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Background Optic neuritis is an inflammation of the optic nerve caused by genetic factors, external influences, and the activation of cross-reactive immune responses to infections.

Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding of the factors leading to heterogeneity within the same disease, development of targeted therapies, and strategies to tailor therapies to each patient. This review explores the impact of precision medicine on various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, and immune-mediated neuropathies. We discuss advances in disease subtyping, recognition of novel entities, promising biomarkers, and the development of more selective monoclonal antibodies and cutting-edge synthetic cell-based immunotherapies in neuroimmunological disorders. In addition, we analyze the challenges related to affordability and equity in the implementation of these emerging technologies, especially in situations with limited resources.

Plasma exchange (PLEX) is a therapeutic apheresis modality in which the plasma is separated from inflammatory factors such as circulating autoreactive immunoglobulins, the complement system, and cytokines, and its therapeutic effect is based on the removal of these mediators of pathological processes. Plasma exchange is well established for various neurological disorders, and it is applied successfully in central nervous system inflammatory demyelinating diseases (CNS-IDD). It mainly modulates the humoral immune system; thus, it has a greater theoretical effect in diseases with prominent humoral mechanisms, such as neuromyelitis optica (NMO). However, it also has a proven therapeutic effect in multiple sclerosis (MS) attacks. Several studies have suggested that patients with severe attacks of CNS-IDD have poor response to steroid therapy but show clinical improvement after the PLEX treatment. Currently, PLEX is generally established only as a rescue therapy for steroid unresponsive relapses. However, there are still research gaps in the literature regarding plasma volume, number of sessions, and how early the apheresis treatment needs to started. Thus, in the present article, we summarize the clinical studies and meta-analyses, especially about MS and NMO, outlining clinical data regarding the experience with therapeutic PLEX in severe attacks of CNS-IDD, the clinical improvement rates, the prognostic factors of a favorable response, and highlighting the likely role of the early apheresis treatment. Further, we have gathered this evidence and suggested a protocol for the treatment of CNS-IDD with PLEX in the routine clinical practice.

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.

Neuromyelitis optica spectrum disorders (NMOSD) are characterized by severe optic neuritis and/or longitudinally extensive transverse myelitis, and some brain lesions are also unique to NMOSD. Serum autoantibodies against aquaporin-4 (AQP4) are detected in most cases of NMOSD. However, some patients with NMOSD remain seronegative despite repetitive testing during attacks with highly sensitive cell-based assays. The differential diagnosis of NMOSD is not restricted to multiple sclerosis and it includes many diseases that can produce longitudinally extensive myelitis and/or optic neuritis. We review the clinical features, imaging, and laboratory findings that can be helpful on the diagnostic work-up, discuss the differences between AQP4 antibody positive and negative patients with NMOSD, including features of NMOSD with antibodies against myelin oligodendrocyte glycoprotein.

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.

The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS), neuromyelitis optic (NMO) and acute disseminated encephalomyelitis (ADEM). The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the probability of Clinical Isolated Syndrome turn into multiple sclerosis.

The aim of the present research was to investigate cognitive pattern of patients with neuromyelitis optica (NMO) and to compare it with multiple sclerosis (MS) patients' performance. Methods: Fourteen NMO, 14 relapsing remitting multiple sclerosis (RRMS), and 14 healthy control patients participated in the investigation. Neuropsychological functions were evaluated with the Brief Repeatable Neuropsychological Battery for MS; Symbol Digit Modalities Test; Digit Span; and Semantic Fluency. Results: Fifty-seven percent of NMO patients and 42.85% of the MS ones had abnormal performance in at least two cognitive tests. The NMO Group showed abnormal performance in verbal fluency, verbal and visual memories, with greater attention deficits. NMO patients outperformed healthy control in the paced auditory serial addition test (PASAT). However, no difference was found between NMO and RRMS patients. Conclusions: The NMO Group showed more dysfunction in attention and verbal fluencies than in verbal and visual memories. When compared with the MS patients, a similar dysfunction pattern was found. O objetivo da presente pesquisa foi investigar o padrão cognitivo de pacientes com neuromielite óptica (NMO) e compará-lo com o desempenho de pacientes com esclerose múltipla (EM). Métodos: Quatorze pacientes com NMO, 14 com esclerose múltipla recorrente remitente (EMRR) e 14 participantes do Controle saudáveis participaram da presente investigação. As funções neuropsicológicas foram avaliadas com a Bateria Breve de Testes Neuropsicológicos de Rao, Teste Símbolo Digit e a Fluência Semântica. Resultados: Cinquenta e sete por cento dos pacientes com NMO e 42,85% daqueles com EM apresentaram desempenho anormal em pelo menos dois testes cognitivos. O Grupo NMO apresentarou desempenho anormal na fluência verbal e nas memórias visual e verbal, com maiores déficits de atenção. Pacientes com NMO superaram os controles saudáveis em PASAT. No entanto, não foi encontrada diferença entre os pacientes com NMO e aqueles com EMRR. Conclusões: O Grupo NMO mostrou mais disfunção nas fluências de atenção e verbais do que nas memórias verbal e visual. Quando comparados com os pacientes com EM, um padrão de disfunção semelhante foi encontrado.

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.

Tonic spasms have been most commonly associated with multiple sclerosis. To date, few reports of series of patients with neuromyelitis optica and tonic spasms have been published. Methods: We analyzed the characteristics and frequency of tonic spasms in 19 subjects with neuromyelitis optica. Data was collected using a semi-structured questionnaire for tonic spasms, by both retrospectively reviewing medical records and performing clinical assessment. Results: All patients except one developed this symptom. The main triggering factors were sudden movements and emotional factors. Spasms were commonly associated to sensory disturbances and worsened during the acute phases of the disease. Carbamazepine was most commonly used to treat the symptom and patients showed good response to the drug. Conclusions: Tonic spasms are a common clinical manifestation in patients with neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS), and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4) has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks.

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.

OBJECTIVE: To compare optical coherence tomography (OCT) measurements on the retinal nerve fiber layer (RNFL) of healthy controls and patients with longitudinally extensive transverse myelitis (LETM) without previous optic neuritis. METHOD: Twenty-six eyes from 26 patients with LETM and 26 control eyes were subjected to automated perimetry and OCT for comparison of RNFL measurements. RESULTS: The mean deviation values from perimetry were significantly lower in patients with LETM than in controls (p

Devic's neuromyelitis optica (NMO) is an idiopathic inflammatory demyelinating and necrotizing disease characterized by predominant involvement of the optic nerves and spinal cord. In Asian countries relapsing NMO has been known as opticospinal multiple sclerosis. It has long been debated if NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recent studies have shown that NMO has more frequently a relapsing course, and results from attack to aquaporin-4 which is the dominant water channel in the central nervous system, located in foot processes of the astrocytes. Distinctive pathological features of NMO include perivascular deposition of IgG and complement in the perivascular space, granulocyte and eosinophil infiltrates and hyalinization of the vascular walls. These features distinguish NMO from other demyelinating diseases such as MS and acute demyelinating encephalomyelopathy. An IgG-antibody that binds to aquaporin-4, named NMO-IgG has high sensitivity and specificity. Magnetic resonance imaging (MRI) studies have revealed that more frequently there is a long spinal cord lesion that extends through three or more vertebral segments in length. Brain MRI lesions atypical for MS are found in the majority of cases. Treatment in the acute phase includes intravenous steroids and plasma exchange therapy. Immunosupressive agents are recommended for prophylaxis of relapses.Neuromielite óptica ou doença de Devic (NMO) é uma doença inflamatória com desmielinização e necrose envolvendo preferencialmente os nervos ópticos e a medula espinal. Desde sua descrição inicial tem havido controvérsia se a NMO é uma variante da esclerose múltipla (EM) ou se é uma entidade independente. Na Ásia a doença é conhecida como esclerose múltipla óptico-espinal. Recentes avanços tem demonstrado que na maioria dos casos a NMO é recorrente e resulta de alterações inflamatórias por ataque à aquaporina-4, uma proteína localizada nos pés dos astrócitos na barreira hemato-encefálica. Patologicamente a NMO difere da EM pela presença de necrose e cavitação no centro da medula, deposição perivascular de IgG e complemento, infiltração de neutrófilos e eosinófilos, assim como por hiperplasia e hialinização dos vasos. O anticorpo contra a aquaporina-4 (IgG-NMO), detectado no soro dos pacientes, tem alta sensibilidade e especificidade. Imagem por ressonância magnética demonstra lesão medular que se estende três ou mais segmentos vertebrais. Na maioria dos casos há lesões cerebrais atípicas para EM. Corticosteróide venoso em altas doses e plasmaférese são usados no tratamento das fases agudas, enquanto os imunossupressores devem ser usados na profilaxia das recorrências.

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.Neuromielite óptica (NMO) é doença desmielinizante, remitente-recorrente, com acometimento predominante dos nervos ópticos e medula espinal e uma evolução mais grave comparada à esclerose múltipla. Estudos recentes demonstraram que até 50% dos pacientes com NMO podem apresentar lesões encefálicas à ressonância magnética (RM). Relatamos seis pacientes brasileiros com NMO, que satisfazem os critérios diagnósticos de Wingerchuck (1999) para NMO, com alterações encefálicas em RM de encéfalo e discutimos seus dados clínicos e de imagem.

Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system characterized by the association of a serious myelitis and unilateral or bilateral optic neuritis. The present study aimed to analyze the immunological parameters of NMO patients with diagnosis established based on Wingerchuck et al. (1999) criteria. Production of IgG and IgA antibodies to antigens of MBP, PLP 95-116, MOG 92-106, and the cytokines interleukin-4 (IL-4) and interferon-γ (INF-γ) were assessed by Elisa assay. The cohort was formed by 28 NMO patients and a matched healthy control group. NMO patients had significant high levels of IgG to MOG (pA neuromielite óptica (NMO) é doença inflamatória do sistema nervoso central, caracterizada por mielite aguda ou subaguda grave e neurite óptica unilateral ou bilateral. Este estudo objetiva analisar parâmetros imunológicos de pacientes com critérios de Wingerchuck et al. (1999) para NMO. O método de ELISA avaliou a produção de IgG e IgA para antígenos da proteína básica da mielina (MBP), o proteolipídeo (PLP) 95-116, a glicoproteina associada ao oligodendrócito (MOG) 92-106 e as citocinas interleucina-4 (IL-4) e interferon-gama (INF-γ). Foram incluνdos 28 pacientes com NMO pareados com controles saudáveis. Pacientes com NMO apresentaram níveis significativamente elevados de imunoglobulinas reativas dos isotipos IgG para MOG (p

Several demyelinating disorders can affect children. The differential diagnosis between these diseases is usually an arduous task. Diagnostic criteria have been proposed for some of these disorders, however most of them have not yet been clinically and prospectively validated. Here we present a case of a ten year-old boy with recurrent bilateral optic neuritis and spinal cord involvement. Clinical and cerebrospinal fluid data have fulfilled diagnostic criteria for Devic's neuromyelitis optica (NMO). The differential diagnosis with multiple sclerosis (MS) has become troublesome since not only optic nerves and spinal cord were involved. In one of the relapses a left hemiparesis with facial involvement was registered. Magnetic resonance imaging was also compatible with MS. This case illustrates that CNS demyelinating disorders can fulfill diagnostic criteria for more than one demyelinating disease, making the clinical judgment an important tool in the management of these patients.Diversas doenças desmielinizantes podem ocorrer em crianças, sendo muitas vezes o diagnóstico diferencial entre elas difícil. Critérios diagnósticos têm sido propostos para algumas destas entidades, entretanto nenhum deles pode ser considerado definitivo. O objetivo deste trabalho é apresentar o caso de um paciente de 10 anos de idade, com quadro recorrente de neurite óptica bilateral e mielopatia. Os dados clínicos e liquóricos preencheram critérios para o diagnóstico de neuromielite óptica de Devic. O diagnóstico diferencial foi especialmente difícil em relação à esclerose múltipla, pois não apenas os nervos ópticos e medula foram acometidos, visto que em um dos surtos registrou-se hemiparesia, com acometimento facial. A ressonância magnética foi também compatível com esclerose múltipla. Este caso ilustra que pacientes com doenças desmielinizantes do SNC podem preencher critérios diagnósticos para mais de uma delas, o que torna o julgamento clínico uma ferramenta ainda importante na abordagem e condução clínica destes casos.

OBJECTIVE: To determine the seroprevalence of neuromyelitis optica antibody (NMO)-IgG in Brazilian patients with clinical diagnosis of relapsing neuromyelitis optica, also known as Devic's disease. METHOD: We determined NMO-IgG titers in 28 patients (25 of them females) that fulfilled the 1999 NMO diagnostic criteria proposed by Wingerchuk et al. RESULTS: NMO-IgG was detected in 18 NMO patients (64.3%). CONCLUSION: Our results showed that seroprevalence of NMO-IgG in Brazilian NMO patients was similar to the observed in other studies.OBJETIVO: Determinar a soroprevalência do anticorpo neuromielite óptica (NMO)-IgG em pacientes brasileiros com diagnóstico de neuromielite óptica recorrente, também conhecida como doença de Devic. MÉTODO: Nós pesquisamos a presença do anticorpo NMO-IgG em 28 pacientes (25 do sexo feminino) que preenchiam os critérios diagnósticos para NMO propostos por Wingerchuk et al. em 1999. RESULTADOS: Dezoito pacientes (64,3%) apresentaram a pesquisa positiva do NMO-IgG. CONCLUSÃO: Nossos resultados demonstraram que a soroprevalência do anticorpo NMO-IgG em pacientes brasileiros com NMO é semelhante àquela encontrada em outros estudos.

Paroxysmal dyskinesias (PD) are thought to be rare movement disorders. The overwhelming majority of reported cases are primary. Secondary PD has seen reported to occur in some conditions, mainly in multiple sclerosis and head trauma. The anatomic origin of the lesion is also rarely seen at the spinal cord. Our objective was to describe four patients with paroxysmal dystonia secondary to spinal lesions during the recovering phase of a neuromyelitis optica (NMO) bout. In the reviewed literature, we do not find any report of PD related to NMO.Discinesias paroxísticas (DP) são distúrbios do movimento raros. A maioria dos casos relatados é de origem primária. DP secundárias têm sido relatadas em algumas condições, principalmente na esclerose múltipla e no trauma craniano. A origem anatômica da lesão também é raramente observada na medula. O objetivo deste trabalho foi descrever quatro pacientes com distonia paroxística secundária a lesões medulares, ocorrida durante a fase de recuperação do surto de neuromielite óptica (NMO). Na literatura consultada, não encontramos qualquer relato de DP secundárias à NMO.

Tonic spasms have been most commonly associated with multiple sclerosis. To date, few reports of series of patients with neuromyelitis optica and tonic spasms have been published.Methods:We analyzed the characteristics and frequency of tonic spasms in 19 subjects with neuromyelitis optica. Data was collected using a semi-structured questionnaire for tonic spasms, by both retrospectively reviewing medical records and performing clinical assessment.Results:All patients except one developed this symptom. The main triggering factors were sudden movements and emotional factors. Spasms were commonly associated to sensory disturbances and worsened during the acute phases of the disease. Carbamazepine was most commonly used to treat the symptom and patients showed good response to the drug.Conclusions:Tonic spasms are a common clinical manifestation in patients with neuromyelitis optica.Espasmos tônicos têm sido mais frequentemente associados com esclerose múltipla. Foram publicados até agora poucos relatos de série de pacientes com neuromielite óptica e espasmos tônicos.Métodos:Foram analisadas as características e a frequência de espasmos tônicos em 19 indivíduos com neuromielite óptica. Os dados foram coletados por meio de um questionário semiestruturado para espasmos tônicos, mediante a avaliação retrospectiva dos prontuários e a análise dos dados clínicosResultados:Todos os pacientes com neuromielite óptica exceto um apresentaram espasmos tônicos. Os principais fatores desencadeantes foram movimentos bruscos e fatores emocionais. Espasmos foram frequentemente associados a perturbações sensoriais e se agravaram durante a fase aguda da doença. A carbamazepina foi utilizada frequentemente para tratar os sintomas, com boa resposta.Conclusões:Os espasmos tônicos são manifestações clínicas frequentes em pacientes com neuromielite óptica.

ABSTRACT The definition of neuromyelitis optica (NMO) is still evolving. In 2015, the International Panel for NMO Diagnosis was convened to develop revised diagnostic criteria. There have been few studies on NMO in the Brazilian population. Objective To describe the characteristics of 34 Brazilian NMO patients. To evaluate the contribution of the 2015 criteria to the diagnosis of NMO spectrum disorders (NMOSD) in 40 patients with longitudinal extensive transverse myelitis (LEMT). Methods This is a retrospective, descriptive and analytic study. Results Among NMO patients, there was a predominance of women, with onset in the fourth decade of life, and AQP4-IgG seropositivity in 73.5%. The diagnosis of NMOSD was established in 37.5% of LETM patients according to AQP4-IgG positivity and in 5% of LETM patients if the AQP4-IgG result was unknown. Conclusions The characteristics of this series are similar to those of other Western populations. The AQP4-IgG testing assists in the diagnosis of NMOSD.