Background: Stroke mimics are common in the emergency department (ED) and early detection is important to initiate appropriate treatment and withhold unnecessary procedures. We aimed to compare the frequency, clinical characteristics and predictors of non-neurological and neurological stroke mimics transferred to our ED for suspected stroke.

Methods: This was a cross-sectional study of consecutive patients with suspected stroke transported to the ED of the University Hospital Essen between January 2017 and December 2021 by the city’s Emergency Medical Service. We investigated patient characteristics, preclinical data, symptoms and final diagnoses in patients with non-neurological and neurological stroke mimics. Multinominal logistic regression analysis was performed to assess predictors of both etiologic groups.

Results: Of 2167 patients with suspected stroke, 762 (35.2%) were diagnosed with a stroke mimic. Etiology was non-neurological in 369 (48.4%) and neurological in 393 (51.6%) cases. The most common diagnoses were seizures (23.2%) and infections (14.7%). Patients with non-neurological mimics were older (78.0 vs. 72.0 y, p < 0.001) and more likely to have chronic kidney disease (17.3% vs. 9.2%, p < 0.001) or heart failure (12.5% vs. 7.1%, p = 0.014). Prevalence of malignancy (8.7% vs. 13.7%, p = 0.031) and focal symptoms (38.8 vs. 57.3%, p < 0.001) was lower in this group. More than two-fifths required hospitalization (39.3 vs. 47.1%, p = 0.034). Adjusted multinominal logistic regression revealed chronic kidney and liver disease as independent positive predictors of stroke mimics regardless of etiology, while atrial fibrillation and hypertension were negative predictors in both groups. Prehospital vital signs were independently associated with non-neurological stroke mimics only, while age was exclusively associated with neurological mimics.

Conclusions: Up to half of stroke mimics in the neurological ED are of non-neurological origin. Preclinical identification is challenging and a high proportion requires hospitalization. Awareness of underlying etiologies and differences in clinical characteristics is important to provide optimal care.