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DOUBT Study Clarifies Role of MRI for TIA or Stroke
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Study Authors: Shelagh B. Coutts, Francois Moreau, et al.; Margy E. McCullough-Hicks, Gregory W. Albers
Target Audience and Goal Statement: Neurologists, radiologists, emergency department physicians, hospitalists, internists
The goal of this study was to establish the frequency of acute infarct defined by diffusion restriction detected on diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI).
Question Addressed:What was the rate of stroke defined by diffusion restriction detected on MRI scans among patients with low-risk suspected transient ischemic attack (TIA) or minor stroke presentations?
Study Synopsis and Perspective:
Patients with low-risk suspected TIA and minor stroke had a higher-than-expected rate of true ischemia on MRI, suggesting neurologists' clinical assessment alone did not reliably produce the correct diagnosis, researchers for the prospective observational DOUBT study reported.
In 1,028 patients with low-risk transient focal neurologic events, DWI MRI scans found a 13.5% rate of acute ischemic stroke; 30% of patients had their final diagnosis changed after MRI, reported Shelagh Coutts, MD, of the University of Calgary in Canada, and co-authors, in JAMA Neurology.
Expert opinion holds that the chain of events that leads to a TIA are basically the same as for a stroke. Although a TIA is typically brief, the presence of the same symptoms means that the person is at risk of a stroke in the near future. Indeed, among the half a million Americans who experience a TIA or minor stroke annually, 10% to 17% will experience an early recurrent stroke within 90 days.
While patients with motor or speech symptoms lasting more than 5 minutes are at high risk of having a stroke, half of all patients presenting with transient or mild neurologic deficits have low-risk symptoms and an uncertain diagnosis or prognosis. Half of diagnoses may also be attributed to stroke mimics (e.g., migrainous phenomena, epilepsy, anxiety, peripheral vestibulopathy, somatoform disorder, or bizarre spell), which typically have more benign prognoses.
"If you don't have motor and speech symptoms, the diagnosis is a lot less clear -- so patients with numbness, dizziness or with difficulty walking may not be diagnosed with a stroke syndrome. These patients are, overall, felt to be at low-risk of having stroke," explained Coutts in a press release.
From 2010 through 2016, researchers from the Czech Republic, Australia, and Canada recruited 1,028 eligible patients (522 women, 506 men, mean age 63 years) as part of the multicenter, international, prospective, observational cohort study known as DOUBT. These patients experienced a number of symptoms atypical of a stroke, such as numbness, dizziness, or very short episodes of weakness or difficulty with speech. Detailed neurologic assessments were performed prior to a brain MRI within 8 days of symptom onset.
Patients with lower-risk clinical presentations have been underrepresented in past studies and were excluded from most modern stroke prevention clinical trials. In this study, participant retention and follow-up was high, at 96.8%.
Of the 139 patients (13.5%) who had a DWI-positive lesion identified on MRI, 92 (8.9%) had a single lesion and 47 (4.6%) had multiple lesions. A total of seven strokes (0.7%) were seen at 1 year.
Absence of a DWI-positive lesion on MRI had a 99.8% negative predictive value for recurrent stroke, the researchers noted.
Older age (OR 1.02, 95% CI 1.00-1.04), male sex (OR 2.03, 95% CI 1.39-2.96), motor or speech symptoms on presentation (OR 2.12, 95% CI 1.37-3.29), persistent symptoms (OR 1.97, 95% CI 1.29-3.02), no history of a similar prior event (OR 1.87, 95% CI 1.12-3.11), and abnormal results of neurologic examination at time of evaluation (OR 1.71, 95% CI 1.11-2.65) were all associated with a higher risk of DWI positivity.
A total of seven patients (0.7%) had a recurrent stroke, four (0.4%) had a myocardial infarction, nine (0.9%) had a recurrent TIA, and nine (0.9%) died. All recurrent strokes occurred within the first month of presentation, with a DWI-positive lesion on MRI correlating with an increased risk of recurrent stroke (relative risk 6.4, 95% CI 2.4-16.8).
Compared with a single lesion or no lesion, the presence of multiple DWI-positive lesions was associated with an increased risk of recurrent stroke (2 of 47 [4.3%] vs 2 of 92 [2.2%] vs 2 of 889 [0.2%], P=0.002).
Nearly two-thirds of patients (63.8%) reported that all symptoms had resolved at the time of assessment. For those with resolved symptoms, the median duration was 2 hours. The median National Institutes of Health Stroke Scale score was 0, the median time from symptom onset to neurologic evaluation was 50 hours, and the median time from symptom onset to MRI was 102 hours.
Limited generalizability, a longer median time to MRI (4 days, which is longer than in similar studies of patients with high-risk TIA or mild stroke), lack of vascular imaging (which might have identified more patients with recurrent events), the potential for telephone follow-up to miss outcome events, and the self-reported nature of TIA and myocardial infarction outcomes were listed among the study limitations.
Source References: JAMA Neurology 2019; DOI: 10.1001/jamaneurol.2019.3063
Editorial: JAMA Neurology 2019; DOI: 10.1001/jamaneurol.2019.2963
Study Highlights and Explanation of Findings:
Imaging evidence of acute stroke was seen for 13.5% of DOUBT study participants referred to stroke neurologists with a possible diagnosis of TIA or minor stroke. These patients had experienced transient or minor persistent non-motor or non-speech neurologic symptoms or 5 minutes or less of motor or speech symptoms.
"A total of 30.0% of patients in this population had a change in their final clinical diagnosis, partially based on findings from an urgent MRI," the researchers wrote.
"Even experts are not always correct in the diagnosis of TIA mimics," Coutts told MedPage Today.
"Many of the traditional teaching points regarding clinical symptoms can be incorrect, such as slow progression of symptoms from one body part to another," she added. "Classically, we think of that as being a migraine aura. But sometimes, it can be from ischemia."
Because clinical symptoms alone were not adequate to identify all TIAs, the team favored adding a simple short-sequence brain MRI (e.g., axial DWI, fluid-attenuated inversion recovery, or gradient recalled echo).
"The MRI can be done in the first week as an outpatient," noted co-author Michael Hill, MD, a neurologist at Alberta Health Services' Foothills Medical Centre and member of the CSM's Hotchkiss Brain Institute and the O'Brien Institute for Public Health, in the press release.
"It is not an emergency, same-day test. The MRI has an important predictive value. A normal test means that the patient most likely has not suffered a stroke syndrome and the risk of future stroke is very, very low," Hill added.
"We applaud the authors on completing this important study and encourage the stroke community to embrace the evidence and increase the use of MRI for these patients," wrote Margy McCullough-Hicks, MD, and Gregory Albers, MD, both of Stanford University, in an accompanying editorial.
They agreed with Coutts and colleagues that accurate diagnosis of patients with TIA or stroke is important, noting that some secondary preventive strategies carry risks of their own and are usually not appropriate for patients who did not have a TIA or stroke.
Definitive diagnosis can be elusive in some patients, especially those whose symptoms don't last long or who appear to have a low-risk event. "Patients with symptoms considered low risk often undergo less extensive evaluations, and differentiating between a cerebrovascular ischemic event vs another diagnosis (such as migraine, seizure, or peripheral vertigo) can be particularly difficult based solely on history and results of physical examination," wrote McCullough-Hicks and Albers.
"Guidelines recommend performing magnetic resonance imaging (MRI) for patients with transient neurologic symptoms to help distinguish TIA from acute infarction," they continued. "However, despite the increasing use of MRI for such patients, current practice does not match the guideline recommendations to obtain an MRI scan as part of the routine evaluation of TIA."
"Future studies should include the role of vessel imaging in this population, particularly in regard to its value in determining recurrent ischemic events," they concluded.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical CollegeTake Posttest
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