Killian O'Rourke

University College Dublin, Dublin, Leinster, Ireland

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Publications (42)186.67 Total impact

  • No preview · Article · Dec 2015 · Stroke
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    ABSTRACT: Background and purpose: Few recent studies have investigated the rates and predictors of early and late stroke recurrence using prospective population-based methodology. We investigated recurrent stroke at 2 years in the North Dublin Population Stroke Study (NDPSS). Methods: Patients were ascertained from December 2005 to 2006 from overlapping community and hospital sources using hot and cold pursuit. Stroke recurrence, survival, and functional outcome were ascertained at 72 hours, 7 days, 28 days, 90 days, 1 year, and 2 years. Results: Of 567 patients, cumulative 2-year stroke recurrence rate was 10.8% and case fatality was 38.6%. Recurrence subtype was associated with initial stroke subtype (P<0.001). On multivariable Cox regression, hyperlipidemia (adjusted hazard ratio, 3.32; P=0.005) and prior stroke (adjusted hazard ratio, 2.92; P=0.01) were independent predictors of 2-year recurrence in 28-day survivors. Conclusion: Despite rigorous ascertainment, recurrent stroke rates were lower in current study than in earlier studies. Our data suggest that large sample sizes may be needed for future secondary prevention trials in patients treated with modern preventive medications.
    No preview · Article · Nov 2015 · Stroke
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    ABSTRACT: Background and purpose: Demographic trends in atrial fibrillation (AF) incidence may yield a substantial rise in the societal burden of AF-related stroke (AF-stroke). Accurate population-wide outcome data are essential to inform health service planning to improve AF-stroke prevention, and provision of rehabilitation, nursing home, and community supports for AF-stroke survivors. Methods: We investigated rates and determinants of 5-year fatality, stroke recurrence, functional outcomes, and prescribing of secondary prevention medications in AF-stroke in the North Dublin Population Stroke Study. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using lifetables and Kaplan-Meier survival curves, and Cox proportional hazard modeling was performed to identify predictors of death and recurrent stroke. Results: Five hundred sixty-eight patients with new stroke were identified, including 177 (31.2%) AF-stroke. At 5 years, 39.2% (confidence interval, 31.5-46.8) of ischemic AF-stroke patients were alive. Congestive heart failure, hypertension, age <65, 65-74 years, and ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack or thromboembolism, vascular disease and female sex (CHA2DS2-VASc) score (hazard ratio [HR], 1.34; P<0.001), CHADS2 score (HR 1.42, P=0.004), National Institute of Health Stroke Scale (HR, 1.09; P<0.0001), and subtherapeutic international normalized ratio (<2.0) at stroke onset (HR, 3.29; P=0.003) were independently associated with 5-year fatality, whereas warfarin (HR, 0.40; P=0.001) and statin use after index stroke (HR, 0.52; P=0.005) were associated with improved survival. The 5-year recurrence rate after ischemic AF-stroke was 21.5% (confidence interval, 14.5-31.3). Trends toward greater risk of recurrence were observed for persistent AF (HR, 3.09; P=0.07) and CHA2DS2-VASc score (HR, 1.34; P=0.07). Nursing home care was needed for 25.9% of patients. Conclusion: AF-stroke is associated with considerable long-term morbidity, fatality, stroke recurrence, and nursing home requirement. Adequately resourced national AF strategies to improve AF detection and prevention are needed.
    No preview · Article · Oct 2015 · Stroke
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    ABSTRACT: Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family with frontotemporal dementia linked to chromosome 17 associated with extensive tau pathology. We named this disinhibition-dementia-parkinsonism-amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven MAPT gene splice site stem loop mutations were identified over time except for 5' splice site of exon 10. We recently identified another Irish family with autosomal dominant early amnesia and behavioural change or parkinsonism associated with the 'missing' +15 mutation at the intronic boundary of exon 10. We performed a clinical, neuropsychological and neuroimaging study on the proband and four siblings, including two affected siblings. We sequenced MAPT and performed segregation analysis. We looked for a biological effect of the tau variant by performing real-time polymerase chain reaction analysis of RNA extracted from human embryonic kidney cells transfected with exon trapping constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all affected subjects but not in the unaffected. The c.915+15A>C variant caused a shift in tau splicing pattern to a predominantly exon 10+ pattern presumably resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly suggests that the c.915+15A>C variant is a mutation and that it causes frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau transcription and translation to +4 repeat tau. Tau (MAPT) screening should be considered in families where amnesia or atypical parkinsonism coexists with behavioural disturbance early in the disease process. We describe the final missing stem loop tau mutation predicted 15 years ago. Mutations have now been identified at all predicted sites within the 'stem' when the stem-loop model was first proposed and no mutations have been found within the 'loop' region as expected. Therefore we 'close the tau loop' having 'opened the loop' 21 years ago. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
    No preview · Article · Aug 2015 · Brain
  • I Welaratne · T. Lynch · K. O'Rourke

    No preview · Article · Jul 2015 · Irish Journal of Medical Science
  • D Curtin · D Costigan · C McCarthy · M Jansen · M Farrell · V Reid · K O'Rourke
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    ABSTRACT: Introduction: The patient presenting with proximal muscle weakness, elevated serum creatinine kinase and myopathic electromyography and biopsy findings has a wide differential diagnosis that includes toxic, autoimmune, paraneoplastic and congenital myopathies. Autoimmune myopathies are important to identify because they may respond to immunosuppressive therapies. Methods: We describe two cases of immune-mediated necrotizing myopathy each associated with a novel antibody. Results: Case 1 describes a progressive myopathy in a statin user. Antibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase were identified and the patient responded to steroid therapy. Case 2 describes an aggressive myopathy associated with antibodies to signal recognition particle. There was no response to steroids. Clinical improvement followed treatment with rituximab and cyclophosphamide. Conclusion: The identification of myositis-specific antibodies is important because they are associated with distinct clinical phenotypes and may guide the physician in terms of treatment strategies.
    No preview · Article · Oct 2014 · Irish Journal of Medical Science
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    ABSTRACT: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on (18)fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. 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). 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. 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.
    No preview · Article · Apr 2014 · Neurology
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    ABSTRACT: Natalizumab, a monoclonal α-4-integren receptor antibody, is an effective immunomodulator in highly active relapsing remitting Multiple Sclerosis (HARRMS). Natalizumab has been associated with PML (progressive multifocal leucoencephaopathy), due to opportunistic reactivation of JC polyomavirus (JCv). PML risk may influence decisions to continue therapy. Risk relates to 3 identified risk factors: serum anti-JCv antibodies, prior immunosuppression and prolonged natalizumab therapy (>2 years). Recent commercial availability of a serum JCv-antibody screening test (STRATIFY JCV TM) has been incorporated into a risk-stratification algorithm, presented to patients to help guide treatment. Influence of antibody testing on risk perception and decision to proceed with treatment has not been widely established. To examine treatment decisions of patients receiving natalizumab based on their JCv-antibody status. Serum JCv-antibodies tested annually in patients receiving natalizumab for HARRMS. Clinical data and decisions to stop natalizumab based on JCv status recorded. JCv antibody status was available in 112 natalizumab patients. Mean natalizumab duration 27.4 months (2-72). Antibodies detected in 55 (49.1%): 2 (3.6%) stopped due to JCv+ve alone, 14 (25.5%) due to prolonged therapy (>2years), 1 (1.8%) due to prolonged therapy and past immuosuppression, 3 (5.5%) disability progression, 1 (1.8%) to conceive. (12.3% of JCv negative patients stopped due to prolonged therapy). No significant difference in mean natalizumab duration or disease-modifying therapy history between JCv Ab+ve and Ab-ve groups (p>0.05). Other PML risks (>2 years, past immunosuppression) did not differ significantly between JCv+ve patients who opted to continue compared to those choosing to stop (p>0.05). JCv antibody status had little influence on this cohort's decision to discontinue or remain on natalizumab therapy. It is important that patients understand therapeutic benefits and potential risks of alternative treatments before discontinuing due to JCv status alone. Further validation of this risk stratification measure is important.
    No preview · Article · Nov 2013 · Journal of neurology, neurosurgery, and psychiatry

  • No preview · Article · Oct 2013
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    ABSTRACT: Mitoxantrone is an effective disease-modifying therapy in multiple sclerosis (MS), but its use is limited by cardiotoxicity. We evaluated global myocardial function, including myocardial performance index (MPI), on echocardiography in MS patients after remote mitoxantrone treatment. Consecutive patients (n = 50) treated with standard-protocol mitoxantrone from 2002 to 2010 in our center were identified. After exclusion of those who had died (n = 4; all noncardiac) or had developed interim cardiovascular disease or risk factors (n = 3), 33 (mean age 49 ± 11 years, 45% male, median follow-up 77 months, mean cumulative dose 72 mg/m(2)) of the remaining patients (77%) underwent 2-dimensional echocardiography. A comparison group of 17 age- and sex-matched control subjects were included. No significant differences occurred in standard echocardiographic parameters between groups. However, mean MPI (defined as isovolumic contraction time plus isovolumic relaxation time (IVRT) divided by ejection time) was significantly higher in patients (0.51 ± 0.12 vs 0.39 ± 0.06; P = .02) owing to a significantly prolonged IVRT (81 ± 25 vs 60 ± 9 ms; P = .04). Overall MPI was >0.5 in 18 patients compared with none of the control subjects (54.5% vs 0%; P < .001). A subclinical form of global myocardial dysfunction reflecting primarily diastolic dysfunction may be present in MS patients after remote standard-dose mitoxantrone treatment.
    No preview · Article · Aug 2013 · Journal of cardiac failure
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    Kinley Roberts · Barry Mahon · Killian O'Rourke · Timothy Lynch
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    ABSTRACT: 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. Herein we report a novel task-specific dystonic tremor in a 44-year-old Irish hairdresser due to club-cutting, a standard haircutting technique. Hairdresser's dystonia is a novel task-specific dystonia.
    Full-text · Article · Aug 2013
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    ABSTRACT: A 25-year-old man presented with subacute spastic paraparesis. He reported 2 previous episodes of spastic paraparesis with partial recovery. Recurrent oral and genital ulceration, pustular skin eruptions, and fever coexisted. Profound motor weakness, a sensory level at T10, oral ulceration, and a pustular eruption on the anterior abdominal wall were noted. Marked neutrophilia was noted in both blood and CSF. Neuromyelitis optica-immunoglobulin G autoantibody was negative. MRI (figure) demonstrated marked inflammatory changes. IV and oral steroids, followed by 6 months of pulsed IV cyclophosphamide, resulted in marked clinical improvement. Neuro-Behçet disease lies within the clinical differential for longitudinally extensive transverse myelitis.(1,2.)
    Full-text · Article · Apr 2013 · Neurology

  • No preview · Article · Apr 2013 · Journal of Neurology
  • A McCarthy · J Dineen · P McKenna · M Keogan · J Sheehan · T Lynch · K O'Rourke
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    ABSTRACT: Anti-NMDA-R encephalitis has been described as a cause of acute psychosis in young females. It is rare during pregnancy. We describe a primigravida 32-year-old woman with acute onset psychosis during the first trimester. Eight weeks after becoming pregnant, the patient became psychotic with associated catatonia and autonomic disturbance. Serum anti-NMDA-R antibodies were found. She responded to plasma exchange. At caesarean section, a healthy baby boy was born and a benign mature cystic teratoma was removed from the left ovary. Catatonia associated with psychosis may occur in pregnancy secondary to anti-NMDA-R encephalitis. Prompt and aggressive treatment can lead to a good outcome for both baby and mother.
    No preview · Article · Jul 2012 · Journal of Neurology
  • A. Mc Carthy · E. Mulroy · K. O'Rourke · T. Lynch

    No preview · Conference Paper · Jun 2012
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    ABSTRACT: 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 (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography, we investigated the relation between inflammation-related FDG uptake and stroke recurrence. Consecutive patients with a recent (median, 6.5 days; interquartile range, 4-8) stroke, transient ischemic attack (TIA), or retinal embolism and ipsilateral carotid stenosis (≥50%) were included. FDG uptake was quantified as mean standardized uptake values (SUVs, g/ml). Patients were followed prospectively for stroke recurrence. Sixty patients were included (25 stroke, 29 TIA, 6 retinal embolism). Twenty-two percent (13 of 60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV, 1.85 g/ml; standard deviation [SD], 0.44 vs 1.58 g/ml; SD, 0.32, p = 0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14 g/ml threshold were 80% (95% confidence interval [CI], 41.8-99.2) versus 22.9% (95% CI, 12.3-40.3) with SUV ≤2.14 g/ml (log-rank, p < 0.0001). In a Cox regression model including age and degree of stenosis (50-69% or ≥70%), mean plaque FDG uptake was the only independent predictor of stroke recurrence (adjusted hazard ratio, 6.1; 95% CI, 1.3-28.8; p = 0.02). In recently symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularization or intensive medical treatment.
    No preview · Article · May 2012 · Annals of Neurology
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    Full-text · Article · Mar 2012 · Movement Disorders
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    J Yssel · E Casey · K O'Rourke · B Magennis · T Lynch
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    ABSTRACT: Ireland's ageing population will result in a substantial increase in neurodegenerative disease with a projected increase in prevalence of Idiopathic Parkinson's disease (IPD) to 9,000 by 2021. There are few published audits of neurology services to assist care planning. As a first step towards evaluating future service needs for this group of patients, we audited a single tertiary referral IPD and Other Movement Disorders clinic for 2006. A total of 497 patients from all counties in Ireland were seen; 225 (59%) of patients had IPD, 32 (8.2%) had atypical parkinsonism, and 22 (5.8%) dystonia. In a subset of 275 patients, 151 (55%) were referred by GPs, 74 (27%) by other consultants, and 49 (18%) by other consultant neurologists. Diagnosis was changed in 22 (38%) and medication was adjusted in 203 (74%). A telephone survey of 50 patients demonstrated 100% satisfaction with the improved access to the clinical nurse specialist, telephone support and improved continuity of care. The IPD and Other Movement Disorders clinic provides an important local, regional, and national diagnostic and therapeutic service for complex movement disorders. It is proposed that a national registry of IPD and audit of the delivery of care to patients with movement disorders is needed.
    Full-text · Article · Feb 2012 · Irish medical journal

  • No preview · Article · Jan 2012 · Annals of Neurology
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    ABSTRACT: Mitoxantrone has been extensively used as a disease-modifying therapy for multiple sclerosis. However, estimates of the associated risk of therapy-related acute leukaemia and cardiomyopathy have been derived from short-term studies. This study aimed to ascertain the long-term risk of therapy-related acute leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis. Between 2002 and 2010, 50 patients were treated with mitoxantrone at a single centre using a standard protocol (12 mg/m(2) body surface area monthly for 6 months as tolerated to a maximum of 72 mg/m(2) body surface area). Follow-up haematologic and echocardiographic data were collected in March 2011. Fifteen patients (30%) were excluded from analysis either because of lack of follow-up data, death due to non-cardiac and non-haematologic causes, or comorbid cardiovascular disease. The remaining 35 patients (70%) were followed for a median of 75 months (range: 9-103). The median cumulative mitoxantrone dose given was 72 mg/m(2) body surface area (range: 24-123). At the end of follow-up, no patients had developed therapy-related acute leukaemia. One patient suffered an asymptomatic drop in left ventricular ejection fraction from 55 to 47%. This series of patients followed for up to 8.5 years suggests that the risk of either therapy-related acute leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis is low when patients are treated within standard protocol.
    No preview · Article · Dec 2011 · European Neurology

Publication Stats

355 Citations
186.67 Total Impact Points


  • 2009-2015
    • University College Dublin
      • School of Public Health, Physiotherapy & Population Science
      Dublin, Leinster, Ireland
    • St. Vincent's Private Hospital
      Dublin, Leinster, Ireland
  • 2009-2013
    • Mater Misericordiae University Hospital
      • Dublin Neurological Institute
      Dublin, Leinster, Ireland
  • 2007-2010
    • St Vincent's University Hospital
      Dublin, Leinster, Ireland
    • St. Vincent Hospital
      Green Bay, Wisconsin, United States
  • 2008-2009
    • St. Vincents University Hospital
      Dublin, Leinster, Ireland
  • 2006
    • Queen's University Belfast
      • School of Pharmacy
      Béal Feirste, Northern Ireland, United Kingdom