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Publication Does prior administration of rtPA influence acute ischemic stroke clot composition? Findings from the analysis of clots retrieved with mechanical thrombectomy from the RESTORE registry(Springer, 2021-08-20) Rossi, Rosanna; Molina, Sara; Mereuta, Oana Madalina; Douglas, Andrew; Fitzgerald, Seán; Tierney, Ciara; Pandit, Abhay; Brennan, Paul; Power, Sarah; O’Hare, Alan; Gilvarry, Michael; McCarthy, Ray; Magoufis, Georgios; Tsivgoulis, Georgios; Nagy, András; Vadász, Ágnes; Jood, Katarina; Redfors, Petra; Nordanstig, Annika; Ceder, Erik; Dunker, Dennis; Carlqvist, Jeanette; Psychogios, Klearchos; Szikora, István; Tatlisumak, Turgut; Rentzos, Alexandros; Thornton, John; Doyle, Karen M.; Science Foundation Ireland; European Regional Development FundBackground and purpose There is still much debate whether bridging-therapy [intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT)] might be beneficial compared to MT alone. We investigated the effect of IVT on size and histological composition of the clots retrieved from patients undergoing bridging-therapy or MT alone. Methods We collected mechanically extracted thrombi from 1000 acute ischemic stroke (AIS) patients included in RESTORE registry. Patients were grouped according to the administration (or not) of IVT before thrombectomy. Gross photos of each clot were taken and Extracted Clot Area (ECA) was measured using ImageJ software. Martius Scarlett Blue stain was used to characterize the main histological clot components [red blood cells (RBCs), fibrin (FIB), platelets/other (PTL)] and Orbit Image Analysis was used for quantification. Additionally, we calculated the area of each main component by multiplying the component percent by ECA. Chi-squared and Kruskal–Wallis tests were used for statistical analysis. Results 451 patients (45%) were treated with bridging-therapy while 549 (55%) underwent MT alone. When considering only percent histological composition, we did not find any difference in RBC% (P = 0.895), FIB% (P = 0.458) and PTL% (P = 0.905). However, bridging-therapy clots were significantly smaller than MT-alone clots [32.7 (14.8–64.9) versus 36.8 (20.1–79.8) mm2, N = 1000, H1 = 7.679, P = 0.006*]. A further analysis expressing components per clot area showed that clots retrieved from bridging-therapy cases contained less RBCs [13.25 (4.29–32.06) versus 14.97 (4.93–39.80) mm2, H1 = 3.637, P = 0.056] and significantly less fibrin [9.10 (4.62–17.98) versus 10.54 (5.57–22.48) mm2, H1 = 7.920, P = 0.005*] and platelets/other [5.04 (2.26–11.32) versus 6.54 (2.94–13.79) mm2, H1 = 9.380, P = 0.002*] than MT-alone clots. Conclusions Our results suggest that previous IVT administration significantly reduces thrombus size, proportionally releasing all the main histological components.Publication Cognitive course in first-episode psychosis and clinical correlates: A 4year longitudinal study using the MATRICS Consensus Cognitive Battery.(2015-09-26) Kenney, Joanne; Anderson-Schmidt, Heike; Scanlon, Cathy; Arndt, Sophia; Scherz, Elisabeth; McInerney, Shane; McFarland, John; Byrne, Fintan; Ahmed, Mohamed; Donohoe, Gary; Hallahan, Brian; McDonald, Colm; Cannon, Dara M.; |~|While cognitive impairments are prevalent in first-episode psychosis, the course of these deficits is not fully understood. Most deficits appear to remain stable, however there is uncertainty regarding the trajectory of specific cognitive domains after illness onset. This study investigates the longitudinal course of cognitive deficits four years after a first-episode of psychosis and the relationship of performance with clinical course and response to treatment. Twenty three individuals with psychotic illness, matched with 21 healthy volunteers, were assessed using the MATRICS Consensus Cognitive Battery at illness onset and 4years later. We also investigated the relationship between cognitive deficits and quality of life and clinical indices. Verbal learning and two measures of processing speed had marked poorer trajectory over four years compared to the remaining cognitive domains. Processing speed performance was found to contribute to the cognitive deficits in psychosis. Poorer clinical outcome was associated with greater deficits at illness onset in reasoning and problem solving and social cognition. Cognitive deficits did not predict quality of life at follow-up, nor did diagnosis subtype differentiate cognitive performance. In conclusion, an initial psychotic episode may be associated with an additional cost on verbal learning and two measures of processing speed over a time spanning at least four years. Moreover, processing speed, which has been manipulated through intervention in previous studies, may represent a viable therapeutic target. Finally, cognition at illness onset may have a predictive capability of illness course..Publication Cortical thinning and caudate abnormalities in first episode psychosis and their association with clinical outcome.(Elsevier, 2014-08-11) Scanlon, Cathy; Anderson-Schmidt, Heike; McInerney, Shane; Kenney, Joanne; McFarland, John; Waldron, Mairead; Ambati, Srinath; Fullard, Anna; Logan, Sam; Hallahan, Brian; Elliott, Mark A.; Cannon, Dara M.; McDonald, Colm; |~|First episode psychosis (FEP) has been associated with structural brain changes, largely identified by volumetric analyses. Advances in neuroimaging processing have made it possible to measure geometric properties that may identify subtle structural changes not appreciated by a measure of volume alone. In this study we adopt complementary methods of assessing the structural integrity of grey matter in FEP patients and assess whether these relate to patient clinical and functional outcome at 3year follow-up. 1.5Tesla T1-weighted Magnetic Resonance (MR) images were acquired for 46 patients experiencing their first episode of psychosis and 46 healthy controls. Cerebral cortical thickness and local gyrification index (LGI) were investigated using FreeSurfer software. Volume and shape of the hippocampus, caudate and lateral ventricles were assessed using manual tracing and spherical harmonics applied for shape description. A cluster of cortical thinning was identified in FEP compared to controls; this was located in the right superior temporal gyrus, sulcus, extended into the middle temporal gyrus (lateral temporal cortex - LTC). Bilateral caudate volumes were significantly lower in FEP relative to controls and the right caudate also displayed regions of shape deflation in the FEP group. No significant structural abnormalities were identified in cortical LGI or hippocampal or lateral ventricle volume/shape. Neither LTC nor caudate abnormalities were related to change in symptom severity or global functioning 3years later. LTC and caudate abnormalities are present at the first episode of psychosis but do not appear to directly affect clinical or functional outcome.