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BACKGROUND AND OBJECTIVES: Race and ethnicity may influence the efficacy of disease-modifying therapies in patients with multiple sclerosis (MS). Incidence of MS in ethnically diverse groups may be higher; however, these populations are under-represented in MS trials. This post hoc analysis compared the proportion of patients achieving 3-parameter no evidence of disease activity (NEDA-3) with ofatumumab vs teriflunomide in participants with relapsing MS (RMS) enrolled in the ASCLEPIOS I/II trials by race/ethnicity subgroup. METHODS: ASCLEPIOS I/II were identical, double-blind, double-dummy, active-controlled, multicenter, phase 3 trials. Participants were randomized (1:1) to receive ofatumumab 20 mg every 4 weeks or teriflunomide 14 mg once daily for up to 30 months. Pooled data were used to determine the efficacy/safety of ofatumumab vs teriflunomide in participants who self-identified as non-Hispanic Black, non-Hispanic Asian, Hispanic/Latino, or non-Hispanic White. Participants who did not self-identify into one of these groups were classified as other/unknown. RESULTS: Of the 1,882 participants, 64 (3.4%) self-identified as non-Hispanic Black, 71 (3.8%) as non-Hispanic Asian, 145 (7.7%) as Hispanic/Latino, and 1,538 (81.7%) as non-Hispanic White. Baseline participant demographics/characteristics were largely balanced across subgroups, aside from minor variations in sex, disease duration, and MRI lesions. From months 0 to 24, the proportion of ofatumumab vs teriflunomide-treated patients achieving NEDA-3 (odds ratio [95% CI]) was as follows: non-Hispanic Black, 33.3% vs 3.4% (15.9 [1.67-151.71; p = 0.0162]); non-Hispanic Asian, 42.9% vs 21.9% (3.18 [0.95-10.59; p = 0.06]); Hispanic/Latino, 36.6% vs 18.6% (3.21 [1.32-7.79; p = 0.01]); and non-Hispanic White, 37.4% vs 16.6% (3.57 [2.73-4.67; p < 0.0001]). Rates of AEs were generally similar between treatment groups and across race/ethnicity subgroups; no new or unexpected safety signals were identified. DISCUSSION: Ofatumumab was associated with greater proportions of NEDA-3 achievement than teriflunomide across race/ethnicity subgroups in the ASCLEPIOS trials. Within each treatment group, the proportion of patients achieving NEDA-3 from months 0 to 24 was similar across the subgroups and overall pooled population. Both ofatumumab and teriflunomide were well tolerated. Future MS trials should include ethnically diverse groups to better inform treatment decisions and improve real-world patient outcomes. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT02792218 (clinicaltrials.gov/ct2/show/NCT02792218), NCT02792231 (clinicaltrials.gov/ct2/show/NCT02792231). Submission date: June 2, 2016. First enrollment: August 26, 2016. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients aged 18-55 years with RMS, the improvement in NEDA-3 with ofatumumab was comparably better than with teriflunomide among patients self-identified as non-Hispanic Black, non-Hispanic Asian, non-Hispanic White, Hispanic/Latino, and other/unknown.
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Anticorpos Monoclonais Humanizados , Crotonatos , Hidroxibutiratos , Esclerose Múltipla Recidivante-Remitente , Nitrilas , Toluidinas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Crotonatos/uso terapêutico , Método Duplo-Cego , Etnicidade , Hispânico ou Latino , Hidroxibutiratos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/etnologia , Nitrilas/uso terapêutico , Toluidinas/uso terapêutico , Resultado do Tratamento , Negro ou Afro-Americano , BrancosRESUMO
Hypogammaglobulinemia is characterized by reduced serum immunoglobulin levels. Secondary hypogammaglobulinemia is of considerable interest to the practicing physician because it is a potential complication of some medications and may predispose patients to serious infections. Patients with multiple sclerosis (MS) treated with B-cell-depleting anti-CD20 therapies are particularly at risk of developing hypogammaglobulinemia. Among these patients, hypogammaglobulinemia has been associated with an increased risk of infections. The mechanism by which hypogammaglobulinemia arises with anti-CD20 therapies (ocrelizumab, ofatumumab, ublituximab, rituximab) remains unclear and does not appear to be simply due to the reduction in circulating B-cell levels. Further, despite the association between anti-CD20 therapies, hypogammaglobulinemia, and infections, there is currently no generally accepted monitoring and treatment approach among clinicians treating patients with MS. Here, we review the literature and discuss possible mechanisms of secondary hypogammaglobulinemia in patients with MS, hypogammaglobulinemia results in MS anti-CD20 therapy clinical trials, the risk of infection for patients with hypogammaglobulinemia, and possible strategies for disease management. We also include a suggested best-practice approach to specifically address secondary hypogammaglobulinemia in patients with MS treated with anti-CD20 therapies.
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Agamaglobulinemia , Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/induzido quimicamente , Antígenos CD20 , Agamaglobulinemia/induzido quimicamente , Agamaglobulinemia/complicações , Rituximab/efeitos adversos , Gerenciamento ClínicoRESUMO
BACKGROUND: There are limited data available regarding the impact of ofatumumab, an anti-CD20 B-cell-depleting monoclonal antibody for relapsing multiple sclerosis (RMS), on vaccination response. The study objective was to assess humoral immune response (HIR) to non-live coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination in patients with RMS treated with ofatumumab. METHODS: This was an open-label, single-arm, multicenter, prospective pilot study of patients with RMS aged 18-55 years who received 2 or 3 doses of a COVID-19 mRNA vaccine after ≥1 month of subcutaneous ofatumumab (20 mg/month) treatment. The primary endpoint was the proportion of patients achieving HIR, as defined by local laboratory severe acute respiratory syndrome coronavirus-2 qualitative immunoglobulin G assays. Assay No. 1 was ≥14 days after the second or third vaccine dose. Assay No. 2 was 90 days thereafter. RESULTS: Of the 26 patients enrolled (median [range] age: 42 [27-54] years; median [range] ofatumumab treatment duration: 237 [50-364] days), HIR was achieved by 53.9% (14/26; 95% CI: 33.4 - 73.4%) at Assay No. 1 and 50.0% (13/26; 95% CI: 29.9 - 70.1%) at Assay No. 2. Patients who received 3 vaccine doses had higher HIR rates (Assay No. 1: 70.0% [7/10]; Assay No. 2: 77.8% [7/9]) than those who received 2 doses (Assay No. 1: 46.7% [7/15]; Assay No. 2: 42.9% [6/14]). Of patients aged <40 years without previous anti-CD20 therapy, HIR was achieved by 90.0% (9/10) at Assay No. 1 and 75.0% (6/8) at Assay No. 2. No serious adverse events were reported. CONCLUSION: Patients with RMS treated with ofatumumab can mount HIRs following COVID-19 vaccination. A plain language summary, infographic and a short video summarizing the key results are provided in supplementary material. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04847596 (https://clinicaltrials.gov/ct2/show/NCT04847596).
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COVID-19 , Esclerose Múltipla , Humanos , Adulto , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Imunidade Humoral , Projetos Piloto , Estudos Prospectivos , Recidiva , Vacinas de mRNA , Anticorpos AntiviraisRESUMO
BACKGROUND: The orbital complication rate during endoscopic sinus surgery (ESS) is <1%. Orbital fat exposure during ESS can herald orbital complications including orbital hematoma, extraocular muscle trauma, optic nerve injury, or blindness. The objective of this study was to evaluate the current consensus regarding diagnosis and management of orbital fat exposure during ESS. METHODS: A 24-point survey focused on orbital fat exposure during ESS was distributed to American Rhinologic Society members. Also, a retrospective review of 25 cases of orbital fat exposure drawn from the principal investigator's 30-year experience was performed. RESULTS: Over 10 000 surgical cases of the principal investigator were reviewed. Twenty-five patients had orbital fat exposure. Five developed minor complications while 2 were major (ie, temporary vision changes). Two hundred thirty-six surgeons responded to the survey; 93% had encountered orbital fat during ESS; 88% of surgeons identify orbital fat by either its appearance endoscopically or the "bulb press" test. Almost every responding surgeon will cautiously avoid further manipulation in the area of orbital fat exposure. Nearly half will immediately curtail the extent of surgery. Surgeons do not significantly change postoperative management. Considerations regarding observation in postanesthesia care unit, close follow-up, and strict nose blowing precautions are common. CONCLUSION: Orbital fat exposure during ESS is a rarely discussed, but clinically important. Orbital fat exposure can be a harbinger for major orbital complications that should be recognized by endoscopic appearance and confirmed with the bulb press test. Caution with "no further manipulation" of orbital fat is the guiding principle for intraoperative management, while postoperative management is generally expectant.Level 4 Evidence.
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Endoscopia , Órbita , Humanos , Endoscopia/efeitos adversos , Órbita/cirurgia , Estudos Retrospectivos , Músculos Oculomotores , Cegueira/etiologiaRESUMO
BACKGROUND: To compare the effectiveness of dimethyl fumarate (DMF) with subcutaneous interferon beta-1a (IFNß-1a) in controlling disease activity in patients with relapsing-remitting Multiple Sclerosis (MS). METHODS: Clinical and imaging data from patients treated with either IFNß-1a or DMF for at least one year were reviewed. The proportion of patients with at least one clinical relapse within 3-15 months after treatment onset, the proportion of patients with new T2 or gadolinium-enhancing lesions, and the proportion of subjects who achieved no evidence of disease activity (NEDA) status were assessed. RESULTS: Three hundred sixteen (98 on IFNß-1a, 218 on DMF) subjects were included. Baseline demographics were comparable between groups except for age, disease duration, and the number of previous treatments being higher and relapse rate in the prior year being lower in the DMF-treated group. The proportion of patients having a clinical relapse (24.5% vs. 9.6%; OR = 3.04; P < 0.001) or a new MRI lesion (28.6% vs. 8.7%; OR = 4.19, P < 0.001) at 15 months were higher on IFNß-1a. 79.9% of the patients achieved NEDA status at 15 months on DMF (vs. 51.1% for IFNß-1a; OR = 0.26, P < 0.001). Further adjustment for demographics, disease characteristics, treatment and relapse history, and subgroup analyses confirmed these findings. CONCLUSION: DMF was associated with less clinical and radiological disease activity compared to IFNß-1a.
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Fumarato de Dimetilo , Interferons , Adjuvantes Imunológicos/uso terapêutico , Antivirais , Fumarato de Dimetilo/uso terapêutico , Humanos , Interferon beta-1a/uso terapêutico , Interferon beta/uso terapêutico , RecidivaRESUMO
OBJECTIVE: Few satisfyingly effective treatments exist for patients with Secondary Progressive Multiple Sclerosis (SPMS). Our goal in conducting this review is to highlight clinical outcomes and study design, which may be applied to future phase III clinical trials for patients with SPMS. METHODS: A review of the available literature of phase III clinical trials since 1990 that specifically studied patients with SPMS. PubMed and ClinicalTrials.org were searched using appropriate terms. RESULTS: Expanded Disability Status Scale (EDSS) was most often used as an outcome measure, with time to confirmed disability progression at three months being used most often. Components of the Multiple Sclerosis Functional Composite (MSFC) were the next most frequent primary outcome measure used. Patient Reported Outcomes (PROs) were frequently used as secondary outcome measures with specific PROs more successful than others. MRI measures related to brain parenchymal volume have recently started to be used in phase III clinical trials. CONCLUSIONS: Some successful trials may have been related to patient selection for less inflammatory disease, which confounds the comparison between successful trials. Time to confirmed disability at three months or changes in composite MSFC are reasonable primary outcome measures to use in future SPMS trials with a suggestion that the MSFC may be more sensitive to progressive disease changes. PROs and MRI measures following brain parenchymal volume are reasonable secondary outcome measures to incorporate into future phase III trials in SPMS.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Ensaios Clínicos Fase III como Assunto , Avaliação da Deficiência , Progressão da Doença , Humanos , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Seleção de Pacientes , PubMed , Projetos de PesquisaRESUMO
BACKGROUND: There is limited data analyzing the safety and effectiveness of dimethyl fumarate (DMF) in the progressive multiple sclerosis (PMS) population. OBJECTIVE: To analyze the safety and effectiveness of DMF in patients with PMS. METHODS: We used Cox proportional hazards models to compare the time to confirmed worsening and improvement on the Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) between patients treated with DMF and glatiramer acetate (GA) for at least one year. RESULTS: We included 46 patients treated with DMF and 42 patients treated with GA. The safety and tolerability of GA and DMF were consistent with established profiles. There was no difference in confirmed EDSS progression. A trend towards reduced T25FW was seen in the DMF compared to GA after adjustment (HR = 0.86; 95% CI:0.37, 1.98; p = 0.72 and HR = 0.60; 95% CI:0.27, 1.34; p = 0.21, respectively). CONCLUSION: Dimethyl fumarate showed a trend towards reduction in T25FW but no evidence of clinically significant impact on EDSS. The small sample precluded definitive determination.
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BACKGROUND: The importance of supporting pregnancy-related decisions in multiple sclerosis (MS) patients has increasingly been recognized and hence the need for prospective data on pregnancy and pediatric outcomes in this patient population. OBJECTIVE: To assess prospective growth and developmental outcomes of infants born to mothers with multiple sclerosis (IMS). METHODS: PREG-MS is a prospective multicenter cohort study in New England, United States. We followed 65 women with MS and their infants with up to 12 months consistent pediatric follow-up. Pediatric, neurologic, and demographic information was obtained via structured telephone interviews and validated with medical records. RESULTS: No differences in infant weights and lengths with World Health Organization (WHO) 50th percentile standards were observed (p > 0.05). However, larger head circumference (HC) measurements than WHO standards were reported in cohort infants (p < 0.05). There was no association between HC and markers of maternal MS activity, demographic, or social factors. No irreversible pediatric developmental abnormalities were observed. CONCLUSION: This first prospective study on pediatric anthropometry in IMS suggests a possible increase in HC compared to WHO standards without an increase in irreversible developmental abnormalities. The observations are exploratory and require confirmation with larger prospective studies in diverse groups of MS patients.
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Mães , Esclerose Múltipla , Antropometria , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Gravidez , Estudos Prospectivos , Estados UnidosRESUMO
A 41-year-old female diagnosed with multiple sclerosis began ocrelizumab treatment. She received her first treatment course without significant complication. After receiving the first maintenance dose 6 months later, she developed weakness, myalgias, gastrointestinal symptoms, headache, and intermittent fever persisting for 4 weeks. A working diagnosis of serum sickness was determined after excluding other probable entities. She received 3 days of 1 g methylprednisolone intravenously and five plasma exchanges, experiencing gradual improvement. Serum sickness has occurred with monoclonal antibodies including rituximab. This case of possible ocrelizumab-associated serum sickness suggests that clinicians should remain vigilant about this possibility with this medication.
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Doença do Soro , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Humanos , Metilprednisolona , Rituximab , Doença do Soro/induzido quimicamenteAssuntos
Atresia das Cóanas/cirurgia , Endoscopia/métodos , Stents , Retalhos Cirúrgicos , Adulto , Feminino , Humanos , Ilustração Médica , Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To explore the safety and efficacy profile of teriflunomide in progressive multiple sclerosis. METHODS: We conducted a single-center retrospective observational analysis of a progressive multiple sclerosis population, assessing safety and efficacy in patients treated at least one year with teriflunomide or glatiramer acetate. Sustained progression of expanded disability status scale and sustained worsening of timed 25-foot walk were compared using a Cox proportional hazards model. RESULTS: Teriflunomide group (n = 29) mean characteristics: age = 58 years (SD ± 7.6), disease duration = 16.7 years (SD ± 9.5), expanded disability status score = 5.9 (SD ± 1.3), and follow - up = 32.4 months (SD ± 13.6). Glatiramer acetate group (n = 30) mean characteristics: age = 52.4 years (SD ± 11.3), disease duration = 15.1 years (SD ± 10.4), expanded disability status score = 5.7 (SD ± 1.6), and follow - up = 46.9 months (SD ± 43.9). Both treatments were well tolerated without serious side effects. After adjustment for age, sex, and baseline expanded disability status score, sustained expanded disability status score progression did not differ between groups (hazard ratio = 1.17; 95% confidence interval: 0.45, 3.08; p = 0.75). Sustained timed 25-foot walk worsening after adjustment also did not differ (hazard ratio = 0.56; 95% confidence interval: 0.2, 1.53; p = 0.26). CONCLUSION: In an advanced progressive multiple sclerosis population, no substantial differences in tolerability, safety, sustained EDSS progression, or sustained T25FW worsening over time were observed between glatiramer acetate and teriflunomide-treated groups. The small sample precluded definitive determination.
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The outbreak of a severe acute respiratory syndrome caused by a novel coronavirus (COVID-19), has raised health concerns for patients with multiple sclerosis (MS) who are commonly on long-term immunotherapies. Managing MS during the pandemic remains challenging with little published experience and no evidence-based guidelines. We present five teriflunomide-treated patients with MS who subsequently developed active COVID-19 infection. The patients continued teriflunomide therapy and had self-limiting infection, without relapse of their MS. These observations have implications for the management of MS in the setting of the COVID-19 pandemic.
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Infecções por Coronavirus/complicações , Crotonatos/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Pneumonia Viral/complicações , Toluidinas/uso terapêutico , Adulto , Idoso , Betacoronavirus , COVID-19 , Feminino , Humanos , Hidroxibutiratos , Masculino , Pessoa de Meia-Idade , Nitrilas , Pandemias , SARS-CoV-2RESUMO
Two different treatment paradigms are most often used in multiple sclerosis (MS). An escalation or induction approach is considered when treating a patient early in the disease course. An escalator prioritizes safety, whereas an inducer would favor efficacy. Our understanding of MS pathophysiology has evolved with novel in vivo and in vitro observations. The treatment landscape has also shifted significantly with the approval of over 10 new medications over the past decade alone. Here, we re-examine the treatment approach in light of these recent developments. We believe that recent work suggests that early prediction of the disease course is fraught, the amount of damage to the brain that MS causes is underappreciated, and its impact on patient function oftentimes is underestimated. These concerns, coupled with the recent availability of agents that allow a better therapeutic effect without compromising safety, lead us to believe that initiating higher efficacy treatments early is the best way to achieve the best possible long-term outcomes for people with MS.
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Fatores Imunológicos/administração & dosagem , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológico , HumanosAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/diagnóstico por imagem , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Adulto , Humanos , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológicoRESUMO
OBJECTIVES: There are increasingly effective therapies for relapsing forms of multiple sclerosis (MS); however, the options for the progressive patient population are limited. The effect of mycophenolate mofetil (MMF), a disease-modifying agent for several autoimmune diseases, in progressive MS has not been explored effectively. We performed a prospective study to assess the safety and efficacy of MMF in progressive MS patients. METHODS: We identified 64 patients enrolled in the comprehensive longitudinal database at the Partners MS Center, who fulfilled our inclusion criteria. They were exposed to MMF for at least 1 year with recorded clinical outcomes. Efficacy was assessed by comparing the absolute relapse rate (ARR), and the mean Expanded Disability Status Scale (EDSS) and timed 25 foot walk (T25FW) test scores before and after MMF treatment. RESULTS: At the start of MMF, 78% of patients (n = 50) were in the 4-7.5 EDSS range. There was a slight increase in mean EDSS from 5.49 ± 1.65 (n = 48) 1 year before MMF start to 5.85 ± 1.56 (n = 48) 1 year after (p = 0.020). The mean T25FW score increased 1 year before MMF from 12.3 ± 9.6 s (n = 38) to 15.6 ± 12.3 s (n = 38) 1 year after (p = 0.009). The ARR in the 2 years pre-MMF period was 0.30 ± 0.63, which decreased to a 0.09 ± 0.29 (p = 0.022) 2 years post MMF. CONCLUSION: MMF did not affect disease progression but did influence relapse rate. We believe that other medication options should be considered before MMF in advanced progressive patients.
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Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Progressão da Doença , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Teste de CaminhadaRESUMO
OBJECTIVE: Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (MS) patients. METHODS: MS patients (N = 9) and controls (N = 13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium, and Streptococcus twice-daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy. Frozen peripheral blood mononuclear cells (PBMCs) were used for immune cell profiling. Stool samples were used for 16S rRNA profiling and metabolomics. RESULTS: Probiotic administration increased the abundance of several taxa known to be depleted in MS such as Lactobacillus. We found that probiotic use decreased the abundance of taxa previously associated with dysbiosis in MS, including Akkermansia and Blautia. Predictive metagenomic analysis revealed a decrease in the abundance of several KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways associated with altered gut microbiota function in MS patients, such as methane metabolism, following probiotic supplementation. At the immune level, probiotic administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of inflammatory monocytes, decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes, as well as decreased human leukocyte antigen (HLA) D related MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA-DQA1 in controls. Probiotic-induced increase in abundance of Lactobacillus and Bifidobacterium was associated with decreased expression of MS risk allele HLA.DPB1 in controls. INTERPRETATION: Our results suggest that probiotics could have a synergistic effect with current MS therapies. Ann Neurol 2018.
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Bifidobacterium/imunologia , Microbiota/imunologia , Esclerose Múltipla/genética , Probióticos/metabolismo , Adulto , Bifidobacterium/genética , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Lactobacillus/genética , Lactobacillus/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Microbiota/genética , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , RNA Ribossômico 16S/genética , Adulto JovemRESUMO
PURPOSE OF REVIEW: Acute and chronic sinusitis can give rise to a wide array of intracranial and orbital complications. These complications include brain abscess, subdural empyema, epidural abscess, meningitis, venous sinus thrombosis, frontal bone osteomyelitis, and orbital cellulitis and abscess. Despite numerous medical advances, these complications carry a risk of mortality and significant morbidity. RECENT FINDINGS: Recent studies have shown improvement in both the mortality and the morbidity associated with the neurologic complications of acute and chronic sinusitis. However, there are still a large portion of patients with long-term sequelae, and the literature reports a morbidity rate of approximately 30%. The most common post-treatment morbidities include permanent changes in vision, seizures, and hemiparesis. Although the overall incidence of neurologic complications from a sinogenic source are rare, the potential long-term complications can be devastating making prompt diagnosis and treatment vital to improving outcomes.
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Sinusite/complicações , Doença Aguda , Adolescente , Abscesso Encefálico/etiologia , Doença Crônica , Empiema Subdural/etiologia , Feminino , Humanos , Masculino , Meningite/etiologia , Celulite Orbitária/etiologia , Trombose dos Seios Intracranianos/etiologiaRESUMO
None of the disease-modifying therapies (DMTs) currently being used for the management of multiple sclerosis (MS) are 100% effective. In addition, side effects associated with the use of these DMTs have limited the practice of combination therapy. Hence, there is a need for safe immunomodulatory agents to fine-tune the management of MS. The gut microbiome plays an important role in autoimmunity, and several studies have reported alterations in the gut microbiome of MS patients. Studies in animal model of MS have identified members of the gut commensal microflora that exacerbate or ameliorate neuroinflammation. Probiotics represent an oral, non-toxic immunomodulatory agent that could be used in combination with current MS therapy. We designed a pilot study to investigate the effect of VSL3 on the gut microbiome and peripheral immune system function in healthy controls and MS patients. VSL3 administration was associated with increased abundance of many taxa with enriched taxa predominated by Lactobacillus, Streptococcus, and Bifidobacterium species. At the immune level, VSL3 administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of intermediate monocytes (CD14highCD16low), decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes as well as decreased human leukocyte antigen-antigen D related (HLA-DR) MFI on dendritic cells.
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Microbioma Gastrointestinal , Monócitos/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Probióticos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/microbiologiaRESUMO
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by exacerbations of neurological dysfunction due to inflammatory demyelination. Neurologic symptoms typically present in young adulthood and vary based on the site of inflammation, although weakness, sensory impairment, brainstem dysfunction, and vision loss are common. MS occurs more frequently in women and its development is complex-genetics, hormones, geography, vitamin D, and viral exposure all play roles. Early MS is characterized by relapsing-remitting course and inflammation of the white matter, although as patients age, the disease often transitions to a pathologically distinct secondary progressive phase with gradual disability accrual affecting gait, coordination, and bladder function. A minority of patients (10%) have disease that is progressive at onset. In the past decade, there has been a remarkable expansion in disease-modifying therapy for MS, but treatment of progressive disease remains a challenge. This article reviews foundational concepts in MS and emerging work that has reshaped understanding of the disease, providing new insight for therapeutic advance.