--the LION procedure--was first described as a rescue procedure in patients with local complications of a Brindley procedure. The objective of this video article is to demonstrate the technique for the laparoscopic implantation of electrodes for bilateral neuromodulation of femoral, sciatic and pudendal nerves and describe our initial experience with two multiple sclerosis (MS) patients. 
Method: This is a retrospective analysis of two patients with MS and neurogenic detrusor overactivity. A quadripolar electrode was implanted with two poles into the Alcock's canal and the two other laying over the lumbosacral trunk. The other two electrodes were implanted posteriorly to the femoral nerves. 
Results: At the neuromodulation trial, both patients presented a full recovery of urinary symptoms. One of them found it easier to stand up for transfers and daily activities and the other managed to advance from the wheelchair to the walker and both patients received the permanent implant. At 1-year follow up, urinary results were maintained and 1 patient presented a disease relapse, demanding multiple reprogramming sessions. 
Conclusion: Our initial observations are encouraging and indicate that the LION procedure seems to produce in MS patients similar results to those observed in patients with spinal cord injury. Patients, however, should be advised that MS is a progressive disease and that the positive effects of neuromodulation can potentially fade with time and that multiple reprogramming sessions might be necessary. 
Keywords: LION procedure; Laparoscopy; Locomotion; Multiple sclerosis; Neuromodulation; Urinary incontinence. 
	•	Cited by 2 articles 
	•	7 references 
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23. 	Biological and nonbiological complex drugs for multiple sclerosis in Latin America: regulations and risk management 
Expert Rev Neurother. 2015 Jun;15(6):597-600. doi: 10.1586/14737175.2015.1042456. Epub 2015 Apr 30.
Authors 
Adriana Carrá  1 , Miguel Angel Macías Islas, Adriana Tarulla, Denis Bernardi Bichuetti, Alessandro Finkelsztejn, Yara Dadalti Fragoso, Raul Árcega-Revilla, Claudia Cárcamo Rodríguez, Juan Carlos Durán, Juan García Bonitto, Rosalba León, Carlos Oehninger Gatti, Geraldine Orozco, Darwin Vizcarra Escobar
Affiliation 
	•	1 Hospital Británico, Buenos Aires, Buenos Aires, Argentina.
	•	PMID: 25924772 
	•	DOI: 10.1586/14737175.2015.1042456 
Abstract 
Biological drugs and nonbiological complex drugs with expired patents are followed by biosimilars and follow-on drugs that are supposedly similar and comparable with the reference product in terms of quality, safety and efficacy. Unlike simple molecules that can be copied and reproduced, biosimilars and follow-on complex drugs are heterogeneous and need specific regulations from health and pharmacovigilance agencies. A panel of 14 Latin American experts on multiple sclerosis from nine different countries met to discuss the recommendations regarding biosimilars and follow-on complex drugs for treating multiple sclerosis. Specific measures relating to manufacturing, therapeutic equivalence assessment and pharmacovigilance reports need to be implemented before commercialization. Physical, chemical, biological and immunogenic characterizations of the new product need to be available before clinical trials start. The new product must maintain the same immunogenicity as the original. Automatic substitution of biological and complex drugs poses unacceptable risks to the patient. 
Keywords: biosimilars; glatiramer acetate; interferon; monoclonal antibodies; multiple sclerosis. 
	•	Cited by 3 articles 
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24. 	Neuromyelitis optica spectrum disorders: beyond longitudinally extensive transverse myelitis 
Clin Radiol. 2015 Jun;70(6):630-7. doi: 10.1016/j.crad.2015.02.016. Epub 2015 Apr 7.
Authors 
M D Lemos  1 , G B S Carvalho  2 , R S Carvalho  2 , D B Bichuetti  3 , E M L de Oliveira  3 , N Abdala  2 
Affiliations 
	•	1 Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo, Brazil. Electronic address: marcelodelbonilemos@gmail.com.
	•	2 Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo, Brazil.
	•	3 Disciplina de Neurologia, Universidade Federal de São Paulo, Brazil.
	•	PMID: 25861875 
	•	DOI: 10.1016/j.crad.2015.02.016 
Abstract 
Aim: To describe the neuroradiological features and their prevalence in patients with neuromyelitis optica (NMO). 
Materials and methods: Two neuroradiologists independently reviewed 35 spinal cord and 37 brain MRI studies from patients with NMO. The examinations were analysed for the presence of lesion, topography, enhancement, and brain lesions suggestive of multiple sclerosis and/or NMO. 
Results: Seventy percent of the spinal cord lesions involved over three or more vertebral segments. Seventy-eight percent of brain scans were abnormal, and the most prevalent findings were non-specific foci of T2 hyperintensities in the cerebral white matter (55%) and brainstem lesions (52%). One patient had lesions disseminated in space compatible with multiple sclerosis according to 2010 revised McDonald criteria. Brain lesions suggestive of NMO occurred at least once in 17 (59%) patients. 
Conclusion: Spinal cord lesions were often longitudinally extensive and brain lesions were common, with the majority of patients having at least one distinctive NMO lesion. 
Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. 
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25. 	[Devic's disease in an adolescent girl with juvenile dermatomyositis] 
Rev Bras Reumatol. 2015 Jan 28;S0482-5004(15)00020-0. doi: 10.1016/j.rbr.2014.12.004. Online ahead of print.
[Article in Portuguese] 
Authors 
Melissa Mariti Fraga  1 , Enedina Maria Lobato de Oliveira  2 , Claudio Arnaldo Len  1 , Maria Fernanda Campos  2 , Maria Teresa Terreri  3 
Affiliations 
	•	1 Unidade de Reumatologia Pediátrica do Departamento de Pediatria, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
	•	2 Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
	•	3 Unidade de Reumatologia Pediátrica do Departamento de Pediatria, Universidade Federal de São Paulo, São Paulo, SP, Brasil. Electronic address: teterreri@terra.com.br.
	•	PMID: 25772655 
	•	DOI: 10.1016/j.rbr.2014.12.004 
Free article
Abstract 
Devic's disease, also known as neuromyelitis optica, is an autoimmune inflammatory demyelinating disorder of the central nervous system that mainly affects the optic nerve and spinal cord. Recently, Devic's disease was demonstrated to be a channelopathy due to the presence of antibodies against the water channel aquaporin-4 in the blood-brain barrier. There have been reports of Devic's disease in infancy, but there are few reported associations of Devic's disease with other diseases. The association of Devic's disease with dermatomyositis has not yet been described in the literature. The aim of this paper is to describe the first case of Devic's disease in an adolescent with juvenile dermatomyositis. 
Keywords: Adolescent; Adolescente; Dermatomiosite juvenil; Devic's disease; Juvenile dermatomyositis; Neuromielite óptica. 
Copyright © 2015 Elsevier Editora Ltda. All rights reserved. 
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26. 	Seasonality of 278 neuromyelitis optica relapses in a Brazilian cohort 
Arq Neuropsiquiatr. 2015 Feb;73(2):177-8. doi: 10.1590/0004-282X20140213.
Authors 
Denis Bernardi Bichuetti  1 , Manuela de Oliveira Fragomeni  1 , Nilton Amorim de Souza  1 , Enedina Maria Lobato Oliveira  1 
Affiliation 
	•	1 Departamento de Neurologia, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
	•	PMID: 25742595 
	•	DOI: 10.1590/0004-282X20140213 
Free article
No abstract available
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27. 	The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis 
Arq Neuropsiquiatr. 2014 Sep;72(9):712-4. doi: 10.1590/0004-282x20140102.
Authors 
Yara Dadalti Fragoso  1 , Christian Cardoso Arruda  2 , Walter Oleschko Arruda  3 , Joseph Bruno Bidin Brooks  1 , Alfredo Damasceno  4 , Carlos Augusto de Albuquerque Damasceno  5 , Alessandro Finkelsztejn  6 , Juliana Finkelsztejn  6 , Paulo Diniz da Gama  7 , Maria Cristina Brandão Giacomo  8 , Sidney Gomes  9 , Marcus Vinicius Magno Goncalves  10 , Andre Palma da Cunha Matta  11 , Marilia Manprim de Morais  12 , Enedina Maria Lobato de Oliveira  12 , Yuna Ribeiro  13 , Henry Koiti Sato  14 , Carlos Bernardo Tauil  13 
Affiliations 
	•	1 Departamento de Neurologia, Universidade Metropolitana de Santos, Santos, SP, Brazil.
	•	2 Departamento de Neurologia, Universidade Positivo, Curitiba, PR, Brazil.
	•	3 Departamento de Neurologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
	•	4 Departamento de Neurologia, Universidade Estadual de Campinas, Campinas, SP, Brazil.
	•	5 Departamento de Neurologia, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil.
	•	6 Departamento de Neurologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
	•	7 Departamento de Neurologia, Pontifícia Universidade Católica Sorocaba, Sorocaba, SP, Brazil.
	•	8 Clínica Holus MedService, Sao Paulo, SP, Brazil.
	•	9 Departamento de Neurologia, Hospital Beneficência Portuguesa de São Paulo, São Paulo, SP, Brazil.
	•	10 Departamento de Neurologia, Centro Hospitalar Unimed, Joinville, SC, Brazil.
	•	11 Departamento de Neurologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
	•	12 Departamento de Neurologia, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
	•	13 Departamento de Neurologia, Hospital de Base do Distrito Federal, Brasília, DF, Brazil.
	•	14 Departamento de Neurologia, Instituto de Neurologia de Curitiba, Curitiba, PR, Brazil.
	•	PMID: 25252236 
	•	DOI: 10.1590/0004-282x20140102 
Free article
Abstract 
Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world. 
Comment in 
	•	Oral fingolimod to treat multiple sclerosis: see your cardiologist first. Sato DK, Callegaro D. Arq Neuropsiquiatr. 2014 Sep;72(9):651-2. doi: 10.1590/0004-282x20140171. PMID: 25252227No abstract available. 
	•	Cited by 9 articles 
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28. 	Diffusion tensor imaging of the cervical spinal cord of patients with Neuromyelitis Optica 
Magn Reson Imaging. 2014 Jun;32(5):457-63. doi: 10.1016/j.mri.2014.01.023. Epub 2014 Feb 7.
Authors 
René L M Rivero  1 , Enedina M L Oliveira  2 , Denis B Bichuetti  2 , Alberto A Gabbai  2 , Roberto G Nogueira  3 , Nitamar Abdala  3 
Affiliations 
	•	1 Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo-UNIFESP, Brasil. Electronic address: reneleandro3@hotmail.com.
	•	2 Departamento de Neurologia, Universidade Federal de São Paulo-UNIFESP, Brasil.
	•	3 Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo-UNIFESP, Brasil.
	•	PMID: 24636569 
	•	DOI: 10.1016/j.mri.2014.01.023 
Abstract 
Background: Previous studies have demonstrated a correlation between Expanded Disability Status Scale (EDSS) and Diffusion Tensor Imaging (DTI) metrics, but the conclusions were based on evaluations of the entire cervical spinal cord. 
Objectives: The purpose of this study was to quantify the FA and MD values in the spinal cord of NMO patients, separating the lesion sites from the preserved sites, which has not been previously preformed. In addition, we attempted to identify a correlation with EDSS. 
Methods: DTI was performed in 11 NMO patients and 11 healthy individuals using a 1.5-T MRI scanner. We measured the FA and MD at ROIs positioned along the cervical spinal cord. The mean values of FA and MD at lesion, preserved and spinal cord sites were compared with those of a control group. We tested the correlations between the mean FA and MD with EDSS. 
Results: FA in NMO patients was significantly reduced in lesion sites (0.44 vs. 0.55, p=0.0046), preserved sites (0.46 vs. 0.55, p=0.0015), and all sites (0.45 vs 0.55, p=0.0013) while MD increased only in lesion sites (1.03×10(-3)mm(2)/s vs. 0.90×10(-3)mm(2)/s, p=0.009). The FA demonstrated the best correlation with EDSS (r=-0.7603, p=0.0086), particularly at lesion sites. 
Conclusions: The results reinforce the importance of the FA index and confirm the hypothesis that NMO is a diffuse disease. 
Keywords: Diffusion tensor imaging; Disability evaluation; Neuromyelitis optica; Spinal cord. 
Copyright © 2014 Elsevier Inc. All rights reserved. 
	•	Cited by 4 articles 
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29. 	Neuromyelitis optica with onset in childhood and adolescence 
Pediatr Neurol. 2014 Jan;50(1):66-8. doi: 10.1016/j.pediatrneurol.2013.07.003. Epub 2013 Oct 13.
Authors 
Yara Dadalti Fragoso  1 , Maria L B Ferreira  2 , Enedina M L Oliveira  3 , Renan B Domingues  4 , Taysa A G J Ribeiro  5 , Joseph B B Brooks  6 , Rinaldo Claudino  7 , Jussara M K Netto  8 , Sidney Gomes  9 , Tarso Adoni  10 , Denise S D Carneiro  5 , Daiana R P Fonseca  2 , Manuela O Fragomeni  3 , Francisco T M Oliveira  9 , Celso L S Oliveira  6 , Patricia C O Saldanha  4 , Jorge M B Souza  7 
Affiliations 
	•	1 Universidade Metropolitana de Santos, Santos, Brazil. Electronic address: yara@bsnet.com.br.
	•	2 Hospital da Restauracao, Recife, Brazil.
	•	3 Universidade Federal do Estado de Sao Paulo, Sao Paulo, Brazil.
	•	4 Faculdade de Ciencias da Saude, Santa Casa de Vitoria, Vitoria, Brazil.
	•	5 Universidade Federal de Goias, Goiania, Brazil.
	•	6 Universidade Metropolitana de Santos, Santos, Brazil.
	•	7 Universidade Federal de Santa Catarina, Florianopolis, Brazil.
	•	8 Universidade Federal do Rio de Janeiro, Macae, Brazil.
	•	9 Hospital Beneficencia Portuguesa and Hospital Paulistano, Sao Paulo, Brazil.
	•	10 Hospital Sirio Libanes, Sao Paulo, Brazil.
	•	PMID: 24131583 
	•	DOI: 10.1016/j.pediatrneurol.2013.07.003 
Abstract 
Background: Neuromyelitis optica with onset before the age of 18 years is a relatively rare, yet potentially devastating condition. The objective of the present study was to contribute to the study of early-onset neuromyelitis optica with a case series. 
Patients: Data were collected from medical records of Brazilian neurologists caring for patients with neuromyelitis optica occurring in childhood and adolescence. 
Results: Twenty-nine patients with neuromyelitis optica occurring before the age of 18 years and fulfilling the diagnostic criteria were identified. The average age at disease onset was 13 years and the patients had had an average disease duration of 6 years. The expanded disability scale score at the latest consultation was, on average, 4.7, and one patient had died from the disease. The 29 patients had had an average 4.5 relapses during the disease, accounting for 0.75 relapses per year, irrespective of the medication used. All patients were using one or more of the following medications: azathioprine, prednisone, immunoglobulin, and glatiramer acetate. 
Conclusions: Neuromyelitis optica with onset in childhood and adolescence is a poorly understood condition that is often disabling and difficult to manage. 
Keywords: Devic; adolescents; children; demyelinating diseases; multiple sclerosis; neuromyelitis optica. 
Copyright © 2014 Elsevier Inc. All rights reserved. 
	•	Cited by 6 articles 
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30. 	The retinal nerve fiber layer of patients with neuromyelitis optica and chronic relapsing optic neuritis is more severely damaged than patients with multiple sclerosis 
J Neuroophthalmol. 2013 Sep;33(3):220-4. doi: 10.1097/WNO.0b013e31829f39f1.
Authors 
Denis B Bichuetti  1 , André S de Camargo, Alessandra B Falcão, Fabiana F Gonçalves, Ivan M Tavares, Enedina M L de Oliveira
Affiliation 
	•	1 Departamento de Neurologia e Neurocirurgia (DBB, ABF, EMLdO) and Departamento de Oftalmologia (ASdC, FFG, IMT), Universidade Federal de São Paulo, São Paulo, Brazil. bichuetti@unifesp.com
	•	PMID: 23917443 
	•	DOI: 10.1097/WNO.0b013e31829f39f1 
Abstract 
Background: To compare the retinal nerve fiber layer (RNFL) in eyes of patients with relapsing remitting multiple sclerosis (RRMS), neuromyelitis optica (NMO) and chronic relapsing inflammatory optic neuritis (CRION). 
Methods: Evaluation of 62 patients with RRMS, NMO, and CRION in a cross-sectional study with spectral domain optical coherence tomography. 
Results: A total of 124 eyes were evaluated (96 RRMS, 18 NMO, and 10 CRION). Frequency of optic neuritis for each disease was: 34% for RRMS, 84% for NMO, and 100% for CRION. Visual acuity and RNFL thickness were significantly worse in NMO and CRION eyes than in RRMS, but there were no differences between NMO and CRION eyes. A RNFL of 41 μm was 100% specific for optic neuritis associated with NMO and CRION when compared to RRMS. 
Conclusion: This study established RNFL values to differentiate optic neuritis of RRMS from NMO and CRION. Although similarities observed between NMO and CRION eyes might suggest that they are within the same disease spectrum, it is still recommended that these 2 conditions be differentiated on clinical grounds. Optical coherence tomography serves as an additional diagnostic tool and can be used to monitor disease progression. 
	•	Cited by 10 articles 
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31. 	Neuromyelitis optica and pregnancy 
J Neurol. 2013 Oct;260(10):2614-9. doi: 10.1007/s00415-013-7031-y. Epub 2013 Jul 9.
Authors 
Yára Dadalti Fragoso  1 , Tarso Adoni, Denis Bernardi Bichuetti, Joseph Bruno Bidin Brooks, Maria Lucia Brito Ferreira, Enedina Maria Lobato Oliveira, Celso Luis Silva Oliveira, Sonia Beatriz Felix Ribeiro, Alex Eduardo Silva, Fabio Siquineli
Affiliation 
	•	1 Department of Neurology, Medical School, Universidade Metropolitana de Santos (UNIMES), Rua da Constituicao 374, Santos, SP, CEP 11015-470, Brazil, yara@bsnet.com.br.
	•	PMID: 23835638 
	•	DOI: 10.1007/s00415-013-7031-y 
Abstract 
Less than a hundred cases of pregnancies in women with neuromyelitis optica (NMO) have been published in the world. The aim of the present study was to add the Brazilian experience to this subject. Cases of women with NMO who became pregnant, or who developed NMO soon after pregnancy, were included. Retrospective analysis of medical data from these patients was carried out by the neurologist responsible for the case. Seventeen cases of pregnancies (16 full-term pregnancies, one miscarriage) were identified. The relapse rate of demyelinating events in the first trimester after pregnancy was significantly higher than at any other time. Disability progression was significantly worse 1 year after delivery. Pregnancy negatively influenced the disease course of NMO in these women. These results are similar to those of other authors, although the total number of cases so far described is still small. Obstetricians must be aware of the potential complications of a pregnancy in a woman who has NMO. 
	•	Cited by 23 articles 
	•	29 references 
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32. 	Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease 
Arq Neuropsiquiatr. 2013 May;71(5):275-9. doi: 10.1590/0004-282x20130020.
Authors 
Denis Bernardi Bichuetti  1 , Enedina Maria Lobato de Oliveira, Nilton Amorin de Souza, Mar Tintoré, Alberto Alain Gabbai
Affiliation 
	•	1 Setor de Neuroimunologia, Universidade Federal de São Paulo (UNIFESP), São Paulo SP, Brazil. bichuetti@unifesp.br
	•	PMID: 23689404 
	•	DOI: 10.1590/0004-282x20130020 
Free article
Abstract 
Although neuromyelitis optica (NMO) is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS), few studies comparing both conditions in a single center have been done. 
Methods: Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007. 
Results: Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062) with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013) and progression index (0.9 versus 0.6, p<0.0001), with more patients reaching expanded disability status scale (EDSS) 6.0 (39 versus 17%, p=0.0036). The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15. 
Conclusion: Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease. 
	•	Cited by 3 articles 
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33. 	European ancestry predominates in neuromyelitis optica and multiple sclerosis patients from Brazil 
PLoS One. 2013;8(3):e58925. doi: 10.1371/journal.pone.0058925. Epub 2013 Mar 20.
Authors 
Doralina Guimarães Brum  1 , Marcelo Rizzatti Luizon, Antônio Carlos Santos, Marco Aurélio Lana-Peixoto, Cristiane Franklin Rocha, Maria Lucia Brito, Enedina Maria Lobato de Oliveira, Denis Bernardi Bichuetti, Alberto Alan Gabbai, Denise Sisterolli Diniz, Damacio Ramon Kaimen-Maciel, Elizabeth Regina Comini-Frota, Claudia E Vieira Wiezel, Yara Costa Netto Muniz, Roberta Martins da Silva Costa, Celso Teixeira Mendes-Junior, Eduardo Antônio Donadi, Amilton Antunes Barreira, Aguinaldo Luiz Simões
Affiliation 
	•	1 Departamento de Neurociências e Ciências do Comportamento da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto, São Paulo, Brazil.
	•	PMID: 23527051 
	•	PMCID: PMC3604018 
	•	DOI: 10.1371/journal.pone.0058925 
Free PMC article
Abstract 
Background: Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. 
Methods: Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). 
Principal findings: European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. 
Conclusions: Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil. 
Conflict of interest statement 
Competing Interests: The authors have declared that no competing interests exist.
	•	Cited by 7 articles 
	•	14 references 
	•	2 figures 
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34. 	Comment on neuromyelitis optica: potential roles for intravenous immunoglobulin 
J Clin Immunol. 2013 Feb;33(2):307. doi: 10.1007/s10875-012-9808-7. Epub 2012 Sep 30.
Authors 
Denis Bernardi Bichuetti, Enedina Maria Lobato de Oliveira
	•	PMID: 23054342 
	•	DOI: 10.1007/s10875-012-9808-7 
No abstract available
Comment in 
	•	"Response to the commentary on "neuromyelitis optica: potential roles for intravenous immunoglobulin"". Wingerchuk DM. J Clin Immunol. 2013 Feb;33(2):308. doi: 10.1007/s10875-012-9809-6. Epub 2012 Oct 3. PMID: 23054343No abstract available. 
Comment on 
	•	Neuromyelitis optica: potential roles for intravenous immunoglobulin. Wingerchuk DM. J Clin Immunol. 2013 Jan;33 Suppl 1:S33-7. doi: 10.1007/s10875-012-9796-7. Epub 2012 Sep 14. PMID: 22976554Review. 
	•	Cited by 1 article 
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35. 	Lack of response to pulse cyclophosphamide in neuromyelitis optica: evaluation of 7 patients 
Arch Neurol. 2012 Jul;69(7):938-9. doi: 10.1001/archneurol.2012.545.
Authors 
Denis B Bichuetti  1 , Enedina M Lobato Oliveira, Fernanda de Castro Boulos, Alberto A Gabbai
Affiliation 
	•	1 Department of Neurology and Neurosurgery, Federal University of São Paulo, Brazil. denisbichuetti@globo.com
	•	PMID: 22777264 
	•	DOI: 10.1001/archneurol.2012.545 
No abstract available
	•	Cited by 12 articles 
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36. 	Neuromyelitis optica treatment: analysis of 36 patients 
Arch Neurol. 2010 Sep;67(9):1131-6. doi: 10.1001/archneurol.2010.203.
Authors 
Denis Bernardi Bichuetti  1 , Enedina Maria Lobato de Oliveira, Daniel May Oliveira, Nilton Amorin de Souza, Alberto Alain Gabbai
Affiliation 
	•	1 Departamento de Neurologia, Universidade Federal de São Paulo, Rua Botucatu, São Paulo, Brazil. denisbichuetti@globo.com
	•	PMID: 20837859 
	•	DOI: 10.1001/archneurol.2010.203 
Abstract 
Objective: To analyze treatment response in Brazilian patients with neuromyelitis optica. 
Design: Retrospective review. 
Setting: Neuroimmunology Clinic of the Federal University of São Paulo, São Paulo, Brazil. Patients Thirty-six patients with relapsing-remitting optic-spinal disease; long, extending spinal cord lesions; and brain magnetic resonance images not meeting Barkhof criteria for multiple sclerosis, thus fulfilling the 1999 and 2006 criteria for neuromyelitis optica. Patients were followed up from 1994 to 2007. 
Main outcome measures: Relapses and accumulation of disability. 
Results: Mean follow-up time was 47.2 months and mean age at onset was 32.3 years. Sixty-four treatments were implemented in 36 patients, which included interferon beta, methotrexate, cyclophosphamide, prednisone, and azathioprine solely or plus prednisone. Patients who were treated with azathioprine or azathioprine with prednisone had a reduction in the occurrence of relapses and Expanded Disability Severity Scale score stabilization, as opposed to patients who received other treatments. Of the 4 patients who died, only 1 had received azathioprine treatment. 
Conclusion: Azathioprine as monotherapy or with prednisone seems to have reduced the relapse frequency and halted disability progression in the majority of patients treated, with minor and manageable adverse effects. 
	•	Cited by 27 articles 
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37. 	Neuromyelitis optica in Brazil: a study on clinical and prognostic factors 
Mult Scler. 2009 May;15(5):613-9. doi: 10.1177/1352458508101935. Epub 2009 Mar 19.
Authors 
D B Bichuetti  1 , E M L Oliveira, N A Souza, R L M Rivero, A A Gabbai
Affiliation 
	•	1 Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo - SP, Brazil. denisbichuetti@globo.com
	•	PMID: 19299436 
	•	DOI: 10.1177/1352458508101935 
Abstract 
Objectives: To describe the clinical characteristics of patients with relapsing neuromyelitis optica (NMO) from a tertiary care center in Brazil and compare the groups with normal and abnormal brain magnetic resonance imaging (MRI). 
Methods: Retrospective review of 41 patients followed at the Neuroimmunology Clinic of the Federal University of São Paulo, Brazil, from 1994 to 2007. 
Results: All patients had relapsing-remitting optic-spinal disease, long extending spinal cord lesions, and brain MRI not meeting Barkhof criteria for multiple sclerosis (MS), thus fulfilling the 1999 and 2006 Wingerchuck criteria for NMO. Mean follow-up time was 52 months; mean age of onset was 32.6 years. The mean relapse rate (RR) and progression index (PI) were 1.0 and 0.9, respectively. Twenty-four patients had brain lesions not compatible with MS on MRI, and there were no statistical differences on PI and RR between patients who had brain lesions and patients who did not. Incomplete recovery, but not the type of first relapse, correlated with a worse prognosis. Seventeen patients were tested for NMO-IgG (anti-aquaporin-4 antibody) with 41% positivity. 
Conclusions: In this series, we did not find a statistical difference of disease progression between patients with and without brain lesions, suggesting that the presence of brain abnormalities is not a marker of disease severity. 
	•	Cited by 13 articles 
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38. 	White matter spectroscopy in neuromyelitis optica: a case control study 
J Neurol. 2008 Dec;255(12):1895-9. doi: 10.1007/s00415-009-0940-0. Epub 2009 Jan 22.
Authors 
Denis Bernardi Bichuetti  1 , René Leandro Magalhães Rivero, Enedina Maria Lobato de Oliveira, Daniel May Oliveira, Nilton Amorin de Souza, Roberto Gomes Nogueira, Nitamar Abdala, Alberto Gabbai
Affiliation 
	•	1 Dept. of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), Rua Pedro de Toledo 377, São Paulo, SP, Brazil.
	•	PMID: 19159058 
	•	DOI: 10.1007/s00415-009-0940-0 
Abstract 
Background: Naa/Cr ratio in normal appearing white matter (NAWM) of patients with multiple sclerosis (MS) is altered beyond plaques, suggesting early axonal loss, and correlates to clinical disability. Brain lesions not typical of MS have been described in Neuromyelitis optica (NMO), and correspond to brain aquaporin-4 channel sites, but the evaluation of Naa/Cr ratio in NAWM of patients with NMO and its association to the presence of brain lesions and clinical disability have not been described. 
Objectives: To evaluate the Naa/Cr of normal appearing white matter (NAWM) in 16 patients with NMO compared to healthy controls. 
Methods: We performed brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of 16 patients with NMO and compared to age matched healthy controls. 
Results: NAWM Naa/Cr did not show statistical difference among patients and controls, neither between patients that had normal brain MRI and atypical brain lesions. 
Conclusion: NAWM was found to have a normal Naa/Cr in patients with NMO, reinforcing the concept that the white matter is not primarily affected in this disease. 
	•	Cited by 11 articles 
	•	19 references 
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39. 	Demyelinating disease in patients with myasthenia gravis 
Arq Neuropsiquiatr. 2008 Mar;66(1):5-7. doi: 10.1590/s0004-282x2008000100002.
Authors 
Denis Bernardi Bichuetti  1 , Tatiane Martins de Barros, Enedina Maria Lobato Oliveira, Marcelo Annes, Alberto Alain Gabbai
Affiliation 
	•	1 Neurology and Neurosurgery Department, Federal University of São Paulo, São Paulo, SP, Brazil. denisbichuetti@globo.com
	•	PMID: 18392404 
	•	DOI: 10.1590/s0004-282x2008000100002 
Free article
Abstract 
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. 
	•	Cited by 1 article 
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40. 	Neuromyelitis optica: brain abnormalities in a Brazilian cohort 
Arq Neuropsiquiatr. 2008 Mar;66(1):1-4. doi: 10.1590/s0004-282x2008000100001.
Authors 
Denis Bernardi Bichuetti  1 , René Leandro Magalhães Rivero, Daniel May Oliveira, Nilton Amorin de Souza, Nitamar Abdala, Enedina Maria Lobato Oliveira, Alberto Alain Gabbai
Affiliation 
	•	1 Neurology and Neurosurgery Department, Federal University of São Paulo, São Paulo, SP, Brazil. denisbichuetti@globo.com
	•	PMID: 18392403 
	•	DOI: 10.1590/s0004-282x2008000100001 
Free article
Abstract 
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. 
	•	Cited by 6 articles 
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41. 	PD-1 ligands, negative regulators for activation of naive, memory, and recently activated human CD4+ T cells 
Cell Immunol. 2004 Aug;230(2):89-98. doi: 10.1016/j.cellimm.2004.09.004.
Authors 
Guifang Cai  1 , Arnon Karni, Enedina M L Oliveira, Howard L Weiner, David A Hafler, Gordon J Freeman
Affiliation 
	•	1 Laboratory of Molecular Immunology, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
	•	PMID: 15598424 
	•	DOI: 10.1016/j.cellimm.2004.09.004 
Abstract 
We examined the role of the PD-1 pathway on the activation of naive, memory, and recently activated human CD4+ T cells to test whether they responded differently. PD-1 ligand blockade modestly enhanced the percentage of responding T cells and production of IFN-gamma in a primary response to myelin basic protein (MBP) in normal donors. PD-1 ligand blockade strongly enhanced proliferation and cytokine production by memory or recently activated T cells (tetanus toxoid and MBP). Blockade of PD-L1 alone had more effect than PD-L2, consistent with its higher expression on ex vivo dendritic cells; furthermore, anti-PD-L1 plus anti-PD-L2 resulted in the greatest enhancement. Moreover, PD-L1-Ig inhibited anti-CD3 induced activation of naive, memory, and recently activated CD4+ T cells. Together, our data demonstrated PD-1 functioned as a negative regulatory pathway on naive T cells during a primary response, and more potently, on memory or recently activated T cells during a secondary response. 
	•	Cited by 35 articles 
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42. 	Semantic relations and repetition of items enhance the free recall of words by multiple sclerosis patients 
J Clin Exp Neuropsychol. 2003 Dec;25(8):1070-8. doi: 10.1076/jcen.25.8.1070.16730.
Authors 
Vivian M Andrade  1 , Maria Gabriela M Oliveira, Monica C Miranda, Acary S B Oliveira, Enedina M L Oliveira, Orlando F A Bueno
Affiliation 
	•	1 Department of Psychobiology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil
	•	PMID: 14566581 
	•	DOI: 10.1076/jcen.25.8.1070.16730 
Abstract 
We compared 25 patients with multiple sclerosis (MS) and 24 normal controls on a test of free recall of words. Some lists contained words that were all unrelated, while in others the intermediary words were semantically related. In another set, the mid-list words were repeated across the lists, or, in addition to the repetition, were semantically associated. Immediate recall was assessed using these lists. Delayed recall was assessed using different lists (delay-unrelated and delay-related) after distractor tasks. Recency was not affected in MS patients, but the primacy effect was lower than in controls, this effect being interpreted as due to a deficiency in articulatory rehearsal. The delay interval after each list abolished recency in both groups and resulted in impaired recall in MS patients. However the patients, like the controls, benefited from semantic relations in the middle of the lists and from spaced repetition of words across the lists, in either immediate and delayed recall. The enhancing effects of word relatedness and of spaced repetition are seen as being due to automatic processes preserved in MS patients. 
	•	Cited by 3 articles 	
43. 	CTLA-4 dysregulation in the activation of myelin basic protein reactive T cells may distinguish patients with multiple sclerosis from healthy controls 
J Autoimmun. 2003 Feb;20(1):71-81. doi: 10.1016/s0896-8411(02)00106-3.
Authors 
Enedina M L Oliveira  1 , Amit Bar-Or, Alicja I Waliszewska, Guifang Cai, David E Anderson, Jeffrey I Krieger, David A Hafler
Affiliation 
	•	1 Laboratory of Molecular and Cellular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
	•	PMID: 12604314 
	•	DOI: 10.1016/s0896-8411(02)00106-3 
Abstract 
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, thought to be mediated in part by an autoimmune response of T cells to protein components of the myelin sheath. The reaction of naïve T cells against these antigens requires co-stimulation through CD28. However, the proliferative response of peripheral blood mononuclear cells isolated from patients with MS and stimulated with myelin basic protein (MBP) has been shown to be relatively independent of B7-CD28 co-stimulation, suggesting that dysregulation of co-stimulatory pathways may be involved in the pathogenesis of MS. Here, the role of CTLA-4 engagement was investigated. As expected, blocking CTLA-4-mediated signaling during stimulation of MBP-reactive T cells from healthy controls enhanced the proliferative and cytokine responses. In contrast, CTLA-4 blockade had less effect in patients with MS, suggesting that at least two regulatory mechanisms may be impaired in these individuals. Understanding how co-stimulatory signals may be dysregulated in patients with MS is important at a time when targeting of these pathways is being developed. 
	•	Cited by 10 articles 
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