135 research outputs found
Upper Motor Neuron Disorders Hereditary Spastic Paraplegia and Primary Lateral Sclerosis
No full textUpper motor neuron (UMN) syndromes are a group of rare, degenerative neurological disorders that are classified as either hereditary spastic paraplegia (HSP) or primary lateral sclerosis (PLS). Our understanding of their underlying pathophysiology is unfortunately very limited and has been a significant barrier to the development of disease-modifying treatments. Recent advances in genetics and in vitro and in vivo disease modeling have provided new insights into disease mechanisms and hold the promise to lead to the future development of mechanism-based therapies.</p
Adjusted cost analysis of video televisits for the care of people with amyotrophic lateral sclerosis
No full textWe previously reported our amyotrophic lateral sclerosis (ALS) video televisit experience. Here we report on video televisit versus in-clinic costs, adjusting for perceived medical usefulness (MU)
Pseudoreference Regions for Glial Imaging with <sup>11</sup>C-PBR28: Investigation in 2 Clinical Cohorts
Get PDFThe translocator protein (TSPO) is a commonly used imaging target to investigate neuroinflammation. While TSPO imaging demonstrates great promise, its signal exhibits substantial interindividual variability, which needs to be accounted for to uncover group effects that are truly reflective of neuroimmune activation. Recent evidence suggests that relative metrics computed using pseudo-reference approaches can minimize within-group variability, and increase sensitivity to detect physiologically meaningful group differences. Here, we evaluated various ratio approaches for TSPO imaging and compared them with standard kinetic modeling techniques, analyzing two different disease cohorts. Patients with chronic low back pain (cLBP) or amyotrophic lateral sclerosis (ALS) and matching healthy controls received (11)C-PBR28 PET scans. Occipital cortex, cerebellum and whole brain were first evaluated as candidate pseudo-reference regions by testing for the absence of group differences in Standardized Uptake Value (SUV) and distribution volume (VT) estimated with an arterial input function (AIF). SUV from target regions (cLBP study - thalamus; ALS study - precentral gyrus) was normalized with SUV from candidate pseudo-reference regions to obtain SUVRoccip, SUVRcereb, and SUVRWB The sensitivity to detect group differences in target regions was compared using various SUVR approaches, as well as distribution volume ratio (DVR) estimated with (blDVR) or without AIF (refDVR), and VT Additional voxelwise SUVR group analyses were performed. We observed no significant group differences in pseudo-reference VT or SUV, excepting whole-brain VT, which was higher in cLBP patients than controls. Target VT elevations in patients (P = 0.028 and 0.051 in cLBP and ALS, respectively) were similarly detected by SUVRoccip and SUVRWB, and by refDVR and blDVR (less reliably by SUVRcereb). In voxelwise analyses, SUVRoccip, but not SUVRcereb, identified regional group differences initially observed with SUVRWB, and in additional areas suspected to be affected in the pathology examined. All ratio metrics were highly cross-correlated, but generally were not associated with VT While important caveats need to be considered when using relative metrics, ratio analyses appear to be similarly sensitive to detect pathology-related group differences in (11)C-PBR28 signal as classic kinetic modeling techniques. Occipital cortex may be a suitable pseudo-reference region, at least for the populations evaluated, pending further validation in larger cohorts
Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials?
No full textIntraspinal stem cell (SC) transplantation represents a new therapeutic approach for amyotrophic lateral sclerosis (ALS) clinical trials. There are considerable difficulties in designing future efficacy trials, some related to the field of ALS and some that are specific to SCs or the mode of delivery. In October 2015, the most controversial points on SC transplantation were addressed during an international workshop intended to bring together international SC and ALS researchers in a public discussion on a topic for which expertise is limited. During the meeting, a discussion was started on the basic structure of the ideal clinical trial testing the efficacy and safety of SC transplantation. The current document includes a number of consensus points reflecting the design of phase II/III clinical trials
RETRACTED ARTICLE: Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis
No full textStatement of RetractionWe, the Editors and Publisher of the journal Immunological Investigations, have retracted the following article:Merhdad Farrokhi, Pedram Moeini, Mohammada Fazilati, Habibollah Nazem, Shahla Faraji, Zahra Saadatpour, Elyas Fadaei, Leila Saadatpour, Ali Rezaei, Sadra Ansaripour and Ali Amani-Beni (2016) Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis, Immunological Investigations, DOI: https://doi.org/10.1080/08820139.2016.1226897Since publication, significant concerns have been raised about the author affiliations, ethical approval, and the integrity of the data in the article.When approached for an explanation, the authors provided responses to our queries regarding the flow cytometry data, but they have not sufficiently addressed all of our concerns. In particular, the authors and institution did not respond to our requests for proof that the research was conducted at the Isfahan University of Medical Sciences or provide proof of ethical approval.As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed.We have been informed in our decision-making by our Editorial Policies and COPE guidelines.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'
Moving Toward Multicenter Therapeutic Trials in Amyotrophic Lateral Sclerosis: Feasibility of Data Pooling Using Different Translocator Protein PET Radioligands
No full textNeuroinflammation has been implicated in amyotrophic lateral sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, TSPO radioligands have some challenges to overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (11C-PBR28 and 18F-DPA714) is feasible, after validation of an established 11C-PBR28 PET pseudo reference analysis technique for 18F-DPA714. Methods: Seven ALS patients from Belgium (58.9 ± 6.7 y old, 5 men and 2 women), 8 healthy volunteers from Belgium (52.1 ± 15.2 y old, 3 men and 5 women), 7 ALS patients from the United States (53.4 ± 9.8 y old, 5 men and 2 women), and 7 healthy volunteers from the United States (54.6 ± 9.6 y old, 4 men and 3 women) from a previously published study underwent dynamic 18F-DPA714 (Leuven, Belgium) or 11C-PBR28 (Boston, Massachusetts) PET/MRI. For 18F-DPA714, maps of total volume of distribution (VT) were compared with SUV ratio (SUVR) images from 40 to 60 min after injection (SUVR40-60) calculated using the pseudo reference regions cerebellum, occipital cortex, and whole brain (WB) without ventricles. For 11C-PBR28, SUVR images from 60 to 90 min after injection using the WB without ventricles were calculated. Results: In line with previous studies, increased 18F-DPA714 uptake (17.0% ± 5.6%) in primary motor cortices was observed in ALS subjects, as measured by both VT and SUVR40-60 approaches. The highest sensitivity was found for SUVR calculated using the WB without ventricles (average cluster, 21.6% ± 0.1%). 18F-DPA714 VT ratio was highly correlated with the SUVR40-60 (r > 0.8, P < 0.001). A similar pattern of increased uptake (average cluster, 20.5% ± 0.5%) in the primary motor cortices was observed in ALS subjects for 11C-PBR28 SUVR calculated using the WB without ventricles. Analysis of the 18F-DPA714 and 11C-PBR28 data together resulted in a more extensive pattern of significantly increased glial activation bilaterally in the primary motor cortices. Conclusion: The same pseudo reference region analysis technique for 11C-PBR28 PET can be extended toward 18F-DPA714 PET. Therefore, in ALS, standardized analysis across these 2 tracers enables pooling of TSPO PET data across multiple centers and increases the power of TSPO as a biomarker for future therapeutic trials.sponsorship: Koen Van Laere and Philip Van Damme are senior clinical investigators of the Fund for Scientific Research, Flanders, Belgium (FWO). Donatienne Van Weehaeghe is a PhD fellow of the FWO (1179620N). Philip Van Damme is supported through the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga Belgie and KU Leuven funds "Een Hart voor ALS'' and "Laeversfonds voor ALS Onderzoek,'' and the "Valery Perrier race against ALS'' fund. Nazem Atassi is supported through NIH-K23-NS083715, the Muscular Dystrophy Association, the ALS Association, and ALS Finding a Cure. The postdoc position of Georg Schramm is funded by NIH grant 1P41EB017183-01A1. No other potential conflict of interest relevant to this article was reported. (E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, ALS Liga Belgie, KU Leuven fund "Een Hart voor ALS'', KU Leuven fund "Laeversfonds voor ALS Onderzoek'', "Valery Perrier race against ALS'' fund, Muscular Dystrophy Association, ALS Association, ALS Finding a Cure, NIH|1P41EB017183-01A1, NIH-K23-NS083715)status: Publishe
Advanced statistical methods to study the effects of gastric tube and non-invasive ventilation on functional decline and survival in amyotrophic lateral sclerosis
No full textCausal inference methods to study gastric tube use in amyotrophic lateral sclerosis
No full textObjective:To estimate effects of gastric tube (G-tube) on survival and quality of life (QOL) in people with amyotrophic lateral sclerosis (ALS) correcting for confounding by indication inherent in nonrandomized observational data.Methods:To complement a recent causal inference analysis, which concluded that G-tube placement increases the hazard of death, permanent assisted ventilation, or tracheostomy by 28%, we fit causal inference models on a different sample of 481 patients with ALS enrolled in a recent clinical trial of ceftriaxone. Forward selection identified predictors of G-tube placement. Effects of G-tube on survival and QOL were estimated using structural nested models and marginal structural models, accounting for predictors of G-tube treatment.Results:Forced vital capacity and the total score and bulbar subscale of the revised ALS Functional Rating Scale best predicted G-tube placement. Correcting for these confounders, G-tube placement decreased survival time by 46% (p < 0.001) and had no effect on QOL (p = 0.078). Sensitivity survival analyses varied in significance, but none revealed a survival benefit.Conclusions:In the absence of randomization, causal inference methods are necessary to correct for time-varying confounding. G-tube placement may have a negative effect on survival with no QOL-related benefit for people with ALS. A randomized controlled trial is warranted to further evaluate the efficacy of this widely used intervention.Clinicaltrials.gov identifier:NCT00349622.Classification of evidence:This study provides Class III evidence that for patients with ALS, G-tube placement decreases survival time and does not affect QOL.</jats:sec
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