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These include increased P wave terminal force, P or PR prolongation, or excessive supraventricular ectopic activity, 75 , — or short atrial runs.

Echocardiographic measures of left atrial LA size and function are broadly available. Rheumatic mitral stenosis indicates a highly prothrombotic milieu.

Blood biomarkers and genetics applied as polygenic risk scores may be indicative of AF-related stroke. Markers of hypercoagulability have been related to post-stroke AF, , or, more generally, thyroid-stimulating hormone.

Recently, atrial cardiomyopathy has been characterized as any complex of structural, architectural, contractile, or electrophysiological changes affecting the atria with the potential to produce clinically relevant manifestations.

Echocardiography is currently the imaging technique of choice. Two-dimensional speckle-tracking echocardiography and atrial strain have been used as more sensitive markers to detect early functional remodelling before anatomical changes occur.

Cardiac CT computed tomography or MRI magnetic resonance imaging can be used for a more accurate assessment of atrial volumes, while late gadolinium enhancement on MRI may quantify atrial fibrosis.

Cardiac disease is clearly associated with VBI. The relationship between AF, cardiac disease, and VBI remains enigmatic and will require much future research to determine whether AF is more bystander than a villain.

This paper was published as part of a supplement financially supported by the European Society of Cardiology ESC , Council on Stroke.

Conflict of interest: B. La Fibrillazione Atriale in Italia. Prevalence of atrial fibrillation in the Italian elderly population and projections from to for Italy and the European Union: the FAI Project.

Google Scholar. Chugh SS , Havmoeller R , Narayanan K , Singh D , Rienstra M , Benjamin EJ , Gillum RF , Kim YH , McAnulty JH Jr , Zheng ZJ , Forouzanfar MH , Naghavi M , Mensah GA , Ezzati M , Murray CJ.

Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease Study. Lifetime risk of atrial fibrillation by race and socioeconomic status: ARIC study Atherosclerosis Risk in Communities.

Schnabel RB , Yin X , Gona P , Larson MG , Beiser AS , McManus DD , Newton-Cheh C , Lubitz SA , Magnani JW , Ellinor PT , Seshadri S , Wolf PA , Vasan RS , Benjamin EJ , Levy D.

Chamberlain AM , Brown RD , Alonso A , Gersh BJ , Killian JM , Sa W , Vl R. No decline in the risk of stroke following incident atrial fibrillation since in the community: a concerning trend.

Cowan JC , Wu J , Hall M , Orlowski A , West RM , Gale CP. A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation.

Freedman B. Major progress in anticoagulant uptake for atrial fibrillation at last: does it translate into stroke prevention? Alkhouli M , Alqahtani F , Aljohani S , Alvi M , Holmes DR.

Burden of atrial fibrillation-associated ischemic stroke in the United States. Yiin GS , Li L , Bejot Y , Rothwell PMJS. Time trends in atrial fibrillation-associated stroke and premorbid anticoagulation: population-based study and systematic review.

Aparicio HJ , Himali JJ , Satizabal CL , Pase MP , Romero JR , Kase CS , Beiser AS , Seshadri SJS. Temporal trends in ischemic stroke incidence in younger adults in the Framingham Study.

GBD Stroke Collaborators Global, regional, and national burden of stroke, — a systematic analysis for the Global Burden of Disease Study Koton S , Schneider AL , Rosamond WD , Shahar E , Sang Y , Gottesman RF , Coresh JJJ.

Stroke incidence and mortality trends in US communities, to Fewer ischemic strokes, despite an ageing population: stroke models from observed incidence in Norway — George MG , Tong X , Bowman B.

Prevalence of cardiovascular risk factors and strokes in younger adults. Lackland DT , Roccella EJ , Deutsch AF , Fornage M , George MG , Howard G , Kissela BM , Kittner SJ , Lichtman JH , Lisabeth LDJS.

George MG , Tong X , Kuklina EV , Labarthe D. Trends in stroke hospitalizations and associated risk factors among children and young adults, — Yiin GS , Howard DP , Paul NL , Li L , Luengo-Fernandez R , Bull LM , Welch SJ , Gutnikov SA , Mehta Z , Rothwell PMJC.

Age-specific incidence, outcome, cost, and projected future burden of atrial fibrillation-related embolic vascular events: a population-based study.

The impact of atrial fibrillation on the cost of stroke: the Berlin acute stroke study. Kirchhof P , Benussi S , Kotecha D , Ahlsson A , Atar D , Casadei B , Castella M , Diener HC , Heidbuchel H , Hendriks J , Hindricks G , Manolis AS , Oldgren J , Popescu BA , Schotten U , Van Putte B , Vardas P.

Hart RG , Pearce LA , Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.

Santangeli P , Di Biase L , Bai R , Mohanty S , Pump A , Cereceda Brantes M , Horton R , Burkhardt JD , Lakkireddy D , Reddy YM , Casella M , Dello Russo A , Tondo C , Natale A.

Atrial fibrillation and the risk of incident dementia: a meta-analysis. Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data from a population-based cohort.

Madhavan M , Graff-Radford J , Piccini JP , Gersh BJ. Cognitive dysfunction in atrial fibrillation. Liu DS , Chen J , Jian WM , Zhang GR , Liu ZR.

The association of atrial fibrillation and dementia incidence: a meta-analysis of prospective cohort studies. Relationships of overt and silent brain lesions with cognitive function in patients with atrial fibrillation.

Friberg L , Rosenqvist M. Less dementia with oral anticoagulation in atrial fibrillation. Friberg L , Andersson T , Rosenqvist M.

Less dementia and stroke in low-risk patients with atrial fibrillation taking oral anticoagulation. Madhavan M , Hu TY , Gersh BJ , Roger VL , Killian J , Weston SA , Graff-Radford J , Asirvatham SJ , Chamberlain AM.

Efficacy of warfarin anticoagulation and incident dementia in a community-based cohort of atrial fibrillation. Rivard L , Khairy P , Talajic M , Tardif JC , Nattel S , Bherer L , Black S , Healey J , Lanthier S , Andrade J , Massoud F , Nault I , Guertin MC , Dorian P , Kouz S , Essebag V , Ellenbogen KA , Wyse G , Racine N , Macle L , Mondesert B , Dyrda K , Tadros R , Guerra P , Thibault B , Cadrin-Tourigny J , Dubuc M , Roux JF , Mayrand H , Greiss I , Roy D.

Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation BRAIN-AF : methods and design.

Kalantarian S , Ruskin JN. Atrial fibrillation and cognitive decline: phenomenon or epiphenomenon? Kuhne M , Krisai P , Conen D , Osswald S.

The heart-brain connection: further establishing the relationship between atrial fibrillation and dementia?

Efimova I , Efimova N , Chernov V , Popov S , Lishmanov Y. Ablation and pacing: improving brain perfusion and cognitive function in patients with atrial fibrillation and uncontrolled ventricular rates.

Friedman HS , O'Connor J , Kottmeier S , Shaughnessy E , McGuinn R. The effects of atrial fibrillation on regional blood flow in the awake dog.

Demeestere J , Lemmens R. Anticoagulation in low-risk patients with atrial fibrillation: beyond prevention of ischaemic stroke. Cortes-Canteli M , Kruyer A , Fernandez-Nueda I , Marcos-Diaz A , Ceron C , Richards AT , Jno-Charles OC , Rodriguez I , Callejas S , Norris EH , Sanchez-Gonzalez J , Ruiz-Cabello J , Ibanez B , Strickland S , Fuster V.

J Am Coll Cardiol ; 74 : — Festoff BW , Sajja RK , van Dreden P , Cucullo L. Machida T , Dohgu S , Takata F , Matsumoto J , Kimura I , Koga M , Nakamoto K , Yamauchi A , Kataoka Y.

Google Preview. Zamolodchikov D , Renne T , Strickland S. Lackay H , Housel EL. The arrest of recurrent embolism due to auricular fibrillation with mitral stenosis by quinidine-anticoagulant therapy.

Turakhia MP , Ziegler PD , Schmitt SK , Chang Y , Fan J , Than CT , Keung EK , Singer DE. Atrial fibrillation burden and short-term risk of stroke: case-crossover analysis of continuously recorded heart rhythm from cardiac electronic implanted devices.

Glotzer TV , Daoud EG , Wyse DG , Singer DE , Ezekowitz MD , Hilker C , Miller C , Qi D , Ziegler PD. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study.

Brambatti M , Connolly SJ , Gold MR , Morillo CA , Capucci A , Muto C , Lau CP , Van Gelder IC , Hohnloser SH , Carlson M , Fain E , Nakamya J , Mairesse GH , Halytska M , Deng WQ , Israel CW , Healey JS ; ASSERT Investigators.

Temporal relationship between subclinical atrial fibrillation and embolic events. Martin DT , Bersohn MM , Waldo AL , Wathen MS , Choucair WK , Lip GY , Ip J , Holcomb R , Akar JG , Halperin JL ; IMPACT Investigators.

Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices.

Mahajan R , Perera T , Elliott AD , Twomey DJ , Kumar S , Munwar DA , Khokhar KB , Thiyagarajah A , Middeldorp ME , Nalliah CJ , Hendriks JML , Kalman JM , Lau DH , Sanders P.

Subclinical device-detected atrial fibrillation and stroke risk: a systematic review and meta-analysis. Kamel H , Okin PM , Elkind MS , Iadecola C.

Atrial fibrillation and mechanisms of stroke: time for a new model. Left atrial size and the risk of stroke and death. The Framingham Heart Study.

Folsom AR , Nambi V , Bell EJ , Oluleye OW , Gottesman RF , Lutsey PL , Huxley RR , Ballantyne CM. Troponin T, N-terminal pro-B-type natriuretic peptide, and incidence of stroke: the Atherosclerosis Risk In Communities study.

Kamel H , Soliman EZ , Heckbert SR , Kronmal RA , Longstreth WT Jr , Nazarian S , Okin PM. P-wave morphology and the risk of incident ischemic stroke in the Multi-Ethnic Study of Atherosclerosis.

King JB , Azadani PN , Suksaranjit P , Bress AP , Witt DM , Han FT , Chelu MG , Silver MA , Biskupiak J , Wilson BD , Morris AK , Kholmovski EG , Marrouche N.

Left atrial fibrosis and risk of cerebrovascular and cardiovascular events in patients with atrial fibrillation.

Habibi M , Zareian M , Ambale Venkatesh B , Samiei S , Imai M , Wu C , Launer LJ , Shea S , Gottesman RF , Heckbert SR , Bluemke DA , Lima JAC.

Left atrial mechanical function and incident ischemic cerebrovascular events independent of AF: insights from the MESA study.

Atrial fibrillation and the risk of ischemic stroke: does it still matter in patients with a CHA2DS2-VASc score of 0 or 1?

Healey JS , Connolly SJ , Gold MR , Israel CW , Van Gelder IC , Capucci A , Lau CP , Fain E , Yang S , Bailleul C , Morillo CA , Carlson M , Themeles E , Kaufman ES , Hohnloser SH , Investigators A.

Subclinical atrial fibrillation and the risk of stroke. Hobbelt AH , Spronk HM , Crijns H , Ten Cate H , Rienstra M , Van Gelder IC. Prethrombotic state in young very low-risk patients with atrial fibrillation.

Lip GY , Nieuwlaat R , Pisters R , Lane DA , Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation.

Gialdini G , Nearing K , Bhave PD , Bonuccelli U , Iadecola C , Healey JS , Kamel H. Perioperative atrial fibrillation and the long-term risk of ischemic stroke.

Bjerkelund CJ , Orning OM. The efficacy of anticoagulant therapy in preventing embolism related to D.

Moreyra E , Finkelhor RS , Cebul RD. Limitations of transesophageal echocardiography in the risk assessment of patients before nonanticoagulated cardioversion from atrial fibrillation and flutter: an analysis of pooled trials.

Lip GYH , Banerjee A , Boriani G , Chiang CE , Fargo R , Freedman B , Lane DA , Ruff CT , Turakhia M , Werring D , Patel S , Moores L. Antithrombotic therapy for atrial fibrillation : CHEST Guideline and Expert Panel Report.

Brieger D , Amerena J , Attia JR , Bajorek B , Chan KH , Connell C , Freedman B , Ferguson C , Hall T , Haqqani HM , Hendriks J , Hespe CM , Hung J , Kalman JM , Sanders P , Worthington J , Yan T , Zwar NA.

National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the diagnosis and management of atrial fibrillation Thomas L , McKay T , Byth K , Marwick TH.

Abnormalities of left atrial function after cardioversion: an atrial strain rate study. Kirchhof P , Benussi S , Kotecha D , Ahlsson A , Atar D , Casadei B , Castella M , Diener H-C , Heidbuchel H , Hendriks J , Hindricks G , Manolis AS , Oldgren J , Popescu BA , Schotten U , Van Putte B , Vardas P , Agewall S , Camm J , Baron Esquivias G , Budts W , Carerj S , Casselman F , Coca A , De Caterina R , Deftereos S , Dobrev D , Ferro JM , Filippatos G , Fitzsimons D , Gorenek B , Guenoun M , Hohnloser SH , Kolh P , Lip GYH , Manolis A , McMurray J , Ponikowski P , Rosenhek R , Ruschitzka F , Savelieva I , Sharma S , Suwalski P , Tamargo JL , Taylor CJ , Van Gelder IC , Voors AA , Windecker S , Zamorano JL , Zeppenfeld K.

Nuotio I , Hartikainen JE , Gronberg T , Biancari F , Airaksinen KE. Time to cardioversion for acute atrial fibrillation and thromboembolic complications.

Garg A , Khunger M , Seicean S , Chung MK , Tchou PJ. Incidence of thromboembolic complications within 30 days of electrical cardioversion performed within 48 hours of atrial fibrillation onset.

McIntyre WF , Connolly SJ , Wang J , Masiero S , Benz AP , Conen D , Wong JA , Beresh H , Healey JS.

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Magn Reson Med. Download references. The study was funded by a Rosalind Franklin Fellowship by the University of Groningen DSV , Netherlands Organization for Health Research and Development ZonMw MAJT , Fonds Nuts-Ohra MAJT , Princes Beatrix Muscle fund MAJT , Gossweiler foundation MAJT , Science Foundation Dystonia Society MAJT , Funds Mental Health MAJT , Phelps Foundation MAJT , Beatrix Children Hospital Fund MAJT , Healthy Aging Fund UMCG MAJT.

Department of Neurology, University Medical Center Groningen, Hanzeplein 1, RB, Groningen, The Netherlands. Marlous C. Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.

Department of Radiology, University Medical Center Groningen, Groningen, The Netherlands. Department of Radiology, Zorggroep Twente, Almelo and Hengelo, The Netherlands.

Department of Cell Biology, University Medical Center Groningen, Groningen, The Netherlands. Research project - Conception: MW, PL, MT Organization: MW Execution: MW, PL, DV, MT Statistical analysis - Design: MW, PL Execution: MW, PL Review and Critique: MW, PL, RL, DV, MT Manuscript preparation - Writing of the first draft: MW; Review and Critique: PL, RL, DV, MT.

All authors read and approved the final manuscript. Correspondence to Marlous C. The study was approved by the Medical Ethics Committee of the University Medical Center Groningen and participants or their parents gave written informed consent.

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NBIA patient demographics. Figure S1. SWI with the positioning of the circular region-of-interest. Figure S2. Presence or absence of cortical pencil lining.

Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and Permissions.

Cortical pencil lining on SWI MRI in NBIA and healthy aging. BMC Neurol 19, Download citation. Received : 25 May Accepted : 20 September Published : 14 October Skip to main content.

Search all BMC articles Search. Download PDF. Research article Open Access Published: 14 October Cortical pencil lining on SWI MRI in NBIA and healthy aging Marlous C.

Lambrechts 1 , 5 , Dineke S. Abstract Background Neurodegeneration with brain iron accumulation NBIA is characterized by pathological iron accumulation in the subcortical nuclei and the cortex.

Results In healthy subjects, an age-dependent increase of pencil lining occurred starting from the second decade of life and was present in all cases at the age of Conclusions Cortical pencil lining is part of healthy aging.

Background Iron is an essential component for normal brain function including energy production, mitochondrial respiration, protein and DNA synthesis, as well as in the biosynthesis of neurotransmitters and myelin [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].

Methods Participants Brain MRI scans of healthy subjects without known neurodegenerative, psychiatric, cerebrovascular or post-traumatic disease, were included from a research database of the department of Radiology of the University Medical Center Groningen UMCG , Groningen, the Netherlands.

Table 1 Demographic data of healthy study subjects per decade at moment of scanning Full size table. Results Cortical pencil lining The qualitative SWI scan analysis revealed that the presence of cortical pencil lining was positively correlated with age.

Full size image. Table 2 Quantitative age-related iron accumulation indicated by NSIR signal intensities per nucleus Full size table. Discussion This study, where iron imaging data from the very early decades of life are reported, showed that cortical pencil lining is potentially less specific as a general marker for NBIA.

Conclusions In this study, we showed that cortical pencil lining may not be a biomarker for NBIA in general. Abbreviations ALS: Amyotrophic lateral sclerosis ANOVA: Analysis of variance BPAN: Beta-propeller protein-associated neurodegeneration CSF: Cerebrospinal fluid LV: Lateral ventricle NBIA: Neurodegeneration with brain iron accumulation NSIR: Normalized SWI signal intensity ratio PKAN: Pantothenate kinase associated neurodegeneration PLA: primary lateral sclerosis PLAN: PLA2G6-Associated Neurodegeneration ROI: Region-of-interest SWI: Susceptibility-weighted imaging TE: Echo time TR: Repetition time.

References 1. Acknowledgments The authors wish to extend their gratitude to the study participants and their families.

Funding The study was funded by a Rosalind Franklin Fellowship by the University of Groningen DSV , Netherlands Organization for Health Research and Development ZonMw MAJT , Fonds Nuts-Ohra MAJT , Princes Beatrix Muscle fund MAJT , Gossweiler foundation MAJT , Science Foundation Dystonia Society MAJT , Funds Mental Health MAJT , Phelps Foundation MAJT , Beatrix Children Hospital Fund MAJT , Healthy Aging Fund UMCG MAJT.

Author information Author notes Dineke S. Verbeek and Marina A. Tijssen Shared last authors Affiliations Department of Neurology, University Medical Center Groningen, Hanzeplein 1, RB, Groningen, The Netherlands Marlous C.

Tijssen Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands Marlous C.

Verbeek Department of Radiology, University Medical Center Groningen, Groningen, The Netherlands Peter Jan van Laar Department of Radiology, Zorggroep Twente, Almelo and Hengelo, The Netherlands Peter Jan van Laar Department of Cell Biology, University Medical Center Groningen, Groningen, The Netherlands Roald A.

Lambrechts Authors Marlous C. View author publications. Ethics declarations Ethics approval and consent to participate The study was approved by the Medical Ethics Committee of the University Medical Center Groningen and participants or their parents gave written informed consent.

Consent for publication Not applicable. Competing interests The authors declare that there are no disclosures or competing interests relevant to this work.

Additional file. Additional file 1: Table S1.

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1 Kommentar

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