Killian O'Rourke
Mater Misericordiae University Hospital
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Publication
Featured researches published by Killian O'Rourke.
Annals of Neurology | 2012
Michael Marnane; Áine Merwick; Orla C. Sheehan; Niamh Hannon; Paul Foran; Tim Grant; Eamon Dolan; Joan T. Moroney; Sean Murphy; Killian O'Rourke; Kevin O'Malley; Martin K. O'Donohoe; Ciaran McDonnell; Imelda Noone; Mary Barry; Morgan Crowe; Eoin C. Kavanagh; Martin O'Connell; Peter J. Kelly
Symptomatic carotid stenosis is associated with a 3‐fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque‐related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined 18F‐fluorodeoxyglucose positron‐emission tomography (FDG‐PET)/computed tomography, we investigated the relation between inflammation‐related FDG uptake and stroke recurrence.
Clinical Pharmacology & Therapeutics | 2005
Stephen Cunningham; Colin A. Graham; Michael Hutchinson; Aidan Droogan; Killian O'Rourke; Christopher Patterson; Gavin McDonnell; Stanley Hawkins; Koen Vandenbroeck
Interferon IFN‐β is indicated for the treatment of multiple sclerosis. A significant proportion of patients show a poor clinical response to therapy. Type I interferon exerts its effect at least partially through interaction of specific transcription factors with interferon‐stimulated response elements (ISREs), mostly located in promoter regions of its target genes. We hypothesized that polymorphisms may occur within or close to ISRE elements, altering type I interferon inducibility and ultimately leading to a modified clinical response in carriers.
Journal of Neurology, Neurosurgery, and Psychiatry | 2007
Lisa Costelloe; Killian O'Rourke; Hugh Kearney; Christopher McGuigan; Lisa Gribbin; M Duggan; Leslie Daly; Niall Tubridy; Michael Hutchinson
Aim: The aims of this study were to determine the reliability, responsiveness and minimally important change score of the Multiple Sclerosis Impact Scale (MSIS)-29 physical using the Expanded Disability Status Scale (EDSS) as an anchor measure. Methods: 214 patients with multiple sclerosis (MS) (EDSS 0–8.5) had concurrent MSIS-29 and EDSS assessments at baseline and at up to 4 years of follow-up. Results: 116 patients had unchanged EDSS scores. Stability of the MSIS-29 physical (mean change 0.1 points) was better in the 85 patients with EDSS 0–5.0 than in the 31 patients with EDSS 5.5–8.5 in whom the MSIS-29 physical score fell by 8 points, a response shift phenomenon. A floor effect for the MSIS-29 was observed in 5% of stable patients at both time points. 98 patients experienced EDSS change with moderately strong statistically significant correlations between change scores in the EDSS and the MSIS-29 physical (r = 0.523, p<0.0001). Effect sizes for MSIS-29 physical change were moderate to large. Using receiver operating characteristic curves, the MSIS-29 change score which produced a combination of optimal sensitivity and specificity was chosen for both EDSS ranges. For EDSS range 5.5–8, a change score of 8 had a sensitivity of 87% and specificity of 67%. For EDSS 0–5.0, a change score of 7 had a sensitivity of 78% and a specificity of 51%. Conclusions: The MSIS-29 physical performs well over time, and is suitable for use in trials; a minimal change score of 8 points in the MSIS-29 is clinically significant.
Multiple Sclerosis Journal | 2007
Killian O'Rourke; Cathal Walsh; Guido Antonelli; Michael Hutchinson
Proposed beta-interferon (IFNβ) treatment failure criteria for patients with relapsing-remitting multiple sclerosis (RRMS) have not been validated in clinical practice. This study aimed to establish (a) whether IFNβ attenuated accumulation of fixed disability in comparison to a cohort of matched historical control subjects from the Sylvia Lawry centre for MS research, and (b) whether relapse-based treatment failure criteria or clinical and demographic variables had predictive value for the accumulation of fixed disability. Of the 175 IFNβ-treated RRMS patients, 60 (34%) developed accumulation of fixed disability over a median of five years follow-up, which was significantly less than the rate of accumulation of fixed disability in the control group (P<0.0001). Any relapse in the treatment period predicted accumulation of fixed disability with a sensitivity of 80% and specificity of 43%; patients totally relapse free were less likely to develop accumulation of fixed disability (P <0.002). Multivariate analysis confirmed that a greater risk of accumulation of fixed disability was conferred by a higher Expanded Disability Status Scale (EDSS) score starting IFNβ (P=0.02), and by failure of IFNβ to completely suppress relapses (P=0.004). In conclusion, IFNβ therapy reduced the accumulation of fixed disability in a cohort of RRMS patients, followed for a median of five years. Higher baseline EDSS and failure of complete relapse suppression were associated with a significantly greater likelihood of accumulation of fixed disability. Multiple Sclerosis 2007; 13: 336-342. http://msj.sagepub.com
Multiple Sclerosis Journal | 2008
Lisa Costelloe; Killian O'Rourke; Christopher McGuigan; Cathal Walsh; Niall Tubridy; Michael Hutchinson
Background To examine the longitudinal relationship between the patient-rated Multiple Sclerosis Impact Scale (MSIS-29) and the doctor-reported Multiple Sclerosis Functional Composite (MSFC). Methods Two-hundred and four MS patients at baseline and 150 patients one to three years later had MSFC and MSIS-29 assessments. Cross-sectional correlations between these measures and correlations of change in scores were examined. Minimally important change (MIC) in the MSFC was defined at either 0.5 or 0.32 SD from baseline. Effect sizes (ES) were calculated. Results Validity: The MSIS-29 physical correlated moderately with the total MSFC score and the 25-foot timed walk and 9-hole peg test. Correlations of the MSIS-29 physical with the PASAT, and the MSFC with the MSIS-29 psychological were weak. Responsiveness: When MIC in the MSFC was defined as 0.5, mean MSIS-29 physical change was 11.26 (ES = 0.53). At MSFC change of 0.32, mean MSIS-29 physical change was 10.4 (ES = 0.52). Change in MSFC scores correlated weakly with change in the MSIS-29 scores. Stability: In patients with stable MSFC scores, the mean MSIS-29 physical scores improved minimally over time with negligible ES. Conclusions Although the MSIS-29 physical demonstrates moderate cross-sectional correlation with the MSFC, the weak correlations of change scores between the two instruments indicate that they measure different aspects of the effects of multiple sclerosis morbidity. Multiple Sclerosis 2008; 14: 255—258. http://msj.sagepub.com
Muscle & Nerve | 2009
John C. McHugh; Roisin Lonergan; Rachel Howley; Killian O'Rourke; Robert W. Taylor; Michael Farrell; Michael Hutchinson; Sean Connolly
Two siblings who developed fifth‐decade‐onset, concurrent progressive sensory ataxia, dysarthria, and ophthalmoparesis were found to be homozygous for the p.A467T mutation of the polymerase gamma (POLG) gene. The clinical course in both subjects was progression to severe disability. The enlarging spectrum of sensory ataxic neuropathies associated with mitochondrial DNA (mtDNA) instability and POLG mutations should be recognized and considered in the differential diagnosis of this unusual presentation. Muscle Nerve, 2010
Neurology | 2010
M. O'Brien; Roisin Lonergan; Lisa Costelloe; Killian O'Rourke; Jean M. Fletcher; Katie Kinsella; Christopher Sweeney; G. Antonelli; Kingston H. G. Mills; Cliona O'Farrelly; Michael Hutchinson; Niall Tubridy
Background:Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. Methods:We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-&bgr; (IFN&bgr;) assessed as 1) having no or minimal disease activity on IFN&bgr;, 2) having disease activity despite IFN&bgr;, and 3) 65 patients with RRMS with highly active disease. Results:The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFN&bgr; had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFN&bgr;, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFN&bgr; was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). Conclusions:A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity. GLOSSARYEDSS = Expanded Disability Status Scale; HCV = hepatitis C virus; HW = Hardy-Weinberg; IFN = interferon; IFN&bgr; = interferon-&bgr;; MS = multiple sclerosis; MxA = myxovirus A; NAb = neutralizing antibody; OAS1 = oligoadenylate synthetase 1; RRMS = relapsing-remitting multiple sclerosis; SNP = single nucleotide polymorphism; TRU = 10-fold reduction units; TTFR = time to first relapse.
Neurology | 2014
Danielle Ní Chróinín; Michael Marnane; Layan Akijian; Áine Merwick; Emer Fallon; Gillian Horgan; Eamon Dolan; Sean Murphy; Killian O'Rourke; Kevin O'Malley; Martin K. O'Donohoe; Ciaran McDonnell; Imelda Noone; Mary Barry; Morgan Crowe; Eoin C. Kavanagh; Martin O'Connell; Peter J. Kelly
Objective: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on 18fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. Methods: In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUVmax) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs (SUVmean). Results: Sixty-one patients were included. Plaque inflammatory FDG SUVmax was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol (p = 0.009), and triglycerides (p = 0.01), and with lower high-density lipoprotein (HDL) (p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUVmean (Spearman rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p = 0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho 0.35, p = 0.005). HDL was associated with lower SUVmax (rho −0.37, p = 0.004) and SUVROImax (rho −0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL (p = 0.008) and total cholesterol (p = 0.04) were independently associated with SUVmax. Conclusion: Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.
Tremor and other hyperkinetic movements (New York, N.Y.) | 2013
Kinley Roberts; Barry Mahon; Killian O'Rourke; Timothy Lynch
Background Focal task-specific dystonic postures are well recognized. Often a tremor may be the main feature with little or no dystonia. These have been well reported in writers, musicians, and sportspeople. Case Report Herein we report a novel task-specific dystonic tremor in a 44-year-old Irish hairdresser due to club-cutting, a standard haircutting technique. Discussion Hairdresser’s dystonia is a novel task-specific dystonia.
Journal of Neurology | 2007
Killian O'Rourke; Cathal Walsh; Michael Hutchinson
Observational studies of the effect of beta-interferon (IFNβ) on accumulation of fixed disability in relapsing remitting multiple sclerosis (RRMS) in clinical practice have been difficult to interpret due to bias. The aim of this study of 175 RRMS patients was to use Bayesian analysis to establish whether IFNβ attenuates disability relative to a cohort of matched historical control subjects from the Sylvia Lawry Centre for MS Research. A sensitivity analysis was based on a range of prior probability distributions for IFNβ efficacy derived from a published meta-analysis of randomised controlled trials (RCTs) of IFNβ, and the data were interpreted both unmodified and using variance inflation and point estimate bias correction; the corrected data interpreted in the light of the most likely prior probability distribution yielded a 95 % posterior credible interval for the odds ratio of accumulation of fixed disability after two years of IFNβ therapy of 0.52, 0.94. It is concluded that two years of IFNβ therapy for RRMS reduces accumulation of fixed disability in clinical practice.