Diagnosis of non-consensus transient ischaemic attacks with focal, negative, and non-progressive symptoms: population-based validation by investigation and prognosis

Abstract

Background: Diagnosis of transient ischaemic attacks (TIAs) can be difficult. There is consensus on classic symptoms (eg, motor weakness, dysphasia, hemianopia, monocular visual loss) but no consensus on several monosymptomatic events with sudden-onset, non-progressive, focal negative symptoms (eg, isolated diplopia, dysarthria, vertigo, ataxia, sensory loss, and bilateral visual disturbance), with much variation in investigation and treatment.

Methods: We prospectively ascertained and investigated all strokes and sudden onset transient neurological symptoms in a population of 92 728 people (no age restrictions) from Oxfordshire, UK, who sought medical attention at nine primary care practices or at the John Radcliffe Hospital, Oxford, UK (Oxford Vascular Study). Patients classified at baseline with minor ischaemic stroke (National Institutes of Health Stroke Score <5), classic TIA, or non-consensus TIA were treated according to secondary prevention guidelines. Risks of stroke (7-day, 90-day, and 10-year risks) and risks of all major vascular events (from the time of first event, and from the time of seeking medical attention) were established by face-to-face follow-up visits and were compared with the risk expected from age and sex-specific stroke incidence in the underlying study population.

Findings: Between April 1, 2002, and March 31, 2018, 2878 patients were identified with minor ischaemic stroke (n=1287), classic TIA (n=1021), or non-consensus TIA (n=570). Follow-up was to Oct 1, 2018 (median 5·2 [IQR 2·6-9·2] years). 577 first recurrent strokes after the index event occurred during 17 009 person-years of follow-up. 90-day stroke risk from time of the index event after a non-consensus TIA was similar to that after classic TIA (10·6% [95% CI 7·8-12·9] vs 11·6% [95% CI 9·6-13·6]; hazard ratio 0·87, 95% CI 0·64-1·19; p=0·43), and higher than after amaurosis fugax (4·3% [95% CI 0·6-8·0]; p=0·042). However, patients with non-consensus TIA were less likely to seek medical attention on the day of the event than were those with classic TIA (336 of 570 [59%] vs 768 of 1021 [75%]; odds ratio [OR] 0·47, 95% CI 0·38-0·59; p<0·0001) and were more likely to have recurrent strokes before seeking attention (45 of 570 [8%] vs 47 of 1021 [5%]; OR 1·77, 95% CI 1·16-2·71; p=0·007). After excluding such recurrent strokes, 7-day stroke risk after seeking attention for non-consensus TIA (2·9% [95% CI 1·5-4·3]) was still considerably higher than the expected background risk (relative risk [RR] 203, 95% CI 113-334), particularly if the patient sought attention on the day of the index event (5·0% [2·1-7·9]; RR 300, 137-569). 10-year risk of all major vascular events was similar for non-consensus and classic TIAs (27·1% [95% CI 22·8-31·4] vs 30·9% [27·2-33·7]; p=0·12). Baseline prevalence of atrial fibrillation, patent foramen ovale, and arterial stenoses were also similar for non-consensus TIA and classic TIA, although stenoses in the posterior circulation were more frequent with non-consensus TIA (OR 2·21, 95% CI 1·59-3·08; p<0·0001).

Interpretation: Patients with non-consensus TIA are at high early and long-term risk of stroke and have cardiovascular pathological findings on investigation similar to those of classic TIA. Designation of non-consensus TIAs as definite cerebrovascular events will increase overall TIA diagnoses by about 50%.

Funding: Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Wolfson Foundation, Masonic Charitable Foundation, and British Heart Foundation.

Figure 1

MRIs of sudden onset monosymptomatic non-consensus TIAs in eight different patients with a causative ischaemic lesion (A) Two patients with transient isolated dysarthria. (i) 59-year-old patient who had 30 s episode of slurred speech; examination normal; MRI shows restricted diffusion in right post-central gyrus; MRA normal; grade 2 shunt on bubble TCD. (ii) 64-year-old patient who had sudden onset isolated slurred speech for 12 h, which fully resolved; examination normal next day; MRI shows restricted diffusion in left parietal cortex; MRA normal; grade 2 shunt on bubble TCD. (B) Two patients with transient isolated vertigo or ataxia. (iii) 65-year-old patient with sudden onset isolated vertigo, which lasted 3 min; several recurrences over next few hours; examination showed nystagmus on left lateral gaze; CT brain scan in emergency department was normal; all symptoms resolved after 6·5 h; no hearing loss or tinnitus, but reported episodes of isolated unsteadiness lasting a few seconds, occurring daily for several weeks; MRI shows partial right PICA territory infarct, with tight stenosis of the proximal right vertebral artery on MRA. (iv) 45-year-old patient, heavy smoker, with sudden onset of rotatory vertigo and nausea lasting 12 h; examination normal the following day; MRI shows restricted diffusion in right cerebellum; MRA was normal. (C) Two patients with transient isolated double vision. (v) 64-year-old patient with sudden onset of double vision lasting 30 min; could see normally if covered either eye; saw an optician the following day and no abnormalities were detected; MRI shows restricted diffusion in right thalamus; MRA normal; grade 2 shunt on bubble TCD. (vi) 58-year-old patient woke up with diplopia, with one image diagonally above the other, which resolved on closing either eye; lasted 90 min but had mild headache for 24 h; past history of anxiety and migraine; examination normal; MRI shows restricted diffusion in right thalamus. (D) Two patients with transient isolated bilateral visual disturbance. (vii) 61-year-old patient with sudden onset blurring of the whole visual field; vision was not double; symptoms fully resolved after 30 min; examination normal; MRI shows restricted diffusion in right thalamus; MRA normal; grade 2 shunt on bubble TCD. (viii) 74-year-old with sudden onset blurring of whole visual field lasting 15 min; examination normal; MRI shows bilateral restricted diffusion in occipital lobes (arrows); CT angiography showed bilateral vertebral artery stenosis. MRA=magnetic resonance angiography. TCD=transcranial doppler. PICA=posterior inferior cerebellar artery.

Figure 2

90-day stroke risk in patients with classic TIA and non-consensus TIA Plots show 90-day stroke risk from time of index event (A), from time of seeking medical attention (B), from time of seeking medical attention in patients who sought attention on the day of the index event (C), and from time of seeking medical attention in patients in whom antiplatelet treatment was not started at initial presentation (D). TIA=transient ischaemic attack.

Figure 3

90-day stroke risk from time of index event in patients with classic TIA and non-consensus TIA Plots show 90-day stroke risk in patients with classic TIA and non-consensus TIA (A) and non-consensus TIA stratified by symptoms (B), and 10-year stroke risk from time of seeking medical attention in patients with classic TIA and non-consensus TIA (C) and non-consensus TIA stratified by symptoms (D). TIA=transient ischaemic attack.

Figure 4

10-year risk of all major vascular events in patients with non-consensus TIA, classic TIA, and minor ischaemic stroke Plots show 10-year risk from time of index event (A) and from time of seeking medical attention (B). TIA=transient ischaemic attack.