Spectrum of Transient Visual Symptoms in a Transient Ischemic Attack Cohort
Background and Purpose—Transient visual symptoms (TVS) are common complaints. They can be related to transient ischemic attacks, but the nature of the symptoms often remains uncertain, and data on prognosis are scarce. We studied the prevalence, presentation, and effect of different types of TVS, paying particular attention to the association with high-risk pathology of embolism.
Methods—A total of 2398 patients with suspected transient ischemic attack admitted to the SOS-TIA clinic between January 2003 and December 2008 underwent immediate evaluation and treatment.
Results—Eight hundred twenty-six (34.5%) patients had TVS, including 422 (17.6%) patients with isolated TVS. Transient monocular blindness was the most frequent TVS (36.3%), followed by diplopia (13.4%), homonymous lateral hemianopia (12.3%), bilateral positive visual phenomena (10.8%), and lone bilateral blindness (4.5%). Positive diffusion-weighted imaging was found in 11.8%, 8.1%, 8.1%, and 5.0% of patients with homonymous lateral hemianopia, diplopia, lone bilateral blindness, and transient monocular blindness, respectively. Among 1850 patients (595 patients with TVS) with definite/possible transient ischemic attack or minor stroke, a major source of embolism of cardiac or arterial origin was found less frequently in patients with isolated or nonisolated TVS than in patients without TVS (19.6%; 19.7% versus 28.1%, respectively; P<0.001). However, we found a higher rate of atrial fibrillation in patients with homonymous lateral hemianopia (23.2%) than in patients with other TVS (4.0%; adjusted odds ratio, 6.71; 95% confidence interval, 2.99–15.06) or nonvisual symptoms (9.1%; adjusted odds ratio, 4.39; 95% confidence interval, 2.26–8.50).
Conclusions—Approximately 20% of patients with TVS had a major source of embolism detected, requiring urgent management. Atrial fibrillation was particularly frequent in patients with transient homonymous lateral hemianopia.
Transient visual symptoms (TVS) are common complaints among patients seeking medical attention in transient ischemic attack (TIA) clinics. Transient monocular blindness (TMB), homonymous lateral hemianopia (HLH), lone bilateral blindness (LBB), bilateral positive visual phenomena (BPVP), and diplopia are the most often encountered TVS. Accurate diagnosis of TVS is often challenging and requires experience. The range of symptoms is wide; patients often find it difficult to describe what happened to their vision some time ago, and visual disturbances can have many other causes than transient ischemia. Some TVS, such as isolated BPVP, diplopia, and LBB, do not even fulfill the National Institute of Neurological Disorders and Stroke (NINDS) criteria for TIA.1 The cause of these symptoms is often unknown, and there is uncertainty whether these patients are at increased risk of stroke and should be considered as emergencies. For example, the Face–Arms–Speech–Time message for public education on stroke symptom recognition does not include visual symptoms.
Only 1 large population-based study has looked at the effect of different types of TIA symptoms on prognosis and found that TVS were not associated with an increased risk of stroke.2 However, clinical data were recorded retrospectively from emergency department physician files rather than prospectively from neurologist observations, and subtle clinical signs were not studied in detail. TVS were simply quoted as present or absent, with no distinction between the different types of visual deficits.
Identifying patients with isolated TVS as a population at risk of recurrent stroke is important because recent studies have found that emergent appropriate treatment in TIA clinic reduces the risk of stroke by 80%.3,4 In the present study, we aimed to determine the incidence, diagnostic findings, and prognosis associated with TVS in a large cohort of patients presenting in a TIA clinic, with particular attention on the association with high-risk pathology.
The SOS-TIA methods have previously been described.3 Briefly, SOS-TIA is an outpatient round-the-clock access TIA clinic located in a stroke unit. Primary care physicians and emergency physicians in Paris and its administrative regions can contact the SOS-TIA clinic to refer patients with suspected TIA. Patients are admitted to the clinic if the suspicion of TIA is confirmed by a trained nurse or a senior vascular neurologist after a telephone interview. Admission criteria are based on the presence of transient focal cerebral or visual function disturbances.
All patients were questioned by direct interview by a senior vascular neurologist about their symptoms based on a standardized questionnaire. This questionnaire includes TVS divided into 6 categories: TMB, HLH, LBB, BPVP (phosphenes, photopsias, complex visual hallucinations, and palinopsias), diplopia, and other unclassifiable visual and nonvisual symptoms, including motor deficit, sensory deficit, speech disturbance, vertigo/unsteadiness, limb incoordination, amnesia, transient loss of consciousness, headache, and other symptoms. Depending on the clinical presentation, patients with TVS were further divided into 2 groups: (1) isolated TVS, if only visual symptoms occurred, and (2) associated TVS, if patients had transient nonvisual symptoms concurrently with TVS (in case of crescendo TIA, TVS was classified as associated TVS if nonvisual symptoms occurred at the same time as TVS or during a previous event).
Investigations and TIA Classification
If a TIA was clinically confirmed by a senior vascular neurologist, the patients entered into a standardized evaluation process, which included brain MRI (or a default computed tomographic scan), extracranial and intracranial arterial evaluation (cervical duplex ultrasonography and transcranial Doppler, most often completed by MR angiography or computed tomographic angiography), cardiac investigations (electrocardiography and echocardiography), and standard blood chemistry. Vascular risk factors were systematically reported. Patients were classified according to 5 final diagnoses: definite TIA with a recent infarct on brain imaging, definite TIA without a new lesion on brain imaging, minor stroke, possible TIA, and nonischemic diagnosis.3
Definition of Major Examination Findings
Major examination findings are defined as underlying causes of TIA that carry a short-term high risk of recurrent stroke or can lead to serious non-neurological events: symptomatic intracranial or extracranial atherosclerotic stenosis ≥50%, cervical arterial dissection, and a major source of cardiac embolism, as defined by the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other causes, and dissection) classification grade 1.5
Follow-up information on the occurrence of any vascular events or death was obtained by neurologists during face-to-face interviews or by research nurses via telephone calls at 90 days and 1 year using a standardized questionnaire. If the patient could not be contacted, a close relative or their family practitioner was interviewed. In cases of reported stroke, myocardial infarction, or vascular death, medical records were obtained whenever possible and reviewed by 2 neurologists (P.C.L. and P.A.).
Prevalence of TVS was described for all patients with a suspected TIA (n=2398), overall and according to final vascular diagnosis. Further analyses on the association of TVS with vascular risk factors, major examination findings, and vascular recurrences were based on 1850 patients with a definite or possible diagnosis of TIA or minor stroke.
Bivariate comparisons were made using the χ2 or Fisher exact tests (when the expected cell frequency was <5) for categorical variables and Student t test or ANOVA (when comparing >2 groups) for continuous variables. We studied the independent association of TVS with patient characteristics using a stepwise logistic regression analysis with entry and removal values set to 0.10; candidate variables were all patient characteristics associated with TVS in univariate analysis (P<0.20). Characteristics that remained in the stepwise regression model were subsequently used to adjust the association of TVS with major examination findings. Adjusted odds ratios and their 95% confidence intervals (CIs) for the presence of major examination findings (overall and for each subtype) associated with TVS were calculated using logistic regression analysis. Primary analyses were conducted using all TVS; they were repeated using only isolated TVS.
Finally, we compared the 1-year composite outcome (stroke, myocardial infarction, or vascular death) and the individual outcomes (including all-cause mortality) between patients with and without TVS using the log-rank test. Patients who died from causes other than stroke or vascular disease were censored at the time of their death, depending on outcome. Survival analyses were adjusted for age using a Cox proportional hazard model. Statistical testing was performed at the 2-tailed α level of 0.05. Data were analyzed using SAS version 9.3 (SAS Institute, Cary, NC).
Between January 2003 and December 2008, 2398 patients with a suspected TIA were admitted to our SOS-TIA clinic. Among them, 826 (34.4%) patients had TVS as the qualifying event. Half of these patients had an isolated TVS (n=422), and 14.3% (n=118) of patients had a recurrent TVS (<1 week of the last symptom onset). Patients with TVS (especially those with isolated symptom) were less likely to arrive at the TIA clinic within 24 hours of symptom onset than other patients (44% for patients with isolated TVS versus 61% for patients with associated TVS versus 67% for patients without visual symptom; P<0.001), despite a similar rate of patients seen within 24 hours of the phone call (75% versus 75% versus 77%, respectively; P=0.59).
Prevalence of the Different Types of Visual Symptoms
Among the 826 patients with TVS, TMB was the most frequent encountered visual disturbance (36.3%), followed by diplopia (13.4%), HLH (12.3%), BPVP (10.8%), and LBB (4.5%). TVS were unclassifiable in 22.6% of cases (Figure 1). Similar results were observed when only isolated TVS or recurrent symptoms were considered. Among the patients with TVS, a diagnosis of a nonischemic event was established in 28.2% of patients, and migraine attack was the most frequent cause (n=133; 57.1%; Table I in the online-only Data Supplement).
Regarding the type of TVS, 88.0% of patients with TMB had a diagnosis of definite TIA or minor stroke, whereas BPVP were rarely (7.8%) related to an ischemic event (Table 1). Only 49 patients with TVS (5.9%) had an ischemic lesion. This subgroup of patients had a symptom duration more longer than TVS patients with negative cerebral imaging (median, 180 versus 7 minutes; duration >60 minutes; 59.2% versus 17.2%; P<0.001). HLH was the TVS most frequently associated with an ischemic lesion (11.8%), followed by diplopia (8.1%), LBB (8.1%), and TMB (5.0%). Similar results were found when only isolated TVS were considered, except for LBB, because no patient with isolated LBB had an ischemic lesion (Table II in the online-only Data Supplement).
TVS and Vascular Risk Factors
Among the 1850 patients with a final diagnosis of TIA (possible or definite) or minor stroke, TVS were significantly associated with younger age; lower prevalence of hypertension, diabetes mellitus, and history of cardiovascular events; higher prevalence of smoking; and a shorter duration of symptoms than those with nonvisual symptoms (Table 2). Similar results were found when only isolated TVS were considered (Table 2). As a consequence, mean ABCD2 score was significantly lower in patients with TVS in comparison with patients without TVS, especially when isolated TVS were considered (3.7, 2.0, and 1.7, respectively; P<0.001). In multivariate analysis, only smoking remained unassociated with TVS (data not shown). Regarding the type of TVS, the main difference in patient characteristics was symptom duration (P<0.001), which was shortest in patients with TMB and longest in patients with HLH (Table III in the online-only Data Supplement).
TVS and Major Examination Findings
Major examination findings were significantly, less frequently found in patients with TVS compared with patients without TVS (Table 3). After adjustment, this difference was of borderline significance (odds ratio, 0.77; 95% CI, 0.60–1.00; P=0.051). Regarding the underlying cause of TIA, the main difference between patients with and without TVS was observed for symptomatic intracranial stenosis, diagnosed in 2.9% of patients with TVS compared with 6.1% of patients without TVS. Similar results were found when only isolated TVS were considered (Table 3).
Table 4 summarizes the major causes of TIA depending on the type of TVS. A major examination finding was found more frequently in patients with HLH than in patients with other TVS (36.2% versus 9.5%–21.4%) because of higher rate of atrial fibrillation (AF) in patients with HLH. In multivariable analysis, the rate of AF in patients with HLH (23.2%) was significantly higher than in patients with other TVS (4.0%; adjusted odds ratio, 6.71; 95% CI, 2.99–15.06) or nonvisual symptoms (9.1%; adjusted odds ratio, 4.39; 95% CI, 2.26–8.50). Extracranial large artery atherosclerosis was the main cause of TMB, whereas for the other types of TVS, the different major examination findings were equally represented (Table 4). In addition, when patients with single TVS were compared with those with recurrent TVS (Table IV in the online-only Data Supplement), only a higher rate of symptomatic extracranial atherosclerosis was found in patients with recurrent TVS. This difference was observed in patients with TMB; 22.2% of patients with recurrent TMB (n=12/54) had a symptomatic extracranial atherosclerosis in comparison with 10.2% of patients with single TMB (n=23/226).
TVS and Risk of Recurrent Vascular Events
A total of 1810 patients (97.8%) with a diagnosis of TIA (possible or definite) or minor stroke were followed for a median of 13 months (interquartile range, 12–16 months). At 1 year, 52 strokes (37 within 90 days; 6 fatal), 6 myocardial infarction (2 fatal), and 6 other vascular deaths had occurred. A further 14 nonvascular deaths and 5 deaths of unknown cause also occurred.
There was no significant difference in all-cause death between patients with and without TVS (1.5% and 2.0%, respectively), whereas patients with TVS had a significantly lower rate of the combined outcome of stroke, myocardial infarction, or vascular death than those with nonvisual symptoms (2.2% versus 4.1%; P=0.042; Table V in the online-only Data Supplement) because of a lower rate of stroke recurrence (Figure 2), with an age-adjusted hazard ratio of 0.41 (95% CI, 0.19–0.88; P=0.021). However, these differences disappeared when patients with TMB were excluded with a recurrent rate of 3.2% (n=10; P=0.48) for combined outcome and 2.3% (n=7; P=0.24) for stroke. The clinical characteristics of the 8 patients with TVS and stroke recurrence are available in Table VI in the online-only Data Supplement.
To the best of our knowledge, this is the first prospective report of consecutive patients with TVS presenting in a TIA clinic with systematic complete investigation of stroke subtypes. In this large cohort of 2398 consecutive patients with suspected TIA, TVS were frequent, representing approximately one third of the cohort. Baseline characteristics and diagnostic findings were similar in patients with isolated and associated TVS. Interestingly, we confirmed an ischemic origin of the symptoms in ≈80% of the patients sent to our clinic by first-line physicians. An ischemic diagnosis was particularly likely in patients with TMB (93.3%). This was not surprising because symptoms are usually easy for patients to describe, and differential diagnoses are rare. However, it was more surprising for patients with transient isolated diplopia or LBB, for whom ischemia was confirmed or considered possible in 82.6% and 93.3% of cases, respectively, whereas NINDS criteria state that these symptoms should not be defined as TIA.1 These results are in line with a recent study that found that isolated transient brain stem symptoms including diplopia and binocular visual disturbances preceded 16% of vertebrobasilar strokes.6 Taken together, these studies have major implications. They argue for the inclusion of broader diagnostic criteria of TIA symptoms than those previously defined by the NINDS1 and public education about the importance of abrupt onset of visual disturbances, even if the pending risk is to generate too many unnecessary consultations for TIA mimics.
The risk of stroke after a TIA is generally high but depends on the underlying cause. It is particularly elevated in patients with a major source of cardiac emboli and in cases of severe extracranial or intracranial atherosclerosis.7 However, this risk can be reduced by 80% when patients are treated appropriately in dedicated TIA clinics.3,4 In this case, stroke occurrence is no longer a good marker to evaluate the risk of these patients. In the present study, we evaluated the risk of patients with TVS by analyzing the underlying cause of TIA in addition to measuring major vascular event occurrence. We found that 1 of 5 patients with TVS from ischemic origin had an underlying disease associated with a high risk of stroke recurrence. This rate was lower than in patients with nonvisual neurological symptoms (28.1%) but high enough to conclude that patients with TVS should undergo immediate investigation and treatment in TIA clinics.
We also found that the risk of finding a major source of embolism was strongly related to TVS subtype. Among patients with possible/definite TIA or minor stroke, approximately one third of patients with HLH had an underlying disease, putting them at high risk of embolism. This was particularly elevated in comparison with other subgroups of patients with TVS but also in comparison with patients with nonvisual symptoms. Although less important, there was still a risk among patients with other types of TVS because we found a major source of emboli in ≈20% of patients with BPVP, LBB, or TMB and 13% of patients with diplopia. This result has major implications in terms of public education programs because visual disturbances are not currently mentioned as warning signs of stroke in these programs. As a consequence, it seems that TVS convey a relative benign significance in the general population as we observed that patients with TVS arrived significantly later in our clinic than patients with other transient neurological deficits.
Importantly, we found that the type of TVS was related to the underlying cause of stroke. This was not because of a difference in diagnosis workup because all the patients had the same investigations. AF was reported in 23% of the patients with HLH, which was 2.5× higher than that in patients without TVS and >6× more frequent than that in patients with other visual disturbances. Similar results have been found in a cohort of patients with posterior cerebral artery territory infarction8 but have not been reported in patients with TIA. This result has major implications in daily practice on diagnostic evaluation of these patients. Paroxysmal AF accounts for 25% to 62% of AF cases. The self-terminating nature of paroxysmal AF may lead to its underdiagnosis and consequent use of less effective treatment strategies (eg, aspirin instead of oral anticoagulation) in post-TIA patients. On the basis of limited data, it has been suggested that extended duration of monitoring may improve the detection rate of paroxysmal AF.9,10 We think that such monitoring could be helpful in selected patients; however, appropriate studies are required to test this hypothesis. In accordance with previous studies,11–14 severe extracranial internal carotid artery atherosclerosis was the most frequent major examination findings in patients with TMB. However, we found a prevalence of 12.5%, which was unexpectedly low in comparison with previous studies that have reported rates of severe extracranial carotid arterial lesions among patients experiencing TMB of 21% to 75%.11–14 Population differences probably largely explain the observed discrepancy. The previous studies were mainly relatively small,11,12,14 retrospective,11,12 or highly selected,11–14 whereas we systematically and prospectively enrolled a large cohort of patients presenting in a TIA clinic, which drains the large population of Paris and its administrative region without selection criteria such as age but only on the occurrence of acute and transient deficit. It is possible that TMB causes not related to age or traditional risk factors, such as vasospasm,15 are more frequent in an unselected population. Severe intracranial carotid arterial stenosis or occlusion was rarely found (2.1%) contrary to what has been observed in Chinese patients,16 but Asian patients are under-represented in French population, whereas a major source of cardiac embolism was not so rare, reported in 8.7% of the patients, and should be sought if carotid investigations are normal. None of the patients with TMB had giant-cell arteritis. In our study, diplopia, BPVP, and LBB were not associated with a specific major source of embolism, but these results should be regarded with caution considering the relatively small number of patients included.
Finally, we found that, as suggested by a lower mean ABCD2 score, patients with TVS had a better prognosis than patients with nonvisual symptoms, with a significantly lower 1-year stroke risk. The reasons for this difference are unclear, and the small number of events limits further analysis. However, it could partly be explained by the large proportion of patients with TMB in the cohort. It has previously been shown that the risk of stroke after TMB associated with atheromatous disease is about half the risk after a hemispheric TIA.17,18 Furthermore, ischemic TMB can be produced by local disease, such as vasospasm or disturbance of orbital venous circulation, with benign prognosis.15,19
The main strengths of our study are the prospective design, the large number of patients included, the rigorous case ascertainment by stroke specialists, the prospective definition and classification of the various types of TVS, and the wide admission criteria, limiting population bias. However, our study also has limitations. Diagnostic accuracy of TIA is difficult, even for stroke specialists,20 and we cannot exclude the possibility that some of the patients experienced TIA mimics rather than true TIA. Furthermore, most, but not all, patients had a full evaluation by an ophthalmologist.
In conclusion, an underlying cause that puts patients at high risk of recurrent emboli was frequent in patients with TVS presenting in our TIA clinic. These patients should be evaluated as an emergency as other patients with suspected TIA are.
Jenny Lloyd, PhD, provided editorial assistance in editing the English of the final draft of this article and was funded by SOS-ATTAQUE CEREBRALE.
Sources of Funding
Funding for this study was provided, in part, by SOS-ATTAQUE CEREBRALE and supported by the Département Hospitalo-Universitaire FIRE (Fibrosis Inflammation Remodeling) of Université Paris-Diderot, France.
Guest Editor for this article was Stephen M. Davis, MD.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.113.002420/-/DC1.
- Received June 7, 2013.
- Accepted September 9, 2013.
- © 2013 American Heart Association, Inc.
- 1.↵A classification and outline of cerebrovascular diseases II. Stroke. 1975;6:564–616.
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