Serial treatments of primed low-frequency rTMS in stroke: characteristics of responders vs. nonresponders.
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ABSTRACT:
SUBMITTER: Carey JR
PROVIDER: S-EPMC5560130 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:Preceding low-frequency repetitive transcranial magnetic stimulation (rTMS) with a bout of high-frequency rTMS called priming potentiates the after-effects of the former in healthy adults. The utility of primed rTMS in stroke remains under-explored despite its theoretical benefits in enhancing cortical excitability and motor function.To ascertain the efficacy of priming in chronic stroke by comparing changes in cortical excitability and paretic hand function following three types of primed low-frequency rTMS treatments.Eleven individuals with chronic stroke participated in this repeated-measures study receiving three treatments to the contralesional primary motor cortex in randomized order: 6 Hz primed 1 Hz rTMS, 1 Hz primed 1 Hz rTMS, and sham 6 Hz primed active 1 Hz rTMS. Within- and between-treatment differences from baseline in cortical excitability and paretic hand function from baseline were analyzed using mixed effects linear models.6 Hz primed 1 Hz rTMS produced significant within-treatment differences from baseline in ipsilesional cortical silent period (CSP) duration and short-interval intracortical inhibition. Compared to 1 Hz priming and sham 6 Hz priming of 1 Hz rTMS, active 6 Hz priming generated significantly greater decreases in ipsilesional CSP duration. These heightened effects were not observed for intracortical facilitation or interhemispheric inhibition excitability measures.Our findings demonstrate the efficacy of 6 Hz primed 1 Hz rTMS in probing homeostatic plasticity mechanisms in the stroke brain as best demonstrated by differences CSP duration and SICI from baseline. Though 6 Hz priming did not universally enhance cortical excitability across measures, our findings pose important implications in non-invasive brain stimulation application in stroke rehabilitation.
| S-EPMC4656059 | biostudies-literature
Project description:Alzheimer's disease (AD) patients have varying responses to AD drugs and there may be no single treatment for all AD patients. Trial after trial shows that identifying non-responsive and responsive subgroups and their corresponding moderators will provide better insights into subject selection and interpretation in future clinical trials. We aim to extensively investigate pre-treatment features that moderate treatment effect of Galantamine, Bapineuzumab, and Semagacestat from completed trial data. We obtained individual-level patient data from ten randomized clinical trials. Six Galantamine trials and two Bapineuzumab trials were from Yale University Open Data Access Project and two Semagacestat trials were from the Center for Global Clinical Research Data. We included a total of 10,948 subjects. The trials were conducted worldwide from 2001 to 2012. We estimated treatment effect using causal forest modeling on each trial. Finally, we identified important pre-treatment features that determine treatment efficacy and identified responsive or nonresponsive subgroups. As a result, patient's pre-treatment conditions that determined the treatment efficacy of Galantamine differed by dementia stages, but we consistently observed that non-responders in Galantamine trials had lower BMI (25 vs 28, P < .001) and increased ages (74 vs 68, P < .001). Responders in Bapineuzumab and Semagacestat trials had lower Aβ42 levels (6.41 vs 6.53 pg/ml, P < .001) and smaller whole brain volumes (983.13 vs 1052.78 ml, P < .001). 6 'positive' treatment trials had subsets of patients who had, in fact, not responded. 4 "negative" treatment trials had subsets of patients who had, in fact, responded. This study suggests that analyzing heterogeneity in treatment effects in "positive" or "negative" trials may be a very powerful tool for identifying distinct subgroups that are responsive to treatments, which may significantly benefit future clinical trial design and interpretation.
| S-EPMC10635230 | biostudies-literature
Project description:Background and Purpose- We aim to determine the potential impact on stroke thrombolysis of drip-and-ship helicopter flights and specifically of their low-frequency vibrations (LFVs). Methods- Mice with a middle cerebral artery autologous thromboembolic occlusion were randomized to receive rtPA (recombinant tissue-type plasminogen activator; or saline) 90 minutes later in 3 different settings: (1) a motion platform simulator that reproduced the LFV signature of the helicopter, (2) a standardized actual helicopter flight, and (3) a ground control. Results- Mice assigned to the LFV simulation while receiving tPA had smaller infarctions (31.6 versus 54.9 mm3; P=0.007) and increased favorable neurological outcomes (86% versus 28%; P=0.0001) when compared with ground controls. Surprisingly, mice receiving tPA in the helicopter did not exhibit smaller infarctions (47.8 versus 54.9 mm3; P=0.58) nor improved neurological outcomes (37% versus 28%; P=0.71). This could be due to a causative effect of the 20- to 30-Hz band, which was inadvertently attenuated during actual flights. Mice using saline showed no differences between the LFV simulator and controls with respect to infarct size (80.9 versus 95.3; P=0.81) or neurological outcomes (25% versus 11%; P=0.24), ruling out an effect of LFV alone. There were no differences in blood-brain barrier permeability between LFV simulator or helicopter, compared with controls (2.45-3.02 versus 4.82 mm3; P=0.14). Conclusions- Vibration in the low-frequency range (0.5-120 Hz) is synergistic with rtPA, significantly improving the effectiveness of thrombolysis without impairing blood-brain barrier permeability. Our findings reveal LFV as a novel, safe, and simple-to-deliver intervention that could improve the outcomes of patients. Visual Overview- An online visual overview is available for this article.
| S-EPMC7263385 | biostudies-literature
Project description:Aerobic exercise capacity is a strong predictor of disease and survivability but the utility of exercise intervention is largely dependent on how one’s genome interacts with an exercise-training environment. A newly developed rat model selectively bred for inherited differences in response to aerobic exercise training shows to be a useful resource to sort out the networks of genes responsible for signalling exercise-induced changes that benefit cardiac function.
2012-01-01 | GSE20997 | GEO
Project description:BackgroundAlthough low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise in the treatment of poststroke aphasia, the efficacy of high-frequency rTMS (HF-rTMS) has yet to be determined.PurposeWe investigated the efficacy of intermittent theta burst stimulation (iTBS) in ameliorating chronic non-fluent aphasia and compared it with that of LF-rTMS.MethodsWe randomly assigned patients with poststroke non-fluent aphasia to an ipsilesional iTBS (n = 29), contralesional 1-Hz rTMS (n = 27), or sham (n = 29) group. Each group received the rTMS protocol executed in 10 daily sessions over 2 weeks. We evaluated language function before and after the intervention by using the Concise Chinese Aphasia Test (CCAT).ResultsCompared with the sham group, the iTBS group exhibited significant improvements in conversation, description, and expression scores (P = 0.0004-0.031), which characterize verbal production, as well as in auditory comprehension, reading comprehension, and matching scores (P < 0.01), which characterize language perception. The 1-Hz group exhibited superior improvements in expression, reading comprehension, and imitation writing scores compared with the sham group (P < 0.05). The iTBS group had significantly superior results in CCAT total score, matching and auditory comprehension (P < 0.05) relative to the 1-Hz group.ConclusionOur study findings contribute to a growing body of evidence that ipsilesional iTBS enhances the language recovery of patients with non-fluent aphasia after a chronic stroke. Auditory comprehension was more preferentially enhanced by iTBS compared with the 1-Hz protocol. Our findings highlight the importance of ipsilesional modulation through excitatory rTMS for the recovery of non-fluent aphasia in patients with chronic stroke.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT03059225].
| S-EPMC8795082 | biostudies-literature
Project description:Aerobic exercise capacity is a strong predictor of disease and survivability but the utility of exercise intervention is largely dependent on how one’s genome interacts with an exercise-training environment. A newly developed rat model selectively bred for inherited differences in response to aerobic exercise training shows to be a useful resource to sort out the networks of genes responsible for signalling exercise-induced changes that benefit cardiac function. Animals The study consisted of four groups: 1) HRT trained rats (HRT-T), 2) LRT trained rats (LRT-T) 3) HRT untrained sedentary rats (HRT-S) and 4) LRT untrained sedentary rats (LRT-S) (n=5 in each group). Experimental protocols were approved by the Institutional Animal Research Ethics Council, Norway. Sample collection Left ventricle tissue was snap-frozen in liquid nitrogen and stored at -80oC to time of analysis. RNA isolation RNA was isolated from the left ventricle (20 mg) with the mirVana RNA isolation kit (Ambion) according to the manufacturer's instructions. RNA integrity, purity and quantity were assessed by Bioanalyzer (Agilent Technologies, Santa Clara, US) and Nanodrop (NanoDrop Technologies, Baltimore, US). The concentration of total RNA was measured by Nanodrop with ultraviolet spectrophotometry at 260/280 nm. RNA quality was assessed by electrophoresis on Bioanalyzer chips (Agilent Technologies, Santa Clara, US). Only samples with a 260/280-ratio of more than 1.8, and RNA integrity number (RIN) value above 8 was analyzed. Microarray analysis Samples were hybridized to Applied Biosystems Rat Genome Survey chips v.1.0. All samples were labelled at the same time, and hybridised over two days. The biological groups were balanced between the two hybridisation batches and the samples randomly distributed within this format. Samples were analyzed by the Applied Biosystems 1700 Array Expression System. The following threes comparisons were done: A: HRT-S vs. LRT-S B: HRT-S vs. HRT-T C: LRT-S vs. LRT-T Differentially expressed gene analysis The data files from the AB 1700 Chemiluminescent Microarray Analyzer Software were processed using J-Express Pro v.2.8. The signal intensity values were extracted per spot, and all flagged and control spots were filtered out. Before compiled into an expression profile data matrix, all arrays were quantile normalized to be comparable. Genes with at most 20% missing values were allowed in the final dataset. The signal intensities in the dataset were further log transformed, and missing values were replaced using the method LSimpute Adaptive. The search for differentially expressed genes was performed both on a single gene and gene set level. Rank Product was used to look for differentially expressed genes on a gene by gene basis, while Gene Set Enrichment Analysis (GSEA) was used to look for sets of genes sharing common characteristics that were differentially expressed between the classes examined. Gene sets were created using the Panther Biological Processes (241 gene sets) and Panther Molcular Functions (252 gene sets). This information was extracted from the Applied Biosystems Human Annotation File, dated September 30th 2006, with updated information from a Panther search carried out on February 1st 2008. Gene sets smaller than 15 and larger than 500 were excluded from the GSEA. GSEA First the genes were ranked according to Golub score, which t is the default method for GSEA. Next an enrichment score (ES) was calculated for each gene set. For instance, when calculating the ES for the gene set “T-cell mediated immunity”, GSEA starts by looking at the gene ranked on top of the genelist. If this gene is a member of T-cell mediated immunity, a positive score is added to the ES, otherwise a negative score is added. Then the next gene on the gene list is evaluated and the ES is updated. This process is repeated for every gene in the entire gene list. The green line in Figure 1 shows how the value of ES changes when evaluating the genes in the ranked list. The maximum value obtained during this “walk” is used as ES for the gene set. Also worth noting is that the positive score that is added to the enrichment score is weigthed, so that a higher score is added when a gene higher on the ranked list is found to be a member of the gene set than when a gene lower on the ranked list is marked with a hit. Therefore, a high ES means that the gene set is overrepresented towards the top of the ranked list. Gene sets with less than 10 members or more than 500 members were removed from the analysis.
2012-01-01 | E-GEOD-20997 | biostudies-arrayexpress
Project description:Depression is a common outcome following stroke, associated with reduced quality of life and poorer recovery. Despite attempts to associate depression symptoms with specific lesion sites, the neural basis of post-stroke depression remains poorly understood. Resting state fMRI has provided new insights into the neural underpinnings of post-stroke depression, but has been limited to connectivity analyses exploring interregional correlations in the time-course of activity. Other aspects of resting state BOLD signal remain unexamined. Measuring the amplitude of low frequency fluctuations allows the detection of spontaneous neural activity across the whole brain. It provides complementary information about frequency-specific local neural activity. We calculated the fractional amplitude of low frequency fluctuations (fALFF) in a group of 64 participants scanned 3 months post-stroke. Twenty showed depression symptoms when assessed with the Patient Health Questionnaire (PHQ-9). We performed analyses in both the typical 0.01-0.08 Hz range, as well as separately in the slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz) ranges. We found significantly higher fALFF in the depressed compared to non-depressed participants in the left dorsolateral prefrontal cortex (DLPFC) and the right precentral gyrus, and a significant association between higher depression scores and higher fALFF in the left insula. The group differences were detected in the slow-5 fluctuations, while the association with depression severity was observed in the slow-4 range. We conclude that post-stroke depression can be characterised by aberrant spontaneous local neural activity, which in small samples could be a more sensitive measure than lesion volume and location.
| S-EPMC5537409 | biostudies-other
Project description:Polymorphonuclear neutrophils (PMNs) are the most abundant circulating leukocytes, and the first cells recruited to sites of tissue inflammation. Using a fixation method to preserve native CD marker expression prior to immunophenotyping, we identified a distinct population of "primed for recruitment" PMNs in healthy mouse and human blood that has high expression of adhesion and activation markers compared with the bulk resting-state PMNs. In response to acute tissue inflammation, primed PMNs (pPMNs) were rapidly depleted from the circulation and recruited to the tissue. One hour after acute peritoneal insult, pPMNs became the dominant PMN population in bone marrow (BM) and blood, returning to baseline levels with resolution of inflammation. PMN priming was induced by the granulopoietic factors granulocyte-macrophage-colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF). High levels of pPMNs were observed in neutropenic mice and in pediatric neutropenic patients who were resistant to infection, highlighting an important role of this population in innate immune function.
| S-EPMC6538871 | biostudies-literature
Project description:The immune pathways that define treatment response and non-response in lupus nephritis (LN) are unknown. To characterize these intra-renal pathways, transcriptomic analysis of protocol kidney biopsies was done. Kidney biopsies were done at flare (Bx1) and after treatment (Bx2) in 58 LN patients and healthy controls (HC). Glomeruli and tubulointerstitium (TI) were isolated using laser microdissection. RNA was extracted and analyzed by nanostring. Transcript expression from clinical complete (CR), partial (PR) and non-responders (NR) were compared at Bx1 and Bx2 and to HC. Top transcripts that differentiate CR from NR were identified. Confocal microscopy and urine ELISA was done to evaluate the protein expression of top transcripts. At Bx1 cluster analysis determined that glomerular integrin, neutrophil, and chemokine/cytokine, and TI chemokine, T cell and leukocyte adhesion genes differentiated NR from CR. At Bx2, glomerular monocyte, extracellular matrix, and interferon, and TI interferon, complement, and T cell transcripts differentiated NR from CR. Protein analysis recapitulated top transcript findings. Urine C5a and FN1 differentiated NR from CR after treatment. Transcript analysis of serial kidney biopsies taken during the treatment of LN demonstrated how gene expression in the kidney changes with clinically successful and unsuccessful therapy. These insights into the molecular landscape of response and non-response may help better align LN management with the pathogenesis of kidney injury.
2022-07-15 | GSE200306 | GEO
Project description:Objectives: Fulminant myocarditis (FM) is a rapidly progressive and frequently fatal form of myocarditis that has been difficult to classify. This study aims to compare the clinical characteristics, treatments and outcomes in patients with fulminant giant cell myocarditis (FGCM) and fulminant lymphocytic myocarditis (FLM). Methods and Results: In our retrospective study, nine patients with FGCM (mean age 47.9 ± 7.5 years, six female) and 7 FLM (mean age 42.1 ± 12.3 years, four female) patients confirmed by histology in the last 11 years were included. Most patients with FGCM and FLM were NYHA functional class IV (56 vs. 100%, p = 0.132). Patients with FGCM had significantly lower levels of high-sensitivity C-reactive protein [hs-CRP, 4.4 (2.0-10.2) mg/L vs. 13.6 (12.6-14.6) mg/L, P = 0.004, data shown as the median with IQR], creatine kinase-myoglobin [CK-MB, 1.4 (1.0-3.2) ng/ml vs. 14.6 (3.0-64.9) ng/ml, P = 0.025, median with IQR], and alanine aminotransferase [ALT, 38.0 (25.0-61.5) IU/L vs. 997.0 (50.0-3,080.0) IU/L, P = 0.030, median with IQR] and greater right ventricular end-diastolic diameter (RVEDD) [2.9 ± 0.3 cm vs. 2.4 ± 0.6 cm, P = 0.034, mean ± SD] than those with FLM. No differences were observed in the use of intra-aortic balloon pump (44 vs. 43%, p = 1.000) and extracorporeal membrane oxygenation (11 vs. 43%, p = 0.262) between the two groups. The long-term survival rate was significantly lower in FGCM group compared with FLM group (0 vs. 71.4%, p = 0.022). A multivariate cox regression analysis showed the level of hs-CRP (hazard ratio = 0.871, 95% confidence interval: 0.761-0.996, P = 0.043) was an independent prognostic factor for FM patients. Furthermore, the level of hs-CRP had a good ability to discriminate between patients with FGCM and FLM (AUC = 0.94, 95% confidence interval: 0.4213-0.9964). Conclusions: The inflammatory response and myocardial damage in the patients with FGCM were milder than those with FLM. Patients with FGCM had distinctly poorer prognoses compared with those with FLM. Our results suggest that hs-CRP could be a promising prognostic biomarker and a hs-CRP level of 11.71 mg/L is an appropriate cutoff point for the differentiating diagnosis between patients with FGCM and FLM.
| S-EPMC8678080 | biostudies-literature