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Multiple sclerosis (MS) onset is believed to result from a combination of environmental and genetic factors. A prevailing theory addresses the influence of hypovitaminosis D in the development of MS. This research aimed to study the association between vitamin D serum levels and MS, as a prognostic and risk factor for the development and progression of the disease. A cross-sectional multicenter study was conducted in patients with relapsing-remitting MS (n = 67), according to the revised McDonald criteria (2010), accompanied in three MS centers in different Brazilian states. A control group consisted of healthy volunteers (n = 61). Blood collections were carried out in late summer and late winter. This seems to be the first study of this kind in Latin America. The vitamin D serum levels for MS patients (29.63 ± 8.08) in summer were similar to the controls (29.71 ± 8.28); however, in winter they were lower than the healthy individuals (24.05 ± 7.47 vs 26.56 ± 8.01). No significant difference between the three cities was observed. No association was noted between vitamin D serum levels and gender, race and age, nor correlation of these levels with the EDSS or disease duration. In contrast, a significant association was seen between deficient vitamin D serum levels in late winter with disease activity, characterized by the onset of relapses (19.73 ± 5.69 vs 25.30 ± 6.22) or Gd + lesions (17.22 ± 3.11 vs 22.79 ± 7.22). [ABSTRACT FROM AUTHOR]

To elucidate immunopathogenetic roles of aquaporin-4 antibodies in the cerebrospinal fluid (CSF) of neuromyelitis optica spectrum disorders (NMOSD), we analyzed aquaporin-4 antibody titers, cellular and inflammatory markers in the CSF collected from 11 aquaporin-4 antibody seropositive patients. The CSF aquaporin-4 antibody levels during attacks (but not in sera) closely correlated with pleocytosis, inflammatory cytokines including interleukin-6 that can regulate antibody-producing plasmablasts, and glial fibrillary acidic protein levels in the CSF. The amount of aquaporin-4 antibodies present in the central nervous system may have therapeutic implications, as it is associated with astrocyte injury and inflammatory responses during NMOSD attacks. [ABSTRACT FROM AUTHOR]

To elucidate immunopathogenetic roles of aquaporin-4 antibodies in the cerebrospinal fluid (CSF) of neuromyelitis optica spectrum disorders (NMOSD), we analyzed aquaporin-4 antibody titers, cellular and inflammatory markers in the CSF collected from 11 aquaporin-4 antibody seropositive patients. The CSF aquaporin-4 antibody levels during attacks (but not in sera) closely correlated with pleocytosis, inflammatory cytokines including interleukin-6 that can regulate antibody-producing plasmablasts, and glial fibrillary acidic protein levels in the CSF. The amount of aquaporin-4 antibodies present in the central nervous system may have therapeutic implications, as it is associated with astrocyte injury and inflammatory responses during NMOSD attacks. Ann Neurol 2014;76:305-309 [ABSTRACT FROM AUTHOR]

Abstract: Risk factors for development of multiple sclerosis (MS) are still a matter of debate. Latitude gradient, vitamin D deficiency and season of birth are among the most investigated environmental factors associated with the disease. Several international studies suggest that birth in spring is a substantial risk factor for MS. We investigated the season of birth as a potential risk for MS in different geographical regions of Brazil. We conducted a cross-sectional retrospective study with 2257 clinically definite MS patients enrolled in 13 Brazilian MS clinics in the south, southeast, and northeast regions of Brazil. Demographic and clinical data relating to date of birth and clinical features of the disease were collected and analysed, and subsequently compared with birth date among the general Brazilian population. The distribution of date of birth of MS patients showed an increase in spring and a decrease in autumn, with no difference being observed in the other seasons. In conclusion, season of birth is a probable risk factor for MS in most parts of Brazil. These findings may be related to the role that vitamin D plays in MS pathogenesis. [Copyright &y& Elsevier]

Introduction/Aims: Objective and practical biomarkers to determine the need for gastrostomy in patients with amyotrophic lateral sclerosis (ALS) are lacking. Tongue pressure (TP) is a promising biomarker because it is associated with bulbar dysfunction. The aims of this study were to evaluate the association of TP with the need for gastrostomy, and to determine its optimal cut‐off value. Methods: This prospective observational study included participants with ALS taking nutrition orally. TP was evaluated using the Iowa Oral Performance Instrument. Need for gastrostomy as determined by a multidisciplinary team during a 12‐month follow up period was recorded. Associations between TP and need for gastrostomy placement were performed. ROC curve analysis determined the optimal cut‐off value of TP to predict gastrostomy. Results: Of 208 screened participants, 119 were included. Gastrostomy was indicated in 45% (53), in a 12‐month follow up period. TP of ≤20 kPA was a strong predictor of gastrostomy indication (OR 11.8, CI 95% [4.61, 34.7], p <.001). The association persisted even after adjustment for weight loss, pneumonia, prolonged feeding duration, Revised ALS Functional Rating Scale score, and American Speech‐Language‐Hearing Association scale score (OR 4.51, CI 95% [1.50, 14.9], p =.009). By receiver operating characteristic curve analysis, 20 kPA represented the optimal cut‐off value (sensitivity 0.75, specificity 0.89). Discussion: TP is a strong independent predictor of gastrostomy indication in the subsequent 12 months in patients with ALS, with good sensitivity and specificity at a cutoff value of ≤20 kPA, suggesting that it may be a promising biomarker in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis misdiagnosis remains a problem despite the well-validated McDonald 2017. For proper evaluation of errors in the diagnostic process that lead to misdiagnosis, it is adequate to incorporate patients who are already under regular follow-up at reference centers of demyelinating diseases. Objectives: To evaluate multiple sclerosis misdiagnosis in patients who are on follow-up at a reference center of demyelinating diseases in Brazil. Methods: We designed an observational study including patients in regular follow-up, who were diagnosed with multiple sclerosis at our specialized outpatient clinic in the Hospital of Clinics in the University of Sao Paulo, from 1996 to 2021, and were reassessed for misdiagnosis in 2022. We evaluated demographic information, clinical profile, and complementary exams and classified participants as "established multiple sclerosis," "non-multiple sclerosis, diagnosed," and "non-multiple sclerosis, undiagnosed." Failures in the diagnostic process were assessed by the modified Diagnostic Error Evaluation and Research tool. Results: A total of 201 patients were included. After analysis, 191/201 (95.02%) participants were confirmed as "established multiple sclerosis," 5/201 (2.49%) were defined as "non-multiple sclerosis, diagnosed," and 5/201 (2.49%) were defined as "non-multiple sclerosis, undiagnosed." Conclusions: Multiple sclerosis misdiagnosis persists in reference centers, emphasizing the need for careful interpretation of clinical findings to prevent errors. [ABSTRACT FROM AUTHOR]

Retinal complications in patients with inflammatory optic neuritis (ON) are generally related to post-infectious neuroretinitis and are considered uncommon in autoimmune/demyelinating ON, whether isolated or caused by multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). More recently, however, cases with retinal complications have been reported in subjects positive for myelin oligodendrocyte glycoprotein (MOG) antibodies. We report a 53-year-old woman presenting with severe bilateral ON associated with a focal area of paracentral acute middle maculopathy (PAMM) in one eye. Visual loss recovered remarkably after high-dose intravenous corticosteroid treatment and plasmapheresis, but the PAMM lesion remained visible on both optical coherence tomography and angiography as an ischaemic lesion affecting the middle layers of the retina. The report emphasises the possible occurrence of retinal vascular complications in MOG–related optic neuritis, an important addition to the diagnosis of, and possible differentiation from, MS–related or NMOSD–related ON. [ABSTRACT FROM AUTHOR]

MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0–7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0–8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0–8)] and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson's fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity. Methods: We used the 18-kDa translocator protein (TSPO) tracer (R)-[11C]PK11195 and [11C]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)–based analysis of the dynamic data, (R)-[11C]PK11195 distribution volume (VT) was determined for each subject using a metabolite-corrected arterial plasma input function while [11C]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT). Results: In the VOI-based analysis, [11C]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[11C]PK11195 VT were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[11C]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [11C]PIB uptake was observed in certain WM regions when comparing the relapsing–remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[11C]PK11195 VT and lower [11C]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [11C]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[11C]PK11195 VT (P = 0.013). Conclusions: Widespread innate immune cells profile and marked loss of myelin in T2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures. [ABSTRACT FROM AUTHOR]

Ocrelizumab and siponimod are the two on‐label drugs used for progressive forms of multiple sclerosis (PMS). However, many patients with PMS do not have access to these high‐efficacy disease‐modifying drugs (DMDs). Off‐label prescription of other high‐efficacy DMDs (fingolimod, rituximab and natalizumab) may be a strategy to improve access to immunotherapy for these patients. We aim to compare on‐label and off‐label high‐efficacy drugs for their effect on disability progression in PMS. In December 2021, we searched MEDLINE (PubMed), Embase, Cochrane Central and Scopus databases for randomized clinical trials involving patients with PMS. High‐efficacy drugs were considered as intervention and placebos as comparison. The outcome contemplated was risk of Expanded Disability Severity Scale (EDSS) progression at 2 years. A network meta‐analysis was performed to compare the relative risk of EDSS progression at 2 years compared with placebo in on‐label and off‐label drugs. We included five studies with 4526 patients. The median EDSS progression at 2 years in patients that received any immunotherapy was 30%, compared with 35% in placebo groups. Overall, the risk of bias of individual studies was low. Network analysis revealed overlapping confidence intervals in off‐label drugs (CI95% 0.51–2.16) versus ocrelizumab (reference) and off‐label drugs (CI 95% 0.53–1.96) versus siponimod (reference), suggesting similar efficacy. The same result was found even after excluding studies with the risk of publication bias. Off‐label high efficacy immunotherapy in PMS has biological plausibility and presented similar effectiveness to on‐label DMDs in this network meta‐analysis. The use of fingolimod, rituximab or natalizumab may be a strategy that reduces costs and improves access to immunotherapy for patients with PMS. [ABSTRACT FROM AUTHOR]

We aimed to quantify fatigue frequency and evolution in amyotrophic lateral sclerosis (ALS), and to correlate fatigue with factors such as age, sex, educational level, disease duration, functionality, quality of life, dyspnoea, depression and sleepiness. Sixty ALS patients (test group: TG) selected by El Escorial criteria and 60 normal individuals (control group: CG) matched according to sex and age, were followed every three months, during 9 months, by means of self-report scales: Fatigue Assessment Instrument (Fatigue Severity Scale plus three qualitative subscales); ALS Functional Rating Scale; McGill Quality of Life Questionnaire; dyspnoea analogical scale; Beck Depression Inventory and Epworth Sleepiness Scale. Fatigue was reported by 83% of TG (median: 3.6, interquartile range 1.5-5.4), compared with 20% of CG (median: 1, 1-1), and was significantly greater in the TG (p<0.001, Mann-Whitney test). Fatigue severity increased by the ninth month of the study (p = 0.0008, Friedman, Müller-Dunn post test). There was no correlation between fatigue and other parameters, except for an inverse correlation with age at disease onset (p = 0.0395, Spearman rank correlation). In conclusion, fatigue was frequent in ALS, greater in the youngest patients and worsened during follow-up. Possibly, ALS related fatigue is an independent factor, which deserves individualized approach and treatment. [ABSTRACT FROM AUTHOR]

Therapeutic plasma exchange (TPE) can improve disability recovery after neuromyelitis optica spectrum disease (NMOSD) attacks, but its effectiveness and safety in Latin-American patients with access barriers and diverse ethnicity is underexplored. We carried out a retrospective cohort study with NMOSD patients that underwent TPE. 84 NMOSD attacks in 68 patients were evaluated. Despite a median 25-day delay from symptom onset to TPE, 65,5% of patients showed significant improvement. Adverse events occurred in 39% of patients, usually transitory and with no fatalities. • Retrospective cohort from Brazil to assess TPE efficacy and safety for acute NMOSD attacks. • 84 attacks from 68 NMOSD patients: 65.5% of NMOSD attacks showed moderate to marked improvement. • 39% treatments had adverse events: arterial hypotension (15%) and central line infection (7/1,000 catheter days). • Favorable TPE response linked to brainstem syndrome and lower baseline EDSS. No impact of time from symptoms to TPE. • TPE is a viable treatment for NMOSD attacks in Latin America [ABSTRACT FROM AUTHOR]

Background: MOG-IgG-associated optic neuritis, encephalitis and myelitis (MONEM) is a recently recognized group of inflammatory central nervous system (CNS) disorders distinct from multiple sclerosis and neuromyelitis optica spectrum disorders. Limited data are available regarding the predictors of relapse in this condition. Objective: We aimed to evaluate the longitudinal serostatus of patients with MOG-IgG and to correlate serostatus with long-term clinical outcomes. Methods: Of 574 consecutive patients who presented with demyelinating inflammatory CNS disorders, we included 31 patients who were MOG-IgG-positive. Patients with MOG-IgG were followed up from 2011 to 2017 at the School of Medicine, University of São Paulo, Brazil. Results: Relapsing disease occurred in 23 out of 31 patients (74%), while 8 (26%) exhibited a monophasic course. All monophasic patients, as well as the majority of relapsing patients, became seronegative during clinical remission. Patients exhibiting disease activity in the last 2 years were more likely to remain positive, with higher medium titres than those found in patients in clinical remission. Conclusion: MOG-IgG patients usually present with a relapsing course, and the risk of relapse was associated with longitudinally persistent MOG-IgG seropositivity. In contrast, patients who experienced a single attack became spontaneously seronegative for MOG-IgG during long-term follow-up. [ABSTRACT FROM AUTHOR]

Optic neuritis (ON) admits diverse differential diagnoses. Petzold proposed diagnostic criteria for ON in 2022, although real-world application of these criteria is missing. We conducted a retrospective review of patients with ON. We classified patients into definite or possible ON, and into groups A (typical neuritis), B (painless), or C (binocular) and estimated the frequency of etiologies for each group. We included 77 patients, with 62% definite and 38% possible ON. CRION and NMOSD-AQP4 negative-ON were less commonly seen in definite ON. Application of the 2022 criteria revealed a lower-than-expected frequency of definite ON, particularly for seronegative non-MS causes. • Optic neuritis diagnostic criteria 2022 may have higher sensitivity for typical ON. • Non-MS seronegative ON may be underrepresented by diagnostic criteria. • Access to biomarkers may be an obstacle for diagnosis of ON in low-income scenarios. [ABSTRACT FROM AUTHOR]

Objective: To investigate gene mutations in familial form (FALS) and sporadic form (SALS) of amyotrophic lateral sclerosis (ALS) in a highly miscegenated population. Methods: Frequencies of mutations in the C9orfF72, TARDBP, SOD1, FUS and VAPB genes were investigated in a cohort of FALS (n = 39) and SALS (n = 189) subjects from the Research Centre of the University of São Paulo School of Medicine. All patients were subjected to C9orf72 and TARDBP analyses. SOD1, FUS and VAPB were also evaluated in FALS subjects. Results: Mutations were identified in FALS (61.3%) and SALS (5.3%) patients. Mutations in C9orf72 (12.8%, >45 GGGGCC hexanucleotide repeats), VAPB (43.6%, P56S) and SOD1 (7.7%, L145S) were identified in FALS subjects. Pathogenic C9orf72 expansions (2.64%) were identified in some SALS patients. Similar changes of TARDBP were found in SALS (2.64%) but not in FALS subjects. No FUS mutations were seen in any FALS subjects. Conclusions: TARDBP and C9orf72 mutations in this cohort were similar to those found in other centres worldwide. VAPB mutation (P56S) was highly prevalent in Brazilian FALS patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Primary angiitis of the central nervous system is a rare inflammatory vasculopathy and it is a difficult diagnosis to make because of its kaleidoscopic presentation and its multiple mimics, including multiple sclerosis. A 21-year-old men presented a four-year history of progressive gait deterioration. Magnetic resonance imaging of the brain and spine showed hyperintense round-shaped lesions on T2 images, many with contrast enhancement, in supra/infratentorial and spinal segments. He received treatment for multiple sclerosis but presented clinical worsening, and follow-up neuroimaging showed persistent contrast enhancement lesions and a cerebellar hematoma. Brain biopsy was performed and demonstrated inflammatory infiltrations in blood vessels. The patient received 6 monthly schedules of 5 g methylprednisolone and 1 g cyclophosphamide with clinical stabilization. Our patient presented a primary angiitis central nervous system according to the Birnbaum and Hellmann proposed criteria. This case reinforces the importance of advancing the differential diagnosis of patients that present red flags in brain neuroimaging. The presence of the micro/macrobleeds and persistent contrast enhancing lesions should raise the suspicion of vasculitis in the differential diagnosis of multiple sclerosis. [ABSTRACT FROM AUTHOR]

A 44-year-old man presented with severe right visual loss. The right fundus examination showed marked optic disc oedema associated with partial macular star. Serological blood tests for infectious agents were all negative. Serum aquaporin-4 antibody was negative but anti-MOG (myelin oligodendrocyte glycoprotein) was positive. Magnetic resonance revealed extensive lesion in right optic nerve. There was no visual improvement after intravenous therapy. Patient had no further attacks after follow-up. Optic disc oedema with macular star is found in several infectious and non-inflammatory disorders, but it has not been reported in optic neuritis (ON) associated with autoantibodies to myelin oligodendrocyte glycoprotein (anti-MOG). [ABSTRACT FROM AUTHOR]

Background: Association of leukoencephalopathy and atypical mycobacteriosis has been rarely reported. We present a case that is relevant for its unusual presentation and because it may shed further light on the pathogenic mechanisms underlying reversible encephalopathies. Case report: We report the case of a Hispanic 64-year-old woman with cognitive decline and extensive leukoencephalopathy. Magnetic resonance imaging revealed white-matter lesions with increased water diffusivity, without blood-brain-barrier disruption. Brain biopsy showed tissue rarefaction with vacuolation, mild inflammation, few reactive astrocytes and decreased aquaporin water-channel expression in the lesions. Six months later, she was diagnosed with atypical mycobacterial pulmonary infection. Brain lesions resolved after antimycobacterial treatment. Conclusion: We hypothesize leukoencephalopathic changes and vasogenic edema were associated with decreased aquaporin expression. Further studies should clarify if reversible leukoencephalopathy has a causal relationship with decreased aquaporin expression and atypical mycobacterial infection, and mechanisms underlying leukoencephalopathy resolution after antimycobacterial treatment. This article may contribute to the understanding of pathogenic mechanisms underlying magnetic resonance imaging subcortical lesions and edema, which remain incompletely understood. [ABSTRACT FROM AUTHOR]

Two patients with longitudinally extensive myelopathy were initially biopsied for suspected spinal cord tumors. Both patients were later diagnosed with neuromyelitis optica spectrum disorders (NMOSD) supported by their AQP4-seropositivity. Pathological review of both biopsies revealed demyelinated lesions with thickened vessel walls and tissue rarefaction. Immunohistochemical staining demonstrated findings compatible with acute NMOSD lesions in one case while the other case exhibited findings consistent with chronic NMOSD lesions. A pre-biopsy differential diagnosis of longitudinally extensive spinal cord tumors should include NMOSD. Specific biopsy features, such as cystic changes with vascular wall thickening and astrocyte injury, should raise suspicion for NMOSD. [ABSTRACT FROM PUBLISHER]

Purpose: To evaluate the thickness of the inner retinal layers in the macula using frequency-domain optical coherence tomography (fd-OCT) in patients with demyelinating diseases. Design: Cross-sectional study. Participants: A total of 301 eyes of 176 subjects were evaluated. Subjects were divided in 5 different groups: controls, neuromyelitis optica (NMO), longitudinally extensive transverse myelitis (LETM), multiple sclerosis with a history of optic neuritis (MS-ON), and multiple sclerosis without a history of optic neuritis (MS non-ON). Methods: The individual layers from macular fd-OCT cube scans were segmented with an automated algorithm and then manually hand-corrected. For each scan, we determined the thickness of the retinal nerve fiber layer (RNFL), the combined retinal ganglion cell and inner plexiform layers (RGCL+), and the inner nuclear layer (INL). Main Outcome Measures: Macular RNFL, RGCL+, and INL thickness. Results: The RNFL was significantly thinner than in controls for all patient groups (P≤0.01). Macular RGCL+ thickness was significantly thinner than in controls for the NMO, MS-ON, and MS non-ON groups (P<0.001 for the 3 groups). The INL thickness was significantly thicker than in controls for the patients with NMO (P = 0.003) and LETM (P = 0.006) but not for those with MS-ON or MS non-ON. Although the RNFL and RGCL+ were not significantly different between the NMO and MS-ON groups, the patients with NMO had a significantly thicker INL than the patients with MS-ON (P = 0.02). Conclusions: Macular RNFL and RGCL+ demonstrate axonal and neural loss in patients with MS, either with or without ON, and in patients with NMO. In addition, the INL thickening occurs in patients with NMO and patients with LETM, and study of this layer may hold promise for differentiating between NMO and MS. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Background There have been no clinical trials for approval of medications for treating multiple sclerosis in patients younger than age 18 years. All treatments are based on personal experience and data from open observational studies. Fingolimod is an oral drug for multiple sclerosis that has been shown to be efficient and safe in adults. The aim of our study is to describe patients with multiple sclerosis who started treatment with fingolimod before the age of 18 years. Participants and methods Seventeen patients treated with fingolimod were identified in the Brazilian database of children and adolescents with multiple sclerosis. The average time of use of the drug was 8.6 months. Results Fingolimod showed a good safety and efficacy profile in these patients, all of whom had very active multiple sclerosis. After starting treatment with fingolimod, only one patient had a relapse and a new lesion on magnetic resonance imaging. The patients' degree of disability did not progress. No major adverse events were reported in relation to the first dose of the drug, nor in the short- and medium-term treatment. No patient has been followed for longer than 18 months, thus limiting long-term conclusions. Conclusions Off-label use of fingolimod in patients younger than age 18 years may be a good therapeutic option for multiple sclerosis control. [ABSTRACT FROM AUTHOR]

Genetic susceptibility is a well-recognized factor in the onset of multiple sclerosis (MS). The objective of this study was to determine the frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid, in an ethnically mixed group of MS patients in the city of São Paulo, Brazil. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. OCB were found in 49 (54.4%) out of 90 patients with clinically definite MS; out of the 23 brown/black patients, 17 (73.9%) were OCB+; out of the 66 white patients, 32 (48.5%) were OCB+; and the only patient yellow was OCB+ (p = 0.05). Analysis of the IgG index was also consistent with the findings, but with lower statistical significance. The data presented in our study show that the ethnic differences in MS extend to the immune response. [ABSTRACT FROM AUTHOR]

Background: Association of leukoencephalopathy and atypical mycobacteriosis has been rarely reported. We present a case that is relevant for its unusual presentation and because it may shed further light on the pathogenic mechanisms underlying reversible encephalopathies.Case Report: We report the case of a Hispanic 64-year-old woman with cognitive decline and extensive leukoencephalopathy. Magnetic resonance imaging revealed white-matter lesions with increased water diffusivity, without blood-brain-barrier disruption. Brain biopsy showed tissue rarefaction with vacuolation, mild inflammation, few reactive astrocytes and decreased aquaporin water-channel expression in the lesions. Six months later, she was diagnosed with atypical mycobacterial pulmonary infection. Brain lesions resolved after antimycobacterial treatment.Conclusion: We hypothesize leukoencephalopathic changes and vasogenic edema were associated with decreased aquaporin expression. Further studies should clarify if reversible leukoencephalopathy has a causal relationship with decreased aquaporin expression and atypical mycobacterial infection, and mechanisms underlying leukoencephalopathy resolution after antimycobacterial treatment. This article may contribute to the understanding of pathogenic mechanisms underlying magnetic resonance imaging subcortical lesions and edema, which remain incompletely understood. [ABSTRACT FROM AUTHOR]