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(Stroke. 2003;34:2894.)
© 2003 American Heart Association, Inc.

Original Contributions

Head Computed Tomography Findings Predict Short-Term Stroke Risk After Transient Ischemic Attack

Vanja C. Douglas, BS; Clarissa M. Johnston, MD; Jacob Elkins, MD; Stephen Sidney, MD, MPH; Daryl R. Gress, MD S. Claiborne Johnston, MD, PhD

From the Department of Neurology, University of California, San Francisco (V.C.D, S.C.J., J.E.); Kaiser Permanente Medical Group, San Francisco, Calif (C.M.J.); Kaiser Permanente Division of Research, Oakland, Calif (S.S.); and Lynchburg Neurology Association, Lynchburg, Va (D.R.G.).

Correspondence to S. Claiborne Johnston, MD, PhD, Department of Neurology, Box 0114, University of California, San Francisco, 505 Parnassus Ave, M-798, San Francisco, CA 94143-0114. E-mail clay.johnston{at}ucsfmedctr.org

	Abstract

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Background and Purpose— Current guidelines recommend the use of head CT in the evaluation of patients with transient ischemic attack (TIA), but data supporting its value are sparse.

Methods— Patients who presented to 1 of 16 emergency departments of a large Northern California health maintenance organization and received a diagnosis of TIA from November 1997 through February 1998 were enrolled and followed up for 90 days. Clinical, demographic, and outcome data were obtained from computerized databases and medical records. Physicians blinded to patient characteristics and outcomes abstracted head CT findings from radiology reports. Abstracted findings included evidence of old or new infarct, periventricular white-matter disease, cerebral atrophy, cerebral vascular calcification, and nonischemic lesions.

Results— Head CT was performed in 67% of eligible patients (n=322) diagnosed with TIA. Evidence of a new infarct was seen on head CT in 13 patients (4%). A nonischemic cause of TIA symptoms was found in 4 patients (1.2%). During follow-up, 10.9% of TIA patients experienced subsequent stroke. After adjustment for confounders, risk for stroke during follow-up was significantly higher in those with a new infarct on head CT compared with others with TIA (odds ratio, 4.06; 95% confidence interval, 1.16 to 14.14; P=0.028). Old infarction, periventricular white-matter disease, cerebral atrophy, and cerebral vascular calcification were not predictors of subsequent risk of stroke.

Conclusions— Evidence of a new infarct on head CT in patients presenting with TIA is associated with increased short-term risk for stroke. Head CT appears to have prognostic value in patients with TIA and, for this reason alone, may be justified in their evaluation.

Key Words: cerebral ischemia, transient • cerebrovascular accident • computed tomography

	Introduction

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Current guidelines recommend the use of head CT in the evaluation of patients with transient ischemic attack (TIA).^1,2 Several benefits have been proposed, including the identification of radiographic evidence for infarction, cerebrovascular atherosclerosis, and nonischemic causes of symptoms such as subdural hematoma, brain tumor, or arteriovenous malformation. However, evidence supporting the recommendation for routine head CT after TIA is sparse.

The value of CT findings for determining short-term prognosis after TIA has not been previously investigated. Earlier studies of the relationship between infarction on head CT and outcomes have used scans obtained up to 1 month after the TIA and did not differentiate between old and new infarcts. Some have suggested that evidence for infarction on CT predicts an increase in the risk of death or recurrent stroke in the years after TIA,^3–5 but others have failed to confirm this association.^6–8 Because these earlier studies focused only on long-term prognosis, these data are difficult to generalize to the short-term period after TIA diagnosis, when the risk of stroke appears to be highest.⁹

See Editorial Comment, page 2898

To assess the utility of head CT in TIA and to test the hypothesis that head CT findings are significant predictors of short-term outcome after TIA, we conducted a retrospective, population-based cohort study in a group of consecutive patients diagnosed with TIA in the emergency departments (EDs) of a large Northern California health maintenance organization. We examined the relationship between findings on CT scans obtained within 48 hours of presentation and the occurrence of stroke during a 90-day follow-up period. We also cataloged events diagnosed as TIA in which the head CT revealed another potential etiology.

	Methods

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Patient Selection and Outcome
The methods used in the identification of patients, chart review, and determination of outcomes have been described previously.⁹ Patients were drawn from Kaiser-Permanente Northern California (KPNC), a large health maintenance organization with 16 hospitals in Sacramento, Santa Rosa, and the San Francisco Bay Area. Its 2.9 million enrollees are demographically representative of the regional population.¹⁰ Beginning in November 1997, all radiology reports were entered into a systemwide database. Patients with a primary diagnosis of TIA were identified from a database of all KPNC ED visits from November 1997 through February 1998. Those who did not have ED records available, were not members of the health plan, had coded diagnoses other than TIA, or had a prior TIA treated in the ED during the study period were excluded.

Patients’ demographic characteristics, medical history, TIA symptoms, examination findings, and medications were abstracted from medical records with the use of predefined criteria. All events occurring within 90 days of the TIA were identified from computerized databases and medical record review. Hospitalizations outside the KPNC system were available for review in a separate database, enabling nearly complete follow-up.^11,12 Stroke was defined as rapidly developing signs of focal or global disturbance of cerebral function, with no apparent nonvascular cause, lasting >24 hours or resulting in death.¹³ The diagnosis of stroke required an event that was distinguishable from the initial presentation of TIA, and all stroke diagnoses were independently confirmed by 2 neurologists.

Physicians blinded to patient characteristics and outcome abstracted head CT findings from radiology reports. Head CT scans obtained >48 hours after presentation to the ED or after the onset of new symptoms leading to a diagnosis of recurrent TIA or new stroke were excluded. Abstracted findings included evidence of old or new infarct, periventricular white-matter disease, cerebral atrophy, cerebral vascular calcification, and nonischemic lesions.

Statistical Analysis
We calculated the 90-day risk of stroke in those with or without specific findings on head CT. Continuous variables such as age and blood pressure were dichotomized at prespecified values.⁹ Fisher’s exact test was used for univariate analyses. We used multivariable logistic regression to control for variables that have previously been associated with an increase the short-term risk of stroke (age >60 years; diabetes mellitus; duration of TIA >10 minutes; symptoms on arrival in the ED; and weakness, speech deficit, or gait abnormality by history or examination).⁹

Kaplan-Meier survival-time curves were computed using time from evaluation to stroke onset during the 90-day follow-up. Follow-up was censored at stroke, death, or carotid endarterectomy. Survival curves were compared by use of the log-rank test. All calculations were performed with the Stata statistical package (version 7.0, Stata Corp).

	Results

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During the study period, 478 patients met the entry criteria. In this cohort (median age, 73 years; range, 33 to 94 years), stroke risk factors were common (Table 1). The most common TIA symptoms were weakness (45%), speech deficit (45%), sensory symptoms (37%), and gait disturbance (26%). The median duration of TIAs was 60 minutes, and a clear time of complete symptom resolution was not documented in 4 patients. One half of patients displayed symptoms in the ED. A subsequent stroke occurred in 52 patients (10.9%) during the 90-day follow-up period.

View this table: [in this window] [in a new window]   TABLE 1. Characteristics of TIA Patients With and Without Head CT*

Among those diagnosed with TIA, 322 patients (67%) underwent a head CT scan within 48 hours of their presentation and before new neurological symptoms occurred. Head CT scans were performed within the first 24 hours in 96% of these individuals. Patients who received a head CT were more likely to report sensory symptoms or a gait disturbance, manifest symptoms in the ED, and have weakness or numbness on physical examination (Table 1). Additionally, those for whom a neurological consultation was called were more likely to have had a head CT performed. There was no significant difference in the proportion of patients with strokes during follow-up between those who underwent head CT and those who did not (10.9% versus 10.9%; P=0.99). Furthermore, the distribution of stroke risk factors was similar between these 2 groups (P>0.05).

Of the head CT scans performed within 48 hours of TIA presentation, no abnormality was present in 148 (46%). There was evidence of new infarction in 13 (4%), old infarction in 69 (21%), and periventricular white-matter disease in 75 (23%). Cerebral atrophy was reported in 96 (30%), and vascular calcifications were described in 8 scans (2.5%). In all 13 cases with a new infarct, TIA symptoms were documented to have resolved within 24 hours. All new infarctions were located on the side of the brain appropriate to the symptoms manifested in the TIA. There was evidence of prior infarction in 2 patients with a new infarct.

Stroke occurred during follow-up in 5 of the 13 patients (38%) with a new infarct on head CT. Evidence of a new infarct substantially increased the odds of having a stroke within the next 90 days (odds ratio [OR], 5.81; 95% confidence interval [CI], 1.79 to 18.90). This association remained significant (OR, 4.06; 95% CI, 1.16 to 14.14) after adjustment for variables that have previously been associated with an increase in the short-term stroke risk after TIA. Most strokes in these individuals occurred within the first week after TIA (the Figure). Although other abnormal findings on head CT were associated with an increased stroke risk, the results were not statistically significant (Table 2).

View larger version (12K): [in this window] [in a new window]   Kaplan-Meier life-table analysis of survival free from stroke for patients with (dotted line) and without (solid line) new infarct on head CT. Log-rank test for equality of survivor functions, P=0.001.

View this table: [in this window] [in a new window]   TABLE 2. Head CT Findings and Stroke During 90-Day Follow-Up

Nonischemic lesions were identified in 4 scans (1.2%). One scan showed a chronic subdural hematoma, and 3 revealed brain tumors: a pontine angle mass, a corpus callosum lipoma, and multiple brain metastases.

	Discussion

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We found that evidence of a new infarct on head CT is associated with an increased 90-day risk of subsequent stroke in patients presenting to the ED with TIA. Of the patients with a new infarct on CT, 38% had a stroke within the following 3 months compared with 10% of those without an initial new infarct on CT. This association remained significant after controlling for clinical characteristics that have been shown to predict short-term risk of stroke. In addition, we found a nonischemic abnormality on head CT, which may have been the cause of neurological symptoms, in 1% of patients.

Two prior studies have reported an association between infarct on head CT and adverse outcomes after TIA. These studies enrolled patients who presented up to 30 days after a TIA and thus focused on long-term follow-up. In a study of 350 patients with TIA, Evans et al⁴ found that after adjustment for numerous cardiovascular risk factors, those with a CT-verified infarct carried a 70% increased risk of death over at least 2 years of follow-up. In the Dutch TIA Trial, patients with CT evidence of any cerebral infarct, and especially border-zone infarct, were at an increased risk of stroke or a composite outcome of stroke, myocardial infarction, or vascular death during a mean follow-up of 2.6 years.⁵ The association between infarct on head CT and outcome after TIA, however, has not been confirmed in all studies.^7,8

These and other earlier studies have reported the presence of any infarct on head CT in 12% to 35% of TIA patients.^{4,6–8,14–16} These analyses, however, did not differentiate between old and new infarcts. The number of patients in our cohort with an old or a new infarct on head CT was 25%, which falls within the range previously reported.

We are unaware of other studies that have specifically focused on the association of CT findings with short-term prognosis after TIA. Furthermore, we are unaware of prior studies that have differentiated between new and old infarcts on head CT in TIA patients. These differences may explain the novel findings reported here: Old infarction may be a marker of chronic atherosclerotic disease, whereas new infarction may identify the presence of active thrombosis at risk for symptomatic progression in the short-term period after TIA. In addition, the presence of new infarction confirms that the neurological symptoms are due to cerebral ischemia and not another cause such as migraine or seizure, a distinction that is difficult to make on clinical grounds alone. This identifies a group at higher risk for subsequent cerebral ischemia by excluding those with very low risk of stroke.

In this cohort, the rate of subsequent stroke was the same for patients regardless of whether they underwent head CT (10.9% in both groups). This indicates that, although findings on head CT may affect prognosis, the imaging procedure itself does not alter the risk of stroke after TIA. Our results, however, suggest that head CT may identify a group of TIA patients for whom more aggressive interventions such as hospital admission or urgent carotid ultrasound and possible carotid endarterectomy may be warranted.¹⁷

In our study, only 4% of patients with TIA had a new infarct detected on head CT during routine interpretation. Although we detected a statistically significant association between new infarct and increased short-term stroke risk and this is the largest study thus far to address this question, this result is nonetheless based on a small number of patients. Therefore, further investigation using a larger cohort of patients is warranted to confirm our finding. Several recent studies using diffusion-weighted MRI have reported detecting acute ischemic lesions in 35% to 48% of TIA patients, suggesting that the small number of new infarcts seen in this cohort may be due to the limited sensitivity of CT for detecting hyperacute ischemia, particularly when scans are read as part of routine clinical care.^18–20 The greater sensitivity of diffusion-weighted MRI for identifying new cerebral ischemia may allow more reliable prediction of short-term stroke risk because misclassification would be reduced. However, no studies have examined the relationship between acute ischemia on diffusion-weighted MRI and prognosis after TIA.

Several factors such as the manifestation of symptoms in the ED and the proportion of patients for whom a neurologist was called were different between TIA patients who had a head CT scan and those who did not. Such differences may reflect a selection bias in the ordering of head CT scans, with those more likely to have an ischemic origin for their symptoms being referred for imaging. However, none of the patient characteristics associated with performing a head CT predicted the presence of an old or a new infarct on CT (data not shown). Furthermore, compared with those who were not imaged acutely, patients who had CT scans were not more likely to experience a stroke during follow-up. These findings indicate that selection for head CT was not associated with prognosis overall and is unlikely to affect the generalizability of our findings.

We found that 1% of patients diagnosed with TIA had a nonischemic finding on head CT that could have explained their neurological symptoms. However, this finding may not be generalizable to all patients who present to the ED with transient neurological symptoms. Our cohort was selected on the basis of the ED physician’s coded diagnosis of TIA, generally at the time of ED discharge. We suspect that some patients who were initially thought to have had a TIA may have received an alternative diagnosis in the ED after the results of head CT became available. Previous studies that also identified patients by a discharge diagnosis reported similar percentages of patients in whom a nonischemic origin for TIA was discovered after head CT.^7,21 One small prospective study found that head CT identified a nonischemic lesion in 10% of patients presenting with clinical symptoms consistent with TIA.²² Thus, head CT appears to contribute importantly to the evaluation of suspected TIA by identifying nonischemic etiologies.

Our findings support current guidelines that recommend the use of CT in the evaluation of patients with TIA. In addition to its role in the diagnosis of nonischemic causes of transient neurological symptoms, head CT findings are useful for short-term prognosis after TIA, especially in the first few days after the ictus. Some have advocated for a redefinition of TIA in which the presence of acute infarction on head CT would preclude the diagnosis of TIA and signify that the index event was in fact a stroke.²³ Our data indicate that those with rapidly resolved clinical symptoms and evidence of acute infarction on head CT may make up a population especially vulnerable to recurrent ischemic events. Further studies are needed to evaluate whether immediate interventions can prevent irreversible symptomatic injury in this high-risk population.¹⁷

	Acknowledgments

 
Dr Johnston is supported by the National Institutes of Health (NS 02254).

Received August 14, 2003; accepted August 26, 2003.

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This Article Abstract Full Text (PDF) All Versions of this Article: 34/12/2894    most recent 01.STR.0000102900.74360.D9v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Douglas, V. C. Articles by Johnston, S. C. Search for Related Content PubMed PubMed Citation Articles by Douglas, V. C. Articles by Johnston, S. C. Pubmed/NCBI databases Medline Plus Health Information CT Scans Stroke Transient Ischemic Attack Related Collections Acute Cerebral Infarction Acute Stroke Syndromes Risk Factors for Stroke Transient Ischemic Attacks