Percutaneous Endoscopic Gastrostomy Tube Insertion in Neurodegenerative Disease:a Retrospective Study and Literature Review

Background/Aims With the notable exceptions of dementia, stroke, and motor neuron disease, relatively little is known about the safety and utility of percutaneous endoscopic gastrostomy (PEG) tube insertion in patients with neurodegenerative disease. We aimed to determine the safety and utility of PEG feeding in the context of neurodegenerative disease and to complete a literature review in order to identify whether particular factors need to be considered to improve safety and outcome. Methods A retrospective case note review of patients referred for PEG insertion by neurologists in a single neuroscience center was conducted according to a pre-determined set of standards. For the literature review, we identified references from searches of PubMed, mainly with the search items “percutaneous endoscopic gastrostomy” and “neurology” or “neurodegenerative disease.” Results Short-term mortality and morbidity associated with PEG in patients with neurological disease were significant. Age greater than 75 years was associated with poor outcome, and a trend toward adverse outcome was observed in patients with low serum albumin. Conclusions This study highlights the relatively high risk of PEG in patients with neurodegenerative disease. We present points for consideration to improve outcome in this particularly vulnerable group of patients

Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort

Background: Alemtuzumab has recently been approved for treatment of relapsing MS, but concerns remain about its use since long-term studies of adverse events remain limited. Furthermore, a clear understanding of its application and durability of effect in clinical practice has yet to evolve. Objectives: To investigate long-term efficacy and safety outcomes in a multicentre cohort of patients treated with alemtuzumab. Methods: Patients treated from 2000 and followed-up at three regional centres were identified. Baseline and prospective data were obtained and validated by clinical record review. Results: One hundred patients were identified with a mean follow-up of 6.1 years (range 1–13). Forty patients were retreated with at least one further treatment cycle. Annualized relapse rates fell from 2.1 to 0.2 (p<0.0001) post-treatment and were sustained for up to eight years of follow-up. Mean change in EDSS score was +0.14. Forty-seven patients developed secondary autoimmunity. Conclusion: Observed reduction in relapse rates reflected those reported in clinical trials, but we were unable to corroborate previous observations of disability reversal. 40% of patients required additional treatment cycles. Autoimmune adverse events were common, occurring at a higher rate than previously reported, but were largely predictable, and could be managed effectively within a rigorous monitoring regime

Reduced expression of mitochondrial fumarate hydratase in progressive multiple sclerosis contributes to impaired in vitro mesenchymal stromal cell-mediated neuroprotection

BACKGROUND: Cell-based therapies for multiple sclerosis (MS), including those employing autologous bone marrow-derived mesenchymal stromal cells (MSC) are being examined in clinical trials. However, recent studies have identified abnormalities in the MS bone marrow microenvironment. OBJECTIVE: We aimed to compare the secretome of MSC isolated from control subjects (C-MSC) and people with MS (MS-MSC) and explore the functional relevance of findings. METHODS: We employed high throughput proteomic analysis, enzyme-linked immunosorbent assays and immunoblotting, as well as in vitro assays of enzyme activity and neuroprotection. RESULTS: We demonstrated that, in progressive MS, the MSC secretome has lower levels of mitochondrial fumarate hydratase (mFH). Exogenous mFH restores the in vitro neuroprotective potential of MS-MSC. Furthermore, MS-MSC expresses reduced levels of fumarate hydratase (FH) with downstream reduction in expression of master regulators of oxidative stress. CONCLUSIONS: Our findings are further evidence of dysregulation of the bone marrow microenvironment in progressive MS with respect to anti-oxidative capacity and immunoregulatory potential. Given the clinical utility of the fumaric acid ester dimethyl fumarate in relapsing–remitting MS, our findings have potential implication for understanding MS pathophysiology and personalised therapeutic intervention