Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders.

BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.

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.

Neuromyelitis optica spectrum disorders with a benign course. Analysis of 544 patients.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) most commonly cause severe disability which is related to disease attacks. However, some patients retain good neurological function for a long time after disease onset. OBJECTIVES: To determine the frequency, demographic and the clinical features of good outcome NMOSD, and analyze their predictive factors. METHODS: We selected patients who met the 2015 International Panel for NMOSD diagnostic criteria from seven MS Centers. Assessed data included age at disease onset, sex, race, number of attacks within the first and three years from onset, annualized relapsing rate (ARR), total number of attacks, aquaporin-IgG serum status, presence of cerebrospinal fluid (CSF)-specific oligoclonal bands (OCB) and the Expanded Disability Status Scale (EDSS) score at the last follow-up visit. NMOSD was classified as non-benign if patients developed sustained EDSS score >3.0 during the disease course, or benign if patients had EDSS score ≤3.0 after ≥15 years from disease onset. Patients with EDSS <3.0 and disease duration shorter than 15 years were not qualified for classification. We compared the demographic and clinical characteristics of benign and non-benign NMOSD. Logistic regression analysis identified predictive factors of outcome. RESULTS: There were 16 patients with benign NMOSD (3% of the entire cohort; 4.2% of those qualified for classification; and 4.1% of those who tested positive for aquaporin 4-IgG), and 362 (67.7%) with non-benign NMOSD, whereas 157 (29.3%) did not qualify for classification. All patients with benign NMOSD were female, 75% were Caucasian, 75% tested positive for AQP4-IgG, and 28.6% had CSF-specific OCB. Regression analysis showed that female sex, pediatric onset, and optic neuritis, area postrema syndrome, and brainstem symptoms at disease onset, as well as fewer relapses in the first year and three years from onset, and CSF-specific OCB were more commonly found in benign NMOSD, but the difference did not reach statistical significance. Conversely, non-Caucasian race (OR: 0.29, 95% CI: 0.07-0.99; p = 0.038), myelitis at disease presentation (OR: 0.07, 95% CI: 0.01-0.52; p <0.001), and high ARR (OR: 0.07, 95% CI: 0.01-0.67; p = 0.011) were negative risk factors for benign NMOSD. CONCLUSION: Benign NMOSD is very rare and occurs more frequently in Caucasians, patients with low ARR, and those who do not have myelitis at disease onset.

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.

Status of the neuromyelitis optica spectrum disorder in Latin America.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES: To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS: The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS: We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. CONCLUSIONS: This is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.

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.

Neuromyelitis optica spectrum disorder associated with dengue virus infection.

Dengue virus infection is a disease with high incidence in some tropical and subtropical countries. A variety of neurological complications of dengue fever (DF) has been described including two cases with the phenotype of neuromyelitis optica spectrum disorder (NMOSD). However, aquaporin-4 serostatus was unknown or negative in these patients. We report two patients with NMOSD occurring in association with DF. The first patient presented with brainstem symptoms and the second one with isolated unilateral optic neuritis. Both patients tested positive for serum AQP4-antibody. This report shows that DF may trigger seropositive NMOSD.

Myelitis and cauda equina involvement following dengue fever. A case report and review of the literature.

Dengue fever (DF) is a common arbovirosis in tropical and subtropical countries and may be associated with a wide range of neurological complications. We describe a 41-year-old man who developed weakness in the right arm and lower limbs, paresthesia in the upper and lower limbs, and sphincter disturbance four weeks following DF. Examination disclosed a wheel-chair bound patient with urinary catheter, areflexia in the lower limbs, and a sensation level at T10. Spinal magnetic resonance imaging showed diffuse lesions with contrast-enhanced areas extending from the medullary-cervical junction to the conus medullaris and cauda equina. A review of the literature reveals that this is the first report of clinical and imaging signs of myeloradiculitis with cauda equina involvement following DF infection.

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.

MRI characteristics of neuromyelitis optica spectrum disorder: an international update.

Since its initial reports in the 19th century, neuromyelitis optica (NMO) had been thought to involve only the optic nerves and spinal cord. However, the discovery of highly specific anti-aquaporin-4 antibody diagnostic biomarker for NMO enabled recognition of more diverse clinical spectrum of manifestations. Brain MRI abnormalities in patients seropositive for anti-aquaporin-4 antibody are common and some may be relatively unique by virtue of localization and configuration. Some seropositive patients present with brain involvement during their first attack and/or continue to relapse in the same location without optic nerve and spinal cord involvement. Thus, characteristics of brain abnormalities in such patients have become of increased interest. In this regard, MRI has an increasingly important role in the differential diagnosis of NMO and its spectrum disorder (NMOSD), particularly from multiple sclerosis. Differentiating these conditions is of prime importance because early initiation of effective immunosuppressive therapy is the key to preventing attack-related disability in NMOSD, whereas some disease-modifying drugs for multiple sclerosis may exacerbate the disease. Therefore, identifying the MRI features suggestive of NMOSD has diagnostic and prognostic implications. We herein review the brain, optic nerve, and spinal cord MRI findings of NMOSD.

Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder.

Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than gray matter degradation. These findings could be confirmed by ultrahigh-field MRI. The use of nonconventional MRI techniques may further our understanding of the pathogenic processes in NMO spectrum disorders and may help us identify the distinct radiographic features corresponding to specific phenotypic manifestations of this disease.

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.

Pathologic yawning in neuromyelitis optica spectrum disorders.

INTRODUCTION: Brainstem, hypothalamic and cerebral symptoms may occur in neuromyelitis optica spectrum disorders (NMOSD). However, pathologic yawning has not been previously described in NMOSD patients. PATIENTS AND METHODS: Nine AQP4-IgG seropositive NMOSD patients experienced excessive yawning not related to sleep deprivation or fatigue. RESULTS: Patients were female, aged 19-57 years (median, 39 years) at disease onset. Excessive yawning spells were the presenting symptom of the disease in five patients, lasted 2-16 weeks, and usually occurred in association with nausea, vomiting and hiccups. Brain MRI was abnormal in all patients and most frequently showed brainstem and hypothalamic lesions. CONCLUSION: Pathologic yawning may be a neglected although not a rare symptom in NMOSD.

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 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.

Treatment of Neuromyelitis Optica: Review and Recommendations.

Neuromyelitis optica (NMO) is an autoimmune demyelinating disease preferentially targeting the optic nerves and spinal cord. Once regarded as a variant of multiple sclerosis (MS), NMO is now recognized to be a different disease with unique pathology and immunopathogenesis that does not respond to traditional MS immunomodulators such as interferons. Preventive therapy in NMO has focused on a range of immunosuppressive medications, none of which have been validated in a rigorous randomized trial. However, multiple retrospective and a few recent prospective studies have provided evidence for the use of six medications for the prevention of NMO exacerbations: azathioprine, rituximab, mycophenolate mofetil, prednisone, methotrexate and mitoxantrone. This review provides a comprehensive analysis of each of these medications in NMO and concludes with a set of recommended consensus practices.

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.

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.