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
Affiliations
B. Ratajczak-Tretel
Department of Neurology, Østfold Hospital Trust
A. Tancin Lambert
Department of Neurology, Østfold Hospital Trust
R. Al-Ani
Department of Cardiology, Østfold Hospital Trust
K. Arntzen
Department for Neurology, Nordlandssykehuset
G. K. Bakkejord
Department for Neurology, Nordlandssykehuset
H. M.O. Bekkeseth
Lillehammer Hospital, Department of Neurology, Innlandet Hospital Trust
V. Bjerkeli
Research Institute of Internal Medicine, Oslo University Hospital
G. Eldøen
Department of Neurology, Molde Hospital
A. K. Gulsvik
Department of Internal Medicine, Diakonhjemmet Hospital
B. Halvorsen
Institute of Clinical Medicine, University of Oslo
G. A. Høie
Department of Cardiology, Østfold Hospital Trust
H. Ihle-Hansen
Stroke Unit, Oslo University Hospital
S. Ingebrigtsen
Department of Neurology, University Hospital of North Norway
C. Kremer
Department of Neurology, Skåne University Hospital
S. B. Krogseth
Department of Neurology, Vestfold Hospital
C. Kruuse
Department of Neurology, Herlev Gentofte Hospital
M. Kurz
Department of Neurology, Stavanger University Hospital
I. Nakstad
Drammen Hospital, Department of Neurology, Vestre Viken Hospital Trust
V. Novotny
Department of Neurology, Haukeland University Hospital
H. Naess
Department of Neurology, Haukeland University Hospital
R. Qazi
Department of Internal Medicine, Diakonhjemmet Hospital
M. K. Rezaj
Department of Neurology, Stavanger University Hospital
D. M. Rørholt
Department of Neurology, Molde Hospital
L. H. Steffensen
Department of Neurology, University Hospital of North Norway
J. Sømark
Lillehammer Hospital, Department of Neurology, Innlandet Hospital Trust
H. Tobro
Department of Neurology, Telemark Hospital
T. C. Truelsen
Department of Neurology, Rigshospitalet University Hospital
L. Wassvik
Department of Neurology, Bispebjerg University Hospital
K. L. Ægidius
Department of Neurology, Bispebjerg University Hospital
D. Atar
Institute of Clinical Medicine, University of Oslo
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.
