For November 2015, we have selected: Kalra L, Irshad J, Simpson J, et al., on behalf of the STROKE-INF Investigators. Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled trial. Lancet Neurology 2015; September 4.
Dysphagia is common after a stroke, and associated with an increased risk of pneumonia and mortality. However, the use of antibiotics to prevent post-stroke pneumonia has been controversial. Although some studies had previously showed reduced infections by using preventive antibiotic treatment, they failed in documenting a reduced risk of death and dependency, the main objective of acute stroke care.
To provide more evidence about the role of prophylactic antibiotics on reducing aspiration pneumonia and mortality, 48 stroke unit centers in the UK were involved in a prospective, cluster-randomised, open-label controlled study with masked endpoint patient assessment (STROKE-INF). Patients at high risk of aspiration after a stroke occurred within 48 hours at the study inclusion were given either standard stroke unit care (24 centers) or preventive antibiotics for one week together with standard stroke unit care (24 centers). The occurrence of pneumonia within 14 days, and mortality and dependence at 90 days were the main outcomes. Both a statistician masked to allocation using a criteria-based hierarchical algorithm, and the local treating physician made the diagnosis of post-stroke pneumonia. An intention-to-treat analysis was made in 615 patients of the group assigned to preventive antibiotics and 602 patients of the control group. At the 14-day end point there was no difference in the number of algorithm-diagnosed pneumonia between the two groups of patients (11% as overall frequency, 13% in the interventional group, and 10% in the control group). Moreover, the physician-diagnosed post-stroke pneumonia incidence did not differ in the two groups. At 90 days, mortality rates were similar in both groups. Good functional outcomes (using the modified Rankin Scale) were similar in both groups, but there was a shift toward worse outcomes in the interventional group. Urinary infections were more frequent in the control group. Diarrhea from Clostridium difficile and methicillin-resistant Staphylococcus aureus colonisation occurred rarely and equally in both groups.
“This study further supports previous evidence and several national guidelines recommendations that antibiotic treatment does not prevent post-stroke pneumonia in patients with dysphagia,” says Prof. D. Leys, Department of Neurology, University of Lille, France. “However, the pneumonia rate at 14 days was low here compared to previous studies. This difference might be explained by the use of two different diagnostic methods to increase the accuracy of post-stroke pneumonia diagnosis (algorithm-based and physician-based). Nevertheless, this discrepancy stresses the need of more accurate diagnostic parameters for pneumonia to avoid both false positive and negative disease.”
“From another perspective, these results can show that standard unit stroke care, which encompasses preventive measures to minimise aspiration pneumonia, is efficient as prophylactic antibiotic treatment in preventing post-stroke pneumonia”, says Prof. V. Di Piero, Department of Neurology, La Sapienza University, Rome, Italy. “However, post-stroke pneumonia might also represent a biomarker of stroke severity, and thus be insensitive to any preventive antibiotic therapy. It would have been interesting to know whether the evolution of dysphagia was different in the two groups of patients in the short and long-term follow-up.”
The other nominees for the November’s paper of the month are:
- Prusiner SB, Woerman AL, Mordes DA, et al. Evidence for alpha-synuclein prions causing multiple system atrophy in humans with parkinsonism. PNAS 2015; doi/10.1073/pnas.1514475112.
This paper supports the hypothesis that multiple system atrophy (MSA) is caused by an alpha-synuclein prion. Brain extracts from 14 MSA cases were able to transmit neurodegenerative changes in TgM83+/- mice expressing alpha-synuclein, particularly inducing deposition of alpha-synuclein in neuronal cell bodies and axons. This alpha-synuclein strain would be different from the one causing PD.
- De Bruijn RFAG, Heeringa J, Wolters FJ, et al. Association between atrial fibrillation and dementia in the general population. JAMA Sept 21, 2015;doi:10.1001/ jamaneurol.2015.2161.
The impact of atrial fibrillation (AF) on the risk of developing dementia was longitudinally assessed over 20 years in 6514 participants in the prospective population-based Rotterdam Study. There was an increased risk of developing dementia, independently from stroke, in AF subjects, especially if young and with long AF duration.
- Nagel MA, White T, Khmeleva, et al. Analysis of Varicella-Zoster virus in temporal arteries biopsy positive and negative for giant cell arteritis. JAMA Neurol Sept 8, 2015; doi:10.1001/jamaneurol.2015.2101.
This study investigates the possibility of a casual link between varicella zoster virus (VZV) and giant cell arteritis (GCA) in temporal artery biopsy specimens previously considered negative or positive for temporal arteritis (TA). VZV antigen was found in 64% of the GCA-negative TA biopsies, in 73% of the GCA-positive TA biopsies, and in 22% of the control biopsies. The similar prevalence of VZV in both GCA-positive and -negative TA biopsies supports the evidence that VZV triggers the immunopathology of GCA, and the need of investigational antiviral treatment in biopsy-negative GCA patients.