Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation

B Ratajczak-Tretel; A Tancin Lambert; R Al-Ani; K Arntzen; G K Bakkejord; H M O Bekkeseth; V Bjerkeli; G Eldøen; A K Gulsvik; B Halvorsen; G A Høie; H Ihle-Hansen; S Ingebrigtsen; C Kremer; S B Krogseth; C Kruuse; M Kurz; I Nakstad; V Novotny; H Naess; R Qazi; M K Rezaj; D M Rørholt; L H Steffensen; J Sømark; H Tobro; T C Truelsen; L Wassvik; K L Ægidius; D Atar; A H Aamodt

doi:10.1186/s12883-023-03155-0

Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation

BMC Neurol. 2023 Mar 21;23(1):115. doi: 10.1186/s12883-023-03155-0.

Authors

B Ratajczak-Tretel^{1

2}, A Tancin Lambert^{3

4}, R Al-Ani⁵, K Arntzen⁶, G K Bakkejord⁶, H M O Bekkeseth⁷, V Bjerkeli⁸, G Eldøen⁹, A K Gulsvik¹⁰, B Halvorsen^{4

8}, G A Høie⁵, H Ihle-Hansen^{11

12}, S Ingebrigtsen¹³, C Kremer^{14

15}, S B Krogseth¹⁶, C Kruuse¹⁷, M Kurz¹⁸, I Nakstad¹⁹, V Novotny²⁰, H Naess²⁰, R Qazi¹⁰, M K Rezaj¹⁸, D M Rørholt⁹, L H Steffensen¹³, J Sømark⁷, H Tobro²¹, T C Truelsen²², L Wassvik²³, K L Ægidius²³, D Atar^{4

24}, A H Aamodt^{25

26}

Affiliations

¹ Department of Neurology, Østfold Hospital Trust, Postboks 300, Grålum, 1714, Norway. barbara.ratajczak@so-hf.no.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway. barbara.ratajczak@so-hf.no.
³ Department of Neurology, Østfold Hospital Trust, Postboks 300, Grålum, 1714, Norway.
⁴ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Department of Cardiology, Østfold Hospital Trust, Grålum, Norway.
⁶ Department for Neurology, Nordlandssykehuset, Bodø, Norway.
⁷ Lillehammer Hospital, Department of Neurology, Innlandet Hospital Trust, Lillehammer, Norway.
⁸ Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
⁹ Department of Neurology, Molde Hospital, Molde, Norway.
¹⁰ Department of Internal Medicine, Diakonhjemmet Hospital, Oslo, Norway.
¹¹ Stroke Unit, Oslo University Hospital, Ullevål, Oslo, Norway.
¹² Department of Internal Medicine, Vestre Viken Hospital Trust, Baerum Hospital, Gjettum, Norway.
¹³ Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
¹⁴ Department of Neurology, Skåne University Hospital, Malmö, Sweden.
¹⁵ Department of Clinical Sciences, Lund University, Lund, Sweden.
¹⁶ Department of Neurology, Vestfold Hospital, Tønsberg, Norway.
¹⁷ Department of Neurology, Herlev Gentofte Hospital, Herlev, Denmark.
¹⁸ Department of Neurology, Stavanger University Hospital, Stavanger, Norway.
¹⁹ Drammen Hospital, Department of Neurology, Vestre Viken Hospital Trust, Drammen, Norway.
²⁰ Department of Neurology, Haukeland University Hospital, Bergen, Norway.
²¹ Department of Neurology, Telemark Hospital, Skien, Norway.
²² Department of Neurology, Rigshospitalet University Hospital, Copenhagen, Denmark.
²³ Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark.
²⁴ Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway.
²⁵ Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
²⁶ Department of Neuromedicine and Movement science, The Norwegian University of Science and Technology, Trondheim, Norway.

Abstract

Background: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management.

Methods: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis.

Results: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA₂DS₂-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091).

Conclusion: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal.

Trial registration: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Keywords: Atrial fibrillation; Cryptogenic stroke; Guidelines; Insertable cardiac monitor; Secondary prevention; Stroke cause.

Publication types

Observational Study
Multicenter Study

MeSH terms

Atrial Fibrillation* / complications
Atrial Fibrillation* / epidemiology
Causality
Electrocardiography, Ambulatory / adverse effects
Humans
Ischemic Attack, Transient* / complications
Ischemic Attack, Transient* / diagnosis
Ischemic Attack, Transient* / epidemiology
Ischemic Stroke* / complications
Stroke* / diagnosis
Stroke* / epidemiology
Stroke* / etiology

Associated data

ClinicalTrials.gov/NCT02937077