Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes, predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form ...the human microbiota, with most colonizing the gut. Recent technological advances, open access data libraries, and application of high‐throughput sequencing have allowed these microbes to be identified and their contribution to neurological health to be examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression. This review provides an overview of the recent advances in microbiome research in relation to neuro(auto)immune and neurodegenerative conditions affecting humans, such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Study design and terminology used in this rapidly evolving, highly multidisciplinary field are summarized to empower and engage the neurology community in this “newly discovered organ.” Ann Neurol 2017;81:369–382
The latest revision of the McDonald criteria for the diagnosis of multiple sclerosis (MS) was published online in 2017. New features of the criteria, which were designed to facilitate earlier ...diagnosis of MS, include the recognition of oligoclonal bands in the cerebrospinal fluid as a possible marker of dissemination of MS pathology in time, the introduction of symptomatic lesions as a parameter to demonstrate spatial or temporal pathology dissemination, and the use of cortical lesions to demonstrate dissemination in space. In this Viewpoint, a panel of world-renowned MS specialists share their personal experiences of the new criteria to date.
New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system ...lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use. Ann Neurol 2011
Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS.
To evaluate the efficacy and safety of ...rituximab for MS treatment.
Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies.
Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events. AUTHOR’S CONCLUSION: Despite the frequent mild/moderate adverse events related to the drug, rituximab appears overall safe for up to 2 years of therapy and has a substantial impact on the inflammatory disease activity (clinical and/or radiological) of RRMS. The effect of rituximab on disease progression in PPMS appears to be marginal.
Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and ...evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota.
Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray.
While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation.
While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.
Recent findings have provided a molecular basis for the combined contributions of multifaceted risk factors for the onset of multiple sclerosis (MS). MS appears to start as a chronic dysregulation of ...immune homeostasis resulting from complex interactions between genetic predispositions, infectious exposures, and factors that lead to pro‐inflammatory states, including smoking, obesity, and low sun exposure. This is supported by the discovery of gene–environment (GxE) interactions and epigenetic alterations triggered by environmental exposures in individuals with particular genetic make‐ups. It is notable that several of these pro‐inflammatory factors have not emerged as strong prognostic indicators. Biological processes at play during the relapsing phase of the disease may result from initial inflammatory‐mediated injury, while risk factors for the later phase of MS, which is weighted toward neurodegeneration, are not yet well defined. This integrated review of current evidence guides recommendations for clinical practice and highlights research gaps.
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