Richard Jackson, MD

Ishihara T, Sato S, Uehara T, Ohara T, Hayakawa M, Kimura K, et al. Significance of Nonfocal Symptoms in Patients With Transient Ischemic Attack: The PROMISE-TIA Study. Stroke. 2018

Anyone who takes calls or sees patients in the emergency room is all too familiar with acute symptoms in patients with vascular risk factors for stroke, but which are non-localizing, anatomically unlikely to be vascular, or classically associated with non-vascular problems. This paper is a valuable step in the identification of patients who would benefit from treatment and risk-stratification but who present with atypical symptoms by building on previous observational studies using modern-day MRI imaging to assess the localization and prognosis of this symptoms.  The main limitation is that the study population is limited to people of Asian ancestry, which limits generalizability.

Historical review of the beginnings of the analysis of non-focal symptoms starts in the article with Dutch TIA Trial (DTT) in 1992, where it was found that non-focal TIA symptoms alongside focal symptoms were associated with a higher risk of cardiac death but not stroke. There have been two significant retrospective analyses since that trial continuing to investigate non-focal symptoms.  A retrospective analysis in 2005 by Compter found no difference in outcomes between focal and non-focal symptoms, but non-focal symptoms in isolation were not included in the study and the imaging modality used was CT. The Rotterdam study by Bos J et al in 2007 was a retrospective analysis from 1990 to 2005, which found that patients with both focal and non-focal symptoms of TIA each had an increased risk of stroke and the imaging modality was MRI.

The purpose of the PROMISE-TIA trial is clarifying the characteristics and 1-year prognosis of patients with TIA accompanied by non-focal symptoms using MRI. The Prospective Multicenter Registry to Identify Subsequent Cardiovascular Events After Transient Ischemic Attack (PROMISE-TIA) was a nationwide prospective multi-center observational registration study in 57 centers in Japan. Patients with TIA were enrolled within 7 days of onset from 2011-2013. TIA was defined as “focal neurological symptoms ascribable to a vascular pathogenesis and lasting <24 hours, regardless of the presence of ischemic lesions on imaging.” Retrospectively, some diagnoses of “TIA” were changed to “mimic” after the work-up was completed. Classic TIA symptoms of paresis, hypoesthesia, dysarthria, amaurosis, dizziness, unsteadiness, and amnesia were included in questionnaires. Descriptions of non-focal symptoms of decreased consciousness, confusion, amnesia, unsteadiness, cardiac signs, bilateral weakness, feeling unwell or hearing impairment were extracted from descriptive answer text and then classified using the Rotterdam study classification system.

Of interest, 22% of the 219 patients with non-focal TIA symptoms had anterior circulation symptoms compared to 30% of the 1143 focal TIA symptom population. The reverse was true for posterior circulation with 20% of the 219 patients with non-focal symptoms compared to 11% of the 1143 focal TIA population. There was also a higher percentage of posterior circulation lesions found in the non-focal group than the focal (20 vs. 11%), while similar rates were found in the anterior circulation (31 vs. 35%). These patients with non-focal symptoms were less likely to be smokers, have lower blood pressure, a lower ABCD2 score, lower HDL, but more likely to have vascular lesions (OR 1.94) and DWI lesions in the posterior circulation (OR 3.07). In the 1-year follow-up visit, ischemic stroke occurred in 7.5% of the non-focal symptom group and 8.1% in the focal symptom group. This difference was not significant.

Limitations acknowledged by the authors include the lack of generalizability of results to populations other than Asian, the observational nature, and the individualized treatment of each patient by different physicians.