Radiology

Background: A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose: To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods: In this secondary analysis, two prospectively collected independent stroke data sets (2012–2015 and 2017–2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1–3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion–related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results: Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58–80 years]; 207 men) and 173 (median age, 74 years [IQR, 65–82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P =.02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P =.004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P =.20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P =.01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P =.03). Conclusion: Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. © RSNA, 2022.Translational Research and Advanced Imaging Laborator

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer’s disease

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer’s disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=

Effet nocebo dans la maladie de Parkinson (étude rétrospective sur 10 ans)

Le placebo est une substance totalement dénuée de principes actifs qui peut parfois exercer un effet positif chez les patients. A l'inverse, cette même substance peut occasionner des effets secondaires désagréables : c'est l'effet nocebo. Cette étude a été consacrée à l'évaluation de l'effet nocebo dans le cadre d'essais cliniques pharmacologiques comparatifs avec tirage au sort effectués en double aveugle. Nous avons analysé l'ensemble des études cliniques réalisées dans le Centre d'Investigation Clinique (CIC) de Toulouse entre 1994 et 2004 chez des patients parkinsoniens. Puis nous avons identifié les facteurs impliqués dans la survenue de ces évènements indésirables. Nous avons analysé 11 essais cliniques concernant un total de 92 patients dont 37 recevaient un placebo. Parmi les 37 patients, 19 ont présenté au moins un évènement indésirable. Au total 53 évènements indésirables ont été observés, dont 31 pouvaient être considérés comme des effets nocebo.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Efficacy of traumatic memory reactivation with or without propranolol in PTSD with high dissociative experiences

Background: Post-traumatic stress disorder (PTSD) with dissociative symptoms is now a full-fledged subtype of this disorder. The dissociative subtype is associated with a greater number of psychiatric comorbidities. To date, the impact of dissociation on the efficacy of PTSD treatment remains unclear. Objective: The aim of this study was to compare the efficacy of a traumatic memory reactivation procedure with the administration of propranolol or a placebo once a week for six consecutive weeks in reducing PTSD and MDE symptoms between PTSD subjects with or without high dissociative symptoms. Method: For that, we conducted a randomized clinical trial in 66 adults diagnosed with longstanding PTSD and measured the SCID PTSD module, the PTSD Checklist (PCL-S), Beck’s Depression Inventory-II (BDI-II), and the Dissociative Experiences Scale (DES). Results: Patients with and without high dissociative experience had significant improvement in their PCL-S scores over the 6 treatment sessions, and PCL-S scores continued to decline in all patients during the post-treatment period. However, there was no correlation between the presence/absence of high dissociative experiences and no specific effect of propranolol treatment. We found exactly the same results for MDE symptoms. Interestingly, patients with high dissociative experiences before treatment exhibited very significant improvement in their DES scores after the 6 treatment sessions, and patients maintained this improvement 3 months post-treatment. Conclusions: The traumatic memory reactivation procedure is an effective way to treat dissociative symptoms in patients with PTSD, and improvement of these dissociative symptoms was associated with a decrease in both PTSD and depression severity

Endurance exercise training up-regulates lipolytic proteins and reduces triglyceride content in skeletal muscle of obese subjects.

International audienceCONTEXT: Skeletal muscle lipase and intramyocellular triglyceride (IMTG) play a role in obesity-related metabolic disorders. OBJECTIVES: The aim of the present study was to investigate the impact of 8 weeks of endurance exercise training on IMTG content and lipolytic proteins in obese male subjects. DESIGN AND VOLUNTEERS: Ten obese subjects completed an 8-week supervised endurance exercise training intervention in which vastus lateralis muscle biopsy samples were collected before and after training. MAIN OUTCOME MEASURES: Clinical characteristics and ex vivo substrate oxidation rates were measured pre- and posttraining. Skeletal muscle lipid content and lipolytic protein expression were also investigated. RESULTS: Our data show that exercise training reduced IMTG content by 42% (P < .01) and increased skeletal muscle oxidative capacity, whereas no change in total diacylglycerol content and glucose oxidation was found. Exercise training up-regulated adipose triglyceride lipase, perilipin (PLIN) 3 protein, and PLIN5 protein contents in skeletal muscle despite no change in mRNA levels. Training also increased hormone sensitive-lipase Ser660 phosphorylation. No significant changes in comparative gene identification 58, G₀/G₁ switch gene 2, and PLIN2 protein and mRNA levels were observed in response to training. Interestingly, we noted a strong relationship between skeletal muscle comparative gene identification 58 and mitochondrial respiratory chain complex I protein contents at baseline (r = 0.87, P < .0001). CONCLUSIONS: Endurance exercise training coordinately up-regulates fat oxidative capacity and lipolytic protein expression in skeletal muscle of obese subjects. This physiological adaptation probably favors fat oxidation and may alleviate the lipotoxic lipid pressure in skeletal muscle. Enhancement of IMTG turnover may be required for the beneficial metabolic effects of exercise in obesity