We found that vertigo (+) patients had less male predominance, larger infarction volume and were less likely to have focal neurological manifestations in comparison to vertigo (-) patients. Similar to previous authors [2, 3, 8-11], we found that an infarction location in the cerebellum or dorsal brain stem was very strongly related to the development of vertigo. Moreover, the infarction volume, especially for cerebellar infarction, was evidently related to the occurrence of vertigo among our patients. To our knowledge, no similar reports exist in literature. We speculate that larger infarcts, especially in the cerebellum, mediate the development of vascular vertigo through affection of several brain structures and interconnections. Similar to our results, previous authors identified small lesions ≤ 10 mm in axial diameter in only 14% of patients with vascular vertigo [11]. The authors found focal neurological signs among 27% of their patients with small lesions, whereby the inferior cerebellar peduncle and the lateral medulla were most often involved.
The incidence of stroke in men is 32% higher than in women [14]. Furthermore, the odds ratio for the development of vertebrobasilar stroke rather than stroke in the anterior circulation was even found to be higher among men [15]. Contrarily, men represent around one-third of the vertigo population [2, 3]. In our cohort, we found less male predominance among vertigo (+) stroke patients in comparison vertigo (-) stroke patients. It might be speculated that females were more prone to develop vascular vertigo and hence the male percentage among our vertigo (+) stroke patients was diluted. In line with our findings, previous authors found male percentage of 55-57% among patients with acute vascular vertigo [4, 9]. In the current work, the infarction volume was statistically insignificantly larger among women. In other terms, the female sex predisposed to vascular vertigo and might be related to the development of larger infarcts. Previous authors found a median infarction volume, assessed using computer tomography, of 79.4 in women versus 29 cm3 in men (p=0.15) among stroke patients with non-valvular atrial fibrillation. Similarly, another study showed a negative statistically insignificant association between male sex and infarction volume in the anterior circulation (p=0.147) [16]. In our cohort, the median infarction volume among women was 3.99 cm3 versus 2.32 cm3 among men (p=0.11). Conversely, in experimental stroke models, female rats experienced smaller infarction volume in the middle cerebral artery as compared to males, whereas ovariectomized rats experienced similar infarction volumes to male rats [17].
We found a “borderline” statistically significant tendency for vertigo (+) patients to have a delayed presentation in comparison to vertigo (-) patients. This can be attributed to less predominance of focal neurological manifestations among vertigo (+) patients. In line with these findings, other authors showed that 37% of patients with vertebrobasilar stroke versus 16% of patients with stroke in anterior circulation were misdiagnosed (p<0.001) and the presence of focal neurological signs helped to pave the way for the accurate diagnosis [18]. In a previous cohort, only 42% of patients with vertebrobasilar stroke presenting with vertigo had obvious neurological signs [8]. In the current cohort, 65.6% of patients with vascular vertigo had focal neurological manifestations.
NIHSS score is lower among patients with vertebrobasilar stroke in comparison to those with stroke in the anterior circulation [19-21]. This can be explained by the fact that several clinical manifestations related to the posterior circulation like vertigo, nystagmus, nausea or vomiting are not considered in NIHSS [4], but may lead to a worse score on mRS or Barthel index. For example, a patient with vertebrobasilar stroke presenting with severe vertigo and nystagmus may have an NIHSS-score of 0 but a mRS-score of 3, if he requires some help for the activities of daily living. In our cohort, the infarction volume did not correlate with NIHSS-score on admission but correlated with mRS and Barthel-index on discharge.
Historically, the World Health Organisation (WHO) defined transient ischemic attack (TIA) as a transient focal neurological deficit lasting less than 24 hours [22]. This definition was introduced in the 1960s, at the time when magnetic resonance imaging (MRI) was not yet invented. Later on, it was found that 30-50% of patients with this classical TIA definition do have brain infarctions on MRI [23-25]. In 2009, the American Heart Association/American Stroke Association (AHA/ASA) revised the historical TIA definition, stating that a TIA is “a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction” [23]. The implementation of this AHA/ASA definition “moved” a significant proportion of patients from the TIA to the stroke category [26]. In the current work, 12/59 (20.3%) of the patients had no focal neurological manifestations, yet they had a brain infarction on MRI. In other words, those patients corresponded to the old TIA definition of the WHO but to the modern AHA/ASA stroke definition.
We found a positive association between the infarction volume and the serum levels of HbA1c. Previous authors found larger infarction volumes in the anterior circulation in patients with higher serum levels of HbA1c [16]. In another study, the infarction volume was found to be largest in patients with high-risk cardioembolic infarction, followed by infarctions on top of internal carotid artery occlusion and smallest in patients with medium-risk cardioembolic infarction and in patients with internal carotid artery stenosis [13]. Of note, male sex and diabetes were statistically significantly different between the four study groups (male sex: 52%, 77.3%, 84% and 63.6%, p=0.009 and diabetes: 19.4%, 13.6%, 40% and 40.9%, p=0.029, respectively). Whether, diabetes and female sex, in the aforementioned cohort and possibly in our study potentiated the development of larger infarctions remains a subject for future research.
Inflammation is increasingly recognized to have a potential pathophysiological mechanism in ischemic stroke [27]. Previous authors found a positive relation between polymorphonuclear leucocytes accumulation in brain infarction, assessed using single-photon emission tomography, and infarction volume in patients with middle cerebral artery infarction [28]. In our patients, a statistically significant correlation was found between serum levels of white blood cells and the infarction volume. We did not find similar reports in the literature.
There are several limitations in this study. The variability of time between symptom onset and MRI is a drawback for this study. However, this time was slightly greater in patients with vertigo, who were also found to have larger infarction volume. In order to minimize this drawback, we included patients, who underwent MRI imaging within 4 days of symptom onset. Although a non-blinded examiner (AME) assessed the images, we do not think that the non-blindness influenced our results. The dichotomization of our patients according to the presence or absence of vertigo was not initially planned and was done first after the impressive statistical results. The non-randomized nature of our relatively small cohort should be kept in mind before a conclusion can be drawn. The good NIHSS scores of our cohort may partially related to a selection bias, whereby patients, who were able to communicate the presence or absence of vertigo, were selected.