Killian O'Rourke

Mater Misericordiae University Hospital, Dublin, Leinster, Ireland

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Publications (26)101.08 Total impact

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    ABSTRACT: 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.
    Irish Journal of Medical Science 10/2014; · 0.51 Impact Factor
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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.
    Neurology 04/2014; · 8.30 Impact Factor
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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.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. · 4.87 Impact Factor
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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.
    Journal of cardiac failure 08/2013; 19(8):571-6. · 3.25 Impact Factor
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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.)
    Neurology 04/2013; 80(18):e189-90. · 8.30 Impact Factor
  • Journal of Neurology 04/2013; · 3.58 Impact Factor
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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.
    Tremor and other hyperkinetic movements (New York, N.Y.). 01/2013; 3.
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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.
    Journal of Neurology 07/2012; · 3.58 Impact Factor
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    Movement Disorders 03/2012; 27(3):346-8. · 5.63 Impact Factor
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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.
    Annals of Neurology 02/2012; 71(5):709-18. · 11.19 Impact Factor
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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.
    Irish medical journal 02/2012; 105(2):57-9. · 0.51 Impact Factor
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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.
    European Neurology 12/2011; 67(1):45-7. · 1.50 Impact Factor
  • Journal of Neurology 02/2011; 258(2):330-2. · 3.58 Impact Factor
  • Journal of Neurology 01/2011; 258(7):1347-8. · 3.58 Impact Factor
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    ABSTRACT: Hepatitis E infection is most prevalent in developing countries with poor sanitation, but can also occur apparently sporadically in more developed areas. We here report a second European case of Guillain-Barre syndrome due to hepatitis E infection in association with anti-glycolipid GM2 antibody. This is likely to be a specific association involving molecular mimicry, and further European cases can therefore be expected.
    Irish Journal of Medical Science 11/2010; 180(1):255-7. · 0.51 Impact Factor
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    ABSTRACT: KeywordsWarfarin-Flucloxacillin-Antibiotic-Interaction-Sub-therapeutic anticoagulation-Stroke
    European Journal of Clinical Pharmacology 03/2010; 66(6):643-4. · 2.74 Impact Factor
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    ABSTRACT: Most disabling strokes are due to blockage of a large artery in the brain by a blood clot. Prompt removal of the clot with intra-arterial thrombolytic drugs or mechanical devices, or both, can restore blood flow before major brain damage has occurred, leading to improved recovery. However, these so-called percutaneous vascular interventions can cause bleeding in the brain. To assess the safety and efficacy of percutaneous vascular interventions in patients with acute ischaemic stroke. We searched the Trials Registers of the Cochrane Stroke Group and Cochrane Peripheral Vascular Diseases Group (last searched May 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 5), MEDLINE (1980 to May 2010), EMBASE (1980 to May 2010) and eight additional databases. We also searched trials registers, screened reference lists, contacted researchers and equipment manufacturers, and handsearched journals and conference proceedings. Randomised, controlled and unconfounded trials of any percutaneous vascular intervention compared with control in patients with definite ischaemic stroke. Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We obtained both published and unpublished data if available We included four trials involving 350 patients. Not all trials contributed data to each outcome. The trials tested either intra-arterial urokinase or recombinant pro-urokinase versus an open control. One trial used guidewire-mediated clot disruption in some patients randomised to the intervention group. Most data came from trials that started treatment up to six hours after stroke; one small trial started treatment up to a median of 12.5 hours after stroke. Most data came from trials of middle cerebral artery territory infarction. Compared with non-thrombolytic standard medical treatment, the intervention administered up to six hours after ischaemic stroke significantly increased the proportion of patients with favourable outcome (modified Rankin 0 to 2) three months after stroke (relative risk (RR) 1.47, 95% confidence interval (CI) 1.07 to 2.02). The intervention also significantly increased the risk of symptomatic intracranial haemorrhage within 24 hours of treatment (RR 3.85, 95% CI 0.91 to 16.36). There was no significant heterogeneity between the included trials. Overall, intervention results in a significant increase in the proportion of patients with a favourable outcome, despite a significant increase in intracranial haemorrhage. Further trials are needed to confirm or refute these findings and, given the cost and practical difficulties, to establish whether percutaneous techniques are feasible and cost effective in wider clinical practice.
    Cochrane database of systematic reviews (Online) 01/2010; · 5.70 Impact Factor
  • Journal of Neurology 12/2009; 257(4):669-71. · 3.58 Impact Factor
  • Killian E T O'Rourke, Cathal D Walsh, Peter J Kelly
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    ABSTRACT: Observational studies of new treatments in routine practice are clinically important but may be limited by bias. We used a Bayesian approach to interpret and sequentially combine phase 4 studies of IV-TPA within 3 h for acute ischaemic stroke to quantify the cumulative evidence for the efficacy and safety of this therapy in clinical practice. Prior probability distributions for favourable outcome (modified Rankin Score, mRS, 0-1), symptomatic intracerebral haemorrhage, and mortality 3 months after IV-TPA were derived from the NINDS trial. Phase 4 studies from observational case series and from regulator-mandated large registries were included. A cumulative analysis was performed to quantify the increase in the total evidence base over time, unadjusted and adjusted for potential bias. The cumulative analysis indicated that IV-TPA <3 h was associated with 3-month favourable outcome in 37.1% (95% credible interval, CrI, 36.1-38.0%, n = 9,578) compared to 26% (95% confidence interval, CI, 19.6-32.9%, n = 165) in placebo-treated patients in NINDS, symptomatic intracranial haemorrhage in 6.6% (95% CrI 5.9-7.4%, n = 10, 834) compared to 6.4% (95% CI 4.0-9.4%) in the NINDS IV-TPA group, and 3-month mortality in 13.6% (95% CrI 12.6-14.8%, n = 9, 901) compared to 20.5% (95% CI 16.0-25.0%, n = 312) in the NINDS placebo group. A Bayesian approach provides further confirmatory evidence of the efficacy and safety of IV-TPA for treatment of acute ischaemic stroke within 3 h in diverse clinical practice settings, after adjusting for potential observational bias.
    Cerebrovascular Diseases 10/2009; 28(6):572-81. · 2.81 Impact Factor
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    ABSTRACT: 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 10/2009; 41(2):265-9. · 2.31 Impact Factor