Abstract Objective Wernicke's encephalopathy (WE) is an acute disorder due to thiamine deficiency, characterized by ophthalmoplegia, ataxia, and mental confusion, similar to that classically observed ...in alcoholism. Some cases of WE were reported to coincide with other conditions such as hyperemesis gravidarum, bariatric surgery, and total parenteral nutrition. In this study the objective was to retrospectively evaluate the prevalence of WE among intravenously fed patients in our hospital during the previous 2 y. Methods Among all cases of WE diagnosed by cranial magnetic resonance scan during a 2-y period in the Azienda Ospedaliera of Padua, we identified patients who exhibited WE during parenteral feeding. Albumin plasma levels, measured at the onset of WE symptoms, were used to estimate nutritional status. Results We found seven cases of WE that coincided with intravenous feeding. WE occurred, on average, 13 d after the start of glucose infusion. The five subjects with albumin plasma levels lower than 35 g/L at the onset of WE received glucose infusion for fewer days. In six cases the clinical signs disappeared the day after thiamine infusion. In one case mental function did not normalize and the patient developed Korsakoff's syndrome despite prolonged thiamine treatment. Conclusion During a 2-y period we observed a high prevalence of WE in intravenously fed patients due to lack of thiamine supplementation. A prophylactic treatment must be performed in at-risk patients and multivitamin infusion containing thiamine must be administered daily during the course of intravenous feeding.
Baseline MRI activity is a major determinant of treatment choice, which should be adjusted for. ...MRI activity might drive treatment switch, introducing potential biases when censoring data as ...patients changed therapy. ...because of the peculiar treatment schedule of alemtuzumab, treatment persistence is not comparable with that of the other drugs assessed in this study.
To perform their distinct effector functions, pathogen‐specific T cells have to migrate to target tissue where they recognize antigens and produce cytokines that elicit appropriate types of ...protective responses. Similarly, migration of pathogenic self‐reactive T cells to target organs is an essential step required for tissue‐specific autoimmunity. In this article, we review data from our laboratory as well as other laboratories that have established that effector function and migratory capacity are coordinately regulated in different T‐cell subsets. We then describe how pathogenic T cells can enter into intact or inflamed central nervous system (CNS) to cause experimental autoimmune encephalomyelitis or multiple sclerosis. In particular, we elaborate on the role of CCR6/CCL20 axis in migration through the choroid plexus and the involvement of this pathway in immune surveillance of and autoimmunity in the CNS.
The aryl hydrocarbon receptor (AhR) participates in the differentiation of mouse regulatory T cells (T(reg) cells) and interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells), but its role in ...human T cell differentiation is unknown. We investigated the role of AhR in the differentiation of human induced T(reg) cells (iT(reg) cells). We found that AhR activation promoted the differentiation of CD4(+)Foxp3(-) T cells, which produce IL-10 and control responder T cells through granzyme B. However, activation of AhR in the presence of transforming growth factor-beta1 induced Foxp3(+) iT(reg) cells, which suppress responder T cells through the ectonucleoside triphosphate diphosphohydrolase CD39. The induction of functional Foxp3(+) iT(reg) cells required coordinated action of the transcriptional regulators Smad1 and Aiolos. Thus, AhR is a potential target through which functional iT(reg) cells could be induced in human autoimmune disorders.
To summarize the evidence on immunoablative therapy followed by autologous hematopoietic stem cell transplantation (aHSCT) to manage severe and treatment-refractory multiple sclerosis (MS).
We ...collected all the published studies of aHSCT in any form of MS from 1995 to 2016, carefully excluding reports that were updated in subsequent studies. Endpoints were transplant-related mortality (TRM), rate of disease progression, and no evidence of disease activity (NEDA) status. A weighted metaregression based on a Poisson model was run, assessing whether there were study-specific characteristics with an effect on TRM and progression.
Fifteen studies including 764 transplanted patients were pooled in the meta-analysis. The pooled estimate of TRM was 2.1% (95% confidence interval CI 1.3%-3.4%). TRM was higher in older studies (
= 0.014) and in studies with a lower proportion of patients with relapsing-remitting MS (RRMS) (
= 0.028). A higher baseline Expanded Disability Status Scale (
= 0.013) was also significantly associated with a higher TRM. Pooled rate of progression was 17.1% at 2 years (95% CI 9.7%-24.5%) and 23.3% (95% CI 16.3%-31.8%) at 5 years. Lower 2-year progression rate was significantly associated with higher proportions of patients with RRMS (
= 0.004). The pooled proportion of NEDA patients at 2 years was 83% (range 70%-92%) and at 5 years was 67% (range 59%-70%).
The emerging evidence on this therapeutic approach in MS indicates that the largest benefit/risk profile form this therapeutic approach can be obtained in patients with aggressive MS with a relapsing-remitting course and who have not yet accumulated a high level of disability.
The unmet need for therapies capable of repairing the central nervous system (CNS) damage occurring in many diseases including multiple sclerosis (MS) has sparked the interest of the neurological ...community for stem cell-based therapies. An exhaustive amount of preclinical data has shown that the intravenous administration of mesenchymal stem cells (MSC), a subset of progenitor cells isolated from many mesodermal tissues, effectively ameliorates experimental autoimmune encephalomyelitis (EAE), a model of MS, through the release of anti-inflammatory and neuroprotective molecules. Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair as realized clinically, with functional recovery, or visualized by magnetic resonance imaging (MRI).
Highlights • Treatment with MSCs impacts on immune responses associated to neurological diseases. • MSCs modulate peripheral and central immune responses in EAE. • MSCs switch microglial cells from ...detrimental to beneficial in AD and ALS models. • MSCs dampen detrimental inflammation and strengthen beneficial inflammation in SCI. • MSCs induce angiogenesis and restore BBB integrity in stroke models.
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