Occurrence of area postrema syndrome during follow-up: phenotype and influence over NMOSD activity in LATAM in real-world settings.

INTRODUCTION: We aimed to assess the frequency, duration, and severity of area postrema syndrome (APS) during follow-up in neuromyelitis optica spectrum disorder (NMOSD) patients, as well as its association with inflammatory activity and prognostic factors of APS severity in a real-world setting. METHODS: We conducted a retrospective study on a cohort of Latin American (LATAM) NMOSD patients who had experienced APS during their follow-up. Patients from Mexico, Peru, Brazil, Colombia, Panama, Chile and Argentina patients who met 2015 NMOSD criteria were included. We evaluated data on symptom type (nausea, vomiting and/or hiccups), frequency, duration, severity (measured by APS severity scale), association with other NMOSD core relapses, and acute treatments (symptomatic and immunotherapy or plasmapheresis). Logistic regression was conducted to evaluate factors associated with APS severity (vs. mild-moderate). RESULTS: Out of 631 NMOSD patients, 116 (18.3%) developed APS during their follow-up. The most common APS phenotype was severe. Inflammatory activity (i.e., relapses) significantly decreased after the onset of APS. Half of the patients experienced isolated APS with a median duration of 10 days, and the most frequently used acute treatment was IV steroids. All three symptoms were present in 44.6% of the patients. APS symptoms resolved following immunotherapy. Logistic regression did not identify independent factors associated with the severity of APS. CONCLUSIONS: Our findings indicate that 18.3% of NMOSD patients developed APS during the follow-up period, with most patients fulfilling criteria for severe APS. The inflammatory activity decreased after the onset of APS compared to the previous year.

Prevalence of neuromyelitis optica spectrum disorder in Belo Horizonte, Southeast Brazil.

BACKGROUND: Studies on the prevalence of neuromyelitis optica spectrum disorder (NMOSD) are still scarce. The aim of the current study was to determine the prevalence rate of NMOSD in Belo Horizonte, southeast Brazil, where the prevalence rate of multiple sclerosis (MS) has already been established. METHODS: For this observational study, eligible patients had to meet the 2015 International Panel for Neuromyelitis Optica Diagnosis, be seen at the study center between January 2000 and February 2019 and live in Belo Horizonte. The prevalence rate of NMOSD was estimated based on the number of MS and NMOSD patients seen at same Center during the same period, and the previously established prevalence of MS in Belo Horizonte. RESULTS: During the study period, there were 69 patients with NMOSD, 60 (87.0%) of whom were females, and 44 (63.8%) non-whites. The median age at disease onset was 36.7 (4-72) years, the mean EDSS score 4.78±2.36, and the mean ARR 0.57±0.43. Anti-aquaporin-4 immunoglobulin testing was available for 61 (88.4%) patients, of whom 41 (67.2%) had a positive result. During the same period, 280 MS patients were seen. Considering the local known prevalence rate of MS of 18.1/100,000 inhabitants, the estimated NMOSD prevalence rate in Belo Horizonte was 4.52/100,000 (95% CI 3.72-5.43) inhabitants. CONCLUSION: The prevalence rate of NMOSD in Belo Horizonte is high as compared with those found in most of the studies reported to date.

Optic neuritis at disease onset predicts poor visual outcome in neuromyelitis optica spectrum disorders.

INTRODUCTION: Optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD) may occur at the onset of the disease, during relapse attacks, or both. It is well known that ON in NMOSD may cause permanent visual disability, but the influence of the time of its occurrence has not been investigated. OBJECTIVE: We evaluated the effect of the time of ON occurrence on visual outcome in a cohort of NMOSD patients. METHODS: We retrospectively analyzed the medical records of NMOSD patients with ON who met the 2015 International consensus criteria for NMOSD diagnosis. We assessed demographic and clinical data, the Expanded Disability Status Scale (EDSS), and visual disability according to the scores of the Kurtzke Visual Function Scale (KVS) and Wingerchuk's Optic Nerve Impairment Scale (WONIS). We divided patients into three groups according to the time of ON occurrence: (1) ON at disease onset; (2) ON exclusively in relapse attacks; and (3) ON at both disease onset and in relapse attacks. RESULTS: Out of 187 patients with suspected NMOSD, 85 (42.4%) met the inclusion criteria. ON occurred exclusively at the disease onset in 16 (18.8%) patients, exclusively in relapse attacks in 43 (50.6%) patients, and at both the onset and in relapse attacks in 26 (30.6%) patients. There was no significant difference in the EDSS scores of the groups. In comparison with patients with ON exclusively occurring during relapse attacks, patients with ON at disease onset had higher KVS scores (p = 0.009) and WONIS scores (p = 0.005). Patients with ON at both onset and in relapses had a larger number of ON attacks and NMOSD relapses, as well as the poorest visual outcome. CONCLUSIONS: ON at disease onset is a predictive factor for poor visual outcome in NMOSD patients.

Neuromyelitis Optica Spectrum Disorder and Anti-MOG Syndromes.

Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes are immune-mediated inflammatory conditions of the central nervous system that frequently involve the optic nerves and the spinal cord. Because of their similar clinical manifestations and habitual relapsing course they are frequently confounded with multiple sclerosis (MS). Early and accurate diagnosis of these distinct conditions is relevant as they have different treatments. Some agents used for MS treatment may be deleterious to NMOSD. NMOSD is frequently associated with antibodies which target aquaporin-4 (AQP4), the most abundant water channel in the CNS, located in the astrocytic processes at the blood-brain barrier (BBB). On the other hand, anti-MOG syndromes result from damage to myelin oligodendrocyte glycoprotein (MOG), expressed on surfaces of oligodendrocytes and myelin sheaths. Acute transverse myelitis with longitudinally extensive lesion on spinal MRI is the most frequent inaugural manifestation of NMOSD, usually followed by optic neuritis. Other core clinical characteristics include area postrema syndrome, brainstem, diencephalic and cerebral symptoms that may be associated with typical MRI abnormalities. Acute disseminated encephalomyelitis and bilateral or recurrent optic neuritis are the most frequent anti-MOG syndromes in children and adults, respectively. Attacks are usually treated with steroids, and relapses prevention with immunosuppressive drugs. Promising emerging therapies for NMOSD include monoclonal antibodies and tolerization.

Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu.

The relationship between Sjögren's syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.

Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu / Síndrome de Sjögren e espectro da neuromielite óptica coexistem em meio de autoimunidade

The relationship between Sjögren’s syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.

A relação entre síndrome de Sjögren (SS) e espectro da neuromielite óptica (ENMO) ainda não é bem compreendida. Relatamos dois pacientes com ambas as condições e revisamos 47 casos que preenchem critérios diagnósticos das duas doenças, descritos em 17 artigos extraídos da PubMed. Dos 44 pacientes cujo gênero foi informado 42 eram mulheres. A idade média ao início das manifestações neurológicas foi 36,2 anos (10-74). O anticorpo anti-AQP4 foi positivo em 32 dos 37 pacientes, em 1 foi “borderline”. Nosso Caso 1 era soronegativo para AQP4-IgG, não tinha autoanticorpos não-órgão específicos, exceto anti-SSB. O Caso 2 era soropositivo para anticorpos anti-AQP4, anti-SSA/SSB, anti-tireoglobulina, e anti-receptor da acetilcolina; apresentava hipotireoidismo, mas não havia evidêncas de miastenia gravis. Nossos casos e outros similares, previamente relatados na literatura, com resposta autoimune heterogênea à aquaporina-4 sugerem que a SS e o ENMO coexistem em meio de autoimunidade não dependente da aquaporina-4.

The expanded spectrum of neuromyelitis optica: evidences for a new definition.

Neuromyelitis optica (NMO) has been traditionally described as the association of recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM). Identification of aquaporin-4 antibody (AQP4-IgG) has deeply changed the concept of NMO. A spectrum of NMO disorders (NMOSD) has been formulated comprising conditions which include both AQP4-IgG seropositivity and one of the index events of the disease (recurrent or bilateral optic neuritis and LETM). Most NMO patients harbor asymptomatic brain MRI lesions, some of them considered as typical of NMO. Some patients with aquaporin-4 autoimmunity present brainstem, hypothalamic or encephalopathy symptoms either preceding an index event or occurring isolatedly with no evidence of optic nerve or spinal involvement. On the opposite way, other patients have optic neuritis or LETM in association with typical lesions of NMO on brain MRI and yet are AQP4-IgG seronegative. An expanded spectrum of NMO disorders is proposed to include these cases.

The expanded spectrum of neuromyelitis optica: evidences for a new definition / O espectro expandido da neuromielite óptica: as evidências para nova definição

Neuromyelitis optica (NMO) has been traditionally described as the association of recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM). Identification of aquaporin-4 antibody (AQP4-IgG) has deeply changed the concept of NMO. A spectrum of NMO disorders (NMOSD) has been formulated comprising conditions which include both AQP4-IgG seropositivity and one of the index events of the disease (recurrent or bilateral optic neuritis and LETM). Most NMO patients harbor asymptomatic brain MRI lesions, some of them considered as typical of NMO. Some patients with aquaporin-4 autoimmunity present brainstem, hypothalamic or encephalopathy symptoms either preceding an index event or occurring isolatedly with no evidence of optic nerve or spinal involvement. On the opposite way, other patients have optic neuritis or LETM in association with typical lesions of NMO on brain MRI and yet are AQP4-IgG seronegative. An expanded spectrum of NMO disorders is proposed to include these cases.

Neuromielite óptica (NMO) tem sido tradicionalmente caracterizada como associação de neurite óptica recorrente ou bilateral e mielite tranversa longitudinalmente extensa (MTLE). O conceito de NMO tem mudado desde a identificação do anticorpo antiaquaporina-4. A NMO é atualmente considerada como um espectro de condições contendo pelo menos um dos eventos índices da doença (neurite óptica recorrente ou bilateral e MTLE) e soropositividade para AQP4-IgG. A maioria dos pacientes apresenta lesões cerebrais à imagem por ressonância magnética (IRM), algumas delas típicas de NMO. Pacientes soropositivos podem desenvolver sintomas de tronco encefálico, hipotálamo e de encefalopatia precedendo os eventos índices, ou isoladamente, na ausência de qualquer evidência de alteração visual ou espinal. Por outro lado, há pacientes soronegativos que apresentam ou neurite óptica ou MTLE associada a lesões cerebrais típicas de NMO à IRM. Todas essas situações estão incluídas no espectro expandido de NMO aqui proposto.

The prevalence of multiple sclerosis in Belo Horizonte, Brazil.

UNLABELLED: Investigations on the prevalence rates of multiple sclerosis (MS) around the world have yielded important clues on the interplay between genetic susceptibility and environmental factors. As Brazil is a huge country laid on many latitudes and inhabited by population with distinct ethnic backgrounds, it might be assumed that the frequency of MS varies in its different regions. OBJECTIVE: To determine the prevalence rate of MS in Belo Horizonte, the capital of the State of Minas Gerais, Southeastern Brazil. METHODS: We used six sources to draw up a provisional list of identified cases of MS. Only patients with diagnosis of clinically definite MS according to Poser Committee criteria were included. RESULTS: The calculated crude MS prevalence was 18.1/100,000 inhabitants. CONCLUSIONS: The MS prevalence in Belo Horizonte is similar to that found in São Paulo and Botucatu, two other cities in southeastern Brazil with similar ethnic background.

The prevalence of multiple sclerosis in Belo Horizonte, Brazil / Prevalência da esclerose múltipla em Belo Horizonte, Brasil

Investigations on the prevalence rates of multiple sclerosis (MS) around the world have yielded important clues on the interplay between genetic susceptibility and environmental factors. As Brazil is a huge country laid on many latitudes and inhabited by population with distinct ethnic backgrounds, it might be assumed that the frequency of MS varies in its different regions. Objective: To determine the prevalence rate of MS in Belo Horizonte, the capital of the State of Minas Gerais, Southeastern Brazil. Methods: We used six sources to draw up a provisional list of identified cases of MS. Only patients with diagnosis of clinically definite MS according to Poser Committee criteria were included. Results: The calculated crude MS prevalence was 18.1/100,000 inhabitants. Conclusions: The MS prevalence in Belo Horizonte is similar to that found in São Paulo and Botucatu, two other cities in southeastern Brazil with similar ethnic background.

Estudos sobre as taxas de prevalência da esclerose múltipla (EM) no mundo têm fornecido importantes evidências do papel da inter-relação dos fatores genéticos e ambientais determinando estas frequências. Como o Brasil é um país muito extenso e com populações de diversas origens étnicas, supõe-se que a frequência da EM seja variável em suas diferentes regiões. Objetivo: Determinar a taxa de prevalência da esclerose múltipla (EM) em Belo Horizonte, capital do estado de Minas Gerais, no sudeste do Brasil. Métodos: Nós usamos seis fontes para a identificação dos pacientes que preenchiam os critérios diagnósticos de EM clinicamente definida de acordo com o Comitê de Poser. Resultados: A taxa de prevalência encontrada foi de 18,1/100.000 habitantes. Conclusões: A prevalência em Belo Horizonte de EM é semelhante à encontrada nos estudos em São Paulo e Botucatu, duas outras cidades na região sudeste do Brasil habitadas por populações com similar origem étnica.

NMO-DBr: the Brazilian Neuromyelitis Optica Database System.

OBJECTIVE: To present the Brazilian Neuromyelitis Optica Database System (NMO-DBr), a database system which collects, stores, retrieves, and analyzes information from patients with NMO and NMO-related disorders. METHOD: NMO-DBr uses Flux, a LIMS (Laboratory Information Management Systems) for data management. We used information from medical records of patients with NMO spectrum disorders, and NMO variants, the latter defined by the presence of neurological symptoms associated with typical lesions on brain magnetic resonance imaging (MRI) or aquaporin-4 antibody seropositivity. RESULTS: NMO-DBr contains data related to patient's identification, symptoms, associated conditions, index events, recurrences, family history, visual and spinal cord evaluation, disability, cerebrospinal fluid and blood tests, MRI, optic coherence tomography, diagnosis and treatment. It guarantees confidentiality, performs cross-checking and statistical analysis. CONCLUSION: NMO-DBr is a tool which guides professionals to take the history, record and analyze information making medical practice more consistent and improving research in the area.

NMO-DBr: the Brazilian Neuromyelitis Optica Database System / NMO-DBr: o banco de dados brasileiro em neuromielite óptica

OBJECTIVE: To present the Brazilian Neuromyelitis Optica Database System (NMO-DBr), a database system which collects, stores, retrieves, and analyzes information from patients with NMO and NMO-related disorders. METHOD: NMO-DBr uses Flux, a LIMS (Laboratory Information Management Systems) for data management. We used information from medical records of patients with NMO spectrum disorders, and NMO variants, the latter defined by the presence of neurological symptoms associated with typical lesions on brain magnetic resonance imaging (MRI) or aquaporin-4 antibody seropositivity. RESULTS: NMO-DBr contains data related to patient's identification, symptoms, associated conditions, index events, recurrences, family history, visual and spinal cord evaluation, disability, cerebrospinal fluid and blood tests, MRI, optic coherence tomography, diagnosis and treatment. It guarantees confidentiality, performs cross-checking and statistical analysis. CONCLUSION: NMO-DBr is a tool which guides professionals to take the history, record and analyze information making medical practice more consistent and improving research in the area.

OBJETIVO: Apresentar o Brazilian Neuromyelitis Optica Database System (NMO-DBr), um sistema de banco de dados que coleta, arquiva, recupera e analisa informações de pacientes com neuromielite óptica (NMO) e doenças relacionadas. MÉTODO: NMO-DBr usa o sistema Flux, um LIMS (Laboratory Information Management Systems) para gerenciamento de informações. As informações foram colhidas dos prontuários de pacientes com espectro de NMO e variantes de NMO, estas últimas definidas por quadro neurológico associado a lesões encefálicas típicas à imagem pela ressonância magnética (IRM) ou à soropositividade do anticorpo anti-aquaporina-4. RESULTADOS: NMO-DBr contém dados relativos a identificação, sintomas, condições associadas, eventos índices, recorrências, história familiar, avaliação visual e da medula, incapacidade, exames do líquor e de sangue, IRM, tomografia de coerência óptica (OCT), diagnóstico e tratamento. O sistema assegura confidencialidade, cruza dados e faz análises estatísticas. CONCLUSÃO: NMO-DBr é uma ferramenta que possibilita a prática médica mais consistente e promove a pesquisa na área.

Validation of the Brazilian version of Guy's neurological disability scale.

The Guy's neurological disability scale (GNDS) has recently been introduced as a new measure of disability in multiple sclerosis. It is patient-oriented, multidimensional, and not biased towards any particular disability. The purpose of the present study was to validate the Brazilian version of the GNDS. The adaptation of the scale was based on the translation/back-translation methodology. Sixty-two patients with clinically definite multiple sclerosis (CDMS) according to Poser's criteria were recruited for this study. GNDS was administered individually to each subject. The EDSS and the ambulation index (AI) scores were assigned by a neurologist. The intraclass correlation coefficient and the Cronbach's alpha values of the Brazilian version of GNDS (0.94 and 0.83, respectively) were comparable to the original one (0.98 and 0.79, respectively). Furthermore, the factor analysis of the Brazilian version of GNDS suggested, as the original article, a four-factor solution which accounted for 68.8% of the total variance. The Brazilian version of GNDS was found to be clinically relevant as it correlated significantly with the EDSS and AI. In conclusion, the Brazilian version of GNDS can be considered an important tool to evaluate the disability in MS patients, with clinical usefulness and psychometrics soundness.

Validation of the brazilian version of Guy's neurological disability scale

The Guy's neurological disability scale (GNDS) has recently been introduced as a new measure of disability in multiple sclerosis. It is patient-oriented, multidimensional, and not biased towards any particular disability. The purpose of the present study was to validate the Brazilian version of the GNDS. The adaptation of the scale was based on the translation/back-translation methodology. Sixty-two patients with clinically definite multiple sclerosis (CDMS) according to Poser's criteria were recruited for this study. GNDS was administered individually to each subject. The EDSS and the ambulation index (AI) scores were assigned by a neurologist. The intraclass correlation coefficient and the Cronbach's alpha values of the Brazilian version of GNDS (0.94 and 0.83, respectively) were comparable to the original one (0.98 and 0.79, respectively). Furthermore, the factor analysis of the Brazilian version of GNDS suggested, as the original article, a four-factor solution which accounted for 68.8 percent of the total variance. The Brazilian version of GNDS was found to be clinically relevant as it correlated significantly with the EDSS and AI. In conclusion, the Brazilian version of GNDS can be considered an important tool to evaluate the disability in MS patients, with clinical usefulness and psychometrics soundness.

A Guy's neurological disability scale (GNDS) é uma escala de incapacidade criada recentemente, orientada para o paciente, multidimensional, e que não privilegia nenhum tipo específico de incapacidade. O objetivo deste estudo é validar a GNDS para a língua portuguesa. A adaptação da escala foi feita através do método de tradução e re-tradução. Sessenta e dois pacientes com esclerose múltipla (EM) clinicamente definida de acordo com os critérios de Poser participaram deste estudo. A GNDS foi aplicada individualmente em cada paciente. O EDSS e o índice ambulatorial (IA) foram determinados por neurologista. A correlação intra-classe e o valor de Cronbach's alfa da versão brasileira da GNDS (0.94 e 0.83, respectivamente) foram comparáveis aos do artigo original (0.98 e 0.79, respectivamente). Como no artigo original, a análise fatorial da versão brasileira da GNDS sugeriu uma solução de quatro fatores que explicaria 68.8 por cento da variação total. A versão brasileira da GNDS mostrou-se clinicamente relevante uma vez que se correlacionou com o EDSS e o IA. Em conclusão, a versão brasileira da GNDS pode ser considerada como um importante instrumento de avaliação incapacidade na EM com significado clínico e relevância psicométrica.

Asymptomatic intracranial gumma in a patient with syphilitic uveitis and human immunodeficiency virus infection.

The case is described of a 51-y-old man with uveitis as the first clinical manifestation of syphilis and in whom laboratory work-up disclosed human immunodeficiency virus infection and asymptomatic brain gummata. The case illustrates the need for a comprehensive work-up in previously asymptomatic patients with uveitis.